Combined liver transplantation and sleeve gastrectomy: Report of a brief-interval staged approach.

Pretransplantation bariatric surgery in patients with high Model for End-Stage Liver Disease (MELD) score is fraught with risks. Bariatric surgery after liver transplantation (LT) may be complicated by surgical adhesions but could have advantages if performed at the time of transplantation. We investigated a method of brief-interval staging combining LT and sleeve gastrectomy (SG). LT recipients with a body mass index (BMI) > 40 kg/m 2 received an SG during the same hospitalization as the LT (LT/SG), at the same time as a planned brief-interval return to the operating room for biliary anastomosis. Differences in intraoperative attributes of the LT (Stage 1) versus SG (Stage 2) procedures were analyzed using Wilcoxon signed-rank test with significance p < 0.05 and compared with patients with obesity having a two-stage LT without SG. A total of 14 cases {median MELD score 33 (interquartile range [IQR], 18-40)} were compared with 28 controls; 60% were critically ill prior to surgery with mechanical ventilation, vasopressors, or continuous renal replacement therapy. Median interval between procedures was 16.1 (IQR, 12.5-22.7) hours for cases and 12.2 (IQR, 11.1-16.6) hours for controls, p  = 0.27. Median BMI at LT/SG was 47.0 (IQR, 41.7-51.3) kg/m 2 versus 38.1 (IQR, 35.7-39.8) kg/m 2 for controls, p < 0.001. At 1 year, median excess body weight loss was 74.0% (IQR, 46.2%-78.7%) in cases and 15.8% (IQR, -5.4% to 62.6%) in controls, p  = 0.13; total weight loss was 38.1% (IQR, 23.9-42.9) in cases versus 7.7% (IQR, -2.4% to 27.6%) for controls, p  = 0.03. Graft survival at 1 year was 92.9% for cases and 89.3% for controls with similar early postoperative outcomes. This proof-of-concept study revealed that a brief-interval SG during LT is feasible in patients with high MELD and resulted in sustained weight loss at 1 year with similar graft survival. Further studies are needed to determine an optimal strategy.

Nutritional and Dietary Management of Chronic Kidney Disease Under Conservative and Preservative Kidney Care Without Dialysis.

While dialysis has been the prevailing treatment paradigm for patients with advanced chronic kidney disease (CKD), emphasis on conservative and preservative management in which dietary interventions are a major cornerstone have emerged. Based on high-quality evidence, international guidelines support the utilization of low-protein diets as an intervention to reduce CKD progression and mortality risk, although the precise thresholds (if any) for dietary protein intake vary across recommendations. There is also increasing evidence demonstrating that plant-dominant low-protein diets reduce the risk of developing incident CKD, CKD progression, and its related complications including cardiometabolic disease, metabolic acidosis, mineral and bone disorders, and uremic toxin generation. In this review, we discuss the premise for conservative and preservative dietary interventions, specific dietary approaches used in conservative and preservative care, potential benefits of a plant-dominant low-protein diet, and practical implementation of these nutritional strategies without dialysis.

mTOR inhibitors, mycophenolates, and other immunosuppression regimens on antibody response to SARS-CoV-2 mRNA vaccines in solid organ transplant recipients.

A recent study concluded that SARS-CoV-2 mRNA vaccine responses were improved among transplant patients taking mTOR inhibitors (mTORi). This could have profound implications for vaccine strategies in transplant patients; however, limitations in the study design raise concerns about the conclusions. To address this issue more robustly, in a large cohort with appropriate adjustment for confounders, we conducted various regression- and machine learning-based analyses to compare antibody responses by immunosuppressive agents in a national cohort (n = 1037). MMF was associated with significantly lower odds of positive antibody response (aOR = 0.09 0.130.18 ). Consistent with the recent mTORi study, the odds tended to be higher with mTORi (aOR = 1.00 1.452.13 ); however, importantly, this seemingly protective tendency disappeared (aOR = 0.47 0.731.12 ) after adjusting for MMF. We repeated this comparison by combinations of immunosuppression agents. Compared to MMF + tacrolimus, MMF-free regimens were associated with higher odds of positive antibody response (aOR = 2.39 4.267.92 for mTORi+tacrolimus; 2.34 5.5415.32 for mTORi-only; and 6.78 10.2515.93 for tacrolimus-only), whereas MMF-including regimens were not, regardless of mTORi use (aOR = 0.81 1.542.98 for MMF + mTORi; and 0.81 1.512.87 for MMF-only). We repeated these analyses in an independent cohort (n = 512) and found similar results. Our study demonstrates that the recently reported findings were confounded by MMF, and that mTORi is not independently associated with improved vaccine responses.

