Impact of first-line antiretroviral therapy regimens on the restoration of the CD4/CD8 ratio in the CNICS cohort

Background: The CD4/CD8 ratio is an indicator of immunosenescence and a predictor of all-cause mortality in HIV-infected patients. The effects of different ART regimens on CD4/CD8 ratio recovery remain unclear. Methods: Clinical cohort study of ART-treated patients from the CFAR Network of Integrated Clinical Systems (CNICS). We included ART-naive adults with HIV infection who achieved undetectable HIV RNA during the first 48 weeks of treatment and had additional follow-up 48 weeks after virological suppression (VS). Primary endpoints included increase in CD4/CD8 ratio at both timepoints and secondary endpoints were CD4/CD8 ratio recovery at cut-offs of ≥0.5 or ≥1.0. Results: Of 3971 subjects who met the study criteria, 1876 started ART with an NNRTI, 1804 with a PI and 291 with an integrase strand transfer inhibitor (INSTI). After adjusting for age, sex, race, year of entry, risk group, HCV serostatus, baseline viral load and baseline CD4/CD8 ratio, subjects on an NNRTI showed a significantly greater CD4/CD8 ratio gain compared with those on a PI, either 48 weeks after ART initiation or after 48 weeks of HIV RNA VS. The greater CD4/CD8 ratio improvement in the NNRTI arm was driven by a higher decline in CD8 counts. The INSTI group showed increased rates of CD4/CD8 ratio normalization at the ≥1.0 cut-off compared with the PI group. Conclusions: NNRTI therapy was associated with a greater increase in the CD4/CD8 ratio compared with PIs. NNRTI- and INSTI-based first-line ART were associated with higher rates of CD4/CD8 ratio normalization at a cutoff of 1.0 than a PI-based regimen, which might have clinical implications

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

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

Registro ACESUR: atención de pacientes adultos con crisis epilépticas en servicios de urgencias: diferencias entre primer episodio y recurrencia

Objetivo. Describir las características y la atención recibida de pacientes adultos que consultan por crisis epiléptica (CE) en los servicios de urgencias hospitalarios (SUH), diferenciando entre primera crisis y recurrencia en epiléptico conocido. Método. ACESUR es un registro observacional de cohortes multipropósito, prospectivo y multicéntrico con un muestreo sistemático, los días pares de febrero y julio alternando con los impares de abril y octubre de 2017. Se incluyeron pacientes 18 años con diagnóstico de CE en los SUH. Se recogieron variables clínico-asistenciales de la visita índice de pacientes, distinguiendo entre primera CE y recurrencia en epiléptico. Resultados. El registro ACESUR recogió a 664 pacientes procedentes de 18 SUH españoles, 229 (34, 5%) con primera CE y 435 (65, 5%) con CE recurrentes. Los pacientes con primera CE fueron de mayor edad (p < 0, 001), presentaron motivos de consulta distintos (p < 0, 001) y requirieron más traslados en ambulancia (p < 0, 001). La atención recibida en el SUH fue diferente, en pacientes con primera CE se solicitó con mayor probabilidad una prueba complementaria específica (OR ajustada = 13, 94; IC95%:7, 29-26, 7; p < 0, 001) y se necesitó mayor hospitalización o estancia prolongada en el SUH (OR ajustada = 1, 69; IC95%:1, 11-2, 58; p = 0, 015). No hubo diferencias en cuanto al tratamiento farmacológico en fase aguda ni preventivo (OR ajustada = 1, 40; IC95%:0, 94-2, 09; p = 0, 096). Se inició tratamiento con fármacos antiepiépticos (FAE) en 100 pacientes (43, 7%) tras primera CE y se reinició o modificó añadiendo nuevo FAE en 142 pacientes (32, 6%) con CE recurrentes. Conclusiones. Las características clínicas y la atención recibida de pacientes adultos con primera CE en SUH en España difieren de las recurrencias en epiléptico conocido. Objective. To describe the characteristics of care received by patients who come to the emergency department with a first epileptic seizure versus a recurrent seizure in a patient with diagnosed epilepsy. Methods. ACESUR (Acute Epileptic Seizures in the Emergency Department) is a prospective multicenter, multipurpose registry of cases obtained by systematic sampling on even days in February and July 2017 and on odd days in April and October 2017. Patients were aged 18 years or older and had an emergency department diagnosis of epileptic seizure. We recorded clinical variables and details related to care given during each patient''s visit, including whether the event was a first or recurrent seizure. Results. A total of 664 patients attended by 18 Spanish emergency departments were entered into the ACESUR registry. Two hundred twenty-nine (34.5%) were first seizures and 435 (65.5%) were recurrences. Patients who were attended for first seizures were older, consulted for a wider variety of reasons, and were transported in ambulances (P<.001, all comparisons). Care received differed between patients with first seizures versus recurrent seizures. Specific complementary testing was more likely in patients with first seizures (adjusted odds ratio [aOR], 13.94; 95% CI, 29-26.7; P<.001), and they were more often hospitalized or stayed longer in the emergency department, (aOR, 1.69; 95% CI, 1.11-2.58; P=.015). Pharmacologic treatment did not differ between the groups, either in the acute phase or for prevention (aOR, 1.40; 95% CI, 0.94-2.09; P=.096). Antiepileptic drugs were given to 100 patients (43.7%) after a first seizure and were restarted or changed in 142 patients with recurrent seizure (32.6%). Conclusions. The clinical characteristics of adults attended for a first epileptic seizure differ from those of patients with diagnosed epilepsy who were attended for recurrent seizures in Spain. The care received also differs

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele