Craniofacial and Velopharyngeal Dimensions in Infants 0-12 Months: Between- and Within-Group Differences Based on Age and Sex.

PURPOSE: The purpose of the present study is to (a) provide quantitative data on the growth of levator veli palatini (LVP), velopharyngeal (VP), and craniofacial dimensions in children under 12 months while controlling for corrected age and sex and (b) compare variability within age and sex groups. METHOD: Magnetic resonance imaging scans of 75 infants between 0 and 12 months were measured and divided into four age groups. These data were obtained as part of a larger retrospective study. Following exclusion criteria, scans were analyzed, and dependent variables were obtained. RESULTS: There was a statistically significant (p < .0001) difference between corrected age groups on LVP muscle, VP, and craniofacial variables while controlling for sex. Significant growth effects were observed for LVP length (p < .0001), extravelar length (p < .0001), intravelar length (p = .048), midline thickness (p = .0001), origin-origin distance (p < .0001), velar length (p < .0001), velar thickness (p = .003), nasion-sella turcica distance (p < .0001), sella turcica-basion distance (p < .0001), and hard palate length (p < .0001). Significant sex effects were observed for pharyngeal depth (p = .026) and effective VP ratio (p = .014). When age was treated as a continuous variable, similar results were observed for all variables except pharyngeal depth. Within-group comparisons revealed the most variability occurs between 3 and 5.99 months for LVP and craniofacial variables and between 9 and 11.99 months of age for VP variables. Male participants demonstrated greater variability than female participants. CONCLUSIONS: Differences were observed in LVP, VP, and craniofacial variables in children under 12 months while controlling for sex. Males demonstrated larger values and greater variability for most variables.

Early Circulating Tumor DNA Shedding Kinetics for Prediction of Platinum Sensitivity in Patients With Small Cell Lung Cancer.

PURPOSE: Small cell lung cancer (SCLC) is characterized by rapid progression after platinum resistance. Circulating tumor (ctDNA) dynamics early in treatment may help determine platinum sensitivity. MATERIALS AND METHODS: Serial plasma samples were collected from patients receiving platinum-based chemotherapy for SCLC on the first 3 days of cycle one and on the first days of subsequent cycles with paired samples collected both before and again after infusions. Tumor-informed plasma analysis was carried out using CAncer Personalized Profiling by deep Sequencing (CAPP-Seq). The mean variant allele frequency (VAF) of all pretreatment mutations was tracked in subsequent blood draws and correlated with radiologic response. RESULTS: ctDNA kinetics were assessed in 122 samples from 21 patients. Pretreatment VAF did not differ significantly between patients who did and did not respond to chemotherapy (mean 22.5% v 4.6%, P = .17). A slight increase in ctDNA on cycle 1, day 1 immediately post-treatment was seen in six of the seven patients with available draws (fold change from baseline: 1.01-1.44), half of whom achieved a response. All patients who responded had a >2-fold decrease in mean VAF on cycle 2 day 1 (C2D1). Progression-free survival (PFS) and overall survival (OS) were significantly longer in patients with a >2-fold decrease in mean VAF after one treatment cycle (6.8 v 2.6 months, log-rank P = .0004 and 21.7 v 6.4 months, log rank P = .04, respectively). CONCLUSION: A >2-fold decrease in ctDNA concentration was observed by C2D1 in all patients who were sensitive to platinum-based therapy and was associated with longer PFS and OS.

Hot melt extruded High-Dose amorphous solid dispersions containing lumefantrine and Soluplus.

Over the last 15 years, a small number of paediatric artemisinin-based combination therapy products have been marketed. These included Riamet® and Coartem® dispersible tablets, a combination of artemether and lumefantrine, co-developed by the Medicines for Malaria Venture and Novartis. Disappointingly, patient compliance, requirement for high-fat meal, and sporadic drug dissolution behaviours following administration still result in considerable challenges for these products. The first and foremost barrier that needs addressed for successful delivery of the artemether/lumefantrine combination is the poor solubility of lumefantrine within the gastrointestinal fluids. In this work, amorphous solid dispersions of lumefantrine within Soluplus®-based matrices have been manufactured using hot melt extrusion as a potential formulation strategy to achieve enhanced dissolution and apparent solubility. The drug loading capacity of Soluplus® to accommodate amorphous lumefantrine, whilst ensuring improved in-vitro dissolution performance, was investigated. The extrusion process employed a variety of processing parameters, including various temperature profiles and different production scales. The influence of variation in extrusion conditions upon the physical stability of manufactured amorphous solid dispersions was also examined. This allowed for a greater understanding of the role of extrusion processing conditions on the performance of supersaturated amorphous solid dispersions during dissolution and storage. This may allow for the design and manufacture of drug enabled formulations with lower drug dosing and thus a lower risk of adverse effects.

