Evaluating the efficacy of surgical and conservative approaches in mild autonomous cortisol secretion: a meta-analysis.

Introduction: The management of Mild Autonomous Cortisol Secretion (MACS) remains a topic of debate among clinicians, with differing opinions on the effectiveness of surgical intervention compared to conservative treatment methods. This meta-analysis provides a comprehensive assessment of available literature to determine the most effective approach for treating this condition. Methods: On December 1, 2023, an exhaustive literature search of English databases Embase, PubMed, the Cochrane Library, Scopus, Web of Science, as well as the Chinese databases China HowNet, Wanfang Database, SinoMed Database, and Weipu Database using the keywords "Mild Autonomous Cortisol Secretion", "Subclinical Cushing's Syndrome", "Subclinical Hypercortisolism", "Mild Cortisol Autonomous Secretion", "Adrenal Incidentaloma", "Surgical Treatment" and "Adrenalectomy". The data were statistically analyzed using STATA version 15.0. Results: In this comprehensive analysis involving 629 patients with MACS, the therapeutic efficacy of adrenalectomy was evident. The meta-analysis results indicate that compared to conservative treatment, surgical intervention more effectively improves obesity indicators in patients: waist circumference (SMD=-0.62, 95% CI: -1.06 to -0.18), BMI (SMD=-0.41, 95% CI: -0.62 to -0.20), enhances glycemic control: fasting blood glucose (SMD=-0.47, 95% CI: -0.68 to -0.26), glycated hemoglobin (SMD=-0.66, 95% CI: -0.95 to -0.38), improves lipid metabolism: triglycerides (SMD=-0.45, 95% CI: -0.73 to -0.16), lowers blood pressure: systolic blood pressure (SMD=-1.04, 95% CI: -1.25 to -0.83), diastolic blood pressure (SMD=-0.89, 95% CI: -1.12 to -0.65), and ameliorates hormonal metabolic disorder: 24h urinary free cortisol (SMD=-1.10, 95% CI: -1.33 to -0.87), ACTH (SMD=2.30, 95% CI: 1.63 to 2.97). All these differences are statistically significant. Conclusion: This meta-analysis shows that, compared to conservative treatment, surgical treatment is more effective in improving obesity indicators, glycemic control, lipid metabolism, reducing blood pressure, and ameliorating hormonal metabolic disorders in patients with MACS. These statistically significant results highlight the importance of considering surgical intervention in the management of patients with MACS. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023492527.

Pregnancy outcome in subclinical hypothyroidism with and without thyroid peroxidase antibodies-a prospective cohort study.

BACKGROUND: Subclinical hypothyroidism (SCH) in pregnancy is associated with adverse foetomaternal outcomes. The literature is scarce with respect to maternal and perinatal outcomes in women with mild SCH (TSH levels between 2.5-4 mIU/L). OBJECTIVES: The primary objective of the study was to compare the pregnancy outcome between SCH and euthyroid women. The secondary objectives were to find out the proportion of women with SCH having thyroid peroxidase antibodies (TPOAb) and to see the effect of TPOAb positivity on foetomaternal outcomes. MATERIALS AND METHODS: A total of 178 pregnant women were recruited in the first trimester, and those with TSH between 0.1 and 2.4 mIU/L were considered as euthyroid and 2.5-4mIU/L were labelled as SCH. Women with SCH underwent testing for TPOAb. All women were followed until delivery, and foetomaternal outcomes were assessed. RESULTS: Amongst SCH group, there was a significantly higher proportion of overweight and obese women (76/91 (83.51%) vs 59/87 (68%), p = 0.031). The neonatal intensive care unit (NICU) admission was higher with adjusted odds ratio of 3.24 (1.41-7.43) in women with SCH as compared to euthyroid women. Otherwise, there was no difference in foetomaternal outcomes between the two groups. The proportion of gestational diabetes mellitus, intrauterine growth retardation and still birth were higher in SCH women with TPOAb as compared to euthyroid. Amongst SCH women, the proportion of induced labour was lower (aOR:0.27 (0.08-0.93) whereas the proportion of stillbirth and low APGAR scores were higher in TPOAb-positive women with a statistically significant difference and adjusted odds ratio (aOR:20.18 (1.84-220.83)) and (aOR:4.77 (1.06-21.3)), respectively, when compared to TPOAb-negative women. CONCLUSION: There appears to be no difference in pregnancy outcomes between women with SCH and euthyroid women except higher NICU admission in SCH group. Future multi-centre large prospective studies are required to understand better about the pregnancy outcomes in these women.

