Treatment Patterns and Clinical Outcomes Among Patients With Metastatic Prostate Cancer Harboring Homologous Recombination Repair Mutations.

BACKGROUND: There is currently limited literature assessing the real-world treatment patterns and clinical outcomes of patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) mutations. METHODS: Medical charts were abstracted for mCRPC patients with ≥ 1 of 12 HRR somatic gene alterations treated at US oncology centers participating in the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange. Treatment patterns and clinical outcomes were assessed from the initiation of first-line or later (1L+) mCRPC therapy received on or after July 1, 2014. RESULTS: Among 138 patients included in the study, the most common somatic HRR mutations were CDK12 (47.8%), BRCA2 (22.5%), and ATM (21.0%). Novel hormonal therapy and taxane chemotherapy were most commonly used in 1L; taxane use increased in later lines. Median overall survival (95% confidence interval [CI]) was 36.3 (30.7-47.8) months from initiation of 1L therapy and decreased for subsequent lines. Similarly, there was a trend of decreasing progression-free survival and prostate-specific antigen response from 1L to 4L+ therapy. CONCLUSIONS: Treatment patterns identified in this study were similar to those among patients with mCRPC regardless of tumor HRR mutation status in the literature.

Management of Hemorrhoids and Anal Fissures.

Hemorrhoids and anal fissures are two of the most common benign anorectal diseases. Despite their high prevalence, diagnostic accuracy of benign anorectal disease is suboptimal at 70% for surgeons, especially for hemorrhoidal diseases. Once the diagnosis is correctly made, numerous medical and surgical treatment options are available, each with different rates of success and complications. In this article, the authors review each step of patient management, with emphasis on evidence-based treatment options for hemorrhoids and anal fissures. The article discusses the pathophysiology, diagnosis, medical management, and procedures for hemorrhoids followed by a detailed overview on the management of anal fissures.

Higher fluid and lower caloric intakes: associated risk of severe bronchopulmonary dysplasia in ELBW infants.

OBJECTIVE: To examine nutritional intake profiles and growth trajectories of extremely low birth weight (ELBW) infants who develop severe bronchopulmonary dysplasia (BPD). STUDY DESIGN: Case-control study using multiple logistic regression analysis with generalized estimating equations (GEE) to adjust for matching. RESULTS: Cumulative and mean fluid intakes were higher (p = 0.003) and caloric intakes lower (p < 0.0001) through week two in infants who developed severe BPD (n = 120) versus those without severe BPD (n = 104). Mean caloric intake through week 12 was lower in infants who developed severe BPD (102 ± 10.1 vs. 107 ± 8.5 kcal/kg/day, p < 0.0001). In the logistic regression models, lower mean caloric intake through week 12 was associated with increased risk of developing severe BPD. Linear growth reduced the odds of BPD by ~30% for each Z-score point. CONCLUSIONS: Higher fluid and lower total caloric intakes and reductions in linear growth were independently associated with an increased risk of developing severe BPD in ELBW infants.

Risk Factors for Early Treatment Discontinuation Due to Toxicity Among Patients With Metastatic Castration-resistant Prostate Cancer Receiving Androgen Receptor-targeted Therapy.

