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.

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.

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.

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.

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.

The Impact of Uterine Incision Closure Techniques on Post-cesarean Delivery Niche Formation and Size: Sonohysterographic Examination of Nonpregnant Women.

OBJECTIVE: To compare the prevalence and size of residual niche in the nongravid uterus following Cesarean delivery (CD) with different hysterotomy closure techniques (HCTs). METHODS: Saline infusion sonohysterogram (SIS) was performed in women after one prior CD, documenting the presence or absence of a postoperative niche and measuring its depth, width, length, and residual myometrial thickness. Women were grouped by HCT: Technique A (endometrium-free) and Technique B (routine non-endometrium-free). The primary outcome was the prevalence of a clinically significant niche, defined as a depth of >2 mm. HCT groups were compared using χ2 , T-test (ANOVA), and analyzed using logistic regression and two-sided test (P < .05). RESULTS: Forty-five women had SIS performed, 25 and 20 via Technique A and B, respectively. Technique groups varied by average interval time from CD to SIS (13.6 versus 74.5 months, P = 0.006) but were otherwise similar. Twenty niches were diagnosed, 85% of which were clinically significant, including five following Technique A, nine following Technique B with double-layer closure, and three following Technique B with single-layer (P = .018). The average niche depth was 2.4 mm and 4.9 mm among the two-layer subgroups following Techniques A and B, respectively (P = .005). A clinically significant niche development was six times higher with Technique B when compared to Technique A (OR 6.0, 95% CI 1.6-22.6, P = .008); this significance persisted after controlling for SIS interval on multivariate analysis (OR 4.4, 95% CI 1.1-18.3, P = .04). The average niche depth was 5.7 ± 2.9 mm following Technique B with single-layer. CONCLUSION: Hysterotomy closure techniques determine the prevalence of post-Cesarean delivery niche formation and size. Exclusion of the endometrium at uterine closure reduces the development of significant scar defects.

Patient Acceptable Symptom State for the Forgotten Joint Score in Primary Total Knee Arthroplasty.

BACKGROUND: In order to better understand the clinical benefits of total knee arthroplasty (TKA) and improve the interpretability of the Forgotten Joint Score (FJS-12), the establishment of a meaningful change in score is necessary. The purpose of this study is to determine the threshold of the FJS-12 for detecting the patient acceptable symptom state (PASS) following primary TKA. METHODS: We retrospectively reviewed all patients who underwent elective, primary TKA and answered both the FJS-12 and the Knee Injury Osteoarthritis Outcome Survey, Joint Replacement KOOS, JR surveys 1-year postoperatively. The questionnaires were administered via a web-based electronic application. KOOS, JR score was used as the anchor. The anchor for PASS calculation should relate pain, physical function, and patient satisfaction. Two statistical methods were employed: (1) the receiver operating characteristic (ROC) curve point; (2) 75th percentile of the cumulative percentage curve of patients who had the KOOS, JR score difference larger than the cut-off value. RESULTS: This study included 457 patients. The mean 1-year FJS-12 score was 42.6 ± 27.8. The mean 1-year KOOS, JR score was 68.0 ± 17.2. A high positive correlation between FJS-12 and KOOS, JR was found (r = 0.72, P < .001) making the KOOS, JR a valid external anchor. The threshold score of the FJS-12 which maximized the sensitivity and specificity for detecting a PASS was 33.3 (AUC = 0.78, 95% CI [0.74, 0.83]). The cut-off value computed with the 75th percentile approach was 77.1 (95% CI [73.9, 81.5]). CONCLUSION: The PASS threshold for the FJS-12 was 33.3 and 77.1 at 1-year follow-up after primary TKA using the receiver operating characteristic (ROC) curve and 75th percentile approaches, respectively. These values can be used to assess the successful achievement of a forgotten joint. LEVEL III EVIDENCE: Retrospective Cohort Study.

Outcomes of HER2-positive non-metastatic breast cancer patients treated with anti-HER2 therapy without chemotherapy.

