Comparison of Magnetic Resonance Imaging-Based Risk Calculators to Predict Prostate Cancer Risk.

Importance: Magnetic resonance imaging (MRI)-based risk calculators can replace or augment traditional prostate cancer (PCa) risk prediction tools. However, few data are available comparing performance of different MRI-based risk calculators in external cohorts across different countries or screening paradigms. Objective: To externally validate and compare MRI-based PCa risk calculators (Prospective Loyola University Multiparametric MRI [PLUM], UCLA [University of California, Los Angeles]-Cornell, Van Leeuwen, and Rotterdam Prostate Cancer Risk Calculator-MRI [RPCRC-MRI]) in cohorts from Europe and North America. Design, Setting, and Participants: This multi-institutional, external validation diagnostic study of 3 unique cohorts was performed from January 1, 2015, to December 31, 2022. Two cohorts from Europe and North America used MRI before biopsy, while a third cohort used an advanced serum biomarker, the Prostate Health Index (PHI), before MRI or biopsy. Participants included adult men without a PCa diagnosis receiving MRI before prostate biopsy. Interventions: Prostate MRI followed by prostate biopsy. Main Outcomes and Measures: The primary outcome was diagnosis of clinically significant PCa (grade group ≥2). Receiver operating characteristics for area under the curve (AUC) estimates, calibration plots, and decision curve analysis were evaluated. Results: A total of 2181 patients across the 3 cohorts were included, with a median age of 65 (IQR, 58-70) years and a median prostate-specific antigen level of 5.92 (IQR, 4.32-8.94) ng/mL. All models had good diagnostic discrimination in the European cohort, with AUCs of 0.90 for the PLUM (95% CI, 0.86-0.93), UCLA-Cornell (95% CI, 0.86-0.93), Van Leeuwen (95% CI, 0.87-0.93), and RPCRC-MRI (95% CI, 0.86-0.93) models. All models had good discrimination in the North American cohort, with an AUC of 0.85 (95% CI, 0.80-0.89) for PLUM and AUCs of 0.83 for the UCLA-Cornell (95% CI, 0.80-0.88), Van Leeuwen (95% CI, 0.79-0.88), and RPCRC-MRI (95% CI, 0.78-0.87) models, with somewhat better calibration for the RPCRC-MRI and PLUM models. In the PHI cohort, all models were prone to underestimate clinically significant PCa risk, with best calibration and discrimination for the UCLA-Cornell (AUC, 0.83 [95% CI, 0.81-0.85]) model, followed by the PLUM model (AUC, 0.82 [95% CI, 0.80-0.84]). The Van Leeuwen model was poorly calibrated in all 3 cohorts. On decision curve analysis, all models provided similar net benefit in the European cohort, with higher benefit for the PLUM and RPCRC-MRI models at a threshold greater than 22% in the North American cohort. The UCLA-Cornell model demonstrated highest net benefit in the PHI cohort. Conclusions and Relevance: In this external validation study of patients receiving MRI and prostate biopsy, the results support the use of the PLUM or RPCRC-MRI models in MRI-based screening pathways regardless of European or North American setting. However, tools specific to screening pathways incorporating advanced biomarkers as reflex tests are needed due to underprediction.

