Contemporary conditional cancer-specific survival rates in surgically treated nonmetastatic primary urethral carcinoma.

BACKGROUND: We examined the effect of disease-free interval (DFI) duration on cancer-specific mortality (CSM)-free survival, otherwise known as the effect of conditional survival, in radical urethrectomy nonmetastatic primary urethral carcinoma (PUC) patients. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database 2000-2020, patient (age, sex, race/ethnicity, and marital status) and tumor (stage and histology) characteristics, as well as systemic therapy exposure status of nonmetastatic PUC patients were tabulated. Conditional survival estimates at 5-year were assessed based on DFI duration and according to stage at presentation (T1 -2N0 vs. T3-4N0-2). RESULTS: Of all 512 radical urethrectomy PUC patients, 278 (54%) harbored T1-2N0 stage versus 234 (46%) harbored T3-4N0-2 stage. In 512 PUC patients, 5-year CSM-free survival at initial diagnosis was 61.8%. Provided a DFI duration of 36 months, 5-year CSM-free survival was 85.6%. In 278 T1-2N0 PUC patients, 5-year CSM-free survival at initial diagnosis was 68.4%. Provided a DFI duration of 36 months, 5-year CSM-free survival was 86.9%. In 234 T3-4N0-2 PUC patients, 5-year CSM-free survival at initial diagnosis was 53.8%. Provided a DFI duration of 36 months, 5-year CSM-free survival was 83.6%. CONCLUSIONS: Although intuitively, clinicians and patients are well aware of the concept that increasing DFI duration improves survival probability, only a few clinicians can accurately estimate the magnitude of survival improvement, as was done within the current study. Such information is crucial to survivors, especially in those diagnosed with rare malignancies, where the survival estimation according to DFI duration is even more challenging.

Which Factors Are Associated With Comorbid Psychiatric Conditions in Patients Affected by Substance Use Disorders? The Impact of COVID-19 Pandemic on Dual-Diagnosis Subjects.

OBJECTIVE: To investigate demographic/cinical variables associated to dual diagnosis and the psychological reaction of dual-diagnosis patients to COVID-19 pandemic. METHODS: Information was collected at the Addiction Service of Monza, Italy. The Impact of Event Scale-Revised (IES-R), a self-report questionnaire measuring the subjective response to a traumatic event, was administered. Univariate analyses and binary logistic regression were performed. IES-R scores were compared between groups defined by qualitative variables through one-way analyses of variance (ANOVA). RESULTS: 118 outpatients were included, 48.3% with dual diagnosis. Alcohol use disorder and being female were associated to dual diagnosis. IES-R scores were significantly higher in the dual-diagnosis group, especially for personality disorders (PDs). IES-R scores were higher in patients taking treatment for substance use disorder (SUD). CONCLUSIONS: Females and alcohol abusers were at-risk subjects for dual diagnosis. Patients with SUD and PDs may benefit from additional support, especially when traumatic life events occur. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04694482.

Candidate Biological Markers for Social Anxiety Disorder: A Systematic Review.

Social anxiety disorder (SAD) is a common psychiatric condition associated with a high risk of psychiatric comorbidity and impaired social/occupational functioning when not promptly treated. The identification of biological markers may facilitate the diagnostic process, leading to an early and proper treatment. Our aim was to systematically review the available literature about potential biomarkers for SAD. A search in the main online repositories (PubMed, ISI Web of Knowledge, PsychInfo, etc.) was performed. Of the 662 records screened, 61 were included. Results concerning cortisol, neuropeptides and inflammatory/immunological/neurotrophic markers remain inconsistent. Preliminary evidence emerged about the role of chromosome 16 and the endomannosidase gene, as well as of epigenetic factors, in increasing vulnerability to SAD. Neuroimaging findings revealed an altered connectivity of different cerebral areas in SAD patients and amygdala activation under social threat. Some parameters such as salivary alpha amylase levels, changes in antioxidant defenses, increased gaze avoidance and QT dispersion seem to be associated with SAD and may represent promising biomarkers of this condition. However, the preliminary positive correlations have been poorly replicated. Further studies on larger samples and investigating the same biomarkers are needed to identify more specific biological markers for SAD.

