Disease Patients Research Articles

Perivascular space dysfunction in cerebral small vessel disease is related to neuroinflammation

Abstract Enlarged perivascular spaces are a feature of cerebral small vessel disease, and it has been hypothesized that they may reflect impaired glymphatic drainage. The mechanisms underlying perivascular spaces enlargement are not fully understood, but both increased inflammation and blood brain barrier permeability have been hypothesized to play a role. We investigated the relationship between perivascular spaces and both CNS and peripheral inflammation, as well as blood brain barrier permeability, in cerebral small vessel disease. Fifty-four symptomatic sporadic cerebral small vessel disease patients were studied. perivascular spaces were quantified using both a visual rating scale, and by measurement of perivascular spaces volume, in both the white matter and basal ganglia. PET-MRI was used to simultaneously measure microglial activation using the radioligand 11C-PK11195, and blood brain barrier permeability was acquired using dynamic contrast enhanced MRI. We determined 11C-PK11195 binding and blood brain barrier permeability in the local vicinity of individual perivascular spaces in concentric shells surrounding perivascular spaces. In addition, both mean 11C-PK11195 binding and blood brain barrier permeability in both the white matter and basal ganglia were determined. To assess systemic inflammation a panel of 93 blood biomarkers relating to cardiovascular disease, inflammation and endothelial activation were measured. Within the white matter tissue in closest proximity to perivascular spaces displayed greater 11C-PK11195 binding (p < 0.001), in the vicinity of perivascular spaces. Higher white matter perivascular spaces burden on the visual rating scale was associated with higher white matter 11C-PK11195 binding (rho = 0.469, FDR-p =0.009); values for perivascular spaces volume showed a similar trend. In contrast there were no associations between basal ganglia perivascular spaces burden and 11C-PK11195 binding. No perivascular spaces marker correlated with blood brain barrier permeability. There was no association between perivascular spaces markers and systemic inflammation blood biomarkers. Our findings demonstrate that white matter perivascular spaces are associated with increased 11C-PK11195 binding, consistent with neuroinflammation playing a role in white matter perivascular spaces enlargement. Further longitudinal and intervention studies and required to determine whether the relationship between neuroinflammation with enlarged perivascular spaces is causal.

Brodalumab is Effective for Psoriasis Patients with Difficult-to-treat Body Regions: Results from an Observational Clinical Study.

Brodalumab, a human monoclonal antibody that selectively inhibits the interleukin (IL)-17 receptor subunit A, has been approved for the treatment of moderate-to-severe plaque psoriasis. The treatment benefit of brodalumab has been clearly demonstrated in multiple clinical studies. However, data on effectiveness for difficult-to-treat body regions, especially in everyday clinical practice, are still limited. In this exploratory observational clinical study, psoriasis patients suffering from nail and scalp involvement who received brodalumab during routine clinical care were enrolled at 7 centers in Germany. Patients were observed over 60 weeks. The co-primary endpoints were 75% improvement in Psoriasis Scalp Severity Index (PSSI75) at week 12 and 75% improvement in Nail Psoriasis Severity Index (NAPSI75) at week 24. Secondary endpoints included assessment of general skin and disease outcomes, quality-of-life, and patient satisfaction with treatment. Eighty-seven patients were included. Mean age was 46.8 years, 70.1% patients were male, and mean body mass index was 28.9 kg/m². The co-primary endpoints were achieved by more than 90% of patients who met criteria for effectiveness analyses (n=62): 93.6% of patients achieved PSSI75 at week 12 and 90.3% of patients achieved NAPSI75 at week 24. Median body surface area involvement improved from 14% at baseline to 1.5% and 1% at weeks 12 and 24, respectively. Median Dermatology Life Quality Index scores improved from 16 at baseline to 2 and 1 at weeks 12 and 24, respectively. Improvements were maintained in the majority of patients throughout the 60-week study. Brodalumab was well tolerated and patients were highly satisfied with treatment. Outcomes assessed in this study, including assessments of scalp and nail symptoms, improved following initiation of brodalumab therapy. This study of psoriasis patients in a real-world setting supports the long-term clinical effectiveness of brodalumab on difficult-to-treat body regions.

Diagnosis and treatment of patients with gastroesophageal reflux disease - a systematic review of cost-effectiveness and economic burden.

