Early Diagnosis Research Articles

Evaluating trends and insights in cardiovascular risk among the polish population

Abstract Introduction Cardiovascular diseases (CVD) are the leading cause of death in Poland and worldwide. Lifestyle changes and early diagnosis can reverse this unfavorable trend. In the face of escalating global health challenges, the identification of CVD risk factors becomes paramount, especially within national contexts where demographic shifts and lifestyle changes can significantly impact the health profile of the population. Aim of the study. Determining the prevalence of CVD risk factors in the Polish population and analyzing their changes over time. Material and Methods Data of 705,420 Poles aged 35-55 years who were enrolled in CVD disease prevention programme between 2012 and 2021 were analysed. The prevalence of the following CVD risk factors was determined: nicotinism, hypertension, elevated total cholesterol, elevated LDL, reduced HDL, elevated triglycerides, elevated glucose (indicating pre-diabetes), low physical activity, overweight, obesity, SCORE ≥5%. In addition, we assessed how the mean SCORE, BMI, systolic blood pressure, diastolic blood pressure, total cholesterol, LDL cholesterol, LDL cholesterol, triglycerides, glucose levels and waist circumference changed over time. Results Nicotinism affected 17.98%-24% of women (W) and 27.29%-36% of men (M). Hypertension was in 7.04%-8.58% of W and 17.45%-19.62% of M. Elevated total cholesterol were in 55.69%-63.64% of W and 65.91%-72.68% of M. Elevated LDL were in 44.77%-54.2% of W and 58.26%-65.48% of M. Reduced HDL were in 9.84%-11.52% of W and 14.48%-16.57% of M. Elevated triglyceride were in 13.44%-15.37% of W and in 33.81%-36.29% of M. Elevated glucose indicating a pre-diabetic status were in 10.70%-13.16% of W and in 18.91%-22.76% of M. Low physical activity was in 75.96%-82.2% of W and 73.32%-81.67% of M. Overweight conditions were in 30.37%-31.67% of W and 48.61%-49.45% of M. Obesity affected 14.04%-17.12% of W and 20.67%-24.69% of M. SCORE ≥ 5% was in 0.23%-0.38% of W and in 13.08%-18.72% of M. There was a decrease in the mean SCORE value (-0.08; 95%CI: -0.09 - -0.06) from 2012. An increase over time was noted in mean BMI (-0.01; 95%CI: -0.05 - 0.04). There was a slight decrease followed by a notable increase over time in mean systolic (-0.35; 95%CI: -0.47 - -0.24) and diastolic blood pressure (-0.25; 95%CI: -0.32 - -0.18). There was a decrease in mean total cholesterol (-3.29; 95%CI: -4.27 - -2.31) and mean LDL cholesterol (-3.11 95%CI: -4.22 - -2.01). A notable increase was observed in mean glucose values (0.01; 95%CI: 0-0.01). Over time, there was an increase in mean waist circumference value (-0.19; 95%CI: -0.54-0.16). Conclusions The escalation of CVD risk among the Polish population is illustrated, with a marked increase in obesity, sedentary lifestyles and indicators of metabolic syndrome. These trends highlight the urgent need for targeted public health initiatives and for the implementation of comprehensive strategies to mitigate these risks

Neonatal screening for hearing loss and its associated factors: A pediatric hospital experience

Abstract Introduction Hearing impairment affects 0.6% of children worldwide, with 60% of cases being preventable. Identifying risk factors for hearing impairment would facilitate early detection and better patient prognosis. Objectives To identify factors associated with abnormalities in auditory screening in a pediatric hospital. Methods A cross-sectional study was conducted on patients assessed in the early hearing detection program at the Pediatric Tower of the High Specialty Hospital of Veracruz, Mexico, between June 2022 and 2023. Screening was performed using otoacoustic emissions initially. Those with abnormalities underwent two retests, and those positive in all three evaluations underwent confirmatory testing. Newborn screening was conducted at discharge for healthy neonates and after reaching a weight of over 1.8 kg and more than 34 gestational weeks for preterm infants. For term and low-birth-weight babies, screening occurred when they reached 2 kg, considering positive results in any of the three tests indicative of altered screening and probable hearing impairment. Results A total of 2731 patients were fully evaluated, with 1416 (51.8%) being male, and a median Apgar score of 9 at 5 minutes. The incidence of hearing impairment was 0.7%, comprising 19 patients. Evaluation of sex, 5-minute Apgar score, weight, gestational age, congenital malformations, history of neonatal asphyxia, hyperbilirubinemia, sepsis, TORCH infections, family history of hearing impairment, maternal exposure to ototoxic drugs, substances, COVID-19, gestational diabetes, or maternal hypertension obtaining values of p > 0.05 in each of them. Conclusions The prevalence of hearing loss is similar to that reported in the literature. In our population, auditory screening abnormalities are not associated with classic perinatal factors, indicating the complexity of contributors to neonatal hearing impairment. Key messages • The neonatal screening program plays a fundamental role in identifying patients with hearing loss even without any clinical factor that arouses suspicion of hearing loss. • Early diagnosis will favor timely care for patients with hearing loss, favoring their development with adequate care to improve their quality of life.

