Low Number Research Articles

An aged-related structural study of DHPR tetrads in peripheral couplings of human skeletal muscle.

Among the numerous changes that occur in skeletal muscle during aging, the reduced regeneration potential after an injury is largely due to the impaired ability of satellite cells to proliferate and differentiate. Herein, using the freeze-fracture electron microscopy technique, we analyzed both the incidence and size of dihydropyridine receptors (DHPRs) tetrads (4 particles) in cultured myotubes from a young subject (28 years) after 9 days of differentiation and from an old subject (71 years) after 9 and 12 days of differentiation. Compared to young myotubes, at 9 days of differentiation old myotubes exhibited: i) a lower incidence and a smaller size of DHPR clusters and ii) a lower number of complete tetrads. At 12 days of differentiation values of incidence, size and number of complete tetrads in old myotubes were instead comparable with those of young myotubes at 9 days of differentiation. Collectively, these results indicate that in aged myotubes the synthesis process of the proteins involved in the excitation-contraction coupling mechanism, such as the DHPR, is somehow slowed, supporting previous studies evidence of a decrease in the differentiation potential of myotubes from elderly individuals.

Automatic setting optimization for robotic upper-extremity rehabilitation in patients with stroke using ReoGo-J: a cross-sectional clinical trial

Stroke-induced upper-extremity paralysis affects a substantial portion of the population, necessitating effective rehabilitation strategies. This study aimed to develop an automated program, incorporating the item response theory, for rehabilitation in patients with post-stroke upper-extremity paralysis, focusing on the ReoGo-J device, and to identify suitable robot parameters for robotic rehabilitation. ReoGo-J, a training device for upper-extremity disorders including 71 items, was administered to over 300 patients with varying degrees of post-stroke upper-extremity paralysis. Each item was rated on a three-point scale (0, very difficult; 1, adequate; 2, very easy). The results were analyzed using the graded response model, an extension of the two-parameter logistic model within the framework of the item response theory, to grade the training items based on ability of the patients. The relationship between the predicted ability, an indicator of the predicted ability the paralyzed upper-extremity to perform an item in the item response theory analysis (higher numbers indicate higher ability, lower numbers indicate lower ability), and the items in the Fugl–Meyer assessment (FMA), which indicate the degree of paralysis, was analyzed using Pearson’s correlation coefficient. This study included 312 patients with post-stroke upper-extremity paralysis. The predicted ability (θ) of the tasks included in the original ReoGo-J test for forward reaching, reaching for mouth, rotational reaching, radial reaching (2D), abduction reaching, reaching in eight directions, radial reach (3D), and reaching for head ranged from − 2.0 to − 0.8, − 1.3 to − 0.8, − 1.0 to − 0.1, − 0.7 to 0.3, − 0.2 to 0.4, − 0.4 to 0.6, − 0.1 to 0.6, and 0.5 to 0.6, respectively. Significantly high correlations (r = 0.80) were observed between the predicted ability of all patients and the upper-extremity items of shoulder-elbow-forearm in the FMA. We have introduced an automated program based on item response theory and determined the order of difficulty of the 71 training items in ReoGo-J. The strong correlation between the predicted ability and the shoulder-elbow-forearm items in FMA may be used to ameliorate post-stroke upper-extremity paralysis. Notably, the program allows for estimation of appropriate ReoGo-J tasks, enhancing clinical efficiency.Trial registration: https://www.umin.ac.jp/ctr/index-j.htm (UMIN000040127).

Volume-outcome relationships for intra-aortic balloon pump in acute myocardial infarction

Abstract Background Acute myocardial infarction (MI) is one of the major scenarios of intra-aortic balloon pump (IABP) use, particularly when complicated by cardiogenic shock. The utilization of mechanical circulatory support devices including IABP varies widely per hospital, while whether a higher IABP volume at each hospital is translated into better outcomes in acute MI is unclear. Purpose To evaluate the relationship between the volume of IABP use and mortality at the hospital level in patients with acute MI undergoing percutaneous coronary intervention (PCI). Methods Using a Japanese nationwide administrative database, a total of 26,490 patients with acute MI undergoing primary PCI from 154 hospitals were included. The primary endpoint was the observed/predicted in-hospital mortality ratio. The predicted mortality per patient was calculated using baseline variables and was averaged for each hospital. The associations among PCI volume for acute MI, observed and predicted in-hospital mortality, and observed and predicted IABP use were assessed at the hospital level. Results Of the 26,490 patients, 2,959 (11.2%) were treated with IABP and 1,283 (4.8%) died during hospitalization. The annualized number of IABP use per hospital in acute MI was 4.5 [2.4-10.7]. In lower primary PCI volume centers, IABP was more likely to be underused than expected, and the observed/predicted in-hospital mortality ratio was higher than in higher volume centers (Figure). The observed/predicted mortality ratio seemed lowest in hospitals where the observed/predicted IABP use ratio was around one. Conclusions The present study showed that the lower annual number of IABP use was associated with an increased mortality risk at the hospital level, and suggested that standardized IABP use can be an institutional quality indicator in a setting of acute MI.