Survival following liver transplantation for locally advanced, unresectable intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) has previously been considered a contraindication to liver transplantation (LT). However, recent series showed favorable outcomes for LT after neoadjuvant therapy. Our center developed a protocol for neoadjuvant therapy and LT for patients with locally advanced, unresectable iCCA in 2010. Patients undergoing LT were required to demonstrate disease stability for 6 months on neoadjuvant therapy with no extrahepatic disease. During the study period, 32 patients were listed for LT and 18 patients underwent LT. For transplanted patients, the median number of iCCA tumors was 2, and the median cumulative tumor diameter was 10.4 cm. Patients receiving LT had an overall survival at 1-, 3-, and 5-years of 100%, 71%, and 57%. Recurrences occurred in seven patients and were treated with systemic therapy and resection. The study population had a higher than expected proportion of patients with genetic alterations in fibroblast growth factor receptor (FGFR) and DNA damage repair pathways. These data support LT as a treatment for highly selected patients with locally advanced, unresectable iCCA. Further studies to identify criteria for LT in iCCA and factors predicting survival are warranted.

Early humoral immune response to two doses of severe acute respiratory syndrome coronavirus 2 vaccine in a diverse group of solid organ transplant candidates and recipients.

Response to two doses of a nucleoside-modified messenger ribonucleic acid (mRNA) vaccine was evaluated in a large solid-organ transplant program. mRNA COVID-19 vaccine was administered to transplant candidates and recipients who met study inclusion criteria. Qualitative anti-SARS-CoV-2 Spike Total Immunoglobulin (Ig) and IgG-specific assays, and a semi-quantitative test for anti-SARS-CoV-2 Spike protein IgG were measured in 241 (17.2%) transplant candidates and 1163 (82.8%) transplant recipients; 55.2% of whom were non-Hispanic White and 44.8% identified as another race. Transplant recipients were a median (IQR) of 3.2 (1.1, 6.8) years from transplantation. Response differed by transplant status: 96.0% versus 43.2% by the anti-SARS-CoV-2 Total Ig (candidates vs. recipients, respectively), 93.5% versus 11.6% by the anti-SARS-CoV-2 IgG assay, and 91.9% versus 30.1% by anti-spike titers after two doses of vaccine. Multivariable analysis revealed candidates had higher likelihood of response versus recipients (odds ratio [OR], 14.6; 95 %CI 2.19, 98.11; P = .02). A slightly lower response was demonstrated in older patients (OR .96; 95 %CI .94, .99; P = .002), patients taking antimetabolites (OR, .21; 95% CI .08, .51; P = .001). Vaccination prior to transplantation should be encouraged.

Pre-transplant T-cell Clonality: An Observational Study of a Biomarker for Prediction of Sepsis in Liver Transplant Recipients.

OBJECTIVE: This study investigated the ability of pre-transplant T-cell clonality to predict sepsis after liver transplant (LT). SUMMARY BACKGROUND DATA: Sepsis is a leading cause of death in LT recipients. Currently, no biomarkers predict sepsis before clinical symptom manifestation. METHODS: Between December 2013 and March 2018, our institution performed 478 LTs. After exclusions (eg, patients with marginal donor livers, autoimmune disorders, nonabdominal multi-organ, and liver retransplantations), 180 consecutive LT were enrolled. T-cell characterization was assessed within 48 hours before LT (immunoSEQ Assay, Adaptive Biotechnologies, Seattle, WA). Sepsis-2 and Sepsis-3 cases, defined by presence of acute infection plus ≥2 SIRS criteria, or clinical documentation of sepsis, were identified by chart review. Receiver-operating characteristic analyses determined optimal T-cell repertoire clonality for predicting post-LT sepsis. Kaplan-Meier and Cox proportional hazard modeling assessed outcome-associated prognostic variables. RESULTS: Patients with baseline T-cell repertoire clonality ≥0.072 were 3.82 (1.25, 11.40; P = 0.02), and 2.40 (1.00, 5.75; P = 0.049) times more likely to develop sepsis 3 and 12 months post-LT, respectively, when compared to recipients with lower (<0.072) clonality. T-cell repertoire clonality was the only predictor of sepsis 3 months post-LT in multivariate analysis (C-Statistic, 0.75). Adequate treatment resulted in equivalent survival rates between both groups: (93.4% vs 96.2%, respectively, P = 0.41) at 12 months post-LT. CONCLUSIONS: T-cell repertoire clonality is a novel biomarker predictor of sepsis before development of clinical symptoms. Early sepsis monitoring and management may reduce post-LT mortality. These findings have implications for developing sepsis-prevention protocols in transplantation and potentially other populations.

