Revision of the duodenal switch: indications, technique, and outcomes

BACKGROUND: Duodenal switch (DS) operation combines both restrictive and malabsorptive components and has become an accepted operation in selected patients with morbid obesity. Complications develop in some patients, which are refractory to dietary supplementation. We report a series of 33 patients who required partial revision of the DS. STUDY DESIGN: During the 10-year period after September 1992, 701 patients had DS operation performed; of these, 33 (5 men and 28 women) patients required revision. Revision was performed by side to side enteroenterostomy 100 cm proximal to the original anastamosis. Outcomes measures reviewed include postoperative complications, nutritional parameters, and weight change. RESULTS: Revision was performed a median of 17 (range 7 to 63) months after DS. Indications for revision included protein malnutrition (n = 20), diarrhea (n = 9), metabolic abnormalities (n = 5), abdominal pain (n = 3), liver disease (n = 2), emesis (n = 2), and gastrointestinal bleed (n = 1). Median body mass index at the time of revision was 28. Median serum albumin was 3.6 g/dL and improved to 4.0 g/dL postoperatively (p = 0.01). Complications occurred in 5 of 32 patients (15%) and included wound infection (n = 2), respiratory failure (n = 1), gastrointestinal bleed (n = 1), and small bowel obstruction (n = 1). There was no perioperative mortality. During a median followup period after revision of 39 months, the median weight gain was 18 pounds. Three patients requested repeat operation because of weight regain. CONCLUSIONS: Patients requiring revision of DS for malnutrition can be corrected by a technically simple procedure, but they are at considerable risk for complications. Although many patients are anxious about regaining their weight after reversal, they can be reassured that substantial weight gain is unlikely.     

Pharmacologic characterization of a potent inhibitor of class I phosphatidylinositide 3-kinases

Extensive evidence implicates activation of the lipid phosphatidylinositide 3-kinase (PI3K) pathway in the genesis and progression of various human cancers. PI3K inhibitors thus have considerable potential as molecular cancer therapeutics. Here, we detail the pharmacologic properties of a prototype of a new series of inhibitors of class I PI3K. PI103 is a potent inhibitor with low IC50 values against recombinant PI3K isoforms p110alpha (2 nmol/L), p110beta (3 nmol/L), p110delta (3 nmol/L), and p110gamma (15 nmol/L). PI103 also inhibited TORC1 by 83.9% at 0.5 micromol/L and exhibited an IC50 of 14 nmol/L against DNA-PK. A high degree of selectivity for the PI3K family was shown by the lack of activity of PI103 in a panel of 70 protein kinases. PI103 potently inhibited proliferation and invasion of a wide variety of human cancer cells in vitro and showed biomarker modulation consistent with inhibition of PI3K signaling. PI103 was extensively metabolized, but distributed rapidly to tissues and tumors. This resulted in tumor growth delay in eight different human cancer xenograft models with various PI3K pathway abnormalities. Decreased phosphorylation of AKT was observed in U87MG gliomas, consistent with drug levels achieved. We also showed inhibition of invasion in orthotopic breast and ovarian cancer xenograft models and obtained evidence that PI103 has antiangiogenic potential. Despite its rapid in vivo metabolism, PI103 is a valuable tool compound for exploring the biological function of class I PI3K and importantly represents a lead for further optimization of this novel class of targeted molecular cancer therapeutic.     

Evaluating the Effect of an Educational Intervention for Nursing Managers on the Rate of Incidents Reported at University Hospitals of Iran

In this semiexperimental study conducted at the university hospitals in an urban area of Iran, the number of reported incidents—as per the information from offices—was evaluated and recorded for the improvement of the quality of hospitals. Subsequently, an educational intervention was conducted for nursing managers. Three months later, the number of reported incidents was again evaluated and recorded. According to the results, the number of reported incidents increased in the hospitals after the educational intervention. The results of this study could be helpful for hospital personnel, especially nurses, to improve the culture of incident self-reporting.     

Leishmanial antigens in liposomes promote protective immunity and provide immunotherapy against visceral leishmaniasis via polarized Th1 response

Leishmaniasis affects 12 million people, and it is generally agreed that vaccination provides the best long-term strategy for its control. An ideal vaccine should be effective in both preventing and treating leishmaniasis. However, immunological correlates to predict vaccine efficacy and success of treatment in visceral leishmaniasis (VL) remain ill defined. Here, we correlated the vaccine efficacy of soluble leishmanial antigens (SLA) from Leishmania donovani promastigote membrane, entrapped in negative, neutral and positively charged liposomes with the elicited immune responses to predict vaccine success in experimental VL. Production of both IFN-gamma and IL-4 with a dominance of Th1 response following immunization was required for optimum success against L. donovani infection in BALB/c mice. The best vaccine formulation, SLA in positively charged liposomes, was then used for immunotherapy. This vaccine induced more than 90% elimination of parasites from both liver and spleen. The success of immunotherapy exhibited an immune modulation with surge in Th1 cytokines, IFN-gamma and IL-12 with extreme down regulation of disease promoting IL-4 and IL-10. These findings suggest that an immune modulation towards Th1 is effective for both successful vaccination and immunotherapy.     

