Predictive factors of recurrence in adenocarcinoma of the esophagogastric junction in the multimodal era

IntroductionAdenocarcinoma of the esophagogastric junction (AEGJ) represents a poor prognostic tumor. We evaluated the recurrence pattern and risk factors associated with recurrence in patients undergoing surgical resection by AEJG.MethodsRecurrences were categorized as locoregional, peritoneal, or distant. These three recurrence groups and a non-recurrence group were compared, and overall survival (OS) and disease-free survival (DFS) for each one was obtained.ResultsWe analyzed 188 patients with curative surgical treatment. Recurrence was observed in 72 (38.3%) patients. Locoregional recurrence was observed in 17 (23.6%); 20 (27.8%) peritoneal recurrence and 35 (48.6%) distant metastasis. DFS was 9, 5, and 8 months, and OS was 21.8, 13.2, and 20.8, respectively. Tumors larger than 5 cm are risk factors for peritoneal recurrence (OR:2.88, p = 0.012). Positive lymph nodes were related to distant metastasis (OR:9.15, p = 0.040), and lymphatic invasion for locoregional recurrence (OR:3.81, p = 0.028).ConclusionAEGJ is associated with high rates of early recurrence.     

Safety and efficacy of the cystic fibrosis transmembrane conductance regulator potentiator icenticaftor (QBW251)

BackgroundThis is the first-in-human study of icenticaftor, an oral potentiator of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) channel. Restoration of CFTR activity has shown significant clinical benefits, but more studies are needed to address all CFTR mutations.MethodsSafety, pharmacodynamics/pharmacokinetics of icenticaftor were evaluated in a randomized, double-blind, placebo-controlled study in healthy volunteers. Efficacy was assessed in adult CF patients with ≥1 pre-specified CFTR Class III or IV mutation (150 and 450 mg bid), or homozygous for F508del mutation (450 mg bid). Primary efficacy endpoint was change from baseline in lung clearance index (LCI_2.5). Secondary endpoints included %predicted FEV₁ and sweat chloride level.ResultsClass IV mutations were present in 22 patients, Class III in 2 (both S549N), and 25 were homozygous for F508del. Icenticaftor was well-tolerated in healthy and CF subjects with no unexpected events or discontinuations in the CF groups. The most frequent study-drug related adverse events in CF patients were nausea (12.2%), headache (10.2%), and fatigue (6.1%). Icenticaftor 450 mg bid for 14 days showed significant improvements in all endpoints versus placebo in patients with Class III and IV mutations; mean %predicted FEV₁ increased by 6.46%, LCI_2.5 decreased by 1.13 points and sweat chloride decreased by 8.36 mmol/L. No significant efficacy was observed in patients homozygous for a single F508del.ConclusionsIcenticaftor was safe and well-tolerated in healthy volunteers and CF patients, and demonstrated clinically meaningful changes in lung function and sweat chloride level in CF patients with Class III and IV CFTR mutations.ClinicalTrials.gov: NCT02190604     

How Stigma Toward Anal Sexuality Promotes Concealment and Impedes Health-Seeking Behavior in the U.S. Among Cisgender Men Who Have Sex with Men

Archives of Sexual Behavior - Gay, bisexual, and other men who have sex with men (MSM) experience alarming HIV disparities alongside sub-optimal engagement in HIV interventions. Among MSM, stigma...     

Estimation of the Impact of Migraine on Self-rated Health: A Cross-sectional Study in Slovenia

AimWith the aim of providing a foundation for evidence-based public health actions, as well as the more individualised clinical treatment of migraine in Slovenia, the objective of our study was to assess the association between poor self-rated health (PSRH) and migraine, adjusted for selected comorbidity and socioeconomic factors.MethodsThe survey, conducted between August and December 2014, involved included 6,262 adults aged 15 years and over. Binary logistic regression was used in univariate as well as multivariate analysis. Three multivariate models were defined: MODEL 1 (migraine and comorbidities related to the physical dimension of health); MODEL 2 (comorbidities related to the mental dimension of health); MODEL 3 (demographic and socioeconomic factors).ResultsIn univariate as well as all three multivariate models, the odds of PSRH were statistically significantly higher in migraine sufferers in comparison to non-sufferers (univariate model: ORmigraine=yes vs. migraine=no=2.22 (p<0.001); MODEL 1: ORmigraine=yes vs. migraine=no=2.27 (p<0.001); MODEL 2: ORmigraine=yes vs. migraine=no=1.51 (p=0.002); MODEL 3: ORmigraine=yes vs. migraine=no=1.56 (p=0.001)).ConclusionMigraine is an important PSRH-related factor. Comorbidities related to the physical dimension of health do not reduce the power of association between migraine and PRSH, while comorbidities related to the mental dimension reduce the power of association of migraine and other health conditions. The power of the association between migraine and PRSH is also independent of demographic/socioeconomic factors. We can also conclude that migraine seems to be a phenomenon that is in a bi-directional relationship with mental states (thus having an impact on PSRH) and is itself a stressor.     