Early improvement in left ventricular microvascular flow post sonothrombolysis is associated with better left ventricular systolic function in st elevation myocardial infarction patients

Abstract Background/Introduction Acute coronary syndromes are the main cause of death worldwide and the timely application of proper therapy is critical for patient outcome. However, even when state of the art treatment is implemented, significant no-reflow phenomenon may occur. In this scenario, sonothrombolysis, which consists of a continuous infusion of an ultrasound-enhancing agent associated with high-energy intermittent ultrasound impulses, may restore cardiac microcirculation and improve left ventricular (LV) systolic function. Purpose We aimed to evaluate LV segmental microvascular flow, LV mechanics and function in patients with ST-elevation myocardial infarction (STEMI) after sonothrombolysis therapy and evaluate whether an early (immediately post percutaneous coronary intervention – PCI or PCI+Sonothrombolysis) improvement in myocardial microvascular flow could predict better LV systolic function at 1-month. Methods STEMI patients receiving conventional treatment (PCI with or without previous fibrinolytic therapy) were randomized to sonothrombolysis (therapy group - TG) or conventional treatment (control group - CG). This study included 143 patients (interim analysis) who compose the HUBBLE I databank (High-intensity Ultrasonic impulses and microbuBBles to Limit the Extent of acute myocardial infarction I) and were randomized from two clinical trials (NCT04732091 and NCT02410330): CG, N=74 and TG, N=69 patients. There were 25 patients treated previously with fibrinolytic therapy (14 in CG and 11 in TG) and the percentage of left anterior descending artery as culprit vessel was similar between groups (59 vs. 54%, P=0.482). Sonothrombolysis was initiated after patient admission to the emergency room and continued after PCI for a total of 50 minutes. Echocardiography was carried out immediately after PCI or PCI+Sonothrombolysis and at 1-month for assessing LV ejection fraction (LVEF) and perfusion score index (PSI) in contrasted imaging and global longitudinal strain (GLS) in 2D imaging, that was presented in [module]. Results Demographic characteristics, cardiovascular risk factors and echocardiographic variables immediately after PCI or PCI+Sonothrombolysis were similar between groups (P>0.05). At 1-month follow up, TG presented higher LVEF (46.4±10.5 vs. 50.9±11.1%, P=0.018) and GLS (13.0±3.6 vs. 14.9±4.3%, P=0.008) and lower PSI (1.56±0.4 vs. 1.39±0.3, P=0.007) and number of segments with perfusion defects (5.8±3.7 vs. 4.6±3.3, P=0.050) compared with CG. There was a negative correlation between early PSI and 1-month LVEF (r=-0.701, p<0.0001). Conclusions The preliminary data indicates that sonothrombolysis can be an effective adjuvant treatment in STEMI patients previously treated or not with fibrinolytic therapy, contributing to a better myocardial microvascular flow and LV systolic performance. Early myocardial microvascular reperfusion improvement can predict whether cardiac function will improve in this setting.

Clinical validated risk prediction model for development of heart failure after contemporary breast cancer treatment

Abstract Background Patients receiving breast cancer (BC) treatment are at risk for heart failure and cardiomyopathy (HF/CM). European Society of Cardiology (ESC) cardio-oncology guidelines recommend baseline cardiovascular (CV) assessment, however, there is limited data about cardiotoxicity risk specific to patients with BC. Our aim was to develop and validate model for prediction of HF/CM in women receiving contemporary treatment for invasive early-stage BC. Methods We assembled a cohort women diagnosed with Stage I-III BC from 2008-2020 and followed through 2021 in a large health care plan. Women age >80, with history of HF/CM, and women who received both anthracyclines and trastuzumab were excluded, leaving N=26,044 for analysis. Study cohort was randomly split into derivation (60%) and validation (40%) datasets. Elastic-net penalized Cox proportional hazard model was created using the derivation dataset to select risk factors and to calculate the panelized coefficient which defined the HF/CM risk score. Risk score system was assessed by Hosmer-Lemeshow goodness-of-fit test and area under the ROC curve (AUC). Event rates of <5% constituted low risk; 5-14% moderate; and >15% high risk category. Incident HF/CM events were examined using Kaplan-Meier approach in derivation and validation datasets. Results HF/CM risk score had high discrimination ability and sufficiently good model of fit regarding HF/CM events (P value=0.163 and 0.667 from Hosmer–Lemeshow test;AUC 0.751 and 0.764, in derivation and validation sets, respectively). There were 10% of women in the high risk; 30% in moderate; and 60% in low-risk group. Variables associated with the higher HF/CM risk score included age, receipt of anthracycline-based chemotherapy or anti-HER2 therapy, presence of hypertension, diabetes, or history of other CV conditions at baseline. The score pattern showed major effect of age, with anthracycline and anti-HER2 therapy increasing the risk across all age groups (Figure 1). Kaplan-Meier analysis of incident HF/CM over 14 years after BC diagnosis showed significantly lower number of HF/CM events in low risk compared to moderate and high-risk score groups (p<0.0001, Figure 2). Conclusion Our robust risk prediction model for HF/CM among women with early-stage BC provides a new tool to identify women at higher CV risk and inform cardiac function monitoring during and after BC treatment. Our findings may guide further validation studies and build evidence for the cardiotoxicity risk stratification in patients with BC.Risk Score for HF/CM by Age/ChemoTxK-M curves of freedom from HF/CM

