Reduction In Mortality Research Articles

Assessing the clinical efficacy of low-volume therapeutic plasma exchange in achieving recovery from acute liver failure induced by yellow phosphorous poisoning.

Acute liver failure (ALF) following yellow phosphorous (YP) ingestion is similar to acetaminophen-induced ALF and it has become a public concern in our region. This study assessed low volume therapeutic plasma exchange (LV-TPE) efficacy in improving the transplant free survival in YP poisoning. Adult patients with toxicology reports of YP and ALF requiring critical care were included in the study. LV-TPE was planned for three consecutive days and three more if required. Performed 1.3 to 1.5 plasma volume replacing with 0.9% normal saline, 5% human albumin solution, and fresh frozen plasma based on ASFA 2019 criteria. MELD score, laboratory parameters, LV-TPE details were captured. The study end point was clinical outcome of the patients. Among 36 patients, 19 underwent LV-TPE and 17 opted out of LV-TPE and they were included as a control arm. The MELD score was 32.64 ± 8.05 and 37.83 ± 9.37 in both groups. There were 13 survivors in LV-TPE group leading to a 68.42% reduction in mortality. The coagulation and biochemical parameters showed a significant percentage change after LV-TPE. Refractory shock, delay in initiating procedure and acidosis were independent predictors of mortality. A well-timed LV-TPE improves the survival of patients with ALF due to YP poisoning.

Patterns of Acute Ischemic Stroke Treatment from 2010 to 2020: An Evolving Landscape in Stroke Management Following Thrombectomy Trials.

Population-based studies on stroke can help guide the care of patients with acute ischemic stroke (AIS) by providing health care communities with information regarding the current usage of stroke treatments. It remains unclear how rapidly new techniques, particularly endovascular stroke treatment (EST), are being adopted and whether there is any disparity in their availability. Although studies using the National Inpatient Sample (NIS) have been conducted, updated studies over a longer period may provide further insights. This study aimed to understand patterns of AIS treatment, discharge disposition, in-hospital mortality, and mean length of stay (LOS) for each modality from 2010 to 2020 using the NIS database. This retrospective longitudinal study was conducted using NIS data from 2010 to 2020. Patients were categorized into groups based on whether they received intravenous recombinant tissue plasminogen activator (rt-PA), EST, both rt-PA and EST (combined therapy), or supportive care alone. Demographic, socioeconomic, regional, insurance, and hospital data were also obtained. The primary outcome was the proportion of patients receiving each modality, whereas the secondary outcomes were in-hospital mortality, mean LOS, and discharge disposition. The usage rates increased (p < 0.001) in all groups between 2010 and 2020 (rt-PA: 5.09% to 8.39%, EST: 0.31% to 4.40%, and rt-PA+EST: 0.46% to 1.09%). The highest increase in usage was observed for EST, with a thirteen-fold increase. Mortality decreased from 2010 to 2020 in all groups (rt-PA: 8.45% to 3.54%, EST: 25.22% to 12.50%, and rt-PA+EST: 21.12% in 2010 to 9.30%) (p < 0.001). Combination therapy demonstrated the greatest improvement, with an 11.2% reduction in absolute mortality. Mean LOS was reduced for patients who received rt-PA (6.8 to 4.8 days), EST (9.3 to 8.9 days), and combined therapy (10.0 to 8.3 days) (p < 0.001) over the study period. The proportion of patients discharged to home increased for rt-PA (29.01% to 41.85%), EST (14.13% to 17.70%), and combined therapy (12.89% to 24.29%) (p < 0.001). Overall, stroke treatment usage was higher among the higher income groups, regardless of race. Higher usage was also observed for Whites in the West and Hispanic ethnicities in the South and West. Regardless of income or treatment method, utilization rates were lower for Black patients. Utilization rates were lower for Black patients with Medicare, Medicaid, or self-pay than for White patients. Our study demonstrated that endovascular stroke treatment continues to expand, leading to better outcomes for mortality, LOS, and home discharge. Despite these positive patterns, there are visible inequities across regions, income status, and races.

Strong association between reduction of late-stage cancers and reduction of cancer-specific mortality in meta-regression of randomized screening trials across multiple cancer types.

Late-stage cancer incidence has been proposed as an early surrogate for mortality in randomized controlled trials (RCTs) of cancer screening; however, its validity has not been systematically evaluated across screening RCTs of different cancers. We conducted a meta-regression analysis of cancer screening RCTs that reported both late-stage cancer incidence and cancer mortality. Based on a systematic literature review, we included 33 RCTs of screening programs targeting seven cancer types, including lung (n = 12), colorectal (n = 8), breast (n = 5), and prostate (n = 4), among others. We regressed the relative reduction of cancer mortality on the relative reduction of late-stage cancer incidence, inversely weighted for each RCT by the variance of estimated mortality reduction. Across cancer types, the relative reduction of late-stage cancer incidence was linearly associated with the relative reduction of cancer mortality. Specifically, we observed this association for lung (R2 = 0.79 and 0.996 in three recent large trials), breast (R2 = 0.94), prostate (R2 = 0.98), and colorectal cancer (R2 = 0.75 for stage III/IV cancers and 0.93 for stage IV cancers). Trials with a 20% or greater reduction in late-stage cancers were more likely to achieve a significant reduction in cancer mortality. Our results also showed that no reduction of late-stage cancer incidence was associated with no or minimal reduction in cancer mortality. Meta-regression of historical screening RCTs showed a strong linear association between reductions in late-stage cancer incidence and cancer mortality.

