Interplay Between the Intestinal Microbiota and Acute Graft-Versus-Host Disease: Experimental Evidence and Clinical Significance.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for many hematological disorders and autoimmune diseases, but acute graft-versus-host disease (aGVHD) has remained a major obstacle that limits allo-HSCT and exhibits a daunting mortality rate. The gastrointestinal system is among the most common sites affected by aGVHD. Experimental advances in the field of intestinal microbiota research enhanced our understanding - not only of the quantity and diversity of intestinal microbiota - but also their association with homeostasis of the immune system and disease pathogenesis, including that of aGVHD. Meanwhile, ever-growing clinical evidence suggest that the intestinal microbiota is dysregulated in patients who develop aGVHD and that the imbalance may affect clinical outcomes, indicating a potential predictive role for microbiota dysregulation in aGVHD severity and prognosis. The current animal and human studies investigating the intestinal microbiota in aGVHD and the understanding of the influence and management of the microbiota in the clinic are reviewed herein. Taken together, monitoring and remodeling the intestinal microecology following allo-HSCT may provide us with promising avenues for diagnosing, preventing or treating aGVHD in the clinic.

Management of Home Parenteral Nutrition: Complications and Survival.

BACKGROUND AND AIMS: Parenteral nutrition (PN) has become an efficient, safe, and convenient treatment over years for patients suffering from intestinal failure. Home PN (HPN) enables the patients to have a high quality of life in their own environment. The therapy management however implies many restrictions and potentially severe lethal complications. Prevention and therapy of the latter are therefore of utmost importance. This study aims to assess and characterize the situation of patients with HPN focusing on prevalence of catheter-related complications and mortality. METHODS: Swiss multicentre prospective observational study collecting demographic, anthropometric, and catheter-related data by means of questionnaires every sixth month from 2017 to 2019 (24 months), focusing on survival and complications. Data were analysed using descriptive statistics. Logistic regression models were fitted to investigate association between infection and potential co-factors. RESULTS: Seventy adult patients (50% women) on HPN were included (≈5 patients/million adult inhabitants/year). The most common underlying diseases were cancer (23%), bariatric surgery (11%), and Crohn's disease (10%). The most prevalent indication was short bowel syndrome (30%). During the study period, 47% of the patients were weaned off PN; mortality rate reached 7% for a median treatment duration of 1.31 years. The rate of catheter-related infection was 0.66/1,000 catheter-days (0.28/catheter-year) while the rate of central venous thrombosis was 0.13/1,000 catheter-days (0.05/catheter-year). CONCLUSION: This prospective study gives a comprehensive overview of the adult Swiss HPN patient population. The collected data are prerequisite for evaluation, comparison, and improvement of recommendations to ensure best treatment quality and safety.

Percutaneous Enteral Stent Placement Using a Transhepatic Access for Palliation of Malignant Bowel Obstruction after Surgery.

OBJECTIVE: To assess the safety and clinical efficacy of percutaneous transhepatic enteral stent placement for recurrent malignant obstruction in patients with surgically altered bowel anatomy. MATERIALS AND METHODS: Between July 2009 and May 2019, 36 patients (27 men and 9 women; mean age, 62.7 ± 12.0 years) underwent percutaneous transhepatic stent placement for recurrent malignant bowel obstruction after surgery. In all patients, conventional endoscopic peroral stent placement failed due to altered bowel anatomy. The stent was placed with a transhepatic approach for an afferent loop obstruction (n = 27) with a combined transhepatic and peroral approach for simultaneous stent placement in afferent and efferent loop obstruction (n = 9). Technical and clinical success, complications, stent patency, and patient survival were retrospectively evaluated. RESULTS: The stent placement was technically successful in all patients. Clinical success was achieved in 30 patients (83.3%). Three patients required re-intervention (balloon dilatation [n = 1] and additional stent placement [n = 2] for insufficient stent expansion). Major complications included transhepatic access-related perihepatic biloma (n = 2), hepatic artery bleeding (n = 2), bowel perforation (n = 1), and sepsis (n = 1). The 3- and 12-months stent patency and patient survival rates were 91.2%, 66.5% and 78.9%, 47.9%, respectively. CONCLUSION: Percutaneous enteral stent placement using transhepatic access for recurrent malignant obstruction in patients with surgically altered bowel anatomy is safe and clinically efficacious. Transhepatic access is a good alternative route for afferent loop obstruction and can be combined with a peroral approach for simultaneous afferent and efferent loop obstruction.

