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The NCCN Guidelines for Prostate Cancer Early Detection provide recommendations for individuals with a prostate who opt to participate in an early detection program after receiving the appropriate counseling on the pros and cons. These NCCN Guidelines Insights provide a summary of recent updates to the NCCN Guidelines with regard to the testing protocol, use of multiparametric MRI, and management of negative biopsy results to optimize the detection of clinically significant prostate cancer and minimize the detection of indolent disease.

To assess long-term outcomes with robotic versus laparoscopic/thoracoscopic and open surgery for colorectal, urologic, endometrial, cervical, and thoracic cancers.Minimally invasive surgery provides perioperative benefits and similar oncological outcomes compared with open surgery. Recent robotic surgery data have questioned long-term benefits.A systematic review and meta-analysis of cancer outcomes based on surgical approach was conducted based on PRISMA guidelines using Pubmed, Scopus, and Embase. HRs for recurrence, disease-free survival (DFS), and overall survival (OS) were extracted/estimated using a hierarchical decision-tree and pooled in RevMan 5.4 using inverse-variance fixed effect (heterogeneity non-significant) or random effect models.Of 31,204 references, 199 were included (7 randomized, 23 database, 15 prospective, 154 retrospective studies)-157,876 robotic, 68,007 laparoscopic/thoracoscopic, and 234,649 open cases. Cervical cancer: OS and DFS were similar between robotic and laparoscopic (1.01[0.56, 1.80], P=0.98) or open (1.18[0.99, 1.41], P=0.06) surgery; two papers reported less recurrence with open surgery (2.30[1.32, 4.01], P=0.003). Endometrial cancer: the only significant result favored robotic over open surgery (OS; 0.77[0.71, 0.83], P0.001). Lobectomy: DFS favored robotic over thoracoscopic surgery (0.74[0.59, 0.93], P=0.009); OS favored robotic over open surgery (0.93[0.87, 1.00], P=0.04). Prostatectomy: recurrence was less with robotic versus laparoscopic surgery (0.77[0.68, 0.87], P0.0001); OS favored robotic over open surgery (0.78[0.72, 0.85], P0.0001). Low-anterior resection: OS significantly favored robotic over laparoscopic (0.76[0.63, 0.91], P=0.004) and open surgery (0.83[0.74, 0.93], P=0.001).Long-term outcomes were similar for robotic versus laparoscopic/thoracoscopic and open surgery, with no safety signal or indication requiring further research (PROSPERO Reg#CRD42021240519).

The summary presented herein represents Part II of the three-part series dedicated to Clinically Localized Prostate Cancer: AUA/ASTRO Guideline, discussing principles of active surveillance and surgery as well as follow-up for patients after primary treatment. Please refer to Parts I and III for discussion of risk assessment, staging, and risk-based management (Part I), and principles of radiation and future directions (Part III).The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. A research librarian conducted searches in Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. The methodology team supplemented searches of electronic databases with the studies included in the prior AUA review and by reviewing reference lists of relevant articles.The Clinically Localized Prostate Cancer Panel created evidence- and consensus-based guideline statements to aid clinicians in the management of patients with clinically localized prostate cancer. Statements regarding active surveillance, surgical management, and patient follow-up are detailed.This guideline aims to inform clinicians treating patients with clinically localized prostate cancer. Continued research and publication of high-quality evidence from future trials will be essential to further improve care for these men.

The summary presented herein represents Part I of the three-part series dedicated to Clinically Localized Prostate Cancer: AUA/ASTRO Guideline, discussing risk assessment, staging, and risk-based management in patients diagnosed with clinically localized prostate cancer. Please refer to Parts II and III for discussion of principles of active surveillance, surgery and follow-up (Part II), and principles of radiation and future directions (Part III).The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. A research librarian conducted searches in Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. The methodology team supplemented searches of electronic databases with the studies included in the prior AUA review and by reviewing reference lists of relevant articles.The Clinically Localized Prostate Cancer Panel created evidence- and consensus-based guideline statements to aid clinicians in the management of patients with clinically localized prostate cancer. Statements regarding risk assessment, staging, and risk-based management are detailed herein.This guideline aims to inform clinicians treating patients with clinically localized prostate cancer. Continued research and publication of high-quality evidence from future trials will be essential to further improve care for these men.

