Enhancing Pulmonary Embolism Mortality Risk Stratification Using Machine Learning: The Role of the Neutrophil-to-Lymphocyte Ratio.

(1) Background: Acute pulmonary embolism (PE) is a significant public health concern that requires efficient risk estimation to optimize patient care and resource allocation. The purpose of this retrospective study was to show the correlation of NLR (neutrophil-to-lymphocyte ratio) and PESI (pulmonary embolism severity index)/sPESI (simplified PESI) in determining the risk of in-hospital mortality in patients with pulmonary thromboembolism. (2) Methods: A total of 160 patients admitted at the County Clinical Emergency Hospital of Sibiu from 2019 to 2022 were included and their hospital records were analyzed. (3) Results: Elevated NLR values were significantly correlated with increased in-hospital mortality. Furthermore, elevated NLR was associated with PESI and sPESI scores and their categories, as well as the individual components of these parameters, namely increasing age, hypotension, hypoxemia, and altered mental status. We leveraged the advantages of machine learning algorithms to integrate elevated NLR into PE risk stratification. Utilizing two-step cluster analysis and CART (classification and regression trees), several distinct patient subgroups emerged with varying in-hospital mortality rates based on combinations of previously validated score categories or their defining elements and elevated NLR, WBC (white blood cell) count, or the presence COVID-19 infection. (4) Conclusion: The findings suggest that integrating these parameters in risk stratification can aid in improving predictive accuracy of estimating the in-hospital mortality of PE patients.

IGF-1 Levels are Dependent on Age, but Not Weight Status in Children.

Introduction: The intersecting pathways involved in linear growth, glucose, and lipid metabolism may play a key part in the imbalances leading to the dysmetabolic changes observed in obese children, and later adults. The growth-hormone/insulin growth factor 1 (GH/IGF-1) axis is a prime example in this regard and IGF-1 levels have been shown to correlate with insulin resistance. Objectives: The aim of this study is to examine whether there is a relationship between circulating IGF levels and weight status in children as an independent relationship, regardless of insulin sensitivity. Materials and method: We retrospectively collected data from patients aged 5-12 years referred to the Pediatric Clinical Hospital Sibiu between January 2010 and May 2023, for which IGF-1 levels were documented. We excluded patients with pathologies or medication which could have influenced weight status, glucose and lipid metabolism, or growth hormone secretion, and those with short stature or a growth velocity of under 5 cm a year. Anthropometric measurements were retrieved and BMI Z-score was calculated. Results: Our study included 66 patients (32 females and 34 males) with a mean age of 100,09 months (SD: 24,754 months). Initial bivariate analysis showed a significant negative correlation between BMI Z-score and IGF-1 values. However, adjusting for age indicated that there was in fact no significant relationship between these two parameters. Insulin-like growth factor 1 levels did however vary significantly with patient age. Conclusions: Levels of IGF-1 showed an age-dependent variation which should be accounted for in data analysis. Our study found no correlation between weight status and IGF-1 levels when adjusting for age-dependent variation. Further studies may shed light on the possible role of IGF-1 in discerning between obese children with or without increased insulin resistance.

Assessing Obesogenic School Environments in Sibiu County, Romania: Adapting the ISCOLE School Environment Questionnaire.