The effect of comorbidity on mortality in elderly patients undergoing emergency abdominal surgery: a systematic review and metaanalysis

Background/aim: With the increase in the elderly population, the elderly proportion needing emergency surgery is also increasing. Despite medical advances in surgery and anesthesia, negative postoperative outcomes and high mortality rates are still present in elderly patients undergoing emergency surgery. Comorbidities are described as the main determining factors in poor outcomes. In this metaanalysis, it was aimed to investigate the effect of comorbidity on mortality in elderly patients undergoing emergency abdominal surgery. Materials and methods: The studies published between 2010-2019 were scanned from databases of Google Scholar, Cinahl, Pub Med, Medline and Web of Science. Quality criteria proposed by Polit and Beck were used in the evaluation of the included studies. Interrater agreement was calculated by using the Kappa statistic, effect size by using the odds ratio, and heterogeneity among studies by using the Cochran's Q statistics. Kendall's Tau-b coefficient and funnel plot were used to determine publication bias. Results: A total of 9 studies were included in the research. There was a total of 1330 cases in the studies. The total mortality rate was 21% (n = 279), the total rate of having a comorbid factor was 83.6% (n = 1112), and the rate of having a comorbid factor in mortality was 89.2% (n = 249). According to the fixed effects model, the total effect size of comorbid factors on causing mortality was not statistically significant with a value of 1.296 (C.I; 0.84-1.97; P > 0.05). Conclusion: Our study revealed that comorbidity had no significant effect on causing mortality in geriatric patients undergoing emergency abdominal surgery. There are controversial results in the literature, and in order to reach more precise results, studies involving wider groups of patients and further studies examining the specific effect of certain comorbid conditions are needed.

Tissue immune profiles supporting response to mesenchymal stromal cell therapy in acute graft-versus-host disease-a gut feeling.

Acute graft-versus-host disease (aGvHD), post-allogeneic hematopoietic stem cell transplantation, is associated with high mortality rates in patients not responding to standard line care with steroids. Adoptive mesenchymal stromal cell (MSC) therapy has been established in some countries as a second-line treatment.Limitations in our understanding as to MSC mode of action and what segregates patient responders from non-responders to MSC therapy remain. The principal aim of this study was to evaluate the immune cell profile in gut biopsies of patients diagnosed with aGvHD and establish differences in baseline cellular composition between responders and non-responders to subsequent MSC therapy.Our findings indicate that a pro-inflammatory immune profile within the gut at the point of MSC treatment may impede their therapeutic potential. These findings support the need for further validation in a larger cohort of patients and the development of improved biomarkers in predicting responsiveness to MSC therapy.

[Independent risk factors for severity and mortality in lower gastrointestinal bleeding]. / Hemorragia digestiva baja, factores predictores de severidad y mortalidad en un hospital p úblico de Lima.

In lower gastrointestinal bleeding (LGIB), it is very important to stratify the risk of LGIB for a proper management. OBJECTIVE: Identity the independent risk factors to mortality and severity (require critical care, prolonged hospitalization, reebleding, re hospitalization, politrasfusion, surgery for bleeding control) in LGIB. MATERIALS AND METHODS: It is an analytic prospective cohort study, performed between June 2016 and April 2018 in a tertiary care hospital. Independent factors were determined using binomial logistic regression. RESULTS: A total of 98 patients were included, of which 13 patients (13,3%) died, and 56 (57,1%) met severity criteria. The independent risk factor for mortality was Glasgow scale under 15, and for severe bleeding were: Systolic blood pressure under 100 mm Hg, albumin lower than 2,8 g/dL. CONCLUSIONS: The frequency of mortality and severe LGIB is high in our population, the principal risk factors were systolic blood pressure under than 100 mm Hg, Glasgow score lower than 15, albumin lower than 2,8 g/dL. Identifying these associated factors would improve the management of LGB in the emergency room.

Intestinal thrombotic microangiopathy: a distinct entity in the spectrum of graft-versus-host disease.

