Advocating for the inclusion of therapeutic drug monitoring in the national essential diagnostic list: Perspectives from psychiatrists.

India published its first edition of the National Essential Diagnostics List in 2019. The list depicts the list of diagnostic tests that can ensure affordable and quality healthcare delivery by removing barriers toward accessibility and reducing out-of-pocket expenditure. In 2024, the Indian Council of Medical Research has invited suggestions for revision of the list. Therapeutic drug monitoring (TDM) has been a promising modality and has been useful for a range of indications like monitoring medication adherence, diagnosing suboptimal treatment, detecting drug interactions, and guiding initiation or withdrawal of therapy. In this article, the authors make a case for inclusion of TDM for certain psychotropic drugs like lithium, sodium valproate, carbamazepine, and clozapine at the district hospital level. The authors have tried to justify the inclusion backed by recent evolving evidence.

Rapid and non-invasive diagnosis of hyperkalemia in patients with systolic myocardial failure using a model based on machine learning algorithms.

Background: Hyperkalemia is a potentially life-threatening electrolyte disturbance that if not diagnosed on time may lead to devastating conditions and sudden cardiac death. Blood sampling for potassium level checks is time-consuming and can delay the treatment of severe hyperkalemia on time. So, we propose a non-invasive method for correct and rapid hyperkalemia detection. Methods: The cardiac signal of patients referred to the Pediatrics Emergency room of Shahid Rejaee Hospital was measured by a 12-lead Philips electrocardiogram (ECG) device. Immediately, the blood samples of the patients were sent to the laboratory for potassium serum level determination. We defined 16 features for each cardiac signal at lead 2 and extracted them automatically using the algorithm developed. With the help of the principal component analysis (PCA) algorithm, the dimension reduction operation was performed. The algorithms of decision tree (DT), random forest (RF), logistic regression, and support vector machine (SVM) were used to classify serum potassium levels. Finally, we used the receiver operation characteristic (ROC) curve to display the results. Results: In the period of 5 months, 126 patients with a serum level above 4.5 (hyperkalemia) and 152 patients with a serum potassium level below 4.5 (normal potassium) were included in the study. Classification with the help of a RF algorithm has the best result. Accuracy, Precision, Recall, F1, and area under the curve (AUC) of this algorithm are 0.71, 0.87, 0.53, 0.66, and 0.69, respectively. Conclusions: A lead2-based RF classification model may help clinicians to rapidly detect severe dyskalemias as a non-invasive method and prevent life-threatening cardiac conditions due to hyperkalemia.

Evaluation of vitamin D in the diagnosis of infants with respiratory distress, the clinical value: A systematic review and meta-analysis.

INTRODUCTION: Respiratory distress (RD) is the most common cause of admission to the Neonatal Intensive Care Unit (NICU). The role of Vitamin D in the development and fortification of fetal pulmonary architecture and the synthesis of surfactants is well-documented. While different serum levels of 25-hydroxyvitamin D (Vit. D) have been studied for their diagnostic significance in RD, there is limited research on how it specifically affects the development of respiratory problems in infants and their mothers. The purpose of the present study is a systematic review and meta-analysis to evaluate the correlation between serum levels of Vit. D in mothers and newborns with RD, and to determine the impact of treating either population on the clinical outcomes of afflicted infants. METHODS: A comprehensive literature search was conducted across various databases, including PubMed, ScienceDirect, Cochrane Library, ISI, and Google Scholar, using a combination of keywords such as RD, diagnosis, vitamin D, mothers, infants, vitamin D supplementation, Respiratory distress syndrome(RDS), and Transient Tachypnea of Newborn (TTN). The search was carried out until March 2024.The level of vitamin D in both mothers and their infants was systematically extracted and analyzed to determine the diagnostic efficacy of Vit. D levels. The mean difference (MD) was calculated along with a 95% confidence interval to determine the association between the Vit. D levels in newborns and their mothers and the likelihood of RD, RDS and TTN in infants. To assess potential publication bias, a funnel plot was generated and Egger's regression test was applied, utilizing a random-effects model. RESULTS: Initially a total of 298 relevant articles was retrieved. Among them, 17 articles with a total of 1,582 infants (745 cases and 837 healthy controls) met the criteria as eligible studies. Of these six were prospective cohort studies, four retrospective case-control studies, four randomized controlled trials (RCTs), and three descriptive-analytical studies. The meta-results revealed a significant association between Vit. D levels and risk of RD in infants (MD = 6.240, 95 %CI: 4.840-7.840, P < 0.001) and mothers (MD = 8.053, 95 %CI: 4.920-11.186, P < 0.001). Furthermore, a strong association was found for risk of RDS (MD = 5.493, 95 %CI: 3.356-7.631, P < 0.001) in infants and TTN (MD = 6.672, 95 %CI: 4.072-9.272, P < 0.001), (MD = 8.595, 95%CI: 4.604-12.586, P < 0.001) both in infants and mothers. Administering 50,000 units of vitamin D to mothers (MD = 8.595, 95 %CI: 4.604-12.586, P < 0.001) prior to childbirth was observed to reduce the likelihood of RD in newborns by 64 % (RR = 0.36, 95 %CI: 0.23-0.57, P < 0.001). Supplemental vitamin D provided to infants was associated with several clinical benefits. CONCLUSION: Our meta-results indicated a significant correlation between serum levels of Vit. D and the risk of RD, RDS and TTN in infants. Prophylactic maternal administration of vitamin D plays a protective role against neonatal RD. Additionally, providing vitamin D to premature infants has shown a significant impact in reducing the incidence of respiratory complications.

