Citations

Abstract The emergency department ( ED ) occupies a unique position within the healthcare system, serving as a safety net for vulnerable patients, regardless of their race, ethnicity, religion, country of origin, sexual orientation, socioeconomic status, or medical diagnosis. Shared decision making ( SDM ) presents special challenges when used with vulnerable population groups. The differing circumstances, needs, and perspectives of vulnerable groups invoke issues of provider bias, disrespect, judgmental attitudes, and lack of cultural competence, as well as patient mistrust and the consequences of their social and economic disenfranchisement. A research agenda that includes community‐engaged approaches, mixed‐methods studies, and cost‐effectiveness analyses is proposed to address the following questions: 1) What are the best processes/formats for SDM among racial, ethnic, cultural, religious, linguistic, social, or otherwise vulnerable groups who experience disadvantage in the healthcare system? 2) What organizational or systemic changes are needed to support SDM in the ED whenever appropriate? 3) What competencies are needed to enable emergency providers to consider patients’ situation/context in an unbiased way? 4) How do we teach these competencies to students and residents? 5) How do we cultivate these competencies in practicing emergency physicians, nurses, and other clinical providers who lack them? The authors also identify the importance of using accurate, group‐specific data to inform risk estimates for SDM decision aids for vulnerable populations and the need for increased ED ‐based care coordination and transitional care management capabilities to create additional care options that align with the needs and preferences of vulnerable populations.

Background The Effects of the P‐Selectin Antagonist Inclacumab on Myocardial Damage After Percutaneous Coronary Intervention for Non‐ST‐Segment Elevation Myocardial Infarction ( SELECT ‐ ACS ) trial suggested beneficial effects of inclacumab, a monoclonal antibody directed against P‐selectin, on periprocedural myocardial damage. This study evaluated the effect of inclacumab on myocardial damage according to varying time intervals between study drug infusion and percutaneous coronary intervention ( PCI ). Methods and Results Patients (n=544) enrolled in the SELECT ‐ ACS trial and randomized to receive 1 infusion of placebo or inclacumab (5 or 20 mg/kg, administered between 1 and 24 hours before PCI ) were divided according to the time interval between study drug infusion and PCI . The primary end point was the change in troponin I from baseline at 16 and 24 hours after PCI . In patients receiving inclacumab 20 mg/kg with a short (less than median) time interval between infusion and PCI , placebo‐adjusted geometric mean percent changes in troponin I, creatine kinase–myocardial band, and peak troponin I at 24 hours were −45.6% ( P =0.005), −30.7% ( P =0.01), and −37.3% ( P =0.02), respectively. No significant changes were observed in patients with a long (greater than median) time interval between infusion and PCI . Placebo‐adjusted geometric mean percent changes in troponin I and creatine kinase–myocardial band were −43.5% ( P =0.02) and −26.0% ( P =0.07), respectively, when inclacumab 20 mg/kg was administered between 1 and 3 hours before PCI , whereas the drug had no effect with longer intervals. Conclusions Inclacumab 20 mg/kg significantly reduces myocardial damage after PCI in patients with non– ST ‐segment elevation myocardial infarction, and benefits are larger when the infusion is administered <3 hours before PCI . Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01327183.