Optimal timing of a colonoscopy screening schedule depends on adenoma detection, adenoma risk, adherence to screening and the screening objective: A microsimulation study.

Colonoscopy-based screening provides protection against colorectal cancer (CRC), but the optimal starting age and time intervals of screening colonoscopies are unknown. We aimed to determine an optimal screening schedule for the US population and its dependencies on the objective of screening (life years gained or incidence, mortality, or cost reduction) and the setting in which screening is performed. We used our established open-source microsimulation model CMOST to calculate optimized colonoscopy schedules with one, two, three or four screening colonoscopies between 20 and 90 years of age. A single screening colonoscopy was most effective in reducing life years lost from CRC when performed at 55 years of age. Two, three and four screening colonoscopy schedules saved a maximum number of life years when performed between 49-64 years; 44-69 years; and 40-72 years; respectively. However, for maximum incidence and mortality reduction, screening colonoscopies needed to be scheduled 4-8 years later in life. The optimum was also influenced by adenoma detection efficiency with lower values for these parameters favoring a later starting age of screening. Low adherence to screening consistently favored a later start and an earlier end of screening. In a personalized approach, optimal screening would start earlier for high-risk patients and later for low-risk individuals. In conclusion, our microsimulation-based approach supports colonoscopy screening schedule between 45 and 75 years of age but the precise timing depends on the objective of screening, as well as assumptions regarding individual CRC risk, efficiency of adenoma detection during colonoscopy and adherence to screening.

Tranexamic Acid to Prevent Obstetrical Hemorrhage After Cesarean Delivery

(N Engl J Med 2023;388(15):1365–1375) Postpartum hemorrhage is the second leading cause of pregnancy-related death in the United States, and accounts for up to 27.1% of global maternal deaths. Tranexamic acid has been previously associated with a reduction in overall mortality in several different settings, but majorly in obstetrical contexts. Research has not discovered, however, if the use of tranexamic acid is beneficial when it comes to its prophylactic use to prevent significant blood loss after birth or related other outcomes such as incidence of blood transfusion products or need for additional intervention to control bleeding. This study was a randomized trial to assess the effectiveness of tranexamic acid administered immediately after umbilical cord clamping in reducing the risk of maternal death or blood transfusion compared to placebo.

Cost-Effectiveness of Adjuvanted Quadrivalent Influenza Vaccine for Adults over 65 in France

Background: In France, influenza accounts for an average of over one million consultations with GPs, 20,000 hospitalizations, and 9000 deaths per year, particularly among the over-65s. This study evaluates the cost-effectiveness of the adjuvanted quadrivalent influenza vaccine (aQIV) compared to standard (SD-QIV) and high-dose (HD-QIV) quadrivalent influenza vaccines for individuals aged 65 and older in France. Methods: The age-structured SEIR transmission model, calibrated to simulate a mean influenza season, incorporates a contact matrix to estimate intergroup contact rates. Epidemiological, economic, and utility outcomes are evaluated. Vaccine effectiveness and costs are derived from literature and national insurance data. Quality of life adjustments for influenza attack rates and hospitalizations are applied. Deterministic and probabilistic analyses are also conducted. Results: Compared to SD-QIV, aQIV demonstrates substantial reductions in healthcare utilization and mortality, avoiding 89,485 GP consultations, 2144 hospitalizations, and preventing 1611 deaths. Despite an investment of EUR 110 million, aQIV yields a net saving of EUR 14 million in healthcare spending. Compared to HD-QIV, aQIV saves 62 million euros on vaccination costs. Cost-effectiveness analysis reveals an incremental cost-effectiveness ratio of EUR 7062 per QALY. Conclusions: This study highlights the cost-effectiveness of aQIV versus SD-QIV and HD-QIV, preventing influenza cases, hospitalizations, and deaths.

A study to evaluate WASH interventions and risk factors of diarrhoea among children under five years, Anloga district, Ghana: A research protocol.