Evaluation of ovarian reserve and the assisted reproductive technology (ART) cycles' outcome as well as the relapse rate within one year after ART in women with multiple sclerosis: a case-control study.

OBJECTIVE: To compare the ovarian reserve and the results of infertility treatment, as well as to investigate the relapse rate in the first year after the assisted reproductive technology (ART) cycle in patients with multiple sclerosis (MS) referred to Royan Institute. MATERIALS AND METHODS: This retrospective study was carried out to evaluate all women diagnosed with MS and referred to Royan Institute for assessment and treatment of possible infertility between 2011 and 2022. The control group consisted of randomly selected healthy women with tubal factor infertility who were referred for treatment during the same time period and matched in terms of age. A comparison was made between groups in terms of ovarian reserve and infertility treatment outcomes. Additionally, patients with MS who met the criteria were monitored via telephone to evaluate the symptoms, disability and relapse rate both pre- and post-ART. RESULTS: Over the course of a decade, the database documented a total of 60 cases diagnosed with MS. Upon examination of the records, it was found that in 27 patients only admission was done without any hormonal assessment or infertility treatment cycle and 5 patients proceeded with the intrauterine insemination cycle. Eventually, 28 women with MS underwent the ART cycle and all of them were treated with interferon beta, glatiramer acetate, or some oral disease modifying therapies. No statistically significant difference in terms of the basal levels of luteinizing hormone, follicle-stimulating hormone and anti-Müllerian hormone was found between the MS and control groups (P > 0.05). Two groups were comparable in terms of menstrual status. The study revealed that both groups exhibited similarities in terms of the controlled ovarian stimulation protocol and duration, the dosage of gonadotropin administered, as well as the ovarian response type, clinical pregnancy rate, and live birth rate (P > 0.05). After follow up, only 2 patients (9.5%) reported relapse of symptoms within one year after ART. CONCLUSION: The ovarian reserve and ovarian stimulation cycle and pregnancy outcomes following the ART cycle in MS patients were similar to the age-matched control group. The relapse rate of multiple sclerosis did not show a significant increase within a year following the ART cycle.

Major Adverse Cardiovascular Events: The Importance of Serum Levels and Haplotypes of the Anti-Inflammatory Cytokine Interleukin 10.

