E-scooter incidents in Berlin: an evaluation of risk factors and injury patterns.

BACKGROUND: E-scooters have emerged as a frequently used vehicle in German cities due to their high availability and easy access. However, investigations about the causes and mechanisms of E-scooter incidents and their trauma-specific consequences are rare. METHODS: We analysed all patients involved in E-scooter incidents from June to December 2019 who presented to four inner-city EDs in Berlin. The prospective data included patient-related and incident-related data, information on injury patterns and therapy, responses in a voluntary questionnaire concerning E-scooter use and general traffic experience. RESULTS: 248 patients (129 males; median age 29 years (5-81)) were included: 41% were tourists and 4% were children. Most incidents (71%) occurred between July and September 2019, the majority occurring at weekends (58%). The injury pattern was mostly multifocal, affecting the lower (42%) and upper limbs (37%) and the head (40%). Traumatic brain injury was associated with alcohol consumption. Inpatient admission was recorded in 25%, surgery in 23%. CONCLUSION: This study has defined the incidence of injury related to E-scooter use in a major European city. Stricter laws governing the use of E-scooters, the wearing of helmets and technical modifications to the E-scooter platforms might decrease E-scooter-associated incidents and resulting injuries in the future. TRIAL REGISTRATION NUMBER: German Clinical Trials Registry (DRKS00018061).

Impact of the COVID-19 shutdown on orthopedic trauma numbers and patterns in an academic Level I Trauma Center in Berlin, Germany.

BACKGROUND: The COVID-19 pandemic led to the implementation of drastic shutdown measures worldwide. While quarantine, self-isolation and shutdown laws helped to effectively contain and control the spread of SARS-CoV-2, the impact of COVID-19 shutdowns on trauma care in emergency departments (EDs) remains elusive. METHODS: All ED patient records from the 35-day COVID-19 shutdown (SHUTDOWN) period were retrospectively compared to a calendar-matched control period in 2019 (CTRL) as well as to a pre (PRE)- and post (POST)-shutdown period in an academic Level I Trauma Center in Berlin, Germany. Total patient and orthopedic trauma cases and contacts as well as trauma causes and injury patterns were evaluated during respective periods regarding absolute numbers, incidence rate ratios (IRRs) and risk ratios (RRs). FINDINGS: Daily total patient cases (SHUTDOWN vs. CTRL, 106.94 vs. 167.54) and orthopedic trauma cases (SHUTDOWN vs. CTRL, 30.91 vs. 52.06) decreased during the SHUTDOWN compared to the CTRL period with IRRs of 0.64 and 0.59. While absolute numbers decreased for most trauma causes during the SHUTDOWN period, we observed increased incidence proportions of household injuries and bicycle accidents with RRs of 1.31 and 1.68 respectively. An RR of 2.41 was observed for injuries due to domestic violence. We further recorded increased incidence proportions of acute and regular substance abuse during the SHUTDOWN period with RRs of 1.63 and 3.22, respectively. CONCLUSIONS: While we observed a relevant decrease in total patient cases, relative proportions of specific trauma causes and injury patterns increased during the COVID-19 shutdown in Berlin, Germany. As government programs offered prompt financial aid during the pandemic to individuals and businesses, additional social support may be considered for vulnerable domestic environments.

Oral intake and plasma citrulline predict quality of life in patients with intestinal failure.

OBJECTIVE: Chronic intestinal failure (cIF) is a rare medical condition usually treated by long-term parenteral nutrition (PN). Owing to disease-associated symptoms and treatment-specific complications, patients with cIF commonly present with reduced quality of life (QoL) compared with healthy controls. The aim of this study was to identify factors associated with QoL in patients with cIF. METHODS: Ninety adult patients with cIF receiving PN were included in an observational study between 2014 and 2017. QoL based on the novel Short Bowel Syndrome-Quality of Life (SBS-QoL) scale and the Short-Form 36 (SF-36) health survey and nutritional status, liver function, and standard blood chemistry were assessed in every study patient. Univariate and multivariable regressions were conducted to determine independent predictors of QoL. RESULTS: Oral food intake and plasma citrulline were the two independent variables associated with the SBS-QoL subscale 1 (R2 = 0.240) and subscale 2 (R2 = 0.235). Oral intake (ß = -43.909, P = 0.015) and citrulline (ß = -0.952, P = 0.003) were also significantly associated with the SBS-QoL sum scale (R2 = 0.209). The results of SF-36 health survey were significantly associated with both SBS-QoL subscale 1 (P <0.001) and subscale 2 (P <0.001) and the SBS-QoL sum scale (P <0.001). CONCLUSIONS: Citrulline and oral intake are predictors of QoL in patients with cIF. Although citrulline appears to be good screening tool, oral food ingestion should be considered as key goal in patients with cIF.

