A Phase II Prospective Blinded Trial of Magnetic Resonance Imaging and In-Bore Biopsy in Active Surveillance for Prostate Cancer.

OBJECTIVE: To demonstrate the added benefit of multiparametric (mp)MRI risk stratification during active surveillance. METHODS: This prospective, single-arm, nonrandomized study included 82 men with low-risk prostate cancer (PCa). We compared two biopsy strategies in parallel. The first biopsy strategy was an in-bore and transrectal ultrasound (TRUS) biopsy in men with suspicious mpMRI findings. The second was a TRUS biopsy in all 82 men, blinded to the results of the previously performed mpMRI. RESULTS: We identified 27/82 men with suspicious mpMRI. Of those 27 men, we detected 8/27 with csPCa on biopsy, and we identified two men with in-bore biopsy exclusively, three men with TRUS biopsy exclusively, and three men with both biopsy strategies. Of the 55/82 men with nonsuspicious mpMRI (who only received TRUS biopsies), two men had csPCa. TRUS biopsy of the entire cohort of 82 men would have led to the correct diagnosis of 80% men with csPCa, requiring all 82 men to receive biopsies (csPCa in 10% of the 82 biopsies). Conducting in-bore biopsies plus TRUS biopsies in men with suspicious mpMRI would have also led to the detection of 80% of men with csPCa, requiring only 27 men to receive biopsies (csPCa in 30% of the 27 biopsies). CONCLUSION: The combination of TRUS and in-bore biopsies, limited to men with suspicious mpMRI, resulted in a similar detection rate of csPCa compared to TRUS biopsies of all men but required only one-third of men to undergo biopsy. Our results indicate that in-bore and TRUS biopsies continue to complement each other.

Positive predictive value of axillary lymph node cortical thickness and nodal, clinical, and tumor characteristics in newly diagnosed breast cancer patients.

PURPOSE: Axillary lymph nodes (LNs) with cortical thickness > 3 mm have a higher likelihood of malignancy. To examine the positive predictive value (PPV) of axillary LN cortical thickness in newly diagnosed breast cancer patients, and nodal, clinical, and tumor characteristics associated with axillary LN metastasis. METHODS: Retrospective review of axillary LN fine needle aspirations (FNAs) performed 1/1/2018-12/31/2019 included 135 axillary FNAs in 134 patients who underwent axillary surgery. Patient demographics, clinical characteristics, histopathology, and imaging features were obtained from medical records. Hypothesis testing was performed to identify predictors of axillary LN metastasis. RESULTS: Cytology was positive in 72/135 (53.3%), negative in 61/135 (45.2%), and non-diagnostic in 2/135 (1.5%). At surgery, histopathology was positive in 84 (62.2%) and negative in 51 (37.8%). LN cortices were thicker in metastatic compared to negative nodes (p < 0.0001). PPV of axillary LNs with cortical thickness ≥ 3 mm, ≥ 3.5 mm, ≥ 4 mm and, ≥ 4.25 mm was 0.62 [95% CI 0.53, 0.70], 0.63 [0.54, 0.72], 0.67 [0.57, 0.76] , and 0.74 [0.64, 0.83], respectively. At multivariable analysis, abnormal hilum (OR = 3.44, p = 0.016) and diffuse cortical thickening (OR = 2.86, p = 0.038) were associated with nodal metastasis. CONCLUSION: In newly diagnosed breast cancer patients, increasing axillary LN cortical thickness, abnormal fatty hilum, and diffuse cortical thickening are associated with nodal metastasis. PPV of axillary LN cortical thickness ≥ 3 mm and ≥ 3.5 mm is similar but increases for cortical thickness ≥ 4 mm. FNA of axillary LNs with cortex < 4 mm may be unnecessary for some patients undergoing sentinel LN biopsy.

Coronary Microcirculatory Dysfunction in People With HIV and Its Association With Antiretroviral Therapy.