Determinants of successful minimally invasive surgery (MIS) for resectable non-small cell lung cancer (NSCLC) after neoadjuvant therapy.

OBJECTIVE: MIS (VATS, RATS) for pulmonary resection is standard in early stage NSCLC as it is associated with better perioperative outcomes than thoracotomy. MIS for resection of more advanced NSCLC (Stages IB-IIIB) treated with neoadjuvant therapy has been utilized. However, the determinants of success are not well-defined. METHODS: A single institution retrospective review of a prospectively maintained database was conducted, querying for patients with clinical Stage IB-IIIB NSCLC who had resection after neoadjuvant systemic therapy without radiation from 2013-2022. Patients were grouped by surgical approach, open vs. MIS. Successful MIS was defined by no conversion, R0 resection, and no major (≥grade 3) morbidity. Analyses by intent-to-treat assessed outcomes by Wilcoxon rank sum test and Fisher's exact test. (MVA identified variables that contributed to successful MIS resection. RESULTS: Of 627 eligible patients, 360 (57%) had open and 267 (43%) had MIS procedures. Most patients (79.1%) received neoadjuvant platinum-based chemotherapy, and 21.9% were treated with immunotherapy or targeted therapy alone or combined with chemotherapy. Among MIS resections, 179 (67%) were performed by VATS and 88 (33%) by RATS. The conversion rate was 16% (n=43). Successful MIS resection was achieved in 77% of patients. MVA showed that pre-treatment clinical N stage was a significant determinant of success, but not pre-treatment clinical T stage or type of neoadjuvant therapy. CONCLUSION: Following neoadjuvant systemic therapy for clinical stage IB-IIIB NSCLC, MIS resection can be successfully accomplished and should be considered in appropriate patients. Presence of pre-treatment nodal disease is associated with higher odds of conversion, major morbidity, and incomplete resection.

Reliability and validity of belt-stabilized and tension dynamometry for assessing hip strength and power in uninjured adults.

OBJECTIVES: To investigate the intra-rater reliability and validity of belt-stabilized and tension dynamometry to assess hip muscle strength and power. DESIGN: Repeated measures. SETTING: Biomechanics laboratory. PARTICIPANTS: Seventeen uninjured adults (age = 22.0 ± 2.3y; 13 females). MAIN OUTCOMES MEASURES: Peak torque (strength) and rate of torque development (RTD; power) were measured for hip abduction, internal rotation, external rotation and extension using an isokinetic dynamometer, and belt-stabilized and tension dynamometry. RESULTS: For peak torque assessment, belt-stabilized and tension dynamometry showed good (Intraclass Correlation Coefficient [ICC] = 0.848-0.899) and good-to-excellent (ICC = 0.848-0.942) reliability, respectively. For RTD, belt-stabilized dynamometry showed fair reliability for abduction (ICC = 0.524) and good reliability for hip internal rotation, external rotation, and extension (ICC = 0.702-0.899). Tension dynamometry showed good reliability for all motions when measuring RTD (ICC = 0.737-0.897). Compared to isokinetic dynamometry, belt-stabilized and tension dynamometry showed good-to-excellent correlations for peak torque assessment (r = 0.503-0.870), and fair-to-good correlations for RTD (r = 0.438-0.674). Bland-Altman analysis showed that measures from belt-stabilized and tension dynamometry had clinically meaningful disagreement with isokinetic dynamometry. CONCLUSION: Tension dynamometry is reliable for assessing hip strength and power in all assessed motions. Belt-stabilized dynamometry is reliable for assessing internal rotation, external rotation, and extension. Validity of both methods is questionable, considering the lack of agreement with isokinetic dynamometry.

A Novel Frailty Index Can Predict the Short-Term Outcomes of Esophagectomy in Older Patients with Esophageal Cancer.