Changes in renal function after nephroureterectomy for upper urinary tract carcinoma: analysis of a large multicenter cohort (Radical Nephroureterectomy Outcomes (RaNeO) Research Consortium).

PURPOSE: To investigate prevalence and predictors of renal function variation in a multicenter cohort treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: Patients from 17 tertiary centers were included. Renal function variation was evaluated at postoperative day (POD)-1, 6 and 12 months. Timepoints differences were Δ1 = POD-1 eGFR - baseline eGFR; Δ2 = 6 months eGFR - POD-1 eGFR; Δ3 = 12 months eGFR - 6 months eGFR. We defined POD-1 acute kidney injury (AKI) as an increase in serum creatinine by ≥ 0.3 mg/dl or a 1.5 1.9-fold from baseline. Additionally, a cutoff of 60 ml/min in eGFR was considered to define renal function decline at 6 and 12 months. Logistic regression (LR) and linear mixed (LM) models were used to evaluate the association between clinical factors and eGFR decline and their interaction with follow-up. RESULTS: A total of 576 were included, of these 409(71.0%) and 403(70.0%) had an eGFR < 60 ml/min at 6 and 12 months, respectively, and 239(41.5%) developed POD-1 AKI. In multivariable LR analysis, age (Odds Ratio, OR 1.05, p < 0.001), male gender (OR 0.44, p = 0.003), POD-1 AKI (OR 2.88, p < 0.001) and preoperative eGFR < 60 ml/min (OR 7.58, p < 0.001) were predictors of renal function decline at 6 months. Age (OR 1.06, p < 0.001), coronary artery disease (OR 2.68, p = 0.007), POD-1 AKI (OR 1.83, p = 0.02), and preoperative eGFR < 60 ml/min (OR 7.80, p < 0.001) were predictors of renal function decline at 12 months. In LM models, age (p = 0.019), hydronephrosis (p < 0.001), POD-1 AKI (p < 0.001) and pT-stage (p = 0.001) influenced renal function variation (ß 9.2 ± 0.7, p < 0.001) during follow-up. CONCLUSION: Age, preoperative eGFR and POD-1 AKI are independent predictors of 6 and 12 months renal function decline after RNU for UTUC.

Knowledge, attitudes, and experiences in suicide assessment and management: a qualitative study among primary health care workers in southwestern Uganda.

BACKGROUND: Suicide is one of the leading causes of death globally, with over 75% of all suicides occurring in low-and middle-income Countries. Although 25% of people have contact with their health care workers before suicide attempts, most never receive proper suicide assessment and management. We explored primary care health workers' knowledge, attitudes, and experiences in evaluating and managing suicidality in structured primary healthcare services in Uganda. METHODS: This was a cross-sectional qualitative study among health workers in southwestern Uganda from purposively selected health facilities. A semi-structured interview guide was used, and data were analyzed using thematic analysis. RESULTS: The in-depth interviews were conducted with 18 individuals (i.e., five medical doctors, two clinical officers, two midwives, and nine nurses) from 12 health facilities in the five selected districts. Four themes emerged from the discussions: a) Knowledge and attitudes of primary healthcare workers in the assessment and management of suicidality, b) Experiences in the assessment and management of suicidality, c) challenges faced by primary healthcare workers while assessing and managing suicidality, and d) Recommendations for improving assessment and management of suicidality in PHC. Most participants were knowledgeable about suicide and the associated risk factors but reported challenges in assessing and managing individuals with suicide risk. The participants freely shared individual experiences and attitudes in the assessment and management of suicide. They also proposed possible ways to improve the evaluation and management of suicidality in PHC, such as setting up a system of managing suicidality, regularizing community sensitization, and training health workers. CONCLUSION: Suicidality is commonly encountered by primary health care workers in Uganda who struggle with its assessment and management. Improving the knowledge and attitudes of primary health care workers would be a big step towards ensuring equitable services.

