Oral administration of CXCL12-expressing Limosilactobacillus reuteri improves colitis by local immunomodulatory actions in preclinical models.

Treatments of colitis, inflammation of the intestine, is today relying on induction of immune suppression associated with systemic adverse events including recurrent infections. This treatment strategy is specifically problematic in the increasing population of cancer patients with immune checkpoint inhibitor (ICI)-induced colitis, as immune suppression also interferes with the ICI-treatment response. Thus, there is a need for local-acting treatments which reduce inflammation and enhance intestinal healing. Here, we investigated the effect and safety of bacterial delivery of short-lived immunomodulating chemokines to the inflamed intestine in mice with colitis. Colitis was induced by DSS alone or in combination with ICI (anti-PD1, anti-CTLA-4) and L. reuteri R2LC genetically modified to express the chemokine CXCL12-1α (R2LC_CXCL12, emilimogene sigulactibac) was given perorally. In addition, pharmacology and safety of the formulated drug candidate, ILP100-Oral, was evaluated in rabbits. Peroral CXCL12-producing L. reuteri R2LC significantly improved colitis symptoms already after 2 days in mice with overt DSS and ICI-induced colitis, which in benchmarking experiments was demonstrated to be superior to treatments with anti-TNF-α, anti-α4ꞵ7 and corticosteroids. The mechanism of action involved chemokine delivery to Peyer´s Patches (PPs), confirmed by local CXCR4 signaling, and increased numbers of colonic, regulatory immune cells expressing IL-10 and TGF-ß1. No systemic exposure or engraftment could be detected in mice, and product feasibility, pharmacology and safety were confirmed in rabbits. In conclusion, peroral CXCL12-producing L. reuteri R2LC efficiently ameliorates colitis and enhances mucosal healing, and has a favorable safety profile.

Three-dimensional collagen type I matrix up-regulates nuclear isoforms of the microtubule associated protein tau implicated in resistance to paclitaxel therapy in ovarian carcinoma.

Epithelial ovarian carcinoma is the deadliest gynecologic malignancy. One reason underlying treatment failure is resistance to paclitaxel. Expression of the microtubule associated protein tau has recently been proposed as a predictor of response to paclitaxel in ovarian carcinoma patients. Expression of tau was probed using immunohistochemistry in 312 specimens of primary, and 40 specimens of metastatic, ovarian carcinoma. Serous epithelial ovarian carcinoma cell line models were used to determine the expression of tau by Western blot and immunofluorescence staining. Subcellular fractionation and Western blot were employed to examine nuclear and cytoplasmic localization of tau. Gene silencing and clonogenic assays were used to evaluate paclitaxel response. Tau was expressed in 44% of all tested cases. Among the primary serous epithelial ovarian carcinoma cases, 46% were tau-positive. Among the metastatic serous epithelial ovarian carcinomas, 63% were tau-positive. Cell culture experiments demonstrated that tau was expressed in multiple isoforms. Three-dimensional collagen I matrix culture conditions resulted in up-regulation of tau protein. Silencing of tau with specific siRNAs in a combination with three-dimensional culture conditions led to a significant decrease of the clonogenic ability of cells treated with paclitaxel. The data suggest that reduction of tau expression may sensitize ovarian carcinoma to the paclitaxel treatment.

Use of mesh during ventral hernia repair in clean-contaminated and contaminated cases: outcomes of 33,832 cases.

OBJECTIVE: To analyze and compare postoperative occurrences following ventral hernia repairs (VHRs) using mesh in clean-contaminated and contaminated wounds. BACKGROUND: Ventral hernia repairs using mesh is one of the most common surgical procedures performed. However, guidelines and outcomes of repairs in clean-contaminated or grossly contaminated ventral hernias have not been established. METHODS: Patients who underwent VHR with mesh between the dates January 1, 2005 and April 4, 2010 at all hospitals in the United States participating in the National Surgical Quality Improvement Program (NSQIP) were reviewed. Data from 33,832 patients were analyzed by field contamination level and then compared with data from patients who underwent VHR without mesh. Data were analyzed using the odds ratio test with a 95% confidence interval. RESULTS: The odds of having one or more postoperative occurrences were significantly greater in clean-contaminated and contaminated cases using mesh when compared with clean cases, with odds ratios of 3.56 (3.25-3.89) and 5.05 (1.78-12.41), respectively. There was a significantly increased risk of superficial surgical site infections (SSI) (2.53), deep SSI (3.09) and organ/space SSI (6.16), wound disruption (4.41), pneumonia (4.43), and sepsis (4.90) for clean-contaminated cases. Both clean-contaminated and contaminated cases had an increased risk of septic shock (5.82 and 26.74, respectively), and need for ventilator for more than 48 hours (5.59 and 26.76, respectively). In addition, there was a significantly increased odds ratio of complications in patients who underwent VHR with mesh (3.56) to nonmesh (2.52) in clean-contaminated cases. CONCLUSION: There is a significant increase in risk of postoperative occurrences following VHRs using mesh in clean-contaminated and contaminated cases relative to clean cases. We recommend avoiding the use of mesh in any level of contamination.