Background: Frailty, rather than age, is associated with postoperative morbidity and mortality. We sought to determine whether preoperative frailty as defined by a novel scoring system could predict the outcomes among older patients undergoing esophagectomy. Methods: We identified patients 65 years or older who underwent esophagectomy between 2011 and 2021 at our institution. Frailty was assessed using the MSK-FI, which consists of 1 component related to functional status and 10 medical comorbidities. We used a multivariable logistic regression model to test for the associations between frailty and short-term outcomes, with continuous frailty score as the predictor and additionally adjusted for age and Eastern Cooperative Oncology Group performance status. Results: In total, 447 patients were included in the analysis (median age of 71 years [interquartile range, 68-75]). Most of the patients underwent neoadjuvant treatment (81%), an Ivor Lewis esophagectomy (86%), and minimally invasive surgery (55%). A total of 22 patients (4.9%) died within 90 days of surgery, 144 (32%) had a major complication, 81 (19%) were readmitted, and 31 (7.2%) were discharged to a facility. Of the patients who died within 90 days, 19 had a major complication, yielding a failure-to-rescue rate of 13%. The risk of 30-day major complications (OR, 1.24 [95% CI, 1.09-1.41]; p = 0.001), readmissions (OR, 1.31 [95% CI, 1.13-1.52]; p < 0.001), and discharge to a facility (OR, 1.86 [95% CI, 1.49-2.37]; p < 0.001) increased with increasing frailty. Frailty and 90-day mortality were not associated. Conclusions: Frailty assessment during surgery decision-making can identify patients with a high risk of morbidity.

Data-driven retrieval of population-level EEG features and their role in neurodegenerative diseases.

Electrophysiologic disturbances due to neurodegenerative disorders such as Alzheimer's disease and Lewy Body disease are detectable by scalp EEG and can serve as a functional measure of disease severity. Traditional quantitative methods of EEG analysis often require an a-priori selection of clinically meaningful EEG features and are susceptible to bias, limiting the clinical utility of routine EEGs in the diagnosis and management of neurodegenerative disorders. We present a data-driven tensor decomposition approach to extract the top 6 spectral and spatial features representing commonly known sources of EEG activity during eyes-closed wakefulness. As part of their neurologic evaluation at Mayo Clinic, 11 001 patients underwent 12 176 routine, standard 10-20 scalp EEG studies. From these raw EEGs, we developed an algorithm based on posterior alpha activity and eye movement to automatically select awake-eyes-closed epochs and estimated average spectral power density (SPD) between 1 and 45 Hz for each channel. We then created a three-dimensional (3D) tensor (record × channel × frequency) and applied a canonical polyadic decomposition to extract the top six factors. We further identified an independent cohort of patients meeting consensus criteria for mild cognitive impairment (30) or dementia (39) due to Alzheimer's disease and dementia with Lewy Bodies (31) and similarly aged cognitively normal controls (36). We evaluated the ability of the six factors in differentiating these subgroups using a Naïve Bayes classification approach and assessed for linear associations between factor loadings and Kokmen short test of mental status scores, fluorodeoxyglucose (FDG) PET uptake ratios and CSF Alzheimer's Disease biomarker measures. Factors represented biologically meaningful brain activities including posterior alpha rhythm, anterior delta/theta rhythms and centroparietal beta, which correlated with patient age and EEG dysrhythmia grade. These factors were also able to distinguish patients from controls with a moderate to high degree of accuracy (Area Under the Curve (AUC) 0.59-0.91) and Alzheimer's disease dementia from dementia with Lewy Bodies (AUC 0.61). Furthermore, relevant EEG features correlated with cognitive test performance, PET metabolism and CSF AB42 measures in the Alzheimer's subgroup. This study demonstrates that data-driven approaches can extract biologically meaningful features from population-level clinical EEGs without artefact rejection or a-priori selection of channels or frequency bands. With continued development, such data-driven methods may improve the clinical utility of EEG in memory care by assisting in early identification of mild cognitive impairment and differentiating between different neurodegenerative causes of cognitive impairment.

Barramundi (Lates calcarifer) rare coloration patterns: a multiomics approach to understand the "panda" phenotype.

