Association of the apoptotic markers Apo1/Fas and cCK-18 and the adhesion molecule ICAM-1 with Type 1 diabetes mellitus in children and adolescents.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is characterized by immune and metabolic dysregulation. Apo1/Fas is implicated in maintaining homeostasis of the immune system. Cytokeratin-18 (cCK-18) is a predictive marker of liver disorders in T2DM. Intercellular adhesion molecule-1 (ICAM-1) is considered to increase susceptibility to diabetes mellitus. All three markers are associated with endothelial function, apoptosis and diabetes-related complications. The possible role of Apo1/Fas, cCK-18 and ICAM-1 was investigated in children and adolescents with T1DM. METHOD: Forty-nine (49) children and adolescents with T1DM and 49 controls were included in the study. Somatometric measurements were obtained and the Body Mass Index (BMI) of the participants was calculated. Biochemical parameters were measured by standard laboratory methods and Apo1/Fas, cCK-18 and ICAM-1 were measured using appropriate ELISA kits. The statistical analysis was performed using the IBM SPSS Statistics 23 program. RESULTS: Apo1/Fas (p = 0.001), cCK-18 (p < 0.001) and ICAM-1 (p < 0.001) were higher in patients with T1DM compared to the controls. Apo1Fas was negatively correlated with glucose (p = 0.042), uric acid (p = 0.026), creatinine (p = 0.022), total cholesterol (p = 0.023) and LDL (p = 0.005) in the controls. In children and adolescents with T1DM, Apo1/Fas was positively correlated with total cholesterol (p = 0.013) and LDL (p = 0.003). ICAM-1 was negatively correlated with creatinine (p = 0.019) in the controls, whereas in patients with T1DM it was negatively correlated with HbA1c (p = 0.05). CONCLUSIONS: Apo1/Fas, cCK-18 and ICAM-1 may be useful as serological markers for immune and metabolic dysregulation in children and adolescents with T1DM. Also, Apo1/Fas may have a protective role against metabolic complications in healthy children.

Optimizing intrauterine insemination: A systematic review and meta-analysis of the effectiveness and safety of clinical treatment add-ons.

INTRODUCTION: Intrauterine insemination (IUI) is one of the most widespread fertility treatments. However, IUI protocols vary significantly amongst fertility clinics. Various add-on interventions have been proposed to boost success rates. These are mostly chosen arbitrarily or empirically. The aim of this systematic review and meta-analysis is to assess the effectiveness and safety of add-on interventions to the standard IUI protocol and to provide evidence-based recommendations on techniques used to optimize the clinical outcomes of IUI treatment. MATERIAL AND METHODS: Systematic review and meta-analyses were performed in accordance with PRISMA guidelines. A computerized literature search was performed from database inception to May 2023. Randomized controlled trials (RCTs) were included reporting on couples/single women undergoing IUI with any protocol for any indication using partner's or donor sperm. A meta-analysis based on random effects was performed for each outcome and add-on. Three authors independently assessed the trials for quality and risk of bias and overall certainty of evidence. Uncertainties were resolved through consensus. Primary outcomes were ongoing pregnancy rate (OPR) or live birth rate (LBR) per cycle/per woman randomized. Registration number PROSPERO: CRD42022300857. RESULTS: Sixty-six RCTs were included in the analysis (16 305 participants across 20 countries). Vaginal progesterone as luteal phase support in stimulated cycles was found to significantly increase LBR/OPR (RR 1.37, 95% CI 1.09-1.72, I2 = 4.9%) (moderate/low certainty of the evidence). Endometrial scratch prior/during stimulated IUI cycles may increase LBR/OPR (RR 1.44, 95% CI 1.03-2.01, I2 = 1.8%), but evidence is very uncertain. Results from two studies suggest that follicular phase ovarian stimulation increases LBR/OPR (RR 1.39, 95% CI 1.00-1.94, I2 = 0%) (low certainty of evidence). No significant difference was seen for the primary outcome for the other studied interventions. CONCLUSIONS: The findings of this systematic review and meta-analysis suggest that vaginal luteal phase progesterone support probably improves LBR/OPR in stimulated IUI treatments. In view of moderate/low certainty of the evidence more research is needed for solid conclusions. Further research is also recommended for the use of endometrial scratch and ovarian stimulation. Future studies should report on results according to subfertility background as it is possible that different add-ons could benefit specific patient groups.

Diagnosis of Thyroid Nodules in Children and Adolescents with Subclinical Hypothyroidism and Their Outcomes after Early Thyroxine Treatment-A Longitudinal Study.

