There are few reports on the preventative value of intensive blood pressure (BP) management for stroke, especially hemorrhagic stroke (HS), after new criteria for hypertension (HTN) were announced by the American College of Cardiology/American Heart Association in 2017.This study aimed to identify the optimal BP for the primary prevention of HS in a healthy population aged between 20 and 65 years.We conducted a 10-year observational study on the risk of HS, subclassified as intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) according to BP categories  using the National Health Insurance Service Database.Out of 8,327,751 participants who underwent a health checkup in 2008, 949,550 were included in this study and observed from 2009 to 2018. The risk of ICH was significantly increased in men with stage 2 HTN {adjusted hazard ratio [aHR] 2.002 [95% confidence interval (CI) 1.203–3.332]} and in women with stage 1 HTN [aHR 2.021 ]. The risk of SAH was significantly increased in both men [aHR 1.637 ] and women [aHR 4.217 ] with stage 1 HTN. Additionally, the risk of HS was significantly increased in men with stage 2 HTN [aHR 3.034 ] and in women with stage 1 HTN [aHR 2.976 ].To prevent primary HS, including ICH and SAH, BP management is recommended for adults under the age of 65 years with stage 1 HTN. The incidence and diagnosis rates of cerebrovascular diseases related to stroke are increasing as the population ages and diagnostic technology is developed –3. AccorHowever, although several studies have reported new diagnostic criteria for HTN that lower the incidence of various cardiovascular events (CVEs) –8, thereTherefore, we conducted a large-scale observational study on the risk of hemorrhagic stroke (HS), subclassified as subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH) according to BP based on the new diagnostic criteria for HTN in a healthy population using a nationwide cohort.We conducted a nationwide observational study using the National Health Claims Database, which is available from Korea's National Health Insurance Service (NHIS). The NHIS is a nationwide universal insurance system in Korea responsible for the nation's healthcare and medical bills. The database consists of hospital records, including admission and outpatient visit records, drug prescriptions, and national health examination data, for 97% of the Korean population. Adults in Korea are required to undergo national health examinations biannually, provided by the NHIS . The heaAdults aged 20 years or older who underwent a national health examination in 2008 were included in this study, and patients aged 65 years or older were excluded to limit the number of participants who had missing values or who died from causes other than stroke to <5% during the observation period.Among participants who were under 65 years of age, those who had missing values or who died from causes other than stroke during the observation period were subject to listwise deletion. Furthermore, participants who had a history of brain trauma (ICD-10 codes S06–S09) or brain tumor  during the observation period or who had been diagnosed with brain trauma, brain tumor, or stroke (ICD-10 codes I60–I63) during the preceding 5-year period were excluded to extract only those who were diagnosed with stroke for the first time during the observation period and to minimize the effects of other causes on the brain. To increase the reliability of the medical data, we used data extracted exclusively from tertiary general referral hospitals, general hospitals, and semi-general hospitals.BP was measured three times after participants rested for at least 2 min in a sitting position by digital or automatic monitors during the health examination, and mean BP was recorded. All participants were categorized by BP measurements: low normal , high normal , elevated , stage 1 HTN , and stage 2 HTN . Four conditions were established on the premise that participants classified into each category stayed in the same category during the 10-year observation period. First, only participants classified into the same BP category in 2008 and at previous health examinations  were enrolled in this study. Second, only participants remained in the same BP category at the additional health examination for the previous 3 years, including the year of stroke occurrence, were included in this study . Third, participants who had a stroke after January 2014 or remained stroke-free during the observation period were included in this study only if they underwent an additional health examination between 2009 and 2013, and their BP category remained unchanged and the same. Fourth, participants who had no stroke during the 10-year observation period had to have undergone additional health examinations at least once in both 2009–2013 and 2014–2018, and all had to have been classified into the same BP group as that of the first examination. Therefore, only participants classified in the same category three to four times during the health examinations were included in this study. Finally, only patients who did not take BP medication before study enrollment until stroke occurred were included to assess the natural association between BP categories and stroke risk.Primary outcomes were HS, including ICH and SAH, and secondary outcomes were analyzed by dividing the participants into those with ICH and those with SAH. The ICH (ICD-10 code I61) and SAH (ICD-10 code I60) groups included only patients who were hospitalized for more than 5 days or died within 5 days with an ICD-10 code. Since the risk for stroke differs by sex –16, eachp-value <0.1 in univariable analysis and was fitted using the backward selection method to eliminate interactions between variables. The Grambsch–Therneau method based on the Schoenfeld residual was tested, and the proportional hazard assumptions for all selected variables were satisfied with a p-value of >0.05. Missing data were excluded. Data manipulation and extraction were performed using SAS software, version 9.4 .Participants were followed up from 1 January 2009, until the date of an HS or 31 December 2018. The multivariable-adjusted hazard ratio (HR) and 95% confidence intervals (CIs) for ICH, SAH, and HS were determined by Cox proportional hazard regression analysis according to BP after adjustments for all covariates. The variables included sex, age , BP , body mass index (BMI) , fasting serum glucose (FSG) , total cholesterol , heart disease , family history  , alcohol consumption , current smoking , and physical activity . Cox proportional hazard regression analysis was performed for all covariates to identify risk factors for HS. Multivariable analysis was performed for variables with a In 2008, 8,325,579 adults between the ages of 20 and 65 underwent a health examination. Among them, 7,433,485 participants had health examinations in 2005, 2006, or 2007. Excluding those who had a history of stroke until 2008 or who had a brain tumor or head trauma during the observation period out of 7,433,485 participants, 6,538,351 remained. Of those, 170,156 participants (2.6%) with missing values for BP or missing covariates were excluded. A total of 31,383 participants (0.49%) who died from reasons other than CVD during the observation period were also excluded. Among 6,336,812 participants, 588,950 (9.3%) who had taken antihypertensive medications until 2008 or took antihypertensive medications during the observation period were also excluded. Among 4,864,995 participants who met the conditions for the number of health examinations during the observation period, the number of participants included in the same BP category at all three or four health examinations was 947,378. These were finally enrolled in this study and classified into the low normal group, high normal group, elevated group, stage 1 HTN group, and stage 2 HTN group with 243,718, 319,381, 64,988, 257,699, and 61,492 participants, respectively .Among 528,178 men and 419,200 women, HS occurred in 560 (0.11%) and 353 (0.084%) patients, respectively. Among men, age, BP, FSG, and alcohol consumption in the HS group showed significantly higher trends than in the non-HS group, and in the case of women, age, BP, and BMI in the HS group showed significantly higher trends than in the non-HS group. The proportion of current smokers was significantly higher in the HS group for both men and women. The incidence and risk of ICH and SAH according to BP categories are shown in Regarding SAH, compared with men with low normal BP, those with stage 1 HTN  and stage 2 HTN  had a significantly higher risk. Similarly, compared with women with low normal BP, those with stage 1 HTN  and stage 2 HTN  had a significantly higher risk of SAH.The incidence and risk of HS, including ICH and SAH, according to BP categories are shown in Age, BP, BMI, FSG, total cholesterol, history of heart disease, family history , alcohol consumption, smoking status, and exercise habits were included in the initial model. To evaluate risk factors for HS in men, after univariable analysis, four variables  were removed . Advancep = 0.1106) and ICH (p = 0.1445).The association between intensive BP control and stroke incidence has been studied in several randomized controlled trials (RCTs). In 2010, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, which included 4,733 type 2 DM patients with an intensive BP control group (SBP <120 mm Hg) and a standard BP control group, showed that a significant result in the HR of stroke in the intensive BP control group was lower than that of the standard BP control group [HR 0.59 (95% CI 0.39–0.89)] . In 2013Overall, the STEP trial  was the This study demonstrated that the AHR for ICH increased significantly for women with stage 1 HTN although that of ICH increased significantly for men with stage 2 HTN. This result seems to be contradictory to previous studies that showed a higher risk of ICH among men than among women . The reaOn the other hand, the AHR for the incidence of SAH was significantly increased for both men and women with stage 1 HTN. Among women with stage 1 HTN, the incidence of SAH was almost twice as high as that among men. The reason can be considered based on the study by Kim et al., who analyzed the epidemiology of unruptured intracranial aneurysm (UIA) using the same NHIS database . AccordiFor overall HS, men with stage 2 HTN showed a significant increase in incidence, and women with stage 1 HTN showed a significant increase in incidence as well. Therefore, for the primary prevention of HS, men need to manage a SBP of <140 mm Hg and a DBP of <90 mm Hg, and women need to manage a SBP of <130 mm Hg and a DBP of <80 mm Hg. However, for SAH, men with stage 1 HTN also had a statistically significant increase in the AHR. Accordingly, these results indicate that it is reasonable to start BP management from stage 1 HTN for both men and women to prevent ICH or SAH, the leading causes of HS. According to the risk factors for HS demonstrated in this study, more attention should be given to BP management at advanced ages since the risk of HS increases significantly with age for both men and women. For women, BP management is more important at advanced ages because an increase in HR with age is greater than that for men due to the effects of estrogen deficiency after menopause . On the The several limitations of this study are that it is an observational study using NHIS data rather than an RCT. Second, despite the premise that BP control was consistent during the 10-year observation period, based on the study design in which only subjects classified into the same blood pressure group were enrolled in the study for a total of 3–4 checkups, it is also possible that intraday fluctuations in BP or white coat HTN may have influenced the results. Third, since only those who had not taken HTN medications for 10 years were included in this study, there may be a selection bias in that these participants are relatively less strict about their healthcare. Finally, it is essential to recognize that the study population solely represents individuals from a single country. Consequently, the generalizability of the findings to other racial or ethnic groups should be interpreted with caution, considering potential geographic and racial disparities in stroke incidence and risk factors.Despite these limitations, the study has notable strengths, primarily its robust statistical power, which involved nearly 1 million patients over a 10-year observation period. This extensive dataset has provided valuable insights and yielded statistically significant results for certain aspects of hemorrhagic stroke that were not previously demonstrated in randomized controlled trials (RCTs). As with any research, it is crucial to have a comprehensive understanding of both the strengths and limitations to interpret the implications and practical applications of the findings effectively.This study demonstrated the risk of HS and its subtypes according to BP classification based on 2017 ACC/AHA guidelines by sex in the healthy young adult population. In conclusion, to prevent HS, both men and women between the ages of 20 and 65 years should manage their BP starting from stage 1 HTN, and stricter BP management should be required at advanced ages. In addition, smoking should be avoided, especially for men, who should also avoid excessive drinking and maintain a normal weight.Due to the stringent privacy regulations enforced by the NHIS, the raw data cannot be made publicly accessible. However, processed data used in the analysis phase is exempt from these restrictions and can be found in the The studies involving humans were approved by the Seoul National University Bundang Hospital Institutional Review Board (IRB number: X-1910-572-903). The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required from the participants or the participants' legal guardians/next of kin because due to the retrospective nature of this study.HSS: Visualization, Writing—original draft. J-MP: Writing—original draft, Writing—review and editing. YJL: Data curation. Y-DK: Data curation. TK: Methodology. SPB: Formal analysis. JSB: Formal analysis, Methodology. O-KK: Supervision, Writing—review and editing. CWO: Supervision, Writing—review and editing. SUL: Conceptualization, Funding acquisition, Methodology, Project administration, Supervision, Writing—review and editing.