PURPOSE: Anti-HER2 therapy delivered in the adjuvant setting for breast cancer is given in conjunction with cytotoxic chemotherapy. For HER2-positive (HER2+) patients who cannot tolerate chemotherapy, there is no randomized data regarding the role of anti-HER2 therapy without chemotherapy. METHODS: The National Cancer Database (NCDB) was queried for non-metastatic breast cancer patients with estrogen receptor-positive (ER+) and HER2+ breast cancer who received surgery and endocrine therapy, without chemotherapy from 2013 to 2016. Outcomes were compared between endocrine therapy alone (ET) or endocrine therapy with anti-HER2 therapy (ET + aHER2). Univariate and multivariate Cox-proportional hazards models were used to analyze the association between clinical characteristics and survival outcomes between groups. Propensity score matching (PSM) was performed to account for differences between the two groups. RESULTS: Of all patients with non-metastatic ER+/HER2+ breast cancer, we identified 9458 (20.5%) who did not receive chemotherapy. Of the 6741 patients who received ET, 17.2% also received aHER2 therapy. Median follow-up was 31.7 months (IQR 21.1-42.1). In the aHER2 group (vs. ET), there were more patients with older age, higher stage, node positivity, poorly or undifferentiated disease, lymphovascular invasion, lobular cancer, and Medicare insurance. Compared to the ET cohort, ET + aHER2 was not significantly associated with improved OS on multivariate analysis (HR 0.88 95% CI 0.68-1.15) or after propensity score matching (HR 0.80 95% CI 0.57-1.11). CONCLUSIONS: There is no significant difference in survival with the addition of HER2 therapy to endocrine therapy in ER+/HER2+ non-metastatic breast cancer patients who do not receive chemotherapy. To our knowledge, this is the largest series investigating this question.

Racial and ethnic representation in primary research contributing to pelvic organ prolapse treatment guidelines.

INTRODUCTION AND HYPOTHESIS: To evaluate whether the studies contributing to the national treatment guidelines on pelvic organ prolapse adequately represent the racial and/or ethnic makeup of the American population. METHODS: This analysis examines the racial and ethnic makeup of all primary study cohorts contributing to the American College of Obstetricians and Gynecologists/American Urogynecologic Society Practice Bulletin No. 214 on pelvic organ prolapse. References were excluded if they lacked a primary patient population or were from outside the US. Mean proportional representation of racial/ethnic groups was compared to the 2018 United States Census data on race/ethnicity. The representation quotient was also calculated to evaluate for relative representation of each group. Descriptive statistics were used. RESULTS: Of the 110 references, 53 primary studies were included in the final analysis with 30 studies reporting on race/ethnicity. On average, 82% (SD = 15%) of study populations were White, while Blacks, Hispanics, and Asians represented 67% (SD = 7%), 4% (SD = 8%), and < 1% (SD = 1%), respectively, differing significantly from the 2018 US Census (p < 0.01.) The representation quotients for White women was 1.36, demonstrating a 36% overrepresentation, while Black, Hispanic, and Asian women were underrepresented among studies of all evidence levels, with representative quotients of 0.50, 0.23, and 0.09, respectively. CONCLUSIONS: Our study demonstrates a significant underrepresentation of non-White populations in primary cohorts of studies contributing to the ACOG/AUGS Practice Bulletin No. 214 on POP. This analysis reinforces that more efforts are required to include and report on racial and ethnically diverse cohorts to better serve all patients.

Oocyte stimulation parameters influence the number and proportion of mature oocytes retrieved in assisted reproductive technology cycles.

PURPOSE: Whether differences in stimulation parameters alter the number and proportion of MII oocytes retrieved. METHODS: Records of 2546 patients were examined, looking at age, day 2/3 follicle-stimulating hormone (FSH) and estradiol (E2) levels, total dose of gonadotropins administered (including FSH and human menopausal gonadotropin [hMG]), fraction of hMG administered, number of days of treatment with gonadotropins, and the dose of gonadotropins administered per day. We segregated the patients into 3 different classes depending on the trigger method used and 2 groups based on egg freeze vs. ICSI. Multiple regression methods were used to examine associations between stimulation parameters and the total number of eggs, number of immature oocytes (Poisson regression), and the fraction of retrieved oocytes that were immature (Logistic regression). RESULTS: After adjustments for different triggers and egg freeze versus ICSI, both the #immature oocytes and the immature fraction of oocytes were associated with the total gonadotropin dose (inversely) and the gonadotropin dose/day (positively). Other parameters were associated with the number of immature oocytes but were also associated with the number of oocytes retrieved. CONCLUSIONS: Stimulations using less total gonadotropin and more gonadotropin per day were associated with more immaturity. The type of trigger method used for final maturation was associated with immaturity but was believed to be predominantly due to trigger assignment to patients based on response. The association between use of ICSI and less immaturity was believed to be due to additional time for maturation in the ICSI group.

Incidence of Congenital Spinal Abnormalities Among Pediatric Patients and Their Association With Scoliosis and Systemic Anomalies.