Pediatric thyroid nodules (TNs) present a higher malignancy rate compared to adults. We sought to diagnose the frequency and characteristics of TNs in children and adolescents with subclinical hypothyroidism (SH) and their outcomes after levothyroxine (LT4) therapy. A total of 256 children with TNs and SH were followed every semester from 2006 to 2018. All patients were treated with LT4. Clinical and radiologic findings, such as the size and texture of the nodules, were documented. Analysis included one-way ANOVA, Kruskal-Wallis, Chi-square, and Fisher's exact tests. After initial LT4 therapy, TNs disappeared in 85.5% and did not reappear throughout follow-up. In 14.5%, TNs remained the same or increased in size, but they decreased after subsequent LT4 administration with an increased dose. Thyroid disease family history (FHTD) was documented in 77.0%. In total, 64.5% developed a goiter, 46.0% exhibited thyroid heterogeneity on ultrasound, 23.4% had positive Anti-Tg, and 25.4% had positive anti-TPO autoantibodies. Our findings support the possible premise that early pharmacologic intervention with LT4 may be beneficial in children and adolescents with TNs and SH. The increased frequency of FHTD, goiter, thyroid heterogeneity, and Hashimoto in our patients emphasizes that thyroid ultrasounds may be warranted in children and adolescents with these characteristics in order to rule out the presence of TNs.

Basic host response parameters to classify mortality risk in COVID-19 and community-acquired pneumonia.

Improved phenotyping in pneumonia is necessary to strengthen risk assessment. Via a feasible and multidimensional approach with basic parameters, we aimed to evaluate the effect of host response at admission on severity stratification in COVID-19 and community-acquired pneumonia (CAP). Three COVID-19 and one CAP multicenter cohorts including hospitalized patients were recruited. Three easily available variables reflecting different pathophysiologic mechanisms-immune, inflammation, and respiratory-were selected (absolute lymphocyte count [ALC], C-reactive protein [CRP] and, SpO2/FiO2). In-hospital mortality and intensive care unit (ICU) admission were analyzed as outcomes. A multivariable, penalized maximum likelihood logistic regression was performed with ALC (< 724 lymphocytes/mm3), CRP (> 60 mg/L), and, SpO2/FiO2 (< 450). A total of 1452, 1222 and 462 patients were included in the three COVID-19 and 1292 in the CAP cohort for the analysis. Mortality ranged between 4 and 32% (0 to 3 abnormal biomarkers) and 0-9% in SARS-CoV-2 pneumonia and CAP, respectively. In the first COVID-19 cohort, adjusted for age and sex, we observed an increased odds ratio for in-hospital mortality in COVID-19 with elevated biomarkers altered (OR 1.8, 3, and 6.3 with 1, 2, and 3 abnormal biomarkers, respectively). The model had an AUROC of 0.83. Comparable findings were found for ICU admission, with an AUROC of 0.76. These results were confirmed in the other COVID-19 cohorts Similar OR trends were reported in the CAP cohort; however, results were not statistically significant. Assessing the host response via accessible biomarkers is a simple and rapidly applicable approach for pneumonia.

The Association between the Dietary Antioxidant Index and Weight Status in Primary School Students: An Epidemiological Study.

Obesity is an emerging threat and a current challenge for children and adolescents worldwide. The aim of the present work was to evaluate the relationship between the Dietary Antioxidant Index (DAI) and the weight status of students in early adolescence. A sample of 1580 students aged 10-12 years from 47 primary schools in Greece were enrolled. Anthropometric characteristics were assessed, and calculation of the Body Mass Index (BMI) was used to categorize students into two weight-status groups. Dietary habits and physical activity were evaluated using a self-completed questionnaire, and the DAI was calculated through derived micronutrients' content, along with energy, macro-, and micro-nutrient intake. Crude and adjusted regression analysis showed a significant inverse association of the DAI and body weight status (Odds Ratio (OR): 0.719, 95% Confidence Interval (CI): 0.576; 0.897, and adjusted Odds Ration (aOR): 0.667, 95% CI: 0.489; 0.907). An antioxidant diet seems to play a protective role against increased body weight among students in early adolescence. Thus, dietary patterns rich in antioxidants should be promoted to facilitate healthy habits early in life, and to fight the obesity threat.

New Clinical Markers of Oxidized Lipid-Associated Protein Damage in Children and Adolescents with Obesity.

Obesity in children and adolescents has been associated with oxidative stress (OS). The lipid hydroperoxides (LOOH) and the malondialdehyde (MDA) and thiobarbituric reactive substances (TBARS) that oxidatively modify proteins (Pr) (i.e., PrMDA and PrTBARS, respectively) represent markers of OS-associated lipid peroxidation. We aimed to assess OS in children and adolescents with obesity using-for the first time-markers involved in the early and late lipid oxidation process. LOOH, PrMDA, and PrTBARS were investigated in 41 children and adolescents with obesity and 31 controls. Obesity was defined as BMI > 95% for age and sex. The PrMDA/PrTBARS pair, which reflects a late peroxidation stage, was found to be significantly high (39%/180%) in children and adolescents with obesity compared to controls (p < 0.001). Similarly, the early LOOH peroxidation stage marker was increased by 30%. The studied OS parameters were not influenced by sex or age. Our study introduces LOOH, PrTBARS, and PrMDA as markers for evaluating OS in children and adolescents with obesity. LOOH, PrTBARS, and PrMDA may also hold promise as prognostic markers for potential obesity-associated long-term complications.