A comparison of clinical, utilization, and cost outcomes between oral treatments for multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) affects nearly 1 million people in the United States and causes significant disability and economic loss. Among the first available oral MS treatment options, clinical outcome comparisons and associated health care resource utilization are not clearly defined. OBJECTIVE: To compare MS outcomes, health care resource utilization, and relative costs across treatment with dimethyl fumarate (DMF), fingolimod (FG), or teriflunomide (TERI) among Medicare Advantage Prescription Drug (MAPD) plan and commercially insured beneficiaries. METHODS: This retrospective cohort study used the Humana Research Database. Eligible study patients had their first MS medication claim for oral DMG, FG, or TERI between January 1, 2013, and December 31, 2018. Patients were followed for a minimum of 12 months (mean follow-up = 3.8 years), until the earliest of the following occurred: health plan disenrollment, the end of the study period, or death. Study cohorts were balanced with inverse probability of treatment weighting. All-cause and MS-related health care resource utilization, time on therapy, and time after therapy were compared using inverse probability of treatment-adjusted multivariate generalized linear models across treatment groups. Relative costs were compared using a generalized linear model with a gamma distribution and log link. RESULTS: We identified 1,442 patients in 3 medication groups: DMF (n = 843), FG (n = 213), and TERI (n = 386). After weighting, there were no significant differences between the medication groups on demographic and clinical characteristics. Time on therapy (days) was significantly different across medication groups (P < 0.001). Time on therapy was longest for FG compared with the DM and TERI groups (644 vs 462 vs 521). The number discontinuing the index medication was significantly different for FG vs DMF vs TERI (74.7% vs 85.3% vs 80.7%; P < 0.001). FG had the lowest discontinuation rate. The mean (SD) annualized relapse rates (ARRs) were 0.47 (0.80), 0.42 (1.3), and 0.53 (1.3) (P = 0.037) for DMF, FG, and TERI, respectively. The percentage of those experiencing inpatient stays and the number of stays (mean [SD]) were significantly different among the FG group vs DMF vs TERI (29.9% vs 34.1% vs 40.9%; P < 0.001) and (0.57 [2.9] vs 0.74 [1.9] vs 0.91 [3.5]; P = 0.007), respectively. All-cause emergency department visits and the number of visits (mean [SD]) were significantly different for the FG cohort vs DMF vs TERI (46% vs 54.3% vs 61%; P < 0.001) and (1.84 [7.7] vs 2.38 [5.9] vs 2.87 [8.8]; P = 0.002), respectively. FG had the lowest impatient stays and emergency department visits of the 3 groups. CONCLUSIONS: Patients with MS initiated on FG used fewer health care resources and experienced lower ARR compared with patients on DMF and TERI.

Risk of pseudoaneurysm and bleeding complications after partial nephrectomy: comparison of tumor enucleation to standard margin technique.

Partial nephrectomy (PN) is the gold standard for the resection of amenable small renal masses. Some surgeons have adopted tumor enucleation (TE) over the standard margin PN (SPN) technique based on preservation of healthy renal parenchyma by following the tumor pseudocapsule. However, TE may also confer additional advantages due to avoidance of sharp incision including reduction in perioperative and bleeding complications. Therefore, we evaluated the rate of pseudoaneurysms and other complications following TE vs. SPN. A retrospective cohort study of patients undergoing PN (TE and SPN) between 2008 and 2020 was conducted. Baseline characteristics were compared between the TE and SPN cohorts with univariable and multivariable logistic regression models. A total of 534 patients were included, 195 (36.5%) receiving TE and 339 (63.5%) SPN. There were no differences in baseline patient demographics. There was no difference in RENAL nephrometry scores between the two groups (p = 0.47). TE had lower rates of postoperative complications (11.3 vs. 21.5%, p = 0.002). TE had less bleeding complications (2.1 vs. 8.0%, p = 0.002) with no pseudoaneurysm events following TE compared to 12 following SPN (0.0 vs. 3.5%, p = 0.008). Need for interventional radiology largely reflected pseudoaneurysm differences (0 (0.0%) TE vs. 13 (3.8%) SPN, p = 0.006. Readmission occurred less often after TE vs. SPN (4.1 vs. 8.3%, p = 0.07). Patients receiving TE experienced no clinically significant pseudoaneurysm formation and were less likely to have any bleeding complication or major complication postoperatively. TE may be preferred when minimizing morbidity aligns with patient selection and preferences.

Robotic transperitoneal versus retroperitoneal approach for anterior renal mass nephron-sparing surgery.