Chronic kidney disease in patients with heart failure in German primary care practices: the InspeCKD study

Abstract Background Chronic kidney disease (CKD) is, alongside type 2 diabetes mellitus, the most common comorbidity in patients with heart failure (HF), with a prevalence of 40-50%. HF patients should therefore be screened, monitored, and treated according to international Kidney Disease Improving Global Outcomes (KDIGO) conclusions for early identification and intervention of CKD, with annual determination of eGFR to monitor kidney function and annual urine albumin-to-creatinine ratio (UACR) testing as appropriate. Early diagnosis is important as therapeutic options can be offered to slow the progression of CKD and reduce the risk of cardiovascular complications and mortality. Purpose Currently, there are only limited data available regarding screening, diagnosis and treatment of CKD for HF patients in German primary care physician (PCP) practices. Therefore, this analysis of the InspeCKD study was designed to examine the frequency of use of CKD-specific laboratory diagnostics in HF patients in routine PCP care. Methods In the current data analysis, fully anonymized patient data from German PCP practices were evaluated. In accordance with the screening recommendation of the KDIGO guideline, adult patients with diabetes, hypertension and/or cardiovascular disease, including HF, with at least one year of observation period were included in the analysis. Results The overall patient cohort comprised 448.837 patients from 1.244 German PCP practices. Of the 7.9% HF patients, 6.1% participated in a disease management program (DMP) for coronary heart disease. The average age of HF patients was 74 years. The prevalence of diagnosed CKD in HF patients during the observational period (mean: 1.7 years) was 26.8%. Within the subgroup of patients with HF, serum creatinine to estimate GFR was measured at least once in 48.5% of patients. Urine dipstick testing for albuminuria was performed in 7.4% of patients and UACR was measured at least once in 0.3% of patients. In patients with at least one documented measurement, eGFR and UACR were checked 2.2 and 0.9 times, respectively, per patient and year. Of the HF patients with laboratory-confirmed CKD according to KDIGO criteria, 81.8% were not diagnosed with CKD. Conclusion The analysis shows that, given the high prevalence of CKD in HF patients and the current KDIGO recommendations for early identification and intervention of CKD, a substantial proportion of HF patients in German PCP practices did not receive adequate laboratory diagnostics for early diagnosis of CKD. In addition, the majority of patients with laboratory-confirmed CKD were not diagnosed. Early detection of CKD and the use of evidence-based therapeutic options can significantly reduce the risk of CKD progression. In conclusion, there is an urgent need to raise awareness among PCPs about secondary and tertiary prevention of CKD in patients with HF and to include coordinated CKD screening recommendations in HF guidelines.

Detecting Unrecognized Dementia Using Deep Learning Methods with Korean National Claims Data

Abstract Background Dementia is one of the leading causes of death in elderly people. In Korea, the government supports dementia screening for people aged 60 and older, but it is not a population-based organized screening program. It is difficult to achieve early diagnosis and early treatment. The objective of this study is to detect unrecognized dementia using Korean National Claims Data for early diagnosis. Methods This study used the National Health Insurance Claims data in Korea. The case group is the new dementia visit as an unrecognized group, while the control group was randomly selected from the general population without dementia. The predictors included health utilization, socioeconomic and demographic, procedure codes, diagnostic codes and health screenings data. The health utilization variables included length of stay, the number of outpatient visits, health expenditures and other encounter information. All medical utilization data was aggregated monthly. In the case group, 12 months of data from 6-month or 2-years before the onset of dementia were used. In the control group, 12 months of data from randomly selected time point were included. Transformer, embedding methods, and Time2Vec were used as the deep learning methods. This study included 453,306 incidents of dementia, representing almost all cases reported from 2010 to 2019 in Korea. The control group consisted of 669,873. Results After training the deep learning prediction model, the AUC for 6-month dementia prediction on the test dataset was 0.87, and for 2-year dementia prediction, it was 0.76. The most important variables were health utilization variables, especially health expenditures. The health utilization trajectories of the case group were significantly different from those of the control group. Conclusions Based on the claims data, we could detect unrecognized dementia case. We can extend the model to other chronic disease such as cancer and stroke, which are significant burden of disease. Key messages • Screening in healthcare facilities or using lab test results would be more accurate, but it would be difficult to apply to a large population due to the cost-effectiveness and timeliness constraints. • On the other hand, the detection model using the existing claims data would be helpful to to develop cost-effective mass screening program. It can cover the weakness of current screening program.

New clinical staging proposal applied to a Fabry cardiomyopathy cohort

Abstract Background Fabry disease (FD) is a rare cause of hypertrophic cardiomyopathy (HCM), and early diagnosis is important considering the response to enzyme replacement or chaperone therapies. Recently, a practical clinical staging for Fabry cardiomyopathy was proposed by Olivotto et al 2023, considering several features, being potentially useful for standardizing the criteria for initiation and response assessment to therapy. Imaging characterization of hypertrophy and fibrosis are critical key items to determine stages. This new proposal suggested 4 main stages (0, I, II, III) according to these parameters. Stages 0 and I are further divided in 2 sub-stages according to minor findings and hypertrophy severity, respectively. Unfortunately, not all patients with Fabry cardiomyopathy are identified early in the disease, limiting the response to treatment. Aim Our study aimed to evaluate retrospectively the staging of Fabry cardiomyopathy at first imaging cardiac evaluation according to the recent proposal (1), in a cohort of 35 patients with FD at a reference centre of Fabry disease. Results At the first cardiac evaluation, the group of patients had a median age of 46 years (28-68 years), 69% were female and 5% were already under enzymatic therapy. The majority of Fabry patients (66%) were in non-hypertrophic stage 0: 4 patients in 0A with no detected cardiac involvement and 19 patients in 0B with subclinical cardiac findings (17% presenting diastolic dysfunction, 14% impaired global longitudinal strain, 6% hypertrabeculation, 6% reduced native T1, 3% short PR duration, 3% cardiac symptoms). In hypertrophic stage I, 14% of patients were classified according to the presence and severity of LVH: 3 in IA (12-15 mm) and 2 in IB (>15mm). All patients (n=3, 9%) in hypertrophic fibrotic stage II presented non-extensive late enhancement (< 3 LV segments) in the first CMR. Patients with overt dysfunction or stage III (n=4; 11%), presented diffuse myocardial fibrosis (> 3 LV segments) or impaired systolic function (LVEF < 50%). Conclusion In our cohort patients, the new staging scheme allows us to identify and classify the different stages of FD cardiomyopathy. The majority of patients were unexpectedly identified in early disease stages, but that could be related to diagnosis in the context of familial screening. This proposal seems useful for clinical staging standardization to facilitate the evaluation of responses to treatments and to predict outcomes, however, needs to be validated in larger and prospective studies.

