Prostate-specific antigen screening for prostate cancer: Diagnostic performance, clinical thresholds, and strategies for refinement.

Prostate specific antigen (PSA) has transformed the diagnosis and treatment of prostate cancer by enabling early detection at global scale. Due to expression in both benign and malignant cells, PSA-based prostate cancer screening using single cut-points yields imperfect diagnostic performance and has led to the detection and over-treatment of low-grade prostate cancer. Additional challenges in the interpretation of PSA include substantial inter and intrapersonal variation, differences with age and prostate volume, and selection of standardized PSA value cutoffs for clinical application. In response, refinements to PSA including risk and age-based thresholds, age and genetic adjustments, PSA density, percentage free PSA, and PSA velocity have been proposed and extensively studied. In this review, we focus on the clinical role of PSA as a screening biomarker with a particular emphasis on its test characteristics, clinically actionable thresholds, and strategies to refine its clinical interpretation.

Classification and Risk Factors for Surgical Site Infections in Radical Cystectomy: A 16-Year Analysis.

Introduction: Surgical site infection (SSI) is a substantial cause of peri-operative morbidity among patients undergoing radical cystectomy (RC). The purpose of this study was to identify the risk factors of SSI after RC and to classify and characterize treatment of SSIs. Methods: We retrospectively analyzed peri-operative characteristics and SSI, for patients undergoing RC from 2007 to 2022. Patients were stratified by SSI versus no SSI and differences were assessed. Uni-variable/multi-variable logistic regression analyses were performed to identify factors associated with SSI. SSIs were categorized by the Centers for Disease Control and Prevention (CDC) type: Superficial incisional, deep incisional, and organ/space confined. Results: Three hundred and ninety-eight patients had RC, 279 open, and 119 robotic; 78 (19.6%) developed SSI. Cohorts were similar demographically. Length of stay (LOS) was longer in the SSI cohort (8.8 d versus 12.4 d, p < 0.001), and body mass index (BMI) was greater in patients with SSI (24.34 vs. 25.39, p = 0.0003). On uni-variable analysis, age, gender, Charlson Comorbidity Index, diabetes mellitus, diversion, odds ratio (OR) time, blood loss, and open versus robotic technique were not substantial SSI predictors. BMI was an independent risk factor for SSI on both uni-variable (OR: 1.07, 95% confidence interval [CI]: 1.018-1.115, p = 0.0061) and multi-variable analysis (OR: 1.06, 95% CI: 1.009-1.109, p = 0.02) for 10 (12.8%) and 24 (30.8%) superficial and deep-incisional SSIs, respectively. Superficial wound SSI was treated conservatively with 60% receiving antibiotic agents and no procedural intervention. Deep SSIs received antibiotic agents and 50% required surgical intervention. There were 44 (56.4%) organ/space SSIs, and the most common treatment was antibiotic agents (100%) and IR drain placement (30, 68.2%). Conclusion: In patients undergoing RC, BMI was an independent risk factor for SSI. Type of the surgical procedure, robotic versus open, was not predictive of SSI. LOS was longer for patients with SSI. SSI was managed differently depending on CDC classification.

Association between sociodemographic factors and diagnosis of lethal prostate cancer in early life.

OBJECTIVE: A subset of patients are diagnosed with lethal prostate cancer (CaP) early in life before prostate-specific antigen (PSA) screening is typically initiated. To identify opportunities for improved detection, we evaluated patient sociodemographic factors associated with advanced vs. localized (CaP) diagnosis across the age spectrum. METHODS: We conducted a retrospective cohort study using the National Cancer Database, identifying patients diagnosed with CaP from 2004 to 2020. We compared characteristics of patients diagnosed at the advanced (cN1 or M1) versus localized (cT1-4N0M0) stage. Using multivariable logistic regression, we evaluated the associations among patient clinical and sociodemographic factors and advanced diagnosis, stratifying patients by age as ≤55 (before screening is recommended for most patients), 56 to 65, 66 to 75, and ≥76 years. RESULTS: We identified 977,722 patients who met the inclusion criteria. The mean age at diagnosis was 65.3 years and 50,663 (5.1%) had advanced disease. Overall, uninsured (OR = 3.20, 95% CI 3.03-3.78) and Medicaid-insured (OR 2.58, 95% CI 2.48-2.69) vs. privately insured status was associated with higher odds of diagnosis with advanced disease and this effect was more pronounced for younger patients. Among patients ≤55 years, uninsured (OR 4.14, 95% CI 3.69-4.65) and Medicaid-insured (OR 3.39, 95% CI 3.10-3.72) vs. privately insured patients were associated with higher odds of advanced cancer at diagnosis. Similarly, residence in the lowest vs. highest income quartile was associated with increased odds of advanced CaP in patients ≤55 years (OR 1.15, 95% CI 1.02-1.30). Black vs. White race was associated with increased odds of advanced CaP at diagnosis later in life (OR 1.17, 95% CI 1.09-1.25); however, race was not significantly associated with advanced stage CaP in those ≤55 years (P = 0.635). CONCLUSIONS: Sociodemographic disparities in diagnosis at advanced stages of CaP were more pronounced in younger patients, particularly with respect to insurance status. These findings may support greater attention to differential use of early CaP screening based on patient health insurance.

