The diagnostic and clinical significance of granulomas in gastrointestinal biopsies from haematopoietic transplant patients.

Aims: The diagnostic and clinical significance of granulomas in gastrointestinal (GI) biopsies from haematopoietic transplant patients remains disputed, especially following the proposal of cord colitis syndrome (CCS) as a new entity. The aim of the following study was to explore this controversy by identifying such biopsies with granulomas and detailing their clinicopathological associations.

Methods And Results: Twelve patients with granuloma-containing biopsies were identified from across three scenarios: prospectively during a GI pathologist's routine practice over a period of 5 years; retrospectively from a cohort of transplant patients with clinically validated GI graft versus host disease (GVHD); and retrospectively from a cohort of patients who had received umbilical cord blood (UCB).

Rapid generation of potent antibodies by autonomous hypermutation in yeast.

The predominant approach for antibody generation remains animal immunization, which can yield exceptionally selective and potent antibody clones owing to the powerful evolutionary process of somatic hypermutation. However, animal immunization is inherently slow, has poor compatibility with certain antigens ( . .

Real-world experience with implantable loop recorder monitoring to detect subclinical atrial fibrillation in patients with cryptogenic stroke: The value of p wave dispersion in predicting arrhythmia occurrence.

Purpose: We hypothesized patients implanted with ILRs for cryptogenic stroke in "real life" clinical practice will show an AF detection rate comparable to prior clinical studies, and that clinical or imaging features may help to identify those at higher risk of AF detection.

Methods: A retrospective chart review was conducted of all patients who presented with cryptogenic stroke and received an ILR at an academic medical center from 2015 to 2017 with an active inpatient stroke service. The electronic health record and remote monitoring were used to identify occurrence of AF.

An investigation of the measurement properties of the de Morton Mobility Index for measuring mobility capacity in hospital patients with Parkinson's disease.

Objective: To examine the measurement properties of the de Morton Mobility Index (DEMMI), a performance-based clinical outcome assessment of mobility capacity, in hospital patients with Parkinson's disease.

Design: Cross-sectional study.

Participants: Hospital patients with Parkinson's disease.

Qualitative process evaluation from a complex systems perspective: A systematic review and framework for public health evaluators.

Background: Public health evaluation methods have been criticized for being overly reductionist and failing to generate suitable evidence for public health decision-making. A "complex systems approach" has been advocated to account for real world complexity. Qualitative methods may be well suited to understanding change in complex social environments, but guidance on applying a complex systems approach to inform qualitative research remains limited and underdeveloped.

A Potential Role for IL-4 and IL-13 in an Alopecia Areata-Like Phenotype: A Clinical Perspective.

Although alopecia areata (AA) has been traditionally classified as a strictly T helper type 1-mediated process, the T helper type 2 (Th2) pathway may contribute to an AA-like phenotype in some individuals. Herein, we describe three clinical cases that support the potential role of Th2 activity through the upregulation of IL-4 and IL-13 in an AA-like phenotype.

Extended storage of thawed platelets: Refrigeration supports postthaw quality for 10 days.

Background: Cryopreservation of platelets with dimethylsulfoxide (DMSO) at -80°C increases their shelf life from days to years. Once thawed, platelets are stored at room temperature (RT), and the shelf life is limited to 4-6 hours. However, refrigeration (cold storage) may facilitate a prolongation of the shelf life of thawed platelets.

Diverging metabolic programmes and behaviours during states of starvation, protein malnutrition, and cachexia.

Background: Our evolutionary history is defined, in part, by our ability to survive times of nutrient scarcity. The outcomes of the metabolic and behavioural adaptations during starvation are highly efficient macronutrient allocation, minimization of energy expenditure, and maximized odds of finding food. However, in different contexts, caloric deprivation is met with vastly different physiologic and behavioural responses, which challenge the primacy of energy homeostasis.

BEAM-Campath Allogeneic Stem Cell Transplant for Patients with Relapsed/Refractory Lymphoma: High Incidence of Long-Term Mixed Donor-Recipient Chimerism and the Response to Donor Lymphocyte Infusions.

BiCNU (carmustine), etoposide, Ara-C, melphalan (BEAM) and Campath conditioning was developed to reduce the high transplant-related mortality in patients with lymphoma while delivering intensive antilymphoma immunotherapy, as well as to some extent a platform for allogeneic stem cell engraftment. Significant numbers of patients appeared to have persistent recipient-derived hematopoiesis, and therefore we retrospectively analyzed patients with lymphoma undergoing BEAM-Campath conditioned allogeneic stem cell transplantation at our center (2003 to 2017) to characterize the patterns of chimerism and patient outcomes. Chimerism was analyzed with short tandem repeat PCR.

Multiplexed measurement of variant abundance and activity reveals VKOR topology, active site and human variant impact.

Vitamin K epoxide reductase (VKOR) drives the vitamin K cycle, activating vitamin K-dependent blood clotting factors. VKOR is also the target of the widely used anticoagulant drug, warfarin. Despite VKOR's pivotal role in coagulation, its structure and active site remain poorly understood.