Atypical malignancies after intestinal transplantation in children: A European single-centre experience.

BACKGROUND: Post-transplant malignancies, that is, lymphomas, are a recognized complication in intestinal transplant recipients but are mostly secondary to EBV infection. There is an increased risk for malignancies in unusual sites in intestinal transplant recipients as compared to other solid organ transplants and the general population. OBJECTIVE: To evaluate the incidence, course, and outcome of unusual malignancies in children after ITx. METHODS: Retrospective analysis of children who underwent ITx for primary digestive disorders at Birmingham Children's Hospital between January 1989 and December 2017. RESULTS: Ninety-eight intestinal transplants were performed in 90 children (49 males and 41 females) with an underlying primary digestive disorder. Median age was 2.7 years (0.6-16.2), and median weight was 14.5 kg (5.7-53.2) at the time of transplant. Within this cohort, we identified four cases of unusual malignancies at rare sites of presentation. One patient developed cerebral PTLD, two patients were diagnosed with SMT, located at the stomal orifice and in cervicothoracic paravertebral area, respectively, and the last patient developed a retroperitoneal angiosarcoma. Unfortunately, the overall patient outcome was poor in all but one child with SMT, who currently survives with cytotoxic T-cell therapy. CONCLUSION: Unusual malignancies can occur in approximately 5% of children following ITx. A high index of suspicion is required for a timely diagnosis and adequate treatment.

Determinants of Quality of Life in Patients With Intestinal Failure Receiving Long-Term Parenteral Nutrition Using the SF-36 Questionnaire: A German Single-Center Prospective Observational Study.

BACKGROUND: Parenteral nutrition (PN) is a life-sustaining therapy for patients with chronic intestinal failure (IF) but inevitably has an impact on patients' quality of life (QoL). The purpose of this study was to examine multiple aspects of QoL by utilizing the standardized Short Form 36 (SF-36) health survey. METHODS: Between 2014 and 2017, a total of 90 adult patients with IF who were receiving PN were prospectively enrolled in an observational study. All subjects underwent nutrition status assessment, liver assessment, blood tests, and QoL assessment based on the SF-36. Univariate and multivariable analyses were performed to identify determinants of 8 domains and 2 summary scales of the SF-36. RESULTS: Analysis of the SF-36 questionnaire data showed that QoL was significantly worse compared with the general German population across all categories. Multivariable analysis revealed that bioelectrical impedance analysis of phase angle (1/10 categories), stoma/fistula (4/10 categories), oral intake (4/10 categories), infusions per week (1/10 categories), duration of PN (1/10 categories), citrulline (4/10 categories), and hemoglobin levels (1/10 categories) are independent risk factors affecting QoL. CONCLUSION: This study uses the largest cohort of IF patients assessed by the standardized SF-36 questionnaire to comprehensively analyze QoL. Presence of oral intake, presence of ostomy, and citrulline levels were independently correlated with 4 of 10 categories of the SF-36. These results indicate that to improve QoL for IF patients, clinical care should focus on addressing the social and emotional value of oral intake, educational interventions, early stoma closure, and application of new targeted therapies.

Advanced liver function assessment in patients with intestinal failure on long-term parenteral nutrition.

