Category: Nevin Manimala

Circ Arrhythm Electrophysiol. 2023 Aug 17:e010891. doi: 10.1161/CIRCEP.122.010891. Online ahead of print.

ABSTRACT

BACKGROUND: Pathogenic variants in genes encoding CaM (calmodulin) are associated with a life-threatening ventricular arrhythmia syndrome (calmodulinopathy). The in vivo consequences of CaM variants have not been studied extensively and there is incomplete understanding of the genotype-phenotype relationship for recurrent variants. We investigated effects of different factors on calmodulinopathy phenotypes using 2 mouse models with a recurrent pathogenic variant (N98S) in Calm1 or Calm2.

METHODS: Genetically engineered mice with heterozygous N98S pathogenic variants in Calm1 or Calm2 genes were generated. Differences between the sexes and affected genes were assessed using multiple physiological assays at the cellular and whole animal levels. Statistical significance among groups was evaluated using 1-way ANOVA or the Kruskal-Wallis test when data were not normally distributed.

RESULTS: Calm1^N98S/+ (Calm1^S/+) or Calm2 ^N98S/+ (Calm2^S/+) mice exhibited sinus bradycardia and were more susceptible to arrhythmias after exposure to epinephrine and caffeine. Male Calm1^S/+ mice had the most severe arrhythmia phenotype with evidence of early embryonic lethality, greater susceptibility for arrhythmic events, frequent premature beats, corrected QT prolongation, and more heart rate variability after epinephrine and caffeine than females with the same genotype. Calm2^S/+ mice exhibited a less severe phenotype, with female Calm2^S/+ mice having the least severe arrhythmia susceptibility. Flecainide was not effective in preventing arrhythmias in heterozygous CaM-N98S mice. Intracellular Ca²⁺ transients observed in isolated ventricular cardiomyocytes from male heterozygous CaM-N98S mice had lower peak amplitudes and slower sarcoplasmic reticulum Ca²⁺ release following in vitro exposure to epinephrine and caffeine, which were not observed in cardiomyocytes from heterozygous female CaM-N98S mice.

CONCLUSIONS: We report heterogeneity in arrhythmia susceptibility and cardiomyocyte Ca²⁺ dynamics among male and female mice heterozygous for a recurrent pathogenic variant in Calm1 or Calm2, illustrating a complex calmodulinopathy phenotype in vivo. Further investigation of sex and genetic differences may help identify the molecular basis for this heterogeneity.

PMID:37589122 | DOI:10.1161/CIRCEP.122.010891

Pol Merkur Lekarski. 2023;51(3):250-254. doi: 10.36740/Merkur202303111.

ABSTRACT

OBJECTIVE: Aim: To study the risk factors in patients with prediabetes that can lead to the progression of impaired glucose tolerance in the form of type 2 diabetes mellitus.

PATIENTS AND METHODS: Materials and methods: The selection of patients for this study was carried out on an outpatient basis at the Department of Therapy and Family Medicine, Uzhhorod National University. Patients with prediabetes were identified based on the American Diabetes Association criteria. Informed consent was obtained from all patients before the start of the study. Patients were randomly assigned to one of two groups: Group 1 (n=37) that received typical treatment according to the recommendations of the American Diabetes Association and the control Group 2 (n=42). At the 3rd year of the study, we determined the body mass index, glucose levels and glycated hemoglobin levels of the patients, also their medical documentation was analyzed and patients were interviewed about concomitant diseases.

RESULTS: Results: Analyzing the 3-year follow-up of patients with prediabetes, cases of type 2 diabetes mellitus were detected in both groups, but there is no statistically significant difference when comparing the indicators between the groups (p>0.05).

CONCLUSION: Conclusions: In our study, we analyzed the risk factors in patients with prediabetes that can lead to type 2 diabetes. During a 3-year follow-up, we identified cases of type 2 diabetes mellitus.

PMID:37589111 | DOI:10.36740/Merkur202303111

Pol Merkur Lekarski. 2023;51(3):245-249. doi: 10.36740/Merkur202303110.

ABSTRACT

OBJECTIVE: Aim: To study the risk factors in patients with prediabetes that can lead to the progression of impaired glucose tolerance in the form of type 2 diabetes mellitus.

