Psychological Risk Factors for Delayed Recovery Among Active Duty Service Members Seeking Treatment for Musculoskeletal Complaints at a Navy Shore-Based Military Medical Treatment Facility.

INTRODUCTION: Musculoskeletal injuries (MSIs) are a leading cause of separation from the U.S. Navy. Data have shown that several psychological responses to MSI are associated with treatment outcomes. Yellow flags are maladaptive psychological responses to injury and predict delayed recovery, whereas pink flags indicate resilience after MSI and are associated with good treatment outcomes. Identifying these factors in patients with MSI would permit early targeted care to address factors that may delay their readiness for deployment and enhance factors that support recovery. MATERIALS AND METHODS: Active duty service members with MSI who reported to physical therapy outpatient services at a naval hospital were recruited for the study. Yellow flags were assessed at baseline as part of a larger study. Participants completed the Fear Avoidance Beliefs Questionnaire (with two subscales, physical activity and work), the Pain Catastrophizing Scale, and the Hospital Anxiety and Depression Scale. Clinically relevant cut-off scores were used to indicate risk factors of delayed recovery. Pink flags were assessed with the Pain Self-Efficacy Questionnaire and a measure of positive outcome expectations for recovery. RESULTS: Two hundred and ninety participants responded to some or all of the questionnaires. Of these, 82% exceeded the cut-off scores on the physical activity subscale of the Fear Avoidance Beliefs Questionnaire, and 39% did so on the work subscale. Pain catastrophizing exceeded the cut-off in only 4.9% of the sample. Forty-three percent of these exceeded the cut-off for the anxiety subscale of the Hospital Anxiety and Depression Scale; 27% exceeded the cut-off on the depression subscale of the Hospital Anxiety and Depression Scale. Additionally, 54% endorsed scores greater than 40 on the Pain Self-Efficacy Questionnaire, and 53% endorsed a high score on the positive outcome expectations. CONCLUSIONS: A substantial portion of the sample endorsed elevated scores on one or more indicators of delayed recovery from MSI. Most participants showed a fear of physical activity, and approximately half reported pain-related distress (anxiety and depression). In addition, feelings of self-efficacy and positive outcome expectations of treatment were endorsed by only about half of the participants, indicating that the remaining half did not report adaptive responses to MSI. Early identification of these risk factors will allow for targeted treatment approaches that incorporate these yellow flags into treatment and support a psychologically informed approach to physical therapy. This approach is likely to reduce delayed recovery and improve deployment readiness.

Musculoskeletal Complaints Among Active Duty Service Members Seeking Treatment at a Navy Military Treatment Facility.

INTRODUCTION: Musculoskeletal injuries (MSIs) pose a significant problem for active duty service members (ADSMs). MSIs may compromise readiness and are one of the main reasons for separation from the Navy and long-term disability. Implementation of optimal treatment strategies rests on understanding the characteristics of MSI complaints in a given population. This study reports on the frequency and nature of MSI complaints of ADSMs seeking care at a military treatment facility (MTF). MATERIALS AND METHODS: As part of a larger quasi-experimental study, data on MSIs from ADSMs reporting to an MTF were collected. Subjects completed a baseline questionnaire during an initial evaluation, including the self-reported MSIs for which participants were seeking care, time since onset, and other MSI comorbidities. RESULTS: Of the 289 respondents, 118 (41%) were female and 172 (59%) were male. The mean age was 33 years (SD = 8). The most frequently reported injury was low-back pain (n = 79, 27%), followed by knee pain (n = 60, 21%) and shoulder pain (n = 55, 19%). Thirty-four (12%) respondents reported injuries to the ankle or foot. The remaining respondents (21%) reported injuries to the neck, mid-back, arm or hand, hip, or other. Sixty-five (22%) reported an acute/subacute injury of less than 3 months, whereas 224 (78%) reported chronic injury >3 months. Furthermore, MSI comorbidities were reported by 233 (80%) of respondents with 128 of those reporting more than one. CONCLUSIONS: Back and knee injuries were most prevalent in ADSMs reporting an MSI at a Navy shore-based MTF. Shoulder injuries were also common. Of interest, 80% of ADSMs reported at least one MSI comorbidity and 80% reported chronic injury in this study. These rates are higher than those found in a previous study of ADSMs deployed on a carrier. This is notable because chronicity and multiple MSIs are obstacles to readiness. Our findings suggest that ADSMs reporting to shore-based facilities may be at higher risk for disability than their deployed counterparts. This information is important to the development of targeted care to improve readiness in this population.

Skeletal muscle mass and quality in gout patients versus non-gout controls: A computed tomography imaging study.

