Survival Probability Research Articles

Ambient beta particle radioactivity and lung cancer survival: Results from the Boston Lung Cancer Study

BackgroundExposure to ionizing radiation is known to increase the risk of lung cancer. However, studies on the effect of environmental radiation associated with ambient particle air pollution on lung cancer survival are limited. We investigated the association between ambient beta particle radioactivity (PR-β) after a diagnosis and lung cancer survivals. MethodsThe Boston Lung Cancer Survival (BLCS) cohort consisted of histologically confirmed patients enrolled at Massachusetts General Hospital (MGH) and the Dana-Farber Cancer Institute (DFCI) in Boston, U.S. The primary outcomes included overall survival, 5-year survival, and 3-year survival probability. We estimated ambient PR-β exposure at the ZIP code of residence from 2001 through 2017. Cox-proportional hazards models were constructed to estimate hazard ratios (HRs) for the associations between ambient PR-β and survival outcomes while controlling for covariates. ResultsThe analysis included 2795 patients with complete information, with 97,330 person-months of follow-up. The interquartile range (IQR) increase in PR-β was significantly associated with worse overall survival (HR:1.63, 95% CI:1.52, 1.76), 5-year survival (HR:1.33, 95% CI:1.23, 1.44), and 3-year survival (HR:1.22, 95% CI:1.12, 1.33) while adjusting for covariates, including age at diagnosis, sex, race, smoking, stage, histology, and adjusted gross income. Similar associations were found while additionally adjusting for the estimated residential radon exposure. In addition, the survival associated with PR-β exposure was significantly worse for patients in the early stages (HR:2.16, 95% CI:1.84, 2.52). ConclusionThe findings from this study provide new evidence suggesting that environmental exposure to radioactive particles after lung cancer diagnosis may have a pronounced effect on survival, particularly in patients with early stages.

Does regression of skin thickening predict improvement of internal organ involvement and survival in patients with diffuse cutaneous systemic sclerosis? A EUSTAR analysis

ObjectivePatients with diffuse cutaneous systemic sclerosis (dcSSc) frequently show spontaneous improvement of skin fibrosis. Our aim was to examine whether an improvement in skin fibrosis predicts lower likelihood of visceral organ progression and better survival.MethodsPatients from the European Scleroderma Trials and Research (EUSTAR) cohort with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, and valid mRSS at 12±3 months follow up were included. Regression/progression of skin fibrosis was defined as a decrease/increase in mRSS >5 points and≥25% from baseline to follow up. The outcomes included progression of lung, renal, cardiac and gastrointestinal manifestations using consensus derived definitions and all-cause death. Regressive, stable and progressive patients were compared by univariate, Kaplan-Meier survival curve and Cox regression analysis.ResultsOf 1257 included patients, 883 (70.2%) were stable, 282 (22.4%) regressive, and 92 (7.3%) progressive. Regressive patients, adjusted for baseline mRSS, baseline immunosuppression, baseline FVC, and disease duration, showed a significantly lower probability of FVC decline ≥10% than progressive patients (p=0.00003), lower probability of all-cause mortality during follow up (p=0.035) compared to progressive patients. .Improvement of skin fibrosis was not associated with progression of other organ manifestations.ConclusionWe found that regression of skin fibrosis is associated with a lower probability of lung progression and better survival at follow up. The link between the disease course of skin and lung fibrosis in SSc can help to better stratify patients in clinical practice and enrich for ILD progressive patients in clinical trials.

Outcomes of children and young adults with B-cell acute lymphoblastic leukemia given blinatumomab as last consolidation treatment before allogeneic hematopoietic stem cell transplantation.

Blinatumomab has remarkable efficacy in patients with relapsed/refractory (r/r) or measurable residual disease (MRD)-positive B-cell acute lymphoblastic leukemia (B-ALL). In many patients, blinatumomab treatment is followed by allogeneic hematopoietic stem cell transplantation (HSCT). However, the influence of blinatumomab on HSCT outcomes in children and young adults (YA) remains to be fully elucidated. We conducted a single-center, retrospective analysis on patients given blinatumomab as last treatment before HSCT. Seventy-eight pediatric and YA patients were evaluated. With a median follow-up of 23.23 months, the 2-year disease-free (DFS) and overall survival (OS) probability were 72.2% and 89.2%, respectively, with a 2-year cumulative incidence (CI) of non-relapse mortality (NRM) of 2.6%. A trend toward improved 2-year DFS, but not OS, was noted in patients transplanted in first complete remission (CR1) (92.9%) compared to those in second or greater remission (CR2/3) (68.5%, p=0.18) due to a lower CI of relapse (0% vs. 29.9%, p=0.05). Among CR2/3 patients, those receiving the sequential combination of inotuzumab and blinatumomab had a significantly lower CI of relapse as compared to those who did not receive inotuzumab (9.5% vs. 40.4%, p=0.023). Relapse after HSCT occurred in 16 patients, all exhibiting CD19-positive blasts; 10 of them received anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy and 2 inotuzumab as salvage therapy, leading to a 2-year post-relapse OS of 52.7%. Our results indicate that HSCT following blinatumomab in children and YA with B-ALL is highly effective, being associated with low NRM and not affecting the efficacy of subsequent salvage immunotherapies, including CAR-T cells.

