Citations

Accurate staging of nodal involvement in pediatric sarcoma patients is important to determine correct systemic and local therapy, with the goal to reduce subsequent recurrences. However, differences in lymph node staging strategies, definitions, and treatment protocols between the Children’s Oncology Group (COG), European Pediatric Soft Tissue Sarcoma Study Group (EpSSG), and the Cooperative Weichteil Sarkom Studiengruppe (CWS), complicate comparisons. In this article we try to establish internationally recognized recommendations for lymph node assessment and treatment of children and adolescents diagnosed with RMS and NRSTS according to the Consensus Conference Standard Operating Procedure methodology.

Background A combination of intravenous (IVT) or intra-arterial (IAT) thrombolysis with mechanical thrombectomy (MT) for acute ischemic stroke due to large vessel occlusion (AIS-LVO) has been investigated. However, there is limited data on patients who receive both IVT and IAT compared with IVT alone before MT. Methods STAR data from 2013 to 2023 was utilized. We performed propensity score matching between the two groups. The primary outcomes were symptomatic intracranial hemorrhage (sICH) and 90-day modified Rankin Scale (mRS) score 0–2. Secondary outcomes included successful recanalization (modified treatment in cerebral infarction (mTICI) ≥2B, ≥2C), early neurological improvement, any intracranial hemorrhage (ICH), and 90-day mortality. Results A total of 2454 AIS-LVO patients were included. Propensity matching yielded 190 well-matched patients in each group. No significant differences were observed between the groups in either ICH or sICH (odds ratio (OR): 0.80, 95% confidence interval (CI) 0.51–1.24, P=0.37; OR: 0.60, 95% CI 0.29 to 1.24, P=0.21, respectively). Rates of successful recanalization and early neurological improvement (ENI) were significantly lower in MT+IVT + IAT. mRS 0–1 and mortality were not significantly different between the two groups. However, the MT+IVT + IAT group demonstrated superior rates of good functional outcomes (90-day mRS 0–1) compared with patients in the MT+IVT group who had mTICI ≤2B, (OR: 2.18, 95% CI 1.05 to 3.99, P=0.04). Conclusion The combined use of IAT and IVT thrombolysis in AIS-LVO patients undergoing MT is safe. Although the MT+IVT+ IAT group demonstrated lower rates of recanalization and early neurological improvement, long-term functional outcomes were favorable in this group suggesting a potential delayed benefit of IAT.

ObjectivesUpdated retrospective review of the sonographic appearance of palmar fibromatosis (PF) with evaluation of the utility of the Comb Sign previously described in plantar fibromas. Additional evaluation was conducted on the location relative to the flexor tendon, anatomic proximity of palmar fibromas to the A1 pulley and evaluate any potential association with trigger finger.MethodsMedical record and imaging review was performed from 2017 to 2023, for patients with a new onset ultrasound or clinical diagnosis of PF. Clinical associations and imaging morphology were reviewed including presence of the Comb Sign, fibroma association with the A1 pulley, and fibroma association with trigger finger.ResultsExactly 87 total fibromas in 53 patients were evaluated. The Comb Sign was present in 39% of fibromas, usually seen in transverse plane, more prevalent in multifocal disease and larger fibromas. Most (72%) palmar fibromas were within 1 cm of, contacted, or covered the A1 pulley (P < .001). Lateral extension beyond the flexor tendon axis can be seen (44%). Trigger finger and tenosynovitis were rare. However, volume and SI dimension of fibromas were associated with tenosynovitis (P < .0001) and all nine patients with concomitant trigger finger had fibromas within 1 cm from the A1 pulley.ConclusionsThe Comb Sign can aid in sonographic diagnosis of PF. Lateral extension of fibromas can occur. Most palmar fibromas have a significant intimate association with the A1 pulley, and presence of trigger finger with adjacent palmar fibroma can exist and is important for hand surgeons to know preoperatively.

Obesity hypoventilation syndrome (OHS) can often be underdiagnosed or misdiagnosed and has been shown to pose significant risks in perioperative situations. Patients with OHS have a higher prevalence of baseline morbid conditions like hypertension, congestive heart failure (CHF), diabetes mellitus, atrial fibrillation, and pulmonary hypertension (PH), which contribute to adverse postoperative outcomes. The potential challenges include difficult intubation and loss of airway, postoperative respiratory failure, worsening heart failure, pulmonary hypertensive crisis, and opioid-induced respiratory depression (OIRD). It is, therefore, important to screen all obese patients for obstructive sleep apnea (OSA) and OHS before elective surgical procedures. The aim of this review is to discuss the preoperative screening and evaluation and safe anesthetic and up-to-date ventilatory management of this complex group of patients. This review also intends to increase the awareness of OHS in the adult population among hospitalists, surgeons, and cardiologists who may find themselves taking care of these patients in complex multidisciplinary settings.