BACKGROUND: Androgen receptor-targeted therapies (ARTs) improve survival outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC); however, a significant portion of patients discontinue treatment for various reasons including treatment-related toxicity. We aim to describe reasons for ART treatment discontinuation and identify predictors associated with increased risk of treatment discontinuation due to toxicity. METHODS: We performed a single-institution retrospective review of patients with mCRPC receiving ART between 2010 and 2021. Our primary aim was to identify risk factors for treatment discontinuation due to toxicity. Our secondary aim was to describe ART discontinuation patterns among patients with mCRPC. RESULTS: One hundred thirty-three patients with mCRPC started and discontinued ARTs. Fourteen patients (10.5%) discontinued treatment due to toxicity. Common reasons for treatment discontinuation include Prostate Specific Antigen test progression, radiographic progression, toxicity, and death. Significant predictors of treatment discontinuation due to toxicity on bivariate analysis and multivariate analysis included patient-reported falls (odds ratio [OR]: 7.67, CI: [1.31-40.42]; P=0.016), rash (OR: 13.4, CI: [1.35-134.81]; P=0.026), and weakness (OR: 4.16, CI: [1.15-15.0]; P=0.019). CONCLUSIONS: Our work presents the first description of ART treatment discontinuation and its causes in the real-world setting, as well as patient-reported side effects. Most patients with mCRPC discontinued treatment due to the progression of disease and a minority of patients discontinued secondary to treatment toxicity. Initial multivariable analysis suggests that patient-reported weakness, falls, and rash were associated with a higher likelihood of treatment discontinuation due to toxicity. Early monitoring of this population can prolong the duration of treatment and prevent unnecessary treatment burden.

Analysis of real-world data to investigate evolving treatment sequencing patterns in advanced non-small cell lung cancers and their impact on survival.

Background: Although optimal sequencing of systemic therapy in cancer care is critical to achieving maximal clinical benefit, there is a lack of analysis of treatment sequencing in advanced non-small cell lung cancer (aNSCLC) in real-world settings. Methods: A retrospective cohort study of 13,340 lung cancer patients within the Mount Sinai Health System (MSHS) was performed. Systemic therapy data of aNSCLC in 2,106 patients was the starting point in our analysis to investigate how treatment sequencing has evolved, the impact of sequencing patterns on clinical outcomes, and the effectiveness of 2nd line chemotherapy after patients progressed on immune checkpoint inhibitor (ICI)-based therapy as the 1st line of therapy (LOT). Results: There is a significant shift to more ICI-based therapy and multiple lines of targeted therapy after 2015. We compared clinical outcomes of two patient populations with different treatment sequencing patterns, with the 1st group receiving chemotherapy as the 1st LOT followed by ICI-based treatment, and the 2nd group treated in the opposite order receiving a 1st line ICI-containing regimen followed by a 2nd line chemotherapy. No statistically significant difference in overall survival (OS) was observed between the two groups [group 2 vs. group 1, adjusted hazard ratio (aHR) =1.36, P=0.39]. We assessed the efficacy of the 2nd line chemotherapy in three patient populations given either 1st line ICI single agent, 1st line ICI-chemotherapy combination, or 1st line chemotherapy alone, there was no statistically significant difference in time-to-next treatment (TTNT) and in OS among the three patient groups. Conclusions: Analysis of real-world data has shown two treatment sequencing patterns in aNSCLC, ICI followed by chemotherapy or chemotherapy followed by ICI, achieved similar clinical benefit. The chemotherapies routinely used following platinum doublet 1st LOT, is effective as the 2nd line option after ICI-chemotherapy combination in the 1st line setting.

Routine versus no assessment of gastric residual volumes in preterm infants receiving enteral feeding via intermittent feeding tubes: a randomized controlled trial.

OBJECTIVE: To evaluate whether eliminating routine gastric residual volume (GRV) assessments would lead to quicker attainment of full feeding volumes in preterm infants. STUDY DESIGN: This is a prospective randomized controlled trial of infants ≤32 weeks gestation and birthweight ≤1250 g admitted to a tertiary care NICU. Infants were randomized to assess or not assess GRV before enteral tube feedings. The primary outcome was time to attain full enteral feeding volume defined as 120 ml/kg/day. The Wilcoxon rank sum test was used to compare the days to reach full enteral feeds between the two groups. RESULTS: 80 infants were randomized, 39 to the GRV assessing and 41 to the No-GRV assessing group. A predetermined interim analysis at 50% enrollment showed no difference in primary outcome and the study was stopped as recommended by the Data Safety Monitoring Committee. There was no significant difference in median days to reach full enteral feeds between the two groups [GRV assessment: 12d (5) vs. No-GRV assessment:13d (9)]. There was no mortality in either group, one infant in each group developed necrotizing enterocolitis stage 2 or greater. CONCLUSION: Eliminating the practice of gastric residual volume assessment before feeding did not result in shorter time to attain full feeding.

