Я пыталась сеять разумное и даже где- то вечное на совершенно поразительном по скоплению своеобразных личностей форуме Врачи РФ, но потерпела фиаско и сейчас попробую свою записную книжку ( что показалось любопытным) начать на любимом форуме РМС
Выйдет русский перевод Эндокринологии старения , вот любопытные зарисовки
Macimorelin - синтетический агонист Рецептора к грелину для тестов на секрецию СТГ, прирост оценивается при пероральном ( !) приеме.
Неужели мы простимся с инсулиновой гипогликемией как тестом ? По крайней мере в поисках дефицита ГР?
Melnichenko
20.01.2021, 12:47
"The current study confirms and extends earlier reports showing that antibody blockade of ActRII [activin type II receptor] with bimagrumab in human participants leads to a marked loss in fat mass, an increase in lean mass, and improvement in a range of metabolic biomarkers," the team wrote. "These findings suggest that blockade of the activin receptor with bimagrumab could provide a novel pharmacologic approach for managing patients with type 2 diabetes with excess adiposity."
Melnichenko
20.01.2021, 16:23
Metformin as a stand-alone or adjuvant therapy was associated with improvement in acne in patients with polycystic ovary syndrome (PCOS), researchers reported in a study published the American Journal of Clinical Dermatology.
The investigators conducted a systematic review and meta-analysis regarding the efficacy of metformin in treating patients with acne related to PCOS. The review included randomized controlled trials, nonrandomized controlled trials, and open-label studies of patients with PCOS who were treated with metformin. Standardized mean differences (SMDs) were calculated for acne scores and odds ratios (ORs) for the presence of acne, with 95% confidence intervals (CIs).
The analysis included 51 studies with a total of 2405 patients with PCOS. The researchers found that metformin as adjuvant therapy led to greater improvement of acne scores compared with the same therapy without metformin (SMD −0.256; 95% CI −0.439 to −0.074). Pooling pre-metformin and post-metformin treatment data showed a significant decrease in acne scores after metformin use (SMD −0.712; 95% CI −0.949 to −0.476). The presence of acne decreased significantly after metformin treatment (odds ratio [OR] 0.362; 95% CI 0.271-0.485).
Among several limitations, the included studies varied regarding grading acne severity or assessing the presence of acne, metformin dosage, and treatment duration. Also, the investigators could not account for confounding factors such as body mass index, glucose, insulin, and hormone status or assess medication adherence.
The researchers noted that further studies with standardized acne grading scales are needed to more precisely assess the effect of metformin on acne in women who have PCOS.
“Based on this systematic review and meta-analysis, metformin, either as individual or adjuvant therapy, may be effective in treating acne in women with PCOS, especially among those who have diabetes or wish to conceive,” stated the study authors.
“After considering other indications and contraindications, metformin can be considered for use in women with polycystic ovary syndrome for treatment of acne,” the study authors stated.
Reference
Yen H, Chang Y-T, Yee FJ, Huang Y-C. Metformin therapy for acne in patients with polycystic ovary syndrome: A systematic review and meta‑analysis [published online October 13, 2020]. Am J Clin Dermatol. doi: 10.1007/s40257-020-00565-5
This article originally appeared on Dermatology Advisor
ghrh44
22.01.2021, 21:59
Давно идёт вежливый, но ожесточённый спор: в чём причина СПКЯ? Андреа Дунайф ратует за инсулин, Джон Маршалл за частые пульсы ГнРГ, не подавляемые прогестероном. Его данные безупречно доказаны шаг за шагом. Но как ни крути, а ановуляция с образованием кист это частая черта ожирения. И то, что снижение инсулина восстанавливает овуляции и снижает андрогены это факт. И нужен кто-то умный, который придумает протокол ( или серию их) как сложить эти 2 и 2 вместе.
Melnichenko
22.01.2021, 22:04
СПКЯ мы лечили кломифенoм, диетой, витаминами, адипозином ( мир его праху) и даже бийохинолом - и все равно кто- то беременел.
Боюсь, что СПКЯ разные.
Melnichenko
09.02.2021, 08:49
A phase I study is now underway for an investigational, oral adrenocorticotropic hormone antagonist, CRN04894, aimed at the treatment of congenial adrenal hyperplasia and Cushing's disease, Crinetics Pharmaceuticals announced.
Melnichenko
09.02.2021, 08:58
А вот это уже похуже:
Brain Tumor Risk Upped With Synthetic Progestogen
— Absolute risk still low, however, and product not currently approved in U.S.
by Kristen Monaco, Staff Writer, MedPage Today February 3, 2021
A box of cyproterone acetate tablets over a computer rendering of a brain tumor
Women taking the synthetic progestogen cyproterone acetate were at increased risk for brain tumors, a French study found.
The analysis of data on over 250,000 girls and women who filled a prescription for cyproterone acetate showed that these individuals had a six-fold higher risk for developing an intracranial meningiomas compared with women not using the hormone (adjusted hazard ratio 6.6, 95% CI 4.0-11.1), reported Alain Weill, MD, of EPI-PHARE Scientific Interest Group in France, and colleagues in The BMJ.
Cyproterone acetate, a synthetic progestogen with antiandrogen effects, is currently approved in most European countries but not in the U.S. Across Europe, the drug has varying indications, including for hirsutism or hyperandrogenism spectrum in women and inoperable prostate cancer and paraphilias in men. In addition, given the antiandrogen properties, cyproterone acetate is also used as feminizing hormone therapy for transgender women.
Weill and colleagues also found that the relationship was dose-dependent, with women exposed to a cumulative dose of more than 60 g of cyproterone acetate -- the highest exposure group -- showing a nearly 22-fold increased risk (aHR 21.7, 95% CI 10.8-43.5).
Although the absolute risk for intracranial meningiomas requiring surgery or radiotherapy was low, there were 69 cases of meningiomas reported in women exposed to the hormone (289,544 person-years of follow-up) compared with 20 cases in the control group not exposed (439,949 person-years of follow-up).
This increased risk rapidly dropped off after discontinuation of cyproterone acetate. After the hormone was stopped for 1 year, the risk for meningioma dropped to only 1.8-fold higher than women never exposed (aHR 1.8, 95% CI 1.0 to 3.2). However, the risk was still more than four times higher if the cumulative dose prior to discontinuation was 12 g or more (aHR 4.2, 95% CI 2.2-8.0).
These new meningioma cases specifically tied to cyproterone acetate tended to be located in the anterior skull base and middle skull base -- mostly in the medial third of the middle skull base involving the spheno-orbital region, the researchers noted. In particular, there was a 47-fold (95% CI 14.9 -149.1) increased risk for meningiomas in the anterior skull base tied to prolonged use of cyproterone acetate.
Nearly all were treated with a neurosurgical procedure, while few received radiotherapy alone.
"Most of the participants with meningioma had taken cyproterone acetate for off-label indications, and around 30% had even continued or resumed cyproterone acetate after treatment of the meningioma, which has been formally contraindicated since 2011," the team wrote.
The observational analysis included data from 253,777 girls and women ages 7 to 70 from SNDS, a French administrative healthcare database covering the entire population of the country. All had been recorded as having at least one reimbursement for cyproterone acetate between 2007 and 2014; the majority were prescribed the therapy by a gynecologist (57%), followed by a general practitioner (18%), dermatologist (12%), or endocrinologist (10%).
Similar findings were seen in a separate analysis looking only at transgender patients prescribed the agent. There was a high risk for meningioma among these patients, with an incidence rate of 20.7 cases per 100,000 person-years. Notably, these patients tended to receive much higher daily doses compared with other patient populations, with all cases of meningioma occurring in those taking daily doses of 100-150 mg, the researchers said.
"People who use high-dose cyproterone acetate for at least 3 to 5 years should be informed about the increased risk of intracranial meningioma," Weill's group wrote. "The indication of cyproterone acetate should be clearly defined and the lowest possible daily dose used."
However, if prolonged high-dose use is necessary, patients should be screened for meningioma via magnetic resonance imaging, the researchers advised.
"In patients with a documented meningioma, cyproterone acetate should be discontinued, because the meningioma might regress in response to treatment discontinuation and invasive treatment could be avoided," the team concluded.
Melnichenko
07.04.2021, 11:32
SAN DIEGO, March 20, 2021 /PRNewswire/ -- Neurocrine Biosciences, Inc. (Nasdaq: NBIX) today announced that it will present additional positive data from its Phase II CAHlibrate study of crinecerfont, an investigational, oral, non-steroidal corticotropin-releasing factor type 1 (CRF1) receptor antagonist for the potential treatment of classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD), at ENDO 2021, the Endocrine Society's annual meeting, on March 20–23, 2021. These new analyses, based on data from seven male subjects with classic CAH receiving crinecerfont, demonstrate dose-dependent decreases in androstenedione (A4), a key marker of CAH control and precursor to testosterone, with similar dose-dependent decreases in the A4 to testosterone ratio. Testosterone levels were preserved despite the marked reductions in A4, suggesting a positive effect on reproductive hormones and providing early indications of improved testicular function. During the ENDO 2021 Virtual Poster Hall, Neurocrine Biosciences will present the Phase II CAHlibrate data, along with two additional abstracts that highlight real-world data evaluating the impact of CAH in adult and pediatric patients.
ghrh44
07.04.2021, 14:33
Начинается эра синтетических модуляторов разных рецепторов.
Сомаверт был первой ласточкой: оба связывающих места гормона роста были модифицированы чисто по конформационным соображениям, одно место с усиленным связыванием с одним рецептором, другое с конформацией , не дающей ему связаться с другом рецептором. Как результат, получился антагонист гормона роста: нет димеризации рецепторов, - нет эффекта.
Компания Кринетикс уже сделала чистый агонист соматостатинового рецептора Тип 2: это маленькая молекула, структурально ничего общего с соматостатином не имеющая, чисто конформация связывающего места. Очень хорошо работает при акромегалии.
У них есть подобного же типа антагонист для 5 типа: для гипогликемии у детей и при инсулиномах
Есть у них и small molecule антагонист кортиколиберина, как и описанный выше Г.А.
Антагонисты гонадолиберина для преждевременного полового созревания, антагонисты ТТГ и ИФР-1 для офтальмопатии Грейвса на горизонте.
Громадный плюс такого подхода это то, что все они не разрушаются пептидазами ( они не пептиды) , и они эффективны пер ос.
То, что менингиомы растут на прогестероне, известно давно, и назначение агонистов прогестерона было крайне ограничено у людей с менингиомами. Мифепристон применяется при них широко. Так что сюрприз малый, но аргумент сильный.
Вот понять бы нейротрансмиттер аппетита, так в течение года будет антагонист.
Благодарить за всё это надо бывшего президента США Ричарда Никсона: он создал программу "Война Против Рака". Как результат её, начались широчайшие исследования в молекулярной биологии и смежных дисциплинах. Начали практически с нуля, но мы теперь чуть ли не каждые пару месяцев пожинаем плоды этой " войны" в виде новых и новых лекарств.
А Сан Диего это Кремниевая Долина всяческих " либеринов" и агонистов/антагонистов их. Там этих маленьких стартапов вагон. Уверен, что кто-то работает над не-пептидным антагонистом гормона роста.
Melnichenko
07.04.2021, 14:43
Я прошу прощения у администрации форума- когда -то, на заре нашей работы, мы старательно переводили все наши новые сведения, сейчас, думаю,нет такой необходимости и, знаю, нет времени. И спасибо проф Баркану за очень важный комментарий
ghrh44
05.05.2021, 17:11
А вот потенциальный переворот в диагностике и локализации кортикотропином
doi: 10.1210/clinem/dgaa755
Группа из Индии создала радиомеченый CRH .100% идентификация кортикотропином, причем даже не видных на МРТ(!). Накладывание изображения ПЭТ на МРТ локализовало опухоли к правильному гемигипофизу. А эктопические кортикотропиномы давали отрицательный аптэйк в гипофизе.
Пока только 24 случая, так что нужен намного больший опыт с молекулой, но вангую, что это полностью заменит катетеризацию каменистых синусов, причем с лучшими результатами.
Я не упомню другой статьи в JCEM за последние годы, которая заставила бы меня встать и снять шляпу.
Я им написал поздравление, и они мне ответили, что это еще ничего: у них уже есть еще лучшая молекула:-)
Абсолютные молодцы!
Melnichenko
28.06.2021, 16:01
For patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, oral tildacerfont for up to 12 weeks helped to normalize adrenocorticotropic hormone and androstenedione levels in two phase II studies. (Journal of Clinical Endocrinology & Metabolism)
ghrh44
24.07.2021, 19:20
Macimorelin - синтетический агонист Рецептора к грелину для тестов на секрецию СТГ, прирост оценивается при пероральном ( !) приеме.
Неужели мы простимся с инсулиновой гипогликемией как тестом ? По крайней мере в поисках дефицита ГР?
Одна доза Макрелина ( масиморелин) продаётся за ... присядьте, пожалуйста.... $4,500 ( для полуобморочных словами: четыре тысячи пятьсот долларов. Американских).
Учитывая, что число больных с эпилепсией, аритмиями , стенокардией, которым надо исключать дефицит ГР можно сосчитать на пальцах одной, ешё не ампутированной, ноги, все остальные взрослые кандидаты на выявление этой "смертельной болезни" могут проходить инсулиновую гипогликемию или тест с глюкагоном, или аргинином. Макрелин не оценивает АКТГ/Кортизол. Детям надо делать ИТТ ( кроме эпилепсии, конечно, для них глюкагон или аргинин).
А вот вместо ИТТ для дефицита АКТГ хорошо бы попробовать мифепристон: намного проще, чем метопирон, не даёт тошноты, одна доза вечером (может быть ещё одна доза рано утром) и в 8-9 утра взять АКТГ и кортизол.
Кто-то хочет сделать работу?
Первым делом, конечно, у мужчин.
ghrh44
24.07.2021, 19:24
Дубль. Прошу пардону.
Melnichenko
24.07.2021, 19:28
Мифипристон- гениально, надо попробовать.
Поговорю с производителями ( у меня Жанна не очень любит этот препарат, к сожалению)
ghrh44
04.08.2021, 07:49
Я его тоже не люблю. На мифепристоне невозможно следить за объективными лабораторными параметрами контроля Кушинга: они либо повышаются ( болезнь Кушинга), либо более-менее стоят на месте при всех остальных формах. Все решения принимаются на основании жалоб, что-то похожее на лечение антидепрессантами. Марк Молич мне плакался, что первые 3 месяца очень тяжелы для больного: качели от продолжения симптомов до надпочечниковой недостаточности ( причем кортизол при этом пробивает потолок, гипотония и пр.). А врачу надо отвечать на одно трагическое послание за другим, причем в громадном большинстве случаев все срочно, но заочно: телефонное решение полу-смертельных жалоб. Жалоба на тошноту: надпоч. недостаточность или семгу второй категории поел? Начинать дексаметазон 6-8 мг в день или рискнуть ?
Кетоконазол прост, дешев, надежен, и при этом заповедь Олбрайта «Измеряй что-то!» работает.
А вот как диагностический тест мифепристон может быть интересен. Для дефицита АКТГ уж точно, но можно попробовать его и при других « АКТГ/ кортизол» состояниях ( как насчет диф.диагноза энзиматических дефектов надпочечников? Если мне мой Альцхаймер не изменяет, здесь вроде говорили, что в РФ Синактена короткодействующего нет). Или диф. диагностика болезни Кушинга?
Назад к эндокринологии 30-40-х годов: есть какое-то соединение,- пробуй его при всех мыслимых и немыслимых болячках: Олбрайт так ввел эстрогены при акромегалии:-)
Эндокринология это такая большая и уютная песочница... играй в свое удовольствие.
