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ContextIn preclinical studies, high androgen levels during pregnancy are associated with low birth weight and rapid postnatal weight gain in the offspring. However, human data linking prenatal androgens with birth weight and early life weight gain in the offspring are scarce.DesignWe evaluated 516 mother-child pairs enrolled in the New England birth cohorts of the Collaborative Perinatal Project (1959-1966). We assayed androgen bioactivity in maternal sera during third-trimester using a receptor-mediated luciferase expression bioassay. Age and sex-specific BMI Z-scores (BMIz), defined using established standards, were assessed at birth, 4 months, 1 year, 4 years, and 7 years. We used linear mixed models to evaluate the relation of maternal androgens with childhood BMIz overall and by sex. We examined the association of maternal androgens with fetal growth restriction. The association of weight trajectories with maternal androgens was examined using multinomial logistic regression.ResultsHigher maternal androgen levels associated with lower BMIz at birth (β = - 0.39, 95% CI: - 0.73, - 0.06); this relation was sex-dependent, such that maternal androgens significantly associated with BMIz at birth in girls alone (β = - 0.72, 95% CI: - 1.40, - 0.04). The relation of maternal androgens with fetal growth restriction revealed dose threshold effects that differed by sex. There was no significant association between maternal androgens and weight trajectory overall. However, we found a significant sex interaction (p = 0.01); higher maternal androgen levels associated with accelerated catch-up growth in boys (aOR = 2.14, 95% CI: 1.14, 4.03).ConclusionOur findings provide evidence that maternal androgens may have differential effects on the programming of intrauterine growth and postnatal weight gain depending on fetal sex.

Rationale and Objectives: To address existing educational gaps in the business of radiology and medicine, we developed, implemented, and evaluated an Academic Radiology Business Series (ARBS) as part of a longitudinal noninterpretive skills curriculum in our radiology residency program., Materials and Methods: Mixed lecture- and discussion-based sessions were prepared and taught by content experts and radiologist-leaders at our institution in the style of a typical MBA curriculum, drawing on five core pillars: strategy, management, operations, finance, and health policy and economics. The series concluded with an interactive discussion of a Harvard Business School case study. To study the effectiveness of the curriculum, Wilcoxon rank-sum test was used to compare survey results before and after the curriculum., Results: Nearly 80% of the pre-curriculum survey respondents were not satisfied with the current training offered in the business of medicine. Although 94% of trainees were interested in pursuing leadership positions in healthcare, they have self-reported knowledge gaps in the fundamentals of the business of medicine. There were significant improvements in satisfaction with their training in the business of medicine and perceived improvements in knowledge of important concepts in the business of medicine after participating in the curriculum (p < 0.001)., Conclusion: Radiology trainees have strong interest in the business of radiology and appreciate its importance yet feel inadequately prepared during training. Intentional training incorporated into residency education in the form of an innovative educational initiative that brings radiology trainees together and utilizes an institution's own leaders to teach is feasible and effective., (Copyright © 2022 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Rationale and Objectives: The study aims to propose an optimal workflow in patients with a PI-RADS 3 (PR-3) assessment category (AC) through determining the timing and type of pathology interrogation used for the detection of clinically significant prostate cancer (csPCa) in these men based upon a 5-year retrospective review in a large academic medical center., Materials and Methods: This United States Health