Effects on Mouse Food Consumption After Exposure to Bedding from Sick Mice or Healthy Mice.

Control mice housed in the same room as mice with pancreatic ductal adenocarcinoma (PDAC) demonstrate decreased food intake coincident with the cachexia experienced by the mice with PDAC. Mice are considered an empathetic species, and we hypothesized that the reduced food intake in normal mice was an "empathy state" that was mediated by olfactory cues. Naïve male and female C57BL/6 mice were exposed to soiled bedding from mice experiencing PDAC induced cachexia or from control mice in the PDAC study.

Acyclovir-induced neurotoxicity in an immunocompromised patient.

This is a case report of a 75-year-old immunocompromised male who developed encephalopathy while undergoing treatment for disseminated herpes zoster with peripheral nerve involvement. While his initial presentation involved primarily profound lower extremity weakness, he developed progressive confusion to the point of obtundation only after initiation of standard therapy with intravenous acyclovir. The evaluation of his altered mental status was largely unremarkable.

Inactivation of Japanese encephalitis virus in plasma by methylene blue combined with visible light and in platelet concentrates by ultraviolet C light.

Unlabelled: Japanese encephalitis virus (JEV) is endemic to tropical areas in Asia and the Western Pacific. It can cause fatal encephalitis, although most infected individuals are asymptomatic. JEV is mainly transmitted to humans through the bite of an infected mosquito, but can also be transmitted through blood transfusion.

Vaccination Against Human Papillomavirus.

Clinical Question: Who should receive human papillomavirus (HPV) vaccination?

Bottom Line: Catch-up vaccination is now recommended for all persons through age 26 years. For persons aged 27 through 45 years, clinicians and patients should now jointly decide whether HPV vaccination is appropriate. Routine HPV vaccination at age 11 or 12 years (or as early as age 9 years) continues to be recommended.

Targeting of the Hedgehog/GLI and mTOR pathways in advanced pancreatic cancer, a phase 1 trial of Vismodegib and Sirolimus combination.

Background/objectives: Preclinical data indicated a functional and molecular interaction between Hedgehog (HH)/GLI and PI3K-AKT-mTOR pathways promoting pancreatic ductal adenocarcinoma (PDAC). A phase I study was conducted of Vismodegib and Sirolimus combination to evaluate maximum tolerated dose (MTD) and preliminary anti-tumor efficacy.

Methods: Cohort I included advanced solid tumors patients following a traditional 3 + 3 design.

Minimum 5-Year Follow-up on Graduates of Growing Spine Surgery for Early Onset Scoliosis.

Introduction: After discontinuation of growth friendly (GF) surgery for early onset scoliosis, patients undergo spinal fusion or continued observation. This last planned treatment is colloquially called "definitive" treatment, conferring these patients as "graduates" of a growing program. The 5-year radiographic and clinical outcomes of this cohort are unknown.

Inotuzumab ozogamicin for relapsed/refractory acute lymphoblastic leukemia: outcomes by disease burden.

Adults with relapsed/refractory acute lymphoblastic leukemia (R/R ALL) have a poor prognosis, especially if disease burden is high. This post hoc analysis of the phase 3 INO-VATE trial examined the efficacy and safety of inotuzumab ozogamicin (InO) vs. standard of care chemotherapy (SC) among R/R ALL patients with low, moderate, or high disease burden, respectively, defined as bone marrow blasts (BMB) < 50% (n = 53 vs.

GLI1/GLI2 functional interplay is required to control Hedgehog/GLI targets gene expression.

The Hedgehog-regulated transcription factors GLI1 and GLI2 play overlapping roles in development and disease; however, the mechanisms underlying their interplay remain elusive. We report for the first time that GLI1 and GLI2 physically and functionally interact in cancer cells. GLI1 and GLI2 were shown to co-immunoprecipitate in PANC1 pancreatic cancer cells and RMS13 rhabdomyosarcoma cells.

Characterizing the ability of an ice recrystallization inhibitor to improve platelet cryopreservation.

Improving aspects of platelet cryopreservation would help ease logistical challenges and potentially expand the utility of frozen platelets. Current cryopreservation procedures damage platelets, which may be caused by ice recrystallization. We hypothesized that the addition of a small molecule ice recrystallization inhibitor (IRI) to platelets prior to freezing may reduce cryopreservation-induced damage and/or improve the logistics of freezing and storage.

Multidisciplinary standards of care and recent progress in pancreatic ductal adenocarcinoma.

Despite tremendous gains in the molecular understanding of exocrine pancreatic cancer, the prognosis for this disease remains very poor, largely because of delayed disease detection and limited effectiveness of systemic therapies. Both incidence rates and mortality rates for pancreatic cancer have increased during the past decade, in contrast to most other solid tumor types. Recent improvements in multimodality care have substantially improved overall survival, local control, and metastasis-free survival for patients who have localized tumors that are amenable to surgical resection.

Reduced intensity conditioning for acute myeloid leukemia using melphalan- vs busulfan-based regimens: a CIBMTR report.

There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion.