Monitoring Patients With Inflammatory Bowel Disease at High Risk of Anal Cancer.

Anal cancer is a rare but deadly disease that disproportionately affects patients with inflammatory bowel disease (IBD). Rates of adenocarcinoma and human papillomavirus-related squamous cell carcinoma have been consistently demonstrated to be higher in patients with ulcerative colitis and Crohn's disease. Despite this increased risk, uniform screening, diagnosis, and treatment algorithms are lacking. This review describes the most recent literature surrounding anal cancer in the IBD population as well as the unique challenges inherent in diagnosing and treating this population. We conclude by proposing a new screening motif based off literature review and multidisciplinary clinical experience that aims to increase early detection of anal cancers in the IBD population.

Sex-Based Differences in IBD Surgical Outcomes.

BACKGROUND: Although there are discrepancies in the development and progression of IBD based on biologic sex, little is known about differences in postoperative outcomes between men and women undergoing surgery for this condition. OBJECTIVE: To compare rates of anastomotic leaks, wound complications, and serious adverse events between men and women undergoing surgery for IBD. DESIGN: This was a retrospective cohort study. SETTINGS: Data were obtained from the American College of Surgeons National Surgical Quality Improvement Program IBD Collaborative database, which includes 15 high-volume IBD surgery centers. PATIENTS: All adult patients undergoing surgery for IBD were included. Participants with missing data for exposure or outcome variables were excluded. MAIN OUTCOME MEASURES: Rates of anastomotic leaks, wound complications, and serious adverse events were compared between women and men. RESULTS: A total of 3143 patients were included. There was a significant association between sex and BMI, IBD type, and preoperative medication use. Women had decreased odds of serious adverse events compared to men (OR 0.73; 95% CI, 0.55-0.96), but there was no significant association between sex and anastomotic leaks or wound complications. IBD type was found to be an effect measure modifier of the relationship between sex and serious adverse events. Among patients with ulcerative colitis, women had a 54% decrease in the odds of serious adverse events compared to men, whereas there was no significant difference between women and men with Crohn's disease. LIMITATIONS: This study was limited by capturing only 30 days of postoperative outcomes. CONCLUSIONS: Women undergoing surgery for ulcerative colitis had decreased odds of serious adverse events compared to men. Understanding sex-based differences in outcomes allows clinicians to make patient-centered decisions regarding surgical planning and perioperative management for patients with IBD. See Video Abstract . DIFERENCIAS BASADAS EN EL SEXO EN LOS RESULTADOS QUIRRGICOS DE LA ENFERMEDAD INFLAMATORIA INTESTINAL: ANTECEDENTES:Aunque existen discrepancias en el desarrollo y la progresión de la enfermedad inflamatoria intestinal según el sexo biológico, se sabe poco sobre las diferencias en los resultados postoperatorios entre hombres y mujeres sometidos a cirugía por esta afección.OBJETIVO:Nuestro objetivo fue comparar las tasas de fugas anastomóticas, complicaciones de las heridas y eventos adversos graves entre hombres y mujeres sometidos a cirugía por enfermedad inflamatoria intestinal.DISEÑO:Este fue un estudio de cohorte retrospectivo.AJUSTES:Los datos se obtuvieron de la base de datos del Programa Nacional de Mejora de la Calidad Quirúrgica del Colegio Americano de Cirujanos para la Enfermedad Inflamatoria Intestinal, que incluye 15 centros de cirugía de enfermedad inflamatoria intestinal de alto volumen.PACIENTES:Se incluyeron todos los pacientes adultos sometidos a cirugía por enfermedad inflamatoria intestinal. Se excluyeron los sujetos a los que les faltaban datos sobre exposición o variables de resultado.PRINCIPALES MEDIDAS DE RESULTADO:Se compararon las tasas de fugas anastomóticas, complicaciones de las heridas y eventos adversos graves entre mujeres y hombres.RESULTADOS:Se incluyeron un total de 3.143 pacientes. Hubo una asociación significativa entre el sexo y el índice de masa corporal, el tipo de enfermedad inflamatoria intestinal y el uso de medicación preoperatoria. Las mujeres tuvieron menores probabilidades de sufrir eventos adversos graves en comparación con los hombres (OR = 0,73; IC del 95 %: 0,55 a 0,96), pero no hubo una relacion significativa entre el sexo y las fugas anastomóticas o las complicaciones de las heridas. Se encontró que el tipo de enfermedad inflamatoria intestinal era un modificador de la medida del efecto de la relación entre el sexo y los eventos adversos graves. Entre los pacientes con colitis ulcerosa, las mujeres tuvieron una disminución del 54 % en las probabilidades de sufrir eventos adversos graves en comparación con los hombres, mientras que no hubo diferencias significativas entre mujeres y hombres con enfermedad de Crohn.LIMITACIONES:Este estudio estuvo limitado al capturar solo 30 días de resultados posoperatorios.CONCLUSIONES:Las mujeres sometidas a cirugía por colitis ulcerosa tuvieron menores probabilidades de sufrir eventos adversos graves en comparación con los hombres. Comprender las diferencias en los resultados basadas en el sexo permite a los médicos tomar decisiones centradas en el paciente con respecto a la planificación quirúrgica y el manejo perioperatorio de los pacientes con enfermedad inflamatoria intestinal. (Traducción-Dr Yolanda Colorado).

Secretory-IgA binding to intestinal microbiota attenuates inflammatory reactions as the intestinal barrier of preterm infants matures.

Previous work has shown that Secretory-IgA (SIgA) binding to the intestinal microbiota is variable and may regulate host inflammatory bowel responses. Nevertheless, the impact of the SIgA functional binding to the microbiota remains largely unknown in preterm infants whose immature epithelial barriers make them particularly susceptible to inflammation. Here, we investigated SIgA binding to intestinal microbiota isolated from stools of preterm infants <33 weeks gestation with various levels of intestinal permeability. We found that SIgA binding to intestinal microbiota attenuates inflammatory reactions in preterm infants. We also observed a significant correlation between SIgA affinity to the microbiota and the infant's intestinal barrier maturation. Still, SIgA affinity was not associated with developing host defenses, such as the production of mucus and inflammatory calprotectin protein, but it depended on the microbiota shifts as the intestinal barrier matures. In conclusion, we reported an association between the SIgA functional binding to the microbiota and the maturity of the preterm infant's intestinal barrier, indicating that the pattern of SIgA coating is altered as the intestinal barrier matures.

Limited Role for Routine Restaging After Neoadjuvant Therapy in Locally Advanced Rectal Cancer.

BACKGROUND: Although many patients with locally advanced rectal cancer undergo restaging imaging after neoadjuvant chemoradiotherapy and before surgery, the benefit of this practice is unclear. The purpose of this study was to examine the impact of reimaging on outcomes. MATERIALS AND METHODS: We performed a retrospective analysis of consecutive patients with stage 2 and 3 rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy between May 2005 and April 2018. Patient and disease characteristics, imaging, treatment, and oncologic outcomes were compared between those who underwent restaging and those who went directly to surgery. Predictors of outcomes and cost effectiveness of restaging were determined. RESULTS: Of 224 patients, 146 underwent restaging. Six restaged patients had findings leading to a change in management. There was no difference in freedom from recurrence (P = 0.807) and overall survival (P = 0.684) based on restaging. Pretreatment carcinoembryonic antigen level >3 ng/mL (P = 0.010), clinical T stage 4 (P = 0.016), and pathologic T4 (P = 0.047) and N2 (P = 0.002) disease increased the risk of death, whereas adjuvant chemotherapy decreased the risk of death (P < 0.001) on multivariate analysis. Disease recurrence was lower with pelvic exenteration (P = 0.005) and in females (P = 0.039) and higher with pathologic N2 (P = 0.003) and N3 (P = 0.002) disease. The average cost of reimaging is $40,309 per change in management; however, $45 is saved per patient when downstream surgical costs are considered. CONCLUSIONS: Imaging restaging after neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer rarely changes treatment and does not improve survival. In a subset of patients at higher risk for worse outcome, reimaging may be beneficial.

A Distinct Gut Microbiota Exists Within Crohn's Disease-Related Perianal Fistulae.