Good Water, Sanitation and Hygiene (WASH) practices, introduction of Rotavirus vaccination, zinc supplementation and improved nutrition have contributed significantly to the reduction of diarrhoea morbidity and mortality globally by 50%. In spite of these gains, diarrhoea still remains a leading cause of morbidity and mortality in children under-five. Causes of diarrhoea are multifaceted with many factors such as seasonality, behaviour, pathogenicity, epidemiology, etc. However, assessments on the causes of diarrhoea have generally been tackled in silos over the years focusing only on particular causes. In this study, we describe an integrated approach (evaluating WASH interventions implantation processes, assessing epidemiolocal risk factors, and identifying pathogens causing diarrhoea) for assessing determinants of diarrhoea. The study has ethical approval from the Ghana Health Service Ethical Review Committee (GHSERC:020/07/22). It will employ three approaches; a process evaluation and a case-control study and laboratory analysis of diarrhoea samples. The process evaluation will assess the detailed procedures taken by the Anloga district to implement WASH interventions. A desk review and qualitative interviews with WASH stakeholders purposively sampled will be done. The evaluation will provide insight into bottlenecks in the implementation processes. Transcribed interviews will be analysed thematically and data triangulated with reviews. A 1:1 unmatched case-control study with 206 cases and 206 controls to determine risk factors associated with diarrhoea in children under-five will also be done. Odds ratios at 5.0% significance level would be calculated. Stool samples of cases will be taken and tested for diarrhoea pathogens using Standard ELISA and TAQMAN Array Card laboratory procedures. It is expected that this framework proposed would become one of the robust approaches for assessing public health community interventions for diseases. Through the process evaluation, epidemiological case-control study and pathogen identification, we would be able to identify the gaps in the current diarrhoea assessments, come up with tailored recommendations considering the existing risk and assumptions and involve the relevant stakeholders in reducing the diarrhoea burden in a coastal setting in Ghana.

Comparative analysis of clinical outcomes in patients undergoing primary CRT implantation versus CRT upgrade: single center experience

Abstract Background As heart failure (HF) management evolves, cardiac resynchronization therapy (CRT) has emerged as a cornerstone intervention, improving left ventricular (LV) function and reducing morbidity and mortality. The Budapest trial specifically addressed upgrading from permanent pacemaker (PPM) to CRT, emphasizing the potential for improved clinical outcomes and quality of life in this population. The findings highlighted the impact of CRT upgrade and contribute valuable insights to the cardiac device strategies for HF patients. This study aims to compare clinical outcomes between patients undergoing primary CRT implantation and those undergoing CRT upgrade. Methods A retrospective analysis was conducted on a cohort of heart failure patients who received CRT devices between 2015 and 2019. Patients were categorized into two groups: those undergoing primary CRT implantation and those undergoing CRT upgrade. Clinical outcomes, including mortality rate, hospitalization for HF exacerbation, and improvements in left ventricular ejection fraction (LVEF), were assessed and compared between the two groups. Results A total of 847 patients were included in the study, with 74,5% (n=631) undergoing primary CRT implantation and 13,5% (n=114) receiving CRT upgrades. The mean age was 72±10 years-old and 57% (n=485) were women, and a mean follow-up time of 23±8 months. 33.7% (n=285) of the total were of ischemic etiology. The primary CRT implantation group demonstrated a mortality of 34% (n=215) and 13% (n=84) of hospitalization due to HF; NYHA functional class improvement in 58% (n=369), and 35,7% (n=225) were CRT responders with a mean LV ejection fraction (EF) improvement of ±10%, while the CRT upgrade group had a 31% (n=36) mortality and 19% (n=22) of hospitalization due to HF; NYHA functional class improvement in 60% (n=68), and 27% (n=31) were CRT responders with a mean LV EF improvement of 8,7%. There were no statistically significant differences regarding each endpoint, namely mortality, HF hospitalizations, NYHA functional class improvement, CRT responders and mean LVEF improvement. Conclusion A clear benefit from implantation of a primary CRT device implantation has already been demonstrated. However, recent trials revealed there was also benefit in upgrading from PPM to CRT patients with decrease LVEF, comparing with PPM. This study showed that the benefits from primary CRT were similar to the benefits from upgrading CRT, in terms of mortality reduction, HF hospitalizations, NYHA functional class improvement, CRT responders and mean LVEF improvement. Once again, just like in the most recent trials, this study demonstrates the clear benefit of upgrading from a PPM to CRT in patients with decreased LVEF.

Clinical impact of ICD implantation in octogenarians: a longitudinal cohort study