BACKGROUND: Cardiovascular diseases (CVDs) represent major medical and socio-economic challenges worldwide. There is substantial evidence that CVD is closely linked to inflammatory changes triggered by a complex cytokine network. In this context, interleukin 10 (IL-10) plays an important role as a pleiotropic cytokine with an anti-inflammatory capacity. In this study (a substudy of ClinTrials.gov, identifier: NCT01045070), the prognostic relevance of IL-10 levels and IL-10 haplotypes (rs1800896/rs1800871/rs1800872) was assessed regarding adverse cardiovascular outcomes (combined endpoint: myocardial infarction, stroke/transient ischemic attack, cardiac death and death according to stroke) within a 10-year follow-up. PATIENTS AND METHODS: At baseline, 1002 in-patients with CVD were enrolled. Serum levels of IL-10 were evaluated utilizing flow cytometry (BD™ Cytometric Bead Array). Haplotype analyses were carried out by polymerase chain reactions with sequence-specific primers (PCR-SSP). RESULTS: In a survival analysis, IL-10 haplotypes were not proven to be cardiovascular prognostic factors in a 10-year follow-up (Breslow test: p = 0.423). However, a higher IL-10 level was associated with adverse cardiovascular outcomes (Breslow test: p = 0.047). A survival analysis considering adjusted hazard ratios (HRs) could not confirm this correlation (Cox regression: adjusted HR = 1.26, p = 0.168). CONCLUSION: In the present study, an elevated IL-10 level but not IL-10 haplotypes was linked to adverse cardiovascular outcomes (10-year follow-up) in a cohort of CVD patients.

The Association Between Psoriasis and Trace Element Serum Levels and Dietary Intake: Results from USA National Health and Nutrition Examination Survey 2011-2014.

Objective: Psoriasis is a common chronic inflammatory disease. However, trace elements are essential to biochemical processes of the skin, it is suspected that the trace elements are vital in the pathogenesis of psoriasis. Our research is aimed to investigate the association between serum levels and dietary intake levels of selenium, zinc, and copper with psoriasis. Methods: In this cross-sectional study, we utilized the National Health and Nutrition Examination Survey data from 2011 to 2014 to examine the association between psoriasis and serum concentration and dietary intake of trace elements including copper, zinc, and selenium in the US individuals. Our research combined two cycles and weighted the data. Student's t-tests and χ2 test were used. Subgroup analyses and interaction tests were conducted by IBM SPSS Statistics 22 and EmpowerStats. Results: This study indicates that the population with psoriasis has a lower dose of dietary intake selenium than the controls, and risk analysis showed that the men with selenium daily intake >150 mcg/day have a decreasing risk for psoriasis compared to those with daily intaking selenium <75 mcg/day. However, there are no differences on daily intake of selenium, zinc, and copper and serum levels of Zinc and Copper between psoriasis and healthy controls. The current study showed that the psoriasis group was significantly older with a bigger waist circumference, a higher education level, a higher ratio of people with smoke every day, and a higher ratio of people in USA and being non-Hispanic White. Conclusion: This cross-section study showed that a high selenium intake may benefit USA adults from psoriasis, especially for males. The social and cultural background and ethnic differences between the two groups influence the eating and living models, including the trace element intake. The national recommended dietary allowances (RDAs) might be considered to be modified with more reliable investigative clinical data and certain considering the social and cultural models.

Evaluation of the Circulatory Levels of Heat Shock Protein 60 Levels in Periodontitis and Cardiovascular Disease Patients.

Introduction: HSP is arguably the most thoroughly studied self-antigens connected to Cardio Vascular Diseases (CVD) and periodontal disease. Hence, the major goal of this analysis was to determine the amount of HSP60 in patients' Chronic Periodontitis (CP) patients' serum. Materials and Methods: The current investigation involved 100 patients in all. Based on the patients' periodontal and cardiovascular health, the patients were divided. The patients were made aware that this research had no direct bearing on disease treatment or cure. Results: In contrast to periodontal disease, which had a mean serum HSP60 of 59.94 ng/dl, CVD had a mean serum HSP60 of 85.98 ng/dl. When compared to periodontal disease, the CVD increased significantly (P < 0.05, 0.03). Discussion and Conclusion: We emphasize the function of HSP60 in the pathophysiology of individuals with chronic periodontitis based on the findings of the current investigation. Serum HSP60 concentrations can serve as a biomarker for periodontal inflammation. More longitudinal and interventional research with a larger sample size is required to validate the present findings. In periodontal therapies, targeting HSP60 may enhance results.

Serum CCDC25 Levels as a Potential Marker for Metabolic Syndrome.