OBJECTIVE: Patients with gout are at elevated risk of multiple vascular and metabolic comorbidities. Whether they are also at risk of sarcopenia, which is known to affect patients with other rheumatic diseases, has not been previously assessed. We examined whether patients with gout have decreased lumbar muscle quality and quantity, indicating an association between gout and sarcopenia. METHODS: Fifty gout subjects and 25 controls, ages 45-80, underwent computed tomography imaging of the lumbosacral spine. We measured muscle quantity (skeletal muscle area [SMA] and index [SMI]) and quality (skeletal muscle radiation attenuation [SMRA] and intermuscular adipose tissue [IMAT] area and index [IMATI]) of the psoas and erector spinae muscles at the L3 level. RESULTS: Seventy subjects (45 gout and 25 controls) were included in the analysis. Gout subjects had higher BMI, more kidney disease and hypertension, lower exercise frequency, and higher mean serum urate and creatinine vs. controls. Lumbar SMRA was significantly lower in gout subjects vs. controls, indicating reduced muscle quality. Lumbar IMAT area was significantly higher in gout subjects vs. controls, as was lumbar IMATI, indicating increased muscle adiposity. These differences persisted after adjusting for potential confounders. In contrast, there was no significant difference between gout and control groups in lumbar SMA or lumbar SMI, suggesting that muscle quantity may not be routinely affected by the diagnosis of gout. CONCLUSIONS: Gout patients exhibit decreased lumbar muscle quality compared with controls, consistent with an association between gout and sarcopenia.

Infection Rates of an Intraoral Versus Extraoral Approach to Mandibular Fracture Repairs are Equal: A Systematic Review and Meta-Analysis.

PURPOSE: This study investigates whether the intraoral approach to mandibular open reduction and internal fixation, through exposure to the oral cavity's microbiome, results in higher infection rates compared to the extraoral approach, thus addressing a critical public health concern, potentially offering an opportunity to reduce health-care costs, and aiming to guide effective clinical practice. METHODS: In this systematic review with meta-analyses, a review of the literature was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. A comprehensive literature search was conducted using Embase and PubMed for articles published between 1989 and 2023. Inclusion criteria targeted studies on open reduction and internal fixation mandibular fractures comparing intraoral and extraoral approaches and reporting infection rates. Exclusion criteria eliminated non-English articles, case reports, and studies with insufficient approach-specific data. The primary outcome was the postoperative infection rate, with surgical approach as the predictor. Covariates such as age, sex, diabetes, and smoking status were included when reported. Data were analyzed using R software, employing random-effects models due to anticipated heterogeneity (I2 statistics). RESULTS: From 61 studies, 11 provided direct comparisons involving 1,317 patients-937 intraoral and 380 extraoral. Infection rates were 5.9% for intraoral and 10% for extraoral approaches. Pooled relative risk was 0.94 [95% confidence interval, 0.63, 1.39], suggesting no significant risk difference. Prevalence of infections was estimated at 9% for intraoral and 6.1% for extraoral procedures, with significant heterogeneity (I2 = 84% for intraoral and 56% for extraoral). CONCLUSION: Our meta-analysis found no significant difference in infection rates between the two approaches. There is opportunity to expand on reporting complication rates comparing the various approaches to mandibular fixation. Until these data are presented, surgeon preference may dictate the operative approach to expose the mandible for reduction and fixation.

Predictive Factors Associated With Radiation Myelopathy in Pediatric Patients With Cancer: A PENTEC Comprehensive Review.

PURPOSE: Radiation myelitis (RM) is a rare complication of radiation therapy (RT). The Pediatric Normal Tissue Effects in the Clinic spinal cord task force aimed to identify RT dose effects and assess risk factors for RM in children. Through systematic review, we analyzed RT dose, fraction size, latency between completion of RT and toxicity, chemotherapy use, age when irradiated, and sex. METHODS AND MATERIALS: We conducted literature searches of peer-reviewed manuscripts published from 1964 to June 2017 evaluating RM among children. Normality of variables was assessed with Kolmogorov-Smirnov or Shapiro-Wilk tests. Spearman's rank correlation coefficients were used to test correlations between RT dose/fraction size and latency between RT and development of toxicity. RESULTS: Of 1329 identified and screened reports, 144 reports were fully reviewed and determined to have adequate data for analysis; 16 of these reports had a total of 33 cases of RM with a median age of 13 years (range, 0.2-18) at the time of RT. The most common primary tumor histologies were rhabdomyosarcoma (n = 9), medulloblastoma (n = 5), and Hodgkin lymphoma (n = 2); the most common chemotherapy agents given were vincristine (n = 15), intrathecal methotrexate (n = 12), and intrathecal cytarabine (n = 10). The median RT dose and fraction size were 40 Gy (range, 24-57.4 Gy) and 1.8 Gy (range, 1.3-2.6 Gy), respectively. RT dose resulting in RM in patients who also received chemotherapy was lower than in those not receiving chemotherapy (mean 39.6 vs 49.7 Gy; P = .04). There was no association of age with RT dose. The median latency period was 7 months (range, 1-29). Higher RT dose was correlated with longer latency periods (P = .03) to RM whereas sex, age, fraction size, and chemotherapy use were not. Two of 17 patients with adequate follow-up recovered from RM; unfortunately, it was fatal in 6 of 15 evaluable patients. Complication probability modeling was not possible because of the rarity of events. CONCLUSIONS: This report demonstrates a relatively short latency from RT (with or without chemotherapy) to RM and a wide range of doses (including fraction sizes) associated with RM. No apparent association with age at the time of RT could be discerned. Chemotherapy appears to reduce spinal cord tolerance. Recovery from RM is rare, and it is often fatal.