Maternal and perinatal outcomes in twin pregnancies following assisted reproduction: a systematic review and meta-analysis involving 802 462 pregnancies.

BACKGROUND: ART is associated with higher rates of twin pregnancies than singleton pregnancies. Whether twin pregnancies conceived following ART have additional maternal and neonatal complications compared with non-ART twin pregnancies is not known. OBJECTIVE AND RATIONALE: The objective was to quantify the risk of adverse maternal and perinatal outcomes among twin pregnancies conceived following ART compared with non-ART and natural conception. Existing reviews vary in the reported outcomes, with many studies including triplet pregnancies in the study population. Therefore, we aimed to perform an up-to-date review with an in-depth analysis of maternal and perinatal outcomes limited to twin pregnancies. SEARCH METHODS: We searched electronic databases MEDLINE and EMBASE from January 1990 to May 2023 without language restrictions. All cohort studies reporting maternal and perinatal outcomes following ART compared with non-ART twin pregnancies and natural conception were included. Case-control studies, case reports, case series, animal studies, and in vitro studies were excluded. The Newcastle-Ottawa Scale was used to assess the methodological quality of the studies. Using random-effects meta-analysis, the estimates were pooled and the findings were reported as odds ratios (OR) with 95% CI. OUTCOMES: We included 111 studies (802 462 pregnancies). Twin pregnancies conceived following ART were at higher risk of preterm birth at <34 weeks (OR 1.33, 95% CI 1.14-1.56, 29 studies, I2 = 73%), <37 weeks (OR 1.26, 95% CI 1.19-1.33, 70 studies, I2 = 76%), hypertensive disorders in pregnancy (OR 1.29, 95% CI 1.14-1.46, 59 studies, I2 = 87%), gestational diabetes mellitus (OR 1.61, 95% CI 1.48-1.75, 51 studies, I2 = 65%), and caesarean delivery (OR 1.80, 95% CI 1.65-1.97, 70 studies, I2 = 89%) compared with non-ART twins. The risks for the above maternal outcomes were also increased in the ART group compared with natural conception. Of the perinatal outcomes, ART twins were at significantly increased risk of congenital malformations (OR 1.17, 95% CI 1.05-1.30, 39 studies, I2 = 59%), birthweight discordance (>25% (OR 1.31, 95% CI 1.05-1.63, 7 studies, I2 = 0%)), respiratory distress syndrome (OR 1.32, 95% CI 1.09-1.60, 16 studies, I2 = 61%), and neonatal intensive care unit admission (OR 1.24, 95% CI 1.14-1.35, 32 studies, I2 = 87%) compared with non-ART twins. When comparing ART with natural conception, the risk of respiratory distress syndrome, intensive care admissions, and birthweight discordance >25% was higher among the ART group. Perinatal complications, such as stillbirth (OR 0.83, 95% CI 0.70-0.99, 33 studies, I2 = 49%), small for gestational age <10th centile (OR 0.90, 95% CI 0.85-0.95, 26 studies, I2 = 36%), and twin-twin transfusion syndrome (OR 0.45, 95% CI 0.25-0.82, 9 studies, I2 = 25%), were reduced in twin pregnancies conceived with ART versus those without ART. The above perinatal complications were also fewer amongst the ART group than natural conception. WIDER IMPLICATIONS: ART twin pregnancies are associated with higher maternal complications than non-ART pregnancies and natural conception, with varied perinatal outcomes. Women seeking ART should be counselled about the increased risks of ART twin pregnancies and should be closely monitored in pregnancy for complications. We recommend exercising caution when interpreting the study findings owing to the study's limitations.

Acute Antiplatelet Effects of an Oleocanthal-Rich Olive Oil in Type II Diabetic Patients: A Postprandial Study.

Postprandial dysmetabolism is a common entity of type 2 diabetes mellitus (T2DM) and may act as a daily stressor of the already dysfunctional diabetic platelets. This study aims to investigate whether oleocanthal-rich olive oils (OO), incorporated into a carbohydrate-rich meal, can affect postprandial dysmetabolism and platelet aggregation. Oleocanthal is a cyclooxygenase inhibitor with putative antiplatelet properties. In this randomized, single-blinded, crossover study, ten T2DM patients consumed five isocaloric meals containing 120 g white bread combined with: (i) 39 g butter, (ii) 39 g butter and 400 mg ibuprofen, (iii) 40 mL OO (phenolic content < 10 mg/Kg), (iv) 40 mL OO with 250 mg/Kg oleocanthal and (v) 40 mL OO with 500 mg/Kg oleocanthal. Metabolic markers along with ex vivo ADP- and thrombin receptor-activating peptide (TRAP)-induced platelet aggregation were measured before and for 4 h after the meals. The glycemic and lipidemic response was similar between meals. However, a sustained (90-240 min) dose-dependent reduction in platelets' sensitivity to both ADP (50-100%) and TRAP (20-50%) was observed after the oleocanthal meals in comparison to OO or butter meals. The antiplatelet effect of the OO containing 500 mg/Kg oleocanthal was comparable to that of the ibuprofen meal. In conclusion, the consumption of meals containing oleocanthal-rich OO can reduce platelet activity during the postprandial period, irrespective of postprandial hyperglycemia and lipidemia.

