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Background: Chronic urticaria (CU) has been associated with several systemic and autoimmune disorders. The association with atopic disorders is however controversial. The objective of this study was to perform a systematic review and meta-analysis to assess the association between CU and the atopic disorders: atopic dermatitis (AD), asthma, and allergic rhinoconjunctivitis (ARC). Methods: Search hits from PubMed, Embase, Cochrane Library, and Web of Science were systematically reviewed. English papers from 2000 to present, containing original data of the association (prevalence, incidence, or risk) between CU and any atopic disorder(s), were included. Pooled point prevalence and OR with 95% confidence intervals were calculated with a random effects model. Results: A total of 8,108 search hits were screened and reviewed. Thirty-eight studies met all inclusion criteria. The estimated pooled point prevalence of AD, asthma, and ARC in CU was 7% (5–11%, I2 = 99%), 12% (9–15%, I2 = 100%), and 22% (16–29%, I2 = 100%), respectively. Pooled ORs were estimated to 2.75 (2.05–3.68, I2 = 94%) for AD, 1.87 (1.01–3.45, I2 = 100%) for asthma, and 2.94 (1.84–4.68, I2 = 100%) for ARC. Conclusion: Pooled point prevalences of atopic disorders in CU were comparable to the general population. However, studies that compared prevalences with controls from the same population all found a significantly increased risk of atopic disorders in CU. Results should however be interpreted with caution as high heterogeneity was found in all analyses.

BackgroundIn colorectal cancer, the effects of immune checkpoint inhibitors are mostly limited to patients with deficient mismatch repair tumors, characterized by a high grade infiltration of CD8+T cells. Interventions aimed at increasing intratumoral CD8+T-cell infiltration in proficient mismatch repair tumors are lacking.MethodsWe conducted a proof of concept phase 1/2 clinical trial, where patients with non-metastasizing sigmoid or rectal cancer, scheduled for curative intended surgery, were treated with an endoscopic intratumorally administered neoadjuvant influenza vaccine. Blood and tumor samples were collected before the injection and at the time of surgery. The primary outcome was safety of the intervention. Evaluation of pathological tumor regression grade, immunohistochemistry, flow cytometry of blood, tissue bulk transcriptional analyses, and spatial protein profiling of tumor regions were all secondary outcomes.ResultsA total of 10 patients were included in the trial. Median patient age was 70 years (range 54–78), with 30% women. All patients had proficient mismatch repair Union of International Cancer Control stage I–III tumors. No endoscopic safety events occurred, with all patients undergoing curative surgery as scheduled (median 9 days after intervention). Increased CD8+T-cell tumor infiltration was evident after vaccination (median 73 vs 315 cells/mm2, pConclusionsNeoadjuvant intratumoral influenza vaccine treatment in this cohort was demonstrated to be safe and feasible, and to induce CD8+T-cell infiltration and upregulation of PD-L1 proficient mismatch repair sigmoid and rectal tumors. Definitive conclusions regarding safety and efficacy can only be made in larger cohorts.Trial registration numberNCT04591379.