Advancing mastitis assessment in dairy bovines via short milking tube thermography: A seasonal perspective.

In India, where dairy production leads globally, infrared thermography (IRT) and short milking tube thermography specifically are vital for managing mastitis. Therefore, the present study focuses on thermal imaging of the udder and short milking tube (SMT) of the milking machine during the peak milking process of Sahiwal cows and Murrah buffaloes during winter, summer, rainy and autumn seasons to identify sub-clinical (SCM) and clinical mastitis (CM) cases using the Darvi DTL007 camera. The udder health was assessed using the California Mastitis Test, Somatic Cell Count (SCC) and IRT throughout the year. Log10SCC and thermogram analysis revealed a difference (p < 0.01) between healthy, SCM, and CM cases during different seasons in both breeds. Further results showed an increase (p < 0.01) in SMT thermograms of SCM and CM cases compared to healthy quarters in Sahiwal cows during winter, summer, rainy, and autumn were 4.26 and 7.51, 2.37 and 4.47, 2.20 and 3.64, 2.90 and 4.94 ºC, respectively and for Murrah buffaloes were 3.56 and 5.55, 2.70 and 3.81, 1.72 and 3.10, 3.14 and 4.42ºC, respectively. The highest degree of increase in milking udder skin surface temperature and SMT of SCM and CM cases compared to healthy quarters was observed during the winter and the least during the rainy season. Thus, regardless of the seasons examined in this study, SMT thermograms effectively assessed SCM and CM.

Estimating the impact of tuberculosis pathways on transmission - what is the gap left by passive case-finding?

Current passive case-finding policies have not resulted in the expected decline in tuberculosis incidence. Recognition of the variety of disease pathways experienced by individuals with tuberculosis highlights how many are not served by the current prevention and care system, and how much transmission is missed.

Direct oral anticoagulants for stroke prevention in patients with device-detected atrial fibrillation: assessing net clinical benefit.

Subclinical, device-detected atrial fibrillation (AF) is frequently recorded by pacemakers and other implanted cardiac rhythm devices. Patients with device-detected AF have an elevated risk of stroke, but a lower risk of stroke than similar patients with clinical AF captured with surface electrocardiogram. Two randomized clinical trials (NOAH-AFNET 6 and ARTESiA) have tested a direct oral anticoagulant (DOAC) against aspirin or placebo. A study-level meta-analysis of the two trials found that treatment with a DOAC resulted in a 32% reduction in ischaemic stroke and a 62% increase in major bleeding; the results of the two trials were consistent. The annualized rate of stroke in the control arms was ∼1%. Several factors point towards overall net benefit from DOAC treatment for patients with device-detected AF. Strokes in ARTESiA were frequently fatal or disabling and bleeds were rarely lethal. The higher absolute rates of major bleeding compared with ischaemic stroke while on treatment with a DOAC in the two trials are consistent with the ratio of bleeds to strokes seen in the pivotal DOAC vs. warfarin trials in patients with clinical AF. Prior research has concluded that patients place a higher emphasis on stroke prevention than on bleeding. Further research is needed to identify the characteristics that will help identify patients with device-detected AF who will receive the greatest benefit from DOAC treatment.

Efficacy of a transdiagnostic Internet prevention approach in adolescents (EMPATIA study): study protocol of a randomized controlled trial.