Craniocervical Posture Assessed With Photogrammetry and the Accuracy of Palpation Methods for Locating the Seventh Cervical Spinous Process: A Cross-sectional Study.

OBJECTIVE: The purpose of this study was to compare craniocervical posture assessed by photogrammetry using 2 distinct palpation methods for locating the spinous process of the seventh cervical vertebra (C7SP). METHODS: This cross-sectional study was conducted in 2 phases. In phase I (n = 42), the assessor's accuracy in locating the C7SP using the flexion-extension and the modified thorax-rib static methods was compared to radiography. In phase II (n = 68), the craniocervical posture was analyzed with photogrammetry after palpation using the 2 methods. Neck pain intensity and disability were also determined. RESULTS: The accuracy in locating the C7SP was higher using the modified thorax-rib static method (67%, 95% confidence interval [CI], 55-79) compared to the flexion-extension method (38%, 95% CI, 26-50, P = .016). Lower values of the craniocervical angle were obtained with the flexion-extension method than the modified thorax-rib static method (mean difference = -1.1°, 95% CI, -1.6 to -0.6, P < .001). However, both palpation methods resulted in similar classifications of participants as with or without forward head posture (P = .096). Weak correlations were observed between the craniocervical angle and neck pain intensity (ρ = -0.088 and -0.099, respectively) and disability (ρ = -0.231 and -0.249, respectively). CONCLUSION: Craniocervical angles obtained using palpation methods with different accuracies were different, although the magnitude of the difference was insufficient to lead to different classifications of a forward head posture in adults with mild neck pain and disability. Craniocervical posture was weakly correlated with neck-pain intensity and disability.

Aspirin or anticoagulation after cryptogenic stroke with patent foramen ovale: systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Since closure has restrictive eligibility criteria, the vast majority of patients with cryptogenic stroke and patent foramen ovale (PFO) receive medical treatment. However, the optimal antithrombotic strategy is still unclear. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to define risk/benefit profile of anticoagulation compared with antiplatelet treatment in PFO-related stroke. METHODS: Systematic review protocol was registered in PROSPERO (CRD42019117559). Following PRISMA guidelines, we searched MEDLINE, EMBASE, and Cochrane CENTRAL database (2000-2019) for RCTs randomly allocating patients with cryptogenic stroke and PFO to medical treatment. Risk of bias was assessed with Cochrane RoB tool. Main outcomes were stroke recurrence and major bleeding. RoPE score-dependent analysis was implemented to define a possible role for patient selection. RESULTS: Five RCTs met inclusion criteria (3 high-, 1 fair-, 1 poor-quality RCTs). Overall, meta-analysis included 1565 patients (mean age 55.5 years), 753 (48.1%) receiving anticoagulation. Compared with antiplatelet treatment, anticoagulation conveyed no net benefit in prevention of recurrent stroke (OR = 0.66, 95% CI 0.41-1.07, pheterogeneity = 0.46), and associated with a non-significant higher risk of major bleeding (OR = 1.64, 95% CI 0.79-3.43, pheterogeneity = 0.57). In patients with high RoPE score, anticoagulation significantly reduced the risk of recurrent stroke (OR = 0.22, 95% CI 0.06-0.8, pheterogeneity = 0.88). CONCLUSION: Our meta-analysis shows that anticoagulation confers no net benefit in recurrent stroke prevention over antiplatelets in patients with PFO-related stroke. RoPE score might help in selecting patients benefiting from anticoagulation, but further trials are needed to delineate risk/benefit profile of anticoagulation.

Bioimpedance analysis, metabolic effects and safety of the association Berberis aristata/Bilybum marianum: a 52-week double-blind, placebo-controlled study in obese patients with type 2 diabetes.