Antenatal Steroids, Prophylactic Indomethacin, and the Risk of Spontaneous Intestinal Perforation.

OBJECTIVE: To estimate if the odds of spontaneous intestinal perforation (SIP) are increased when antenatal steroids (ANS) given close to delivery are combined with indomethacin on day 1 after birth (Indo-D1). STUDY DESIGN: A retrospective cohort study using the Neonatal Research Network (NRN) database of inborn infants, gestational age 220-286 weeks or birth weight of 401-1000 g, born between January 1, 2016 and December 31, 2019, and surviving >12 hours. The primary outcome was SIP through 14 days. Time of last ANS dose prior to delivery was analyzed as a continuous variable (using 169 hours for durations >168 hours or no steroid exposure). Associations between ANS, Indo-D1, and SIP were obtained from a multilevel hierarchical generalized linear mixed model after covariate adjustment. This yielded aOR and 95% CI. RESULTS: Of 6851 infants, 243 had SIP (3.5%). ANS exposure occurred in 6393 infants (93.3%) and IndoD1 was given to 1863 infants (27.2%). The time (median, IQR) from last dose of ANS to delivery was 32.5 hours (6-81) vs 37.1 hours (7-110) for infants with or without SIP, respectively (P = .10). Indo-D1 was given to 51.9 vs 26.3% of infants with SIP vs no SIP, respectively (P < .0001). Adjusted analysis indicated no interaction between time of last ANS dose and Indo-D1 for SIP (P = .7). Indo-D1 but not ANS was associated with increased odds of SIP (aOR: 1.73, 1.21-2.48, P = .003). CONCLUSION: The odds of SIP were increased after receipt of Indo-D1. Exposure to ANS prior to Indo-D1 was not associated with an increase in SIP.

Biomarker Development Trial of Satraplatin in Patients with Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND: In the phase III SPARC trial, satraplatin, an oral platinum analogue, demonstrated anticancer activity in men with metastatic castration-resistant prostate cancer (mCRPC). Repeat biopsies are uncommon in mCRPC, limiting the feasibility of tissue-based biomarkers. This phase II study sought to evaluate the feasibility and utility of blood-based biomarkers to identify platinum-sensitive mCRPC. METHODS: Patients with mCRPC who had progressed on docetaxel were enrolled at a single center from 2011 to 2013. Subjects received satraplatin 80 mg/m2 by mouth daily on days 1-5 and prednisone 5 mg PO twice daily, on a 35-day cycle. Serial peripheral blood samples were collected for biomarker assessment. RESULTS: Thirteen docetaxel-refractory mCRPC patients were enrolled, with a median age of 69 years (range 54-77 years) and median PSA of 71.7 ng/mL (range 0.04-3057). Four of 13 patients (31%) responded to satraplatin (defined as a PSA decline of ≥30%). Responders demonstrated improved time to disease progression (206 vs. 35 days, HR 0.26, 95% CI, 0.02-0.24, P = .003). A 6-gene peripheral blood RNA signature and serum tissue inhibitor of metalloproteinase-1 (TIMP-1) levels were assessed as biomarkers, but neither was significantly associated with response to satraplatin. CONCLUSION: In this small series, one-third of mCRPC patients responded to platinum-based chemotherapy. Peripheral blood biomarker measurement is feasible in mCRPC, though the biomarkers we investigated were not associated with platinum response. Other biomarkers, such as DNA damage repair mutations, should be evaluated.

Effect of concurrent beta-blocker use in patients receiving immune checkpoint inhibitors for advanced solid tumors.