Insurance Probability and Accountability Act (HIPAA)-compliant, institutional review board-approved retrospective study included men without prior csPCa diagnosis who received PR-3 AC on magnetic resonance (MR) imaging (MRI). Subsequent incidence and time to csPCa diagnosis and number/type of prostate interventions was recorded. Categorical data were compared using Fisher's exact test and continuous data using ANOVA omnibus F -test., Results: Our cohort of 3238 men identified 332 who received PR-3 as their highest AC on MRI, 240 (72.3%) of whom had pathology follow-up within 5 years. csPCa was detected in 76/240 (32%) and non-csPCa in 109/240 (45%) within 9.0 ± 10.6 months. Using a non-targeted trans-rectal ultrasound biopsy as the initial approach ( n  = 55), another diagnostic procedure was required to diagnose csPCa in 42/55 (76.4%) of men, compared with 3/21(14.3%) men with an initial MR targeted-biopsy approach ( n  = 21); ( p  < 0.0001). Those with csPCa had higher median serum prostate-specific antigen (PSA) and PSA density, and lower median prostate volume ( p  < 0.003) compared with non-csPCa/no PCa., Conclusion: Most patients with PR-3 AC underwent prostate pathology exams within 5 years, 32% of whom were found to have csPCa within 1 year of MRI, most often with a higher PSA density and a prior non-csPCa diagnosis. Addition of a targeted biopsy approach initially reduced the need for a second biopsy to reach a for csPCa diagnosis. Thus, a combination of systematic and targeted biopsy is advised in men with PR-3 and a co-existing abnormal PSA and PSA density., Competing Interests: Grant disclosures are added at the beginning of the article. The remaining authors have no disclosures or possible conflict of interest and/or commercial involvement related to contents of his manuscript., (© 2023 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Background There is uncertainty in the management of renal masses diagnosed as oncocytomas with image-guided percutaneous biopsy. Purpose To assess the reliability of a diagnosis of oncocytoma based on image-guided percutaneous renal mass biopsy and evaluate patient outcomes following different management strategies. Materials and Methods In this retrospective study, image-guided percutaneous biopsy pathology reports from April 2004 to April 2019 were searched for keywords "oncocytoma" and "oncocytic neoplasm" and compared with surgical pathology or repeat biopsy results. Patients with at least 12 months of clinical follow-up and known cause of death were grouped according to management strategies, and disease-specific survival and metastatic renal cell carcinoma (RCC)-free survival were compared. Mass growth rates were calculated with use of a normal linear mixed model. Results The database yielded 160 biopsy reports of 149 renal masses in 139 patients; 149 masses were categorized as oncocytoma ( n = 107), likely oncocytoma ( n = 12), oncocytic neoplasm ( n = 28), and indeterminate with oncocytoma in differential ( n = 2). Biopsied masses categorized as oncocytoma or likely oncocytoma were oncocytomas in 16 of 17 masses (94%) based on surgical pathology or repeat biopsy; four of eight masses (50%) categorized as oncocytic neoplasms were low-grade RCCs. Outcome analysis included 121 patients (mean age ± SD, 68 years ± 9.1; 82 men); 80 patients initially underwent active surveillance (11 were later treated), 33 underwent ablation, and eight underwent surgery. Disease-specific survival and metastatic-free survival were 100% after each management strategy (median follow-up, 86.6 months; range, 14.2-207.9 months). Mass growth rate (mean, 1.7 mm per year) showed no evidence of a significant difference among biopsy result categories ( P = .37) or initial ( P = .84) or final management strategies ( P = .11). Conclusion Image-guided percutaneous biopsy diagnosis of renal oncocytoma was reliable. Although some masses diagnosed as oncocytic neoplasms were low-grade renal cell carcinomas (RCCs) at final diagnosis, no patients died of RCC, including those managed with active surveillance. © RSNA, 2023 See also the editorial by Lockhart in this issue.