The barramundi (Lates calcarifer), a significant aquaculture species, typically displays silver to bronze coloration. However, attention is now drawn to rare variants like the "panda" phenotype, characterized by blotch-like patterns of black (PB) and golden (PG) patches. This phenotype presents an opportunity to explore the molecular mechanisms underlying color variations in teleosts. Unlike stable color patterns in many fish, the "panda" variant demonstrates phenotypic plasticity, responding dynamically to unknown cues. We propose a complex interplay of genetic factors and epigenetic modifications, focusing on DNA methylation. Through a multiomics approach, we analyze transcriptomic and methylation patterns between PB and PG patches. Our study reveals differential gene expression related to melanosome trafficking and chromatophore differentiation. Although the specific gene responsible for the PB-PG difference remains elusive, candidate genes like asip1, asip2, mlph, and mreg have been identified. Methylation emerges as a potential contributor to the "panda" phenotype, with changes in gene promoters like hand2 and dynamin possibly influencing coloration. This research lays the groundwork for further exploration into rare barramundi color patterns, enhancing our understanding of color diversity in teleosts. Additionally, it underscores the "panda" phenotype's potential as a model for studying adult skin coloration.

In Situ Eutectic Formation in a Polymeric Matrix via Hot-Melt Reactive Extrusion and the Use of Partial Least Squares Regression Modeling for Reaction Yield Determination.

There has been a significant volume of work investigating the design and synthesis of new crystalline multicomponent systems via examining complementary functional groups that can reliably interact through the formation of noncovalent bonds, such as hydrogen bonds (H-bonds). Crystalline multicomponent molecular adducts formed using this approach, such as cocrystals, salts, and eutectics, have emerged as drug product intermediates that can lead to effective drug property modifications. Recent advancement in the production for these multicomponent molecular adducts has moved from batch techniques that rely upon intensive solvent use to those that are solvent-free, continuous, and industry-ready, such as reactive extrusion. In this study, a novel eutectic system was found when processing albendazole and maleic acid at a 1:2 molar ratio and successfully prepared using mechanochemical methods including liquid-assisted grinding and hot-melt reactive extrusion. The produced eutectic was characterized to exhibit a 100 °C reduction in melting temperature and enhanced dissolution performance (>12-fold increase at 2 h point), when compared to the native drug compound. To remove handling of the eutectic as a formulation intermediate, an end-to-end continuous-manufacturing-ready process enables feeding of the raw parent reagents in their respective natural forms along with a chosen polymeric excipient, Eudragit EPO. The formation of the eutectic was confirmed to have taken place in situ in the presence of the polymer, with the reaction yield determined using a multivariate calibration model constructed by combining spectroscopic analysis with partial least-squares regression modeling. The ternary extrudates exhibited a dissolution profile similar to that of the 1:2 prepared eutectic, suggesting a physical distribution (or suspension) of the in situ synthesized eutectic contents within the polymeric matrix.

Recurrence of Non-Small Cell Lung Cancer With Visceral Pleural Invasion: A Seconday Analysis of a Randomized Clinical Trial.

Importance: The randomized clinical trial Cancer and Leukemia Group B (CALGB) 140503 showed that for patients with clinically staged T1N0 non-small cell lung cancer (NSCLC; ≤2 cm), sublobar resections were associated with similar oncological outcomes to those after lobar resection. The association of the extent of parenchymal resection with recurrence and survival in patients with tumors pathologically upstaged to T2 based on visceral pleural invasion (VPI) is controversial. Objective: To determine survival and recurrence rates in patients with small peripheral pT2 NSCLC (≤2 cm) that was treated by either lobar or sublobar resection in CALGB 140503. Design, Participants, and Setting: CALGB 140503, a randomized multicenter noninferiority trial, included 697 patients with small peripheral NSCLC that was clinically staged as T1N0. Enrollment was from June 2007 through March 2017 at 83 participating institutions, and after a median follow-up of 7 years, the primary outcome of disease-free survival after sublobar resection was noninferior to that after lobar resection. Intervention: Lobar or sublobar resection. Main Outcomes and Measures: Survival end points were estimated by the Kaplan-Meier estimator. Hazard ratios and 95% CIs were estimated using stratified Cox proportional hazard models. Results: Of 679 participants, 390 (57.4%) were female, and the median (range) age was 67.8 (37.8-89.7) years. Among 697 patients randomized, 566 (81.2%) had pT1 tumors (no VPI) and 113 (16.2%) had pT2 tumors (VPI). Five-year disease-free survival was 65.9% (95% CI, 61.9%-70.2%) in patients with pT1 compared with 53.3% (95% CI, 44.3%-64.1%) in patients with pT2 tumors (stratified log-rank: P = .02). Disease recurrence developed in 27.6% of patients with pT1 (locoregional only: 60 [10.8%]; distant only: 81 [14.6%]) and 41.6% of those with pT2 (locoregional only: 17 [15.0%]; distant only: 27 [23.9%]). Five-year recurrence-free survival was 73.1% (95% CI, 69.2%-77.1%) for pT1 tumors and 58.2% (95% CI, 49.2%-68.8%) for pT2 tumors (stratified log-rank: P = .01). There were no intergroup differences in disease-free or recurrence-free survival based on the extent of parenchymal resection. Conclusions and Relevance: The results of this secondary analysis suggest that compared with patients with tumors without VPI, patients who had tumors with VPI had worse disease-free and recurrence-free survival and a higher rate of local and distant disease recurrence. These high rates of recurrence were independent of the extent of parenchymal resection, and these data support the inclusion of these patients in adjuvant therapy trials. Trial Registration: ClinicalTrials.gov Identifier: NCT0049933.

