Background: Hidradenitis suppurativa (HS) is a chronic, relapsing inflammatory skin disease that significantly affects the quality of life of patients. Multiple factors affect the disease's course and severity. HS is a debilitating disease and often recalcitrant to treatment, resulting in a deterioration of quality of life; hence, there is a need to evaluate the factors affecting the quality of life in patients with HS.Objectives: The objective of the study was to evaluate the various demographic and disease-related factors that affect the quality of life of patients with HS.Materials and methods: This is a prospectively scored questionnaire-based observational study. Data from 30 patients with HS were analyzed for the association of disease-related factors like Hurley’s staging, site, duration, past history, and comorbidities with the Dermatology Life Quality Index (DLQI).Results: A statistically significant relationship was found between DLQI and Hurley staging (p=0.000). The most common sites involved were the axilla and inguinal regions. Among the sites involved, the neck (p=0.002), abdomen (p=0.002), back (p=0.002), thighs (p=0.042), and gluteal (p=0.000) regions have a statistically significant association with DLQI. Prior histories of rheumatoid arthritis, scarring, surgery, lymphadenitis, and pilonidal sinus showed a statistically significant association with DLQI.Conclusion: The disease severity significantly hampers the quality of life of patients with HS. The disease site and presence of other comorbidities also influence the outcome. Our study will help healthcare providers better understand and fulfill the needs of patients suffering from HS. Hidradenitis suppurativa (HS), also called acne inversa, is a chronic relapsing inflammatory skin disease with different phenotypes and varied severity . The lesHS involves extensive areas. It manifests as difficulty in everyday activities due to pain, purulent discharge, and malodorous oozing, leading to social embarrassment and a significant impact on quality of life .There is a lacuna in the knowledge of this disease, resulting in delays in the correct diagnosis and management of patients because of a lack of specific diagnostic criteria. It is important to document the quality of life and damage caused by patients with HS, as in India, healthcare policy planning is patient-oriented .This study aims to improve knowledge pertaining to the risk factors for Hidradenitis suppurativa by correlating the demographic features, duration of disease, and comorbidities with the Hurley staging system. We also tried to find a correlation between the Dermatology Life Quality Index (DLQI) score and the Hurley staging system. Hurley's staging is as follows: stage 1 - the presence of abscesses with no sinus tracts and no cicatrisation; stage 2 - recurrent abscesses with tract formation and cicatrisation; and stage 3 - diffuse or near-diffuse involvement, multiple interconnected tracts, and abscesses across the entire area.This was a prospective study conducted in the dermatology outpatient department of Dr. D. Y. Patil Hospital, Navi Mumbai, Maharashtra, India. We initiated the study after receiving approval from the Institutional Ethics Committee for Biomedical and Health Research (Reference no. DYP/IECBH/2022/009).Thirty patients with HS were included in the study after confirmation of the clinical diagnosis by a dermatologist. The data collected from the individual subject were demographic details like age, gender, height, weight, and body mass index (BMI); disease details like disease duration, site, number, and morphology of the lesions; Hurley's staging system; and the DLQI. DLQI was assessed by subjecting the patients to a questionnaire via a physician-assisted interview after taking their informed consent. DLQI consists of 10 questions. It is a simple and validated questionnaire used to report the impact of the dermatological condition on the quality of life of the patients over the last week, as shown in Table Statistical analysisStatistical analysis was done using IBM SPSS Statistics v 26 . The Mann-Whitney u test or student’s t-test were used to evaluate quantitative variables depending on their non-parametric or parametric distribution, respectively. For evaluating qualitative data and the association between the variables, the chi-squared test and Spearman’s test were used, respectively. The difference in total DLQI between patients with different HS severity levels according to Hurley stages was assessed using the Kruskal-Wallis one-way analysis test. A P-value of ≤ 0.05 was considered statistically significant.The study included 30 patients with Hidradenitis suppurativa ranging in age from 18 to 63 years old. The demographic details of the patients are presented in Table A statistically significant relationship was found between DLQI and Hurley staging (p = 0.000), indicating decreased quality of life with increasing severity of disease, supporting the finding. Lesions were most commonly located at the axilla and inguinal regions, but no significant correlation was seen with DLQI. Among the sites involved, the neck (p=0.002), abdomen (p=0.002), back (p=0.002), thighs (p=0.042) and gluteal (p=0.000) regions have a statistically significant association with DLQI. Prior history of rheumatoid arthritis (p=0.002), scar (p=0.042), surgery (p=0.042), lymphadenitis (p=0.002), and pilonidal sinus (p=0.002) showed statistically significant association with DLQI.Out of the total of 30 patients with HS, 17 (56.7%) were males, which confirms the male preponderance of the disease. This finding may be different from those reported by previous studies due to the smaller sample size in our study ,9. The mA statistically significant relationship was found between DLQI and Hurley staging (p = 0.000), indicating the decreasing quality of life with increasing severity of the disease, supporting the findings of Afsaneh et al. and Vassiliki et al. ,11. AmonInterestingly, no significant correlation was found between DLQI and demographic parameters like age, gender, weight, or body mass index supporting the fact that the intensity of disease plays a major role in the impairment of quality of life, unlike the findings in the study done by Krajewski et al. . No corrWhen compared to other chronic skin diseases, the DLQI of HS was found to be higher than most skin disorders like psoriasis, lichen planus, bullous pemphigoid, and vitiligo ,13. HidrA major limitation of our study was the small sample size, which can result in varied outcomes of statistical analysis that do not correlate with the results of previous studies. We suggest considering variables like type and duration of treatment to be included in future studies as they can significantly affect the DLQI of HS patients.Hidradenitis suppurativa is a chronic, debilitating skin condition. Our study shows a significant impairment in the mental and physical quality of life of patients suffering from the disease. We are in need of novel and improved treatment modalities for the treatment of HS to reduce the burden of the disease. We suggest a holistic approach to the treatment of HS patients, which should include psychological counseling along with exploring all possible treatment options, including biologics, according to individual patient needs.


Cardiovascular diseases are the common cause of death in patients with idiopathic inflammatory myopathies (IIMs). Diabetes mellitus was associated with higher cardiovascular mortality, but few studies focused on the risk of diabetes mellitus in IIMs patients. Our study is aimed at developing a predictive model of diabetes mellitus in IIMs patients.A total of 354 patients were included in this study, of whom 35 (9.9%) were diagnosed as new-onset diabetes mellitus. The predictive nomogram was drawn based on the features selected by least absolute shrinkage and selection operator (LASSO) regression, univariate logistic regression, multivariable logistic regression, and clinical relationship. The discriminative capacity of the nomogram was assessed by C-index, calibration plot, and clinical usefulness. The predictive model was verified by the bootstrapping validation.The nomogram mainly included predictors such as age, gender, hypertension, uric acid, and serum creatinine. This predictive model demonstrated good discrimination and calibration in primary cohort  and validation cohort (C-index=0.725). Decision curve analysis indicated that this predictive model was clinically useful.Clinicians can assess the risk of diabetes mellitus in IIMs patients by using this prediction model, and preventive measures should be taken early for high-risk patients, ultimately reducing the adverse cardiovascular prognosis. Numer 0.0001) . In addi 0.0001) . TherefoTo data, some models and clinical nomograms have been developed to predict the incidence of diabetes mellitus, but most of them are focused on the general population and rarely involved in subjects with autoimmune diseases. As far as we know, no study has been conducted to predict the incidence of diabetes mellitus in IIMs patients. Hence, the purpose of the current study is to establish an effective prediction model for diabetes mellitus based on demographic and clinical features of IIMs patients.22.1We conducted a retrospective cohort study including patients with IIMs who underwent a regular follow-up at the Third People’s Hospital of Chengdu between January 2010 and December 2020. The diagnosis of IIMs was determined by experienced clinicians according to the criteria of Bohan and Peter . All parInformation, such as demographic characteristics, clinical manifestations, and drug administration, on each patient was collected through face-to-face interviews by trained physicians. After a 12-h fasting period, venous blood was collected in the morning from all subjects, and laboratory parameters were determined by using standard clinical laboratory techniques.2.2During the study period, a fasting plasma glucose (FPG) ≥7.0 mmol/L, and/or self-reported diabetes can be considered as new-onset diabetes . Plasma 2.3The patients’ data were recorded in electronic medical records system during routine clinical follow-up. Demographics, clinical manifestations, laboratory parameters, and drug administration were systematically extracted from electronic medical records. Data were collected by two trained graduate students and checked by an experienced clinician.2.4In the current study, the diagnosis of overlap syndrome was based on the American College of Rheumatology (ACR) criteria for SLE , RA 19)19) and s2.5https://www.R-project.org). A P-value of less than 0.1 (two-tailed) was considered statistically significant.All data mainly including baseline characteristics, clinical manifestations, laboratory parameters, and drug administration were expressed as count (%) or mean ± SD. All statistical analyses were conducted by using the R software  regression was a punitive regression method, which estimated the regression coefficient by maximizing the logarithmic likelihood function and limited the sum of the absolute values of the regression coefficients . And theThe nomogram was utilized to show the risk prediction model of new-onset diabetes mellitus in patients with IIMs. The prediction model was validated from three aspects: discrimination ability, calibration ability, and clinical usefulness. Harrell’s C-index was used to evaluate the predictive accuracy of the nomogram . The C-i33.1A total of 354 IIMs patients met the inclusion criteria for this study, with the mean age of 48 years (range: 18-82 years), of whom 67.2% were female. This cohort consisted of 95 patients with polymyositis, 247 patients with