The International Society of Renal Nutrition and Metabolism Commentary on the National Kidney Foundation and Academy of Nutrition and Dietetics KDOQI Clinical Practice Guideline for Nutrition in Chronic Kidney Disease.

The Academy of Nutrition and Dietetics and the National Kidney Foundation collaborated to provide an update to the Clinical Practice Guidelines (CPG) for nutrition in chronic kidney disease (CKD). These guidelines provide a valuable update to many aspects of the nutrition care process. They include changes in the recommendations for nutrition screening and assessment, macronutrients, and targets for electrolytes and minerals. The International Society of Renal Nutrition and Metabolism assembled a special review panel of experts and evaluated these recommendations prior to public review. As one of the highlights of the CPG, the recommended dietary protein intake range for patients with diabetic kidney disease is 0.6-0.8 g/kg/day, whereas for CKD patients without diabetes it is 0.55-0.6 g/kg/day. The International Society of Renal Nutrition and Metabolism endorses the CPG with the suggestion that clinicians may consider a more streamlined target of 0.6-0.8 g/kg/day, regardless of CKD etiology, while striving to achieve intakes closer to 0.6 g/kg/day. For implementation of these guidelines, it will be important that all stakeholders work to detect kidney disease early to ensure effective primary and secondary prevention. Once identified, patients should be referred to registered dietitians or the region-specific equivalent, for individualized medical nutrition therapy to slow the progression of CKD. As we turn our attention to the new CPG, we as the renal nutrition community should come together to strengthen the evidence base by standardizing outcomes, increasing collaboration, and funding well-designed observational studies and randomized controlled trials with nutritional and dietary interventions in patients with CKD.

Disparate outcomes observed within Kidney Disease: Improving Global Outcomes (KDIGO) acute kidney injury stage 1.

The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline classifies acute kidney injury (AKI) into 3 stages defined by serum creatinine elevation or urine output decline. We evaluated the potential impact of further categorizing AKI stage 1 into two stages based on serum creatinine criteria, with a focus on how the resulting 4-stage classification would affect the association of AKI stages with clinical outcomes. We defined AKI stage 1a as an absolute increase in serum creatinine of 0.3 mg/dl within 48 hours and stage 1b as a 50% relative increase in serum creatinine within 7 days. We screened all admissions to 5 hospitals from 2012 to 2014 using standardized inclusion and exclusion criteria and included 81,651 admissions in this retrospective cohort study. The incidence of in-hospital AKI was 7.5% for stage 1a, 4.9% for stage 1b, 1.5% for stage 2, and 0.9% for stage 3. Length of stay following the first incidence of AKI was 3.9 days for stage 1a, 6.2 days for stage 1b, 8.8 days for stage 2, and 12.0 days for stage 3. Compared to patients with no AKI, the odds of in-hospital mortality were progressively higher for patients with higher AKI stages (odds ratio 4.3 for patients with stage 1a, 10.9 for stage 1b, 40.6 for stage 2, and 60.0 for stage 3 AKI). Patients with AKI stages 1a and 1b experienced clinically meaningful and statistically significant differences in length of stay and mortality. This study suggests that a modified 4-stage version of the KDIGO AKI classification may provide additional prognostic information.

Ciprofloxacin for BK viremia prophylaxis in kidney transplant recipients: Results of a prospective, double-blind, randomized, placebo-controlled trial.

In kidney transplantation, BK virus infection has historically resulted in high rates of graft dysfunction and graft loss. Unlike other opportunistic infections, no therapies have been shown to prevent BK. The purpose of the current study was to evaluate the safety and efficacy of ciprofloxacin for the prevention of BK viremia in kidney transplant recipients. Two hundred kidney transplant recipients were enrolled in a prospective, randomized, double-blind, placebo-controlled trial comparing a 3-month course of ciprofloxacin (n = 133) vs placebo (n = 67) for the prevention of BK viremia. The primary endpoint of BK viremia at month 6 posttransplant occurred in 25 (18.8%) patients in the ciprofloxacin group and 5 (7.5%) in the placebo group (P = .03). Higher rates of BK viremia (23.3% vs 11.9%; P = .06) and BK nephropathy (5.8% vs 1.5%; P = .26) remained at 12 months in the ciprofloxacin group. Ciprofloxacin use was associated with a significantly higher rate of fluoroquinolone-resistant gram-negative infections (83.3% vs 50%; P = .04). A 3-month course of ciprofloxacin was ineffective at preventing BK viremia in kidney transplant recipients and was associated with an increased risk of fluoroquinolone-resistant infections. Clinical trial registration number: NCT01789203.