PATIENTS AND METHODS: Materials and methods: The selection of patients for this study was carried out on an outpatient basis at the Department of Therapy and Family Medicine, Uzhhorod National University. Patients with prediabetes were identified based on the American Diabetes Association criteria. Informed consent was obtained from all patients before the start of the study. Patients were randomly assigned to one of two groups: Group 1 (n=37) that received typical treatment according to the recommendations of the American Diabetes Association and the control Group 2 (n=42). At the 3rd year of the study, we determined the body mass index, glucose levels and glycated hemoglobin levels of the patients, also their medical documentation was analyzed and patients were interviewed about concomitant diseases.

RESULTS: Results: Analyzing the 3-year follow-up of patients with prediabetes, cases of type 2 diabetes mellitus were detected in both groups, but there is no statistically significant difference when comparing the indicators between the groups (p>0.05).

CONCLUSION: Conclusions: In our study, we analyzed the risk factors in patients with prediabetes that can lead to type 2 diabetes. During a 3-year follow-up, we identified cases of type 2 diabetes mellitus.

PMID:37589110 | DOI:10.36740/Merkur202303110

Pol Merkur Lekarski. 2023;51(3):228-233. doi: 10.36740/Merkur202303107.

ABSTRACT

OBJECTIVE: Aim: The investigation of health professionals’ burnout and depression, working in refugees’ reception centers and their possible intercorrelation.

PATIENTS AND METHODS: Materials and methods: A descriptive correlation study was carried out in health professionals, who worked in refugees’ reception centers and accommodation programs throughout Greece. Data were collected using an anonymous questionnaire through online Google Forms. The questionnaire contained demographics, the Copenhagen Burnout Questionnaire (CBI-Gr) and the Patient Health Questionnaire (PHQ-9). The SPSS 22.00 was used for the statistical analysis and the significance level was set at 0.05.

RESULTS: Results: The sample consisted of 125 healthcare professionals working in refugees’ reception centers and accommodation programs, the majority of tchem were women (62.4%), aged between 30-39 years (39.2%) nurses (24.8%) and with a master’s degree (28%). A strong linear positive correlation was found between depression and burnout (r=0.542, p=0.000). A statistically significant correlation was also recorded between burnout and female gender (p=0.001), the age group of 30-39 (p=0.042) and nursing profession (p=0.003).

CONCLUSION: Conclusions: A strong linear relationship between burnout and depression was revealed, a finding indicating that it is imperative to implement interventions to strengthen the resilience of health professionals working in refugees’ reception centers.

PMID:37589107 | DOI:10.36740/Merkur202303107

Pol Merkur Lekarski. 2023;51(3):216-220. doi: 10.36740/Merkur202303105.

ABSTRACT

OBJECTIVE: Aim: Determination of factors associated with frailty syndrome (FS) in patients with heart failure (HF).

PATIENTS AND METHODS: Materials and methods: Consecutive patients hospitalized in the department were assessed for the presence of FS using L. Fried criteria, Edmonton Frail Scale (EFS) and Tilburg Frailty Indicator (TFI). Presence of arterial hypertension, diabetes, obesity, chronic obstructive pulmonary disease (COPD), and heart failure was included in the analysis based on patients’ medical history and findings from current hospitalization. Patients were assessed for the presence of depression using Beck’s Depression Inventory (BDI). Physical capacity was assessed using NYHA classification.

RESULTS: Results: 87 patients (mean age 81.4±6.7; 57 women; 11 HFrEF, mean NYHA 2.36±1.21; 11 HFmrEF, mean NYHA 2.18±1.08; 65 HFpEF mean NYHA 1.94±1.09) were included in the analysis. Multivariable analysis showed significant relationship between FS assessed with EFS and age (β=0.316, SE=0.08; p=0.0001), arterial hypertension (β=-0.194, SE=0.08; p=0.0173), COPD (β=0.176, SE=0.08; p=0.0300) and depression (β=0.565, SE=0.08; p=0.0000). FS assessed with L. Fried criteria was significantly related to age (β=0.359, SE=0.09; p= 0.0001), NYHA classification (β= 0.336, SE=0.09; p=0.0002) and depression (β=0.297, SE=0.09; p=0.0010). Age (β=0.251, SE=0.10; p=0.0114) and depression (β=0.375, SE=0.1; p=0.0002) were significantly related to FS assessed using TFI. In multivariable analysis HF phenotype was not significantly related to FS.

