Risk factors for non-closure of an intended temporary defunctioning stoma after emergency resection of left-sided obstructive colon cancer

Purpose: A substantial part (21–35%) of defunctioning stomas created during resection for colorectal cancer will never be reversed. Known risk factors for non-closure are age, peri- or postoperative complications, comorbidity, and tumor stage. However, studies performed to identify these risk factors mostly focus on rectal cancer and include both preoperative and postoperative factors. This study aims to identify preoperative risk factors for non-reversal of intended temporary stomas created during acute resection of left-sided obstructive colon cancer (LSOCC) with primary anastomosis. Methods: All patients who underwent emergency resection for LSOCC with primary anastomosis and a defunctioning stoma between 2009 and 2016 were selected from the Dutch ColoRectal Audit, and additional data were collected in the local centers. Multivariable analysis was performed to identify independent preoperative factors for non-closure of the stoma. Results: A total of 155 patients underwent acute resection for LSOCC with primary anastomosis and a defunctioning stoma. Of these, 51 patients (32.9%) did not have their stoma reversed after a median of 53 (range 7–104) months of follow-up. In multivariable analysis, hemoglobin &lt; 7.5 mmol/L (odds ratio (OR) 4.79, 95% confidence interval (95% CI) 1.60–14.38, p = 0.005), estimated glomerular filtration rate (eGFR) ≤ 45 mL/min/1.73 m2 (OR 4.64, 95% CI 1.41–15.10, p = 0.011), and metastatic disease (OR 6.12, 95% CI 2.35–15.94, p &lt; 0.001) revealed to be independent predictors of non-closure. Conclusions: Anemia, impaired renal function, and metastatic disease at presentation were found to be independent predictors for non-reversal of intended temporary stomas in patients who underwent acute resection for LSOCC. In patients who have an increased risk of non-reversal, the surgeon should consider a Hartmann’s procedure.</p

Identification of a brainstem locus that inhibits tumor necrosis factor

In the brain, compact clusters of neuron cell bodies, termed nuclei, are essential for maintaining parameters of host physiology within a narrow range optimal for health. Neurons residing in the brainstem dorsal motor nucleus (DMN) project in the vagus nerve to communicate with the lungs, liver, gastrointestinal tract, and other organs. Vagus nerve-mediated reflexes also control immune system responses to infection and injury by inhibiting the production of tumor necrosis factor (TNF) and other cytokines in the spleen, although the function of DMN neurons in regulating TNF release is not known. Here, optogenetics and functional mapping reveal cholinergic neurons in the DMN, which project to the celiacsuperior mesenteric ganglia, significantly increase splenic nerve activity and inhibit TNF production. Efferent vagus nerve fibers terminating in the celiac-superior mesenteric ganglia form varicose-like structures surrounding individual nerve cell bodies innervating the spleen. Selective optogenetic activation of DMN cholinergic neurons or electrical activation of the cervical vagus nerve evokes action potentials in the splenic nerve. Pharmacological blockade and surgical transection of the vagus nerve inhibit vagus nerve-evoked splenic nerve responses. These results indicate that cholinergic neurons residing in the brainstem DMN control TNF production, revealing a role for brainstem coordination of immunity

Pollen Nightmare: Elevated Airborne Pollen Levels at Night

High airborne pollen concentrations are generally associated with daylight hours when it is sunny and warm and plants release pollen into the air (Alcázar et al. 1999; Dahl et al. 2013). In contrast, cooler night-time periods are usually considered to be the time of low-allergy risk. This opinion is often reflected in pollen allergy avoidance strategies presented by the media, where the most commonly repeated recommendation is to stay indoors during the day and plan outdoor activities for the evening. However, there is evidence to suggest that elevated concentrations of airborne pollen might also occur during the evening (e.g. Norris-Hill and Emberlin 1991). So, is the night really a time of low-allergy risk? We present the results of the comparative analysis of pollen concentrations during daytime and night-time hours for five allergenic pollen types (Burbach et al. 2009), i.e. alder (Alnus sp.), birch (Betula sp.), grasses (Poaceae), mugwort (Artemisia sp.) and ragweed (Ambrosia sp.)

