Background: Privacy restrictions limit access to protected patient-derived health information for research purposes. Consequently, data anonymization is required to allow researchers data access for initial analysis before granting institutional review board approval. A system installed and activated at our institution enables synthetic data generation that mimics data from real electronic medical records, wherein only fictitious patients are listed. Objective: This paper aimed to validate the results obtained when analyzing synthetic structured data for medical research. A comprehensive validation process concerning meaningful clinical questions and various types of data was conducted to assess the accuracy and precision of statistical estimates derived from synthetic patient data. Methods: A cross-hospital project was conducted to validate results obtained from synthetic data produced for five contemporary studies on various topics. For each study, results derived from synthetic data were compared with those based on real data. In addition, repeatedly generated synthetic datasets were used to estimate the bias and stability of results obtained from synthetic data. Results: This study demonstrated that results derived from synthetic data were predictive of results from real data. When the number of patients was large relative to the number of variables used, highly accurate and strongly consistent results were observed between synthetic and real data. For studies based on smaller populations that accounted for confounders and modifiers by multivariate models, predictions were of moderate accuracy, yet clear trends were correctly observed. Conclusions: The use of synthetic structured data provides a close estimate to real data results and is thus a powerful tool in shaping research hypotheses and accessing estimated analyses, without risking patient privacy. Synthetic data enable broad access to data (eg, for out-of-organization researchers), and rapid, safe, and repeatable analysis of data in hospitals or other health organizations where patient privacy is a primary value.

PURPOSE: Current guidelines for the management of metastatic non–small cell lung cancer (NSCLC) without driver mutations recommend checkpoint immunotherapy with PD-1/PD-L1 inhibitors, either alone or in combination with chemotherapy. This approach fails to account for individual patient variability and host immune factors and often results in less-than-ideal outcomes. To address the limitations of the current guidelines, we developed and subsequently blindly validated a machine learning algorithm using pretreatment plasma proteomic profiles for personalized treatment decisions. PATIENTS AND METHODS: We conducted a multicenter observational trial (ClinicalTrials.gov identifier: NCT04056247 ) of patients undergoing PD-1/PD-L1 inhibitor–based therapy (n = 540) and an additional patient cohort receiving chemotherapy (n = 85) who consented to pretreatment plasma and clinical data collection. Plasma proteome profiling was performed using SomaScan Assay v4.1. RESULTS: Our test demonstrates a strong association between model output and clinical benefit (CB) from PD-1/PD-L1 inhibitor–based treatments, evidenced by high concordance between predicted and observed CB ( R² = 0.98, P < .001). The test categorizes patients as either PROphet-positive or PROphet-negative and further stratifies patient outcomes beyond PD-L1 expression levels. The test successfully differentiates between PROphet-negative patients exhibiting high tumor PD-L1 levels (≥50%) who have enhanced overall survival when treated with a combination of immunotherapy and chemotherapy compared with immunotherapy alone (hazard ratio [HR], 0.23 [95% CI, 0.1 to 0.51], P = .0003). By contrast, PROphet-positive patients show comparable outcomes when treated with immunotherapy alone or in combination with chemotherapy (HR, 0.78 [95% CI, 0.42 to 1.44], P = .424). CONCLUSION: Plasma proteome–based testing of individual patients, in combination with standard PD-L1 testing, distinguishes patient subsets with distinct differences in outcomes from PD-1/PD-L1 inhibitor–based therapies. These data suggest that this approach can improve the precision of first-line treatment for metastatic NSCLC.

This study investigates the long-term efficacy of carpal tunnel release surgery (CTR) on patient outcomes. We aimed to assess symptom severity, functional limitations, and quality of life in a large cohort (n = 186) at least five years post-surgery via a retrospective cross-sectional design that evaluated participants using the validated Boston Carpal Tunnel Questionnaire (BCTQ) over a phone interview. The BCTQ measures symptom severity, functional limitations, and quality of life specific to carpal tunnel syndrome. Seventy-three percent (73.1%) of patients reported complete resolution of symptoms and functional limitations (BCTQ = 1) with an average follow-up of 11 years. No statistically significant decline in BCTQ scores was observed over time. Univariate analysis revealed a significant association between poorer outcomes and older age at surgery and current unemployment. Carpal tunnel release surgery demonstrates long-term effectiveness in relieving symptoms and improving function in most patients. These findings contribute to the understanding of CTR’s impact on patient well-being beyond short-term outcomes.