Children with disabilities and inclusive education in general schools: pricipals’ attitudes

Abstract Background As inclusive education is being implemented nationwide in Lithuania, various attitudes towards education of children with disabilities in general schools are observed. We aimed to assess the attitudes of heads of general schools towards the provision of education to children with disabilities in general education schools of Lithuania. Methods Heads of all schools in the Lithuanian capital and its surrounding municipalities implementing general education programmes were invited to take part in this study. 115 persons agreed to participate and completed the questionnaire in spring of 2024. The distribution of the respondents by their answers to the questions about the attitudes towards the provision of inclusive education was compared according to gender, age, education level, work experience, school location (municipality), language of education, type of school, subordination, number of pupils, teachers, teaching assistants and pupils with disabilities. Results The most frequently indicated barriers for inclusive education provision were the lack of specialists, compensatory measures, methodological tools, adaptation of the physical environment, and high number of pupils (87.8%, 84.3%, 78.8% and 76.6% respectively). Attitudes of the respondents were similar in most of the cases when compared according to socio-demographic factors (p more than 0.05). Negative attitudes towards the possibilities for provision of inclusive education were more common among respondents from schools with fewer pupils and higher relative number of teachers, positive attitudes - among those from schools located in municipalities with lower number of residents and schools with more teaching assistants (p less than 0.05). Conclusions While attitudes of heads of general schools towards the provision of inclusive education for children with disabilities are similar in most of the cases, negative attitudes are more common among those from schools with fewer pupils and more teachers. Key messages • While attitudes of heads of general schools towards the inclusive education are similar in most of the cases, negative attitudes are more common among those from smaller schools. • Higher number of teaching assistants and smaller municipalities were associated with positive attitudes towards inclusive education of children with disabilies in general schools.

Defibrillator shocks and their effect on objective asian patient outcomes: results of the painfree SST clinical trial

Abstract Background The implantable cardioverter defibrillator (ICD) reduces mortality in patients at risk of sudden cardiac death. However, the effect of ICD shock on device-measured activity is unknown. The aim of this analysis was to analyze the acute and long-term effects of ICD shock on objective behavioral data. Methods The PainFree SST study was a prospective, multicenter, global study that enrolled 2770 patients including 225 from from Asia (181 from Japan, 25 from India, and 19 from Malaysia). Patient physical activity was determined from the device built-in accelerometer. The device translates the accelerometer output into a count of active minutes, which is stored as a daily total value in device memory for a rolling window of 425 days. Obviously, activity is measured only after device implantation. Early after implant, activity is reduced due to the procedure and thus not representative. Therefore, no baseline can be reported for activity. The follow-up activity data was analyzed with a linear mixed model, with a random effect for patient and an auto-regressive correlation matrix for subsequent measurements of individual patients. Results Figure 1 shows average daily activity between 90 days before and 90 days after a shock. The dashed vertical line indicates the day of shock. Both patients from Asia and from other countries show a drop in activity after a shock with recovery in the subsequent 30-60 days. The curve for Asian patients is more variable than the curve for other countries due to the lower number of patients (there were 33 Asian patients with shocks contributing data). Figure 2 shows average daily activity before and after ATP therapy. Any post shock measurement is excluded. Contrary to the temporary reduction in activity around a shock (Figure 1), ATP therapies do not seem to have an impact on activity. In patients from the other countries, activity is significantly reduced when patients are hospitalized (-66.3 minutes/day, p<0.0001), but not in Asian patients (-5.1 minutes/day, p=0.71). Both in Asian and other countries, activity is significantly reduced after an ICD shock (Asian: -47.5 minutes/day, p=0.0002; Other countries: -21.5 minutes/day, p<0.0001). The effect of shock for Asian is greater than the other countries (p=0.054). In the month after the shock there is a significant recovery, +34.8 minutes/day in Asian patients (p=0.0077) and +7.7 minutes/day in patients from other countries (p=0.031). The recovery is trended to be bigger in Asian patients (p=0.058). Conclusions ICD shocks have a lasting adverse impact on objective, device-measured physical activity, particularly among Asian individuals. Successful management of patients with an ICD necessitates specific attention to clinically relevant behavioral outcomes, aiming to expedite recovery and facilitate a return to activities of daily living, with a particular focus on the Asian population.

Contrast-enhanced ultrasound combined with percutaneous ultrasound-guide core needle biopsies in the diagnosis of pancreatic lesions: a propensity score-matched study

