Median Serum Research Articles

Protective threshold of a potent neutralizing Zika virus monoclonal antibody in rhesus macaques.

Zika virus (ZIKV) is a mosquito-borne flavivirus that caused a global pandemic in 2016-2017 with continued ongoing transmission at low levels in several countries. In the absence of an approved ZIKV vaccine, neutralizing monoclonal antibodies (mAbs) provide an option for the prevention and treatment of ZIKV infection. Previous studies identified a potent neutralizing human mAb ZIKV-117 that reduced fetal infection and death in mice following ZIKV challenge. In this study, we report exquisite potency of ZIKV-117-LALA-YTE, which has been engineered to reduce Fc receptor binding and to extend half-life, in a titration study in rhesus macaques to protect against ZIKV challenge. We show complete protection at a dose of 0.016 mg/kg ZIKV-117-LALA-YTE, which resulted in median serum concentrations of 0.13 µg/mL. The high potency of this mAb supports its potential clinical development as a novel biotherapeutic intervention for ZIKV.IMPORTANCEIn this study, we report the potency of the Zika virus (ZIKV)-specific neutralizing antibody ZIKV-117-LALA-YTE against ZIKV challenge in a titration study rhesus macaques. This high potency supports the further development of this monoclonal antibody for ZIKV.

Cytokine correlations in childhood-onset rheumatic diseases with pulmonary involvement

BackgroundThere was less research about cytokines in lung involvement of childhood-onset rheumatic diseases (RD) patients.ObjectiveIn this investigation, blood levels of 12 cytokines were tested in order to explore their associations with lung involvement in newly diagnosed childhood-onset RD patients.MethodsHigh-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) were performed on 53 newly diagnosed RD patients without any treatment in our department between July 2021 and December 2023. Patients were separated into groups based on whether their lungs were involved or not according to abnormalities found on HRCT or PFTs. We examined the serum cytokines with 41 healthy, age and gender-matched controls.ResultsThe majority of serum cytokine levels were statistically different between the RD group with lung involvement and the control group. The RD group with lung involvement had considerably higher serum IL-6 and IFN-γ levels than the RD group without lung involvement or control group. The median serum IL-6 levels were 19 pg/ml [interquartile range (IQR) 6.9, 27.6], 4.4 pg/ml (IQR 2.0, 10.5), and 2.0 pg/ml (IQR 2.0, 2.0) in RD group with lung involvement, RD group without lung involvement, and control group, respectively. Similarly, the median serum IFN-γ levels were 6.0 pg/ml (IQR 5.0, 15), 5.0 pg/ml (IQR 5.0, 5.0), and 5.0 pg/ml (IQR 5.0, 5.0) in RD group with lung involvement, RD group without lung involvement, and control group, respectively. The receiver operating characteristic (ROC) curve study showed that IL-6 and IFN-γ had area under the curve (AUC) values of 0.782 and 0.742, respectively, indicating their significant diagnostic potential for lung involvement in RD patients.ConclusionOur findings imply that IL-6 and IFN-γ may be associated with the development of lung illnesses and may be involved in the pathophysiology of RD. Thus, in individuals with RD, elevated levels of IFN-γ over 5.42 pg/ml or IL-6 above 6.25 pg/ml may warrant suspicion of lung involvement.

An analysis of vitamin K status in Chinese healthy children aged 0–18 years

BackgroundVitamin K (VK), an essential fat-soluble nutrient, exists in two primary forms, vitamin K1 (VK1), and vitamin K2 (VK2). VK1 plays an essential role in blood coagulation, while VK2 plays a crucial role in managing bone calcification, supporting bone strength and health. However, comprehensive epidemiological data on VK remains sparse, particularly in children. This study aims to evaluate the levels and characteristics of VK in children of Wenzhou area, China.MethodsA total of 3,342 children undergoing routine physical examinations in the outpatient department from December 2020 to August 2022 were recruited. The levels of VK (including VK1 and menaquinones (MK-4), a major form of VK2) and 25-hydroxy vitamin D (25(OH)D) in fasting serum samples from these children were measured using high-performance liquid chromatography-tandem mass spectrometry. The study analyzed the levels and distribution of VK and 25(OH)D across different sex, age, and weight groups, and explored their potential related factors.ResultsThe median serum levels of MK-4 and VK1 were 0.12 (0.07, 0.21) ng/ml and 0.33 (0.18, 0.57) ng/ml, respectively. The reference ranges of MK-4 and VK1 were 0.01–0.58 ng/ml and 0.03–1.48 ng/ml, respectively. The median serum 25(OH)D level was 21.26 (17.30, 25.35) ng/ml. Moreover, there were no significant variations in the levels of MK-4 and VK1 across different age and sex groups. The level of MK-4 in the underweight group was significantly higher than that in the normal weight group. MK-4 level reached its peak in summer, while the VK1 concentration was at its lowest. Furthermore, a very weak positive correlation was revealed between MK-4 and VK1 levels.ConclusionIn this study, we defined the median values and reference ranges of MK-4 and VK1 in a sample of Chinese children aged 0–18 years. MK-4 levels were higher in underweight children. Both MK-4 and VK1 levels exhibited seasonal variations. Further research is needed to explore the factors affecting MK-4 and VK1 levels.