BACKGROUND: Congenital abnormalities when present, according to VACTERL theory, occur nonrandomly with other congenital anomalies. This study estimates the prevalence of congenital spinal anomalies, and their concurrence with other systemic anomalies. METHODS: A retrospective cohort analysis on Health care Cost and Utilization Project's Kids Inpatient Database (KID), years 2000, 2003, 2006, 2009 was performed. ICD-9 coding identified congenital anomalies of the spine and other body systems. OUTCOME MEASURES: Overall incidence of congenital spinal abnormalities in pediatric patients, and the concurrence of spinal anomaly diagnoses with other organ system anomalies. Frequencies of congenital spine anomalies were estimated using KID hospital-and-year-adjusted weights. Poisson distribution in contingency tables tabulated concurrence of other congenital anomalies, grouped by body system. RESULTS: Of 12,039,432 patients, rates per 100,000 cases were: 9.1 hemivertebra, 4.3 Klippel-Fiel, 56.3 Chiari malformation, 52.6 tethered cord, 83.4 spina bifida, 1.2 absence of vertebra, and 6.2 diastematomyelia. Diastematomyelia had the highest concurrence of other anomalies: 70.1% of diastematomyelia patients had at least one other congenital anomaly. Next, 63.2% of hemivertebra, and 35.2% of Klippel-Fiel patients had concurrent anomalies. Of the other systems deformities cooccuring, cardiac system had the highest concurrent incidence (6.5% overall). In light of VACTERL's definition of a patient being diagnosed with at least 3 VACTERL anomalies, hemivertebra patients had the highest cooccurrence of ≥3 anomalies (31.3%). With detailed analysis of hemivertebra patients, secundum ASD (14.49%), atresia of large intestine (10.2%), renal agenesis (7.43%) frequently cooccured. CONCLUSIONS: Congenital abnormalities of the spine are associated with serious systemic anomalies that may have delayed presentations. These patients continue to be at a very high, and maybe higher than previously thought, risk for comorbidities that can cause devastating perioperative complications if not detected preoperatively, and full MRI workups should be considered in all patients with spinal abnormalities. LEVEL OF EVIDENCE: Level III.

Time Trends in Characteristics of Patients Undergoing Primary Total Hip and Knee Arthroplasty in California, 2007-2010.

BACKGROUND: As the number of total hip and knee arthroplasty cases increases, it is important to understand the burden of factors that impact patient outcomes of these procedures. This article examined the time trends in key demographics, clinical characteristics, comorbidity burden (Deyo-Charlson Comorbidity Index [CCI]), and presence of depression in patients undergoing primary total hip arthroplasty and total knee arthroplasty using population-based, all-payer inpatient database, California Healthcare Cost and Utilization Project, from 2007 to 2010. METHODS: Chi-square tests and analysis of variance were used. Multivariate logistic regression analyses were also performed to compare the prevalence of depression in 2007 to later years. RESULTS: In the primary total hip arthroplasty cohort, the prevalence of depression significantly increased by 20%, mean age decreased by 0.4 years, mean length of stay (LOS) decreased by 0.5 days, and having a CCI score of ≥3 increased by 30% (P value < .001 for all) over the study period. Similarly, in the primary total knee arthroplasty cohort, the prevalence of depression increased by 23%, the mean age decreased by 0.4 years, mean LOS decreased by 0.4 days, and the prevalence of CCI score of ≥3 increased by 35% (P value < .001 for all). CONCLUSION: Despite the younger age of the joint arthroplasty population over time, we found increased prevalence of depression and comorbidity scores but shorter LOS. Further study is needed to determine the impact of the changing demographics of the total joint population and the best strategies to optimize their outcome with these procedures.

Association of Depression With 90-Day Hospital Readmission After Total Joint Arthroplasty.

BACKGROUND: Hospital readmission after total joint arthroplasty accounts for substantial resource consumption. Depression has been shown to impact postsurgical outcomes. We therefore aimed to study the association of depression with risk of readmission after total joint arthroplasty. METHODS: Retrospective cohort data from the population-based California Healthcare Cost and Utilization Project database from 2007 to 2010 were analyzed using multivariable logistic regression to predict odds of 90-day readmission after hospital discharge for primary total knee arthroplasty (TKA, n = 132,422) or total hip arthroplasty (THA, n = 65,071) arthroplasty in adults ages 50+ years. We included the primary exposure of depression and controlled for age, sex, race/ethnicity, Medicaid insurance, comorbidities, and admission year. RESULTS: Overall 90-day readmission rates were approximately 8% for TKA and THA. Even after controlling for other chronic conditions and nonmodifiable covariates, we found depression predicted higher likelihood of readmission. The odds of readmission for subjects with depression were 21%-24% higher overall (odds ratio for TKA: 1.21, 95% confidence interval: 1.13-1.29; odds ratio for THR: 1.24, 95% confidence interval: 1.13-1.35; P < .001). Subjects with surgery in earlier years were also more likely to be readmitted (P < .01). CONCLUSION: Depression is associated with a significantly higher risk of readmission after THA and TKA. Hospital readmissions must be minimized to improve care quality, while making these procedures fiscally feasible. Promoting care coordination across disciplines for management of nonorthopedic comorbidities before surgery, particularly in higher risk patients with depression, could optimize orthopedic surgery outcomes, patient well-being, and costs of care. Therefore, every effort to address depression before surgery is warranted.