BACKGROUND/AIM: Metabolic syndrome (MetS) stands as a significant risk for developing various severe health problems. Therefore, the discovery of biomarkers capable of predicting the progression of metabolic conditions is crucial for improving overall health outcomes. Recently, we reported that coiled-coil domain containing 25 (CCDC25) might be associated with key proteins involved in metabolic pathways, by bioinformatics analysis. Thus, we assumed that serum CCDC25 levels might have an association with MetS status. PATIENTS AND METHODS: In this study, based on the modified National Cholesterol Education Program-Adult Treatment Panel III (modified NCEP-ATP III) criteria, the participants who had three or more of abnormal criteria were defined as MetS, and those who had 1 or 2 abnormal criteria as pre-MetS groups; those who had no abnormal criteria were classified as the healthy control (HC) group. Serum CCDC25 levels were measured using the dot blot assay. RESULTS: The results showed that serum CCDC25 levels of the MetS group (0.072±0.026 ng/µl) were significantly higher (p<0.001) than that of pre-MetS (0.031±0.011 ng/µl) or HC groups (0.018±0.007 ng/µl). We can discern a consistent trend indicating that serum CCDC25 level is well correlated with the number of abnormal criteria of MetS of each participant. Although serum CCDC25 levels correlated with the distribution of all 5 MetS criteria, the highest correlation was seen in serum CCDC25 levels and triglyceride (TG) levels, with r=0.563, followed by systolic blood pressure (SBP) levels (r=0.557) and high-density lipoprotein-cholesterol (HDL-C) levels (r=-0.545). CONCLUSION: CCDC25 showed correlations with all MetS parameters, particularly with TG, SBP, and HDL-C. This prompts speculation that heightened CCDC25 levels may indicate the development and/or progression of those MetS-associated diseases.

Prevalence and Time Trends of Low Serum B12 Levels and Inadequate B12 Dietary Intake in Lebanese Adults amidst the Food Insecurity Situation: Findings from a Nationally Representative Cross-Sectional Study.

Rising food insecurity (FI) and the increased prices of animal-based foods could compromise vitamin B12 (B12) intake and serum levels in food-insecure people. Our study aims to determine the prevalence of low levels of serum B12 and its inadequate dietary intake among a nationally representative sample of Lebanese adults aged 18 to 64 years, while exploring the impact of FI and identifying other potential predictors. The B12 intake was assessed using a food frequency questionnaire and the mean of two non-consecutive 24 h recalls. The B12 serum levels were also examined. To examine the time trends in the B12 serum levels and dietary intake, the data from a large representative digitized database of 6290 participants were collected, along with the examination of FAOSTAT food consumption data both before and during the economic crisis period. Our findings revealed that 47.3% of households in Lebanon experienced FI. The inadequate intake of B12 food sources was prevalent in 52.5% of participants, and 61.1% presented with low (23%) or intermediate (38.1%) levels of serum B12. The food-secure households had a higher proportion of B12 intake from meats (p = 0.004), while traditional foods contributed more to food-insecure households (p = 0.000). The participants who were female, unemployed, food-insecure, and had low dietary diversity were about two to three times more likely to have inadequate B12 intake. The predictors of low levels of serum B12 included residing in Beqaa (OR = 2.856 and 95% CI = 1.018-8.01) and having inadequate B12 intake (OR = 1.788 and 95% CI = 1.2-2.65). The findings from observing the time trends in the consumption and the serum levels of B12 indicate a considerable decline in the consumption of most animal-based foods compared to the pre-crisis period, associated with a decline in the serum levels of B12. In conclusion, an alarming prevalence of low dietary intake and low serum levels of B12 was revealed among Lebanese adults, and the indirect effect of FI on B12 serum levels mediated through B12 intake was inferred.

Correlation of serum interleukin-6 levels and neutrophil-lymphocyte ratio in the severity of COVID-19.