Non-coding pDNA bearing immunostimulatory sequences co-entrapped with leishmanial antigens in cationic liposomes elicits almost complete protection against experimental visceral leishmaniasis in BALB/c mice

The difficulty in making successful vaccines against leishmaniasis is partly due to lack of an appropriate adjuvant. Non-coding plasmid DNA (pDNA) bearing immunostimulatory sequences (ISS) is a potent activator of innate immunity, and can thus act as an adjuvant with vaccine antigen. We therefore evaluated the efficacy of pDNA and soluble leishmanial antigens (SLA) to protect against challenge with Leishmania donovani infection. We demonstrate that immunomodulatory activity of pDNA, which potentiated a Th1 immune responses, led to enhanced protection with SLA. Importantly, adding cationic liposomes as vehicle to the antigen, with pDNA either complexed or entrapped within, significantly increased the potentiating effect of pDNA. Further, comparison of the two vaccine formulations demonstrated an impressive increase in the protective efficacy up to two folds when both antigen and pDNA were within the vehicle. Thus, these studies establish the utility of non-coding pDNA bearing ISS as strong promoters of vaccine potency of liposomal antigens especially when co-entrapped with the antigen in cationic liposomes.     

Predictors of Depression in Men With Peyronie's Disease Seeking Evaluation

BackgroundPeyronie's disease (PD) has negative impacts on the psychosocial status of men including depression warranting clinical evaluation in up to 50% of men.AimTo examine predictors of depression in patients with early PD seeking evaluation.MethodsAll PD patients at a high-volume PD practice underwent screening and curvature assessment after intracavernosal injection. Complex deformity was defined as any degree of multiplanar curvature, curvature >60 degrees, or presence of hourglass deformity. Men completed the PD questionnaire (PDQ), a validated depression questionnaire (CES-D) as well as the Self-Esteem and Relationship (SEAR) questionnaire. Scores of ≥16 on CES-D were considered indicative of moderate/severe depression. Predictors of the presence of depression were defined using univariable and multivariable logistic regression.OutcomesDemographic, bother and curve related predictors of depression in men with PD.Results408 men completed all questionnaires. Mean age was similar between depressed and nondepressed groups (57 ± 10 years overall, P = .60 between groups). Proportions of erectile dysfunction were similar between groups (P = .96). Mean PD duration was similar between groups (19 ± 35 months overall, P = .46 between groups). Mean degree of curvature was 38 ± 2 degrees in the depressed vs 33 ± 1 degrees in the nondepressed groups (P = .03). A complex deformity was seen in 64.5% in the depressed vs 61.5% in the nondepressed (P = .56). A total of 110 (27%) patients had CESD scores ≥16. 74% depressed men were in relationships compared to 84% nondepressed men (P < .01). Other characteristics including bother, pain, duration of disease, curve complexity and instability were similar between the two groups. On univariable analysis, factors protective against depression included being partnered (OR 0.42, 95%CI 0.24–0.75, P < .01) and higher total SEAR scores (OR 0.95, 95%CI 0.94–0.97, P < .01). Elevated PDQ domain scores were associated with depression (Psychologic Symptoms 1.05, 95%CI 1.02–1.10, P < .01; Pain 1.08, 95%CI 1.03–1.12, P < .01; Bother 1.11, 95% CI 1.05–1.68, P < .01) as well as baseline history of depression (OR 2.93, 95%CI 1.67–5.14, P < .001). On multivariable analysis, only total SEAR score remained protective against depression (OR 0.96, 95%CI 0.94–0.97, P < .001).Clinical ImplicationsProviders must recognize that men with PD seeking evaluation have meaningful rates of depression for which early recognition is necessary.Strengths and LimitationsRetrospective review of a large prospectively collected dataset from a single center of men with PD utilizing a validated screening tool for depression.ConclusionWhile no significant demographic, bother or curve related factors predicted depression in early PD men seeking evaluation, it remains a significant problem warranting further prospective evaluation.P. Nahid, N. Bruno, S. Carolyn, et al. Predictors of Depression in Men With Peyronie's Disease Seeking Evaluation. J Sex Med 2021;18:783–788.