ObjectiveTo compare the diagnostic performance of pancreatic lesions using percutaneous ultrasound (US)-guided core needle biopsy (CNB) with and without contrast-enhanced ultrasound (CEUS).MethodThe patients were divided into two groups, US and CEUS group, based on whether CEUS was performed prior to biopsy. Before and after propensity score matching (PSM), the CNB-relevant characteristics of the two groups, including the first puncture success rate, the number of sampling, complication rate, type of complications, and degree of abdominal pain, were compared. The accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of percutaneous US-guided CNB were compared between the groups.ResultsThis study included 277 patients (173 men and 104 women) with pancreatic lesions who underwent percutaneous CNB before PSM; 190 patients in the CEUS group, and 87 in the US group prior to CNB. After controlling for potential biases using PSM, no significant differences were observed in the complication rate, type of complications, or degree of abdominal pain between the CEUS and US groups (P > 0.05). However, significant differences were observed in the first puncture success rate and the number of sampling (P < 0.05). Importantly, before and after PSM, the CEUS group achieved a higher first-puncture success rate while obtaining a lower number of sampling (P < 0.05). Compared to the US group, the CEUS group demonstrated improved accuracy, sensitivity, specificity, PPV, and NPV of 13.1%, 14.9%, 13.4%, 2.5%, and 38.7%, respectively. Furthermore, the significant difference was observed in the AUC for diagnostic performance between the two groups when compared using DeLong’s test (P = 0.043).ConclusionsPerforming CEUS before percutaneous CNB for pancreatic lesions can help achieve better biopsy results, reduce the number of punctures samples, increase the success rate of biopsies, and avoid the need for repeat biopsies.

Utility of telephone text messages in secondary prevention after acute coronary syndrome

Abstract Introduction The recurrence of events in patients after an acute coronary syndrome (ACS) represents a great challenge for the health systems due to its high prevalence, morbidity and mortality, and cost. For this reason, secondary prevention measures with low cost and easy to implement are necessary. The objective is to evaluate the usefulness of telephone text messages (TTM) in the control of risk factors and reduction of events in the first year after an ACS. Methods Single-blind 1:1 randomized clinical trial in consecutive patients discharged with ACS between May 2019 and October 2021 in our center. The intervention group received a monthly TTM for 12 months with the recommendations of the Spanish Society of Cardiology regarding secondary prevention measures. Both groups followed the usual review protocol of our center in a specific ischemic heart disease consultation at 3 and 12 months after discharge. The center lacks cardiac rehabilitation. The objectives of the study at 12 months were: total and cardiovascular death, myocardial infarction, stroke, weight, blood pressure, LDL, HDL, triglycerides, glycosylated hemoglobin, smoking habit, and hours of exercise per week. The evaluator in charge of collecting data after the end of the year was unaware of the assignment group. Results N= 370. The patient profile was the usual one for ACS, with a mean age of around 65 years and 25% diabetic, with no differences in any of the baseline characteristics between both groups. An invasive approach was performed in almost all of the subjects, with percutaneous intervention in three-quarters of the cases and also without significant differences in the type of treatment, percentage of multivessel disease, and left main disease between both groups. Only a lower number of stents per patient was recorded in the control group. There were also no differences in medical treatment between both groups. The results are shown in the table. Conclusions In our study, monthly TTM had no influence on the control of risk factors or clinical events during the first year of follow-up after an ACS, and therefore it is not cost-effective to allocate resources for this purpose.

Health literacy in pregnant women facing prenatal screening: a short report from “SaperePer” project

Abstract Advancements in health promotion and prenatal medicine have made noninvasive prenatal testing (NIPT) a common practice during pregnancy, but understanding prenatal health information becomes crucial not only for the well-being of the mother but also for that of the unborn child. Analyze health-related information during pregnancy is fundamental, and this work fits perfectly with this topic, reporting preliminary results from the pilot study “SaperePer”. A health-related questionnaire was administered to 358 women in the first trimester of pregnancy, aiming to study different outcomes: 1.level of knowledge of NIPT; 2.number of screening tests undergone; 3.willingness to undergo a diagnostic test with a high outcome risk of screening test; 4.willingness to end the pregnancy following a diagnosis of pathology. The questionnaire was divided into 3 sections: personal characteristics and lifestyle habits, prenatal health behavior scale (PHBS), and knowledge of NIPT. Preliminary results showed that the level of knowledge of NIPT was higher in older, atheist, working, wealthy highly educated, and preliminary informed women, as well as the higher number of screening tests undergone and the propensity to undergo an invasive diagnostic test after a high-risk screening result (KS and MW tests p &amp;lt; 0.05). On the contrary, women with lower education, faithful and, even more, not preliminary and appropriately informed during prenatal counseling showed lower knowledge of NIPT, lower number of tests undergone, and meager chances to undergo an invasive diagnostic test or to end the pregnancy after a positive diagnosis of pathology (KS and MW tests p &amp;lt; 0.05). In conclusion, this study evaluated health-related information during the first but crucial stages of pregnancy, opening a new understanding of how health literacy and correct prenatal counseling could increase awareness and health promotion in pregnant women, particularly in those women with lower cultural tools. Key messages • Health literacy and correct prenatal counseling could increase awareness and health promotion in pregnant women. • Understanding prenatal health information becomes crucial both for maternal and prenatal well-being.