Effectiveness and toxicity of five-fraction prone accelerated partial breast irradiation.

PURPOSE: Our institution was an early adopter of 5-fraction accelerated partial breast irradiation (ABPI) to treat women with early-stage breast cancer. This study reports long-term oncologic and cosmetic outcomes. METHODS: We included patients receiving APBI 600 cGy × 5 fx delivered every other day or every day between 2010 and 2022. Logistic regression models were used to identify factors associated with development of late toxicities, clinician, and patient-rated cosmesis. Kaplan-Meier methodology was used to calculate overall survival (OS), disease-free survival (DFS), and locoregional recurrence-free survival (LR-RFS). RESULTS: 442 patients received APBI either daily (56%) or every other day (44%) in the prone position (92%). At a median follow-up of 48 months (range: 5.96-155 months), 12 (2.7%) patients developed a local recurrence (LR). Out of 258 patients with > 3-month toxicity data available, the most common late grade ≥ 2 adverse event was breast fibrosis (6.2%). On multivariate analysis, daily APBI treatment (vs every other day) did not correlate with an increased risk of any late grade ≥ 2 toxicity though it did correlate with a lower risk of any late grade ≥ 2 fibrosis. Overall, at a median follow-up of 80 months, the rates of good-excellent physician and patient-rated cosmesis were 95% and 85%, respectively, with no difference between patients treated on consecutive vs. every other day. On multivariate analysis, patients who did not receive any adjuvant therapy were at increased risk of developing a LR. Five-year OS, LRFS, and DFS were 97.2%, 97.7%, and 89.5%, respectively. CONCLUSIONS: Five-fraction APBI delivered primarily in the prone position either daily or every other day was effective with low rates of local recurrence, minimal toxicity, and excellent cosmesis at long-term follow-up.

Risk and Prognostics of Second Primary Cancer After Prostate Radiation Therapy.

INTRODUCTION: As overall survival in prostate cancer increases due to advances in early detection and management, there is a growing need to understand the long-term morbidity associated with treatment, including secondary tumors. The significance of developing radiation-associated secondary cancers in an elderly population remains unknown. METHODS: Patients diagnosed with prostate cancer between 1975 and 2016 in one of 9 Surveillance, Epidemiology, and End Results registries were included in this study. Risk of second primary pelvic malignancies (SPPMs) were assessed with death as a competing risk using the Fine-Gray model. Time-varying Cox proportional hazard models were employed to analyze risk to overall mortality based on secondary tumor status. RESULTS: A total of 569,167 primary prostate cancers were included in analysis with an average follow-up of 89 months. Among all prostate cancer patients, 4956 SPPMs were identified. After controlling for differences in age, year of diagnosis, and surgery at time of prostate cancer treatment, radiation receipt was associated with a significantly higher incidence of SPPMs (1.1% vs 1.8% at 25 years). Among those who received radiation during initial prostate cancer treatment (n = 195,415), developing an SPPM is significantly associated with worse survival (adjusted hazard ratio = 1.76), especially among younger patients (under age 63, adjusted hazard ratio = 2.36). CONCLUSIONS: While developing a secondary malignancy carries a detrimental effect on overall survival, the absolute risk of developing such tumors is exceedingly low regardless of radiation treatment.

Breathing on the mind: Treating dyspnea and anxiety symptoms with biofeedback in chronic lung disease - A qualitative analysis.