BACKGROUND: Gut bacteria are strongly suspected to play a key role in the pathogenesis of Crohn's disease (CD). Studies have demonstrated alterations in the gut microbiota in this patient population. The purpose of this study was to characterize the gut microbiota of fistulizing perianal CD. MATERIALS AND METHODS: Stool and fistula samples were obtained from patients undergoing surgery for CD-related anorectal fistulae. Microbial compositions of matched stool and fistula samples were characterized using 16S rRNA gene profiling. The effect of sample type, patient gender, disease classification (Montreal A/B), disease activity (Harvey Bradshaw Index), antibiotic use, and presence of active proctitis on microbial composition was assessed. RESULTS: Samples were obtained from 18 patients. Bacteroides was the most abundant genera across all samples collected, followed by Streptococcus and Bifidobacterium. Bifidobacterium was present at significantly higher levels in fecal samples than fistula samples, whereas Achromobacter and Corynebacterium were present at significantly higher levels in fistula samples. Antibiotic, but not thiopurine or antitumor necrosis factor medication, exposure affected the gut microbial composition. Patient gender, disease classification, disease activity, and presence of active proctitis did not alter stool or fistula microbiota. CONCLUSIONS: Our data show that the gut microbiota within CD-related anorectal fistulae is distinct from that in stool samples obtained from the same patients. We also observe a dysbiosis in patients treated with antibiotics compared with those not treated with antibiotics.

Financial Toxicity in Crohn's Disease.

BACKGROUND: A patient-reported outcome measure called Comprehensive Score for Financial Toxicity (COST) was previously developed and validated in patients with cancer. GOALS: We sought to assess the financial toxicity associated with Crohn's disease (CD) by administering the COST questionnaire to patients treated at a tertiary care center. STUDY: Forty-eight patients diagnosed with CD completed questionnaires, which included the COST quality of life instrument as well as questions with regard to sociodemographics and clinical characteristics. Analysis of results was performed with Minitab. RESULTS: Forty-eight completed questionnaires were scored. The mean age of the cohort was 37.6±13.4 years and 58% of patients were women. COST scores had a normal distribution (Anderson-Darling, P=0.31). The median COST score was 22, a result associated with mild negative impact on health-related quality of life. Patients' COST score stratum differed based on their education level (P<0.001), employment status (P=0.037), disability status (P=0.016), household income (P=0.004), and housing arrangement (P=0.006). Disease activity in the past 6 months and more frequent feelings of anxiety and depression also correlated with higher COST score. CONCLUSIONS: In this survey study, we found that the majority of our patients with CD experienced at least mild financial distress. Lower income and education level increased disease activity, and the presence of anxiety and depression increased the financial distress experienced by patients. Further research is needed to develop effective interventions to minimize financial toxicity in this patient population.

Early Postoperative Anti-TNF Therapy Does Not Increase Complications Following Abdominal Surgery in Crohn's Disease.

BACKGROUND: The impact of postoperative anti-TNF therapy on infectious complications following Crohn's disease surgery remains controversial. Use of anti-TNF therapy 2-4 weeks postoperatively appears safe, but safety of use within 2 weeks is unknown. AIMS: We sought to evaluate the effect of anti-TNF therapy initiated within 2 weeks of abdominal surgery in patients with Crohn's disease. METHODS: We conducted a retrospective review of adult Crohn's disease patients undergoing abdominal surgery between 2004 and 2011. Infectious and non-infectious complications were compared between patients exposed to anti-TNF therapy within 2 weeks or between 2 and 4 weeks postoperatively and to those without exposure using chi-squared and regression analysis. RESULTS: Three hundred thirty-one abdominal surgeries were included; 241 were without anti-TNF exposure, 46 received postoperative anti-TNF within 2 weeks of surgery, and 44 received anti-TNF therapy 2-4 weeks after surgery. Patients who received anti-TNF therapy within 2 weeks of surgery, those initiated between 2 and 4 weeks of surgery, and those who did not receive anti-TNF therapy within 4 weeks of surgery had no significant difference in rates of infectious complications (22%, 32%, 33%, p = 0.332). Rates of non-infectious complications (4%, 9%, 14%, p = 0.143), mortality (0%, 0%, 3%, p = 0.105), hospital readmission (17%, 16%, 15%, p = 0.940), and reoperation (11%, 11%, 16%, p = 0.563) were also similar between groups. CONCLUSIONS: Use of early anti-TNF therapy within 2 weeks or between 2 and 4 weeks following abdominal surgery did not increase risk of postoperative surgical infections in Crohn's patients.