Abstract Background The implantation of defibrillators (ICDs) in patients over 80 years old is becoming increasingly common; however, evidence-based data regarding the actual clinical benefit in this population remain limited and contradictory. While age seems not to affect mortality and arrhythmia risk in octogenarians undergoing secondary prevention, the mortality reduction benefit given by ICD implantation for primary prevention appears to decrease with advancing age, likely due to the high number of non-arrhythmic deaths. Purpose This study aims to assess the long-term incidence of ventricular arrhythmias and mortality in a real-world cohort of octogenarian patients undergoing ICD implants. Methods This was an observational, retrospective, longitudinal cohort study. Demographic, clinical, and radiological data were collected for all patients undergoing ICD implantation between 2014 and 2021. Deaths from all causes and significant arrhythmic events (sustained ventricular tachycardias and ventricular fibrillation) detected during routine device controls and remote monitoring were recorded. Then was performed an univariate Kaplan-Meier analysis, stratifying the population by age in relation to the two study endpoints: ventricular arrhythmias and all-cause mortality. Results Out of a total of 700 patients, 512 underwent ICD implantation before the age of 80 (mean age at implantation 64±12), while 188 underwent ICD implantation after the age of 80 (mean age at implantation 82±3.2). No significant differences were found between these two groups in terms of gender (82% vs. 83% male; p 0.12), indication for implantation (74% vs. 75% primary prevention; p 0.79), and the presence of late gadolinium enhancement (LGE) on cardiac MRI (68% vs. 77%; p 0.14). Octogenarians were more frequently affected by ischemic heart disease (54% vs. 65%; p 0.01) and were more frequently treated with Amiodarone (17% vs. 24%; p 0.02). At the end of the average 8-year follow-up, octogenarians had significantly higher all-cause mortality than younger patients (HR=2.35 [1.88-3.16]; p&amp;lt;0.05), with survival curves diverging from 3 years after implantation. However, ventricular arrhythmic events were significantly reduced in octogenarian patients (HR=0.88 [0.87-0.89]; p&amp;lt;0.05). Conclusions In a real-world population of octogenarian patients, the clinical benefit of ICD implantation for primary prevention appears diminished, considering the trade-off between ventricular arrhythmias and mortality, in both ischemic and non-ischemic cardiomyopathy patients.

Education in Obstetric Anesthesiology: An International Approach

(Int J Obstet Anesth. 2023;55:103896/https://doi.org/10.1016/j.ijoa.2023.103896 0208-5216/) Obstetric anesthesiology has transformed from administering inhaled anesthetics to handling complex cases in pregnant or postpartum patients, driven by enhanced education in the field. Different countries employ diverse approaches to prepare anesthesiology trainees for obstetric anesthesia, but common threads include competency-based education and the challenge of assessing clinical judgment and skills. In the United States, anesthesiologists undergo basic obstetric anesthesia training with optional advanced programs. Maternal mortality reduction in the 20th century reflects improved education. However, racial disparities persist in pregnancy-related morbidity and mortality, emphasizing the ongoing need for evolving obstetric anesthesiology education to help address this issue and maternal safety in general. The process involves residency and optional fellowship, ensuring competence through clinical experience. Board certification and ongoing education further contribute to advancing obstetric anesthesiology.

Validation of the Castle HTx data in a real world scenario

Abstract Background Pulmonary vein isolation (PVI) is recommended in patients with symptomatic atrial fibrillation (AF) and reduced left ventricular ejection fraction (LVEF). Recently the Castle HTx (CHTx) trial showed a significant mortality reduction in end stage heart failure patients undergoing PVI in addition to optimized medical therapy (OMT) compared to OMT only. Aim Objective of this analysis is to validate results of Castle HTx study in a real world scenario. Methods All patients between September 2021 und September 2023 referred for PVI at our center with symptomatic AF und LVEF ≤35% were included in this retrospective analysis at the University Hospital Cologne. Results A total of 119 PVI in patients with LVEF≤35% were successfully performed (mean age 63.3±10.1 years, 96 patients (81%) male, 43 (36%) paroxysmal AF, 76 (64%) persistent AF) matching inclusion criteria used in CHTx. Cryo-PVI was used in 50 (42%), RF-PVI in 60 (50%) and PFA in 9 (8%) patients. Complete follow-up (FU) with a mean of 549.6±430.2 days was obtained in 108 patients, comparable to CHtx (540 days). During FU 11 patients (10%) died from any cause (CHTx 8 patients (8%)), 2 patients (2%) received a left ventricular assist device (CHTx 1 patient (1%)) and no patient had urgent heart transplantation (CHTx 1 patient (1%)). For 30 patients (28%) recurrence of AF was detected and 72% remained in sinus rhythm. In 6 patients (5%) post-procedural complications occurred: 5 inguinal hematoma, 1 decompensation. During FU LVEF was statistically significantly improved (EF initial 26.9±6.5%, EF FU (n=80) 37.1±12.8%, p&amp;lt;0.001) (CHTx EF initial 29.0±6.4%, EF FU (n=92) 37.2±9.1%). Conclusion The findings of the Castle HTx patients have been validated in a real-world setting. PVI for rhythm control in end stage heart failure patients is safe and highly effective. Our patient cohort, matched to the Castle HTx ablation group, showed freedom from AF rate of 72% after mean FU time of 550 days. Furthermore, LVEF was improved significantly in our cohort echoing the results from CHTx.

Dose-response relationship between physical activity and the morbidity and mortality of cardiovascular disease among individuals with diabetes: A meta-analysis of prospective cohort studies.