Background: Various topical agents have been used to treat melasma; however, a large-scale evaluation among the currently available treatment is lacking., Objectives: The aim of this study was to evaluate the efficacy and safety of topical agents for melasma., Methods: The MEDLINE, Embase, Web of Science, Cochrane, and Alt-Healthwatch databases were searched in November 2021. Original studies that reported pre- and post-treatment Melasma Area Severity Index (MASI)/modified Melasma Area Severity Index (mMASI) scores and/or adverse effects (AEs) were eligible for inclusion. The main outcome was the efficacy analyzed by the changes in the pre- and post-treatment with standardized mean difference (SMD) of MASI/mMASI scores; the AEs were calculated with incidence proportion by the reported percentage of skin irritations., Results: A total of 45 studies (2359 patients) and 55 studies (4539 patients) met the inclusion criteria for efficacy and AEs, respectively. Hydroquinone (HQ) monotherapy (SMD -1.3, 95% CI [-1.6 to -1.0]), HQ-containing combination therapy (-1.4, [-1.7 to -1.1]), cysteamine (-1.6, [-2.0 to -1.2]), tranexamic acid (-1.5, [-2.0 to -1.1]), azelaic acid (-1.3, [-1.7 to -1.0]), and kojic acid (-0.9, [-1.3 to -0.5]) demonstrated comparable efficacy, while zinc sulfate did not exhibit statistically significant improvement (-1.2, [-2.7 to 0.4]). HQ-containing combination therapy (50.9%) and cysteamine (42.2%) demonstrated the highest incidence of irritation, while azelaic acid (18.7%), kojic acid (5.3%), and tranexamic acid (0.8%) revealed a lower risk., Conclusions: In this meta-analysis, non-HQ agents except zinc sulfate may be considered as an alternative to HQ-containing agents. However, treatment should be guided by patient's tolerance, availability, and physicians' experience., (© 2022 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Echocardiographic deformation-based ratios and novel multi-parametric scores have been suggested to discriminate transthyretin cardiac amyloidosis (ATTR-CM) from other causes of increased left ventricular wall thickness among patients referred for ATTR-CM evaluation. Their relative predictive accuracy has not been well studied. We sought to (1) identify echocardiographic parameters predictive of ATTR-CM and (2) compare the diagnostic accuracy of these parameters in patients with suspected ATTR-CM referred for technetium-99m-pyrophosphate scintigraphy., Methods: Echocardiograms from 598 patients referred to 3 major amyloidosis centers for technetium-99m-pyrophosphate to detect ATTR-CM were analyzed, including longitudinal strain (LS) analysis. Deformation ratios (septal apex to base ratio, relative apical sparing, ejection fraction to global LS), a multi-center European increased wall thickness score, and Mayo Clinic derived ATTR score (transthyretin cardiac amyloidosis score) were calculated. A logistic regression model was used to identify the parameters that best associated with a diagnosis of ATTR-CM. Comparison of the diagnostic capacity of the parameters was performed by receiver operating characteristic curves and the area under the curve (AUC)., Results: Over half of the subjects (54.2%) were diagnosed with ATTR-CM (78% were men, median age of 76 years). Age, inferolateral wall thickness, and basal LS were the strongest predictors of ATTR-CM, AUC of 0.87 (95% CI: 0.83, 0.90), superior to the increased wall thickness score AUC of 0.78 (95% CI: 0.73, 0.83; P =0.004). An inferolateral wall thickness of ≥14 mm (AUC: 0.73) was as accurate as the published cut-offs for transthyretin cardiac amyloidosis score and septal apex to base (AUC: 0.72 and 0.69, P =0.8 and P =0.1, respectively), and was superior to ejection fraction to global LS and relative apical sparing (AUC: 0.64 and 0.53, P <0.001, respectively). A cut-off of ≥-8% for average basal LS (AUC: 0.76, CI: 0.72-0.79) had a similar area under the curve to transthyretin cardiac amyloidosis score (TCAS) ( P =0.2); outperforming the other indices ( P <0.01)., Conclusion: Inferolateral wall thickness and average basal LS performed as well as or better than more complex echo ratios and multiparametric scores to predict ATTR-CM.