A Conceptual Framework for Social, Behavioral, and Environmental Change through Stakeholder Engagement in Water Resource Management

Incorporating stakeholder engagement into environmental management may help in the pursuit of novel approaches for addressing complex water resource problems. However, evidence about how and under what circumstances stakeholder engagement enables desirable changes remains elusive. In this paper, we develop a conceptual framework for studying social and environmental changes possible through stakeholder engagement in water resource management, from inception to outcomes. We synthesize concepts from multiple literatures to provide a framework for tracing linkages from contextual conditions, through engagement process design features, to social learning, community capacity building, and behavioral change at individual, group, and group network levels, and ultimately to environmental change. We discuss opportunities to enhance the framework including through empirical applications to delineate scalar and temporal dimensions of social, behavioral, and environmental changes resulting from stakeholder engagement, and the potential for negative outcomes thus far glossed over in research on change through engagement

Early Adversity and the Prospective Prediction of Depressive and Anxiety Disorders in Adolescents

The current study was a prospective exploration of the specificity of early childhood adversities as predictors of anxiety and depressive disorders in adolescents. Participants were 816 adolescents (414 males, 402 females) with diagnostic information collected at age 15; information on early adversities had been collected from the mothers during pregnancy, at birth, age 6 months, and age 5 years for a related study. Adolescents with "pure" anxiety disorders were compared with adolescents with "pure" depressive disorders (major depressive disorder, dysthymia), and these groups were compared to never-ill controls. Analyses controlled for gender and maternal depression and anxiety disorders. Results indicated that adolescents with anxiety disorders were more likely than depressed youth to have been exposed to various early stressors, such as maternal prenatal stress, multiple maternal partner changes, and more total adversities, whereas few early childhood variables predicted depressive disorders. Even when current family stressors at age 15 were controlled, early adversity variables again significantly predicted anxiety disorders. Results suggest that anxiety disorders may be more strongly related to early strees exposure, while depressive disorders may be related to more proximal stressors or to early stressors not assessed in the current study

Efficacy of dose-escalated chemoradiation on complete tumour response in patients with locally advanced rectal cancer (RECTAL-BOOST); a phase 2 randomised controlled trial

Purpose Pathological complete tumour response following chemoradiation in patients with locally advanced rectal cancer (LARC) is associated with favourable prognosis and allows organ-sparing treatment strategies. We aimed to investigate the effect of an external radiation boost to the tumour prior to chemoradiation on pathological or sustained clinical complete tumour response in LARC. Methods and materials This multicentre, non-blinded, phase 2, randomised controlled trial followed the trials within cohorts-design, which is a pragmatic trial design allowing cohort participants to be randomized for an experimental intervention. Patients in the intervention group are offered the intervention (and can accept or refuse this), whereas patients in the control group are not notified about the randomisation. Participants of a colorectal cancer cohort referred for chemoradiation of LARC to either of two radiotherapy centres were eligible. Patients were randomised to no boost or an external radiation boost (5 x 3 Gy) without concurrent chemotherapy directly followed by standard pelvic chemoradiation (25 x 2 Gy with concurrent capecitabine). The primary outcome was pathological complete response (pCR, i.e. ypT0N0) in patients with planned surgery at 12 weeks or, as surrogate for pCR, a 2-year sustained clinical complete response for patients treated with an organ preservation strategy. Analyses were intention to treat. The study was registered with ClinicalTrials.gov, number NCTXXXXXX. Results Between Sept 2014 and July 2018, 128 patients were randomised. Fifty-one of the 64 (79.7%) patients in the intervention group accepted and received a boost. Compared with the control group, fewer patients in the intervention group had a cT4-stage and a low rectal tumour (31.3% versus 17.2% and 56.3% versus 45.3% respectively), and more patients had a cN2-stage (59.4% versus 70.3% respectively). Rate of pathological or sustained clinical complete tumour response was similar between the groups: 23 of 64 (35.9%, 95%CI 24.3-48.9) in the intervention group versus 24 of 64 (37.5%, 95%CI 25.7-50.5) in the control group (OR=0.94 95%CI 0.46-1.92). Near-complete or complete tumour regression was more common in the intervention group: 34 of 49 (69.4%) versus 24 of 53 (45.3%) in the control group (OR=2.74, 95%CI 1.21-6.18). Grade >3 acute toxicity was comparable: 6 of 64 (9.4%) in the intervention group versus 5 of 64 (7.8%) in the control group (OR=1.22 95%CI 0.35-4.22). Conclusion Dose escalation with an external radiotherapy boost to the tumour prior to neoadjuvant chemoradiation did not increase the pathological or sustained clinical complete tumour response rate in LARC