Relative Reduction In Mortality Research Articles

Impact of point-of-care birth test-and-treat on clinical outcomes among infants with HIV: A cluster randomized trial in Mozambique and Tanzania.

We assessed the impact of point-of-care (PoC) test-and-treat at birth on clinical outcomes and viral suppression among HIV-positive infants in Mozambique and Tanzania. This cluster-randomized trial allocated health facilities to intervention, providing PoC-testing and antiretroviral treatment (ART) at birth and week 4-8, or control, starting these at week 4-8. The primary outcome was proportions of clinical events (mortality, morbidity, retention, virological failure, toxicity) among HIV-positive infants at month-18. We estimated incidence rate ratios adjusted for timing of HIV-detection (aIRR) and reported viral suppression <1000 copies/mL. Among 6602 neonates enrolled October 2019-September 2021, 125 were diagnosed HIV-positive by week 12. In the intervention arm, 38/69 (55.1%) were diagnosed at birth with 35 initiating ART within two days. In the control arm, 27/56 (48.2%) were retrospectively detected HIV-positive at birth, of whom 6/56 (10.7%) died or were lost to follow-up before testing. Median age at ART initiation was 6 (intervention) versus 33 days (control). Birth test-and-treat was not associated with a significant reduction in clinical outcomes up to month-18 [53 (76.8%) versus 48 (85.7%); aIRR 0.857; 95% CI 0.505-1.492], but showed a 68% relative reduction in 6-month mortality. Viral suppression was poor overall, but improved in the intervention group at month 18 (65.7% versus 29.6%; p=0.005). PoC test-and-treat at birth is feasible in resource-poor settings and resulted in clinically-relevant reduction of early infant mortality, though improved clinical outcomes were not sustained to month-18. Poor viral suppression may undermine early survival benefits, calling for better paediatric treatments and tailored adherence interventions.

The effects of angiotensin receptor-neprilysin inhibitors on clinical outcomes in heart failure with mildly reduced or preserved ejection fraction: real-world evidence from the CCA Database-HF Center

Abstract Background Recent clinical trials have demonstrated the potential efficacy and safety of angiotensin receptor-neprilysin inhibitors (ARNI) in patients with heart failure (HF) with mildly reduced or preserved ejection fraction. Nevertheless, the generalizability of these findings in real-world clinical settings remains to be determined. We aimed to compare the real-world effectiveness of ARNI versus angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB)on clinical outcomes in HF patients with mildly reduced or preserved ejection fraction. Methods Patient-level data was derived from the China Cardiovascular Association Database-HF Center Registry. We included exclusively a subpopulation of HF patients with left ventricular ejection fraction (LVEF) &amp;gt;40% and comorbid with hypertension. Patients prescripted with ARNI at discharge and sustaining to ARNI therapy during follow-up were categorized as the ARNI group, while those maintaining the usage of ACEI/ARB after discharge were designated as the ACEI/ARB group. In complete cases, the primary endpoint of all-cause mortality at one year was assessed by the 1:1 propensity score matching (PSM) method. Results In all HF patients with LVEF &amp;gt;40% comorbid with hypertension, the usage of ARNI has increased from 0.9% in 2017 to 37.2% in 2021. A total of 3348 patients in the ARNI group and 7688 patients in the ACEI/ARB group were identified for comparative effectiveness. After 1:1 PSM, 5482 patients were included in the primary analysis, with 2741 patients in each treatment arm. The proportion of patients receiving higher dosages of ARNI (200mg/d and 400mg/d) was 20.9%, 26.6%, 29.2%, and 30.3% at discharge, 1-month, 3-month, and 1-year, respectively. Over the 1-year follow-up, ARNI was associated with a 20% relative reduction in all-cause death compared to the ACEI/ARB therapy (10.5% vs. 12.9%, adjusted hazard ratio [HR], 0.80 [95% CI, 0.69-0.94], P=0.005). The absolute risk difference in all-cause death between ARNI and ACEI/ARB arms was 2.88 per 100 patient-years (incidence rate difference, -2.88 [95% CI, -4.86 to -0.9]). Cardiovascular death also tended to decrease in the ARNI group but with missed statistical significance (4.5% vs. 4.9%, adjusted HR, 0.89 [95% CI, 0.70-1.14], P=0.373). Treatment benefits were more significant in those with LVEF between 40-50% (adjusted HR, 0.62 [95% CI, 0.48-0.79]), 50-60% (adjusted HR, 0.85 [95% CI, 0.68-1.06]), but not observed in HF patients with LVEF&amp;gt;60% (adjusted HR, 1.80 [95% CI, 1.08-2.98]; Pinteraction&amp;lt;0.001). Conclusion In real-world clinical settings, treatment with ARNI was associated with a significant relative risk reduction in all-cause mortality compared with ACEI/ARB in HF patients with mildly reduced or preserved LVEF. The cardiovascular benefit was concentrated in patients with LVEF ≤60%.