This study aims to review the existing knowledge on the cost-effectiveness and item costs related to the diagnosis and treatment of gastroesophageal reflux disease (GERD) patients at different stages. The study adhered to the PRISMA guidelines. The systematic search involved several steps: finding and identifying relevant articles, filtering them according to the set criteria, and examining the final number of selected articles to obtain the primary information. The number of articles published between 2013 and September 2024 in the Web of Science and PubMed databases was considered. The CHEERS checklist was used for the risk of bias assessment. Ultimately, 36 studies were included. Regarding the cost-effectiveness of GERD treatment, Proton pump inhibitors (PPIs) appeared to be the dominant solution for non-refractory patients. However, this might change with the adoption of the novel drug vonoprazan, which is more effective and cheaper. With advancements in emerging technologies, new diagnostic and screening approaches such as Endosheath, Cytosponge, and combined multichannel intraluminal impedance and pH monitoring catheters should be considered, with potential implications for optimal GERD management strategies. The new diagnostic methods are reliable, safe, and more comfortable than standard procedures. PPIs are commonly used as the first line of treatment for GERD. Surgery, such as magnetic sphincter augmentation or laparoscopic fundoplication, is only recommended for patients with treatment-resistant GERD or severe symptoms. Advances in emerging technologies for diagnostics and screening may lead to a shift in the entire GERD treatment model, offering less invasive options and potentially improving patients' quality of life.

Case Report: Endovascular approach with kissing stent technique in aortoiliac occlusive disease (Leriche syndrome) patient

Background Aortoiliac occlusive disease (AIOD) or Leriche syndrome, is a form of peripheral arterial disease involving the infrarenal aorta and iliac arteries. The presentation of AIOD ranges from asymptomatic cases to limb-threatening emergencies. Advances and innovations in endovascular devices have replaced traditional surgical interventions for the management of AIOD. Here we report a case of a 52-year-old man presenting with AIOD managed by endovascular approach using kissing stent technique. Case presentation A 52-year-old man, with history of chronic coronary artery disease, diabetes mellitus type 2, long-standing hypertension, and a significant history of smoking, was admitted to our hospital with symptoms of long-standing bilateral claudication which recently progressed to rest pain. A history of AIOD was previously established. AIOD (TASC II Type D) diagnosis was made by lower extremity duplex ultrasound and CT angiography. The patient underwent urgent percutaneous transluminal angioplasty with kissing stent technique. The patient was discharged 4 days after the procedure without any significant complaints, received best medical therapy. Conclusion Endovascular interventions present excellent alternatives to surgical techniques in the treatment of complex AIOD. Herein we presented an endovascular treatment of AIOD utilizing the kissing stent technique which showed satisfactory outcomes.

Drosophila as a Model for Human Disease: Insights into Rare and Ultra-Rare Diseases

Rare and ultra-rare diseases constitute a significant medical challenge due to their low prevalence and the limited understanding of their origin and underlying mechanisms. These disorders often exhibit phenotypic diversity and molecular complexity that represent a challenge to biomedical research. There are more than 6000 different rare diseases that affect nearly 300 million people worldwide. However, the prevalence of each rare disease is low, and in consequence, the biomedical resources dedicated to each rare disease are limited and insufficient to effectively achieve progress in the research. The use of animal models to investigate the mechanisms underlying pathogenesis has become an invaluable tool. Among the animal models commonly used in research, Drosophila melanogaster has emerged as an efficient and reliable experimental model for investigating a wide range of genetic disorders, and to develop therapeutic strategies for rare and ultra-rare diseases. It offers several advantages as a research model including short life cycle, ease of laboratory maintenance, rapid life cycle, and fully sequenced genome that make it highly suitable for studying genetic disorders. Additionally, there is a high degree of genetic conservation from Drosophila melanogaster to humans, which allows the extrapolation of findings at the molecular and cellular levels. Here, I examine the role of Drosophila melanogaster as a model for studying rare and ultra-rare diseases and highlight its significant contributions and potential to biomedical research. High-throughput next-generation sequencing (NGS) technologies, such as whole-exome sequencing and whole-genome sequencing (WGS), are providing massive amounts of information on the genomic modifications present in rare diseases and common complex traits. The sequencing of exomes or genomes of individuals affected by rare diseases has enabled human geneticists to identify rare variants and identify potential loci associated with novel gene–disease relationships. Despite these advances, the average rare disease patient still experiences significant delay until receiving a diagnosis. Furthermore, the vast majority (95%) of patients with rare conditions lack effective treatment or a cure. This scenario is enhanced by frequent misdiagnoses leading to inadequate support. In consequence, there is an urgent need to develop model organisms to explore the molecular mechanisms underlying these diseases and to establish the genetic origin of these maladies. The aim of this review is to discuss the advantages and limitations of Drosophila melanogaster, hereafter referred as Drosophila, as an experimental model for biomedical research, and the applications to study human disease. The main question to address is whether Drosophila is a valid research model to study human disease, and in particular, rare and ultra-rare diseases.