IntroductionHeart Failure disease management clinics have been historically successful in reducing complications, little has been examined in uninsured settings.MethodsThis is a pilot study of HF patients following a recent hospitalization. Uninsured patients were offered enrollment in the disease management clinic during or immediately following hospitalization for a primary HF diagnosis at our institution during 2021. The program included twice-weekly visits with interprofessional support. Patients were scheduled 16 visits (2 months of follow-up) post-hospitalization. Patients who attended two visits were considered enrolled.ResultsOf 59 patients referred, 47(80%) were enrolled. Just 4 patients (8.5%,95%CI:2.5%,20.5%) were readmitted at 30 days, while 4 of 12 (33%,95%CI:13.6%,61.2%) were readmitted at 30 days in those who did not enroll. Program participants were readmitted significantly less frequently than national readmission rate estimates (23%,p=0.02).ConclusionThe CHFC3 program is feasible and holds promise for materially reducing 30-day readmissions for HF complications in the uninsured.

ObjectiveDetermine whether hormone-associated venous thromboembolism (VTE) risk varies by exposure route and formulation in 50-64 year-old US women.DesignNested case-control study.SettingLarge US commercially-insured population with patient-level claims data.ParticipantsWomen aged 50-64 years with at least one year of enrollment. Controls were matched to incident cases (10:1) on VTE date and case’s age (+/− 2yrs). Exclusions included prior VTE, intravascular vena cava (IVC) filter within twelve months, and anticoagulant exposure within 14 days.ExposuresAll estrogen and progestogen prescriptions (with route and formulation) filled within 12 months prior to index date were coded as current (0-60 days), past (61-365 days), or none. Contraceptives were categorized separately.OutcomeAcute VTE cases were identified with ICD codes plus anticoagulant, IVC filter, or death within 30 days.ResultsConditional logic regression analyses controlled for differences between cases (n=20,359) and controls (n=203,590) in Elixhauser comorbidities and VTE risk factors. Odds ratios (OR) were as follows: for current oral, unopposed estradiol 1.24 (95% CI: 1.09 to 1.40) or conjugated equine estrogen (CEE) 1.46 (95% CI: 1.28 to 1.68); for progestogens with estradiol 1.14 (95% CI: 0.95 to 1.37), with CEE 1.52 (95% CI: 1.25 to 1.84), or with ethinyl estradiol 2.35 (95% CI: 1.71 to 3.25). Current transdermal estradiol had the lowest ORs, whether unopposed, 0.70 (95% CI: 0.59 to 0.83) or combined with progestogens, 0.73 (95% CI: 0.56 to 0.96), but varied by progestogen. The OR for estrogen-progestogen contraceptives was 5.22 (95% CI: 4.67 to 5.84) compared to no exposure and 4.24 (95% CI: 3.64 to 4.98) compared to combined MHT.ConclusionsIn 50-64-year-old women, transdermal menopausal hormone therapy (estradiol with or without progestogens) did not elevate VTE risk. In contrast, contraceptives markedly increased VTE risk.Summary BoxesWhat is already known on this topic?Randomized controlled trials indicate that relative risk for venous thromboembolism (VTE) is approximately twice as high with menopausal hormone therapy (MHT) containing conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate compared to no hormone exposure.Recent large, observational studies in the UK and Europe suggest that estradiol is lower risk than CEE and transdermal estradiol does not raise VTE risk compared to no hormone exposure, but results may not generalize to the United States because of differences in formulary, prescribing patterns, and background VTE incidence.What this study addsUsing a large medical record database for US commercially-insured women 50-64 years of age, results confirmed that VTE risk was higher for oral compared to transdermal MHT and transdermal MHT (unopposed estrogen or combined with a progestogen) did not increase risk for VTE compared to no hormone exposure. However, unique US prescribing patterns included MHT with transdermal estradiol plus oral progestogens and MHT with ethinyl estradiol.MHT estrogen formulation affected VTE risk: ethinyl estradiol had higher risk than CEE, and CEE had higher risk than estradiol.Combined hormonal contraceptives (oral, vaginal, transdermal) had a markedly higher increase in VTE compared to MHT.

