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Importance Observational studies have associated use of aspirin and selective cyclooxygenase inhibitors with decreased recurrence and improved survival in patients with colon cancer. While randomized clinical trials have not shown benefit across all patients, these findings suggest that select subgroups may benefit from their use. Despite the well-established prognostic value of circulating tumor DNA (ctDNA), its role in guiding treatment remains unclear. Objective To investigate the predictive value of postoperative ctDNA for survival outcomes with adjuvant celecoxib alongside conventional chemotherapy in patients with stage III colon cancer. Design, Setting, and Participants This was a post hoc analysis of the phase 3 Cancer and Leukemia Group B (now Alliance)/Southwest Oncology Group 80702 randomized clinical trial (2010-2015) assessing adjuvant celecoxib vs placebo and 3 vs 6 months of adjuvant 5-fluorouracil, leucovorin, and oxaliplatin for stage III colon cancer. Patients consented to biospecimen collection and had ctDNA analysis performed. Data analysis was performed from September 2024 to June 2025. Exposures Postoperative ctDNA positivity was determined using a clinically validated, tumor-informed 16-plex-polymerase chain reaction-next-generation sequencing assay (Signatera; Natera Inc) performed between surgery and initiation of adjuvant therapy. Main Outcomes and Measures Disease-free survival (DFS) and overall survival (OS). Survival by ctDNA status and adjuvant celecoxib use were assessed as part of a post hoc companion study with prespecified statistical analysis plan. Results Among 940 patients (mean [SD] age, 60.9 [10.8] years; 426 female [45.3%] and 515 male [54.7%] individuals; 222 [23.6%] with prior low-dose aspirin use; and median follow-up of 6.0 [95% CI, 6.0-6.0] years), 767 (81.6%) were ctDNA negative and 173 (18.4%) were ctDNA positive. ctDNA positivity was highly prognostic of worse DFS (reference, ctDNA negativity; adjusted hazard ratio [aHR], 6.12; 95% CI, 4.66-8.03) and OS (aHR, 5.86; 95% CI, 4.19-8.19). In patients with ctDNA positivity, celecoxib was associated with improved DFS (aHR, 0.61; 95% CI, 0.42-0.89) and OS (aHR, 0.62; 95% CI, 0.40-0.96) compared to placebo. Among patients with ctDNA negativity, celecoxib did not provide survival benefit (DFS: aHR, 0.76; 95% CI, 0.53-1.09; OS: aHR, 0.85; 95% CI, 0.54-1.36), although the interaction was not significant ( P for interaction, .41 and .33 for DFS and OS, respectively). These findings persisted when stratifying patients by microsatellite instability status and PIK3CA mutational status. Conclusion and Relevance The findings of this post hoc analysis suggest that ctDNA status has the potential to inform clinical decision-making among patients with stage III colon cancer who should consider adjuvant celecoxib in addition to conventional chemotherapy. Trial Registration ClinicalTrials.gov Identifier: NCT01150045

Abstract This publication represents the first part of an update to the clinical practice guideline on the diagnosis and management of group A streptococcal (Streptococcus pyogenes or GAS) pharyngitis, developed by the Infectious Diseases Society of America (IDSA). Diagnosis of GAS pharyngitis by clinician judgment alone is unreliable, and unselective testing incurs cost and inconvenience for individuals at low risk of having GAS infection. Clinical scoring systems have been used to quantify the probability of a positive GAS throat culture based on standardized criteria such as the presence of fever; tonsillar enlargement or exudate; tender and enlarged anterior cervical lymph nodes; and the absence of cough. The goal of this article is to determine whether a scoring system should be used to decide which patients should have a diagnostic test performed by rapid antigen detection test, molecular methods, and/or throat culture. We performed a systematic review of randomized and nonrandomized studies that compared the use of a clinical scoring system to clinician judgment alone in predicting the outcome of a throat culture. Evidence from studies in children and adults suggests the diagnostic accuracy of a clinical scoring system is comparable to or slightly higher than clinician judgment alone. However, the studies are limited due to small size, lack of uniformity in outcome measures, and incomplete data. The consensus of the panel is that the balance of benefits and harms favors use of a clinical scoring system as part of the evaluation of patients with sore throat. The principal utility of using a scoring system is to identify patients with low probability of GAS pharyngitis and to reduce unnecessary testing.