CONCLUSION: Conclusions: Age and depression assessed with BDI are related to FS in patients with HF. Arterial hypertension and COPD are linked to FS assessed using EFS, whereas NYHA classification is linked to FS assessed with L. Fried criteria. No statistically significant relationship was found between FS and HF phenotype.

PMID:37589105 | DOI:10.36740/Merkur202303105

Pol Merkur Lekarski. 2023;51(3):201-206. doi: 10.36740/Merkur202303103.

ABSTRACT

OBJECTIVE: Aim: To evaluate primary health physicians’ clinical and behavioral practices towards antibiotics administration in a specific region in Greece.

PATIENTS AND METHODS: Materials and methods: A cross sectional study was conducted using a questionnaire in all structures of primary health care (PHC) of the Peloponnese Region. The study was conducted in May-October 2020.

RESULTS: Results: In total, 306 out of 404 primary healthcare physicians completed the questionnaire (response rate of 75.8%). Our results showed that most of physicians used to prescribing antibiotics empirically in common diseases, except for the prevention of secondary respiratory tract infection. Overall, 66.3% answered that they do not feel diagnostic uncertainty that would lead them to prescribe antibiotics. Approximately 40% of the physicians stated an increase on antibiotics use and patients demand for antibiotic prescribing, however 71.4% “rarely/never” affected by this requirement. 51.9% of the sample used to prescribed brand name antibiotics. Statistically significant differences were found between demographic and professional characteristics, and physicians’ clinical and behavioral practices (p≤ 0.05).

CONCLUSION: Conclusions: Our findings could provide decision makers with information on how to manage antibiotic prescribing in primary health care in the country, focusing mainly on the use of specific diagnostic tests as well as relevant guidelines and protocols for changing prescription behavior.

PMID:37589103 | DOI:10.36740/Merkur202303103

Pediatrics. 2023 Aug 17:e2023061607. doi: 10.1542/peds.2023-061607. Online ahead of print.

ABSTRACT

BACKGROUNDAND OBJECTIVES: Despite being preventable, neonatal hypothermia remains common. We hypothesized that the proportion of newborns with hypothermia on admission would be high in all settings, higher in hospitals in middle-income countries (MIC) compared with high-income countries (HIC), and associated with morbidity and mortality.

METHODS: Using the Vermont Oxford Network database of newborns with birth weights 401 to 1500 g or 22 to 29 weeks’ gestational age from 2018 to 2021, we analyzed maternal and infant characteristics, delivery room management, and outcomes by temperature within 1 hour of admission to the NICU in 12 MICs and 22 HICs.

RESULTS: Among 201 046 newborns, hypothermia was more common in MIC hospitals (64.0%) compared with HIC hospitals (28.6%). Lower birth weight, small for gestational age status, and prolonged resuscitation were perinatal risk factors for hypothermia. The mortality was doubled for hypothermic compared with euthermic newborns in MICs (24.7% and 15.4%) and HICs (12.7% and 7.6%) hospitals. After adjusting for confounders, the relative risk of death among hypothermic newborns compared with euthermic newborns was 1.21 (95% confidence interval 1.09-1.33) in MICs and 1.26 (95% confidence interval 1.21-1.31) in HICs. Every 1°C increase in admission temperature was associated with a 9% and 10% decrease in mortality risk in MICs and HICs, respectively.

CONCLUSIONS: In this large sample of newborns across MICs and HICs, hypothermia remains common and is strongly associated with mortality. The profound burden of hypothermia presents an opportunity for strategies to improve outcomes and achieve the neonatal 2030 Sustainable Development Goal.

PMID:37589082 | DOI:10.1542/peds.2023-061607

Front Endocrinol (Lausanne). 2023 Jul 31;14:1231784. doi: 10.3389/fendo.2023.1231784. eCollection 2023.