А вот уже природа играет в нашей песочнице - если был подострый на ковиде, логично, что он есть и на вакцину.
Melnichenko
22.08.2021, 18:49
Oncology/Hematology
>
Renal Cell Carcinoma
FDA Approves First Drug for Von Hippel-Lindau-Associated Tumors
— Objective response or stable disease in 100% of renal cell carcinomas
by Charles Bankhead, Senior Editor, MedPage Today August 13, 2021
FDA APPROVED belzutifan (Welireg) over a computer rendering of renal carcinoma and an MRI of a hemangioblastoma
The FDA has approved the first therapy for cancers associated with von Hippel-Lindau (VHL) disease.
Belzutifan (Welireg), distributed by Merck, targets hypoxia-inducible factor 2α, which drives growth of malignant and benign tumors in VHL. In the absence of approved systemic therapies, most patients with VHL undergo multiple surgeries in their lifetime to remove renal cell carcinoma (RCC) and other VHL-associated tumors. The approval encompasses VHL-associated RCC, central nervous system (CNS) hemangioblastomas, and pancreatic neuroendocrine tumors not requiring immediate surgery.
Supporting data for the approval included results of a phase II trial of single-agent oral belzutifan in 61 patients with VHL-associated RCC, all of whom had non-RCC tumors as well. Eligible patients had at least one measurable RCC tumor, no prior systemic therapy for cancer, and no evidence of metastatic disease.
Patients received belzutifan once daily, continued until disease progression. The primary endpoint was objective response rate (ORR) in VHL-associated RCC. Secondary endpoints included ORR in non-RCC neoplasms, duration of response in RCC and non-RCC tumors, and safety.
As initially reported at the 2021 virtual meeting of the American Society of Clinical Oncology (ASCO), all 61 patients had some type of pancreatic neoplasm (pancreatic neuroendocrine tumors in 36% of cases), 50 (82%) had CNS hemangioblastomas, and 16 (26%) had retinal lesions.
The results showed that 30 of 61 (49%) patients achieved partial responses in RCC lesions with belzutifan. An additional 30 patients had stable disease, including four who had unconfirmed partial responses. The remaining patient was not evaluable for response, meaning that no patient in the intention-to-treat analysis had progressive disease during treatment with belzutifan. The median time to treatment response was 8.2 months, and median duration of response had yet to be reached.
In the patients with non-RCC tumors, the ORR was 77% in pancreatic lesions (including six complete responses), 90% (20 of 22) in pancreatic neuroendocrine tumors (three complete responses), and 30% (15 of 50) in CNS hemangioblastomas (three complete responses). Two CNS lesions progressed, but no patient had progression of pancreatic or pancreatic neuroendocrine tumors.
The most common adverse event (AE) associated with belzutifan treatment was anemia (90.2% of patients), which is considered an on-target effect of the drug, explained Ramaprasad Srinivasan, MD, of the National Cancer Institute, during an ASCO poster presentation. Other common AEs included fatigue (65.6%), headache (41.0%), dizziness (39.3%), nausea (34.4%), and dyspnea (23.0%). No patients had a grade 4 AE, and the most frequent grade 3 AEs were anemia (8.2%), hypertension (8.2%), and fatigue (4.9%).
Melnichenko
08.10.2021, 14:18
An oral peptide drug with the same amino acid sequence as injectable teriparatide (Forteo) significantly boosted bone mineral density (BMD) in postmenopausal woman at risk for osteoporosis, a researcher reported from a dose-ranging phase II trial.
Six months of treatment with the oral agent, called EBP05, at doses of 2.5 mg/day led to a mean 2.5% increase in lumbar spine BMD versus a slight decrease in women receiving placebo (P<0.002), said Arthur Santora, MD, PhD, of Entera Bio's U.S. office in Boston. (The company, which is developing EBP05, is headquartered in Jerusalem.)
Melnichenko
22.11.2021, 09:51
The FDA granted accelerated approval to the first drug to spur growth in kids with the most common form of dwarfism, the agency announced on Friday.
Vosoritide (Voxzogo), a once-daily injectable treatment, is indicated for children 5 years and older with achondroplasia and who still have open growth plates -- in other words, these children still have the potential to grow.
Дай Бог!
Melnichenko
12.12.2021, 19:27
SAN ANTONIO -- Metformin did not improve outcomes in patients with early breast cancer, regardless of estrogen receptor (ER) or progesterone receptor (PR) status, according to results from the phase III CCTGMA.32 trial.
However, an exploratory analysis suggested that metformin may have a beneficial effect in HER2-positive breast cancer, said Pamela J. Goodwin, MD, MSc, of Mount Sinai Hospital/Lunenfeld-Tanenbaum Research Institute at the University of Toronto, during a presentation at the San Antonio Breast Cancer Symposium.
Of the 620 patients with HER2-positive breast cancer analyzed, invasive disease-free survival (IDFS) was improved in those who received metformin (HR 0.64, 95% CI 0.43-0.95, P=0.03), as was overall survival (OS; HR 0.53, 95% CI 0.30-0.98, P=0.04).
Goodwin explained that this exploratory analysis was informed by the results of the METTEN study, in which the pathologic complete response rate more than doubled when neoadjuvant metformin was added to anthracycline/taxane-based chemotherapy and trastuzumab in HER2-positive patients who had at least one C allele of a prespecified ATM-associated single-nucleotide polymorphism (SNP).
"The presence of any C allele of this SNP is associated with metformin benefit in diabetes," she pointed out.
"Importantly, there was a significant interaction by SNP (P=0.05) on the effect of metformin on IDFS, with those with any C allele having a hazard ratio of 0.51 (95% CI 0.31-0.83, P=0.0067)," the researchers reported. "Whereas those with the AA genotype had no evidence of a benefit with metformin (HR 1.32, 95% CI 0.58-2.96, P=0.51)."
A similar interaction was seen for OS. The 601 patients with any C allele had a reduction in death (HR 0.35, 95% CI 0.17-0.73, P=0.003), while those with the AA genotype showed no evidence of a metformin benefit (HR 2.15, 95% CI 0.56-8.36, P=0.26).
The randomized, placebo-controlled CCTGMA.32 trial enrolled 3,649 patients ages 18 to 74 with T1-3 N0-3 M0 breast cancer and no evidence of distant metastases from 2010 to 2013. All patients were treated with standard therapy and were randomized to receive metformin 850 mg twice daily for 5 years or placebo.
In 2016, futility was declared in ER/PR-negative patients and the intervention was stopped in that group, with blinding and follow-up continuing. Thus, the study's primary analysis focused on the 2,533 ER/PR-positive patients (mean age 52.7, mean BMI 28.8).
At a median follow-up of 96.2 months, 234 IDFS events occurred in the metformin arm versus 321 in the placebo arm, 75.6% of which were due to breast cancer (HR 1.01, 95% CI 0.84-1.21, P=0.92). There were 131 deaths in the metformin arm and 119 in the placebo arm, with 75.8% of deaths related to breast cancer (HR 1.10, 95% CI 0.86-1.41, P=0.47).
Similar results for other breast cancer outcomes were observed, including distant disease-free survival (HR 0.99, 95% CI 0.80-1.23, P=0.94) and breast cancer-free interval (HR 0.98, 95% CI 0.80-1.20, P=0.87).
In a follow-up to the futility results in the 1,116 patients with ER/PR-negative breast cancer at a median follow-up of 96 months, there was no benefit seen with metformin for either IDFS (HR 1.01, 95% CI 0.79-1.30, P=0.92) or OS (HR 0.89, 95% CI 0.64-1.23, P=0.46).
"Subjects with HER2-positive breast cancer -- notably those with at least one C allele of the ATM-associated rs11212617 SNP -- experienced improved IDFS and overall survival with metformin," Goodwin concluded. "However, no P value 'spend' was allocated to this comparison. As a result, it requires replication in a prospective trial focusing on the HER2-positive population."
Melnichenko
29.12.2021, 09:06
WALTHAM, Mass., Dec. 20, 2021 (GLOBE NEWSWIRE) -- Viridian Therapeutics, Inc. (NASDAQ: VRDN), a biotechnology company advancing new treatments for patients suffering from serious diseases underserved by current therapies, today announced the first subject was dosed in a Phase 1/2 proof-of-concept clinical trial for VRDN-001, a monoclonal antibody that blocks the IGF-1 receptor with sub-nanomolar potency. IGF-1R blockade is a clinically validated mechanism of action for the treatment of TED.
The Phase 1/2 trial is designed to evaluate safety, tolerability, pharmacokinetics, and potential efficacy of VRDN-001. The trial includes both healthy volunteers and randomized, placebo-controlled cohorts of TED patients and will assess multiple measures of the signs and symptoms of TED, including proptosis – the bulging of eyes characteristic of TED. The Company expects to announce top line data from the proof-of-concept portion of the trial in the second quarter of 2022. The trial protocol allows for additional TED patient cohorts to assess differing treatment paradigms that may offer advantages over currently available therapies and may reduce the burden of patient treatment.
“We are excited to initiate our first clinical trial of VRDN-001. This trial is designed to quickly assess the potential of VRDN-001 to offer a new option for patients suffering from TED, and to inform how we can optimize VRDN-001 development to best meet patients’ needs,” stated Jonathan Violin, Ph.D., Viridian Therapeutics’ President and CEO. “VRDN-001 exemplifies Viridian’s patient-centric model of innovation that leverages proven biology and technology to efficiently craft medicines to meet the needs of patients and healthcare providers.”
FilippovaYulia
29.12.2021, 09:17
TED - это синдром хронической усталости?
Melnichenko
29.12.2021, 09:23
НЕт , это Thyrоid Eye Disease - так даже назывался журнал для больных , когда -то я написала там заметку и долго получала журнал, поэтому мне не пришла в голову мысль о расшифровке.
Melnichenko
03.01.2022, 16:29
Middle-age and older men with lower total testosterone didn't see any increased risk for myocardial infarction (MI), stroke, heart failure, or major adverse cardiovascular events. However, those with lower sex hormone-binding globulin levels did see a higher risk for MI. (Annals of Internal Medicine)
Saniona announced it initiated a phase IIb clinical trial of Tesomet -- an investigational fixed-dose combination therapy of the triple monoamine reuptake inhibitor tesofensine and the beta-1 selective blocker metoprolol -- for the treatment of Prader-Willi syndrome. The treatment is also being tested for hypothalamic obesity in another phase IIb trial.
Melnichenko
03.02.2022, 10:02
Estrogen and Progesterone Therapy and Meningiomas Get access Arrow
Mirella Hage, Oana Plesa, Isabelle Lemaire, Marie Laure Raffin Sanson
Endocrinology, Volume 163, Issue 2, February 2022, bqab259, [Ссылки могут видеть только зарегистрированные и активированные пользователи]
Published: 22 December 2021 Article history
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Abstract
Meningiomas are common intracranial tumors with a female predominance. Their etiology is still poorly documented. The role of sexual hormones has long been evoked, and data have been conflicting across studies. However, a dose-dependent relationship between the incidence and growth of meningiomas and hormonal treatment with the progestin cyproterone acetate (CPA) has recently been established. CPA-associated meningiomas seem to be mainly located in the anterior and middle skull base, are more likely to be multiple, may harbor P1K3CA mutations in up to one-third of cases, and are more common with a longer duration of treatment. A similar but lower risk of meningiomas has been recently reported with the use of chlormadinone acetate and nomegestrol acetate as progestin treatments. Concerning hormonal replacement therapy (HRT) in menopausal patients, evidence from epidemiological studies seem to favor an increased risk of meningiomas in treated patients although a recent study failed to show an increased growth of meningiomas in HRT treated vs nontreated patients. Until larger studies are available, it seems wise to recommend avoiding HRT in patients with meningiomas. Evidence from published data does not seem to support an increased risk of meningiomas with oral contraceptive oral contraceptive (OR) use. Data are too scarce to conclude on fertility treatments. Based on studies demonstrating the expression of hormonal receptors in meningiomas, therapies targeting these receptors have been tried but have failed to show an overall favorable clinical outcome in meningioma treatment.
Как-то некомфортно
Melnichenko
07.02.2022, 14:30
Viridian Therapeutics announced that the FDA cleared its investigational new drug application for VRDN-002, a next-generation IGF-1R antibody for the treatment of thyroid eye disease, to initiate a first-in-human phase I clinical trial.
Melnichenko
01.03.2022, 09:34
Switching between generic levothyroxine products won't make much of a clinical difference, a new study suggested.
In a comparative effectiveness research study of 15,829 patients, those who switched up their generic levothyroxine product didn't see any change in serum thyrotropin (TSH) levels compared with those who continued taking the same product, Juan Brito, MD, MSc, of the Mayo Clinic in Rochester, Minnesota, and colleagues reported.
Comparing lab results 6 weeks to 12 months after the index date, the proportion with normal TSH levels (0.3-4.4 mIU/L) was no different between the group who switched their levothyroxine product and so-called non-switchers (84.5% vs 82.7%; P=0.07), according to the findings in JAMA Internal Medicine.
Similarly, 3.1% of non-switchers had markedly abnormal TSH levels (<0.1 mIU/L or >10 mIU/L) versus 2.5% of switchers (P=0.14). And there were also no between-group differences in the proportion with abnormal TSH levels. Overall, average TSH levels were the same, at 2.7 mIU/L for both groups.
"Generic levothyroxine preparations are less expensive and have been rated by the FDA as bioequivalent to their brand name reference-listed drugs," Brito's group explained. "However, generic levothyroxine has been less widely prescribed than other generic pharmaceutical products."
"One potential reason for this may be the lingering concerns about an association between switching levothyroxine products sourced from different manufacturers and the stability of thyroid hormone levels," they continued.
"When clinicians prescribe a particular brand name product (indicating dispense as written), that specific product is dispensed to a patient for the duration of the prescription," the researchers pointed out. "In contrast, when clinicians prescribe generic levothyroxine, pharmacists can substitute a variety of generic levothyroxine preparations made by different manufacturers (e.g., Mylan, Sandoz, or Lannett) without requiring clinician notification or approval."
And this sparked concerns in the field, they noted, to the degree that the American Thyroid Association's 2014 clinical guidelines specifically recommended against levothyroxine switching from different manufacturers due to concerns of bioequivalence.
"Given these concerns, it is important to understand the implications of switching among different generic levothyroxine products for TSH levels," Brito's group wrote, explaining the impetus for the study.
For their analysis, the researchers drew upon data from deidentified administrative claims linked to lab results from commercially insured adults and Medicare Advantage enrollees. All patients included had filled a generic levothyroxine preparations from the top three most common manufacturers -- Mylan, Sandoz, and Lannett -- from 2008 to 2019. This included both new and prevalent users.
Roughly three-fourths of the study population were women, and the average age was 59. Over half of the cohort were receiving a daily levothyroxine dose of 50 μg or less. Exclusion criteria included pregnancy, hypopituitarism, hyperthyroidism, or any medical condition that can affect TSH levels.
During the analysis, 13,049 patients (82.4%) continued taking the same sourced preparation, while 2,780 patients (17.6%) switched between generic levothyroxine preparations. Using 1:1 propensity matching, the group compared 2,780 patient pairs to measure the implications of switching products.
Acknowledging that these findings conflict with current clinical practice guidelines, Brito's group said this should only reassure both patients and clinicians that switching among products is unlikely to bear any substantial impact.
They also suggested that these findings may help "curtail the relative underuse of generic levothyroxine in the U.S. because one of the main concerns of prescribing generic levothyroxine is the lack of control over switching among different generic products."