dermatomyositis, and 12 patients with inclusion body myositis. The median follow-up time in the current study was 6 months (ranging from 1 to 120 months). There were 35 out of 354 patients  who developed diabetes mellitus, with the mean age of 55 years (range: 20-76 years). The mean of baseline FPG of the included subjects was 4.72 ± 0.77 mmol/L, and there was no statistical difference in FPG between patients with or without diabetes mellitus (4.87 ± 0.73 mmol/L vs. 4.70 ± 0.78 mmol/L). The detailed characteristics of patients with IIMs were presented in 3.2The LASSO regression model was applied to select the most optimal predictive features. In this study, there were 35 variables for LASSO logistic regression analysis, and 7 of them had nonzero coefficients Figure 13.3As shown in 3.4The calibration curve of the prediction diabetes mellitus nomogram in these patients presented good calibration Figure 34Cardiac involvement in patients with IIMs was mostly atypical and seldom attracted the attention of clinicians. However, increasing amounts of data demonstrated that cardiovascular events were the common cause of death in IIMs. Early identification and control of cardiovascular risk factors can reduce mortality and improve the quality of life in IIMs patients. Diabetes mellitus was an indispensable risk factor for cardiovascular diseases, so it was greatly significant to identify the risk of diabetes mellitus in patients with IIMs. As a tool to evaluate the risk and prognosis of disease, nomogram has been paid more attention and applied in medical research and clinical practice. To the best of our knowledge, our study was the first to provide a relatively accurate prediction model of diabetes mellitus in patients with IIMs based on generally available clinical features. Nomogram illustrated that older age, male, hypertension, low levels of UA and Scr were more likely to develop diabetes mellitus in patients with IIMs. The C-index of the constructed nomogram and the internal validation was up to 0.762 and 0.725, respectively, which demonstrated that this predictive model had adequate discrimination and calibration. Furthermore, the decision curve analysis indicated this nomogram also had good clinical usefulness. Therefore, we think that clinicians can assess the risk of diabetes mellitus in IIMs patients by referring to this prediction model. For high-risk patients, preventive measures should be taken as soon as possible to reduce or delay the occurrence of diabetes mellitus.The findings of our study were consistent with those of previous studies in other CTD or general population. For example, age and gender were considered to be important risk factors for diabetes mellitus, and the risk of diabetes mellitus increased with age. Similarly, a cross-sectional study demonstrated that the prevalence of diabetes mellitus increased with age, and subjects aged 60 years or older and aged 44-59 years had 2.35-fold and 2.77-fold increased risk of diabetes mellitus compared to subjects younger than 44 years, respectively . It may There are currently no studies on diabetes risk prediction models in connective tissue diseases; But in recent years, multivariate risk scores have been developed to predict the risk of diabetes in healthy individuals and most risk scores contain typical diabetes risk factors such as age, gender, degree of obesity, family history of diabetes and blood pressure status –50. In tThere are some limitations to this study that are worth mentioning. First, our study is a retrospective study in which individuals with incomplete data are exclude, which may lead to selection bias. Second, although this study includes a wide range of potential predictors, there are other factors that cannot be acquired, such as drinking status, family history of diabetes, and the dosage of drugs, etc, which may lead to the limited prediction power of the model. Third, the sample size of this cohort is relatively small and it is not representative of all Chinese patients with IIMs. Nonetheless, as far as we know, this is the largest prediction model focused on diabetes mellitus in autoimmune diseases. Fourth, the prediction model is not validated externally. Therefore, more prospective studies are needed to further confirm the current results and make it universally applicable.In conclusion, we have established a relatively accurate and simple nomogram based on five risk factors, namely age, male, hypertension, hypouricemia, and low serum creatinine, to predict the risk of developing diabetes mellitus in IIMs patients. Clinicians and patients can take more necessary measures early to reduce the incidence of diabetes mellitus for high-risk patients.The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethic Committee of the Third People’s Hospital of Chengdu (2019 S-20) on 20 March 2021. The patients/participants provided their written informed consent to participate in this study.QN and LQ performed the study design and wrote the manuscript. QN, WY and QL performed data collection and analysis. LQ and TY conducted validation and formal analysis. HW and JW substantially revised, commented on and approved the final manuscript. All authors contributed to the article and approved the submitted version.


At the second week evaluation, patients treated with steroids showed significant improvement compared to patients treated with PRP and autologous blood (p < 0.001). The fourth-week evaluation revealed the VAS, DASH, and Nirschl scores of the patients treated with steroids to have improved more significantly than those of patients treated with PRP and autologous blood (p < 0.001). The third month, when the results of all three groups were compared, revealed similar results (p > 0.050). The sixth-month evaluation, when the results of all three groups were compared, revealed the autologous blood and PRP applications provided significantly better results than the group treated with steroids (p < 0.001). Conclusion: We concluded that steroid administration is effective in the short term, while PRP and autologous blood applications are more effective than steroid administration in the long term.Background: The aim of our study is to compare the efficacy of PRP, steroids, and autologous blood injection in patients with chronic lateral epicondylitis. Method: A total of 120 patients comprised our study. Three groups of 40 patients each received only one of the following: PRP, steroids, or autologous blood injections. Thereafter, VAS , DASH , and Nirschl scores of those treated were evaluated in the second week, the fourth week, the third month, and the sixth month. Results: The baseline evaluation revealed no significant change in VAS, DASH, and Nirschl scores among the three groups ( Lateral epicondylitis, also known as tennis elbow, is a clinical condition seen in approximately 1–3% of the population. The disease usually affects individuals between the ages of 35 and 50 . The undMany different treatment methods have been described in the treatment of lateral epicondylitis. Activity modification, NSAID use, bracing, extracorporeal shock wave therapy, YAG laser treatment, and acupuncture are among the treatment options. Manual therapy, TECAR therapy, ultrasound and TENS applications, and exercises  can also be counted. Botulinum toxin, PRP, steroids, and autologous whole-blood injections are also frequently used in lateral epicondylitis . DespiteOur retrospective study scanned our hospital information management system to review cases originating between 2017 and 2020. Patients evidencing pain with pressure to the lateral epicondyle; pain with active wrist extension against resistance in forearm pronation; pain with full elbow extension; and a diagnosis of lateral epicondylitis were evaluated for inclusion in the study. Patients admitted to our hospital with a diagnosis of lateral epicondylitis whose complaints did not improve despite traditional treatments  and who had undergone elbow injections for lateral epicondylitis were included in the study, as were patients who were examined, followed up, and treated by a single clinician. Where files contained incomplete or suspicious data, patients were telephoned to confirm their occupation, dominant arm, and affected arm.Criteria for inclusion in the study included patients who were followed up for three months with traditional treatment methods ; patients whose complaints did not resolve after treatment; patients who were 17 years of age or older and had direct radiographs and no pathologies ; and patients who attended the polyclinic controls on the fifteenth day, fourth week, third month, and sixth month and for whom no other treatment occurred during these follow-ups. Criteria for exclusion from the study included patients with a history of acute elbow trauma; diagnosis of systemic diseases such as rheumatoid arthritis, DM (diabetes mellitus), hepatitis, anemia, and bleeding disorders; patients who must use anticoagulant or antiaggregant treatment; patients with severe weight change in the last year ; patients with a history of malignancy, pregnancy, previous elbow fractures, epilepsy, or cervical radiculopathy; patients with a history of elbow surgery; patients with an elbow injection history in the last six months; patients with additional pathologies in the elbow (such as pin neuropathy); patients with diagnosed psychiatric disorders; patients lacking necessary data in the patient file for the study; and patients unable to communicate.The minimum number of patients to be included in the study groups was determined through power analysis. Afterward, the patients were divided into subgroups by making stratified sampling according to gender from the determined patient group pools.With the patients’ elbows flexed at 90 degrees, 2 mL autologous whole blood + 1 mL prilocaine hydrochloride (20 mg/mL), 2 mL prilocaine hydrochloride (20 mg/mL) + 1 mL betamethasone , or 2 mL PRP + 1 mL prilocaine hydrochloride (20 mg/mL) were applied with the help of 21 G injector to the area with the most pain on the lateral epicondyle using the technique of peppering. Afterward, patients in all groups were advised to rest their elbows the first day after injection, to adhere to immobilization with a shoulder arm sling, to avoid anti-inflammatory drugs other than paracetamol the first two weeks after injection, to avoid cold or hot application, and to avoid anticoagulant and anti-aggregate drugs during the follow-up. The patients were warned during the follow-up against making additional injections to the elbow area. Control polyclinic data of the patients were evaluated on the fifteenth day, fourth week, third month, and sixth month. VAS, DASH, Nirschl  scores, and clinical results were evaluated in the pre- and post-injection follow-ups.2 Ca for 1 mL PRP) was applied by palpation under sterile conditions to the most sensitive point in the lateral epicondyle area at the elbow.Preparation and administration of platelet-rich plasma were performed in all patients under the same conditions, according to the method described by Anitua et al. ,9. A totFor autologous blood injection, 2 mL of venous blood taken from the other upper extremity of the patient was mixed with 1 mL of prilocaine hydrochloride (20 mg/mL) and made ready for injection.t-test was used to compare the measurements at two-time points. The Statistical significance level was accepted as p < 0.001.Statistical analysis was performed using SPSS software . The conformity of the numerical variables to the normal distribution was performed using visual (histogram and probability graphs) and analytical methods (Kolmogorov-Smirnov/Shapiro-Wilk tests). The descriptive statistics for numerical variables showing