Ametropia detection using a novel, compact wavefront autorefractor.

INTRODUCTION: Despite the well-known reproducibility issues of subjective refraction, most studies evaluating autorefractors compared differences between the device and subjective refraction. This work evaluated the performance of a novel handheld Hartmann-Shack-based autorefractor using an alternative protocol, which considered the inherent variability of subjective refraction. METHODS: Participants underwent an initial measurement with a desktop autorefractor, two subjective refractions (SR1 and SR2) and a final measurement with the QuickSee Free (QSFree) portable autorefractor. Autorefractor performance was evaluated by comparing the differences between the QSFree and each of the subjective refractions with the difference between the subjective refractions (SR1 vs. SR2) using Bland-Altman analysis and percentage of agreement. RESULTS: A total of 75 subjects (53 ± 14 years) were enrolled in the study. The average difference in the absolute spherical equivalent (M) between the QSFree and the SR1 and SR2 was ±0.24 and ±0.02 D, respectively, that is, very similar or smaller than the SR1 versus SR2 difference (±0.26 D). Average differences in astigmatic components were found to be negligible. The results demonstrate that differences between QSFree and both subjective refractions in J0 and J45 were within ±0.50 D for at least 96% of the measurements. The limits of agreement (LOAs) of the differences between QSFree and SR1, as well as QSFree and SR2, were higher than those observed between SR1 and SR2 for M, J0 and J45 . CONCLUSIONS: A protocol was designed and validated for the evaluation of a refractive device to account for the variability of subjective refraction. This protocol was used to evaluate a novel portable autorefractor and observed a smaller difference between the device and subjective refractions than the difference between the two subjective refraction measurements in terms of mean bias error, although the standard deviation was higher.

The Response of Antioxidant Enzymes and Antiapoptotic Markers to an Oral Glucose Tolerance Test (OGTT) in Children and Adolescents with Excess Body Weight.

Oxidative stress and apoptosis are involved in the pathogenesis of obesity-related diseases. This observational study investigates the antioxidant and apoptotic markers response to an oral glucose tolerance test (OGTT) in a population of overweight children and adolescents, with normal (NGT) or impaired glucose tolerance (IGT). Glucose, insulin, and C-peptide concentrations, as well as oxidative stress (SOD, GPx3) and apoptotic markers (Apo1fas, cck18), were determined at T = 0, 30, 60, 90, 120, and 180 min after glucose intake during OGTT. The lipid profile, thyroid function, insulin-like growth factor1, leptin, ghrelin, and adiponectin were also measured at baseline. The 45 participants, with a mean age of 12.15 (±2.3) years old, were divided into two subcategories: those with NGΤ (n = 31) and those with IGT (n = 14). The area under the curve (AUC) of glucose, insulin, and C-peptide was greater in children with IGT; however, only glucose differences were statistically significant. SOD and GPx3 levels were higher at all time points in the IGT children. Apo1fas and cck18 levels were higher in the NGT children at most time points, whereas Adiponectin was lower in the IGT group. Glucose increased during an OGTT accompanied by a simultaneous increase in antioxidant factors, which may reflect a compensatory mechanism against the impending increase in oxidative stress in children with IGT.

Lipid Disturbances in Breast Cancer Patients during Chemotherapy.

Breast cancer is the most common cancer in women. Cardiovascular diseases are common complications after chemotherapy due to the effect of the drug on lipid levels. This study aimed to explore the changes in lipid profiles in patients with breast cancer under chemotherapy. METHODS: In this prospective study, 50 patients with breast cancer participated. Three biochemical-lipid hematological tests were performed: total cholesterol (TC), triglycerides (TGs), High-Density Lipoprotein (HDL-C), and Low-Density Lipoprotein (LDL-C) before initiation (pre-chemotherapy), at the start (first follow-up), and at the completion (second follow-up) of the first cycle of chemotherapy. Statistical significance was set at p < 0.05. Analyses were conducted using SPSS Statistical Software (version 22.0). RESULTS: Mean TC values increased significantly at second follow-up. TGs values decreased significantly from first to second follow-up. HDL-C was significantly lower at first follow-up compared with pre-chemotherapy and was similar to the pre-chemotherapy levels at second follow-up. LDL-C values were significantly higher at second follow-up compared with pre-chemotherapy measurement. Significantly positive correlations of BMI with pre-chemotherapy LDL-C, first follow-up TC, first follow-up LDL-C, second follow-up TC, and second follow-up LDL-C were found. CONCLUSIONS: There is a statistically significant increase in the levels of TC and LDL-C in breast cancer patients during chemotherapy. This study was not registered.

