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Although penile carcinoma is a rare malignancy, there is still an unmet need to identify prognostic factors associated with poor survival. In this study, we utilized demographic and clinical information to identify the most informative variables associated with overall survival in patients with penile cancer. From a full model including all covariates found to be statistically significant in univariable analyses, we identified a parsimonious reduced model containing tumor site (penis glans: hazard ratio [HR] = 0.48; 95% CI: 0.28-0.85 and penis not otherwise specified: HR = 0.45; 95% CI: 0.25-0.84), undetermined tumor differentiation (HR = 0.48; 95% CI: 0.27-0.86), and TNM stage III/IV (HR = 2.83; 95% CI: 1.68-4.75). When all of the covariates from the full model were subjected to classification and regression tree analysis, we identified 6 novel risk groups. Of particular interest, we found marriage was associated with substantial improvement in survival among men with the same stage and disease site. Specifically, among single/widowed/divorced men with TNM stage 0-II and prepuce/penis corpus/overlapping lesions had worse survival (5-year survival = 18.2%) versus married men (5-year survival = 62.5%). Since marital status is linked to social support, these findings warrant a deeper investigation into the relationships between disease prognosis and social support in patients with penile carcinoma.

Purpose Racial disparities are evident in colorectal cancer (CRC) prognosis with black patients experiencing worse outcomes than Hispanics and whites, yet mediators of these disparities are not fully known. The aim of this study is to identify variables that contribute to racial/ethnic disparities in health-related quality of life (HR-QoL) and overall survival in CRC. Methods Using SF-12 questionnaires, we assessed HR-QoL in 1132 CRC patients by calculating their physical (PCS) and mental composite summary (MCS) scores. Associations between poor PCS/MCS and sociodemographic factors were estimated and survival differences were identified by race/ethnicity. Results Hispanic patients who never married were at greater risk of poor PCS (OR 2.69; 95% CI 1.11–6.49; P  = 0.028) than were currently married patients. College education was associated with a decreased risk of poor PCS in Hispanic and white, but not black, patients. Gender was significantly associated with poor MCS among white patients only. CRC patients who reported a poor PCS or MCS had poor survival, with differences in median survival times (MSTs) by race. The effect of PCS was strongest in white CRC patients with a difference in overall MST of > 116 months between those with favorable versus poor physical HR-QoL. Black patients who reported poor Physical and Mental HR-QoL showed significant risk of a poor outcome. Conclusion These findings suggest that racial/ethnic disparities in CRC survival may be related to differences in HR-QoL. Identified mediators of HR-QoL could supplement current CRC management strategies to improve patients’ survival.

Purpose To investigate the mediators of health-related quality of life (HR-QoL) in colorectal cancer (CRC) patients and effect on overall survival. Methods We analyzed baseline (within 1 year of diagnosis) SF-12v1 questionnaire data from 3734 CRC patients and assessed the differences in mental composite scores (MCS) and physical composite scores (PCS) by socio-demographics and risks of poor HR-QoL by these factors. Hazard ratios were generated using univariate Cox regression for MCS and PCS dichotomized using the normalized scoring-based mean of 50 and survival estimates generated using the Kaplan-Meier method. Results Differences in MCS and PCS were identified by sex, age, education level, alcohol use, tobacco use, and stage. Race, marital status, and cancer site differed only by PCS. Being female, never married, former alcohol user, or with stage IV disease significantly increased risk of a poor HR-QoL, with magnitudes of risk from 1.25- to 1.97-fold. Higher education level had a protective effect (MCS: Ptrend, = 2.32 ×10 ⁻⁷; PCS: Ptrend = 5.62 ×10⁻¹⁴ Hispanics and African-Americans had a 1.35- and 1.57-fold risk of poor PCS, and increase in age had a protective effect for risk of poor MCS (P trend = 1.84 ×10⁻⁷ ). Poor MCS or PCS were associated with poor prognosis and decreased survival at 5 years (HRMCS 1-57, 95 % CI 1.41-1.76 and HR PCS 2.38, 95 % CI 2.08-2.72), and both remained significant when adjusting for age, gender, race, education level, tumor stage, and tumor site. Conclusions Our findings identify potential mediators for HR-QoL and suggest that baseline HR-QoL assessment may be prognostic for CRC.

Purpose As clinical studies have correlated RANK expression levels with survival in breast cancer, and that RANK signaling is dependent on its cognate ligand RANKL, we hypothesized that dual protein expression further stratifies the poor outcome in TNBC. Methods RANK mRNA and protein expression was evaluated in TNBC using genomic databases, cell lines and in a tissue microarray of curated primary tumor samples derived from 87 patients with TNBC. RANK expression was evaluated either by Mann–Whitney U test on log-normalized gene expression data or by Student’s t test on FACS data. Analysis of RANK and RANKL immunostaining was calculated by H-score, and correlations to clinical factors performed using χ 2 or Fisher’s exact test. Associations with RFS and OS were assessed using univariate and multivariate Cox proportional hazard models. Survival estimates were generated using the Kaplan–Meier method. Results In three distinct datasets spanning 684 samples, RANK mRNA expression was higher in primary tumors derived from TNBC patients than from those with other molecular subtypes ( P  < 0.01). Cell surface-localized RANK protein was consistently higher in TNBC cell lines ( P  = 0.037). In clinical samples, TNBC patients that expressed both RANK and RANKL proteins had significantly worse RFS ( P  = 0.0032) and OS ( P  = 0.004) than patients with RANK-positive, RANKL-negative tumors. RANKL was an independent, poor prognostic factor for RFS ( P  = 0.04) and OS ( P  = 0.01) in multivariate analysis in samples that expressed both RANK and RANKL. Conclusions RANK and RANKL co-expression is associated with poor RFS and OS in patients with TNBC.