A novel non-contrast agent-enhanced 3D whole-heart magnetic resonance sequence for congenital heart disease patients: the REACT Study.

The three-dimensional balanced-steady-state-free-precession (3D bSSFP) whole-heart (WH) technique has long been used to depict cardiac morphology in congenital heart disease (CHD) but is prone to banding artifacts. The Relaxation Enhanced Angiography without Contrast and Triggering (REACT) sequence is an alternative method that is resistant to off-resonance effects. To evaluate cardiac structures and great vessels in CHD patients using 3D WH REACT sequence and compare it to 3D WH bSSFP sequence. This study was approved by the Institutional Review Board. Thirty CHD patients were prospectively enrolled. Contrast-to-noise ratio (CNR), image quality, and cross-sectional area (CSA) were analyzed. Categorical data were compared with a Wilcoxon signed-rank test and normally distributed variables with a t-test. Thirty patients (16 females) participated in this study (median age 17, range 5months to 52years). REACT showed higher CNR in all pulmonary veins (all P<0.05), while 3D bSSFP had higher CNR in the right ventricle (P<0.001) and right pulmonary artery, (P=0.04). Image quality favored 3D bSSFP in the right atrium and ventricle (both P<0.001), main pulmonary artery (P=0.02), and coronary arteries (left: P<0.001, right: P=0.01). REACT outperformed 3D bSSFP for the pulmonary veins (all P<0.05) from image quality perspective. CSA measurements were not significantly different between REACT and 3D bSSFP (all P≥0.05). The REACT method is associated with improved image quality and CNR for pulmonary veins, with CSA measurements concordant with 3D bSSFP in CHD patients, while bSSFP shows better performance for imaging cardiac chambers and coronary arteries.

Predictive modeling of COVID-19 mortality risk in chronic kidney disease patients using multiple machine learning algorithms

Predictive modeling of COVID-19 mortality risk in chronic kidney disease patients using multiple machine learning algorithms

Hyperparameter Tuning Decision Tree and Recursive Feature Elimination Technique for Improved Chronic Kidney Disease Classification

Purpose: This study has the purpose of classifying patients with chronic kidney disease based on specific features and improving the classification models by tuning hyperparameters. This study aims to detect chronic kidney disease at an early stage. Methods: In this study, a machine learning classifier in the form of a decision tree is used to classify chronic kidney disease on the Risk Factor Prediction of Chronic Kidney Disease dataset. After that, the performance of the classifier model is improved by using feature selection, namely Recursive Feature Elimination and Hyperparameter tuning with GridSearchCV. Result: After tests were conducted 3 times namely testing with Decision Tree, Recursive Feature Elimination, and Hyperparameter tuning GridSearchCV which is the proposed method, then compared to other tests. The results from this study is using that method can improve the Decision Tree classifier in classifying chronic kidney disease patients. Novelty: Dataset that have been used in this study is from UCI machine learning repository namely Risk Factor Prediction of Chronic Kidney Disease that have 202 instances and 28 feature and after being processess and conducting test, Recursive Feature Elimination and Hyperparameter tuning GridSearchCV can improve the Decision Tree classifier in classifying chronic kidney disease.