To analyze the effect on biochemical recurrence (BCR) of omitting PLND in subsequently upgraded/upstaged patients (pNx regret). Using nomograms, patients with low to intermediate-risk prostate cancer can be selected to omit a pelvic lymph node dissection (PLND) at the time of a radical prostatectomy (RP). However, some patients will experience upgraded pathology and/or stage.We searched a prospectively maintained single institution/multi-surgeon cohort of patients treated by RP and5-year follow-up. From 2006-2012, 1026 (521 pNx and 505 pN0/1) eligible patients with biopsy Gleason Score ≤3+4 and cT1c-cT2 undergoing RARP were included in the study.Gleason upgrading from ≤3+4 to3+4 and/or pT3-4 occurred in 17% of pNx and 32% of pN0/N1 (p0.001). BCR occurred in 5% of the pNx, and 7% of the PLND group. Five-year BCR free survival was higher in the pNx group (94.7% vs. 91%, P = .048). BCR occurred in 3% in the non-pNx regret and 18% in the pNx regret patients. However, with propensity score matching with pNx regret and pN0/N1 patients, 5-year BCR free survival rates were similar (81% vs 77%, P = .466).Low to favorable intermediate-risk patients who PLND was omitted and experienced upgrading or upstaging (pNx regret), have a higher predicted BCR. However, when matched to a similar cohort with pN0/N1, the BCR did not differ. Omission of a PLND does not appear to alter the rates of BCR compared to PLND inclusion.

Cardiac response to prolonged, intense exercise induces phenotypic and physiologic adaptive changes that improve myocardial ability to meet oxygen demands. These adaptations, termed "athletes' heart," have been extensively studied. The importance of this entity arises from the increasing numbers of athletes as well as the drive for physical fitness in the general population leading to adaptive cardiac changes that need to be differentiated from life-threatening cardiovascular diseases. A number of pathologic entities may share phenotypic changes with the athletes' heart such as hypertrophic cardiomyopathy, dilated cardiomyopathy, Marfan's syndrome, and arrhythmogenic right ventricular cardiomyopathy. Cardiologists need to be cognizant of these overlapping findings to appropriately diagnose diseases and prevent catastrophic outcomes especially in young and healthy individuals who may not show any symptoms until they engage in intense exercise. It is equally important to recognize and distinguish normal, exercise-adaptive cardiac changes to provide accurate screening and guidance to young elite athletes. Echocardiography is a valuable modality that allows comprehensive initial evaluation of cardiac structures, function, and response to exercise. Several different echocardiographic techniques including M-Mode, 2D echo, Doppler, tissue Doppler, color tissue Doppler, and speckle tracking have been used in the evaluation of cardiac adaptation to exercise. The following discussion is a review of literature that has expanded our knowledge of the athlete's heart.

Progress in understanding prostate cancer (PCa) metastasis and therapy resistance has been hampered by the lack of models, representative of the clinical spectrum and biologic complexity of the disease. Our laboratory is home to one of the largest worldwide repositories of PCa patient-derived xenografts (PDXs), the MDA PCa PDX series, a collection of clinically annotated PDXs reflecting the full spectrum of potentially lethal disease, that includes tumors that are not end stage and not castration-resistant PCa. We performed whole genome sequencing, targeted sequencing and RNA sequencing of 46 MDA PCa PDX models derived from biopsy and surgical specimens from 39 patients, selected in order to reflect the clinicopathological PCa subtypes (data available in cBioPortal). MDA PCa PDXs genomic characterization shows that the cohort recapitulates the mutational landscape found in PCa, highlighting the clinical relevance of these models. Interestingly and consistently with the clinic, certain models lack the typical PCa driver alterations, thus providing a suitable tool for discovery of novel drivers. Our cohort also includes PDXs derived from different areas of the same tumor and longitudinal samples, allowing to study disease heterogeneity and progression. Finally, we have developed a procedure to grow organoids from PDXs, thus providing a powerful in vitro platform that supports hypothesis generation, and testing of clinically relevant observations. Genomic and transcriptomic characterization of MDA PCa PDXs together with the ability to grow them as organoids for in vitro experimentation, provides a unique resource to address the existing clinical gap in PCa, helping to better understand mechanisms of response and resistance.One Sentence SummaryMDA PCa PDX series is a dynamic resource capturing the molecular landscape of prostate cancer; a platform for discovery and personalized medicine