Impact of Lp(a) on lipid control in patients with acute coronary syndrome

Abstract Background The lipoprotein(a) (Lp[a]) is a genetically determined low-density lipoprotein (LDL)-like particle. Lp(a) levels above 50mg/dl have been correlated to an increased risk of atherosclerosis and major adverse cardiovascular events. Thus, treatments designed to reduce Lp(a) levels are currently under investigation. However, it is unknown how high Lp(a) concentrations affect the control of lipid profile. Purpose The purpose of this project is to investigate how Lp(a) impacts lipid profile control in individuals with acute coronary syndromes (ACS). Methods We designed a single-center prospective registry including consecutive patients admitted for ACS. Lp(a) levels were obtained from all enrolled patients during hospitalization; lipid profile (total cholesterol (TC), LDL-cholesterol, HDL-cholesterol, triglycerides) was obtained at admission and at the 6-month follow-up (6MFU). Patients were stratified according Lp(a) concentration (low-Lp(a): Lp(a) &amp;lt; 50 mg/dL; high-Lp(a): Lp(a) ≥ 50 mg/dL). LDL-cholesterol (LDLcorr) levels corrected for concentration of Lp(a) were calculated as LDLcorr= LDLmeasured – 30%Lp(a). At discharge cholesterol lowering drugs were introduced or titrated as standard of care. The primary endpoint was the percentage of patients reaching target LDL and LDLcorr (&amp;lt;55 mg/dL) at 6MFU. The secondary endpoints were the correlations between Lp(a) levels and lipid profile, both at baseline and at 6MFU, as well as the correlation between Lp(a) levels and the total number of traditional cardiovascular risk factors in the study population. Results From February 2020 through September 2023, a total of 409 patients were included: 305 (74.6%) with Lp(a) &amp;lt; 50 mg/dL; 104 (25.4%) with Lp(a) ≥ 50 mg/dL (Table 1). High-Lp(a) patients showed a lower prevalence of diabetes (14.2% vs 27.87%, P = 0.0055), an overall lower number of traditional cardiovascular risk factors (&amp;gt;2 in 25.9% vs 38.1%, P=0.0244). High-Lp(a) patients showed higher level of LDL-cholesterol compared to the low-Lp(a) population both at baseline (124±52 mg/dL vs 110.4±44 mg/dL, P= 0.0263) and at 6MFU (70.5±21 vs 63.8±29, P= 0.0208) with fewer patients achieving the target LDL cholesterol levels (21.57% vs 40.13%, P=0.0184). Estimating the true LDL concentration (LDLcorr) the percentage of patients reaching target LDL cholesterol levels at FU significantly increased in the high-Lp(a) group (from 21.57% to 76.5%), with a minimal increase noticeable in the low-Lp(a) population (from 40.13% to 48.41%, p 0,1870). Conclusions In ACS population, patients with high Lp(a) concentrations have fewer traditional CV risk factors and a lower prevalence of diabetes. High-Lp(a) patients, furthermore, seem more challenging to meet LDL target at 6 month follow up, but not when the LDL values are adjusted for Lp(a).

Control for multiple risk factors and incident heart failure and mortality in patients with diabetes mellitus: insights from the kailuan cohort study

Abstract Purpose This study aimed to evaluate the relationship between control for multiple risk factors and diabetes-related heart failure and all-cause mortality, and to explore the extent to which the excess risk can be reduced. Methods Diabetes participants with pre-existing heart failure documented in discharge register or medical insurance records and incomplete baseline risk factor information were excluded. Each of these patients was then matched randomly to four control subjects. The degree of risk factor control was defined by attainment of target values for blood pressure, body mass index , low-density lipoprotein cholesterol, fasting blood glucose, high-sensitive C-reactive protein and smoking. The primary outcome was newly diagnosed heart failure, and the secondary outcome was all-cause mortality.Fine-Gray and Cox regression were performed to estimate the risk of heart failure and all-cause mortality among diabetes patients in relation to the degree of control for multiple risk factors respectively, and the group with ≤1 risk factor control was set as the reference group. All-cause mortality was used as a competing risk in the Fine-Gray model. Results A total of 17,676 patients with diabetes and 69,493 matched non-diabetic control subjects were included. Of these, 84.2% were men and the mean age was 56.2±10.7 years. Over a median follow-up of 11.2 (13.1-15.0) years, a total of 1,070 cases of heart failure and 4,121 cases of all-cause mortality were identified among patients with diabetes. Significant inverse associations were observed between the number of well-controlled risk factors and the risk of incident adverse outcomes in diabetes patients. For each additional risk factor that was controlled, there was an associated 16% decrease in the risk of heart failure and a 10% decrease in the risk of all-cause mortality. The incidence rate of heart failure among diabetes patients was at its lowest for those with ≥5 risk factors (HR: 0.46, 95% CI: 0.34-0.62), and it constantly increased with a lower number of well-controlled risk factors. As for all-cause mortality, the lowest risk was associated with optimal risk factor control (HR: 0.59, 95% CI: 0.50-0.68). Among diabetes patients with ≥5 risk factors that were well controlled, the adjusted hazard ratio for heart failure and all-cause mortality was 1.25 (95%CI: 0.99-1.56) and 1.17(95%CI: 1.05-1.31) respectively, as compared with controls. The protective impact of comprehensive risk factor control on the risk of heart failure was more pronounced among men than women, as well as among those using antihypertensive medications than non-users. Conclusions Control for multiple risk factors is related to a lower risk of heart failure and all-cause mortality in an accumulative and sex-specific manner. Compared to the general population, patients with diabetes mellitus remains associated with an increased risk for the outcomes in spite of the optimization of risk factor control.