Berberine, a quaternary isoquinoline alkaloid present in Berberis aristata, is well known in terms of cholesterol-lowering, hypoglycemic, and insulin sensitizing effects. Because of its low oral bioavailability, to improve intestinal absorption it has been recently combined with silymarin (Silybum marianum). The aim of our placebo controlled study was to evaluate the effects of its association with silymarin on abdominal fat in overweight/obese patients with type 2 diabetes mellitus (T2DM). To do so, 136 obese subjects with T2DM and metabolic syndrome were analyzed for fasting blood glucose and insulin, Insulin Resistance index according to the Homeostatic Model Assessment (HOMA-R), total, HDL and LDL cholesterol, triglycerides, uric acid, BMI, waist circumference, waist to hip ratio and underwent bioelectrical impedance to assess % of abdominal fat. All the above-mentioned parameters, as recorded at enrollment, after 6 months and at the end of the study, had significantly improved in the BBR-treated group in respect to baseline and to the control group. A validated national cardiovascular risk score also improved significantly after BBR treatment in respect to placebo. Our results point to a clinically significant effect in obese people with T2DM and metabolic syndrome. Moreover, for the first time, they provide evidence of a significant uric acid lowering activity as an additive beneficial effect of the association BBR + silymarin.

HDAC3 role in medication consumption in medication overuse headache patients: a pilot study.

BACKGROUND: Medication overuse headache (MOH) is a common and debilitating disorder characterized by generation, perpetuation, and persistence of intense chronic migraine, caused by overuse of analgesics, triptans, or other acute headache compounds. It has been suggested that MOH could share some pathogenetic mechanisms with other kinds of drug addiction. In this regard, histone deacetylases 3 (HDAC3) seems to have a role in the memory processes involved in extinction of drug-seeking behavior in animal models. HDAC3 is inhibited by sodium valproate, a drug with proven efficacy in MOH. Recent evidence suggests an involvement of genetic factors in predisposition to medication overuse. RESULTS: In this association study, we sequenced all exons, intron/exon junctions, and 3'-5'UTR regions of HDAC3 in 23 MOH patients to investigate its role in medication overuse. Associations between genotypes with continuous and dichotomous clinical characteristics were tested by multivariate analysis and Fisher's exact test, respectively. Sequencing of HDAC3 revealed six single-nucleotide polymorphisms. The G allele of rs2530223 was significantly associated with the number of acute medications/month used and with the number of days/month in which medications were used (p = 0.006 and p = 0.007, respectively), but neither with headache frequency or intensity. None of the single-nucleotide polymorphisms (SNPs) was associated with clinical characteristics or response to sodium valproate. CONCLUSIONS: HDAC3 could be implicated in excessive medication consumption in MOH patients. Our preliminary findings provide support for the need of further investigation on larger independent samples to confirm and extend the role of HDAC3 in medication overuse headache.

Migraine-specific quality of life questionnaire and relapse of medication overuse headache.

BACKGROUND: The management of Medication overuse headache (MOH) represents a difficult challenge for clinicians and headache experts, particularly for the responder rate after a successful withdrawal treatment. The purpose of this study was to investigate the role of demographic and clinical characteristics as well as the score of Migraine-Specific Quality of Life Questionnaire (MSQ), Migraine Disability Questionnaire and Leeds Dependence Questionnaire in predicting a response after a successful withdrawal treatment in patients with MOH. METHODS: This ancillary study is part of a randomized trial that demonstrated the safety and the efficacy of a 3-month treatment with sodium valproate (VPA) (800 mg/day vs placebo) in MOH. Demographic and clinical characteristics and questionnaire results were obtained from the entire sample. RESULTS: A significant correlation was found only between MOH relapse and the total MSQ score, the Role Preventive sub-scale and the Emotional Function sub-scale, suggesting a poorer quality of life in non responders. CONCLUSION: A high MSQ score could be associated with a poor short-term outcome in MOH patients after a successful treatment with detoxification followed by a new treatment.

Impact of the systematic introduction of low-cost bubble nasal CPAP in a NICU of a developing country: a prospective pre- and post-intervention study.