Spiridon”, Iaşi, and analyzes the factors associated with this outcome. (2) Methods: In this retrospective study, patients with DFUs consecutively referred between 1 January 2007 and 31 December 2017 were followed up until 31 December 2020 (for 13 years). The study group included 659 subjects. (3) Results: During the study period, there were 278 deaths (42.2%) and the average survival time was 9 years. The length of hospitalization, diabetic nephropathy, chronic kidney disease, glomerular filtration rate, cardiovascular disease, hypertension, anemia, and DFU severity were the most significant contributors to the increase in mortality. Patients with severe ulcers, meaning DFUs involving the tendon, joint, or bone, had a higher mortality risk than those with superficial or pre-ulcerative lesions on initial presentation  after adjusting for confounding factors. (4) Conclusions: The findings of this study suggested that patients presenting with severe ulcers involving the tendon, joint, or bone exhibited a significantly higher risk of mortality, even when potential confounders were taken into consideration.  The prevalence of diabetes is increasing worldwide; therefore, one of the main goals of the World Health Organization (WHO) is fighting against this disease due to the impressive data related to diabetic foot epidemiology. Diabetes is the primary cause of 50 to 70% of all lower-limb amputations; 15% of diabetic patients will acquire a foot ulcer and 25–50% of them will need an amputation as a result of complications ,4. Poor The prevalence of foot ulcers varies widely, from 1% in Europe and North America to 11% in certain African countries . AccordiA recent meta-analysis established that the risk factors associated with 5-year mortality in patients with DFU were age, peripheral artery disease, chronic kidney disease, end-stage renal disease, amputation, and history of cardiovascular disease .Clinical classification systems for diabetic foot  Classification System and Score; IWGDF Guidelines on the prevention and management of diabetes-related foot disease; SINBAD  classification) ,13 incluOur study’s primary objective was to evaluate the clinical and biological factors that may influence the survival outcomes of individuals following the onset of diabetic foot ulcers. This study focused on estimating survival rates and identifying mortality predictors among a cohort of patients hospitalized consecutively over a 10-year period at a single regional center specialized in the treatment of DFUs. We used five classification systems to assess the severity of DFU, developing mortality prediction models for each of them. By evaluating these variables, a thorough understanding of the prognosis and influential factors associated with diabetic foot ulcers in hospitalized patients with diabetes may be attained.We conducted a study on patients with DFUs who were consecutively referred to the Diabetes, Nutrition, and Metabolic Diseases Clinic within the Emergency Clinical Hospital “Sf. Spiridon”, Iași, between 1 January 2007 and 31 December 2017. Patients admitted to our regional center were from 8 of the 41 counties in the north-eastern region of Romania. Patients transferred from other clinics or referred through the emergency department or by their diabetologist or family doctor were followed up until death or the final date recorded in the electronic case system for a period of three more years (until 31 December 2020). If there were multiple admissions during the study period, the first hospitalization was considered for the analysis.-Patients over 18 years of age, diagnosed with any type of diabetes ;-Patients admitted to the Diabetes, Nutrition, and Metabolic Diseases Clinic during the aforementioned time period; -Patients with an International Statistical Classification of Diseases, 10th Revision (ICD-10)  code corThe inclusion criteria for data collection were as follows: The exclusion criteria were as follows: previous foot ulcers or amputation, active neoplasia, end-stage organ diseases , dementia or psychiatric illnesses, and collagen vascular diseases.A database including all patients whose discharge files contained ICD-10 codes that could have been linked to diabetic foot pathology  was developed with the assistance of the hospital’s statistics service. A discharge diagnosis analysis was performed, and patients without a diagnosis related to DFU were removed from the database. Then, hospitalizations with the same personal identification code were analyzed, and the first hospitalization was chosen, with the others excluded from the main analysis, but considered as the number of readmissions for the same patient, representing a variable related to the progression of diabetic foot. Thus, 659 patients were entered into the database .Social and demographic factors: area of residence , sex, and age;History of diabetes: disease duration, type of treatment ;Presence of specific diabetic chronic complications , high blood pressure (HBP), and cardiovascular disease evaluated during the first hospitalization;Biological markers: glycated hemoglobin (HbA1c), inflammation markers , lipid profile, renal function, total proteins, albumin, ASAT, ALAT, and uric acid;Clinical characteristics of wounds: location , depth , extension , and perfusion;Infection: the presence of symptoms and signs of inflammation and/or pus, abnormal specific biochemical test results, and the presence of osteolysis on foot X-ray.a.The University of Texas Staging System for Diabetic Foot Ulcers uses four grades , which are influenced by the existence of infection (Stage B), ischemia (Stage C), or both (Stage D) . Scores b.The Wagner–Meggitt classification of foot ulcers evaluates the clinical characteristics of foot ulcers (extent and depth) ; c.The Saint Elian Wound Score System (SEWSS)  includesd.The SINBAD Classification System and Score is an acronym that comes from six elements graded according to their severity: ulcer Site, Ischemia, Neuropathy, Bacterial infection, Area, and Depth . The tote.The Society for Vascular Surgery Lower Extremity Threatened Limb Classification System (WIfI) is a grading system that evaluates the severity of a wound , ischemia , and foot infection (from absent to severe: limb- and/or life-threatening) . Based oIn this study, five clinical classification systems for diabetic foot were used:The necessity of amputation of the lower limb for DFU during the first hospitalization was registered. Patients who needed a limb amputation were transferred to a surgical clinic in the same hospital.We included in our analyses the following potential risk factors associated with DFU outcome:The intended outcome, death or survival, was recorded in the database, being extracted from the regional registry of diabetic patients, so that the authors had access to all information regarding their subsequent evolution.p-value of < 0.05 was considered significant. An HR value > 1 corresponds to an increase in relative risk compared with a reference subject.Data analysis was performed using the Statistical Package for Social Sciences (SPSS software version 20) . In the This study was approved by the Ethics Commission of the University of Medicine and Pharmacy “Gr. T. Popa”, Iaşi, approval number 2324/19 January 2017. Informed consent from patients was not requested because it was a retrospective, observational study. The identification data of the participants have not been and will not be used for any other purpose.p < 0.05) (p = 0.113). Charcot’s foot had a low incidence in our study group (3.2%). Cardiovascular disease was identified in 59.8% of participants. Most patients included in our study had high blood pressure (73.3%). Obesity was identified in 31.6% of the total group. This study was conducted on 659 subjects with a mean age of 61.34 ± 11.06 years and the majority of participants were men (66%). Most patients (51.4%) came from urban areas. Among the patients, a high proportion had had type 2 diabetes (86.19%), followed by type 1 diabetes (12.4%) and other specific types of diabetes (1.67%). Patients with type 1 diabetes had a statistically significantly longer duration of the disease (17.59 years) compared with people with type 2 diabetes (10.37 years) and other specific types of diabetes (10.09 years) ( < 0.05) . A perceRegarding the type of hospitalization, we noticed that 73.6% were emergency admissions, a smaller percentage (0.61%) were hospitalized via transfer from other departments, and the rest were referred to our clinic by family doctors or other specialists. Diabetic ketoacidosis on admission was present in 14.9% of participants, with a higher frequency in men (9.5%). The average length of hospitalization was 19.68 ± 13.38 days. In the studied group, some cases had subsequent readmissions (a percentage of 29.89%). In addition to the usual discharge, which was the majority of cases (89.53%), 3.64% were transferred to other departments, 1.37% died during the first hospitalization, and 4.86% were discharged on request.p = 0.418).According to the University of Texas Staging System for Diabetic Foot Ulcers, 0.2% of DFUs were classified as AIII and the same percentage (0.2%) were categorized as B0. The majority of patients (21.2%) had a stage BI ulcer . There wp = 0.940).According to the Wagner–Meggitt classification, 32.4% of patients had grade 1 ulcers, and 29.2% had grade 2 ulcers. The smallest number of cases had grade 0 ulcers . There wp = 0.625)  evaluation revealed that 85.7% of all cases were moderate., with no differences between men and women (= 0.625) .According to the SINBAD Classification System and Score, only 8.2% of the patients had a high-grade DFU. Almost similar percentages were observed for low- and moderate-grade ulcers .When the WIfI Classification system was applied, we identified that 29.1% of the patients had stage 4 ulcersIn our sample of 659 subjects, 278 deaths were recorded during the 13-year period (42.2%). The average survival time was 9 years, with a median of 12 