RATIONALE: Chronic obstructive pulmonary disease (COPD) is characterized by dysfunctional breathing patterns that contribute to impaired lung function and symptoms of dyspnea, anxiety, and abnormal carbon dioxide (CO2) levels. OBJECTIVE: The study objective was to measure the acceptability of a new mind-body intervention we developed called Capnography-Assisted, Learned Monitored (CALM) Breathing, implemented before pulmonary rehabilitation. METHODS: CALM Breathing is a 4-week (8-session) intervention designed to treat dyspnea and anxiety in adults with COPD by targeting dysfunctional breathing behaviors (guided by end-tidal CO2 levels). CALM Breathing consists of ten core breathing exercises, CO2 biofeedback, and motivational interviewing. Using qualitative methods and semi-structured interviews immediately post-intervention, we evaluated the acceptability and participation process of CALM Breathing. Themes were identified using constant comparative analysis. RESULTS: Sixteen participants were interviewed after receiving CALM Breathing. Three main themes of CALM Breathing were identified: (1) Process of learning self-regulated breathing, (2) Mechanisms of a mind-body intervention, (3) Clinical and implementation outcomes. CONCLUSIONS: Positive themes supported the acceptability of CALM Breathing and described participants' process of learning more self-regulated breathing to manage their dyspnea and anxiety. Positive signals from qualitative participant feedback provided support for CALM Breathing as an intervention for COPD, but larger scale efficacy trials are needed.

Protocol for the Implementation of Psychologically Informed Physical Therapy to Prevent Chronification in Service Members With Musculoskeletal Disorders.

INTRODUCTION: Musculoskeletal disorders (MSDs) are a primary cause of separation and long-term disability in active duty service members (ADSMs). Psychologically informed physical therapy (PiPT) is designed to identify and address modifiable psychological risk factors early in an MSD episode and has been proven effective in preventing chronicity in civilian populations. We developed a course to train military physical therapy (PT) personnel in PiPT for treating ADSM with MSD. This study tests the feasibility and effectiveness of our training. OBJECTIVE: Establish the feasibility of implementing PiPT and its effectiveness in the U.S. military. MATERIALS AND METHODS: An observational, prospective, comparative cohort study will test implementation and effectiveness. First, we will observe clinical outcomes in a cohort of ADSM with MSD receiving usual PT care at a military outpatient PT clinic. Next, we will train all PT staff in PiPT. Finally, PiPT will be implemented in a second cohort of ADSM. Data will be collected from each cohort at pre-treatment, fourth PT visit, 6 months post enrollment, and 12 months post enrollment. The primary outcomes are pain interference and psychological risk for chronicity. RESULTS AND CONCLUSIONS: Data collection is ongoing. Findings will identify the factors associated with PiPT outcomes in ADSM, inform the implementation of PiPT across health care settings, and allow us to document the prevalence of risk factors for chronicity in ADSM. Findings can help to prevent chronification from MSD, thereby reducing lost man-hours and enhancing military readiness, contribute to the development of a highly skilled workforce for the provision of health services to ADSM, and enhance the efficiency of health care delivery through optimal allocation of PT resources, resulting in significant cost savings for the military.

Capnography-Assisted Learned, Monitored (CALM) breathing therapy for dysfunctional breathing in COPD: A bridge to pulmonary rehabilitation.

BACKGROUND: Although dyspnea is a primary symptom of chronic obstructive pulmonary disease (COPD), its treatment is suboptimal. In both COPD and acute anxiety, breathing patterns become dysregulated, contributing to abnormal CO2, dyspnea, and inefficient recovery from breathing challenges. While pulmonary rehabilitation (PR) improves dyspnea, only 1-2% of patients access it. Individuals with anxiety who use PR have worse outcomes. METHODS: We present the protocol of a randomized controlled trial designed to determine the feasibility and acceptability of a new, four-week mind-body intervention that we developed, called "Capnography-Assisted Learned, Monitored (CALM) Breathing," as an adjunct to PR. Eligible participants are randomized in a 1:1 ratio to either CALM Breathing program or Usual Care. CALM Breathing consists of 10 core, slow breathing exercises combined with real time biofeedback (of end-tidal CO2, respiratory rate, and airflow) and motivational interviewing. CALM Breathing promotes self-regulated breathing, linking CO2 changes to dyspnea and anxiety symptoms and targeting breathing efficiency and self-efficacy in COPD. Participants are randomized to CALM Breathing or a Usual Care control group. RESULTS: Primary outcomes include feasibility and acceptability metrics of recruitment efficiency, participant retention, intervention adherence and fidelity, PR facilitation, patient satisfaction, and favorable themes from interviews. Secondary outcomes include breathing biomarkers, symptoms, health-related quality of life, six-minute walk distance, lung function, mood, physical activity, and PR utilization and engagement. CONCLUSION: By disrupting the cycle of dyspnea and anxiety, and providing a needed bridge to PR, CALM Breathing may address a substantive gap in healthcare and optimize treatment for patients with COPD.

No Increase in Symptoms Toward the End of the Ocrelizumab Infusion Cycle in Patients With Multiple Sclerosis: Symptom Burden on Ocrelizumab: A Longitudinal Study (SymBOLS).