BACKGROUND & AIMS: Intestinal failure associated liver disease (IFALD) is one of the leading complications and causes of deaths in adult patients receiving home parenteral nutrition for chronic intestinal failure (CIF). Early diagnosis of IFALD is key to alleviate the progression of hepatic dysfunction. The aim of this study was to evaluate the capability of noninvasive liver function tests. METHODS: 90 adult patients with CIF receiving long-term home parenteral nutrition were included in a prospective cross-sectional study at our department between 2014 and 2017. All participants underwent dynamic liver function assessment (maximum liver function capacity [LiMAx] test, indocyanine green [ICG] test), transient elastography (FibroScan), blood tests and comprehensive nutritional status assessment. Univariate and multivariable analysis were performed to identify predictors of liver function. RESULTS: LiMAx, ICG test, and FibroScan highly correlated with standard liver function tests. Multivariable analysis identified intact ileum (B = 520.895; p = 0.010), digestive anatomy type 3 (B = 75.612; p = 0.025), citrulline level (B = 3.428; p = 0.040), parenteral olive oil intake (B = -0.570; p = 0.043), and oral intake (B = 182.227; p = 0.040) as independent risk factors affecting liver function determined by LiMAx test. ICG test and FibroScan showed no correlation with gastrointestinal and nutrition-related parameters. CONCLUSION: The LiMAx test is significantly associated with widely accepted risk factors for IFALD by multivariable analysis, whereas ICG test and FibroScan failed to show significant correlations. Liver function assessment by LiMAx test may therefore have the potential to detect alterations in liver function and identify patients at risk for the development of IFALD. Longitudinal studies are needed to investigate the impact of liver function determined by LiMAx test on long-term outcome in patients with CIF.

Effects of expanded allocation programmes and organ and recipient quality metrics on transplant-related costs in kidney transplantation - an institutional analysis.

Expansions of donor pools have a controversial impact on healthcare expenditures. The aim of this study was to investigate the emerging costs of expanded criteria donor (ECD) kidney transplantations (KT) and to identify independent risk factors for increased transplant-related costs. We present a retrospective explorative analysis of hospital costs and reimbursements of KTs performed between 2012 and 2016 in a German university hospital. A total of 174 KTs were examined, including 92 (52.9%) ECD organ transplantations. The ECD group comprised 43 (24.7%) 'old-for-old' transplantations. Median healthcare costs were 19 570€ (IQR 18 735-27 405€) in the standard criteria donor (SCD) group versus 25 478€ (IQR 19 957-29 634€) in the ECD group (+30%; P = 0.076). 'Old-for-old' transplantations showed the highest healthcare expenditures [26 702€ (19 570-33 940€)]. Irrespective of the allocation group, transplant-related costs increased significantly in obese (+6221€; P = 0.009) and elderly recipients (+6717€; P = 0.019), in warm ischaemia time exceeding 30 min (+3212€; P = 0.009) and in kidneys with DGF or surgical complications (+8976€ and +10 624€; both P < 0.001). Transplantation of ECD organs is associated with incremental costs, especially in elderly and obese recipients. A critical patient selection, treatment of obesity before KT and keeping warm ischaemia times short seem to be crucial, in order to achieve a cost-effective KT regardless of the allocation group.

Long-Term Signs of T Cell and Myeloid Cell Activation After Intestinal Transplantation With Cellular Rejections Contributing to Further Increase of CD16+ Cell Subsets.

The intestine mediates a delicate balance between tolerogenic and inflammatory immune responses. The continuous pathogen encounter might also augment immune cell responses contributing to complications observed upon intestinal transplantation (ITx). We thus hypothesized that ITx patients show persistent signs of immune cell activation affecting both the adaptive and innate immune cell compartment. Information on the impact of intestinal grafts on immune cell composition, however, especially in the long-term is sparse. We here assessed activated and differentiated adaptive and innate immune subsets according to time, previous experience of cellular or antibody-mediated rejections or type of transplant after ITx applying multi-parametric flow cytometry, gene expression, serum cytokine and chemokine profiling. ITx patients showed an increase in CD16 expressing monocytes and myeloid dendritic cells (DCs) compared to healthy controls. This was even detectable in patients who were transplanted more than 10 years ago. Also, conventional CD4+ and CD8+ T cells showed persistent signs of activation counterbalanced by increased activated CCR4+ regulatory T cells. Patients with previous cellular rejections had even higher proportions of CD16+ monocytes and DCs, whereas transplanting higher donor mass with multi-visceral grafts was associated with increased T cell activation. The persistent inflammation and innate immune cell activation might contribute to unsatisfactory results after ITx.

Killer-like receptors and GPR56 progressive expression defines cytokine production of human CD4+ memory T cells.

All memory T cells mount an accelerated response on antigen reencounter, but significant functional heterogeneity is present within the respective memory T-cell subsets as defined by CCR7 and CD45RA expression, thereby warranting further stratification. Here we show that several surface markers, including KLRB1, KLRG1, GPR56, and KLRF1, help define low, high, or exhausted cytokine producers within human peripheral and intrahepatic CD4+ memory T-cell populations. Highest simultaneous production of TNF and IFN-γ is observed in KLRB1+KLRG1+GPR56+ CD4 T cells. By contrast, KLRF1 expression is associated with T-cell exhaustion and reduced TNF/IFN-γ production. Lastly, TCRß repertoire analysis and in vitro differentiation support a regulated, progressive expression for these markers during CD4+ memory T-cell differentiation. Our results thus help refine the classification of human memory T cells to provide insights on inflammatory disease progression and immunotherapy development.