Abstract Anaplastic large cell lymphomas (ALCLs) are CD30+ T-cell lymphomas that share pathologic features but differ in presentation, outcome, and genetics. Current classification incorporates clinical presentation and anaplastic lymphoma kinase (ALK) status but inadequately addresses molecular heterogeneity and therapeutic vulnerabilities. We studied 689 patients with ALCL in the LLMPP (Lymphoma/Leukemia Molecular Profiling Project) and performed expert consensus review, genetic subtyping (ALK, DUSP22, TP63, and triple negative), and immunohistochemistry for phosphorylated STAT3Tyr705. RNA sequencing with unsupervised gene expression profiling in 393 patients identified 2 main molecular types of ALCL that could be predicted with 91% accuracy based on the presence (type I) or absence (type II) of phosphorylated STAT3Y705 expression. Type I ALCLs included ALK+ ALCL and a subset of triple-negative ALCLs (TN-I); type II ALCLs included tumors with DUSP22 and/or TP63 rearrangements and the remaining triple-negative ALCLs (TN-II). Type I ALCLs were enriched for JAK-STAT3, whereas type II ALCLs were enriched for non–tyrosine kinase pathways, particularly epigenetic regulators such as EZH2. Immunohistochemistry showed overexpression of EZH2 and its trimethylated substrate H3K27. Prognosis in systemic ALCL was favorable for DUSP22-rearranged ALCL (5-year overall survival, 95%) and ALK+ ALCL (88%), intermediate for triple-negative ALCL (TN-I, 52% and TN-II, 37%), and poor for TP63-rearranged ALCL (0%). We introduce an integrated molecular classification that preserves currently diagnosed ALCL entities but identifies 4 molecularly distinct ALK− ALCL subtypes (DUSP22-rearranged, TP63-rearranged, TN-I, and TN-II). This classification can be easily implemented on paraffin tissue in routine practice or clinical trials, and stratifies ALCL into diagnostically, prognostically, biologically, and potentially therapeutically relevant subtypes.

The breadth of medical practice for a physical medicine and rehabilitation (PM&R) physician is quite extensive. Not only are practice areas quite different among PM&R physicians, but practice settings, procedures, and salary models also vary significantly. For PM&R residents and fellows who are making career decisions regarding specialization versus general practice and/or in the process of negotiating contracts, salary is a significant influence in their decision of clinical practice. Physician payment models may create inadvertent bias against women, those seeking less than full time clinical employment, and those interested in an academic career. In this review and commentary, we will discuss the more common payment models encountered, with a focus on a fixed salary payment model. We will also discuss our experiences as pediatric and adult PM&R providers in a salaried payment model at a not-for-profit academic institution.

Background: Sleep is vital for an athlete’s recovery, physical and mental health, and athletic performance. The impact on circadian rhythm from long-distance travel across multiple time zones has not been studied using wearable technology in female professional tennis players. Hypothesis: Travel between time zones in female professional tennis players leads to circadian desynchronization, causing disruption in sleep patterns, changes in physiologic parameters, and decreased athletic performance. Study Design: Retrospective cohort study. Level of Evidence: Level 3. Methods: A total of 52 female professional tennis players consented to wear, and share the data of, WHOOP 3.0 while traveling and competing on the Women’s Tennis Association (WTA) Tour. Linear mixed models examined the relationship between (1) travel and sleep/recovery and (2) sleep/recovery and match performance. Results: Sleep duration without travel averaged 437 minutes (436.8 ± 2.8). On the first night after travel, for every hour time zone difference (TZD) traveled regardless of direction, players slept 11 minutes less (−11.3 ± 0.96; P < 0.05). Eastward travel further reduced sleep (−24.5 ± 4.2; P < 0.05), while westward travel increased sleep duration (+30.0 ± 4.2; P < 0.05). These effects were reduced on the subsequent 2 nights. Conclusion: Sleep duration reduction was most prominent on the first night after travel, particularly with eastward travel, but improved on subsequent nights. The number of time zones crossed predictably increases the vulnerability for insufficient sleep duration, whereby a 2-hour TZD easterly, and 4-hour TZD westerly, reduces sleep duration <7 hours on the first night. No significant correlation was found between sleep disruption and competition performance in our female professional tennis population. Clinical Relevance: The findings suggest that professional tennis players should, and generally do, arrive at competition locations with enough time to resynchronize their circadian rhythm to the destination time zone; particularly if traveling eastward.

