Henry Ford Hospital

RET fusions appear in 1%-2% of non-small cell lung cancers (NSCLCs). The results from the ARROW study (ClinicalTrials.gov identifier: NCT03037385) supported US Food and Drug Administration approval of pralsetinib, an oral selective RET inhibitor, for metastatic RET-altered NSCLC and RET fusion-positive thyroid cancers. ARROW was a phase I/II open-label study of pralsetinib 400 mg once daily in RET fusion-positive NSCLCs. Coprimary end points were overall response rate (ORR) and safety. Key secondary end points included duration of response, progression-free survival, and overall survival (OS). At data lock (May 20, 2024), 281 patients initiated pralsetinib (median treatment duration, 15.0 months). ORR (measurable disease patients; n = 259) was 78% (95% CI, 69 to 86) for treatment-naïve patients and 63% (95% CI, 54 to 71) for prior platinum-based chemotherapy patients. Median OS was 44.3 months (95% CI, 30.9 to 53.1), 50.1 months (95% CI, 28.3 to not reached) in treatment-naïve patients, and 39.7 months (95% CI, 27.8 to 53.2) in prior platinum patients. Common grade ≥3 treatment-related adverse events were anemia (21%), hypertension (15%), and decreased neutrophils (13%). Three treatment-related deaths occurred (pneumonia, n = 2; interstitial lung disease and rhabdomyolysis, n = 1 each). Safety was consistent with previous ARROW reports; no hypersensitivity was reported in patients receiving prior immunotherapies. Pralsetinib produced robust, durable responses with manageable safety in treatment-naïve and previously treated patients with RET fusion-positive NSCLCs, confirming previous findings with longer follow-up.

To evaluate the use of povidone-iodine infusion during pars plana vitrectomy and to assess its clinical outcomes in the treatment of severe endophthalmitis. A retrospective case series of 40 patients (41 eyes) with clinically or culture-confirmed endophthalmitis underwent pars plana vitrectomy with 0.025% povidone-iodine in the infusion solution. Outcomes included infection resolution, improvements in visual acuity, the need for additional surgeries, and signs of ocular toxicity. Of the 41 eyes treated, infection resolved in 33 (80.4%) eyes postoperatively. Visual acuity improved postoperatively in 29 eyes (70.7%). Mean uncorrected visual acuity improved from 20/3,337 (2.22 ± 0.70 logMAR) preoperatively to 20/540 (1.43 ± 0.88 logMAR) postoperatively ( P < 0.0001). No ocular toxicity or unexplained vision loss related to povidone-iodine infusion was observed. The addition of 0.025% povidone-iodine infusion during pars plana vitrectomy appears safe and led to favorable post-surgical outcomes in a traditionally high-risk cohort.

Endoscopy access is limited nationwide. We aimed to characterize the burden of repeated upper endoscopies for indications of abdominal pain, heartburn, and dysphagia. We reviewed all patients undergoing diagnostic endoscopy in a large health system between 2000 and 2023 who did not have medical conditions requiring repeat endoscopy. A Cox model was developed to predict the hazard of repeating a diagnostic endoscopy within three years as a primary outcome, represented using hazard ratios (HR) with 95% confidence intervals (CI). Over a 23year period, three-fifths of all diagnostic upper endoscopies performed were for abdominal pain (n = 5176), heartburn (n = 1535), or dysphagia (n = 3266). 90% of these procedures were ordered by gastroenterologists. The endoscopy was repeated within three years in 4.4% of patients with abdominal pain, 4.3% of patients with heartburn, and 5.6% of patients with dysphagia, usually for the same indication as the original procedure and without any intervention performed. In a multivariable model, the risk of repeating an endoscopy was either not influenced or only weakly influenced by age, sex, and mortality risk (measured using the Charlson Comorbidity Index). Findings were similar regardless of the dominant gastrointestinal symptom complaint. Gastroenterologists were no less likely to order a repeat endoscopy than primary care. Most repeat endoscopies occurred within one year of the index endoscopy. An average gastroenterologist performs a repeat diagnostic upper endoscopy almost every day.