normal distribution in the comparisons were given by mean and standard deviation. Descriptive statistics of categorical variables were given by numbers and percentage values. One-way ANOVA was used to compare the parameters, and Paired Student’s Clinical research ethics committee approval was obtained for this study. The ethics committee number is E-10879717-050.01.04-2580.p > 0.050)    .Analysis of the samples of all the patients undergoing PRP showed that the platelet count of the applied PRP content was at least 2.5 times higher than the number of platelets in the peripheral blood, and the platelet count of the applied PRP content was above 300,000 platelets/μL ,10.p > 0.050)  .p > 0.050). Day zero and day 15 comparison of the VAS, DASH, and Nirschl scores of patients undergoing autologous blood injection showed no significant change (p > 0.050). Day zero and day 15 comparison of the VAS, DASH and Nirschl scores of the patients undergoing steroid application showed a significant decrease (p < 0.001). Day 15 comparison of the VAS, DASH, and Nirschl scores of the patients treated with steroids, as well as the patients treated with PRP and autologous blood injection, showed a significant improvement (p < 0.001).In the statistical evaluation, when the VAS, DASH, and Nirschl scores of the patients who underwent PRP were compared on day zero and day 15, no significant change was found (p < 0.001). In patients who underwent autologous blood injection, a significant decrease in DASH score (p < 0.001), a significant decrease in VAS score (p < 0.001), and the same Nirschl score (p > 0.050) were found. In patients treated with steroids, a significant decrease in DASH score (p < 0.001), a significant decrease in VAS score (p < 0.001), and a significant decrease in the Nirschl score (p < 0.001) were found. At the fourth week evaluation, patients who received steroids showed a significantly greater improvement in VAS, DASH, and Nirschl scores compared to the scores of the patients undergoing PRP and autologous blood injections (p < 0.001).When Day 15 and Week Four values were compared, a significant decrease in the DASH score, a significant decrease in the VAS score, and a significant decrease in the Nirschl score were found in patients who underwent PRP (p < 0.001), a significant decrease in the VAS score (p < 0.001), and a significant decrease in the Nirschl score (p < 0.001) were found in patients who underwent PRP. In patients undergoing autologous blood injection, a significant decrease in DASH score (p < 0.001), a significant decrease in the VAS score (p < 0.001), and a significant decrease in the Nirschl score (p < 0.001) were found. In patients treated with steroids, there was a significant increase in the VAS score (p < 0.001) and a significant increase in the Nirschl score (p < 0.001), but the DASH score was the same (p > 0.050). Similar results were obtained when the results of all three groups were compared (p > 0.050).When the scores of the fourth week and the third month were compared, a significant decrease in the DASH score (p < 0.001), a significant decrease in the VAS score (p < 0.001), and a significant decrease in the Nirschl score (p < 0.001) in patients who underwent PRP. A significant decrease in the DASH score (p < 0.001), a significant decrease in the VAS score (p < 0.001), and a significant decrease in the Nirschl score (p < 0.001) were seen in patients who underwent autologous blood injections. A significant increase in the DASH score (p < 0.001), a significant increase in the VAS score (p < 0.001), and the same values in the Nirschl score (p > 0.05) were seen in patients treated with steroids. A comparison of the results of the three groups at the sixth-month evaluation determined that the autologous blood and PRP administrations resulted in significantly better outcomes than the steroid-applied group (p < 0.001). No local or systemic complications were observed in any of the patients during the application and follow-up.A comparison of the values of the third month and the sixth month showed a significant decrease in the DASH score (Our study examined the VAS, DASH, and Nirschl scores of patients diagnosed with lateral epicondylitis who received autologous blood, PRP, and steroid injections to their elbow area and who were followed up on the fifteenth day, in the fourth week, third month, and sixth month after injection. According to the results of our study, although there was a significant early regression in the complaints of patients treated with steroids, the severity of complaints increased in the fourth week, and the complaints recurred during the six-month follow-up evaluation. In contrast, there was no early improvement in complaints with PRP and autologous blood injection, and gradual improvement was observed in patients’ complaints after the fourth week .In the treatment of lateral epicondylitis, activity modification, ice application, and non-steroid medication can be used. There are also treatment methods such as steroid, PRP, and autologous blood injection to the elbow area. Though previously considered to be the gold standard of treatment, steroid injection is now controversial . In a raRecent histological findings have shown that tendinosis is not an acute inflammatory condition but a pathology in which normal tendon repair fails. Researchers have thus turned to biological treatment methods such as autologous whole blood injection and PRP application . VariousUnlike corticosteroids, PRP and autologous blood injections aim to trigger inflammation rather than suppress it ,24,25. PThe limiting factors of our study are the lack of histopathological and radiological examinations; the use of data belonging to a single center and to people living in a single region; the lack of a standard treatment protocol surrounding dose, frequency, and number of PRP injection applications in the literature; and the limitation of patient follow-up past six months.Although PRP and autologous blood injections are not as effective as steroid injections in the short term, they are more effective in the long-term treatment of lateral epicondylitis. Performing these treatments with autologous biological agents increases the trust people place in these treatments, but the low density of platelets in autologous blood compared to PRP decreases its effectiveness; the use of special devices and the time and costs required to prepare PRP can also be counted among its disadvantages. In order to obtain a standard treatment protocol for lateral epicondylitis, studies with longer follow-up periods and clinical, radiological, and histopathological evaluations are needed in large patient groups.


Throughout the intervention, the PEDAL students pedaled 4 days a week for 10 weeks during their Spanish-language arts lessons. The comparisons between the PEDAL group and the control group, as well as the pre- and post-test results, were statistically analyzed to verify the students’ physical activity , cardiorespiratory capacity (20 m shuttle run test), and academic performance (d2 test of attention and language proficiency test). Regarding the physical aspect, only the PEDAL group showed significant growth in their physical activity levels as compared to the pre-test data (p = 0.001), and they achieved higher results compared with the control group (p = 0.022) and less sedentary time than control students (p = 0.012). Concerning cardiorespiratory fitness, there were no post-test differences between the two groups (p = 0.697), probably because the physical activity performed with the bike desks was light–moderate. As far as academic performance is concerned, no significant post-test effects were discovered in either group on the levels of language competence (p = 0.48), attention , and concentration . In conclusion, adolescents who move while learning, using bike desks, increase their light and moderate physical activity without any detriment to academic performance.The aim of this study was to assess the effects of a classroom-based physical activity program, using bike desks, on academic and physical performance in adolescents. The Program to Enhance and Develop Active Lessons (PEDAL) was designed for this purpose, expecting an increase in students’ physical activity without any decrease in academic performance. This intervention based on pedal or bike desks—stationary bikes that integrate with a desk workspace—was conducted with 55 high- school students who were randomly assigned to two groups: a PEDAL group ( Globally, the levels of overweight and obesity in children and adolescents are showing a rising trend , and an This paper compiles the physical and academic outcomes discovered after the implementation of the Program to Enhance and Develop Active Lessons (PEDAL), a physical activity intervention. This program is based on physically active learning (PAL), an opportunity for learning combined with movement within the school day . There aActive desks can also be called active workstations, fit desks, or dynamic seating devices, and they are a way to learn academic content while moving. There are different types of active desks, including standing desks, balance desks, stepper desks, strider desks, treadmill desks, fitballs, wobble chairs, and bike desks. They all have in common a strategy to integrate different devices into the traditional school desk to practice physical activity.The PEDAL program analyzed the effects of bike desks during Spanish-language arts lessons. Only a few studies have implemented bike desks for secondary students in a real education context; most of them were conducted in the US . Concernn = 28, 14.86 ± 0.65 years old, 46.4% girls) and a control group . Data collection took place from October 2019 to December 2019. The study protocol passed the Review Committee for Research Involving Human Subjects evaluation from a renowned university and adhered to the Helsinki Declaration of 1961, revised in Fortaleza (Brazil) in 2013.A total of 60 students in their fourth year of secondary education were eligible for participation in the study. Due to the lack of financial support to provide PEDAL with more bike desks, and the organizational requirements of the school, the program could only be implemented in two different classes. In this regard, it should be noted that previous experimental studies on bicycle desks with students have had similar sample sizes, with an average of 52.83 students . FinallyTM  bike desks. Neither the PEDAL nor the control group changed their usual language arts lessons in terms of dynamics and tasks; the only difference resided in the voluntary pedaling for PEDAL group students during the aforementioned lessons. They could choose individually the moments throughout the lesson to pedal, while listening, speaking, reading, or writing. Students in this intervention group collected their time and distance data as well as the resistance applied during the active lessons and recorded themin their logs. Moreover, within each group, 18 participants were asked to wear an HR monitor, the Polar OH1+ , throughout the entire school day for five academic days of the week, during four different assessment periods .Two classes participated in the study, both being randomly divided into two groups as previously mentioned. Both classes used an active-desk-enabled classroom during their language arts courses, equipped with 15 DeskCycle2The school day ran from 8:15 a.m. to 2:10 p.m. and was divided into 55-min blocks for each subject . In total, all the students, in both the control and the PEDAL groups, had 220 min of language arts per week.The PEDAL program was applied in 35 active lessons and it lasted 10 weeks. Before starting the study (familiarization stage) and during the 10th week of the intervention period, students were physically evaluated with a 20 m shuttle run test , a languCardiorespiratory fitness. This variable was assessed using a 20 m shuttle run test  in whichPhysical activity. The level of physical activity was measured using the International Physical Activity Questionnaire Short Form (IPAQ-SF) . This quLanguage competence. This was measured and evaluated using a regional test. The Community of Madrid (a region of Spain) has been using this test to assess secondary-school last-year students in language, math, and social and civic competence for several years. An official handbook to apply and correct this test is available (Resolución de 8 de marzo de 2019).Attention (TOT) and concentration (CON). These abilities were measured using the d2 Test of Attention . The parHeart rate (HR). The monitoring of HR was used to analyze the intensity of the physical activity performed. It is an objective method and, along with accelerometers, is the best way to detect and evaluate physical activity patterns in children and adolescents . The difPrior to the implementation of the PEDAL program, during the 2018–2019 school year, a pilot project was carried out in order to help students to become familiar with some of the instruments.p < 0.05. The descriptive characteristics of the sample were calculated. Normality was checked using the Kolmogorov–Smirnov test. The main analysis searched for differences in the following dependent variables: pedaling characteristics , physical conditions, language competences, and attention abilities (effectiveness and concentration), as well as analyzed physical activity variables (MET-minute/week and sedentary time) and HR, using an analysis of variance (ANOVA) of repeated measures. We compared the data based on the independent variables intervention group (PEDAL or control) and gender (boy or girl). Additionally, cardiorespiratory fitness, language competence, attention (effectiveness and concentration), physical activity, and changes in the amount of sedentary time were analyzed depending on their initial physical activity groups by an analysis of variance (ANOVA) of repeated measures, for the PEDAL group. The effect size was calculated using the partial eta-squared (ηp2) ratio of variance, and small, moderate, and large effects corresponded to values equal to or greater than 0.10, 0.25, and 0.40 [Statistical analyses were conducted using the SPSS software . The significance level was set at and 0.40 .p = 0.892), distance accomplished (p = 0.928), and applied resistance (p = 1.000).In every active lesson, students pedaled a mean of 33.82 ± 1.13 min, covering 13.12 ± 0.87 km (8.15 ± 0.54 miles), with a resistance of 2.84 ± 0.0.10. There were no significant differences between boys and girls in the PEDAL group in terms of the daily mean pedal time , time , and distance . The main effect of moment was observed for all pedaling assessments: resistance  but there was no double interaction between the moment and the group   see .2 = 0.150; F1,45 = 7.914; p = 0.007) and PEDAL METs , but not for PEDAL sedentary time , for the physical activity analysis. In addition, there was a significant interaction effect between the moment and the group in every physical activity aspect .As can be observed in 2 = 0.000; F1,46 = 1.000; p = 0.943) and no double interaction between moment and group  was found . However, there was no double interaction between moment and group .With respect to the evaluation of attention, the analysis revealed a main effect of moment for the PEDAL group . However, there was a significant difference between the pre-test HR data (LA) and Week 1 (p = 0.001) and Week 7 (p = 0.009). Moreover, regarding language, there was a significant interaction effect between the moment and the group for the HR (LA) , and the PEDAL group HR (LA) was higher than that of the control group during Week 1 (p = 0.016).p = 0.014) for only the girls from the PEDAL group  and from the HR of the control group . These differences were not found in the boys in the PEDAL group  and moderate-level (p < 0.001) groups . In regard to physical activity (METs), only that in the low subgroup significantly increased (p = 0.007). The high-level subgroup did not improve from the pre-test in any aspect beyond reducing their sedentary time (p = 0.049). Regarding academic performance and attention, non-remarkable differences were found. Finally, within the PEDAL analysis subgroups , there was a significant difference in onset between the physical activity performed by the high-level group and that in the low-level (oups see . PhysicaIt is crucial to increase children and adolescents’ physical activity to ameliorate the pandemic-induced inactivity and sedentarism, especially in certain groups of the population. The implementation of bike desks positively influenced students’ overall physical activity and reduced their sedentary time without compromising their academic performance. Therefore, it could be considered a good strategy to implement in schools.Regarding physical condition, both the PEDAL and the control group significantly improved their cardiorespiratory fitness but no significant differences between the groups were found at the end of the intervention. Since both groups improved their physical condition, it seemed to be due to the restart of physical education lessons and other active routines after the summer, during the first few months of the school year. Based on previous studies ,27, we wThe previously mentioned benefits in the reported physical activity were in favor of the PEDAL group. Only this group increased their physical activity levels and energy expenditure from the pre-test. Moreover, after the intervention, the PEDAL group registered significantly less sedentary time and more physical activity than the control group. Previous studies with active desks are in line with this result; they recorded less sedentary time for the intervention group during academic lessons  and in wAccording to the HR data analysis, during school-time, the statistics disclosed different intervention moments during active language lessons, where the HR was significantly higher in the PEDAL group than in the control group and higher than pre-intervention data from traditional lessons. The HR increase due to physical activity is positive in combating the health risks of a sedentary lifestyle, although the bike desks did not manage to achieve the MVPA, the recommended physical activity for children and adolescents’ health . Thus, aIn terms of academic performance, there were no effects on language competence, attention, and concentration since these variables were significantly better in both groups after the intervention, with no post-test differences between groups. This finding of no academic detriment agrees with earlier active desk studies  and bikeFurthermore, this is the first study disentangling the possible effects of bike desks in terms of gender and physical activity baseline levels. The lack of data collection regarding gender was a recurring limitation in previous bike desk studies in education . The hypFinally, the analysis appeared to confirm the hypothesis that adolescents with low activity levels could benefit more from the PEDAL intervention. In the same vein, several school interventions have found significant increases in step counts among children with low activity levels ,39.Like all research, this investigation has strengths as well as some limitations that must be taken into account when interpreting the results. Future investigations, with larger sample sizes, are necessary to analyze intervention effects in specific groups, and a more extended program could have revealed a wider range of benefits after the intervention. Moreover, the incorporation of different locations could allow for generalizability. Furthermore, the language competence test was not validated and some biometric variables, such as body mass and BMI, were not recorded, but both aspects could have conditioned the results obtained.Taking all of the limitations into account, future lines of research could check students’ long-term adherence to the PEDAL program and they could explore the effects according to the intensity of the physical activity performed using bike desks.In conclusion, the presented bike desk educational intervention is a feasible way to increase students’ daily light–moderate physical activity during school time, with no negative academic interference. A minor trend, which needs to be studied in depth, suggests that the intervention could impact certain subgroups of the population, such as girls and adolescents with low to moderate physical activity levels, who are usually difficult to reach.


Female genital mutilation/cutting (FGM/C), a violation of human rights, remains common in the coastal areas of Yemen.This study aimed to identify the prevalence of FGM/C and its risk factors among the youngest daughters in families in the Yemeni coastal areas, as well as the knowledge and attitudes of the local population towards FGM/C.A cross-sectional survey was conducted among 646 women and 345 men from six districts in three Yemeni coastal governorates between July and September 2020 using a structured questionnaire. Categorical data were described by proportion. The chi-square test was used to identify factors associated with FGM/C. All factors with a p-value of ≤ 0.05 were included in the multivariate analysis. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were calculated in the multivariate logistic regression analysis.The prevalence of FGM/C in Yemeni coastal areas was 89.0% (95% CI 84.0%-92.5%) among women and 79.8% (95% CI 73.5%-84.8%) among the youngest daughters in the surveyed families. Nearly two-thirds of women and half of the men recorded a poor knowledge level about the harms of FGM/C. Furthermore, almost two-thirds of both women and men would like to continue the practice of FGM/C. Among women, significant predictors of FGM/C among youngest daughters included advanced maternal age of ≥ 40 years , mother’s desire to continue FGM/C , and living in a rural area . Daughters of mothers who did not undergo FGM/C were more protected from FGM/C than those whose mothers had undergone FGM/C . Among men, the father’s desire to continue FGM/C  was significantly associated with FGM/C among the youngest daughters.This study confirmed that FGM/C is still prevalent among communities in Yemeni coastal areas. Thus, community-based interventions with a focus on the rural population are vital to improving the awareness of various harms of FGM/C. Female genital mutilation/cutting (FGM/C) is a form of violence against women that entails partial or complete removal of their external genitalia. It is widely practised in Africa and Asia –3. FGM/CThere are four types of FGM/C. Type 1 is the partial or total removal of the glans of the clitoris. Type 2 is the partial or total removal of the glans clitoris and the labia minora, with or without removal of the labia majora. Type 3, known as suturing, is the narrowing of the vaginal opening. Lastly, type 4 includes all other harmful procedures involving the female genitals for non-medical purposes, such as pricking, piercing, incision, scraping, and cauterisation . FGM/C iSituated in the Arab Peninsula, Yemen has been plagued by a series of wars, making it a country that suffers some of the worst humanitarian crises in the world, accompanied by a high rate of violence against women . The oveTo date, no law or regulation in Yemen prohibits the practice of FGM/C. In 2008, a Safe Motherhood bill was submitted to the Yemeni Parliament, but it was subsequently