Clinical utility of the neutrophil elastase inhibitor sivelestat for the treatment of ALI/ARDS patients with COVID-19

BackgroundSivelestat, a neutrophil elastase inhibitor, is postulated to mitigate acute lung injury in patients following emergency surgery. However, its efficacy in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) induced by coronavirus disease 2019 (COVID-19) remains uncertain. This study aims to evaluate the pulmonary protective effects of sivelestat in COVID-19 patients with ALI/ARDS. MethodsA retrospective study was conducted involving 2454 COVID-19 patients between October 5, 2022, and February 1, 2023. Of these, 102 patients received sivelestat (0.2 mg/kg/h), while 2352 age- and sex-matched controls were identified. Propensity score matching (PSM) analysis was used to match sivelestat and non-sivelestat subgroups in ratios of 1:1 and 1:3 for sensitivity analysis. The primary outcome was a composite of effective outcomes, including 30-day mortality. Secondary outcomes included changes in partial pressure of arterial oxygen (PaO2), the ratio of PaO2 to the fraction of inspired oxygen (PaO2/FiO2), and various cytokine levels. Safety evaluations included assessments of liver function, kidney function, and leukopenia. ResultsIn the propensity score-matched analysis, the sivelestat group had a higher proportion of severe/critical patients (87.26 % vs. 51.02 %, P < 0.001), more ARDS patients (4.9 % vs. 0.43 %, P < 0.001), and more patients with interstitial lung disease (4.9 % vs. 1.49 %, P = 0.023), but fewer patients with stroke (17.65 % vs. 19.86 %, P < 0.001). Oxygen therapy rates were similar between the groups (79.41 % vs. 80.95 %, P = 0.9). The relative risk reduction in 30-day mortality was 88.45 % (95 % confidence interval [CI] 81.23%–93.21 %) for severe/critical COVID-19 patients treated with sivelestat. Sivelestat significantly decreased cytokine levels of interferon alpha (IFNα), interleukin-1 beta (IL-1β), and interleukin-2 (IL-2).In the sivelestat group, the mortality rate was significantly reduced with standard oxygenation and HFNC therapy(P < 0.05). The treatment with sivelestat did not increase side effects. ConclusionThe administration of the neutrophil elastase inhibitor sivelestat may improve clinical outcomes in COVID-19 patients with ALI/ARDS. These findings suggest that sivelestat could be considered an effective treatment option to alleviate pulmonary inflammatory injury caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Percent Predicted Peak Exercise Oxygen Pulse Provides Insights Into Ventricular-Vascular Response and Prognosticates HFpEF

BackgroundPeak oxygen consumption and oxygen pulse along with their respective percent predicted measures are gold standards of exercise capacity. To date, no studies have investigated the relationship between percent predicted peak oxygen pulse (%PredO2P) and ventricular-vascular response (VVR) and the association of %PredO2P with all-cause mortality in heart failure with preserved ejection fraction (HFpEF) patients. ObjectivesThe authors investigated the association between: 1) CPET measures of %PredO2P and VVR; and 2) %PredO2P and all-cause mortality in HFpEF patients. MethodsOur cohort of 154 HFpEF patients underwent invasive CPET and were grouped into %PredO2P tertiles. The association between percent predicted Fick components and markers of VVR (ie, proportionate pulse pressure, effective arterial elastance) was determined with correlation analysis. The Cox proportional hazards model was used to identify predictors of mortality. ResultsThe participants’ mean age was 57 ± 15 years. Higher %PredO2P correlated with higher exercise capacity. In terms of VVR, higher %PredO2P correlated with a lower pressure for a given preload (effective arterial elastance r = −0.45, P < 0.001 and proportionate pulse pressure r = −0.22, P = 0.008). %PredO2P distinguished normal and abnormal percent predicted peak stroke volume and correlated positively with %PredVO2 (r = 0.61, P < 0.001). Participants had a median follow-up time of 5.6 years and 15% death. Adjusted for age and body mass index, there was a 5% relative reduction in mortality (HR: 0.95, 95% CI: 0.92-0.98, P = 0.003) for every percent increase in %PredO2P. ConclusionsIn HFpEF, %PredO2P is a VVR marker that can stratify invasive parameters such as percent predicted peak stroke volume. %PredO2P is an independent prognostic marker for all-cause mortality and those with higher %PredO2P exhibited longer survival.

