Faculty Bibliography

Clinical trials in the past decade have established the antitumor effects of immune checkpoint inhibition as a revolutionary treatment for cancer. Namely, blocking antibodies to cytotoxic T-lymphocyte antigen 4 and programmed death 1 or its ligand have reached routine clinical use. Manipulation of the immune system is not without side effects, and autoimmune toxicities often known as immune-related adverse events (IRAEs) are observed. Endocrine IRAEs, such as hypophysitis, thyroid dysfunction, and insulin-dependent diabetes mellitus, can present with unique profiles that are not seen with the use of traditional chemotherapeutics. In this Review, we discuss the current hypotheses regarding the mechanism of these endocrinopathies and their clinical presentations. Further, we suggest guidelines and algorithms for patient management and future clinical trials to optimize the detection and treatment of immune checkpoint-related endocrinopathies.

Advances in cancer therapy in the past few years include the development of medications that modulate immune checkpoint proteins. Cytotoxic T-lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) are two co-inhibitory receptors that are expressed on activated T cells against which therapeutic blocking antibodies have reached routine clinical use. Immune checkpoint blockade can induce inflammatory adverse effects, termed immune-related adverse events (IRAEs), which resemble autoimmune disease. In this Review, we describe the current data regarding immune-related endocrinopathies, including hypophysitis, thyroid dysfunction and diabetes mellitus. We discuss the clinical management of these endocrinopathies within the context of our current understanding of the mechanisms of IRAEs.

OBJECTIVE: The purpose of this study was to determine if smoking status is associated with 30-day postoperative complications following radical prostatectomy. METHODS: From the American College of Surgeons National Surgical Quality Improvement Program's (NSQIP) 2005-2013 database, we identified patients who underwent prostatectomy for treatment of prostate cancer. The cohort was stratified into current smokers, former smokers, and never smokers. Bivariable and multivariable analysis was utilized to assess the association between smoking status and risk of complications. RESULTS: We identified 22,802 patients who underwent malignancy-related prostatectomy and met inclusion criteria. Based on reported smoking history, 2799 (12.3%) were current smokers, 1879 (8.2%) were former smokers, and 18,124 (79.5%) were never smokers. Current smokers had a higher rate of total complications (5.7%) in comparison with former (4.8%) and never smokers (4.6%; P = .050). Postoperative pneumonia was more frequent in current smokers (0.4%) compared with former smokers (0.2%) and never smokers (0.2%; P = .039). Unplanned intubation occurred more frequently in current smokers (0.4%) when compared with former smokers (0.3%) and never smokers (0.1%; P = .002). Multivariable analysis found that current smoking status was an independent predictor of an increased risk of unplanned intubation (odds ratio, 5.87; 95% confidence interval, 2.18-15.8; P < .001). CONCLUSION: Smoking status influences the risk of postoperative complications following prostatectomy. Specifically, current smoking status is an independent predictor of unplanned intubation within 30 days of the procedure.

PURPOSE/OBJECTIVE:To evaluate the relative axonal match between potential donor and recipient nerves, so that maximal reinnervation potential may be reached with the least chance of donor site morbidity. METHODS:In 10 fresh-frozen cadaveric specimens, the main trunk and anterior, posterior, sensory and teres minor branches of the axillary nerve were identified, as were the radial nerve branches to the long, medial, and lateral heads of the triceps. The swing distances of the triceps fascicular nerve branches and the axillary nerve branches relative to the inferior border of the teres major muscle were recorded. Histomorphological analysis and axon counts were performed on sections of each branch. RESULTS:The median number of axons in the main axillary trunk was 7,887, with 4,052, 1,242, and 1,161 axons in the anterior, posterior, and teres minor branches, respectively. All specimens had a single long head triceps branch (median, 2,302 axons), a range of 1 to 3 branches to the medial head of the triceps (composite axon count, 2,198 axons), and 1 to 3 branches to the lateral head of the triceps (composite average, 1,462 axons). The medial and lateral head branches had sufficient swing distance to reach the anterior branch of the axillary nerve in all 10 specimens, with only 4 specimens having adequate long head branch swing distances. CONCLUSIONS:It is anatomically feasible to transfer multiple branches of the radial nerve supplying the medial, lateral, and sometimes, long head of the triceps to all branches of the axillary nerve in an attempt to reinnervate the deltoid and teres minor muscles. CLINICAL RELEVANCE/CONCLUSIONS:Understanding the axon counts of the different possible transfer combinations will improve operative flexibility and enable peripheral nerve surgeons to reinnervate for both abduction and external rotation with the highest donor/recipient axon count ratios.