They noted that between 2007 to 2016, roughly three-fourths of thyroid hormone prescriptions were for generic levothyroxine versus 97% of other drugs that had both brand-name and generic options available.
"The underuse of generic levothyroxine has considerable financial implications for patients and health care systems," the group underscored.
One limitation to the study was the lack of a comparison group that specifically measured switching from brand-name levothyroxine products to generics.
НО лучше все же попусту не менять
FilippovaYulia
01.03.2022, 17:17
Я с крайней осторожностью бы экстраполировала результаты исследования брендовых дженериков на продукты российского фармпроизводства...
Melnichenko
02.03.2022, 10:04
Adding recombinant human (rh) insulin to human milk and formula helped preterm infants reach full enteral feeding faster, the randomized FIT-04 study found.
Among 303 infants with a gestational age of 26 to 32 weeks, those receiving either low-dose rh insulin (400 μIU/mL milk) or high-dose rh insulin (2,000 μIU/mL milk) for 28 days were able to achieve an enteral intake of ≥150 mL/kg per day for 3 consecutive days more quickly than infants on placebo, reported Johannes B. van Goudoever, MD, PhD, of Amsterdam University Medical Centers in the Netherlands, and colleagues in JAMA Pediatrics.
Как Вам?
FilippovaYulia
03.03.2022, 18:27
Во-первых, инсулин сам по себе легкоусваиваемый белок :) а во-вторых, так анаболическое же действие у инсулина... а учитывая повышенную проницаемость кишечника у новорожденных, особенно недоношенных, и несовершенство ферментных систем, вполне возможно, что микроколичества доходят в кровоток "непереваренными" и малость стимулируют все, что только могут...
Melnichenko
28.03.2022, 09:59
Dramatic, Durable Hair Growth With Oral JAK Inhibitor
— Oral baricitinib superior to placebo at 36 weeks in BRAVE-AA1 and BRAVE-AA2 trials
by Charles Bankhead, Senior Editor, MedPage Today March 27, 2022
BOSTON -- An oral Janus kinase (JAK) inhibitor produced significant, durable hair growth, including scalp, eyebrows, and eyelashes in patients with severe alopecia areata, according to long-term data from two randomized trials.
Almost 40% of patients achieved a Severity of Alopecia Tool (SALT) score ≤20 (total percentage of hair loss) at 52 weeks with a higher dose of baricitinib (Olumiant), and almost 30% had a SALT score ≤10. The patients had a mean SALT score >80 at baseline. Almost half of the patients had met response criteria for eyebrow and eyelash regrowth, reported Brett King, MD, PhD, of Yale School of Medicine in New Haven, Connecticut.
Adverse events (AEs) that occurred more often with baricitinib than with placebo were acne, elevated creatinine kinase levels, and increased LDL and HDL cholesterol, King said in a presentation at the American Academy of Dermatology (AAD) meeting.
The 52-week results showed continued improvement as compared with results after 36 weeks of follow-up, which were reported simultaneously in the New England Journal of Medicine.
"Continued treatment with baricitinib after 36 weeks resulted in further increases in the proportion of patients who achieved scalp, eyebrow, and eyelash hair regrowth," said King. "The proportion of patients achieving a SALT score <20 and/or a SALT score <10 -- and that's kind of a high bar -- continued to increase. The proportion of patients achieving ClinRO [Clinician Reported Outcome] for eyebrow and eyelash hair loss ... also continued to increase, restoring to nearly normal or normal."
"This is truly transformational for patients," he added. "These patients start out looking nothing like themselves, and they finish study, at least when it works, looking like themselves again, restored to normal."
Limited Treatment Options
An autoimmune condition with no approved therapies, alopecia areata affects men and women alike and causes rapid hair loss in the scalp, eyebrows, and eyelashes. The pathogenesis of the condition involves genetic and immune factors. Cytokines implicated in alopecia areata depend on the JAK pathway for intracellular signaling, providing a rationale for evaluating the therapeutic potential of JAK inhibition.
King reported findings from 52 weeks of follow-up in the BRAVE-AA1 and BRAVE-AA2 randomized, placebo-controlled evaluations of baricitinib in adults with active alopecia areata associated with a SALT score ≥50 (at least 50% hair loss). Investigators at 169 centers in 10 countries randomized 1,200 patients 2:2:3 to placebo, baricitinib 2 mg, or baricitinib 4 mg.
The primary endpoint was the proportion of patients achieving a SALT score ≤20 at 36 weeks. Secondary endpoints included a SALT score ≤10 and a ClinRO of 0 or 1 (full eyebrow/eyelash coverage or minimal gaps) with at least a 2-point improvement from baseline. The 52-week assessment focused on the same three outcomes. Patients allocated to the JAK inhibitor remained in their assigned dose groups, and placebo-treated patients with SALT score >20 switched to baricitinib after 36 weeks.
The study population had a median age of about 37, and women accounted for about 60% of all patients. About two-thirds of the patients had an alopecia duration of <4 years, and >40% had alopecia universalis. Baseline SALT score averaged about 85 across the placebo and baricitinib groups.
Key Results
The 36-week results showed that 34% of patients in the baricitinib 4-mg arm had a SALT score ≤20, as compared with 19.7% of the 2-mg arm, and 4.1% of the placebo group. At 52 weeks, the proportion of patients with SALT score ≤20 had increased to 39% with the 4-mg baricitinib dose and 22.6% with the lower dose.
For the more stringent SALT score ≤10, response rates at 36 weeks were 24.9%, 11.8%, and 2.3%, respectively for baricitinib 4 mg, baricitinib 2 mg, and placebo. Rates increased to 28.9% and 15.3% for the baricitinib arms at 52 weeks.
Rates of ClinRO response for eyebrows increased from 33.0% at 36 weeks to 44.1% at 52 weeks with the higher dose of baricitinib and from 15.8% to 22.9% with the 2-mg dose. In the placebo group, 3.8% of patients met ClinRO response criteria at 36 weeks.
Changes in ClinRO response for eyelashes from 36 to 52 weeks were 33.6% to 45.3% with baricitinib 4 mg and from 12.0% to 25.5% with baricitinib 2 mg. The placebo group had a 4.3% ClinRO response at 36 weeks.
In response to a question from the audience, King said patients with longstanding alopecia areata are not good candidates for treatment with the JAK inhibitor. A patient with a 10-year history of the hair loss is unlikely to benefit, although outliers do exist.
Similar results emerged from a subgroup analysis of phase IIb/III placebo-controlled study of a different JAK inhibitor. An analysis of 105 adolescents (mean age 15) included in the overall study population showed that the JAK3/TEC inhibitor ritlecitinib led to SALT score ≤20 responses in 17%-28% of patients treated for 24 weeks with one of five doses of the drug. Additionally, 17%-28% of patients met criteria for SALT ≤10 responses.
From 22%-61% of patients treated with ritlecitinib rated results as improved or much improved on Patient Global Impression of Change index. The best results occurred in patients randomized to a 200-mg loading dose of the drug followed by 50 or 30 mg daily, reported Maria Hordinsky, MD, of the University of Minnesota in Minneapolis, and colleagues, in an AAD poster presentation. The most common AEs (including the placebo group) were headache, nasopharyngitis, and upper respiratory infection.
Melnichenko
30.03.2022, 08:56
The FDA has approved a new oral testosterone undecanoate capsule (Tlando) for hypogonadism, Antares Pharma announced.
This androgen is indicated for testosterone replacement therapy in adult men for conditions associated with a deficiency or absence of endogenous testosterone, including congenital or acquired primary hypogonadism, as well as congenital or acquired hypogonadotropic hypogonadism.
"The FDA approval of Tlando brings to market an oral formulation of testosterone that we believe will prove beneficial to physicians and their patients," said Robert F. Apple, president and CEO of Antares Pharma.
The approval was based on a phase III trial in which about 80% of participants achieved 24-hour average serum testosterone concentrations within the normal range between 300 to 1,080 ng/dL with Tlando, meeting the primary efficacy endpoint.
Prior to treatment initiation, diagnosis of hypogonadism must be confirmed via morning measurements of serum testosterone concentrations on at least two separate days to see if levels are below the normal range.
The recommended dosage is 225 mg orally twice daily with food. It does not require dose titration.
"We believe Tlando's oral formulation and convenient dosing, which requires no titration, differentiates it from other treatment options," noted Apple.
The drug was also deemed a Schedule III controlled substance, due to risks of abuse and misuse of testosterone.
FilippovaYulia
30.03.2022, 10:02
Отлично. Давно не хватало хорошего перорального тестостерона. Хотя посмотрим еще, сколько будет стоить...
Melnichenko
30.03.2022, 15:26
BOSTON -- About half of patients with longstanding vitiligo obtained significant repigmentation that persisted for at least a year with the topical Janus kinase (JAK) inhibitor ruxolitinib (Opzelura), two randomized trials showed.
In one trial, 52.6% of patients randomized to ruxolitinib cream had at least 75% improvement in the Facial Vitiligo Area Scoring Index (F-VASI75) at 52 weeks. In the second trial, 48% of patients met F-VASI75 response criteria at 52 weeks. Patients in the trials who switched from placebo to ruxolitinib after 24 weeks also had substantial improvement at 52 weeks.
The most common treatment-related adverse events (TRAEs) with ruxolitinib were application-site acne and pruritus, reported David Rosmarin, MD, of Tufts Medical Center in Boston, during the American Academy of Dermatology (AAD) meeting here.
"Half of patients who applied ruxolitinib cream from day 1 achieved F-VASI75 and T-VASI50 [trunk] responses by week 52," said Rosmarin. "Efficacy at week 52 in crossover patients, after 28 weeks of ruxolitinib cream, was consistent with week-24 data in patients who applied ruxolitinib cream from day 1. Ruxolitinib cream was well tolerated, and no serious treatment-related adverse events were reported."
Also at AAD, preliminary data from a trial of oral JAK inhibitor ritlecitinib, presented by Yuji Yamaguchi, MD, PhD, of Pfizer, provided evidence that the drug halted progression of active vitiligo lesions and induced repigmentation in stable lesions, with consistent results for up to 48 weeks across the range of Fitzpatrick skin types.
Long-Term Ruxolitinib Outcomes
Rosmarin previously reported the primary outcome for the TRuE-V1 and TRuE-V2 trials, which showed that ruxolitinib 1.5% cream BID significantly increased the F-VASI75 response rate at 24 weeks versus vehicle. The updated report included ruxolitinib-treated patients who continued the JAK inhibitor to week 52, as well as placebo-treated patients who switched to ruxolitinib after completing the 24-week randomized trial.
Ожидаемый прорыв
Melnichenko
30.03.2022, 20:23
Men taking metformin were more likely to have offspring with birth defects, a Danish study found.
Newborns with fathers who took metformin during the development of fertilizing sperm had a 40% higher frequency of birth defects compared with newborns whose fathers used insulin (adjusted OR 1.40, 95% CI 1.08-1.82), reported Maarten J. Wensink, MD, PhD, of the University of Southern Denmark, and colleagues.
The same did not hold true for offspring with fathers who took sulfonylureas versus insulin (aOR 1.34, 95% CI 0.94-1.92), they pointed out in the Annals of Internal Medicine.
Неприятно... Мб, что-то не так посчитали?
FilippovaYulia
30.03.2022, 20:27
Как-то с трудом верится. А поправки на длительность диабета, метаболический синдром, прием препаратов от АГ, наличие осложнений?.. надо будет вчитаться в трайл.
Dr.Vad
30.03.2022, 20:43
это не трайл, а ретро-наблюдение [Ссылки могут видеть только зарегистрированные и активированные пользователи]
Dr.Vad
30.03.2022, 20:49
простой пример, как выводы зависят от статистики:
и на метформине и на сульф-мочевине был прирост на 35-40%, по сравнению с инсулином, НО на метФ было в 2 раза больше пациентов, поэтому 40% прирост оказался стат. состоверным, на на СуМо 34% повышение - нет, лишь потому, что метф прописывали в 2 раза чаще: Metformin-exposed offspring (n = 1451) had an elevated birth defect frequency (aOR, 1.40 [CI, 1.08 to 1.82]). For sulfonylurea-exposed offspring (n = 647), the aOR was 1.34 (CI, 0.94 to 1.92).
прямо скажем, что из-за редкости назначения сульфМ она статистически не дотянула до 1/3 избыточных врожденных проблем, а метформин - оказался инфант-террибль
Melnichenko
30.03.2022, 21:00
очень хочется думать так.
Melnichenko
04.04.2022, 11:18
Targeting 11-Beta Hydroxylase With [131I]IMAZA: A Novel Approach for the Treatment of Advanced Adrenocortical Carcinoma Get access Arrow
Stefanie Hahner, Philipp E Hartrampf, Patrick W Mihatsch, Marc Nauerz, Britta Heinze, Heribert Hänscheid, Carmina Teresa Fuß, Rudolf A Werner, Christina Pamporaki, Matthias Kroiss ... Show more
The Journal of Clinical Endocrinology & Metabolism, Volume 107, Issue 4, April 2022, Pages e1348–e1355, [Ссылки могут видеть только зарегистрированные и активированные пользователи]
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with limited treatment options. Theranostic approaches with adrenal specific radiotracers hold promise for improved diagnostics and treatment.
Objective
Here, we report a new theranostic approach to advanced ACC applying (R)-1-[1-(4-[123I]iodophenyl)ethyl]-1H-imidazole-5-carboxylic acid azetidinyl amide ([123I]IMAZA) for diagnostic imaging and [131I]IMAZA for radionuclide therapy.
Methods
Sixty-nine patients with nonresectable, metastatic ACCs were screened using a diagnostic [123I]IMAZA scan. Patients with significant uptake in all tumoral lesions were offered treatment with [131I]IMAZA. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1), and adverse effects were assessed by Common Toxicity Criteria (version 5.0).
Results
After screening, 13 patients were treated with a median of 25.7 GBq [131I]IMAZA (range 18.1-30.7 GBq). Five individuals received a second treatment course. Best response was a decrease in the RECIST target lesions of –26% in 2 patients. Five patients with disease stabilization experienced a median progression-free survival of 14.3 months (range 8.3-21.9). Median overall survival in all patients was 14.1 months (4.0-56.5) after therapy. Treatment was well tolerated, in other words no severe toxicities (CTCAE grade ≥3) were observed.
Conclusion
In patients with advanced ACC refractory to standard therapeutic regimens, [131I]IMAZA treatment was associated with disease stabilization and nonsignificant tumor size reduction in a significant patient fraction and only limited toxicities. High [131I]IMAZA-uptake in tumor lesions was observed in 38.5% of patients with advanced ACC, rendering [131I] IMAZA a potential treatment option in a limited, well-defined patient fraction. Further clinical trials will be necessary to evaluate the full potential of this novel theranostic approach.
Melnichenko
05.04.2022, 11:53
Как-то напряжно...Ther Clin Risk Manag. 2020; 16: 245–259.
Published online 2020 Apr 8. doi: 10.2147/TCRM.S243462
PMCID: PMC7152545
PMID: 32308402
Hypophosphatemia Associated with Intravenous Iron Therapies for Iron Deficiency Anemia: A Systematic Literature Review
John A Glaspy,1 Michelle Z Lim-Watson,2 Michael A Libre,3 Swagata S Karkare,3 Nandini Hadker,3 Aleksandra Bajic-Lucas,2 William E Strauss,2 and Naomi V Dahl2
Author information Article notes Copyright and License information
Iron deficiency anemia (IDA) is a prevalent yet underdiagnosed condition with a significant impact on quality of life. Oral iron supplementation is often poorly tolerated or yields inadequate response, requiring the use of intravenous iron (IVI) in some patients. Administration of certain IVI preparations has been associated with decreases in serum phosphate levels and clinically significant hypophosphatemia, which has been reported to lead to adverse events including serious fatigue and osteomalacia.