7.G. Round table: Primary prevention and management of NCDs – the added value of joint actions across Europe

Abstract Two ambitious European joint action projects, funded through the EU4Health programme, are ongoing to reduce the burden of non-communicable diseases (NCDs) and related risk factors in Europe, targeting both individual and societal levels. Together, these projects aim to scale up effective prevention and management strategies, strengthen public health policies and promote equitable and sustainable healthcare systems across Europe. The Joint Action on CARdiovascular Diseases and DIabetes (JACARDI), with 21 participating countries and a total budget of over €66 million, is focusing on enhancing the implementation of evidence-based innovative pilot projects across the entire patient journey. This includes efforts to improve prevention, early diagnosis, and proactive management of NCDs. The Joint Action Prevent Non-Communicable Diseases (JA PreventNCD), with 25 participating countries and a total budget of over €95 million, particularly aims to enhance joint capacities of countries for implementing, scaling up and evaluating prevention policies and actions at various levels. These projects represent complementary responses to calls for action in Europe’s Beating Cancer Plan and the Healthier Together - EU NCD Initiative, with JA PreventNCD emphasizing primary prevention and policy while JACARDI focuses on secondary prevention and health systems strengthening. Both projects will generate new policy-relevant evidence based on implementation, monitoring and scaling-up of best and innovative practices and policies across Europe. The projects share a focus on equity, diversity, scalability and sustainability, while avoiding fragmentation and duplication of actions. Under the EU4Health programme, launched to strengthen European health collaboration in the wake of the COVID-19 pandemic, the EU has recently invested over €200 million in public health initiatives, with additional investments from national authorities participating in the joint actions. With this new wave of funding, real population impact should be anticipated, but what can we realistically expect to be the outcomes and what are the criteria for success? In this round table discussion 1) these two joint action projects will be presented, highlighting their innovative aspects; 2) views on the added value and potential in cross-national collaborations for prevention and management of NCDs will be debated, and 3) how synergies will be leveraged for maximum impact will be explored. Panelists will share their perspectives on the projects’ potential to change the public health landscape in Europe. Workshop participants will subsequently be encouraged to engage in the discussion with the objective that views and experiences are exchanged, opportunities for collaboration and engagement are shared and energy is mobilized to harness the benefits of such large-scale policy-relevant collaborations. Key messages • Synergies and collaboration to drive policy development and foster increased capacity are the pillars to build a healthier Europe. • Two large-scale Joint Actions drive impact by highlighting innovative NCD prevention strategies and fostering collaborative engagement.

Healthcare utilization in general practice and hospitals preceding a diagnosis of systemic sclerosis: a nationwide registry study.

Irreversible tissue damage is frequently present at the time of diagnosis in systemic sclerosis (SSc), which calls for earlier diagnosis. This study estimated healthcare utilization three years before the diagnosis of SSc. We conducted a population-based cohort study using data from Danish national registries. Incident patients diagnosed with SSc between January 1, 2005, and December 31, 2018, were matched by age and gender with 10 references without SSc. The date of diagnosis was the index date. We estimated quarterly rates and adjusted incidence rate ratios (IRRs) with 95% confidence intervals (CI) of healthcare utilization in the three years preceding the diagnosis for patients with SSc and their references. A total of 1,650 SSc patients (1,255 women and 395 men) and 16 500 non-SSc references were included. The mean age was 58 years (interquartile range 48-68). Three years before diagnosis, patients with SSc had more contacts with general practice (IRRwomen= 1.43 [95% CI: 1.33; 1.53], IRRmen= 1.47 [95% CI: 1.26; 1.71]) and hospitals (IRRwomen= 1.86 [95% CI: 1.62; 2.14], IRRmen= 2.70 [95% CI: 2.04; 3.58]) compared with their references. In the last three months before diagnosis, patients with SSc had significantly more contacts with general practice (IRRwomen= 2.30 [95% CI: 2.16; 2.44], IRRmen= 2.98 [95% CI: 2.64; 3.35]) and hospitals (IRRwomen= 5.62 [95% CI: 5.08; 6.20], IRRmen= 9.53 [95% CI: 7.81; 11.63]). The higher use of healthcare services in general practice and hospitals in the three years before diagnosis suggests an opportunity to facilitate earlier diagnosis and treatment of SSc.