The impact of the school environment on childhood weight status has garnered significant attention in recent years. This study aimed to adapt and validate the International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE) School and Environment questionnaire in order to assess the potential obesogenic impact of school environments in Sibiu County, Romania. The ISCOLE questionnaire was chosen for its rigorous methodology. It was derived from a comprehensive study conducted across 12 countries which aimed to capture multifaceted influences on childhood weight while emphasizing educational settings in the collection of data. To guide the translation and adaptation of the questionnaire, a multidisciplinary committee was assembled which comprised experts in teaching and school administration to ensure target responder relevance, experts in clinical research to ensure methodological robustness, experts in language adaptation to preserve the original intent of the survey, and experts in public health to steer the interpretation of the results, with potential policy implications. The data were analyzed by distinguishing between urban and rural settings, and a two-step cluster analysis was implemented to identify potential intervention targets. To assess the validity of the adapted tool, the questionnaire's construct validity and internal consistency were explored. A response rate of 71.2% of the approached schools in Sibiu County was achieved. Of the 84 responding school representatives, 37 (44%) were from a rural setting. The rural schools had significantly more limited access to gymnasiums, secured lockers, showers, and bicycle racks, and exhibited more serious problems regarding the inadequate disposal of garbage in the school vicinity. A two-step cluster analysis revealed distinct school categories, providing opportunities for public policy interventions. One of these primarily concerned rural schools with limited infrastructure but with proactive practices and policies which were termed "unable but willing"; on the opposing spectrum, the category "able but unwilling" mainly comprised urban schools which had available facilities but lacked local proactive initiatives. The findings emphasize the urgent need for targeted measures to bridge these discrepancies by investing in infrastructure in rural schools and promoting active school practices and policies in urban settings. The assessment of obesogenic school environments in Sibiu County provides a pilot model for broader applications due to the diverse school landscape and supportive local authorities. The results, which were achieved using low-cost methods, can guide future educational policies, health promotion initiatives, and preventive interventions.

Interactions between Metabolic Syndrome, MASLD, and Arterial Stiffening: A Single-Center Cross-Sectional Study.

Metabolic-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), has emerged as a prominent global cause of chronic liver disease and is increasingly recognized as associated with atherosclerotic vascular illness, consolidating its position along traditional cardiovascular risk factors. Individuals with MASLD exhibit a combination of metabolic syndrome risk factors, carotid atherosclerosis, and increased arterial stiffness, hinting at shared pathogenesis. In this study, we aim to explore liver involvement and arterial stiffness within metabolic syndrome. We enrolled 75 patients (30 male and 45 female) with either liver steatosis on conventional ultrasound, altered liver function tests, or the presence of cardiometabolic risk factors after excluding liver pathology other than MASLD. Clinical evaluation, laboratory measurements, abdominal and carotid ultrasounds, vibration-controlled transient elastography (VCTE, Fibroscan), and assessment with the Arteriograph (Tensiomed) were performed. The 26 patients diagnosed with MetS had significantly higher liver involvement as quantified via the hepatic steatosis index (HSI), Fibrosis-4 (FIB4), aspartate aminotransferase to platelet ratio index (APRI) category, and VCTE measurements, as well as Agile 3+ and Agile 4 scores which use a combination of clinical and laboratory parameters together with results obtained from VCTE to reflect the probability of advanced liver fibrosis or cirrhosis. Patients with MetS also exhibited more pronounced vascular involvement as quantified via arterial stiffness measurements and CIMT (carotid intima-media thickness). We applied a two-step clustering algorithm to enhance our analysis, which gave us pertinent insight into the interplay between metabolic syndrome elements and typologies of hepatic steatosis and arterial stiffness degrees. Notably, of the three obtained clusters, the cluster showing increased levels of hepatic steatosis and arterial stiffness also exhibited the highest prevalence of metabolic syndrome and its constituting components. The results have significant clinical implications, advocating for a comprehensive diagnostic approach when MetS or MASLD is suspected.

Hepatic Involvement across the Metabolic Syndrome Spectrum: Non-Invasive Assessment and Risk Prediction Using Machine Learning.

Metabolic-dysfunction-associated steatotic liver disease (MASLD) and metabolic syndrome (MetS) are inextricably linked conditions, both of which are experiencing an upward trend in prevalence, thereby exerting a substantial clinical and economic burden. The presence of MetS should prompt the search for metabolic-associated liver disease. Liver fibrosis is the main predictor of liver-related morbidity and mortality. Non-invasive tests (NIT) such as the Fibrosis-4 index (FIB4), aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), hepatic steatosis index (HIS), transient elastography (TE), and combined scores (AGILE3+, AGILE4) facilitate the detection of liver fibrosis or steatosis. Our study enrolled 217 patients with suspected MASLD, 109 of whom were diagnosed with MetS. We implemented clinical and biological evaluations complemented by transient elastography (TE) to discern the most robust predictors for liver disease manifestation patterns. Patients with MetS had significantly higher values of FIB4, APRI, HSI, liver stiffness, and steatosis parameters measured by TE, as well as AGILE3+ and AGILE4 scores. Machine-learning algorithms enhanced our evaluation. A two-step cluster algorithm yielded three clusters with reliable model quality. Cluster 1 contained patients without significant fibrosis or steatosis, while clusters 2 and 3 showed a higher prevalence of significant liver fibrosis or at least moderate steatosis as measured by TE. A decision tree algorithm identified age, BMI, liver enzyme levels, and metabolic syndrome characteristics as significant factors in predicting cluster membership with an overall accuracy of 89.4%. Combining NITs improves the accuracy of detecting patterns of liver involvement in patients with suspected MASLD.