Routine Clinical Breast Examination Is a Low-Yield Practice Among Women at High Risk of Breast Cancer.

For women at increased risk of breast cancer, the National Comprehensive Cancer Network (NCCN) guidelines recommend clinical encounters every 6-12 months. While screening mammography has corresponded with a relative risk reduction in breast cancer mortality of approximately 20%, evidence validating clinical breast examination (CBE) as an efficacious screening modality is deficient. Our study aimed to assess the conventional merit of regular CBE for breast cancer detection among individuals at increased risk of breast cancer development. Women > 18 years with documented high-risk encounters at Corewell Health West from 1 January 2018 to 31 December 22 were retrospectively reviewed. High-risk criteria included genetic predisposition, 5-year (> 1.7%) or lifetime (> 20%) Tyrer-Cuzick and/or Gail Model risk estimations, thoracic radiotherapy before age 30 years, lobular carcinoma in-situ, or atypical hyperplasia. Patients with a history of breast cancer or bilateral prophylactic mastectomy prior to 2018 were excluded. Of the 9171 cumulative high-risk encounters among 2493 women, only one breast cancer was detected by CBE. CBE resulted in 1 (0.04%) cancer diagnosis compared with 30 (1.2%) detected on screening imaging and 10 (0.4%) self-reported. Of the 30 image-detected cancers, 28 (93.3%) had no detectable clinical findings at the time of preoperative consultation. Self-reported and CBE-detected cancers were more likely to be of higher clinical stage compared with imaging-detected malignancies. The role of routine CBE as a cancer detection modality in the high-risk patient population appears to be limited. Telemedicine can be offered to individuals who have completed screening imaging but are unable to commit and/or are inconvenienced by in-person high-risk breast cancer assessments.

The Incidence and Outcomes of Major Limb Amputation in New Zealand from 2010 to 2021.

Background: Major limb amputation (MLA) can be a common outcome due to severe peripheral artery disease (PAD) and diabetic foot disease (DFD), and it carries a significant mortality burden. In New Zealand (NZ), there is little documentation of the incidence rate and mortality after MLA. The aim was to report the national crude and standardised rates and the mortality post MLA. Methods: This retrospective observational study included all MLAs that occurred within NZ from 1/1/2010 to 31/12/2021 due to DFD and/or PAD. Two national databases (National Minimum Dataset and the Australasian Vascular Audit) were utilised. The crude rates were calculated as cases per 100,000 in the NZ population per year including all ages (using the 2013 and 2018 NZ census figures). The age-standardised rates used the World Health Organization standard population. Post-operative mortality was calculated from the date of first hospitalisation for MLA. Results: From 2010 to 2021, there were 5293 MLA procedures in 4242 patients. On average, there were 8.5 MLAs per week and 441.1 MLAs annually. The overall crude rate was 9.44 per 100,000, and the standardised rate was 6.12 per 100,000. Over the 12 years, the crude rate decreased by 22% (p < 0.001), and the standardised rate decreased by 20.4% (p < 0.001). After MLA, the 30-day and 1-year mortality was 9.5% and 29.6%, respectively. From 2010 to 2021, the relative reduction in 30-day mortality was 45.1% (p < 0.001), and the reduction in 1-year mortality was 24.5% (p < 0.001). Increasing age, female sex and end-stage renal failure were predictors of 30-day and 1-year mortality. Conclusions: A considerable number of MLAs occur in NZ, with substantial perioperative mortality; however, the national incidence rates and mortality have improved over the last 12 years. This data might serve as benchmark to further reduce MLAs and improve patient outcomes.

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.

Screening for Lung Cancer in India: Expert Opinion Statement.