rejected due to a clause prohibiting FGM/C . ContinuA cross-sectional survey was conducted between July and September 2020 in the Hadramout, Al-Mahrah, and Al-Hodeidah governorates in Yemen.The study population included women and men in the six districts within the three governorates. The targeted districts were Seiyun, Mukalla, and Ash Shihr in Hadramout; Hays and Al Khawkha in Al-Hodeidah; and Al Ghaydah in Al-Mahrah. This study was part of the GBV Protection Project implemented by the Human Access for Partnership and Development.A multiple indicator cluster survey strategy developed by UNICEF was used to calculate the required sample size. Using a 20% prevalence of violence among women and men based on a previous study , the samA multistage cluster sampling was used. Each district was first divided into enumeration areas according to the 2004 census data from the Central Statistical Organisation. The sample size for each district was then determined proportionally according to population size based on the UN Office for the Coordination of Humanitarian Affairs projection for the year 2019 . EnumeraFace-to-face interviews with women and men were carried out using structured questionnaires in their homes or places that ensured privacy and confidentiality. If the mothers were not available due to death, travel, or inability to remember, the eldest daughter who was the household’s primary caregiver would be interviewed instead. Similarly, if the fathers were unavailable on the interview days, the eldest son would be interviewed. The questionnaire contained different sections that captured data related to GBV, including FGM/C practice, knowledge, and attitude, as well as the characteristics of households, parents, and heads of households. The interviews were conducted by nine teams, each consisting of three women, a man, and a supervisor. All the team members received two days of training on data collection and questioning methods. On the third day, a pilot study was conducted before the actual data collection.The outcome variable was the practice of FGM/C. A woman was considered to have had FGM/C if she reported the removal of any part of external genitalia for non-medical reasons. A daughter was considered to have had FGM/C if her mother or father reported the removal of any part of her external genitalia for non-medical reasons . To measUsing 11 questions about the respondent’s knowledge of the physical, psychological, and social harms of FGM/C, an index was established to indicate the knowledge as either good or poor. A respondent’s attitude toward FGM/C was measured by their future desires to continue or stop the practice. For those who stated the desire to continue, potential reasons were enquired based on the five categories of virginity preservation, purity, societal acceptance, for religious requirement, and improved marriage prospects. The person who performed FGM/C could be a healthcare worker or a traditional practitioner. Other sociodemographic characteristics of the respondents that were obtained included their age in years , education level , employment status (employed and unemployed), and place of residence .Stata 16  was used to analyse the data. Missing values were excluded. To adjust for the unequal probability of selection among the clusters, data were weighted using the “svy” command. Descriptive statistics were used to present the variables. To reduce the number of items under the knowledge category, principal components analysis with varimax rotation was used. A predictive value was then generated based on the median score. Scores above the median value indicate good knowledge while scores below the median indicate poor knowledge. The internal consistency was assessed using Cronbach’s alpha, which yielded a value of 0.794, indicating good consistency.To obtain an updated understanding of the risk factors of FGM/C, bivariate analysis (Chi-square test) was performed to determine the risk factors associated with FGM/C among youngest daughters. Only variables with p-values of ≤ 0.05 were included in the multivariate logistic regression, except for the mother’s education which was included prior. In the bivariate analysis for the men’s group, the association between the sex of the head of the household and FGM/C among the youngest daughters was significant. However, one cell was zero. Thus, the variable of the gender of the household head was not included in the multivariate analysis.Four of the 650 women and five of the 350 men refused to participate in the study, resulting in a final sample size of 646 women and 345 men. Approximately 20.0% of women n = 138) and men (n = 65) were younger than 30 years old. Most of them were of a low education level as only less than 20.0% (n = 105) of women and 45.0% (n = 150) of men had secondary education or higher. The majority of women  and two-thirds of men  were not employed. In terms of marital status, around 90.0% of women (n = 602) and men (n = 307) were married or have been married. Generally, most of the households (n = 931) were headed by men and almost half of the households (n = 497) stayed in rural areas . The prevalence was higher among those whose fathers had primary education (83.0%) than those with no education (77.8%) or secondary education and higher (66.7%). Furthermore, daughters whose fathers expressed a desire to continue the practice of FGM/C reported a higher prevalence of FGM/C among their youngest daughters compared to their counterparts (Table 3). Additionally, for both male and women, the prevalence of FGM/C was higher in Hadramout compared to Al-Hodeidah and Al-Mahrah (Table 3).In the multivariate analysis involving women, the odds of FGM/C were 7.16 times higher among the youngest daughters whose mothers’ age were ≥ 40 years  than those younger than 30 years old. In addition, the odds of FGM/C were eight times higher among the youngest daughters whose mothers support the continuation of FGM/C . Furthermore, those whose mothers did not undergo FGM/C before were less likely to have FGM/C . In terms of residence, those living in rural areas were at 3.95 times higher risk of being subjected to FGM/C  while those residing in Al-Hodeidah  and Al-Mahrah  governorates were less likely to have FGM/C compared with those residing in Hadramout. Lastly, mothers ’education and mothers’ knowledge were not significantly associated with FGM/C among the youngest daughters. As for men, the significant predictor of FGM/C among youngest daughters was fathers who supported the continuation of FGM/C   differed widely from the prevalence obtained in a national survey (19.0%) . One of In comparison with other countries, the prevalence of FGM/C in this study was close to that in Sudan (87.2%) , Egypt (When compared to mothers, the prevalence of FGM/C among the youngest daughters was slightly lower by approximately 9%. This cross-generational gap may be a good indication of the attempts to combat the practice of FGM/C in these societies via the collaboration between the Yemeni government and international partners. However, more awareness programmes to deter the practice of FGM/C are still needed to further reduce the prevalence. The prevalence of FGM/C among the youngest daughters in this study was higher than those reported in the UAE , EthiopiIn addition, this study reported that it was more common for traditional practitioners to perform FGM/C. This was in contrast with the findings from an Ethiopian study in which 94.4% of FGM/C among the surveyed daughters was performed by traditional practitioners . DespiteNevertheless, more than half of the FGM/C of youngest daughters in this study was performed by healthcare staff despite a ministerial decree prohibiting the practice of FGM/C in both governmental and private health facilities . In compSimilar to previous reports, women’s intention to continue the practice of FGM/C for their daughters was statistically related to the presence of FGM/C among existing daughters . The desOur results are consistent with findings from Kenya  and ChadWith regard to the urban-rural difference, the prevalence of FGM/C among the daughters of women was higher in the rural areas while the difference was not significant among the men. Many factors could explain the higher prevalence of FGM/C in rural areas. For instance, Yemeni villages usually consist of a small number of tribally-cohesive families that practised insular customs and traditions. In contrast, urban cities are often inhabited by families from different places with various customs and traditions. Furthermore, as a result of the lack of electricity, there is a low penetration of media and the Internet among rural residents who are mostly agricultural farmers. Last but not least, illiteracy among women, men, boys, and girls in rural areas could have also contributed to the low knowledge and high prevalence of FGM/C.In women, the age of the mother being 40 years and above was statistically linked to FGM/C among youngest daughters. This explains that the practice of FGM/C may decrease in the younger generations. Unexpectedly, and in contrast to previous studies in Chad  and SudaLast but not least, the prevalence of FGM/C among the youngest daughters of women in Al-Hodeidah and Al-Mahrah was lower than in Hadramout. Similarly, the youngest daughters of men in Al-Mahrah were less likely to be subjected to FGM/C than those in Hadramout. The differences between these two areas may be related to their customs and traditions. Likewise, Al-Hodeidah is considered to be more vulnerable among all the provinces. For the past 10 years, international and local organisations have been actively organising various women’s protection programmes in Al-Hodeidah, which may have contributed to a reduced prevalence of FGM/C. Variations in the prevalence of FGM/C between regions in the same country have been reported in different contexts , 49. In The study faced some limitations and challenges. Efforts to minimise non-response and other potential biases were attempted by collecting data in a place with guaranteed privacy. However, some participants were reluctant to answer certain sensitive questions during the pilot study. Thus, the question about the type of FGM/C was removed from the questionnaire. In addition, there was also potential recall bias for questions asked about past events. Furthermore, the sample size was initially calculated for a wider study on GBV. Thus, the sample size might be inadequate for the assessment of certain statistical associations in the multivariate model, for example, the difference between urban and rural men in relation to the practice. Lastly, this study also did not capture important demographic characteristics of the youngest daughters, the age when FGM/C was performed, and other war-related factors.Despite the limitations, there are certain study strengths. Data obtained from 50 clusters or villages with a wide range of practices and beliefs meant that the results from this study are considered generalisable to the coastal areas in Yemen. Furthermore, the availability of trained data collectors who were given sufficient time to conduct interviews increased the accuracy and quality of the results.FGM/C is still a common practice in the coastal areas of Yemen. Mothers’ and fathers’ strong beliefs about FGM/C, advanced maternal age of 40 years and above, rural residence, and mothers’ history of FGM/C were the strongest predictors of FGM/C among the current generation of girls. Interventions targeting different community sectors, such as women and men, religious men, rural societies, male and female students, as well as health workers, are vital to correct the misconceptions surrounding FGM/C.