Revascularization Time in Liver Transplantation: Independent Prediction of Inferior Short- and Long-term Outcomes by Prolonged Graft Implantation.

BACKGROUND: Strategies for successful transplantation are much needed in the era of organ shortage, and there has been a resurgence of interest on the impact of revascularization time (RT) on outcomes in liver transplantation (LT). METHODS: All primary LT performed in Birmingham between 2009 and 2014 (n = 678) with portal reperfusion first were stratified according to RT (<44 minutes vs ≥44 minutes) and graft quality (standard liver graft [SLG], Donor Risk Index < 2.3 vs marginal liver graft [MLG], Donor Risk Index ≥ 2.3). RESULTS: Revascularization time of 44 minutes or longer resulted in significantly greater incidence of early allograft dysfunction (EAD) (29% vs 47%, P < 0.001), posttransplant acute kidney injury (AKI) (39% vs 60%, P < 0.001), and new-onset AKI (37% vs 56%, P < 0.001), along with poor long-term outcome (3-year graft survival 92% vs 83%, P = 0.001; 3-year patient survival 87% vs 79%, P = 0.004). On multivariable analysis, RT ≥ 44 was a significant independent predictor of EAD, renal dysfunction, and overall graft survival, but not patient survival. The cumulative effect of prolonged revascularization in marginal grafts (MLG) resulted in the worst transplant outcome compared with all other groups, which could be mitigated by rapid revascularization (SLG, SLG, MLG vs MLG; EAD 24%, 39%, 39% vs 69%; AKI 32%, 46%, 51% vs 70%; 3-year graft survival 94%, 87%, 88% vs 70%, respectively; each P < 0.001). Factors associated with lack of abdominal space, larger grafts, and surgical skills were predictive of RT ≥ 44. CONCLUSIONS: Shorter graft revascularization is a protective factor in LT, particularly in the setting of graft marginality. Careful graft-recipient matching and emphasis on surgical expertise may aid in achieving better outcomes in LT.

Severe Unresolved Cholestasis Due to Unknown Etiology Leading to Early Allograft Failure Within the First 3 Months of Liver Transplantation.

BACKGROUND: Causes of severe cholestasis after liver transplantation (LT) are multi-factorial. Although the etiology is predictable in some, others culminate in graft/patient loss without a definitive cause identified. Severe cholestasis is usually associated with overlapped histological findings of rejection and biliary features, and diagnostic interpretation may pose a challenge. METHODS: This is 10-year retrospective analysis of patients with unexplained severe cholestasis resulting in death/graft loss within 90 days of LT. Of 1 583 LT during the study period, 90-day graft failure occurred in 129 (8%) cases; a total of 45 (3%) patients had unresolving severe cholestasis (bilirubin, >100 µmol/L; alkaline phosphatase, >400 UI/L after 15 days from LT), excluding those due to primary nonfunction/sepsis/vascular causes (n = 84). Demographics, allograft biopsies, radiological investigations, and clinical outcome were analyzed. RESULTS: All patients had persistent abnormal liver biochemistry. Doppler ultrasound scan was normal in all cases. Thirty-five (78%) recipients had at least 1 allograft biopsy (2 [1-9]). On the first biopsy, 22 (63%) patients had acute rejection, 4 (18%) early-chronic rejection, 12 (34%) antibody-mediated rejection. In subsequent biopsies chronic rejection was evident in 5 (14%) cases. Donor-specific antibodies were detected in all patients tested. Biliary anatomy was studied in detail in 9 (20%) patients, all presenting biliary strictures. The majority (n = 39; 87%) died within 32 (10-91) days, only survivors were from retransplantation (n = 3;6.5%) and biliary intervention (n = 3;6.5%). CONCLUSIONS: Unresolving severe cholestasis after LT is a key parameter predicting patient/allograft outcome. Histologically, rejection seems to overlap with biliary strictures; hence, allograft biopsy with signs of rejection should not be a reason to overlook biliary problems, in particular when biliary features are present. Only extensive radiological investigation/intervention or retransplantation prevents patient/allograft loss.