Upregulation of RASSF1A in Colon Cancer by Suppression of Angiogenesis Signaling and Akt Activation.

BACKGROUND/AIMS: Silencing of tumor suppressor genes (TSGs) and promotion of angiogenesis are associated with tumor development and metastasis. However, little is known if angiogenic molecules directly control TSGs and vice versa. METHODS: A regulatory link between angiogenesis and down regulation of TSGs was evaluated using an anti-cancer agent, andrographolide (AGP) in cancer cells, mouse xenograft tissues and patient derived organoids through gene/protein expression, gene silencing, and immunohistochemical analyses. RESULTS: AGP treatment demonstrated significant expression of RASSF1A and PTEN TSGs in colon cancer and other cancer cells, mouse tissues and organoids. Depletion of RASSF1A with siRNA limited cyclin D1 and BAX expression. SiRNA depletion of PTEN, upstream regulator of RASSF1A resulted in a 50% reduction in RASSF1A expression. Histopathological analysis of the AGP treated tumor sections showed significant reduction in vessel size, microvascular density and tumor mitotic index suggesting suppression of angiogenesis. This was corroborated by protein analysis demonstrating significant reductions in angiogenesis signaling pathway molecules VEGF165, FOXM1, and pAkt, but significant elevation of the endogenous angiogenesis inhibitor Tsp-2. Treatment of cells with exogenous VEGF prevented the suppression of angiogenesis signaling by AGP, resulting in sustained expression of pAkt, an upstream down-regulator of RASSF1A. RASSF1A expression remained low in VEGF treated cells despite the addition of AGP. CONCLUSION: Our results demonstrate for the first time that AGP induces RASSF1A expression in colon cancer cells and is dependent on angiogenesis signaling events. Therefore, our research may facilitate novel therapeutic options for advanced colon cancer therapy.

The Use of Temporary Fecal Diversion in Colonic and Perianal Crohn's Disease Does Not Improve Outcomes.

AIMS: To determine whether temporary fecal diversion for refractory colonic and/or perianal Crohn's disease can lead to clinical remission and restoration of intestinal continuity after optimization of medical therapy. METHODS: We retrospectively reviewed our prospectively maintained database of patients treated at the University of Maryland for Crohn's disease between May 2004 and July 2014. Patients with colonic, perianal, or colonic and perianal Crohn's disease, who had fecal diversion for control of medically refractory and/or severe disease, were included. Outcomes, including disease activity and rate of ileostomy reversal, were evaluated up to 24 months from stoma formation. RESULTS: Thirty patients were identified. Fecal diversion was performed for perianal disease in 37%, colonic disease in 33%, and both in 30% of patients. Twelve (40%) patients underwent ileostomy reversal. Twenty-five percent of patients with perianal disease had their ostomies reversed compared to 70% of patients with colonic disease alone. More patients with complex compared to simple perianal disease remained diverted (p = 0.02). Six (20%) patients required colectomy. Of these, 50% had complex perianal disease, all had received two or more biologics, and two-thirds were on combination therapy pre-diversion. CONCLUSIONS: Our study found that nearly two-thirds of patients with medically refractory colonic and/or severe perianal Crohn's disease treated with fecal diversion and optimization of postoperative medical therapy remain diverted or require colectomy within two years after ileostomy formation. In patients with severe, refractory perianal disease and those treated with combination therapy and >1 biologic exposure pre-diversion, colectomy rather than temporary fecal diversion should be considered.

Using risk-adjusted cumulative sum to evaluate surgeon, divisional, and institutional outcomes-a feasibility study.