Effect of saline infusion on net reabsorption of endogenous sulfate relative to that of phosphate in intact and thyroparathyroidectomized rats

Clearance experiments have been performed to study the effects of saline infusion on the reabsorption of inorganic sulfate (SO₄) at endogenous levels. Adult female Sprague-Dawley rats on a standard diet were used. Both intact and thyroparathyroidectomized (TPTX) animals were infused with a 130 mmol/l sodium chloride solution at a low (0.15 ml/min) and a high (0.375 ml/min) rate. This increase of the infusion rate decreased the reabsorption of SO₄ in both groups of animals significantly. The fractional excretion of SO₄ in theintact rats increased from 9.9±5.6 to 18.4±3.6% (mean values±SD,p<0.001) and in theTPTX rats from 5.3±2.5 to 22.4±6.3% (p<0.001). It is concluded that endogenous parathyroid hormone has no major effect on the saline-induced inhibition of reabsorption of SO₄.This work was supported by a grant from the Deutsche Forschungsgemeinschaft (Fr 239/9-1)     

Overexpression of decoy receptor 3 in precancerous lesions and adenocarcinoma of the esophagus

Overexpression of decoy receptor (DcR) 3 protein, a recently discovered member of the tumor necrosis factor receptor superfamily, was examined in 40 esophagogastrectomy specimens containing areas of Barrett esophagus (n = 27), low-grade dysplasia (n = 27), high-grade dysplasia or carcinoma in situ (n = 22), and esophageal adenocarcinoma (EAC; n = 28) with immunohistochemical analysis. The results revealed significantly more overexpression of DcR3 in high-grade dysplasia or carcinoma in situ and EAC than in benign esophageal mucosa (both P < .0001), Barrett esophagus (both P < .001), and low-grade dysplasia (P < .01 and P = .033, respectively). Low-grade dysplasia also showed significant overexpression of DcR3 compared with benign esophagus (P < .05) but not with Barrett esophagus (P > .05). DcR3 overexpression seems to negatively correlate with the grade of EAC. Our results suggest that overexpression of DcR3 protein might aid in the diagnosis of high-grade dysplasia or carcinoma in situ and EAC and also might serve as a potential therapeutic target.     

Engagement with arts and culture activities in the Danish general population: Longitudinal associations with new onset or persistent depression and mental wellbeing

Objectives

International literature suggests that arts and culture activities may benefit mental health, however, such survey studies conducted in the Danish population are scarce. Further, studies have investigated the associated risk for incident depression, but not for persistent depression. The objective of the current prospective study was to assess associations of engagement in arts and culture activities with incident/persistent depression and also mental wellbeing among Danish adults in the general population.

Design

Observational prospective study.

Methods

Data stem from a Danish nationally representative panel study of 5000 adults (aged 15+ years) conducted in 2019 and 2020, which was linked to Danish register data. An exposure variable was constructed for frequency of attending concerts, theatres, museums, and cinemas. Validated scales were used to assess the presence of depression (PHQ-8) and levels of mental wellbeing (SWEMWBS). Binary logistic regression analyses were conducted to assess the risk of incident depression (among participants free of depression at baseline), as well as the risk of persistent depression (among participants with depression at baseline), while multinomial logistic regression was used to assess odds for moderate and high mental wellbeing (low as base outcome) while adjusting for baseline values.

Result

In terms of incident depression, quarterly engagement in arts and culture activities (compared to never) was associated with an OR of .43 (95%CI .23–.80), while 8 times or more was associated with an OR of .53 (.29–.97). In terms of persistent depression, quarterly engagement was associated with an OR of .30 (.10–.90), while 8 times per year or more was associated with an OR of .26 (.07–.92). Similar to the patterns for incident/persistent depression, associations with moderate mental wellbeing showed higher odds for quarterly engagement and 8 times per year or more. Quarterly engagement was also associated with higher odds for high mental wellbeing but did not reach statistical significance.

Conclusions

The results support the involvement of the cultural and creative sectors in health strategies. Mental health promotion initiatives as well as arts and culture sectors may encourage the general public to engage in arts and culture activities with frequencies of at least once per quarter.