Transplant-associated thrombotic microangiopathy (TA-TMA) is a severe complication of allogeneic hematopoietic cell transplantation (allo-HCT) with multisystem involvement. Cases of TMA in the intestinal vasculature (intestinal TMA/iTMA) have been reported. We hypothesized that iTMA is a distinct entity from TA-TMA. To test this hypothesis, we prospectively recruited allo-HCT recipients with an indication for endoscopy. Among 20 patients, histological features of iTMA, including loss of glands, total denudation of mucosa, apoptosis and detachment of endothelial cells, mucosal hemorrhage, intraluminal fibrin and microthrombi were found in six. Only 2/6 were classified as GVHD/TA-TMA, while the other 4 as GVHD/no TA-TMA. Gastro-intestinal symptoms were similar between the patients with or without iTMA. With a median follow-up of 11.1 (2.1-67.5) months, 1-year overall survival was 22.2% for iTMA, 55% for GVHD and 60% for TA-TMA. On multivariate analysis, independent unfavorable predictors of OS were iTMA (p = 0.048), HLA mismatched donors (p = 0.008) and gastro-intestinal bleeding (p = 0.021). In conclusion, iTMA emerges as a novel distinct entity in patients with GVHD and/or TA-TMA. Distinct histological features may be useful in differential diagnosis of these severe HCT complications. The higher mortality rates of iTMA than TA-TMA highlight the need for further investigation of this condition.

Management of Five Hundred Patients With Gut Failure at a Single Center: Surgical Innovation Versus Transplantation With a Novel Predictive Model.

OBJECTIVE(S): To define the evolving role of integrative surgical management including transplantation for patients gut failure (GF). METHODS: A total of 500 patients with total parenteral nutrition-dependent catastrophic and chronic GF were referred for surgical intervention particularly transplantation and comprised the study population. With a mean age of 45 ±â€Š17 years, 477 (95%) were adults and 23 (5%) were children. Management strategy was guided by clinical status, splanchnic organ functions, anatomy of residual gut, and cause of GF. Surgery was performed in 462 (92%) patients and 38 (8%) continued medical treatment. Definitive autologous gut reconstruction (AGR) was achievable in 378 (82%), primary transplant in 42 (9%), and AGR followed by transplant in 42 (9%). The 84 transplant recipients received 94 allografts; 67 (71%) liver-free and 27 (29%) liver-contained. The 420 AGR patients received a total of 790 reconstructive and remodeling procedures including primary reconstruction, interposition alimentary-conduits, intestinal/colonic lengthening, and reductive/decompressive surgery. Glucagon-like peptide-2 was used in 17 patients. RESULTS: Overall patient survival was 86% at 1-year and 68% at 5-years with restored nutritional autonomy (RNA) in 63% and 78%, respectively. Surgery achieved a 5-year survival of 70% with 82% RNA. AGR achieved better long-term survival and transplantation better (P = 0.03) re-established nutritional autonomy. Both AGR and transplant were cost effective and quality of life better improved after AGR. A model to predict RNA after AGR was developed computing anatomy of reconstructed gut, total parenteral nutrition requirements, cause of GF, and serum bilirubin. CONCLUSIONS: Surgical integration is an effective management strategy for GF. Further progress is foreseen with the herein-described novel techniques and established RNA predictive model.

Current outcomes after pediatric and adult intestinal transplantation.

PURPOSE OF REVIEW: In this article, we will review the outcomes of patients with intestinal transplant (ITx) with a focus on factors affecting long-term graft and patient survival. RECENT FINDINGS: The most recent International Intestinal Transplant Registry reports a 1-, 5-, and 10-year graft survival of 71%, 50%, and 41% respectively, for ITx grafts transplanted since 2000. Over the past decades, significant improvements have been achieved in short-term graft and patient outcomes for ITx recipients. The improvement in short-term outcomes may be related to the focused treatment of antihuman leukocyte antigen antibodies, the use of induction immunotherapy protocols, refinements in surgical techniques, establishment of dedicated ITx units, and improved postoperative management.However, long-term graft and patient outcomes for ITx recipients remain stagnant. Issues impairing long-term outcomes of ITx include the challenges in the diagnosis and treatment of chronic rejection and antibody-mediated rejection, progressive decline in renal function, and long-term infectious and malignancy risks especially related to cytomegalovirus, Epstein-Barr virus and posttransplant lymphoproliferative disorder after ITx. SUMMARY: Addressing and preventing early and late complications is the key to improving short-term and long-term outcomes after ITx.