BACKGROUND: Few objective, real-time measurements of surgeon performance exist. The risk-adjusted cumulative sum is a novel method that can track surgeon-level outcomes on a continuous basis. The objective of this study was to demonstrate the feasibility of using risk-adjusted cumulative sum to monitor outcomes after colorectal operations and identify clinically relevant performance variations. METHODS: The National Surgical Quality Improvement Program was queried to obtain patient-level data for 1,603 colorectal operations at a high-volume center from 2011 to 2020. For each case, expected risks of morbidity, mortality, reoperation, readmission, and prolonged length of stay were estimated using the National Surgical Quality Improvement Program risk calculator. Risk-adjusted cumulative sum curves were generated to signal observed-to-expected odds ratios of 1.5 (poor performance) and 0.5 (exceptional performance). Control limits were set based on a false positive rate of 5% (α = 0.05). RESULTS: The cohort included data on 7 surgeons (those with more than 20 cases in the study period). Institutional observed versus expected outcomes were the following: morbidity 12.5% (vs 15.0%), mortality 2.5% (vs 2.0%), prolonged length of stay 19.7% (vs 19.1%), reoperation 11.1% (vs 11.3%), and 30-day readmission 6.1% (vs 4.8%). Risk-adjusted cumulative sum accurately demonstrated within- and between-surgeon performance variations across these metrics and proved effective when considering division-level data. CONCLUSION: Risk-adjusted cumulative sum adjusts for patient-level risk factors to provide real-time data on surgeon-specific outcomes. This approach enables prompt identification of performance outliers and can contribute to quality assurance, root-cause analysis, and incentivization not only at the surgeon level but at divisional and institutional levels as well.

Early host immune responses in a human organoid-derived gallbladder monolayer to Salmonella Typhi strains from patients with acute and chronic infections: a comparative analysis.

Salmonella enterica serovar Typhi (S. Typhi), a human-restricted pathogen, invades the host through the gut to cause typhoid fever. Recent calculations of the typhoid fever burden estimated that more than 10 million new typhoid fever cases occur in low and middle-income countries, resulting in 65,400-187,700 deaths yearly. Interestingly, if not antibiotic-treated, upon the resolution of acute disease, 1%-5% of patients become asymptomatic chronic carriers. Chronically infected hosts are not only critical reservoirs of infection that transmit the disease to naive individuals but are also predisposed to developing gallbladder carcinoma. Nevertheless, the molecular mechanisms involved in the early interactions between gallbladder epithelial cells and S. Typhi remain largely unknown. Based on our previous studies showing that closely related S. Typhi strains elicit distinct innate immune responses, we hypothesized that host molecular pathways activated by S. Typhi strains derived from acutely and chronically infected patients would differ. To test this hypothesis, we used a novel human organoid-derived polarized gallbladder monolayer model, and S. Typhi strains derived from acutely and chronically infected patients. We found that S. Typhi strains derived from acutely and chronically infected patients differentially regulate host mitogen-activated protein kinase (MAPK) and S6 transcription factors. These variations might be attributed to differential cytokine signaling, predominantly via TNF-α and IL-6 production and appear to be influenced by the duration the isolate was subjected to selective pressures in the gallbladder. These findings represent a significant leap in understanding the complexities behind chronic S. Typhi infections in the gallbladder and may uncover potential intervention targets.

Immunosuppressive therapy does not increase operative morbidity in patients with Crohn's disease.

GOALS: The aim of this study was to examine the impact of immunosuppressive therapy on the morbidity of intestinal surgery in patients with Crohn's disease. BACKGROUND: An increasing number of immunomodulating agents are being used in the treatment of Crohn's disease. The effect of these medications on surgical morbidity is controversial. STUDY: We performed a retrospective review of our prospectively maintained database of patients with Crohn's disease who underwent intestinal surgery between June 1999 and May 2010. The effect of perioperative immunomodulation on postoperative outcomes, specifically anastomotic complications, was evaluated. Predictors of postoperative morbidity among demographic and surgical variables were identified. Length of hospitalization and rate of hospital readmission were compared between groups. Comparisons were made using Student t test and Fisher exact test. RESULTS: One hundred ninety-six intestinal procedures were performed. One hundred twenty-seven (64.8%) of these were performed among patients who received perioperative immunomodulation. Forty-six (23.5%) procedures were in patients who received >1 immunomodulating medication perioperatively. Complications occurred in 45 (23.0%) cases. There were 20 (10.2%) anastomotic complications, including 8 (4.1%) intra-abdominal abscesses, 8 (4.1%) anastomotic leaks, and 4 (2%) enterocutaneous fistulas. Preoperative treatment with steroids (P=0.21), 6-MP (P=0.10), and anti-tumor necrosis factor biologics (P=1.0) was not associated with increased postoperative anastomotic complications. Combination immunosuppressive therapy also did not increase morbidity (P=0.39). CONCLUSIONS: In our series, single agent and combination immunosuppressive therapy given around the time of intestinal surgery did not increase the incidence of surgical complications in patients with Crohn's disease.

Lessons in liability: Examining medical malpractice suits against general surgeons in Maryland.

BACKGROUND: Although medical malpractice lawsuits pose a significant burden, there is a paucity of research on physician-specific characteristics influencing lawsuits against surgeons. Our objective was to identify factors associated with general surgeons being named in malpractice cases. METHODS: This was a cross sectional study of Maryland general surgeons, using malpractice data from a publicly accessible judiciary database. Case number per decade and lifetime lawsuit status were modeled with linear and logistic regression. RESULTS: Male surgeons had a higher average lawsuit volume (p = 0.002) and were more likely to be named in a malpractice case (p < 0.001). In regression analysis, a second graduate degree was a predictor of average cases per 10 years (p = 0.008) and male gender predicted lifetime lawsuit status (OR = 1.73, p = 0.046). CONCLUSIONS: Male gender was associated with increased odds of being named in a malpractice lawsuit. Identifying this difference is a preliminary step in developing interventions to reduce lawsuits amongst surgeons.

Assessing Content of Accredited Colon and Rectal Surgery Fellowship Websites: Is there Adequate Information for Applicants?

Electronic information is a vital resource used by fellowship applicants. This study aimed to assess the completeness of colon and rectal surgery (CRS) fellowship program online information. Program information on the Association of Program Directors for Colon and Rectal Surgery (APDCRS) website as well as each institutional website was evaluated based on templated criteria. Sixty-eight accredited fellowship programs were identified. Six (9%) programs had complete profiles on the APDCRS platform, with an average of 3.5 details completed per program. Sixty-two (91%) websites were easily accessible. None of these contained all 28 criteria assessed and 47 (69%) contained less than half of assessed content. The most common data point was fellowship program description (96%), while board pass rate (1%) was the least common. Most CRS fellowship websites were grossly incomplete. Electronically available information is vital to fellowship applicants, and programs should try to provide easily accessible information about their program.

Muscarinic receptor agonist-induced ßPix binding to ß-catenin promotes colon neoplasia.

M3 muscarinic receptors (M3R) modulate ß-catenin signaling and colon neoplasia. CDC42/RAC guanine nucleotide exchange factor, ßPix, binds to ß-catenin in colon cancer cells, augmenting ß-catenin transcriptional activity. Using in silico, in vitro, and in vivo approaches, we explored whether these actions are regulated by M3R. At the invasive fronts of murine and human colon cancers, we detected co-localized nuclear expression of ßPix and ß-catenin in stem cells overexpressing M3R. Using immunohistochemistry, immunoprecipitation, proximity ligand, and fluorescent cell sorting assays in human tissues and established and primary human colon cancer cell cultures, we detected time-dependent M3R agonist-induced cytoplasmic and nuclear association of ßPix with ß-catenin. ßPix knockdown attenuated M3R agonist-induced human colon cancer cell proliferation, migration, invasion, and expression of PTGS2, the gene encoding cyclooxygenase-2, a key player in colon neoplasia. Overexpressing ßPix dose-dependently augmented ß-catenin binding to the transcription factor TCF4. In a murine model of sporadic colon cancer, advanced neoplasia was attenuated in conditional knockout mice with intestinal epithelial cell deficiency of ßPix. Expression levels of ß-catenin target genes and proteins relevant to colon neoplasia, including c-Myc and Ptgs2, were reduced in colon tumors from ßPix-deficient conditional knockout mice. Targeting the M3R/ßPix/ß-catenin axis may have therapeutic potential.

Salmonella enterica serovar Typhi exposure elicits ex vivo cell-type-specific epigenetic changes in human gut cells.