Oral outpatient treatment for Covid-19 is needed. In this phase 3, double-blind, randomized, controlled trial, molnupiravir, a small-molecule antiviral, was studied in unvaccinated patients with less than 5 days of Covid-19 illness. By day 29, hospitalization for progression of Covid-19 was lower with molnupiravir (6.8%) than with placebo (9.7%).

De Los Reyes reviews This Is the Year by Gloria Muñoz.

Andrographolide, fucoidan, or a combination of both compounds were evaluated to determine their effects on the antiviral response in the Atlantic salmon macrophage-like cell line (SHK-1) infected with infectious pancreatic necrosis virus (IPNV). We assessed the transcript expression levels of key molecules involved in the interferon (IFN)-dependent antiviral response, as well as the viral load in cells treated with these compounds. In non-infected cells, incubation with either fucoidan, andrographolide, or a mixture of both resulted in an increase in the transcript expression of IFNα1 and various interferon-stimulated genes (ISGs). In IPNV-infected cells, treatment with either fucoidan or andrographolide separately did not significantly enhance the antiviral response compared to that of infected cells that had not previously been treated with these compounds. In contrast, the combination of andrographolide and fucoidan led to a marked increase in the transcript expression of viperin and a significant reduction in viral load. Overall, combining andrographolide and fucoidan resulted in a greater reduction in IPNV viral load in infected cells than that noted when the compounds were administered individually. Our findings suggest that pre-incubation with this mixture promotes the establishment of a protective antiviral state against IPNV, likely mediated by an IFN-dependent response.

Background/Objectives Oropharyngeal dysphagia (OD) is a common problem in elderly population that negatively affects the oral intake and body composition resulting in clinical complications as malnutrition and dehydration. The aim of this study was to design, implement, and evaluate the effect of texture-modified foods and thickened drinks diet, with nectar or pudding viscosity and controlled bolus volume in older adults with OD on body composition and oral intake. Subjects/Methods Randomized clinical trial, simple blind. Patients ≥ 65 years, admitted at a national institute, who had a confirmed diagnosis of OD were included. A texture-modified foods and thickened drinks diet, with nectar or pudding viscosity and controlled bolus volume, was compared to isocaloric standard treatment for 12 weeks. Body composition was evaluated by bioelectrical impedance, muscular functionality was evaluated by handgrip strength, and daily energy and protein intake by 24-h recall and evaluated by Food Processor Nutrition Analysis® software. Results Twenty participants were included per group, with mean age 76 years. After 12 weeks, the consumption of energy (29 ± 10 to 40 ± 15 kcal/kg, p  = 0.009) and protein (1.3 ± 0.6 to 1.8 ± 0.7 g/kg, p  = 0.03), as well as phase angle (4.4 ± 1.8 to 5.5 ± 2.5°, p  = 0.05), body weight (56 ± 10 to 60 ± 10 kg, p  < 0.001), and handgrip strength (18 ± 11 to 21 ± 13 kg , p  = 0.004) increased in the intervention group. In control group there were no changes. Conclusions The dietary intervention improved oral intake, weight, handgrip strength, and phase angle, which can prevent or limit the nutritional complications associated with the OD.

Laminin, a non-collagenous glycoprotein present in the brain extracellular matrix, helps to maintain blood–brain barrier (BBB) integrity and regulation. Neuroinflammation can compromise laminin structure and function, increasing BBB permeability. The aim of this paper is to determine if neuroinflammation-induced laminin functional changes may serve as a potential biomarker of alterations in the BBB. The 38 publications included evaluated neuroinflammation, BBB disruption, and laminin, and were assessed for quality and risk of bias (protocol registered in PROSPERO; CRD42020212547). We found that laminin may be a good indicator of BBB overall structural integrity, although changes in expression are dependent on the pathologic or experimental model used. In ischemic stroke, permanent vascular damage correlates with increased laminin expression (β and γ subunits), while transient damage correlates with reduced laminin expression (α subunits). Laminin was reduced in traumatic brain injury and cerebral hemorrhage studies but increased in multiple sclerosis and status epilepticus studies. Despite these observations, there is limited knowledge about the role played by different subunits or isoforms (such as 411 or 511) of laminin in maintaining structural architecture of the BBB under neuroinflammation. Further studies may clarify this aspect and the possibility of using laminin as a biomarker in different pathologies, which have alterations in BBB function in common.

GWAS have repeatedly mapped susceptibility loci for emphysema to genes that modify hedgehog signaling, but the functional relevance of hedgehog signaling to this morbid disease remains unclear. In the current study, we identified a broad population of mesenchymal cells in the adult murine lung receptive to hedgehog signaling, characterized by higher activation of hedgehog surrounding the proximal airway relative to the distal alveoli. Single-cell RNA-sequencing showed that the hedgehog-receptive mesenchyme is composed of mostly fibroblasts with distinct proximal and distal subsets with discrete identities. Ectopic hedgehog activation in the distal fibroblasts promoted expression of proximal fibroblast markers and loss of distal alveoli and airspace enlargement of over 20% compared with controls. We found that hedgehog suppressed mesenchymal-derived mitogens enriched in distal fibroblasts that regulate alveolar stem cell regeneration and airspace size. Finally, single-cell analysis of the human lung mesenchyme showed that segregated proximal-distal identity with preferential hedgehog activation in the proximal fibroblasts was conserved between mice and humans. In conclusion, we showed that differential hedgehog activation segregates mesenchymal identities of distinct fibroblast subsets and that disruption of fibroblast identity can alter the alveolar stem cell niche, leading to emphysematous changes in the murine lung.