Robotic nephron-sparing surgery is traditionally performed via a transperitoneal (TP) approach. However, the retroperitoneal (RP) approach has gained popularity, particularly for posterolateral renal masses. The RP approach is associated with shorter operative time, less blood loss, and shorter length of stay, while preserving oncologic outcomes in selected masses. Here, we aim to assess the feasibility of the RP approach in excising anterior renal masses. Patients ≥ 18 years of age who underwent robotic nephron-sparing surgery for anterior renal masses were retrospectively identified (2008-2022). Baseline demographics, tumor characteristics, and perioperative data were collected and characterized based on TP vs RP approaches. Wilcoxon rank sum test and Pearson's Chi-squared test were used to compare continuous and categorical variables, respectively. Two hundred and sixteen patients were included-178 (82.4%) underwent TP approach and 38 (17.6%) underwent RP approach. Baseline demographics, preoperative tumor size, and renal nephrometry scores were similar. The RP approach was associated with shorter operative (150 vs 203 min, p < 0.001) and warm ischemia time (12 vs 21 min, p < 0.001), and less blood loss (20 vs 100 cc, p = 0.002) (Table 1). The RP approach was associated with shorter length of stay (1 vs 2 days, p < 0.001) and less total complications (5.3% vs 19.1%, p = 0.038). Major complication (Clavien-Dindo Grade > 3) rates were similar. There was no difference in positive surgical margin rates or pathologic characteristics. Robotic RP approach for nephron-sparing surgery is feasible for eligible anterior tumors and is associated with favorable perioperative outcomes with preserved negative surgical margin rates. Table 1 Patient baseline demographics Overall Transperitoneal Retroperitoneal p value Median/N IQR/% Median/N IQR/% Median/N IQR/% N 216 178 82.4% 38 17.6% Age (years) 60.5 (52.1-67.7) 60.4 (52.8-67.7) 61.6 (49.1-69.2) 0.393 Sex Male 126 58.3% 100 56.2% 26 68.4% Female 90 41.7% 78 43.8% 12 31.6% 0.165 Race White 162 75.0% 137 77.0% 25 65.8% Asian 4 1.9% 2 1.1% 2 5.3% Black 21 9.7% 18 10.1% 3 7.9% Hispanic 26 12.0% 18 10.1% 8 21.1% Other 2 0.9% 2 1.1% 0 0.0% 0.197 Body mass index (kg/m2) < 25 32 14.8% 25 14.0% 7 18.4% 25-30 68 31.5% 55 30.9% 13 34.2% 30-35 60 27.8% 50 28.1% 10 26.3% 35 + 56 25.9% 48 27.0% 8 21.1% 0.808 Prior abdominal surgery Yes 118 54.6% 104 58.4% 14 36.8% No 98 45.4% 74 41.6% 24 63.2% 0.015 Prior kidney surgery Yes 10 4.6% 9 5.1% 1 2.6% No 206 95.4% 169 94.9% 37 97.4% 0.518 Chronic kidney disease stage ≥ 3 Yes 45 20.8% 38 21.3% 7 18.4% No 171 79.2% 140 78.7% 31 81.6% 0.687 Charlson comorbidity index 0 138 63.9% 116 65.2% 22 57.9% 1 46 21.3% 38 21.4% 8 21.1% 2 19 8.8% 13 7.3% 6 15.8% ≥ 3 13 6.0% 11 6.2% 2 5.3% 0.412 Tumor size (cm) 2.7 (2-3.6) 2.8 (2-3.5) 2.55 (2-3.7) 0.796 Tumor laterality Left 100 46.3% 78 43.8% 22 57.9% Right 116 53.7% 100 56.2% 16 42.1% 0.114 Clinical T stage cT1a 186 86.1% 152 85.4% 34 89.5% cT1b 30 13.9% 26 14.6% 4 10.5% 0.509 RENAL Nephrometry score Low (4 to 6) 94 43.5% 76 42.7% 18 47.4% Intermediate (7 to 9) 112 51.9% 94 52.8% 18 47.4% High (≥ 10) 19 4.6% 8 4.5% 2 5.3% 0.829 TE tumor enucleation, SPN standard margin partial nephrectomy, IQR interquartile range.

Neoadjuvant Chemotherapy Before Radical Cystectomy for Muscle-Invasive Bladder Cancer: Elective and Eligibility Factors Impacting Utilization.

