Citations

Objective. Guidelines on antiplatelet medication use during endoscopy are based on limited evidence. We investigate the risk of bleeding and ischemic events in patients undergoing endoscopic mucosal resection (EMR) of esophageal lesions in the setting of scheduled cessation and prompt resumption of clopidogrel. Design. Single centre retrospective review. Patients. Patients undergoing EMR of esophageal lesions. Interventions. Use of clopidogrel before EMR and resumption after EMR. Patients cease antiplatelets and anticoagulants 7 days before EMR and resume clopidogrel 2 days after EMR in average risk patients. Main Outcomes. Gastrointestinal bleeding (GIB) and ischemic events (IE) within 30 days of EMR. Results. 798 patients underwent 1716 EMR. 776 EMR were performed on patients on at least 1 antiplatelet/anticoagulant (APAC). 17 EMR were performed following clopidogrel cessation. There were 14 GIB and 2 IE. GIB risk in the setting of recent clopidogrel alone (0%) was comparable to those not on APAC (1.1%) (P=1.0). IE risk on clopidogrel (6.3%) was higher than those not on APAC (0.1%) (P=0.03). Limitations. Retrospective study. Conclusions. Temporary cessation of clopidogrel before EMR and prompt resumption is not associated with an increased risk of gastrointestinal bleeding but may be associated with increased ischemic events.

Mucormycosis is a rare and often fatal invasive fungal infection mostly seen in immune-compromised individuals. A high index of clinical suspicion is necessary, so that effective preemptive therapy can be started, as timely intervention is crucial. In this series we present three cases of invasive mucormycosis in patients with underlying inflammatory bowel disease that had received therapy with immunomodulators prior to the infection. All three had varied clinical manifestations. We also review the literature of invasive mucormycosis in patients with inflammatory bowel disease.

Objective Multiple sclerosis (MS) lesions demonstrate immunopathological heterogeneity in patterns of demyelination. Previous cross‐sectional studies reported immunopatterns of demyelination were identical among multiple active demyelinating lesions from the same individual, but differed between individuals, leading to the hypothesis of intraindividual pathological homogeneity and interindividual heterogeneity. Other groups suggested a time‐dependent heterogeneity of lesions. The objective of our present study was to analyze tissue samples collected longitudinally to determine whether patterns of demyelination persist over time within a given patient. Methods Archival tissue samples derived from patients with pathologically confirmed central nervous system inflammatory demyelinating disease who had undergone either diagnostic serial biopsy or biopsy followed by autopsy were analyzed immunohistochemically. The inclusion criteria consisted of the presence of early active demyelinating lesions—required for immunopattern classification—obtained from the same patient at 2 or more time points. Results Among 1,321 surgical biopsies consistent with MS, 22 cases met the study inclusion criteria. Twenty‐one patients (95%) showed a persistence of immunopathological patterns in tissue sampled from different time points. This persistence was demonstrated for all major patterns of demyelination. A single patient showed features suggestive of both pattern II and pattern III on biopsy, but only pattern II among all active lesions examined at autopsy. Interpretation These findings continue to support the concept of patient‐dependent immunopathological heterogeneity in early MS and suggest that the mechanisms and targets of tissue injury may differ among patient subgroups. These observations have potentially significant implications for individualized therapeutic approaches. Ann Neurol 2014;75:728–738

This is a technical note of pelvic reconstruction performed by an advanced multidisciplinary team. The authors report a new 3-stage reconstruction of the hemipelvis after Type 3 sacrectomy involving instrumented spinoiliac arthrodesis and pedicled fibula grafting in 2 patients. The anterior stage of the procedure begins with a transabdominal approach to mobilize the viscera and to free up the tumor from the vessels. The posterior divisions of internal iliac vessels, the middle sacral vessels, and the lateral sacral vessels are then ligated. An anterior vertebrectomy is done at the appropriate level, followed by an anterior osteotomy through the lateral planed surgical margin of the sacrum close to the salvaged sacroiliac joint. The second stage includes a major sacral resection with lower-extremity amputation from the pubic symphysis through the intact side of the sacrum, ipsilateral pedicled fibula harvesting, and closure with an ipsilateral pedicled quadriceps flap. The final stage involves reconstruction with lumboiliac instrumentation. The pedicled fibular graft left from the second stage is then placed distally within the previously created iliopectineal docking site and proximally within the L-5 docking site. The authors believe that this is a feasible and reproducible technique with theoretical advantages that have to be proved in the long-term follow-up.