ABSTRACT

Differentiating between thyroid and parathyroid lesions by means of ultrasound can be a challenge in some cases. This study explores the diagnostic efficacy of bidimensional shear wave elastography planewave ultrasound (2D SWE PLUS) as an auxiliary technique in distinguishing these superficial structures. We evaluated 86 cases, presenting with concurrent thyroid nodules and hyperparathyroidism, through conventional ultrasound and 2D SWE PLUS, employing an Aixplorer Supersonic Mach30 with a 5-18 MHz linear probe. Statistically significant differences were observed for the elasticity index (EI) between parathyroid and normal thyroid tissue (p<0.0001, U=291), and between parathyroid lesions and thyroid nodules (p<0.0001, U=248.5). An area under the curve (AUC) of 0.961, with an optimal cut-off value of ≤8.9 kPa, was established to effectively distinguish parathyroid tissue from normal thyroid tissue (sensitivity of 91.9%; specificity of 97.5%). Furthermore, an AUC of 0.963 and an optimal cut-off of 9.24 kPa (sensitivity of 94.2%, specificity of 91.1%) were determined for parathyroid vs thyroid lesions. Elasticity values were significantly elevated in the cancer group compared to benign thyroid nodules (p<0.0001). Our findings suggest that 2D SWE PLUS is an effective tool in differentiating between thyroid nodules and parathyroid lesions, enhancing diagnostic performance in neck ultrasonography.

PMID:37588988 | PMC:PMC10425532 | DOI:10.3389/fendo.2023.1231784

Korean J Intern Med. 2023 Aug 17. doi: 10.3904/kjim.2023.115. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: Antimicrobial de-escalation (ADE) remains a challenging strategy in the treatment of pneumonia. We investigated the outcomes of ADE as measured by mortality and duration of the use of antibiotics in patients with culture- negative pneumonia.

METHODS: We performed a systematic review and meta-analysis in accordance with PRISMA guidelines. The primary outcome was inpatient mortality.

RESULTS: We examined six studies comprising 11,933 subjects, of whom 1,152 received ADE. Overall, the ADE strategy was associated with a statistically lower risk of in-hospital mortality compared with non-ADE (risk ratio [RR] = 0.60, 95% confidence interval [CI] = 0.38 to 0.93). Although substantial heterogeneity was found among the included studies (I2 = 66%), a meta-regression analysis could not reveal plausible sources of heterogeneity. And ADE was associated with a shorter duration of total and initial antibiotic therapies and total length of hospital stay compared with non-ADE.

CONCLUSIONS: Our findings suggest that ADE seems to be significantly associated with better clinical outcomes compared with non-ADE. Caution is demanded when interpreting data of this study because of substantial between-study heterogeneity.

PMID:37586813 | DOI:10.3904/kjim.2023.115

BMJ Open Diabetes Res Care. 2023 Aug;11(4):e003278. doi: 10.1136/bmjdrc-2022-003278.

ABSTRACT

INTRODUCTION: To evaluate the degree to which socioeconomic differences in gestational diabetes mellitus (GDM) are accounted for by differences in maternal risk factors, to assess whether age-related risks of GDM differ across socioeconomic groups, and to identify priority populations for future interventions.

RESEARCH DESIGN AND METHODS: We performed a register-based study using data from the Finnish Medical Birth Register and Statistics Finland on the 474 166 women who gave birth in Finland from 2008 to 2015. We collected information on GDM based on the International Classification of Diseases 10th Revision codes O24.4 and O24.9. We used multivariable models to examine the association between socioeconomic status, maternal risk factors, and GDM. We further tested interaction on multiplicative and additive scales.

RESULTS: The incidence of GDM was 8.7% in 2008-2011 and 12.5% in 2012-2015. Lower socioeconomic levels than upper level employees were associated with an increased risk of GDM. Up to 64.0% of socioeconomic differences in GDM were attributed to body mass index and 5.5% to smoking. There was evidence for effect modification. Relative to women in the upper level category who were aged less than 19 years, GDM adjusted ORs (95% CIs) for women 35 years or older in upper level versus long-term unemployed groups were 3.28 (2.08-5.18) and 5.29 (3.35-8.35), respectively.

CONCLUSIONS: There is a paradox that socioeconomic advantage increases the incidence of GDM at the population level while reducing the incidence of GDM within the population. Nevertheless, socioeconomic differences in GDM persist and widen with increasing maternal age, even after accounting for maternal risk factors.

PMID:37586779 | DOI:10.1136/bmjdrc-2022-003278