Congenital Epidermolysis Bullosa Epidemiology among Children of Russian Federation

Background. The prevalence of all types of congenital epidermolysis bullosa (СEB) worldwide is approximately 11 cases per 1 million according to the latest data from the American Epidermolysis Bullosa Registry. Data on the prevalence of СEB in Russian Federation is scattered, while data on life expectancy and mortality for this this disease is absent. This article presents medical and epidemiological data on children with СEB in Russian Federation. Objective. The aim of the study is to analyze clinical and epidemiological features of children with СEB in Russian Federation. Methods. We have performed analysis of the clinical and epidemiological features among pediatric population of Russian Federation with СEB using the “Registers of Genetic and Other Rare Diseases” of the “Butterfly Children” charitable foundation. Results. There are 491 children with СEB in Russian Federation as of 2024 according to the national registry data from “Registers of Genetic and Other Rare Diseases” of the “Butterfly Children” charitable foundation. The ratio of boys and girls was 1.08:1, that is relevant to the global data. The prevalence of CEB in children aged from 0 to 17 years in Russian Federation is 15.48 cases per 1,000,000 children as of January 1, 2024. The highest number of children with CEB were revealed in the Republic of Dagestan — 54 (11%) children, which is apparently due to the high rate of consanguineous marriages (50%). Other regions with high prevalence are Moscow Region (n = 28, 5.7%), Moscow (n = 25, 5.1%), Saint Petersburg (n = 26, 5.2%) and Krasnodar Territory (n = 23, 4.6%). Largest age group of children (from 12 to 18 years) includes 146 patients with mean age of 14.32 ± 1.72 years. The most common form of CEB is dystrophic one — 261 patients, the next one is simplex — 191 patients, then junctional form — 31 patient, and Kindler syndrome — 8 patients. The birth rate of children with CEB by year during the period from 2019 to 2023 (per 100,000 children born): 2019 — 1.42, 2020 — 2.09, 2021 — 2.65, 2022 — 2.76 and 2023 — 1.74. The arithmetic mean birth rate of children with CEB over a five-year period was 2.13 cases per 100,000 children born. The registry contains information on 22 deceased patients, average age was 3.06 ± 4.66 (from 0 to 15 years, median 0.54 years). The highest number of fatal outcomes was observed in the Republic of Dagestan (n = 3). Junctional CBE dominates in fatal outcomes among all the CEB types — 59.1% (n = 13 cases, 0.40 ± 0.22 years). The highest mortality was observed in I age group (from 0 to 1 year), which is 65.2% (15 fatal outcomes). Multisystem organ failure resulting from sepsis was the most common cause of death in both types of CEB (junctional and dystrophic). The mortality trend in the junctional form of CEB shows a decline in mortality, while the dystrophic type shows a stable situation during 2021–2023 years — 2 fatal outcomes per year. Junctional CEB has higher mortality rate at early age: survival curve shows sharp decline in the first months of life indicating high mortality in early life. The probability of survival drops to almost 0% in the first 100 days. Higher survival rate is more specific for the dystrophic type of CEB. Conclusion. This study demonstrates the significance and necessity to create and maintain registers for rare (orphan) diseases. Registry maintenance is an effective model for real understanding of the number of patients and value of needed assistance from the government to this category of patients.

The longitudinal retention of STEM students through a multifaceted mentoring and tutoring program

ABSTRACT This 4-year longitudinal study identified the impact of a multifaceted mentoring and tutoring program on the retention and graduation rates of a diverse body of undergraduate college students enrolled in high-risk science courses. Findings revealed that the program was successful in increasing the retention and graduation rates of students who participated in the program. All student cohorts tutored through the program demonstrated significantly higher survival rates when they increased their usage of tutoring, threby demonstrating greater survival to retention. Notably, cohorts with high as well as those with low academic competencies achieved the highest 4-year retention survival probabilities when they participated in six or more tutoring sessions. Additionally, through further analysis, a predictive model derived from this research offers a valuable tool that can be strategically utilized to improve retention and/or graducation outcomes of at-risk populations and underrepresented populations in STEM education.

Association between dietary patterns and the prognosis of amyotrophic lateral sclerosis in China: a cross-sectional study.