Aims: The minute ventilation-carbon dioxide production relationship (VE/VCO 2 slope) is widely used for prognostication in heart failure (HF) with reduced left ventricular ejection fraction (LVEF). This study explored the prognostic value of VE/VCO 2 slope across the spectrum of HF defined by ranges of LVEF., Methods and Results: In this single-centre retrospective observational study of 1347 patients with HF referred for cardiopulmonary exercise testing, patients with HF were categorized into HF with reduced (HFrEF, LVEF < 40%, n = 598), mid-range (HFmrEF, 40% ≤ LVEF < 50%, n = 164), and preserved (HFpEF, LVEF ≥ 50%, n = 585) LVEF. Four ventilatory efficiency categories (VC) were defined: VC-I, VE/VCO 2 slope ≤ 29; VC-II, 29 < VE/VCO 2 slope < 36; VC-III, 36 ≤ VE/VCO 2 slope < 45; and VC-IV, VE/VCO 2 slope ≥ 45. The associations of these VE/VCO 2 slope categories with a composite outcome of all-cause mortality or HF hospitalization were evaluated for each category of LVEF. Over a median follow-up of 2.0 (interquartile range: 1.9, 2.0) years, 201 patients experienced the composite outcome. Compared with patients in VC-I, those in VC-II, III, and IV demonstrated three-fold, five-fold, and eight-fold increased risk for the composite outcome. This incremental risk was observed across HFrEF, HFmrEF, and HFpEF cohorts., Conclusions: Higher VE/VCO 2 slope is associated with incremental risk of 2 year all-cause mortality and HF hospitalization across the spectrum of HF defined by LVEF. A multilevel categorical approach to the interpretation of VE/VCO 2 slope may offer more refined risk stratification than the current binary approach employed in clinical practice., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objectives: Real-time assessment of treatment response in glioblastoma (GBM) patients on immune checkpoint blockade (ICB) remains challenging because inflammatory effects of therapy may mimic progressive disease, and the temporal evolution of these inflammatory findings is poorly understood. We compare GBM patient response during ICB as assessed with the Immunotherapy Response Assessment in Neuro-Oncology (iRANO) and the standard Response Assessment in Neuro-Oncology (RANO) radiological criteria., Methods: 49 GBM patients (seven newly diagnosed and 42 recurrent) treated with ICBs at a single institution were identified. Tumor burden was quantified on serial MR scans according to RANO criteria during ICB. Radiographic response assessment by iRANO and RANO were compared., Results: 82% (40/49) of patients received anti-PD-1, 16% (8/49) received anti-PD-L1, and 2% (1/49) received anti-PD-1 and anti-CTLA4 treatment. Change in tumor burden and best overall response ranged from -100 to +557% (median: +48%). 12% (6/49) of patients were classified as concordant non-progressors by both RANO and iRANO (best response: one CR, one PR, and four SD). Another12% (6/49) had discordant assessments: 15% (6/41) of RANO grade progressive disease (PD) patients had iRANO grade of progressive disease unconfirmed (PDU). The final classification of these discordant patients was pseudoprogression (PsP) in three of six, PD in two of six, and PDU in one of six who went off study before the iRANO assessment of PDU. iRANO delayed diagnosis of PD by 42 and 93 days in the two PD patients. 76% (37/49) patients were classified as concordant PD by both RANO and iRANO. 12% (6/49) of all patients were classified as PsP, starting at a median of 12 weeks (range, 4-30 weeks) after ICB initiation., Conclusions: Standard RANO and iRANO have high concordance for assessing PD in patients within 6 months of ICB initiation. iRANO was beneficial in 6% (3/49) cases later proven to be PsP, but delayed confirmation of PD by <3 months in 4% (2/49). PsP occurred in 12% of patients, starting at up to 7 months after initiation of ICB. Further study to define the utility of modified RANO compared with iRANO in ICB GBM patients is needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Lim-Fat, Qin, Li, Bryant, Bay, Gao, Miskin, Liu, Iorgulescu, Xu, Reardon and Young.)

Allogeneic hematopoietic cell transplantation (HCT) recipients are at increased risk for varicella zoster virus (VZV) reactivation and associated complications. A nonlive adjuvanted recombinant zoster vaccine (RZV) has been developed to prevent herpes zoster (HZ), but there are no recommendations for use in this population. In this single-center prospective observational cohort study, we assessed the safety and reactogenicity of RZV, as well as incidence of graft-versus-host disease (GVHD) and confirmed cases of HZ after vaccination. Between December of 2018 and June of 2020, patients aged ≥18 years received 2 doses of RZV between 9 and 24 months after HCT, with the doses separated by ≥8 weeks. One hundred and fifty-eight patients (mean age, 55 years; 42% women) received ≥1 dose (total vaccinated cohort), and 150 patients (95%) received 2 doses (modified total vaccinated cohort). Solicited reactions occurred in 92.1% of patients (grade 3, 32.5%), owing mostly to injection site pain, which occurred in 86% (grade 3, 16%). The cumulative incidence of GVHD in the peri-vaccination period was no different than in historical controls (adjusted incidence rate ratio, 1.05; 95% confidence interval, 0.8-1.38). There were 4 cases of HZ in the total vaccinated cohort (2.5%) and 3 cases in the modified total vaccinated cohort (28.3/1000 person-years). Among recipients of allogeneic HCT, RZV was safe, tolerable, and did not increase rates of GVHD. Future clinical trials are needed to determine the immunogenicity and efficacy of RZV in this population., (© 2021 by The American Society of Hematology.)