COVID-19 premature mortality in Serbia: Does the place of death matter?

Abstract Background The COVID-19 pandemic has significantly impacted healthcare services provision in Serbia and globally. Many people did not seek or reach healthcare due to various reasons, and a significant number of COVID-19 deaths were not confirmed by laboratory testing. Within the project of the Laboratory for Strengthening Capacity and Performance of Health System and Workforce for Health Equity, we assessed the differences in years of life lost (YLL) of COVID-19 death cases according to the place of death. Methods The Statistical Office of the Republic of Serbia provided average life expectancy and anonymous individual mortality data of the Serbian population in 2020, 2021, and 2022, where COVID-19 was the underlying cause of death (ICD-X codes: laboratory confirmed - U07.1 and clinically diagnosed - U07.2), also disaggregated by the place of death (at home or in a hospital). Analytical statistics and nonparametric tests were used to assess the differences in premature mortality by place of death with a significance level set at p &amp;lt; 0.05. Results In all observed years, a total of 45,632 death cases due to COVID-19 occurred (94.3% in hospital and 5.7% at home). Most COVID-19 deaths were coded as U07.1 (93.8% in hospital, 91.3% at home). An average of 12.12±7.50 YLLs was estimated per death, with a median of 11.50. There was a significant difference (p &amp;lt; 0.001) in the median number of YLLs between those who died in the hospital (11.50) and those who died at home (6.78). Furthermore, deaths occurring at home had fewer YLLs but were more frequently coded as U07.2 (p &amp;lt; 0.001). Conclusions The place of death is relevant when assessing the impact of COVID-19 on premature mortality in Serbia. On average, persons who died at home due to COVID-19 had a lower number of YLLs compared to those who died in a hospital. More research is necessary on the other factors contributing to premature mortality and inequalities in the COVID-19 burden in Serbia. Key messages • During the first three years of the COVID-19 pandemic in Serbia, 5.7% of COVID-19 deaths occurred at home, resulting in an average of 9.89 years of life lost. • The COVID-19 pandemic highlights the need to investigate deaths that occur at home and improve pandemic preparedness.

Fluoride exposure and risk of fractures: a systematic review and dose-response meta-analysis

Abstract Introduction Fluoride (F) is a widespread natural element, whose exposure occurs mostly through drinking water, fluoridated foods and use of toothpastes. At high levels, it may adversely affect human health by altering thyroid and cognitive function in children, and inducing dental and skeletal fluorosis. Since bone health significantly impacts quality of life, we performed a systematic review and meta-analysis to evaluate the effect of F exposure on risk of bone fractures. Methods We conducted a literature search in online databases and selected studies that were carried out in humans and reported risk estimates with 95% confidence intervals for bone fractures according to F exposure. We eventually performed a meta-analysis using a random effects model, comparing the highest versus the lowest exposure, and one-stage dose-response model, to explore the shape of the association. Results Of the 1052 potentially eligible articles, 28 were included in the quantitative analyses. Most studies were conducted in adults (n = 26) and in Western countries (North America=16, Europe=11) and assessed fluoride exposure in drinking water, urine, serum, toenail or diet. The preliminary dose-response curve showed a positive non-linear relation between F exposure through drinking water and bone fracture risk, regardless of site, starting at 1.5 mg/L. Sex-stratified analyses, based on a lower number of studies, showed similar trends, with an indication of higher susceptibility in males compared with females. Conclusions Overall, risk of bone fractures appears to non-linearly increase along with exposure to fluoride in drinking water, regardless of bone site and sex, at levels of exposure above the WHO standard and similar to those that have associated to altered thyroid and cognitive function. Under a public health perspective, fluoride in drinking water should be kept below 1.5 mg/L to prevent bone fractures. Key messages • Our analysis revealed a positive non-linear association between fluoride in drinking water and bone fracture risk. • Public Health actions should be oriented in keeping fluoride in drinking water below 1.5 mg/L to prevent bone fractures.

The importance of comorbidities in idiopathic and associated with connective tissue disease pulmonary arterial hypertension: from the Spanish Registry of Pulmonary Hypertension (REHAP Registry)

