Natural course of metastatic castration-resistant prostate cancer in the era of intensified androgen deprivation therapy in the hormone-sensitive setting.

BACKGROUND: Androgen deprivation therapy (ADT) intensification (ADTi) (i.e., ADT with androgen receptor pathway inhibitor or docetaxel, or both) has significantly improved survival outcomes of patients with metastatic hormone-sensitive prostate cancer (mHSPC). However, the impact of prior ADTi in the mHSPC setting on the disease presentation and survival outcomes in metastatic castration-resistant prostate cancer (mCRPC) is not well characterized. In this study, our objective was to compare the disease characteristics and survival outcomes of patients with new mCRPC with respect to receipt of intensified or nonintensified ADT in the mHSPC setting. METHODS: In this institutional review board-approved retrospective study, eligibility criteria were as follows: patients diagnosed with mCRPC, treated with an approved first-line mCRPC therapy, and who received either intensified or nonintensified ADT in the mHSPC setting. Progression-free survival (PFS) was defined from the start of first-line therapy for mCRPC to progression per Prostate Cancer Working Group 2 criteria or death, and overall survival (OS) was defined from the start of first-line therapy for mCRPC to death or censored at the last follow-up. A multivariable analysis using the Cox proportional hazards model was used, adjusting for potential confounders. RESULTS: Patients (n = 387) treated between March 20, 2008, and August 18, 2022, were eligible and included: 283 received nonintensified ADT, whereas 104 were treated with ADTi. At mCRPC diagnosis, patients in the ADTi group were significantly younger, had more visceral metastasis, lower baseline prostate-specific antigen (all p < 0.01), and lower hemoglobin (p = 0.027). Furthermore, they had significantly shorter PFS (median 4.8 vs. 8.4 months, adjusted hazard ratio [HR]: 1.46, 95% confidence interval [95% CI]: 1.07-2, p = 0.017) and OS (median 21.3 vs. 33.1 months, adjusted HR: 1.53, 95% CI: 1.06-2.21, p = 0.022) compared to patients in the nonintensified ADT group. CONCLUSION: Patients treated with ADTi in the mHSPC setting and experiencing disease progression to mCRPC had more aggressive disease features of mCRPC (characterized by a higher number of poor prognostic factors at mCRPC presentation). They also had shorter PFS on first-line mCRPC treatment and shorter OS after the onset of mCRPC compared to those not receiving ADTi in the mHSPC setting. Upon external validation, these findings may impact patient counseling, prognostication, treatment selection, and design of future clinical trials in the mCRPC setting. There remains an unmet need to develop novel life-prolonging therapies with new mechanisms of action to improve mCRPC prognosis in the current era.

Impact of androgen receptor alterations on cell-free DNA genomic profiling on survival outcomes in metastatic castration-resistant prostate cancer.

BACKGROUND: Androgen receptor (AR) gene alterations, as detected by circulating tumor cell-free DNA (cfDNA) genomic profiling, have been shown to emerge after a variable duration of androgen signaling inhibition. AR alterations were associated with inferior outcomes on treatment with androgen receptor pathway inhibitors (ARPI) in the first line metastatic castration-resistant prostate cancer (mCRPC) setting in a phase 2 trial. Here in, we assessed the impact of these AR alterations on survival outcomes in a real-world patient population of mCRPC experiencing disease progression on an ARPI. METHODS: In this IRB-approved retrospective study, consecutively seen patients with a confirmed diagnosis of mCRPC, with disease progression on a treatment with ARPIs in the first line mCRPC setting, with no prior exposure to an ARPI in the castration sensitive setting, and with available cfDNA profiling from a CLIA certified laboratory were included. Patients were categorized based on AR status: wild-type (ARwt ) or alteration-positive (AR+ ). The objective was to correlate overall survival (OS) after disease progression on the first-line ARPI with the presence or absence of AR alterations. Kaplan-Meier and Cox Regression Tests were used as implemented in R-Studio (v.4.2). RESULTS: A total of 137 mCRPC patients were eligible: 69 with ARwt versus 68 with AR+ . The median OS posttreatment with the first ARPI was significantly higher for ARwt than AR+ patients (30.1 vs. 15.2 mos; p < 0.001). Of 108 patients who received a subsequent line of therapy, 63 received an alternate ARPI (AR+ 39 vs. 24 ARwt ), while 20 received a taxane-based therapy (11 AR+ vs. 9 ARwt ). Among patients receiving an alternate ARPI, AR+ had numerically shorter OS (16.8 vs. 30.4 mos, p = 0.1). Among patients receiving taxane-based regimens, the OS was not significantly different between AR+ and ARwt (14.5 vs. 10.1 mos, p = 0.18). CONCLUSION: In this real-world study, mCRPC patients with AR alterations on cfDNA had inferior OS after disease progression on the first ARPI, compared to those who did not, and may impact outcomes on a subsequent ARPI but not on subsequent taxane-based therapy received. By providing survival estimates for patients with or without AR alterations, our data may aid in patient counseling, prognostication, treatment decision, and for designing future clinical trials in this setting.