Background Although CT-based body composition (BC) metrics may inform disease risk and outcomes, obtaining these metrics has been too resource intensive for large-scale use. Thus, population-wide distributions of BC remain uncertain. Purpose To demonstrate the validity of fully automated, deep learning BC analysis from abdominal CT examinations, to define demographically adjusted BC reference curves, and to illustrate the advantage of use of these curves compared with standard methods, along with their biologic significance in predicting survival. Materials and Methods After external validation and equivalency testing with manual segmentation, a fully automated deep learning BC analysis pipeline was applied to a cross-sectional population cohort that included any outpatient without a cardiovascular disease or cancer who underwent abdominal CT examination at one of three hospitals in 2012. Demographically adjusted population reference curves were generated for each BC area. The z scores derived from these curves were compared with sex-specific thresholds for sarcopenia by using χ 2 tests and used to predict 2-year survival in multivariable Cox proportional hazards models that included weight and body mass index (BMI). Results External validation showed excellent correlation ( R = 0.99) and equivalency ( P < .001) of the fully automated deep learning BC analysis method with manual segmentation. With use of the fully automated BC data from 12 128 outpatients (mean age, 52 years; 6936 [57%] women), age-, race-, and sex-normalized BC reference curves were generated. All BC areas varied significantly with these variables ( P < .001 except for subcutaneous fat area vs age [ P = .003]). Sex-specific thresholds for sarcopenia demonstrated that age and race bias were not present if z scores derived from the reference curves were used ( P < .001). Skeletal muscle area z scores were significantly predictive of 2-year survival ( P = .04) in combined models that included BMI. Conclusion Fully automated body composition (BC) metrics vary significantly by age, race, and sex. The z scores derived from reference curves for BC parameters better capture the demographic distribution of BC compared with standard methods and can help predict survival. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Summers in this issue.

Background Intimate partner violence (IPV) is a global social and public health problem, but published literature regarding the exacerbation of physical IPV during the coronavirus disease 2019 (COVID-19) pandemic is lacking. Purpose To assess the incidence, patterns, and severity of injuries in IPV victims during the COVID-19 pandemic in 2020 compared with the prior 3 years. Materials and Methods The demographics, clinical presentation, injuries, and radiologic findings of patients reporting physical abuse arising from IPV during the statewide COVID-19 pandemic between March 11 and May 3, 2020, were compared with data from the same period for the past 3 years. Pearson χ 2 and Fisher exact tests were used for analysis. Results A total of 26 victims of physical IPV from 2020 (mean age, 37 years ± 13 [standard deviation]; 25 women) were evaluated and compared with 42 victims of physical IPV (mean age, 41 years ± 15; 40 women) from 2017 to 2019. Although the overall number of patients who reported IPV decreased during the pandemic, the incidence of physical IPV was 1.8 times greater (95% CI: 1.1, 3.0; P = .01). The total number of deep injuries was 28 during 2020 versus 16 from 2017 to 2019; the number of deep injuries per victim was 1.1 during 2020 compared with 0.4 from 2017 to 2019 ( P < .001). The incidence of high-risk abuse defined by mechanism was two times greater in 2020 (95% CI: 1.2, 4.7; P = .01). Patients who experienced IPV during the COVID-19 pandemic were more likely to be White; 17 (65%) victims in 2020 were White compared with 11 (26%) in the prior years ( P = .007). Conclusion There was a higher incidence and severity of physical intimate partner violence (IPV) during the coronavirus disease 2019 (COVID-19) pandemic compared with the prior 3 years. These results suggest that victims of IPV delayed reaching out to health care services until the late stages of the abuse cycle during the COVID-19 pandemic. © RSNA, 2020.