Background: Interleukin-6 (IL-6) is a pro-inflammatory cytokine that is produced at varying levels in patients with coronavirus disease 2019 (COVID-19). The neutrophil-lymphocyte ratio (NLR) is one of the new inflammatory markers of COVID-19. This study aimed to evaluate the differences in IL-6 level and the NLR in mild and severe COVID-19 and assess their correlation with COVID-19 severity and the correlation of IL-6 and NLR in COVID-19. Methods: A total of 91 patients with COVID-19 were divided into mild (n = 57) and severe (n = 34) COVID-19 groups. IL-6 levels were measured using the electrochemiluminescence immunoassay method on Roche Cobas e411. The NLR was the ratio of the total neutrophil and lymphocyte counts from complete haematology on the Sysmex XS-800i. Data were analysed using the Kolmogorov-Smirnov, Mann-Whitney, receiver operating characteristic curve, chi-square and Spearman correlation tests. The statistical test was significant at p <0.05. Results: Serum IL-6 levels and NLR significantly differed in mild and severe COVID-19. The median (min-max) IL-6 levels for mild and severe COVID-19 were 3.59 (1.50-638.30) pg/mL and 28.82 (5.52-926.30) pg/mL, respectively (p <0.001). The median (min-max) NLR in mild and moderate COVID-19 was 2.18 (0.69-15.58) and 8.13 (2.24-30.90), respectively (p <0.001). The obtained cut-off values for IL-6 and NLR were >6.99 pg/mL and >4.18, with odds ratios of 29.29 and 26.19, respectively. A positive correlation was found between IL-6 and NLR and COVID-19 severity (r = 0.612; p <0.001). Conclusions: The results indicated that serum IL-6 levels and NLR are higher in severe COVID-19 than in mild COVID-19. Patients with IL-6 levels >6.99 pg/mL and NLR >4.18 are 29 and 26 times more likely to suffer from severe COVID-19, respectively. Serum IL-6 levels and NLR are strongly correlated with COVID-19 severity. Serum IL-6 levels correlate with NLR in COVID-19.

A Case Control Study Evaluating the Relationship between Vitamin K2 Serum Level and Periodontitis.

BACKGROUND AND AIM: Vitamin K2 (VK2) is an essential co-factor for bone metabolism. There is still very little data regarding possible VK2 relation to periodontitis. This study aimed to investigate any potential link between VK2 serum level and the severity of periodontitis in comparison to a control group of healthy individuals. The trial was performed on 100 patients among whom 50 were diagnosed with periodontitis. The patients underwent full clinical periodontal and radiological examination. The VK2 serum level was assessed using the ELISA kit (Gla-type osteocalcin EIA Kit, Takara, Kusatsu). Patients with periodontitis had mean serum levels of VK2 significantly lower (0.27 ± 0.06 nmol/L; p < 0.001) than the control group (0.43 ± 0.09 nmol/L; p < 0.001) regardless of the patient's age or sex. The VK2 serum level decreased with the severity of periodontitis with the lowest level in stage IV of the disease (0.19 ± 0.01 nmol/L; p < 0.001). Also, a significant drop was noticed between the grades of periodontitis. Individuals with localized forms of the disease had significantly lower VK2 levels (0.26 ± 0.006 nmol/L; p < 0.001) in comparison to subjects with generalized periodontitis (0.30 ± 0.01 nmol/L; p < 0.001). The VK2 serum levels were also associated with most of the clinical parameters such as bleeding on probing (-0.805, 95% CI: -0.894 to -0.654, p < 0.001), attachment loss (-0.752, 95% CI: -0.862 to -0.574, p < 0.001), and bone loss (-0.656, 95% CI: -0.801 to -0.439, p < 0.001). In the present study, the VK2 serum level was correlated to periodontitis, and its severity, complexity, extension, and grade. The range of VK2 was decreasing together with the worsening of all clinical parameters of periodontitis.

Low serum level and chronic toxicity for methotrexate. Case Report.

INTRODUCTION: Methotrexate (MTX) is a folic acid antagonist used to treat different immunological or proliferative illnesses because of its anti-proliferative and anti-inflammatory effects. MTX Toxicity is considered a severe problem. Although acute toxicity related to high-dose administration (doses ≥500 mg/m2) can be predicted based on the given dose, chronic toxicity still has no specific factors to predict it, so treatment depends on the history and symptoms of toxicity. MTX was initially used for oncology indications with high cyclic doses, then expanded to non-oncology indications with different low doses and frequencies. This significant change in doses resulted in dosing errors that contributed to MTX toxicity reports. Measures to prevent the toxicity of MTX should be implemented. CASE: A 66-year-old female patient ingested 10 mg of MTX daily for one month instead of the once-toxicity symptoms. The serum level of MTX was requested, and treatment with folinic acid was initiated until the patient improved with the discontinuation of MTX. DISCUSSION: There is limited literature about the lack the total cumulative dose, duration of intake, or serum level of MTX. All this information was provided in this case report, but drug-drug interactions were not reviewed, although aspirin and pantoprazole were identified as having interactions with methotrexate in this patient. Minimum total cumulative dose identification may help assess the toxicity risk in such patients. CONCLUSION: Low-dose MTX chronic toxicity still needs further information to guide the patient's risk of toxicity and when to initiate treatment. Safety-practical measures should be implemented to prevent such administration errors.