Clinical reality and challenges with familial hypercholesterolemia patients management. 2024 results from the Regional Center for Rare Diseases (RCRD) Registry in Poland

Abstract Background HeFH is one of the most prevalent genetic diseases significantly increasing the risk of CVD events and mortality. Despite new achievements with earlier diagnosis and new effective drugs, most of heFH patients do not achieve LDL-C goal and are still on residual CVD risk. Purpose We aimed to present the most recent data from the regional FH registry in Poland to show the challenges and reality of everyday clinical management with FH patients. Methods The registry is conducted at the RCRD in the 2nd largest, supraregional hospital in Poland. The main inclusion criteria were being phenotypically or genetically diagnosed with FH. Nonadherence was investigated based on detailed interview, monitoring the treatment’s effects and purchasing prescribed medications. For this analysis we investigated only adult FH patients from the registry. Due to small number of cases (n=5), patients treated with inclisiran were not included in this analysis. Results We included 142 consecutive heFH patients at mean age 45,8±14,9 years (min/max 18-75 years; 60% women). Mean BMI was 29.6±5.52 kg/m2, mean baseline TC was 282.9±80 mg/dl (the highest observed was 600 mg/dl), LDL-C 204.2±72.5 mg/dL (the highest observed -762 mg/dl), TG - 151.1±123.4 mg/dl, Lp(a) 37.6±41.5 mg/dl and HDL-C - 52.3±14.2 mg/dl. Most patients were diagnosed with LDLR (72%) or APOB (24%) mutations. High intensity statin therapy was used in 74.3% of patents, ezetimibe (mostly as a part of combination LLT) in 47.2%, and PCSK9 inhibitors in all those that met the reimbursement criteria – 25.6% of FH patients. Non-adherence to statin therapy and ezetimibe in the follow up of 2 years was 27%. In patients treated with statin therapy and ezetimibe mean achieved LDL-C was 153.6±82.82 mg/dl and on triple therapy - 64.5±43.73 mg/dl. Mean achieved LDL-C in the investigated population was 87.9±55.5 mg/dl. LDL-C goal was achieved in 39% of patients – in those treated with triple therapy with PCSK9 inhibitors it was 57.14%, and in those on statins and ezetimibe only 27.1%. Combination therapy of statins and ezetimibe did not significantly change baseline Lp(a) level (p=0.109), but when PCSK9 inhibitors were introduced the mean Lp(a) reduction by 34.2% (p=0.049) was observed. Based on the multivariable regression analysis, the following factors played the most important role for FH patients to be on LDL-C target: DLCN total score (OR 1.21, 95%CI: 1.04-1.40; p=0.013), DLCN category (10.39, 1.43-75.29; p=0.021), ezetimibe use (4.78, 1.15-19.92; p=0.031), and PCSK9 inhibitors use (4.56; 1.40-14.86; p=0.012). Conclusions FH patients in Poland are diagnosed definitely too late (45 years) and most of them are still not on LDL-C goal. Double and especially triple therapy significantly, even 5 times, increase the chance of achieving LDL-C goal, therefore PCSK9 inhibitors should be available for all FH patients, without the limitations existing currently e.g., within B101 drug program in Poland.

The association between drugs and vaccines commonly prescribed to older people and bullous pemphigoid: a case-control study.

Bullous pemphigoid (BP) is an autoimmune skin disease that affects mainly older people. Numerous drugs have been previously associated with BP based on case series and small hospital-based studies. More reliable and precise estimates of associations between a broad selection of drugs/vaccines and BP will enable greater awareness of potential increased risk of BP following certain medicines and help identify clinical, histological and genomic characteristics of drug-induced BP for different types of culprit drugs. Greater awareness could lead to earlier recognition or suspicion of BP and referral to a dermatologist for diagnosis. Earlier diagnosis may lead to less aggressive treatment and improved well-being. To determine the association between drugs/vaccines commonly prescribed to older people and BP risk. We conducted a population-based nested case-control study between 1998-2021 using electronic primary care records from the Clinical Practice Research Datalink. We matched BP cases with up to 5 controls. Exposures were drugs/vaccines commonly prescribed to older people. We used multivariable conditional logistic regression adjusting for multiple drug use. For antibiotics, we considered prescriptions may be prescribed for undiagnosed symptoms of BP which resemble skin infection (protopathic bias) in a sensitivity analysis. Antibiotics were the therapeutic group associated with the highest risk of BP (OR: 4.60; 95%CI 4.40-4.80). However, after adjusting for protopathic bias, the OR reduced to 2.08 (95%CI 1.99-2.17). After adjusting for protopathic bias, of all antibiotic classes and subclasses, penicillins and penicillinase-resistant penicillins had the strongest associations with BP risk (OR: 3.44; 95%CI 3.29-3.60; sensitivity analysis OR; 1.74; 1.66-1.84 and OR: 7.56; 95%CI 7.15-8.00; sensitivity analysis OR: 2.64; 95%CI 2.45-2.85, respectively). Other drugs strongly associated with increased risk were gliptins (OR: 2.77; 95% CI 2.37-3.23), and second-generation antipsychotics (OR: 2.58; 95%CI 2.20-3.03). Healthcare professionals need to be aware of BP risk in older people particularly when prescribing penicillinase-resistant penicillins, gliptins, and second-generation antipsychotic drugs to recognise and manage BP early. Due to the low prevalence of disease, we do not suggest avoidance of drugs/vaccines to prevent BP. Further research should consider recency, dosage, and duration of antibiotic treatments.

Evaluation of cfDNA fragmentation characteristics in plasma for the diagnosis of lung cancer: A prospective cohort study.