Background: Bipolar disorder (BD) involves significant mood and energy shifts reflected in speech patterns. Detecting these patterns is crucial for diagnosis and monitoring, currently assessed subjectively. Advances in natural language processing offer opportunities to objectively analyze them. Aims: To (i) correlate speech features with manic-depressive symptom severity in BD, (ii) develop predictive models for diagnostic and treatment outcomes, and (iii) determine the most relevant speech features and tasks for these analyses. Methods: This naturalistic, observational study involved longitudinal audio recordings of BD patients at euthymia, during acute manic/depressive phases, and after-response. Patients participated in clinical evaluations, cognitive tasks, standard text readings, and storytelling. After automatic diarization and transcription, speech features, including acoustics, content, formal aspects, and emotionality, will be extracted. Statistical analyses will (i) correlate speech features with clinical scales, (ii) use lasso logistic regression to develop predictive models, and (iii) identify relevant speech features. Results: Audio recordings from 76 patients (24 manic, 21 depressed, 31 euthymic) were collected. The mean age was 46.0 ± 14.4 years, with 63.2% female. The mean YMRS score for manic patients was 22.9 ± 7.1, reducing to 5.3 ± 5.3 post-response. Depressed patients had a mean HDRS-17 score of 17.1 ± 4.4, decreasing to 3.3 ± 2.8 post-response. Euthymic patients had mean YMRS and HDRS-17 scores of 0.97 ± 1.4 and 3.9 ± 2.9, respectively. Following data pre-processing, including noise reduction and feature extraction, comprehensive statistical analyses will be conducted to explore correlations and develop predictive models. Conclusions: Automated speech analysis in BD could provide objective markers for psychopathological alterations, improving diagnosis, monitoring, and response prediction. This technology could identify subtle alterations, signaling early signs of relapse. Establishing standardized protocols is crucial for creating a global speech cohort, fostering collaboration, and advancing BD understanding.

The use of 4-drug induction regimens for treatment naïve newly diagnosed multiple myeloma (NDMM) is associated with improved depth of response and progression-free survival (PFS). However, head-to-head trials of 4-drug combinations are lacking, and instead, these regimens are typically compared to 3-drug backbones; limiting the ability to discern whether any additional benefit (or toxicity) is simply additive or represents a synergy (or interaction). We conducted a meta-analysis of phase 2 and phase 3 clinical trials that randomized treatment naïve NDMM patients to either a 4-drug or 3-drug induction regimen. We included 11 trials which represented 6509 unique patients. PFS for all trials in the meta-analysis was 54 months with a 4-drug induction and 8.9 months with a 3-drug induction (HR: 0.49; 95% CI: 0.45; 0.54), but there was no benefit to using a 4-drug induction that did not include an anti-CD38 antibody (PFS 4-drug 8.1 months, PFS 3-drug 8.0 months; HR 0.95; 95% CI 0.86; 1.06). Adverse events were more frequent with the quadruplet regimens but were predominately mild. High-grade (≥3) adverse events (AEs) that were more common with 4-drug regimens were infections (RR: 1.34; 95% CI 1.17; 1.54) and thrombocytopenia (RR: 1.39; 95% CI 1.12; 1.74). This study suggests that 4-drug induction regimens which include an anti-CD38 antibody improve efficacy although with additional toxicity in NDMM patients.

Introduction: Recipients of lung transplants are at heightened risk of developing low bone mineral density (BMD). They also have increased risk of developing osteoporosis-related fractures. This rate of BMD decline is not well characterized. The aim of this manuscript is to characterize the rate of BMD decrease after lung transplant. Methodology: This is a preliminary retrospective cohort study of 200 patients who received lung transplants. Each patient had pre-transplant dual energy X-ray absorptiometry (DXA) and post-transplant DXA scans on the same DXA scanner. The BMD at each lumbar vertebra, total hip, and femoral neck were recorded. Generalized linear mixed effects models with random intercepts and random slopes were used to model the rate of change of BMD after transplant, adjusting for time since transplant, sex, and sex*time interaction. Results: We found that men had higher baseline BMD than women at all sites (P<0.05 for all). The rate of BMD decrease was fastest at the femoral neck (P<0.05). Men lost BMD at a faster rate (-5.23 x10-5 g/cm2/day) than women at the femoral neck (-2.22 x10-5 g/cm2 /day). Conclusion: BMD decreases after lung transplant and occurs faster in men than women.

Abstract Purpose: Metastatic castration-resistant prostate cancer (mCRPC) resistant to androgen receptor signaling inhibitors (ARSI) is often lethal. Liquid biopsy biomarkers for this deadly form of disease remain under investigation, and underpinning mechanisms remain ill-understood. Experimental Design: We applied targeted cell-free DNA (cfDNA) sequencing to 126 patients with mCRPC from three academic cancer centers and separately performed genome-wide cfDNA methylation sequencing on 43 plasma samples collected prior to the initiation of first-line ARSI treatment. To analyze the genome-wide sequencing data, we performed nucleosome positioning and differential methylated region analysis. We additionally analyzed single-cell and bulk RNA sequencing data from 14 and 80 patients with mCRPC, respectively, to develop and validate a stem-like signature, which we inferred from cfDNA. Results: Targeted cfDNA sequencing detected AR/enhancer alterations prior to first-line ARSIs that correlated with significantly worse progression-free survival (P = 0.01; HR = 2.12) and overall survival (P = 0.02; HR = 2.48). Plasma methylome analysis revealed that AR/enhancer lethal mCRPC patients have significantly higher promoter-level hypomethylation than AR/enhancer wild-type mCRPC patients (P &lt; 0.0001). Moreover, gene ontology and CytoTRACE analysis of nucleosomally more accessible transcription factors in cfDNA revealed enrichment for stemness-associated transcription factors in patients with lethal mCRPC. The resulting stemness signature was then validated in a completely held-out cohort of 80 patients with mCRPC profiled by tumor RNA sequencing. Conclusions: We analyzed a total of 220 patients with mCRPC, validated the importance of cell-free AR/enhancer alterations as a prognostic biomarker in lethal mCRPC, and showed that the underlying mechanism for lethality involves reprogramming developmental states toward increased stemness. See related commentary by Nawfal et al., p. 7