Disease overview:Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by stem cell‐derived clonal myeloproliferation that is often but not always accompanied byJAK2,CALRorMPLmutation, abnormal cytokine expression, bone marrow fibrosis, anemia, splenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression and shortened survival.Diagnosis:Diagnosis is based on bone marrow morphology. The presence ofJAK2,CALRorMPLmutation is supportive but not essential for diagnosis; approximately 90% of patients carry one of these mutations and 10% are “triple‐negative.” None of these mutations are specific to PMF and are also seen in essential thrombocythemia (ET). According to the revised 2016 World Health Organization (WHO) classification and diagnostic criteria, “prefibrotic” PMF (pre‐PMF) is distinguished from “overtly fibrotic” PMF; the former might mimic ET in its presentation and it is prognostically relevant to distinguish the two.Risk stratification:The Dynamic International Prognostic Scoring System‐plus (DIPSS‐plus)uses eight predictors of inferior survival: age >65 years, hemoglobin <10 g/dL, leukocytes >25 × 109/L, circulating blasts ≥1%, constitutional symptoms, red cell transfusion dependency, platelet count <100 × 109/L and unfavorable karyotype (i.e., complex karyotype or sole or two abnormalities that include +8, −7/7q‐, i(17q), inv(3), 5/5q‐, 12p‐, or 11q23 rearrangement). The presence of 0, 1, “2 or 3” and ≥4 adverse factors defines low, intermediate‐1, intermediate‐2 and high‐risk disease with median survivals of approximately 15.4, 6.5, 2.9 and 1.3 years, respectively. Most recently, DIPSS‐plus‐independent adverse prognostic relevance has been demonstrated for certain mutations includingASXL1andSRSF2whereas patients with type 1/likeCALRmutations, compared to their counterparts with other driver mutations, displayed significantly better survival.Risk‐adapted therapy:Observation alone is a reasonable treatment strategy for asymptomaticloworintermediate‐1DIPSS‐plus risk disease, especially in the absence of high‐risk mutations. All other patients withhighorintermediate‐2 riskdisease, or those harboring high‐risk mutations such asASXL1orSRSF2, should be considered for stem cell transplant, which is currently the only treatment modality with the potential to favorably modify the natural history of the disease. Non‐transplant candidates should be encouraged to participate in clinical trials, since the value of conventional drug therapy, including the use of JAK2 inhibitors, is limited to symptoms palliation and reduction in spleen size. Specifically, JAK2 inhibitors have not been shown to induce complete clinical or cytogenetic remissions or significantly affectJAK2/CALR/MPLmutant allele burden. Splenectomy is considered for drug‐refractory splenomegaly. Involved field radiotherapy is most useful for post‐splenectomy hepatomegaly, non‐hepatosplenic EMH, PMF‐associated pulmonary hypertension and extremity bone pain. Am. J. Hematol. 91:1262–1271, 2016. © 2016 Wiley Periodicals, Inc.

ABSTRACT A 2-year longitudinal microbiome study of 22 patients who underwent colectomy with an ileal pouch anal anastomosis detected significant increases in distinct populations of Bacteroides during 9 of 11 patient visits that coincided with inflammation (pouchitis). Oligotyping and metagenomic short-read annotation identified Bacteroides populations that occurred in early samples, bloomed during inflammation, and reappeared after antibiotic treatment. Targeted cultivation of Bacteroides isolates from the same individual at multiple time points and from several patients detected subtle genomic changes, including the identification of rapidly evolving genomic elements that differentiate isogenic strains of Bacteroides fragilis from the mucosa versus lumen. Each patient harbored Bacteroides spp. that are closely related to commonly occurring clinical isolates, including Bacteroides ovatus , B. thetaiotaomicron , B. vulgatus , and B. fragilis , which contained unique loci in different patients for synthesis of capsular polysaccharides. The presence of unique Bacteroides capsular polysaccharide loci within different hosts and between the lumen and mucosa may represent adaptations to stimulate, suppress, and evade host-specific immune responses at different microsites of the ileal pouch. IMPORTANCE This longitudinal study provides an opportunity to describe shifts in the microbiomes of individual patients who suffer from ulcerative colitis (UC) prior to and following inflammation. Pouchitis serves as a model for UC with a predictable incidence of disease onset and enables prospective longitudinal investigations of UC etiology prior to inflammation. Because of insufficient criteria for predicting which patients will develop UC or pouchitis, the interpretation of cross-sectional study designs suffers from lack of information about the microbiome structure and host gene expression patterns that directly correlate with the onset of disease. Our unique longitudinal study design allows each patient to serve as their own control, providing information about the state of the microbiome and host prior to and during the course of disease. Of significance to the broader community, this study identifies microbial strains that may have genetic elements that trigger the onset of disease in susceptible hosts.