years .p < 0.001) (p = 0.12 or chronic kidney disease) and cardiovascular diseases  had a shorter average survival time  . Patientval time .p = 0.044). Participants with the Texas A0 to BI stages had a statistically significantly longer survival time than those with stages BII through DIII. There were no differences in survival time between grades 3, 4, and 5, the first two grades in the Wagner–Meggitt classification. The Saint Elian Wound Score System was associated with higher mortality risk  .The potential confounding factors in the multivariate analysis were as follows: age, sex, duration of diabetes, cardiovascular disease, diminished renal function, anemia, and serum albumin, and the adjustment was made accordingly. The Texas classification was divided into two categories: the first included ulcers from stage A0 to BII, and the second category included ulcers from BIII to DIII. Patients with deep ulcers involving the tendon, joint, or bone had a higher mortality risk than those who had superficial or pre-ulcerative lesions  after taking into consideration confounders that could modify the survival time. At the same time, a predictive effect of the associated confounders was observed: age , cardiovascular disease , anemia , and glomerular filtration rate  . Using the same argument, the Wagner–Meggitt classification was divided into two categories: the first category included ulcers with grades 0, 1, and 2, and the second category included those with grades 3, 4, and 5. After inclusion in the multivariate prediction model, patients with bone or joint lesions on admission had an 88.9% higher mortality risk during follow-up (CI: 1.024–3.483) compared with those with superficial ulcers. The presence of cardiovascular comorbidities, chronic kidney disease, anemia, and demographic factors were predictive confounders associated with the risk of mortality .A high grade in the SINBAD Classification System and Score doubled the mortality risk. Furthermore, the presence of a low value of hemoglobin on admission and the association with cardiovascular disease significantly increased the mortality rate during the follow-up period in our sample. p = 0.067, and HR = 1.755, p = 0.077) when other factors influencing survival were taken into account. In this case, survival was influenced by the presence of cardiovascular disease, anemia, and a decreased glomerular filtration rate  ,31, whicIn our study, the mortality of patients with diabetic foot ulcers was high (42.2%) and the average survival time was 9 years, with a median of 12 years. The ten-year mortality in patients with DFUs varies in different studies, from 45%  to 70% . Cumulatp < 0.001 and HR = 1.433, p = 0.14, respectively), cardiovascular disease remained an independent predictor of mortality.In our study, patients with cardiovascular disease and hypertension had a higher mortality risk. In the multivariate analysis  was after major amputation, and age and a history of coronary heart disease were associated with mortality as well .On the other hand, in a study conducted in Spain on 256 patients with DFUs, macrovascular events  were not related to an increased mortality risk . A meta-Several ways of associating DFUs with an increase in cardiovascular mortality have been described, but the mechanisms that explain this connection are not fully understood. In diabetic peripheral neuropathy, oxidative stress and chronic inflammation have deleterious effects on the endothelium, in addition to neuronal cells. Chronic inflammation, a prominent characteristic of type 2 diabetes, serves a crucial role in the development of atherosclerosis and vascular complications resulting from endothelial dysfunction . Periphep = 0.12) had a significantly shorter survival time than those without kidney disease. The estimated glomerular filtration rate was an important predictor for the survival of patients with DFUs in the multivariate analysis.In our study, patients with diabetic nephropathy  [In the study conducted by Aragon-Sanchez et al., an estimated glomerular filtration rate lower than 60 mL/min/1.73 m = 0.01) . Moreove = 0.01) .The mesenchymal cells are progenitors of both renal mesangial cells and smooth muscle vascular cells. Therefore, the pathological processes involved in atherosclerosis will also lead to glomerulosclerosis. Furthermore, these changes lead to a loss of selective permeability of the basal membrane and proteinuria .Cardiometabolic syndrome is characterized by endothelial dysfunction, increased oxidative stress, subclinical proinflammatory status, dyslipidemia, microalbuminuria, and hypertension, all of which contribute to the risk of major cardiovascular events. Glomerulosclerosis and vascular atherosclerosis develop simultaneously in type 2 diabetes, and albuminuria is considered to be predictive for both the progression of diabetic kidney disease and cardiovascular events ,53. Furtp = 0.067) when the other factors influencing the survival of the patients included in the study were taken into account.In our sample, 35.1% of patients had superficial lesions, 33.8% had deep ulcers, and 31.1% had wounds that included all layers. Patients with deep ulcers, according to the Texas Staging System, had a higher mortality risk than those with superficial or pre-ulcerative lesions . Furthermore, patients with a severe ulcer according to the SINBAD Classification System and Score had a higher mortality risk compared with those who had low- and moderate-grade lesions . According to the Wagner–Meggitt classification, patients with bone or joint lesions had an 88.9% higher mortality risk (CI 1.024–3.483). The SEWSS did not have a predictive capacity . However, there was no difference in the overall survival rate between WIfI stages [Classification systems for DFUs take into consideration the extension and depth of the lesions and the presence of infection. Early identification and multidisciplinary management of diabetic foot ulcers are crucial in decreasing morbidity and mortality related to limb amputation. In a recent retrospective study conducted by Rubio et al. , the SINI stages .p = 0.040), thrombocytosis , and polymicrobial culture of deep tissues  were independent risk factors for mortality [In a retrospective analysis that included 401 patients between 2010 and 2019, Sen and Demirdal  evaluateortality .A prospective study conducted by Schofield et al.  showed aIn a retrospective study, Vuorlaakso M et al.  reportedDespite all efforts to achieve early, complex, and multidisciplinary management of diabetic foot, the rate of wound healing is still diminished and has not increased in the last three decades. In patients with diabetes, their chronic pro-inflammatory status creates an imbalance between the two types of cytokines secreted in wounds, with pro- or anti- inflammatory effects. The primary role in this imbalance is played by the macrophages, as they will secrete different types of cytokines, depending on the phase of the wound-healing process. First, the secretion will consist of several pro-inflammatory cytokines with antimicrobial properties, and afterward, the secretion will switch to anti-inflammatory cytokines, which will promote wound healing. In patients with diabetes, this latter phase is altered, explaining the delayed healing. Thus, the opened wound becomes a gateway for infections that, combined with impaired leukocyte function associated with hyperglycemia, can evolve into sepsis and/or limb amputation ,45.We conducted a retrospective study on a sample of patients consecutively hospitalized in the Diabetes, Nutrition, and Metabolic Diseases Clinic at “Sf. Spiridon” Hospital, Iaşi. The design of our study permitted the collection of data from an important number of patients over a significant length of time. According to our knowledge, this is the first comparative analysis of five ulcer severity classification systems in predicting patient mortality using the same sample. These five systems included the oldest ones (Wagner–Meggitt and University of Texas Staging System), but also the newest ones recommended recently by the IWGDF guidelines . Our findings provide additional real-world evidence for predicting long-term mortality in patients with DFU, which can be added to the previous research in this area. However, a prospective design is more appealing, given the possibility to include selected variables to which we did not have access, such as procalcitonin, osteoprotegerin, or RANKL. Also, we could not survey our sample at different points of time to more accurately estimate the glycemic control of our patients. Furthermore, we did not analyze the relationship between DFUs and the cause of death, as we only had access to electronic case histories, which did not register it. Although it would have been important, we did not analyze the relationship with antiplatelet and lipid-lowering medications. Finally, although we conducted our study in a single center, “Sf. Spiridon” Hospital, Iaşi, is a regional center, with a large reach across the north-eastern region of our country, with general surgery and vascular surgery departments, which gave us the opportunity to reduce selection bias.In conclusion, the findings of this study indicate that patients presenting with severe diabetic foot ulcers (according to different classification systems) have a significantly greater likelihood of mortality. Even after adjusting for concomitant factors that might influence survival, the observed association remained significant. These findings highlight the significance of recognizing the severity of diabetic foot ulcers at the time of their initial presentation, as they serve as important prognostic indicators. Identifying high-risk patients enables targeted interventions and individualized management strategies to increase their survival chances. Further research is needed to explore additional contributing factors and refine risk assessment models in order to enhance patient outcomes in the management of diabetic foot ulcers.


