TFEB/3 govern repair Schwann cell generation and function following peripheral nerve injury.

TFEB and TFE3 (TFEB/3), key regulators of lysosomal biogenesis and autophagy, play diverse roles depending on cell type. This study highlights a hitherto unrecognized role of TFEB/3 crucial for peripheral nerve repair. Specifically, they promote the generation of progenitor-like repair Schwann cells after axonal injury. In Schwann cell-specific TFEB/3 double knock-out mice of either sex, the TFEB/3 loss disrupts the transcriptomic reprogramming that is essential for the formation of repair Schwann cells. Consequently, mutant mice fail to populate the injured nerve with repair Schwann cells and exhibit defects in axon-regrowth, target reinnervation, and functional recovery. TFEB/3 deficiency inhibits the expression of injury-responsive repair Schwann cell genes, despite the continued expression of c-Jun, a previously identified regulator of repair Schwann cell function. TFEB/3 binding motifs are enriched in the enhancer regions of injury-responsive genes, suggesting their role in repair gene activation. Autophagy-dependent myelin breakdown is not impaired despite TFEB/3 deficiency. These findings underscore a unique role of TFEB/3 in adult Schwann cells that is required for proper peripheral nerve regeneration.Significance Statement Peripheral nerves have been recognized for their efficient regenerative capabilities compared to the central nervous system neurons. This is due to the remarkable ability of Schwann cells to undergo a reprogramming process, transforming into progenitor-like repair Schwann cells that actively contribute to axon regeneration and overall nerve repair. However, the specific transcriptional regulators responsible for initiating this transformation in the adult peripheral nerve have remained elusive. Our study elucidates a previously undescribed, injury-responsive function of TFEB/3 in adult Schwann cells, showcasing its ability to promote tissue repair. Our findings hold important implications for enhancing nerve regeneration by bolstering the regenerative capacity of glial cells, thereby contributing to advancements in the field of neural tissue repair.

The Impact of Diabetes on Morbidity and Mortality Following Thyroidectomy.

OBJECTIVES: To explore the association between diabetes and outcomes in thyroidectomy patients. METHODS: This retrospective cohort analysis used the 2015-2017 American College of Surgeons National Surgery Quality Improvement Program database. Current Procedural Terminology (CPT) codes were used to identify thyroidectomy cases (60210, 60212, 60220, 60225, 60240, 60252, 60254, 60260, 60270, and 60271). Demographics, comorbidities, and complication incidences were compared between diabetic and nondiabetic patients using Pearson's chi-square test/Fisher's exact test as appropriate. The independent effect of diabetes on outcomes was analyzed using binary logistic regression. RESULTS: A total of 47,776 (95.4%) nondiabetic and 2307 (4.6%) diabetic patients undergoing thyroidectomy were identified from 2015 to 2017. Chi-square analysis demonstrated that diabetic patients had higher incidences of obesity (55.2% vs. 33.2%; p < 0.001), dyspnea (12.7% vs. 4.8%; p < 0.001), poor functional status (1.9% vs. 0.4%; p < 0.001), ventilator dependence (0.6% vs. 0.1%; p < 0.001), chronic obstructive pulmonary disease (COPD; 6.8% vs. 2.2%; p < 0.001), congestive heart failure (1.1% vs. 0.3%; p < 0.001), acute renal failure (0.3% vs. 0.0%; p < 0.001), hypertension (79.2% vs. 32.4%; p < 0.001), dialysis (2.0% vs. 0.4%; p < 0.001), open wound (1.1% vs. 0.1%; p < 0.001), steroid use (5.3% vs. 2.3%; p < 0.001), bleeding disorders (3.6% vs. 0.9%; p < 0.001), preoperative blood transfusions (0.2% vs. 0.0%; p = 0.001), and systemic sepsis (1.0% vs. 0.3%; p < 0.001). Demographic characteristics were significantly different between the cohorts including gender (p < 0.001), age (p < 0.001), race (p < 0.001), and Hispanic ethnicity (p = 0.033). After adjusting for these factors, logistic regression analyses showed that diabetes was associated with acute renal failure (OR: 5.836; 95% CI: 1.060-32.134; p = 0.043), wound disruption (OR: 6.194; 95% CI: 1.752-21.900; p = 0.005), prolonged length of stay (OR: 1.430; 95% CI: 1.261-1.622; p < 0.001), unplanned readmission (OR: 1.380; 95% CI: 1.096-1.737; p = 0.006), superficial incisional surgical site infections (OR: 0.240; 95% CI: 0.058-0.995; p = 0.049), urinary tract infection occurrences (OR: 2.173; 95% CI: 1.186-3.980; p = 0.012), organ space surgical site infection occurrences (OR: 3.322; 95% CI: 1.016-10.864; p = 0.047), pneumonia occurrences (OR: 2.091; 95% CI: 1.125-3.884; p = 0.020), any medical complication (OR: 1.697; 95% CI: 1.246-2.313; p = 0.001), and any complication (OR: 1.495; 95% CI: 1.136-1.968; p = 0.004). CONCLUSION: Diabetes mellitus is a significant factor associated with increased odds of complications following thyroidectomy. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3628-3632, 2023.

Effect of Hypoalbuminemia in Patients Undergoing Parathyroidectomy for Primary Hyperparathyroidism.

OBJECTIVES: Treatment for primary hyperparathyroidism is parathyroidectomy. This study identifies the association between hypoalbuminemia (HA) and outcomes in patients undergoing parathyroidectomy for primary hyperparathyroidism. METHODS: This retrospective cohort analysis utilized the 2006-2015 National Surgical Quality Improvement Program database. Current Procedure Terminology codes were used to identify patients undergoing parathyroidectomy for primary hyperparathyroidism. Prolonged length of stay (LOS) was defined as a duration of 2 days or greater. Demographics and comorbidities were compared between HA (serum albumin <3.5 g/dL) and non-HA cohorts using chi-square analysis. The independent effect of HA on adverse outcomes was analyzed using binary logistic regression. RESULTS: A total of 7183 cases with primary hyperparathyroidism were classified into HA (n = 381) and non-HA (n = 6802) cohorts. HA patients had increased complications, including renal insufficiency (0.8% vs. 0.0%, p = 0.001), sepsis (1.0% vs. 0.1%, p = 0.003), pneumonia (0.8% vs. 0.1%, p = 0.018), acute renal failure (1.0% vs. 0.0%, p < 0.001), and unplanned intubation (1.3% vs. 0.2%, p = 0.004). HA patients had increased risk of death (1.6% vs. 0.1%, p < 0.001), prolonged LOS (40.9% vs. 6.3%, p < 0.001), and any complication (5.5% vs. 1.2%, p < 0.001). Adjusted binary logistic regression indicated HA patients experienced increased odds of progressive renal insufficiency (OR 18.396, 95% CI 1.844-183.571, p = 0.013), prolonged LOS (OR 4.892; 95% CI 3.571-6.703; p < 0.001), unplanned reoperation (OR 2.472; 95% CI 1.012-6.035; p = 0.047), and unplanned readmission (OR 3.541; 95% CI 1.858-6.748; p < 0.001). CONCLUSIONS: HA may be associated with adverse complications in patients undergoing parathyroidectomy for primary hyperparathyroidism. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2035-2039, 2023.