Lung cancer is one of the most prevalent cancers worldwide, yet only approximately 16% of patients are diagnosed in early stage, highlighting the urgent need for novel, highly accurate detection models. In our study, patients with suspected lung cancer or lung disease, as identified through radiographic imaging, along with healthy individuals, were consecutively recruited from Beijing Chest Hospital. Circulating free DNA (cfDNA) was extracted from plasma samples, and low-depth whole-genome sequencing was performed to identify fragmentomic features for model construction. A total of 265 participants were prospectively enrolled, comprising 124 lung cancer patients and 141 noncancer individuals. The model we developed was based on four cfDNA fragmentation characteristics, including 20-bp breakpoint nucleotides motif, fragmentation size coverage, fragmentation size distribution, and copy number variation. In an independent test cohort, the model achieved an area under the curve (AUC) of 0.861 (95% CI: 0.781-0.942) and demonstrated a sensitivity of 70% (95% CI: 53.5%-83.4%) at a specificity of 89.4% (95% CI: 76.9%-96.5%). Notably, the model was also effective in detecting early-stage cancer, with an AUC of 0.808 (95% CI: 0.69-0.925). In summary, our lung cancer detection model shows strong screening capabilities by leveraging four cfDNA fragmentation characteristics, exhibiting robust performance in early cancer diagnosis.

Improving exercise cardiac reserve assessment using a novel cardiopulmonary and echocardiography testing protocol (CPET-ESE) based on individualised exercise intensity domains

Abstract Background Functional exercise stress echocardiography (ESE) is used to quantify changes in cardiac reserve and can improve early cardiac dysfunction diagnosis and follow-up.[1.2] Current ESE protocols do not account for individual variations in fitness and heart rate response, leading to difficulties in defining normal reference values.[2,3] Physiologically defined exercise intensity domains could be implemented as part of combined cardiopulmonary and ESE testing (CPET-ESE) to address this problem. Purpose We propose that using exercise intensity domains as part of CPET-ESE will result in cardiac reserve values not influenced by individual cardiorespiratory fitness or physical activity (PA) levels. We also hypothesise by matching work-rates and heart rates (HR), respectively, cardiac reserve will be higher in those exercising at the higher exercise intensity domain. Methods A total of 45 healthy adults (mean age 43.8 ± 14.2, range 18-65 y) underwent a CPET followed by a CPET-ESE consisting of two 6-minute stages: 1. Moderate intensity (MOD) at 90% of the work-rate at the gas exchange threshold (GET) and 2. High intensity (HIGH) at 40% of the difference between GET and peak. Global left ventricular and right ventricular free wall (LV and RV) longitudinal strain (Sl), RV fractional area change (RV-FAC), peak LV and RV TDI derived systolic (S’) and diastolic velocities (E’) were measured at each step, including rest. HIGH steps were matched 1-to-n with MOD steps from other participants based on work-rate and HR, respectively. Questionnaire derived PA was classified as low, moderate, and high active. Cardiorespiratory fitness was measured as peak oxygen uptake relative to body mass (mL·kg-1·min-1). Results After adjusting for age and sex, neither higher PA nor peak VO2 were associated with higher cardiac function parameters at either intensity (Table 1). Higher peak VO2 was associated with higher work-rate for HIGH only, while higher PA was associated with lower HR for MOD only (interaction term p<0.05). When paired by matching HR and work-rate, respectively, HIGH was associated with higher cardiac function parameters compared to MOD (all except for LV-S’ and RV-FAC when HR matched, Table 2), despite those matched from HIGH being older, less physically active and having lower peak VO2 (p<0.05 for all). Conclusions Current ESE protocols, which define submaximal exercise intensity using arbitrary work-rate or HR targets,[3] do not account for the complex differences in exercise response between healthy individuals. Cardiac function augmentation during exercise is likely a response to VO2 kinetics and this is not accurately described by either HR or work-rate alone. We derived normal reference values for cardiac reserve from implementing physiologically defined exercise intensity domains within the combined CPET-ESE testing frameworks. These values could be more appropriately used when comparing diverse clinical populations using CPET-ESE.

Gender-related differences in clinical characteristics of patients with hypertrophic cardiomyopathy in our city

Abstract Background Female patients with hypertrophic cardiomyopathy (HCM) tend to display a higher rate of heart failure as well as lower survival compared to male patients. Despite this, gender-related differences in the clinical characteristics of HCM patients remain unclear. Methods and Aim Consecutive HCM patients were prospectively enrolled at a tertiary referral center. The primary objective of this study was to investigate and emphasize gender differences in clinical characteristics including imaging and laboratory parameters. Results Between May 2018 and January 2024, a total of 301 HCM patients were included, of which 41.9% were female (n=125). Female patients were significantly older and more symptomatic than male counterparts (59 years [IQR 47-67] vs. 53 years [IQR 39-61], p=0.001; New York Heart Association functional class ³III: 28.8% vs. 17.6%, p=0.002, respectively). No significant differences in body mass index were found (28.4 kg/m² [IQR 24.9-31.6] vs. 28.4 kg/m² [IQR 25.9-31.8], p=0.8). With respect to echocardiographic parameters, although interventricular septal thickness was comparable (19.0 mm [IQR 16.0-22.0] vs. 19.5 mm [IQR 17.0-22.0], p=0.4) left atrial as well as right atrial volume index were higher in women (30.0 cm³/m² [IQR 27.0-35.0] vs. 27.0 cm³/m² [IQR 24.0-30.0], p<0.001; 27.1 cm³/m² [IQR 25.4-29.3] vs. 24.7 cm³/m² [IQR 22.5-28.2], p<0.001). These findings were further supported by elevated filling pressures in female patients reflected by E/e’ ratio (16 [IQR 14-22] vs. 10 [IQR 9-12], p<0.001). Moreover, these patients showed more frequent left ventricular (LV) outflow tract obstruction (50% vs. 33%, p=0.029) which is accompanied by a slightly higher LV ejection fraction compared to men (69% [IQR 62-74] vs. 62% [IQR 55-67], p=0.004). In terms of cardiac biomarkers, female HCM patients presented with higher levels of serum N-terminal pro brain natriuretic peptide (671 pg/ml [IQR 333-1613] vs. 357 pg/ml [IQR 115-959], p<0,001) as well as lower concentrations of serum creatinine (0.84 mg/dl [IQR 0.75-0.95] vs. 0.98 mg/dl [IQR 0.87-1.15], p<0.001) whereas no differences regarding high-sensitive troponin-T levels were observed. Conclusion This single-center analysis illustrates profound gender-related differences among HCM patients in Vienna. Female patients tend to present in a more advanced clinical status, rather reflecting the phenotype of heart failure with preserved ejection fraction. Whether these findings should prompt an early HCM diagnosis in female patients with unspecific symptoms, or may result in early treatment initiation of e.g. sodium-glucose-transporter 2 inhibitors, should be part of future research.