BACKGROUND: Most mental disorders have their onset in adolescence. Preventive interventions during this period are important; however, help-seeking behavior is generally poor in this age group resulting in low treatment rates. Internet interventions are expected to be an effective, low-threshold, and scalable approach to overcome barriers to help-seeking, particularly for individuals experiencing subclinical symptoms. Internet-delivered indicated prevention seems promising as it targets individuals with minimal symptoms of mental disorders who might need care but are not help-seeking yet. Previous indicated prevention-approaches have mainly targeted specific risk-syndromes. However, this contradicts the increasing recognition of emerging psychopathology as a complex system characterized by co-occurrence and rapid shifts of subclinical symptoms cutting across diagnostic categories. Therefore, this study will investigate the efficacy, mediators, moderators, and core symptomatic changes of a transdiagnostic Internet-delivered indicated prevention program (EMPATIA program) for adolescents. METHODS: This randomized controlled trial (RCT) will be conducted in a general population sample (planned n = 152) of adolescents aged 12-18 years with subclinical symptoms but without any current or past mental disorder. Participants will be randomly assigned to the EMPATIA program or a care as usual (CAU) control condition. The 8-week guided EMPATIA program encompasses 8 modules targeting the following transdiagnostic mechanisms: repetitive negative thinking, self-perfectionism, emotion regulation, intolerance of uncertainty, rejection sensitivity, and behavioral avoidance. Participants will be asked to answer online self-report questionnaires at baseline, after 8 weeks, and at 6-, 9-, and 12-month follow-up. Diagnostic telephone interviews will be conducted at baseline and at 12-month follow-up. Additionally, intervention-specific constructs (motivation, alliance, negative effects, satisfaction, adherence) will be assessed during and after the EMPATIA program. The level of self-reported general psychopathology post-intervention is the primary outcome. DISCUSSION: Results will be discussed considering the potential of Internet interventions as a scalable, low-threshold option for indicated prevention in adolescents experiencing subclinical symptoms. The EMPATIA program introduces a novel Internet prevention program targeting six transdiagnostic mechanisms associated with various mental health outcomes. Thereby, this trial pursues a very timely and important topic because it may contribute to narrow the current care gap for adolescents, to prevent mental health problems and related negative consequences, and to promote mental health in the long-term. TRIAL REGISTRATION: The trial was approved by Swissmedic (Registration Number: 10001035, 08/22/2022) and the Ethics Committee of Bern (Registration Number: 2022-D0036, 08/22/2022). The trial was registered at ClinicalTrials.gov NCT05934019 on 07-03-2023.

The role of coffee and potential mediators in subclinical atherosclerosis: insights from Mendelian randomization study.

Background and aims: Coffee contains many bioactive compounds, and its inconsistent association with subclinical atherosclerosis has been reported in observational studies. In this Mendelian randomization study, we investigated whether genetically predicted coffee consumption is associated with subclinical atherosclerosis, as well as the role of potential mediators. Methods: We first conducted a two-sample Mendelian randomization analysis to examine the causal effect of coffee and its subtypes on subclinical atherosclerosis inferred from coronary artery calcification (CAC). Next, the significant results were validated using another independent dataset. Two-step Mendelian randomization analyses were utilized to evaluate the causal pathway from coffee to subclinical atherosclerosis through potential mediators, including blood pressure, blood lipids, body mass index, and glycated hemoglobin. Mendelian randomization analyses were performed using the multiplicative random effects inverse-variance weighted method as the main approach, followed by a series of complementary methods and sensitivity analyses. Results: Coffee, filtered coffee, and instant coffee were associated with the risk of CAC (ß = 0.79, 95% CI: 0.12 to 1.47, p = 0.022; ß = 0.66, 95% CI: 0.17 to 1.15, p = 0.008; ß = 0.66, 95% CI: 0.20 to 1.13, p = 0.005; respectively). While no significant causal relationship was found between decaffeinated coffee and CAC (ß = -1.32, 95% CI: -2.67 to 0.04, p = 0.056). The association between coffee and CAC was validated in the replication analysis (ß = 0.27, 95% CI: 0.07 to 0.48, p = 0.009). Body mass index mediated 39.98% of the effect of coffee on CAC (95% CI: 9.78 to 70.19%, p = 0.009), and 5.79% of the effect of instant coffee on CAC (95% CI: 0.54 to 11.04%, p = 0.030). Conclusion: Our study suggests that coffee other than decaffeinated coffee increases the risk of subclinical atherosclerosis inferred from CAC. Body mass index mediated 39.98 and 5.79% of the causal effects of coffee and instant coffee on CAC, respectively. Coffee should be consumed with caution, especially in individuals with established cardiovascular risk factors, and decaffeinated coffee appears to be a safer choice.

SERIAL EVALUATION OF BIVENTRICULAR FUNCTION IN COVID-19 RECOVERED PATIENTS USING SPECKLE TRACKING ECHOCARDIOGRAPHY.