Intragraft and Systemic Immune Parameters Discriminating Between Rejection and Long-Term Graft Function in a Preclinical Model of Intestinal Transplantation.

BACKGROUND: The pathology and diagnosis of acute and chronic rejection in intestinal transplantation (ITX) are far from being completely understood. We established models of acute and chronic intestinal graft rejection and analyzed peripheral and intragraft immune responses. METHODS: We performed ITX from Dark Agouti into Lewis rats applying single-dose tacrolimus (TAC) at varying concentrations. Graft histology and immunohistology were assessed on postoperative day (POD)7, 14, and 45. Intragraft and peripheral gene expressions of inflammatory and anti-inflammatory markers and lipopolysaccharide binding protein (LBP) plasma as well as alloantibodies were measured simultaneously. RESULTS: A 1-mg TAC resulted in acute rejection and recipient death; 3 mg and 5 mg prolonged survival and led to severe or moderate chronic rejection, respectively, with 50% of the 5-mg TAC recipients surviving the observation period. Consequently, we observed severe infiltration on POD7 in untreated and 1-mg TAC recipients compared with minor histological alterations in 3 and 5 mg TAC groups. Only 5-mg TAC treatment prevented accumulation of CD4+ T cells and ED1+ macrophages over the entire observation period. Peripheral and intragraft expressions of T cell activation inhibitor-mitochondrial were stable in long-term surviving 5-mg TAC recipients but declined before acute or chronic rejection in 1 and 3 mg TAC recipients. In contrast, LBP levels increased during acute and chronic rejections. CONCLUSIONS: We studied acute and chronic rejections in a preclinical model of ITX, which recapitulates clinical findings and highlights the importance of monitoring peripheral T cell activation inhibitor-mitochondrial expression, LBP levels, and antidonor antibodies for revealing rejection.

Non-HLA Antibodies May Accelerate Immune Responses After Intestinal and Multivisceral Transplantation.

BACKGROUND: Non-HLA alloantibodies and autoantibodies are involved in allograft rejection in kidney and heart transplantation. Their role in intestinal transplantation has not yet been described. We examined the development of antiangiotensin II type I receptor antibodies (anti-AT1R) and antiendothelin type A receptor antibodies associated with the clinical course and histopathological findings of intestinal transplantation recipients. METHODS: Thirty-seven patients underwent intestinal or multivisceral transplantation. Non-HLA antibodies (non-HLAabs) were screened in 29 transplant recipients. Antibody-levels greater than 12 U/L were considered positive and were evaluated retrospectively regarding rejection episodes. RESULTS: Twenty patients developed anti-AT1R and/or antiendothelin type A receptor antibodies (non-HLAabs group), 9 did not (control group). The non-HLAabs group had a higher rate of allograft rejection than controls (80% vs 55%), especially a higher rate of antibody-mediated rejections (55% vs 11%, P < 0.01) with detection of donor-specific anti-HLAabs. All rejection episodes in the non-HLAabs group appeared around the time of positive non-HLAabs detection. Five patients had acute cellular rejections at the time of non-HLAabs development, 4 had viral infections. CONCLUSIONS: Our data suggest that antibody-mediated mechanisms targeting antigens beyond HLA may trigger and accelerate immune responses. Given the possibility of pharmacologic targeting of non-HLA receptors, future studies will focus on the explanation of mechanisms how non-HLAabs may enhance rejection and affect long-term allograft survival.

Skype clinics after intestinal transplantation - follow-up beyond post codes.

The follow-up after intestinal transplantation (ITX) is complex and limited to specialized centers. ITX recipients often travel all over the country to be seen in the outpatient clinic of specialized centers which is costly and time-consuming. Videoconferences through Skype have been implemented to eliminate travel time, costs, and to improve patient compliance without jeopardizing safety. Eighteen of 19 patients followed up after ITX or modified multivisceral transplantation (MMVTX) in conventional outpatient clinics in Oxford agreed to attend additional Skype clinics. All patients who were followed up through Skype clinics after ITX/MMVTX received a questionnaire to measure their satisfaction with methods and technical aspects of videoconferencing as well as time/mode of traveling, travel expenses/costs, waiting time in outpatient clinic and patients' satisfaction. Mean travel distance to Oxford was 236 ± 168 miles, mean travel time was 277 ± 175 min, and mean travel cost was 200 ± 56 Great Britain Pounds. A total of 56% had to take time off work and/or find child/family care for the time spent in travel. These patients reported a satisfaction score of 4.38 ± 0.77 of 5 points as opposed to 2.88 ± 0.90 for attending the conventional outpatient clinic. Skype clinics have been proven successful and feasible in highly specialized fields like ITX in eligible patients.