The role of molecular subtypes and immune infiltration characteristics based on disulfidptosis-related genes in ovarian cancer

Ovarian cancer (OC) is the most fatal, gynecological malignancy. Compared with advanced ovarian cancer, the 5 year survival rate of early ovarian cancer is significantly improved, and predicting early detection and diagnosis is very important to improve the prognosis of OC. Recent research has found a new way of cell death: disulfidptosis. Under glucose starvation, abnormal accumulation of disulfide molecules such as Cystine in SLC7A11 overexpression cells induced disulfide stress to trigger cell death. Studies of disulfidptosis are still in their infancy and its role in ovarian cancer progression is unclear. In this study, we used a public database to detect the expression and mutations of disulfidptosis-related genes in OC. Cluster analysis was performed based on disulfidptosis-related genes, and disulfidptosis differential expression genes were analyzed. A prognostic risk model was constructed using three disulfidptosis-related genes, and the reasons for differences in prognosis were explored through immune infiltration analysis and drug sensitivity analysis. The prognostic characteristics of transcriptome based on disulfidptosis-related genes are closely related to the prognosis of OC patients. Finally, quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of three prognostic genes in clinical OC samples.Our study establishes a link between disulfidptosis and OC, providing new ideas for personalized and precise treatment of OC.

Early Internal Short Circuit Diagnosis for Lithium-Ion Battery Packs Based on Dynamic Time Warping of Incremental Capacity

Timely identification of early internal short circuit faults, commonly referred to as micro short circuits (MSCs), is essential yet poses significant challenges for the safe and reliable operation of lithium-ion battery (LIB) energy storage systems. This paper introduces an innovative diagnostic method for early internal short circuits in LIB packs, utilizing dynamic time warping (DTW) applied to incremental capacity (IC). Initially, the terminal voltages of all cells within the LIB pack are ordered at any moment to determine the median terminal voltage, which is then used to generate the median IC curve. This curve acts as a reference benchmark that represents the condition of healthy cells in the pack. Subsequently, the DTW algorithm is utilized to measure the similarity between each cell’s IC curve and the median IC curve. Cells exhibiting similarity scores that exceed a specified threshold are identified as having MSC faults. Lastly, for the cells diagnosed with MSC conditions, a method for estimating short-circuit resistance (SR) based on variations in maximum charging voltage is devised to quantitatively evaluate the severity and evolution of the MSC. Experimental findings reveal that the proposed method effectively identifies MSC cells in the LIB pack and estimates their SRs without the necessity of a battery model, thereby affirming the method’s validity.

Methods to optimize optical sensing of biotic plant stress – combined effects of hyperspectral imaging at night and spatial binning

In spatio-temporal plant monitoring, optical sensing (including hyperspectral imaging), is being deployed to, non-invasively, detect and diagnose plant responses to abiotic and biotic stressors. Early and accurate detection and diagnosis of stressors are key objectives. Level of radiometric repeatability of optical sensing data and ability to accurately detect and diagnose biotic stress are inversely correlated. Accordingly, it may be argued that one of the most significant frontiers and challenges regarding widespread adoption of optical sensing in plant research and crop production hinges on methods to maximize radiometric repeatability. In this study, we acquired hyperspectral optical sensing data at noon and midnight from soybean (Glycine max) and coleus wizard velvet red (Solenostemon scutellarioides) plants with/without experimentally infestation of two-spotted spider mites (Tetranychus urticae). We addressed three questions related to optimization of radiometric repeatability: (1) are reflectance-based plant responses affected by time of optical sensing? (2) if so, are plant responses to two-spotted spider mite infestations (biotic stressor) more pronounced at midnight versus at noon? (3) Is detection of biotic stress enhanced by spatial binning (smoothing) of hyperspectral imaging data? Results from this study provide insight into calculations of radiometric repeatability. Results strongly support claims that acquisition of optical sensing data to detect and characterize stress responses by plants to detect biotic stressors should be performed at night. Moreover, the combination of midnight imaging and spatial binning increased classification accuracies with 29% and 31% for soybean and coleus, respectively. Practical implications of these findings are discussed. Study results are relevant to virtually all applications of optical sensing to detect and diagnose abiotic and biotic stress responses by plants in both controlled environments and in outdoor crop production systems.