Prevalence of Wilson’s disease in Kashmiri population: A tertiary care hospital-based assessment

Background/Problem considered: The clinical symptoms and biochemical data are the most important factors in determining the diagnosis of Wilson's disease (WD). To reduce morbidity and mortality, it is required to establish the diagnosis effectively for its management. Therefore, the study aimed to determine the prevalence of WD and to measure copper and ceruloplasmin levels in the patients visiting Sher-i-Kashmir Institute of Medical Sciences, Srinagar (SKIMS). Methods: It was a hospital-based observational descriptive study that lasted 5- years and involved a total of 1924 patients. Those subjects who visited the SKIMS (both in and out patient departments) with suspected Wilson's illness were included in the study. Results: Out of 1924, males showed predominantly higher presentation than females (57.9% vs 42.1%). Out of 17 (0.8%) subjects initially suspected of having Wilsons’s disease, only 02 subjects were actually positive for WD, and remaining 15 subjects others were diagnosed with other illnesses. The overall median serum levels of copper and ceruloplasmin were 111ug/dl and 37 mg/dl respectively. However, the subjects with confirmed WD included 01 male and 01 female., Moreover these 02 patients diagnosed with WD, had serum ceruloplasmin levels as 13 and 10 mg/dl. The female subject was having positive history of WD, as her sibling had already died from this disease. Conclusion: Serum copper and ceruloplasmin are still a better tool for diagnosis of the WD.

COMPARATIVE ANALYSIS OF THE DIAGNOSTIC ACCURACY OF ENDOSTATIN AND VEGF SERUM LEVELS IN PATIENTS WITH BONE SARCOMAS

Introduction. Angiogenesis regulators are of particular interest as new serum markers in cancer patients, since they reflect the intensity of tumor growth and metastasis. Currently, many works are dedicated to the study of vascular endothelial growth factor (VEGF), which activates angiogenesis, and endostatin, which inhibits it. However, a comparative study of the diagnostic accuracy of serum levels of these two markers in patients with bone sarcomas has not been conducted yet. Аim. A comparative analysis of the diagnostic accuracy indicators and prognostic significance of VEGF and endostatin in the blood serum of patients with primary malignant bone tumors. Methods. During the study, the levels of endostatin and VEGF in blood serum samples from 123 patients with a newly diagnosed and morphologically verified bone sarcoma were measured. Patients were examined at the Federal State Budgetary Institution “National Medical Research Center of Oncology named after N.N. Blokhin” of the Russian Ministry of Health from July 2001 to December 2022. Sixty age- and gender-matched healthy donors were included in the control group. Results. Median serum concentrations of endostatin and VEGF in the patient group were statistically significantly increased compared to the control group by 1.3 and 1.4 times, respectively (p < 0.01). Statistically significant differences in the serum concentrations of VEGF and endostatin depending on the T category and the tumor grade and stage were not identified. The cut-off value of VEGF was 279 pg/ml, and the cut-off value of endostatin was 121 ng/ml. With the same sensitivity of 75.6%, endostatin is characterized by higher specificity than VEGF (73.0 and 67.6%, respectively). The proportional hazards model characterizing the effect of serum VEGF and endostatin levels on overall and survival was not statistically significant. Conclusion. Endostatin in the blood serum of patients with bone tumors is more informative compared to VEGF; however, both markers are not predictors of overall and survival.

A Relationship of Monoamine Oxidase-A with Serotonin in Violent Antisocial Behavior in Iraqi Prisoners

It is thought that the monoamine oxidase-A (MAOA) enzyme, which catalyzes key brain signaling chemicals like serotonin, noradrenaline, and dopamine, indirectly influences antisocial behavior by disrupting the neurotransmitter balance in brain regions and neural networks. This study aims to assess the MAOA enzyme level in serum and serotonin linked to antisocial behavior in cases in the prison of Baghdad City, Iraq. Blood samples were collected from (63) prisoners and (27) control groups, ages 18 years to 65 years, with a mean ± SD of 37.8 ± 8.8, all males, with different prison terms and different crimes for prisoners in the prison at Baghdad City, Iraq. MAOA and serotonin levels were measured in serum in prisoners and healthy men, and the results showed the serum levels of MAOA enzyme and serotonin were decreased in prisoners compared to the healthy (11.5 IU/ml vs. 19.5 IU/ml) and (79 IU/ml vs. 439 IU/ml), respectively, with the observed difference being significant (P < 0.001(. The results of the relationship between education and social violence were: illiterate 11.1%, primary school 27%, secondary 52.4%, and university 9.5%. The median serum level of MAOA and serotonin in the age group 18–39 years was (11.3 IU/ml, 68.3 ng/ml), respectively, and in the age group 40–65 years was (13 IU/ml, 139 ng/ml), respectively.