Intestinal failure after bariatric surgery: Treatment and outcome at a single-intestinal rehabilitation and transplant center.

BACKGROUND: Though intestinal failure (IF) after bariatric surgery (BS) is uncommon, its prevalence is increasing. However, data on the outcomes for these patients are limited. OBJECTIVES: To analyze the outcomes of treatment for patients with IF after BS. SETTING: University hospital. METHODS: A single-center analysis (1991-2016) of outcomes according to treatment arms established by a multidisciplinary team. RESULTS: Twenty-five IF patients were identified (median age 45 yr). BS was 92% Roux-en-Y gastric bypass. The major cause of IF was volvulus/internal hernia (72%). Median time from BS to IF was 48 months. Treatment arms were intestinal rehabilitation (IR, n = 15), transplantation (TXP, n = 5), and parenteral nutrition (PN, n = 5). For IR, median bowel length was 60 cm. Forty-six percent ultimately discontinued PN. Twenty-seven percent were partially weaned PN and 27% failed IR. Common surgical rehabilitation was Roux-en-Y gastric bypass reversal and restoration of gastrointestinal continuity. The 5-year overall survival was 74%. For TXP, 7 patients were listed for TXP (5 initially and 2 after failed IR). Three underwent TXP, 2 isolated intestine and 1 isolated liver. Three were delisted (1 improvement and 2 death). For PN, 6 patients required long-term PN (5 initially and 1 after failed IR). Four patients are alive currently. CONCLUSIONS: IF after BS is an increasing problem facing IR centers. Internal hernia is the major cause. Surgical IR is the first-line therapy and affords the best outcome. TXP is reserved for rescuing patients who failed IR or develop PN complications. Long-term PN is suitable for patients in whom IR or TXP is impractical.

Simultaneous Intestinal and Kidney Transplantation in Adults.

Aim of the study: Intestinal transplantation (IT) is a life-saving procedure for carefully selected patients with intestinal failure. We evaluated patients who had undergone simultaneous intestinal and kidney transplantation (SIKT) to determine whether UK guidelines for inclusion of a renal allograft (dialysis dependent or estimated glomerular filtration rate ((eGFR)) < 45 ml/min/1.73 m2) are justified. Methods: A single centre analysis was undertaken of adults undergoing IT at the Cambridge Transplant Centre between December 2007 and January 2016. A prospectively maintained database was used to identify SIKT recipients and determine outcomes. Results: Over this period, 63 intestinal transplants were performed. Seven (11.1%) recipients received a SIKT. Five were pre-dialysis (median eGFR 29 ml/min/1.73 m2, range 16-36 ml/min/1.73 m2). One recipient was on dialysis, and one needed bilateral nephrectomy at transplant. There were no primary kidney allograft failures and at three months, the median eGFR (55 ml/min/1.73 m2 range 39-124) was similar to recipients of IT alone (median eGFR 56 ml/min/1.73 m2 range 17-143 ml/min/1.73 m2). Two recipients required dialysis due to sepsis related kidney injury and died from multi-organ failure (20 and 63 months). Two died with a functioning renal transplant (10 and 15 months). The remaining three patients are alive at follow up (12-96 months) with an eGFR of 20-45 ml/min/1.73 m2. Conclusion: Patients with significant renal impairment (eGFR <45 ml/min/1.73 m2), and receiving dialysis may benefit from SIKT. Patient survival and renal function are broadly comparable to those undergoing IT alone. Further studies are required to justify allocation of a kidney to this complex high risk group.

Anti-α4ß7 integrin monoclonal antibody (vedolizumab) for the treatment of steroid-resistant severe intestinal acute graft-versus-host disease.