A Family with Myh7 Mutation and Different Forms of Cardiomyopathies.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are common heart muscle disorders that are caused by pathogenic variants in sarcomere protein genes. In this study, we describe a variant in the MHY7 gene, segregating in a family having three different phenotypes of cardiomyopathies. MYH7 encodes for the myosin heavy-chain ß (MHC-ß) isoform involved in cardiac muscle contractility. METHOD AND RESULTS: We present the case of a family with four members diagnosed with HCM and four members with DCM. The proband is a 42-year-old man diagnosed with HCM. He has an extended family of eight siblings; two of them are diagnosed with HCM and are implantable cardioverter-defibrillator (ICD) carriers. One of the siblings died at the age of 23 after suffering a sudden cardiac arrest and DCM of unknown etiology which was diagnosed at autopsy. Another brother was diagnosed with DCM during a routine echocardiographic exam. Genetic testing was performed for the proband and two of his siblings and a niece of the proband, who suffered a cardiac arrest at the age of nine, all being MYH7 mutation positive. For all four of them, cardiac imaging was performed with different findings. They are ICD carriers as well. CONCLUSIONS: Our results reveal three variants in phenotypes of cardiomyopathies in a family with MYH7 mutation associated with high SCD risk and ICD needed for primary and secondary prevention.

Endocarditis with Streptococcus pseudoporcinus Associated with Mastocytosis and Spondylodiscitis-A Coincidental Association? A Case Report.

Streptococcus pseudoporcinus is a nonmotile Gram-positive, catalase, and benzidine negative, arranged in short chains, isolated from the genitourinary tract group B Streptococcus. S. pseudoporcinus was also identified from blood, urine, skin, cervical area, wounds, rectum, and placenta samples. Two cases of infective endocarditis have been reported in the literature. Based on these data, the identification of a case of S. pseudoporcinus infective endocarditis associated with spondylodiscitis in a patient with undiagnosed systemic mastocytosis until the age of 63 years is unusual. Two sets of blood specimens were collected, and both sets were positive for S. pseudoporcinus. Transesophageal echocardiography revealed, multiple vegetations on the mitral valve. A lumbar spine MRI revealed L5-S1 spondylodiscitis that associates prevertebral and right paramedian epidural abscesses with compressive stenosis. The performed bone marrow biopsy, and cellularity examination revealed 5-10% mast cells in the areas of medullary tissue, an aspect that is suggestive of mastocytosis. Antibiotic therapy was initiated, under which the patient presented intermittent fever. A second transesophageal echocardiography revealed a mitral valve abscess. A mitral valve replacement with a mechanical heart valve device through a minimally invasive approach was performed, with a favorable evolution under treatment. S. pseudoporcinus can be responsible for infectious endocarditis in certain immunodepressed cases, but also in a profibrotic, proatherogenic field, as shown by the association with mastocytosis in the presented case.

Post-Marketing Surveillance of Statins-A Descriptive Analysis of Psychiatric Adverse Reactions in EudraVigilance.