BACKGROUND: HIV infection and abacavir-containing antiretroviral regimens are associated with vascular endothelial dysfunction and increased cardiovascular risk. Positron emission tomography (PET)-derived myocardial blood flow reserve (MBFR), the ratio of vasodilator stress to rest myocardial blood flow, is a well-validated measure of coronary microvascular health and marker of cardiovascular risk. Our objective was to compare MBFR among people with HIV (PWH) with matched non-HIV controls and to assess whether switching from dolutegravir/lamivudine/abacavir to the non-abacavir regimen bictegravir/emtricitabine/tenofovir alafenamide (TAF) would improve MBFR. METHODS AND RESULTS: Thirty-seven PWH were 1:2 matched on cardiovascular risk factors to 75 people without HIV, and MBFR corrected for differences in resting hemodynamics was compared in a cross-sectional design. PWH were majority men (68%) with a mean age of 56 years. Mean stress myocardial blood flow (1.83 mL/min per g [95% CI, 1.68-1.98] versus 2.40 mL/min per g [95% CI, 2.25-2.54]; P<0.001) and MBFR (2.18 [95% CI, 1.96-2.40] versus 2.68 [95% CI, 2.47-2.89]; P=0.002) was significantly lower in PWH than in people without HIV. In a single-arm, multicenter trial, a subset of 25 PWH who were virologically suppressed on dolutegravir/lamivudine/abacavir underwent positron emission tomography myocardial perfusion imaging at baseline and after switching to bictegravir/emtricitabine/TAF. MBFR was unchanged after switching to bictegravir/emtricitabine/TAF for a mean of 27 weeks (MBFR, 2.34 to 2.29; P=0.61), except in PWH with impaired MBFR at baseline (<2.00; N=6) in whom MBFR increased from 1.58 to 2.02 (P=0.02). CONCLUSIONS: PWH had reduced coronary microvascular function compared with controls without HIV. Coronary microvascular function did not improve after switching from dolutegravir/lamivudine/abacavir to bictegravir/emtricitabine/TAF. REGISTRATION: URL: https://www.clinicaltrials.gov; unique identifier: NCT03656783.

Evaluation of Risk Prediction with Hierarchical Data: Dependency Adjusted Confidence Intervals for the AUC.

The area under the true ROC curve (AUC) is routinely used to determine how strongly a given model discriminates between the levels of a binary outcome. Standard inference with the AUC requires that outcomes be independent of each other. To overcome this limitation, a method was developed for the estimation of the variance of the AUC in the setting of two-level hierarchical data using probit-transformed prediction scores generated from generalized estimating equation models, thereby allowing for the application of inferential methods. This manuscript presents an extension of this approach so that inference for the AUC may be performed in a three-level hierarchical data setting (e.g., eyes nested within persons and persons nested within families). A method that accounts for the effect of tied prediction scores on inference is also described. The performance of 95% confidence intervals around the AUC was assessed through the simulation of three-level clustered data in multiple settings, including ones with tied data and variable cluster sizes. Across all settings, the actual 95% confidence interval coverage varied from 0.943 to 0.958, and the ratio of the theoretical variance to the empirical variance of the AUC varied from 0.920 to 1.013. The results are better than those from existing methods. Two examples of applying the proposed methodology are presented.

Experience of a single healthcare system with screening mammography before and after COVID-19 shutdown.