PURPOSE: Stress-induced adrenergic signaling can suppress the immune system. In animal models, pharmacological beta-blockade stimulates CD8 + T-cell activity and improves clinical activity of immune checkpoint blockade (ICB) in inhibiting tumor growth. Herein, we investigated the effect of BB on clinical outcomes of patients receiving ICB in advanced solid tumors. METHODS: We retrospectively evaluated patients with solid tumors treated with ICB at our institution from January 1, 2011 to April 28, 2017. The primary clinical outcome was disease control. Secondary clinical outcomes were overall survival (OS), and duration of therapy (DoT). The primary predictor was use of BB. Association between disease control status and BB use was assessed in univariable and multivariable logistic regression. OS was calculated using hazard ratios of BB-recipient patients vs. BB non-recipient patients via Cox proportional hazards regression models. All tests were two-sided at a significance level of 0.05. RESULTS: Of 339 identified patients receiving ICB, 109 (32%) also received BB. In covariate-adjusted analysis, odds of disease control were significantly higher among BB recipients compared to BB-non-recipients (2.79; [1.54-5.03]; P = 0.001). While we did not observe significant association of OS with the use of BB overall, significant association with better OS was observed for the urothelial carcinoma cohort (HR: 0.24; [0.09, 0.62]; P = 0.0031). CONCLUSIONS: Concurrent use of BB may enhance the clinical activity of ICB and influence overall survival, particularly in patients with urothelial carcinoma. Our findings warrant further investigation to understand the interaction of beta adrenergic signaling and antitumor immune activity and explore a combination strategy.

Fluid Intake in the First Week of Life and the Duration of Hemodynamically Significant Patent Ductus Arteriosus in Extremely Preterm Infants.

OBJECTIVE: This study aimed to determine the association between daily fluid intake and the duration of hemodynamically significant patent ductus arteriosus (hsPDA). STUDY DESIGN: This is a retrospective cohort study of extremely preterm infants (<29 weeks) admitted in the Neonatal Intensive Care Unit of the Advent Health for Children from January 2013 to March 2016, if hsPDA was diagnosed in first week of life and serial echocardiograms were available. Diagnosis of hsPDA was based on a scoring system and its duration was estimated from serial echocardiograms. Cohort was divided into two groups based on duration of hsPDA (<1week, group A and ≥1 week, group B). Daily fluid intake was categorized as prescribed and actual. Prescribed volume was ordered by clinicians based on birth weight, not including trophic feeds, intravenous (IV) boluses or transfusions, etc. Actual intake was calculated by the electronic medical records based on daily weights and included all enteral or parenteral fluids. Multivariate analysis was performed to determine an association between total daily fluid intake over the first week of life and the duration of hsPDA. Two groups were compared to observe the difference between prescribed and actual daily fluid intakes. RESULTS: We enrolled 50 infants in group A and 76 in group B. Infants in group B were of significantly lower gestation and required prolonged ventilation and hospitalization. An association between higher fluid intake in the first 2 days of life and prolonged duration of hsPDA was confirmed by multivariate analysis. Actual fluid intake was significantly higher than prescribed total fluid intake in first 4 days of life for infants in both groups. CONCLUSION: In extremely preterm infants, higher fluid intake in first 2 days of life is associated with prolonged duration of hsPDA. Actual daily fluid intake can be significantly higher than prescribed daily fluids due to daily weight changes and additional fluid administration. KEY POINTS: · In preterm infants, actual daily fluid intake may be higher than prescribed volume.. · Higher daily fluid intake in first week of life is associated with prolonged duration of PDA.. · PDA scoring system can be helpful for objective assessment of PDA in preterm infants..

Effects of lipid emulsions on unbound bilirubin and response to phototherapy in preterm infants.

