Burden of illness of non-hematopoietic stem cell transplant-related hepatic sinusoidal obstruction syndrome: A systematic review.

Background: Sinusoidal obstruction syndrome (SOS)/veno-occlusive disease (VOD) is generally associated with hematopoietic cell transplant (HCT), but little is known about this condition outside the HCT setting. This systematic review examines the burden of illness and current management approaches in non-HCT SOS/VOD.

Methods: We searched Embase, Medline, and grey literature sources for non-HCT SOS/VOD studies published 2002-2023.

A phase 2 trial of defibrotide for the prevention of chimeric antigen receptor T-cell-associated neurotoxicity syndrome.

Chimeric antigen receptor T-cell (CAR-T) therapy represents a major advance in cancer immunotherapy; however, it can be associated with life-threatening neurotoxicity linked to blood-brain barrier disruption and endothelial activation. Defibrotide was shown to reduce endothelial cell activation in vitro and is approved in the United States for treatment of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) in patients with renal or pulmonary dysfunction after hematopoietic cell transplantation (HCT), and in the European Union for severe VOD/SOS after HCT in patients aged >1 month. Defibrotide may stabilize the endothelium during CAR-T therapy and reduce the rate of CAR-T-associated neurotoxicity.

Defibrotide plus best standard of care compared with best standard of care alone for the prevention of sinusoidal obstruction syndrome (HARMONY): a randomised, multicentre, phase 3 trial.

Background: Sinusoidal obstruction syndrome, also known as veno-occlusive disease, is a potentially life-threatening complication of haematopoietic stem-cell transplantation (HSCT). We aimed to compare defibrotide prophylaxis plus best supportive care versus best supportive care alone for sinusoidal obstruction syndrome prevention after HSCT.

Methods: This open-label, randomised, multicentre, phase 3 trial was done in 104 centres in 14 countries.

A multicentre, multinational, prospective, observational registry study of defibrotide in patients diagnosed with veno-occlusive disease/sinusoidal obstruction syndrome after haematopoietic cell transplantation: an EBMT study.

Severe hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of haematopoietic cell transplantation (HCT). This multinational, prospective, observational study (NCT03032016), performed by the EBMT, enrolled patients treated with defibrotide from April 2015 to July 2018. This analysis focused on defibrotide-treated patients with VOD/SOS post-HCT.

Observational study of ezetimibe discontinuation in primary care practices in the UK.

Objective: We investigated the circumstances of ezetimibe discontinuation as its prescribing had been discouraged in some publications.

Research Design And Methods: Adults on stable lipid-modifying therapy (LMT) including ezetimibe, who then had >8 weeks cessation in their prescribed ezetimibe regimen (2010-2011) were identified from THIN UK primary care database. Lipid values and parallel changes to other LMT were described overall and in a sub-group with a history of diabetes, cardiovascular disease or familial hypercholesterolaemia (high-risk group).

Total lipid management and cardiovascular disease in the dyslipidemia international study.

Objectives: Despite statin use, many patients with cardiovascular disease (CVD) are not achieving treatment goals. An international observational study was performed to estimate the prevalence of residual lipid abnormalities in statin-treated patients with CVD to assess whether lipid management requires improvement.

Methods: Fasting plasma concentrations of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides were recorded in 11,104 patients with atherosclerotic CVD and ≥3 months of statin therapy.

PYY3-36 and oxyntomodulin can be additive in their effect on food intake in overweight and obese humans.

Objective: Peptide YY(3-36) (PYY(3-36)), a Y2 receptor agonist, and oxyntomodulin, a glucagon-like peptide 1 (GLP-1) receptor agonist, are cosecreted by intestinal L-cells after each meal. Separately each hormone acts as an endogenous satiety signal and reduces appetite in humans when infused intravenously. The aim of the current study was to investigate whether the anorectic effects of PYY(3-36) and oxyntomodulin can be additive.

Serum molecular signatures of weight change during early breast cancer chemotherapy.

Purpose: Weight gain in women receiving chemotherapy for breast cancer is associated with a higher risk of recurrence but its mechanisms are poorly understood.

Experimental Design: To investigate this, we assessed the metabolic, cytokine, and appetite-related peptide alterations during adjuvant chemotherapy for early breast cancer in postmenopausal women, and correlated these with body mass measurements. Specifically, we performed global metabolic profiling using (1)H-nuclear magnetic resonance spectroscopy of sequential sera, examined ghrelin immunoreactivity, RIAs for GLP-1 and peptide YY, and electrochemiluminescent cytokine analyses (tumor necrosis factor-alpha and interleukin-6) on sequential samples.

Kisspeptin-54 stimulates gonadotropin release most potently during the preovulatory phase of the menstrual cycle in women.

Context: Kisspeptin, the endogenous ligand of the G protein-coupled receptor 54, is a key regulator of the hypothalamo-pituitary-gonadal (HPG) axis. GPR54-null mice exhibit reproductive dysfunction, and exogenous kisspeptin potently stimulates the HPG axis in rodents, primates, and human males. The effects of kisspeptin administration to human females are unknown.

Pioglitazone added to conventional lipid-lowering treatment in familial combined hyperlipidaemia improves parameters of metabolic control: relation to liver, muscle and regional body fat content.

Familial combined hyperlipidaemia (FCHL) is a complex genetic disorder conferring high risk of premature atherosclerosis, characterized by high cholesterol and/or triglyceride, low high density lipoprotein (HDL) cholesterol and insulin resistance. We examined whether pioglitazone, added to conventional lipid-lowering therapy, would favourably affect metabolic parameters and alter body fat content. We undertook a randomized, double blind, placebo-controlled study in 22 male patients with FCHL treated with pioglitazone or matching placebo 30 mg daily for 4 weeks, increasing to 45 mg for 12 weeks.

Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males.

Context: Mutation of the G protein-coupled receptor 54 is associated with a failure of reproductive function. The endogenous neuropeptide agonist for G protein-coupled receptor 54, kisspeptin, potently stimulates the hypothalamic-pituitary-gonadal axis in rodents and primates.

Objective: The present study was designed to determine the effects of elevating circulating kisspeptin levels on LH, FSH, and testosterone in male volunteers.