A report of a prospective randomized trial of extended-release tacrolimus versus immediate release tacrolimus after liver transplantation with anti-thymocyte induction in a steroid free protocol.

PURPOSE: Our study hypothesis was that once daily dosing of extended-release tacrolimus (XRT) would be a safe and effective immunosuppression (IS) with the potential to decrease adverse events (AEs) associated with immediate release tacrolimus (IRT) after liver transplantation (LT). METHODS: All patients receiving LT at our center received rabbit anti-thymocyte globulin (RATG) induction therapy. Eligible patients were randomized in a 1:1 fashion to receive either XRT or IRT. Antimicrobial prophylaxis was the same between arms, and both groups received an antimetabolite for the first 6 months following LT. Patients were then followed at pre-determined study intervals for the following year after LT. We administered the RAND-36SF survey to assess patient's health-related quality of life at pre-determined intervals. All analysis was performed with an intention to treat basis. RESULTS: We screened 194 consecutive patients and enrolled 110. Our control and study arms were well matched. Transplant characteristics were similar between groups. At all timepoints, both arms had similar serum creatinine and estimated glomerular filtration rate (eGFR), calculated by MDRD6 equation, with post-transplant GFRs between 60 and 70 mL/min/1.73 m2 . Tacrolimus trough levels were similar between arms. The XRT arm had fewer AEs (166) and fewer serious AEs (70) compared to IRT (201 and 99, respectively). AEs most commonly were renal, infectious, or gastrointestinal in nature. While not statistically significant, XRT was held temporarily (25 vs. 35 cases) or discontinued (3 vs. 11 cases) less frequently than IRT and had fewer instances of rejection (7 vs. 12 cases). CONCLUSION: This analysis showed that XRT is safe and effective as de novo maintenance IS in a steroid-free protocol with RATG.

The utility of intraoperative nerve monitoring in secondary and tertiary Hyperparathyroid surgery.

OBJECTIVES: Recurrent laryngeal nerve (RLN) injury is a well-known complication of parathyroid surgery. Despite ample data, there is still uncertainty about the role of intraoperative monitoring (IONM) in mitigating RLN damage. STUDY DESIGN: A retrospective review. METHODS: We included all patients presenting for total, subtotal, or completion parathyroidectomy at a tertiary referral hospital from 2013 to 2018. Information about demographics, previous neck surgery, perioperative data, pathology, and possible RLN injury was collected. Two groups were formed for analysis: IONM vs. nonmonitored (NM). RESULTS: 105 patients underwent 107 surgeries with IONM utilized in 71 cases. The groups were similar in demographics, but significantly differed (all P < 0.05) in preincision parathyroid hormone level (IONM = 2091.44 vs NM = 1334.87), surgery type (IONM = 62.9% vs NM = 27.8% subtotal), and surgery length in minutes (IONM = 155.21 vs NM = 182.22). We observed six cases (6/71 = 8.45%) of persistent RLN complaints (three or more weeks postoperatively) and four cases (4/71 = 5.63%) of temporary complaints with the use of IONM compared with only one temporary complaint (1/36 = 2.78%) in unmonitored procedures (P = 0.129). CONCLUSIONS: These results suggest that the use of IONM does not provide a protective effect on the RLN in patients with secondary or tertiary hyperparathyroidism undergoing total, subtotal, or completion parathyroidectomy. Prospective, randomized studies with pre- and postoperative flexible laryngoscopy are needed to explore the use of IONM in this patient population further.

Transplantation of kidneys from hepatitis C-infected donors to hepatitis C-negative recipients: Single center experience.

Our aim was to evaluate the safety of transplanting kidneys from HCV-infected donors in HCV-uninfected recipients. Data collected from 53 recipients in a single center, observational study included donor and recipient characteristics, liver and kidney graft function, new infections and de novo donor-specific antibodies and renal histology. Treatment with a direct-acting antiviral regimen was initiated when HCV RNA was detected. The mean ± SD age of recipients was 53 ± 11 years, 34% were female, 19% and 79% of recipients were white and African American, respectively. The median and interquartile range (IQR) time between transplant and treatment initiation was 76 (IQR: 68-88) days. All 53 recipients became viremic (genotype: 1a [N = 34], 1b [N = 1], 2 [N = 3], and 3 [N = 15]). The majority (81%) of recipients did not experience clinically significant increases (>3 times higher than upper limit of the normal value) in aminotransferase levels and their HCV RNA levels were in the 5 to 6 log range. One patient developed fibrosing cholestatic hepatitis with complete resolution. All recipients completed antiviral treatment and 100% were HCV RNA-negative and achieved 12-week sustained virologic response. The estimated GFRs at end of treatment and 12-week posttreatment were 67 ± 21 mL/min/1.73 m2 and 67 ± 17 mL/min/1.73 m2 , respectively. Four recipients developed acute rejection. Kidney transplantation from HCV-infected donors to HCV-negative recipients should be considered in all eligible patients.

A technique for the salvage of megafistulas allowing immediate dialysis access.