Chromophobe renal cell carcinoma (ChRCC) is characterized by the accumulation of abnormal mitochondria, a high rate of mitochondrial DNA (mtDNA) mutations, and altered oxidative metabolism. There are no existing circulating biomarkers to distinguish metastatic ChRCC from clear cell renal cell carcinoma (ccRCC). High-throughput plasma proteomic profiling using the SomaScan platform was performed in 18 ChRCC (including 16 metastatic ChRCC) and 197 metastatic ccRCC patients. Data were harmonized to generate a unified 7K-protein matrix. Differential expression analysis was performed using limma (version 3.62.2). Of 7272 quantified human plasma proteins, 209 were differentially expressed between ChRCC and ccRCC. Upregulated proteins in ChRCC included essential β-oxidation enzymes such as ECH1 (enoyl-CoA hydratase 1) and ECI1 (enoyl-CoA delta-isomerase 1), suggesting increased long-chain fatty acid degradation. Creatine and energy-buffering pathways were also represented, with increased CKMT1A (Creatine Kinase, Mitochondrial 1A) in ChRCC. KIM-1 (Kidney Injury Molecule-1) and leptin were lower in ChRCC, consistent with the known upregulation of these proteins in ccRCC. Pathway enrichment analyses revealed an overrepresentation of mitochondrial protein degradation, fatty acid β-oxidation, and respiratory electron transport in ChRCC, suggesting that ChRCC sheds a unique mitochondrial signature into the peripheral circulation. A bootstrap-based LASSO logistic regression restricted to upregulated mitochondrial proteins in ChRCC vs. ccRCC consistently selected ECI1 and CKMT1A. The LASSO model achieved an AUROC of 0.964. Compared to ccRCC, the plasma proteome of metastatic ChRCC is dominated by mitochondrial metabolic enzymes, revealing a systemic metabolic phenotype strikingly aligned with the known histologic accumulation of abnormal mitochondria in ChRCC cells.

Research suggests fear of sleep (FoS) may be an important consequence of trauma that increases risk for posttraumatic stress disorder (PTSD), especially among patients experiencing ongoing threat after their trauma has ended. Community violence exposure may reinforce perceptions of threat, compounding the pathogenic effect of FoS after trauma. The current study investigated whether FoS increases within the acute aftermath of trauma, and if such increases in FoS predict future PTSD severity. Further, we tested whether community violence exposure moderates the prospective relationship between FoS and PTSD. We recruited patients from an urban Level I trauma center (N = 88; Mage = 39.53 ± SD 14.31, 67.0% male, 67.0% Black). Patients reported FoS within one week of trauma (T1) and again one month later (T2), and PTSD symptoms two months later (T3). We operationalized community violence exposure as the frequency of hearing gunshots in the 90 days prior to trauma. FoS significantly increased from T1 (M = 8.80) to T2 (M = 11.98), p = 0.015, g = 0.28. Change in FoS significantly predicted PTSD symptoms at T3, and this effect was most pronounced among patients who frequently heard gunshots in their community (β = 0.61, SE = 0.35, p = 0.005). Exploratory analyses in a subsample of patients revealed preliminary associations between skin conductance reactivity and sleep fears at T1, tentatively suggesting heightened sympathetic activation as a corollary of fear of sleep. This study provides novel evidence that FoS increases in response to acute trauma exposure and, in turn, predicts future PTSD severity. Moreover, patients exposed to community violence may be especially vulnerable to these effects, perhaps due in part to continued threats to safety. Acute trauma patients who develop sleep fears may be vulnerable to PTSD, particularly those returning to neighborhoods marked by high levels of community violence.