OBJECTIVES: The persistence and outcomes following myocardial injury subsequent to coronavirus disease-2019 (COVID-19) infection has not been properly elucidated. We assessed sub-clinical bi-ventricular dysfunction using speckle tracking echocardiography (STE) in post COVID-19 patients. METHODS: A total of 189 subjects following recovery from COVID-19 infection were enrolled. Detailed echocardiography including STE along with clinical, hematological, biochemical and inflammatory parameters were assessed for all. Patients were divided into four groups (asymptomatic, mild, moderate and severe) based on severity of COVID-19 infection. Additionally, 90 healthy individuals were enrolled as controls. All these patients were followed up for one year following enrolment. RESULTS: Subclinical LV and right ventricle (RV) dysfunction were seen in 58 (30.7%) and 55 (29.1%) patients respectively at baseline. Significant difference was observed in mean LVGLS values among the three groups (mild: -21.5+2.8%; moderate: -17+7.1%; severe: -12.1 ± 4%; P < 0.0001). Over a year of follow-up, significant improvement in LVGLS from baseline (-19.1+5.8%) was observed (-19.9+4.6%; P<0.0001). Similarly, RVFWS (-23.5+6.3% vs -23.8+5.8%; P=0.03) had significant improvement from baseline to one year of follow-up. Reduced LVGLS was reported in 12 (6.3%) subjects while impaired RVFWS was documented in 10 (5.3%) subjects at one year of follow-up. CONCLUSIONS: Subclinical LV and RV dysfunction were seen in nearly a third of recovered COVID-19 patients. Over a year of follow-up, significant improvement in subclinical LV and RV dysfunction was noted.

Transient efficacy of buparvaquone against the US isolate of Theileria orientalis Ikeda genotype in sub-clinically infected cattle.

Introduction: Theileria orientalis, an economically significant tick-borne hemoparasite, infects cattle globally. The T. orientalis Ikeda genotype, transmitted by Haemaphysalis longicornis ticks, is associated with clinical manifestations characterized by anemia, abortions, and mortality, although subclinical infections prevail. Despite the common occurrence of subclinical infections, therapeutic interventions targeting T. orientalis Ikeda in such cases are currently lacking, impeding effective parasite control measures. To address this critical knowledge gap, we assessed the efficacy of buparvaquone (BPQ) in eliminating the T. orientalis Ikeda, US isolate, in sub-clinically infected cattle. Methods: Twelve sub-clinically infected calves, identified by the presence of T. orientalis in peripheral blood alongside the absence of fever and anemia, were enrolled in the study. Six calves received two treatments of the BPQ label dose (2.5 mg/kg) at a 48-h interval, while additional three calves received the drug at a dosage of 6 mg/kg following the same regimen. Three untreated calves served as controls. Results and discussion: Endpoint and quantitative PCR analyses revealed that BPQ exerted a transient effect on T. orientalis parasitemia. Parasites remained undetectable in peripheral blood until weeks 4 and 11 post-treatment in animals administered 2.5 mg/kg and 6 mg/kg of BPQ, respectively. Intriguingly, following recrudescence, administering 6 mg/kg to animals previously treated with 2.5 mg/kg did not result in a reduction in parasite load. Pharmacokinetic analysis data suggested that escalating the dosage led to a less than proportional increase in serum concentrations of BPQ. Moreover, a significant yet reversible decrease (p < 0.05) in blood urea nitrogen was observed in animals treated with the drug, irrespective of the dosage. Despite parasitemia relapse, animals treated with 6 mg/kg BPQ exhibited a noteworthy decrease (p < 0.05) in IgG levels specific to the T. orientalis major piroplasm surface protein compared to controls and animals treated with 2.5 mg/kg of the drug. Conclusion: BPQ did not demonstrate efficacy in clearing subclinical T. orientalis Ikeda infection. Future investigations are warranted to explore innovative therapeutic modalities that, in synergy with vaccines and diagnostic assays, can facilitate the development of comprehensive programs aimed at controlling and eradicating this parasite.

The interplay between vitamin D status, subclinical inflammation, and prediabetes.

