Predictive Power of the "Trigger Tool" for the detection of adverse events in general surgery: a multicenter observational validation study

Background In spite of the global implementation of standardized surgical safety checklists and evidence-based practices, general surgery remains associated with a high residual risk of preventable perioperative complications and adverse events. This study was designed to validate the hypothesis that a new “Trigger Tool” represents a sensitive predictor of adverse events in general surgery. Methods An observational multicenter validation study was performed among 31 hospitals in Spain. The previously described “Trigger Tool” based on 40 specific triggers was applied to validate the predictive power of predicting adverse events in the perioperative care of surgical patients. A prediction model was used by means of a binary logistic regression analysis. Results The prevalence of adverse events among a total of 1,132 surgical cases included in this study was 31.53%. The “Trigger Tool” had a sensitivity and specificity of 86.27% and 79.55% respectively for predicting these adverse events. A total of 12 selected triggers of overall 40 triggers were identified for optimizing the predictive power of the “Trigger Tool”. Conclusions The “Trigger Tool” has a high predictive capacity for predicting adverse events in surgical procedures. We recommend a revision of the original 40 triggers to 12 selected triggers to optimize the predictive power of this tool, which will have to be validated in future studies

Management of acute diverticulitis with pericolic free gas (ADIFAS). an international multicenter observational study

Background: There are no specific recommendations regarding the optimal management of this group of patients. The World Society of Emergency Surgery suggested a nonoperative strategy with antibiotic therapy, but this was a weak recommendation. This study aims to identify the optimal management of patients with acute diverticulitis (AD) presenting with pericolic free air with or without pericolic fluid. Methods: A multicenter, prospective, international study of patients diagnosed with AD and pericolic-free air with or without pericolic free fluid at a computed tomography (CT) scan between May 2020 and June 2021 was included. Patients were excluded if they had intra-abdominal distant free air, an abscess, generalized peritonitis, or less than a 1-year follow-up. The primary outcome was the rate of failure of nonoperative management within the index admission. Secondary outcomes included the rate of failure of nonoperative management within the first year and risk factors for failure. Results: A total of 810 patients were recruited across 69 European and South American centers; 744 patients (92%) were treated nonoperatively, and 66 (8%) underwent immediate surgery. Baseline characteristics were similar between groups. Hinchey II-IV on diagnostic imaging was the only independent risk factor for surgical intervention during index admission (odds ratios: 12.5, 95% CI: 2.4-64, P =0.003). Among patients treated nonoperatively, at index admission, 697 (94%) patients were discharged without any complications, 35 (4.7%) required emergency surgery, and 12 (1.6%) percutaneous drainage. Free pericolic fluid on CT scan was associated with a higher risk of failure of nonoperative management (odds ratios: 4.9, 95% CI: 1.2-19.9, P =0.023), with 88% of success compared to 96% without free fluid ( P <0.001). The rate of treatment failure with nonoperative management during the first year of follow-up was 16.5%. Conclusion: Patients with AD presenting with pericolic free gas can be successfully managed nonoperatively in the vast majority of cases. Patients with both free pericolic gas and free pericolic fluid on a CT scan are at a higher risk of failing nonoperative management and require closer observation

Clasificación de textos adaptada para conversión de texto en habla multidominio

En este trabajo se presenta un sistema de clasificación de textos adaptado a las necesidades que plantea la conversión de texto en habla multidominio. Este sistema, que es una evolución de una propuesta anterior basada en la representación de los textos mediante un grafo de nodos ponderados, ha sido desarrollado para mejorar la eficiencia de clasificación de textos cortos, así como para minimizar el coste computacional de la misma. Para ello, se trabaja sobre el espacio de comparación definido por el texto a clasificar en lugar de utilizar el construido a partir de los documentos de entrenamiento. Los experimentos de clasificación desarrollados sobre un corpus de textos publicitarios muestran la consecución de los objetivos planteados.This paper introduces a text classification system tuned to cope with the requirements of multi-domain text-to-speech synthesis. This method, based on a previous system which represents texts by means of a weighted graph, has been developed to improve the classification efficiency for small texts and to minimize its computational cost. To that effect, the comparison space is built from the input text instead of being built from the training documents. Classification experiments conducted on an advertising text corpus show the achievement of the posed goals.Trabajo financiado en parte por el proyecto IntegraTV-4all (FIT-350301-2004-2) del MCyT

Severe and malignant hypertension are common in primary atypical hemolytic uremic syndrome

Malignant hypertension is listed among the causes of secondary thrombotic microangiopathy (TMA), but pathogenic mutations in complement genes have been reported in patients with hypertension-induced TMA. Here we investigated the frequency and severity of hypertension in 55 patients with primary atypical hemolytic uremic syndrome (aHUS). A genetic analysis was performed in all patients, and funduscopic examination was performed in all the patients with Grades 2 and 3 hypertension. A cohort of 110 patients with malignant hypertension caused by diseases other than aHUS served as control. Thirty-six patients with aHUS presented Grade 2 or Grade 3 hypertension and funduscopic examination showed malignant hypertension in 19. Genetic abnormalities in complement were found in 19 patients (37% among patients with malignant hypertension). Plasmapheresis was performed in 46 patients and 26 received eculizumab. Renal and hematological responses were significantly lower after plasmapheresis (24%) than after eculizumab (81%). Renal survival was significantly higher in patients treated with eculizumab (85% at one, three and five years) compared to patients who did not receive this treatment (54%, 46% and 41%), respectively. Response to eculizumab was independent of hypertension severity and the presence of complement genetic abnormalities. Among patients with malignant hypertension caused by other diseases the prevalence of TMA was very low (5%). Thus, severe and malignant hypertension are common among patients with aHUS and eculizumab treatment leads to a higher renal survival when compared to plasmapheresis. However, TMA is uncommon among patients presenting with malignant hypertension caused by diseases other than aHUS.Work in this study was supported by the Instituto de Salud Carlos III /Fondo Europeo de Desarrollo Regional (ISCIII/FEDER) grants PI13/02502, PICI14/00350, and PI16/01685 (to MP), and grants PI13/00802, PI14/00883 and PI17/00130 (to JAM.); the ISCIII/FEDER Programa Miguel Servet, grants CP10/00479 and CPII16/00017 (to JAM); the Spanish “Ministerio de Economía y Competitividad/FEDER” [SAF2015-66287-R] (to SRdeC); the Autonomous Region of Madrid (S2017/BMD-3673) (to SRdeC, EA and MP); Red de Investigación Renal (RedInRen) (RD12/0021/0029) (to MP), the “Fundación Inocente” (Madrid, Spain).] (to SRdC), and the Spanish Society of Nephrology and Fundación Renal Ínigo Álvarez de Toledo (FRIAT) (to JAM).Peer reviewe

Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial

BackgroundSparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis.MethodsPROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin–angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850.FindingsBetween Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6–110) was −2·7 mL/min per 1·73 m2 per year versus −3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1–week 110) was −2·9 mL/min per 1·73 m2 per year versus −3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI −0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (−42·8%, 95% CI −49·8 to −35·0, with sparsentan versus −4·4%, −15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals.InterpretationOver 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial

Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to 1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics

Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial

Background Sparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis. Methods PROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin–angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850. Findings Between Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6–110) was −2·7 mL/min per 1·73 m2 per year versus −3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1–week 110) was −2·9 mL/min per 1·73 m2 per year versus −3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI −0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (−42·8%, 95% CI −49·8 to −35·0, with sparsentan versus −4·4%, −15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals. Interpretation Over 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function.</p