Rates of spontaneous and therapeutic abortions following use of antidepressants in pregnancy: results from a large prospective database.

OBJECTIVE: The use of antidepressants during pregnancy remains a controversial issue, and there is little information on the risk of spontaneous abortions following antidepressant exposure in early pregnancy. We sought to examine whether use of antidepressants increases the rates of spontaneous abortion (SA) and therapeutic abortion (TA) in women exposed in early pregnancy. METHODS: In a cohort of women who contacted the Motherisk program during pregnancy, we compared two groups of women, one exposed and the other not exposed to antidepressants during pregnancy, and calculated the associated rates of SA and TA. RESULTS: Among 937 women exposed to antidepressants prior to and during early pregnancy, there were 122 SAs (13.0%) including three ectopic pregnancies, and in the comparison group there were 75 SAs (8.0%) and no ectopic pregnancies. The relative risk was 1.63 (95% CI 1.24-2.14). Three-fold more women reported a TA in the exposed group, 26 (2.4%) compared to 8 (0.7%) in the non-exposed group (RR 3.25; 95% CI 1.48-7.14). A sub-analysis revealed that in both groups, of 338 women with a prior SA, 58 (17.2%) reported having a SA in the current pregnancy, compared with 61/652 (9.4%) with no prior SA (chi square = 12.09, P lt; 0.001). In the antidepressant group, the incidence was 20.7%, and in the non-exposed group, it was 13.3%. Logistic regression confirmed that only antidepressant exposure and prior SA were significantly associated with current SA. CONCLUSION: Exposure to antidepressants in the first trimester of pregnancy appears to be associated with a small but statistically significant increased risk of SA and decision to terminate a pregnancy. The risk for SA is further elevated with a history of previous SA. However, any underlying depression must be taken into consideration when evaluating these results.

Prevalence and the factors associated with binge drinking, alcohol abuse, and alcohol dependence: a population-based study of Chinese adults in Hong Kong.

AIMS: To examine the patterns of drinking, the relationship between binge drinking, alcohol abuse, and dependence, and the sociodemographic factors associated with problem drinking among Hong Kong Chinese. METHOD: An anonymous, random telephone survey was conducted on 9860 Hong Kong Chinese adults from April to June, 2006. RESULTS: The age-adjusted prevalence amongst men for binge drinking was 14.4% with 5.3% of males being alcohol abusers and 2.3% dependent on alcohol. The corresponding figures for women were all lower at 3.6%, 1.4%, and 0.7%, respectively. Younger age groups showed the highest prevalence of these drinking problems. Among male binge drinkers, 18.7% were also alcohol abusers and 12.3% were alcohol dependent. Among female binge drinkers, 16% reported alcohol abuse and 9.9% reported dependence. Male binge drinkers were less likely to be older, less likely to be students but more likely to be employed in the service industry. Female binge drinkers were less likely to be over 60 years of age or married but more likely to be smokers. In both genders, smoking was significantly associated with the likelihood of binge drinking (OR = 3.6-12.3), alcohol abuse (OR = 3.0-12.1), and dependence (OR = 5.2-20.6). CONCLUSIONS: Although binge drinking has been well tolerated in Chinese culture, it is strongly associated with alcohol abuse and dependence in both genders in Hong Kong. Our findings suggest that prevalence of problematic alcohol consumption warrants greater promotion of alcohol harms awareness. Higher rates of heavy drinking in younger-aged individuals may reflect changing lifestyle behaviors and herald higher future levels of alcohol-related health and social problems.

Incidental placental site nodule in a fallopian tube.

A placental site nodule is a benign proliferation of intermediate trophoblasts from a previous gestation that failed to completely involute. It is a rare entity that is often asymptomatic and is usually found incidentally weeks or even years after the pregnancy. The most common location for placental site nodules is in the uterus within the endometrium and occasionally in the cervix, diagnosed by uterine curettings or hysterectomy. However, rare extrauterine cases have been documented and should be considered as a differential diagnosis when encountered in locations such as the fallopian tube. Here, we present a case of a 28-year-old woman with a history of spontaneous abortions who was found to have a placental site nodule of the fallopian tube after postpartum tubal ligation.