INTRODUCTION: We aimed to assess utilization of neoadjuvant chemotherapy (NAC) and etiologies for lack of NAC receipt among patients with muscle-invasive bladder cancer (MIBC). METHODS: Patients diagnosed with MIBC undergoing radical cystectomy at a single institution (2005-2021) were included. Patients were categorized by receipt of NAC, and reasons for no NAC were categorized into eligibility and elective factors. Overall survival was analyzed using univariable and multivariable Cox proportional hazards regression models and modeled with Kaplan-Meier curves. RESULTS: Three hundred eighty patients with MIBC were included; 154 (40.5%) received NAC. Patients were not candidates for NAC due to renal dysfunction (16.6%), clinical contraindications (4.7%), salvage setting (2.1%), and histology (5.3%; total N = 109). Among 271 (71.3%) who were eligible, utilization increased from early (2005-2016) to recent (2016-2021) time periods (34.2% to 85.7% among NAC-eligible, P < .001; 22.8% vs 67.1% among all MIBC, P < .001). Elective factors for not receiving NAC included patient symptoms (7.8%), disease progression concern (7.0%), patient preference/refusal (20.3%) and provider discretion (8.1%) among 271 NAC-eligible patients. Notably, patient preference/refusal decreased from 33.6% to 3.4% in recent years (P < .001). On multivariable analysis, lack of NAC utilization due to renal dysfunction (HR 2.18, P = .002), clinical contraindications (HR 2.62, P = .01), and elective factors (HR 1.88, P = .01) were associated with worse overall survival. CONCLUSIONS: NAC utilization increased over time with 85.7% of eligible patients with MIBC receiving NAC in recent years. Renal dysfunction, patient preference, and clinical contraindications were primary etiologies for lack of NAC. Fewer patients refused NAC in recent years leading to a potential ceiling for NAC utilization.

Preoperative optimization of the radical cystectomy patient: Current state and future directions.

Radical cystectomy (RC) is associated with high rates of morbidity and mortality despite adoption of robotics and implementation of enhanced recovery after surgery protocols. There have been increased efforts to investigate preoperative optimization through comprehensive nutritional evaluation, preoperative supplementation, and prehabilitation outside of previously described enhanced recovery after surgery protocols to reduce mortality and morbidity from RC. In this review, we summarize and evaluate the current literature on preoperative assessment and optimization in RC.

The Current Status of Palliative Care, Hospice, and End-of-Life Health Care Utilization in Patients With Malignant Ureteral Obstruction.

INTRODUCTION: Malignant ureteral obstruction is associated with a poor prognosis, with a median survival of 3 to 7 months. These patients are ideal candidates for concurrent palliative care services, consistent with American Society of Clinical Oncology guidelines. We aimed to characterize palliative care, hospice, and end-of-life health care utilization in patients with malignant ureteral obstruction. METHODS: Patients ≥ 18 years old at our institution and diagnosed with malignant ureteral obstruction between May 2014 and August 2020 were retrospectively identified and pertinent data extracted. Palliative care, hospice, and end-of-life health care utilization was described, and factors associated with each were assessed with logistic regression models. Overall survival was assessed with Cox proportional hazard regression models. RESULTS: One hundred fifteen patients qualified for analysis; 39.1% (45/115) utilized palliative care and spent a median of 12.5 days (IQR 3-52 days) on nonhospice palliative care. On adjusted analysis Black ethnicity (aOR 3.44, 95% CI: 1.08-10.94) was associated with palliative care utilization. Of the patients, 53.9% (62/115) utilized hospice. The median time from hospice initiation to death was 12 days (IQR 5-23 days). On adjusted analysis, prior extirpative surgery (aOR 3.63, 95% CI 1.01-13.05) and palliative care utilization (aOR 4.38, 95% CI 1.70-11.31) were associated with hospice utilization. Median survival following diagnosis was 141 days (IQR 37.5-442.5). Of the patients, 43.0% (37/86) had high end-of-life health care utilization. On multivariable analysis, only hospice (aOR 0.03, 95% CI 0.01-0.14) was associated with less end-of-life health care utilization. CONCLUSIONS: Palliative care is underutilized in malignant ureteral obstruction. Hospice, but not palliative care utilization, was associated with decreased end-of-life health care utilization.

HIV preexposure prophylaxis treatment patterns in a national health plan population.