Background and Objectives: Some patients with multiple sclerosis (MS) receiving ocrelizumab (OCR) report worsening symptoms toward the end of the 6-month infusion cycle ('wearing off'). The objective of our study was to comprehensively assess changes in symptom burden across 2 consecutive OCR infusion cycles. Methods: SYMptom Burden on Ocrelizumab, a Longitudinal Study (SymBOLS; NCT04855617) was an investigator-initiated, 2-center study of patients with MS starting or receiving OCR. Patients' symptoms were assessed with NeuroQoL short forms, SymptoMScreen, and Work Productivity and Activity Impairment Questionnaire at the start-cycle, mid-cycle, and end-cycle time points in each of the 2 infusion cycles. Symptom scores at the 3 time points within each cycle were compared with repeated-measures ANOVA or the Friedman rank-sum test for non-normal variables. The proportions of patients with a meaningful symptomatic change from the start to the end of each infusion cycle were calculated, and patients whose symptoms improved, worsened, and stayed the same from the start to the end of the cycle were compared with respect to demographic and clinical characteristics. Results: One hundred three patients with MS provided longitudinal data for analyses (mean age [SD]: 46.7 [12.2] years, 68% female, 33% non-White, disease duration: 15.5 [5] years, 41% with the Extended Disability Status Scale score >3). On a group level, NeuroQoL and SymptoMScreen scores mostly remained stable or even improved slightly toward the end of each cycle. On an individual level, symptoms remained unchanged across either cycle for most patients, and meaningful symptom worsening from the start to the end of the cycle was no more common than improvement. Meaningful change in symptoms in both cycles was very rare and generally in the direction of improvement toward the end cycle. Despite the lack of evidence for symptom worsening with a longer time from infusion, 54% of patients endorsed feeling of "wearing off" at least sometimes, most commonly as an increase in fatigue. Discussion: Our prospective study failed to uncover evidence for the worsening of symptoms with a longer time from OCR infusion. These findings cast doubt on the existence of wearing off as a physiologic phenomenon in OCR-treated patients with MS. The perception of wearing off is likely the result of natural fluctuations in MS symptoms and attribution bias.

Comparing Harmful Behaviors Among Dancers According to Sexual Orientation and Gender Identity Utilizing the RISQ.

INTRODUCTION: There is a dearth of information about whether lesbian, gay, bisexual, transgender, queer/questioning (LGBTQ+) dancers, who often experience increased psychosocial risk factors, are at increased risk of engaging in harmful behaviors compared to their heterosexual cisgender counterparts. This study explores harmful behaviors dancers engage in according to their self-reported sexual orientation and gender identity (SOGI), utilizing the validated Risky, Impulsive, and Self-Destructive Behavior Questionnaire (RISQ). METHODS: Three hundred sixty-four dancers from 7 elite dance entities in New York were contacted by e-mail to participate in the study. Sixty-six participants completed the study through a virtual questionnaire. Chi-square, ANOVA and independent t-test were utilized to assess statistical differences among RISQ outcomes in 4 SOGI groups: Cisgender Heterosexual Female (n = 20); Cisgender Heterosexual Male (n = 7); LGBTQ+ Female (n = 19); and LGBTQ+ Male (n = 20). RESULTS: Chi-square comparing SOGI group frequency of participation within each of the RISQ behaviors revealed statistically significant difference with: difficulty stopping eating (P = .05); gambling illegally (P = .036); betting on sports, horses, or other animals (P = .036); buying expensive items that cannot be afforded at the spur of the moment (P = .019); and drinking 5 or more alcoholic drinks in 3 hours or less (P = .013). Between-group frequency comparison through ANOVA and independent t-test revealed: the LGBTQ+ Male group were 92% more likely to have unprotected sex with someone they just met or did not know well (P < .001) and 83% more likely to use hallucinogens, LSD, or mushrooms (P = .018); the LGBTQ+ Female and LGBTQ+ Male groups were 4.4 times more likely to buy drugs (P = .01) and 4.88 times more likely to think about killing themselves (P = .023); and both male groups were 12.8 times more likely to steal money (P = .006). CONCLUSIONS: This study found significant difference in RISQ scores based on a dancer's SOGI. Harmful behaviors should be taken into consideration when working to improve dancer patient outcomes and quality of life.

Risk of Radiation Dermatitis in Patients With Skin of Color Who Undergo Radiation to the Breast or Chest Wall With and Without Regional Nodal Irradiation.