Steroid-resistant (SR) acute graft-versus-host disease (aGvHD) is a life-threatening complication of allogeneic stem cell transplantation. Vedolizumab is a monoclonal antibody that impairs homing of T cells to the gastrointestinal (GI) endothelium by blocking the α4ß7 integrin. We retrospectively analyzed outcomes following vedolizumab administration for treatment of SR GI GvHD. Overall, 29 patients from three transplantation centers were included. Histopathology was available in 24 (83%) patients. The overall response rate (ORR) was 23/29 (79%); 8 (28%) patients had a complete response and 15 (52%) a partial response. Vedolizumab was administered as a 2nd-line or ≥3rd-line treatment in 13 (45%) and 16 (55%) patients, respectively. ORR in the former groups was 13/13 (100%) versus 10/16 (63%) in the latter (p = 0.012); corresponding CR rates were 7/13 (54%) versus 1/16 (6%) (p = 0.005). Early administration of vedolizumab was also associated with a greater likelihood of patients being off immunosuppression ((9/13 (69%) versus 3/16 (19%), p = 0.007) and free from fatal infectious complications (5/13 versus 14/16, p = 0.006). Overall, our data suggest that vedolizumab, especially if administered early in the disease course, may ameliorate severe SR GI aGvHD. The timing, role, and safety of vedolizumab should be further explored in prospective clinical trials.

Three-Year Prospective Follow-up of Potential Pediatric Candidate for Intestinal Transplantation.

Intestinal transplantation (ITx) is a treatment for refractory intestinal failure (IF). However, the indications for and timing of ITx are still controversial because the course of IF is unknown. We performed a prospective multi-institutional cohort study to identify the prognostic factors for referral to an ITx facility. Patients under 18 years of age in Japan who suffered from IF and had received parenteral nutrition for longer than 6 months were enrolled in this study. They were followed up for 3 years. Seventy-two patients were followed. The mean age at the beginning of the study was 7.0 years. Diagnoses were short gut syndrome (n = 25), motility disorder (n = 45), and other (n = 2). The overall 3-year survival rate was 95%. The 3-year survival rate was 86% in patients with intestinal-failure-associated liver disease (IFALD) (n = 6) compared to 97% in those without IFALD (n = 66) (P = .0003). Furthermore, the 3-year survival rates of patients who did and did not meet the criteria for ITx were 82% (n = 11) and 97% (n = 62), respectively (P = .034). Six (44%) of 14 patients whose performance status (PS) was ≥3 at enrollment were dead or still had a PS ≥ 3 at 3 years. This study indicates that IFALD is a poor prognostic factor in pediatric patients with IF. Our indication for ITx, namely the presence of IFALD or loss of more than 2 parenteral nutrition access sites, seems to be applicable.

Treating Steroid Refractory Intestinal Acute Graft-vs.-Host Disease With Fecal Microbiota Transplantation: A Pilot Study.

Patients with steroid refractory gastrointestinal (GI) tract graft- vs.-host disease (GvHD) face a poor prognosis and limited therapeutic options. To accurately assess the efficacy and safety of fecal microbiota transplantation (FMT) in treating steroid refractory GI tract GvHD, we conducted a pilot study involving eight patients. Having received FMTs, all patients' clinical symptoms relieved, bacteria enriched, and microbiota composition reconstructed. Compared to those who did not receive FMT, these eight patients achieved a higher progression-free survival. FMT can serve as a therapeutic option for GI tract aGVHD, but its effectiveness and safety need further evaluations. Clinical Trial Registration: NCT03148743.

The risk of long-term bowel dysfunction after resection for sigmoid adenocarcinoma: a cross-sectional survey comparing complete mesocolic excision with conventional surgery.

AIM: To investigate whether complete mesocolic excision (CME) might carry a higher risk of bowel dysfunction and subsequent reduction in quality of life compared with conventional resection. METHOD: A cross-sectional questionnaire study based on data from a national survey regarding long-term bowel function and a population-based cohort study comparing CME (study group) with conventional resection (control group). A total of 622 patients undergoing elective resection for Stage I-III sigmoid adenocarcinoma at four university colorectal centres between June 2008 and December 2014 were eligible to receive the questionnaire in mid-November 2015. Primary outcomes were four or more bowel movements daily, nocturnal bowel movements, unproductive call to stool, obstructive sensation and impact of bowel function on quality of life (QOL). RESULTS: One hundred and twenty-seven (69.0%) and 289 (66.0%) patients in the study and control groups, respectively, responded to the questionnaire after medians of 4.41 [interquartile range (IQR) 2.50, 5.83] and 4.57 (IQR 3.15, 5.82) years, respectively (P = 0.048). CME was not associated with: increased risk of four or more bowel movements daily [adjusted OR 1.14 (95% CI 0.59-2.14; P = 0.68)], nocturnal bowel movements [adjusted OR 1.31 (0.66-2.53; P = 0.43)], unproductive call to stool [adjusted OR 0.99 (0.54-1.77; P = 0.97)] or obstructive sensation [adjusted OR 1.01 (0.56-1.78; P = 0.96)]. While one in five patients in both groups had moderate to severe impact of bowel function on QOL, there was no association with CME. CONCLUSION: For patients with sigmoid cancer, CME is associated with neither higher risk of bowel dysfunction nor impaired QOL.