The findings provide evidence between the mass mortality occurrences in SA sea lions and HPAIV, strongly indicating a causal relationship. Further studies are needed to better understand the pathogenesis and transmission.In Chile, since January 2023, a sudden and pronounced increase in strandings and mortality has been observed among South American (SA) sea lions (Otaria flavescens), prompting significant concern. Simultaneously, an outbreak of highly pathogenic avian influenza H5N1 (HPAIV H5N1) in avian species has emerged since December 2022. To investigate the cause of this unexpected mortality, we conducted a comprehensive epidemiological and pathologic study. One hundred sixty-nine SA sea lions were sampled to ascertain their HPAIV H5N1 status, and long-term stranding trends from 2009 to 2023 were analyzed. In addition, two animals were necropsied. Remarkably, a significant surge in SA sea lion strandings was observed initiating in January 2023 and peaking in June 2023, with a count of 4,545 stranded and deceased animals. Notably, this surge in mortality correlates geographically with HPAIV outbreaks affecting wild birds. Among 168 sampled SA sea lions, 34 (20%) tested positive for Influenza A virus, and 21 confirmed for HPAIV H5N1 2.3.4.4b clade in tracheal/rectal swab pools. Clinical and pathological evaluations of the two necropsied stranded sea lions revealed prevalent neurological and respiratory signs, including disorientation, tremors, ataxia, and paralysis, as well as acute dyspnea, tachypnea, profuse nasal secretion, and abdominal breathing. The lesions identified in necropsied animals aligned with observed clinical signs. Detection of the virus  Since its identification in China in 1996, highly pathogenic avian influenza (HPAI) caused by H5N1, has spread throughout the world causing an epizootic that has affected Africa, Asia and the Pacific, the Americas, Europe, and the Middle East. The virus has continually threatened not only wild, captive, and free-range birds, but also wild, captive, and domestic mammals, as well as humans  Sea Lion, in the Antofagasta Region. With an estimated national population of 125,000 individuals, and its presence spanning the entire territory ; gray seals  . The reported species included harbor seals  of Chile. The information encompasses the period from January 2009 to June 2023 and comprises georeferenced points, precise locations, the number of SA sea lions affected in each event, and, when available, additional data such as size, sex, age, body condition, visible lesions, and possible causes of stranding. For the analysis, we considered mortality and strandings as the same, due to strandings in more than 95% of the cases finalized in death. Regarding determining the moment when the stranding of pinnipeds arises statistically significant, statistical process control (SPC) charts were performed using the number of deceased animals per month, considering the whole country , refrigerated at 4 °C, and submitted for real-time RT-PCR at the SAG Livestock Virology Laboratory and Biotechnology Laboratory .The samples were processed within the next two days after arrival. The RNA was obtained using the MagMAX™ Core Viral/Pathogen kit , and the first identification was attempted using the VetMAX-Gold AIV Detection Kit (Applied Biosystems™ Cat No. 4485261) for generic Influenza A virus (IAV) detection, targeting the M gene. From positive animals, real-time RT-PCR and Sanger sequencing were attempted for H5 2.3.4.4b clade confirmation using VSL-USDA protocols NVSL , 2023c.O. flavescens were used for high-risk spatial cluster determination. In addition, publicly available data regarding positivity to HPAIV in avian sources (non-poultry species) was also used, determining high-risk spatial clusters to evaluate geographical relationships (https://www.sag.gob.cl/ia). The presence of spatial clusters or ‘hotspots’ of cases was identified utilizing Scan Statistics, specifically Kulldorff’s space exploration statistic, considering a purely spatial analysis with a Bernoulli distribution  targeting the nucleoprotein of all strains of influenza virus type A was used at a dilution of 1.5 µg/ml for 30 min at room temperature (RT). The slides were then incubated with an indirect peroxidase polymeric detection kit  for 30 min at RT, followed by revelation with Magenta solution . Slides were counterstained with hematoxylin, coverslipped, and examined microscopically. The immunostaining included a positive reference control (brain sample molecularly confirmed positive for H5N1) and a negative control (the same section in which a primary antibody was omitted).Selected fixed tissues including the brain, lungs, heart, and pancreas were processed for Hematoxylin and Eosin (HE) staining and Immunohistochemistry (IHC) targeting the Influenza Nucleoprotein. These analyses were performed at the Institute for Animal Health and Food Safety of The University of Las Palmas de Gran Canaria. Briefly, for IHC, 3-µm-thick FFPE tissue sections that were deparaffinized, hydrated, and subjected to antigen retrieval (the sections were treated with proteinase K for 6 min). Endogenous peroxidase activity was blocked  for 10 min. A mouse primary monoclonal antibody  samples. More in detail, RNA was extracted from four 10 μm-thick FFPE sections of the cerebrum of the male and the cerebellum of the female SA sea lions and deparaffinized using the xylene-alcohol method according to the manufacturer’s recommendations  with some modifications. Specifically, the washing steps involved in xylene deparaffinization were performed twice at 50 °C for 3 min, followed by a twice washing with ethanol after residual xylene was removed and overnight digestion at 37 °C. Molecular detection of type A influenza virus  assay based on the avian influenza virus matrix gene with a set of primers and a TaqMan probe) and the avian H5 and H7 Hemagglutinin subtypes (with two probe sets developed based on North American avian influenza virus sequences) was performed as previously described . From 2009 to 2019, the mortality rate among stranded South African sea lions was 27%. However, in 2023, 95% of stranded sea lions were reported as deceased, these differences were statistically significant.n = 507). The summary of results can be retrieved from The SPC chart shows the increase in the stranding of sea lions in January 2023, surpassing the upper control lines of two and three standard deviations over the average . In Januth to June 30th, 152 stranding cases of SA sea lions, involving 168 SA sea lion individuals were sampled for Influenza A detection by real-time RT-PCR. The complete list is presented in Supplementary Table S1. So far, out of 168 animals, 34 have been confirmed positive for Influenza A virus by real-time RT-PCR, which represent 20% of the animal sampled. The Ct values from swabs ranged between 20 to 35, with a mean of 30.1 [SD = 4.4]. The samples collected from positive specimens were either oropharyngeal or rectal samples, most of them processed in pools. To date, positive HPIAV H5N1 confirmed cases have been detected in 12 out of the 15 coastal Regions of Chile. Twenty-one of the 34 IAV-positive cases were identified and confirmed as H5N1 2.3.4.4b clade, the remaining cases were inconclusive due to concerns of sample quality of high Ct values in the IAV detection.From January 8There is a noticeable correlation between the widespread mortality of SA sea lions and the occurrences of HPAIV in wild birds. This correlation is particularly evident when analyzing the geographic distribution of cases. p = 0.0081) and showcases a high-risk spatial cluster with a relative risk of 3.96. This cluster is situated at coordinates 18.419067 S − 70.321289 W and spans a radius of 202.72 km.A remarkable finding emerges from the analysis of SA sea lions. An observed positivity for IAV in SA sea lions is statistically significant . The main gross lesions observed in this animal were highly hyperemic lungs with atelectasis and emphysematous areas, and in the brain, there was a marked hyperemic appearance in the vessels of the groves suggestive of meningoencephalitis inflammation. In this case, the virus was identified by real-time RT-PCR in several tissues including the brain (Ct: 18.4), lungs (Ct: 26.8), liver (Ct:30.6), kidney(Ct: 27.3), urinary bladder (Ct: 25.2), and heart (Ct: 31.4). The lowest Ct value was observed in the brain (Ct = 18.4). However, this animal was negative in oral, nasal, and rectal swabs.Microscopically, focal isolated pneumonia and bronchial dilation with a protein-rich edematous exudate and fresh blood as well as few peri-bronchial multifocal foci of cell debris, epithelial-like cells and inflammatory cells involving the glandular area were observed in the lungs. No other lesions were histologically detected in the pancreas and heart tissue sections. However, severe multifocal to locally extensive non-suppurative meningoencephalitis and encephalitis, mostly affecting the gray matter, with a large number of lymphohistiocytic and plasmacytic perivascular cuffs, endothelial cells activation, and abundant gliosis, neuronophagia, and neuronal and glial necrosis (characterized by fragmentation and acidophilia) associated with hemorrhages were observed . The othSupplementary Table S2.The IHC revealed the presence of intralesional nucleoprotein antigen of AIV exclusively in the brain of both analyzed sea lions and in the lungs of the male  and 6. SOtaria flavescens observed in Chile and its link with HPAI H5N1. The data indicate that the mortality started in January 2023, where in a month the stranded individuals overpassed the usual events in a calendar year before HPAI H5N1 detection. According to the NOAA, the current data reveals the occurrence of an unusual mortality event (UME), as evidenced by significant increases in morbidity, mortality, or strandings compared to historical records, along with temporal and spatial shifts in these patterns. Furthermore, the affected animals exhibit consistent or uncommon pathological findings, behavioral changes, clinical signs, or overall physical conditions, all of which align with the established criteria for identifying a UME .However, despite the microscopic lesions observed in both necropsied South American sea lions, the antigen was exclusively immunolabeled in the lungs and brain of the male and the cerebellum of the female. This is compatible with the clinical manifestation for the male, but not evident for the female. The most conspicuous neurological syndrome was able to be observed in the male sea lion (Phoca vitulina) which was also found in the brain. On the contrary, in concordance with our study, recent reports of HPAIV H5N1 in pinnipeds have been indicated with partial or extensive evidence of clinical neurological signs  , leading to neurological signs that caused stranding and rapid death, even more as a result of ataxia and paralysis of limbs many of them drowned and washed up dead on the shoreline. In some cases of per-acute infections, the excretion of the virus might not always be detectable, which could explain the lack of detection in certain instances. In this regard, it will be crucial to determine by serology the percentage of sea lions that have recovered.One important question that needs to be addressed is whether transmission occurs from sea lion to sea lion or if the virus is only directly transmitted from avian sources. This inquiry, which was also raised by Gamarra Toledo et al. (preprint), in response to the identification of widespread stranding events in Peru, serves to challenge the previously established assumptions concerning direct avian transmission  and the Biobio Region are the most affected areas. While this pattern could be partly influenced by the size of populations in those regions (Oliva et al. After repeatedly observing wild sea birds interacting with SA sea lions in the field, we developed a hypothesis based on the shared food habitat as the most probable way of virus transmission between these two groups of species. Our hypothesis suggests that when positive HPAI-H5N1 wild avian species attack a school of fish to obtain prey, SA sea lions, also benefit from the abundance of food. This creates an opportunity for interspecies transmission. Interestingly, the regions with the highest number of positive cases are the only areas where both SA sea lions and wild birds share the same school of fish, particularly anchovies and sardines, which happen to be the preferred prey of abundant wild birds and SA sea lions in these regions (Neira and Arancibia The comprehensive analysis of epidemiological, spatial, pathological, and molecular data strongly supports the association between the mortality events and HPAIV H5N1, confirming the high susceptibility of SA sea lions to this virus. Despite this, the pathogen has proven challenging to detect in SA sea lions, particularly in swabs, possibly due to the neurological nature of the infection.The most probable mode of transmission is from avian species during feed-sharing activities, a mechanism that appears to be highly effective. However, transmission between sea lions themselves is considered unlikely. Further research is imperative to fully comprehend the pathogenesis of HPAIV H5N1 in SA sea lions, including disease progression and tissue tropism, as well as the routes of transmission and potential sources of dissemination.Other implications of this study to consider are the potential for sea lions to act as a source of the virus to humans, the importance of sea lion conservation, and the role of sea lions in transmitting the virus to avian species and potentially indirectly to poultry.Click here for additional data file.