Serum levels of lead are associated with venous thromboembolism: a retrospective study based on the NHANES database (1999 to 2018).

Background: Venous thromboembolism (VTE) is a common clinical problem. While lead toxicity is known to affect the nervous, hematopoietic system, skeletal, and cardiovascular system, the relationship between blood lead levels and VTE remains unclear. This study explored whether there is a correlation between the levels of serum lead and VTE through a retrospective analysis based on data from the National Health and Nutrition Examination Survey (NHANES), so as to provide a reference for follow-up research and clinical practice. Methods: According to the inclusion and exclusion criteria, subjects were enrolled from the NHANES (1999 to 2018) database and divided into a VTE group and a non-VTE group. The factors related to VTE were analyzed by single factor and multiple factor logistic regression analysis. Results: A total of 31,081 subjects were included, of which 59 had VTE (0.19%). The higher the levels of serum lead, the higher the incidence of VTE. The univariate analysis revealed that age, male sex, history of cigarette use, hypertension, diabetes, and serum lead levels were factors associated with VTE in the population from the NHANES database. Further multivariate analysis revealed that age, history of cigarette use, hypertension, diabetes, and serum lead levels were factors associated with VTE. Conclusions: The findings of this study suggest that higher serum levels of lead may be associated with VTE.

Retrospective study on the correlation between serum MIF level and the condition and prognosis of patients with traumatic head injury.

Objective: This study aimed to investigate the correlation between serum levels of macrophage migration inhibitory factor (MIF) and the condition and prognosis of patients with traumatic brain injury (TBI). Methods: A retrospective study design was used, and the clinical data of 131 TBI patients from February 2019 to January 2022 were analyzed. Patients were divided into mild (13-15 points), moderate (9-12 points), or severe (3-8 points) groups according to their Glasgow Coma Scale (GCS) score after admission. The serum levels of BDNF, MIF, and MBP in the three groups were compared, and their correlation with the severity of TBI was analyzed. Patients were then separated into a good prognosis group (4-5 points) and a poor prognosis group (≤3 points) based on their Glasgow Prognostic Score (GOS) after 6 months of follow-up. The predictive power of serum indexes and combined detection on prognosis was analyzed. Results: Patients were classified into a mild group (n = 63), moderate group (n = 47), and severe group (n = 21) based on their GCS, with a significant difference noted in serum levels of MIF, MBP, and BDNF among patients with different degrees of severity (all P < 0.001). The MIF, MBP, and BDNF levels were lower in the mild group compared to the moderate (all P < 0.001) and severe group (all P < 0.001). Additionally, the MIF and BDNF levels in the moderate group were lower compared to the severe group (P = 0.011, P = 0.002). Patients with mild severity had lower serum MIF, MBP, and BDNF levels than those with other degrees, and these indexes were positively correlated with the severity of TBI (all P < 0.001, r = 0.62, r = 0.48, r = 0.58). Based on the GOS, patients were divided into a good prognosis group (n = 107) and a poor prognosis group (n = 24), with the levels of MIF, MBP, and BDNF in the good prognosis group being significantly lower than those in the poor prognosis group (P < 0.001, P = 0.007, P = 0.003). The area under the curve (AUC) of MIF was higher than that of MBP and BDNF in predicting the prognosis of TBI patients; however, the statistical differences were not significant (MIF vs. MBP, P = 0.239; MIF vs. BDNF, P = 0.211; BDNF vs. MBP, P = 0.899). The center line has a large displacement, CT annular cisterna compression, increased white blood cell count, MBP and BDNF were risk factors for prognosis in TBI patients (P = 0.005, P = 0.001, P = 0.005, P = 0.033, P = 0.044). Conclusion: The serum levels of MIF, MBP, and BDNF in TBI patients were positively correlated with the severity of the disease, and MBP, BDNF levels had predictive value in determining patient prognosis.

