Development of donor specific antibodies after SARS-CoV-2 vaccination in kidney and heart transplant recipients.

This study examined the development of new or changes in donor specific antibodies (DSA) mean-fluorescence intensity (MFI) after SARS-CoV-2 vaccination in 100 kidney and 50 heart transplant recipients. The study was performed when the Center for Disease Control and Prevention (CDC) recommended two doses of Pfizer/BioNTech [BNT162b2] and Moderna [mRNA-1273 SARS-CoV-2] vaccine or 1 dose Johnson & Johnson/Janssen [Ad26.COV2·S] vaccines for full vaccination in transplant recipients. A novel assay bead-based platform for detecting antibodies against 4 domains of the SARS-CoV-2 spike protein to determine vaccine response (SA) and one nucleocapsid protein (NC) to determine prior SARS-CoV-2 infection was utilized. These assays were performed on the multiplex, bead-based platform utilized to assay DSA levels. 61/150 patients (40.7%) had successful vaccination. 18 patients had confirmed SARS-CoV-2 infection based on positive NC assay or previous Covid-19 oropharyngeal swab. 138 patients had no DSA prior to vaccination but 3 heart recipients developed new DSA's. Among 12 patients with known DSA prior to vaccination, 4 developed new DSA's or increased MFI. All 7 patients with new or increased DSA had stable graft function without rejection and had no changes in immunosuppression. All 8 patients with stable post vaccine DSA had stable graft function and immunosuppression was not changed. The presence of DSA before vaccination was associated with subsequent development of increased MFI or new DSA's (p = 0.001). There was no association between pre-vaccine DSA and positive vaccine response (NS). There was no association with successful vaccination or prior SARS-CoV-2 infection and DSA changes (NS).

Arthroscopic Versus Open Ankle Arthrodesis: A 5-Year Follow Up.

BACKGROUND: End-stage ankle arthritis has long been managed surgically with open ankle arthrodesis (OAA). Since the first published report in 1983, arthroscopic ankle arthrodesis (AAA) has been thought to be associated with improved patient-reported outcome measures (PROMs) and fewer complications. The purpose of the present study was to compare the long-term PROMs, major complications, and reoperations for these 2 approaches at up to 15 years of follow-up. METHODS: This longitudinal cohort study included patients at our institution who underwent primary ankle arthrodesis for the treatment of end-stage arthritis. Demographic data and preoperative COFAS (Canadian Orthopaedic Foot and Ankle Society) ankle arthritis type were collected for all patients. PROMs were completed preoperatively, at 6 months, and annually thereafter to 5 years. PROMs were compared at all time points with use of a mixed-effects regression model that adjusted for preoperative variables and scores. Major complications and reoperations at the site of the ankle arthrodesis were also compared. RESULTS: Of 1,294 patients who were screened for inclusion, 351 who had undergone ankle arthrodesis between 2003 and 2019 were eligible for the study. Of those, 223 had undergone AAA and 128 had undergone OAA. The 2 groups were similar preoperatively with respect to demographics, but COFAS Type-4 arthritis was relatively more common in the OAA group and Type-1 arthritis was relatively more common in the AAA group. In addition, the Ankle Osteoarthritis Scale (AOS) score and Ankle Arthritis Score (AAS) were better in the AAA group. In the mixed-effects model analysis, the differences in postoperative outcome scores between the groups were not significant. The risk of revision due to malunion or nonunion was similar in both groups (6% in the AAA group, compared with 4% in the OAA group). Deep infection and wound complications did not occur in the arthroscopic group but occurred in 4% of the patients in the OAA group. CONCLUSIONS: After adjustment for baseline patient characteristics, there were no differences in PROMs between the 2 techniques. Ankle arthrodeses done arthroscopically had a similar revision rate but lower infection rate compared with those done with the open technique. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Single-Dose Anti-Thymocyte Globulin Compared With Divided-Dose for Induction Therapy in Kidney Transplantation in a Predominantly Black Population.