Lung cancer (LC) has the highest rate of disability-adjusted life years (DALY) of all cancers in India. A large majority of patients with LC present with advanced disease, resulting in poor survival rates. Early diagnosis can improve survival outcomes as the patients can be treated with curative intent. The National Lung Screening Trial (NLST), in 53,454 persons at high risk for LC in the US, showed a 20% (95% confidence interval of 6.8-26.7; p = 0.004) relative reduction in LC-specific mortality in the patients screened with low-dose computed tomography (LDCT) compared with chest X-ray. To date, India does not have a formal LC screening (LCS) program. As a panel of experts, we reviewed a synthesis of a targeted literature search on the burden of LC, the current status of diagnosis of LC, barriers to early diagnosis, current referral pathways, LC risk patterns, use of artificial intelligence (AI) and risk calculators for risk assessment, and a multidisciplinary team (MDT) approach to diagnosis LC. We used the existing international LCS guidelines, data from published literature, and clinical experience to depict the characteristics of the population at risk of LC in India-young age (<40 years), smoking, especially the predominance of bidi smoking (an indigenous form of tobacco smoking), exposure to biomass fuel smoke, especially in rural women, and air pollution being the prominent features. LC in India is characterized by a higher rate of driver mutations and adenocarcinomatous histology. Here, we present the expert opinion on risk-based LCS in India and discuss the challenges, facilitators, and research priorities for the effective rollout of LCS in India.

Abstract 3362: Describing the molecular landscape of cervical cancer metastases: Implications for future therapeutic targets

Abstract Introduction: Cervical Cancer (CC) is a heterogenous disease with multiple histological sub-types. Early screening has led to a reduction in disease related mortality, but a significant number of patients present with or progress to advanced disease. Studies between the molecular and immune alterations in CC primaries (CCP) and CC metastases (CCM) are needed to explore potential therapeutic strategies. Methods: Relationships of CCM and alterations detected by NGS (592, NextSeq; WES, NovaSeq) were investigated in 2,668 (1,393 primary Cervix samples, 383 local metastatic GYN samples, and 892 distant metastatic samples) CC samples (Caris Life Sciences, Phx, AZ). PD-L1+ was tested by IHC (22c3, &amp;gt;1%). Tumor mutational burden (TMB) was measured by summing somatic mutations per tumor (H: &amp;gt;10 mt/MB). Immune infiltrates estimated by deconvolution of WTS data (NovaSeq) using Quantiseq. Statistical significance determined by chi-square and Mann-Whitney U and adjusted for multiple comparisons (q&amp;lt;0.05). Results: Hierarchical clustering of CCM sites by alterations (mutations, amplifications and fusions) frequency revealed CCM to Liver (n=77) and Lymph Nodes (n=265) as the most distinct from CCP while Vagina/Vulva (V/V) (n=196) and Lung (n=115) CCM were most similar. Lymph Nodes had decreased TP53-mt (6.6% vs 14.7%) and ARID1A-mt (4.53% vs 8.27%) but higher BRCA1-mt (3.03% vs 0.87%) compared to CCP (p&amp;lt;0.05). Liver had higher BRCA1-mt (6.67% vs 0.87%), ASXL1-mt (8.47% vs 2.96%) and APC-mt (4% vs 0.65%) compared to CCP (p&amp;lt;0.05). CCM to Lymph Nodes had higher median TMB (median [range]: 6 [0-101] vs 5 [0-460], q&amp;lt;0.05) and HPV16/18+ rate compared to CCP (81.2% vs 66.8%, p&amp;lt;0.05). CCM to Liver had lower expression of CTLA4 compared to CCP (1.67-fold decrease), similarly, Ovary/FT had significantly lower expression of immune checkpoint (IC) gene expression (CD80, CD86, CD274, PDCD1, PDCD1LG2, CTLA4, HAVCR2, IDO1, LAG3, IFNG: 2.23-4.66-fold decrease) (q&amp;lt;0.05). While Lymph Nodes had higher expression of the IC genes compared to CCP (1.30-1.49-fold, q&amp;lt;0.05). CCM to Liver and Ovary/FT had lower median infiltration of immune cells while Lymph Nodes had higher compared to CCP of Macrophage M1 (2.7% vs 1.03% vs 3.35% vs 3.1%), B cells (3.7% vs 3.5% vs 5.6% vs 4.3%), CD8 T cells (0% vs 0% vs 1.01% vs 0.75%), and Tregs (1.6% vs 0.74% vs 2.86% vs 2.5%) (q&amp;lt;0.05). CCM to Liver and Ovary/FT had lower median IFN score while Lymph Nodes had higher median IFN score (q&amp;lt;0.05) compared to CCP, similarly, Ovary/FT had a lower % of T-cell inflamed tumors with Lymph Nodes having higher T-cell inflamed tumors compared to CCP (7.89% vs 47.4% vs 29.3%, q&amp;lt;0.05). Discussion: CCM to Lymph Nodes and Liver had the most distinct molecular and immune landscape compared to CCP while Ovary/FT had a similar molecular profile but a distinctively cold immune profile compared to CCP. Additional studies to evaluate the potential therapeutic targets are warranted. Citation Format: Matthew J. Hadfield, Sharon Wu, Alex Farrell, Matthew Oberly, Grace Sun, Premal Thaker, Jody Wellcome, Matthew Anderson, Don Dizon. Describing the molecular landscape of cervical cancer metastases: Implications for future therapeutic targets [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3362.

