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Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial.

BACKGROUND: Previously reported results from the phase 3 CheckMate 067 trial showed a significant improvement in objective responses, progre … mab group (23 [7%] of 311); the most common grade 4 adverse event in all three groups was increased lipase (15 [5%] of 313 in the combination group, ten [3%] of 313 in the nivolumab group, and four [1%] of 311 in the ipilimumab group). Serious adverse events were not analysed for the 4-year follow-up. In total for the study, there were four treatment-rel …

Antiobesity Medications for Older Adults-the New, the Good, the Bad, and the Unknown.

OBJECTIVE: Obesity affects 42% of older adults, with rates continuing to rise. This a complex condition influenced by non-modifiable as well as modifiable risk factors. The disease can be treated through modifications to diet, physical activity, and behavior and more recently through antiobesity medications (AOMs) and surgery. Treatment must be tailored to individual needs due to age-related metabolic and physiological changes. This review aimed to identify the suitability of seven FDA-approved AOMs in the treatment of obesity in older adults. METHODS: A review of AOMs was performed, focusing

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… Orlistat reduces fat absorption by inhibiting gastrointestinal (GI) and pancreatic lipases [ 26 ]. In a prospective pilot study of 13 older adult women with obesity prescribed orlistat for 6 months, total weight loss was 9.4% [ 23 ]. … Multivitamin supplementation is necessary as it increases intestinal motility, decreases absorption, inactivates lipases, and impairs the absorption of free fatty acids and fat‐soluble vitamins [ 11 , 23 ]. …

Vodobatinib for patients with Philadelphia chromosome-positive chronic myeloid leukaemia resistant or intolerant to multiple lines of previous therapy: an open-label, multicentre, phase 1/2 trial.

BACKGROUND: Resistance or intolerance to the available tyrosine kinase inhibitors (TKIs) remains a treatment challenge for patients with chr … d included thrombocytopenia (14 [18%]), neutropenia (10 [13%]), anaemia (nine [12%]), and increased lipase (eight [10%]). Seven (9%) patients died during the study; one death was considered related to treatment by the clinical investigator. At data cutoff, major cytogenetic response was observed in 44 (70%) of 63 patients with chronic-phase chronic myelo …

Hemophagocytic Lymphohistiocytosis and Pancreatic Cancer: A Rare Association.

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) or hemophagocytic syndrome (HPS) is a life-threatening and relatively rare condition … of 2645 U/L, an alanine transaminase (ALT) of 2935 U/L, alkaline phosphatase (ALP) of 106 U/L, and lipase of 61 U/L, with total and conjugated bilirubin of 3.5 mg/dL and 2.1 mg/dL, respectively. Transthoracic echocardiogram (TTE) showed reduced left ventricular size with hyperdynamic systolic function. Computerized tomography (CT) scan of the abdomen (F …

AGA Clinical Practice Update: Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Lean Individuals: Expert Review.

DESCRIPTION: Nonalcoholic fatty liver disease (NAFLD) is well recognized as a leading etiology for chronic liver disease, affecting >25% of … uld be ruled out, including other causes of fatty liver, such as HIV, lipodystrophy, lysosomal acid lipase deficiency, familial hypobetalipoproteinemia, and medication-induced hepatic steatosis (methotrexate, amiodarone, tamoxifen, and steroids). BEST PRACTICE ADVICE 8: Current evidence is inadequate to support routine testing for genetic variants in pat …

IVF characteristics and the molecular luteal features of random start IVF cycles are not different from conventional cycles in cancer patients.

STUDY QUESTION: Are the IVF parameters and the steroidogenic luteal characteristics of random-start IVF cycles different from conventional c … is (3-hydroxy 3-methylglutaryl Co-A reductase (HMG-Co-A reductase)), utilization (hormone sensitive lipase (HSL)), and storage (Acetyl-Coenzyme A acetyltransferase 1 (ACAT-1)), and gonadotropin receptor expression status were analyzed using immunoblotting and RT-PCR methods. Laser confocal immunofluorescence imaging was applied to analyze and compare the …

Use of Cannabis and Cannabinoids for Treatment of Cancer.