PURPOSE: Acute radiation dermatitis (ARD) is common after radiation therapy for breast cancer, with data indicating that ARD may disproportionately affect Black or African American (AA) patients. We evaluated the effect of skin of color (SOC) on physician-reported ARD in patients treated with radiation therapy. METHODS AND MATERIALS: We identified patients treated with whole breast or chest wall ± regional nodal irradiation or high tangents using 50 Gy in 25 fractions from 2015 to 2018. Baseline skin pigmentation was assessed using the Fitzpatrick scale (I = light/pale white to VI = black/very dark brown) with SOC defined as Fitzpatrick scale IV to VI. We evaluated associations among SOC, physician-reported ARD, late hyperpigmentation, and use of oral and topical treatments for RD using multivariable models. RESULTS: A total of 325 patients met eligibility, of which 40% had SOC (n = 129). On multivariable analysis, Black/AA race and chest wall irradiation had a lower odds of physician-reported grade 2 or 3 ARD (odds ratio [OR], 0.110; 95% confidence interval [CI], 0.030-0.397; P = .001; OR, 0.377; 95% CI, 0.161-0.883; P = .025), whereas skin bolus (OR, 8.029; 95% CI, 3.655-17.635; P = 0) and planning target volume D0.03cc (OR, 1.001; 95% CI, 1.000-1.001; P = .028) were associated with increased odds. On multivariable analysis, SOC (OR, 3.658; 95% CI, 1.236-10.830; P = .019) and skin bolus (OR, 26.786; 95% CI, 4.235-169.432; P = 0) were associated with increased odds of physician-reported late grade 2 or 3 hyperpigmentation. There was less frequent use of topical steroids to treat ARD and more frequent use of oral analgesics in SOC versus non-SOC patients (43% vs 63%, P < .001; 50% vs 38%, P = .05, respectively). CONCLUSIONS: Black/AA patients exhibited lower odds of physician-reported ARD. However, we found higher odds of late hyperpigmentation in SOC patients, independent of self-reported race. These findings suggest that ARD may be underdiagnosed in SOC when using the physician-rated scale despite this late evidence of radiation-induced skin toxicity.

Beyond BRCA: Patterns of risk-reducing surgery for non-BRCA, homologous recombination repair pathway gene variant carriers.

OBJECTIVE: The real-world management of patients with non-BRCA, homologous recombination repair pathway variants with increased or uncertain risks of ovarian cancer is unknown. The objective was to determine the adoption of risk-reducing salpingo-oophorectomy (RRSO) for carriers of variants with increased or uncertain risks of ovarian cancer beyond BRCA. METHODS: This was a retrospective cohort study of patients at three hospitals with non-BRCA, homologous recombination repair pathway variants with increased risk (BRIP1, RAD51C, RAD51D) and uncertain risk (ATM, BARD1, NBN, PALB2) of ovarian cancer. Outcomes of interest were adoption of RRSO and factors associated with adoption of RRSO. Wilcoxon rank-sum, chi-square, and logistic regression were performed with p < 0.05. RESULTS: Of 318 patients, 76 (24%) had pathogenic variants with increased risks of ovarian cancer (BRIP1, 45; RAD51C, 20; RAD51D, 11), and 242 (76%) had variants with uncertain risks of ovarian cancer (ATM, 145; PALB2, 69; NBN, 23; BARD1, 5). Of 64 patients eligible for RRSO by National Comprehensive Cancer Network (NCCN) criteria or family history, 31 (48%) underwent RRSO. Among eligible patients who did not undergo RRSO, 24 (73%) were not referred for gynecologic oncology consultation. Older age at testing (adjusted odds ratio [aOR] 1.08, 95% confidence interval [CI] 1.03-1.13) and referral to gynecologic oncology (aOR 33.48, CI 8.10-138.39) were associated with increased adoption of RRSO when adjusting for personal and family history of breast and ovarian cancer. CONCLUSION: Half of RRSO-eligible patients by NCCN criteria beyond BRCA did not undergo RRSO. Opportunities exist for improving education to increase referrals to facilitate RRSO for these patients.

Moving intra-individual variability (IIV) towards clinical utility: IIV measured using a commercial testing platform.

OBJECTIVES: Intra-individual variability (IIV), measured across repeated response times (RT) during continuous psychomotor tasks, is an early marker of cognitive change in the context of neurodegeneration. To advance IIV towards broader application in clinical research, we evaluated IIV from a commercial cognitive testing platform and compared it to the calculation approaches used in experimental cognitive studies. METHODS: Cognitive assessment was administered in participants with multiple sclerosis (MS) during the baseline of an unrelated study. Cogstate was used for computer-based measures providing three timed-trial tasks measuring simple (Detection; DET) and choice (Identification; IDN) RT and working memory (One-Back; ONB). IIV for each task was automatically output by the program (calculated as a log10-transformed standard deviation or "LSD"). We calculated IIV from the raw RTs using coefficient of variation (CoV), regression-based, and ex-Gaussian methods. The IIV from each calculation was then compared by rank across participants. RESULTS: A total of n = 120 participants with MS aged 20-72 (Mean ± SD, 48.99 ± 12.09) completed the baseline cognitive measures. For each task, the interclass correlation coefficient was generated. Each ICC showed that LSD, CoV, ex-Gaussian, and regression methods clustered strongly (Average ICC for DET: 0.95 with 95% CI [0.93, 0.96]; Average ICC for IDN: 0.92 with 95% CI [0.88 to 0.93]; Average ICC for ONB: 0.93 with 95% CI [0.90 to 0.94]). Correlational analyses indicated the strongest correlation between LSD and CoV for all tasks (rs ≥ 0.94). CONCLUSION: The LSD was consistent with research-based methods for IIV calculations. These findings support the use of LSD for the future measurement of IIV for clinical studies.