Treatment of subclinical hypothyroidism (ScH), especially the mild form of ScH, is controversial because thyroid hormones influence cardiac function. We investigate left ventricular systolic and diastolic function in ScH and evaluate the effect of 5-month levothyroxine treatment.Fifty-four patients with newly diagnosed mild ScH (4.2 <TSH < 10.0 mU/L) and 30 euthyroid subjects matched by age were analysed. Laboratory analyses and an echocardiography study were done at the first visit and after 5 months in euthyroid stage in patients with ScH.Compared to healthy controls, patients with ScH had a lower E/A ratio , higher E/e' sep. ratio , higher myocardial performance index (MPI) , lower global longitudinal strain (GLS) , and lower S wave derived by tissue Doppler imaging . Levothyroxine treatment in patients with ScH contributed to higher EF , lower E/e' sep. ratio , lower MPI , and improved GLS  compared to values in ScH patients at baseline. Furthermore, in all study populations (ScH patients before and after levothyroxine therapy and controls), TSH levels significantly negatively correlated with EF , E/A , GLS , and S/TDI  and positively correlated with E/e' sep. .Patients with subclinical hypothyroidism versus healthy individuals had subtle changes in certain parameters that indicate involvement of systolic and diastolic function of the left ventricle. Although the values of the parameters were in normal range, they were significantly different compared to ScH and the control group at baseline, as well as to the ScH groups before and after treatment.The results of our study suggest that patients with ScH must be followed up during treatment to assess improvement of the disease. Some of the echocardiography obtained parameters were reversible after levothyroxine therapy. Subclinical hypothyroidism (ScH) is defined as a condition with a slight increase in serum concentration of thyrotropin (TSH) with normal values of circulating thyroid hormones, free thyroxine (FT4) and triiodothyronine (FT3).The upper limit of TSH from which thyroid replacement therapy should start is still a topic of debate ,2. TreatThyroid hormones influence cardiac function ,10. TheyResearch has revealed that substitution therapy with levothyroxine in ScH with TSH values above 10 mU/L could improve left ventricular (LV) function -16. WhetThe aim of the study was to evaluate the effect of levothyroxine therapy on LV systolic and diastolic function in patients with a mild form of ScH (4.2 < TSH < 10.0 mU/L) and after 5 months in euthyroid stage, using two-dimensional echocardiography, pulse Doppler, tissue Doppler, and two-dimensional speckle tracking imaging. An additional aim of the study was to predict which parameters derived by echocardiography can be used to monitor patients with ScH.The prospective study was conducted at the University Clinic of Endocrinology and the University Clinic of Cardiology in Skopje, R. Macedonia. The study included a control group and patients with a newly diagnosed mild form of ScH. The control group consisted of 30 healthy euthyroid patients . The criteria for a diagnosis of mild ScH were 4.2 mU/L < TSH < 10.0 mU/L with normal serum FT4 10.3-24.45 pmol/L and FT3 4.2-8.1 pmol/L. According to the recommendations of the British Thyroid Association, patients with ScH were placed on thyroid replacement therapy if one of the following criteria were present: at least three signs or symptoms of hypothyroidism, positive anti-TPO antibodies and positive anti-Tg antibodies, positive family history of thyroid disease, and thyroid enlargement or goiter on ultrasonography . The staThe control group was included to compare echocardiography parameters from the mild form of SCH at baseline.Patients with a previous history of thyroid disease receiving therapy for thyroid or cardiovascular function were not included. Patients who were cigarette smokers or who had cardiovascular disease, hypertension, hypothalamic-pituitary disease, depression, psychosis, bipolar disorders, diabetes, chronic pancreatitis, hepatic or renal disease, ovulatory dysfunction, infertility, or pregnancy were also not included.All patients gave informed consent to participate in the study after careful explanation of the testing protocol. The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee at the Medical Faculty in Skopje, R. Macedonia.At the first visit to the University Clinic of Endocrinology, blood samples for TSH, FT4, and FT3 were taken from all patients. At the same time, at the Outpatient Department of Cardiology Clinic, transthoracic echocardiography was done. Two-dimensional (2D) echocardiography, pulsed wave (PW) Doppler, tissue Doppler imaging (TDI), and 2D speckle tracking echocardiography were used to assess left ventricular systolic and diastolic function.All blood samples for thyroid hormones were collected from the antecubital vein between 08.00 and 09.00 a.m. TSH, FT4, and FT3 were determined by the super-sensitive chemiluminescent immunoassay . The functional sensitivity for TSH was 0.004 μIU/mL, for FT4 0.3 ng/dL, and FT3 0.4 ng/dL.Standard assessments of LV dimensions and wall thickness were performed in standard views on commercially available equipment  according to the joint recommendations of the American Society of Echocardiography and the European Association of Cardiovascular Imaging . LV voluGlobal and regional peak systolic longitudinal strain was assessed from apical 2-chamber, 4-chamber, and long-axis views using speckle tracking analysis . Recordit-test was used for the comparison of the quantitative data between the control group and the ScH group at baseline. Student's paired t-test was used for the comparison of the quantitative data before and after the levothyroxine therapy in the ScH group. For the comparison of categorical variables the chi-square test, Yates correction was used. The correlation between the tested parameters was determined using the Pearson correlation. All data analysis was performed using SPSS version 14.0  and p value ≤ 0.05 was considered significant.Categorical parameters were summarized as percentages and continuous parameters as mean ± SD. The normal distribution of variables was verified with the Shapiro-Wilk test. As the distribution was normal, Student's independent Patients and normal controls were well matched for age, sex, BMI, and BSA. Heart rate was similar in both groups, but significantly increased in the ScH group after the levothyroxine treatment. The systolic blood pressure was significantly higher in the ScH group at baseline than in the control group, but the treatment with levothyroxine didn't make any changes. The diastolic blood pressure was similar in both groups, without difference after levothyroxine treatment. As expected, TSH levels were significantly higher in the ScH group than in the control group. FT4 and FT3 levels, although in the reference range, were significantly lower in the ScH group at baseline than in the control group. Interestingly, after the thyroid substitution therapy, FT4 and FT3 levels significantly increased in the ScH group .The LV diameters and volumes were similar in both groups, ScH at baseline and control groups. Overall, only EF  statistically significantly increased in the ScH group after the levothyroxine therapy .The results from echocardiography (systolic and diastolic parameters) in all analysed groups were in normal range, but some of them were statistically different compared to ScH and the control group at baseline, as well as to the ScH groups before and after treatment. The transmitral E/A ratio was lower and E/e’ sep. ratio was higher in the ScH group at baseline than in the control group. The E/e’ sep. ratio significantly decreased in the ScH group after levothyroxine therapy. The MPI was higher in the ScH group at baseline than in the control group and significantly decreased after levothyroxine therapy. The GLS was significantly reduced in the ScH group at baseline in comparison to the control group and significantly improved after levothyroxine therapy. The S wave estimated from TDI was significantly lower in the ScH group at baseline than in the control group, without changes after the levothyroxine therapy . AnalysiConsidering the entire study population, the TSH levels (before and after levothyroxine therapy) significantly negatively correlated with EF , E/A ratio , GLS , and S/TDI  and positively correlated with E/e’ sep. .The results of the study presented subtle changes in the LV systolic and diastolic function which were reversible after thyroid replacement therapy. Although the values of the echocardiography parameters were in normal range in all analysed groups , there were statistically significant differences between some parameters compared to the control and ScH group at baseline, as well as to the ScH group before and after treatment.Our results show that the ScH group at baseline had statistically significantly higher values for systolic blood pressure. This result is similar to the results in one meta-analysis published in 2014. The study includes the analysis of 20 studies and found a slight increase in systolic blood pressure in patients with ScH versus the control group . SystoliHeart rate statistically significantly increased after thyroid replacement therapy. These changes are consistent with the known mechanism of action of thyroid hormones. From a clinical point of view, the increase in heart rate after treatment was still in the normal range (77.1 ± 9.9 minute), but there was statistical significance. None of the patients after treatment had tachycardia or arrhythmia.At baseline, echocardiographic parameters of LV function were not significantly different between the control and the ScH group, which were similar with results from other studies ,24-28. FThe parameter S derived from TDI, which is a parameter to assess systolic function of LV, was statistically significantly lower in the ScH group compared to the control group. This proves the abnormal longitudinal systolic function of LV in ScH, which is first affected in LV systolic dysfunction ,31. The Results for MPI showed deterioration in global systolic and diastolic function of the LV in ScH, and its reversibility after thyroid replacement therapy. Our results were consistent with those from other clinical studies ,25,29. TGlobal longitudinal strain is considered more sensitive than EF in assessing LV global systolic function, especially when the EF is normal, in favour of subclinical LV dysfunction. Values of GLS in the control group and ScH group at baseline were within the normal range, but still with statistically significantly different values in the ScH group. GLS significantly improved after the levothyroxine therapy. TSH significantly negatively correlated with GLS. Two studies examined GLS in ScH, and both of them showed results similar to ours ,32.The results from Doppler transmitral flow and velocities estimated by TDI showed changes in some parameters which are defined as parameters for diastolic function assessment. Although the values of some parameters were in the normal range, there is a statistically significant difference between the values of the control and ScH groups. This is shown by statistically significantly lower E/A ratio, and higher E/e’ sep. ratio in the ScH group compared to the control group.After 5 months of euthyroid state, the E/A ratio did not increase significantly. In a study by Yazici and cols.  the E/A Statistically significant correlations between TSH and analysed parameters were weak (r < 0.5). The weak correlation coefficient may be due to higher TSH values at the end of the study. The r values were lower for correlations with diastolic parameters. Probably systolic parameters are more sensitive on L-T4 treatment, and diastolic parameters need a longer period of treatment.Summarizing the results, ScH did not cause cardiac failure by itself, but thyroid substitution therapy improves some parameters of LV function. We analysed only patients with mild ScH, which means rapid detection of thyroid dysfunction. If ScH is detected later, according to the correlations, we expected worsening of LV parameters.There are some limitations in this study. The design is not that of a blind or double-blind study which includes L-thyroxine and placebo. We followed the parameters of systolic and diastolic function, but we did not directly observe cardiovascular morbidity and mortality, which requires very long-term monitoring of patients.The advantages of the study compared to previous similar studies are the inclusion of young people with no risk factors for cardiovascular disease which can influence systolic and diastolic parameters, and the inclusion of patients with mild ScH. Thus, this study confirmed the benefit of levothyroxine treatment in patients with ScH with lower values of TSH. Today, when there is a lack of recommendations for treatment of mild ScH, this study moves the limits for initiation with treatment from the lower values of TSH.In conclusion, patients with ScH versus healthy individuals had subtle changes in certain parameters that indicate involvement of systolic and diastolic function of the LV in ScH. Although the values of the parameters were in normal range, they were significantly different compared to ScH and the control group at baseline, as well as to the ScH groups before and after treatment. The results of our study suggest that the patients with ScH deserve to be followed up during treatment.