Key Points: CKD was undiagnosed in 56% of patients and linked to early mortality, kidney failure, and cardiovascular events despite milder disease. First-year mortality was two-fold higher among undiagnosed patients, emphasizing the short-term risks of missed diagnosis. Sodium-glucose cotransporter 2 inhibitors were associated with better cardiovascular and kidney outcomes, yet their uptake remained low. Background: CKD is a global public health challenge, yet underdiagnosis in routine care remains pervasive, leading to missed opportunities for early intervention. Evidence directly linking missed diagnosis to adverse outcomes in large, nationwide populations is limited. Methods: We conducted a nationwide, population-based cohort study including 640,217 adults meeting Kidney Disease Improving Global Outcomes (KDIGO) laboratory criteria for CKD (eGFR30 mg/g on at least two occasions ≥3 months apart) between 2000 and 2023. CKD underdiagnosis was defined as absence of a documented diagnosis in electronic medical records. The primary end point was a composite of all-cause mortality or KRT. Secondary end points included first-year mortality and time to all-cause mortality, KRT, and major cardiovascular events. Associations were assessed using multivariable Cox proportional hazards models, stratified by diabetes status, with additional propensity score–matched sensitivity analyses. Results: Of 640,217 patients who met laboratory criteria for CKD, 359,805 (56%) lacked a documented diagnosis. Undiagnosed patients were younger, more often female, and disproportionately from minoritized populations. Absence of a CKD diagnosis was associated with a markedly shorter time to death or KRT (hazard ratio, 1.10; 95% confidence intervals [CI], 1.09 to 1.11). First-year mortality was higher in undiagnosed versus diagnosed CKD (8.0% [95% CI, 7.9 to 8.1] versus 4.1% [95% CI, 4.0 to 4.2]), despite less advanced disease at baseline. Use of renoprotective and cardioprotective medications was significantly lower in undiagnosed patients. Sodium-glucose cotransporter 2 (SGLT2) inhibitor therapy was independently associated with lower risks of death, kidney failure, and cardiovascular events, showing a consistent protective effect in both diabetic and nondiabetic subgroups. Findings were consistent across sensitivity analyses. Conclusions: In this real-world nationwide CKD cohort, underdiagnosis was common and associated with premature death, kidney failure, and cardiovascular morbidity. There was consistent association of SGLT2 inhibitors with better cardiovascular and kidney health outcomes.

Variants in the Apolipoprotein L1 (APOL1) gene (G1-rs60910145, rs73885319, G2-rs71785313) are common in Africans and in individuals of recent African ancestry and are associated with an increased risk of non-diabetic chronic kidney disease (CKD) and in particular of HIV associated nephropathy (HIVAN). In light of the significantly increased risk of HIVAN in carriers of two APOL1 risk alleles, a role in HIV infectivity has been postulated in the mechanism of APOL1 associated kidney disease. Herein, we aim to explore the association between HIV viremia and APOL1 genotype. In addition, we investigated interaction between BK and JC viruria, CKD and HIV viremia. A total of 199 persons living with HIV/AIDS (comprising 82 CKD cases and 117 controls) from among the participants in the ongoing Human Heredity and Health in Africa (H3Africa) Kidney Disease Research Network case control study have been recruited. The two APOL1 renal risk alleles (RRA) genotypes were associated with a higher risk of CKD (OR 12.6, 95% CI 3.89–40.8, p < 0.0001). Even a single APOL1 RRA was associated with CKD risk (OR 4.42, 95% CI 1.49–13.15, p = 0.007). The 2 APOL1 RRA genotypes were associated with an increased probability of having HIV viremia (OR 2.37 95% CI 1.0–5.63, p = 0.05). HIV viremia was associated with increased CKD risk (OR 7.45, 95% CI 1.66–33.35, P = 0.009) and with a significant reduction of JC virus urine shedding (OR 0.35, 95% CI 0.12–0.98, p = 0.046). In contrast to prior studies, JC viruria was not associated with CKD but was restricted in patients with HIV viremia, regardless of CKD status. These findings suggest a role of APOL1 variants in HIV infectivity and emphasize that JC viruria can serve as biomarker for innate immune system activation.

With an aging population, multiple myeloma (MM) increasingly affects octogenarians (Octos; age of ≥80 years), yet data on their management and outcomes, particularly if treated outside clinical trials, remain limited. This retrospective study analyzed 652 patients aged ≥70 years, diagnosed with active MM between 2014 and 2023, identified in the Maccabi Healthcare Services medical records. Patient characteristics, treatment, time to next treatment (TTNT), overall survival (OS), and factors influencing outcomes, were compared between Octo and older adults (OL) aged 70 to <80 years. Octo patients (median age, 83 years) had more comorbidities and higher Charlson Comorbidity Index (CCI) scores than OL patients (≥6; 53% vs 23%), leading to lower rates of anti-MM therapy administration and reduced triplet/quadruplet regimen use. Over a median follow-up of 25 months, Octo patients had significantly shorter median OS; 25.9 vs 71.3 months, and 33 vs 76.9 months among treated patients only. TTNT was similar (17.8 vs 22.1 months). Multivariate analysis showed that triplet/quadruplet regimen was associated with improved TTNT (hazard ratio [HR], 0.61; P < .001) and OS (HR, 0.63; P < .001) compared with doublets, whereas higher CCI scores and age of ≥80 years predicted worse OS (HR, 1.5; P = .003; and HR, 2.27; P < .001; respectively). Daratumumab-based therapies enhanced TTNT in both age groups (HR, 0.54; P = .017). In conclusion, higher comorbidities in Octo patients adversely affected their management and survival. However, daratumumab positively influenced outcomes, underscoring the need for tailored approaches to optimize treatment in older patients with MM.