Prosthetic replacement of the elbow joint has continued to improve over time. Widespread implantation of certain designs has led to identification a few successful elements of elbow arthroplasty, as well as several opportunities for improvement. Current hot topics in elbow arthroplasty include triceps-preserving exposures, implantation of components with better-expected wear performance, management of the ulnar nerve, prevention of infection, and the development of successful cementless components. Total elbow arthroplasty has the potential to improve pain, function and quality of life for many patients with articular destruction secondary to inflammatory arthropathy or as a consequence of trauma. Continued advances in this field are key to make this operation as reliable and lasting as hip or knee arthroplasty.

Objective The interplay between neuronal innervation and other cell types underlies the physiological functions of the dura mater and contributes to pathophysiological conditions such as migraine. We characterized the extensive, but understudied, non-arterial diffuse dural innervation (DDI) of the rat and Rhesus monkey. Methods We used a comprehensive integrated multi-molecular immunofluorescence labeling strategy to extensively profile the rat DDI and to a lesser extent that of the Rhesus monkey. Results The DDI was distributed across a dense, pervasive capillary network and included free nerve endings of peptidergic CGRP-expressing C fibers that were closely intertwined with noradrenergic (NA) sympathetic fibers and thin-caliber nonpeptidergic “C/Aδ” fibers. These newly identified C/Aδ fibers were unmyelinated, like C fibers, but expressed NF200, usually indicative of Aδ fibers, and uniquely co-labeled for the CGRP co-receptor, RAMP1. Slightly-larger caliber NF200-positive fibers co-labeled for myelin basic protein (MBP) and terminated as unbranched corpuscular endings. The DDI peptidergic fibers co-labeled for the lectin IB4 and expressed presumably excitatory α1-adrenergic receptors, as well as inhibitory 5HT1D receptors and the delta opioid receptor (δOR), but rarely the mu opioid receptor (µOR). Labeling for P2X3, TRPV1, TRPA1, and parasympathetic markers was not observed in the DDI. Interpretation These results suggest potential functional interactions, wherein peptidergic DDI fibers may be activated by stress-related sympathetic activity, resulting in CGRP release that could be detected in the circulation. CGRP may also activate nonpeptidergic C/Aδ fibers that are likely mechanosensitive or polymodal, leading to activation of post-synaptic pain transmission circuits. The distribution of α1-adrenergic receptors, RAMP1, and the unique expression of the δOR on CGRP-expressing DDI fibers suggest strategies for functional modulation and application to therapy.

Aims To examine the need for minimal diagnostic criteria for post-transplant lymphoproliferative disorders (PTLD) in children, we sought to determine the rate of incidental Epstein-Barr virus (EBV)-positivity in tissues from organ transplant recipients (OTR). Methods EBV in situ hybridisation (ISH) was done retrospectively on tissue from 34 paediatric autopsies of OTR and paediatric tonsillectomy specimens from non-OTR (96) and OTR (6). Patients with a history of PTLD were excluded from both data sets. Results EBV-positivity was found incidentally in 2/34 autopsy cases (5.9%). Median time from transplant to death for all patients was 12.8 months (range 0.1–153 months). Median time between transplant and death in EBV-positive cases was 34 months. EBV was positive in 26/102 tonsils (25%). Among tonsils from OTR, 4/6 (67%) were EBV-positive. Conclusions These findings reinforce the need for strict morphological and clinical criteria, other than EBV-positivity, when diagnosing PTLD in the paediatric population.

Valvular interstitial cells from diseased aortic valve leaflets show their ability to regenerate–to proliferate and grow, to express appropriate genes and to deposit suitable proteins–in a non-degenerative nanofibrous substrate.