Objective
The purpose of this study was to systematically assess the prevalence, clinical consequences, and reporting of treatment-emergent hypophosphatemia within literature investigating IVI therapies marketed in the United States (US).
Methods
A systematic literature review (SLR) was conducted using the PubMed database to identify publications reporting serum phosphate levels or rates of hypophosphatemia within adult IDA patient populations receiving current US-marketed IVIs.
Results
The SLR yielded 511 unique publications, with 40 records meeting the final inclusion criteria. Most studies did not report phosphate monitoring methodology or an explicit definition of hypophosphatemia. Hypophosphatemia rates ranged from 0.0% to 92.1% for ferric carboxymaltose (FCM), 0.0% to 40.0% for iron sucrose, 0.4% for ferumoxytol, and 0.0% for low-molecular-weight (LMW) iron dextran. Randomized controlled studies described hypophosphatemia as “asymptomatic” or did not report on other associated sequelae. Eleven case reports detailed treatment-emergent hypophosphatemia in patients treated with FCM. Patients with acute hypophosphatemia primarily developed severe fatigue; those with repeated FCM dosing developed chronic hypophosphatemia associated with osteomalacia and bone deformities.
Conclusion
Studies analyzed in this SLR reported a range of hypophosphatemia rates, with the highest consistently seen in patients treated with FCM. Across the clinical literature, there appeared to be minimal standardization of phosphate monitoring and definitions of hypophosphatemia. Although multiple cases have documented serious clinical consequences of hypophosphatemia associated with certain IVIs, current trials neither consistently nor adequately assess the frequency and severity of treatment-emergent hypophosphatemia and may underestimate its prevalence.
FilippovaYulia
05.04.2022, 12:06
По большому счету не очень напрягает, главное, помнить об этом, отслеживать и при необходимости корректировать.
Конечно, в России сейчас чаще применяют внутривенное введение железа, но все равно это ничтожно мало, особенно вдали от "центров цивилизации", коими являются Москва и Питер.
Melnichenko
05.04.2022, 12:38
Примерно так же ответил и наш гематолог , доктор Шкляев Большое спасибо за интересную статью о том, что терапия внутривенным Карбоксимальтозатом Железа может вызывать тяжелую гипофосфатемию и даже иногда остеомаляции!
Пока с такими проблемами мы не сталкивались, но хорошо знаем о том, что снижение уровня фосфора является наиболее частым побочным эффектом (в инструкции к препарату (Феринжект) это чётко прописано).
На мой взгляд основная причина того, что пока нам не доводилось сталкиваться с развитием выраженной гипофосфатемии и тем более остеомаляциями заключается в используемой нами дозе этого препарата внутривенного железа. В присланной Вами статье в США используют дозу 750 мг в/в 1 раз в неделю (N2). Мы же назначаем этот препарат по 100 мг/сутки (в/в капельно в 100 мл физ. р-ра очень медленно!) и за неделю, таким образом, набираем 500 мг. Далее обязательный перерыв на выходные дни и, если есть необходимость далее продолжаем проводить ещё 5 инфузий железа, т.о. чтобы доза достигла суммарно 1000 мг (за 12 дней).
В любом случае следует по возможности мониторировать уровень фосфора в сыворотке крови хотя бы после каждых 2-3 инфузий.
Dr.Vad
05.04.2022, 19:09
немного по диагностике этого осложнения:
In symptomatic patients a test panel including ionized calcium, total and bone-specific alkaline phosphatase, PTH, 25 (OH) vitamin D and 1,25 (OH)2 vitamin D is recommended. Typical findings in patients with intravenous iron-induced hypophosphatemia include mild hypocalcemia, normal or mildly reduced 25 (OH) vitamin D and markedly reduced 1,25 (OH)2 vitamin D with hyperparathyroidism and elevated total and bone-specific alkaline phosphatase. These changes can persist beyond the resolution of hypophosphatemia...
по ведению-профилактике:
Delay further intravenous iron doses and switch to iron formulations with lower hypophosphatemia risk in patients with hypophosphatemia.
It is unknown if vitamin D supplementation before FCM administration reduces hypophosphatemia and fracture risk.
...treatment was started in the majority of patients including oral (n = 36) or intravenous (n = 20) phosphate, activated vitamin D (n = 21),vitamin D (n = 9) or calcium (n = 10). Treatment outcome was highly variable and inconsistently reported. Considering the underlying pathogenesis driven by elevated intact FGF23, phosphate supplementation would not sustainably correct hypophosphatemia, but increase urinary phosphate excretion [[39], [40], [41]]. As clinical and biochemical changes apparently persist up to several months after the last FCM infusion, rational treatment approaches would include mitigation of secondary hyperparathyroidism with activated vitamin D, which was successfully used in some patients [40,42,43].
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Hypophosphatemia after intravenous iron therapy: Comprehensive review of clinical findings and recommendations for management. 2022
[Ссылки могут видеть только зарегистрированные и активированные пользователи]
ELENA_VLAD
07.04.2022, 14:52
[Ссылки могут видеть только зарегистрированные и активированные пользователи](22)00045-6/fulltext
Background
Women positive for thyroid peroxidase antibodies (TPO-Ab) have a higher risk of recurrent pregnancy loss. Evidence on whether levothyroxine treatment improves pregnancy outcomes in women who are TPO-Ab positive women with recurrent pregnancy loss is scarce. The aim of this study was to determine if levothyroxine increases live birth rates in women who were TPO-Ab positive with recurrent pregnancy loss and normal thyroid function.
Methods
The T4LIFE trial was an international, double-blind, placebo-controlled, phase 3 study done in 13 secondary and tertiary hospitals in the Netherlands, one tertiary hospital in Belgium, and one tertiary hospital in Denmark. Women (18–42 years) who were TPO-Ab positive, had two or more pregnancy losses, and had a thyroid stimulating hormone (TSH) concentration within the institutional reference range were eligible for inclusion. Women were excluded if they had antiphospholipid syndrome (lupus anticoagulant, anticardiolipin IgG or IgM antibodies, or β2-glycoprotein-I IgG or IgM antibodies), other autoimmune diseases, thyroid disease, previous enrolment in this trial, or contraindications for levothyroxine use. Before conception, women were randomly assigned (1:1) to receive either levothyroxine or placebo orally once daily. The daily dose of levothyroxine was based on preconception TSH concentration and ranged from 0·5–1·0 μg/kg bodyweight. Levothyroxine or placebo was continued until the end of pregnancy. The primary outcome was live birth, defined as the birth of a living child beyond 24 weeks of gestation measured in the intention-to-treat population. The trial was registered within the Netherlands Trial Register, NTR3364 and with EudraCT, 2011-001820-39.
Results
Between Jan 1, 2013, and Sept 19, 2019, 187 women were included in the study: 94 (50%) were assigned to the levothyroxine group and 93 (50%) were assigned to the placebo group. The trial was prematurely stopped when 187 (78%) of the 240 predefined patients had been included because of slow recruitment. 47 (50%) women in the levothyroxine group and 45 (48%) women in the placebo group had live births (risk ratio 1·03 [95% CI 0·77 to 1·38]; absolute risk difference 1·6% [95% CI –12·7 to 15·9]). Seven (7%) women in the levothyroxine group and seven (8%) in the placebo group reported adverse events, none of them were directly related to the study procedure.
Interpretation
Compared with placebo, levothyroxine treatment did not result in higher live birth rates in euthyroid women with recurrent pregnancy loss who were positive for TPO-Ab. On the basis of our findings, we do not advise routine use of levothyroxine in women who are TPO-Ab positive with recurrent pregnancy loss and normal thyroid function.
ghrh44
14.04.2022, 01:35
Независимая от ТТГ и свТ4 роль антител в феномене потери беременности была известна давно. Именно поэтому АТА рекомендует тироксин у женщин с ТТГ >10, но без антител, но у женщин с ТТГ 4-10, но с антителами, таки да рекомендует. Тироксин никоим образом не может повлиять на титр антител: разница в риске выкидыша 1.6% ( от -12 до +15). Поэтому смысл делания этой работы заключается в том, что хотя пользы от тироксина во втором случае от мала до нуля, но никто врача обвинить в бездеятельности не сможет:-). Адвокаты кусают локти.
ghrh44
14.04.2022, 01:43
Dramatic, Durable Hair Growth With Oral JAK Inhibitor
— Oral baricitinib superior to placebo at 36 weeks in BRAVE-AA1 and BRAVE-AA2 trials
by Charles Bankhead, Senior Editor, MedPage Today March 27, 2022
BOSTON -- An oral Janus kinase (JAK) inhibitor produced significant, durable hair growth, including scalp, eyebrows, and eyelashes in patients with severe alopecia areata, according to long-term data from two randomized trials.
Almost 40% of patients achieved a Severity of Alopecia Tool (SALT) score ≤20 (total percentage of hair loss) at 52 weeks with a higher dose of baricitinib (Olumiant), and almost 30% had a SALT score ≤10. The patients had a mean SALT score >80 at baseline. Almost half of the patients had met response criteria for eyebrow and eyelash regrowth, reported Brett King, MD, PhD, of Yale School of Medicine in New Haven, Connecticut.
Эх, опубликовали бы это на год раньше, Уилл Смит не дал бы пuбличную пощёчину Крису Року на церемонии Оскара за шутку по поводу алопеции у своей жены.
Но зато, что бы народ читал в "жёлтой прессе" в очередях в супермаркетах и обсуждал в сетях? Других же важных проблем в мире нет, не так ли?
А вот не попробовать ли барицитиниб у акромегаликов? Сигнал ГР передаётся через JAK-STAT комплеkc. Забей JAK и... что будет с ИФР-1?
Очередная сумасшедшенькая идея....
ELENA_VLAD
17.04.2022, 05:02
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The mpact of moderately high preconception TSH levels on ovarian reserve among euthyroid infertile women undergoing ARTBackground: Thyroid dysfunction is prevalent in reproductive-aged women and has been identified as a risk factor for female infertility.
However, it remains largely unclear whether subtle thyroid dysfunction, as estimated by moderately high TSH levels within the normal range, is associated with ovarian reserve in infertile women prior to assisted reproductive technology (ART).
Methods: This cross-sectional study involved 3501 euthyroid infertile women, including 2189 women with TSH levels ≤2.5 μIU/mL and 1312 women with high-normal TSH levels (2.51-4.20 μIU/mL). Ovarian reserve markers were compared between women with low- and high-normal TSH levels. Correlation analysis and regression models were used to estimate the association of TSH levels with ovarian reserve. In addition, the association of subtle thyroid dysfunction with ovarian reserve was further evaluated after stratification for different infertility diagnoses and statuses of thyroid autoimmunity (TAI).
Results: In the total population, women with high-normal TSH levels had significantly decreased AMH concentrations (p<0.001), a lower bilateral AFC (p<0.001), and a higher prevalence of diminished ovarian reserve (DOR) (p=0.018) than women with low-normal TSH levels. The TSH levels showed a negative association with both AMH levels (r=-0.050, p=0.003) and bilateral AFC (r=-0.071, p<0.001). Furthermore, the association of high-normal TSH levels with decreased AMH and AFC was more prominent in infertile women with ovulation dysfunction (p=0.002, p=0.002), unexplained infertility (p=0.020, p=0.028), or negative TAI (both p<0.001).
Conclusions: These data suggested that subtle thyroid dysfunction was associated with DOR in infertile women prior to ART, which will add evidence that strengthens the systematic screening of TSH levels/TAI in infertile women and contribute to the discussion of specific TSH cutoff values in predicting ovarian reserve.
FilippovaYulia
05.05.2022, 17:12
А можно и мне поучаствовать? 28 апреля 2022 г. - новое руководство ESMO по применению системной терапии при тяжелых случаях рака щитовидной железы [Ссылки могут видеть только зарегистрированные и активированные пользователи](22)00694-9/fulltext
ESMO Clinical Practice Guideline update on the use of systemic therapy in
advanced thyroid cancer
S. Filetti, C. Durante, D. M. Hartl, Leboulleux, L.D. Locati, K. Newbold, M.G. Papotti10 & A. Berruti, on behalf of the ESMO Guidelines Committee*
Мощно пробило ностальгией... РНЦРР. Огромный этап в моей жизни, хотя и недолгий. Приятно вспомнить...
Начинали в 2017 году с сорафенибом и ленватинибом, в личном архиве есть красивые картинки редкого вида кожной сыпи на сорафенибе. Сама учила пациентов, как "выбивать" рекомендованный Москвой препарат в регионах (без зазрения совести пользуясь волгоградским опытом в сочетании с московским авторитетом).
И в какую же громаду таргетной терапии нынче оно вырастает. В помощь тераностике.
Melnichenko
23.06.2022, 21:04
Ну, жизнь идёт.
Новости с ENDO: кагрилинтид + семаглутид ( Ново)- ответка на тирзепатит Эли Лилли , но тут любопытен кагрилинид - это амилин и он дополнительно уменьшает опорожнение желудка
Melnichenko
01.07.2022, 12:55
Как страшно жить !Accidental exposure to glimepiride from adulterated medication resulting in severe hypoglycaemia
in Endocrinology, Diabetes & Metabolism Case Reports
Authors: Annabelle G Hayes1,2, Mahesh M Umapathysivam1,2, and David J Torpy1,2
View More
Sulphonylureas are insulinotropic and are not only useful in patients with diabetes but also act in non-diabetic individuals where hypoglycaemia and hyperinsulinism mimic insulinoma. We present a 63-year-old man who presented with inadvertent sulphonylurea-induced life-threatening hypoglycaemia on two occasions, resulting in hazardous and invasive investigation. Biochemistry revealed endogenous hyperinsulinaemia, with elevated serum c-peptide and insulin concentrations during symptomatic hypoglycaemia, and plasma glucose of 1.7 mmol/L. There was no history of sulphonylurea use prompting anatomical insulinoma studies to locate an insulinoma. However, a routine plasma insulinoma screen-detected glimepiride. Directed history implicated a medication taken for erectile dysfunction prior to disturbed consciousness, with alcohol. The tablets, obtained online, were analysed by mass spectrometry and contained tadalafil and dapoxetine as advertised but also contained glimepiride.
Melnichenko
02.07.2022, 09:43
Вот сейчас благодаря нашему кхн Виталию Иоутси - запросто исследовать состав - дЭАС в китайских травках, СМ в крови невинно гипующих и даже аналоги инсулина.
Есть технические сложности, но в целом эпоха тайных поисков под подушками и в вещах ушла в прошлое
FilippovaYulia
02.07.2022, 13:00
Как-то в разговоре с Галиной Афанасьевной упоминалась мудрая мысля, что было бы неплохо проверять и тех, у кого "инсулин колем, а сахара высоченные". Эту мыслю, несомненно, мыслил любой эндокринолог, которому после безвременной кончины "бабушки, которой от сахара никакой инсулин не помогал" скорбящие родственники притаскивали агромадные пакеты с этим самым нетронутым инсулином. Частенько уже изрядно просроченным. В наследство доктору, так сказать.
Melnichenko
02.07.2022, 14:41
Юля, по моему, эту мысль высказали Вы первой, и я на наших конференциях уже говорила, что по сути это заказ от практического здравоохранения. Во всяком случае, некомплаетность при первом типе , наверное, можно было бы доказывать по инсулину крови. Надо помозговать.
