EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference

The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique\u2014Subtype and Stage Inference (SuStaIn)\u2014able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer\u2019s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18 7 10 124 ) or temporal stage (p = 3.96 7 10 125 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine

Local structural preferences in shaping tau amyloid polymorphism

Tauopathies encompass a group of neurodegenerative disorders characterised by diverse tau amyloid fibril structures. The persistence of polymorphism across tauopathies suggests that distinct pathological conditions dictate the adopted polymorph for each disease. However, the extent to which intrinsic structural tendencies of tau amyloid cores contribute to fibril polymorphism remains uncertain. Using a combination of experimental approaches, we here identify a new amyloidogenic motif, PAM4 (Polymorphic Amyloid Motif of Repeat 4), as a significant contributor to tau polymorphism. Calculation of per-residue contributions to the stability of the fibril cores of different pathologic tau structures suggests that PAM4 plays a central role in preserving structural integrity across amyloid polymorphs. Consistent with this, cryo-EM structural analysis of fibrils formed from a synthetic PAM4 peptide shows that the sequence adopts alternative structures that closely correspond to distinct disease-associated tau strains. Furthermore, in-cell experiments revealed that PAM4 deletion hampers the cellular seeding efficiency of tau aggregates extracted from Alzheimer’s disease, corticobasal degeneration, and progressive supranuclear palsy patients, underscoring PAM4’s pivotal role in these tauopathies. Together, our results highlight the importance of the intrinsic structural propensity of amyloid core segments to determine the structure of tau in cells, and in propagating amyloid structures in disease

Morbimortalidade da reconstrução de transito intestinal colônica em hospital universitário: análise de 42 casos

OBJETIVOS: Analisar as características demográficas, a mortalidade e morbidade associada ao procedimento. MÉTODOS: Estudo retrospectivo dos casos de reconstrução intestinal colônica um hospital universitário. Todos os pacientes tiveram o cólon preparado por solução de manitol. RESULTADOS: Do total de 42 pacientes, 80,9% (n=34) eram do sexo masculino com idade média de 42 anos. Causas que levaram a confecção da ostomia: 50% traumáticas, 29% abdome agudo clínico. A colostomia terminal foi o tipo de ostomia preferencialmente realizada em 65% dos casos acompanhado pela colostomia em alça com 35% dos casos. A técnica empregada para a anastomose foi predominantemente a manual, realizada em 69,05% dos casos (n=29). O tempo médio de internação hospitalar foi de 8,74 dias. O índice de morbidade global foi de 26,2% (n=11), destacando-se a reoperação em 9,52% (n=4) e a fístula em 7,14% (n=3) dos casos. Não ocorreu infecção de ferida operatória nessa série. A mortalidade foi de 2,38% (n=1). CONCLUSÕES: Os resultados obtidos em um hospital universitário são semelhantes aos relatados na literatura mundial. Cuidados pré e pós operatórios adequados se somam a experiência do cirurgião nas cirurgias de reconstrução de trânsito. A escolha da técnica cirúrgica deve ser padronizada através de trabalho randomizado, permitindo adoção de protocolo.<br>OBJECTIVES: To study demographyc caractheristics, morbidity and mortality associated to the procedure. METHODS: Retrospective study of colostomy closure in 42 patients. Male sex was predominant (80,9%) with median age of 42 years. Causes of colostomy were traumatic in 50% and clinic acute abdomen in 29% of the cases. Terminal colostomy was the more frequent procedure (65%) followed by loop colostomy in 35% of the cases. The predominant anastomotic technique was manual (69,05%). The morbidity rate was 26,2%, including reoperation (9,52%) and colonic fistulae in 7,14% cases. No postoperative wound infection was observed. Overall mortality rate was 2,38%. CONCLUSION: The results observed in a university hospital are as good as reported in world literature. Adequate pre and postoperative care works together with surgeon experience on colostomy closure surgeries. The surgical technique must be adopted using a randomized study, allowing establishment of a protocol