Outcomes in patients with atypical hemolytic uremic syndrome treated with eculizumab in a long-term observational study.

Background: There are limited long-term outcome data in eculizumab-treated patients with atypical hemolytic uremic syndrome (aHUS). We report final results from the largest prospective, observational, multicenter study of patients with aHUS treated with eculizumab.

Methods: Patients with aHUS who participated in any of five parent eculizumab trials and received at least one eculizumab infusion were eligible for enrollment in a long-term follow-up study.

T Cells Specific for an Unconventional Natural Antigen Fail to Recognize Leukemic Cells.

MHC-bound peptides from aberrant proteins may be a specific immunotherapeutic target on cancer cells. Because of difficulties in identifying such antigens, viral or model antigens have so far been used to study their biological relevance. We here identify a naturally existing human T-cell epitope derived from a truncated protein.

Participant characteristics and clinical trial decision-making factors in AIDS malignancy consortium treatment trials for HIV-infected persons with cancer (AMC #S006).

Background: Overall, people living with HIV/AIDS (PLWHA) are living longer, but compared with the general population, they are at elevated risk for numerous AIDS-defining and non-AIDS-defining cancers. The AIDS Malignancy Consortium (AMC) is dedicated to conducting clinical trials aimed at prevention and treatment of cancers among PLWHA.

Objective: To examine patient-level characteristics and perceptions that influence decision-making regarding AMC treatment trial participation.

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants.

Oral amoxicillin-clavulanate for treating diabetic foot infections.

Aim: To assess amoxicillin-clavulanate (AMC) for the oral therapy of diabetic foot infections (DFIs), especially for diabetic foot osteomyelitis (DFO).

Methods: We performed a retrospective cohort analysis among 794 DFI episodes, including 339 DFO cases.

Results: The median duration of antibiotic therapy after surgical debridement (including partial amputation) was 30 days (DFO, 30 days).

Treatment of thoracolumbar kyphosis in patients with mucopolysaccharidosis type I: results of an international consensus procedure.

Background: In all patients with mucopolysaccharidosis type I (MPS I), skeletal disease (dysostosis multiplex) is a prominent, debilitating, condition related complication that may impact strongly on activities of daily living. Unfortunately, it is not alleviated by treatment with hematopoietic cell transplantation (HCT) or enzyme replacement therapy (ERT). Although early kyphosis is one of the key features of dysostosis multiplex, there is no international consensus on the optimal management.

A whole-blood RNA transcript-based gene signature is associated with the development of CTLA-4 blockade-related diarrhea in patients with advanced melanoma treated with the checkpoint inhibitor tremelimumab.

Background: Anti-CTLA-4 immune checkpoint blockade is associated with immune-related adverse events (irAEs). Grade 3-4 diarrhea/colitis is the most frequent irAE requiring treatment discontinuation. Predicting high-risk diarrhea/colitis patients may facilitate early intervention, limit irAE severity, and extend treatment duration.

Clinical impact of the updated international postoperative pancreatic fistula definition in distal pancreatectomy.

Background: Postoperative pancreatic fistula (POPF) remains the most common complication after distal pancreatectomy. The International Study Group on Pancreatic Surgery definition of POPF is used worldwide. Recently, an update of the definition was published.

Consensus clinical management guidelines for Niemann-Pick disease type C.

Niemann-Pick Type C (NPC) is a progressive and life limiting autosomal recessive disorder caused by mutations in either the NPC1 or NPC2 gene. Mutations in these genes are associated with abnormal endosomal-lysosomal trafficking, resulting in the accumulation of multiple tissue specific lipids in the lysosomes. The clinical spectrum of NPC disease ranges from a neonatal rapidly progressive fatal disorder to an adult-onset chronic neurodegenerative disease.

Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

In the version of this article originally published, one of the two authors with the name Wei Zhao was omitted from the author list and the affiliations for both authors were assigned to the single Wei Zhao in the author list. In addition, the ORCID for Wei Zhao (Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA) was incorrectly assigned to author Wei Zhou. The errors have been corrected in the HTML and PDF versions of the article.

Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

In the published version of this paper, the name of author Emanuele Di Angelantonio was misspelled. This error has now been corrected in the HTML and PDF versions of the article.

Comparison of anthracyclines used for induction chemotherapy in patients with FLT3-ITD-mutated acute myeloid leukemia.

This retrospective analysis compared anthracyclines (as part of an induction regimen) in 128 newly diagnosed FLT3-ITD-mutated AML patients. Induction regimens comprised high-dose daunorubicin (HD-DN; 90 mg/m/d × 3d; n = 44), standard-dose daunorubicin (SD-DN; 45 mg/m/d × 3d; n = 51), or idarubicin (IDA; 12 mg/m/d × 3d; n = 33) in combination with cytarabine (100-200 mg/m/d × 7d). Fifty-three patients showing persistent leukemia on interim bone marrow examination received a second course of induction chemotherapy comprising 2 days of daunorubicin (45 mg/m/d) or IDA (8 or 12 mg/m/d) in addition to 5 days of cytarabine.