Association of renal biomarkers with fast progressor phenotype and related outcomes in anterior circulation large vessel occlusion stroke.

Renal dysfunction is a known predictor of long-term functional dependency after anterior circulation large vessel occlusion (ACLVO) stroke. However, the impact of renal dysfunction on early infarct growth rate (IGR) has not been previously demonstrated. The objective of this study was to define the association of creatinine-based renal biomarkers with fast or slow progressor phenotypes and related clinical outcomes in ACLVO stroke. This retrospective study examined patients with acute intracranial internal carotid artery or middle cerebral artery-M1 occlusions admitted between 2014 and 2019. Patients were included if they received baseline CT perfusion (CTP) or MRI on presentation within 24 h of estimated stroke onset. Infarct growth rate (IGR) was determined by ischemic core volume on CTP or MRI divided by time from stroke onset to imaging. IGR was used to stratify fast progressor (IGR ≥10 mL/h) and slow progressor (IGR < 10 mL/h) status. Renal dysfunction was assessed based on serum creatinine and estimated glomerular filtration rate (eGFR) on presenting laboratories. Logistic regression models, adjusted for significant covariates, identified independent associations between renal dysfunction biomarkers, progressor status, and clinical outcomes based on modified Rankin Scale (mRS) at 90 days. Among 230 patients with ACLVO, 29% were fast progressors, with median serum creatinine levels higher than slow progressors (1.1 vs. 0.9 mg/dL, p < 0.05) and lower median eGFR (66.2 vs. 69.0 mL/min/1.73m2, p < 0.05). Elevated creatinine (≥1.2 mg/dL) was independently associated with fast progressor status (adjusted OR 2.37, 95% CI 1.18-4.77), worse 90-day mRS (adjusted OR 1.88, 95% CI 1.01-3.51) and mortality (adjusted OR 2.57, 95% CI 1.14-5.79). Reduced eGFR (<60 mL/min/1.73m2) was independently associated with fast progressor status (adjusted OR 2.38, 95% CI 1.14-4.94), but not with 90-day mRS or mortality. Serum creatinine-based biomarkers of renal dysfunction were associated with fast progressor phenotype of ACLVO stroke, and worse clinical outcomes, which may help identify such patients earlier during emergency evaluation for expedited access to EVT. Future prospective studies are warranted to confirm and test implementation of these findings.

Lipoprotein(a) levels and cholesterol efflux capacity: inverse association and impact on atherosclerosis in familial hypercholesterolemia patients on lipid-lowering therapy

Abstract Backgrounds Familial hypercholesterolemia (FH) patients have higher serum lipoprotein(a) (Lp(a)) levels than non-FH patients, and high Lp(a) levels raise atherosclerotic cardiovascular disease (ASCVD) risk 1). We previously reported that decreased cholesterol efflux capacity (CEC) is a risk marker for ASCVD in patients with statin-treated FH 2). Others have reported that Lp(a) interferes with the enhancement of ABCA1-mediated cholesterol efflux by plasminogen and that ABCA1-mediated CEC is lower in patients with Lp(a) &amp;gt;50 mg/dL. However, the association of CEC, not necessarily ABCA1-mediated, with Lp(a) is not clear and has not been studied in patients with FH. It is also unclear whether high Lp(a) and low CEC in patients with FH are associated with the severity of atherosclerosis. Purpose We examined whether Lp(a) levels are negatively associated with ABCA1-independent CEC in patients with FH receiving lipid-lowering therapy. We also examined the impact of the combination of high Lp(a) and low CEC on the presence of corneal arcus, Achilles tendon thickness, carotid intima-media thickness (IMT), and pre-existing ASCVD. Methods This cross-sectional study included 371 patients clinically diagnosed with FH receiving lipid-lowering therapy. CEC was measured in apolipoprotein B-depleted plasma and 3H-cholesterol-labeled J774.1 cells without cAMP-stimulated ABCA1 overexpression. Lp(a) was measured by enzymatic methods (Sekisui Medical, Tokyo, Japan) using an automated analyser. Achilles tendon thickness was measured by X-ray and carotid IMT by ultrasound. Results Mean age was 55±16 years, and 191 (51%) were women. The median serum Lp(a) level was 18.7 mg/dL, higher than the previously reported median level (13 mg/dL) in a Japanese population. One hundred nineteen patients (32%) had serum Lp(a) levels of 30 mg/dL or higher, and they had significantly lower CEC (P=0.0015). This negative association persisted after adjusting for age, sex, BMI, smoking status, serum LDL-cholesterol, serum triglycerides, and eGFR in a multiple linear regression model (beta-coefficient: -0.047, 95% CI: -0.075 - -0.019, P=0.0011). In addition, patients with both Lp(a) &amp;gt; 30 mg/dL and CEC lower than the median had a higher percentage of corneal arcus, thicker Achilles tendons, greater carotid IMT, and a higher prevalence of pre-existing ASCVD compared to patients with either or neither. Conclusions We found an inverse relationship between Lp(a) levels and CEC in FH patients receiving lipid-lowering therapy. Our results suggest that Lp(a) may also inhibit ABCA1-independent CEC, including passive cholesterol diffusion from peripheral cells. Furthermore, the combination of high Lp(a) and low CEC may be a residual risk for patients with FH receiving lipid-lowering therapy. Future studies are needed to determine whether agents that decrease Lp(a) levels will increase CEC and thereby resolve part of the residual ASCVD risk in FH.

