CAGS AND ACS EVIDENCE BASED REVIEWS IN SURGERY. 49: Is a diverting loop ileostomy and colonic lavage an alternative to colectomy for the treatment of severe Clostridium difficile–associated disease?

Objective: To determine whether a colon-sparing diverting ileostomy with colonic lavage reduces mortality in patients with severe Clostridium difficile–associated disease (CDAD) when compared with colectomy. Design: Retrospective cohort study. Setting & patients: Forty-two patients with diagnosed severe, complicated CDAD who were treated at the University of Pittsburgh Medical Center or VA Pittsburgh Health Care System between June 2009 and January 2011 with diverting loop ileostomy and colonic lavage (warmed polyethylene glycol 3350/electrolyte solution via the ileostomy and postoperative antegrade instillation of vancomycin flushes via the ileostomy). Patients were compared with a historical control group of 42 patients who had a colectomy. Main outcome: Resolution of CDAD. Results: There was no significant difference in age, sex, pharmacologic immuno-suppression and Acute Physiology and Chronic Health Evaluation-II (APACHE-II) scores between the current cohort and historical controls. In the ileostomy group, surgery was performed laparoscopically in 35 patients (83%). This treatment strategy resulted in reduced mortality compared with the historical population (19% v. 50%; odds ratio [OR] 0.24, p = 0.006). Preservation of the colon was achieved in 39 of 42 patients (93%). Conclusion: Loop ileostomy and colonic lavage are an alternative to colectomy in the treatment of severe, complicated CDAD, resulting in reduced morbidity and preservation of the colon.     

Hepatocellular carcinoma in a large Canadian urban centre: Stage at treatment and its potential determinants

OBJECTIVE:

To determine whether there is a significant difference in tumour stage between patients initially found with hepatocellular carcinoma (HCC) at a tertiary hepatobiliary centre and patients referred with tumours detected elsewhere; and to determine variables associated with referral in a palliative stage.

METHODS:

A retrospective review of 12,199 patients seen at a liver clinic over a 10.5-year period revealed 236 patients with HCC first detected internally (internal) and 163 who were referred with a known mass (referred). All patients were staged at the time of treatment using the Milan criteria for transplantation and Barcelona Clinic Liver Cancer (BCLC) staging system. Curative disease was defined as BCLC stages 0 and A. In the referred group, univariate and multivariate analyses were used to determine which of the following factors were significantly associated with presentation in a palliative stage: age, sex, ethnicity, cause of liver disease, presence of cirrhosis, location of residence and quintile of neighbourhood income.

RESULTS:

In comparing the internal versus referred patients, significant differences were found in the proportion of patients fulfilling Milan criteria (72% versus 36%), those with curative disease (75% versus 49%) and those with very early stage tumour (BCLC stage 0, 23% versus 7%); all differences were statistically significant (P<0.001). In patients referred for treatment of HCC from an outside institution, none of the variables tested were associated with presentation in a palliative stage.

CONCLUSION:

Patients with HCC referred to a liver treatment centre were more likely to be in palliative stages than those whose tumour was detected internally.     

Autophagy and oxidative stress in gliomas with IDH1 mutations

IDH1 mutations in gliomas associate with longer survival. Prooxidant and antiproliferative effects of IDH1 mutations and its d-2-hydroxyglutarate (2-HG) product have been described in vitro, but inconsistently observed. It is also unclear whether overexpression of mutant IDH1 in wild-type cells accurately phenocopies the effects of endogenous IDH1-mutations on tumor apoptosis and autophagy. Herein we investigated the effects of 2-HG and mutant IDH1 overexpression on proliferation, apoptosis, oxidative stress, and autophagy in IDH1 wild-type glioma cells, and compared those results with patient-derived tumors. 2-HG reduced viability and proliferation of U87MG and LN18 cells, triggered apoptosis in LN18 cells, and autophagy in U87MG cells. In vitro studies and flank xenografts of U87MG cells overexpressing R132H IDH1 exhibited increased oxidative stress, including increases of both manganese superoxide dismutase (MnSOD) and p62. Patient-derived IDH1-mutant tumors showed no significant differences in apoptosis or autophagy, but showed p62 accumulation and actually trended toward reduced MnSOD expression. These data indicate that mutant IDH1 and 2-HG can induce oxidative stress, autophagy, and apoptosis, but these effects vary greatly according to cell type.     

Parental Depression Confers Greater Prospective Depression Risk to Females than Males in Emerging Adulthood

Females are at greater risk of depression than males, a pattern arising in adolescence and continuing in adulthood. One hypothesis is that major risk factors operate more robustly for females. We tested whether parental depression history imposes greater prospective depression risk for female emerging adults in a large community sample (ages 18–19, N = 637). Utilizing linear mixed regressions to model symptom changes over 2 years, we found the predictive utility of parental depression varied by gender. Females had higher depression symptoms overall, and those with parental depression remained at high levels throughout the adulthood transition, compared to at-risk males whose elevated symptoms decreased. This effect was specific to offspring depression (versus anxiety) and was found only for parental depression (versus other disorders). Female emerging adults with a parental depression history are at increased risk for future depression symptom elevations, which may partially explain their increased risk for depressive disorders in adulthood.     

Virtual Reality Job Interview Training in Adults with Autism Spectrum Disorder

The feasibility and efficacy of virtual reality job interview training (VR-JIT) was assessed in a single-blinded randomized controlled trial. Adults with autism spectrum disorder were randomized to VR-JIT (n = 16) or treatment-as-usual (TAU) (n = 10) groups. VR-JIT consisted of simulated job interviews with a virtual character and didactic training. Participants attended 90 % of laboratory-based training sessions, found VR-JIT easy to use and enjoyable, and they felt prepared for future interviews. VR-JIT participants had greater improvement during live standardized job interview role-play performances than TAU participants (p = 0.046). A similar pattern was observed for self-reported self-confidence at a trend level (p = 0.060). VR-JIT simulation performance scores increased over time (R ² = 0.83). Results indicate preliminary support for the feasibility and efficacy of VR-JIT, which can be administered using computer software or via the internet.