PURPOSE: To evaluate COVID-19's longitudinal impact on screening mammography volume trends. METHODS: HIPAA-compliant, IRB-approved, single institution, retrospective study of screening mammogram volumes before (10/21/2016-3/16/2020) and greater than two years after (6/17/2020-11/30/2022) a state-mandated COVID-19 shutdown (3/17/2020-6/16/2020) were reviewed. A segmented quasi-poisson linear regression model adjusting for seasonality and network and regional population growth compared volume trends before and after the shutdown of each variable: age, race, language, financial source, risk factor for severe COVID-19, and examination location. RESULTS: Adjusted model demonstrated an overall increase of 65 screening mammograms per month before versus a persistent decrease of 5 mammograms per month for >2 years after the shutdown (p < 0.0001). In subgroup analysis, downward volume trends were noted in all age groups <70 years (age < 50: +9/month before vs. -7/month after shutdown; age 50-60: +17 vs. -7; and age 60-70: +21 vs. -2; all p < 0.001), those identifying as White (+55 vs. -8, p < 0.0001) and Black (+4 vs. +1, p = 0.009), all financial sources (Medicare: +22 vs. -3, p < 0.0001; Medicaid: +5 vs. +2, p = 0.006; private insurance/self-pay: +38 vs. -4, p < 0.0001), women with at least one risk factor for severe COVID-19 (+30 vs. -48, p < 0.0001), and screening mammograms performed at a hospital-based location (+48 vs. -14, p = 0.0001). CONCLUSION: The screening mammogram volume trend more than two years after the COVID-19 shutdown has continued to decline for most patient populations. Findings highlight the need to identify additional areas for education and outreach.

PI-RADS 3 score: A retrospective experience of clinically significant prostate cancer detection.

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.

Evaluation of Standard Response Assessment in Neuro-Oncology, Modified Response Assessment in Neuro-Oncology, and Immunotherapy Response Assessment in Neuro-Oncology in Newly Diagnosed and Recurrent Glioblastoma.

PURPOSE: The Response Assessment in Neuro-Oncology (RANO) criteria are widely used in high-grade glioma clinical trials. We compared the RANO criteria with updated modifications (modified RANO [mRANO] and immunotherapy RANO [iRANO] criteria) in patients with newly diagnosed glioblastoma (nGBM) and recurrent GBM (rGBM) to evaluate the performance of each set of criteria and inform the development of the planned RANO 2.0 update. MATERIALS AND METHODS: Evaluation of tumor measurements and fluid-attenuated inversion recovery (FLAIR) sequences were performed by blinded readers to determine disease progression using RANO, mRANO, iRANO, and other response assessment criteria. Spearman's correlations between progression-free survival (PFS) and overall survival (OS) were calculated. RESULTS: Five hundred twenty-six nGBM and 580 rGBM cases were included. Spearman's correlations were similar between RANO and mRANO (0.69 [95% CI, 0.62 to 0.75] v 0.67 [95% CI, 0.60 to 0.73]) in nGBM and rGBM (0.48 [95% CI, 0.40 to 0.55] v 0.50 [95% CI, 0.42 to 0.57]). In nGBM, requirement of a confirmation scan within 12 weeks of completion of radiotherapy to determine progression was associated with improved correlations. Use of the postradiation magnetic resonance imaging (MRI) as baseline scan was associated with improved correlation compared with use of the pre-radiation MRI (0.67 [95% CI, 0.60 to 0.73] v 0.53 [95% CI, 0.42 to 0.62]). Evaluation of FLAIR sequences did not improve the correlation. Among patients who received immunotherapy, Spearman's correlations were similar among RANO, mRANO, and iRANO. CONCLUSION: RANO and mRANO demonstrated similar correlations between PFS and OS. Confirmation scans were only beneficial in nGBM within 12 weeks of completion of radiotherapy, and there was a trend in favor of the use of postradiation MRI as the baseline scan in nGBM. Evaluation of FLAIR can be omitted. The iRANO criteria did not add significant benefit in patients who received immune checkpoint inhibitors.

Body composition and lung cancer-associated cachexia in TRACERx.