Treatments for alopecia areata: a network meta-analysis.

BACKGROUND: Alopecia areata is an autoimmune disease leading to nonscarring hair loss on the scalp or body. There are different treatments including immunosuppressants, hair growth stimulants, and contact immunotherapy. OBJECTIVES: To assess the benefits and harms of the treatments for alopecia areata (AA), alopecia totalis (AT), and alopecia universalis (AU) in children and adults. SEARCH METHODS: The Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov and WHO ICTRP were searched up to July 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated classical immunosuppressants, biologics, small molecule inhibitors, contact immunotherapy, hair growth stimulants, and other therapies in paediatric and adult populations with AA. DATA COLLECTION AND ANALYSIS: We used the standard procedures expected by Cochrane including assessment of risks of bias using RoB2 and the certainty of the evidence using GRADE. The primary outcomes were short-term hair regrowth ≥ 75% (between 12 and 26 weeks of follow-up), and incidence of serious adverse events. The secondary outcomes were long-term hair regrowth ≥ 75% (greater than 26 weeks of follow-up) and health-related quality of life. We could not perform a network meta-analysis as very few trials compared the same treatments. We presented direct comparisons and made a narrative description of the findings. MAIN RESULTS: We included 63 studies that tested 47 different treatments in 4817 randomised participants. All trials used a parallel-group design except one that used a cross-over design. The mean sample size was 78 participants. All trials recruited outpatients from dermatology clinics. Participants were between 2 and 74 years old. The trials included patients with AA (n = 25), AT (n = 1), AU (n = 1), mixed cases (n = 31), and unclear types of alopecia (n = 4). Thirty-three out of 63 studies (52.3%) reported the proportion of participants achieving short-term hair regrowth ≥ 75% (between 12 and 26 weeks). Forty-seven studies (74.6%) reported serious adverse events and only one study (1.5%) reported health-related quality of life. Five studies (7.9%) reported the proportion of participants with long-term hair regrowth ≥ 75% (greater than 26 weeks). Amongst the variety of interventions found, we prioritised some groups of interventions for their relevance to clinical practice: systemic therapies (classical immunosuppressants, biologics, and small molecule inhibitors), and local therapies (intralesional corticosteroids, topical small molecule inhibitors, contact immunotherapy, hair growth stimulants and cryotherapy). Considering only the prioritised interventions, 14 studies from 12 comparisons reported short-term hair regrowth ≥ 75% and 22 studies from 10 comparisons reported serious adverse events (18 reported zero events and 4 reported at least one). One study (1 comparison) reported quality of life, and two studies (1 comparison) reported long-term hair regrowth ≥ 75%. For the main outcome of short-term hair regrowth ≥ 75%, the evidence is very uncertain about the effect of oral prednisolone or cyclosporine versus placebo (RR 4.68, 95% CI 0.57 to 38.27; 79 participants; 2 studies; very low-certainty evidence), intralesional betamethasone or triamcinolone versus placebo (RR 13.84, 95% CI 0.87 to 219.76; 231 participants; 1 study; very low-certainty evidence), oral ruxolitinib versus oral tofacitinib (RR 1.08, 95% CI 0.77 to 1.52; 80 participants; 1 study; very low-certainty evidence), diphencyprone or squaric acid dibutil ester versus placebo (RR 1.16, 95% CI 0.79 to 1.71; 99 participants; 1 study; very-low-certainty evidence), diphencyprone or squaric acid dibutyl ester versus topical minoxidil (RR 1.16, 95% CI 0.79 to 1.71; 99 participants; 1 study; very low-certainty evidence), diphencyprone plus topical minoxidil versus diphencyprone (RR 0.67, 95% CI 0.13 to 3.44; 30 participants; 1 study; very low-certainty evidence), topical minoxidil 1% and 2% versus placebo (RR 2.31, 95% CI 1.34 to 3.96; 202 participants; 2 studies; very low-certainty evidence) and cryotherapy versus fractional CO2 laser (RR 0.31, 95% CI 0.11 to 0.86; 80 participants; 1 study; very low-certainty evidence). The evidence suggests oral betamethasone may increase short-term hair regrowth ≥ 75% compared to prednisolone or azathioprine (RR 1.67, 95% CI 0.96 to 2.88; 80 participants; 2 studies; low-certainty evidence). There may be little to no difference between subcutaneous dupilumab and placebo in short-term hair regrowth ≥ 75% (RR 3.59, 95% CI 0.19 to 66.22; 60 participants; 1 study; low-certainty evidence) as well as between topical ruxolitinib and placebo (RR 5.00, 95% CI 0.25 to 100.89; 78 participants; 1 study; low-certainty evidence). However, baricitinib results in an increase in short-term hair regrowth ≥ 75% when compared to placebo (RR 7.54, 95% CI 3.90 to 14.58; 1200 participants; 2 studies; high-certainty evidence). For the incidence of serious adverse events, the evidence is very uncertain about the effect of topical ruxolitinib versus placebo (RR 0.33, 95% CI 0.01 to 7.94; 78 participants; 1 study; very low-certainty evidence). Baricitinib and apremilast may result in little to no difference in the incidence of serious adverse events versus placebo (RR 1.47, 95% CI 0.60 to 3.60; 1224 participants; 3 studies; low-certainty evidence). The same result is observed for subcutaneous dupilumab compared to placebo (RR 1.54, 95% CI 0.07 to 36.11; 60 participants; 1 study; low-certainty evidence). For health-related quality of life, the evidence is very uncertain about the effect of oral cyclosporine compared to placebo (MD 0.01, 95% CI -0.04 to 0.07; very low-certainty evidence). Baricitinib results in an increase in long-term hair regrowth ≥ 75% compared to placebo (RR 8.49, 95% CI 4.70 to 15.34; 1200 participants; 2 studies; high-certainty evidence). Regarding the risk of bias, the most relevant issues were the lack of details about randomisation and allocation concealment, the limited efforts to keep patients and assessors unaware of the assigned intervention, and losses to follow-up. AUTHORS' CONCLUSIONS: We found that treatment with baricitinib results in an increase in short- and long-term hair regrowth compared to placebo. Although we found inconclusive results for the risk of serious adverse effects with baricitinib, the reported small incidence of serious adverse events in the baricitinib arm should be balanced with the expected benefits. We also found that the impact of other treatments on hair regrowth is very uncertain. Evidence for health-related quality of life is still scant.