Statins are included in the category of high-frequency prescription drugs, and their use is on an upward trend worldwide. In 2012, the FDA issued a warning about possible cognitive adverse drug reactions (ADRs) related to statins, some of which are listed in the Summary of Product Characteristics, but there are still concerns about their potential risk of psychiatric events. The aim of this research was to investigate spontaneous reports containing psychiatric ADRs associated with statins by analyzing the EudraVigilance (EV) database. From January 2004 to July 2021, a total of 8965 ADRs were reported for the Systems Organ Class (SOC) "psychiatric disorders", of which 88.64% were registered for atorvastatin (3659), simvastatin (2326) and rosuvastatin (1962). Out of a total of 7947 individual case safety reports (ICSRs) of the 3 statins mentioned above, in 36.3% (2885) of them, statins were considered the only suspected drug, and in 42% (3338), no other co-administered drugs were mentioned. Moreover, insomnia has been reported in 19.3% (1536) of cases, being the most frequent adverse reaction. A disproportionality analysis of psychiatric ADRs was performed. The Reporting Odds Ratio (ROR) and 95% confidence interval (95% CI) were calculated for simvastatin, atorvastatin and rosuvastatin compared with antiplatelets and antihypertensive drugs. The reporting probability for most ADRs of these statins compared to antiplatelets was higher. The reporting probability for insomnia, nightmares and depression produced by statins compared to antihypertensive drugs was also higher. The results of this analysis augment the existing data about a possible correlation between the administration of statins and the occurrence of psychiatric side effects.

Gender Particularities and Prevalence of Atypical Clinical Presentation in Non-ST Elevation Acute Coronary Syndrome.

Clinical presentation is one of the factors that can influence how quickly a patient with an acute coronary syndrome is treated, particularly if it is atypical. The purposes of this study are to explore gender-related differences in patients presenting with non-ST elevation acute coronary syndromes (NSTEACS) from the perspective of a series of common risk factors as well as treatment strategies and to evaluate the prevalence of atypical clinical presentation of NSTEACS in the study group. In addition, we explored the differences between the two entities that define NSTEACS: unstable angina (UA) and non-ST elevation myocardial infarction (NSTEMI). We conducted a retrospective study by reviewing discharge documents of patients admitted in the cardiology department of the Clinical Rehabilitation Hospital in Cluj-Napoca with NSTEACS between January 2014 and December 2015. We retrieved demographic data, clinical presentation and history, laboratory tests, and coronary angiography records as well as the implemented treatment strategies. Women in the study group were more frequently hypertensive than men (89.5% vs. 75.4%; p = 0.043), had a higher mean serum HDL cholesterol value (43 vs. 38 mg/dL p = 0.022), were more frequently diagnosed with microvascular coronary heart disease (32% vs. 9.8%, p = 0.036), and were more often treated conservatively (49.1% vs. 30.8%, p = 0.038), while men were significantly more prone to smoking than women (30.8% vs. 14%, p = 0.028) and had higher mean serum creatinine (1.2 vs. 0.8 mg/dL; p = 0.022) and uric acid values (6.9 vs. 6.2 mg/dL; p = 0.048). Out of the 122 included patients, 109 had documented information regarding symptoms. The prevalence of atypical presentation was 4.6% (95% CI 0.7-8.5%). In our study group, patients with UA had a more frequent history of cardiovascular ischemic diseases (77.4% vs. 56.7%, p = 0.015), the mean value for BUN was higher in NSTEMI patients compared to patients with UA (47 vs. 39 mg/dL, p = 0.038) and NSTEMI patients more frequently received interventional treatment compared to patients with UA (60% vs. 41.9%; p = 0.046).

A Decision-Tree Approach to Assist in Forecasting the Outcomes of the Neonatal Brain Injury.

Neonatal brain injury or neonatal encephalopathy (NE) is a significant morbidity and mortality factor in preterm and full-term newborns. NE has an incidence in the range of 2.5 to 3.5 per 1000 live births carrying a considerable burden for neurological outcomes such as epilepsy, cerebral palsy, cognitive impairments, and hydrocephaly. Many scoring systems based on different risk factor combinations in regression models have been proposed to predict abnormal outcomes. Birthweight, gestational age, Apgar scores, pH, ultrasound and MRI biomarkers, seizures onset, EEG pattern, and seizure duration were the most referred predictors in the literature. Our study proposes a decision-tree approach based on clinical risk factors for abnormal outcomes in newborns with the neurological syndrome to assist in neonatal encephalopathy prognosis as a complementary tool to the acknowledged scoring systems. We retrospectively studied 188 newborns with associated encephalopathy and seizures in the perinatal period. Etiology and abnormal outcomes were assessed through correlations with the risk factors. We computed mean, median, odds ratios values for birth weight, gestational age, 1-min Apgar Score, 5-min Apgar score, seizures onset, and seizures duration monitoring, applying standard statistical methods first. Subsequently, CART (classification and regression trees) and cluster analysis were employed, further adjusting the medians. Out of 188 cases, 84 were associated to abnormal outcomes. The hierarchy on etiology frequencies was dominated by cerebrovascular impairments, metabolic anomalies, and infections. Both preterms and full-terms at risk were bundled in specific categories defined as high-risk 75-100%, intermediate risk 52.9%, and low risk 0-25% after CART algorithm implementation. Cluster analysis illustrated the median values, profiling at a glance the preterm model in high-risk groups and a full-term model in the inter-mediate-risk category. Our study illustrates that, in addition to standard statistics methodologies, decision-tree approaches could provide a first-step tool for the prognosis of the abnormal outcome in newborns with encephalopathy.