Successful Kidney Transplantation Is Associated With Weight Gain From Truncal Obesity and Insulin Resistance.

OBJECTIVE: The objective of this study is to compare changes in body composition, lifestyle factors, and metabolic responses occurring in living kidney transplant recipient patients after transplantation. DESIGN AND METHODS: The study was a single-site, prospective, observational study. To identify metabolic responses during the initial years after transplantation, we obtained state-of-the-art, high-resolution measurements of body composition from a 4-compartment model using dual-energy X-ray absorptiometry, air displacement plethysmography, and total body potassium and nitrogen counters. We also assessed dietary recalls and actigraphy before transplantation and 3- and 12-month after transplantation. The study was conducted at a quaternary care hospital outpatient transplant center and a United States Department of Agriculture Agricultural Research Service center. Thirty-one adults receiving a living donor kidney allograft were studied. The main outcome measures were change in body composition at 3 months and 1 year after transplantation, and this was correlated with the occurrence of insulin resistance. RESULTS: In patients receiving a successful kidney transplant from living donors treated with standard immunosuppression, significant increases in body weight were detected at 3 and 12 months after transplantation (2.2 kg, P = .03 and 6.6 kg, P < .0001, respectively). Weight gain was principally due to adipose tissue accumulation in the truncal region. There was no increase in muscle mass or fluid accumulation. Weight gain was not associated with changes in resting energy expenditure or physical activity. Notably, increases in visceral and subcutaneous adipose tissue were positively correlated with insulin resistance. CONCLUSION: Successful transplantation was associated with increased insulin resistance and weight gain without increases in muscle or fluid. This metabolic pattern suggests potential interventions that could prevent or mitigate the consequences of adipose tissue accumulation in transplant recipients.

Trends in laparoscopic colorectal surgery over time from 2005-2014 using the NSQIP database.

BACKGROUND: Laparoscopy, originally pioneered by gynecologists, was first adopted by general surgeons in the late 1980s. Since then, laparoscopy has been adopted in the surgical specialties and colorectal surgery for treatment of benign and malignant disease. Formal laparoscopic training became a required component of surgery residency programs as validated by the Fundamentals of Laparoscopic Surgery curriculum; however, some surgeons may be more apprehensive of widespread adoption of minimally invasive techniques. Although an overall increase in the use of laparoscopy in colorectal surgery is anticipated over a 10-year period, it is unknown if a similar increase will be seen in higher risk or more acutely ill patients. METHODS: Using the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database from 2005-2014, colorectal procedures were identified by Current Procedural Terminology codes and categorized to open or laparoscopic surgery. The proportion of colorectal surgeries performed laparoscopically was calculated for each year. Separate descriptive statistics was performed and categorized by age and body mass index (BMI). American Society of Anesthesiology (ASA) classification and emergency case status variables were added to the project to help assess complexity of cases. RESULTS: During the 10-year study period, the number of colorectal cases increased from 3114 in 2005 to 51,611 in 2014 as more hospitals joined NSQIP. A total of 277,376 colorectal cases were identified; of which, 114,359 (41.2%) were performed laparoscopically. The use of laparoscopy gradually increased each year, from 22.7% in 2005 to 49.8% in 2014. Laparoscopic procedures were most commonly performed in the youngest age group (18-49 years), overweight and obese patients (BMI 25-34.9), and in ASA class 1-2 patients. Over the 10-year period, there was a noted increase in the use of laparoscopy in every age, BMI, and ASA category, except ASA 5. The percent of emergency cases receiving laparoscopic surgery also doubled from 5.5% in 2005 to 11.5% in 2014. CONCLUSIONS: Over a 10-year period, there was a gradual increase in the use of laparoscopy in colorectal surgery. Further, there was a consistent increase of laparoscopic surgery in all age groups, including the elderly, in all BMI classes, including the obese and morbidly obese, and in most ASA classes, including ASA 3-4, as well as in emergency surgeries. These trends suggest that minimally invasive colorectal surgery appears to be widely adopted and performed on more complex or higher risk patients.