BACKGROUND: The use of Nasal Continuous Positive Airway Pressure Ventilation (NCPAP) has begun to increase and is progressively replacing conventional mechanical ventilation (MV), becoming the cornerstone treatment for newborn respiratory distress syndrome (RDS). However, NCPAP use in Lower-Middle Income Countries (LMICs) is poor. Moreover, bubble NCPAP (bNCPAP), for efficacy, cost effectiveness, and ease of use, should be the primary assistance technique employed in newborns with RDS. OBJECTIVE: To measure the impact on in-hospital newborn mortality of using a bNCPAP device as the first intervention on newborns requiring ventilatory assistance. DESIGN: Prospective pre-intervention and post-intervention study. SETTING: The largest Neonatal Intensive Care Unit (NICU) in Nicaragua. PARTICIPANTS: In all, 230 (2006) and 383 (2008) patients were included. INTERVENTION: In May 2006, a strategy was introduced to promote the systematic use of bNCPAP to avoid intubation and MV in newborns requiring ventilatory assistance. Data regarding gestation, delivery, postnatal course, mortality, length of hospitalisation, and duration of ventilatory assistance were collected for infants assisted between May and December 2006, before the project began, and between May and December 2008, two years afterwards. OUTCOME MEASURES: The pre- vs post-intervention proportion of newborns who died in-hospital was the primary end point. Secondary endpoints included rate of intubation and duration of NICU stay. RESULTS: Significant differences were found in the rate of intubation (72 vs 39%; p < 0.0001) and the proportion of patients treated exclusively with bNCPAP (27% vs 61%; p <0.0001). Mortality rate was significantly reduced (40 vs 23%; p < 0.0001); however, an increase in the mean duration of NICU stay was observed (14.6 days in 2006 and 17.5 days in 2008, p = 0.0481). The findings contribute to the evidence that NCPAP, particularly bNCPAP, is the first-line standard of care for efficacy, cost effectiveness, and ease of use in newborns with respiratory distress in LMICs. CONCLUSIONS: This is the first extensive survey performed in a large NICU from a LMICs, proving the efficacy of the systematic use of a bNCPAP device in reducing newborn mortality. These findings are an incentive for considering bNCPAP as an elective strategy to treat newborns with respiratory insufficiency in LMICs.

Critical role of calcitonin gene-related peptide receptors in cortical spreading depression.

Cortical spreading depression (CSD) is a key pathogenetic step in migraine with aura. Dysfunctions of voltage-dependent and receptor-operated channels have been implicated in the generation of CSD and in the pathophysiology of migraine. Although a known correlation exists between migraine and release of the calcitonin gene-related peptide (CGRP), the possibility that CGRP is involved in CSD has not been examined in detail. We analyzed the pharmacological mechanisms underlying CSD and investigated the possibility that endogenous CGRP contributes to this phenomenon. CSD was analyzed in rat neocortical slices by imaging of the intrinsic optical signal. CSD was measured as the percentage of the maximal surface of a cortical slice covered by the propagation of intrinsic optical signal changes during an induction episode. Reproducible CSD episodes were induced through repetitive elevations of extracellular potassium concentration. AMPA glutamate receptor antagonism did not inhibit CSD, whereas NMDA receptor antagonism did inhibit CSD. Blockade of voltage-dependent sodium channels by TTX also reduced CSD. CSD was also decreased by the antiepileptic drug topiramate, but not by carbamazepine. Interestingly, endogenous CGRP was released in the cortical tissue in a calcium-dependent manner during CSD, and three different CGRP receptor antagonists had a dose-dependent inhibitory effect on CSD, suggesting a critical role of CGRP in this phenomenon. Our findings show that both glutamate NMDA receptors and voltage-dependent sodium channels play roles in CSD. They also demonstrate that CGRP antagonism reduces CSD, supporting the possible use of drugs targeting central CGRP receptors as antimigraine agents.

Long term headache duration is a factor predicting nonresponse to detoxification and advice in medication overuse headache.