Dedifferentiated gastrointestinal stromal tumor arising de novo from the small intestine.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and usually display monotonous cytologic features and immunoactivity for CD117. Anaplastic GIST, with pleomorphic cells and loss of CD117, until recently have only been reported in patients with chronic imatinib mesylate treatment. Dedifferentiated GISTs arising de novo is a newly identified entity that may prove to be difficult to diagnose. We present the case of a 52-year-old female found to have a dedifferentiated GIST without prior imatinib mesylate therapy. This case is the first reported dedifferentiated GIST arising de novo from the small bowel, and at 30cm in greatest diameter, the largest reported to date. Additionally, we demonstrate for the first time the loss of DOG1 in the anaplastic component of the tumor. De novo dedifferentiated GIST is a rare and diagnostically challenging tumor that may be mischaracterized unless considered in the differential diagnosis.

Suture versus tack fixation of mesh in laparoscopic umbilical hernia repair.

BACKGROUND AND OBJECTIVES: Mesh fixation in laparoscopic umbilical hernia repair is poorly studied. We compared postoperative outcomes of laparoscopic umbilical hernia repair in suture versus tack mesh fixation. METHODS: Patients who underwent laparoscopic umbilical hernia repair were separated by method of mesh fixation: sutures versus primarily tacks. Medical history and follow-up data were collected through medical records. The primary outcome of this study was the recurrence rates of hernias. Postoperative major and minor complications, such as surgical site infection, small-bowel obstruction, and seroma formation, were regarded as secondary outcomes. Additionally, a telephone interview was conducted to assess postoperative pain, recovery time, and overall patient satisfaction. RESULTS: Eighty-six patients were identified: 33 in the suture group and 53 in the tacks group. The number of emergent cases was increased in the tacks group (6 vs 0; P = .022). Mean follow-up time was 2.7 years for both groups. Documented postoperative follow-up was obtained in 29 (90%) suture group and 31 (58%) tacks group patients. Hernia recurrence occurred in 3 and 2 patients in the sutures and tacks groups, respectively (P was not significant). No differences were found in secondary outcomes, including subjective outcomes from telephone interviews, between groups. CONCLUSIONS: There are no differences in postoperative complication rates in suture versus tack mesh fixation in laparoscopic umbilical hernia repair.

Laparoscopic versus open inguinal hernia repair in octogenarians: a follow-up study.

AIM: The elderly population is the fastest growing demographic in developed countries. It is thus imperative to assess common medical procedures in this age group. Inguinal hernia repair is a commonly carried out operation in the USA with two methods of repair existing - laparoscopic and open. Although the advantages of laparoscopic inguinal hernia repair in the general population have been shown, its role in the elderly has yet to be elucidated. METHODS: A retrospective medical record review with prospective follow up of 115 patients aged over 80 years who underwent either open or laparoscopic inguinal hernia repair was carried out. Outcome measures included postoperative pain score, recovery time, chronic pain, wound infection, urinary retention, urinary tract infection, hematoma and recurrence. Patient satisfaction was measured with the Likert score. RESULTS: Of the 115 repairs, 31 repairs were carried out laparoscopically and 84 open. Mean patient age was 83.3 years (range 80-95 years), with no difference in demographics or comorbidities between the two groups. Mean recovery time was significantly shorter in the laparoscopic group (7.5 vs 23.1 days, P = 0.02), as was the mean duration of pain in the laparoscopic group (1.4 vs 9.6 days, P = 0.04). There were no significant differences in other outcomes. There was a trend towards increased patient satisfaction in the laparoscopic group (P = 0.10). CONCLUSION: In octogenarians, laparoscopic inguinal hernia repair confers a significantly shorter duration of pain and recovery time as compared with open inguinal hernia repair, with no increase in complications. For elderly patients, laparoscopy is a viable alternative to open repair.

Risk factors of portal vein thrombosis in Crohn's disease patients.