Diabetes, a chronic condition affecting various organs, is frequently associated with abnormal lipid metabolism, notably increased cholesterol and triglyceride levels. These lipid abnormalities are closely linked to the development and advancement of cardiovascular disease (CVD). Although regular physical activity (PA) has consistently shown benefits in reducing CVD risk in the general population, its precise influence on CVD risk among diabetic patients remains uncertain, particularly regarding dose-response relationships. This study aimed to summarize the evidence from prospective studies on the association between PA and CVD morbidity and mortality in individuals with diabetes, and to explore the optimal levels for public health recommendation. We systematically reviewed prospective cohort studies in PubMed, EMBASE, and Web of Science up to December 2022, with inclusion criteria specifying the studies published in English and included adult participants diagnosed with diabetes. A random-effects model was used to pool the relative risk (RR) with the corresponding 95% confidence interval (CI) comparing the highest with the lowest PA categories in each study for qualitative evaluation. In addition, linear and spline regression analyses were used to estimate dose-response associations. The meta-analysis included 12 prospective cohort studies, involving a total of 109,820 participants with diabetes. The combined results revealed that higher levels of PA were associated with a reduced risk of CVD. The RR of CVD for the highest compared with the lowest PA category was 0.62 (95% CI, 0.51-0.73). In addition, there were four studies describing leisure-time physical activity (LTPA) and the pooled RR was 0.68 (95% CI, 0.52-0.83) for the highest versus the lowest activity. The linear regression model revealed that each 10 MET-h/week of incrementally higher PA was associated with a 19.0% (95% CI, 11.6%-25.7%) and a 6.9% (95% CI, 4.5%-9.3%) reduction in CVD morbidity and mortality. Additionally, spline regression curves showed nonlinear relationships between PA levels and the risk of CVD and CVD mortality (both P-nonlinearity <0.001), with a limited reduction in CVD risk and some further reduction in CVD mortality above 20 MET-h per week of PA levels. For patients with diabetes, especially type 2 diabetes, there was a dose-response relationship between increased PA and reduced risk of CVD morbidity and mortality. The observed PA threshold is consistent with the recommended level for the general population. Gradually moving from inactivity to a guideline-recommended PA level could therefore significantly reduce the burden of CVD in patients with diabetes.

#1098 Utilizing a novel individual patient performance score for mortality prediction in hemodialysis patients

Abstract Background and Aims Chronic kidney disease (CKD) management has advanced significantly over recent years, yet mortality rates among hemodialysis (HD) patients remain high. This study aims to assess the impact of changes in an individualized patient performance score (IPPS) on survival in a large cohort of HD patients. Method This multicentre, observational, prospective cohort study included HD patients across 19 countries, starting from January 1st, 2022. We followed these patients for one year, categorizing them based on their survival status at year's end. We calculated the mean IPPS monthly, from June to December 2021, and divided the patients into tertiles based on their December 2021 scores. Subsequently, we formed five groups based on their IPPS dynamics over six months. We used Kaplan-Meier and Cox regression analyses to evaluate survival, presenting the results as hazard ratios (HR) and 95% confidence intervals (95% CI). A p-value below 0.05 was considered statistically significant. The IPPS, ranging from 0 to 100, was calculated based on eight key performance areas, with higher scores indicating better medical performance: Vascular Access (20 points): type of vascular access, episodes of thrombosis and infection); HD adequacy (20 points): eKt/V, blood flow and treatment time; Anemia (20 points): hemoglobin concentration, transferrin saturation, ferritin; Arterial hypertension (10 points): mean arterial pressure; Mineral Bone disease (15 points): iPTH, plasmatic phosphorus and calcium; Fluid status (5 points): percentage of interdialytic fluid gain; Nutrition (5 points): plasmatic albumin and phosphorus and Others (5 points): influenzae vaccination, transplantation status and hospitalization events. The final score is obtained by the weighted sum of positive clinical factors, subtracted from the weighted sum of negative clinical factors and is reported as a number ranging from 0 to 100, with a higher score representing a better medical performance. Results The study included 10 458 HD patients. In the survival analysis, a significant increase in mortality odds was observed in patients with a stable IPPS of 72 or lower, compared to those with a score consistently above 86. Patients transitioning from the lowest to the highest tertile in six months had a mortality HR similar to those consistently in the highest tertile. On the other hand, patients showing a decrease in IPPS score from the highest to the lowest tertile in the same period had a mortality HR similar to the intermediate group (Table 1). Conclusion A lower total IPPS score (&amp;lt;72) was associated with a threefold increase in mortality risk compared to scores above 86. An increase in IPPS from the lowest to the highest tertile correlated with a significant reduction in mortality, equating to the survival rates of patients consistently scoring high. These findings underscore the potential of IPPS as a valuable tool for guiding clinical interventions in the HD population to enhance patient survival.