Vitamin D's role extends beyond classical calcium and phosphate homeostasis to encompass a pivotal influence on immune modulation and metabolic health. The mechanisms by which vitamin D exerts these effects involve its conversion to hormonally active calcitriol, which binds intracellular vitamin D receptors, initiating various downstream cascades. In this review, we tease out the evidence showing the relationship between vitamin D deficiency and prediabetes within the context of subclinical inflammation, with a special focus on the novel monocyte-to-HDL ratio (MHR), a novel inflammatory marker reflecting subclinical inflammation. This was based on a thorough literature review using reputable databases covering the period from 1980 to 2024. In light of this, we discuss calcitriol's anti-inflammatory effects and consequently link vitamin D deficiency to both overt and subclinical inflammation. Additionally, the utility of several biomarkers, notably MHR, in investigating this association is also discussed. We further reviewed the role of vitamin D deficiency in precipitating prediabetes and type 2 diabetes mellitus (T2DM) via insulin resistance, decreased insulin synthesis and secretion, and subclinical inflammation. Taken together, this mini review highlights that vitamin D deficiency is significantly associated with subclinical inflammation, playing a critical role in the development of prediabetes and the progression to T2DM. Addressing vitamin D deficiency through appropriate interventions may serve as a preventative measure against the development of prediabetes and T2DM.

Functionalized Graphene-Based Biosensors for Early Detection of Subclinical Ketosis in Dairy Cows.

Precision livestock farming utilizing advanced diagnostic tools, including biosensors, can play a key role in the management of livestock operations to improve the productivity, health, and well-being of animals. Detection of ketosis, a metabolic disease that occurs in early lactation dairy cows due to a negative energy balance, is one potential on-farm use of biosensors. Beta-hydroxybutyrate (ßHB) is an excellent biomarker for monitoring ketosis in dairy cows because ßHB is one of the main ketones produced during this metabolic state. In this report, we developed a low-cost, Keto-sensor (graphene-based sensor) for the detection of ßHB concentrations in less than a minute. On this device, graphene nanosheets were layered onto a screen-printed electrode (SPE), and then, a stabilized enzyme (beta-hydroxybutyrate dehydrogenase, NAD+, and glycerol) was used to functionalize the graphene surface enabled by EDC-NHS conjugation chemistry. The Keto-sensor offers an analytical sensitivity of 10 nm and a limit of detection (LoD) of 0.24 nm within a detection range of 0.01 µm-3.00 mm. Spike testing indicates that the Keto-sensor can detect ßHB in serum samples from bovines with subclinical ketosis. The Keto-sensor developed in this study shows promising results for early detection of subclinical ketosis on farms.

Subclinical myocardial dysfunction among fetal growth restriction neonates: a case-control study.

OBJECTIVES: To evaluate cardiac structural and functional changes in neonates with fetal growth restriction (FGR) compared to appropriate-for-gestational-age (AGA) neonates using conventional echocardiography, tissue Doppler imaging (TDI), and speckle tracking echocardiography. METHOD: This case-control study included 85 FGR neonates and 75 non-FGR, weight adequate for gestational age neonates. Among these, 37 were symmetric FGR and 48 were asymmetric FGR. All the biophysical profiles of these newborns were assessed. An echocardiographic test was performed to evaluate cardiac dimension, Left ventricular ejection fraction (LV EF), Mitral valve Doppler flow velocities, myocardial performance index, tissue annular velocities, and LV global longitudinal strain (GLS). RESULTS: Although LVEF was found to be within the normal range, mean EF was reduced among neonates with FGR than non-FGR controls (EF: 66.14 ± 3.85% vs 69.46 ± 3.58%; p < 0.001, in FGR and non-FGR, respectively). Furthermore, LV E/E' a measure of LV diastolic function was altered among both types of FGR neonates. Similarly, LV GLS was reduced among FGR neonates (LV GLS: -20.69 ± 2.7% vs -19.06 ± 2.9%; p < 0.001 in non-FGR and FGR, respectively). CONCLUSION: FGR neonates exhibit significant alterations in cardiac geometry compared to AGA controls. FGR neonates also demonstrated a significant reduction in LV EF, FS, and LV global longitudinal strain, depicting failure to adapt to the increased cardiac workload after birth.

Treatment of Transcatheter Aortic Valve Thrombosis: JACC Review Topic of the Week.