The endocannabinoid system (ECS) is an ancient homeostasis mechanism operating from embryonic stages to adulthood. It controls the growth and development of many cells and cell lineages. Dysregulation of the components of the ECS may result in uncontrolled proliferation, adhesion, invasion, inhibition of apoptosis and increased vascularization, leading to the development of various malignancies. Cancer is the disease of uncontrolled cell division. In this review, we will discuss whether the changes to the ECS are a cause or a consequence of malignization and whether different tissues react dif

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… It consists of three components—ligands, including 2-arachidonoylglycerol (2-AG) and arachidonoyl ethanolamide (AEA or anandamide), receptors, such as cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), and the metabolizing enzymes—fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase … Changes in the Expression Pattern of Endocannabinoid Hydrolytic Enzymes in Cancer AEA and 2-AG are synthesized from the substances N-arachidonoyl phosphatidylethanolamide (NAPE-PLD) and diacylglycerol (DAG) by phospholipase D and DAG lipase, respectively, and degraded by FAAH and MAGL, respectively. …

Adipocyte-Tumor Interactions in the Bone Marrow Niche: Implications for Metastasis and Therapy.

Bone metastases continue to be a major cause of morbidity and mortality in patients with advanced cancers, driven by the dynamic remodeling of the bone marrow niche. Traditionally viewed as passive space-fillers, bone marrow adipocytes (BMAs) are now recognized as active regulators of tumor growth, therapeutic resistance, and skeletal pathology. BMAs comprise a significant portion of the adult marrow space, particularly in aging and obesity, and facilitate metastatic colonization through various mechanisms. These include metabolic coupling, where adipocyte-derived fatty acids fuel tumor oxidat

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… Metabolic Blockade of BMA Adipose triglyceride lipase (ATGL), encoded by the PNPLA2 gene, mediates prostate cancer growth in vitro and in vivo. PNPLA2 itself exhibits genomic and transcriptomic traits of an oncogene, and its expression has been correlated with worse overall survival [ 167 ]. … A Lipase-Independent Pathway of Lipid Release and Immune Modulation by Adipocytes. Science. 2019;363:989–993. doi: 10.1126/science.aaw2586. 96. Valenzuela Alvarez M., Gutierrez L.M., Correa A., Lazarowski A., Bolontrade M.F. …

Targeting the Endocannabinoidome in Pancreatic Cancer.

Pancreatic Ductal adenocarcinoma (PDAC), the most common malignancy of the pancreas, is an aggressive and lethal form of cancer with a very high mortality rate. High heterogeneity, asymptomatic initial stages and a lack of specific diagnostic markers result in an end-stage diagnosis when the tumour has locally advanced or metastasised. PDAC is resistant to most of the available chemotherapy and radiation therapy treatments, making surgery the most potent curative treatment. The desmoplastic tumour microenvironment contributes to determining PDAC pathophysiology, immune response and therapeutic

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… α and β (DAGLα and DAGLβ) [ 20 , 21 , 22 ]; (4) hydrolase enzymes which non-selectively degrade anandamide (AEA) and 2-arachidonoylglycerol (2-AG), respectively, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) [ 23 , 24 ]. … Brain monoglyceride lipase participating in endocannabinoid inactivation. Proc. Natl. Acad. Sci. USA. 2002;99:10819–10824. doi: 10.1073/pnas.152334899. 25. Ligresti A., De Petrocellis L., Di Marzo V. …

Нейростероиды и неврологические расстройства.