Relation of Mean Platelet Volume (MPV) with Cancer: A Systematic Review with a Focus on Disease Outcome on Twelve Types of Cancer.

Inflammatory proteins activate platelets, which have been observed to be directly related to cancer progression and development. The aim of this systematic review is to investigate the possible association between Mean Platelet Volume (MPV) and cancer (diagnostic capacity of MPV, relation to survival, the severity of the disease, and metastasis). A literature review was performed in the online database PubMed and Google Scholar for the period of 2010-2022. In total, 83 studies including 21,034 participants with 12 different types of cancer (i.e., gastric cancer, colon cancer, esophageal squamous cell carcinoma, renal cancer, breast cancer, ovarian cancer, endometrial cancer, thyroid cancer, lung cancer, bladder cancer, gallbladder cancer, and multiple myeloma) were identified. The role of MPV has been extensively investigated in several types of cancer, such as gastric, colon, breast, and lung cancer, while few data exist for other types, such as renal, gallbladder cancer, and multiple myeloma. Most studies in gastric, breast, endometrium, thyroid, and lung cancer documented an elevated MPV in cancer patients. Data were less clear-cut for esophageal, ovarian, and colon cancer, while reduced MPV was observed in renal cell carcinoma and gallbladder cancer. Several studies on colon cancer (4 out of 6) and fewer on lung cancer (4 out of 10) indicated an unfavorable role of increased MPV regarding mortality. As far as other cancer types are concerned, fewer studies were conducted. MPV can be used as a potential biomarker in cancer diagnosis and could be a useful tool for the optimization of treatment strategies. Possible underlying mechanisms between cancer and MPV are discussed. However, further studies are needed to elucidate the exact role of MPV in cancer progression and metastasis.

Contribution of Low CD4 Cell Counts and High Human Immunodeficiency Virus (HIV) Viral Load to the Efficacy of Preferred First-Line Antiretroviral Regimens for Treating HIV Infection: A Systematic Review and Meta-Analysis.

We assessed whether low CD4 count and high viral load (VL) affect the response to currently preferred ART. We performed a systematic review of randomized, controlled clinical trials that analyzed preferred first-line ART and a subgroup analysis by CD4 count (≤ or >200 CD4/µL) or VL (≤ or >100 000 copies/mL). We computed the odds ratio (OR) of treatment failure (TF) for each subgroup and individual treatment arm. Patients with ≤200 CD4 cells or VL ≥100 000 copies/mL showed an increased likelihood of TF at 48 weeks: OR, 1.94; 95% confidence interval (CI): 1.45-2.61 and OR, 1.75; 95% CI: 1.30-2.35, respectively. A similar increase in the risk of TF was observed at 96 weeks. There was no significant heterogeneity regarding integrase strand transfer inhibitor or nucleoside reverse transcriptase inhibitor backbone. Our results show that CD4 <200 cells/µL and VL ≥100,000 copies/mL impair ART efficacy in all preferred regimens.