OBJECTIVE: Bilirubin-induced neurotoxicity is mediated by the fraction of total serum bilirubin (TSB) not bound to albumin (Bf). Unbound free fatty acids (FFAu) generated from lipid emulsions compete with bilirubin for albumin binding, increasing Bf. Soy-based (IL) and soy-MCT-olive-fish oil-based (SMOF) lipid emulsions contain different fatty acids with distinct albumin binding affinities. IL increases Bf in preterm infants, but the effects of SMOF on Bf are not known. Our objective was to compare changes in TSB, Bf, FFAu, and response to phototherapy in preterm infants receiving SMOF and IL. We hypothesized that SMOF would be associated with lower Bf and better response to phototherapy than IL. METHODS: Very preterm and low birth weight infants (<1500 g, <32 weeks) were infused with IL (n = 20) or SMOF (n = 20) as prescribed by providers. Phototherapy was prescribed using the standard care practice. FFAu profiles and levels, TSB, and Bf were measured on 0, 1, 2, and 3 g/kg/day of lipid infusion and at the initiation and termination of phototherapy. TSB was analyzed in the clinical laboratory using the diazo technique. FFAu and Bf were measured using fluorescent probes. RESULTS: Escalating doses of IL and SMOF increased FFAu levels and Bf, but not TSB. Phototherapy did not significantly decrease Bf for infants receiving either lipid. IL-treated infants had higher levels of unbound linoleic acid, and SMOF-treated infants had higher unbound arachidonic, oleic, and docosahexaenoic acids. CONCLUSIONS: IL and SMOF both increase Bf similarly, and phototherapy does not significantly affect Bf for infants receiving them.

Clinical factors associated with outcome in solid tumor patients treated with immune-checkpoint inhibitors: a single institution retrospective analysis.

OBJECTIVES: Response to immune checkpoint inhibitor (ICI) remains limited to a subset of patients and predictive biomarkers of response remains an unmet need, limiting our ability to provide precision medicine. Using real-world data, we aimed to identify potential clinical prognosticators of ICI response in solid tumor patients. METHODS: We conducted a retrospective analysis of all solid tumor patients treated with ICIs at the Mount Sinai Hospital between January 2011 and April 2017. Predictors assessed included demographics, performance status, co-morbidities, family history of cancer, smoking status, cancer type, metastatic pattern, and type of ICI. Outcomes evaluated include progression free survival (PFS), overall survival (OS), overall response rate (ORR) and disease control rate (DCR). Univariable and multivariable Cox proportional hazard models were constructed to test the association of predictors with outcomes. RESULTS: We identified 297 ICI-treated patients with diagnosis of non-small cell lung cancer (N = 81, 27.3%), melanoma (N = 73, 24.6%), hepatocellular carcinoma (N = 51, 17.2%), urothelial carcinoma (N = 51, 17.2%), head and neck squamous cell carcinoma (N = 23, 7.7%), and renal cell carcinoma (N = 18, 6.1%). In multivariable analysis, good performance status of ECOG ≤ 2 (PFS, ORR, DCR and OS) and family history of cancer (ORR and DCR) associated with improved ICI response. Bone metastasis was associated with worse outcomes (PFS, ORR, and DCR). CONCLUSIONS: Mechanisms underlying the clinical predictors of response observed in this real-world analysis, such as genetic variants and bone metastasis-tumor microenvironment, warrant further exploration in larger studies incorporating translational endpoints. Consistently positive clinical correlates may help inform patient stratification when considering ICI therapy.

Management of de novo metastatic hormone-sensitive prostate cancer: A comprehensive report of a single-center experience.