Recently, a growing number of studies have specifically examined the impact of dietary variables on the development and progression of amyotrophic lateral sclerosis (ALS). The purpose of this study was to investigate the correlation between different dietary patterns and Chinese ALS patients' prognosis. A retrospective study was conducted by recruiting 590 patients with ALS who attended and were regularly followed at hospitals in Nanjing from 2016 to 2023. Nutrient intake was calculated using dietary information collected through the food frequency questionnaire (FFQ), and patients were divided into a control group and special diet groups, including a high-calorie group (HC), a high-protein group (HP), and a ketogenic diet group (KD), based on their specific intake. And used the Kaplan-Meier product limiting distribution to compare the time required to transition between phases of different dietary patterns and to estimate cumulative survival probabilities. Patients in the HP had a better nutritional status. And the disease progression rate (ΔFS) was significantly associated with dietary patterns, with the KD group having the lowest ΔFS. Meanwhile, special diets extended the survival time of stage 4 patients but had no effect on the overall survival of the disease. A special diet can be one of effective options for patients with advanced ALS. Patients with poor nutritional status may choose the HP diet, whereas those with underlying conditions should consider the ketogenic diet with caution.

Entropies, level-density parameters and fission probabilities along the triaxially- and axially-symmetric fission paths in 296Lv

We investigate the variation of statistical properties of the fissile nucleus, especially entropy, and nuclear level density, along different fission paths. The calculations were focused on comparing axial and triaxial trajectories leading to fission of 296Lv. We observe that change of shell effects and their suppression rates with deformation can substantially influence fission dynamics. Furthermore, the fission process exhibits iso-entropic behavior at high excitation energies, while pronounced entropy variations are observed at lower energies. We derive a deformation-dependent level density parameter that plays a critical role in estimating the survival probability of a superheavy nucleus. The competition between different fission paths was further studied by employing a master equation approach, thereby demonstrating the critical role of entropy and thermodynamic properties in shaping fission dynamics within multidimensional deformation spaces.

Sociodemographic Disparities in 1-Year Outcomes of Children With Community-Acquired Acute Kidney Injury

Racial disparities have been identified in pediatric community-acquired acute kidney injury (CA-AKI), and they are associated with increased risk of child mortality, morbidity, and progression of kidney disease. To assess clinical outcomes at 1 year among children with CA-AKI, stratified by age, race, and ethnicity. This retrospective cohort study is a population-based analysis of deidentified, aggregated electronic health record data collected by 61 large health care organizations from 2003 to 2023 and accessed through the TriNetX platform. Outcomes were assessed at 1 year after a CA-AKI episode. Participants included pediatric patients (aged <18 years) with AKI. Data were accessed in January 2024. A diagnosis of CA-AKI and sociodemographic factors such as race, ethnicity, and age, as reported in electronic health records. The primary end point of this study was to assess differences in clinical outcomes within 1 year of an episode of CA-AKI, including all-cause emergency department (ED) visits, intensive care unit (ICU) admissions, mechanical intubation and ventilation, and mortality. Risk was compared between White children and Asian (including Asian, Native Hawaiian, and Other Pacific Islander), Black, and Hispanic children, stratified by age group. Measures of association, Cox proportional hazard analyses, and Kaplan-Meier survival curves were performed within the TriNetX Advanced Analytics Platform between racial and ethnic groups for each analysis. From the total sample of 18 152 children, those with hospital-acquired AKI, chronic kidney disease, end-stage kidney failure, or dialysis dependence were excluded, leaving a final cohort of 17 125 children (mean [SD] age, 11.2 [5.2] years; 9424 male [55.3%]). Eligible patients were divided into racial and ethnic groups as follows: non-Hispanic Asian, 1169 children (6.5%); non-Hispanic Black, 4636 children (27.3%); Hispanic, 1786 children (10.2%); and non-Hispanic White, 9534 children (55.9%). Patients were further subdivided into groups aged 0 to 9 years (546 Asian children, 1675 Black children, 689 Hispanic children, and 3340 White children) and 10 to 18 years (623 Asian children, 2961 Black children, 1091 Hispanic children, and 6104 White children). Within 1 year of CA-AKI diagnosis, compared with White children, Black children experienced greater rates of ED visits (hazard ratio [HR], 1.53; 95% CI, 1.40-1.67), ICU admissions (HR, 1.31; 95% CI, 1.16-1.47), mechanical ventilation (HR, 1.33; 95% CI, 1.13-1.56), and all-cause mortality (HR, 1.27; 95% CI, 1.09-1.48), as well as the greatest risk for composite outcomes (HR, 1.43; 95% CI, 1.33-1.53). Hispanic children experienced greater rates of ED visits (HR, 1.40; 95% CI, 1.21-1.62) and the greatest risk of all-cause mortality (HR, 1.66; 95% CI, 1.31-2.09), whereas Asian children experienced greater rates of mechanical ventilation (HR, 1.69; 95% CI, 1.26-2.27), compared with White children. Black and Hispanic children aged 0 to 9 years were at greatest risk of experiencing poor clinical outcomes. Black children had a 11.41% lower survival probability and Hispanic children had a 7.14% lower survival probability compared with White children after an initial ED encounter. Among children with an identified episode of CA-AKI diagnosed in an ED, within 1 year, Black and Hispanic children had a poorer survival probability compared with White children. Future studies are needed to understand these disparities and improve awareness and follow-up after emergency care.