Predictors of Complication Severity Following Adult Spinal Deformity Surgery: Smoking Rate, Diabetes, and Osteotomy Increase Risk of Severe Adverse Events.

BACKGROUND: Given the physical and economic burden of complications in spine surgery, reducing the prevalence of perioperative adverse events is a primary concern of both patients and health care professionals. This study aims to identify specific perioperative factors predictive of developing varying grades of postoperative complications in adult spinal deformity (ASD) patients, as assessed by the Clavien-Dindo complication classification (Cc) system. METHODS: Surgical ASD patients ≥18 years were identified in the American College of Surgeons' National Surgical Quality Improvement Program from 2005 to 2015. Postoperative complications were stratified by Cc grade severity: minor (I, II, and III) and severe (IV and V). Stepwise regression models generated dataset-specific predictive models for Cc groups. Model internal validation was achieved by bootstrapping and calculating the area under the curve (AUC) of the model. Significance was set at P < 0.05. RESULTS: Included were 3936 patients (59 ± 16 years, 63% women, 29 ± 7 kg/m2) undergoing surgery for ASD (4.4 ± 4.7 levels, 71% posterior approach, 11% anterior, and 18% combined). Overall, 1% of cases were revisions, 39% of procedures involved decompression, 27% osteotomy, and 15% iliac fixation. Additionally, 66% of patients experienced at least 1 complication, 0% of which were Cc grade I, 51% II, 5% III, 43% IV, and 1% V. The final model predicting severe Cc (IV-V) complications yielded an AUC of 75.6% and included male sex, diabetes, increased operative time, central nervous system tumor, osteotomy, cigarette pack-years, anterior decompression, and anterior lumbar interbody fusion. Final models predicting specific Cc grades were created. CONCLUSIONS: Specific predictors of adverse events following ASD-corrective surgery varied for complications of different severities. Multivariate modeling showed smoking rate, osteotomy, diabetes, anterior lumbar interbody fusion, and higher operative time, among other factors, as predictive of severe complications, as classified by the Clavien-Dindo Cc system. These factors can help in the identification of high-risk patients and, consequently, improve preoperative patient counseling. CLINICAL RELEVANCE: The findings of this study provide a foundation for identifying ASD patients at high risk of postoperative complications .

Missed opportunities in the real-world genetic testing in BRCA gene variant carriers with cancers meeting NCCN criteria.

OBJECTIVE: The objective of this study was to determine the proportion of patients meeting the National Comprehensive Cancer Network (NCCN)'s BRCA genetic testing criteria prior to a diagnosis of a BRCA-related cancer. METHODS: This was a cross-sectional study of patients with BRCA pathogenic variants and a diagnosis of a BRCA-related cancer. Patients were included if they had known dates of genetic testing and cancer diagnosis. NCCN criteria (version 2.2021) were applied to determine if patients met criteria for testing before a BRCA-related cancer diagnosis. The outcome of interest was the proportion of patients undergoing genetic testing following a diagnosis of a BRCA-related cancer who qualified for genetic testing based on NCCN criteria. Chi-square, Mann-Whitney U test, and logistic regression were performed with significance at p < 0.05. RESULTS: Of 270 patients with a BRCA-related cancer, 229 (85%) underwent genetic testing after a cancer diagnosis. Most patients (97%) met at least one NCCN criteria for BRCA testing; 166 (73%) of patients who were tested following a BRCA-related cancer diagnosis also met the criteria for testing by family history. Publicly insured or uninsured patients were three times more likely to undergo BRCA testing after a diagnosis of cancer (odds ratio [OR] 3.03, 95% confidence interval [CI] 1.09-8.40). Patients with a family history of pathogenic variants were more likely to undergo testing before a cancer diagnosis (OR 0.10, 95% CI 0.05-0.23). CONCLUSION: Most patients with BRCA-associated cancers undergo genetic testing after their cancer diagnosis. Increased education on genetic testing criteria and novel methods to improve testing are desperately needed.