Melnichenko
18.10.2022, 09:43
Dexamethasone a Safe Premedication Option for Patients With Primary Aldosterone Who Are Allergic to Iodine Contrast Media
– Prednisone is the pretreatment standard, but can make AVS interpretation difficult
by Scott Harris , Contributing Writer, MedPage Today October 17, 2022
For patients allergic to iodine contrast media (ICM), dexamethasone premedication prior to adrenal venous sampling (AVS) is a safe and more effective alternative to prednisone and other approaches when classifying primary aldosteronism (PA).
That's according to recent findings published in the Journal of the Endocrine Society.
Researchers at Centre Hospitalier of the University of Montreal in Canada identified 177 patients with confirmed PA who underwent bilateral simultaneous basal and post-adrenocorticotropic hormone (ACTH) bolus AVS. A total of 7 patients (4%) with previous allergic reactions to ICM were prepared with 3 doses of 7.5 mg of dexamethasone premedication rather than the usual 50 mg of prednisone, which can pose challenges when interpreting AVS results.
No breakthrough allergic reactions occurred in the 7 patients. Despite dexamethasone administration, cortisol response to ACTH was adequate.
Study co-author, Andre Lacroix, MD, is an endocrinologist-researcher with the center. He recently discussed the study and its findings with the Reading Room. The exchange has been edited for length and clarity.
This is something of a controversial topic. Why is that the case?
Lacroix: AVS is the optimal approach to adequately subtype PA into predominantly lateralized or bilateral disease is adrenal venous sampling. However, performing AVS in patients with ICM allergy is challenging.
Limited options are available for these patients. Alternative subtyping techniques include gadolinium-based contrast media for adrenal venography, carbon dioxide as a substitute for contrast dye, and radioiodine-labeled cholesterol analogue adrenal scintigraphy.
Each of these alternatives, however, poses significant clinical or technical challenges.
We've been doing AVS for more than 30 years, and had approached the problem differently.
How does your center approach the issue, and how did that approach lead to this study?
Lacroix: Generally, for people with ICM allergies, oral premedication with glucocorticoids (usually 3 doses of prednisone 50 mg) is administered at 13, 7, and 1 hours prior to the intervention. However, in the case of AVS, this method has long been abandoned, as prednisone can interfere with cortisol assays and suppress basal cortisol levels, rendering AVS interpretation difficult.
So instead of prednisone, we use dexamethasone. The advantage of dexamethasone over prednisone, is that it does not interfere with the measurement of cortisol and blood. At the same time, glucocorticoid pretreatment has been viewed by some as insufficiently safe to prevent ICM allergy.
We decided we would review the data that we had accumulated over the years on cases of AVS in patients with a history of ICM allergy.
How would you summarize what you discovered?
Lacroix: We went back and identified seven cases in which this procedure had been done under dexamethasone suppression. We demonstrated that in all cases, the AVS was adequate, that it allowed us to identify whether the PA was unilateral or bilateral, and that patients responded adequately to surgery when it was indicated.
Simply put, we demonstrated that dexamethasone is safe and allowed confirmation that the technical aspect was accomplished.
What are the clinical messages here that you think are important to emphasize?
Lacroix: This study demonstrated that a very simple substitution of prednisone by dexamethasone is efficient, and that none of the patients had any allergic reactions.
Severe contrast media allergy is not so frequent, but when it exists, you need to have a solution to be able to perform the exam, and to be able to offer the appropriate diagnosis and course of therapy for patients.
Our essential point was that you can substitute prednisone by dexamethasone in equivalent doses, and that it is efficient, safe, and allows adequate interpretation and performance of the examination.
Clinical implications
Dexamethasone is safe and effective as a premedication alternative to prednisone for adrenal venous sampling in patients with primary aldosteronism with iodine contrast media allergies.
Dexamethasone does not interfere with test interpretation like prednisone can.
Alternative subtyping techniques, such as substituting iodine medium for gadolinium, can pose considerable technical or clinical problems.
Melnichenko
18.10.2022, 10:16
Fezolinetant improves vasomotor symptom severity, associated sleep disturbances
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Women taking fezolinetant for moderate to severe vasomotor symptoms experienced a reduction in symptom severity and sleep disturbances, according to data presented at the NAMS Annual Meeting.
Notably, fezolinetant (Astellas Pharma) was associated with reduced vasomotor symptoms across racial subgroups as well as across the entire study population.
Fezolinetant reduced symptoms and improved sleep disturbances among women with moderate to severe vasomotor symptoms. Source: Adobe Stock
Fezolinetant reduced vasomotor symptoms and improved sleep disturbances among women with moderate to severe vasomotor symptoms. Source: Adobe Stock
“This is really exciting because it is truly the first time that we have a treatment that is specifically targeted at what we know causes hot flashes,” Genevieve Neal-Perry, MD, PhD, a member of the Fezolinetant Scientific Advisory Committee for Astellas and chair of the department of obstetrics and gynecology at University of North Carolina School of Medicine, told Healio. “There is great opportunity to meet unmet needs for patients who can’t use hormones, such as breast cancer survivors and patients with blood clot disorders.”
Efficacy by racial group
Neal-Perry and colleagues evaluated the efficacy of the nonhormonal, investigational selective neurokinin-3 receptor agonist among Black and non-Black participants in two phase 3 studies, SKYLIGHT 1 and SKYLIGHT 2. Overall, both double-blind, placebo-controlled trials found fezolinetant — which was administered once daily in 30 mg or 45 mg doses for 12 weeks — to be efficacious and well tolerated by participants.
According to Neal-Perry, Black women experience hot flashes more frequently and over a greater length of time compared with white women and are more likely to have hot flashes before menopause.
Genevieve Neal-Perry, MD, PhD
Genevieve Neal-Perry
“And so why does this really matter?” Neal-Perry said. “It matters because we know that women who have hot flashes are more likely to have heart disease, they’re more likely to have cognitive problems in terms of being able to do daily functions because of the disruption of sleep and the impact on general quality of life.”
In total, 1,022 women took at least one dose of fezolinetant or placebo. Compared with non-Black women, Black women reported hot flashes more frequently at baseline. Black women and non-Black women following either fezolinetant regimen reported significant reductions in the frequency of hot flashes at weeks 4 and 12 compared with their counterparts taking placebo.
Additionally, compared with placebo, 45 mg fezolinetant was associated with a significant reduction in severity of vasomotor symptoms across the study population and among Black and non-Black participants at weeks 4 and 12.
These findings show that despite differences in drug metabolism between white and Black women, “fezolinetant works, it’s highly effective and race does not have an impact on its effectiveness,” Neal-Perry said.
Sleep disturbances
A second study was conducted by Marla Shapiro, MDCM, CCFP, MHSc, FRCP, FCFP, NCMP, an associate professor in the department of family and community medicine at the University of Toronto, and colleagues to identify the impact fezolinetant had on sleep disturbances associated with vasomotor symptoms. Again, the researchers used data from SKYLIGHT trials 1 and 2 for their analyses.
The Patient-Reported Outcomes Measurement Information System Sleep Disturbance – Short Form (PROMIS SD SF) 8b Total Score, Patient Global Impression of Change – Sleep Disturbance (PGI-C SD) and PGI of Severity – Sleep Disturbance (PGI-S SD) were used to assess sleep disturbances among 1,022 participants who had taken fezolinetant or placebo at least once.
Compared with placebo, women who took 45 mg fezolinetant had significant improvements in scores for sleep disturbances on all three assessments at weeks 4 and 12, according to the researchers. Among women taking 30 mg fezolinetant, significant improvements in sleep were observed at week 4 using the PROMIS SD SF and PGI-S SD, and at weeks 4 and 12 using the PGI-C SD.
“We still need to do some additional studies to understand more about who will benefit in terms of sleep,” Neal-Perry said. “[For example], is it possible that people who have more night-time hot flashes are the ones who benefit in terms of overall sleep patterns?”
‘Эпонимические” имена болезней крайне часто основываются на национальности их “первоописателей”.
Истощенный больной с зобом, пучеглазием и тахикардией в Англии страдает от болезни Грейвса, в Германии от болезни Базедова, а в Италии от болезни Флайяни.
Во всем мире все знают о болезни Мари, которую он назвал акромегалией. Но наши итальянские коллеги упрямо зовут ее Прозопэктазия, имя, дaнное ей итальянцем Андреа Верга, описавшим ее на 20 лет раньше Мари. Лет 30 назад они даже создали на первом сабантуе -консенсусе в Кортина д’ Aмпеццо “ Propectazia Society”, членом которого №7 я являюсь ( не потому, что был одним из первых присоединившихся, a просто по алфавиту:-))
Но в Голландии даже выпустили марку с портретом Йоханнесa Вира, oписавшим акромегалию аж в 16 веке, но никакого приоритета голландцы почему-то не требуют.
Нет у них патриотизма!
Так что практически все страны тянут одеяло на себя.
Единственный противоположный случай, который я знаю, это сифилис. Во всей Европе он всегда звался “французской болезнью” но французы щедро отдали приоритет и звали его “ итальянской болезнью”. У россиян претензий к итальянцам не было, и в России он звался “ польской болезнью”:-)
Чем-то похоже на Австрию, где Бетховен считается австрийцем, а Гитлер немцем.
Melnichenko
26.10.2022, 08:37
In a real-world analysis of patients with thyroid eye disease treated with a full course of teprotumumab-trbw (Tepezza), only 4.9% were prescribed a second course within 2 years, maker Horizon Therapeutics said.
Melnichenko
19.11.2022, 11:11
FDA одобрил темплизумаб ( антитело к СD3) для отсрочки прогрессировния СД1
FilippovaYulia
19.11.2022, 11:18
О как! Если не ошибаюсь, это вообще первый препарат, одобренный для этой цели.
"Первая ласточка".
Глядишь, и скрининг пригодится...
ELENA_VLAD
04.03.2023, 14:59
"Несуществующие" заболевания в эндокринологии - YouTube
может быть послушают не только врачи
Melnichenko
15.03.2023, 21:29
Причудливо тасуется колода.
Уже почти позабытый сибутрамин ( а сколько всего было!) заменён младшим очень шустрым братцем тезофензином, причём для очень крутой группы - гипоталамическое ожирение, а чтоб сердечко не выскакивало, заполировали метопрололом, К Нuynh и др, 2022
FilippovaYulia
15.03.2023, 21:52
Ну, в России сибутрамин отнюдь не забыт, младые дамы роскошных размеров отказываются выходить из кабинета эндокринолога, не получив вожделенный рецептик. Еженедельно хоть одна, да есть. Согласны даже на выскакивающее сердечко и повышенное АД (хотя идея "заполировать метопрололом" свежа и заманчива).
На агонисты ГПП-1 не соглашаются, хотя при покупке оных похудеешь уже только от того, что на еду денег не останется.
Почитаем про тезофензин, глядишь, дойдет и до нас препарат (если не отменится прежде, а то сколько уж их, центрального действия, было...).
ELENA_VLAD
19.03.2023, 08:42
Эндокринная миопатия и саркопения - YouTube
Melnichenko
20.03.2023, 10:45
Радует появление в нашем арсенале ( общечеловеческом) препарата селициклиб как непосредственно влияющего на кортикотрофы
Melnichenko
05.04.2023, 08:43
The FDA "identified deficiencies" in Ascendis Pharma's new drug application for its hypoparathyroidism drug palopegteriparatide (TransCon PTH)opens in a new tab or window, putting new labeling and post-marketing discussions on hold for now, the developer said.
Melnichenko
12.04.2023, 10:22
Две новости, как в анекдоте
.
Monthly supplementation with 60,000 IU of oral vitamin D3opens in a new tab or window for older adults didn't appear to increase or decrease overall fracture risk over a 5-year period. The same held true for non-vertebral, major osteoporotic, and hip fractures. (The Lancet Diabetes & Endocrinology)
Teprotumumab (Tepezza)opens in a new tab or window led to a significantly greater reduction in proptosis over placebo in people with chronic thyroid eye disease for an average of 5 years and low levels of disease activity (2.41 vs 0.92 mm, p=0.0004), Horizon announced with its phase IV trial results.
FilippovaYulia
12.04.2023, 14:32
Насколько я помню, нативный Д3 как антиостеопоротический препарат особо и не позиционировался... В этом плане больше интереса было к активным формам витамина Д.
А Тепезза радует. Теперь бы название поблагозвучнее и регистрацию в России.
Melnichenko
19.04.2023, 09:39
Compared with oral bisphosphonates, denosumab (Prolia, Xgeva)opens in a new tab or window was linked with a lower risk for developing type 2 diabetes in adults age 45 and older with osteoporosis. (The BMJ)
The thyroid eye disease drug teprotumumab (Tepezza)opens in a new tab or window is indicated for use in patients with any level of disease activity or duration according to an FDA-cleared label update, said drugmaker Horizon Therapeutics.
FilippovaYulia
19.04.2023, 14:13
Тепезза радует все больше и больше.
Приятный факт о Пролиа.
Melnichenko
09.05.2023, 15:21
SEATTLE -- Adding beta-hydroxybutyrate (BHB) stopping criteria cut down fasting time when detecting insulinomas in patients with hypoglycemia, according to late-breaking findings presented here.
By adding in a stopping point if BHB reached a level of 2.7 mmol/L or higher to the fasting protocol, fasting time was nearly 8 hours shorter on average across the board, said Michelle D. Lundholm, MD, of the Cleveland Clinic.
With this update to the protocol, the average fast duration lasted only 49.7±21.1 hours, she said during a presentation at the American Association of Clinical Endocrinologyopens in a new tab or window (AACE) annual meeting.
вот только не пойму, как это в деньгах
Melnichenko
09.05.2023, 16:30
В принципе исследование внедрено - но кмн Юкина написала мне, что не стоит по бета- гидроксибутирату останавливать пробу, поелику не только инсулинома нас волнует. Пока не знаю
ELENA_VLAD
11.05.2023, 00:36
О метформине
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FilippovaYulia
11.05.2023, 09:02
Старый и вроде бы хорошо изученный алмаз современной диабетологии открывает все новые грани.
Но сердечно-сосудистый прогноз и метформин - данные все еще несколько противоречивы.
Korzun
11.05.2023, 11:29
Но сердечно-сосудистый прогноз и метформин - данные все еще несколько противоречивы.
Противоречия есть, но не при всех сердечно-сосудистых нозологиях.
В целом метформин стоит рассматривать как препарат улучшающий прогноз при ССЗ.
Если идти по ходу сердечно-сосудистого континуума, то:
1. Метформин значимо снижает ЛПНП даже без диабета.
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2. Метформин средне снижает вес и артериальное давление. Но Семаглутид и ингибиторы SGLT-2 делают это лучше.
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3. Метформин по эффективности лечения эректильной дисфункции находится между тадалафилом и вакуумной помпой.
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4. Во время острого инфаркта миокарда может ухудшить прогноз, но принимаемый после инфаркта улучшает его.
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5. Улучшает прогноз при аневризме аорты.
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6. При сердечной недостаточности (финал континуума) немного запутано.
SGLT2 лучше чем метформин при ХСН и делает это и без него.
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Но и с метформином прогноз тоже улучшается.
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Капля дегтя:
Если плясать от СД2, то в общей совокупности в метанализе 29 исследований с 371 смертями в них:
Комбинация метформина с другим гипогликемическим препаратом была связана с более высоким риском смертности от всех причин (ОР: 1,49; 95% ДИ: 1,02, 2,16) и сердечно-сосудистой смертности (ОР: 2,21; 95% ДИ: 1,22, 4,00) по сравнению со схемами приема гипогликемических препаратов без метформина.