Native woody species depend on the soil microbiome to establish on burned soils, while non‐native do not

Abstract Wildfires are important natural disturbances with profound ecological impacts. However, our understanding of how to restore plant–soil microbiome interactions following wildfires remains limited, revealing a key knowledge gap in post‐wildfire ecosystem restoration. To assess the restoration of plant‐microbiome interactions in fire‐affected ecosystems, we conducted greenhouse experiments simulating wildfire effects on soil collected from Maulino Coastal Forest of central Chile, a biodiversity hotspot. We measured the plant height and photosynthesis over 90 days, and two‐year survival probability, of three common native (Aristotelia chilensis, Nothofagus glauca and N. alessandrii) and three non‐native species (Eucalyptus globulus, Pinus radiata and Genista monspessulana) planted in three soils (unburned, burned and burned soil inoculated with the native microbiome). Available nutrient concentrations (N, P and K) and activities of microbial enzymes (dehydrogenase, β‐glucosidase and urease) were also measured over 360 days. Available nutrient concentrations were consistently higher in burned and burned‐inoculated soils than in unburned soils. Enzyme activities in unburned and burned‐inoculated soils remained higher than in burned soil, indicating that the native microbiome restored microbial enzyme activities. The increase in height over 90 days was lower in burned soils compared with unburned soils for native species. However, inoculation with the native microbiome mitigated this negative effect, resulting in height increases similar to those in unburned soils. For non‐native species, burning and inoculation had negligible effects on the height increases. Similar patterns were observed for the increase in photosynthetic rate, with native species showing a reduced rate in burned soils, which was offset by microbiome inoculation, while non‐native species were unaffected by both treatments. Survival probability of native species declined in burned soil, but was the same in burned‐inoculated soil as in unburned soil. That of non‐native species was unaffected by burning or by inoculation with the native microbiome. Synthesis and applications. Native microbiomes are evidently promising tools to safeguard ecosystem functionality and mitigate species extinction risks arising from climate change and human‐induced wildfires. We advocate integrating microbiomes into future active restoration strategies for fire‐affected ecosystems.

Herbivory can reduce perennial grass seedling survival, but temperature and cumulative precipitation are more important predictors in the first growing season

Successful establishment of desired species during restoration is challenging in drylands. Much research has focused on the importance of the critical life stages such as germination and emergence, but factors influencing survival through the seedling stages of perennial grasses may be equally important. We asked whether seedling defoliation by insects and/or mammals could cause restoration failure. We quantified the degree of defoliation on seedlings of common perennial grass species at 46 restoration sites throughout Oregon, Idaho, and Nevada, and calculated survival probabilities during the first growing season after planting. At each site, we excluded small mammals and insects for 6 weeks and compared defoliation and survival probabilities with seedlings in controls without exclusions. Seedlings were classified as either: large perennial grasses (LPG), primarily from the Triticeae tribe, or Bluegrasses (Poa spp.). Defoliation of LPG reduced seedling survival, but the effect was small compared to the influence of meteorological variables, such as precipitation and temperature. Based on bite patterns, most defoliation resulted from insects. Only a small percentage of vegetation was removed (36% of individuals were defoliated, mean = 13.2% vegetation removal). Defoliation of bluegrasses was less common than that of LPG seedlings, with only 16% experiencing defoliation, primarily from insects (mean = 4.3% vegetation removal). Some defoliation did occur within the exclusion treatments, but the effect of defoliation on seedling survival did not appear to interact with treatment. Based on the results of this study, seedling herbivory is unlikely to be a major factor in restoration failure in the Northern Great Basin.

Pediatric B-cell Non-Hodgkin Lymphoma: The Impact of Therapy Response and Relapse on Outcome. A Single-center Analysis.