BACKGROUND: Upfront docetaxel or novel hormonal agents (NHA) such as abiraterone and enzalutamide have become the standard of care for metastatic hormone sensitive prostate cancer (mHSPC). We evaluated real-world management of patients treated with these agents at a single center. PATIENTS AND METHODS: Patients with de novo mHSPC treated with upfront docetaxel or an NHA between January 2014 and April 2019 at Mount Sinai Health System were included. We evaluated time to next treatment (TTNT), PSA progression free survival (PFS) and overall survival (OS) after initial treatment with these drugs. Kaplan Meier method and multivariable Cox proportional hazards models were used for analysis. We additionally assessed the prognostic value of post-treatment PSA. RESULTS: We identified 94 de novo mHSPC patients; 52 and 42 treated with upfront docetaxel and NHAs, respectively. NHAs were associated with a median TTNT of 20.7 months compared to 10.1 months with docetaxel (log-rank p = 0.023). We also observed median PSA PFS of 19 months for NHAs and 13.2 months for docetaxel (p = 0.069). However, OS between the two treatment groups was unchanged. Among docetaxel treated patients, TTNT was shorter among those with high metastasis burden (9.63 vs 25.5 months, p = 0.026) which was not observed among NHA treated patients (25.1 vs 20.7 months, p = 0.79). Regardless of treatment, lower post-treatment PSA levels were associated with improved TTNT (58.95 vs. 11.57 vs. 9.4 months for PSA ≤0.2, 0.2-0.4, >0.4ng/ml, respectively; p<0.001). CONCLUSION: Real world data demonstrated a shorter duration of treatment with docetaxel than NHAs, reflecting the time-limited nature of docetaxel regimens compared to the treat-till-progression approach of NHAs. While TTNT was generally longer for NHAs than docetaxel, some docetaxel-treated patients achieved significant periods of time off treatment. In addition, the depth of PSA response following combination treatment may hold prognostic value for mHSPC outcomes.

The Impact of Androgen Deprivation Therapy on COVID-19 Illness in Men With Prostate Cancer.

BACKGROUND: TMPRSS2, a cell surface protease regulated by androgens and commonly upregulated in prostate cancer (PCa), is a necessary component for SARS-CoV-2 viral entry into respiratory epithelial cells. Previous reports suggested a lower risk of SARS-CoV-2 among PCa patients on androgen deprivation therapy (ADT). However, the impact of ADT on severe COVID-19 illness is poorly understood. METHODS: We performed a multicenter study across 7 US medical centers and evaluated patients with PCa and SARS-CoV-2 detected by polymerase-chain-reaction between March 1, 2020, and May 31, 2020. PCa patients were considered on ADT if they had received appropriate ADT treatment within 6 months of COVID-19 diagnosis. We used multivariable logistic and Cox proportional-hazard regression models for analysis. All statistical tests were 2-sided. RESULTS: We identified 465 PCa patients (median age = 71 years) with a median follow-up of 60 days. Age, body mass index, cardiovascular comorbidity, and PCa clinical disease state adjusted overall survival (hazard ratio [HR] = 1.16, 95% confidence interval [CI] = 0.68 to 1.98, P = .59), hospitalization status (HR = 0.96, 95% CI = 0.52 to 1.77, P = .90), supplemental oxygenation (HR 1.14, 95% CI = 0.66 to 1.99, P = .64), and use of mechanical ventilation (HR = 0.81, 95% CI = 0.25 to 2.66, P = .73) were similar between ADT and non-ADT cohorts. Similarly, the addition of androgen receptor-directed therapy within 30 days of COVID-19 diagnosis to ADT vs ADT alone did not statistically significantly affect overall survival (androgen receptor-directed therapy: HR = 1.27, 95% CI = 0.69 to 2.32, P = .44). CONCLUSIONS: In this retrospective cohort of PCa patients, the use of ADT was not demonstrated to influence severe COVID-19 outcomes, as defined by hospitalization, supplemental oxygen use, or death. Age 70 years and older was statistically significantly associated with a higher risk of developing severe COVID-19 disease.

Extraction of Treatment Information From Electronic Health Records and Evaluation of Testosterone Recovery in Patients With Prostate Cancer.