Optimal systemic treatment and real-world clinical application of ctDNA in patients with metastatic HER2-mutant lung cancer.

INTRODUCTION: No definitive answers currently exist regarding optimal first-line therapy for HER2-mutant NSCLC. Access to rapid tissue sequencing is a major barrier to precision drug development in the first-line setting. ctDNA analysis has the potential to overcome these obstacles and guide treatment. METHODS: We retrospectively analyzed patients with metastatic HER2-mutant NSCLC who underwent prospective clinical ctDNA sequencing and received systemic therapy at Memorial Sloan Kettering Cancer Center (MSK) from January 2016 to September 2022. HER2 mutations were identified by next-generation sequencing through MSK-IMPACT, MSK-ACCESS or Resolution ctDx LungTM assay. Primary endpoints were time to the next treatment (TTNT) and overall survival (OS). RESULTS: Sixty-three patients were included in the primary analysis. Chemoimmunotherapy (33/63, 52.4 %) was the predominant first-line treatment with a median TTNT of 5.1 months (95 %CI 4.1 - 6.1) whereas 55.0 % (22/40) of patients who received second-line T-DXd obtained a median TTNT of 9.2 m (95 % CI, 0-22.2). Plasma ctDNA was tested before first-line therapy in 40 patients with a median OS of 28.0 months (95 % CI 21-34), in whom 31 patients (78.0 %) had detectable ctDNA. HER2 mutations were detected on ctDNA with a median turnaround time of 13 days, occasionally co-occurred with EGFR and MET alterations and were tracked longitudinally correlating with treatment response. Patients with detectable baseline ctDNA had significantly shorter OS (hazard ratio (HR), 5.25; 95 % CI, 1.2-23.9; p = 0.019). CONCLUSION: Chemoimmunotherapy remains a major treatment option for metastatic HER2-mutant NSCLC. ctDNA can rapidly detect HER2 and co-mutations, and it has the potential to guide and monitor optimal first-line therapy. As a negative prognostic biomarker, detectable ctDNA at baseline would need to be taken into account for patient selection in future studies.

COBALT: A Confirmatory Trial of Obeticholic Acid in Primary Biliary Cholangitis With Placebo and External Controls.

OBJECTIVES: Obeticholic acid (OCA) treatment for primary biliary cholangitis (PBC) was conditionally approved in the phase 3 POISE trial. The COBALT confirmatory trial assessed whether clinical outcomes in PBC patients improve with OCA therapy. METHODS: Patients randomized to OCA (5-10 mg) were compared with placebo (randomized controlled trial [RCT]) or external control (EC). The primary composite endpoint was time to death, liver transplant, model for end-stage liver disease score ≥15, uncontrolled ascites, or hospitalization for hepatic decompensation. A prespecified propensity score-weighted EC group was derived from a US healthcare claims database. RESULTS: In the RCT, the primary endpoint occurred in 28.6% of OCA (n=168) and 28.9% of placebo patients (n=166; intent-to-treat [ITT] analysis hazard ratio [HR]=1.01, 95% CI=0.68-1.51), but functional unblinding and crossover to commercial therapy occurred, especially in the placebo arm. Correcting for these using inverse probability of censoring weighting (IPCW) and as-treated analyses shifted the HR to favor OCA. In the EC (n=1051), the weighted primary endpoint occurred in 10.1% of OCA and 21.5% of non-OCA patients (HR=0.39; 95% CI=0.22-0.69; P=0.001). No new safety signals were identified in the RCT. CONCLUSIONS: Functional unblinding and treatment crossover, particularly in the placebo arm, confounded the ITT estimate of outcomes associated with OCA in the RCT. Comparison with the real-world EC showed that OCA treatment significantly reduced the risk of negative clinical outcomes. These analyses demonstrate the value of EC data in confirmatory trials and suggest that treatment with OCA improves clinical outcomes in patients with PBC.