BACKGROUND: Medication overuse headache (MOH) is a very heterogeneous disorder for which a recommended treatment is not yet available. The purpose of this study was to investigate any possible roles of demographic and clinical characteristics of MOH patients that might predict a response to detoxification and advice with or without preventive treatment. FINDINGS: This ancillary study is part of the Sodium vAlproate in the treatment of Medication Overuse HeadAche (SAMOHA) study that randomized 88 MOH patients for 3-month treatment period with sodium valproate (VPA) (800 mg/day) or placebo after a 6-day outpatient detoxification regimen. Demographic and clinical characteristics obtained on patients from both study arms were analyzed to point out an association with the response to the treatment. While for patients from VPA arm no significant results were obtained, comparing responders to non-responders to detoxification and advice to withdraw from MOH, a significant difference in headache duration was observed. Specifically, the efficacy of such treatment resulted ineffective in headache lasting longer than 30 years. CONCLUSIONS: Our findings suggest that the benefit from detoxification and advice can be excluded in MOH of long duration. Therefore, a preventive treatment is suggested particularly for these patients.

The potential use of daridorexant in eating disorders: beyond the treatment of insomnia?

A strong interplay exists between sleep and dietary habits, and sleep disturbances have been repeatedly documented in individuals with eating disorders (EDs). The orexin system - implicated in sleep regulation, energy homeostasis, and food reward - may represent a mechanist link between sleep alterations and disordered eating behaviors. Daridorexant is a dual orexin receptor antagonist (DORA) recently approved for the treatment of insomnia, with demonstrated efficacy and tolerability. Owing to its action on orexin neurons, the compound represents an intriguing option for addressing both sleep-related and core symptoms of EDs. By inhibiting motor hyperactivity, daridorexant may reduce excessive physical exercise in individuals with anorexia nervosa (AN) restricting type. Additionally, the compound may exert anti-binge effects, suggesting broad applicability in binge ED, bulimia nervosa, and binge/purging AN. In this framework, daridorexant emerges as a promising therapeutic option, offering a multifaceted approach to improving circadian rhythms, energy balance, and overall quality of life in individuals with diverse ED subtypes.

Married Status Affects Rates of Treatment and Mortality in Male and Female Renal Cell Carcinoma Patients Across all Stages.

INTRODUCTION: The association between treatment rates and cancer specific mortality (CSM) according to married status in male and female clear cell renal cell carcinoma (ccRCC) patients across all stages is unknown. PATIENT AND METHODS: Using the Surveillance, Epidemiology, and End Results database (2004-2020), ccRCC patients were stratified according to married status (married vs. unmarried). Logistic regression models addressed treatment rates; Cox regression models addressed CSM rates. RESULTS: Of 98,142 patients, 43,999 (72%) males and 20,287 (55%) females were married. In stage-specific analyses, married status independently predicted higher nephrectomy rates in males and females (all P ≤ .03). In stage IV, married status predicted higher systemic therapy rate in males (P < .001), but not in females. In survival analyses, married males exhibited lower CSM rates relative to unmarried males (all P ≤ .02). Conversely, married females exhibited lower CSM rates only in stages I and III (all P ≤ .02), but not in stages II and IV. In subgroup analyses of T1aN0M0 patients, married status was associated with higher partial nephrectomy rates in both males and females (all P ≤ .005). CONCLUSION: In ccRCC, married status invariably predicts higher rates of guideline recommended surgical management (nephrectomy and partial nephrectomy). Moreover, even after adjustment for treatment type, married status independently predicted lower CSM rates in males across all stages. However, the effect of married status in females is only operational in stages I and III. Lack of association between married status in stages II and IV may potentially be explained by stronger association with treatment assignment which reduces the residual effect on survival.

Inpatient palliative care in metastatic adrenocortical carcinoma: a retrospective analysis using the National Inpatient Sample database.