Prognostic values of lipoprotein(a) levels for secondary prevention of acute coronary syndrome among patients who underwent primary percutaneous coronary intervention

Abstract Background Lipoprotein(a) [Lp(a)] is known to be a residual risk factor for acute coronary syndrome(ACS). However, in the current era where primary percutaneous coronary intervention (PCI) and lipid-lowering therapies have advanced, the role of Lp(a) levels in secondary prevention among ACS patients remains unclear. Purpose The purpose of this study is to determine whether Lp(a) levels play a role in secondary prevention by studying patients with ACS who underwent primary PCI and survived discharge. Methods Consecutive ACS patients who were admitted to our institution between December 2016 and March 2021, requiring primary PCI and were discharged alive were enrolled for the current study (n = 471). Of these patients, those with the following circumstances were excluded: (1) multidisciplinary treatment such as mechanical ventilation management and percutaneous cardiopulmonary support (n = 74), (2) incomplete clinical data (n = 34), (3) ACS classified as other than type 1 in the universal definition (n = 6), and (4) unknown prognosis at 6 months after discharge (n = 8). A total of 349 consecutive patients were included in the current study. They were divided into two groups according to Lp(a) levels: Lower Lp(a) group (Lp(a) &amp;lt; 30 mg/dL, n = 277) and Higher Lp(a) group (Lp(a) ≥ 30 mg/dL, n = 72). The primary endpoints were major adverse cardiac events (MACEs), composite of all cause death, nonfatal myocardial infarction, nonfatal stroke and congestive heart failure requiring admission. Event-free survival curves were estimated using Kaplan-Meier method and log-rank test was used to detect statistically significant differences. In addition, influence of Lp(a) levels on MACE was examined using three cox regression analyses. Model 1 was adjusted for age, gender and body mass index, model 2 was adjusted for hypertension, diabetes and chronic kidney disease (CKD), model 3 was adjusted for old myocardial infarction (OMI), smoking and multivessel disease, respectively. Results The mean age was 67.0 ± 12.8 years, and 70.5% were male. The median serum Lp(a) levels of the entire population was 14 mg/dL (interquartile range, 7 to 26). There were no significant differences about baseline patient’s characteristics, laboratory findings, and medications at discharge including statin treatment. The MACE was observed in 15.5% of the Lower Lp(a) group and 20.8% of the Higher Lp(a) group (p=0.29). No difference was observed about MACE between the two groups (log-rank p=0.45). After adjusting for cardiovascular risk factors, Lp(a) levels were not associated with MACEs in all three models. However, in model 2 and model 3, CKD and OMI were associated with MACEs (hazard ratio 4.29, 95% confidence interval 2.17 to 8.46, p &amp;lt; 0.001, hazard ratio 3.02, 95% confidence interval 1.39 to 6.51, p = 0.005, respectively). Conclusions In the current era, Lp(a) levels are not associated with secondary prevention among ACS patients who underwent primary PCI.

Prevalence of Low FIB-4 in MASLD-Related Hepatocellular Carcinoma: A Multicentre Study.

Major society guidelines recommend the fibrosis-4 index (FIB-4) as the initial step to risk stratifying people with metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to evaluate the proportion of people with MASLD-related hepatocellular carcinoma (HCC) and a low FIB-4. This cohort study included 613 consecutive adults (33% female) diagnosed with MASLD-related HCC from January 2008 to August 2023 at seven international centres in Australia, India, Japan, South Korea, Singapore and the United States. The primary objective was to determine the proportion of participants with a low FIB-4, defined as FIB-4 < 1.3, or < 2 if age > 65 years, in people without cirrhosis. The mean (±SD) age and body mass index were 71 (±11) years and 27 (±7) kg/m2, respectively. Overall, 235 participants (38%) did not have known cirrhosis. The median FIB-4 was 3.90 (IQR 2.42-6.42). A total of 78 participants (13%) had a low FIB-4. Among participants without known cirrhosis (n = 235), 62 participants (26%) had a low FIB-4. Participants with a low FIB-4 had larger median total tumour diameter (p < 0.001) and lower median serum alpha-fetoprotein (p = 0.005), compared to participants without a low FIB-4. Cirrhosis was associated with lower odds of low FIB-4, but not other factors such as male sex, type 2 diabetes, or obesity. More than a quarter of those with MASLD-related HCC without cirrhosis have a low FIB-4. The proposed clinical care pathways may not identify these people for further evaluation.