Clustering of Activity-Related Behaviors in Relation to Self-Reported Causes of Stress among Pre-Adolescents: Results from a National Epidemiological Study.

An epidemiological study was conducted among 1728 10-12-year-old students (55.1% girls) and their parents during 2014-2016 in Greece. This study aimed to identify the dominant clusters of physical activity/sedentariness among preadolescents and investigate their association with self-reported sources of stress. Children's physical activity levels and sources of stress were evaluated using validated questionnaires that assessed daily hours of activities, both on weekdays and on weekends, including physical activity, screen-based sedentary time, and non-screen-based sedentary time. The k-means algorithm of cluster analysis was applied. Three clusters of children's physical activity/sedentariness were revealed. Cluster 1 was characterized as "Inactive-Non sedentary", cluster 2 as "Active -Non-screen sedentary", and cluster 3 as "Inactive-Sedentary". Parental needs/expectations were associated with physical activity patterns (p = 0.009), i.e., children assigned to the third and second clusters had 36% and 51% lower odds to be stressed due to parental requirements [(OR for cluster 3 = 0.64, 95% CI = 0.41-0.99), (OR for cluster 2 = 0.49, 95% CI = 0.32-0.76)], compared with their first-cluster counterparts. Considering the need to promote physical activity in early life stages, the identification of these complex activity-related patterns along with their significant interaction with parental expectations as a cause of stress could enhance the effectiveness of targeted behavior change interventions among those parent-child dyads most in need.

The Synergetic Effect of Soft Drinks and Sweet/Salty Snacks Consumption and the Moderating Role of Obesity on Preadolescents' Emotions and Behavior: A School-Based Epidemiological Study.

The consumption of ultra-processed foods (UPFs) is high along with the prevalence of emotional and behavioral problems among children and adolescents. The present study sought to investigate the synergetic effect of soft drinks and sweet/salty snacks consumption, and the moderating role of obesity on preadolescents' emotions and behavior. A cross-sectional study was conducted among 1728 Greek preadolescents aged 10-12 and their parents, during the school years 2014-2016. Parental and child characteristics were collected anonymously, through self-administered and validated questionnaires. Among others, soft drinks and sweet/salty snacks consumption was recorded, classifying preadolescents as low or at least moderate consumers, while anthropometric characteristics (height, weight, Body Mass Index (BMI)) were also recorded. Approximately 6 out of 10 preadolescents were characterized by at least moderate consumption of either sweet/salty snacks, or soft drinks, while 22.7% of the participants had at least moderate consumption of both soft drinks and sweet/salty snacks. Boys and preadolescents with a lower level of adherence to the Mediterranean diet, as well as those living in a more obesogenic family environment were more likely to be in the higher consumption groups. When compared to just either the moderate consumption of sweet/salty snacks, or the moderate consumption of soft drinks, the combination of both unhealthy eating habits was associated with significantly higher odds of both aggressiveness and loneliness, while the examined relationships were significantly stronger in overweight/obese children. The positive synergistic effect of soft drinks and sweet/salty snacks consumption on preadolescents' emotions of loneliness and aggressive behavior is even burdened by obesity status highlighting the urgent need for policymakers to take preventive measures to halt the detrimental consequences of UPFs consumption on health outcomes, particularly in overweight/obese children. The importance of the improvement of children's unhealthy eating habits by emphasizing the association between food intake and emotional and behavioral status is highlighted.

Association between Family and School Pressures, Consumption of Ultra-Processed Beverages, and Obesity in Preadolescents: A School-Based Epidemiological Study.

The aim of the present work was two-fold. Firstly, to evaluate the association between the consumption of ultra-processed beverages (UPB) on preadolescents' likelihood of being obese. Secondly, to investigate the potential impact of family and school environmental stressors on this unhealthy lifestyle habit. A cross-sectional study was conducted among 1718 Greek preadolescents and their parents, during the school years 2014 to 2016. Parental and child characteristics were collected anonymously, through self-administered and validated questionnaires. Among others, UPB consumption (soft and flavored drinks) was recorded, classifying children as low, moderate, or high consumers, while anthropometric characteristics [height, body weight, Body Mass Index (BMI)] were also recorded. Almost seven out of ten preadolescents were classified as at least moderate UPB consumers, while approximately three out of ten were classified as high UPB consumers. Higher UPB consumption was associated with significantly higher levels of BMI, while preadolescents living in a more stressful family and school environment were found to consume significantly higher amounts of UPB. Stakeholders should implement programs that raise awareness among parents and teachers about the sources of stress in preadolescence as a potential "triggering factor" of unhealthy dietary preferences.

The path between breakfast eating habit, sleep duration and physical activity on obesity status: An epidemiological study in schoolchildren.