Osteitis pubis following holmium laser enucleation of the prostate.

Osteitis pubis is a rare, inflammatory condition involving the pubic symphysis. While osteitis pubis has been reported following many urological procedures, including those addressing bladder outlet obstruction such as transurethral resection of the prostate, it has never been reported after holmium laser enucleation of the prostate (HoLEP). Here, we detail the clinical course of a patient found to have osteitis pubis following HoLEP. This patient presented several weeks after surgery with non-specific, persistent symptoms of groin pain and difficulty ambulating, alerting our clinicians to consider osteitis pubis which was confirmed on MRI of the pelvis. While the majority of osteitis pubis cases are managed with locally invasive techniques, our patient's symptoms were successfully managed conservatively with Foley catheter placement, oral antibiotics and close follow-up. At 9 months postoperative, the patient has reported complete resolution of symptoms and continues to be followed closely.

APOE4 Copy Number-Dependent Proteomic Changes in the Cerebrospinal Fluid.

BACKGROUND: APOE4 has been hypothesized to increase Alzheimer's disease risk by increasing neuroinflammation, though the specific neuroinflammatory pathways involved are unclear. OBJECTIVE: Characterize cerebrospinal fluid (CSF) proteomic changes related to APOE4 copy number. METHODS: We analyzed targeted proteomic data from ADNI CSF samples using a linear regression model adjusting for age, sex, and APOE4 copy number, and additional linear models also adjusting for AD clinical status or for CSF Aß, tau, or p-tau levels. False discovery rate was used to correct for multiple comparisons correction. RESULTS: Increasing APOE4 copy number was associated with a significant decrease in a CRP peptide level across all five models (q < 0.05 for each), and with significant increases in ALDOA, CH3L1 (YKL-40), and FABPH peptide levels (q < 0.05 for each) except when controlling for AD clinical status or neurodegeneration biomarkers (i.e., CSF tau or p-tau). In all models except the one controlling for CSF Aß levels, though not statistically significant, there was a consistent inverse direction of association between APOE4 copy number and the levels of all 24 peptides from all 8 different complement proteins measured. The odds of this happening by chance for 24 unrelated peptides would be less than 1 in 16 million. CONCLUSION: Increasing APOE4 copy number was associated with decreased CSF CRP levels across all models, and increased CSF ALDOA, CH3L1, and FABH levels when controlling for CSF Aß levels. Increased APOE4 copy number may also be associated with decreased CSF complement pathway protein levels, a hypothesis for investigation in future studies.

Non-invasive brain stimulation modalities for the treatment and prevention of opioid use disorder: a systematic review of the literature.

The U.S. is currently facing an unprecedented epidemic of opioid-related deaths. Despite the efficacy of the current treatments for opioid use disorder (OUD), including psychosocial interventions and medication-assisted therapy (MAT), many patients remain treatment-resistant and at high risk for overdose. A potential augmentation strategy includes the use of non-invasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and auricular vagus nerve stimulation (aVNS). These approaches may have therapeutic benefits by directly or indirectly modulating the neurocircuitry affected in OUD. In this review, we evaluate the available studies on NIBS in the context of OUD withdrawal and detoxification, maintenance, and cravings, while also considering analgesia and safety concerns. In the context of opioid withdrawal and detoxification, a percutaneous form of aVNS has positive results in open-label trials, but has not yet been tested against sham. No randomized studies have reported on the safety and efficacy of NIBS specifically for maintenance treatment in OUD. TMS and tDCS have demonstrated effects on cravings, although published studies were limited by small sample sizes. NIBS may play a role in reducing exposure to opioids and the risk of developing OUD, as demonstrated by studies using tDCS in an experimental pain condition and TMS in a post-operative setting. Overall, while the preliminary evidence and safety for NIBS in the prevention and treatment of OUD appears promising, further research is needed with larger sample sizes, placebo control, and objective biomarkers as outcome measures before strong conclusions can be drawn.