A validation study demonstrating portable motion capture cameras accurately characterize gait metrics when compared to a pressure-sensitive walkway.

Digital quantification of gait can be used to measure aging- and disease-related decline in mobility. Gait performance also predicts prognosis, disease progression, and response to therapies. Most gait analysis systems require large amounts of space, resources, and expertise to implement and are not widely accessible. Thus, there is a need for a portable system that accurately characterizes gait. Here, depth video from two portable cameras accurately reconstructed gait metrics comparable to those reported by a pressure-sensitive walkway. 392 research participants walked across a four-meter pressure-sensitive walkway while depth video was recorded. Gait speed, cadence, and step and stride durations and lengths strongly correlated (r > 0.9) between modalities, with root-mean-squared-errors (RMSE) of 0.04 m/s, 2.3 steps/min, 0.03 s, and 0.05-0.08 m for speed, cadence, step/stride duration, and step/stride length, respectively. Step, stance, and double support durations (gait cycle percentage) significantly correlated (r > 0.6) between modalities, with 5% RMSE for step and stance and 10% RMSE for double support. In an exploratory analysis, gait speed from both modalities significantly related to healthy, mild, moderate, or severe categorizations of Charleson Comorbidity Indices (ANOVA, Tukey's HSD, p < 0.0125). These findings demonstrate the viability of using depth video to expand access to quantitative gait assessments.

Natural Selection Across Three Generations of Americans.

We investigate natural selection on polygenic scores in the contemporary US, using the Health and Retirement Study. Across three generations, scores which correlate negatively (positively) with education are selected for (against). However, results only partially support the economic theory of fertility as an explanation for natural selection. The theory predicts that selection coefficients should be stronger among low-income, less educated, unmarried and younger parents, but these predictions are only half borne out: coefficients are larger only among low-income parents and unmarried parents. We also estimate effect sizes corrected for noise in the polygenic scores. Selection for some health traits is similar in magnitude to that for cognitive traits.

Late recurrence of completely resected stage I to IIIA lung adenocarcinoma.

OBJECTIVE: Research into the risk factors associated with late recurrence (>2 years after surgery) of lung adenocarcinoma is limited. We investigated the incidence of and clinicopathologic and genomic features associated with late recurrence of resected stage I-IIIA lung adenocarcinoma. METHODS: We performed a retrospective analysis of patients with completely resected pathologic stage I-IIIA lung adenocarcinoma (2010-2019). Patients with a history of lung cancer, neoadjuvant therapy, or mucinous or noninvasive lung adenocarcinoma, or with follow-up of less than 2 years were excluded. Cox and logistic regression modeling were used to compare clinicopathologic variables among patients with no, early (≤2 years), and late recurrence. Comparisons of genomic mutations were corrected for multiple testing. RESULTS: Of the 2349 patients included, 537 developed a recurrence during follow-up. Most recurrences (55% [297/537]) occurred early; 45% (240/537) occurred late. A larger proportion of late recurrences than early recurrences were locoregional (37% vs 29%; P = .047). Patients with late recurrence had more aggressive pathologic features (International Association for the Study of Lung Cancer grade 2 and 3, lymphovascular invasion, visceral pleural invasion) and higher stage than patients without recurrence. Pathologic features were similar between patients with early and late recurrence, except stage IIIA disease was more common in the early cohort. No genomic mutations were associated with late recurrence. CONCLUSIONS: Late recurrence of lung adenocarcinoma after resection is more common than previously reported. Patients without disease more than 2 years after surgery who had aggressive pathologic features at the time of resection have an elevated risk of recurrence and may benefit from more aggressive follow-up.

Test-Retest Reliability and Visual Perturbation Performance Costs During 2 Reactive Agility Tasks.