Effect of degalactosylated bovine glycoprotein formulations MAF and M сapsules on lymphopenia and clinical outcomes in hospitalized COVID-19 patients: a randomized clinical trial

BackgroundTargeting mucosal immunity of the gut, which is known to provide antigen processing, while avoiding excessive or unnecessary inflammation, was tested as a way to modulate COVID-19 severity.MethodsRandomized open-label trial in 204 adults hospitalized with non-critical COVID-19 who received for 14 days in addition to standard of care (SOC) degalactosylated bovine glycoproteins formulations of either MAF capsules (MAF group) or M capsules (M group) or SOC only (control group).ResultsMedian recovery time when patients did not require supplemental oxygen was 6 days in both study groups compared to 9 days in the control (MAF vs. control; P = 0.020 and M vs. control; P = 0.004). A greater reduction in mortality was seen in the MAF group compared to the control by day 14 (8.3% vs. 1.6%; P = 0.121) and by day 29 (15.3% vs. 3.2%; P = 0.020), and similarly in the M group by day 14 (8.3% vs. 2.9%; P = 0.276) and by day 29 (15.3% vs. 2.9%; P = 0.017). The proportion of those who had baseline absolute lymphocyte count (ALC) lower than 0.8 × 109/L was 13/63 (20.6%), 17/69 (24.6%), and 18/72 (25.0%) of patients in MAF, M, and control group respectively. Day 29 mortality among these lymphopenic patients was three times higher than for the intent-to-treat population (21% vs. 7%) and consisted in above subgroups: 2/13 (15%), 2/17 (12%), and 6/18 (33%) of patients. The decreased mortality in both study subgroups correlated with greater ALC restoration above 0.8 × 109/L level seen on day 14 in 91% (11/12) and 87.5% (14/16) of survivors in MAF and M subgroups respectively compared to 53.3% (8/15) of survivors in control subgroup. Incidences of any ALC decrease below the baseline level on day 14 occurred in 25.4% of patients in the MAF group and 29.0% of patients in the M group compared to 45.8% in control and ALC depletion by ≥ 50% from the baseline level consisted of 7.9%, 5.8%, and 15.3% of cases in these groups respectively.ConclusionThis study showed that both study agents prevented ALC depletion and accelerated its restoration, which is believed to be one of the mechanisms of improved crucial clinical outcomes in hospitalized COVID-19 patients.Trial registrationThe trial was registered after the trial start in ClinicalTrials.gov NCT04762628, registered 21/02/2021, https://www.clinicaltrials.gov/ct2/show/NCT04762628.

#1062 Effect of intradialytic resistance exercise on patient survival: a multicenter non-randomized cohort study

Abstract Background and Aims Intradialytic exercise significantly benefits the physical function of patients undergoing hemodialysis. Prior research into its impact on patient longevity has been constrained by small participant numbers and the lack of a control group. This study investigates the influence of exercise therapy during hemodialysis on patient lifespan in a broad multicenter cohort. Method This forward-looking, multicenter, non-randomized clinical investigation included 17 outpatient clinics from the Kaikoukai Medical Group, recruited between April and December 2018. Participants were voluntarily enlisted in an exercise regimen during their dialysis sessions and segregated into exercising and non-exercising cohorts. The trial was not blinded. The intradialytic regimen comprised stretching and four types of resistance exercises utilizing elastic tubes, conducted thrice weekly. Baseline data encompassing age, gender, stature, baseline weight, duration of hemodialysis treatment, and concurrent diabetic conditions were collected. Additional data regarding hemodialysis, including Kt/V ratio, hemodialysis blood flow rate (QB), dialysate volume (QD), and duration of dialysis, were recorded. Laboratory parameters such as albumin (Alb), calcium (Ca), potassium (K), hemoglobin (Hb), C-reactive protein (CRP), and creatinine (Cr) levels were extracted from medical records. Patient outcomes were monitored until either the occurrence of death or the study's culmination in December 2021. In statistical analyses, missing values were addressed using multiple imputation techniques, and baseline characteristics between groups were compared using an unpaired t-test. Cox proportional hazards regression analysis was employed to examine the relationship between the exercise intervention and survival, adjusting for multiple confounding variables. Three models were constructed for analysis: Model 1 incorporated basic patient data, Model 2 included hemodialysis parameters, and Model 3 involved laboratory data. The study was approved by the Ethical Committee of Nagoya Kyoritsu Hospital. Results The study encompassed 2006 subjects (average age 70.1±0.3 years), with 512 (25.5%) in the exercise group and 1494 (74.5%) in the control group. Initial comparisons indicated that the exercise group had significantly lower average height (160.9±0.3 vs. 159.7±0.4 cm, p=0.03), baseline weight (57.2±0.3 vs. 55.9±0.5 kg, p=0.04), Kt/V ratio (1.59±0 vs. 1.64±0, p=0.01), and QD (494±0.9 vs. 486.8±1.9 ml, p&amp;lt;0.01). Over the median observation period of 25 months, 338 (16.9%) patients, comprising 58 (11.3%) from the exercise group and 280 (18.7%) from the control group, succumbed. Survival analysis revealed a significant association between exercise intervention and mortality reduction, adjusted for confounders in Model 1 (HR 0.6, 95%CI 0.4-0.9, p=0.01), Model 2 (HR 0.55, 95%CI 0.37-0.8, p=0.02), and Model 3 (HR 0.57, 95%CI 0.38-0.87, p=0.01). Conclusion This research is the first to demonstrate a significant association between intradialytic resistance training and improved survival in hemodialysis patients within a multicenter, non-randomized cohort. This relationship remained significant after adjusting for multiple confounding factors, suggesting that incorporating resistance training into standard hemodialysis care could markedly enhance patient survival outcomes.

