Fractional excretion of sodium after renal transplantation

Fractional excretion of sodium after renal transplantation. After renal transplantation low urinary sodium concentration (UNa) has been used to diagnose acute rejection (AR), for the early phase of AR is often associated with reduced renal perfusion. Early postoperative graft failure without low UNa favors the diagnosis of ischemic tubular damage (ATN). As fractional excretion of filtered sodium (FENa) better reflects glomerulotubular balance in renal sodium handling, FENa was analyzed during the first 2 weeks in 118 renal allografts. From data on 41 transplants with good early renal function (GEF), a temporal profile of FENa was obtained and used to evaluate the behavior of FFNa by means of standardized FENa (z score). Individual subjects followed their own profile with a small deviation (Δz < 1.4 for 2 days). In 31 instances, acute rejection was diagnosed. In 14 with AR, the z score deviated little; 2 responded to methylprednisolone given intravenously. In 17 with AR, the z score fell significantly (Δz > 1.5 for 2 days), an average of 2.6 days before the first rise in serum creatinine concentration; 15 responded to treatment. The difference between these two groups was significant (P < 0.001). This functional heterogeneity and different responses to treatment may indicate different immunologic mechanisms which damage different target cells in the graft in AR. In 46 patients with acute tubular necrosis after cadaver kidney transplantation FENa was significantly higher than it was in the GEF group as early as the first posttransplantation day and approached normal as the renal function recovered. This behavior of FENa was clearly different from that in AR.Excrétion fractionnelle du sodium après transplantation rénale. Après transplantation rénale une concentration urinaire de sodium (UNa) faible est considérée comme un signe de rejet aigu (AR), du fait que la phase précoce du rejet est souvent associée à une diminution du débit rénal. L'échec précoce d'une greffe sans abaissement de UNa est en faveur d'une tubulopathie ischémique (ATN). Puisque l'excrétion fractionnelle du sodium filtré (FENa) est le meilleur reflet de l'équilibre glomérulo-tubulaire concernant le sodium, FENa a été étudiée pendant les 2 premières semaines d'évolution de 118 allogreffes rénales. A partir de l'observation de 41 transplants ayant eu un bon fonctionnement précoce (GEF) un profil de FENa en fonction du temps a été obtenu et utilisé pour évaluer le comportement de FENa au moyen d'une FENa standardisée (test z). Les sujets ont suivi leur propre profil avec une déviation faible (Δz < 1,4 par 2 jours). Le rejet aigu a été diagnostiqué dans 31 cas. Quatorze d'entre eux avaient une déviation minime de z; deux ont répondu à la methylprednisolone i.v. Dix sept sujets avaient une déviation significative de z (Δz > 1,5 par 2 jours), 2,6 jours en moyenne avant la première augmentation de la créatinine; quinze ont répondu au traitement. La différence entre ces deux groupes est significative (P < 0,001). Cette hétérogénéité fonctionnelle et cette différence de réponse au traitement peuvent être la traduction de mécanismes immunologiques différents qui atteignent des cellules cibles de la greffe différentes au cours du rejet aigu. Chez 46 malades ayant des lésions ischémiques après transplantation de reins de cadavre, FENa était significativement plus élevée que dans le groupe GEF dès le premier jour après la transplantation et revenait vers la normale au fur et à mesure que la fonction rénale s'améliorait. Ce comportement de FENa est nettement différent de celui observé dans les rejets aigus

The International Natural Product Sciences Taskforce (INPST) and the power of Twitter networking exemplified through #INPST hashtag analysis

Background: The development of digital technologies and the evolution of open innovation approaches have enabled the creation of diverse virtual organizations and enterprises coordinating their activities primarily online. The open innovation platform titled "International Natural Product Sciences Taskforce" (INPST) was established in 2018, to bring together in collaborative environment individuals and organizations interested in natural product scientific research, and to empower their interactions by using digital communication tools. Methods: In this work, we present a general overview of INPST activities and showcase the specific use of Twitter as a powerful networking tool that was used to host a one-week "2021 INPST Twitter Networking Event" (spanning from 31st May 2021 to 6th June 2021) based on the application of the Twitter hashtag #INPST. Results and Conclusion: The use of this hashtag during the networking event period was analyzed with Symplur Signals (https://www.symplur.com/), revealing a total of 6,036 tweets, shared by 686 users, which generated a total of 65,004,773 impressions (views of the respective tweets). This networking event's achieved high visibility and participation rate showcases a convincing example of how this social media platform can be used as a highly effective tool to host virtual Twitter-based international biomedical research events

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Regional variations in antimicrobial susceptibility of community-acquired uropathogenic Escherichia coli in India: findings of a multicentric study highlighting the importance of local antibiograms

Background: Evidence-based prescribing is essential to optimise patient outcomes in cystitis. This requires knowledge of local antibiotic resistance rates. DASH to Protect Antibiotics (https://dashuti.com/) is a multicentric mentorship programme guiding centres in preparing, analysing and disseminating local antibiograms to promote antimicrobial stewardship in community UTI. Here we map the susceptibility profile of Escherichia coli from 22 Indian centres. Methods: These centres spanned 10 Indian States and three Union Territories. Antibiograms for urinary E. coli from the outpatient departments were collated. Standardisation was achieved by regional online training; anomalies were resolved via consultation with study experts. Data were collated and analysed. Findings: Nationally, fosfomycin, with 94% susceptibility (inter-centre range 83-97%), and nitrofurantoin with 85% susceptibility (61-97%) retained widest activity. Susceptibility rates were lower for co-trimoxazole (49%), fluoroquinolones (31%) and oral cephalosporins (26%). Rates for third- and fourth- generation cephalosporins were 46% and 52%, respectively, with 54% (33-58%) ESBL prevalence. Piperacillin-tazobactam (81%) amikacin (88%), meropenem (88%) retained better activity, but one centre in Delhi recorded only 42% meropenem susceptibility. Susceptibility rates were mostly higher in South, West and Northeast India; centres in the heavily-populated Gangetic plains, across North and Northwest India, had greater resistance. These findings highlight the importance of local antibiograms in guiding appropriate antimicrobial choices. Interpretation: Fosfomycin and nitrofurantoin are the preferred oral empirical choices for uncomplicated E. coli cystitis in India, though elevated resistance in some areas is concerning. Empiric use of fluoroquinolones and third generation cephalosporins is discouraged whereas piperacillin/tazobactam and aminoglycosides remain carbapenem-sparing parenteral agents