Serum DKK-1 level in ankylosing spondylitis: insights from meta-analysis and Mendelian randomization.

Objective: The purpose of this study was to precisely evaluate the serum Dickkopf-1 (DKK-1) level in patients with ankylosing spondylitis (AS) relative to that in normal controls and to test the causal relationship between DKK-1 and the risk of AS. Methods: Embase, PubMed, Web of Science, WANFANG DATA, VIP, and China National Knowledge Infrastructure (CNKI) were comprehensively searched until July 2022 for pertinent studies. The pooled standardized mean difference (SMD) with a 95% confidence interval (CI) was calculated by the fixed or random-effect model. In Mendelian randomization (MR) analysis on the causal relationship between serum DKK-1 level and AS risk, the inverse variance weighting method (IVW), MR-Egger regression, weighted median method, and weighted pattern method were applied. Sensitivity analyses, including the horizontal pleiotropy test, heterogeneity test, and leave-one-out test, were also performed. Results: The meta-analysis of 40 studies containing 2,371 AS patients and 1,633 healthy controls showed that there was no significant difference in DKK-1 serum level between AS patients and normal controls (pooled SMD=0.207, 95% CI =-0.418-0.832, P=0.516). The subgroup analysis of the CRP ≤ 10 mg/L group showed that AS patients had higher serum DKK-1 concentration than the healthy controls (SMD=2.267, 95% CI = 0.102-4.432, P=0.040). Similarly, MR analysis also demonstrated no significant association between DKK-1 serum level and AS (IVW OR=0.999, 95% CI = 0.989-1.008, P=0.800). All sensitivity analyses revealed consistent results. Conclusions: There was no significant change in serum DKK-1 concentration between AS patients and healthy controls. In addition, no causal relationship exists between serum DKK-1 levels and AS risk.

Vitamin D3 Supplementation: Comparison of 1000 IU and 2000 IU Dose in Healthy Individuals.

BACKGROUND: Scientific studies point to a significant global vitamin D deficiency. The recommended dose of vitamin D for the adult population in Central Europe is 800-2000 IU/day. The aim of our study was to determine whether doses of 1000 IU or 2000 IU of vitamin D3 are adequate to achieve the sufficiency reference values of [25(OH)D]. METHODS: Seventy-two healthy volunteers, average age twenty-two, took part in the study. The study was conducted from October to March in order to eliminate intra-dermal vitamin D production. Vitamin D3 in an oleaginous mixture was used. The participants used either 1000 IU or 2000 IU/daily for two 60-day periods with a 30-day break. RESULTS: The dose of 1000 IU, taken for 60 days, increased vitamin D levels relatively little. Furthermore, serum vitamin D levels decreased in the 30 days following the cessation of supplementation. Taking 2000 IU daily led to a sharp increase in serum levels which plateaued 30 days after the subjects stopped using vitamin D3 drops. CONCLUSIONS: Both doses, taken daily, can help maintain adequate vitamin D levels during the winter months. A daily dose of 2000 IU, however, maintained the desired levels of vitamin D for a longer period.

TCF-1 Is Required for CD4 T Cell Persistence Functions during AlloImmunity.

The transcription factor T cell factor-1 (TCF-1) is encoded by Tcf7 and plays a significant role in regulating immune responses to cancer and pathogens. TCF-1 plays a central role in CD4 T cell development; however, the biological function of TCF-1 on mature peripheral CD4 T cell-mediated alloimmunity is currently unknown. This report reveals that TCF-1 is critical for mature CD4 T cell stemness and their persistence functions. Our data show that mature CD4 T cells from TCF-1 cKO mice did not cause graft versus host disease (GvHD) during allogeneic CD4 T cell transplantation, and donor CD4 T cells did not cause GvHD damage to target organs. For the first time, we showed that TCF-1 regulates CD4 T cell stemness by regulating CD28 expression, which is required for CD4 stemness. Our data showed that TCF-1 regulates CD4 effector and central memory formation. For the first time, we provide evidence that TCF-1 differentially regulates key chemokine and cytokine receptors critical for CD4 T cell migration and inflammation during alloimmunity. Our transcriptomic data uncovered that TCF-1 regulates critical pathways during normal state and alloimmunity. Knowledge acquired from these discoveries will enable us to develop a target-specific approach for treating CD4 T cell-mediated diseases.