Solitary pancreas transplantation: a review of the UK experience over a period of 10 yr.

BACKGROUND: The aim of this study was to see whether lessons could be learned from the prospectively maintained nationwide database on solitary pancreas transplantation (SPTx) performed in the UK. METHODS: Two hundred and forty-five SPTx were utilized from the 2004-2013 period (113 pancreas transplant alone and 132 pancreas after kidney). The statistical analysis included donor, recipient, transplant variables, and the effect of a rejection episode on graft survival. RESULTS: Cold ischemia time (CIT), CIT > 12 h, donor body mass index (BMI) > 30, and non-lymphocyte-depleting induction immunosuppression achieved p-value <0.05 in the unadjusted univariate hazard model analysis. In a multivariate analysis, variables that persisted in demonstrating increased independent risk included CIT > 12 h (hazard ratio [HR] 1.94, p = 0.035) and the use of non-depleting induction immunosuppression (HR 1.95, p = 0.002). Factors such as bladder-drained grafts and donor variables including age, BMI, and donation after cardiac death (DCD) vs. donation after brain-stem death did not attain significance. Rejection reduces the overall graft survival by approximately 1000 d (1841 ± 114 d vs. 915 ± 119 d, p = 0.001). CONCLUSIONS: Cold ischemia time <12 h and the use of depleting antibodies as induction immunosuppression have a positive effect on pancreas allograft survival. Other factors such as bladder-drained grafts and donor variables such as age, BMI, and DCD status did not attain significance in a multivariate analysis.

Chronic intestinal failure after Crohn disease: when to perform transplantation.

IMPORTANCE: Because of the severity of disease and additional surgery, Crohn disease (CD) may result in intestinal failure (IF) and dependency on home parenteral nutrition (HPN). Defining the indication and timing for intestinal transplantation (ITx) is challenging. OBJECTIVES: To determine the limitations of conventional surgery and to facilitate the decision making for transplantation. DESIGN, SETTING, AND PARTICIPANTS: Data were collected prospectively and obtained by retrospective review of medical records from all patients with CD who were assessed for ITx in Oxford, United Kingdom, and Berlin, Germany, from October 10, 2003, through July 31, 2013. Patients were considered suitable for ITx if a diagnosis of irreversible IF was established and life-threatening complications under HPN were unresolvable. Twenty patients with CD and IF, established on HPN, were evaluated for ITx. The mean (SD) age at CD onset was 17.8 (9.8) years. On first diagnosis, most patients had a stricturing CD. By the time of referral, most had a combination of stricturing and fistulizing disease. INTERVENTIONS: New scoring system: a modification of the American Gastroenterology Association guidelines for ITx. Modifications are related to CD-specific issues that potentially lead to a poorer outcome and are based on the findings of the study to determine the expected benefit from ITx. MAIN OUTCOMES AND MEASURES: A scoring system that would alert the physician to the severity of the patient's CD and trigger early referral for ITx. This system may translate into better long-term outcomes for patients with CD. In addition, the Karnofsky performance status score was used to compare pretransplantation and posttransplantation outcomes. RESULTS: Ten patients underwent ITx, 4 were on the waiting list, and 4 were unavailable for follow-up. One patient was taken off the waiting list because of severe deterioration. One patient underwent conventional stricturoplasty and did not need transplantation. Among the transplant recipients, 17 (85%) had a stoma or enterocutaneous fistula, and the mean (SD) residual bowel length was 71.5 (38) cm. A total of 80% of transplant recipients had life-threatening catheter infections, and 13 (65%) had a significant decrease in the estimated glomerular filtration rate. At a mean (SD) follow-up of 27.6 (36.1) months for transplant recipients, the patient and graft survival is 80%, and their Karnofsky performance status score increased by a mean of 18.6%. CONCLUSIONS AND RELEVANCE: Intestinal transplantation is a suitable treatment option for patients with CD and IF. It should be considered before any additional attempts at conventional surgery, which may cause eligible patients to miss this opportunity through perioperative complications. The suggested scoring system enables the physician to identify patients who may benefit from transplantation before HPN-associated secondary organ failure.