Assessing the persistence of chemicals in the environment is a key element in existing regulatory frameworks to protect human health and ecosystems. Persistence in the environment depends on many fate processes, including abiotic and biotic transformations and physical partitioning, which depend on substances' physicochemical properties and environmental conditions. A main challenge in persistence assessment is that existing frameworks rely on simplistic and reductionist evaluation schemes that may lead substances to be falsely assessed as persistent or the other way around-to be falsely assessed as nonpersistent. Those evaluation schemes typically assess persistence against degradation half-lives determined in single-compartment simulation tests or against degradation levels measured in stringent screening tests. Most of the available test methods, however, do not apply to all types of substances, especially substances that are poorly soluble, complex in composition, highly sorptive, or volatile. In addition, the currently applied half-life criteria are derived mainly from a few legacy persistent organic pollutants, which do not represent the large diversity of substances entering the environment. Persistence assessment would undoubtedly benefit from the development of more flexible and holistic evaluation schemes including new concepts and methods. A weight-of-evidence (WoE) approach incorporating multiple influencing factors is needed to account for chemical fate and transformation in the whole environment so as to assess overall persistence. The present paper's aim is to begin to develop an integrated assessment framework that combines multimedia approaches to organize and interpret data using a clear WoE approach to allow for a more consistent, transparent, and thorough assessment of persistence. Integr Environ Assess Manag 2022;18:868-887. © 2021 ExxonMobil Biomedical Sciences, Inc. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental ToxicologyChemistry (SETAC).

The summary presented herein represents Part III of the three-part series dedicated to Clinically Localized Prostate Cancer: AUA/ASTRO Guideline, discussing principles of radiation and offering several future directions of further relevant study in patients diagnosed with clinically localized prostate cancer. Please refer to Parts I and II for discussion of risk assessment, staging, and risk-based management (Part I), and principles of active surveillance and surgery and follow-up (Part II).The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. A research librarian conducted searches in Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. The methodology team supplemented searches of electronic databases with the studies included in the prior AUA review and by reviewing reference lists of relevant articles.The Clinically Localized Prostate Cancer Panel created evidence- and consensus-based guideline statements to aid clinicians in the management of patients with clinically localized prostate cancer. Statements regarding management of patients using radiation therapy as well as important future directions of research are detailed herein.This guideline aims to inform clinicians treating patients with clinically localized prostate cancer. Continued research and publication of high-quality evidence from future trials will be essential to further improve care for these men.

Ductal adenocarcinoma (DAC) is the most common variant histological subtype of prostate carcinoma and has an aggressive clinical course. DAC is usually characterized and treated as high-risk prostatic acinar adenocarcinoma (PAC). However, DAC has a different biology to that of acinar disease, which often poses a challenge for both diagnosis and management. DAC can be difficult to identify using conventional diagnostic modalities such as serum PSA levels and multiparametric MRI, and the optimal management for localized DAC is unknown owing to the rarity of the disease. Following definitive therapy for localized disease with radical prostatectomy or radiotherapy, the majority of DACs recur with visceral metastases at low PSA levels. Various systemic therapies that have been shown to be effective in high-risk PAC have limited use in treating DAC. Although current understanding of the biology of DAC is limited, genomic analyses have provided insights into the pathology behind its aggressive behaviour and potential future therapeutic targets.

BACKGROUND The aim of this study was to describe pathologic and short-term oncologic outcomes among Black and White men with grade group 4 or 5 prostate cancer managed primarily by radical prostatectomy. METHODS This was a multi-institutional, observational study (2005-2015) evaluating radical prostatectomy outcomes by self-identified race. Descriptive analysis was performed via nonparametric statistical testing to compare baseline clinicopathologic data. Univariable and multivariable time-to-event analyses were performed to assess biochemical recurrence (BCR), metastasis, cancer-specific mortality (CSM), and overall survival between Black and White men. RESULTS In total, 1662 men were identified with grade group 4 or 5 prostate cancer initially managed by radical prostatectomy. Black men represented 11.3% of the cohort (n = 188). Black men were younger, demonstrated a longer time from diagnosis to surgery, and were at a lower clinical stage (all P