Transcatheter aortic valve (TAV) thrombosis may manifest as subclinical leaflet thrombosis (SLT) and clinical valve thrombosis. SLT is relatively common (10%-20%) after transcatheter aortic valve replacement, but clinical implications are uncertain. Clinical valve thrombosis is rare (1.2%) and associated with bioprosthetic valve failure, neurologic or thromboembolic events, heart failure, and death. Treatment for TAV thrombosis has been understudied. In principle, anticoagulation may prevent TAV thrombosis. Non-vitamin K oral anticoagulants, as compared to antiplatelet therapy, are associated with reduced incidence of SLT, although at the cost of higher bleeding and all-cause mortality risk. We present an overview of existing literature for management of TAV thrombosis and propose a rational treatment algorithm. Vitamin K antagonists or non-vitamin K oral anticoagulants are the cornerstone of antithrombotic treatment. In therapy-resistant or clinically unstable patients, ultraslow, low-dose infusion of thrombolytics seems effective and safe and may be preferred over redo-transcatheter aortic valve replacement or explant surgery.

Meta-Analytical and Meta-Regression Evaluation of Subclinical Hyperthyroidism's Effect on Male Reproductive Health: Hormonal and Seminal Perspectives.

Subclinical hyperthyroidism (SCH) is a subtle thyroid dysfunction marked by decreased serum thyroid-stimulating hormone (TSH) levels while maintaining a normal thyroid hormone profile. Despite its mild nature, SCH can significantly impact various physiological functions, including male reproductive health. However, the effects of SCH on reproductive hormones and semen quality are less understood compared to overt thyroid disorders. This study employed extensive search methods across various databases from January 2000 to February 2024 to explore the relationship between SCH and Hormonal and Seminal Perspectives. Effect sizes, estimated using the standardized mean difference (SMD) and pooled with a Random-effect model, provided significant insights from 748 participants. Included studies adhered to the following criteria: Patients (male individuals with SCH), Intervention (assessment of reproductive hormones and semen quality), Comparison (SCH patients versus healthy controls), and Outcome (changes in reproductive factors). Significant alterations in reproductive hormones were observed in SCH patients, including reduced LH levels (SMD = - 0.20; p = 0.007), elevated FSH levels (SMD = 0.25; p = 0.002), and stable testosterone levels (SMD = - 0.05; p = 0.50). Regarding thyroid profile, SCH was associated with increased FT3 (SMD = 0.15; p < 0.001) and FT4 (SMD = 0.08; p = 0.002) levels, along with decreased TSH levels (SMD = - 2.00; p < 0.001). Adverse effects on semen quality were also observed. These findings underscore the need to incorporate thyroid health assessments in the evaluation of male infertility, recognizing the impact of minor thyroid hormone deviations on reproductive outcomes.

Genotyping of Holstein Cows by SELL, MX1 and CXCR1 Gene Loci Associated With Mastitis Resistance.

Mastitis is a significant factor that decreases milk production in cows of different breeds in Kazakhstan. The objective of this study was to determine the genetic makeup of Holstein cows by analysing specific gene loci (SELL, MX1, CXCR1+291C>T and CXCR1+1093C>T) that are linked to resistance against mastitis. The goal was to identify cows with favourable genotypes that are less prone to udder diseases. At the SELL gene locus c.567T>C, all three genetic variants were identified in the control population with the respective frequencies: TT (0.20), CT (0.44), and CC (0.36). Genetic variation was also detected at the MX1 gene c.567T>C, CXCR1 c.+291C>T and CXCR1+1093C>T loci. Deviation from the expected Hardy-Weinberg equilibrium was observed for two gene loci, MX1 g.143182088 and CXCR1+1093C>T, with increased chi-square values of 10.6261 and 9.7137, respectively. The analysis of subclinical mastitis incidence indicates that cows carrying the heterozygous CT genotype at the L-selectin gene locus exhibit greater resistance to the disease. Animals carrying the CCCCCT genotype at the MX1 c.567T>C, CXCR1 c.+291C>T and CXCR1+1093C>T gene loci were discovered to have a significant likelihood of developing subclinical mastitis. This suggests that these genes could serve as potential indicators of susceptibility to the condition. The practical significance of this study lies in determining the frequency of genotypes linked to mammary gland morbidity in Holstein breeding farms in Kazakhstan.

