Citations

Abstract Purpose: Rearranged during transfection (RET) alterations are oncogenic drivers across solid tumors. Selective RET inhibitors (SRI) selpercatinib and pralsetinib have transformed outcomes for patients with RET-altered malignancies. Limited knowledge exists on genomic mechanisms of resistance to SRI. Experimental Design: We established “RETgistry,” a global consortium of patients with advanced RET-altered solid tumors who received SRI and underwent postprogression tissue or plasma biopsies assessed by next-generation sequencing. Frequencies of secondary RET resistance mutations and acquired non-RET gene alterations were determined. Progression-free survival (PFS) and time to treatment discontinuation (TTD) on first SRI were estimated with the Kaplan–Meier method. Results: RETgistry included 109 patients with RET-altered advanced solid tumors (lung, n = 94; thyroid, n = 15) who underwent 143 post-SRI progression biopsies (tissue, 91; plasma, 52). The median PFS and TTD were 13.9 months [95% confidence interval (CI), 10.1–16.6] and 17.3 months (95% CI, 14–20.2), respectively. Secondary RET mutations were detected in 20 (14%) biopsies [lung cancer, 15 (12.4%) and thyroid carcinoma, 5 (22.7%)]. Common acquired off-target alterations involved MET (18.2%; amplification, 15%), TP53 (8.2%), APC (7.6%), KRAS (7.1%), KEAP1 (5.9%), and CDKN2A/B (5.3%). MET alterations were enriched in post-SRI versus pre-SRI specimens (full cohort, 17.6% vs. 2.0%, P = 0.022; lung cancer, 19.1% vs. 2.1%, P = 0.022). Conclusions: The prevalence of secondary RET mutations after SRI was low, underscoring a greater role for off-target resistance. Recurrent acquired alterations involving tumor suppressor genes or upstream regulators of MAPK and PI3K pathways were identified, most commonly MET amplification. Continued efforts to characterize SRI resistance biology are critical to guide the development of novel therapeutic strategies.

This scientific commentary refers to ‘Pure autonomic failure: a natural history study of the Queen Square cohort’ by Chiaro et al. (https://doi.org/10.1093/brain/awaf191).

Vaccination remains a cornerstone of infection prevention in adult solid organ transplant (SOT) recipients, a population at heightened risk for vaccine-preventable diseases due to chronic immunosuppression and comorbidities. Updated guidelines from the American Society of Transplantation Infectious Diseases Community of Practice (AST IDCOP) and other international bodies emphasize the need for timely and comprehensive vaccination strategies before and after transplantation. This review synthesizes current literature and practice guidelines on vaccination in adult solid organ transplant (SOT) candidates and recipients. Published peer-reviewed studies, clinical trials, and consensus guidelines were evaluated, with emphasis on vaccination timing, safety, immunogenicity, dosing strategies, and serologic response monitoring in the SOT population. Comprehensive vaccination planning before transplantation, combined with appropriate post-transplant booster strategies, remains vital to improving long-term outcomes in SOT recipients. This review provides clinicians with an updated, evidence-based framework for integrating evolving vaccination guidelines into the care of adult transplant patients.

Objectives: The aim of this study was to investigate differences in utilization of diagnostic imaging between the adult and pediatric trauma teams when caring for adolescent trauma patients. Methods: This was a retrospective observational study from 2015 to 2019 comparing pediatric trauma team activations for patients ages 12 to 14 and adult trauma team activations for patients ages 15 to 17 at a single institution verified as both a level I adult and a level I pediatric trauma center. Data were collected from a prospective trauma registry and manual chart review of the electronic medical records. The primary outcome was the frequency of whole body computed tomography (WBCT) and computed tomography (CT) imaging of individual body regions. Results: We identified 191 adult and 100 pediatric trauma team cases, with similar proportions transferred from outside hospitals (40% vs. 43%). Among patients presenting directly from the scene, WBCT use was significantly higher in the adult trauma team group (64% vs. 12%; RR: 5.21; 95% CI: 2.57-10.58), as was CT of all individual body regions. For transferred patients, the adult trauma team more often performed WBCT and individual CT scans, excluding head CT. CT imaging rates before transfer did not differ between groups. No significant differences were observed in injury severity scores, altered mental status, length of stay, or missed injuries. Conclusions: Among adolescents with similar injury severity, the adult trauma team more frequently utilizes WBCT and regional CT than the pediatric team. However, CT use before transfer from outside hospitals without dedicated pediatric trauma teams was similar across age groups.