BACKGROUND: The use of inpatient palliative care (IPC) in advanced cancer patients represents a well-established guideline recommendation. This study examines the utilization rates and patterns of IPC among patients with metastatic adrenocortical carcinoma (mACC). METHODS: Relying on the Nationwide Inpatient Sample database (2007-2019), we tabulated IPC rates in mACC patients. Estimated annual percentage changes (EAPC) analyses as well as multivariable logistic regression models (MLRM) predicting IPC use were fitted. RESULTS: Of 2040 mACC patients, 238 (12%) received IPC. Overall, the rate of IPC increased from 3.7% to 19.1% between 2007 and 2019 (EAPC +9.6%, P=0.001). During the same period, in-hospital mortality remained unchanged from 12.1 to 13.8% (EAPC 0.1%; P=0.97). Younger age at admission (<60 years; MLRM OR=0.70, P=0.013), solitary metastatic site (OR=0.63; P=0.015), and non-brain metastases (OR=0.62; P=0.033) were all associated with lower IPC use. CONCLUSIONS: In mACC patients, IPC use has increased from a marginal 3.7% to a moderate annual value of 19.1% in the most recent study year. These rates were not driven by a concomitant increase in in-hospital mortality (12.1% to 13.8%; P=0.9). and may be interpreted as an improvement in quality of care. Despite this encouraging increase, some patient characteristics herald lower IPC use. In consequence, younger patients, those with solitary metastatic sites, and non-brain metastases should be carefully considered for IPC to decrease or completely reduce the IPC access barrier maximally.

Validation of lymphovascular invasion as a predictor of lymph-node invasion in squamous cell carcinoma of the penis.

BACKGROUND: The aim of this study was to validate lymphovascular invasion (LVI) as a predictor of lymph-node invasion (LNI) in squamous cell carcinoma of the penis (SCCP). METHODS: Within the Surveillance, Epidemiology, and End Results database (2010-2020), we identified SCCP patients who underwent lymphadenectomy with known LVI status. Univariable logistic regression models (LRMs) addressed LNI. Harrell's concordance index (c-index) quantified accuracy after 2000 bootstrap resamples for internal validation. Multivariable LRMs included the most informative, statistically significant predictors. Subgroup analyses were repeated in organ-confined (T1b-T2) and non-organ confined (T3-T4) stages. RESULTS: Of 586 SCCP patients, 219 (37%) had LVI. LVI was associated with higher rate of LNI (66 vs. 43%; P<0.001). Positive predictive value of LVI was 66 vs. 57% for negative predictive value. In multivariable LRMs, LVI independently predicted LNI (Odds ratio [OR]: 2.41; P<0.001). Bootstrap-adjusted c-index of multivariable model was 0.570 without LVI vs. 0.639 with LVI. In subgroup analyses, LVI independently predicted LNI in organ-confined (OR: 2.23; P<0.001) and in non-organ confined stages (OR: 3.10; P<0.001). In subgroup analyses, addition of LVI increased c-index from 0.530 to 0.595 in organ-confined and from 0.599 to 0.682 in non-organ confined. CONCLUSIONS: The current study validates LVI as an independent predictor of LNI in SCCP. LVI increases the accuracy of LNI predictions in the overall cohort as well as in organ-confined and non-organ confined stages. However, stage and grade even with the added consideration of LVI are not accurate enough to provide LNI prediction in individual patients.

Rates of Systemic Therapy for Metastatic Bladder Cancer Are Lower in Unmarried Males and Females.

OBJECTIVE: Systemic therapy is guideline-recommended for metastatic urothelial carcinoma of the urinary bladder (UCUB). Unmarried status represents an important barrier to treatment access in many primaries. The importance of married status is unknown in the context of systemic therapy in metastatic UCUB and was addressed in the current study. METHODS: We relied on the Surveillance, Epidemiology, and End Results database (2004-2020) to identify patients with metastatic UCUB. Univariable and multivariable logistic regression models were fitted to address systemic therapy rates. Additionally, temporal trends were plotted. RESULTS: Overall, 6873 patients with stage IV UCUB were identified. Of those, 4853 (71%) were male. Of males, 2993 (62%) were married vs. 797 (39%) of females. The rates of systemic therapy were 55% in both married males and married females. Married males and females differed from their unmarried counterparts regarding age and race/ethnicity. In males, prior to any adjustment, married status was associated with an odds ratio of 1.46 (P < .001). After adjustment for age and race/ethnicity, the odds ratio increased to 1.73 (P < .001). In females, prior to any adjustment, married status was associated with an odds ratio of 1.94 (P < .001). After adjustment for age and race/ethnicity, the odds ratio decreased to 1.57 (P < .001). CONCLUSION: Unmarried males and unmarried females are significantly exposed to lower access to systemic therapy compared to their married counterparts. In consequence, both unmarried men and unmarried women should be given very careful consideration when use of systemic therapy in metastatic UCUB is contemplated.