Individual Alpha Peak Frequency, an Important Biomarker for Live Z-Score Training Neurofeedback in Adolescents with Learning Disabilities.

Learning disabilities (LDs) have an estimated prevalence between 5% and 9% in the pediatric population and are associated with difficulties in reading, arithmetic, and writing. Previous electroencephalography (EEG) research has reported a lag in alpha-band development in specific LD phenotypes, which seems to offer a possible explanation for differences in EEG maturation. In this study, 40 adolescents aged 10-15 years with LDs underwent 10 sessions of Live Z-Score Training Neurofeedback (LZT-NF) Training to improve their cognition and behavior. Based on the individual alpha peak frequency (i-APF) values from the spectrogram, a group with normal i-APF (ni-APF) and a group with low i-APF (li-APF) were compared in a pre-and-post-LZT-NF intervention. There were no statistical differences in age, gender, or the distribution of LDs between the groups. The li-APF group showed a higher theta absolute power in P4 (p = 0.016) at baseline and higher Hi-Beta absolute power in F3 (p = 0.007) post-treatment compared with the ni-APF group. In both groups, extreme waves (absolute Z-score of ≥1.5) were more likely to move toward the normative values, with better results in the ni-APF group. Conversely, the waves within the normal range at baseline were more likely to move out of the range after treatment in the li-APF group. Our results provide evidence of a viable biomarker for identifying optimal responders for the LZT-NF technique based on the i-APF metric reflecting the patient's neurophysiological individuality.

Delayed Anaerobic Threshold in Heart Failure Patients With Atrial Fibrillation.

PURPOSE: To assess whether atrial fibrillation (AF) in heart failure (HF) affects oxygen uptake at anaerobic threshold ((Equation is included in full-text article.)O2 AT) and heart rate (HR) kinetics. METHODS: A total of 15 patients with HF and AF and 18 with HF and sinus rhythm (SR) performed a maximal incremental and 2 constant workload cycle ergometer cardiopulmonary exercise tests (below and above AT, at 25% and 75% of maximal workload, respectively). At constant workload tests, kinetics of (Equation is included in full-text article.)O2 and HR were assessed by calculating time constant (τ). RESULTS: HF patients with AF showed a similar peak (Equation is included in full-text article.)O2 to those with SR (16.7 ± 4.5 mL/kg/min vs 16.6 ± 3.9 mL/kg/min). However, (Equation is included in full-text article.)O2 AT (11.3 ± 2.9 mL/kg/min vs 9.3 ± 2.8 mL/kg/min; P < .05), peak HR (149 ± 18.8 bpm vs 116.4 ± 20.4 bpm; P < .001), HR AT (125.3 ± 19.1 bpm vs 90.3 ± 15.5 bpm; P < .001), and HR increase during exercise were greater in HF patients with AF. Finally, τHR and τ(Equation is included in full-text article.)O2 below and above AT were not significantly different. CONCLUSIONS: In HF patients with AF, despite a similar peak (Equation is included in full-text article.)O2 compared with patients with HF and SR, (Equation is included in full-text article.)O2 AT is higher because of a higher HR and a greater HR increase during exercise. One postulated mechanism would be a greater cardiac output increase at the beginning of exercise in HF patients with AF. The delayed AT generates uncertainty about the meaning of a (Equation is included in full-text article.)O2 value at AT in HF patients with AF, because a higher AT is usually associated with better performance and a better prognosis.