Нейростероиды играют важную роль в качестве эндогенных нейромодуляторов, которые производятся на местном уровне в центральной нервной системе и быстро изменяют взрываемость нейронов и активацию микроглиальных клеток и астроцитов. Здесь мы рассматриваем механизмы синтеза, метаболизма и действия нейростероидов в центральной нервной системе. Нейростероиды могут играть различные роли в центральной нервной системе в физиологических условиях, связывая их с мембранными ионными каналами и рецепторами, такими, как рецепторы гамма-аминобутирной кислоты типа А, рецепторы Nметил-D-асортатных рецепторов, к

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… LDLs are processed by lysosomal acid lipase (LAL) to cholesterol in order to be used in neurosteroidogenesis [ 13 ]. On the other hand, cells may synthesize cholesterol from three acetyl CoA molecules [ 14 ]. … Cholesterol is synthesized from low density lipoprotein (LDL) by lysosomal acid lipase (LAL) or from acetyl CoA molecules. Steroidogenic acute regulatory protein (StAR) transfers cholesterol from cytoplasm into the mitochondria across the outer and inner mitochondrial membranes. …

Менделианская случайность не охватывает потенциальные лекарственные средства, которые могут быть восстановлены при нейропсихических расстройствах.

СТРУКТУРА: Растущая распространенность нейропсихиатрических расстройств становится серьезной проблемой в области здравоохранения. Традиционные фармакотерапии сталкиваются с ограничениями, в результате чего лекарственные средства становятся ценной стратегией. Вместе с тем для этих условий используются весьма ограниченные подходы к отбору данных с высокой производительностью. МЕТОДЫ: В этом исследовании используются данные о воздействии, полученные из лаборатории Biobank Neal (N = 361,141) и конечных данных из базы данных FinnGen (N = приблизительно 410,000) использовать результаты анализа менде

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… Creon's pancreatic lipase breaks down dietary fiber to produce short-chain fatty acids (SCFAs), which can inhibit abnormal discharges in the temporal lobe via the vagus nerve [ 57 ]. … The lipase also improves lipid absorption, increasing vitamin D levels (epilepsy control associated) and regulating branched-chain amino acid metabolism [ 58 , 59 ]. …

Research Communications of the 26th ECVIM‐CA Congress

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… | Unterer | Long‐term implications of canine parvovirus infection 14.55–15.10 | ESCG‐O‐3 | Suchodolski | Validation of a dysbiosis index to assess microbiota changes in fecal samples of dogs 15.10–15.25 | ESCG‐O‐4 | Williams | Microbiomic and metabolomic associations with increased serum pancreatic lipase … A retrospective cohort of 19 cases ESCG‐P‐6 | Hugonnard | Agreement of feline and canine pancreas‐specific lipase with pancreatic ultrasonographic findings in 62 cats and 54 dogs with suspicion of pancreatitis: a retrospective study (2007‐2013) ESCG‐P‐7 | Pietra | Inflammatory bowel disease in dogs: …

Technology forecast: advanced therapies in late clinical research, EMA approval or clinical application via hospital exemption.

Background: The umbrella term ATMPs (Advanced Therapy Medicinal Products) comprises cell therapies, gene therapeutics and tissue engineered products. After implementation of the Regulation 1394/2007, only a couple of products have obtained a centralized European marketing authorisation. Objectives: The aim of the presented study is to give an overview on ATMPs available within the European Union either via centralized marketing authorisation or via national Hospital exemption. Additionally, a forecast on innovative ATMPs in the process of EMA approval as well as in phase III and IV clinical tr

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… Glybera ® was an adenoassociated viral vector for treatment of lipoprotein lipase deficiency (LLD), a ultra-rare disease affecting only 1 in a million people [ 12 ]. … Mol Ther . 2012 ; 20 ( 3 ): 471 – 472 . 22378026 10.1038/mt.2012.14 PMC3293610 [13] Glybera (alipogene tiparvovec) for Treatment of Lipoprotein Lipase Deficiency (LPLD) [ cited 2018 18 8 ]. …

Acute Liver Failure due to Disseminated Varicella Zoster Infection.