Sleep-Wake profiles in patients with primary biliary cirrhosis.

BACKGROUND: Impaired sleep quality and daytime sleepiness have been described in patients with primary biliary cirrhosis (PBC). However, no information is available on their sleep timing/diurnal preference. AIMS: To evaluate such variables and determine their relationship with sleep quality, fatigue, pruritus and quality of life. METHODS: Seventy-four patients with PBC (58 ± 12 years), 79 healthy volunteers (56 ± 8 years) and 60 patients with cirrhosis (58 ± 12 years) underwent formal assessment of sleep quality/timing, diurnal preference and daytime sleepiness. Patients with PBC also underwent assessment of fatigue, quality of life and the daytime course of sleepiness/pruritus. RESULTS: Sleep timing was significantly delayed in both patients with PBC and with cirrhosis, compared to healthy volunteers (sleep onset time: 23:18 ± 01:00 vs. 23:30 ± 01:00 vs. 22:54 ± 00:54 hours, respectively; P < 0.05). In patients with PBC, delayed sleep timing was associated with impaired sleep quality (P < 0.05). Sleepiness showed a physiological daily rhythm, with early afternoon/evening peaks. Pruritus was absent in the morning and increased over the afternoon/evening hours. Both the daytime course of pruritus and sleepiness changed in relation to diurnal preference. Patients with PBC and significant pruritus (upper quartile) had prolonged sleep latency (39 ± 37 vs. 21 ± 23 min, P = 0.05) and earlier wake-up times (5.9 ± 0.8 vs. 6.7 ± 0.9 min, P < 0.05). Significant correlations were observed between sleep timing and quality of life. CONCLUSIONS: Patients with PBC exhibited a delay in sleep timing that was associated with impaired sleep quality/quality of life. In addition, an interplay was observed between diurnal preference and the daytime course of pruritus/sleepiness.

Environmental drivers of tropical forest snake phenology: Insights from citizen science.

Museum specimens and citizen science initiatives are valuable sources of information on how anthropogenic activities affect biodiversity and how species respond to rapid global change. Although tropical regions harbor most of the planet's biodiversity, investigations on species' phenological changes are heavily biased toward temperate regions. Such unevenness in phenological research is also taxonomically biased, with reptiles being the least studied group among tetrapod species regarding animal phenology. Herein, we used long-term time-series data to investigate environmentally driven changes in the activity pattern of tropical forest snakes. We gathered natural history collection and citizen science data for 25 snake species (five venomous and 20 non-venomous) from an Atlantic Forest region in southeastern Brazil. Using circular mixed-effects models, we investigate whether snake activity patterns followed the variation in environmental variables over a decade. Our results show that the activity pattern of Atlantic Forest snakes was seasonal and largely driven by average temperature and relative humidity. Since snakes are ectothermic animals, they are particularly sensitive to temperature variations, especially at small scales. Moreover, relative humidity can affect snake's seasonal activities through physiological constraints and/or prey availability. Most specimens were registered during the rainy season, with highly venomous snakes (lanceheads and coral snakes) emerging as the most abundant taxa. We highlight the importance of citizen science and natural history collections in better understanding biodiversity. Furthermore, our data obtained from local collectors underscore the need for environmental education programs and collaboration between researchers and local decision-makers to raise awareness and reduce conflicts between people and snakes in the region.