Pediatric patients with primary refractory or relapsed B-cell non-Hodgkin lymphoma (B-NHL) have highly unfavorable prognosis. In this study, we retrospectively analyzed outcomes in pediatric B-NHL patients treated in a single center in Poland from 1995 to 2022, with emphasis on therapy results in patients with progression or relapse. The primary objectives were a 5-year probability of overall survival (pOS) and a 5-year probability of event-free survival (pEFS). The secondary objectives involved the assessment of prognostic factors. A total of 76 children were eligible for the analysis. The 5-year pOS was 76.7%, and the 5-year pEFS was 72.9%. At diagnosis, elevated lactate dehydrogenase activity, the presence of B symptoms, bone marrow, skeletal or mediastinal involvement, and stage IV disease were associated with inferior outcomes. Nine children experienced progression and four relapse. The 5-year pOS for patients with progression was 38.1%. Two patients treated with hematopoietic stem cell transplantation (HSCT) as part of salvage therapy survived. However, only one out of seven patients who were treated without HSCT survived. The 5-year pOS was 0.0% in patients with relapsed disease. The most significant factor related to outcomes in pediatric B-NHL is therapy response, with a high mortality rate in children with refractory disease and relapse. There is no consensus on the salvage therapy approach; however, HSCT appears to be the optimal choice.

Hematopoietic Cell Transplant compared with Standard Care in Adolescents and Young Adults with Sickle Cell Disease

Disease-modifying therapies are standard of care (SOC) for sickle cell disease (SCD), but hematopoietic cell transplantation (HCT) has curative potential. We compared outcomes prospectively through 2-years after biologic assignment to a Donor or No Donor (SOC) Arm based on the availability of an HLA-matched sibling or unrelated donor (BMTCTN 1503; NCT02766465). A donor search was commenced after eligibility confirmation. The primary endpoint was the comparison of survival 2 years after biologic assignment between treatment arms. Power calculations required 60 participants on the Donor Arm and 140 on the No Donor Arm to determine if early transplant-related mortality might be balanced by disease-related mortality over a longer period of follow-up. Secondary objectives compared changes in SCD-related events, functional outcomes, and organ function. Data were analyzed by the intent-to-treat principle. A total of 113 participants were enrolled, 28 on the Donor and 85 on the No Donor Arm The 2-year probabilities of survival were 89% and 93%, on the Donor and No Donor Arms, respectively. Vaso-occlusive pain (VOC) was less frequent on the Donor Arm in the second year after biologic assignment (p < 0.001). On PROMIS-57 surveys there was decreased fatigue (p=0.003) and an increased ability to participate in social roles and activities (p=0.003) on the Donor Arm 2-years after biologic assignment. Differences in other secondary outcomes did not reach statistical significance. Barriers to accrual prevented an objective comparison of survival. Assignment to the Donor Arm led to improvements in VOC, fatigue, and social function.

Long-Term Recurrence Risk, Metastatic Potential, and Length of Cystoscopic Surveillance of Low-Grade Non-Muscle-Invasive Bladder Cancer.

Patients with Ta low-grade (LG) NMIBC rarely develop metastases or die of it. Long-term data are scant and length of follow-up poorly defined. This retrospective study included 521 patients diagnosed with primary TaLG NMIBC (n = 491) or papillary urothelial neoplasm of low malignant potential (n = 30) from 1989 to 2019 at an academic center. Patient data were acquired using patient records chart review and a bladder cancer informatics registry at the center. Risk of recurrence and progression in stage, to muscle invasion, metastases, and death due to BC were analyzed. RNAseq assessed the transcriptomic profiles of 4 TaLG NMIBCs that metastasized. Interobserver variability in pathological grading (WHO 2004/2022 and 1973, n = 80) was blindly assessed by 3 expert pathologists. The median follow-up was 9.6 (95% CI: 8.6-10.2) years. Among 521 patients (73% men, median age 67.0 years), 350 recurred, 57 progressed in stage, 20 developed metastases, and 15 died of BC (median of 9.6 years after diagnosis). Cancer-specific survival probabilities were 0.99, 0.98, and 0.96 at 5, 10, and 15 years, respectively. Fifty patients who were recurrence free for the first 5 years developed late recurrences and 2 of them died of BC. Metastatic TaLG NMIBC had more adverse transcriptomic findings in keeping with higher grade tumors despite being phenotypically similar to indolent tumors. Grading concordance for the 2004/2022 system and WHO 1973 was 0.78 (95% CI: 0.65-0.90) and 0.41 (95% CI: 0.32-0.50), respectively. This study with long-term data challenges the assumption that primary TaLG NMIBC nearly never progresses to lethal disease if followed long enough. However, the risk of BC-related mortality is extremely low in patients who are recurrence-free for the first 5 years. Minimizing variability in pathological grading remains an unmet need.