PURPOSE: To assess the results of a hybrid Russe procedure using a corticocancellous strut, cancellous autologous nonvascularized bone graft, and cannulated headless compression screw to reduce the deformity reliably from a collapsed scaphoid nonunion, provide osteoinductive stimulus, and stabilize the fracture for predictable union. METHODS: A hybrid Russe procedure was performed for scaphoid waist fracture nonunions with humpback deformity and no evidence of avascular necrosis. A volar distal radius autologous bone graft was harvested and a strut of cortical bone was fashioned and placed into the nonunion site to restore length and alignment. We packed cancellous bone graft in the remainder of the nonunion site and fixed the scaphoid was with a headless compression screw. Union was determined by radiographs or computed tomography, and intrascaphoid, scapholunate, and radiolunate angles were calculated on final radiographs. We recorded wrist range of motion, grip strength, pinch strength, pain, and complications. RESULTS: Fourteen male and 3 female patients (average age, 32 years; range, 16-78 years), with a mean follow-up of 32 months, were examined clinically and radiographically. All 17 scaphoids united with a mean time for union of 3.6 months. The mean postoperative intrascaphoid angle was significantly reduced from 65 degrees preoperatively to 35 degrees postoperatively. The mean radiolunate angle was significantly improved from 20 degrees from neutral (lunate tilted dorsally) preoperatively to 0 degrees postoperatively. The scapholunate angle also demonstrated significant improvement from 70 degrees preoperatively to 56 degrees postoperatively. Grip strength improved from 70% of the contralateral hand to 89% after the procedure. All patients were satisfied with the functional outcome and no donor site morbidity or hardware issues were identified. CONCLUSIONS: This straightforward hybrid Russe technique predictably restored radiolunate, scapholunate, and intrascaphoid angles with a 100% union incidence. The technique provides excellent functional results in patients with a challenging clinical problem, and we recommend it for scaphoid fracture waist nonunions with dorsal intercalated segment instability deformity. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

BACKGROUND:Nerve transfer surgery has revolutionized the management of traumatic brachial plexus injures. However, the optimal size ratio of donor to recipient nerve has yet to be elucidated. The authors investigated the axon count ratios of ulnar and median fascicular transfers to restore elbow flexion. The authors hypothesized that donor nerve axon counts would be correlated with historical success of various nerve transfers used to restore elbow flexion. METHODS:Ten cadaveric specimens were used for a histomorphologic analysis of fascicular nerve transfers. Review of previously published axon counts and clinical results following transfer to the musculocutaneous nerve to restore elbow flexion was performed for the following donor nerves: medial pectoral, spinal accessory, intercostal, thoracodorsal, ulnar, and median fascicular. RESULTS:The average number of fascicles identified was 7.9 in the ulnar nerve and 8.0 in the median nerve. The mean fascicular axon count was 1318 for the ulnar nerve and 1860 for the median nerve. Mean recipient nerve axon count was 1826 for the musculocutaneous biceps branch and 1840 for the brachialis branch. A significant correlation between axon count and clinical results of transfers to restore elbow flexion was observed. Donor-to-recipient nerve axon count ratios below 0.7:1 were associated with a decreased likelihood of a successful outcome. CONCLUSIONS:In nerve transfers to restore elbow flexion, an appropriate size match between donor and recipient nerves appears to be a factor affecting clinical success. These data support a donor-to-recipient axon count ratio greater than 0.7:1 as the goal for brachial plexus nerve transfers to restore elbow flexion.