Background: Prolonged androgen deprivation therapy (ADT) is favored over short-term use in patients with localized high-risk prostate cancer (PC)., Objectives: This study sought to compare cardiorespiratory fitness (CRF) and cardiovascular (CV) mortality among patients with PC with and without ADT exposure and to explore how duration of ADT exposure influences CRF and CV mortality., Methods: Retrospective cohort study of patients referred for exercise treadmill testing (ETT) after a PC diagnosis. PC risk classification was based on Gleason score (GS): high risk if GS ≥8; intermediate risk if GS = 7; and low risk if GS <7. CRF was categorized by metabolic equivalents (METs): METs >8 defined as good CRF and METs ≤8 as reduced CRF. ADT exposure was categorized as short term (≤6 months) versus prolonged (>6 months)., Results: A total of 616 patients underwent an ETT a median of 4.8 years (interquartile range: 2.0, 7.9 years) after PC diagnosis. Of those, 150 patients (24.3%) received ADT prior to the ETT; 99 with short-term and 51 with prolonged exposure. 504 patients (81.8%) had ≥2 CV risk factors. Prolonged ADT was associated with reduced CRF (odds ratio [OR]: 2.71; 95% confidence interval [CI]: 1.31 to 5.61; p = 0.007) and increased CV mortality (hazard ratio [HR]: 3.87; 95% CI: 1.16 to 12.96; p = 0.028) in adjusted analyses. Although the association between short-term ADT exposure and reduced CRF was of borderline significance (OR: 1.71; 95% CI: 1.00 to 2.94; p = 0.052), there was no association with CV mortality (HR: 1.60; 95% CI: 0.51 to 5.01; p = 0.420) in adjusted Cox regression models., Conclusions: Among patients with PC and high baseline CV risk, prolonged ADT exposure was associated with reduced CRF and increased CV mortality., Competing Interests: This work was supported by the Goodman Master Clinician Award from Brigham and Women’s Hospital (to Dr. Groarke) and by the Gelb Master Clinician Award and the Catherine Fitch Fund form Brigham and Women’s Hospital (to Dr. Nohria). Dr. McGregor has served as a consultant for Bayer, Astellas, AstraZeneca, Seattle Genetics, Exelixis, Nektar, Pfizer, Janssen, and Genentech; and has received research support paid to his institution from Bristol Myers Squibb. Dr. Neilan was supported in part through a gift from A. Curt Greer, Pamela Greer, and Kohlberg Foundation, National Institutes of Health/National Heart, Lung, and Blood Institute (grants 1R01HL130539-01A1, 1R01HL137562-01A1, K24HL113128-06), and National Institutes of Health/Harvard Center for AIDS Research (grant P30 AI060354). Dr. Nohria has served as a consultant for Takeda Oncology and Triple Gene Therapy; and has received research support from Amgen, Inc. Dr. Groarke has received research support from Amgen, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2020 The Authors.)

The altered immune states of aging and HIV infection may affect intracellular metabolism of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC); increased cellular senescence decreases FTC-triphosphate (FTCtp) concentrations. The effects of age and inflammation on the ratio of intracellular metabolites (IMs; tenofovir diphosphate [TFVdp] and FTCtp) to their endogenous nucleotides (ENs; dATP and dCTP), a potential treatment efficacy marker, were assessed among participants of the Women's Interagency HIV Study (WIHS), who ranged from 25 to 75 years. Samples from women receiving TDF-FTC with viral loads of <200 copies/ml were dichotomized by age at collection into two groups (≤45 years and ≥60 years). IM/EN concentrations were measured in peripheral blood mononuclear cell (PBMC) pellets; interleukin-6 (IL-6) and sCD163 were measured in plasma; senescent CD8 + T cells were measured in viable PBMCs. The TFVdp:dATP and FTCtp:dCTP ratios had statistically significantly different distributions in older and younger women (log-rank test, P  = 0.0023 and P  = 0.032, respectively); in general, IM and EN concentrations were higher in the older women. After adjusting for potential confounders, these findings were not significant. In women aged ≤45 years, TFVdp was negatively associated with IL-6 and sCD163, while FTCtp was positively associated with sCD163 and IL-6 in women aged ≥60 years. Body mass index (BMI) was positively associated with IL-6 in both age groups and negatively associated with TFVdp in women aged ≤45 years. After adjustment, age remained significant for sCD163, while black race, BMI, and renal function remained significant for several IMs and ENs, suggesting that factors associated with aging, but not age itself, govern intracellular TDF-FTC pharmacology., (Copyright © 2020 American Society for Microbiology.)