Abstract Uterine leiomyosarcoma (ULMS) is an orphan disease that frequently recurs and metastasizes, with patients undergoing multiple lines of chemotherapy due to lack of effective therapeutic targets. To address this gap, we used single-cell RNA sequencing and spatial transcriptomic analysis to comprehensively profile ULMS. We uncovered multiple states of tumor cells, including tumor cells with mesenchyme-like features, ischemic tumor cells defined by a MYC program, inflammatory tumor cells with active interferon signaling, and stem cell-like hormone receptor-positive cells. The inferred spatial correlates of these tumor cell states demonstrated unique localization patterns. By correlating these signatures to bulk RNA sequencing data, we demonstrate the relevance of these findings to clinical outcomes. Finally, using the single-cell integration and drug response prediction algorithm (scIDUC), we propose drug predictions that may target specific tumor states. Our findings suggest new avenues for further exploration of individualized and multifaceted therapeutic strategies to treat ULMS.

Study Design Retrospective cohort study using a nationally representative inpatient database. Objective To determine the incidence, timing, and predictors of new-onset psychiatric disorders following lumbar fusion surgery, and to propose a data-driven risk stratification model for early identification and intervention. Methods We queried the Nationwide Readmissions Database (2016-2019) to identify adults undergoing elective inpatient lumbar fusion. Patients with preexisting psychiatric diagnoses were excluded. Outcomes included new-onset depression, anxiety, suicidal ideation, and homicidal ideation within 12 months postoperatively. Predictors were assessed using odds ratios. Timing of onset was evaluated with density plots. Results Among 839,576 patients, 12,011 developed depression, 11,828 anxiety, 916 suicidal ideation, and 63 homicidal ideation. Most diagnoses occurred within 90 days postoperatively, with peak incidence around 3 weeks. Opioid use during the index admission significantly increased odds of suicidal ideation (OR 2.13, P = 0.001), anxiety (OR 1.26, P = 0.002), and showed a trend toward depression (OR 1.14, P = 0.087). Medicaid insurance was the strongest predictor of suicidal (OR 3.69) and homicidal ideation (OR 6.41). Female sex and younger age were associated with anxiety and depression; older age was protective against ideation. Conclusions New-onset psychiatric disorders are a frequent and early complication following lumbar fusion. Several modifiable and demographic factors - including perioperative opioid use and socioeconomic status - significantly predict risk. These findings underscore the need for structured mental health screening within the first 3 months post-surgery. Implementing a predictive risk stratification tool could enable earlier psychiatric referral, reduce long-term morbidity, and improve both recovery trajectories and overall quality of life.

Background: Patellofemoral dislocations are often associated with chondral injuries. In adults, diagnostic arthroscopy (DA) has identified chondral injuries in up to one-third of cases where magnetic resonance imaging (MRI) was negative. However, the value of DA in detecting cartilage injuries in pediatric patients undergoing medial patellofemoral ligament reconstruction (MPFLR) has not been well studied. Purposes: To evaluate the utility of DA in diagnosing cartilaginous injuries in pediatric patients undergoing MPFLR with negative preoperative MRI findings and to compare postoperative outcomes between patients with and without chondral injury findings on DA. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: A retrospective review was conducted on patients aged 0 to 18 years who underwent combined MPFLR and DA procedures from 2015 to 2023 at a single institution. The exclusion criteria were as follows: revision MPFLR; tibial tubercle osteotomy; multiligament reconstructions; and previous meniscal injury. MRI and DA reports were reviewed for chondral findings. Patients were classified into 3 groups: +MRI/+DA, –MRI/+DA, and –MRI/–DA. Subgroup analysis was performed within the –MRI/+DA group to compare outcomes in the immediate postoperative recovery period between those who underwent a chondroplasty versus those who did not. Results: Of the 155 patients included, follow-up averaged 7.8 months (median, 5 months [range, 0-41 months]). Among 89 patients with negative MRI findings, 39 (43.8%) had chondral injuries detected on DA. Targeted treatment was performed in 22 (56.4%) of these patients, a lower rate than in those with positive MRI findings (80.3%; P = .02). No significant differences were observed in knee flexion at 2 weeks postoperatively: +MRI/+DA (77.9°± 23°), –MRI/+DA (66.5°± 30.2°), and –MRI/–DA (73.3°± 30°) ( P = .14). Similarly, no significant differences were found at 12 weeks: +MRI/+DA (135.3°± 13°), –MRI/+DA (127.8°± 21°), and –MRI/–DA (134.1°± 13.4°) ( P = .10). Range of motion and complication rates were comparable across all groups ( P > .05). A subgroup analysis in the –MRI/+DA cohort comparing patients who underwent an arthroscopic procedure (n = 22) with those who did not (n = 17) showed no significant differences in range of motion or complication rates ( P > .05). Conclusion: Diagnostic arthroscopy detected cartilaginous injuries in 43.8% of pediatric patients with negative preoperative MRI undergoing MPFLR. This highlights the diagnostic value of DA in identifying injuries that would otherwise remain undetected.