Detection and risk stratification of cardiac amyloidosis patients by integration of imaging and non-imaging data using a machine learning approach

Abstract Background With the advent of amyloid-targeting therapies, early and reliable diagnosis as well as precise risk estimation of cardiac amyloidosis (CA) have become of substantial importance. While the current diagnostic approach relies on difficult-to-standardize, visual interpretation of 99mTc-scintigraphy, risk assessment is largely based on a combination of blood and imaging parameters. Purpose Aim of this study is to assess the possibility of machine learning-based integration of scintigraphy, echocardiography, and non-imaging parameters such as blood parameters and comorbidities for the detection and risk stratification of patients with CA. Methods This study included all patients who underwent 99mTc-scintigraphy at a university affiliated tertiary care centre between 2010 and 2023. Two machine learning models were developed, and the relative predictive importance of their parameters were assessed (Figure 1): First, a model to detect patients with CA-suggestive uptake (Perugini grade 2/3) on 99mTc-scintigraphy scans; Second, a model to assess the risk of patients with CA-suggestive uptake for future heart failure hospitalization (HFH). A total of 58 features were extracted from electronic health records including blood, echocardiographic, demographic parameters and comorbidities. Scintigraphy imaging features were extracted from the raw imaging data using a deep learning approach. For the time to HFH prediction, a random survival forest machine learning model was employed. Results Overall, 12 380 consecutively enrolled patients were included, 279 (2.3%) of which were affected by CA-suggestive uptake. The machine learning model showed higher accuracy for the detection of CA (AUC 0.96 [95% CI 0.95-0.97], sensitivity 0.78 [95% CI 0.77-0.80] and specificity 0.99 [95% CI 0.99-0.99]. In the outcome analysis, the machine model showed good accuracy in predicting future HFH (C-index 0.71 [95% CI 0.68-0.75]). Parameter importance for the time to event analysis revealed right ventricular diameter, previous diagnosis of chronic heart failure and creatine kinase as the three most important predictors (Figure 2). Conclusions Detection of patients with cardiac amyloidosis and their risk estimation for heart failure can be aided using machine learning-based integration of imaging and non-imaging data. Our findings may guide novel approaches for assessing disease progression and treatment response.

The predisposing factors to heart failure diagnosis and early mortality among young adults in Africa: a narrative review

Abstract Introduction Heart failure (HF) is a major health concern mainly diagnosed among elderly individuals. Primarily, researchers have focused on this age group, nevertheless, compared to individuals from other regions of the world, Africans presents with HF two decades sooner (52 versus 79 years). Even though it manifests early, young persons (18–35 years old) are also diagnosed with HF with prognoses comparable to the older group. Less is known about how much study is concentrated on this age range, although globally, young adults of African origin make up the majority of those with an early onset of heart failure. Additionally, obtaining information about how HF impacts African youth remains challenging. Purpose To determine the cause of Africans' early HF diagnosis as well as the risk factors for HF diagnosis and early mortality among young adults. Methodology Three electronic databases— MEDLINE Ovid, Scopus, and CINAHL Plus—were searched using the Boolean operators. The first retrieved hits were checked for relevancy by titles and abstracts. Then, publications were fully screened for inclusion in the review based on the pre-established criteria. Also, reference lists of the articles were snowballed for pertinent studies. The scientific integrity of the studies was evaluated using a guided, in-depth peer-reviewed article on how to critically analyse clinical research and the Critical Appraisal Skill Programme (CASP) tool cohort checklist. Pertinent information regarding the study was analysed using a narrative review methodology. Eleven (11) articles out of the 135 pulled from the databases met the requirements for inclusion in the review after a thorough screening. One article was eliminated upon critical evaluation of the research's methodology, and an eligible article was discovered from snowballing reference lists. Therefore, only 11 articles qualified for this review study. Results Findings from the review show that HF is diagnosed earlier among Africans due to the early presentation of the major causes of HF before the age of 30 years. Rheumatic heart disease, cardiomyopathy, ischemic heart disease, HTN, and pulmonary illnesses (COPD, TB, and pulmonary arterial hypertension) are known aetiologies. More so, young adults who are diabetic, obese, have hyperlipidaemia or smoke cigarettes are more likely to develop HF. Furthermore, socioeconomic status, alcohol use, smoking, renal dysfunction, higher serum levels of brain natriuretic peptide (BNP) and creatine kinase (Isomer MB), cardiogenic shock, and decreased ejection fraction were the predictors of death with significant p-values (0.05). Conclusion Although HF affects young African adults disproportionately causing them to live lower quality of life and shorter lives, no research before this has been conducted. Therefore, further study is required to understand how HF affects this target age range (18 to 35 years) and to develop a long-term plan to fight this illness before it worsens.

The Effectiveness of Whole Body Magnetic Resonance Imaging Used in Health Screening Programs in Early Stage Cancer Diagnosis

Objective: We aim to present the findings and effectiveness of Whole Body Magnetic Resonance Imaging (WBMRI), which we use in the Health Screening Program (HSP) to diagnose cancer in early stage. Methods: This retrospective study was conducted between January 2017-February 2023. 393 individuals, between the ages of 18 and 85, who underwent WBMRI for HSP purposes, were included. The mean age was 50. Results: Malignancy suspicious lesions were observed in the head/neck region in 25 cases. Additional Magnetic Resonance (MRI) and Ultrasound (US) were performed. Mediastinal pathology was observed in 23 cases, and non-mediastinal thoracic pathologies were detected in 15. Therefore thorax Computed Tomography (CT), mammography, and breast US were performed. Benign lesions were observed in the liver in 44 cases, and US was performed. Malignancy-suspicious lesions in the liver were observed in 4, and dynamic abdominal MRI was performed. Cholelithiasis was observed in 16, and confirmed by US. The most common renal findings were; cysts and pelvicalyceal ectasia. Adrenal adenoma was observed in 5 cases. Two of the females had suspicion of gynecological malignancy. Massive diffuse concentric wall thickening was observed in the sigmoid colon, and colonoscopy was performed on one male. Musculoskeletal benign lesions were detected in 99 cases, and malignancy-suspicious lesions were detected in 35. Additional examinations such as US, CT, MRI, PET-CT, scintigraphy, and colonoscopy were performed on 172 cases. Malignancy was detected in 11 cases (2.8%). Conclusion: WBMRI is a radiation-free, non-invasive, short-term examination method. WBMRI is beneficial in diagnosing early-stage cancer.