Assessing the one-month mortality impact of civilian-setting prehospital transfusion: A systematic review and meta-analysis.

Based on convincing evidence for outcomes improvement in the military setting, the past decade has seen evaluation of prehospital transfusion (PHT) in the civilian emergency medical services (EMS) setting. Evidence synthesis has been challenging, due to study design variation with respect to both exposure (type of blood product administered) and outcome (endpoint definitions and timing). The goal of the current meta-analysis was to execute an overarching assessment of all civilian-arena randomized controlled trial (RCT) evidence focusing on administration of blood products compared to control of no blood products. The review structure followed the Cochrane group's Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). Using the Transfusion Evidence Library (transfusionevidencelibrary.com), the multidatabase (e.g. PubMed, EMBASE) Harvard On-Line Library Information System (HOLLIS), and GoogleScholar, we accessed many databases and gray literature sources. RCTs of PHT in the civilian setting with a comparison group receiving no blood products with 1-month mortality outcomes were identified. In assessing a single patient-centered endpoint-1-month mortality-we calculated an overall risk ratio (RR) estimate. Analysis of three RCTs yielded a model with acceptable heterogeneity (I2 = 48%, Q-test p = 0.13). Pooled estimate revealed civilian PHT results in a statistically nonsignificant (p = 0.38) relative mortality reduction of 13% (RR 0.87, 95% CI 0.63-1.19). Current evidence does not demonstrate 1-month mortality benefit of civilian-setting PHT. This should give pause to EMS systems considering adoption of civilian-setting PHT programs. Further studies should not only focus on which formulations of blood products might improve outcomes but also focus on which patients are most likely to benefit from any form of civilian-setting PHT.

Maternal and child life years gained by transfusing low titer group O whole blood in trauma: A computer simulation.

Using low titer group O whole blood (LTOWB) is increasingly popular for resuscitating trauma patients. LTOWB is often RhD-positive, which might cause D-alloimmunization and hemolytic disease of the fetus and newborn (HDFN) if transfused to RhD-negative females of childbearing potential (FCP). This simulation determined the number of life years gained by the FCP and her future children if she was resuscitated with LTOWB compared with conventional component therapy (CCT). The model simulated 500,000 injured FCPs of each age between 0 and 49 years with LTOWB mortality relative reductions (MRRs) compared with components between 0.1% and 25%. For each surviving FCP, number of life years gained was calculated using her age at injury and average life expectancy for American women. The number of expected future pregnancies for FCPs that did not survive was also based on her age at injury; each future child was assigned the maximum lifespan unless they suffered perinatal mortality or serious neurological events from HDFN. The LTOWB group with an MRR 25% compared with CCT had the largest total life years gained. The point of equivalence for RhD-positive LTOWB compared to CCT, where life years lost due to severe HDFN was equivalent to life years gained due to FCP survival/future childbearing, occurred at an MRR of approximately 0.1%. In this model, RhD-positive LTOWB resulted in substantial gains in maternal and child life years compared with CCT. A >0.1% relative mortality reduction from LTOWB offset the life years lost to HDFN mortality and severe neurological events.

Impact of postoperative cardiovascular complications on 30-day mortality after major abdominal surgery: an international prospective cohort study.