INTRODUCTION: Patients with inflammatory bowel disease, such as Crohn's disease (CD), suffer from a threefold increase in the risk of venous thromboembolism. Small bowel, segmental bowel, or ileocolonic resection to treat Crohn's disease can lead to rare complications of portal vein thrombosis (PVT), which can lead to further poor health outcomes, such as small bowel ischemia. The study attempts to find different risk factors that may be associated with postoperative complications of PVT in Crohn's disease patients. METHODS: In a 1 to 3 case-control study following Institutional Review Board approval, 13 Crohn's disease patients with documented radiological postoperative diagnosis of PVT from 2004 to 2011 and 39 CD patients who did not have postoperative PVT were matched by retrospective chart review for patient demographics, preoperative course and workup, anticoagulant use, and operative procedure. Univariate analysis was performed to draw correlations on risk factors for the development of PVT. RESULTS: In the 13 CD patients with PVT, concurrent cancer, liver disease, and dyslipidemia were present in 23.1%, 23.1%, and 15.4% of the population, respectively. Compared to the 39 CD only patients, concurrent cancer, liver disease, and dyslipidemia were present in only 2.6%, 2.6%, and 0% of the population, respectively. Of the CD patients with PVT, 61.5% were on preoperative steroids compared to 28.9% of the CD only patients. PVT development in CD patients is correlated with concurrent cancer (p = 0.016), liver disease (p = 0.016), dyslipidemia (p = 0.012), and preoperative steroid usage (p = 0.036). CONCLUSIONS: Concurrent cancer, liver disease, dyslipidemia, and preoperative steroid usage were risk factors associated with the development of PVT in Crohn's patients. Since there is limited literature on PVT in CD, more data needs to be collected, and additional studies should be done to further assess the prevention, diagnosis, and management of the disease.

Appendectomy during pregnancy: follow-up of progeny.

BACKGROUND: The incidence of appendicitis in pregnant patients is 0.04% to 0.20%, making it the most common nonobstetric surgical procedure in pregnancy. This study examines whether an appendectomy during any stage of pregnancy affects future development of motor, sensory, and social skills of the progeny. STUDY DESIGN: A prospective survey was administered to women who underwent an appendectomy during pregnancy at Mount Sinai Hospital from 2000 to 2009. The survey, which ranged from 1 to 9 years postpartum, consisted of questions about motor, sensory, and social development of their progeny, based on established pediatric milestones. Data were collected from the medical records of mother and child. Additional follow-up was gathered from outpatient and emergency room records. RESULTS: Fifty-two pregnant patients underwent an appendectomy during our study period. All pregnancies continued to full term with the exception of one fetal death due to extreme prematurity. Twenty-nine patients completed the follow-up survey, making the yield response rate 55.8%. There were 7 (26.9%), 14 (48.3%), and 8 (27.6%) appendectomies in the first, second, and third trimesters, respectively. Mean follow-up time was 47.2 months (range 13 to 117 months) after delivery. None of the children exhibited any developmental delay by their third year of life. Timing of the surgery (trimester) had no effect on child development. CONCLUSIONS: Appendectomy during pregnancy is not associated with developmental delays in children, regardless of which trimester the procedure was performed. All children in this study had normal motor, sensory, and social development by 3 years of age.

Postoperative antibiotics correlate with worse outcomes after appendectomy for nonperforated appendicitis.

BACKGROUND: Acute appendicitis remains the most common cause of acute abdominal pain necessitating operative intervention. Although postoperative antibiotics are universally used for perforated appendicitis, no consensus exists on whether postoperative antibiotics are beneficial for preventing surgical site infections (SSIs) in nonperforated cases. We set out to determine how postoperative antibiotic therapy affects outcomes after appendectomy for nonperforated appendicitis. STUDY DESIGN: The medical records of 1,000 patients undergoing appendectomy for nonperforated appendicitis at The Mount Sinai Medical Center from January 2005 through July 2010 were retrospectively reviewed. RESULTS: In total, 728 cases contained sufficient follow-up data for analysis; 334 of these patients received postoperative antibiotics and 394 did not. There were no significant differences in patient demographics, medical comorbidities, American Society of Anesthesiologists (ASA) class, admission temperature, preoperative antibiotic treatment, operating room time, estimated blood loss, appendiceal diameter, or intraoperative transfusion between the two groups, although WBC was higher for patients receiving postoperative antibiotics (12.3 vs 14 cells/mm(3), p = 0.001). Postoperative antibiotics did not alter the incidence of superficial SSIs, deep SSIs, or organ space SSIs (all p = 0.1), but did correlate with higher rates of Clostridium difficile infection (p = 0.02), urinary tract infection (p = 0.05), postoperative diarrhea (p < 0.001), and longer length of stay (LOS) (1.1 vs 2.4 days, p < 0.001). Patients receiving postoperative antibiotics also showed trends toward higher readmission and reoperation rates (both p = 0.06). CONCLUSIONS: Postoperative antibiotic treatment for nonperforated appendicitis did not reduce infectious complications and prolonged LOS while increasing postoperative morbidity. Therefore, postoperative antibiotics likely increase the treatment cost for nonperforated appendicitis while not adding an appreciable clinical benefit and, in some cases, actually worsening outcomes.