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Perianal fistula is a debilitating disease and challenging condition to treat. Recently, the use of stem cells has been shown to improve healing of fistulas.We wish to examine the use of an umbilical cord derived stem cell graft in a pilot study as a novel scaffold/stem inlay implanted into fistula repairs for anovaginal fistula to examine healing rates.This was a pilot study.This study took place in a colorectal surgery practice.Patients with anovaginal fistula were consented to participate. Cryopreserved umbilical cord tissue graft with viable cells was incorporated as an in-lay using a previously reported technique by the authors. Demographic data including history of prior repairs and inflammatory bowel disease were included. All patients were followed for a minimum of 6 weeks.The primary measures were safety and efficacy of novel stem cell graft in the treatment of anovaginal fistula.From 9/2017-9/2019, 15 patients underwent anovaginal fistula repair. Three of these patients underwent a second repair, for a total of 18 repairs. No patient was intentionally diverted while 3 patients presented for repair with a pre-existing stoma. The majority of repairs were previous repair failures (12, 67%) and seven repairs were performed on 5 patients with inflammatory bowel disease (IBD). Median follow-up was 30 weeks (6 - 104). The safety profile for cryopreserved umbilical cord tissue graft was excellent as no adverse events occurred. Overall complete healing rate was 39% and 12 (67%) repairs resulted in improvement of symptoms.This was a small pilot study.This is the largest series using cryopreserved umbilical cord graft for anovaginal fistula repair. The utilization of umbilical cord was safe and effective at closing defects. Randomized studies are necessary to determine added benefits over current standard of care. See Video Abstract at http://links.lww.com/DCR/B896.

Purpose: Microsporidium is a spore-forming intracellular parasite that affects a wide range of hosts including humans. The tumor necrosis factor alpha (TNF-α) plays a key role in the immunity to infection with microsporidia. Recently, the TNF-α antagonists have proven successful in treating variable autoimmune diseases. In the current study, we aimed to investigate the impact of using TNF-α antagonists as a therapeutic regimen in the prevalence of infections with microsporidia. Materials and Methods: Diarrheal patients with distinct autoimmune diseases (n = 100) were assigned to the study. Patients taking anti-TNF-α medications (n = 60) were allocated to Group 1A and those undergoing non-TNF-α inhibitor treatment (n = 40) to Group 1B. Furthermore, patients with diarrhea without autoimmune disorders (n = 20) were allocated as controls. Stool specimens, 3 per patient, were collected and microscopically examined for microsporidia spores. A microsporidia-specific stool polymerase chain reaction was used to confirm the microscopic findings. Results: Microsporidia infection was identified in 28.3% (17/60), 10% (4/40), and in 5% (1/20) of patients in Group 1A, Group 1B, and in the control group, respectively. Overall, infection was significantly high in cases compared to the controls and in patients receiving TNF-α antagonists compared to patients not given TNF-α inhibitors (P < 0.05). Finally, infection was significantly higher in cases treated with TNF-α antagonists for ≥2 months compared to cases treated for

Summary Although 2-nitropropane is a potentially harmful compound present in cigarette smoke, there are few fully-validated, modern methods to quantitate it in mainstream cigarette smoke. We developed an isotope dilution gas chromatography-tandem mass spectrometry (ID-GC-MS/MS) method for the detection of 2-nitropropane in mainstream cigarette smoke. The vapor fraction of mainstream cigarette smoke was collected in inert polyvinyl fluoride gas sampling bags and extracted with hexanes containing isotopically labeled internal standard, then purified and concentrated via solid-phase extraction using a normal phase silica adsorbent and a 100% dichloromethane eluant. This method is sensitive enough to measure vapor phase 2-nitro-propane concentrations in the nanogram range, with a 19 ng per cigarette method limit of detection. Product variability estimated from the analysis of 15 cigarette products yielded relative standard deviations ranging from 5.4% to 15.7%, and estimates of precision from two quality control products yielded relative standard deviations of 9.49% and 14.9%. Under the Health Canada Intense smoking regimen, 2-nitropropane in machine-generated mainstream smoke from 15 cigarette products ranged from 98.3 to 363 ng per cigarette.

BackgroundPerianal Crohn’s disease (pCD) is a debilitating complication affecting up to 30% of Crohn’s disease (CD) population, leading to increased morbidity, mortality and decreased quality of life. Despite the growing armamentarium of medications for luminal CD, their efficacy in pCD remains poorly studied.AimTo determine the efficacy of ustekinumab, a biologic approved for luminal CD, in pCD through a retrospective cohort study and systematic review.MethodsA retrospective cohort study on patients with CD with active perianal fistulae treated with ustekinumab from September 2013 to August 2019 was performed to determine perianal fistula response and remission at 6 and 12 months after ustekinumab induction. A systematic review was performed to further establish rates of fistula response and remission with ustekinumab.ResultsAt 6 months, 48.1% (13/27) patients achieved fistula response with none achieving fistula remission on provider exam, and 59.3% (16/27) achieved patient-reported symptomatic improvement with 3.7% (1/27) achieving symptomatic remission. At 1 year, on provider exam, 55.6% (5/9) had fistula response with none achieving fistula remission, and 100% (9/9) had symptomatic improvement with 22.2% (2/9) achieving symptomatic remission. There were no major safety signals during 1-year follow-up. The systematic review of 25 studies found 44% (92/209) of patients with active perianal fistulas had a clinical response within 6 months of follow-up, and 53.9% (85/152) of patients with 12 months of follow-up achieved clinical response.ConclusionUstekinumab presents a safe and effective therapy for treatment of pCD. Prospective, randomised trials are needed to further elucidate long-term efficacy of ustekinumab for pCD.