Pediatric Intestinal Failure: The Key Outcomes for the First 100 Patients Treated in a National Tertiary Referral Center During 1984-2017.

BACKGROUND: Pediatric-onset intestinal failure (IF) remains a severe illness with life-threatening consequences. In this study, we analyzed a single center's outcomes of IF over 3 decades. METHODS: All children with IF who required parenteral nutrition (PN) >2 months or small-intestinal resection ≥50% managed since 1984 were included for retrospective outcome analyses. RESULTS: In total, 100 patients with median PN duration of 1.2 (interquartile range, 0.4-3.5) years were identified. Causes of IF were short bowel syndrome (SBS; n = 78), primary intestinal motility disorders (n = 14), and congenital intestinopathies (n = 8). Patients with SBS had median 40 (25-60) cm of small bowel remaining. Overall, Kaplan-Meier 5- and 10-year weaning-off estimates were 67% (95% CI, 57-77) and 73% (95% CI, 63-84), respectively. Weaning off PN was predicted by remaining bowel anatomy, multidisciplinary treatment era, and absence of immune deficiency. Catheter-related bloodstream infections decreased from 1.4 to 0.6/1000 PN days (P = .0003) with systematic use of taurolidine locks. None had progressive liver disease. Thirty-one percent of patients with SBS underwent autologous intestinal reconstructive surgery. Five patients received and 2 were listed for isolated intestinal transplantation. Eight patients died, and overall 15-year survival rate estimate was 91% (95% CI, 85-98). CONCLUSIONS: Despite reassuring rates of survival and weaning off PN, long-term PN failed in 14% of patients solely because of catheter complications in the recent era. Achievement of enteral autonomy in those with the shortest remaining small bowel and functional cause of IF remains challenging.

Hospital variation in mortality after emergent bowel resections: The role of failure-to-rescue.

BACKGROUND: Hospital variation in failure-to-rescue (FTR) rates has partially explained nationwide differences in mortality after elective surgeries. To examine the role of FTR among emergency general surgery, we compared nationwide risk-adjusted mortality, complications, and FTR rates after emergent bowel resections. METHODS: We identified patients who underwent emergent small or large bowel resections in the 2010 to 2011 Nationwide Inpatient Sample using the American Association for the Surgery of Trauma criteria. We then calculated risk-adjusted mortality rates for each hospital using multivariable logistic regressions and postestimation, which adjusted for patient age, sex, race and ethnicity, payer status, comorbidities, and hospital clustering. After excluding hospitals with fewer than 10 resections per year, we ranked the remaining hospitals by their risk-adjusted mortality rates and divided them into five quintiles. We compared both risk-adjusted complication rates and FTR rates between the top (lowest mortality) and bottom (highest mortality) quintiles. RESULTS: We identified 21,564 emergent bowel resections, weighted to 105,925 procedures nationwide. The bottom quintile of hospitals had an overall risk-adjusted mortality rate that was 10.9 times higher than that of the top quintile of hospitals (15.3% vs. 1.4%). While risk-adjusted complication rates were similarly high for both the bottom and the top quintiles of hospitals (22.5% vs. 15.7%), the risk-adjusted FTR rates were 10.8 times higher in the bottom quintile of hospitals relative to the top quintile of hospitals (33.4% vs. 3.1%). Using larger hospital volume thresholds yielded similar findings. Furthermore, large variations existed in complication-specific FTR rates (surgical site infection [6.6%] to myocardial infarction [29.4%]). CONCLUSION: Nationwide hospital variation in risk-adjusted mortality rates exist after emergent bowel resections. As complication rates were similar across hospitals, the significantly higher FTR rates at higher-mortality hospitals may drive this variation in mortality. System-level initiatives addressing the management of postoperative complications may improve patient care and reduce variation in outcomes. LEVEL OF EVIDENCE: Prognostic and epidemiological study, level IV.