Age-Period-Cohort approaches to back-calculation of cancer incidence rate.

A compartment model for cancer incidence and mortality is developed in which healthy subjects may develop cancer and subsequently die of cancer or another cause. In order to adequately represent the experience of a defined population, it is also necessary to allow for subjects who are diagnosed at death, as well as subjects who migrate and are subsequently lost to follow-up. Expressions are derived for the number of cancer deaths as a function of the number of incidence cases and vice versa, which allows for the use of mortality statistics to obtain estimates of incidence using survival information. In addition, the model can be used to obtain estimates of cancer prevalence, which is useful for health care planning. The method is illustrated using data on lung cancer among males in Connecticut.

Early second-trimester sonography to improve the fetal anatomic survey in obese patients.

OBJECTIVES: Fetal anatomic surveys are difficult to perform on obese patients. However, there are limited data available on methods to improve the rate of complete anatomy scans in these patients. The objective of this study was to determine whether the addition of an early second-trimester fetal anatomy scan improves the rate of complete anatomy scans in obese patients. METHODS: We conducted a prospective cohort study of 100 obese patients at a city hospital who were scheduled for a fetal anatomy scan using transvaginal and transabdominal sonography at 14 to 16 weeks (early anatomy scan) and an anatomy scan at 18 to 22 weeks ("routine" anatomy scan). Inclusion criteria were a body mass index of 30 kg/m(2) or higher, singleton pregnancy, and presentation for prenatal care before 16 weeks. Data for the routine anatomy scan alone versus a combination of early and routine anatomy scans was calculated by the McNemar χ(2) test for categorical variables and the Wilcoxon signed ranks test for continuous variables. RESULTS: The addition of the early anatomy scan significantly increased the rate of complete anatomy scans from 42% to 51% (P < .01). It also significantly improved visualization of the head, thorax, and abdomen and significantly increased the mean number of items seen (P < .05). CONCLUSIONS: The addition of an early second-trimester fetal anatomy scan to a routine anatomy scan performed later in the second trimester significantly improves the rate of complete anatomy scans in obese patients.

Age-dependent ferritin elevations and HFE C282Y mutation as risk factors for symptomatic knee osteoarthritis in males: a longitudinal cohort study.

BACKGROUND: Age, gender and genetic predisposition are major intrinsic risk factors for osteoarthritis (OA). Iron increases are associated with age and gene mutation. In the present study, we examined whether serum ferritin, an indicator of total body iron stores, correlates with clinical features in patients with OA, and whether the hemochromatosis Fe (HFE) gene mutation plays a role. METHODS: In a 2-year longitudinal observational study, 127 patients with knee OA and 20 healthy individuals (controls) were enrolled. All patients underwent standardized weight-bearing fixed-flexion posteroanterior knee radiographs. Peripheral blood samples were analyzed for serum ferritin, and genotyped for HFE using allelic discrimination methods. RESULTS: Higher levels of serum ferritin were found in patients older than 56 years (P =0.0186) and males (P =0.0006), with a trend toward higher ferritin in patients with OA. HFE gene mutation carriers were more prevalent among patients with OA than among healthy controls. When stratified further by gender, we found that male patients with OA had higher levels of serum ferritin than male control subjects [odds ratio = 4.18 (limits of 95% confidence interval: 0.86-27.69, P = 0.048)]. Analyses of radiographic data indicated that higher ferritin was associated with narrower joint space width at baseline (P = 0.032) in male patients. Additionally, among men, risk prediction of radiographic severity [Kellgren-Lawrence (KL) grade >2)] in the higher ferritin group was almost five times that of the lower ferritin group (odds ratio = 4.74, P = 0.023). CONCLUSION: Our data suggest that increased ferritin levels are associated with symptomatic knee OA in males. This finding needs to be validated in a larger cohort of patients.

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.

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.

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.