Cardiovascular complications after major surgery are associated with increases in morbidity and mortality. There is confusion over definitions of cardiac injury or complications, and variability in the assessment and management of patients. This international prospective cohort study aimed to define the incidence and timing of these complications and to investigate their impact on 30-day all-cause mortality. We performed a prospective, international cohort study between January 2022 and May 2022. Data were collected on consecutive patients undergoing major abdominal surgery in 446 hospitals from 28 countries across Europe. The primary outcome measure was cardiovascular complications as defined by the Standardised Endpoints for Perioperative Medicine-Core Outcome Measures for Perioperative and Anaesthetic Care initiative up to 30 days after surgery. The secondary outcome was 30-day postoperative mortality. This study included 24,203 patients, of whom 611 (2.5%) developed cardiovascular complications. In total, 458 (1.9%) patients died within 30 days of surgery, of which 123 (26.9%) deaths were judged to be cardiac-related. Mortality rates were higher in patients who developed postoperative cardiovascular complications than in those who did not (19.8% vs. 1.4%), which persisted after risk adjustment (hazard ratio (95%CI) 4.15 (3.14-5.48)). We estimated an absolute risk reduction (95%CI) of 0.4 (0.3-0.5) in mortality in the absence of all cardiovascular complications. This would confer a relative risk reduction in mortality of 21.1% if all cardiovascular complications were prevented. Postoperative cardiovascular complications are relatively common and occur early after major abdominal surgery. However, over 1 in 5 postoperative deaths were attributable to these complications, highlighting an important area for future randomised trials.

VPExam and Virtual Care: Novel Cardiology Tools

Virtual Physical examination (VPExam) combines augmented reality guidance with Bluetooth stethoscopes and ECG to improve diagnostic accuracy of assessing volume status, auscultation, and arrythmia detection resulting in 84% modification of clinical management, 40% relative risk reduction in 30-day readmissions and a 56% relative risk reduction in 30-day mortality.

Atrial fibrillation ablation in patients with reduced left ventricular ejection fraction: does it only improve hemodynamics or does it affect the prognosis? (A systematic review)

Objective: To critically evaluate the results of studies concerning the impact of atrial fibrillation ablation on hemodynamics and prognosis in patients with heart failure with reduced left ventricular ejection fraction.Methods: We searched via keywords in the PubMed, Embase, Cochrane Library, and Web of Science databases and selected the most-cited studies containing data on the ablation treatment of patients with atrial fibrillation and heart failure with reduced left ventricular ejection fraction, including such treatment end points as left ventricular ejection fraction, mortality, etc. We analyzed the effect of ablation on changes in left ventricular ejection fraction and clinical outcomes in patients with atrial fibrillation compared with that of drug therapy.Results: We screened 4581 literature sources: of them, 48 were selected for the review. Compared with drug therapy in similar patients with atrial fibrillation and heart failure, there is a 4-fold absolute increase (P &lt; .001) in left ventricular ejection fraction after endocardial catheter ablation, thoracoscopic or hybrid ablation of atrial fibrillation. Some studies show a relative risk reduction in mortality (max 47%; P = .01) following the ablation in patients with atrial fibrillation and baseline reduced left ventricular ejection fraction.Conclusion: After atrial fibrillation ablation (regardless of the technique used and left ventricular dysfunction severity), patients with heart failure with reduced left ventricular ejection fraction show a statistically significant improvement in systolic function probably due to a decreased arrhythmia burden. Further research could determine the population of heart failure patients who would benefit most from atrial fibrillation ablation. Received 20 April 2023. Revised 6 June 2023. Accepted 7 June 2023. Funding: The study did not have sponsorship. Conflict of interest: The authors declare no conflict of interest. Contribution of the authors: The authors contributed equally to this article.

Health-related quality of life trajectories in critical illness: Protocol for a Monte Carlo simulation study.