Effectiveness of Coronary Artery Disease Health Education among the patients of Coronary Artery Disease in Tertiary Cardiac Centre

Background and Aims: Secondary prevention of coronary artery disease is vital in preventing the future cardiac events. Inadequate knowledge of the disease is related to non-compliance with the treatment therapy which directly results in disease progression and its complication. The objective of this study is to assess the effectiveness of health education about coronary artery disease among the patients of coronary artery disease in a tertiary cardiac centre. Methods: A quantitative, prospective, interventional research design was designed to collect the data by non-probability convenience sampling method. Patients diagnosed with coronary artery disease and admitted in different wards of Shahid Gangalal National Heart Centre were included. Data was collected from July 2022 to December 2022 in three phases: prior to health education; within 24 hours of health education and after 3 months. A semi structured face to face interview was used to collect data from the patients, which was then filled in the web-based questionnaire and appropriate statistical methods were used for analysis. Results: A total of 167 patients were enrolled during the study period. Only 145 (86.8%) patients completed the 3rd phase of data collection. There was a significant improvement in patients’ overall knowledge (P value; &lt;.01) as well as knowledge regarding medical (P value; &lt;.01), coronary artery disease risk factors (P value; &lt;.01), exercise (P value; &lt;.01), nutrition (P value; &lt;.01) and psychological risk (P value; &lt;.05). There was a significant improvement (P value; &lt;.01) related to behavior related characteristics like smoking, tobacco consumption, alcohol consumption and physical activity. However, correlation between health behaviors and post intervention knowledge showed a non-significant weakly positive relation of knowledge with education (r=.081), whereas there was non-significant weakly negative relation with physical activity (r=-.0126). Conclusion: The educational intervention has significant improvement in level of knowledge and change in behavior pattern among the patients of coronary artery disease. This study demonstrates that targeted health education programs can lead to significant improvements in knowledge and behavior among coronary artery disease patients, potentially reducing hospital readmission rates and promoting better long-term disease management.

Manifestations of and factors influencing posttraumatic growth among Chinese Crohn's disease patients: a qualitative exploration.

This qualitative study aims to explore the manifestations of posttraumatic growth among Chinese patients with Crohn's disease from a cultural perspective and to identify the factors influencing it. A descriptive qualitative research method was used. Semistructured interviews were conducted with 19 patients with Crohn's disease from several hospitals in Hangzhou, Zhejiang Province, China, and the China Crohn's and Colitis Foundation. There were five key manifestations of posttraumatic growth experienced by Chinese patients with Crohn's disease: improving interpersonal relationships, enhancing personal strengths, changing life priorities, expanding possibilities and gaining religious faith. Posttraumatic growth among patients was predominantly influenced by individual factors, the disease condition and social support. The findings regarding the manifestations of and factors influencing posttraumatic growth in Chinese patients with Crohn's disease are consistent with those in previous studies in patients with chronic diseases. However, our study underscores the multifaceted impact of Chinese cultural characteristics on posttraumatic growth among Crohn's disease patients. These findings can offer valuable guidance for future complex interventions and relevant clinical studies conducted within the Chinese population.

Association of Clinical and Paraclinical Factors with Pain Crisis Severity in Sickle-Thalassemia Patients in Iran

Objectives: This study aimed to evaluate the effects of several factors, including hospitalization frequency, inflammatory and hemolytic markers, and the numbers of blood transfusions and crises, on the severity of pain crises in sickle-thalassemia patients. Methods: Of all patients visiting hematologists in university-affiliated hospitals and clinics, only 75 sickle cell disease (SCD) and sickle-thalassemia patients met the inclusion criteria for this study. Disease severity was measured based on pain crises per year and laboratory markers, including hemolytic and inflammatory indicators, outpatient or inpatient status, the number of hospital admissions, and the number of blood units transfused over one year. Results: In sickle cell patients, a significant correlation was observed between hospital admission and WBC (0.01), ALP (0.001), MCHC (0.001), ferritin (0.021), and ESR (0.006). Additionally, pain crises were positively correlated with transferrin saturation (TS) (+0.28) and the number of transfused blood units (+0.49) and negatively correlated with Hb (-0.30) and total iron binding capacity (TIBC) (-0.23). Blood unit transfusions showed a positive correlation with serum iron (+0.44), RDW (+0.36), ferritin (+0.39), pain crises (+0.49), and TS (+0.49), along with a negative correlation with Hb (-0.75) and MCHC (-0.33). When categorizing pain crises into two groups, patients experiencing more frequent crises generally exhibited lower hemoglobin levels and a higher number of blood units transfused. Hemoglobin also showed a significant negative correlation with lactate dehydrogenase (LDH) level in both groups: -0.604 (P = 0.005) in patients with ≥ 3 crises per year and -0.368 (P = 0.006) in patients with &lt; 3 crises per year. Patients with hemoglobin levels of 7.5 or higher tended to maintain an LDH level below 1000. Among patients referred with pain crises, hemoglobin was negatively correlated with hemolytic markers such as LDH (-0.41) and retic (-0.29). Conclusions: Hemoglobin and LDH can serve as follow-up markers, as they are routinely measured in all sickle cell patients and, in this study, hemoglobin levels of 7.5 or higher and LDH levels below 1000 were associated with fewer and less severe pain crises. Regular monitoring of hemolytic markers may help in pain crisis prevention, as this study found that hemolytic crises frequently coincided with pain crises. Further research is needed to provide conclusive evidence in this area.