#206 The effect of dapagliflozin on anemia in patients with CKD

Abstract Background and Aims SGLT2 inhibitors confer kidney and cardiovascular protection in patients with chronic kidney disease (CKD). Some studies have analyzed the effects of SGLT2is on hemoglobin levels. Potential mechanisms for rising hemoglobin include hypoxia-induced activation of HIF2α, hepcidin inhibition resulting in iron metabolism modulation, and hemoconcentration. We aimed to evaluate the effect of dapagliflozin on anemia in CKD patients. Method We conducted a prospective study in patients in a single center with eGFR 35-90 ml/min/1.73 m2 who received dapagliflozin 10 mg daily between 6/2022 and 10/2023. The primary outcome was the mean difference in hemoglobin levels 5 months prior and 8 months after initiation of SGLT2i therapy. Results Among 132 patients screened from 6/2022 to 10/2023, 53 were prescribed dapagliflozin 10 mg daily, with a mean eGFR of 53.2 ml/min/1.73 m2. Of those 53 patients, 28 (52.8%) were males and 25 (47.2%) females. No one received any iron supplements or erythropoietin therapy. The mean hemoglobin level 5 months before initiating SGLT2i therapy was 10.5 g/dL, with a mean drop of 0.10 g/dL (95% CI, –0.22 to + 0.06) in 5 months. Eight months following the addition of SGLT2is, patients experienced an increase in hemoglobin levels of 1.03 g/dL (95% CI, 0.84 to 1.14). Overall, we observed a mean hemoglobin difference of 1.13 g/dL (95% CI, 0.84 to 1.41, p &amp;lt; 0.01) before and after initiating SGLT2i therapy. Conclusion The use of dapagliflozin for eight months resulted in a significant elevation in hemoglobin levels in patients with CKD. Further studies can explore of better understanding of the effect and confirm the mechanisms that explain this finding. Elevation of hemoglobin with SGLT2is may be closely linked to the reduction of cardiovascular mortality and heart failure.

#1399 Hemodiafiltration or haemodialysis for kidney failure: updated systematic review and individual participant data meta-analysis

Abstract Background and Aims A recent large European randomised controlled trial (RCT) showed a 23% reduction in all-cause mortality in favour of high dose haemodiafiltration (HDF) compared to high flux haemodialysis (HD). Several reactions critically questioned the main outcome and subgroup results and thereby its implications. Implications, however, should not be viewed based on results of one trial, but rather on the combined available evidence. Therefore, we set out to update our previous 2016 individual patient data meta-analysis (IPA-MA). An IPA-MA was chosen over an aggregated data meta-analysis as it allows more powerful and uniformly consistent analyses of subgroups and outcomes. Method The study was conducted according to PRISMA-IPD guidelines. We performed searches in MEDLINE, Embase and CENTRAL to identify RCTs in kidney failure patients with at least one year follow-up after randomisation, comparing on-line HDF with HD on mortality outcomes. Investigators were invited to share participant level data. The primary outcome was all-cause mortality. Secondary outcomes were cause-specific death (cardiovascular, only cardiac, only non-cardiac, infection-related, sudden death). We ran Cox proportional hazards models using intention to treat samples with a random effect for study, reporting hazard ratios (HR) and 95% confidence intervals (95% CI), overall and stratified by several predefined patient characteristics. Also, we ran Cox models using HDF patient data to estimate relations between achieved convective volume and mortality outcomes. Results Data from five European RCTs (i.e. ESHOL, CONTRAST, French HDF Study, Turkish HDF Study, and CONVINCE) were included, comprising 4153 patients. After a median follow-up of 30 months (Q1-Q3: 24-36), death from any cause occurred in 558 patients (27.2%) in the HD group and in 477 patients (23.3%) in the HDF group (HR: 0.84; 95% CI: 0.74 to 0.95). There was no evidence for a differential effect across subgroups. Cause specific analyses showed, compared to the HD, a lower risk of cardiovascular death in the HDF group (HR: 0.78; 95% CI: 0.63 to 0.96), which seemed to be driven by a lower risk for cardiac death (HR: 0.67, 95% CI: 0.50 to 0.89). The largest survival benefit was found for patients achieving a convective volume of 23 L or above, with a multivariable adjusted HR of 0.63 (95% CI: 0.50 to 0.79) for all-cause death, of 0.58 (95% CI: 0.40 to 0.85) for cardiovascular death and of 0.51 (0.28 – 0.93) for infection related death. The relation between achieved convection volume and mortality outcomes seemed gradual: the higher achieved the volume, the lower the risk compared to HD. Conclusion The combined available individual patient data from RCTs indicate that on-line HDF treatment improves survival with, at present, no clear differences across patient subgroups, when identified based on single characteristics. Our finding “the higher dose of HDF achieved, the lower the risk” seems congruent with that reported previously from observation studies.