Changes of bone turnover markers and bone mineral density among postmenopausal Thai women with osteoporosis receiving generic risedronate

BackgroundOsteoporosis has been recognized as a significant health issue in Thailand. Pharmacological interventions are important way to prevent fracture. However, one of the main challenges in selecting a medication is high cost, particularly for brand-name drugs. Data on generic bisphosphonate use in Thai are still lacking. Therefore, our study aimed to assess the efficacy and safety of generic risedronate in postmenopausal Thai women with osteoporosis.MethodsThis prospective study was conducted at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, from December 2022 to January 2024. Serum C-terminal cross-linking telopeptide of type I collagen (CTX) and procollagen type I N-propeptide (P1NP) were measured at baseline. All participants subsequently received 35 milligrams of oral risedronate once weekly for 52 weeks. Serum CTX and P1NP were remeasured at different time points. BMD was reevaluated at 52 weeks after risedronate treatment initiation.ResultsA total of 80 participants were included. The mean age was 65.2 ± 6.6 years. The mean body mass index (BMI) was 23.45 ± 3.49 kg/m2. The median (IQR) serum CTX level at 12 weeks was significantly lower than that at baseline (0.28 (0.16–0.46) ng/mL versus 0.44 (0.26–0.64) ng/mL, respectively; p value < 0.01). The suppression of serum CTX was confirmed at 52 weeks after treatment initiation. Compared with those at baseline, the serum P1NP levels were significantly lower at 24 weeks after treatment initiation (30.33 (19.19–39.58) ng/mL versus 41.90 (30.33–68.67) ng/mL, respectively; p value < 0.01). In terms of the BMD assessment at 52 weeks, significant improvements were observed in both areal BMD (g/cm2) and T scores at all measured sites compared with baseline. The lumbar spine, femoral neck, and total hip BMD increased from baseline by 4.76%, 3.84% and 4.54%, respectively.ConclusionPostmenopausal women with osteoporosis who were treated with generic risedronate demonstrated significant suppression of the bone remodelling process at 3, 6, and 12 months after treatment initiation. Additionally, significant improvements in the lumbar spine, femoral neck, and total hip BMD were observed at 12 months of therapy. These findings suggest that generic risedronate could be considered a reasonable and interesting option for treating postmenopausal women with osteoporosis in Thailand.

Improvement of serum folate status in the US women of reproductive age with fortified iodised salt with folic acid (FISFA study).

Mandatory folic acid fortification of enriched grains has reduced neural tube defect prevalence in several countries. We examined salt as an additional vehicle for folic acid fortification. The primary objective was to examine the change in serum folate concentration after 1 month of consumption of fortified iodised salt with folic acid (FISFA) among women of reproductive age. The secondary objectives were to examine (1) the feasibility of implementing FISFA intervention and (2) the acceptability of FISFA. We conducted a pre–post intervention study (January–April 2023). Participants received a FISFA saltshaker with the study salt (1 g of sodium chloride salt fortified with 100 mcg of folic acid) to use instead of regular table salt for 1 month. Serum folate was measured using the Elecsys Folate-III immunoassay method at baseline and 1-month endpoint. Change in serum folate was assessed using a two-tailed Wilcoxon signed rank test for paired samples. Metropolitan city, Southern USA. Non-pregnant, 18–40-year-old women who lived alone/with a partner. Thirty-two eligible women consented to participate, including eleven non-Hispanic-White, eleven non-Hispanic-Black and ten Hispanic. Post-intervention, there was a significant increase in median serum folate concentration of 1·40 nmol/l (IQR 0·74–2·05; P < 0·001) from 24·08 nmol/l to 25·96 nmol/l in an analytical sample of n 29. An increase was seen in 28/29 (93 %) participants. Feasibility: 100 % study consent and compliance. FISFA acceptability: 25 d average use; 1·28 g average daily intake; 96·7 % and 90 % reported taste and colour of FISFA as highly acceptable, respectively. FISFA is an effective approach to increasing serum folate concentrations among women of reproductive age. Findings should be replicated in a larger study.

Low Serum Fibroblast Growth Factor 21 Level and Its Altered Regulation by Thyroid Hormones in Patients with Hashimoto's Thyroiditis on Levothyroxine Substitution.