Objective: To determine the efficacy of fibroblast growth factor-2 (FGF-2) in treating chronic nonhealing tympanic membrane (TM) perforations., Method: Double-blinded, randomized placebo controlled phase 2 clinical trial for patients with chronic TM perforations of more than 3 months duration with a cross-over arm. Patients received either FGF-2 or placebo (sterile water) saturated gelatin sponge in the perforation after rimming the perforation under topical anesthesia. The perforation was then covered with Tisseel fibrin glue. The primary endpoint was complete closure of the TM perforation. Secondary end points included change in hearing and partial TM closure rates. The TM was examined every 3 weeks with otoendoscopy for closure. The treatment was repeated if there was incomplete closure every 3 weeks up to a total of three treatments per arm., Results: Seventy four patients were recruited for the study. Fifty seven met eligibility criteria and fifty four completed the study. Ten of 14 perforations closed completely in the placebo group (71.4%) and 23 of 40 perforations closed completely in the FGF-2 treatment group (57.5%), P value = .36. Pure tone averages and word recognition scores were not statistically significantly different between study groups post-treatment. After initial complete closure, re-perforation occurred in seven FGF-2 treated patients and two placebo patients making the effective final closure rate 40% for FGF and 57% for placebo, respectively., Conclusion: No statistically significant difference in tympanic membrane perforation closure rate was found between the FGF-2 and placebo groups. There were no differences in hearing outcomes between the groups., Level of Evidence: 1b., Competing Interests: The authors certify that they have no affiliations with or involvement in any organization or entity with any financial or nonfinancial interests in the subject matter or materials discussed in this manuscript., (© 2020 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals, Inc. on behalf of The Triological Society.)

Introduction: Converging evidence suggests that increasing healthy behaviors may slow or prevent cognitive decline., Methods: We piloted a six-month, randomized, controlled investigation of 40 patients with mild dementia, mild cognitive impairment, or subjective cognitive decline. The intervention consisted of weekly motivational interviewing phone calls and three visits with a "Brain Health Champion" health coach, who guided participants to achieve personalized goals. Changes in behavior were measured using validated questionnaires., Results: Compared with the standard-of-care control group, Brain Health Champion participants had statistically significant and clinically meaningful increases in physical activity (Cohen's d = 1.37, P  < .001), adherence to the Mediterranean diet (Cohen's d = 0.87, P  = .016), cognitive/social activity (Cohen's d = 1.09, P  = .003), and quality of life (Cohen's d = 1.23, P  < .001). The magnitude of behavior change strongly predicted improvement in quality of life., Discussion: Our results demonstrate the feasibility and potential efficacy of a health coaching approach in changing health behaviors in cognitively impaired and at-risk patients., (© 2019 The Authors.)