PURPOSE: Data quality and standardization remain a challenge when analyzing real-world clinical data. We built a clinical research database, using machine learning and natural learning processing, and investigated factors influencing testosterone recovery (T-recovery) in patients with localized prostate cancer (LPC) after initial androgen deprivation therapy (ADT). METHODS: Medication and treatment-associated dates missing in structured tables were extracted from patient notes using ConceptMapper, an automated data extraction tool, standardized and curated in Sema4 clinical research database. ADT usage duration was evaluated, and T-recovery in patients with LPC was analyzed by the Kaplan-Meier method and multivariable Cox proportional hazards models. We assessed the prognostic value of post-ADT T-recovery with prostate-specific antigen progression-free survival and failure-free survival. RESULTS: In total, 4,125 of 30,832 (13.4%) patients with prostate cancer had medication exclusively from notes with high precision and recall, F1 score ≥ 0.95. Association of dates with medication usage had a F1 score of 0.76. ADT duration estimation had higher accuracy combining information from notes to tables from electronic medical record (70% v 45%). Baseline testosterone was the strongest predictor of T-recovery in these patients. Patients with a baseline testosterone ≥ 300 ng/dL recovered in 9.79 versus 38 months for patients with baseline testosterone < 300 ng/dL (P < .0001). Shorter prostate-specific antigen progression-free interval was observed for patients with T-recovery (≥ 300 ng/dL) at 6 months after ADT cessation compared with patients without T-recovery (< 300 ng/dL; 13.7 v 25.1 months; P = .055). CONCLUSION: We augmented structured electronic medical record data with data extracted from notes and improved the accuracy of medication information for patients. ADT exposure and T-recovery in patients with LPC produced results consistent with the literature and clinical experience and illustrates the power of applying machine learning methods to enhance the quality of real-world evidence in answering clinically relevant questions.

The effects of betamethasone on the amplitude integrated EEG of infants born at 34- or 35-weeks gestation.

OBJECTIVE: Assess if maternal betamethasone administration at 34-35 weeks accelerated neonatal amplitude integrated EEG (aEEG) maturation. STUDY DESIGN: Nested, observational cohort in 7 centers participating in the Antenatal Late Preterm Steroid randomized trial. Up to 2 aEEGs were obtained in neonates born from 340-356 weeks gestation before 72 h (aEEG 1) and at 5-7 days (aEEG 2) if hospitalized. Personnel and aEEG central readers were masked to the intervention. The primary outcome was maturation reflected by cycle frequency; secondary outcomes were border voltage, span, and discontinuity. RESULTS: 58 neonates were enrolled (betamethasone, 28, placebo, 30). On aEEG 1, cycle frequency did not differ, but betamethasone exposed infants had a greater lower border voltage and a broader span. On aEEG 2, both groups displayed increases in lower border voltage. CONCLUSIONS: Betamethasone associated changes in lower border voltage support accelerated electrical activity. Further investigation is needed to understand the broader span.

Factors that guide selection among androgen receptor inhibitors in patients with nonmetastatic castration-resistant prostate cancer.

Prostate cancer is the most common cancer affecting men in the United States. A significant proportion of men have nonmetastatic castration-resistant prostate cancer (CRPC), in which biochemical progression is evidenced by rising levels of prostate-specific antigen without radiographic progression in the setting of castrate levels of testosterone. Historically, the preferred treatment for these patients has been observation and continued treatment with androgen deprivation therapy (ADT). The standard of care has recently evolved to include the addition of androgen receptor (AR) inhibitors to ADT. The US Food and Drug Administration has approved 3 next-generation AR inhibitors for nonmetastatic CRPC: apalutamide, enzalutamide, and darolutamide. These agents were approved based on data from phase 3 randomized trials. There is now a significant amount of data from these trials. All 3 agents improve metastasis-free survival and overall survival. Selection of treatment can be guided by factors such as the patient's overall health and frailty, potential drug-drug interactions, and the safety profile associated with each agent.