Lack of Efficacy of Pomegranate Supplementation on Insulin Resistance and Sensitivity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The objective of this study is to assess the impact of pomegranate supplements on insulin resistance (IR) and insulin sensitivity through a systematic review and meta-analysis of randomized controlled trials (RCTs). Additionally, we aim to analyze the differences in efficacy among various pomegranate extracts and the sensitivity of different diseases to pomegranate supplementation. We conducted searches in PubMed, Embase, Web of Science, and Cochrane Library up to October 30, 2023, for relevant studies published in English. The treatment group required the intake of pomegranate extract for a minimum of 4 weeks, with no restrictions on the extract type. The control group received a placebo or a treatment excluding pomegranate extract. The primary outcome was homeostatic model assessment for insulin resistance (HOMA-IR) and fasting insulin (FI), and the secondary outcome was quantitative insulin sensitivity check index (QUICKI). RoB 2 was used to assess the risk of bias in the original studies. We pre-specified subgroup analyses based on types of intervention, intervention duration, health condition, and intervention dose. Sensitivity analysis was conducted to validate result stability, utilizing Begg's test and Egger's test for publication bias. Data synthesis and analysis were performed using Stata 15.1 software. This study included a total of 15 RCTs with 673 participants conducted in 7 countries. Risk of bias results indicated an overall low risk of bias of the articles. Participants included healthy individuals, overweight and obese individuals, non-alcoholic fatty liver disease (NAFLD) patients, type 2 diabetes (T2DM) patients, polycystic ovary syndrome (PCOS) patients, metabolic syndrome (MS) patients, and individuals with hyperlipidemia. Pomegranate extract variations included pomegranate juice (PJ), pomegranate seed oil (PSO) capsule, pomegranate/pomegranate peel (PP) extract capsule, and pomegranate peel-added bread. The control groups primarily received placebo treatments with varying dosage and frequency. No adverse reactions were reported in any of the studies. The summary results showed that compared to the control groups, pomegranate extract had no significant impact on improving HOMA-IR levels in participants (WMD = -0.03, 95%CI: -0.37 to 0.31, and p = 0.851) and FI (WMD = -0.03, 95%CI: -0.42 to 0.36, and p = 0.862). Additionally, there was no significant advantage of pomegranate extract on QUICKI changes in T2DM and PCOS patients (WMD = 0.00, 95%CI: 0.00 to 0.01, and p = 0.002). Subgroup analysis results indicated that pomegranate extract could improve HOMA-IR levels in PCOS patients (WMD = -0.42, 95%CI: -0.54 to -0.29, and p < 0.001) and FI levels in T2DM, PCOS, and NAFLD patients. Our results indicate that pomegranate extract only improves HOMA-IR and FI levels in PCOS patients and FI levels in T2DM and NAFLD patients. No significant difference has been found for HOMA-IR, FI, or QUICKI in other metabolic diseases. The current evidence suggests that we should interpret the value of pomegranate extract in regulating IR and sensitivity cautiously. In the future, there is a need for more rigorously designed RCTs to specifically evaluate the impact of pomegranate supplementation on insulin sensitivity in patients with NAFLD, PCOS, and T2DM.

Sickle cell disease in India: Not just a mild condition.

Sickle cell disease (SCD) is a common and life-threatening global health problem, with more than 500 000 affected infants born annually. The burden of SCD in sub-Saharan Africa is well established, but the comparably high prevalence in India is not well recognized and many consider SCD in India to be less severe. In their paper, a national study in India demonstrated the significant impact of SCD for patients, families and the healthcare system, supporting a call to action to recognize and address SCD as a serious and common health condition in India. Commentary on: Seth etal. Burden of vaso-occlusive crisis, its management, and impact on quality of life of Indian sickle cell disease patients. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19829.