Association between C-reactive protein to albumin ratio and subclinical myocardial injury in the general population free from cardiovascular disease.

OBJECTIVE: The study aimed to examine the role of the C-reactive protein to albumin ratio (CAR) as an inflammatory biomarker in relation to subclinical myocardial injury (SC-MI), addressing the limited knowledge of their association. METHODS: The study included 5,949 individuals without cardiovascular disease (CVD) from the National Health and Nutrition Examination Survey. SC-MI was identified through a Cardiac Infarction Injury Score (CIIS) of ≥ 10 units based on a 12-lead electrocardiogram. The study used multivariate logistic regression models, adjusted for potential confounders, to evaluate the relationship between CAR and SC-MI. Subgroup analyses were conducted to substantiate the results, and the non-linear correlation was assessed via restricted cubic spline (RCS) regression. RESULTS: The RCS curve showed a significant positive correlation between CAR and SC-MI (P for nonlinear = 0.2496). When adjusted for all confounders, individuals in the highest tertile of CAR exhibited a higher likelihood of SC-MI compared to those in the lowest tertile, with an odds ratio (OR) of 1.21 (95% CI: 1.06-1.39, P for trend = 0.029). A 10-unit increment in CAR was linked to a 3.6% heightened risk of SC-MI [OR = 1.036 (95% CI: 1.006, 1.066)], with this association being more prominent among male adults, non-smokers, married individuals, those without diabetes mellitus, and those with no history of cancer. CONCLUSION: The findings of this study suggest a positive correlation between CAR and SC-MI among the US adult population, indicating the potential of CAR in enhancing SC-MI prevention strategies in the general population.

Low incidence of late-onset giant cell arteritis during the first year in patients with polymyalgia rheumatica-a repeated imaging study.

OBJECTIVE: The objective was to investigate the incidence of late-onset giant cell arteritis (GCA) within the first year in patients diagnosed with polymyalgia rheumatica (PMR). METHODS: In this prospective study, treatment-naïve individuals with a new clinical diagnosis of PMR and without GCA symptoms underwent baseline assessments, including vascular ultrasonography and 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography computed tomography (FDG-PET/CT). To prevent biased inclusion, rapid referral clinics were established for all patients suspected of PMR. Additionally, the patients underwent GCA monitoring during clinical visits at weeks 8 and 10, which involved vascular ultrasonography and FDG-PET/CT scans. After one year, a follow-up visit was performed to confirm the PMR diagnosis and perform vascular ultrasonography. RESULTS: A final PMR diagnosis was assigned to 62 patients, excluding 2 patients with concurrent subclinical GCA and PMR at baseline, corresponding to a baseline prevalence of subclinical GCA of 3%. During the one-year follow-up, two PMR patients developed late-onset GCA corresponding to an incidence rate of 32 per 1000 person-years. One patient developed GCA 14 weeks after the PMR diagnosis, exhibiting cranial symptoms and positive vascular ultrasonography. The other patient presented with subclinical large vessel GCA at the one-year visit detected with vascular ultrasonography and confirmed by FDG-PET/CT. CONCLUSION: This study is the first to demonstrate a low incidence rate of late-onset GCA in PMR patients within the first year, employing repeated imaging to exclude GCA at baseline and diagnose GCA during follow-up. Additionally, it provides evidence of a low prevalence of subclinical GCA across the entire PMR population. TRIAL REGISTRATION: ClinicalTrials.Gov, NCT04519580.

Present outlooks on the prevalence of minimal and subclinical tuberculosis and current diagnostic tests: A systematic review and meta-analysis.