Но есть оговорки по дизайну:
Однако вывод должен быть объяснен с осторожностью, учитывая ограничения Британского проспективного исследования диабета (UKPDS).
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Чуть более поздний системный обзор приходит к немного другим выводам:
В целом, несмотря на то, что такие положительные эффекты наблюдались при лечении метформином, необходимы дополнительные РКИ для улучшения нашего понимания его модулирующего воздействия на исходы, связанные с сердечной недостаточностью, особенно у пациентов с сахарным диабетом.
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Вишенка на торте:
Метформин улучшает прогноз при Ковиде-19, а летальность при нем все-таки сердечно-сосудистая (тромбоз, ОРДС, аритмии).
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Т.е. метформин нельзя при остром инфаркте и осторожно при ХСН.
А вот все начальные стадии ССЗ, постинфарктное состояние и аневризма аорты - прямо нужно.
P.S. То, что он лучше ежедневного тадалафила при ЭД, немного удивило. :rolleyes:
ELENA_VLAD
11.05.2023, 23:15
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Melnichenko
14.06.2023, 15:45
А здесь можно не быть осторожным ?
The FDA has granted over-the-counter marketing authorization to MED3000 (Eroxon), the first nonprescription topical gel for treating erectile dysfunction (ED), maker Futura Medical announcedopens in a new tab or window on Monday.
According to the company, MED3000 has "a 10-minute onset of action" that sets it apart from prescription PDE5 inhibitors such as sildenafil (Viagra) and tadalafil (Cialis), which typically require a longer period of time to take effect.
The gel was initially tested as the placeboopens in a new tab or window comparator in studies of a nitroglycerin gel the company was developing, but in a large phase III trialopens in a new tab or window it turned out MED3000 worked just as well.
"FDA set a very high standard in evaluating the effectiveness and safety," James Barder, Chief Executive Officer of Futura Medical, said in a statement. "I am delighted that we met this standard with MED3000's submission of 22 clinical, biocompatibility, human factors studies and performance bench tests which were rigorously reviewed and accepted by the FDA."
Last August, the company announced positive results from FM71, a confirmatory 24-week multicenter phase III trialopens in a new tab or window that compared MED3000 to oral tadalafil in 96 ED patients.
Both primary endpoints were achieved in the open-label study. At 24 weeks, scores on the International Index of Erectile Function – Erectile Function (IIEF-EF) scale were significantly improved across mild, moderate, and severe ED (P<0.001), with a demonstrated durability of response beyond 12 weeks. And patients assigned to the gel experienced an average 5.73-unit change from baseline in IIEF-EF score at 24 weeks, exceeding the 4-unit difference required by the FDA and defined as the minimal clinically important difference.
MED3000 also met FDA criteria for rapid onset, a secondary endpoint of the trial, with a significant improvement in erectile function at 10 minutes; tadalafil did not meet the criteria at that time.
Headache was reported in 19% of those randomized to tadalafil versus 4% of those assigned to the topical gel, while noncardiac chest pain and back pain were only reported in the PDE5 inhibitor group (4% for each). Nausea was reported in 4% of those using MED3000, along with one instance of "mild local burning," the company said. No local side effects were reported among sexual partners.
Korzun
14.06.2023, 16:08
Как в старом анекдоте.
Средство для потенции - Три богатыря.
Три - это глагол.
:ag:
Dr.Vad
14.06.2023, 17:23
Слышал в свою бытность молодым врачом, что до виагры доктора использовали гель с нитроглицерином (что ранее использовался для лечения стенокардии) как топическое эректильное средство, прошло более 25 лет и опять приходят "натирания"
Dr.Vad
14.06.2023, 17:33
PS. ой, его предшественник по номеру и был нитратом
MED2005, a 0.2% glyceryl trinitrate topical gel, formulated into an enhanced absorption topical delivery system (DermaSys), administered on demand, in the treatment of ED.
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Dr.Vad
14.06.2023, 17:45
ох, и детективная история - опять случайные находки: плацебо гель работал также хорошо, как и нитрат на гелевой плацебо-основе
The gel was initially used as a placebo in studies of a nitroglycerin gel called MED2005. Early trial results of MED2005 in 2018 spawned media buzz, with headlines playing on the word "dynamite" ... However, a 2019 phase III trial of 1,000 men with ED in Europe found that the nitroglycerin gel didn't reach primary endpoints versus the placebo. In fact, the placebo's effectiveness was roughly equal to that of the active treatment per multiple measurements.
Futura Medical has declined to identify the components of the placebo gel, now called MED3000... Futura Medical said the product "gently evaporates to create a unique cooling effect followed by a warming effect. This stimulates nerve sensors in the highly innervated glans penis, leading to smooth muscle relaxation, tumescence and erection."
Korzun
14.06.2023, 20:00
Посмотрел состав MED3000 - спирт, глицерил - точно за счет массажа весь эффект.
После покупки 5 тюбиков вакуумная помпа в подарок :ah:
Melnichenko
15.06.2023, 07:55
Personalized recombinant leptin treatment helped reverse severe, early-onset obesity in two children carrying rare antagonistic leptin genetic variants, a study showed.
In the double case report, two unrelated children -- a 14-year-old boy and a 2-year-old girl -- presented with what appeared to be leptin dysfunction, marked by intense hyperphagia, lack of satiety, and severe obesity, Martin Wabitsch, MD, PhD, of Ulm University Medical Center in Germany, and colleagues detailed in a New England Journal of Medicineopens in a new tab or window (NEJM) brief report.
Of note, the parents of the boy were second-degree cousins and parents of the girl were first-degree cousins.
The researchers confirmed that both patients had abnormally high levels of circulating leptin. Conditions like Prader-Willi and Bardet-Biedl syndromes were both ruled out.
Based on in vitro experiments they performed, Wabitsch's group found that these patients had impaired binding between leptin proteins and leptin receptors. Treatment was started at the recommended dose of 0.03 mg/kg of lean body weight, but because of the agonist activity, the initial metreleptin treatment -- a recombinant human leptin -- given to these patients flopped, having virtually no effect.
Following the in vitro results, the researchers opted to bump up the doses for both patients.
For the boy (a carrier of leptin variant P64S), the dose was increased to 0.14 mg/kg on day 2 of treatment, to 0.70 mg/kg on day 5, and was tapered down starting on day 131, reaching an end dose of 0.15 mg/kg.
For the girl (a carrier of leptin variant G59S), the dose was increased to 0.15 mg/kg on day 2 of treatment, and tapered down starting on day 264, with an ending dose of 0.07 mg/kg.
In addition to the increased metreleptin doses, both patients participated in exercise programs and "vigorous" fasts in order to magnify the effect of exogenous leptin. After achieving a therapeutic response, patients lost weight, normalized food intake, and achieved satiety. Both also developed antibodies against metreleptin.
After 1,188 days of treatment, the 14-year-old boy achieved a near-normal weight of 94.1 kg (207.5 lb). He lost 49.9 kg (110 lb) -- a weight loss of 27.8% -- by day 131, and lost 72.9 kg (160.7 lb) -- a weight loss of 40.5% -- by day 264. The boy's body mass index (BMI) also dropped from 54.3 at baseline to 26.9 by day 1,188.
After 1,260 days of treatment, the 2-year-old girl achieved a near-normal weight of 23.2 kg (51.1 lb). She lost 9.6 kg (21.2 lb) -- a weight loss of 36.5% -- by day 238 of treatment. The girl's BMI dropped from 31.6 at baseline to 17.6 on day 1,260.
"To be honest, after our initial descriptionopens in a new tab or window of biologically inactive leptin variants in 2015, we had expected that sooner or later a patient would present at our Centre for Genetic Obesity who had an antagonizing leptin variant," Wabitsch told MedPage Today. "Based on the knowledge of the molecular ligand-receptor interaction of leptin and its receptor, the existence of antagonizing variants of leptin in humans was likely."
"We hypothesized that specific rare human gene variants in the leptin gene will result in leptin molecules with an impaired interaction with interaction site III of the leptin receptor responsible for receptor activation but with high affinity to the interaction site II responsible for receptor binding. We further hypothesized that these leptin variants would block the receptor when metreleptin treatment is initiated and behave as antagonizing ligands at the receptor level," he explained. "The fact that we were then presented with two patients within a short period of time with two different variants that had these characteristics was a surprise."
"But that was only the first step," Wabitsch added. "Our elaborate in vitro experiments then paved the way for a successful therapy. Based on the in vitro results, we were able to calculate the dose we needed to overcome the antagonism in vivo by substituting metreleptin."
"This was the basis for a successful treatment," he said, noting that this was the first time this had been done in humans. "This is exciting and a novelty for human medicine."
In an accompanying editorialopens in a new tab or window, Clifford J. Rosen, MD, of the MaineHealth Institute for Research in Scarborough and an associate editor for NEJM, pointed out how leptin "was once hailed as a treatment for most cases of childhood obesity but quickly lost favor when resistance to leptin was noted."
"It is apparent that there is a narrow appropriate dose-response effect of leptin on leptin-receptor signaling in the hypothalamus. Further research into the use of monoclonal antibodies as a potential therapeutic tool for obesity is warranted," he suggested, also noting that these findings have implications for more general treatments of obesity.
Wabitsch advised that clinicians "should first think of and look for a genetic cause in children with extreme obesity and hyperphagia."
"In the rare case of a pathogenic leptin gene variant, the effects of this variant should be examined in detail. Colleagues are welcome to contact our center," he added. "If necessary, in vitro experiments can help to determine the therapy with leptin."
Melnichenko
21.06.2023, 08:41
CHICAGO -- Some of the latest research in the field of endocrinology presented at ENDO 2023opens in a new tab or window, the annual meeting of the Endocrine Society, included studies on testosterone-replacement therapyopens in a new tab or window and the risk of major cardiac events, the incongruence between BMI and body fat percentageopens in a new tab or window, and the glucose benefits of time-restricted eatingopens in a new tab or window. Below are a few more highlights.
Treatment for Hypothalamic Obesity Shows Promise
In an extension of a phase II trial including 13 patients with hypothalamic obesity, treatment with setmelanotide (Imcivree) was associated with an average reduction in body mass index (BMI) of 21% after 6 months, reported Christian Roth, MD, of the University of Washington in Seattle, and colleagues.
Most of this weight loss was achieved within the first 16 weeks of treatment, with an average BMI reduction of 16.8%. All participants achieved a BMI reduction of at least 5%, while 10 of the 13 participants were able to achieve at least a 10% reduction.
The most commonly reported adverse events were nausea (69.2%), skin hyperpigmentation (38.5%), and vomiting (30.8%). The most common cause of hypothalamic obesity was treatment of craniopharyngioma, followed by hypothalamic hamartoma, and juvenile pilocytic astrocytoma.
"This impressive response adds to the evidence suggesting setmelanotide may provide a meaningful clinical benefit for patients with this disease who currently have no approved therapeutic options," said Roth in a statement.
Setmelanotide is currently FDA-approved for certain genetic causes of obesity.
New Scientific Statement on Aging
During the meeting, the Endocrine Society released a scientific statement -- also published in the Journal of Clinical Endocrinology & Metabolismopens in a new tab or window -- outlining the differences between normal aging and treatable conditions.
Menopause was one of the highlighted conditions in the new statement, as many women experience bothersome symptoms but few actually receive treatment for it. The statement suggested that hormone therapy is safest for women within a 10-year window of the menopause transition or those younger than 60. New non-hormonal hot flash treatments have also shown promise for this population.
"The statement discusses how menopausal symptoms and osteoporosis are often undertreated in the older population, despite evidence that the treatments are both safe and effective," said lead author Anne Cappola, MD, ScM, of the University of Pennsylvania in Philadelphia, in a statement. "Treating these symptoms and screening for common endocrine conditions that develop or worsen with age could really improve the quality of life for older people."
Eneboparatide for Chronic Hypoparathyroidism
In a phase II trial, eneboparatide, an investigational long-acting parathyroid hormone 1 receptor agonist, helped patients with chronic hypoparathyroidism achieve independence from conventional therapy.
In the 14-person trial, more than 90% of patients were off active vitamin D and oral calcium therapy after 3 months of eneboparatide treatment, according to Peter Kamenický, MD, PhD, of Le Kremlin-Bicêtre in France, and colleagues.
While nearly half of patients had osteopenia or osteoporosis in at least one site at baseline, bone mineral density scores didn't significantly change during the trial. On top of that, in the half of patients who had hypercalciuria at baseline, mean 24-hour urinary excretion of calcium dropped by 49%.
No patients in the trial experienced a serious adverse event.
Based on these positive findings, developer Amolyt Pharma said it was initiating a 165-participant phase III trialopens in a new tab or window.
FilippovaYulia
21.06.2023, 14:13
Интересно.
Но, боюсь, буде сетмеланотид зарегистрирован в России, им тут же начнут лечить "гипоталамический синдром пубертатного возраста"...
Отлично, что есть перспективы по гипопаратиреозу. Очень часто "агонисты рецепторов" оказываются перспективнее, чем аналог нативного гормона.
Melnichenko
21.06.2023, 14:31
Юля, очень правильная мысль насчет агонистов...
ghrh44
28.06.2023, 12:43
Психиатры долго искали метаболичесие маркеры шизофрении и депрессии. Все их попытки были безуспешны. Но относительно недавно новые методы обнаружили пониженные уровни глютамина и глютамата в мозгу и крови у больных с биполярной болезнью. Кетамин, агонист GABA, ворвался в психиатрию буквально в последние несколько лет и показал высокий и быстрый эффект на депрессию. Но он требует периодических в/венных инфузий. Но вот недавно появилась новая таблетка, Auvelity, агонист GABA с крохотной дозой бупропиона, эффективная при депрессии, с быстрым (1-2 недели) действием у больных с резистентностью к обычным препаратам , кроме бупропиона. Но причинно-следственная связь глютамина и депрессии еще не была доказана.
В последнм выпуске JCEM есть статья из Китая со сложнейшим и дотошнейшим статистическим анализом возможной связи между уровнем глютамина крови и ожирением ( состоянием пониженного глютамина в крови) и депрессией.
Эта группа выявила тесную связь уровня глютамина и ожирения как факторов риска депрессии.
Неужто найден молекулярный маркер депрессии? Если так, то это первый прорыв в диагностику и патогенез биполярного расстройства, и идея психонейроэндокринологии как легитимной области эндокринологии в целом, получает поддержку.
Скрещивам пальцы и плюем три раза через левое плечо.
The Journal of Clinical Endocrinology & Metabolism, Volume 108, Issue 6, June 2023, Pages 1370–1375, [Ссылки могут видеть только зарегистрированные и активированные пользователи]
Melnichenko
28.06.2023, 12:47
плюем строго в рамках ЕВМ!
ghrh44
28.06.2023, 13:06
Мы согласилиcь с рекомендациями, что шитовидные узлы <1 см не должны не только оперироваться, но и проходить биопсию.
Но вот группа из Кореи ( Южной, естественно) показала, что в ~1.5% эти крохотные опухоли таких больных агрессивны (“ Aggressive subtypes included diffuse sclerosing, solid, tall cell, columnar cell, and hobnail subtypes.”). Семь из 177 выдали релапс (3.95%), в то время , когда 12 из 11,393 (1.7%) гистологически неагрессивных тоже выдали релапс.
Что это? Должны ли мы пересмотреть наши рекомендации или это просто артефакт неполного удаления?
Запасаемся попкорном и ждем работ из других центров.
