Prognostic Significance of Wnt-1, β-catenin and E-cadherin Expression in Advanced Colorectal Carcinoma

Wnt/β-catenin pathway plays an important role in initiation and progression of colorectal oncogenesis. The aim of this study was to determine expression and localization of E-cadherin, β-catenin and Wnt-1 proteins in colorectal tumors. Expression of β-catenin, E-cadherin and Wnt-1 was determined by immunohistochemistry on advanced colorectal cancers. Abnormal expression of E-cadherin, β-catenin, Wnt-1 was observed. Additionally, we revealed correlations between levels of studied proteins and histoclinical data. In multivariate analysis nuclear β-catenin, higher carcinoembryonic antigen serum level before treatment, female sex and tumor localized in colon or rectum were independent unfavorable prognostic factors. These findings support the hypothesis that Wnt/β-catenin pathway plays an important role in advanced colorectal carcinoma

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Brief and Telehealth Acceptance and Commitment Therapy (ACT) Interventions for Stress in Inflammatory Bowel Disease (IBD): A Series of Single Case Experimental Design (SCED) Studies

Psychological intervention targeting distress is now considered an integral component of inflammatory bowel disease (IBD) management. However, significant barriers to access exist which necessitate the development of effective, economic, and accessible brief and remote interventions. Acceptance and commitment therapy (ACT) is a therapy with demonstrated acceptability and a growing evidence base for the treatment of distress in IBD populations. The present paper trialled two brief ACT interventions via randomized multiple baseline designs. Study 1 trialled a single-session ACT intervention (delivered face-to-face and lasting approximately two hours) targeting stress and experiential avoidance, respectively. Participants were seven people with an IBD diagnosis who presented with moderate to extremely severe stress (five females, two males; M age = 39.57, SD = 5.74). The findings of study 1 indicate that a single-session ACT intervention represented an insufficient dosage to reduce stress and experiential avoidance. Study 2 investigated a brief telehealth ACT intervention (delivered via a video conferencing platform and lasting approximately four hours) targeting stress and increased psychological flexibility. Participants (N = 12 people with an IBD diagnosis and mild to extremely severe stress) completed baselines lasting from 21 to 66 days before receiving a two-session ACT telehealth intervention supplemented by a workbook and phone consultation. Approximately half of participants experienced reduced stress, increased engagement in valued action, and increased functioning. Despite shortcomings such as missing data and the context of COVID-19, the present findings suggest that brief ACT interventions in this population may be effective and economic, though further research and replications are necessary

Severe Symptomatic Primary CMV Infection in Inflammatory Bowel Disease Patients with Low Population Seroprevalence

Background. Cytomegalovirus disease in patients with inflammatory bowel disease is frequently the result of viral reactivation. Conversely, primary CMV infection is believed to be uncommon in immunocompetent adults due to high population seroprevalence. Objectives. The aim of this study was to examine the frequency and severity of primary cytomegalovirus infection in an adult cohort of IBD patients. Study Design. A retrospective review of a prospectively maintained database of 3200 IBD patients attending a single academic centre was performed. Patients with primary CMV infection 2010–13 were identified; clinical, serologic, and virologic parameters were studied in detail. The seroprevalence of CMV in the patient population was also evaluated. Results. Eight patients with IBD (UC = 3, IBD-U = 1, CD = 4) presented with primary CMV infection. Patients presented with both gastrointestinal and extraintestinal symptoms. Mean age was 33 years, and median duration of disease was 72 months. All eight patients were receiving a thiopurine immunomodulator. Median duration of IM use was 144 weeks (range 7–720 weeks). All 8 patients required hospitalisation, with 1 ICU admission; the median length of hospital stay was 11 days (range 6–27). Infection resolved in all cases with withdrawal of immunomodulator and/or antiviral therapy. Seroprevalence of IgG to CMV, indicating prior exposure, in a subgroup of IBD patients (n=80) was 30.5% and increased with age. Conclusion. Primary cytomegalovirus infection can cause a severe illness in IBD patients, particularly those receiving immunosuppression. In areas where adult CMV seroprevalence is low, evidence of CMV should be sought in IBD patients presenting with any febrile systemic illness