Background: Cardiac arrest is a medical emergency marked by the cessation of cardiac mechanical activity and insufficient blood flow. CPR (cardiopulmonary resuscitation) is a life-saving method that involves restoring the essential functions of two vital organs: the heart and lungs. This study was conducted to identify the outcome of CPR in cardiac arrest patients presented to the emergency department (ED) and to identify predictors of CPR outcomes.Methodology: This was a retrospective, descriptive study. All in-hospital cardiac arrest patients who underwent CPR in the King Saud Medical City (KSMC) ED between January 2017 and January 2020 were analyzed, with a sample size of 351 patients.Results: Overall return of spontaneous circulation (ROSC) and survival to discharge (STD) were achieved in 106 (30.2%) and 40 (11.39%) patients, respectively. When assessing the predictors of ROSC, the analyses showed that patient age, pre-arrest intubation, the method used to deliver oxygen, and CPR duration were all statistically significant predictors for ROSC. Similarly, when assessing predictors associated with STD, the analyses showed that patient age, pre-arrest intubation, the method used to deliver oxygen, and CPR duration were positively associated with STD.Conclusion: Comparing the study's findings to those of similar studies, it shows a CPR outcome rate within the range of similar studies. It also highlights that CPR outcomes are highly associated with CPR duration (a maximum of 30 minutes), younger age, and endotracheal intubation. Cardiac arrest is a medical emergency marked by the cessation of cardiac mechanical activity and insufficient blood flow, as evidenced by the lack of a palpable central pulse, apnea, loss of pulse, blood pressure, and spontaneous breathing . AlthougCPR (cardiopulmonary resuscitation) is a life-saving method that involves restoring the essential functions of two vital organs: the heart and lungs ,4. In a The emergency department (ED) of a hospital is responsible for most cardiac arrest patients, whether they are brought in from outside the hospital or are critically ill patients who go into cardiac arrest while receiving initial care in the ED. Existing research shows that a variety of factors influence the outcome of CPR done in the emergency room. Patient variables such as age and gender are included, as well as clinical and CPR-specific characteristics such as cardiac arrest mechanism, initial rhythm observed after cardiac arrest, clinical environment, response time, and CPR duration, among others -10.It is becoming more vital to investigate pre-arrest and arrest parameters and gain better knowledge of their prognostic implications so that high-quality CPR may be given in a rational, productive, and successful manner to those patients who would benefit the most. This study was conducted to identify the outcomes of CPR in cardiac arrest patients presented to the emergency department at King Saud Medical City in Riyadh, Saudi Arabia, and identify predictors associated with improved outcomes.Subjects and study designThis was a retrospective, descriptive study of all in-hospital cardiac arrest patients who underwent CPR in the King Saud Medical City (KSMC) ED for a period of three years, from January 2017 to January 2020. KSMC is a tertiary care center located in Riyadh, the capital city of Saudi Arabia.InclusionPatients who had sustained an in-hospital cardiac arrest in the ED and underwent CPR between January 2017 and January 2020 were included. The medical records of 351 patients were included in this study's final analysis.ExclusionOut-of-hospital cardiac arrest patients (age < 14 years old), those who were reported dead on hospital arrival, and those with missing records or incomplete data were excluded. Those with existing do-not-resuscitate orders and those who were immediately shifted to another facility for post-arrest care were excluded from the final analysis. Additionally, in patients who had more than one episode of cardiac arrest, the first event was considered to be the seminal event.Data collectionData were extracted from the KSMC emergency database, electronic medical records, and patient paper notes on patient demographics, clinical history, and cardiac arrest clinical features such as location, likely cause of arrest, monitored arrest, and initial rhythm. CPR variables such as the time that CPR started, CPR duration, and intubation during CPR were included in the study. The CPR outcomes were determined to be ROSC and STD for the purpose of this research. Patients who were discharged home from the hospital as well as those who were moved to another facility after a minimum of 24 hours following ROSC were included in the STD category.Data analysisData were analyzed using SPSS version 26  and Microsoft Excel  to generate tables and charts with a P-value of less than 0.05 considered significant. Means and standard deviation were recorded for continuous variables for descriptive analysis. As previously mentioned, ROSC and STD were the outcomes of interest.Ethical considerationEthical approval from the Institutional Review Board (IRB) of King Saud Medical City (IRB registration number: H-01-R-053) was obtained before data collection began. Regarding confidentiality and privacy, the personal information (name and contact information) of patients was not included in the study. Since we used medical records, informed consent was waived.Three hundred and fifty-one patients presented to the ER-KSMC. In total, 264 (75.2%) were males, and 87 (24.8%) were females. More than 60% were of cardiac etiology (212 patients); 45 patients (12.8) had respiratory etiologies; all other etiologies were less than 10%. As for the pre-arrest characteristics of these patients, 12 (3.4%) were on dialysis, 147 (41.9%) were intubated, 304 (86.6%) had IV access, 95 (55.6%) were under mechanical ventilation, 345 (98.3%) were monitored, 169 (48.1%) were receiving IV vasopressors, 164 (46.7%) of patients’ blood pressures were not recorded, 162 (46.2%) were hypotensive, 17 (4.8%) were hypertensive, and 8 (2.3%) were found to have normal blood pressure. More than 328 patients (93%) received the first dose of epinephrine within less than five minutes, and only 23 (6.6%) patients received the first dose of epinephrine after more than five minutes. Results showed that an endotracheal tube was used on 128 of the patients (36.5%). It was placed at the time of the event, and they were not reintubated again after the cardiac arrest took place. About 19 of the patients (5.4%) were reintubated, and 130 (37%) were intubated during the event of CPR. Almost 74 of the patients (21.1%) required an ambu bag instead of an endotracheal tube. Regarding the rhythm, results showed that 173 (49%) of the patients had an asystole rhythm, 120 (34.2%) had a rhythm of pulseless electrical activity, and 35 (10%) were found to have bradycardia. As for shockable rhythms, 16 (4.6%) of the patients had ventricular fibrillation, and 7 (2%) had ventricular tachycardia . The ROSC group had an average age of 52.17 (±13.98 SD), compared with the STD group, which had an average age of 48.3 years (±15.7 SD). The mean CPR duration for all patients was 26.5 minutes (±8 SD). The CPR duration was 23.4 minutes (±8.5 SD) for the ROSC group compared with the STD group, with an average duration of 18.3 minutes (±7.76 SD).Males made up a larger fraction of the patients who achieved ROSC and STD . Younger patients, compared to older patients, had a considerably higher chance of maintaining ROSC (p = 0.032), and the same was true for the STD group (p = 0.001). Analysis showed that as the CPR duration increases, the chance of maintaining ROSC (p=0.016) decreases, and the same is true for the STD group (p=0.015).When assessing the predictors of ROSC, the analysis shows that patient age, pre-arrest intubated patient, method used to deliver oxygen, and CPR duration were all statistically significant for ROSC Table .Similarly, when assessing predictors associated with STD, the analysis shows that patient age, pre-arrest intubated patient, the method used to deliver oxygen, and CPR duration were all associated with STD Table .Cardiac arrest is characterized by a sudden loss of breathing and heart function. If not treated immediately, poor blood supply to the brain and other organs can result in a person losing consciousness or even passing away . This stSome studies have shown how advancing age is associated with a reduced likelihood of survival to hospital discharge, whereas others claim that there is no association between age and the outcome of CPR ,14. The Surprisingly, there was no association between the cardiac rhythm and ROSC/STD; this could be explained by the fact that the shockable rhythms in this study were 6.6% compared to other studies that were conducted in Pakistan and Norway that included 25% and 27% shockable rhythms, respectively ,15. AdulThe largest number of resuscitated patients in this study (75.2%) were male. Contrary to a study done in Iran , the resIn our study, we demonstrated a significant association between endotracheal intubation and favorable CPR outcomes, which is in line with a study done in China . HoweverAlthough this study provides valuable insights into the predictors of favorable CPR outcomes in the emergency department, there are some limitations that should be considered. First, this study was a retrospective analysis, and as such, the data collected was reliant on medical records. Therefore, this could potentially lead to inaccuracies in the data, as not all the data points may have been accurately recorded. Additionally, this study was conducted in only one center, which may limit the generalizability of the results. Several patients lacked post-hospitalization patient data, making it impossible to study the relationship between CPR and survival and longer-term benefits. Finally, the sample size of this study was relatively small, with only 351 patients included. This may limit the statistical power of the analysis and lead to potential biases in the results.This was a retrospective study carried out at KSMC that focuses on identifying the outcome of CPR in cardiac arrest patients presented to the emergency department between January 2017 and January 2020 and identifying predictors of these outcomes. Comparing the study's findings in relation to those of similar studies, it shows a CPR outcome rate within the similar studies' range. It also highlights that CPR outcomes are associated with CPR duration not exceeding 30 minutes, younger age, and endotracheal intubation. Multi-center prospective studies should be conducted in the future, enabling standardized recording of events and prognostic factors, enabling more precise knowledge of the factors that predict CPR outcomes, and increasing the generalizability of the results.