BACKGROUND: The aim of this study was to compare single-dose rabbit anti-thymocyte globulin (rATG) with a divided dose in kidney transplant recipients within a majority Black patient population. METHODS: We analyzed the outcomes before and after a change in protocol from divided-dose (1.5 mg/kg/day over 4 days) to single-dose (6 mg/kg over 24 hours) rATG in a retrospective cohort study. All patients who received rATG for kidney transplant induction between December 2015 and July 2018 were included. RESULTS: A total of 197 patients (n = 98 in the divided-dose group, n = 99 in the single-dose group) received rATG. There was no difference in time to rejection at 1 year (P = .82) or incidence of rejection (P = .80). There was also no difference in delayed graft function, serum creatinine, or survival at 1 year. Patients in the single-dose group were more likely to leave the hospital by postoperative day 3 (12% vs 2%, P = .006). The cytomegalovirus infection rate was higher in the single-dose group (P = .031). CONCLUSIONS: Use of a single-dose rATG regimen is an acceptable accelerated induction compared with the standard divided dose for induction therapy in kidney transplant in a predominantly Black population.

Variability in the Reporting Terminology of Adverse Events and Complications in Ankle Fracture Fixation: A Systematic Review.

BACKGROUND: Classification systems for the reporting of surgical complications have been developed and adapted for many surgical subspecialties. The purpose of this systematic review was to examine the variability and frequency of reporting terms used to describe adverse events and complications in ankle fracture fixation. We hypothesized that the terminology used would be highly variable and inconsistent, corroborating previous results that have suggested a need for standardized reporting terminology in orthopedics. METHODS: Ankle fracture outcome studies meeting predetermined inclusion and exclusion criteria were selected for analysis by 2 independent observers. Terms used to define adverse events and complications were identified and recorded. Discrepancies were resolved by consensus with the aid of a third observer. All terms were then compiled and assessed for variability and frequency of use throughout the studies involved. Reporting terminology was subsequently grouped into 10 categories. RESULTS: In the 48 studies analyzed, 301 distinct terms were utilized to describe complications or adverse events. Of these terms, 74.4% (224/301) were found in a single study each. Only 1 term, "infection," was present in 50% of studies, and only 19 of 301 terms (6.3%) were used in at least 10% of papers. The category that was most frequently reported was "infection," with 89.6% of studies reporting on this type of adverse event using 25 distinct terms. Other categories were "wound healing complications" (72.9% of papers, 38 terms), "bone/joint complications" (66.7% of papers, 35 terms), "hardware/implant complications" (56.3% of papers, 47 terms), "revision" (56.3% of papers, 35 terms), "cartilage/soft tissue injuries" (45.8% of papers, 31 terms), "reduction/alignment issues" (45.8% of papers, 29 terms), "medical complications" (43.8% of papers, 32 terms), "pain" (29.2% of papers, 16 terms), and "other complications" (20.8% of papers, 13 terms). There was a 78.6% interobserver agreement in the identification of terms across the 48 studies included. CONCLUSION: The reporting terminology utilized to describe complications and adverse events in ankle fracture fixation was found to be highly variable and inconsistent. This variability prevents accurate reporting of complications and adverse events and makes the analysis of potential outcomes difficult. The development of standardized reporting terminology in orthopedics would be instrumental in addressing these challenges and allow for more accurate and consistent outcome reporting. LEVEL OF EVIDENCE: Level III; systematic review of Level III studies and above.

ESRD impairs nonrenal clearance of fexofenadine but not midazolam.

ESRD can affect the pharmacokinetic disposition of drugs subject to nonrenal clearance. Cytochrome P450 (CYP) enzymes, including CYP3A, and multiple intestinal and hepatic drug transporters are thought to mediate this process, but the extent to which kidney disease alters the function of these proteins in humans is unknown. We used midazolam and fexofenadine to assess CYP3A (intestinal and hepatic) and drug transport, respectively, in patients with ESRD and healthy control subjects. We evaluated the effect of uremia on CYP3A and transporter expression in vitro by incubating normal rat hepatocytes and enterocytes with serum drawn from study participants. ESRD dramatically reduced nonrenal transporter function, evidenced by a 63% decrease in clearance (P < 0.001) and a 2.8-fold increase in area under the plasma concentration-time curve for fexofenadine (P = 0.002), compared with control subjects. We did not observe significant differences in midazolam or 1'-hydroxymidazolam clearance or area under the curve after oral administration, suggesting that CYP3A function is not changed by ESRD. Changes in hepatocyte and enterocyte protein expression in the presence of uremic serum were consistent with in vivo results. These findings demonstrate a mechanism for altered drug disposition in kidney disease, which may partially account for the high rates of drug toxicity in this population.