Fibroblast growth factor 21 (FGF21) is a hormonal regulator of lipid and glucose metabolism exerting protection against atherosclerosis by multiple actions on the blood vessels, liver, and adipose tissues. We aimed to investigate serum FGF21 level and its relation to thyroid hormones and metabolic parameters among patients with Hashimoto's thyroiditis (HT). Eighty patients with HT on levothyroxine treatment and eighty-two age- and BMI-matched adults without thyroid disease serving as controls were enrolled. Serum FGF21 concentrations were determined with an enzyme-linked immunosorbent assay. Median serum FGF21 level was significantly lower in HT patients compared with controls (74.2 (33.4-148.3) pg/mL vs. 131.9 (44.8-236.3) pg/mL; p = 0.03). We found a positive correlation between FGF21 and age, triglyceride, total cholesterol, and low-density lipoprotein cholesterol in both groups, while thyroid stimulating hormone and C-reactive protein showed a positive correlation, and thyroxine had an inverse correlation with FGF21 only in control subjects. According to multiple regression analyses, thyroid status is the main predictor of FGF21 in healthy controls, while it is not a significant predictor of FGF21 among HT patients on levothyroxine supplementation therapy. Our results indicate that the physiological role of thyroid function in the regulation of FGF21 synthesis is impaired in HT patients, which may contribute to the metabolic alterations characteristic of HT patients.

The polar vessel sign: insights from CT imaging analysis in Asian Indian primary hyperparathyroidism.

Data on the polar vessel sign (enlarged feeding vessel terminating in parathyroid lesions) on four-dimensional computed tomography (4D-CT) is limited. We performed a retrospective analysis to determine the prevalence, predictors, and adjunctive utility of polar vessel sign in pre-operative 4D-CT of patients with primary hyperparathyroidism (PHPT). One radiologist blinded to the patients' details reported the 4D-CT of eighty-four operated patients with histopathology-proven single-gland PHPT. Two protocols were used to obtain arterial-phase images: timed via bolus tracking (n = 41) or fixed at 20 s after contrast injection (n = 43). Seventy-one patients were symptomatic for PHPT, with median serum calcium 12.1 mg/dL. On the arterial phase of 4D-CT, 88.1% of lesions had the polar vessel sign, including 7/9 asymptomatic patients, 6/6 parathyroid carcinomas, and 3/4 ectopic(1:mediastinum, 2:thyro-thymic ligament). Predictors of polar vessel sign were maximum lesion dimension (2.2 vs. 1.4 cm; P = 0.03), solid-cystic CT morphology (47.3% vs. none; P = 0.004), and bolus tracking-timed arterial phase (55.4% vs. none; P = 0.001). Of these, bolus tracking improved the polar vessel's visualization (100% vs. 76.7%; P = 0.001) independent of lesion dimension and solid-cystic morphology. The latter two predicted polar vessel sign in images obtained at a fixed interval (20 s). A significantly lower proportion of bolus tracking-timed scans had lesion percentage arterial enhancement (PAE) < 128.9% (2/41 vs. 9/43; P = 0.04). Even with suboptimal PAE, the polar vessel helped identify 9/11 lesions. The polar vessel sign demonstrated an additive role to PAE during CT reporting. Bolus tracking is valuable in optimizing vessel and tumor arterial enhancement and is easily incorporated into parathyroid 4D-CT protocol.

Exploring the Link between Serum Klotho and High-Frequency Hearing Loss in Older Adults.

Klotho is a protein with various biological functions, including anti-aging effects. Although research suggests Klotho plays a key role in auditory function, the relationship between serum Klotho levels and high-frequency hearing loss (HFHL) in older adults remains unclear. We analyzed data from individuals aged 70-79 years participating in the 2009-2010 cycle of the National Health and Nutrition Examination Survey. Multivariate logistic regression models were employed to assess the relationship between serum Klotho levels and HFHL. Restricted cubic splines were utilized to evaluate linearity and examine the dose-response relationship. Additionally, we performed subgroup analyses to evaluate the consistency of this relationship across various subgroups. In this study of 422 elderly individuals aged 70-79 years (mean age 73.8 years, with 47.4% male participants), the median serum Klotho concentration was 754.6 pg/mL. Multivariable logistic regression analysis consistently demonstrated that higher serum Klotho levels were associated with a reduced risk of HFHL across various models (ORs: 0.24-0.32, p = 0.020-0.028). Additionally, restricted cubic spline analysis confirmed a linear negative association between serum Klotho levels and HFHL risk, with a p-value for nonlinearity of 0.474. Subgroup analyses did not reveal any statistically significant interactions modifying this relationship. Serum Klotho levels are inversely associated with the risk of HFHL. 3 Laryngoscope, 2024 Laryngoscope, 2024.