BACKGROUND: Medication nonadherence diminishes the benefits of preexposure prophylaxis (PrEP) for the 1.2 million Americans at risk for HIV exposure. OBJECTIVE: To describe HIV PrEP treatment patterns among Medicare Advantage Prescription Drug (MAPD) plan and commercially insured beneficiaries. METHODS: This retrospective cohort study identified patients aged 16 to 89 years with at least 1 dispensing of emtricitabine-tenofovir disoproxil fumarate from July 2012, through December 2020, or emtricitabine-tenofovir alafenamide from October 2019 through December 2020, and who were continuously enrolled at least 12 months prior to and following the earliest PrEP claim. Outcomes were HIV PrEP adherence measured by proportion of days covered (PDC) using 2 binary thresholds of 0.60 (4 doses/week) and 0.80 (5-6 doses/week) and duration of index treatment episode, total time on treatment, and total number of prescription fills. RESULTS: The study cohort of 707 (292 MAPD plan, 415 commercial) was predominantly made up of male patients (90.0%) and resided in the South (78.9%) with a mean age of 46.2 years (MAPD plan: 54.5, commercial: 40.4). Both populations engaged in high-risk sexual behavior (All: 18.7%, MAPD plan: 16.8%, commercial: 20.0%) and experienced sexually transmitted infections (All: 3.3%, MAPD plan: 2.1%, commercial: 4.1%). The mean index treatment episode length was 297.0 days (MAPD plan: 283.6, commercial: 306.5). Total time on treatment was 477.3 days (MAPD plan: 450.7, commercial 496.0). At 3 months, 84.9% (MAPD plan: 83.6%, commercial: 85.8%) and at 12 months, 58.7% (MAPD plan: 57.2, commercial: 59.8) of patients achieved a PDC of at least 0.80. At 3 months, 100.0% (MAPD plan: 100.0%, commercial: 100.0%), and at 12 months, 74.3% (MAPD plan: 70.2%, commercial: 76.9%) of patients achieved a PDC of at least 0.60. The cohort had a mean of 16.4 fills of 30 days (MAPD plan: 16.4, commercial: 16.3) supply. CONCLUSIONS: There is an opportunity for clinical programs to focus on improving longer-term PrEP adherence among individuals at risk for HIV exposure.

Incidental Discovery of Hepatocellular Carcinoma on 18F-PSMA PET CT Performed for Prostate Cancer Reassessment.

Prostate-specific membrane antigen positron emission tomography (PSMA PET) has been approved by the Food and Drug Administration (FDA) to identify prostate cancer in the setting of biochemical recurrence but can also identify other malignancies. 18F-PSMA PET has not been studied as a potential tool for hepatocellular carcinoma (HCC). We describe the case of a 76-year-old male with a rising prostate-specific antigen (PSA) after definitive prostate cancer treatment and no prior liver pathology who was incidentally found to have HCC on 18F-PSMA PET.

Validation of a Deep Learning Algorithm for Continuous, Real-Time Detection of Atrial Fibrillation Using a Wrist-Worn Device in an Ambulatory Environment.

BACKGROUND: Wearable devices may be useful for identification, quantification and characterization, and management of atrial fibrillation (AF). To date, consumer wrist-worn devices for AF detection using photoplethysmography-based algorithms perform only periodic checks when the user is stationary and are US Food and Drug Administration cleared for prediagnostic uses without intended use for clinical decision-making. There is an unmet need for medical-grade diagnostic wrist-worn devices that provide long-term, continuous AF monitoring. METHODS AND RESULTS: We evaluated the performance of a wrist-worn device with lead-I ECG and continuous photoplethysmography (Verily Study Watch) and photoplethysmography-based convolutional neural network for AF detection and burden estimation in a prospective multicenter study that enrolled 117 patients with paroxysmal AF. A 14-day continuous ECG monitor (Zio XT) served as the reference device to evaluate algorithm sensitivity and specificity for detection of AF in 15-minute intervals. A total of 91 857 intervals were contributed by 111 subjects with evaluable reference and test data (18.3 h/d median watch wear time). The watch was 96.1% sensitive (95% CI, 92.7%-98.0%) and 98.1% specific (95% CI, 97.2%-99.1%) for interval-level AF detection. Photoplethysmography-derived AF burden estimation was highly correlated with the reference device burden (R2=0.986) with a mean difference of 0.8% (95% limits of agreement, -6.6% to 8.2%). CONCLUSIONS: Continuous monitoring using a photoplethysmography-based convolutional neural network incorporated in a wrist-worn device has clinical-grade performance for AF detection and burden estimation. These findings suggest that monitoring can be performed with wrist-worn wearables for diagnosis and clinical management of AF. REGISTRATION INFORMATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04546763.

Home versus outpatient hospital intravenous immunoglobulin infusion and health care resource utilization.