The extent of intestinal failure-associated liver disease in patients referred for intestinal rehabilitation is associated with increased mortality: an analysis of the Pediatric Intestinal Failure Consortium database.

BACKGROUND: The advent of regional multidisciplinary intestinal rehabilitation programs has been associated with improved survival in pediatric intestinal failure. Yet, the optimal timing of referral for intestinal rehabilitation remains unknown. We hypothesized that the degree of intestinal failure-associated liver disease (IFALD) at initiation of intestinal rehabilitation would be associated with overall outcome. METHODS: The multicenter, retrospective Pediatric Intestinal Failure Consortium (PIFCon) database was used to identify all subjects with baseline bilirubin data. Conjugated bilirubin (CBili) was used as a marker for IFALD, and we stratified baseline bilirubin values as CBili<2 mg/dL, CBili 2-4 mg/dL, and CBili>4 mg/dL. The association between baseline CBili and mortality was examined using Cox proportional hazards regression. RESULTS: Of 272 subjects in the database, 191 (70%) children had baseline bilirubin data collected. 38% and 28% of patients had CBili >4 mg/dL and CBili <2 mg/dL, respectively, at baseline. All-cause mortality was 23%. On univariate analysis, mortality was associated with CBili 2-4 mg/dL, CBili >4 mg/dL, prematurity, race, and small bowel atresia. On regression analysis controlling for age, prematurity, and diagnosis, the risk of mortality was increased by 3-fold for baseline CBili 2-4 mg/dL (HR 3.25 [1.07-9.92], p=0.04) and 4-fold for baseline CBili >4 mg/dL (HR 4.24 [1.51-11.92], p=0.006). On secondary analysis, CBili >4 mg/dL at baseline was associated with a lower chance of attaining enteral autonomy. CONCLUSION: In children with intestinal failure treated at intestinal rehabilitation programs, more advanced IFALD at referral is associated with increased mortality and decreased prospect of attaining enteral autonomy. Early referral of children with intestinal failure to intestinal rehabilitation programs should be strongly encouraged. LEVEL OF EVIDENCE: Treatment Study, Level III.

Non-endoscopic biopsy techniques: a review.

INTRODUCTION: Diseases of the stomach and small intestine account for approximately 20% of all gastrointestinal (GI)-related mortality. Biopsy of the stomach and small intestine remains a key diagnostic tool for most of the major diseases that affect the GI tract. While endoscopic means for obtaining biopsy is generally the standard of care, it has several limitations that make it less ideal for pediatric patients and in low resource areas of the world. Therefore, non-endoscopic means for obtaining biopsy samples is of interest in these settings. Areas covered: We review non-endoscopic biopsy techniques reported thus far, and critically examine their merits and demerits regarding their suitability for obtaining biopsy samples in non-sedated subjects. Expert commentary: Esophagogastroduodenoscopy (EGD) is the current standard for acquiring biopsy from the GI tract, however, its limitations include subject sedation, expensive endoscopy infrastructure, expert personnel, and a small but significant risk of complications. A less costly, minimally-invasive and non-endoscopic means for obtaining biopsy samples is therefore of interest for addressing these issues. Such a technology would be of significant impact in low- and middle-income countries where conducting endoscopy is challenging.

Long-term outcomes of pediatric intestinal failure.

Management of pediatric intestinal failure has evolved in recent decades, with improved survival since the advent of specialized multidisciplinary intestinal failure centers. Though sepsis and intestinal failure associated liver disease still contribute to mortality, we now have growing data on the long-term outcomes for this population. While intestinal adaptation and parenteral nutrition weaning is most rapid during the first year on parenteral support, achievement of enteral autonomy is possible even after many years as energy and protein requirements decline dramatically with age. Intestinal transplant is an option for patients experiencing complications of long-term parenteral nutrition who are expected to have permanent intestinal failure, but outcomes are hindered by immunosuppression-related complications. Much of the available data comes from single center retrospective reports, with variable inclusion criteria, intestinal failure definitions, and follow-up durations; this limits the ability to analyze outcomes and identify best practices. As most children now survive long-term, the focus of management has shifted to the avoidance and management of comorbidities, support of normal growth and development, and optimization of quality of life for these medically and surgically complex patients.