The Journal of Clinical Endocrinology & Metabolism, Volume 108, Issue 6, June 2023, Pages 1370–1375, [Ссылки могут видеть только зарегистрированные и активированные пользователи]
Melnichenko
28.06.2023, 13:40
Ожирение просто исчезнет вот - вот
Novel Triple Agonist Nabs Biggest Weight Loss Yet in Obesity Trial
— Plus, two other studies on retatrutide show benefit in type 2 diabetes, fatty liver disease
by Kristen Monaco, Senior Staff Writer, MedPage Today June 26, 2023
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SAN DIEGO -- An investigational triple-hormone receptor agonist yielded major weight loss in people with obesity, a phase II trial showed.
By 24 weeks, patients on any of the four doses of once-weekly injectable retatrutide lost a significantly greater amount of weight than those on placebo -- achieving the trial's primary endpoint -- reported Ania M. Jastreboff, MD, PhD, of Yale University School of Medicine in New Haven, Connecticut, and colleagues, during the American Diabetes Association (ADA) Scientific Sessionsopens in a new tab or window and in the New England Journal of Medicineopens in a new tab or window.
Average change in body weight among the groups at this time were:
-7.2% for the 1-mg group
-12.9% for the combined 4-mg group
-17.3% for the combined 8-mg group
-17.5% for the 12-mg group
-1.6% for the placebo group
Patients taking retatrutide continued to lose a substantial amount of weight compared with placebo at week 48, achieving one of the trial's secondary endpoints. By this time point, patients in the highest-dose group lost nearly a quarter of their body weight, with average changes of -8.7%, -17.1%, -22.8%, -24.2% for the 1-mg, combined 4-mg, combined 8-mg, and 12-mg groups compared with -2.1% with placebo.
"We have not seen results like this before in a trial of less than 1-year duration with an anti-obesity medication," Jastreboff said during an ADA press conference. "The weight loss had not yet plateaued, meaning that participants were [still] losing weight at the time the trial product was discontinued."
"I think this raises the bar," added panel member Carel Le Roux, PhD, of University College Dublin in Ireland, who wasn't involved with the study. "This is really impressive. This is beyond my wildest dreams. To see something like this in my lifetime is pretty impressive."
Retatrutide acts as an agonist of the glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), and glucagon receptors.
All of the patients in the highest-dose group achieved a clinically relevant weight loss of at least 5% by week 48, while 93% achieved a ≥10% weight loss and 83% achieved a ≥15% weight loss.
A total of 13 retatrutide patients and one placebo patient had a body mass index (BMI) decrease to 22 or lower, but none decreased below 19.
Average waist circumference drops with retatrutide ranged from -6.5 cm up to -19.6 cm compared with -2.6 cm with placebo.
The triple agent tended to yield larger magnitudes of weight loss in people with more severe obesity (BMI 35+), as well as female patients. Jastreboff pointed out that these agents tend to induce greater weight loss in women and that prior trials of obesity drugs typically enroll more women. However, her group made it a point to enroll an equal number of men (51.8% of participants), which "may have dampened the efficacy results."
As expected with an agent containing a GLP-1 receptor agonist, the most common adverse events were gastrointestinal-related, but were mostly mild to moderate, including nausea, diarrhea, vomiting, and constipation. Similarly, there was a slight heart rate increase also seen with other agents in this class, which peaked at week 24 of treatment and then declined.
Among the 338 adults enrolled, all had a BMI of 30 or higher or a BMI of 27 plus a weight-related condition (average baseline BMI 37.3). Those with diabetes were excluded from this trial, although 36% had prediabetes.
Randomized in a 2:1:1:1:1:2:2 ratio, participants received either 1 mg, 4 mg (initial dose of 2 mg), 4 mg (initial dose of 4 mg), 8 mg (initial dose of 2 mg), 8 mg (initial dose of 4 mg), or 12 mg (initial dose of 2 mg), or placebo once weekly. In addition, all the participants were guided on lifestyle interventions in the form of dietary counseling, but did not adhere to a specific calorie deficit.
Jastreboff said the phase III TRIUMPH-3 trialopens in a new tab or window will test retatrutide on obesity and obesity-related conditions.
Big Benefits in Type 2 Diabetes, Too
Retatrutide also yielded significant improvements in glycemic control in another phase II trial focused on people with type 2 diabetes.
Also presented at ADA and published in The Lancetopens in a new tab or window, all doses tested outperformed placebo at reducing HbA1c, and most were also better than dulaglutide (Trulicity) 1.5 mg by week 24:
Retatrutide 0.5 mg: -0.43% change in HbA1c
4-mg escalation group: -1.39%
4-mg group: -1.30%
8-mg slow escalation group: -1.99%
8-mg fast escalation group: -1.88%
12-mg escalation group: -2.02%
Dulaglutide: -1.41%
Placebo: -0.01%
These HbA1c improvements were all maintained through to the end of the trial at 36 weeks. Significantly more patients on maintenance doses of 4 mg or higher achieved an HbA1c below 5.7% -- attaining normoglycemia, including 27% of patients on the 12-mg dose.
Substantial drops in body weight were also noted, with patients seeing up to a 16.94% weight loss by week 36.
"This you have never seen in type 2 diabetes. This is a real wow," said lead investigator Julio Rosenstock, MD, of Velocity Clinical Research at Medical City Dallas. "Not a single drug has achieved 17% [weight loss in type 2 diabetes]. And you ain't seen nothing yet, because you see at 36 weeks, you continue to lose weight."
"In type 2 diabetes, for whatever reason, we get 30% less weight loss, but this [weight loss] is consistent with what you get with semaglutide [Wegovyopens in a new tab or window]," he noted.
Again, the most common adverse events reported were mild-to-moderate gastrointestinal events, including nausea, diarrhea, vomiting, and constipation. While there were no severe events, three retatrutide patients experienced moderate hypoglycemia.
Discussing the mechanism behind the glucagon agonist component of the triple agonist, Stephen Bain, MD, and Thinzar Min, MD, both of Swansea University Medical School in Wales, noted in an accompanying commentaryopens in a new tab or window that "if glucagon agonism induces increased energy expenditure, a mechanism quite different to the satiety induced by GLP-1, then long-term cardiovascular outcome trials will almost certainly be requested by regulators, slowing the pathway to clinical use."
Also Works for NAFLD
Retatrutide was also able to reduce the amount of liver fat in a subset of patients with obesity and nonalcoholic fatty liver disease (NAFLD).
In a third study presented at ADA, the highest two doses were able to reduce liver fat by over 80% by week 24 compared with placebo:
1 mg: -42.9%
4 mg: -57.0%
8 mg: -81.4%
12 mg: -82.4%
Placebo: 0.3%
While most liver fat reduction occurred in the first 24 weeks, the 12-mg dose reduced liver fat by 86% by week 48.
Liver fat content dropped below 5% at week 24 in the majority of patients on the highest three doses, leading to resolution of NAFLD. This occurred in 52% of the 4-mg group, 79% of the 8-mg group, and 86% of the 12-mg group.
"Biologically, the addition of glucagon receptor agonism to GIP and GLP-1 ... enhances liver fat clearance and may provide greater efficacy in the treatment of NAFLD and NASH [nonalcoholic steatohepatitis]," said co-author Lee Kaplan, MD, PhD, of the Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital in Boston.
Weight loss was similar in the NAFLD subgroup and the larger obesity trial population.
FilippovaYulia
29.06.2023, 08:43
Было бы неплохо получить альтернативу бариатрической операции, но важна цена вопроса (даже саксенду абсолютное большинство тех, кому она нужна, не могли себе позволить) и смотря что еще выявится в побочках в постмаркетинговом наблюдении.
Хотя для таких препаратов вроде особо вредных неожиданностей не предвидится, не центрального действия - уже хорошо.
ghrh44
29.06.2023, 19:16
То,что постмаркетовые наблюдения могут выявлять что-то неожиданное и нехорошее,- вполне возможно, но компании не глупее нас с Вами, и тратят много денег на определение дозы, продолжительность протокола и число участников. Это в добавление на расходы на открытия, разработки, до-клинические исследования и пр.
Это все связано с ценой препаратов. Множество современных лекарств создано очень сложными процессами и компании обязаны приносить прибыль своим акционерам, иначе им хана.
Но во всех цивилизованных странах цена лекарств покрывается страховками, частными или государственными. Больные платят очень маленький процент из своих карманов. Более того, сами фармацевтические компании дают колоссальные скидки людям на покрытие этих расходов. Как результат, за всю свою профессиональную жизнь я не видел ни одного больного, который был бы не способен оплатить необходимое лекарство после утверждения его ФДА. Да, я должен был иногда звонить в страховые компании и говорить с их “специалистом”. Это занимало у меня 10-15 минут и всегда страховая компания утверждала покрытие этого лекарства.
И не забывайте о разнице в зарплатах. Минимальная в Штатах сейчас $15 в час, $120 за 8-часовый в день, $600 за пятидневную неделю, $2400 в месяц. Нам с женой из-за возраста приходится пить много таблеток , и наша доля оплаты ~$ 100-120 за 3 месяца. Минимальная государственная пенсия ( автоматически после 62 лет) порядка $ 1200 в месяц и включает почти полную цену страховки на любые лекарства.
Бедные и неработавшие сидят на Medicaid, и получают приблизительно столько же + карточки на еду, принимающиеся в любом супермаркете. Но лекарства и вся другая медицинская помощь им бесплатна.
В социалистической Европе никто вообще ничего не платит, но у них налоги на все заработанные деньги в 2-3 раза выше, чем в Штатах.
Так что как ни крути, вв всех странах первого мра и во многих даже второго, дюбые новейшие и более эффективные лекарства доступны всем нуждающимся в них или по крайней мере значительному проценту. Мои коллеги из Южной Америки и Мексики ( небогатые страны) говорят мне, что у них есть все, что есть в Штатах.
Но расходы больных за лекарства разнятся колоссально между РФ и Штатами , учитывая разницу в доходах . Фармацевтические компании продают свои лекарства в другие страны бaзируясь на цену в странах своей регистрации и делая скидки за массовые закупки плюс коеффициент на разные страны. Но доля американского больного после покрытия страховками небольшая. Даже лекарство , официально стоящее $3000 за 30 таблеток или один укол в месяц будет стоить ему , скажем $50 , и он будет стонать и ругать жадность компании. Но он в состоянии заплатить эту сумму без особого напряжения для своего семейного бюджета. Но то же самое лекарство даже если оно будет продаваться в РФ за $1000, то aптека будет просить $1500, что по нынешнему курсу будет 132,000 рублей.
Это просто пример, измените цифры как вам угодно, но что бы вы не делали, а доля цены этого лекарства заберет громадную часть семейного бюджета, если не весь и выше, делая его недоступным для 99% больных.
Eсли бы эти лекарства производились в РФ, то можно бы с этим что-то сделать,
. Но Россия от царской империи до нынешнего своего названия, -РФ,- никогда не создала ни одного нового лекарства, в лучшем случае делая копии вышедших из-под патента, причем с сомнительным качеством. Новый закон в РФ поощряет незаконное производство патентованных лекарств из других стран, то есть откровенную кражу. Злые языки из фармацевтических компаний говорили мне, что они не хотят иметь дела с РФ вообще в ответ на это.
В общем, то, что происходит в РФ с лекарственной помощью это катастрофа. Рынок заполнен старыми продуктами 20 века и откровенным фуфлом, но потрясающие прорывы западных компаний в лечении массы болезней и основанные на новых открытиях и технологиях недоступны громадному большинству людей. Больные в отчаянии, врачи тоже. Я не завидую своим российским коллегам, читающим о новых и крайне эффективных лекарствах и не могущих их использовать. Кроме того, некоторые “светила” пропагандируют не подтвержденные никем и никогда потенциальные осложнения новых лекарств, как например развитие злокачественных процессов при применении теплизумаба для предотвращения ДМ-1. Эндокринологи знают, о чем я говорю:-(((
Не уверен, что с этим вы все можете сделать. Больных мне бесконечно жаль, как и коллег.
Melnichenko
19.07.2023, 10:39
Eli Lilly announced plans to buy obesity drug developer Versanisopens in a new tab or window for $1.93 billion during early-stage trials of its investigational drug bimagrumabopens in a new tab or window -- a first-in-class monoclonal antibody that binds activin type II A and B receptors, which reduces fat mass and increases lean muscle mass in patients with obesity and type 2 diabetes.
FilippovaYulia
19.07.2023, 12:22
Моноклональные антитела применяются в лечении ЭОП, гиперхолестеринемии, исследуются для лечения артериальной гипертонии - вопрос их применения в лечении ожирения и сахарного диабета явно был вопросом только времени и разработки препарата.
Melnichenko
20.08.2023, 19:46
The FDA approved the oral retinoid palovarotene (Sohonos) for treating abnormal bone growth associated with fibrodysplasia ossificans progressiva (FOP), drugmaker Ipsen announcedopens in a new tab or window on Wednesday.
Palovarotene, a selective retinoic acid receptor gamma agonist, is indicated for reducing the volume of new heterotopic ossification in adults and children: boys ages 10 years and up and girls ages 8 and up.
FOP is an ultra-rare, progressive disease that affects an estimated 400 people in the U.S., according to the company. It is characterized by episodes of rapid bone growth that can seriously impede patients' mobility and daily function, including their ability to eat, drink, or use the restroom independently.
Most patients need a wheelchair by the age of 30, and the disease can significantly shorten lives -- bone growth around the rib cage can result in breathing problems and cardiorespiratory failure.
"As a clinician caring for patients with FOP, I personally see the daily challenges and stresses that our patients and their families must contend with," Edward Hsiao, MD, PhD, of the University of California San Francisco, said in a statement.
Approval of palovarotene was based on findings from the single-arm, open-label phase III MOVE studyopens in a new tab or window, which included 107 adult and pediatric patients with FOP. Treatment with the retinoid reduced annualized heterotopic ossification volume compared with a natural history study, where patients received standard care but without the drug.
"The published phase III MOVE study showed that Sohonos can decrease new heterotopic ossification, and that palovarotene can be tolerated by many patients with FOP," said Hsiao, an investigator on the study.
But the drug is not for everyone, he cautioned.
"As with all medicines there are risks, in this case especially for young children who may develop early growth plate closure," he said. "In addition, Sohonos has the same side effects as other retinoids, including dryness of the skin and mucus membranes. However, since the accumulation of [heterotopic ossification] in FOP is progressive, irreversible, and life altering, this medication is an important treatment option for our FOP community."
While there were data issuesopens in a new tab or window with the trial, the FDA's Endocrinologic and Metabolic Drugs Advisory Committee largely agreed earlier this year that palovarotene's benefits outweighed its risksopens in a new tab or window for patients with this debilitating condition.
The most common adverse events in MOVE included dry skin, lip dryness, alopecia, drug eruption, rash, pruritus, arthralgia, and premature growth plate closure in children.
In the FDA's announcementopens in a new tab or window, the agency recommended that pediatric patients be monitored for linear growth due to the risk for premature growth plate closure.
"Before taking Sohonos, all growing pediatric patients should undergo skeletal maturity baseline assessments. Continued monitoring is recommended every 6 to 12 months until patients reach skeletal maturity or final adult height," the FDA said.
Palovarotene is contraindicated in pregnant patients and people with a known allergy to retinoids. Prescribing informationopens in a new tab or window for the drug also includes warnings and precautions related to the premature epiphyseal closure in growing pediatric patients, mucocutaneous side effects, metabolic bone disorders, psychiatric disorders, and night blindness. Given the risk of metabolic bone disorders, patients should periodically be radiologically assessed for spinal fractures, according to the FDA.