Identification and Experimental Verification of PDK4 as a Potential Biomarker for Diagnosis and Treatment in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder marked by sustained joint inflammation, with an etiology that remains elusive. Achieving an early and precise diagnosis poses significant challenges. This study aims to elucidate the molecular pathways involved in RA pathogenesis by screening genes associated with its occurrence, analyzing the related molecular activities, and ultimately developing more effective molecular-level treatments for RA. Microarray expression profiling datasets GSE1919, GSE10500, GSE15573, GSE77298, GSE206848, and GSE236924 were sourced from the Gene Expression Omnibus (GEO) database. Samples were divided into experimental (RA) and control (normal) groups. Differentially expressed genes (DEGs) were identified using R software packages such as limma, glmnet, e1071 as well as randomForest. Cross-validation of DEGs was conducted using lasso regression and the random forest (RF) algorithm in R software to pinpoint intersecting genes that met the criteria. Among these, one gene was selected as the target for correlation analysis to identify DEGs related to the target gene. Enrichment analysis utilized the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway databases and Gene Ontology (GO) data. Gene Set Enrichment Analysis (GSEA) was performed to compare the expression levels of the target gene (PDK4) across various biological pathways and functions in groups with high and low expression. The relationship between target gene expression levels and cellular immune function was assessed using the immune function score technique. The discrepancy in immune cell distribution between the control and experimental groups, as well as their correlation with target gene expression levels, was elucidated using CIBERSORT. The relationships between mRNA, lncRNA, and miRNA were depicted in the ceRNA regulation network. The expression levels of the target gene were validated using Western blot and qRT-PCR. In this study, six intersecting genes meeting the criteria were identified through cross-validation, and PDK4 was chosen as the target gene for further investigation. Functional analysis using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) revealed that PDK4-associated DEGs are primarily enriched in the PPAR signaling pathway, thereby regulating synovial cell proliferation and migration, ultimately influencing the onset and progression of rheumatoid arthritis (RA). Immune infiltration analysis suggested that eosinophil quantity may influence the progression of RA. Experimental results from PCR and Western blot confirmed the downregulation of PDK4 in the RA group. The significant downregulation of PDK4 expression in patients diagnosed with rheumatoid arthritis (RA) was confirmed. PDK4 may function as a novel regulatory factor in the onset and progression of RA, with potential applications as a diagnostic biomarker for the condition.

Continuous monitoring of heart failure biomarker using a sensitive graphene-based electrical sensor

Abstract Heart Failure (HF) is a complex condition that imposes significant burdens on both patients and healthcare systems. The economic impact of HF therapy and management is substantial, underscoring the urgency for proactive measures to mitigate its development. Regular assessments play a pivotal role in identifying individuals at risk and initiating timely interventions to prevent or delay HF progression [1, 2]. NT-proBNP, an amine-terminated form of brain natriuretic peptide, emerges as a promising biomarker in the realm of chronic HF diagnosis, prognosis, and risk assessment [3]. Its utility lies in providing valuable insights into disease progression and prognosis. In recent years, biosensors based on Field Effect Transistors with Graphene (Gr) gate (GFET) have garnered attention for their rapid response, sensitivity, and on-chip integration [4]. Here, we present a sensitive miniaturized GFET sensor for continuous NT-proBNP measurement. The sensor is an array of GFET devices with sensing gates of a monolayer Gr decorated with aptamers as catch probes. Averaging over similar devices in an array approach ensures measurement consistency throughout the experiment. Moreover, the significant challenge posed by the Debye length in FET biosensors is effectively addressed through the functionalization with short folding aptamers [4]. The sensor is built based on a chip comprising an array of 28 individual micro GFETs (Fig. 1a). For the functionalization of Gr gates, we utilized 1-pyrene butyric acid N-hydroxysuccinimide ester as a linker between the aptamer probes and the Gr surface. Subsequently, the Gr surface was incubated with an amine-terminated aptamer solution (Fig. 1c). A schematic diagram of the sensory chip having a droplet of the sample is shown in Fig. 1b. To quantify NT-proBNP levels an 8µL droplet of the buffer solution containing a specific NT-proBNP concentration was deposited onto the sensor. The drain current (IDS) served as the sensor signal for each target concentration (Figs. 2a and 2b). The sensor signal decreased with increasing target concentration, while negligible response was observed when injecting blank buffers. This phenomenon can be attributed to the folding of aptamers upon binding to their target. Also, continuous measurement was conducted at a fixed gate voltage of 0.9V, recording the drain current while the target concentration gradually increased in the sample droplet. This process revealed a decrease in sensor current as we expected (Fig. 2c). The sensor exhibits remarkably low detection limits of 50 pg/mL and a linear range from 100 pg/mL to 10 ng/mL, which are highly conducive for early HF diagnosis and aligning well with reported NT-proBNP levels in patient biofluid [5]. The proposed sensor holds promise as a wearable device for continuous monitoring of high-risk patients. Additionally, this technology shows potential as a detection tool for acute heart failure in hospitalized patients.Sensor viewSensor responses