Objectives: Objectives of this study were to (1) assess the needs and preferred resources of Iowa physicians to inform the development of educational resources for best practice dementia care and (2) compare the responses of nursing home medical directors with nonmedical directors., Methods: Of 498 physicians, 101 (20%) completed and returned the survey. Family physicians were obtained from a list of family physicians from the Iowa Board of Medical Examiners. Respondent answers were summarized and presented as total numbers and percentages in tables. Significant differences between medical directors and nonmedical directors were evaluated using chi-square tests, Fisher exact tests, and Wilcoxon rank-sum tests., Results: Medical directors and nonmedical directors had similar preferences for resources used and information needs. Online resources, pocket guides, a handbook, consulting pharmacists, and facility in-services were the most commonly preferred sources of new information. Medical directors were significantly more aware of the Food and Drug Administration warning on antipsychotic use in dementia and treated more nursing home patients. No differences were observed between groups related to confidence in and use of nondrug strategies instead of antipsychotics to manage behavioral symptoms of dementia., Conclusion: The results of this survey illustrate physician preferences for information and resources on the management of behavioral and psychological symptoms in dementia. Information was used to inform the development of resources to aid physicians and other health care providers in making decisions about managing these symptoms.

Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) contributes to an estimated 150,000 new infections annually. Maternal vaccination has proven safe and effective at mitigating the impact of other neonatal pathogens and is one avenue toward generating the potentially protective immune responses necessary to inhibit HIV-1 infection of infants through breastfeeding. In the present study, we tested the efficacy of a maternal vaccine regimen consisting of a modified vaccinia virus Ankara (MVA) 1086.C gp120 prime-combined intramuscular-intranasal gp120 boost administered during pregnancy and postpartum to confer passive protection on infant rhesus macaques against weekly oral exposure to subtype C simian-human immunodeficiency virus 1157ipd3N4 (SHIV1157ipd3N4) starting 6 weeks after birth. Despite eliciting a robust systemic envelope (Env)-specific IgG response, as well as durable milk IgA responses, the maternal vaccine did not have a discernible impact on infant oral SHIV acquisition. This study revealed considerable variation in vaccine-elicited IgG placental transfer and a swift decline of both Env-specific antibodies (Abs) and functional Ab responses in the infants prior to the first challenge, illustrating the importance of pregnancy immunization timing to elicit optimal systemic Ab levels at birth. Interestingly, the strongest correlation to the number of challenges required to infect the infants was the percentage of activated CD4 + T cells in the infant peripheral blood at the time of the first challenge. These findings suggest that, in addition to maternal immunization, interventions that limit the activation of target cells that contribute to susceptibility to oral HIV-1 acquisition independently of vaccination may be required to reduce infant HIV-1 acquisition via breastfeeding. IMPORTANCE Without novel strategies to prevent mother-to-child HIV-1 transmission, more than 5% of HIV-1-exposed infants will continue to acquire HIV-1, most through breastfeeding. This study of rhesus macaque dam-and-infant pairs is the first preclinical study to investigate the protective role of transplacentally transferred HIV-1 vaccine-elicited antibodies and HIV-1 vaccine-elicited breast milk antibody responses in infant oral virus acquisition. It revealed highly variable placental transfer of potentially protective antibodies and emphasized the importance of pregnancy immunization timing to reach peak antibody levels prior to delivery. While there was no discernible impact of maternal immunization on late infant oral virus acquisition, we observed a strong correlation between the percentage of activated CD4 + T cells in infant peripheral blood and a reduced number of challenges to infection. This finding highlights an important consideration for future studies evaluating alternative strategies to further reduce the vertical HIV-1 transmission risk.

Objectives. We assessed the protocols and system processes for colorectal cancer (CRC) screening at federally qualified health centers (FQHCs) in 4 midwestern states. Methods. We identified 49 FQHCs in 4 states. In January 2013, we mailed their medical directors a 49-item questionnaire about policies on CRC screening, use of electronic medical records, types of CRC screening recommended, clinic tracking systems, referrals for colonoscopy, and barriers to providing CRC. Results. Forty-four questionnaires (90%) were returned. Thirty-three of the respondents (75%) estimated the proportion of their patients up-to-date with CRC screening, with a mean of 35%. One major barrier to screening was inability to provide colonoscopy for patients with a positive fecal occult blood test (59%). The correlation of system strategies and estimated percentage of patients up-to-date with CRC screening was 0.43 (P = .01). Conclusions. CRC system strategies were associated with higher CRC screening rates. Implementing system strategies for CRC screening takes time and effort and is important to maintain, to help prevent, or to cure many cases of CRC, the second leading cause of cancer in the United States.