Cause-Specific Excess Mortality During the COVID-19 Pandemic (2020-2021) in 12 Countries of the C-MOR Consortium.

This study investigated cause-specific mortality rates in 12 countries during the COVID-19 pandemic in 2020 and 2021. We collected weekly cause-specific mortality data from respiratory disease, pneumonia, cardiovascular disease (CVD) and cancer from national vital statistic databases. We calculated excess mortality for respiratory disease (excluding COVID-19 codes), pneumonia, and CVD in 2020 and 2021 by comparing observed weekly against expected mortality based on historical data (2015-2019), accounting for seasonal trends. We used multilevel regression models to investigate the association between country-level pandemic-related variables and cause-specific mortality. Significant reductions in cumulative mortality from respiratory disease and pneumonia were observed in 2020 and/or 2021, except for Georgia, Northern Ireland, Kazakhstan, and Ukraine, which exhibited excess mortality for one or both causes. Australia, Austria, Cyprus, Georgia, and Northern Ireland experienced excess cumulative CVD mortalityin 2020 and/or 2021. Australia, Austria, Brazil, Cyprus, Georgia, Northern Ireland, Scotland and Slovenia, experienced increased crude cumulative cancer mortality during 2020 and/or 2021 compared to previous years. Among pandemic-related variables, reported COVID-19 incidence was negatively associated with increased cancer mortality, excess respiratory, (2020) and pneumonia (2021) mortality, and positively associated with respiratory and CVD mortality (2021). Stringency of control measures were negatively associated with excess respiratory disease, CVD, and increased cancer mortality (2021). This study provides evidence of substantial excess mortality from CVD, and notable reductions in respiratory disease and pneumonia in both years across most countries investigated. Our study also highlights the beneficial impact of stringent control measures in mitigating excess mortality from most causes in 2021.

Evaluation of the Efficacy and Safety of Intravenous Immunoglobulin (IVIG) in Moderate-to-Severe Hospitalized COVID-19 Patients: A Randomized, Open-Label Parallel-Group Study.

Since February 2020, the world has been overwhelmed by the SARS-CoV-2 outbreak, and several patients suffered interstitial pneumonia and respiratory failure requiring mechanical ventilation, threatening the capability of healthcare systems to handle this amount of critical cases. Intravenous immunoglobulins (IVIG) possess potential immunomodulatory properties beneficial for COVID-19 patients, yet evidence supporting IVIG as adjunctive therapy remains sparse. This study evaluated the outcomes of adjunctive IVIG with the standard of care (SoC) in moderate-to-severe COVID-19 patients. This randomized study included 59 moderate-to-severe COVID-19 patients with known comorbidities. One arm (n = 33) received high-dose IVIG (400 mg/kg/day) within 48 hours for five days alongside SoC, while the other arm (n = 26) received SoC, comprising steroids, enoxaparin, and remdesivir. The primary endpoint was clinical improvement, as measured by the National Early Warning Score 2 (NEWS2) and discharged/death proportions. Secondary outcomes included IVIG safety, hospitalization duration, changes in oxygen saturation, inflammatory markers, IgG titer, CTSS (CT severity score), and radiological findings. There was an improvement in the NEWS2 at the end of treatment in the IVIG arm (5.67 vs. 5.96). A significant absolute effect improvement (Day 1 vs. Day 9) was seen in serum LDH, D-dimer, hs-CRP, IL-6, CTSS, procalcitonin, respiratory rate, and chest radiographic findings. SARS-CoV-2 IgG titer increased significantly in the IVIG arm. There was a statistically significant reduction in mortality in the IVIG group (5 vs. 10). IVIG was a safe and effective adjunctive therapy to SoC treatment in moderate-to-severe COVID-19 patients needing ventilatory support. Furthermore, studies are required to validate our findings. This trial is registered with CTRI/2021/05/033622.

Lung cancer screening: new frontiers

Lung cancer is the leading cause of cancer-related deaths worldwide. In early, asymptomatic stages, curative treatment is possible, but the disease is often diagnosed too late. Lung cancer screening (LCS) using low-dose computed tomography (LDCT) helps to detect potentially malignant lesions in early stages and to reduce lung cancer mortality. The application of artificial intelligence (AI) algorithms enables amore precise analysis of LDCT scans. Ameta-analysis of eight LCS studies revealed astatistically significant 12% relative reduction in lung cancer mortality. Based on strong scientific evidence, arecommendation for astructured lung cancer screening program using LDCT for the high-risk population in Germany was issued. The holistic LCS program requires aclear definition of the high-risk population, individual risk assessment, qualified personnel for conducting and reading examinations, verification of all diagnostic and therapeutic steps, central documentation and quality assurance, as well as the integration of tobacco cessation programs.