The recently published “Life’s Essential 8” (LE8) by the American Heart Association has overcome some limitations in evaluating cardiovascular health (CVH) in the previous “Life’s Simple 7.”We aimed to examine the secular trends in CVH, as assessed by the LE8, in US adults from 2005 to 2018.Using cross-sectional data from the National Health and Nutrition Examination Survey between 2005-2006 and 2017-2018, we calculated the age-standardized mean scores of overall CVH and each of the LE8 components, where a higher score (range 0-100 points) means a better health status. A total of 21,667 adults aged 20-79 years were included in this analysis.P=.82). The individual metrics did not significantly change for diet , physical activity , and blood pressure , improved for nicotine exposure , sleep health , and blood lipids , and worsened for BMI  and blood glucose .The overall CVH did not significantly change between 2005-2006 and 2017-2018 . Other metrics such as nicotine exposure, blood lipids, and sleep health improved, while BMI and blood glucose deteriorated over time. Cardiovascular disease (CVD) is a major public health issue worldwide . In the Given that a large part of the CVD burden is attributable to a limited number of health and behavioral factors, the American Heart Association (AHA) promoted 7 cardiovascular health (CVH) metrics  in 2010 , includiThe LS7 was widely used in the past decade and had played an important role in promoting CVH in the United States and around the world. However, there are some limitations to the LS7 . First, 1c level has been added in addition to fasting glucose, and non–high-density lipoprotein cholesterol is used rather than total cholesterol to assess blood lipids [The newly released Life’s Essential 8 (LE8) metrics proposed by the AHA  addressed lipids . One recd lipids , suggestd lipids , these fThe new CVH score defined by the LE8 has recently been shown to be inversely associated with the risk of all-cause and CVD mortality . One stuData were obtained from the National Health and Nutrition Examination Survey (NHANES), which consists of serial cross-sectional surveys conducted by the National Center for Health Statistic of the US Centers for Disease Control and Prevention to evaluate the health and nutritional status in US adults and children. Participants were selected using a multistage cluster probability sampling method, and all eligible participants were invited to complete a household interview and a physical examination. The questionnaire includes information on demographic, socioeconomic, lifestyle, and other health-related variables, and the physical examination consists of anthropometric and biological measurements. Data from the NHANES are publicly available . The NHAWe performed analyses in consideration of several demographic characteristics: age, sex, race or ethnicity, educational level, marital status, and household income. We classified participants into three age groups: 20-39, 40-64, and 65-79 years . Self-reThe NHANES was approved by the National Center for Health Statistics Research Ethics Review Board. Written informed consent was obtained from all participants. This study was exempted from ethical approval by the institutional review board of Shandong University given the use of deidentified and open access data.2). BP was measured for three consecutive times after 5 minutes of seated rest, and the average of the second and third readings was used (or the average of the first and second measurements for participants who only had 2 readings or using the first measurement for participants who only had 1 reading). Information on the use of antihypertensive drugs was obtained from the interviewed questionnaire at home. Blood samples were collected at a mobile examination center and sent to a central laboratory for the assessment of blood lipids, fasting glucose, and hemoglobin A1c. Data on the use of lipid-lowering medications, insulin, or oral hypoglycemic agents were obtained from the interviewed questionnaire at home. Changes for some biochemical indexes in measurement methods and used instruments over time were adjusted according to the official recommendation to make them comparable across different survey years [The LE8 score is based on 4 “behavioral factors”  and 4 “health factors” . Diet quality was assessed using the Healthy Eating Index 2015 (HEI-2015) based on data from 2 interviewer-administered 24-hour dietary recalls. Diet was assessed using the “Food Patterns Equivalents Database 14” from the US Department of Agriculture [ey years . The 8 bey years , with a ey years .P values of <.05 were considered statistically significant.Differences in percentages of demographic characteristics across the 7 survey waves were assessed with the chi-square test. We calculated the age-standardized mean scores and their 95% CI for the overall CVH score and for each of the 8 CVH components. We performed stratified analysis by sex, age group, educational level, marital status, race or ethnicity, and family income category. We used linear regression model to estimate the linear trends between 2005 and 2018 with adjustments for sex, age group, educational level, marital status, and family income category if appropriate. Data were standardized for age using a direct standardization method based on the age distribution of the 2018 US population  . Since oP=.01; A total of 21,667 participants aged 20-79 years were included in this study. The distributions of sex, age group, race or ethnicity, marital status, and family income did not differ across the survey waves. Participants with an educational level lower than high school decreased from 13.9% in 2005 to 8.6% in 2018 P=.01; .P for trend=.82), as well as in almost all subgroups  in 2005 to 65.0 (95% CI 62.8-67.1) in 2018 , but theubgroups . Trends ubgroups . Adults ubgroups . The resubgroups . The oveThe age-standardized mean scores of diets, PA, and BP did not significantly change from 2005 to 2018 , as wellBy 2018, Americans who were female , young adults aged 20-34 years , non-Hispanic White , or in the “Other” category  had (or tended to had) higher (better) age-standardized mean LE8 scores of overall CVH than those who were male  and non-Hispanic Black , and the age-standardized mean LE8 scores of overall CVH were also much higher in Americans with higher educational level  versus lower educational level , in those who were married  versus those who were unmarried , and in those with higher family income  versus those with lower family income  but 3 components  significantly improved, whereas 2 components (BMI and blood glucose) significantly, and markedly, worsened over time.Although a number of public health and health care policies and programs have been implemented to prevent CVD since 2010 -20, the 2 in 1999-2000 to 29.8 kg/m2 in 2017-2018 [The stable trends in the overall CVH score may mask disparities in trends in CVH components. We found that the mean scores of 4 CVH metrics including nicotine exposure (increase), BMI (decrease), non–high-density lipoprotein cholesterol (increase), and blood glucose (decrease) changed over time but not all in the same direction, and some (diet) did not change over time. Unhealthy diet is a major risk factor for CVD , but unf017-2018 . He et a017-2018 , consist017-2018 , as wellHowever, there were also several inconsistent findings in our study compared with previous studies regarding the secular trends in 2 CVH components (PA and BP) ,32,33. IConsistent with previous studies ,14, the P for trend=.77) with the primary ones.Our study is the first to examine the secular trends in CVH from 2005 to 2018 among US adults based on the nationally representative NHANES data using the new AHA LE8 metrics. However, several limitations should be mentioned. First, our study was based on data from 7 surveys over a rather short time period (<15 years). Second, data on diet, PA, nicotine exposure, and sleep health were obtained by self-report, which may be inaccurate due to recall and social desirability biases. Third, the 8 behavioral and health components are given equal weight (implying the same predictive performance) in calculating the LE8 overall CVH score. Fourth, although the 8 components constitute major or important risk/preventive factors for CVH, a number of other factors  can largely alter CVD risk, particularly at the individual level. Fifth, missing values on relevant variables, especially for dietary variables, might have affected the representativeness of the study population. However, the inclusion of data on one 24-hour dietary recall showed similar results , 3 improved , and 2 worsened (BMI and blood glucose), suggesting avenues for improving CVH status among US adults.


