Flavio Paterno

The Etiology and Pathogenesis of Vascular Disorders of the Intestine

Intestinal ischemia includes all the conditions in which the blood supply to the gastrointestinal tract is not adequate to its metabolic demand. Several ischemic intestinal disorders differ in clinical presentation (acute versus chronic), etiology (occlusive versus nonocclusive), pathophysiology (arterial or venous), severity (mucosal versus transmural necrosis), and location (small bowel versus large bowel). Atherosclerosis, thromboembolic disease, hypoperfusion states, and hypercoagulable disorders are the most common causes. Reperfusion, oxygen-derived free radicals, and eicosanoids contribute to the pathogenesis of bowel injury and the systemic response that occur after ischemia. The diagnosis and treatment of intestinal ischemia are still challenging despite the advances of radiology, intensive care, and surgery. This article reviews the latest data about etiology and pathophysiology of bowel ischemia to explain the bases of diagnosis and treatment of this condition.

Bortezomib for acute antibody-mediated rejection in liver transplantation.

Antibody‐mediated rejection (AMR) is an uncommon, but challenging type of rejection after solid organ transplantation. We review three cases of AMR in ABO‐compatible liver transplant recipients. These cases were characterized by severe acute rejection resistant to steroids and antithymocyte globulin, histologic evidence of plasma cell infiltrates, C4d positivity and high serum anti‐HLA donor‐specific antibodies. All three patients were treated with bortezomib, a proteasome inhibitor effective in depleting plasma cells. After treatment, all patients had improved or normal liver function tests, resolution of C4d deposition and significant decline in their HLA donor‐specific antibodies.

Impact of recipient morbid obesity on outcomes after liver transplantation

The aim of this study was to analyze the impact of morbid obesity in recipients on peritransplant resource utilization and survival outcomes. Using a linkage between the University HealthSystem Consortium and Scientific Registry of Transplant Recipients databases, we identified 12 445 patients who underwent liver transplantation (LT) between 2007 and 2011 and divided them into two cohorts based on recipient body mass index (BMI; <40 vs. ≥40 kg/m²). Recipients with BMI ≥40 comprised 3.3% (n = 416) of all LTs in the studied population. There were no significant differences in donor characteristics between two groups. Recipients with BMI ≥40 were significant for being female, diabetic, and with NASH cirrhosis. Patients with a BMI ≥40 had a higher median MELD score, limited physical capacity, and were more likely to be hospitalized at LT. BMI ≥40 recipients had higher post‐LT length of stay and were less often discharged to home. With a median follow‐up of 2 years, patient and graft survival were equivalent between the two groups. In conclusion, morbidly obese LT recipients appear sicker at time of LT with an increase in resource utilization but have similar short‐term outcomes.

Ischemic colitis: risk factors for eventual surgery.

BACKGROUND Ischemic colitis is a common disorder often without clear indications for surgical management. The aim of this study was to identify risk factors that predict the need for surgery. METHODS Patients were identified retrospectively based on International Classification of Disease codes and admission over an 8-year period. RESULTS A total of 253 patients presented with ischemic colitis. A total of 205 patients were managed nonsurgically, 12 underwent immediate surgery (within 12 hours of presentation), and 36 had delayed surgery. On univariate analysis, risk factors that predicted delayed surgery were peripheral vascular disease, atrial fibrillation, hypotension, tachycardia, absence of bleeding per rectum, free intraperitoneal fluid on computed tomography scan, intensive care unit admission, vasopressors, mechanical ventilation, and increased lactate level on admission. Intraperitoneal fluid on computed tomography scan and absence of bleeding per rectum were predictive of surgical intervention on multivariate analysis. CONCLUSIONS In patients with ischemic colitis, several risk factors were associated with the need for subsequent surgery during the same admission. These factors could be used to select patients for immediate surgery before worsening of their clinical condition.

Addressing Morbid Obesity as a Barrier to Renal Transplantation With Laparoscopic Sleeve Gastrectomy

Morbid obesity is a barrier to renal transplantation and is inadequately addressed by medical therapy. We present results of a prospective evaluation of laparoscopic sleeve gastrectomy (LSG) for patients failing to achieve significant weight loss with medical therapy. Over a 25‐month period, 52 obese renal transplant candidates meeting NIH guidelines for metabolic surgery underwent LSG. Mean age was 50.0 ± 10.0 years with an average preoperative BMI of 43.0 ± 5.4 kg/m2 (range 35.8–67.7 kg/m2). Follow‐up after LSG was 220 ± 152 days (range 26–733 days) with last BMI of 36.3 ± 5.3 kg/m2 (range 29.2–49.8 kg/m2) with 29 (55.8%) patients achieving goal BMI of <35 kg/m2 at 92 ± 92 days (range 13–420 days). The mean percentage of excess weight loss (%EWL) was 32.1 ± 17.6% (range 6.7–93.8%). A segmented regression model was used to compare medical therapy versus LSG. This revealed a statistically significant increase in the BMI reduction rate (0.3 kg/m2/month versus 1.1 kg/m2/month, p < 0.0001). Patients also experienced a 40.9% decrease in anti‐hypertensive medications (p < 0.001) and a 49.7% decrease in total daily insulin dose (p < 0.001). LSG is a safe and effective means for addressing obesity in kidney transplant candidates in the context of a multidisciplinary approach.