Health-related quality of life (HRQoL) is a patient-centred outcome increasingly used as a secondary outcome in critical care research. It may cover several important dimensions of clinical status in intensive care unit (ICU) patients that arguably elude other more easily quantified outcomes such as mortality. Poor associations with harder outcomes, conflicting data on HRQoL in critically ill compared to the background population, and paradoxical effects on HRQoL and mortality complicate the current operationalisation in critical care trials. This protocol outlines a simulation study that will gauge if the areas under the HRQoL trajectories could be a viable alternative. We will gauge the behaviour of the proposed HRQoL operationalisation through Monte Carlo simulations, under clinical scenarios that reflect a broad critical care population eligible for inclusion in a large pragmatic trial. We will simulate 15,360 clinical scenarios based on a full factorial design with the following seven simulation parameters: number of patients per arm, relative mortality reduction in the interventional arm, acceleration of HRQoL improvement in the interventional arm, the relative improvement in final HRQoL in the interventional arm, dampening effect of mortality on HRQoL values at discharge from the ICU, proportion of so-called mortality benefiters in the interventional arm and mortality trajectory shape. For each clinical scenario, we will simulate 100,000 two-arm trials with 1:1 randomisation. HRQoL will be sampled fortnightly after ICU discharge. Outcomes will include HRQoL in survivors and all patients at the end of follow-up; mean areas under the HRQoL trajectories in both arms; and mean difference between areas under the HRQoL trajectories and single-sampled HRQoLs at the end of follow-up. In the outlined simulation study, we aim to assess whether the area under the HRQoL trajectory curve could be a candidate for reconciling the seemingly paradoxical effects on improved mortality and reduced HRQoL while remaining sensitive to early or accelerated improvement in patient outcomes. The resultant insights will inform subsequent methodological work on prudent collection and statistical analysis of such data from real critically ill patients.

A review of stem cell therapy in ischemic heart disease, where are we now?

Background: Regenerative therapies to rejuvenate the heart have a significant appeal for researchers. Preliminary findings from pre-clinical studies suggest that bone marrow cells may have reparative and regenerative effects on heart muscles, creating a ripe area for research. Many generations of stem cells used in pre-clinical and early clinical studies have shown promising but variable results. Objective: The current review article discusses the dilemmas in applying stem cell therapy to cardiovascular diseases and possible strategies to make it feasible. Methods: The field of regenerative therapies continued to progress with second-generation cells, third-generation cells, combination cell therapy, and the use of cell products alone. Research showed promising positive results in multiple randomized phases 1, 2, and 3 clinical trials in addition to numerous meta-analyses. The gaps in knowledge included stem-cell sources, their delivery routes, dosing, types of cells, and the indicated cardiac conditions. Results: The results from the latest randomized clinical trials, namely the Dream-HF, showed improved left ventricle function, symptoms, and overall survival. Studied patient populations include post-myocardial infarction (MI), ischemic/non-ischemic cardiomyopathy, intractable/microvascular angina, and cardiac surgery for congenital and valvular heart disease. The phase 3 DREAM-HF trial did not meet the primary heart failure endpoint of reducing hospital admission. Still, it showed a clinically significant reduction in major adverse cardiovascular events (MACE), including recurrent MI and stroke, by 60%. A 60% reduction in cardiovascular mortality and a 79% reduction in cardiovascular mortality in patients with evidence of inflammation (high CRP). The latter finding suggests a more anti-inflammatory effect. This effect was much higher than that observed in the PARADIGM-HF trial, which showed a 20% relative risk reduction in cardiovascular mortality. By combining the results of the DREAM-HF trial with MSC-HF, ixCELL-DCM, CONCERT-HF, and REGENERATE-DCM, the potential for clinical applications of cell therapy is promising. Conclusion: There is a promising role for cell therapy in the management of cardiovascular diseases. Results of trials in the setting of heart failure are more encouraging in both ischemic and non-ischemic cardiomyopathy. This is in contrast with acute myocardial infarction, where the results have been variable. Amongst all the various cell types tested MSCs show the most significant promise for treating HF.

Bleeding related hospitalizations and mortality in England 2014-2019.

Acute bleeding is common and associated with increased morbidity and mortality. Epidemiological studies evaluating trends in bleeding-related hospitalisations and mortality are important as they have potential to guide resource allocation and service provision, however, despite this literature evaluating the national burden and annual trends are lacking. Our objective was to report the national burden and incidence of bleeding-related hospitalisation and mortality.This was a population-based review of all people in England between 2014 and 2019 either admitted to an acute care ward of a National Health Service (NHS) English hospital, or who died. Admissions and deaths were required to have a primary diagnosis of significant bleeding.There was a total of 3,238,427 hospitalisations with a mean of 539,738 ± 6033 per year and 81,264 deaths with a mean of 13,544 ± 331 per year attributable to bleeding. The mean annual incident rate for bleeding-related hospitalisations was 975 per 100,000 patient years and for mortality was 24.45. Over the study period there was a significant 8.2% reduction in bleeding related deaths (χ2 test for trend 91.4, p < 0.001). A direct relationship between increasing age and incidence of bleeding-related hospitalisation and mortality was seen.Bleeding remains a common cause of hospitalisation and death. The reduction in bleeding related mortality requires further investigation. This data may serve to guide future interventions designed to reduce bleeding-related morbidity and mortality.

