PURPOSE:To validate the American Joint Committee on Cancer (AJCC) 9th edition M1-stage subdivision for de novo metastatic nasopharyngeal carcinoma (DM-NPC) and explore preliminary evidence for a refined classification using 18F-FDG positron emission tomography/computed tomography (PET/CT)-derived metastatic burden. PATIENTS AND METHODS:A retrospective cohort of 185 DM-NPC patients diagnosed between 2000 and 2022, who underwent pretreatment 18F-FDG PET/CT, was analyzed. Recursive partitioning analysis (RPA) identified prognostic cutoffs for metastatic lesions. Survival outcomes were compared between AJCC 9th edition M1 subgroups (M1a: ≤3 lesions; M1b: >3 lesions) and a redefined PET-based classification (Rd-M1a: single-organ, ≤4 lesions; Rd-M1b: >5 lesions or multiorgan). RESULTS:Patients with single-organ metastases and ≤4 lesions showed potentially superior overall survival (OS) (2-y OS: 60.4% vs. 29.0%; 3-y OS: 46.2% vs. 19.6%; P<0.001). Higher metastatic burden (>5 lesions) was independently associated with worse OS (HR: 1.81; 95% CI: 1.24-2.64; P=0.002). The redefined classification suggested better prognostic discrimination than the AJCC 9th edition (C-index: 0.594 vs. 0.562; AUC at 36 mo: 0.649 vs. 0.598). Patients classified as Rd-M1b had a significantly unfavorable OS compared with those in the Rd-M1a group (HR: 2.02, 95% CI: 1.39-2.92; P=0.002). CONCLUSIONS:These preliminary findings suggest that 18F-FDG PET/CT may enhance M1-stage stratification by quantifying metastatic burden and distribution in patients with DM-NPC, potentially offering improved prognostic accuracy. However, as a single-institution retrospective study, external validation is essential to confirm these observations and guide personalized treatment strategies.
BACKGROUND:FOLFIRINOX is a standard first-line therapy for metastatic pancreatic ductal adenocarcinoma (PDAC), but its toxicity often necessitates dose adjustments. This study evaluated the impact of first relative dose intensity (RDI) of irinotecan and oxaliplatin on treatment outcomes and safety in PDAC patients. METHODS:This retrospective multi-center cohort study included 109 PDAC patients treated with FOLFIRINOX across 12 Taiwanese hospitals from 2017 to 2020. Initial RDI was defined as the ratio of actual to standard doses of irinotecan and oxaliplatin in the first cycle. Patients were categorized into three RDI groups: <70%, 70-90%, and ≥90%. RESULTS:The median PFS was 5.1 months and median OS was 11.6 months. In the <70%, 70-90%, and ≥90% RDI groups, median PFS was 4.9, 7.1, and 3.5 months, and median OS was 10.7, 16.2, and 7.0 months, respectively. The 70-90% group had significantly longer OS than the <70% and ≥90% groups and PFS in the 70-90% group was significantly longer than in the ≥90% group. Grade ≥3 adverse events occurred in 49.5% of patients, mainly hematologic. The ≥90% group had the highest toxicity despite receiving a median of 3.5 cycles. CONCLUSION:The initial RDI of 70-90% for irinotecan and oxaliplatin may optimize both efficacy and tolerability in Taiwanese PDAC patients treated with FOLFIRINOX.
Psychotic disorders in solid organ transplant recipients present complex diagnostic and therapeutic challenges. Tacrolimus, a commonly used immunosuppressant, is associated with neuropsychiatric side effects, yet discontinuation carries the risk of graft rejection. We describe a 65-year-old heart transplant recipient who developed very late-onset schizophrenia-like psychosis 54 weeks after transplantation while on tacrolimus. His psychotic symptoms—including hallucinations and delusions—were refractory to multiple antipsychotics, including clozapine, but responded substantially to bifrontal electroconvulsive therapy (ECT), with preservation of cardiac graft function. A relapse later improved with a second course of ECT. To contextualize this case, we reviewed 18 published reports of ECT in solid organ transplant recipients. Across depression, psychosis, catatonia, and suicidality, ECT consistently demonstrated effectiveness with mostly mild and manageable side effects, while rare severe complications were attributable to underlying medical conditions rather than ECT itself. These findings suggest that ECT is an effective consideration for refractory psychiatric syndromes in transplant recipients, even when immunosuppressant regimens cannot be altered. Careful pre-ECT evaluation, interdisciplinary collaboration, and vigilant peri-procedural monitoring remain essential for optimizing outcomes in this medically fragile population.
IMPORTANCE:Pediatric flexible flatfoot (PFF) is a common condition affecting children's foot biomechanics. While various conservative treatments exist, their relative effectiveness remains unclear. OBJECTIVE:The objective was to compare the effectiveness of non-surgical interventions-orthotic devices, active exercise-based interventions, and neuromuscular electrical stimulation (NMES)-for managing PFF. DESIGN:A systematic review and network meta-analysis of randomized controlled trials was conducted and registered in PROSPERO (CRD42024539990). PARTICIPANTS:Eleven trials encompassing 761 children with flexible flatfoot were included. INTERVENTIONS:Non-surgical interventions included orthotic devices (traditional insoles, talus control insoles, corrective shoes, heel cups) and active exercise-based physical therapist interventions (corrective exercises, core stabilization exercises, and NMES combined with corrective exercises). OUTCOME MEASURES:Outcome measures included the Staheli index (static footprint measurement), barefoot radiological measures (anterior-posterior and lateral talocalcaneal angles, calcaneal pitch angle), pain scores, and treatment discontinuation rates. RESULTS:NMES combined with corrective exercises demonstrated significant improvement in the Staheli index compared to no intervention (mean difference [MD] = -0.28, 95% CI = -0.35 to -0.22; certainty of evidence [CoE]: moderate). Talus control insoles showed significant improvements in radiological outcomes compared to conventional flat footwear, including lateral talocalcaneal angle (MD = -5.56°, 95% CI = -9.81 to -1.30; CoE: low) and calcaneal pitch angle (MD = 2.74°, 95% CI = 0.41 to 5.06; CoE: low). Traditional insoles effectively reduced pain scores compared to flat insoles (MD = -2.92 points, 95% CI = -3.73 to -2.11; CoE: very low). Pain outcomes were not assessed in exercise or NMES studies, preventing comparative effectiveness conclusions across intervention types. No significant differences in treatment discontinuation rates were observed among orthotic interventions. CONCLUSIONS:Both active exercise-based and orthotic interventions demonstrated beneficial effects. NMES with corrective exercises improved standing foot alignment by static footprint analysis, while orthotic interventions enhanced radiological alignment (talus control insoles) and pain relief (traditional insoles) compared to conventional footwear. Outcome measurement differences between intervention types limited direct comparisons. Ten studies measuring gait, functional, or developmental outcomes were excluded due to insufficient outcome overlap. RELEVANCE:This network meta-analysis provides evidence-based guidance for selecting conservative PFF interventions based on primary treatment objectives.