Myocardial injury after noncardiac surgery is a strong predictor of 30-day mortality and morbidity.The purpose of this study was to examine the incidence of myocardial injury in patients undergoing colorectal cancer surgery in an enhanced recovery after surgery protocol and its association with 90-day mortality and morbidity.This is a retrospective cohort study.This study was conducted at Zealand University Hospital, Denmark, between June 2015 and July 2017.Adult patients undergoing colorectal cancer surgery were included if troponin was measured at least twice during the first 7 days after surgery. The patients were followed for 90 days.Myocardial injury was defined as an elevated troponin I measurement (45 ng/L) without evidence of a nonischemic origin causing the elevation. Ninety-day mortality and complications were assessed.A total of 586 patients were included of which 42 were diagnosed with myocardial injury. Thirteen patients (2%) died within 90 days of surgery. There was no significant difference in 90-day mortality between patients with and without myocardial injury (5% (2/42) versus 2% (11/544); p = 0.24). We found a higher incidence of postoperative complications within 90 days of surgery in the myocardial injury group than in the nonmyocardial injury group (43% (18/42) versus 20% (107/544); p0.01). We found a significant difference between the myocardial injury group and nonmyocardial injury group in terms of medical complications (33% (14/42) versus 9% (50/544); p0.01) but not surgical complications (19% (8/42) versus 16% (85/544); p = 0.56). Myocardial injury was an independent predictor of postoperative complications within 90 days of surgery (adjusted OR, 2.69; 95% CI, 1.31-5.55).This study was limited by its retrospective design.Myocardial injury occurs frequently in patients undergoing colorectal cancer surgery in an enhanced recovery after surgery protocol. Patients with myocardial injury did not have a significantly higher 90-day mortality but had higher risk of 90-day postoperative complications than patients without myocardial injury. Future research should examine the prevention and treatment of myocardial injury. See Video Abstract at http://links.lww.com/DCR/B692.ANTECEDENTES:La lesión del miocardio después de una cirugía no cardíaca es un fuerte predictor de mortalidad y morbilidad a los 30 días.OBJETIVO:El propósito fue examinar la incidencia de lesión miocárdica en pacientes sometidos a cirugía de cáncer colorrectal en un protocolo de recuperación mejorada después de la cirugía y su asociación con la mortalidad y morbilidad a los 90 días.DISEÑO:Estudio de cohorte retrospectivo.AJUSTE:Realizado en el Hospital Universitario de Zelanda, Dinamarca, entre junio de 2015 y julio de 2017.PACIENTES:Se incluyeron pacientes adultos sometidos a cirugía de cáncer colorrectal, si la troponina se midió al menos dos veces durante los primeros siete días después de la cirugía. Los pacientes fueron seguidos durante 90 días.PRINCIPALES MEDIDAS DE RESULTADO:La lesión miocárdica se definió como una medición de troponina I elevada (45 ng / l) sin evidencia de una etiología no isquémica que causara la elevación. Se evaluaron la mortalidad y las complicaciones a los noventa días.RESULTADOS:Se incluyeron un total de 586 pacientes, de los cuales 42 fueron diagnosticados de lesión miocárdica. Trece pacientes (2%) murieron dentro de los 90 días posteriores a la cirugía. No hubo diferencias significativas en la mortalidad a 90 días entre los pacientes con y sin lesión del miocardio, 5% [2/42] versus 2% [11/544], p = 0,24. Encontramos una mayor incidencia de complicaciones posoperatorias dentro de los 90 días de la cirugía en el grupo de lesión miocárdica en comparación con el grupo de lesión no miocárdica, 43% [18/42] versus 20% [107/544], p0,01. Encontramos una diferencia significativa entre el grupo de lesión miocárdica y el grupo de lesión no miocárdica en términos de complicaciones médicas (33% [14/42] versus 9% [50/544]; p0,01) pero no complicaciones quirúrgicas (19% [8/42] versus 16% [85/544]; p = 0,56). La lesión miocárdica fue un predictor independiente de complicaciones posoperatorias dentro de los 90 días posteriores a la cirugía (razón de probabilidades ajustada: 2,69; intervalo de confianza del 95%: 1,31 - 5,55).LIMITACIONES:Limitado por su diseño retrospectivo.CONCLUSIÓN:La lesión del miocardio ocurre con frecuencia en pacientes sometidos a cirugía de cáncer colorrectal en un protocolo de recuperación mejorada después de la cirugía. Los pacientes con lesión miocárdica no tuvieron una mortalidad significativamente mayor a los 90 días, pero tuvieron un mayor riesgo de complicaciones posoperatorias a los 90 días en comparación con los pacientes sin lesión miocárdica. Las investigaciones futuras deben examinar la prevención y el tratamiento de la lesión miocárdica. Consulte Video Resumen en http://links.lww.com/DCR/B692.

Background Depression following acute coronary syndrome is prevalent and associated with increased mortality and morbidity. Melatonin may function as a primary prophylactic antidepressant substance and alleviate depressive symptoms. The study was undertaken to determine if melatonin administered following an acute coronary syndrome (ACS) could prevent development of depression. Methods The study was a double-blinded, placebo-controlled, multicenter, randomized clinical trial performed in five primary care cardiology departments at Zealand, Denmark. Included patients were adults patients, free of depression at baseline, included at the latest 4 weeks after acute coronary syndrome. Twenty-five mg melatonin or placebo was administered 1 h before participants’ bedtime for 12 weeks. The primary outcome is Major Depression Inventory (MDI) measured every two weeks throughout the trial. Incidence of depression was apriori defined as MDI score ≥ 21 during the trial. Reported exploratory outcomes were patterns of dropout and safety outcomes. Results 1220 patients were screened and 252 participants were randomized in a 1:1 ratio. Baseline MDI score in the melatonin and placebo group were, respectively, 6.18 (CI 5.32–7.05) and 5.98 (CI 5.19–6.77). No significant intergroup differences were found during the study in the intention-to-treat analysis or per-protocol analysis. Cumulative events of depressive episodes during the 12 weeks were six in the melatonin group and four in the placebo group. A significant drop in depressive symptoms were present throughout the study period. No intergroup differences were present in dropouts or adverse events. Conclusions Melatonin showed no prophylactic antidepressant effect following acute coronary syndrome. The non-significant results might be due to a type II error or melatonin might not be able to prevent development of depressive symptoms following ACS.

Endothelial dysfunction (ED) precedes acute coronary syndrome. Oxidative stress results in ED but is reversible. Melatonin is aside from being a circadian hormone, also an antioxidant. The aim of this study was to investigate whether 25 mg melatonin administered for twelve weeks following acute coronary syndrome (ACS) could improve ED. In this placebo-controlled randomized trial, ED was measured as reactive hyperemia index (RHI) at baseline, day 14, and day 84. The effect was assessed using a generalized estimating equation adjusted for the baseline RHI. As secondary outcome, the concentrations of three biomarkers were measured: l-arginine, asymmetric dimethylarginine, and uric acid. Thirty-one patients were included in the study. The intention-to-treat analysis of the primary outcome had 26 patients due to missing data. The estimated marginal mean difference in RHI at day 14 and day 84 between the groups was 0.15 (95% CI: 0.29-0.01, P = .039) in favor of the placebo group. No significant differences in the biomarker concentrations were found. Melatonin treatment after ACS did not improve but may have aggravated ED. The significant difference between groups was in favor of placebo, but this might be due to the effect of missing data or uneven distribution of comorbidities.