Cancer-associated cachexia (CAC) is a major contributor to morbidity and mortality in individuals with non-small cell lung cancer. Key features of CAC include alterations in body composition and body weight. Here, we explore the association between body composition and body weight with survival and delineate potential biological processes and mediators that contribute to the development of CAC. Computed tomography-based body composition analysis of 651 individuals in the TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study suggested that individuals in the bottom 20th percentile of the distribution of skeletal muscle or adipose tissue area at the time of lung cancer diagnosis, had significantly shorter lung cancer-specific survival and overall survival. This finding was validated in 420 individuals in the independent Boston Lung Cancer Study. Individuals classified as having developed CAC according to one or more features at relapse encompassing loss of adipose or muscle tissue, or body mass index-adjusted weight loss were found to have distinct tumor genomic and transcriptomic profiles compared with individuals who did not develop such features. Primary non-small cell lung cancers from individuals who developed CAC were characterized by enrichment of inflammatory signaling and epithelial-mesenchymal transitional pathways, and differentially expressed genes upregulated in these tumors included cancer-testis antigen MAGEA6 and matrix metalloproteinases, such as ADAMTS3. In an exploratory proteomic analysis of circulating putative mediators of cachexia performed in a subset of 110 individuals from TRACERx, a significant association between circulating GDF15 and loss of body weight, skeletal muscle and adipose tissue was identified at relapse, supporting the potential therapeutic relevance of targeting GDF15 in the management of CAC.

Estimation and testing for clustered interval-censored bivariate survival data with application using the semi-parametric version of the Clayton-Oakes model.

The Kaplan-Meier estimator is ubiquitously used to estimate survival probabilities for time-to-event data. It is nonparametric, and thus does not require specification of a survival distribution, but it does assume that the risk set at any time t consists of independent observations. This assumption does not hold for data from paired organ systems such as occur in ophthalmology (eyes) or otolaryngology (ears), or for other types of clustered data. In this article, we estimate marginal survival probabilities in the setting of clustered data, and provide confidence limits for these estimates with intra-cluster correlation accounted for by an interval-censored version of the Clayton-Oakes model. We develop a goodness-of-fit test for general bivariate interval-censored data and apply it to the proposed interval-censored version of the Clayton-Oakes model. We also propose a likelihood ratio test for the comparison of survival distributions between two groups in the setting of clustered data under the assumption of a constant between-group hazard ratio. This methodology can be used both for balanced and unbalanced cluster sizes, and also when the cluster size is informative. We compare our test to the ordinary log rank test and the Lin-Wei (LW) test based on the marginal Cox proportional Hazards model with robust standard errors obtained from the sandwich estimator. Simulation results indicate that the ordinary log rank test over-inflates type I error, while the proposed unconditional likelihood ratio test has appropriate type I error and higher power than the LW test. The method is demonstrated in real examples from the Sorbinil Retinopathy Trial, and the Age-Related Macular Degeneration Study. Raw data from these two trials are provided.

Reliability and Management Outcomes Following a Percutaneous Biopsy Diagnosis of Oncocytoma: A 15-year Retrospective Analysis.

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.

Diagnostic performance of computed tomography features in detecting oropharyngeal squamous cell carcinoma extranodal extension.