Acute liver failure (ALF) can be due to numerous causes and result in fatality or necessitate liver transplantation if left untreated. Possible etiologies of ALF include ischemia, venous obstruction, medications, toxins, autoimmune hepatitis, metabolic and infectious causes including hepatitis A-E, varicella-zoster virus (VZV), cytomegalovirus (CMV), herpes simplex virus (HSV), Epstein-Barr virus (EBV), and adenovirus with VZV being the most rarely reported. Pathognomonic skin lesions facilitate diagnosis of VZV hepatitis, but definitive diagnosis is secured with liver biopsy, tissue histopath

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… Lipase was 675 U/L and CMP was remarkable for sodium 129 mEq/L, amino alanine transferase (ALT) 158 U/L, and aspartate aminotransferase (AST) 111 U/L; the rest of the CMP including alkaline phosphatase (ALP) was normal. CXR was normal and abdominal radiograph showed evidence of constipation. … An abdominal ultrasound was ordered due to elevated lipase and LFTs and showed no evidence of gallbladder dysfunction or liver lesions. …

Polatuzumab vedotin plus obinutuzumab and lenalidomide in patients with relapsed or refractory follicular lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study.

BACKGROUND: Obinutuzumab with polatuzumab vedotin or lenalidomide showed tolerability and activity in phase 1b/2 trials that recruited patie … reported dose-limiting toxicity events during dose escalation (one patient had grade 4 amylase and lipase elevation and one patient had grade 4 neutropenia and grade 3 thrombocytopenia), and there were no dose-limiting toxicities observed in cohorts 3 or 5; therefore, the recommended phase 2 dose for the dose-expansion was 1·4 mg/kg polatuzumab vedotin …

A Preliminary Investigation towards the Risk Stratification of Allogeneic Stem Cell Recipients with Respect to the Potential for Development of GVHD via Their Pre-Transplant Plasma Lipid and Metabolic Signature.

The clinical outcome of allogeneic hematopoietic stem cell transplantation (SCT) may be influenced by the metabolic status of the recipient following conditioning, which in turn may enable risk stratification with respect to the development of transplant-associated complications such as graft vs. host disease (GVHD). To better understand the impact of the metabolic profile of transplant recipients on post-transplant alloreactivity, we investigated the metabolic signature of 14 patients undergoing myeloablative conditioning followed by either human leukocyte antigen (HLA)-matched related or unr

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… and monoacylglycerol lipase activity to produce monoacylglycerols (MAGs) and free fatty acids (FFA), respectively. … Under oxidative stress, ROS induces activation of PKD to protect the cell from oxidative-stress-induced cell death [ 50 ]. 1-monopalmitin is a MAG formed via release of a fatty acid from DAG by diacylglycerol lipase. …

Close interactions between lncRNAs, lipid metabolism and ferroptosis in cancer.

Abnormal lipid metabolism including synthesis, uptake, modification, degradation and transport has been considered a hallmark of malignant tumors and contributes to the supply of substances and energy for rapid cell growth. Meanwhile, abnormal lipid metabolism is also associated with lipid peroxidation, which plays an important role in a newly discovered type of regulated cell death termed ferroptosis. Long noncoding RNAs (lncRNAs) have been proven to be associated with the occurrence and progression of cancer. Growing evidence indicates that lncRNAs are key regulators of abnormal lipid metabo

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… When needed, each TG molecule can be sequentially catalyzed by triglyceride lipase (ATGL), hormone-sensitive lipase (HSL) and monoacylglycerol lipase (MAGL) to release three FAs. ATGL is usually considered the key enzyme for the release of FAs from TG stores 154 , 155 . … hormone-sensitive lipase monoacylglycerol lipase sphingosine kinases sphingosine-1-phosphate papillary thyroid carcinoma phospholipase D phosphatidylcholine phospholipase A2 DNA (Cytosin-5-)-methyltransferase 1 lipid hydrogen peroxide glutathione glutaminase2 nicotinamide adenine dinucleotide …

За пределами границы - это осложнение импортного японского энцефалита: отчет о деле.