Minimizing drug-drug interactions between dabigatran and levetiracetam through clinical management: a case report.

Background: Direct oral anticoagulants (DOACs) are useful for stroke prevention in atrial fibrillation (AF) patients. However, the concomitant administration of Levetiracetam limited their use in clinical practice, although some authors raise doubts about clinical relevance of the interaction. Case summary: We report a case of a 54-year-old male with AF, cirrhosis, and seizures, in which the assessment of Dabigatran plasma concentration was needed due to the concomitant use of Levetiracetam. In this case, no relevant reduction of trough Dabigatran plasma concentration was found. An increased peak serum level of dabigatran may be obtained delaying levetiracetam administration. The patient was then followed in our clinic and during 32 months of follow-up no ischaemic or haemorrhagic events occurred. Discussion: The evaluation of DOACs concentration could be helpful to start a tailored therapy in frailty patients.

Alteration in IFN-γ and CCL2 serum levels at first trimester of pregnancy contribute to development of preeclampsia and fetal growth restriction.

OBJECTIVE: Pregnancy is a unique challenge for the immune system. Any disturbance in the immune system in the first trimester could result in further pregnancy complications. In this regard, the current study aimed to investigate the association between serum levels of a group of cytokines in the first trimester of pregnancy with the onset of preeclampsia (PE) and fetal growth restriction (FGR). MATERIALS AND METHODS: Serum samples were collected from 550 pregnant women at their 11th - 13th weeks of pregnancy and followed up to delivery. Out of all cases, 15 women complicated with preeclampsia and 15 ones diagnosed with FGR were included in the study. The serum levels of IFN-γ, CCL2, IL-10, IL-35 and IL-27 were checked in the collected sera of mentioned patients and compared to 60 women with normal pregnancy outcomes. RESULTS: In the preeclampsia group, the mean level of IFN-γ was significantly higher (p < 0.001) while the CCL2 serum level was significantly lower (p < 0.003) as compared to control group. There was no significant difference between the preeclampsia group and controls regarding other cytokines. In the FGR group, the mean serum level of IFN-γ was significantly higher compared to the healthy pregnancy group (p < 0.001) but other cytokines showed no significant differences. In the FGR group, a significant positive correlation was found between IL-10 level and neonates' weight (p < 0.05). CONCLUSION: Based on the results of the present study, an elevated level of IFN-γ and a reduced level of CCL2 at the first trimester of pregnancy could lead to complications such as PE and/or FGR.

Serum Level of Soluble Human Leukocyte Antigen G in Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis.

BACKGROUND: This study aimed to evaluate the serum level of human leukocyte antigen G [HLA-G] in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) compared to healthy controls; moreover, it attempted to assess its relationship with SLE and RA disease activity indices. METHODS: This descriptive study was conducted on 31 SLE patients (17 cases with a recent diagnosis and 14 cases with a previous diagnosis), 21 RA patients (7 cases with a recent diagnosis and 14 cases with a previous diagnosis), and 18 healthy controls who visited Ghaem Hospital affiliated to Mashhad University of Medical Sciences, Mahhad, Iran. SLE and RA activity indices were measured and recorded. Furthemore, soluble isoforms, including shed HLA-G1 and HLA-G5, were measured in serum samples via the ELISA method. RESULTS: A comparison of the five groups showed no significant differences in the serum level of sHLA-G. However, sHLA-G serum level was significantly higher in SLE and RA patients compared to healthy controls (P<0.05). sHLA-G level showed no correlation with disease duration and activity in SLE and RA patients (P>0.05). However, a strong positive correlation was observed between the serum level of sHLA-G and 24-h urine protein in the previously diagnosed SLE group (r=0.83, P=0.01). CONCLUSION: It seems that the serum level of sHLA-G is higher in RA and SLE patients compared to healthy controls. Furthermore, a strong correlation was found between sHLA-G serum levels and 24-h urine protein in cases with a previous diagnosis of SLE.