Bile duct strictures after liver transplantation.

PURPOSE OF REVIEW: Biliary complications account for relevant morbidity and mortality after liver transplantation. Advances have taken place in understanding their aetiology, in preventive operative techniques, imaging procedures, as well as interventional and endoscopic management. However, progress in living donation, donation after cardiac death as well as paediatric transplant procedures have changed the incidence and causes of biliary complications. This review summarizes recent progress in the field, particularly related to biliary strictures after liver transplantation. RECENT FINDINGS: Significant findings in the period of interest for this review focussed on improvements of endoscopic treatment of postliver transplant biliary complications, including novel stenting devices, the routine analysis of bacterial and fungal flora, and the use of steroids to prevent postendoscopic retrograde cholangiopancreaticography pancreatitis. The importance of cytomegalovirus and hepatitis C in the aetiology of biliary complications was highlighted. Under certain circumstances, biliary complications after liver transplantation of organs secondary to donation after cardiac death may be reduced to a level known from liver transplantation after brain death. Further evidence was added to support the risk-adapted use of biliary drainage during liver transplantation. SUMMARY: The ongoing research in the aetiology, prevention, and treatment of biliary strictures after liver transplantation highlights the significance of biliary complications for patient and graft outcome.

Short-term TNF-alpha inhibition reduces short-term and long-term inflammatory changes post-ischemia/reperfusion in rat intestinal transplantation.

BACKGROUND: Tumor necrosis factor (TNF)-α inhibition was shown to reduce ischemia/reperfusion injury (IRI) after intestinal transplantation (ITX). We studied the effects of different TNFα inhibitors on acute IRI and long-term inflammatory responses in experimental ITX. METHODS: Orthotopic ITX was performed in an isogenic ischemia/reperfusion model in Lewis rats. The TNFα inhibition groups received infliximab post-reperfusion; etanercept pre-reperfusion and at postoperative days (POD) 1, 3, 5, and 7; or pentoxifylline pre-reperfusion and at POD 1 to 5. Tissue samples were taken from proximal and distal graft sections and mesenteric lymph nodes at 20 min, 12 hr, 7 day, and 6 months post-reperfusion for histopathology, immunohistology, terminal deoxyribosyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, and real-time RT-PCR. Lung sections were stained for the myeloperoxidase assay. RESULTS: TNFα inhibitors decreased inflammatory changes after IRI in all treatment groups. Infliximab significantly improved 7-day survival and reduced the histological and immunohistochemical signs of IRI, the numbers of graft-infiltrating T cells and ED1 monocytes and macrophages, and pulmonary neutrophil infiltration, and also enhanced the accumulation of cytoprotective markers. Graft injury was more prominent in the distal graft than in the proximal graft in all groups, regardless of TNFα inhibition. CONCLUSION: Infliximab significantly reduced both acute IRI and, as with other TNFα inhibitors, long-term inflammatory responses after rat ITX. TNFα inhibition may help diminish chronic inflammatory long-term effects and avoid chronic allograft enteropathy.

Clinical relevance of the de novo production of anti-HLA antibodies following intestinal and multivisceral transplantation.

Despite a negative pretransplant cross-match, intestinal transplant recipients can mount humoral immune responses soon after transplantation. Moreover, the development of donor-specific anti-HLA antibodies (DSAs) is associated with severe graft injury. Between June 2000 and August 2011, 30 patients (median age 37.6±9.8 years) received isolated intestinal transplantations (ITX, n=18) or multivisceral transplantations (MVTXs, n=12) at our center. We screened for human leukocyte antigen (HLA) antibodies pre- and post-transplant. If patients produced DSAs, treatment with plasmapheresis and intravenous immunoglobulin (IVIG) was initiated. In the event of DSA persistence and/or treatment-refractory rejection, rituximab and/or bortezomib were added. Ten patients developed DSAs and simultaneously showed significant signs of rejection. These patients received plasmapheresis and IVIG. Eight patients additionally received rituximab, and two patients were treated with bortezomib. DSA values decreased upon antirejection therapy in 8 of the 10 patients. The development of DSAs following ITX is often associated with acute rejection. We observed that the number of mismatched antigens and epitopes correlates with the probability of developing de novo DSAs. Early diagnosis and therapy, including B-cell depletion and plasma cell inhibition, are crucial to preventing further graft injury.