Identification of clinical risk factors for coronary artery lesions in children with Kawasaki disease: a retrospective cohort study.

Coronary artery lesions are the most severe complications of Kawasaki disease. Despite recent advances, evidence of the association between risk factors and coronary artery lesion is lacking. In this study, we demonstrated the potential clinical indicators that could assist to evaluate the prevalence of coronary artery lesion among paediatric patients with Kawasaki disease. We retrospectively enrolled 260 paediatric patients with Kawasaki disease. Patients with coronary dilation, coronary aneurysm, and intimal thickening of coronary arteries were included in this study. Medical records of each patient were collected. Logistic regression analysis was performed to explore risk factors and the occurrence of coronary artery lesion in patients with Kawasaki disease. Respectively, 64 (24.6%), 39 (15%), and 56 patients (21.5%) of the participants had coronary dilation, coronary aneurysm, and intimal thickening of coronary arteries. Univariate analysis revealed that age, gender, duration of fever, time of initial use of intravenous immunoglobulin, erythrocyte sedimentation rate, white blood cell counts, time of platelet increase, the maximum value of platelet, albumin, and immunoglobulin G level was associated with coronary artery lesion. In multivariable logistic analysis, those younger and mainly males were associated with all three outcomes of coronary artery lesion, lower serum albumin levels, and later initial use of intravenous immunoglobulin were linked to a higher risk of coronary dilation and coronary aneurysm. The potential risk factors that could be used to estimate the occurrence of coronary artery lesion in Kawasaki disease patients are young age, male, lower serum albumin lever, and later initial use of intravenous immunoglobulin. However, long-term follow-up and multi-centre studies are required to verify our findings in the future.

Use of Basket Trials to Solve Sleep Problems in Patients with Rare Diseases

The need for sleep is universal, and the ability to meet this need impacts the quality of life for patients, families, and caregivers. Although substantial progress has been made in treating rare diseases, many patients have unmet medical sleep needs, and current regulatory policy makes it prohibitively difficult to address those needs medically. This opinion reviews the rare disease experience with sleep disorders and explores potential solutions. First, we provide case profiles for the rare diseases Wilson’s Disease, Angelman Syndrome, and Prader–Willi Syndrome. These profiles highlight challenges in rare disease diagnosis and barriers to pinpointing disease pathophysiology, including biomarkers that intersect with sleep disorders. Second, we transition to a bird’s eye view of sleep disorders and rare diseases by reporting input from a stakeholder discussion with the U.S. Food and Drug Administration regarding abnormal sleep patterns in various rare diseases. Last, in response to the profound unmet medical needs of patients with rare diseases and sleep disorders, we propose adapting and using the clinical trial design known as a “basket trial”. In this case, a basket trial would include patients with different rare diseases but the same debilitating symptoms. This research approach has the potential to benefit many rare disease patients who are otherwise left with profound unmet medical needs.

Precision Cut Lung Slices: Emerging Tools for Preclinical and Translational Lung Research. An Official American Thoracic Society Workshop Report.

The urgent need for effective treatments for acute and chronic lung diseases underscores the significance of developing innovative preclinical human research tools. The 2023 ATS Workshop on Precision Cut Lung Slices (PCLS) brought together 35 experts to discuss and address the role of human tissue-derived PCLS as a unique tool for target and drug discovery and validation in pulmonary medicine. With increasing interest and usage, along with advancements in methods and technology, there is a growing need for consensus on PCLS methodology and readouts. The current document recommends standard reporting criteria and emphasizes the requirement for careful collection and integration of clinical metadata. We further discuss current clinically relevant readouts that can be applied to PCLS and highlight recent developments and future steps for implementing novel technologies for PCLS modeling and analysis. The collection and correlation of clinical metadata and multiomic analysis will further advent the integration of this preclinical platform into patient endotyping and the development of tailored therapies for lung disease patients.

Elevated Perspectives: Unraveling Cardiovascular Dynamics in High-Altitude Realms.