OBJECTIVES: Accurate pre-treatment imaging determination of extranodal extension (ENE) could facilitate the selection of appropriate initial therapy for HPV-positive oropharyngeal squamous cell carcinoma (HPV + OPSCC). Small studies have associated 7 CT features with ENE with varied results and agreement. This article seeks to determine the replicable diagnostic performance of these CT features for ENE. METHODS: Five expert academic head/neck neuroradiologists from 5 institutions evaluate a single academic cancer center cohort of 75 consecutive HPV + OPSCC patients. In a web-based virtual laboratory for imaging research and education, the experts performed training on 7 published CT features associated with ENE and then independently identified the "single most (if any) suspicious" lymph node and presence/absence of each of the features. Inter-rater agreement was assessed using percentage agreement, Gwet's AC1, and Fleiss' kappa. Sensitivity, specificity, and positive and negative predictive values were calculated for each CT feature based on histologic ENE. RESULTS: All 5 raters identified the same node in 52 cases (69%). In 15 cases (20%), at least one rater selected a node and at least one rater did not. In 8 cases (11%), all raters selected a node, but at least one rater selected a different node. Percentage agreement and Gwet's AC1 coefficients were > 0.80 for lesion identification, matted/conglomerated nodes, and central necrosis. Fleiss' kappa was always < 0.6. CT sensitivity for histologically confirmed ENE ranged 0.18-0.94, specificity 0.41-0.88, PPV 0.26-0.36, and NPV 0.78-0.96. CONCLUSIONS: Previously described CT features appear to have poor reproducibility among expert head/neck neuroradiologists and poor predictive value for histologic ENE. KEY POINTS: • Previously described CT imaging features appear to have poor reproducibility among expert head and neck subspecialized neuroradiologists as well as poor predictive value for histologic ENE. • Although it may still be appropriate to comment on the presence or absence of these CT features in imaging reports, the evidence indicates that caution is warranted when incorporating these features into clinical decision-making regarding the likelihood of ENE.

Dual Energy-Derived Metrics for Differentiating Adrenal Adenomas From Nonadenomas on Single-Phase Contrast-Enhanced CT.

BACKGROUND. Adrenal masses are often indeterminate on single-phase postcontrast CT. Dual-energy CT (DECT) with three-material decomposition algorithms may aid characterization. OBJECTIVE. The purpose of this study was to compare the diagnostic performance of metrics derived from portal venous phase DECT, including virtual noncontrast (VNC) attenuation, fat fraction, iodine density, and relative enhancement ratio, for characterizing adrenal masses. METHODS. This retrospective study included 128 patients (82 women, 46 men; mean age, 64.6 ± 12.7 [SD] years) who between January 2016 and December 2019 underwent portal venous phase abdominopelvic DECT that showed a total of 139 adrenal lesions with an available reference standard based on all imaging, clinical, and pathologic records (87 adenomas, 52 nonadenomas [48 metastases, two adrenal cortical carcinomas, one ganglioneuroma, one hematoma]). Two radiologists placed ROIs to determine the following characteristics of the masses: VNC attenuation, fat fraction, iodine density normalized to portal vein, and for masses with VNC greater than 10 HU, relative enhancement ratio (ratio of portal venous phase attenuation to VNC attenuation). Readers' mean measurements were used for ROC analyses, and clinically optimal thresholds were derived as thresholds yielding the highest sensitivity at 100% specificity. RESULTS. Adenomas and nonadenomas were significantly different (all p < .001) in VNC attenuation (mean ± SD, 18.5 ± 12.9 vs 34.1 ± 8.9 HU), fat fraction (mean ± SD, 24.3% ± 8.2% vs 14.2% ± 5.6%), normalized iodine density (mean ± SD, 0.34 ± 0.15 vs 0.17 ± 0.17), and relative enhancement ratio (mean ± SD, 186% ± 96% vs 58% ± 59%). AUCs for all metrics ranged from 0.81 through 0.91. The metric with highest sensitivity for adenoma at the clinically optimal threshold (i.e., 100% specificity) was fat fraction (threshold, ≥ 23.8%; sensitivity, 59% [95% CI, 48-69%]) followed by VNC attenuation (≤ 15.2 HU; sensitivity, 39% [95% CI, 29-50%]), relative enhancement ratio (≥ 214%; sensitivity, 37% [95% CI, 25-50%]), and normalized iodine density (≥ 0.90; sensitivity, 1% (95% CI, 0-60%]). VNC attenuation at the traditional true noncontrast attenuation threshold of 10 HU or lower had sensitivity of 28% (95% CI, 19-38%) and 100% specificity. Presence of fat fraction 23.8% or greater or relative enhancement ratio 214% or greater yielded sensitivity of 68% (95% CI, 57-77%) with 100% specificity. CONCLUSION. For adrenal lesions evaluated with single-phase DECT, fat fraction had higher sensitivity than VNC attenuation at both the clinically optimal threshold and the traditional threshold of 10 HU or lower. CLINICAL IMPACT. By helping to definitively diagnose adenomas, DECT-derived metrics can help avoid downstream imaging for incidental adrenal lesions.

