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After progression, approximately 54.3% of patients received additional systemic therapy. A total of 41 patients received BRAF/MEK inhibition (ORR of 58.6%, including 70.4% for BRAF/MEK-naive patients), 30 patients received ipilimumab (ORR of 0%), and 11 patients received ipilimumab plus nivolumab (ORR of 27.3%). Conclusions The current study identified prognostic factors in advanced melanoma for patients who experienced disease progression while receiving anti-PD-1, including lactate dehydrogenase, stage of disease, site of disease progression, tumor size, and mutation status.Background Thalassaemia is a recessively-inherited blood disorder that leads to anaemia of varying severity. In those affected by the more severe forms, regular blood transfusions are required which may lead to iron overload. Accumulated iron from blood transfusions may be deposited in vital organs including the heart, liver and endocrine organs such as the pituitary glands which can affect growth hormone production. Growth hormone deficiency is one of the factors that can lead to short stature, a common complication in people with thalassaemia. Growth hormone replacement therapy has been used in children with thalassaemia who have short stature and growth hormone deficiency. This review on the role of growth hormone was originally published in September 2017 and updated in April 2020. Objectives To assess the benefits and safety of growth hormone therapy in people with thalassaemia. Search methods We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and han remain uncertain. Large well-designed randomised controlled trials over a longer period with sufficient duration of follow up are needed.Anaphylaxis in pregnancy is a rare but severe complication for both mother and infant. Population-based data on anaphylaxis in pregnancy are lacking from mainland European countries. This multinational study presents the incidence, causative agents, management and maternal and infant outcomes of anaphylaxis in pregnancy. This descriptive multinational study used a combination of retrospective (Finnish medical registries) and prospective population-based studies (UK, France, Belgium and the Netherlands) to identify cases of anaphylaxis. Sixty-five cases were identified among 4,446,120 maternities (1.5 per 100,000 maternities; 95%CI 1.1-1.9). The incidence did not vary between countries. Approximately three-quarters of reactions occurred at the time of delivery. The most common causes were antibiotics in 27 women (43%), and anaesthetic agents in 11 women (17%; including neuromuscular blocking drugs, 7), which varied between countries. Anaphylaxis had very poor outcomes for one in seven mothers and one in seven babies; the maternal case fatality rate was 3.2% (95%CI 0.4-11.0) and the neonatal encephalopathy rate was 14.3% (95%CI 4.8-30.3). Across Europe, anaphylaxis related to pregnancy is rare despite having a multitude of causative agents and different antibiotic prophylaxis protocols.Background Earlier studies provided considerably variable estimates on the prevalence and control rates of hypertension in hemodialysis because of their heterogeneity in definitions and blood pressure (BP) measurement techniques applied to detect hypertension. Material and methods In this cross-sectional study, 116 clinically stable hemodialysis patients from 3 dialysis centers of Northern Greece underwent home BP monitoring for 1 week with the validated automatic device HEM-705 (Omron, Healthcare). Routine BP recordings taken before and after dialysis over 6 consecutive sessions were also prospectively collected and averaged. Hypertension was defined as (i) 1-week averaged home BP ≥135/85 mmHg; (ii) 2-week averaged predialysis BP ≥140/90 mmHg; (iii) 2-week averaged postdialysis BP ≥130/80 mmHg. Participants on treatment with ≥1 antihypertensives were also classified as hypertensives. Results The prevalence of hypertension was 88.8% by home, 86.2% by predialysis and 91.4% by postdialysis BP recordings. In all, 96 participants (82.7%) were being treated with an average of 2.0±1.1 antihypertensive medications. Among drug-treated participants, 32.6% were controlled by home, 50.5% by predialysis and 45.3% by postdialysis BP recordings. In multivariate logistic regression analysis, greater use of antihypertensive medications and postdialysis overhydration, assessed with bioimpendence spectroscopy, were both independently associated with higher odds of inadequate home BP control. Conclusions this study shows that the prevalence, but mainly the control rates of hypertension in patients on hemodialysis, differ between peridialytic and interdialytic BP recordings. Therefore, the wider use of home BP monitoring may improve the determination of BP control status in this high-risk population.Purpose Metal implants in the patient's body can generate severe metal artifacts in x-ray computed tomography (CT) images. These artifacts may cover the tissues around the metal implants in CT images and even corrupt the tissue regions, thus affecting disease diagnosis using these images. Previous deep learning metal trace inpainting methods used both valid pixels of uncorrupted areas and invalid pixels of corrupted areas to patch metal trace (i.e., the holes of removed metal-corrupted regions). Such methods cannot recover fine details well and often suffer information mismatch due to interference of invalid pixels, thus incurring considerable secondary artifacts. In this paper, we develop a new irregular metal trace inpainting network for reducing metal artifacts. Methods We develop a new deep learning network to patch irregular metal trace in metal-corrupted sinograms to reduce metal artifacts for isometric fan-beam CT. Our new method patches irregular metal trace in CT sinograms using only valid pixels, av metal artifacts and produces the best quality CT images. Additionally, our proposed