CONTEXT: High secondary injury rates after orthopedic surgeries have motivated concern toward the construct validity of return-to-sport test batteries, as it is evident that common strength and functional assessments fail to elicit pertinent behaviors like visual search and reactive decision making. This study aimed to establish the test-retest reliability of 2 reactive agility tasks and evaluate the impact of visual perturbation on physical performance. METHODS: Fourteen physically active individuals completed 2 agility tasks with reaction time (ie, 4 corner agility), working memory, and pathfinding (ie, color recall) components. Participants completed both tasks 4 times in 2 sessions scheduled 7 days apart. Outcomes included performance metrics of reaction time, time to target, number of targets, and total time assessed with reactive training timing gates. To assess test-retest reliability, we used intraclass correlation coefficients (ICCs), standard error of measurement (SEM), and minimal detectable change (MDC). Stroboscopic goggles induced visual perturbation during the fourth trial of each task. To assess the effect of visual perturbation, we used paired t tests and calculated performance costs. RESULTS: The 4-corner agility task demonstrated excellent reliability with respect to reaction time (ICC3,1 = .907, SEM = 0.13, MDC = 0.35 s); time to light (ICC3,1 = .935, SEM = 0.07, MDC = 0.18 s); and number of lights (ICC3,1 = .800, SEM = 0.24, MDC = 0.66 lights). The color recall task demonstrated good-to-excellent test-retest reliability for time to lights (ICC3,1 = .818-.953, SEM = 0.07-0.27, MDC = 0.19-0.74 s); test time (ICC3,1 = .969, SEM = 5.43, MDC = 15.04 s); and errors (ICC3,1 = .882, SEM = 0.19, MDC = 0.53 errors). Visual perturbation resulted in increased time to target (P = .022-.011), number of targets (P = .039), and total test time (P = .013) representing moderate magnitude degradation of performance (d = 0.55-0.87, performance costs = 5%-12%). CONCLUSIONS: Both tasks demonstrated acceptable test-retest reliability. Performance degraded on both tasks with the presence of visual perturbation. These results suggest standardized reactive agility tasks are reliable and could be developed as components of dynamic RTS testing.

Paclitaxel, Ifosfamide, and Cisplatin as Initial Salvage Chemotherapy for Germ Cell Tumors: Long-Term Follow-Up and Outcomes for Favorable- and Unfavorable-Risk Disease.

PURPOSE: Paclitaxel, ifosfamide, and cisplatin (TIP) is an established salvage regimen for germ cell tumors (GCT) on the basis of a phase II trial, but efficacy on a large patient cohort including patients with unfavorable risk features and long-term outcomes has not been reported. Herein, we report updated treatment efficacy and long-term follow-up with TIP. PATIENTS AND METHODS: Patients with GCT who received TIP after cisplatin-based chemotherapy were eligible. Favorable response (complete response or partial response with negative tumor markers), overall survival (OS) and progression-free survival (PFS) rates, relapse, and toxicity were determined. Disease was reclassified according to the International Prognostic Factor Study Group (IPFSG) score. RESULTS: Of the 104 patients, 87 had favorable risk factors and 17 had at least one unfavorable factor by Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Ten patients were treated for a second gonadal primary GCT. With a median follow-up of 8.9 years, the 5-year PFS and OS rates were 66% (95% CI, 55 to 74) and 69% (95% CI, 59 to 77), respectively. Among 87 patients with favorable-risk disease, 69 (79%) achieved a favorable response with 5-year PFS and OS rates of 67% (95% CI, 56 to 76) and 72% (95% CI, 61 to 80), respectively. Among 17 patients with MSKCC unfavorable-risk disease, 13 (76%) achieved a favorable response with 5-year PFS and OS rates of 59% (95% CI, 33 to 78) and 56% (95% CI, 28 to 76), respectively. After IPFSG reclassification, 5-year PFS and OS rates for patients with ≤intermediate-risk disease were 75% (95% CI, 50 to 89) and 73% (95% CI, 55 to 85), respectively. CONCLUSION: TIP is an effective second-line regimen for patients with GCT. Similar outcomes were observed in patients with favorable- and unfavorable-risk disease. The randomized TIGER trial (ClinicalTrials.gov identifier: NCT02375204) comparing TIP with high-dose chemotherapy will determine the optimal second-line treatment approach.