Osteoporosis, defined as low bone mass leading to increased fracture risk, is a major health problem that affects approximately 10 million Americans. The aging U.S. population is predicted to contribute to as much as a 50% increase in prevalence by 2025. Although common, osteoporosis can be clinically silent, and without prevention and screening, the costs of osteoporotic fracture–related morbidity and mortality will burden the U.S. healthcare system. This is a particularly relevant concern in the context of diminishing health care resources. Dual-energy X-ray absorptiometry is the most widely used, validated technique for measuring bone mineral density (BMD) and diagnosing osteoporosis. Cost-effectiveness analyses support early detection and treatment of high-risk patients with antiresorptive medications such as bisphosphonates. Moreover, optimization of bone health throughout life can help prevent osteoporosis. Current guidelines recommend screening women by age 65 years, but because no guidelines for screening intervals exist, decisions are made on the basis of clinical judgment alone. Although the recent literature provides some guidance, this review further explores current recommendations in light of newer evidence to provide more clarity on prevention, screening, and management strategies for patients with osteoporosis in the primary care setting.

Our aim was to conduct a pilot case-control study of RNA expression profile using RNA sequencing of rectosigmoid mucosa of nine females with -diarrhea-predominant irritable bowel syndrome (IBS-D) with accelerated colonic transit and nine female healthy controls. Mucosal total RNA was isolated and purified, and next-generation pair-end sequencing was performed using Illumina TruSeq. Analysis was carried out using a targeted approach toward 12 genes previously associated with IBS and a hypothesis-generating approach. Of the 12 targeted genes tested, patients with IBS-D had decreased mRNA expression of TNFSF15 (fold change controls to IBS-D: 1.53, P = 0.01). Overall, up- and downregulated mRNA expressions of 21 genes ( P = 10−5 to 10−8; P values with false detection rates are shown) were potentially relevant to IBS-D including the following: neurotransmitters [ P2RY4 ( P = 0.001), vasoactive intestinal peptide ( VIP, P = 0.02)]; cytokines [ CCL20 ( P = 0.019)]; immune function [ C4BPA complement cascade ( P = 0.0187)]; interferon-related [ IFIT3 ( P = 0.016)]; mucosal repair and cell adhesion [trefoil protein ( TFF1, P = 0.012)], retinol binding protein [ RBP2 ( P = 0.017)]; fibronectin ( FN1, P = 0.009); and ion channel functions [guanylate cyclase ( GUCA2B, P = 0.017), PDZ domain-containing protein 3 ( PDZD3, P = 0.029)]. Ten genes associated with functions related to pathobiology of IBS-D were validated by RT-PCR. There was significant correlation in fold changes of the selected genes ( Rs = 0.73, P = 0.013). Up- or downregulation of P2RY4, GUC2AB, RBP2, FNI, and C4BPA genes were confirmed on RT-PCR, which also revealed upregulation of farnesoid X receptor ( FXR) and apical sodium-coupled bile acid transporter ( IBAT/ASBT). RNA-Seq and RT-PCR analysis of rectosigmoid mucosa in IBS-D show transcriptome changes that provide the rationale for validation studies to explore the role of mucosal factors in the pathobiology of IBS-D.

Significance Our study not only reveals a novel role of peroxisome proliferator-activated receptor δ (PPARδ) in colonic inflammation and colitis-associated tumorigenesis, but also provides some rationale for development of PPARδ antagonists as new therapeutic agents in the treatment of inflammatory bowel disease and colitis-associated colorectal cancer. Moreover, our findings indicate that prostaglandin E 2 generated by chronic inflammation is a crucial mediator connecting chronic inflammation and colorectal carcinogenesis.