The drug can be prescribed immediately to eligible patients, Ipsen said. Palovarotene's recommended dosing is 5 mg daily for adults and kids 14 and older (or the weight-based equivalent for younger patients). The dose can also be modified to deal with flare-up symptoms.
Melnichenko
02.09.2023, 13:01
Не забыть ( может, все таки придет в страну) Тирзепатид улучшает абсорбцию тироксина еще до снижения массы
Melnichenko
12.09.2023, 19:38
А вот и первые неприятные новости.
АнестезиологиСША рекомендуют минимум за неделю до плановых операций отменять агонистыGLP1 ( плохое опорожнение желудка, аспирации) Но операции не всегда плановые
Melnichenko
12.09.2023, 21:28
Ожидаемо, но неприятно- и, главное, пока не произойдет , сам не додумаешься
ELENA_VLAD
12.09.2023, 22:18
Наутро даже после Виктозы вчерашняя пища на ФГС в желудке присутствовала зачастую
Melnichenko
10.10.2023, 20:15
Обалдеть! ISGLT предложили использовать при SIAD ! И получилось!
ghrh44
11.10.2023, 05:16
Да, таки довольно интересная работа, использующая лекарство, утверждённое для СД2 как относительно эффективное средство для лечения SIADH.
doi: 10.1681/ASN.2019090944
Это аналог истории сильденафила для гипертонии, ставшем знаменитой " Голубой Таблеткой" у мужчин с эректильной дисфункцией и миноксидила ( тоже антигипертенсивное лекарство) в разы обошедшем своё оригинальное назначение как средство от облысения. Не забудем также аспирин ( вместо жаропонижающего ставшим антитромботиком). Побочное действие может стать очень ценным показанием для другой болезни.
Но я советую также прочесть превосходный анализ этой статьи в том же номере журнала. Редко я видел такую тщательную и вдумчивую критику!
doi: 10.1159/000509082
В заключение авторы этой рецензии предостерегают от рутинного применения эмпаглифлозина при гипонатремии. Слишком рано .
Оригинальная статья была опубликована в Марте 2020. Три с половиной года позже я не нашёл ни одной статьи, подтверждающей оригинальную находку. Разве что один случай, где гипонатремия частично контролировалась мочевиной и добавка эмпаглифлозина нормализовала натрий. Но... попытка отмены мочевины и продолжения эмпаглифлозина привела к возврату гипонатремии :-(((
DOI: 10.1007/s42000-023-00430-0
Авторы рецензии могли быть правы. Но попытку использовать эмпаглифлозин у больных с острым SIADH после операции на гипофизе стоило бы сделать. Если получится, лечение их сможет проходить в обычной палате вместо реанимации, и облегчит жизнь ординаторам, которых будят среди ночи бежать в больницу из-за натрия 125:-)
Melnichenko
06.12.2023, 15:41
Pemvidutide (2.4 mg), an investigational GLP-1/glucagon dual receptor agonistopens in a new tab or window, helped people with obesity achieve an average 15.6% weight loss after 48 weeks in the phase II MOMENTUM trial, developer Altimmune announced.
ELENA_VLAD
06.12.2023, 18:08
Мне кажется, что люди с ожирением, используя эти препараты , не будут повышать физическую активность, уповая только на снижение аппетита . Это плохо, потому что физическая активность кране важна для профилактики ХСН и всего связанного с ними
FilippovaYulia
07.12.2023, 09:24
"Нейроэндокринная система ЖКТ" оказалась весьма перспективной в поисках новых методов обмануть ненасытные мозги...
Что же касается физической активности - эти препараты будут крайне ценны для тех, кто физически не мобилен и крайне ограничен даже в ходьбе (остеоартриты, тяжелое поражение ног при сахарном диабете).
Melnichenko
21.12.2023, 13:39
A three-pronged acne treatment known as IDP-26 demonstrated greater efficacy than single and double treatments recently in matching randomized phase 3 trials.
IDP-126 gel is a fixed-dose therapy consisting of topical clindamycin phosphate 1.2%, adapalene 0.15%, and benzoyl peroxide 3.1%. The report was published in JAAD.
The 12-week studies randomized participants ages 9 or older with moderate or severe acne (n=183 and n=180, respectively) to receive either daily IDP-126 or a control treatment.
ELENA_VLAD
26.12.2023, 05:12
Хотелось бы знать мнение коллег о таком докладе
Миф о тонкоигольной аспирационной биопсии щитовидной железы 2023 - YouTube
Melnichenko
26.12.2023, 14:07
Рады увидеть Сергея Александровича практически вживую, он активен на форуме.
Что именно мы должны подчеркнуть из ролика?
ELENA_VLAD
26.12.2023, 17:14
Мы привыкли работать по правилам - УЗИ, ТАБ - стандартизированные параметры. Насколько можно использовать предложенный им метод , является ли он основным или дополнительным? Насколько доказателен? Спрашиваю именно об этом.
Melnichenko
26.12.2023, 17:23
Мне, честно, не хватает времени дослушать. В чем предложение? Кто проверял?
ELENA_VLAD
26.12.2023, 18:58
Сцинтиграфия с Тс - миби как альтернатива ТАБ с 17,5 минуты
Melnichenko
26.12.2023, 19:00
Полноте, как сие доказано? Дизайн исследования ? Количество наблюдений? Публикации?
Dr.Vad
26.12.2023, 21:07
не самое последнее в публикациях, но в полном тексте:
МИБИ как и ПЭТ дорого стоят, нужны специалисты в интерпретации и соотв. оборудование плюс не самая высокая точность:
The average cost of FDG-PET/CT is 1,132 USD/test [92] and it is similar to that for MIBI-Scan (1,648 USD/test) [48]. Both these procedures can only be performed in a highly specialized radiology and nuclear medicine Units, and they expose patients to radiations, that can be reduced if only the thyroid bed is scanned. However, for these reasons they are not recommended as routine screening methods.
FDG-PET/CT and MIBI-Scan showed a combination of intermediate values of both accuracy (65% and 79% respectively) and cost (both tests 1,000 - 2,000 USD).
поэтому авторами предлагается Galectin-3-ICC (GAL-3-ICC)
...GAL-3-ICC performed well as rule-out (sensitivity = 83%) and rule-in test (specificity = 85%), with good accuracy (84%)...
The clinically validated test-method with one of the lowest cost is, indeed, the GAL-3-ICC. The cost of this test-method (113 USD/test) is very competitive, compared with those estimated for FDG-PET/CT and is remarkably low compared to that reported for the molecular genetic test-methods (up to 20 times cheaper). For this reason it has been previously suggested that GAL-3-ICC could have a potential screening role, particularly in low-income Countries [31]. The present comparative analysis shows that GAL-3-ICC performs well both as an efficient rule-out and rule-in test-method, with rather good likelihood ratios and diagnostic accuracy. Visualization of sensitivity, specificity, likelihood ratios, accuracy and, more importantly, cost, in both two- and three-dimensional scatterplot diagrams, clearly indicates that GAL-3-ICC represents, at the present time, the candidate test-method to be chosen on large-scale basis. Moreover, GAL-3-ICC uses conventional FNA cytological substrates, is very easy to be performed in different clinical settings and does not require to be centralized in high specialized laboratories. Recently, we demonstrated that the sensitivity of GAL-3-ICC can be further improved by combination with clinical and ultrasound follow-up of negative nodules [93]. For all these reasons GAL-3-ICC can be proposed as a screening test-method for the preoperative characterization of indeterminate thyroid nodules in different clinical settings. GAL-3-ICC was recently included in a new algorithm for the management of patients with indeterminate FNA that was based on four different markers...
Comparative analysis of diagnostic performance, feasibility and cost of different test-methods for thyroid nodules with indeterminate cytology
[Ссылки могут видеть только зарегистрированные и активированные пользователи]
Polyakov A.V.
09.01.2024, 07:11
У нас была горячая дискуссия с Сергеем Александровичем конкретно по этому вопросу два года назад. Основное, что я пытался донести – это, то, что пунктировать нужно только избранные узлы, в зависимости от категории TIRADS, и то, что вероятность точного ответа ТАБ зависит от категории bethesda. А когда он говорит про огромную ошибку ТАБ, он опирался на данные где пунктировалось все подряд и не было гистологической стратификации риска вообще. Причем, когда я приводил аргументы, что ни в одном современном гайде нет вообще речи о сцинтиграфии, как о методе диагностики рака это вообще игнорировалось.
Причем я даже был согласен подружить ТАБ с сцинтиргафию с МИБИ и предложил вот такой алгоритм:
1) УЗИ назначается при низком ТТГ или при наличии пальпируемого образования
2) ТАБ назначается всегда при ответе УЗИ TIRADS 4-5, или TIRADS 3 более 2 см, или при быстром росте узла при любом TIRADS
3) При ответе ТАБ Bethesda 2 – наблюдать, при Bethesda 3 переделать ТАБ, при Bethesda 4-5 выполнить сцинтиграфию с МИБИ
4) После МИБИ: при наличии горячего узла на первой фазе – наблюдать узел по УЗИ (можно даже не вводить МИБИ), при отсутствии накопления МИБИ на второй фазе – наблюдать узел по УЗИ, при наличии накопления МИБИ на второй фазе – оперировать
5) При низком ТТГ, после УЗИ сразу сделать сцинтиграмму с пертехнетатом, и если горячий узел ТАБ не затевать вообще.
Но он же настаивал на полной замене ТАБ сцинтирграфией с МИБИ, что мне показалось совершенно не реальным и дискуссия зашла в тупик.
ELENA_VLAD
09.01.2024, 10:28
Но он продолжает искать новые аудитории, теперь он Лайн . Нашел группу эндокринологов Новосибирска , там я и нашла сей ролик . Сложно понять, чем это обусловлено .
n December, the U.S. Food and Drug Administration (FDA) approved crinecerfont capsules and oral solution adjunctive treatment to glucocorticoid replacement to control androgens in adult and pediatric patients four years of age and older with classic congenital adrenal hyperplasia (CAH).
Crinecerfont is a selective oral corticotropin-releasing factor type 1 receptor (CRF1) antagonist that directly reduces excess adrenocorticotropic hormone (ACTH) and downstream adrenal androgen production, allowing for glucocorticoid dose reduction. Neurocrine Biosciences is marketing the drug as CRENESSITY.
The FDA approval is supported by the largest-ever clinical trial program of classic CAH, the CAHtalyst Pediatric and Adult Phase 3 global registrational studies. CAHtalyst Phase 3 data results in pediatric and adult patients with classic CAH were published in The New England Journal of Medicine.
In both CAHtalyst studies, CRENESSITY enabled lower steroid doses and decreased androgen levels.
Phase 3 CAHtalyst Pediatric Study:
The CAHtalyst Pediatric study met its primary endpoint, with CRENESSITY significantly decreasing androstenedione levels from baseline to Week 4 versus patients taking placebo who experienced a substantial increase in androstenedione levels.
Children taking CRENESSITY were also able to significantly reduce their GC doses at Week 28 while maintaining or improving androgen levels, a key secondary endpoint.
Children taking CRENESSITY saw approximately four times greater reduction in androstenedione compared with those taking placebo.
Approximately four times greater steroid dose reduction in children taking CRENESSITY was seen compared with those taking placebo.
Children taking CRENESSITY saw approximately 12 times greater reduction in 17-hydroxyprogesterone (17-OHP) compared with those taking placebo.
Headache, abdominal pain, fatigue, nasal congestion and nosebleed were the most common adverse drug reactions (ADRs) among the pediatric population treated with CRENESSITY. Most side effects were temporary and mild to moderate in severity.
“In this phase 3 trial,” the authors write in their conclusion, “crinecerfont was superior to placebo in reducing elevated androstenedione levels in pediatric participants with CAH and was also associated with a decrease in the glucocorticoid dose from supraphysiologic to physiologic levels while androstenedione control was maintained.
“Chronic treatment with supraphysiologic glucocorticoids can cause a number of short- and long-term health consequences, such as obesity, hypertension, and osteoporosis, so the ability for patients with CAH to lower their glucocorticoid dose to a more physiologic level can have profound benefits.” – Richard Auchus, MD, PhD, professor, University of Michigan Health
Phase 3 CAHtalyst Adult Study:
The CAHtalyst Adult study met its primary endpoint with CRENESSITY enabling significant GC dose reductions at Week 24 (while maintaining or improving baseline androstenedione levels) and key secondary endpoint of decreasing androstenedione levels at Week 4.
A significantly higher number of patients taking CRENESSITY (63%) achieved a GC dose in the physiologic range while androstenedione was maintained or improved compared with patients taking placebo (18%).
Approximately two times greater steroid dose reduction was seen in people taking CRENESSITY compared with those taking placebo.
People taking CRENESSITY saw an eight times greater reduction in androstenedione compared with those taking placebo.
People taking CRENESSITY saw a 37 times greater reduction in 17-OHP compared with those taking placebo.
Fatigue, headache, dizziness, joint pain, back pain, decreased appetite and muscle pain were the most common ADRs in the CRENESSITY treatment group. Most side effects were temporary and mild to moderate in severity.
The authors conclude: “Among patients with CAH, the use of crinecerfont resulted in a greater decrease from baseline in the mean daily glucocorticoid dose, including a reduction to the physiologic range, than placebo following evaluation of adrenal androgen levels.”
“The clinical results across both CAHtalyst studies support the efficacy and safety profile of CRENESSITY and its ability to reduce the overproduction of adrenal androgens, allowing for a meaningful reduction in glucocorticoid dosage, while maintaining or enhancing control of these androgens,” says Richard Auchus, MD, PhD, a professor at the University of Michigan Health, and principal investigator. “Chronic treatment with supraphysiologic glucocorticoids can cause a number of short- and long-term health consequences, such as obesity, hypertension, and osteoporosis, so the ability for patients with CAH to lower their glucocorticoid dose to a more physiologic level can have profound benefits.”
Melnichenko
22.01.2025, 12:12
Давно не было никаких особых новостей- эта долгожданная
FilippovaYulia
23.01.2025, 11:29
Агонисты и антагонисты рецепторов к различным субстанциям - огромное поле деятельности, обычно великолепно эффективные препараты.
Подвох, как правило, таится в селективности препарата и разнообразии эффектов одних и тех же рецепторов в различных тканях...
Но глюкокортикоиды детям - это действительно плохо, и вариант лечения да, долгожданный.
ghrh44
25.01.2025, 20:05
Последний выпуск JCEM
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Мы были первыми в этом протоколе , но наш университет запретил больным приходить в клиники из-за Ковида. Пришлось отдать больных в другой центр. Цифр снижения ИФР-1 не знаю, но пока они были у нас, жалобы уходили одна за другой, а гипертрофия тканей таяла на глазах. Кусаю себе локти…
И ДАВНО ПОРА!!!!
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Очень советую просмотреть или ,если возможно,- то тщательно прочитать.
Cтатьи важные: новые подходы, предупреждения о потенциальных проблемах и призыв к переоценке восторженных фантазий.
Ну, тут уже грустная весть: неизбежная, но все равно на душе свербит.
Я Марию знал неплохо: категоричная, с итальянским темпераментом, острая на язык, непобедимая в спорах, но талантливая до удивления, заботяющаяся о своих учениках, пионер врожденной гиперплазии у детей и взрослых, но сейчас отбросила бы без сожаления свою методику высоких доз стероидов и переключилась бы нп антагонист СRH. Абсолютно честная в своих работах.За больными следила как за своими внуками. Была прекрасным Президентом Эндокринного Общества.
Светлая ей память!
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Melnichenko
06.06.2025, 18:32
Хорошая новость :диазоксид- холин как аноректик при Прадере - Вилли с 4 - х лет