Evaluation of a novel cryoballoon swipe ablation system in bench, porcine, and human esophagus models.

Current ablation devices for dysplastic Barrett's esophagus are effective but have significant limitations. This pilot study aims to evaluate the safety, feasibility, and dose response of a novel cryoballoon swipe ablation system (CbSAS) in three experimental in vitro and in vivo models. CbSAS is a through-the-scope compliant balloon that is simultaneously inflated and cooled by liquid nitrous oxide delivered from a disposable handheld unit.

Safety and Preliminary Efficacy of Vorinostat With R-EPOCH in High-risk HIV-associated Non-Hodgkin's Lymphoma (AMC-075).

Introduction: Vorinostat (VOR), a histone deacetylase inhibitor, enhances the anti-tumor effects of rituximab (R) and cytotoxic chemotherapy, induces viral lytic expression and cell killing in Epstein-Barr virus-positive (EBV) or human herpesvirus-8-positive (HHV-8) tumors, and reactivates latent human immunodeficiency virus (HIV) for possible eradication by combination antiretroviral therapy (cART).

Patients And Methods: We performed a phase I trial of VOR given with R-based infusional EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin hydrochloride) (n = 12) and cART in aggressive HIV-associated B-cell non-Hodgkin lymphoma (NHL) in order to identify safe dosing and schedule. VOR (300 or 400 mg) was given orally on days 1 to 5 with each cycle of R-EPOCH for 10 high-risk patients with diffuse large B-cell lymphoma (1 EBV), 1 EBV/HHV-8 primary effusion lymphoma, and 1 unclassifiable NHL.

Initial strides for invent-VTE: Towards global collaboration to accelerate clinical research in venous thromboembolism.

Venous thromboembolism (VTE) represents a major global burden of disease and requires collaborative efforts to conduct large, high-quality investigator-initiated and academically sponsored studies addressing the most relevant clinical questions. Owing to increasing regulatory requirements, the highly competitive nature of peer-reviewed funding and costs associated with conducting large, multinational clinical trials, completing practice-changing research constitutes a growing challenge for clinical investigators. As clinical trialists interested in VTE, we founded INVENT (International Network of Venous Thromboembolism Clinical Research Networks) in an effort to promote and accelerate patient-oriented, investigator-initiated, international collaborative research, to identify, prioritize and answer key clinical research questions for patients with VTE.

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes.

Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels.

Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent).

Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI.

Corrigendum: Natural Killer Cells from Patients with Recombinase-Activating Gene and Non-Homologous End Joining Gene Defects Comprise a Higher Frequency of CD56 NKG2A Cells, and Yet Display Increased Degranulation and Higher Perforin Content.

[This corrects the article on p. 798 in vol. 8, PMID: 28769923.

The effect of raloxifene on bone marrow adipose tissue and bone turnover in postmenopausal women with osteoporosis.

In patients with postmenopausal osteoporosis low bone volume is associated with high bone marrow adipose tissue (MAT). Moreover, high MAT is associated with increased fracture risk. This suggests an interaction between MAT and bone turnover, however literature remains equivocal.

A New Community Health Center/Academic Medicine Partnership for Medicaid Cost Control, Powered by the Mega Teaching Health Center.

Community health centers (CHCs), a principal source of primary care for over 24 million patients, provide high-quality affordable care for medically underserved and lower-income populations in urban and rural communities. The authors propose that CHCs can assume an important role in the quest for health care reform by serving substantially more Medicaid patients. Major expansion of CHCs, powered by mega teaching health centers (THCs) in partnership with regional academic medical centers (AMCs) or teaching hospitals, could increase Medicaid beneficiaries' access to cost-effective care.

Patient Willingness to Have Tests to Guide Antibiotic Use for Respiratory Tract Infections: From the WWAMI Region Practice and Research Network (WPRN).

Introduction: The majority of consultations for acute respiratory tract infections (RTIs) lead to prescriptions for antibiotics, which have limited clinical benefit. We explored patients' willingness to have blood tests as part of the diagnostic work-up for RTIs, and patient knowledge about antibiotics.

Methods: Patients at 6 family medicine clinics were surveyed.

Metabolic syndrome cluster does not provide incremental prognostic information in patients with stable cardiovascular disease: A post hoc analysis of the AIM-HIGH trial.

Background: Metabolic syndrome (MS) is a well-known risk factor for the development of cardiovascular (CV) disease; yet, controversy persists whether it adds incremental prognostic value in patients with established CV disease.

Objectives: This study was performed to determine if MS is associated with worse CV outcomes in patients with established CV disease treated intensively with statins.

Methods: We performed a post hoc analysis of the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes trial, in which patients with established CV disease and atherogenic dyslipidemia (n = 3414) were randomly assigned to receive extended release niacin or placebo during a mean 36-month follow-up, to assess whether the presence of MS or the number of MS components contributed to CV outcomes.