Impact of chromosomal aberrations detected by chromosome banding analysis in symptomatic Waldenström's macroglobulinemia.

The clinicopathologic features and prognostic impact of MYD88 L265P (MYDL265P) and CXCR4 mutations (CXCR4Mut) have been well reported, although little is known regarding the impact of chromosomal aberrations (CA) detected by chromosome banding analysis (CBA) in symptomatic Waldenström's macroglobulinemia (sWM). Thus, we investigated the clinicopathologic features and prognostic impact in sWM with CAs identified by CBA. We retrospectively analyzed the clinicopathologic results and genomic alterations by droplet digital PCR, fluorescence in situ hybridization (FISH), and CBA using the G-banding method in bone marrow samples from sWM patients collected between April 2010 and March 2024 at our institute. The relationship between CAs and clinicopathologic features was evaluated, as well as the time to next treatment (TTNT). Thirty-five patients were enrolled. The median age was 71 years, and the median hemoglobin level was 10.1g/dL. The median serum IgM and M-protein levels were 3,009mg/dL and 2.95g/dL, respectively. MYDL265P was found in 30/35 patients (85.7%), whereas CXCR4Mut was found in 3/35 patients (8.6%). Deletion 6q identified by FISH in 5/18 patients (28%), and CAs using CBA in 9/34 patients (26%), including 4/34 (12%) complex karyotypes. sWM with CAs had more anemia (p = 0.04) and hypoalbuminemia (p = 0.007), in addition to higher serum M-protein and IgM levels (p = 0.03). With a median follow-up of 73 months, the median TTNT in patients with and without CAs was 27 and 68 months, respectively. CAs with CBA may be associated with clinical aggressiveness and shorter TTNT in sWM.

Liberalization of the Systemic Glucose Management is Associated with a Reduced Frequency of Neuroglucopenia in Subarachnoid Hemorrhage Patients: An Observational Cohort Study.

Pathologically low brain glucose levels, referred to as neuroglucopenia, are associated with unfavorable outcomes in neurocritical care patients. We sought to investigate whether an increase in serum glucose levels would be associated with a reduction of neuroglucopenia. In this retrospective analysis of prospectively collected data, we included 55 consecutive patients with spontaneous subarachnoid hemorrhage who underwent cerebral microdialysis (CMD) monitoring. Neuroglucopenia was defined as CMD-glucose levels < 0.7mmol/l. We identified systemic glucose liberalization events, defined as a day with median serum glucose levels < 150mg/dl, followed by a day with median serum glucose levels > 150mg/dl, and compared concentrations of cerebral metabolites between these days. Unfavorable outcome was defined as modified Rankin Scale score ≥ 3 at 3 months after the bleeding. Episodes of neuroglucopenia were more frequent in patients with unfavorable outcome (19.8% [19.3-20.3%] vs. 10.9% [10.4-11.5%], p = 0.007). Sixty-nine systemic glucose liberalization events were identified in 40 patients. Blood glucose levels increased from 141.2 (138.7-143.6) mg/dl to 159.5 (157.0-162.2) mg/dl (p < 0.001), CMD-glucose levels increased from 1.44 (1.39-1.50) mmol/l to 1.68 (1.62-1.75) mmol/l (p = 0.001), and the frequency of neuroglucopenia decreased from 24.7% (22.9-26.5%) to 20.2% (18.7-21.8%) (p = 0.002) during these events. Liberalization was not associated with changes in CMD-lactate, CMD-pyruvate, CMD-lactate-to-pyruvate ratio, CMD-glutamate, or CMD-glycerol. In conclusion, the liberalization of serum glucose concentrations to levels between 150 and 180 mg/dl was associated with a significant reduction of neuroglucopenia.

Elevated serum IL-17 A and CCL20 levels as potential biomarkers in major psychotic disorders: a case-control study

