J Shin, Junghee

Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), is characterized by lifelong immune dysregulation leading to high rates of autoimmune disorders, elevated risk of complications from infections, immune hypersensitivity, and a unique form of immunodeficiency. It is now appreciated that DS shares key hallmarks with interferonopathies, with vast remodeling of all branches of the immune system, hypercytokinemia, and widespread autoantibody production. Here within, we review the existing literature with an emphasis on clinical considerations toward monitoring, management, and therapeutic opportunities. We highlight recent research advances that illuminate diagnostic approaches to evaluate immune dysregulation in DS. We also discuss the evidence supporting specific immunomodulatory strategies that could have multidimensional benefits in this population, including JAK inhibitors, intravenous immunoglobulin, and B cell–depleting agents.

Importance A greater proportion of older patients (age ≥65 years) are undergoing thyroidectomy amidst an aging population. Given the elusive results in the literature, clarifying whether older patients face different thyroidectomy safety profiles is crucial for optimizing risk assessment and patient counseling. Objective To evaluate the association between older age (age ≥65 years) and thyroidectomy safety by comparing endocrine-related complications, including recurrent laryngeal nerve injury, hypocalcemia, hematoma, and mortality in older compared with younger patients. Data Sources Ovid MEDLINE, CINAHL, Ovid Embase, and the Cochrane Library were systematically searched from inception to May 29, 2025; only English-language studies were included. Study Selection Cohort studies comparing thyroidectomy outcomes between older and younger patients and reporting endocrine-related complications were included. Two independent reviewers screened abstracts and full texts. Of 3192 studies identified, 11 met inclusion criteria. Data Extraction and Synthesis Two independent reviewers extracted data following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Risk of bias across studies was evaluated using the ROBINS-I (Risk of Bias in Nonrandomized Studies of Interventions) tool. Random-effects models were used to pool data. Main Outcomes and Measures Incidence of recurrent laryngeal nerve injury, hypocalcemia, and hematoma; odds ratios (ORs) with 95% CIs were calculated. Results The analysis included 11 studies with a total of 427 886 patients of whom 104 232 (24.4%) were older adults (≥65 years). Older adults had greater odds of overall recurrent laryngeal nerve injury (2.3% vs 1.0%; OR, 1.58; 95% CI, 1.15-2.16; I 2 = 76%), hematoma (2.4% vs 1.0%; OR, 2.32; 95% CI, 1.70-3.16; I 2 = 0%), and mortality at last follow-up (0.3% vs 0.01%; OR, 11.09; 95% CI, 1.77-69.52; I 2 = 90%) compared with younger patients. However, rates of overall hypocalcemia (OR, 0.80; 95% CI, 0.61-1.05; I 2 = 71%) and wound complications (OR, 1.38; 95% CI, 0.92-2.06; I 2 = 0%) were similar. Conclusions and Relevance This systematic review and meta-analysis found that thyroidectomy is safe in older patients, with only small absolute increases in recurrent laryngeal nerve injury, hematoma, and mortality despite statistical significance. These findings support individualized counseling and perioperative planning while acknowledging the overall safety of thyroidectomy in this population.