Summary In adults with classic Hodgkin lymphoma (cHL), metabolic tumour volume (MTV) is valuable for risk stratification. This systematic review explored the role of volumetric parameters in children, adolescents and young adults (CAYA) with cHL. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) method. Five databases were searched on 16 October 2024. Eligible studies were peer‐reviewed manuscripts, written in English, published since database inception that included patients ≤21 years of age with a diagnosis of cHL treated with chemotherapy ± radiotherapy with a baseline 18 F‐Fluorodeoxyglucose (F‐FDG) PET/CT scan for MTV quantification. The search strategy identified 3669 studies, of which 35 were eligible for inclusion. Fifteen studies (43%) evaluated a cohort exclusively ≤21 years of age. All eight studies that explored the association of baseline PET parameters with known risk factors identified a significant correlation. Nine of 12 papers (75%) demonstrated a statistically significant correlation with disease response to therapy on PET/CT. Fifteen of 20 papers (75%) demonstrated an independent statistically significant correlation with clinical outcomes. In the CAYAHL population, volumetric PET parameters are valuable for risk stratification despite heterogeneity in results. Future harmonization of the segmentation approach will facilitate incorporation of MTV into clinical practice.

Abstract Diameter of the aorta is a significant contributor and predictor for complications and a fundamental parameter for intervention. It is recognized that age, sex, and ethnicity play a role in aortic size. We thus sought to determine the normal dimensions among our population. A retrospective analysis of images was done of all polytrauma patients admitted between January 2018 and December 2022 who underwent protocolized noncontrast computed tomography of the chest and abdomen to measure the aortic diameter at established reference points. There were 513 patients; the mean age was 36.5 ± 14.6 (range: 18–86), and 382 (74.5%) were males. Aortic dimensions at sinus, mid-ascending, arch, descending, suprarenal, and infrarenal aorta were 30.7 ± 3.8, 29.3 ± 4.5, 24.9 ± 3.3, 20.1 ± 3.0, 19.4 ± 2.9, and 15.3 ± 2.2, respectively. Age demonstrated a positive correlation to the diameter at the ascending, descending, and infrarenal aorta (r = 0.58, p = 0.001 [95% confidence interval, CI = 0.519; 0.634]; r = 0.69, p = 0.001 [95% CI = 0.641; 0.732]; r = 0.57, p = 0.001 [95% CI = 0.509; 0.626]) along with the length of the ascending aorta (r = 0.420, p = 0.001 [95% CI = 0.345; 0.488]; r = 0.536, p = 0.001 [95% CI = 0.471; 0.595]; r = 0.476, p = 0.001 [95% CI = 0.406; 0.540), respectively. There was a positive correlation of aortic diameters to body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Females had smaller dimension at the reference points, but without any statistical significance. There were 50 (9.8%) patients with bovine aortic arch and 10 (1.9%) with separate origin of left vertebral artery. Normal values of the diameter of the aorta for a South Asian population are provided. Diameter is affected by age, length of the ascending aorta, BMI, SBP, and DBP. This study suggests that the aorta size is smaller in the South Asian population than the referenced Western population, more significantly for distal descending and abdominal aorta and that ethnicity plays a role in determining aortic dimensions.

Abstract Despite the reported benefits of testosterone replacement therapy (TRT), prior studies have shown that TRT is correlated with increased incidence of adverse outcomes after orthopedic procedures. There is a paucity of literature assessing the outcomes of patients on preoperative TRT undergoing distal radius open reduction and internal fixation (DR-ORIF). Our purpose was to evaluate rates of surgical and medical complications in patients on TRT undergoing DR-ORIF with a matched control cohort. The PearlDiver database was queried for patients who used TRT within 3 months prior to the index procedure. Patients were matched 1:4 with nonuser controls using propensity score matching. Matching was conducted based on age, Elixhauser Comorbidity Index, hypogonadism, osteoporosis, and other comorbidities. Complications were assessed at 90 days and 2 years. Statistical analyses were conducted using chi-square tests. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for each complication. Statistical significance was determined at a p-value of < 0.05. The matched group included 657 TRT users and 2,236 controls. There were significant differences in depression (control: 40.6% vs. TRT: 45.7%, p = 0.02) and rates of hypogonadism (control: 74.1% vs. TRT: 77.9%, p = 0.05) between the groups. No other statistically significant demographic or characteristic differences were noted. TRT use was not associated with increased surgical or medical complication rates at 90 days postoperatively. At 2 years, TRT use was associated with a greater incidence of revision (OR: 2.80, 95% CI: 1.34–5.85) and nonunion (OR: 2.76, 95% CI: 1.59–4.81). There were no other associations noted at 2 years. Preoperative TRT was associated with an increased risk of revision surgery and nonunion at 2 years postoperatively. No other significant associations in the risk of major or minor complications were observed. Level III

Abstract Management of scapholunate advanced collapse (SLAC) wrist arthritis remains challenging in physically high-demand patients with primarily salvage options described for advanced SLAC wrist. Microfracture resurfacing of the scaphoid fossa may be a potential option for this condition. A case of a physically active farmer with advanced SLAC wrist arthritis underwent arthroscopic dorsal capsulodesis of the scapholunate interval, microfracture of the scaphoid fossa chondral defect, and application of cartilage allograft is reported. At 1-year follow-up, there is continued resolution of his wrist pain, and function had improved with increased grip strength and wrist range of motion. Radioscaphoid microfracture and dorsal capsulodesis for SLAC wrist can be a potential dual-pronged reconstructive strategy for the physically high-demand patient that may obviate the need for salvage procedures.