Impact of second-generation transoral incisionless fundoplication on atypical GERD symptoms: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Transoral incisionless fundoplication (TIF) using the EsophyX device (EndoGastric Solutions, Inc, Redmond, Wash, USA) is a minimally invasive endoscopic fundoplication technique. Our study aimed to assess the efficacy of TIF for atypical GERD symptoms in patients with chronic or refractory GERD. METHODS: A systematic search of 4 major databases was performed. All original studies assessing atypical GERD using a validated symptom questionnaire (the reflux symptom index [RSI]) were included. The RSI score was assessed before and after TIF at a 6- and 12-month follow-up. Data on technical success rate, adverse events, proton pump inhibitor (PPI) use, and patient satisfaction were also collected. Only TIF procedures currently in practice using the EsophyX device (ie, TIF 2.0) and TIF with concomitant hiatal hernia repair were included in the review. RESULTS: Ten studies (564 patients) were included. At the 6- and 12- month follow-up, there was a mean reduction of 15.72 (95% confidence interval, 12.15-19.29) and 14.73 (95% confidence interval, 11.74-17.72) points, respectively, in the RSI score post-TIF, with a technical success rate of 99.5% and a pooled adverse event rate of 1%. At both time intervals, more than two-thirds of the patients were satisfied with their health condition and roughly three-fourths of the patients were off daily PPIs. CONCLUSIONS: Our study shows that TIF using the EsophyX device is safe and effective in reducing atypical GERD symptoms at 6 and 12 months of follow-up. It improves patient-centered outcomes and can be a minimally invasive therapeutic option for patients suffering from atypical GERD symptoms on chronic medical therapy.

Efficacy and safety of topical agents in the treatment of melasma: What's evidence? A systematic review and meta-analysis.

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.

A Team-Based Approach to Radiology Resident Case Conference to Improve Camaraderie Among Trainees.

INTRODUCTION: In light of increasing concerns regarding resident burnout, we developed a team-based approach (TBA) to radiology resident case conference to foster wellness by cultivating camaraderie and a positive learning environment. METHODS: Teaching faculty provided both a traditional hot-seat and a TBA format case conference. Resident perceptions of each conference format were assessed using a 16-item questionnaire, with 14 of the items utilizing a 7-point Likert scale to assess the learning environment, including measures related to wellness. A two-sided Wilcoxon rank-sum test was used to compare responses between the 2 formats of teaching conferences. RESULTS: Four paired teaching sessions were performed by 4 individual faculty. Sixty-six individual resident responses were received for the hot-seat and TBA conferences in aggregate. Residents responded "strongly agree" to positive statements more often for the TBA format compared with hot-seat for 13 out of the 14 items used to assess perceptions of the learning environment, including measures of wellness and camaraderie. The level of agreement on a 7-point Likert scale pertaining to the statement "The format of this case conference improves camaraderie among my co-residents" had a median value of 4.5 for the hot-seat format and 7 for the TBA format (P = 0.002). DISCUSSION: A TBA format for resident case conference may foster a sense of camaraderie among trainees. Residency programs may consider supplementing hot-seat conferences with the TBA method to address increasing burnout among trainees and promote resident wellbeing.

Short-term neurochemical effects of transcutaneous trigeminal nerve stimulation using 7T magnetic resonance spectroscopy.