Kidney–ureter–bladder (KUB) imaging is used as a frontline investigation for patients with suspected renal stones. In this study, we designed a computer-aided diagnostic system for KUB imaging to assist clinicians in accurately diagnosing urinary tract stones. The image dataset used for training and testing the model comprised 485 images provided by Kaohsiung Chang Gung Memorial Hospital. The proposed system was divided into two subsystems, 1 and 2. Subsystem 1 used Inception-ResNetV2 to train a deep learning model on preprocessed KUB images to verify the improvement in diagnostic accuracy with image preprocessing. Subsystem 2 trained an image segmentation model using the ResNet hybrid, U-net, to accurately identify the contours of renal stones. The performance was evaluated using a confusion matrix for the classification model. We conclude that the model can assist clinicians in accurately diagnosing renal stones via KUB imaging. Therefore, the proposed system can assist doctors in diagnosis, reduce patients’ waiting time for CT scans, and minimize the radiation dose absorbed by the body. Current research indicates a global increase in the incidence of renal stones, as observed in various studies conducted worldwide  ,2,3. SevX-rays are low-cost and low-radiation imaging modalities that are widely used in various stutabledies for computer-aided diagnosis (CAD) development, including chest X-rays for COVID-19 detection with DL models , breast CT is commonly used for whole-body screening to detect tumors or inflammation in organs and is highly reliable for diagnosing diseases such as liver, lung, and brain cancers ,10. SeveHowever, CT is more expensive and produces higher radiation doses than X-ray imaging. For adult abdominal X-ray examinations, the radiation dose of CT in the same area ranges from 8 to 34 mGy ,17, wherRecently, the rapid development of machine learning and artificial intelligence has facilitated the application of CAD in medical image processing. The exceptional performance of convolutional neural networks (CNNs) in learning and computation across various domains ,22,23,24KUB imaging remains the primary examination method for detecting urinary stones in emergency rooms owing to its convenience, affordability, and low radiation dose. However, only experienced urologists and radiologists can accurately diagnose urinary stones from KUB images. Inexperienced physicians may make errors or further prescribe CT scanning, thus increasing the medical costs and radiation exposure. Compared to deep learning, traditional image processing algorithms do not demonstrate robust generalization capabilities, mainly because of the large size of KUB images and the small dimensions of kidney stones. Furthermore, conventional approaches face challenges when effectively detecting irregular features. To address this issue, we developed a CAD system based on a DL model to assist emergency physicians in accurately diagnosing urinary stones based on KUB imaging. The system was validated through experimental data and specialist evaluations.Renal stones consist of urinary solutes  in an unstable supersaturation state  due to imbalances between the promoters and inhibitors of stone formation. Renal stone formation occurs in four phases: nucleation, crystal growth, aggregation, and retention . FinallyCalcium (Ca)-containing stones:The primary classifications of renal stones with their molecular formula and occurrence are listed as follows :Calcium 2O4 (H2O)2 or CaC2O4H2O (60%)Calcium oxalate, CaC10(PO4)6(OH)2 (20%)Hydroxyapatite, Ca4·(H2O)2 (2%)Brushite, CaHPONon-calcium-containing stones:5H4N4O3 (7%)Uric acid, C4MgPO4·(H2O)6 (7%)Struvite, NH6H12N2O4S2 (1–3%)Cystine, CCa-containing stones represent the majority of renal stones, making it theoretically possible to detect most renal stones using X-ray imaging. KUB imaging, a rapid and cost-effective X-ray imaging technique, is an ideal first-line examination for renal stone detection.We collected 485 abdominal radiographs of patients diagnosed with upper urinary tract stones by urologists at Kaohsiung Chang Gung Memorial Hospital. Owing to the varying lengths of the follow-up, each patient had KUB images taken at different times, and some KUB images contained multiple urinary tract stones; therefore, they were divided into single or multiple training images with urinary tract stones .Histogram equalization (HE)  enhancesA 100 × 100-pixel image was cropped from the KUB image. An image with urinary tract stones was positioned at the center of the image. Cropped images without urinary tract stones were randomly selected from the KUB images, as illustrated in Studies have shown that data augmentation can effectively prevent overfitting of the model, with the probability of overfitting in small datasets during training being higher than in large datasets ,42,43,44To increase the amount and diversity of data, random angle rotation, horizontal and vertical displacements, and flipping were applied to the original images  52]. In. In52]. Previous studies have shown that the deeper the CNN, the finer the features it can extract . HoweverIn 2016, Google proposed Inception-ResNetV2 as an improved version of Inception-ResNetV1 , which aProposed in 2015, U-Net is widely used in medical image segmentation owing to its unique structure  Figure . The strIn this study, we proposed a computer-aided diagnostic system consisting of two subsystems. The overall system architecture is illustrated in Windows 10 was used as the operating system for testing the model; the hardware information is listed in In this study, all images were divided into three datasets, with a total of 1340 images. Among these, 970 images were used for training (80%) and validating (20%) the model; the training set contained 776 images, and the validation set 194 images. The remaining 370 images were used as the test set to evaluate the performance of the model and its generalization ability. Both subsystems used Ranger as the optimizer , which iWe generated a confusion matrix from the prediction results, which had four categories of correct and incorrect predictions. The categories for correct predictions were true positive (TP) and true negative (TN), whereas those for incorrect predictions were FP and FN. The confusion matrix is depicted in In addition to determining the model’s accuracy, we used seven other metrics, four of which were used to evaluate the classification and semantic segmentation models: sensitivity, specificity, precision, and F1-measure. The other three metrics, IoU, MIoU, and FWIoU, were used to evaluate the quality of the predicted masks of the semantic segmentation model. The formula for sensitivity is as follows:The formula for specificity is as follows:The formula for precision is as follows:We used the F-measure to comprehensively evaluate the performance of the model. The higher the F1-measure value, the better the performance of the model. The formula for the F1-measure is as follows:The formula for the IoU is as follows:The formula for the MIoU is as follows:The FWIoU is a modification of the MIoU in which weights are assigned based on the frequency of occurrence of each class. The formula for the FWIoU is as follows:In this study, ResNet50 models were trained using both augmented and nonaugmented datasets. Data augmentation was performed by rotating, horizontally and vertically shifting, and magnifying and demagnifying of the original images. The difference between the effects of using and not using data augmentation was compared based on the accuracy and loss during the training process of the ResNet50 model. In this study, we trained two models, ResNet50 and Inception-ResNetV2, for 50 epochs with an initial learning rate of 0.001. The specific model initialization parameters are listed in This study employed two different backbone networks, ResNet34 and ResNet50, to implement four U-net models using different loss functions, including bce_dice_loss, bce_jaccard_loss, binary_focal_dice_loss, and binary_focal_jaccard_loss, as shown in Equations (9)–(12), respectively. The specific U-net model initialization parameters are listed in In this study, two CNN models, Inception-ResNetV2 and U-Net, were utilized for training the network. The core concept of Inception-ResNetV2 is to combine inception modules and residual direct connections using residual connection shortcuts to successfully train deeper neural networks, while significantly simplifying inception modules. As indicated in Proposed in 2015, U-Net is widely used in medical image segmentation owing to its unique structure , as showIn this study, KUB images were used to train the model. According to a systematic review of the latest advancements in the use of artificial intelligence in urology conducted by Dai et al. , only onFirst, we classified the KUB images based on the presence or absence of renal stones and masked the images with renal stones after classification. The preprocessed and classified renal stone images have reduced misjudgments during segmentation. The segmented stone positions will further assist physicians in diagnosis. Our CAD system has demonstrated that X-ray images can be effective in detecting renal stones, offering a promising research direction and providing an alternative system in renal stone diagnosis using KUB imaging, in addition to CT imaging. While research on the use of plain film X-ray images to detect renal stones is sparse, the results of this study are promising and indicate bright prospects for future research.In this study, we proposed a computer-aided diagnostic system, which was divided into two subsystems. Both subsystems used CNN models to train the DL models. Subsystem 1 classifies and subsystem 2 segments the urinary stones on KUB images. First, subsystem 1 adopts the image preprocessing procedure designed in this study, for which we proposed a method based on subsystem 1 for image cropping. Images of the entire renal stone can be obtained to the greatest extent possible using a sliding window combined with the classification model, avoiding the division of stones into multiple images for recognition owing to average cropping. Experimental data showed that preprocessing, which included image masking, contrast-limited AHE, and image cropping, helped the model to effectively classify the stones and non-stones. Moreover, the Inception-ResNetV2 model was validated to further improve its accuracy over the ResNet50 model. Based on the experimental data, U-Net can accurately generate a urinary stone mask; however, the MIoU data showed that the accuracy of the background was low, and a few erroneous masks were misidentified as urinary stones. In clinical medicine, conventional radiography for detecting stones may exhibit unique characteristics that are less frequently encountered. Due to the scarcity of such images, it is difficult to train the model effectively. Therefore, most training images used in this study were of stones that could be observed with the naked eye. In the future, if several difficult-to-judge KUB images can be collected and trained using the proposed image preprocessing architecture, the generalization ability of the model can be further improved. This will render the diagnostic tool more reliable and enhance its potential. In this study, although the U-Net model in subsystem 2 achieved good performance, misjudgment of feature masks is a problem that needs to be addressed in future research. Some ribs, gas, or fecal matter commonly present in KUB images can cause dense white areas in the images, which are uncontrollable factors that cannot be removed by image masking, such as in the spine and pelvis. Solving these problems is a direction for future research.


The COVID-19 pandemic has generated substantial changes in the lives of the population, such as increased physical inactivity, which can lead to being overweight and, consequently, repercussions on glucose homeostasis. A cross-sectional study based on the adult population of Brazil was conducted by stratified, multistage probability cluster sampling (October and December 2020). Participants were classified as physically active or inactive during leisure time according to the recommendations of the World Health Organization. HbA1c levels were categorized as normal (≤6.4%) or with glycemic changes (≥6.5%). The mediating variable was being overweight (overweight and obese). Descriptive, univariate, and multivariate logistic regression analyses examined the association between physical inactivity and glycemic changes. Mediation was analyzed using the Karlson–Holm–Breen method to verify the influence of being overweight on the association. We interviewed 1685 individuals, mostly women (52.4%), 35–59 years old (45.8%), race/ethnicity brown (48.1%), and overweight (56.5%). The mean HbA1c was 5.68% (95% CI: 5.58–5.77). Mediation analysis verified that physically inactive participants during leisure time were 2.62 times more likely to have high levels of HbA1c , and 26.87% of this effect was mediated by over-weight (OR: 1.30: 95% CI: 1.06–1.57). Physical inactivity at leisure increases the chances of high levels of HbA1c, and part of this association can be explained by being overweight. The COVID-19 pandemic promoted profound changes in the daily lives of citizens around the world; the social restriction, although necessary, negatively altered some health behaviors, especially those related to lifestyle habits, such as food consumption and physical activity practice ,3,4,5. IT2DM has emerged as a serious public health problem due to a modern lifestyle characterized by increased sedentary behavior and the consumption of ultra-processed foods . The IntAbnormalities in serum HbA1c concentrations are implicated in disease progression and physical disability, resulting in microvascular and macrovascular risks, neuropathy, retinopathy, renal dysfunction, and cardiovascular disease ,12.Some behaviors