Early effectiveness and toxicity outcomes of reirradiation after breast conserving surgery for recurrent or new primary breast cancer.

PURPOSE: Breast reirradiation (reRT) after breast conserving surgery (BCS) has emerged as a viable alternative to mastectomy for women presenting with recurrent or new primary breast cancer. There are limited data on safety of different fractionation regimens. This study reports safety and efficacy among women treated with repeat BCS and reRT. METHODS AND MATERIALS: Patients who underwent repeat BCS followed by RT from 2015 to 2021 at 2 institutions were analyzed. Univariate logistic regression models were used to identify predictors of acute and late toxicities. Kaplan-Meier estimates were used to evaluate overall survival (OS), distant metastasis-free survival (DMFS) and locoregional recurrence-free survival (LR-RFS). RESULTS: Sixty-six patients were reviewed with median follow-up of 16 months (range: 3-60 months). At time of first recurrence, 41% had invasive carcinoma with a ductal carcinoma in situ (DCIS) component, 41% had invasive carcinoma alone and 18% had DCIS alone. All were clinically node negative. For the reirradiation course, 95% received partial breast irradiation (PBI) (57.5% with 1.5 Gy BID; 27% with 1.8 Gy daily; 10.5% with hypofractionation), and 5% received whole breast irradiation (1.8-2 Gy/fx), all of whom had received PBI for initial course. One patient experienced grade 3 fibrosis, and one patient experienced grade 3 telangiectasia. None had grade 4 or higher late adverse events. We found no association between the fractionation of the second course of RT or the cumulative dose (measured as EQD2) with acute or late toxicity. At 2 years, OS was 100%, DMFS was 91.6%, and LR-RFS was 100%. CONCLUSION: In this series of patients with recurrent or new primary breast cancer, a second breast conservation surgery followed by reirradiation was effective with no local recurrences and an acceptable toxicity profile across a range of available fractionation regimens at a median follow up of 16 months. Longer follow up is required.

Definitive Radiation With Nodal Boost for Patients With Locally Advanced Breast Cancer.

PURPOSE: The optimal local therapy of patients with nodal disease in supraclavicular (SCV), internal mammary nodes (IMN) and level III axilla is not well studied. We aimed to evaluate the outcomes of patients with breast cancer and advanced nodal disease that received a nodal boost. METHODS AND MATERIALS: This retrospective study included 79 patients with advanced nodal disease who underwent adjuvant radiation with a nodal boost to the SCV, IMNs, and/or axilla. All patients had radiographic changes after systemic therapy concerning for gross nodal disease. Overall survival, disease-free survival (DFS), and local recurrence-free survival were estimated using the Kaplan-Meier method. RESULTS: All patients received an initial 50 Gy to the breast/chest wall and regional nodes, of whom 46.8% received an IMN boost, 38.0% axillary (ax)/SCV boost, and 15.2% both IMN and ax/SCV boost (IMN + ax/SCV). Most patients had hormone receptor positive (74.7%) and human epidermal growth factor receptor 2 negative disease (83.5%). In addition, 12.7% of patients had clinical (c) N2 disease, 21.5% cN3A disease, 51.9% cN3B disease, and 5.1% cN3C disease. Most patients received chemotherapy (97.5%). The median nodal boost dose was 10 Gy (range, 10-20 Gy), with 21.6% of IMN, 16.7% of ax/SCV, and 16.7% of IMN + ax/SCV receiving 14 to 20 Gy. With a median follow up of 30 months, the 3-year local recurrence-free survival, DFS, and overall survival rates were 94.5%, 86.3%, and 93.8%, respectively. Crude rates of failure were 13.9% (10.1% distant failure [DF] alone; 3.8% DF + locoregional failure [LRF]). Rates of failure by boost group were 13.3% for ax/SCV (10.0% DF alone; 3.3% DF + LRF), 5.4% for IMN (2.7% DF alone, 2.7% DF + LRF), and 41.7% for IMN + ax/SCV (33.3% DF, 8.3% DF + LRF). There were no LRFs without DFs. The median time to failure was 22.8 months (interquartile range, 18-34 months). Clinical tumor size and IMN + ax/SCV versus IMN or ax/SCV alone was associated with worse DFS (hazard ratio [HR]: 9.78; 95% confidence interval [CI], 2.07-46.2; P = .004 and HR: 9.49; 95% CI, 2.67-33.7; P = .001, respectively). On multivariate analysis, IMN + ax/SCV versus IMN or ax/SCV alone retained significance (HR: 4.80; 95% CI, 1.27-18.13; P = .02). CONCLUSIONS: In this population of patients with locally advanced breast cancer, the majority of failures were distant with no isolated LRFs. Failures were the highest in the IMN + ax/SCV group (∼40%). Further treatment escalation is necessary for these patients.