BACKGROUND AND PURPOSE: The purpose was to explore the effects of transcutaneous trigeminal nerve stimulation (TNS) on neurochemical concentrations (brainstem, anterior cingulate cortex [ACC], dorsolateral prefrontal cortex [DLPFC], ventromedial prefrontal cortex [VMPFC], and the posterior cingulate cortex [PCC]) using ultrahigh-field magnetic resonance spectroscopy. METHODS: This double-blinded study tested 32 healthy males (age: 25.4 ± 7.3 years) on two separate occasions where participants received either a 20-minute TNS or sham session. Participants were scanned at baseline and twice post-TNS/sham administration. RESULTS: There were no group differences in concentration changes of glutamate, gamma-aminobutyric acid, glutamine, myoinositol (mI), total N-acetylaspartate, total creatine (tCr), and total choline between the baseline scan and the first post-TNS/sham scan and between the first and second post-TNS/sham scan in the brainstem, ACC, DLPFC, VMPFC, and PCC. Between the baseline scan and the second post-TNS/sham scan, changes in tCr (mean difference = 0.280 mM [0.075 to 0.485], p = .026) and mI (mean difference = 0.662 mM [0.203 to 1.122], p = .026) in the DLPFC differed between groups. Post hoc analyses indicated that there was a decrease in tCr (mean change = -0.201 mM [-0.335 to -0.067], p = .003) and no change in mI (mean change = -0.327 mM [-0.737 to 0.083], p = .118) in the TNS group; conversely, there was no change in tCr (mean change = -0.100 mM [-0.074 to 0.274], p = .259) and an increase in mI (mean change = 0.347 mM [0.106 to 0.588], p = .005) in the sham group. CONCLUSION: These data demonstrate that a single session of unilateral TNS slightly decreased tCr concentrations in the DLPFC region.

Think Like an MBA: Development, Implementation, and Evaluation of an Academic Radiology Business Series (ARBS) for Radiology Trainees.

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.

Feasibility, effectiveness and patient satisfaction of telerehabilitation after thumb carpometacarpal arthroplasty and reverse total shoulder arthroplasty: A pilot study.

INTRODUCTION: Telemedicine is an effective, emerging interface to connect practitioners with patients. It facilitates access to healthcare expertise, reduces costs, time demands and health disparities while improving satisfaction. This pilot study evaluated the feasibility, effectiveness and patient satisfaction of telerehabilitation for thumb carpometacarpal (CMC) arthroplasty and reverse shoulder arthroplasty (rTSA). METHODS: This prospective investigation was performed at a single academic institution with two hand and upper extremity fellowship-trained orthopaedic surgeons. All patients undergoing CMC arthroplasty or rTSA were eligible for inclusion. Telerehabilitation was delivered by a hybrid model including an in-person post-operative visit, followed by alternating in-clinic and virtual videoconference visits. All patients were offered participation in the study arm; those that preferred in-person therapy were included as a control group. Therapy was initiated two weeks post-operative with an in-clinic evaluation. Patients then participated in alternating in-clinic and virtual visits weekly for eight weeks, followed by one virtual visit at 14-weeks post-operative and one clinical visit at 16-weeks post-operative. Patient reported and functional outcomes were collected at each visit. RESULTS: In the CMC group, 19 study and 11 control patients were enrolled. In the rTSA group, five study and 14 control patients were enrolled. No statistically significant differences between telerehabilitation and control for range-of-motion, pain and patient-reported functional outcomes was noted. All patients in the telerehabilitation arms reported high satisfaction. DISCUSSION: Utilizing telehealth in rehabilitation may be a viable option in upper extremity recovery. We hope this pilot programme can be a model for development of future telerehabilitation programmes.

Effect of Plastic Bag Extraction in Minimally Invasive Appendectomy.