To describe injury incidence, time trends in injury incidence, and injury characteristics among Swedish Olympic athletes over 22 years based on insurance data, as a first step to inform injury preventive measures among Olympic athletes.The cohort comprised 762 elite athletes  in 38 sports in the Swedish Olympic Committee support program ‘Top and Talent’ between 1999 and 2020, with total 3427 athlete-years included. Acute and gradual onset injuries were reported to the insurance registry by the athletes’ medical staff.A total of 1635 injuries in 468 athletes were registered. The overall injury incidence was 47.7 injuries/100 athlete-years (one injury per athlete every second year). An increasing trend in injury incidence was observed in the first decade 2001 to 2010 , while in the second decade 2011 to 2020 no change was evident . Gymnastics, tennis, and athletics had the highest incidence . Among sport categories, mixed and power sports had the highest incidence . Higher incidences were seen in the younger age groups (≤ 25 years) in mixed and skill sports. The injury incidence was comparable between male and female athletes, and summer and winter sports. Most injuries occurred in the lower limb, and specifically the knee (24%), foot/ankle (15%) and spine/pelvis (13%).The results on injury patterns in different sports and age groups may guide preventive focus for health and performance teams working with Olympic athletes.II.The online version contains supplementary material available at 10.1007/s00167-023-07511-y. Injuries entail major challenges for sports teams and athletes, as they have a negative impact on athletes’ health, sports performance, and success , 12, 26.For the 2008 Olympic Games, the International Olympic Committee implemented a health surveillance programme which has been conducted ever since , 19–22. Insurance registries have been used to collect injury surveillance data , 29, 30.This was a cohort study based on insurance registry data from the Swedish insurance company Folksam Insurance Group (Folksam). All data were handled confidentially in line with the Declaration of Helsinki. The study was approved by the Swedish Ethical Review Authority (reg. no 2022-00438-01). The study was reported according to the Strengthening the Reporting of Observational Studies in Epidemiology and the Sport Injury and Illness Surveillance extension .The study population includes Swedish elite male and female athletes, covering a wide range of sports, within the Swedish Olympic Committee (SOC) support programme Top and Talent Table . InclusiInjury insurance claims were reported to the registry prospectively between 1999 and 2020 by a physician or physiotherapist from SOC via the athletes’ health insurance, after a median of 5 days (IQR 0–22) from date of injury. Only injuries occurring while the athletes participated in Top and Talent were registered. An administrator from Folksam was responsible for recording the injury in the registry. Injuries were diagnosed according to an insurance-specific coding system. The registry contained data about the insured athletes and about each injury. Details on the collected data are presented in Table The health insurance covers both injuries and illnesses, but only injuries were included in this study. An eligible injury, as per the insurance policy, was defined as any physical damage with a sudden or gradual onset occurring while the athlete participated in Top and Talent. Pre-existing injuries present prior to start of the insurance were not included. Multiple injuries sustained by an athlete in a single event were recorded as one injury with multiple injury types or locations. Injury type was classified into eight different categories. Due to irregular reporting in the insurance registry, injuries reported as joint/ligament sprains, dislocations, and muscle/tendon strains and ruptures were combined by the authors to the same injury type category for descriptive statistics, named ‘soft tissue/joint injury’. The other injury type categories were contusion, fracture/bone injury, inflammation, concussion, laceration/abrasion, multiple injury types, and ‘unspecified’. Injuries were classified to a body region and location based on the reports made to the insurance registry.Data were summarised using descriptive statistics, with mean, median, frequencies, standard deviations (SD), interquartile ranges (IQR) and/or 95% confidence intervals (CI), as appropriate. Incidence and characteristics (i.e. type and location) of injuries were presented for the total population and stratified for subgroups based on sex , competitive season (summer and winter sports), sport category  , and ageIn total, 1635 injuries sustained by 468 athletes  were registered ). The overall incidence was 47.7 injuries/100 athlete-years, with 46.4 and 49.3 injuries/100 athlete-years among male and female athletes, respectively. The highest incidence per individual sport was seen in gymnastics, tennis, and athletics . Injury incidence in the total population and for subgroups is presented in Tables The time trend analysis showed that the overall injury incidence increased by 3.0% annually over the full 20-years period between 2001 and 2020 . Males had an 2.5% annual increased incidence  and females an 3.7% increase . Noteworthy was that the injury incidence increase was evident only in the first 10-years period of 2001–2010 , while the second 10-year period of 2011–2020 showed no such trend ) Year-by-year injury incidences for subgroups  are presented in Fig. The lower limb region, and specifically the knee, had the highest injury frequency, and soft tissue/joint injury was the most common injury type category among the specified injury types. Injury characteristics are presented in Tables The principal findings of the study were that the overall injury incidence among Swedish Olympic athletes increased by six percent annually between 2001 and 2010, after which the curve flattened with no change between 2011 and 2020. Athletes report approximately one injury to the insurance registry every second year, where most injuries affect the knee, foot/ankle, and spine/pelvis. There is a paucity of research on the year-round injury incidence and characteristics among Olympic athletes and the present study is, to the best of our knowledge, the first to describe injuries over a two-decade long period using insurance data.The injury incidence was 47.7 injuries/100 athlete-years. Compared to previous studies in Olympic athletes, this incidence rate is low. During the Olympic Games of 2014 to 2020, the injury incidence was between 5.4 and 7.8 injuries/1000 athlete-days  , and amoInjury incidence was highest among power and mixed sports, possibly due to the nature and demands of these sports, which often involve high forces and athlete-to-athlete contacts. It should be noted, however, that there was a variation in injury incidence among single sports within the four sport categories. For instance, in mixed sports, the injury incidence ranged between 16.3 and 99.3 injuries/100 athlete-years, and among power sports between 45.0 and 100.0 injuries/100 athlete-years. All sports that had a higher injury incidence than the total population average belonged to the mixed or power sport categories. Previously, Ranson et al. reported that the injury incidence was highest in combat sports , and comIn the present study the overall injury incidence was comparable between males and females, which is in line with previous reports during the Olympic Games –22. In tComparing age groups, the highest overall injury incidence was seen among athletes ≤ 20 years, with a trend that the injury incidence decreases with higher age. This age–injury relationship was evident in the mixed and skill sport categories, but not in power and endurance sports. It should be noted, however, that comparison within single sports were not possible due to small samples, and large variations may exist. Further, there were differences in the number of athlete-years in different sports within the sport categories and age groups (Online Resource 4), and the reason for the observed age-injury relationship is unclear.The observed variation in injury incidence and characteristics between sports and subgroups emphasises the importance of considering the contextual factors—such as environmental factors and sport and athlete characteristics—when implementing injury prevention interventions .A significant time trend was noted with a three percent annual increase in injury incidence over the full 20-years period, which was evident in both males and females. However, when analysing time trends for the first and second 10-years periods separately, the increasing trend was evident only during the first decade of 2001 to 2010, after which the injury incidence remained fairly stable between 2011 and 2020. This indicates that there is currently no trend of increasing injury incidence in the Swedish Top and Talent athlete population. Looking at the time trends year-by-year, some variations could be seen within subgroups. For example, in winter sports, there was a tendency towards a high injury incidence the year prior to each Winter Olympic Games, and low incidence the year of the Olympic Games. While not as obvious, this tendency was also seen in summer sports in relation to the Summer Olympic Games. Based on the data it is not possible to explain the observed increasing time trend or year-by-year fluctuations in injury incidence with any certainty. It may be the result of sporting factors; e.g. changes in sporting/physical demands, competition and training schedules, or rules or equipment, but also due to methodological factors such as varying population characteristics or reporting patterns.Strengths of the study include the long time period of data collection, and a large sample of athletes who had participated in Top and Talent between 1999 and 2020. In contrast to most previous research of injuries in Olympic athletes , but simAnother limitation is that many injuries were registered in the insurance registry as unspecified for injury type. Information about these injuries is therefore limited, and it is possible that the proportion of injuries in specific injury types would be different if all injuries had more specified information. More specific injury registration is important to increase the quality of the registry and to allow more definitive conclusions about injury rates and patterns.Registry data from 1999, shortly after the inception of Top and Talent in 1998, was included. Due to low awareness of the health insurance in the initial years and likely some missing injury data, this results in underestimation of the injury incidence in these years, and to a smaller extent also the overall injury incidence. It is likely that insurance registry data includes primarily more severe injuries. Minor injuries—for example certain gradual onset injuries, or injuries not resulting in time-loss or affecting athlete performance—may go unreported to the insurance company. Given the insurance registry-based data collection, the generalisability of the findings to other populations and surveillance methods is unclear. Gradual onset injuries and non-time loss injuries dominate the injury pattern in Olympic sports , 19, 20,The overall injury incidence increased by six percent annually between 2001 and 2010, after which the curve flattened with no change between 2011 and 2020. Swedish Olympic athletes report approximately one injury to the insurance registry every second year, where most injuries affect the knee, foot/ankle, and spine/pelvis. The highest injury incidence was seen in gymnastics, tennis, and athletics, and for specific subgroups, in mixed and power sports and younger age groups. Injury prevention interventions should be a high priority in these sports and subgroups. The findings may support health and performance teams working with Olympic athletes in their work to improve athlete health, by highlighting incidence rates and common injury locations in different subgroups and sports.Supplementary file1 (PDF 169 KB)Supplementary file2 (PDF 215 KB)Supplementary file3 (PDF 155 KB)Supplementary file4 (PDF 109 KB)Supplementary file5 (PDF 90 KB)Supplementary file6 (PDF 565 KB)Below is the link to the electronic supplementary material.