Graphical abstract, Highlights • A novel method was developed to detect nitromethane in cigarette smoke. • The method is sensitive, accurate, and fit for high-throughput applications. • The new method was used to quantify nitromethane in smoke from 10 cigarette brands. • Differences were observed depending on tobacco types used., Nitromethane is a volatile organic compound categorized as a Group 2B carcinogen by the International Agency for Research on Cancer. It has been detected in mainstream cigarette smoke, but few reliable methods have been reported for accurate quantification. We developed, a sensitive, selective, fully validated method for the targeted determination of nitromethane in mainstream tobacco smoke in ten U.S. domestic brands and two quality control materials (3R4F and CM6). The vapor phase portion of machine-generated cigarette mainstream smoke, under modified ISO 3308:2000 regime (ISO) and modified intense regime (HCI), from single cigarettes was collected using airtight polyvinylfluoride sampling bags. The bags’ contents were extracted using methanol containing an isotopically labeled internal standard followed by gas chromatography-tandem mass spectrometry. This approach is sufficiently sensitive to measure nitromethane levels in the nanogram range, with a method limit of detection of 72.3 ng/cig. Within-product variability estimated from the replicate analysis of 10 products ranged from 4.6%–16.3% (n = 6) over the two different smoking regimes, and method reproducibility estimated from two products used as quality control materials (3R4F and CM6) yielded intermediate precision values ranging from 16.6 to 20.8% (n = 20). Under HCI, nitromethane yields in machine-generated cigarette smoke from ten different domestic cigarette products ranged from 3.2 to 12 μg/cig; under ISO yields ranged from 1.6 to 4.9 μg/cig under standardized smoking machine conditions. Nitromethane yields are related to both the smoke regime (blocking of vent holes, puff duration and puff volume) and the heterogeneity of tobacco mixtures. This method provides a selective and fully validated technique to accurately quantify nitromethane in mainstream cigarette smoke, with minimal waste generation. It is an improvement over previous methods with regards to specificity, throughput, and simplicity of the sample collection process.

Nitrobenzene, a potentially harmful compound found in tobacco smoke, has been largely excluded from prior analysis due to difficulties with quantification. Quantifying harmful compounds in cigarette smoke is useful to compare products, to examine the impact of design parameters on delivery, and to help estimate exposures. A sensitive high-throughput method has been developed for quantifying nitrobenzene in machine-generated mainstream cigarette smoke using isotope dilution gas chromatography-tandem mass spectrometry (ID-GC-MS/MS). This method has sufficient sensitivity to measure vapor phase nitrobenzene concentrations in the low nanogram range, with a 418 pg/cig method limit of detection. Precision estimates from two quality control cigarette products resulted in percent relative standard deviations of 11.5% and 14.9%; product variability estimates from 13 cigarette products resulted in percent relative standard deviations ranging from 2.8% to 16.9%. Nitrobenzene in the machine-generated, mainstream smoke from 15 cigarette products are reported and range from 18 to 38 ng/cig under the Health Canada Intense smoking regimen.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10 −8 , bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development. © 2018, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

International audience; Marie-Galante Island (Guadeloupe, French West-Indies) has recently been the object of several paleontological investigations in order to characterize the evolution of its terrestrial vertebrate paleobiodiversity during the last 40 000 years. This paper consists in a synthesis these recently obtained results obtained by crossed studies of several large vertebrate fossil assemblages (mammal, bird, squamate, and amphibian) collected in Late Pleistocene and Holocene deposits. Our work reveals apreviously inconspicuous now-extinct Pleistocene and Holocene vertebrate biodiversity. We observed that this past diversity was recently modified to become very different from what it is nowadays. Indeed, while a small number of extinction or extirpation events can be related to the Pleistocene-Holocene climatic transition, the faunal community of the island is nearly completely modified during the last millenaries. These modifications include the arrival of several exogenous taxa, and an extinction/extirpation rate of native species between 54% and 100% depending of taxa.Our results suggest that human impact was the main factor driving the evolution of the island terrestrial faunal diversity. We also demonstrate a possible impact of Pre-Columbian human populations on the faunal diversity of Marie-Galante Island which however remains minor in respect to the overwhelming modifications possibly related to the European colonization and subsequent anthropization of the island.

OBJECTIVE To characterize transitional care needs (TCNs) after colorectal cancer (CRC) surgery and examine their association with age and impact on overall survival (OS). BACKGROUND TCNs after cancer surgery represent additional burden for patients and are associated with higher short-term mortality. They are not well-characterized in CRC patients, particularly in the context of a growing elderly population, and their effect on long-term survival is unknown. METHODS A retrospective cohort study of CRC patients (N = 486) having curative surgery at a tertiary referral center (2002-2011) was conducted. Outcomes included TCNs (home health or nonhome destination at discharge) and OS. Patients were compared on the basis of age: young (