SHIFT@LHC: Searches for new physics with shifted interaction on a fixed target at the Large Hadron Collider

New low-mass particles with very small couplings to standard model particles that travel significant distances before decaying are interesting candidates to address some of the most intriguing questions of modern physics. In this paper, I propose to extend the LHC’s research program by installing a gaseous fixed target referred to as SHIFT at around 160 meters from the CMS interaction point. When the LHC proton beam collides with this target, interactions at a center of mass energy of ≈113 GeV would occur. The particles produced in such collisions, or their decay products, would travel through the rock and other material on their path, potentially reaching the CMS detector where they can be registered and studied. Such an approach would allow us to access otherwise uncovered regions of parameters phase space at a relatively low cost since it does not require constructing a new detector. Various aspects such as angular and lifetime coverage or material survival probability have been studied. The results are interpreted within two new physics models, namely, the Dark Photons and the Hidden Valley scenarios, and compared with the standard proton-proton physics program of CMS. A comparison is also made with the fixed target program at LHCb, as well as parasitic detectors such as FASER or MATHUSLA. The obtained results indicate that, despite assuming just 1% of the nominal CMS luminosity to be available to SHIFT, the physics reach could be extended by a factor of up to 150 (1000) for Dark Photon (Hidden Valley) scenarios, depending on the signal model parameters.

The V410L kdr allele in the VGSC confers higher levels of field resistance to permethrin in urban mosquito populations of Aedes aegypti (L.).

Females of Aedes aegypti transmit emerging arboviruses including Zika, dengue, yellow fever, and chikungunya. Control of these adult mosquitoes heavily relies on synthetic insecticides, including pyrethroids. However, insecticide resistance development in populations poses a significant challenge to vector control, particularly from knockdown resistance (kdr) mutations in the voltage-gated sodium channel (VGSC), the target of pyrethroids. This study investigated the field efficacy of Permanone, a pyrethroid-based insecticide, against Ae. aegypti by assessing the impact of three common kdr mutations (V410L, V1016I, F1534C) on mosquito survival under a real operational mosquito control scenario, by quantifying the pesticide delivered in the field. Field cage tests (FCTs) were conducted while conducting a realistic mosquito control application. Female mosquitoes from six operational areas from Harris County, TX, USA were exposed to Permanone delivered with a handheld sprayer. Permanone deposited near the cages was estimated from aluminum boats placed in the field during FCTs using gas chromatography-mass spectrometry (GC-MS). Mortality rates were recorded, and individual mosquitoes were genotyped for kdr mutations. A probit regression model was used to analyze the factors influencing mosquito survivorship. As the distance from the application source route increased, the amount of Permanone deposited decreased, resulting in higher survivorship frequency of Ae. aegypti females with the triple-resistant kdr genotype (LL/II/CC). The L allele at the 410-site significantly contributed to an increased resistance level when co-occurring with other kdr mutations. This study linked the survival probabilities of mosquitoes with different kdr genotypes, and the amount of pesticide they received in the field. Pesticide quantification, control efficacy results and genotyping allowed us to empirically determine the impact of genotypic resistance on vector control in the field. © 2024 Society of Chemical Industry.

Temporal trends in initiation of oral anticoagulants and stroke-free survival among elderly and very elderly patients with new onset atrial fibrillation - a 20-year perspective.

Abstract Background Oral anticoagulants (OACs) significantly reduce the risk of ischemic stroke in patients with atrial fibrillation (AF). However, evidence regarding efficacy of OACs are lacking in the very elderly patients. Aim To examine temporal trends in initiation of OACs and five-year stroke-free survival in the very elderly patients with new onset AF over a time span of 20 years. Methods From the Danish nationwide registries, we identified patients ≥ 65 years of age with new onset AF from 1999 to 2018. The index date was defined as the day of AF diagnosis for outpatients and as the day of discharge for inpatients. Patients with a prescription of OAC, history of bleeding events, or history of stroke/transient ischemic attack prior to index were excluded. Patients were divided into two age groups based on their age at index: 1) 65-84 years (elderly); and 2) ≥ 85 years (very elderly). Patients were further divided into four calendar year groups from 1999-2018, based on the year of inclusion. We investigated the initiation of OACs and calculated the absolute five-year probability of stroke-free survival in both age groups. Results We included 167,122 patients with new-onset AF between January 1st, 1999, and December 31st, 2018. Among the patients, 23.1 % were aged 85 years or older, 48 % were male and 80.5 % had a CHA2DS2-VASc score equivalent to 2 or higher for men and 3 or higher for women. Initiation of OACs increased in both age groups after the guideline implementation of DOACs in 2010 (Figure 1). In the elderly age group, the proportion of patients receiving OACs increased from 50% in 2010 to almost 90% in 2018. In the very elderly age group, the proportion increased from 25% in 2010 to almost 90% in 2018. The probability of the five-year stroke-free survival improved by approximately 15% from 1999 to 2018 in the elderly age group, with no significant changes in the very elderly age group. Conclusion The proportion of elderly AF patients receiving OAC has increased markedly in the last 20 years. Even so, stroke-free survival remains the same among the very elderly patients.Five-year stroke-free survival