Background: Although the literature suggests that skipping breakfast, insufficient sleep, and reduced physical activity are associated with childhood obesity their co-influence and their in-between interactions on weight status have rarely been studied. Aim: To examine the co-influence of breakfast eating habits, sleep duration, and physical activity on the weight status of children 10-12 years old from several schools of Greece. Methods: A cross-sectional study was conducted on 1688 students in Greece, during 2014-2016. Children's Body Mass Index (BMI) was calculated and classified according to the International Obesity Task Force (IOTF) classification. Logistic regression models and path analysis were used. Results: Overweight/obesity prevalence was higher in boys (32.5% vs. 20.4%; p < 0.001). Average sleep duration decreased the odds of overweight/obesity [OR (95% CI): 0.86 (0.76, 0.97)] independently of the frequency of breakfast habit. Interaction between sleep duration with breakfast habit (p = 0.002) and physical activity (p < 0.001) was observed. Path analysis showed a negative association of BMI with sleep duration (standardized beta = -0.095, p < 0.001). A third-order interaction between breakfast habit, sleep duration, and physical activity revealed that daily breakfast eating along with adequate sleep and moderate/adequate physical activity levels, decreased the odds of over-weight/obesity by 55% [OR 0.45, 95% CI (0.27, 0.72)]. Conclusion: Although sleep duration is inversely associated with weight status independently of breakfast habit, the co-influence of adequate sleep duration with frequent breakfast eating and moderate/adequate physical activity seems to be a profoundly higher associated as a result of synergy against childhood obesity.

Granulocyte-colony stimulating factor in acute-on-chronic liver failure: Systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: A dysfunctional immune response is key to the pathogenesis of acute-on-chronic liver failure (ACLF). It has been suggested that treatment with granulocyte colony-stimulating factor (G-CSF) increases survival in patients with ACLF by improving immune cell dysfunction and promoting liver regeneration. The aim of the study is to evaluate the survival benefit associated with G-CSF administration compared with standard medical therapy (SMT) in ACLF. METHODS: Systematic review and meta-analysis of randomized controlled trials. The primary outcome was survival at 60-90 days. We searched Ovid Medline, EMBASE, and Cochrane Central Register of Controlled Trials from inception to August 2021. Manual searches of reference lists in relevant articles and conference proceedings were also included. The revised Cochrane risk-of-bias tool was used for quality and risk of bias assessment. Two independent investigators extracted the data, and disagreements were solved by a third collaborator. RESULTS: The initial search identified 142 studies. Four randomized controlled trials were selected for quantitative analysis including 310 patients (154 G-CSF and 156 SMT). Significant heterogeneity was observed (I2=74%, Chi2=11.57, p=0.009). G-CSF administration did not improve survival in patients with ACLF (random-effects model, risk ratio=0.64 [95% CI 0.39, 1.07]). However, when considering only the results from the studies performed in Asia, a significant decrease on mortality was observed (risk ratio=0.53 [95% CI 0.35, 0.81]). Severity scores (MELD and Child) and CD34+ peripheral cells mobilization did not significantly improve with G-CSF. CONCLUSION: In a systematic review and meta-analysis, G-CSF administration did not significantly improve overall survival compared to SMT in patients with ACLF. The beneficial effects observed in Asian studies, as opposed to the European region, suggest that specific populations may benefit from further research aiming to identify certain subgroups with favourable outcomes when using G-CSF.

The Association of Junk Food Consumption with Preadolescents' Environmental Influences: A School-Based Epidemiological Study in Greece.

The aim of the present study was to evaluate the impact of environmental influences on Greek preadolescents' junk food consumption. A cross-sectional study, was conducted among 1718 preadolescents (mean (standard deviation(SD)) age: 11.2(0.8) years old; 54% girls) and their parents, during the school years 2014-2016. Parental and child characteristics were collected anonymously, through self-administered and validated questionnaires. Among others, junk food consumption was recorded, classifying children as low, moderate, and high consumers. The majority of the preadolescents were classified as at least moderate junk food consumers, while almost 3/10 children were classified as high junk food consumers. A significantly lower junk food consumption was observed among preadolescents with a healthier family environment, consisting of normal-weight parents who consume junk foods less frequently, prefer home-cooked meals and adhere more to the Mediterranean diet, while more frequent family meals were also associated with lower junk food consumption. In addition, influence from teachers and participation in extracurricular sports activities were significantly associated with lower junk food consumption, while advertisements were found to have a significant negative impact on preadolescents' eating habits. Notwithstanding, peers were not found to influence their dietary choices in terms of junk food consumption. Both parents and teachers seem to be positive influencers on preadolescents' low junk food consumption. The detrimental role of advertisements on junk food consumption is reconfirmed, while peers' influence is not significant on junk food consumption. The need for urgent public health initiatives for the promotion of healthy dietary habits among preadolescents is warranted.