BackgroundMajor psychotic disorders (MPD), including schizophrenia (SCZ) and schizoaffective disorder (SAD), are severe neuropsychiatric conditions with unclear causes. Understanding their pathophysiology is essential for better diagnosis, treatment, and prognosis. Recent research highlights the role of inflammation and the immune system, particularly the Interleukin 17 (IL-17) family, in these disorders. Elevated IL-17 levels have been found in MPD, and human IL-17 A antibodies are available. Changes in chemokine levels, such as CCL20, are also noted in SCZ. This study investigates the relationship between serum levels of IL-17 A and CCL20 in MPD patients and their clinical characteristics.MethodWe conducted a case-control study at the Ibn Sina Psychiatric Hospital (Mashhad, Iran) in 2023. The study involved 101 participants, of which 71 were MPD patients and 30 were healthy controls (HC). The Positive and Negative Symptom Scale (PANSS) was utilized to assess the symptoms of MPD patients. Serum levels of CCL20 and IL-17 A were measured using Enzyme-Linked Immunosorbent Assay (ELISA) kits. We also gathered data on lipid profiles and Fasting Blood Glucose (FBS).ResultsThe mean age of patients was 41.04 ± 9.93 years. The median serum levels of CCL20 and IL-17 A were significantly elevated in MPD patients compared to HC (5.8 (4.1–15.3) pg/mL and 4.2 (3–5) pg/mL, respectively; p < 0.001). Furthermore, CCL20 and IL-17 A levels showed a positive correlation with the severity of MPD. MPD patients also had significantly higher FBS, cholesterol, and Low-Density Lipoprotein (LDL) levels, and lower High-Density Lipoprotein (HDL) levels compared to HC. No significant relationship was found between PANSS components and blood levels of IL17 and CCL20.ConclusionThe current study revealed that the serum levels of IL-17 A and CCL20 in schizophrenia patients are higher than those in the control group. Metabolic factors such as FBS, cholesterol, HDL, and LDL also showed significant differences between MPD and HC. In conclusion, the findings suggest that these two inflammatory factors could serve as potential therapeutic targets and prognostic biomarkers for schizophrenia.

Pediatric Headache Patients Are at High Risk of Vitamin D Insufficiency.

Vitamin D deficiency has been associated with headaches in adults, but data for children with headaches are sparse. To describe vitamin D levels in children with headaches. We retrospectively analyzed serum 25(OH)D concentrations in children aged 2-17 years with headaches compared to children with epilepsy at the Children's Hospital of Eastern Ontario between October 1, 2014, and August 19, 2021. Serum 25(OH)D <50 nmol/L was classified as insufficient. Vitamin D concentrations of 353 children (117 with headaches; 236 with epilepsy) were analyzed. The median age in years was 10 (interquartile range [IQR] 5, 14); 50.4% of subjects were female. The median serum 25(OH)D was 56 nmol/L (IQR 41, 69) in children with headaches and 70 nmol/L (IQR 50, 95) in children with epilepsy. Vitamin D insufficiency was present in 42% of children with headaches and 25% of children with epilepsy (P = .002). In a multivariable linear regression model adjusting for age, sex and seasonality, children with headaches had serum 25(OH)D concentrations that were on average 9 nmol/L (95% CI-16.76, -0.96) lower compared to children with epilepsy (P = .029). The prevalence of vitamin D insufficiency is higher in children with headaches compared to children with epilepsy. Prospective studies are needed to assess if vitamin D supplementation may have a therapeutic effect on pediatric headaches.

Serum per- and polyfluoroalkyl substance (PFAS) levels and health-related biomarkers in a pilot study of skiers in New England

BackgroundPer- and polyfluoroalkyl substances (PFAS), synthetic chemicals with adverse health effects, are used extensively in consumer products. Ski waxes, applied to the base of skis, contain up to 100% PFAS by mass, but exposure and health effects are poorly characterized. ObjectivesOur objectives were to quantify serum PFAS concentrations among skiers and explore associations with reported ski wax use and biomarkers of cardiometabolic, thyroid, and immune health. MethodsWe recruited 30 active adult skiers to provide non-fasting blood samples and complete questionnaires. We quantified 18 PFAS using mass spectrometry, and measured serum lipids, thyroid hormones, and immunoglobulins. We explored associations of individual and aggregate measures of serum PFAS with wax use indicators and health biomarkers using multivariable regression models, adjusted for age and gender identity. ResultsNine PFAS (PFBS, PFHpS, PFHxS, Sm-PFOS, n-PFOS, PFDA, PFNA, PFUnDA, n-PFOA) were detected in 100% of participants, and MeFOSAA in 93%. Compared to NHANES, median serum concentrations (ng/ml) were similar, but higher in coaches (e.g., PFOAall: 1.1, PFOAcoaches: 2.7, PFOANHANES: 1.2; PFNAall: 0.5, PFNAcoaches: 1.7, PFNANHANES: 0.4). Factors reflecting wax exposure were positively associated with PFAS: e.g., >10 years as a snow sport athlete, compared to ≤10 years, was associated with 3.2 (95% CI: 0.7, 5.6) ng/ml higher aggregate PFAS, as defined by National Academies of Science, Engineering, and Medicine (NASEM). An IQR (6.3 ng/ml) increase in NASEM PFAS was associated with 32.1 (95% CI: 7.0, 57.2), 35.5 (13.5, 57.5), and 12.8 (0.6, 25.1) mg/dl higher total cholesterol, LDL-C, and sdLDL-C, respectively. DiscussionOur study provides early evidence that recreational skiers, particularly coaches, are exposed to PFAS through ski wax. Several PFAS were associated with higher serum lipids among these physically active adults. Interventions to remove PFAS from fluorinated wax could decrease direct exposure to skiers and reduce PFAS release into the environment.