Abstract Introduction Comorbidities play a major role in the prognosis of patients with pulmonary arterial hypertension (PAH). These comorbidities are present in more than 80% of patients diagnosed in the last years with idiopathic PAH (iPAH) and their presence is associated with increased morbidity and mortality although its influence on PAH associated with connective tissue disease (PAH-SSc) is unknown. We studied the impact of comorbidities on iPAH and PAH-SSc in the Spanish population. Methods We collected patients diagnosed with iPAH, heritable, associated with drug or toxine exposure and PAH-SSc between 2014 and 2023 from the Spanish Registry of Pulmonary Hypertension. Patients are classified into: no comorbidities, 1-2 comorbidities and ≥3 comorbidities. We analyzed the impact of comorbidities in baseline characteristics, exercise capacity and hemodynamic profile, as well as in the risk profile and initial treatment. Survival analyses estimated by Kaplan-Meier analysis using the log-rank test and Cox proportional hazard analyses were performed to determine the effects of baseline characteristics on survival. Results 757 patients were selected for this study. The characteristics of the patients are shown in Table 1. As the number of comorbidities increases (0/1-2/≥3) we found higher age (49/59/67 years; p&amp;lt;0.001), higher percentage of male sex (12.9/29.9/43.4%; p&amp;lt;0.001) and higher FC III at diagnosis (42.7/46.9/59.6%; p=0.013). We observed a shorter distance in 6MWD, higher NT-proBNP levels, lower DLCO and a less unfavorable hemodynamic profile (PAPm, PAWP, CI and PVR). The most frequent comorbidities were a history of smoking (46.4%), followed by arterial hypertension (41.5%), obesity (24.6%) and chronic kidney disease (19.2%). Diabetes mellitus, although less frequent, reached more than 55% in patients with ≥3 comorbidities (p&amp;lt;0.001). The presence of ≥ 3 comorbidities was more frequent in iPAH than PAH-SSc (p&amp;lt;0,001). Intermediate risk profile was the most common (58.4%) and this reached 68.7% in those with ≥3 comorbidities due to a lower number of patients in a low-risk profile (p&amp;lt;0.001). A statistically significant lower survival (p&amp;lt;0.001) was observed in patients with ≥ 3 comorbidities; however, we found no differences between 0 and 1-2 comorbidities at 7-year follow-up (Figure 1). Variables associated with mortality were male sex (HR 1.88, 95% CI 1,26 – 2.8), age (HR 1.04, 95% CI 1.02 – 1.06) and the presence of ≥3 comorbidities (HR 1.49, 95% CI 0.98 – 2.27), not the presence of connective tissue diseases, which were not associated with increased mortality in our study. Conclusions The presence of comorbidities in iPAH and PAH-SSc is very frequent in the Spanish population. They are associated with a worse clinical profile, risk profile, lower use of oral double theraphy and prostacyclins. The presence of ≥3 comorbidities is associated with worse survival, not the presence of 1-2 comorbidities or connective tissue disease.

Post-Exercise Syncope in a Previously Healthy 67-Year-Old Man: The Bezold–Jarisch Reflex and the Role of Autonomic Nervous System Dysfunction

A 67-year-old man started treatment due to frequent asymptomatic premature ventricular complexes (PVCs) accidentally being registered during a preventive examination by a specialist, because of which he was referred to cardiologist. During the initial 24-hour (h) ECG monitoring, 4.5% PVCs and one episode of asymptomatic non-sustained ventricular tachycardia (NSVT) with three PVCs in row, at a frequency of 150 beats per minute (bpm), were detected. After the introduction of beta blockers into therapy, a lower number of PVCs, without NSVT, were recorded in the control 24 h Holter ECG, while transthoracic echocardiography (TTE) showed normal left ventricular (LV) systolic function without cardiomyopathy. So, an exercise test was indicated, and it was interrupted in the third minute at 120 beats per minute (bpm) due to fatigue and pain in the hips, without malignant arrhythmias, angina or dyspneic complaints. During the rest period, a significant inferolateral depression of the ST junction was observed, which recovered in the ninth minute. Immediately after the ECG monitoring stopped, the patient lost consciousness; his pulse was not palpable, but breathing was audible, so cardiac massage was started. After he had regained consciousness, the ECG showed alternating sinus and junctional rhythm with the lowest frequency of 33 bpm, which was accompanied by marked hypotension (80/50 mmHg). The patient was immediately hospitalized; coronary angiography and repeated TTE were completely normal, while continuous ECG monitoring did not confirm malignant rhythm disorders or asystole. It was concluded that it was vasovagal syncope (VVS), most likely caused by the Bezold–Jarisch reflex (BJR).

Identification of diagnostic markers pyrodeath-related genes in non-alcoholic fatty liver disease based on machine learning and experiment validation

Non-alcoholic fatty liver disease (NAFLD) poses a global health challenge. While pyroptosis is implicated in various diseases, its specific involvement in NAFLD remains unclear. Thus, our study aims to elucidate the role and mechanisms of pyroptosis in NAFLD. Utilizing data from the Gene Expression Omnibus (GEO) database, we analyzed the expression levels of pyroptosis-related genes (PRGs) in NAFLD and normal tissues using the R data package. We investigated protein interactions, correlations, and functional enrichment of these genes. Key genes were identified employing multiple machine learning techniques. Immunoinfiltration analyses were conducted to discern differences in immune cell populations between NAFLD patients and controls. Key gene expression was validated using a cell model. Analysis of GEO datasets, comprising 206 NAFLD samples and 10 controls, revealed two key PRGs (TIRAP, and GSDMD). Combining these genes yielded an area under the curve (AUC) of 0.996 for diagnosing NAFLD. In an external dataset, the AUC for the two key genes was 0.825. Nomogram, decision curve, and calibration curve analyses further validated their diagnostic efficacy. These genes were implicated in multiple pathways associated with NAFLD progression. Immunoinfiltration analysis showed significantly lower numbers of various immune cell types in NAFLD patient samples compared to controls. Single sample gene set enrichment analysis (ssGSEA) was employed to assess the immune microenvironment. Finally, the expression of the two key genes was validated in cell NAFLD model using qRT-PCR. We developed a prognostic model for NAFLD based on two PRGs, demonstrating robust predictive efficacy. Our findings enhance the understanding of pyroptosis in NAFLD and suggest potential avenues for therapeutic exploration.