OBJECTIVE: Almost two million individuals are undergoing renal replacement therapy worldwide, with hemodialysis being the common form. Many factors influence the primary patency of an arteriovenous fistula (AVF), including vessel size, fistula flow rates, cannulation practice, and thrombotic tendencies. Excess dilation of the AVF, resulting in the development of a megafistula, is a complication that can result in a need for AVF revision and subsequent failure. METHODS: The charts of patients who underwent autogenous AVF revision because of the development of a megafistula with aneurysmectomy and vein transposition by a single surgeon during a 7-year period from 2009 through 2016 were reviewed. A technique is described in which after aneurysmorrhaphy, the repaired venous component of the AVF is transposed through a new tunnel while the vein is rotated 90 degrees. This allows the AVF to be accessed immediately, making placement of a tunneled dialysis catheter unnecessary. RESULTS: There were 102 patients included in the study, with follow-up ranging from 7 to 95 months. In our cohort, 92 of the 102 revised AVFs (90.2%) maintained primary functional patency. Of the 102 patients who underwent this revision technique, there were 10 fistulas that subsequently failed after a mean of 29 months. There were only seven patients who experienced recurrent fistula dilation requiring repeated aneurysmectomy. CONCLUSIONS: We describe a technique for management of the development of a megafistula that uses only autogenous tissue and, perhaps most important, eliminates the need for temporary dialysis catheter placement.

Prospective observational study of sirolimus as primary immunosuppression after renal transplantation.

BACKGROUND.: Sirolimus (SRL) is an important component of clinical immunosuppression in renal transplantation, but few international studies have examined how this agent is used in routine practice. METHODS.: Within a large prospective pharmacoepidemiological study, 718 de novo renal graft recipients treated with SRL in 65 centers in 10 countries were monitored for up to 5 years posttransplant to compare the principal outcomes and adverse effects by treatment regimen. RESULTS.: Principal treatment regimens were SRL without a calcineurin inhibitor (33%), SRL+cyclosporine A (CsA) (33%), and SRL+tacrolimus (TAC) (34%); 18% of subjects discontinued SRL, 124/718 (17%) developed biopsy-confirmed acute rejection (BCAR), 64/718 (9%) lost their graft, and 50/718 (7%) died during follow-up. Calculated creatinine clearance was 66+/-26 mL/min at 2 years. The most common adverse events were hypertension, hyperlipidemia, anemia, urinary tract infections, and diabetes. BCAR was significantly lower in subjects receiving SRL+TAC (hazard ratio [HR] 0.46, P=0.009) but not significantly lower in those receiving SRL+CsA (HR 0.62, P=0.102) compared with SRL without a calcineurin inhibitor. Graft loss or death did not significantly differ between treatment groups but were associated, respectively, with deceased donor grafts (HR 3.33, P<0.001) and increased age (HR 1.04, P<0.001). No improvement was observed in patients receiving mycophenolate mofetil in any treatment combination (HR 0.80, P=0.438 for BCAR; HR 0.93, P=0.849 for graft loss; and HR 0.75, P=0.531 for death). CONCLUSIONS.: SRL is most commonly used in combination with mycophenolate mofetil, CsA, or TAC. BCAR was least common in subjects receiving SRL+TAC, but other outcomes seemed comparable between the treatment regimens in routine practice.

Foregut cystic developmental malformation: new taxonomy and classification--unifying embryopathological concepts.

Foregut cystic developmental malformations are rare developmental anomalies. The problems inherent to these malformations are their presentation across specialties that include embryology, anatomy, pathology, thoracic foregut surgery, pediatric surgery and general abdominal surgery. The direct consequence of this variation has resulted in diverse terminology, classification and a failure to identify the correlation. The article aims to summarize and unify the embryological concepts of foregut cystic malformation, to suggest a generic title to the various groups of these interrelated disorders and a uniform use of nomenclature on the basis of unifying concepts of embryopathogeneis.

Comparison of sirolimus-based calcineurin inhibitor-sparing and calcineurin inhibitor-free regimens in cadaveric renal transplantation.

INTRODUCTION: This study examines the efficacy and toxicity of sirolimus used as primary immunosuppression in combination with reduced dose tacrolimus (calcineurin inhibitor [CI]-sparing regimen) or mycophenolate mofetil (CI-free regimen) in high-risk cadaveric renal transplantation. METHODS: Seventy subjects were treated in a quadruple sequential protocol in which 41 were treated with a CI-sparing regimen and 29 were treated with a CI-free regimen. The efficacy and toxicity profiles of these regimens were prospectively monitored and compared. RESULTS: The study consisted of African Americans (71%), cadaveric donors (100%), donors aged more than 50 years (30%), and patients with delayed graft function (47%). At 1 year, patient survival, graft survival, and incidence of biopsy-proven acute rejection were 98%, 80%, and 10%, respectively, in the CI-sparing group and 100%, 89%, and 7%, respectively, in the CI-free group. Three-month protocol biopsies were performed in 41% (17/41) and 67% (20/29) of the subjects in the CI-sparing and CI-free groups, respectively. Subclinical rejection was detected in 6% (1/17) and 15% (3/20) of the subjects in the CI-sparing and CI-free groups, respectively. Histologic evidence of chronic allograft nephropathy was more prevalent in the CI-sparing group. At 1 year, the mean estimated creatinine clearance was higher in the CI-free group than in the CI-sparing group (72.4 +/-20.0 mL/min vs. 50.5 +/-20.8 mL/min, P <0.01). The two regimens had similar toxicity profiles (hospital readmission, infection, wound complications, and metabolic complications). CONCLUSIONS: Both sirolimus-based CI-sparing and CI-free regimens are safe and effective in a population with high immunologic risk. The CI-free regimen is associated with better renal function at 1 year post-transplant. Long-term follow-up will aid in determining the risk and benefit ratio of these regimens.