Sterile Water Versus Glycine in Transurethral Resection of Bladder Tumors-Immunogenic and Clinical Implications.

BACKGROUND AND OBJECTIVE: We compared the oncologic outcomes of patients with non-muscle invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumor (TUBRT) using sterile water vs glycine irrigation. The tumoricidal and immunogenic effects of these solutions on urothelial cancer cell lines were investigated. METHODS: The medical records of 530 consecutive patients who underwent TURBT using sterile water or glycine irrigation for NMIBC were reviewed. Recurrence and progression rates were evaluated using time dependent analyses.Bladder cancer cell lines (RT4, T24 and 5637) were treated with glycine and sterile water. Cell viability was evaluated with the XTT assay. Cell membrane calreticulin levels were evaluated with flow cytometry. Extracellular high mobility group box 1 (HMGB1) and heat shock 70 (HSP70) protein levels were evaluated using western blots. KEY FINDINGS AND LIMITATIONS: After propensity score matching each study arm comprised 161 patients. Median follow-up was 13.6 months (IQR 6.2, 24.5). The 2-year recurrence free survival was significantly lower in the sterile water vs glycine group (43% vs 71%, respectively, p<0.0001). Similarly, the 2-years progression free survival was significantly lower in the sterile water vs glycine group (85% vs 94%, respectively, p<0.014). Sterile water treatment resulted in the lowest number of viable cells. Early and late immunogenic cell death markers were markedly elevated in cells treated with glycine. CONCLUSIONS AND CLINICAL IMPLICATIONS: Sterile water compared to glycine irrigation during TURBT for NMIBC was associated with higher recurrence and progression rates. Possible explanation for these findings is the diminished immune response associated with sterile water reflected in a comparatively lesser expression of immune response inducers. PATIENT SUMMARY: We compared two irrigation fluids in non-muscle-invasive bladder cancer surgery: glycine and sterile water. Glycine outperformed sterile water in cancer recurrence, possibly boosting immunogenicity over sterile water.

Fascial dehiscence after radical cystectomy: Is abdominal exploration mandatory?

BACKGROUND: Fascial dehiscence after radical cystectomy may have serious clinical implications. To optimize its management, we sought to describe accompanying intraabdominal findings of post-cystectomy dehiscence repair and determine whether a thorough intraabdominal exploration during its operation is mandatory. METHODS: We retrospectively reviewed a multi-institutional cohort of patients who underwent open radical cystectomy between 2005 and 2020. Patients who underwent exploratory surgery due to fascial dehiscence within 30 days post-cystectomy were included in the analysis. Data collected included demographic characteristics, the clinical presentation of dehiscence, associated laboratory findings, imaging results, surgical parameters, operative findings, and clinical implications. Potential predictors of accompanying intraabdominal complications were investigated. RESULTS: Of 1301 consecutive patients that underwent cystectomy, 27 (2%) had dehiscence repair during a median of 7 days post-surgery. Seven patients (26%) had accompanying intraabdominal pathologies, including urine leaks, a fecal leak, and an internal hernia in 5 (19%), 1 (4%), and 1 (4%) patients, respectively. Accompanying intraabdominal findings were associated with longer hospital stay [20 (IQR 17, 23) vs. 41 (IQR 29, 47) days, P = 0.03] and later dehiscence identification (postoperative day 7 [IQR 5, 9] vs. 10 [IQR 6, 15], P = 0.03). However, the rate of post-exploration complications was similar in both groups. A history of ischemic heart disease was the only predictor for accompanying intraabdominal pathologies (67% vs. 24%; P = 0.02). CONCLUSIONS: A substantial proportion of patients undergoing post-cystectomy fascial dehiscence repair may have unrecognized accompanying surgical complications without prior clinical suspicion. While cardiovascular disease is a risk factor for accompanying findings, meticulous abdominal inspection is imperative in all patients during dehiscence repair. Identification and repair during the surgical intervention may prevent further adverse, possibly life-threatening consequences with minimal risk for iatrogenic injury.

Validation of parental reports of rotavirus vaccination of their children compared to the national immunization registry.

BACKGROUND: The introduction of rotavirus vaccines into national immunization programs necessitates vaccine effectiveness evaluations. Parental report of vaccination status is a simple and accessible source of information; however, its validity is unclear. AIMS: To validate parental reports of rotavirus immunization compared to documentation of vaccination in national immunization registry, and to assess vaccine effectiveness by each method. METHODS: Parents of 1272 children aged 2-59 months from northern Israel hospitalized for gastroenteritis in 2011-2015 were interviewed on the sociodemographics and rotavirus vaccination status of their child. Rotavirus immunization status based on parental report was compared to that documented in the national immunization registry, which was considered the gold standard. Stool samples collected from patients were tested for rotavirus antigen by immunochromotgraphy. In a rotavirus test-negative case-control study, vaccination history was compared between children found positive for rotavirus and those who tested negative. Vaccine effectiveness for ≥ 1 dose vs. zero doses was calculated as: (1-adjusted odds ratio) * 100. RESULTS: The sensitivity and specificity of parental report of their child's immunization with a rotavirus vaccine were 97% (95% CI 96-98), and 75% (95% CI 65-82), respectively. Kappa coefficient was 0.69 (p < 0.001) for the agreement between the two methods. Rotavirus vaccine effectiveness was 72% (95% CI 54-84) when using parental report of rotavirus immunization and 79% (95% CI 62-88) when using the registry. CONCLUSION: Parental report of their child's immunization with a rotavirus vaccine demonstrated high sensitivity, although the specificity was relatively low. Vaccine effectiveness was similar regardless of method used to determine rotavirus immunization status. Parental report of vaccination status can be useful in vaccine effectiveness assessment.

In vivo, in vitro and in silico correlations of four de novo SCN1A missense mutations.

Mutations in the SCN1A gene, which encodes for the voltage-gated sodium channel NaV1.1, cause Dravet syndrome, a severe developmental and epileptic encephalopathy. Genetic testing of this gene is recommended early in life. However, predicting the outcome of de novo missense SCN1A mutations is difficult, since milder epileptic syndromes may also be associated. In this study, we correlated clinical severity with functional in vitro electrophysiological testing of channel activity and bioinformatics prediction of damaging mutational effects. Three patients, bearing the mutations p.Gly177Ala, p.Ser259Arg and p.Glu1923Arg, showed frequent intractable seizures that had started early in life, with cognitive and behavioral deterioration, consistent with classical Dravet phenotypes. These mutations failed to produce measurable sodium currents in a mammalian expression system, indicating complete loss of channel function. A fourth patient, who harbored the mutation p.Met1267Ile, though presenting with seizures early in life, showed lower seizure burden and higher cognitive function, matching borderland Dravet phenotypes. In correlation with this, functional analysis demonstrated the presence of sodium currents, but with partial loss of function. In contrast, six bioinformatics tools for predicting mutational pathogenicity suggested similar impact for all mutations. Likewise, homology modeling of the secondary and tertiary structures failed to reveal misfolding. In conclusion, functional studies using patch clamp are suggested as a prognostic tool, whereby detectable currents imply milder phenotypes and absence of currents indicate an unfavorable prognosis. Future development of automated patch clamp systems will facilitate the inclusion of such functional testing as part of personalized patient diagnostic schemes.