increase the risk of HbA1c changes, including smoking, poor eating habits, being overweight, and physical inactivity . HoweverFaced with the scarcity of biochemical data during the period of social restriction due to the COVID-19 pandemic and the prospect of intense modification in lifestyle and health behavior, especially physical activity, which may have influenced weight gain and, consequently, glycemic change, it is important to understand the mechanisms associated with this clinical condition to try to minimize negative health impacts, in addition to a higher prevalence of diabetes in the medium/long term. Therefore, this study aimed to evaluate serum HbA1c levels and their association with overweight-related physical inactivity. We hypothesized that high levels of HbA1c may be associated with physical inactivity at leisure during the social restriction and that being overweight may be a mediating variable in this association.This was a cross-sectional study using data from the COVID-Inconfidentes project, a population-based household epidemiological survey conducted between October and December 2020 in two municipalities (Ouro Preto and Mariana) in Minas Gerais, Brazil. Participants eligible for the study were permanent residents of households in the urban area of the municipalities, aged 18 years or older, and who consented to participate in the study. Individuals with impaired cognitive function, difficulty answering the questionnaire, or inability to provide blood samples due to difficulties in venous access were excluded.https://www.openepi.com/Menu/OE_Menu.htm, accessed on 7 February 2023), the minimum number of volunteers after the sample calculation for both municipalities (Ouro Preto and Mariana/MG) with 732 interviews, respectively. A three-stage sampling was used: census sector , household (selected from systematic sampling), and residents . The sample weight of each selected unit  was calculated to correlate with the 2019 population projections (DATASUS) [For data collection, a sample calculation was performed based on the 2010 population census for the urban area of each city, adopting a confidence level of 95% and an effect size equal to 1.5. Furthermore, 20% was added to the sample size of each city for possible refusals, absence of the resident selected, or people not at home during the visit. The sample size was calculated using OpenEpi (DATASUS) . In thisDATASUS) .In each municipality, data were collected on three weekends , with intervals of 21 days between each. In the week preceding the data collection weekend, actions were carried out to disseminate the survey in selected census sectors, draw households, draw lots, and approach households to increase awareness and adherence to the survey. On the days of data collection, a resident was selected, followed by blood collection and face-to-face interviews. For venous blood collection, a 2.7 mL S-Monovette (Sarstedt) tube containing sodium fluoride/EDTA was used to analyze serum HbA1c levels.Face-to-face interviews lasted 30 to 45 min, using the questionnaire in the DataGoal application via tablets. The interviewers maintained a minimum distance of 1.5 m from the interviewee as a protective measure against COVID-19, and physical contact was restricted to the point of collection of biological material.The questionnaire included sociodemographic and economic variables, lifestyle habits, and general health status.HbA1c was measured in the Clinical Analysis Pilot Laboratory (LAPAC) of the School of Pharmacy/Federal University of Ouro Preto using the immunoturbidimetry method in the COBAS INTEGRA 400 plus automatic analyzer , following a protocol standardized by the manufacturer. Before each analysis, the device was calibrated with quality controls . A minimum volume of 400 µL of whole blood was used for the samples. The normal range adopted for the HbA1c level was ≤6.4%, and levels ≥ 6.5% were classified as having high levels of HbA1c .The self-reported physical activity during leisure time was evaluated by weekly frequency, duration, and type of physical exercise. Moderate physical activity was defined as walking, treadmill walking, weight training, water aerobics, Pilates, volleyball, and dancing, and vigorous physical activity included running, cycling, swimming, treadmill running, aerobics in general, wrestling, soccer/futsal, basketball, and tennis ,20,21,222). kg/m2 if <60 years to WHO cut-off points into “not overweight” (BMI < 25.0 kg/m2 if <60 years or BMI < 28.0 kg/m2 if ≥60 years) and “overweight” (BMI ≥ 25.0 kg/m2 if <60 years or BMI ≥ 28.0 kg/m2 if ≥60 years) [Overweight was used as a mediation variable, measured by body mass index (BMI), calculated from self-reported weight and height according to the following formula: BMI = body weight (kg)/height (m0 years) .Sociodemographic covariates, tobacco use, and morbidities were included. The sociodemographic covariates determined were sex (women and men), age group , race/ethnicity categories were self-reported , marital status (single or married), current family income , and education .Tobacco consumption was determined using the question, “Do you smoke, or have you ever smoked cigarettes or any other tobacco product?” The answer options were yes and no.Reported morbidity was determined by self-reporting the following diseases: high blood pressure, asthma, lung disease, chronic kidney disease, depression, anxiety disorder, obstructive sleep apnea, cancer, heart disease, or thyroid disease. Individuals who reported having at least one of the diseases were classified as having morbidity, and those with no disease had no morbidity.This study was approved by the Ethics Committee on Human Research of the Federal University of Minas Gerais (protocol number:32815620.0.1001.5149). All procedures followed the Brazilian guidelines and standards for human research. Participants were informed about the research objectives, the steps to be taken, and the risks and benefits of their participation. Those who agreed to participate signed an informed consent form.The study population was characterized using descriptive calculations, such as relative frequencies, mean values, and 95% confidence intervals (CI). Pearson chi-square test was used to verify the relationship between high levels of HbA1c and the sociodemographic characteristics of the study population. Univariate and multivariate logistic regression analyses assessed the association between physical inactivity and glycemic changes.A theoretical causality model based on a directed acyclic graph (DAG) was developed based on exposure , outcome , and covariate variables using online Dagitty software, software version 3.2  Figure . DAG wasTo verify whether overweight could be a mediating variable between the association of PI and glycemic changes, we used mediation analysis using the Karlson–Holm–Breen method, package “khb” in Stata . This mep < 0.05.Results were analyzed using the Stata statistical program, version 15.1, operating the “svy” command, which considers a complex sample design. Statistical significance was established at We evaluated 1685 individuals, most of whom were women , aged 35–59 years old , married , self-reported as brown , less than nine years of schooling , income less than or equal to two minimum wages , and overweight . In addition, most of the respondents reported having one or more morbidities , as shown in The mean HbA1c was 5.68% (95% CI: 5.58–5.77). We observed that 92.9% (95% CI: 90.6–94.7) of the subjects had normal levels of HbA1c, and 7.1% (95% CI: 5.3–9.4) had glycemic changes. In addition, 69.2% (95% CI: 64.2–73.7) of the participants were physically inactive at leisure .p < 0.05) were age ≥ 60 years, female, education ≤ 9 years, overweight, black race/ethnicity, and presence of morbidities  that individuals who were physically inactive during leisure time were 2.62 times more likely to have high levels of HbA1c , as presented in This study investigated the association between physical activity and high levels of HbA1c, as well as the mediation of overweight in this association. Our findings confirm the initial hypothesis that adults who accumulate 150 min of moderate or 75 min of vigorous physical activity per week are less likely to have glycemic changes than individuals who do not reach the weekly minutes of physical activity recommended by the guidelines ,24. To oThese results are important regarding public health and clinical practice, as approximately 70% of the population in this study did not meet the minimum guidelines for physical activity. Although our study did not allow us to assess the change in physical activity practice during the COVID-19 pandemic, it is believed that the pandemic may have contributed substantially to the increased prevalence of physical inactivity  due to tThus, some studies show a worsening prevalence of physical inactivity and overweight due to social restrictions and reduced urban mobility worldwide ,31,32,33Regular physical activity has long been considered a non-pharmacological way to improve general health, manage glycemic control, and treat T2DM, and its low cost has increased its appeal ,38. AccoA study of Brazilian women before (January and February 2020) and after 16 weeks of the COVID-19 pandemic (June and July 2020) showed that confinement promoted important changes in health-related parameters. HbA1c levels increased significantly by 9.7%, which was explained by reduced physical activity . ConsequOur results show an association between physical inactivity and high levels of HbA1c, and a part of this association can be explained by being overweight. These findings demonstrate clinical relevance, with physical activity effectively mitigating the risk of developing T2DM, both for body weight maintenance and through metabolic mechanisms that help glycemic control. A similar effect to ours was found in a systematic review and dose-response meta-analysis, which compared risk estimates of T2DM in relation to leisure time physical activity, with and without adjustment for the BMI covariate. The results with adjustment weakened the association by about 20%-30% when compared to the results unadjusted for BMI , thus deThus, a consistent justification for this association may be positive energy balance, that is, increased habitual food intake compared to the period before the COVID-19 pandemic (mainly of ultra-processed foods) and reduced energy expenditure by reducing urban mobility and physical activity. This may lead to weight gain and increase the risk of T2DM in individuals who are physically inactive ,44. ConsThe findings of this study are of great value to the scientific community, leaders, and health professionals to better understand the side effects on short- and long-term health conditions of the COVID-19 pandemic and to devise strategies to mitigate these impacts. The COVID-19 pandemic may have provided a favorable scenario for morbidity and a poorer health prognosis. Furthermore, there are no structured educational programs for the self-management of T2DM in Brazil . PA actsAlthough robust and with relevant results in the scientific literature, this study had some limitations. The level of physical activity was obtained by self-reporting; therefore, it is subject to memory and other bias, which may underestimate or overestimate the data. Furthermore, calorie intake and added sugars, important covariates in the present association, were not assessed. Methodologically, the cross-sectional design of this study did not allow the establishment of causalities. However, using the counterfactual approach from directed acyclic graphs (DAG), it is possible to infer and verify the causal effect of associations from the observed variables and the assumptions in the diagram. It is emphasized that the hypotheses were carefully defined according to the current scientific literature and articulated in counterfactual terms to build theories that can underpin the driving assumptions of the analyses. In this regard, incorporating directed graphical models is of great importance and brings robustness to the study . HoweverIn addition, our study has other strengths, such as a robust sample methodology with probability selection and sample weight, providing statistical power to the study. Furthermore, the interviews were conducted face-to-face, allowing greater accuracy in the information obtained. In addition, assessing glycemic homeostasis through Hb1Ac is noteworthy, as it represents glycemic levels during the last four months and not only at the current time.Leisure time physical activity is associated with greater high levels of HbA1c and part of this association is explained by being overweight. Therefore, our data suggest that physical activity may attenuate the risk of developing T2DM, partly by controlling overweight but also independently of adiposity. In addition, glycemic changes are metabolic changes that require regular attention, given their implications for the worsening of population health and high costs to the public health system. Therefore, we believe that maintaining regular physical activity is essential for the management of glycemic control in periods of restricted social mobility.During the pandemic, there was a great deal of uncertainty and fear around physical activity, especially in open areas, since little was known about the forms of contamination. This favored an increase in physical inactivity during data collection. However, with current knowledge, encouraging physical activity in open environments should be encouraged in times of restricted social mobility. Taking the necessary precautions to reduce contagion, or at least the encouragement of physical activity at home, through online classes and simple exercises with body weight, will prevent the harmful effects on health since increased physical inactivity can lead to an increase in weight and an increased risk of T2DM together with other pathophysiology.