Японский энцефалит (JE) — инфекция, эндемичная во многих странах Азии и западной части Тихого океана. Хотя большинство инфекций носит асимптомический характер, они меньше 1% Клинические заболевания, как правило, вызывают острый энцефалит. Коэффициент смертности колеблется от 20 в адрес 30%, и до половины выживших развивают долгосрочные неврологические или психиатрические сиквелы. Несмотря на то, что среди путешественников из неэпидемиологических районов редкость, риск возрастает в результате продолжительного воздействия на сельские районы или отсутствия вакцинации. Иммунокомпромированные люди,

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… ) 141 136–145 Potassium (mmol/L) 4.4 3.5–5.1 Calcium (mg/dL) 9.1 8.4–10.5 Glucose (mg/dL) 99 70–105 Blood urea nitrogen (mg/dL) 18.5 8.4–25.7 Creatinine (mg/dL) 1.6 0.7–1.3 Albumin (g/dL) 1.7 3.5–5.0 Alanine aminotransferase (ALT) (units/L) 29 0–55 Aspartate aminotransferase (AST) (units/L) 47 5–34 Lipase … | 4.4 | 3.5–5.1 Calcium (mg/dL) | 9.1 | 8.4–10.5 Glucose (mg/dL) | 99 | 70–105 Blood urea nitrogen (mg/dL) | 18.5 | 8.4–25.7 Creatinine (mg/dL) | 1.6 | 0.7–1.3 Albumin (g/dL) | 1.7 | 3.5–5.0 Alanine aminotransferase (ALT) (units/L) | 29 | 0–55 Aspartate aminotransferase (AST) (units/L) | 47 | 5–34 Lipase …

Development and Clinical Translation of Approved Gene Therapy Products for Genetic Disorders.

The field of gene therapy is striving more than ever to define a path to the clinic and the market. Twenty gene therapy products have already been approved and over two thousand human gene therapy clinical trials have been reported worldwide. These advances raise great hope to treat devastating rare and inherited diseases as well as incurable illnesses. Understanding of the precise pathomechanisms of diseases as well as the development of efficient and specific gene targeting and delivery tools are revolutionizing the global market. Currently, human cancers and monogenic disorders are indicati

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… Glybera (Alipogenetiparvovec) Alipogenetiparvovec, marketed as Glybera, is a gene therapy drug for Lipoprotein Lipase Deficiency (LPLD) treatment. It was developed by Amsterdam Molecular Therapeutics (AMT) in April 2012. … W. ( 2013 ). 33An update on gene therapy for the treatment of lipoprotein lipase deficiency . DovePress 4 , 47 — 54 . 10.2147/ODRR.S39979 Andtbacka R. H. Kaufman H. L. Collichio F. Amatruda T. Senzer N. Chesney J. ( 2015 ). …

Gene Therapy for Pancreatic Diseases: Current Status.

The pancreas is a key organ involved in digestion and endocrine functions in the body. The major diseases of the pancreas include pancreatitis, pancreatic cancer, cystic diseases, pancreatic divisum, islet cell tumors, endocrine tumors, diabetes mellitus, and pancreatic pain induced by these diseases. While various therapeutic methodologies have been established to date, however, the improvement of conventional treatments and establishment of novel therapies are essential to improve the efficacy. For example, conventional therapeutic options, including chemotherapy, are not effective against p

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… And gene therapy was studied in patients with genetic lipoprotein lipase deficiency-induced pancreatitis [ 66 ]. … Long-term retrospective analysis of gene therapy with alipogene tiparvovec and its effect on lipoprotein lipase deficiency-induced pancreatitis Hum. Gene Ther. 2016 27 916 925 10.1089/hum.2015.158 27412455 67. Talukdar R. Reddy D.N. …