Salmonella enterica serovar Typhi (S. Typhi) causes substantial morbidity and mortality worldwide, particularly among young children. Humans develop an array of mucosal immune responses following S. Typhi infection. Whereas the cellular mechanisms involved in S. Typhi infection have been intensively studied, very little is known about the early chromatin modifications occurring in the human gut microenvironment that influence downstream immune responses. To address this gap in knowledge, cells isolated from human terminal ileum exposed ex vivo to the wild-type S. Typhi strain were stained with a 33-metal-labeled antibody panel for mass cytometry analyses of the early chromatin modifications modulated by S. Typhi. We measured the cellular levels of 6 classes of histone modifications, and 1 histone variant in 11 major cell subsets (i.e., B, CD3 + T, CD4 + T, CD8 + T, NK, TCR-γδ, Mucosal associated invariant (MAIT), and NKT cells as well as monocytes, macrophages, and epithelial cells). We found that arginine methylation might regulate the early-differentiation of effector-memory CD4+ T-cells following exposure to S. Typhi. We also found S. Typhi-induced post-translational modifications in histone methylation and acetylation associated with epithelial cells, NKT, MAIT, TCR-γδ, Monocytes, and CD8 + T-cells that are related to both gene activation and silencing.

Postoperative small bowel obstruction secondary to single malformed staple following laparoscopic total abdominal colectomy.

Surgical staplers are ubiquitous in gastrointestinal surgery, especially laparoscopy. Intraperitoneal staples are designed to be inert and are generally regarded as benign; however, complications from primarily malformed staples can rarely occur. Here, we present a case of early mechanical postoperative small bowel obstruction due to a surgical staple following laparoscopic total abdominal colectomy and end ileostomy creation performed for medically refractory ulcerative colitis. Management consisted of diagnostic laparoscopy and careful extraction of a malformed surgical staple tethering a loop of small bowel to the rectal stump. Eight similar cases following gastrointestinal surgery have been identified in the literature, all occurring in the first 2 weeks following laparoscopic appendectomy. To our knowledge, this is the first case described following laparoscopic total abdominal colectomy, with high-grade small bowel obstruction at the level of the rectal stump staple line.

Trends in female surgeon authorship - The role of the middle author.

BACKGROUND: The objective of this study was to compare middle authorships between male and female general surgeons in the United States. METHODS: A stratified random sample of American College of Surgeons general surgery fellows was identified. Relevant author demographic, affiliation, and publication metrics were collected and compared across cohorts to determine which demographics were prognostic for each outcome variable. The primary endpoint was the number of middle author papers between genders. RESULTS: Males were more likely to enter into practice earlier (p<0.001), be fellowship-trained (p<0.001), obtain higher academic rank (p<0.001), and practice at more highly ranked academic institutions (p=0.019). Females had fewer middle author publications (p=0.044) and higher annual rates of first author publications (p=0.020) despite similar rates of total publications. CONCLUSIONS: Female surgeons hold the middle author position less frequently than males despite similar total publication numbers. Reasons for this finding should be the target of future study.

Injury Characteristics and Outcomes of Patients With Inflammatory Bowel Disease After Trauma: A Propensity Score Matched Analysis.

BACKGROUND: The clinical course of patients with inflammatory bowel disease (IBD) after trauma is largely unknown. We sought to compare the clinical course of patients with IBD to those without. METHODS: We conducted a retrospective case-control study of adult patients admitted to a level-1 trauma center from January 1, 2008, through October 1, 2015. Seventy-five patients with IBD were identified. Cases were matched to controls by age, sex, injury severity, and mechanism using 4:1 propensity score-matching analysis. Injury characteristics, clinical course, and infectious and noninfectious complications were compared using bivariate and multivariate analysis. RESULTS: Participants had a mean age of 56 years and mean injury severity score of 15. Of the 75 cases, 44% had ulcerative colitis, 44% had Crohn's disease, and 12% had undetermined type. More cases were on an immunosuppressant (19% vs 2%, P < 0.01) or steroids (8% vs 2%, P = 0.02) on admission compared with controls. More cases had prior abdominal surgery (P = 0.01). Cases had fewer brain injuries (P = 0.02) and higher admission Glasgow Coma Scale (P < 0.01) but required more neurosurgical intervention (P = 0.03). Cases required more orthopedic surgeries (P < 0.01) and more pain management consultations (P = 0.04). In multivariable analysis, IBD was associated with increased odds of operative intervention, pain management consultation, venous thromboembolism, and longer hospital stay (P < 0.05). Patients on immunosuppressants had increased odds of requiring surgery (P = 0.04), particularly orthopedic surgery (P < 0.01). CONCLUSIONS: Baseline factors associated with inflammatory bowel disease may place patients at higher risk for surgery and complications after trauma.