Prognostic staging system correctly identifies high risk groups in cardiac transthyretin amyloidosis treated with tafamidis

Abstract Background The development of different multiparametric staging systems improved the risk assessment of cardiac transthyretin amyloidosis (ATTR-CA) patients substantially. However, to date, all staging systems were validated in treatment-naive ATTR-CA patients. The introduction of tafamidis led to significant changes in the disease trajectory of ATTR-CA, indicating that it may also have an impact on the prognostic accuracy of these staging systems. Purpose Thus, we sought to assess whether the prognostic value of the National Amyloidosis Centre (NAC) staging system, currently considered as the most accurate, is sustained in ATTR-CA patients treated with tafamidis. Methods This retrospective observational study included ATTR-CA patients treated with tafamidis. Patients were continuously followed from treatment initiation to time of death. NT-proBNP and eGFR data collected at baseline were used to stratify patients into low (stage I), intermediate (stage II) and high-risk (stage III) subgroups according to the NAC staging system. Kaplan-Meier analyses were conducted to illustrate overall survival. Differences in overall survival between subgroups were assessed by log rank tests. P-values &amp;lt;0.05 were considered statistically significant. Results A total of 166 ATTR-CA patients (95.2% wild-type) were enrolled. 81 (48.8%), 51 (30.7%) and 34 (20.5%) patients were stratified into stages I, II and III, respectively. Median follow-up was 539 [323-865] days, during which 20 deaths were recorded. Overall survival of the subgroups over time is demonstrated in figure 1. The probability of overall survival was significantly lower for patients in stage III compared to patients in stages I (log rank; p=0.002) and II (log rank; p=0.031). However, no differences in the probability of overall survival were identified between patients in stage I and II (log rank; p=0.679). Conclusions In this cohort of ATTR-CA patients treated with tafamidis, the NAC staging system effectively identified patients at elevated risk of mortality. However, the distinction in survival rates between low- and intermediate-risk groups was less pronounced, suggesting that tafamidis may have a stronger prognostic impact in these groups.Overall Survival across NAC Stages

Combined evaluation of liver and kidney function improves prediction of clinical outcome in patients with chronic heart failure and reduced ejection fraction

Abstract Background/Introduction The liver and the kidneys are important organs for body homeostasis and are both affected by heart failure (HF) either by systemic venous congestion or hypoperfusion. Purpose We aimed to verify whether the Model for End-stage Liver Disease eXcluding International normalized ratio (MELD-XI), as well as a combination of cholestatic liver and kidney function tests carry prognostic value in patients with chronic HF with reduced ejection fraction (HFrEF). The liver parameters included alkaline phosphatase (ALP), gamma glutamyl-transpeptidase (GGT), and total bilirubin, while kidney parameters consisted of eGFR and the tubular damage markers urinary N-acetyl-beta-D-glucosaminidase (NAG) and kidney injury molecule (KIM)-1. Methods We categorized 250 patients with HFrEF on the basis of baseline biomarker levels. We assumed elevated NT-proBNP indicates hemodynamic congestion necessary to induce congestive liver or kidney dysfunction. Thus, in every organ damage category, NT-proBNP level above median was incorporated, next to any 2 out of 3: ALP, GGT or total bilirubin above median for liver dysfunction; any 2 out of 3 NAG or KIM-1 above median or eGFR below median for kidney dysfunction; or coexistence of liver and kidney dysfunction as defined above. Additionally, a subgroup of patients with both NT-proBNP and MELD-XI above the median was analyzed. The primary endpoint was a composite of cardiovascular death, heart transplantation, LVAD implantation, and hospitalization for acute or worsened HF, whichever occurred first. Univariable and multivariable Cox proportional hazard regression models were used. Results Median (Q1-Q3) age of the study population was 68 (58-76) years; 184 (74%) were men, 62 (25%) in NYHA class III or IV, and mean left ventricular ejection fraction (LVEF) was 31±9%. During a median (Q1-Q3) follow-up of 2.2 (1.4-2.5) years, 66 (26%) patients reached the primary endpoint. We observed that liver dysfunction, kidney dysfunction or their coexistence was associated with significantly higher risk of reaching the primary endpoint (HR 3.54, 95% CI 1.75–7.16; HR 1.85, 95% CI 1.00–3.41; HR 2.52, 95% CI 1.03–6.11 respectively) in the clinically adjusted model (Table 1). Higher MELD-XI was associated with higher risk of reaching the primary endpoint in an unadjusted model but not in a clinically adjusted model. Figure 1 presents event-free survival probability of patients falling into organ dysfunction categories. Conclusions Our results show that markers of cholestatic liver function and kidney function predict unfavorable clinical outcome and provide better prognostic value in chronic HFrEF patients than the MELD-XI alone. Thus, screening for liver and kidney damage may help identify high-risk patients in whom more careful observation and individualized therapy is warranted.Fig 1.Event-free survival probability