High-altitude regions pose distinctive challenges for cardiovascular health because of decreased oxygen levels, reduced barometric pressure, and colder temperatures. Approximately 82 million people live above 2400 meters, while over 100 million people visit these heights annually. Individuals ascending rapidly or those with pre-existing cardiovascular conditions are particularly vulnerable to altitude-related illnesses, including Acute Mountain Sickness (AMS) and Chronic Mountain Sickness (CMS). The cardiovascular system struggles to adapt to hypoxic stress, which can lead to arrhythmias, systemic hypertension, and right ventricular failure. Pathophysiologically, high-altitude exposure triggers immediate increases in cardiac output and heart rate, often due to enhanced sympathetic activity. Over time, acclimatisation involves complex changes, such as reduced stroke volume and increased blood volume. The pulmonary vasculature also undergoes significant alterations, including hypoxic pulmonary vasoconstriction and vascular remodelling, contributing to conditions, like pulmonary hypertension and high-altitude pulmonary edema. Genetic adaptations in populations living at high altitudes, such as gene variations linked to hypoxia response, further influence these physiological processes. Regarding cardiovascular disease risk, stable coronary artery disease patients generally do not face significant adverse outcomes at altitudes up to 3500 meters. However, those with unstable angina or recent cardiac interventions should avoid high-altitude exposure to prevent exacerbation. Remarkably, high-altitude living correlates with reduced cardiovascular mortality rates, possibly due to improved air quality and hypoxia-induced adaptations. Additionally, there is a higher incidence of congenital heart disease among children born at high altitudes, highlighting the profound impact of hypoxia on heart development. Understanding these dynamics is crucial for managing risks and improving health outcomes in high-altitude environments.

A novel light GBM framework combined with gain optimization for predicting dementia severity of Alzheimer’s disease

ABSTRACT Introduction Alzheimer’s disease (AD) is a severe brain disorder, which comprises almost 75% of all types of dementia cases. As per the latest report, the global count of Alzheimer’s disease patients is 131 million, due to which the treatment of Alzheimer’s disease is becoming a major burden to the world healthcare system. However, Alzheimer’s disease still remains incurable due to its multifactorial nature of symptoms. Therefore, early-stage diagnosis of Alzheimer’s disease is essential, which helps in the treatment and recovery of patients to a greater extent. Background In the existing literature, few research attempts are carried out for Alzheimer’s disease prediction using machine learning algorithms; yet, most of the existing techniques fail to focus on aspects such as gain-optimisation, dementia severity identification and accuracy enhancement. Methodology To solve these issues, this article presents a light gradient boosting machine-based framework, which employs a gain-optimisation algorithm using multi-category factors for the early stage prediction of Alzheimer’s disease. Further, the proposed framework introduces a detailed feature analysis for identifying the key features needed for the disease prediction and thereby classifies the Alzheimer’s disease patients into different dementia severity types. Results The extensive evaluations of the proposed framework on different dataset sizes using real-world MRI datasets of patients, clearly demonstrate the performance of the proposed work in terms of gain-optimised accuracy metrics. Further, experimental evaluations clearly prove the better performance of the proposed framework when compared to that of other ML techniques including LR, RFC, SVR, SVC and existing methods in terms of Recall, F1-score and accuracy metrics.

Depression and Quality of Life in Parkinson’s Disease Patients: A Cross-Sectional Study

Depression and Quality of Life in Parkinson’s Disease Patients: A Cross-Sectional Study

Reliable change indices for the Italian version of the Montreal Cognitive Assessment (MoCA) in non-demented Parkinson’s disease patients

Background. The present study aimed at deriving regression-based reliable change indices (RCIs) for the Montreal Cognitive Assessment (MoCA) in an Italian cohort of non-demented Parkinson’s disease (PD) patients.MethodsN = 33 consecutive, non-demented PD patients were followed-up at a 5-to-8-month interval (M = 6.6; SD = 0.6) with the MoCA. Practice effects and test-retest reliability were assessed via dependent-sample t-tests and intra-class correlation (ICC) coefficients, respectively. RCIs were derived separately for raw and demographically adjusted MoCA scores according to a standardized regression-based approach by accounting for both baseline confounders (i.e., demographics, disease duration and Unified Parkinson’s Disease Rating Scale scores) and retest interval.ResultsNo practice effects were found (t(32) = 0.29; p = .778), with acceptable test-retest reliability being detected (ICC = 0.67). MoCA scores at T0 proved to be the only significant predictor of T1 MoCA performances within both the model addressing raw scores and that addressing adjusted scores (ps < 0.001).ConclusionsThe present study provides Italian practitioners and researchers with regression-based RCIs for the MoCA in non-demented PD patients, which can be reliably adopted for retest interval ≥ 5 and ≤ 8 months without encountering any practice effect.