Host Plants for the Lanternfly Saiva formosana Kato, 1929 (Hemiptera, Fulgoridae) Endemic to Taiwan, and Parasitism of Its Eggs by Wasps

Since Saiva formosana Kato, 1929 was first reported as a new species in Taiwan; there have been few published reports on its ecology, and fundamental knowledge of this species is still lacking. The objectives of this study are to (1) determine the preferred plants of adults, egg-laying, and nymphs, (2) analyze the change in host plants with time and development, and (3) explore the relationship between the survival of eggs and parasitism by their wasps. We detected the adults of this species between May and September 2023, and again in April 2024, mainly on Elaeocarpus decipiens F. B. Forbes &amp; Hemsl. During our investigation, we frequently observed parasitic wasps ovipositing on the egg masses. We established that most egg masses produced only Saiva nymphs or Anastatus adults. This lanternfly might better survive parasitic pressure by laying lower numbers of eggs per mass across a broader range of plant species. The first batch of hatching nymphs was found on Magnolia compresssa Maxim. on 20 June 2023; however, most nymphs in the second and third instars were detected on Ficus fistulosa Reinw. ex Blume, between August and October 2023. After the autumn, the occurrences of nymphs increased on Heptapleurum heptaphyllum (L.) Y. F. Deng which probably served as a shelter for overwintering.

Prevalence, reasons, and attitude towards abortion among Iranian married women of reproductive age in Qazvin province

Background and aimsAbortion influences the composition and size of population. Estimating the overall and type-specific abortion rates, the reasons to choose the abortion can be helpful in designing and implementing preventive intervention. Therefore, the present study was designed to determine the: (i) prevalence of abortion, (ii) attitude of married women of reproductive age towards abortion, and (iii) reasons for choosing abortion by married women of reproductive age in Qazvin province.MethodsA cross-sectional study was conducted between February and April 2023, and comprised married women of reproductive age (N = 1571) referred to urban and rural comprehensive health centers in five cities of Qazvin province. Utilizing multi-stage proportional sampling process, data for the survey (including demographic and fertility information, reasons for choosing abortion, and attitudes toward abortion) were collected online.ResultsThe lifetime prevalence of abortion was 18.6% (among the total sample). The past-year prevalence was 22.3% (among those who reported having had an abortion). Of those reporting having had an abortion, 73.6% reported it was their first one, and 65.1% reported it was non-spontaneous . Women’s reasons for choosing abortion fell into one of three main clusters: (i) couple’s behavior, health and relationship problems, (ii) fertility-related stressful experiences, and (iii) family economic situations. The main reported reason to choose abortion was a couple’s behavior (e.g., drug use), health (e.g., physical disease, psychological problems), and relationship problems (e.g., sexual infidelity, divorce) explaining 27% of the variance. Also, pro-abortion attitude was the most important attitude towards non-spontaneous abortion explaining 26.33% of variance. The variables that increased the likelihood of non-spontaneous abortion included choosing a reason for abortion vs. having no reason (OR = 1.77, p = 0.05), having poor vs. good mental health (OR = 1.74, p = 0.03), having a pro-abortion attitude (OR = 1.09, p = 0.09), and having ≥ 3 children vs. having no children (OR = 0.53, p = 0.06).ConclusionWomen in high-risk groups for non-spontaneous abortion (i.e., those aged over 35 years, those married for more than five years, those with an infertility history, those with a lower number of children, those living in rural areas, and those having poor mental health status) should be assessed by primary healthcare services during preconception and have early prenatal counseling to help in decisions regarding abortion.

Matching-Adjusted Indirect Comparison of Risankizumab Versus Deucravacitinib in Patients with Moderate-to-Severe Plaque Psoriasis.

Despite advancements in the treatment of psoriasis (PsO), there are few head-to-head studies assessing comparative effectiveness of the newest therapies approved to treat PsO. Our objective was to assess the comparative clinical effectiveness of risankizumab and deucravacitinib in patients with moderate-to-severe PsO. This placebo-anchored matching-adjusted indirect comparison (MAIC) analysis utilized data from UltIMMa-1/2 risankizumab and POETYK PSO-1/2 deucravacitinib trials. Individual patient data from UltiMMA-1/2 were weighted via propensity score to match POETYK PSO-1/2 published summary data. Rate differences between risankizumab and deucravacitinib were assessed for Psoriasis Area and Severity Index (PASI) 75/90/100, the Static Physician Global Assessment (sPGA = 0 or 0/1), and the Dermatology Life Quality Index (DLQI) 0/1. At 16weeks, risankizumab-treated patients demonstrated statistically significantly higher rates of skin clearance and greater improvement in quality of life (QoL) compared to those treated with deucravacitinib. Across all outcomes, risankizumab demonstrated a lower number needed to treat compared to deucravacitinib. Limitations are potential bias due to unobserved/unmeasurable differences and limited generalizability of the results. This indirect comparison demonstrates that risankizumab has higher rates of skin clearance and greater improvements in QoL than deucravacitinib. This study will help inform healthcare providers in their treatment and management strategy of PsO.