A multivariate analysis of low-dose CT lung cancer screening in a Michigan community hospital network.

10576 Background: Lung cancer is the leading cause of cancer deaths in the United States. The USPSTF recommended screening for lung cancer with low-dose chest computer tomography (LDCT) in 2013. This was based on the National Lung Screening Trial (NLST) which showed a 20% relative reduction in mortality from LDCT compared with chest radiography in high-risk individuals. The major NLST eligibility criteria were age 55-74, a 30 + pack year smoking history and current smoking status or having quit in the last 15 years. The impact of other risk factors on screening results besides inclusion criteria is unknown. We sought to identify other factors for the risk of lung cancer detection in screened individuals. Methods: This was a retrospective cohort study employing a Michigan based McLaren Hospital Network Lung Cancer Screening Program (LCSP) database from 2015-2022. Participant eligibility in screening was the USPSTF criteria except for an age range of 50-80. Analyses were stratified by BMI, smoking pack-years, insurance status, smoking status, sex, other CT findings, pre- vs. during COVID pandemic (before and after January 2020). Multivariate logistic regression analysis was used for odds ratios (OR) with 95% confidence intervals (CI) as estimates of the relative risk of an elevated Lung-RADS category ≥3 (high risk of detecting lung cancer). Results: A total of 2638 subjects, 49.91% females, 50.09% males, mean BMI 29.50 ± 7.17 (SD), pack-years 44.52 ±18.29, Medicaid 6.66%, Medicare 32.01%, Private Insurance 57.62%, Self-pay /unknown 3.71%. Current smoker 65.49%, Former smoker 34.51%, other CT findings 51.99%, pre-COVID 46.08%, during COVID pandemic 53.92%. Lung-RADS category 0 (0.04%), 1 (35.33%), 2, (50.61%), 3 (6.56%), 4a (4.85%), 4b (1.55%), 4x (1.06%). A statistically significant association with a Lung-RADS category ≥3 was found with lower BMI, OR=0.980 (95% CI, 0.969-0.991), p=0.0005, and female gender, OR=1.232 (95% CI, 1.039-1.462), p=0.0166 (Table). Conclusions: In our study cohort a lower-than-average BMI and also female gender were statistically correlated with an elevated Lung-RADS category ≥3. These findings might be incorporated into a risk stratification model, however further larger studies are needed to validate our findings. [Table: see text]

Study protocol of a randomised, double-blind, placebo-controlled, two-arm parallel-group, multi-centre phase 3 pivotal trial to investigate the efficacy and safety of recombinant human alkaline phosphatase for treatment of patients with sepsis-associated acute kidney injury

IntroductionSepsis, the leading cause of acute kidney injury (AKI), is associated with a high morbidity and mortality. Alkaline phosphatase (ALP) is an endogenous detoxifying enzyme. A recombinant human ALP compound,...

Biomarkers in Lung Cancer Screening: a Narrative Review.

Although when used as a lung cancer screening tool low-dose computed tomography (LDCT) has demonstrated a significant reduction in lung cancer related mortality, it is not without pitfalls. The associated high false positive rate, inability to distinguish between benign and malignant nodules, cumulative radiation exposure, and resulting patient anxiety have all demonstrated the need for adjunctive testing in lung cancer screening. Current research focuses on developing liquid biomarkers to complement imaging as non-invasive lung cancer diagnostics. Biomarkers can be useful for both the early detection and diagnosis of disease, thereby decreasing the number of unnecessary radiologic tests performed. Biomarkers can stratify cancer risk to further enrich the screening population and augment existing risk prediction. Finally, biomarkers can be used to distinguish benign from malignant nodules in lung cancer screening. While many biomarkers require further validation studies, several, including autoantibodies and blood protein profiling, are available for clinical use. This paper describes the need for biomarkers as a lung cancer screening tool, both in terms of diagnosis and risk assessment. Additionally, this paper will discuss the goals of biomarker use, describe properties of a good biomarker, and review several of the most promising biomarkers currently being studied including autoantibodies, complement fragments, microRNA, blood proteins, circulating tumor DNA, and DNA methylation. Finally, we will describe future directions in the field of biomarker development.