method takes 0.1512 s on average to process a CT slice, which meets the clinical requirement. Conclusions This paper proposes a new deep learning network to patch irregular metal trace in corrupted sinograms to reduce metal artifacts. Our method restores more fine details in irregular metal trace and has a superior capability on metal artifact reduction compared with state-of-the-art methods.Background and aims Neutrophil infiltration is a hallmark of nonalcoholic steatohepatitis (NASH), but how this occurs during the progression from steatosis to NASH remains obscure. Human NASH features hepatic neutrophil infiltration and upregulation of major neutrophil-recruiting chemokines (e.g., CXCL1 and IL-8). However, mice fed a high-fat diet (HFD) only develop fatty liver without significant neutrophil infiltration or elevation of chemokines. The aim of this study was to determine why mice are resistant to NASH development and the involvement of p38 mitogen-activated protein kinase (p38) activated by neutrophil-derived oxidative stress in the pathogenesis of NASH. Approaches and results Inflamed human hepatocytes attracted neutrophils more effectively than inflamed mouse hepatocytes due to the greater induction of CXCL1 and IL-8 in human hepatocytes. Hepatic overexpression of Cxcl1 and/or IL8 promoted steatosis-to-NASH progression in HFD-fed mice by inducing liver inflammation, injury, and p38 activation. Pharmacological inhibition of p38α/β or hepatocyte-specific deletion of p38a (a predominant form in the liver) attenuated liver injury and fibrosis in the HFD+Cxcl1 -induced NASH model that is associated with strong hepatic p38α activation. In contrast, hepatocyte-specific deletion of p38a in HFD-induced fatty liver where p38α activation is relatively weak exacerbated steatosis and liver injury. Mechanistically, weak p38α activation in fatty liver upregulated the genes involved in fatty acid β-oxidation via PPARα phosphorylation, thereby reducing steatosis. Conversely, strong p38α activation in NASH promoted CASP3 cleavage, CHOP expression, and BCL2 phosphorylation, thereby exacerbating hepatocyte death. Conclusions Genetic ablation of hepatic p38a increases simple steatosis but ameliorates oxidative stress-driven NASH, indicating that p38α plays distinct roles depending on the disease stages, which may set the stage for investigating p38α as a therapeutic target for the treatment of NASH.In this letter we discuss the proposition of Bristian BR (2020) to use the intravenous administration of fish-oil emulsions in critically ill patients with Coronavirus Disease 2019 (COVID-19). We consider that immune-modulatory properties of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, rapidly provided in high amounts by fish-oil emulsions, may be important to change the course of COVID-19's death pathway. Prescriptions should be based on body weight (eg, 0.2-g pure fish-oil lipid emulsion/kg body weight/d) and also should consider combining the parenteral administration of fish-oil emulsions with low oral aspirin intake to trigger resolvin synthesis from EPA and DHA.Cardiomyopathy can be a severe complication in patients with long-chain fatty acid β-oxidation disorders (LCFAOD), particularly during episodes of metabolic derangement. It is unknown whether latent cardiac abnormalities exist in adult patients. To investigate cardiac involvement in LCFAOD, we used proton magnetic resonance imaging (MRI) and spectroscopy (1 H-MRS) to quantify heart function, myocardial tissue characteristics, and myocardial lipid content in 14 adult patients (two with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD); four with carnitine palmitoyltransferase II deficiency (CPT2D); and eight with very long-chain acyl-CoA dehydrogenase deficiency (VLCADD)) and 14 gender-, age-, and BMI-matched control subjects. Examinations included cine MRI, MR tagging, native myocardial T1 and T2 mapping, and localized 1 H-MRS at 3 Tesla. Left ventricular (LV) myocardial mass (P = .011) and the LV myocardial mass-to-volume ratio (P = .008) were higher in patients, while ejection fraction (EF) was normal (P = .397). LV torsion was higher in patients (P = .026), whereas circumferential shortening was similar compared with controls (P = .875). LV hypertrophy was accompanied by high myocardial T1 values (indicative of diffuse fibrosis) in two patients, and additionally a low EF in one case. Myocardial lipid content was similar in patients and controls. Menadione We identified subclinical morphological and functional differences between the hearts of LCFAOD patients and matched control subjects using state-of-the-art MR methods. Our results suggest a chronic cardiac disease phenotype and hypertrophic LV remodeling of the heart in LCFAOD, potentially triggered by a mild, but chronic, energy deficiency, rather than by lipotoxic effects of accumulating lipid metabolites.Gut microbial communities are capable of enzymatically transforming pharmaceutical compounds into active, inactive, and toxic metabolites, thus potentially affecting the pharmacokinetics and bioavailability of orally administered medications. Our understanding of the impact and clinical relevance of how gut microbial communities can directly and indirectly affect drug metabolism, and ultimately, clinical outcomes, is limited. Interindividual variability of gut microbial composition may partially explain differences observed in drug efficacy and toxicity in certain patient populations. This review provides an overview of how gut microbial communities can potentially contribute to individual drug response. This review focuses on the current landscape of clinical and preclinical research that defines the microbiome contribution on medication response with the goal of improving medication efficacy and decreasing medication toxicity.
Website: https://www.selleckchem.com/products/Menadione.html
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