Heart failure (HF) is a complex and multifactorial syndrome caused by impaired heart function. The high morbidity and mortality of HF cause a heavy burden of illness worldwide. Non-thyroidal illness syndrome (NTIS) refers to aberrant serum thyroid parameters in patients without past thyroid disease. Observational studies have indicated that NTIS is associated with a higher risk of all-cause mortality in HF. This meta-analysis aimed to investigate the association between NTIS and HF prognosis.I2 and Cochran's Q statistics. Sensitivity analysis and publication bias analysis were also conducted.Medline, Embase, Web of Science, and the Cochrane database were searched for any studies reporting an association between NTIS and HF prognosis from inception to 1 July 2022. A meta-analysis was then performed. The quality of studies was assessed using the Newcastle–Ottawa Scale. The heterogeneity of the results was assessed with A total of 626 studies were retrieved, and 18 studies were finally included in the meta-analysis. The results showed that NTIS in HF patients was significantly associated with an increased risk of all-cause mortality and major cardiovascular events (MACE), but not with in-hospital mortality. The stability of the data was validated by the sensitivity analysis. There was no indication of a publication bias in the pooled results for all-cause mortality and MACE.This meta-analysis showed that NTIS was associated with a worse outcome in HF patients. However, the association between NTIS and in-hospital mortality of HF patients requires further investigation. Heart failure (HF) is a complex, multifactorial clinical syndrome characterized by dyspnea and fluid retention caused by impaired systolic or diastolic cardiac function , 2. In 2Non-thyroidal illness syndrome (NTIS) was first discovered in the 1970s and described as abnormal serum thyroid parameters in patients with acute illness but without prior thyroid disease. The most common abnormality is low triiodothyronine T3) levels with normal thyroid-stimulating hormone levels  levels w. FurtherTherefore, we performed this meta-analysis to explore the association between NTIS and the HF prognosis for various endpoints and subgroups. To our knowledge, this is the first meta-analysis to systematically review these associations.https://www.crd.york.ac.uk/PROSPERO).This meta-analysis was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guideline 2020 . We regi3 syndrome OR low triiodothyronine syndrome OR euthyroid sick syndrome OR ESS). Two reviewers (XYQ and YXZ) screened the titles and abstracts of the retrieved studies. The full texts of relevant studies were further evaluated, and reviews, case reports, animal experiments, and studies without prognosis information were excluded. A third reviewer (YJC) was consulted when there was a difference of opinion between the first two reviewers.We conducted a comprehensive literature search of the Medline, Embase, Web of Science, and Cochrane databases to obtain studies focused on the association between NTIS and the HF prognosis, published from inception to 1 July 2022. The inclusion criteria were as follows: (i) HF patients were included in the study populations; (ii) cohort studies; (iii) studies investigating the association between NTIS and HF prognosis; (iv) study endpoints included all-cause mortality or major cardiovascular events (MACE), or in-hospital mortality; and (v) studies published in English. Our search strategy was therefore: (heart failure OR heart decompensation OR congestive heart failure OR HF) AND , relative risk (RR), HR), with 95% confidence intervals (95% CIs) and adjusted covariates for multivariable analysis.We used the Newcastle–Ottawa Scale (NOS) to evaluate the quality of the eligible cohort studies . The NOSI² and Cochran’s Q statistics were used to assess heterogeneity. A P-value < 0.05 for Q statistic and I² > 50% was considered substantial heterogeneity. The sensitivity analysis was performed by omitting each study to evaluate the consistency of the pooled results. Publication bias was assessed using the funnel plot and Egger’s test. Obvious asymmetry of the funnel plot and a P-value < 0.05 for Egger’s test indicated significant publication bias. The trim and fill method would be used if publication bias existed. Subgroup analyses were conducted on disease onset of HF, NTIS definition, continent of origin of the study population, and source of HRs among different endpoints, that is, whether the HRs were reported or extracted from survival curves. A subgroup analysis according to MACE subtypes was also performed. All statistical analysis was performed using Stata software (Version 14.0). A two-sided P-value<0.05 was considered statistically significant.The RR, OR, or HR were extracted from the original studies. In studies that only gave survival curves, we calculated the crude HR using Engauge Digitizer 4.1 software , 11. Poon = 263), animal studies (n = 10), case reports (n = 21), and reviews (n = 98), were excluded. Forty-two reports were retained for further examination. We excluded four further studies that were conference abstracts or for which we had no access to the full text, five studies that were not focused on HF patients, ten that were cross-sectional studies, and five that did not have data that would enable the determination of effect size. Finally, our meta-analysis included 18 cohort studies that examined the relationship between NTIS and HF prognosis. The workflow is shown in The initial database search identified 656 articles. After eliminating 222 duplicate studies, we screened the titles and abstracts of the remaining records. Studies not relevant to our topic . The pooled ORs also demonstrated a consistent result with high heterogeneity .Of the 12 studies that explored the association between NTIS and all-cause mortality in HF patients , HRs werP < 0.001, I2 = 0; AHF: HR: 2.12, 95% CI: 1.53–2.94, P < 0.001, I2 = 0). For subgroup analysis based on the definition of NTIS, the synthesis of HRs showed that the association between NTIS and all-cause mortality of patients with HF was significant in both groups . Subgroup analysis based on the different continents of origin showed that NTIS was significantly associated with an elevated risk of all-cause mortality in studies from Europe, America, and Asia . Finally, subgroup analysis of the source of the HRs indicated that the association between NTIS and all-cause mortality in HF patients was significant regardless of the HRs origins, that is, reported or extracted from survival curves . However, the heterogeneity of pooled HRs from the survival curve (SC) group increased (I2 = 53.6%).The results of the subgroup analyses of pooled HRs are shown in P < 0.05)  .A sensitivity analysis was performed to assess the stability of the pooled HRs/ORs by omitting each study. The association between NTIS and all-cause mortality of HF patients remained significant after the removal of each study . Further, pooled ORs also confirmed a significant association between NTIS and MACE in HF patients . The heterogeneity of the pooled HRs and ORs was significant (I2 > 50%), so we conducted the following subgroup analyses  but not in AHF patients . For subgroup analysis based on the definition of NTIS, the association between NTIS and MACE in HF patients was significant under both strict and no-strict definition . Subgroup analysis based on the continents of origin demonstrated that NTIS was significantly associated with an elevated risk of MACE in HF patients in studies from Europe and America , but not significant in studies from Asia . Further subgroup analysis on the source of HR indicated the significant association between NTIS and MACE in HF patients with both reported and extracted HRs . For the subgroup analysis of the type of MACE, the result showed that NTIS was significantly associated with an increased risk of MACE for major adverse events (MAE), readmission for HF, and cardiac death . However, the association was not significant in the subgroup of cardiac death and readmission for HF . Additionally, the heterogeneity of subgroups on disease onset, definition of NTIS, continents, and source of HR decreased compared to the pooled result, which suggests the potential source of heterogeneity.The subgroup analysis of disease onset showed that NTIS was significantly associated with a higher risk of MACE in CHF patients  .Sensitivity analysis confirmed the stability of pooled HRs and ORs . The funnel plot and Egger’s test did not reveal a tendency for publication bias (P > 0.05). We did not perform subgroup and sensitivity analysis due to the limited number of studies. The Egger’s test revealed a potential publication bias (P < 0.05), but the use of the trim and fill method did not produce a reversion of the pooled result .Two studies that reported endpoints of in-hospital mortality in HF patients were included in the meta-analysis . The pooIn this meta-analysis, we explored the association between NTIS and both short- and long-term outcomes of HF patients. The results indicate that NTIS is significantly associated with an increased risk of all-cause mortality, and MACE in HF patients, whereas the association with in-hospital mortality was not significant. In addition, the association between NTIS and all-cause mortality remained significant in several subgroups. However, the association between NTIS and MACE was not significant in the subgroup of AHF patients, studies from Asia and MACE defined as cardiac death and readmission to hospital.In contrast to the earlier meta-analysis focusing on the association between NTIS and cardiovascular disease, we discussed NTIS and HF prognosis. Additionally, we analyzed the association between NTIS and multiple outcomes of HF with more studies included. In the original studies, the effect size reporting the association between NTIS and HF prognosis was not uniform. To avoid potential bias, we performed separate meta-analyses for HRs and ORs. The pooled HRs and ORs confirmed that the association between NTIS and all-cause mortality, and MACE in HF patients was significant. There was no heterogeneity in the pooled HRs for all-cause mortality. In the subgroup analysis based on the source of HRs, the heterogeneity increased in the pooled HRs extracted from survival curves, which might be due to the differences in the ethnic and exclusion criteria of the two studies. However, after the exclusion of HRs extracted from survival curves, the result still supports the association of NTIS with HF prognosis. On the other hand, the meta-analysis of MACE revealed significant heterogeneity. However, the heterogeneity among subgroups including disease onset, definition of NTIS, source of HR, and continents of origin, was not significant, which indicated the heterogeneity source. Additionally, the association between NTIS and MACE in HF patients was not significant in several subgroups. The association was not significant in AHF patients, which may be explained by the limited number of studies, or a difference in the disease prognosis profile. A survey by the European Society of Cardiology (ESC), the ESC-HF pilot study survey, revealed that, compared with AHF, CHF had a better medium-term prognosis due to more mature therapies . Further3), by the deiodinase enzyme  α, and calcium ATPase protein of the sarcoplasmic reticulum (SERCA2α), which enhance systolic and diastolic cardiac function. Indirect effects of T3 on the cardiovascular system include the activation of sodium, potassium, and calcium membrane channels, which induces the endothelial nitric oxide production, and the activation of PI3K/AKT pathways to reduce vascular resistance  plays a central role in regulating the cardiovascular system. Thyroxine is converted to the biologically active form of TH, triiodothyronine  and Guangdong-Shenzhen Joint Fund Youth Project (No. 2021A1515111110).