Effect of pretransplant diabetes on short-term outcomes after liver transplantation: A National cohort study

We sought to analyse the effect of pretransplant diabetes on post‐operative outcomes and resource utilization following liver transplantation.

Variation by center and economic burden of readmissions after liver transplantation

The rate and causes of hospital readmissions after liver transplantation (LT) remain largely unknown in the United States. Adult patients (n = 11,937; 43.1% of all LT cases) undergoing LT from 2007 to 2011 were examined with a linkage of the University HealthSystem Consortium and Scientific Registry of Transplant Recipients databases to determine the incidence and risk factors for 30‐day readmissions and utilization metrics 90 days after LT. The overall 30‐day hospital readmission rate after LT was 37.9%, with half of patients admitted within 7 days after discharge. Readmitted patients had worse overall graft and patient survival with a 2‐year follow‐up. Multivariate analysis identified risk factors associated with 30‐day hospital readmission, including a higher Model for End‐Stage Liver Disease score, diabetes at LT, dialysis dependence, a high donor risk index allograft, and discharge to a rehabilitation facility. After adjustments for donor, recipient, and geographic factors in a hierarchical model, we found significant variation in readmission rates among hospitals ranging from 26.3% to 50.8% (odds ratio, 0.53‐1.90). In the 90‐day analysis after LT, readmissions accounted for

Is liver transplantation safe and effective in elderly (≥70 years) recipients? A case-controlled analysis

43,785 of added costs in comparison with patients who were not readmitted in the first 90 days. This is the first national report showing that more than one‐third of LT recipients are readmitted to their center within 30 days and that readmissions are associated with center variation and increased resource utilization. Liver Transpl 21:953‐960, 2015.

Hepatitis C transmission from seropositive, nonviremic donors to non–hepatitis C liver transplant recipients

BACKGROUND Elderly patients are evaluated for liver transplantation (LT) with increasing frequency, but outcomes in this group have not been well defined. METHODS A linkage of the Scientific Registry of Transplant Recipients (SRTR) and the University HealthSystem Consortium (UHC) databases identified 12,445 patients who underwent LT during 2007-2011. Two cohorts were created consisting of, respectively, elderly recipients aged ≥70 years (n = 323) and recipients aged 18-69 years (n = 12,122). A 1:1 case-matched analysis was performed based on propensity scores. RESULTS Elderly recipients had lower Model for End-stage Liver Disease (MELD) scores at LT (median 15 versus 19; P < 0.0001), more often underwent transplantation at high-volume centres (46% versus 33%; P < 0.0001) and more often received grafts from donors aged >60 years (24% versus 15%; P < 0.0001). The two cohorts had similar hospital lengths of stay, in-hospital mortality, hospital costs and 30-day readmission rates. There were no differences in graft survival between the two cohorts (P = 0.10), but elderly recipients had worse longterm overall survival (P = 0.009). However, a case-controlled analysis confirmed similar perioperative hospital outcomes, graft survival and longterm patient survival in the two matched cohorts. CONCLUSIONS Elderly LT recipients accounted for <3% of all LTs performed during 2007-2011. Selected elderly recipients have perioperative outcomes and survival similar to those in younger adults.

Hospital Resource Use with Donation after Cardiac Death Allografts in Liver Transplantation: A Matched Controlled Analysis from 2007 to 2011

Breakthroughs in hepatitis C virus (HCV) treatment and rising rates of intravenous drug use have led to an increase in the number of organ donors who are HCV antibody–positive but serum nucleic acid test (NAT)–negative. The risk of HCV transmission from the liver grafts of these donors to recipients is unknown. To estimate the incidence of HCV transmission, we prospectively followed 26 consecutive HCV antibody–negative (n = 25) or NAT‐negative (n = 1) transplant recipients who received a liver graft from donors who were HCV antibody–positive but serum NAT‐negative between March 2016 and March 2017. HCV transmission was considered to have occurred if recipients exhibited a positive HCV PCR test by 3 months following transplantation. Drug overdose was listed as the cause of death in 15 (60%) of the donors. One recipient died 18 days after transplantation from primary graft nonfunction and was excluded. Of the remaining 25 recipients, HCV transmission occurred in 4 (16%), at a median follow‐up of 11 months, all from donors who died of drug overdose. Three of these patients were treated with direct‐acting antiviral therapy, with two achieving a sustained virologic response and one an end‐of‐treatment response. One patient with HCV transmission died after a complicated postoperative course and did not receive antiviral therapy. Conclusion: In this prospective cohort of non‐HCV liver recipients receiving grafts from HCV antibody–positive/NAT‐negative donors, the incidence of HCV transmission was 16%, with the highest risk conferred by donors who died of drug overdose; given the availability of safe and highly effective antiviral therapies, use of such organs could be considered to expand the donor pool. (Hepatology 2018;67:1673‐1682).