BACKGROUND: Home health care delivery is projected to increase. Intravenous immunoglobulin (IVIG) therapy has high potential to move from the outpatient hospital (OPH) setting to home delivery. OBJECTIVE: This study examined the relationship between home and OPH IVIG infusions and health care utilization. METHODS: We used a retrospective cohort study design and the Humana Research Database to identify patients with 1 or more medical or pharmacy claims for an IVIG infusion agent from January 1, 2017, to December 31, 2018. Eligible patients were enrolled in a Medicare Advantage Prescription Drug (MAPD) or commercial health plan, with at least 12 months of continuous enrollment before and after their first infusion (i.e., index date) received in the home or OPH setting. We measured the odds of experiencing an inpatient (IP) stay or emergency department (ED) visit, adjusted for baseline differences in age, sex, race, region, population density, low-income, and dual eligibility status, MAPD or commercial health plan, plan type, treatment-naïve status, home health use, RxRisk-V comorbidity burden score, and indications for IVIG use. RESULTS: A total of 208 and 1079 patients received IVIG infusions in the home and OPH setting, respectively. The odds for an IP stay (odds ratio [OR] 0.56 [95% CI 0.38-0.82]) and ED visit (OR 0.62 [95% CI 0.41-0.93]) were significantly lower in patients who received IVIG infusion in the home than patients receiving infusion in the OPH setting. CONCLUSIONS: Our findings suggest there may be value to increasing referrals for IVIG home infusion. Decreased health care utilization provides value to the system in cost savings and to patients and families owing to less disruption and improved clinical outcomes. Further study can help inform health policy designed to maximize the benefits of IVIG home infusion while minimizing potential risks.

Early vs late filling of new heart failure prescription and its association with avoidable hospital admissions.

BACKGROUND: Individuals with heart failure (HF) are at increased risk for hospitalization and readmission after discharge. The impact of timing to new prescription filling on avoidable HF hospitalization is understudied in HF management. The Agency of Healthcare Research and Quality identifies HF-related inpatient admissions as potentially avoidable if they could be managed successfully in outpatient settings. OBJECTIVE: To compare avoidable HF hospitalization rate and all-cause and HF-related costs in patients who were early fillers (≤30 days) vs late fillers (>30 days) of newly prescribed HF medications following an HF-related inpatient stay or emergency department visit. METHODS: This retrospective cohort study used the Humana Research Database to identify patients with at least 1 claim for a new HF medication from January 1, 2018, to June 30, 2019. Eligible patients were enrolled in a Medicare Advantage Prescription Drug plan for at least 12 months pre-index and 6-months post-index (ie, first new HF prescription). Individuals who were early (n = 794) vs late fillers (n = 397) were propensity-score matched in a 2:1 ratio to balance baseline characteristics. A logistic regression model was fitted to compare avoidable HF hospitalization in those who were late fillers vs early fillers. Mean cost differences were compared using paired t-test. Outcomes were measured 6-months post-index. RESULTS: Late fillers had greater odds of experiencing an avoidable HF hospitalization compared with early fillers (odds ratio = 1.65; P = 0.001). Late filling was associated with a 49.5% increase in average all-cause medical costs (P < 0.0001), a 13.6% decrease in average all-cause pharmacy costs (P = 0.0929), and a 39.4% increase in average all-cause total costs (P < 0.0001). HF-related costs showed similar trends. CONCLUSION: Compared with patients who filled their prescription within 30 days of discharge following an HF admission, those who delayed the filling of a new HF prescription experienced increased likelihood of an avoidable readmission, and late filling was associated with increased 6-month total and medical costs. DISCLOSURES: Humana Healthcare Research, Inc., funded the research and article development. No external funds were used in the creation of this work. All authors are/were employees of Humana Inc. and/or Humana Healthcare Research, Inc., at the time of the work.

Profound facial bleeding after buccal mucosa graft harvest - A rare case of facial artery pseudoaneurysm.

Facial artery pseudoaneurysms are exceedingly rare events that can occur as a complication of oral maxillofacial surgery or facial trauma. The management of such pseudoaneurysms following buccal mucosa graft harvest for urinary reconstructive indications has not previously been described. Here, we describe a facial artery pseudoaneurysm that presented as repeated, episodic facial bleeding episodes following buccal mucosal harvest for a patient undergoing urethroplasty.

Estradiol-secreting adrenal oncocytoma in a 31-year old male.

Oncocytic adrenocortical tumors (OAT) are rare and often are non-functional. We report a unique case of an estradiol-secreting adrenal oncocytoma in a 31-year-old male discovered upon an infertility and gynecomastia work-up. After resection of the 9 cm adrenal mass, the patient's estradiol levels normalized from 83.2 pg/ml to 19.0 pg/ml. Gonadotropins and serum dehydroepiandrosterone sulfate also normalized.