Carotid-Femoral pulse wave velocity progression in hypertensive patients is associated with subsequent cardiovascular outcomes

Abstract Background Arterial stiffness (Pulse Wave Velocity - PWV) is associated with CV events and mortality. However, little is known on the relationship of its progression (ΔPWV) over time with CV outcomes. Purpose The aim of our study was to evaluate the relationship between PWV progression and all-cause mortality and CV events in hypertensive subjects. Methods We enrolled 402 consecutive hypertensive outpatients. At baseline anamnestic, clinical, BP, laboratory data and PWV were assessed. We performed a PWV follow-up examination at a median time of 3.7±0.5 years. Patients were subsequently followed for a median time of 10.1 (IQR 9.5 -10.5) years recording all-cause mortality and CV events. Results At baseline the mean age was 53.2±13.0 years, SBP and DBP were 141.8±17.5 and 86.8±10.5 mmHg and PWV was 8.5±1.9 m/s. Despite an improvement in BP control (- 9.2±19.5 and -8.0±12.3 for SBP and DBP respectively), at follow-up the population showed a PWV increase (ΔPWV +0.6±1.9 m/s). Progressors (ΔPWV ≥ 0.5 m/s, 204 patients, 50.7%) had a significantly lower survival probability and higher cumulative incidence of composite events, while no differences were seen for CV events (unadjusted analysis). At cox multivariable analysis neither ΔPWV ≥ 0.5 m/s (progressors) nor ΔPWV (as a spline function) were associated with CV events and with all-cause mortality. However, the association with survival probability and cumulative incidence of CV events, as a composite outcome, was significant (HR = 2.32, 95% CI: 1.33 – 4.04, p=0.003). Conclusions In conclusion, our study shows that PWV progression of at least 0.5 m/s is frequent in hypertensive patients and that it is associated with a significantly higher risk of developing CV events or dying (composite outcome).

PRIORiTize-TAVI might predict more than transcatheter aortic valve replacement waiting list priorities

Abstract Background PRIORiTize-TAVI (Predicting moRtalIty Or uRgent TAVI on waiting list) is a novel scoring system targeting identification of patients at risk of urgent hospitalization or death whilst waiting for transcatheter aortic valve replacement (TAVR) (1). Patients are divided into those with low (&amp;lt;2 points), intermediate (3-4 points) and high (&amp;gt;5) waiting risk. Given the novelty of the score, additional research is required to further validate it. However, being compiled of parameters applied in everyday practice that are readily available, the application of the score might have the potential to go beyond its original purpose. Purpose We aimed to investigate whether PRIORiTize-TAVI score can predict postprocedural complications and survival following TAVR. Methods We conducted a registry-based study including patients who underwent TAVR at our institution from 2018 to 2023. PRIORiTize-TAVI was calculated summarizing points according to NYHA status, left ventricular ejection fraction (LVEF), NTproBNP, mean pressure gradient (meanPG) and Charlson comorbidity index (CCI) at the time of patient placement onto TAVR waiting list. Results This registry-based study included 252 patients with median age 80 (interquartile range (IQR) 76-84) years, 50% female. Median PRIORiTize score was 5 (IQR 3-7). There were 41 (16%) low, 51 (20%) intermediate and 160 (64%) high risk patients. High risk patients had more frequently atrial fibrillation and ischaemic stroke, had lower LVEF and estimated glomerular filtration rate (eGFR), higher NTproBNP levels and CCI (Table 1). MeanPG also statistically differed between intermediate risk group and low risk group, but not with high risk group (Table 1). TAVR waiting time was significantly shorter in high-risk patients in comparison to intermediate risk patients. There was no statistical difference regarding baseline characteristics between the three groups (Table 1). There was no statistical difference in post-TAVR complications between the three groups. Survival significantly differed depending on PRIORiTize risk stratification (P=.023), as shown in Figure 1. Median survival time for high risk patients was 49 months (IQR 42-49), whereas the median survival time for intermediate and low risk patients could not be reached. High risk patients had lower survival probability compared to both intermediate (HR 4.089; CI 1.91-8.73) and low risk (HR 2.078; CI 0.77-5.59) patients. Intermediate risk patients had a higher survival probability compared to low risk patients (HR 0.508; CI 1.67-1.54). Length of TAVR waiting time had no significant association with overall survival (P=.891). Conclusions Our data show that PRIORiTize-TAVI has a potential to be used as a prognostic tool to predict survival probability post-TAVR. Our results suggest that prolonged time on TAVR waiting list did not negatively impact patient postprocedural complications nor survival.Table 1Figure 1