Harms and Contributors of Leaving Against Medical Advice in Patients With Infective Endocarditis.

INTRODUCTION: Patients leaving against medical advice (AMA) are commonly encountered in hospital medicine. The problem is prevalent worldwide and across all fields of medicine. A retrospective study of 47,583 patients reported a 3.3% AMA rate in 2015. OBJECTIVES: In this retrospective study, we aimed (1) to study the demographic, clinical, and laboratory parameters of infective endocarditis (IE) patients leaving AMA. We also compared (2) the various risk factors and outcomes of these patients with IE patients who completed treatment. RESULTS: A total of 111 patients diagnosed with IE were recruited for 36 months. Of the 74 patients with available details, 32 patients (29%) left AMA during their treatment. The mean age of patients leaving AMA was 39, and among those who left AMA, 66% were females. As compared with patients completing therapy, patients leaving AMA tend to have higher comorbidities, including injection drug use (68.1% versus 31.9%), prior IE (83.3% versus 16.7%), and chronic hepatitis C (72.4% versus 27.8%). Rates of consumption of substances of abuse were higher among those who left AMA. Patients leaving AMA also had higher psychiatric comorbidities (63% versus 37.5%), history of leaving AMA (70.5% versus 29.5%), and consumption of more than 2 substances of abuse. Morbidity was higher in patients leaving AMA. There was a statistically significant association between the development of distal embolus ( P < 0.001), the need for recurrent admissions ( P = 0.002), recurrent bacteremia ( P < 0.001), developing new embolus ( P < 0.001), and overall morbidity ( P = 0.002) among IE patients leaving AMA. CONCLUSIONS: Infective endocarditis patients leaving AMA tend to be younger females. These patients have prior comorbidities of injection drug use, prior IE, multiple psychiatric comorbidities, drug use, and multiple socioeconomic issues. Patients leaving AMA tend to develop further non-Central nervous system embolic events, recurrent bacteremia, and require frequent admissions. Morbidity in these patients was higher.

Mechanism and Management of Checkpoint Inhibitor-Related Toxicities in Genitourinary Cancers.

The use of immune checkpoint inhibitors (ICIs) is rapidly increasing as more combinations and clinical indications are approved in the field of genitourinary malignancies. Most immunotherapeutic agents being approved are for the treatment of renal cell carcinoma and bladder cancer, which mainly involve PD-1/PD-L1 and CTLA-4 pathways. There is an ongoing need for recognizing and treating immunotherapy-related autoimmune adverse effects (irAEs). This review aims to critically appraise the recent literature on the mechanism, common patterns, and treatment recommendations of irAEs in genitourinary malignancies. We review the epidemiology of these adverse effects as well as general treatment strategies. The underlying mechanisms will also be discussed. Diagnostic considerations including differential diagnosis are also included in this review.

Role of 2-Deoxy-D-Glucose (2-DG) in COVID-19 disease: A potential game-changer.

Virus infections can cause tissue damage in many ways. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a cause of the current COVID-19 pandemic, has been extensively studied so far to investigate its pathophysiology and evaluate its impact on the metabolic system of human cells. This has given a lead to study the role of 2-deoxy-D-glucose (2DG) against COVID-19 disease. We hereby would like to briefly discuss the concept and rationale behind the use of 2DG COVID-19.

Current Perspectives on Diagnostic Assays and Anti-PF4 Antibodies for the Diagnosis of Heparin-Induced Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a recognized clinical entity in patients receiving unfractionated heparin and low-molecular weight heparin. Currently, diagnosing HIT includes the combination of a physician's clinical suspicion based on a clinical scoring system and a series of laboratory tests. In the present article, we discuss challenges in suspecting and diagnosing HIT in consideration of the turnaround time of available tests and recent advances in techniques and methodologies of newer immunoassays and functional assays.

Comparison between two different successful approaches to COVID-19 pandemic in India (Dharavi versus Kerala).

Various factors interplay when it comes to successful containment of pandemic. In last one year, we have witnessed various countries formulating and practicing their own unique ways to tackle coronavirus. We have seen the most developed countries failing terribly and unable to slow the COVID-19 spread, but at the same time also endorsed the comparatively less resourceful countries outperforming in terms of reduced disease morbidity and mortality. Current review is about two regions from India (Dharavi and Kerala) who were different in their approach as compared to rest of the country and were able to keep the COVID-19 cases to the minimum.

Ocular chemical burns from accidental exposure to topical dermatological medicinal agent.

We report a case of accidental ocular chemical injury by self-medication with a single application of a topical ayurvedic medication containing salicylic acid, phenol, and tincture iodine, which is being used in developing countries for treatment of various dermatological conditions.