Cohort profile: a migratory cohort study of US Marines who train in Australia.

PURPOSE: In 2012, US Marines and Sailors began annual deployments to Australia to participate in joint training exercises with the Australian Defence Force and other partners in the region. During their training, US service members are exposed to a variety of infectious disease threats not normally encountered by American citizens. This paper describes a cohort of US Marines and Sailors enrolled during five rotations to Australia between 2016 and 2020. PARTICIPANTS: Study participation is strictly voluntary. Group informational sessions are held prior to deployment to describe the study structure and goals, as well as the infectious disease threats that participants may encounter while in Australia. All participants provided written informed consent. Consented participants complete a pre-deployment questionnaire to collect data including basic demographic information, military occupational specialty, travel history, family history, basic health status and personal habits such as alcohol consumption. Blood is collected for serum, plasma and peripheral blood mononuclear cells (PBMC) processing. Data and specimen collection is repeated up to three times: before, during and after deployment. FINDINGS TO DATE: From the five rotations that comprised the 2016-2020 Marine Rotational Force-Darwin, we enrolled 1289 volunteers. Enrolments during this period were overwhelmingly white male under the age of 24 years. Most of the enrollees were junior enlisted and non-commissioned officers, with a smaller number of staff non-commissioned officers and commissioned officers, and minimal warrant officers. Over half of the enrollees had occupational specialty designations for infantry. FUTURE PLANS: In the future, we will screen samples for serological evidence of infection with Burkholderia pseudomallei, Coxiella burnetii, Ross River virus, SARS-CoV-2 and other operationally relevant pathogens endemic in Australia. Antigenic stimulation assays will be performed on PBMCs collected from seropositive individuals to characterise the immune response to these infections in this healthy American population.

Genomics accelerated isolation of a new stem rust avirulence gene-wheat resistance gene pair.

Stem rust caused by the fungus Puccinia graminis f. sp. tritici (Pgt) is a devastating disease of the global staple crop wheat. Although this disease was largely controlled in the latter half of the twentieth century, new virulent strains of Pgt, such as Ug99, have recently evolved1,2. These strains have caused notable losses worldwide and their continued spread threatens global wheat production. Breeding for disease resistance provides the most cost-effective control of wheat rust diseases3. A number of rust resistance genes have been characterized in wheat and most encode immune receptors of the nucleotide-binding leucine-rich repeat (NLR) class4, which recognize pathogen effector proteins known as avirulence (Avr) proteins5. However, only two Avr genes have been identified in Pgt so far, AvrSr35 and AvrSr50 (refs. 6,7), and none in other cereal rusts8,9. The Sr27 resistance gene was first identified in a wheat line carrying an introgression of the 3R chromosome from Imperial rye10. Although not deployed widely in wheat, Sr27 is widespread in the artificial crop species Triticosecale (triticale), which is a wheat-rye hybrid and is a host for Pgt11,12. Sr27 is effective against Ug99 (ref. 13) and other recent Pgt strains14,15. Here, we identify both the Sr27 gene in wheat and the corresponding AvrSr27 gene in Pgt and show that virulence to Sr27 can arise experimentally and in the field through deletion mutations, copy number variation and expression level polymorphisms at the AvrSr27 locus.

Enhanced recovery strategies after penile implantation: a narrative review.

Optimizing pain management strategies in penile implantation has historically been a challenge to urologists assuming care of patients post-operatively. In addition to the complex pathophysiology of male genital pain, the responsibility of opioid stewardship in the face of the ongoing narcotics epidemic presents its own set of challenges to experienced implanters. Recent innovations in pre- and intra-operative analgesia have provided some improvement in patient-reported pain outcomes. When used together in protocols spanning each phase of operative care, multimodal analgesia (MMA) regimens provide superior patient pain control and successfully decrease opioid usage compared to traditional opioid-based pain control. This review will systematically present literature that discusses interventions in the preoperative and intraoperative spaces aimed at optimally controlling pain. We will also highlight surgical techniques that have been demonstrated to help ameliorate post-operative pain in penile implant recipients. We will discuss the impact of MMA protocols across urology and further explore its larger impact on reducing opioid burden in the ongoing epidemic.