Patients with diabetes are at increased risk for postoperative complications after ankle arthrodesis (AA) and total ankle arthroplasty (TAA), yet few studies directly compare outcomes between these procedures in a matched diabetic cohort. This study evaluates outcomes of TAA vs AA in patients with diabetes with end-stage ankle arthritis. We performed a retrospective cohort study using the TriNetX Research Network. Adults undergoing primary TAA (Current Procedural Terminology [CPT] 27702) or ankle arthrodesis (CPT 27870 or 29899) between 2005 and 2025 were included. Diabetes was defined by hemoglobin A1c (HbA1c) ≥6.5% recorded at any point within 1 year prior to surgery. Propensity score matching (1:1) was performed using demographic and clinical covariates. Outcomes included 1-year infection and 1-, 3-, and 5-year structural complications and emergency department (ED) visits. ED visits captured all-cause encounters rather than ankle-specific presentations. The pre-specified primary endpoint was 1-year structural complication; secondary endpoints included infection at 1 year and ED visits and structural complications at 3 and 5 years, with FDR applied to secondary outcomes. Risk estimates, Kaplan-Meier analyses, and Benjamini-Hochberg false discovery rate (FDR) correction were applied. After propensity score matching, 255 patients remained in each group. At 1 year, postoperative infection occurred in 5.5% of TAA patients and 9.4% of AA patients; this difference did not meet statistical significance after false discovery rate (FDR) adjustment. ED visits were more common in the AA cohort at 1, 3, and 5 years after FDR correction. Structural complications occurred more frequently in the AA cohort at 1 year (29.8% vs 15.3%; RR 0.51), 3 years (38.8% vs 20.0%; RR 0.52), and 5 years (39.6% vs 21.2%; RR 0.54), and these differences were statistically supported after FDR adjustment. In patients with a recorded HbA1c ≥6.5% at any point within the previous year undergoing surgery for end-stage ankle arthritis, TAA demonstrated non-inferior structural complication rates across 1-, 3-, and 5-year follow-up without evidence of increased early infection risk after FDR adjustment.

Background and Objectives Observational data can provide evidence of treatment effects in a low-burden, cost-effective manner. Using a causal inference framework to address selection bias, we illustrate the approach in ALS by examining previously researched associations, baseline function and sex, and evaluating metformin’s survival benefits. Methods Data are from the ALS Natural History Study collected in the United States, Israel, and Italy from 2015 to 2025. We employ propensity score matching, two approaches to address loss to follow-up (i.e. a naive exclusion and principal stratification), and randomization-based inference to evaluate difference in 18-month restricted mean survival time. Results For the function investigation, estimated survival is 16.39, 16.14, 16.09, and 16.24 months for the high ALSFRS-R group and 14.04, 14.42, 14.72, and 14.60 months for the low ALSFRS-R group using the non imputed and imputed datasets 1-3, respectively (p&lt;0.0001, N=450; p&lt;0.00001, N=1,485; p&lt;0.00001, N=1,492; p&lt;0.00001, N=1,600). Using principal stratification, estimated survival is 16.38, 16.14, 16.09, and 16.23 months for the high ALSFRS-R group and 14.04, 14.42, 14.72, and 14.59 months for the low ALSFRS-R group with the non imputed and imputed datasets 1-3, respectively (p&lt;0.0001, N=449; p&lt;0.00001, N=1,483; p&lt; 0.00001, N=1,491; p&lt;0.00001, N=1,596). For the sex investigation, estimated survival is 15.20, 15.16, 15.20, and 15.17 months for females and 15.41, 14.84, 14.91, and 14.97 months for males using the non imputed and imputed datasets 1-3, respectively (p≈0.594, N=612; p≈0.155, N=2,081; p≈0.200, N=2,104; p≈0.359, N=2,111). Using principal stratification, estimated survival is 15.20, 15.16, 15.20, and 15.17 months for females and 15.41, 14.83, 14.91, and 14.97 months for males with the non imputed and imputed datasets 1-3, respectively (p≈0.598, N=612; p≈0.146, N=2,079; p≈0.195, N=2,102; p≈0.364, N=2,110). For the metformin investigation, estimated survival is 14.77, 14.87, and 14.57 months for metformin users and 14.59, 14.43, and 13.97 months for non metformin users using imputed datasets 1-3, respectively (p≈0.391, N=289; p≈0.257, N=279; p≈0.191, N=301). Using principal stratification, estimated survival is 14.75, 14.85, and 14.55 months for metformin users and 14.68, 14.58, and 13.97 months for non metformin users with imputed datasets 1-3, respectively (p≈0.458, N=286; p≈0.351, N=275; p≈0.201, N=300). Discussion We reject the sharp null hypothesis for the function investigation and fail to reject it for the sex and metformin investigations. Trial Registration Information ClinicalTrials.gov Identifier: NCT05966038 .