BACKGROUND: Evidence regarding the effects of plastic bag use for appendix removal during minimally invasive appendectomy remains scarce and conflicting. OBJECTIVE: This study aimed to analyze the effects of plastic bag use during minimally invasive appendectomy on preoperative infection risk, morbidity and mortality. DESIGN: This retrospective analysis of the prospective National Surgical Quality Improvement Program (NSQIP) cohort program. SETTING: This study included data from the NSQIP database between the years of 2016 and 2019. PATIENT: Adult patients undergoing minimally invasive (laparoscopic or robotic) without unplanned conversion to open surgery. INTERVENTION: Use of plastic bag for specimen removal during appendectomy. MAIN OUTCOME MEASURES: Risk ratios for the incidence of superficial surgical site infection, intra-abdominal abscess, overall medical morbidity, and overall mortality. RESULTS: There were 43 783 cases of minimally invasive appendectomy in the NSQIP database between the years of 2016 and 2019. Among those who reported information regarding use of plastic bag, 28 589 (91.87%) reported use of plastic bag for specimen removal. Use of plastic bag was associated with a significant decrease in superficial surgical site infection (RR .39 (95% CI: .31-.49), P < .001), and in the risk of postoperative intra-abdominal abscess (RR: 0.66 (.57-.77), P < .001)). We also observed a robust reduction in overall medical-related morbidity and overall mortality, even after adjusting for multiple confounders. LIMITATIONS: Observational nature of the study cannot exclude residual bias. Also, there was a significant rate of missing values for plastic bag use, which may bias results. CONCLUSIONS: In this global prospective cohort using NSQIP database, use of plastic bag for appendix removal during minimally invasive appendectomy was associated with a significant improvement in surgical related outcomes and reduction in morbidity and overall mortality.

Utility of Normalized Body Composition Areas, Derived From Outpatient Abdominal CT Using a Fully Automated Deep Learning Method, for Predicting Subsequent Cardiovascular Events.

BACKGROUND. CT-based body composition (BC) measurements have historically been too resource intensive to analyze for widespread use and have lacked robust comparison with traditional weight metrics for predicting cardiovascular risk. OBJECTIVE. The aim of this study was to determine whether BC measurements obtained from routine CT scans by use of a fully automated deep learning algorithm could predict subsequent cardiovascular events independently from weight, BMI, and additional cardiovascular risk factors. METHODS. This retrospective study included 9752 outpatients (5519 women and 4233 men; mean age, 53.2 years; 890 patients self-reported their race as Black and 8862 self-reported their race as White) who underwent routine abdominal CT at a single health system from January 2012 through December 2012 and who were given no major cardiovascular or oncologic diagnosis within 3 months of undergoing CT. Using publicly available code, fully automated deep learning BC analysis was performed at the L3 vertebral body level to determine three BC areas (skeletal muscle area [SMA], visceral fat area [VFA], and subcutaneous fat area [SFA]). Age-, sex-, and race-normalized reference curves were used to generate z scores for the three BC areas. Subsequent myocardial infarction (MI) or stroke was determined from the electronic medical record. Multivariable-adjusted Cox proportional hazards models were used to determine hazard ratios (HRs) for MI or stroke within 5 years after CT for the three BC area z scores, with adjustment for normalized weight, normalized BMI, and additional cardiovascular risk factors (smoking status, diabetes diagnosis, and systolic blood pressure). RESULTS. In multivariable models, age-, race-, and sex-normalized VFA was associated with subsequent MI risk (HR of highest quartile compared with lowest quartile, 1.31 [95% CI, 1.03-1.67], p = .04 for overall effect) and stroke risk (HR of highest compared with lowest quartile, 1.46 [95% CI, 1.07-2.00], p = .04 for overall effect). In multivariable models, normalized SMA, SFA, weight, and BMI were not associated with subsequent MI or stroke risk. CONCLUSION. VFA derived from fully automated and normalized analysis of abdominal CT examinations predicts subsequent MI or stroke in Black and White patients, independent of traditional weight metrics, and should be considered an adjunct to BMI in risk models. CLINICAL IMPACT. Fully automated and normalized BC analysis of abdominal CT has promise to augment traditional cardiovascular risk prediction models.