BACKGROUND: Tuberculosis (TB) is a major global health issue, particularly in its minimal and subclinical forms, which often go undetected and contribute to transmission. Accurate prevalence assessment of these forms and the effectiveness of diagnostic tests are crucial for improving TB control, especially in high-risk populations such as those with HIV. OBJECTIVES: This study aimed to determine the prevalence of minimal and subclinical TB and evaluate the positivity rates of current diagnostic tests. METHODS: We conducted a meta-analysis of studies published from January 2000 to December 2022. Prevalence rates and diagnostic test results, including sputum culture, smear microscopy, TST/IGRA, and chest X-ray, were analyzed, with pooled prevalence calculated and comparisons made between geographic regions. RESULTS: Minimal TB prevalence ranged from 0.9 % to 22.9 % in the general population, while subclinical TB prevalence was 0.05 % to 0.64 %, and 1.57 % to 14.63 % among individuals with HIV. The overall pooled prevalence of minimal TB was 7 % (95 % CI: 5-9 %), with higher rates in Asia (8 %, 95 % CI: 5-12 %) compared to Africa (6 %, 95 % CI: 4-8 %). Subclinical TB had a pooled prevalence of 0.2 % (95 % CI: 0.2-0.3 %) overall and 52 % (95 % CI: 46-58 %) among TB cases, with higher rates in Asia (60 %) compared to Africa (44 %). Diagnostic test positivity was 77 % (sputum culture), 15 % (smear microscopy), 64 % (TST/IGRA), and 53 % (chest X-ray). CONCLUSIONS: This study reveals significant variability in the prevalence of minimal and subclinical TB. The findings highlight the need for improved diagnostic methods to reduce undetected cases, especially in high-risk populations.

Impact of Subclinical Hypothyroidism on Lipid Profile in Jeddah: A Retrospective Cohort Study.

Background Patients with subclinical hypothyroidism (SCH) have a high serum concentration of thyroid-stimulating hormone (TSH), whereas their serum-free thyroxine concentrations are normal. Lipid metabolism is regulated in large part by thyroid hormones. It could be connected to a changed lipid profile. This study aimed to evaluate the relationship between SCH and alterations in the lipid profile. Methodology Data from 99 patients with SCH and 109 euthyroid cases were collected from King Abdulaziz Medical City, Jeddah, Saudi Arabia, from 2016 to 2022. Patients older than 18 years were included in the study. The groups were matched in terms of gender, age, and body mass index. SCH was defined as a TSH value of 4.5 to 10 mIU/L, and normal T4 as 5 to 18 µg/dL. Control cases had a normal TSH ranging from 0.45 to 4.5 mIU/L. The total serum cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride (TG) levels in both groups were examined and the results were recorded. Results In comparison to the control group, SCH patients had greater median glycated hemoglobin (HbA1C) (p = 0.001) and lower median vitamin D levels (p = 0.004) before therapy. Before therapy, SCH patients also showed considerably lower HDL levels and significantly higher LDL and TG levels (p < 0.001). Conclusions There is a substantial correlation between SCH and reduced HDL and vitamin D levels. It was linked to increased TG, LDL, and HbA1c levels. Only vitamin D and LDL were pathologically high. Treatment with levothyroxine raised total and LDL cholesterol levels. Future research should look into the affordability of treating SCH.

Unraveling the Link: Seizure Characteristics and Ammonia Levels in Urea Cycle Disorder During Hyperammonemic Crises.

BACKGROUND: This retrospective clinical study performed at a single clinical center aimed to identify the prevalence of seizures in individuals with urea cycle disorders (UCDs) with and without hyperammonemic (HA) crises. In addition, we sought to correlate the utility of biochemical markers and electroencephalography (EEG) in detecting subclinical seizures during HA. METHODS: Medical records of individuals with UCDs enrolled in Urea Cycle Disorders Consortium Longitudinal Study (UCDC-LS) (NCT00237315) at Children's National Hospital between 2006 and 2022 were reviewed for evidence of clinical and subclinical seizuress during HA crises, and initial biochemical levels concurrently. RESULTS: Eighty-five individuals with UCD were included in the analyses. Fifty-six of the 85 patients (66%) experienced HA crises, with a total of 163 HA events. Seizures are observed in 13% of HA events. Among all HA events with concomitant EEG, subclinical seizures were identified in 27% of crises of encephalopathy without clinical seizures and 53% of crises with clinical seizures. The odds of seizures increases 2.65 (95% confidence interval [CI], 1.51 to 4.66) times for every 100 µmol/L increase in ammonia and 1.14 (95% CI, 1.04 to 1.25) times for every 100 µmol/L increase in glutamine. CONCLUSIONS: This study highlights the utility of EEG monitoring during crises for patients presenting with clinical seizures or encephalopathy with HA. During HA events, measurement of initial ammonia and glutamine can help determine risk for seizures and guide EEG monitoring decisions.