Times Higher Risk Research Articles

Role of Matrix Metalloproteinase-17 in knee osteoarthritis and its association with disease severity

MMP-17 plays a vital role in the activation of ADAMTS4, a key aggrecanase involved in cartilage degradation and Osteoarthritis development. The present study focused on MMP-17 expression in patients with knee OA and its advancement. A total of 98 study subjects were enrolled (n=98), of which 49 were cases and 49 controls. Quantitative estimation of MMP-17 in serum and synovial fluid of study subjects was assessed by sandwich ELISA and statistically analyzed by one way ANOVA, bivariate analysis and receiver operating characteristic (ROC) curve analysis. The mean value of Serum MMP-17 was significantly higher in cases than controls (15.43±0.91 vs 14.71±1.04ng/ml respectively). ROC curve cut off value was 14.82ng/ml (75.5% sensitivity and 71.4% specificity), which increased with disease severity. The value >15ng/ml in serum had approximately 11 fold risk of OA [OR=11.333, 95% CI=(2.209-58.147)]. SF MMP-17 were assessed only from OA patients due to ethical concerns and the level >4.6ng/ml had 27.5 times higher risk for disease severity [OR=27.556, 95% CI=(3.031-250.524)]. The levels of MMP-17 in serum and synovial fluid were significantly associated with knee OA and its severity. Thus serum MMP-17 level could be a potential marker for knee OA and may be a target for therapeutics.

Modern interpretation of risk factors in breast cancer of women

Breast cancer is a major public health problem, being the most common cancer diagnosed in women and accounting for more than 1 in 10 new diagnoses of cancer each year. It is the most common neoplasm of women under the age of 40 and the second leading cause of cancer death in this age group, with more frequent detection of pathogenic mutations in breast cancer susceptibility genes. Women with BRCA1 and BRCA2 mutations are about 70% more likely to develop breast cancer. The incidence is rising in most countries and it is expected to have a growing trend in the next 20 years, despite the current efforts to prevent the disease. In order to improve the survival rate, it is necessary to make a diagnosis as early as possible and to initiate the appropriate therapeutic management as soon as possible. Therefore, in order to detect breast formations, mammography screening is very important, breast density being an important factor in predicting the risk of breast cancer. Thus, the presence of high breast density represents a 4-6 times higher risk of developing breast cancer compared to women with low breast density. Aging and menopause are also risk factors for breast cancer. Hormone replacement therapy for postmenopausal women has the benefit of relieving symptoms such as hot flashes, depression or sleep disturbances, but it increases the risk of developing breast cancer.

Pharmacokinetic Impact of Posaconazole Discontinuation on Tacrolimus Levels in Heart Transplant Recipients

<h3>Purpose</h3> Azole antifungals are CYP3A4 inhibitors known to significantly impact tacrolimus levels. Required tacrolimus dose reduction with azole initiation is well known; however, little is reported on empiric tacrolimus dose adjustments with azole discontinuation (d/c). We describe our experience with tacrolimus adjustment after d/c of posaconazole. <h3>Methods</h3> This is a retrospective single center review of heart transplant recipients who received 3 months of posaconazole prophylaxis immediately post-transplant. Upon d/c, our protocol increased total tacrolimus dose by 2-3 fold with level monitoring twice weekly for at least two weeks until at target. We analyzed the first 7 tacrolimus troughs and total daily doses (TDD) after d/c. Stable target levels post d/c were defined as first trough at goal with the TDD equivalent to doses at 3 months post d/c. Intrapatient tacrolimus level variability (IPV) was calculated using mean absolute deviation of dose corrected tacrolimus levels, with paired t test and descriptive statistics. <h3>Results</h3> Among 28 patients who received posaconazole from January 2020 to May 2021, average age was 55.5 years, 75% were male and 82% white. Tacrolimus TDD was significantly lower on posaconazole compared to 3 months post-d/c (0.02 vs 0.09 mg/kg/day, p = 0.0001). Analysis of target trough achievement is shown in Figure 1. Significant difference in IPV was noted between early (first 3) and late (next 4) levels, p=0.0004 (Figure 2). Median time to stable target levels was 21.5 (11-48) days. Four patients (14%) had 2R rejection within one month of d/c at which time median lowest tacrolimus level was 4.2 ng/mL (3.4-8.2 ng/mL). <h3>Conclusion</h3> Discontinuation of posaconazole leads to significant tacrolimus variability that can persist for weeks. A more conservative tacrolimus dose adjustment at time of d/c, with close monitoring throughout the first 3 weeks may be needed. Additional data is necessary to develop defined empiric dose adjustments for tacrolimus during this high-risk time.

Transition Navigator Intervention Improves Transition Readiness to Adult Care for Youth With Sickle Cell Disease.

Adolescents and young adults (AYA) with sickle cell disease (SCD) experience high rates of acute care utilization and increased morbidity. At this high-risk time, they also face the need to transition from pediatric to adult services, which, if poorly coordinated, adds to heightened morbidity and acute care utilization. The study objective was to characterize the feasibility, acceptability, and short-term efficacy of a protocolized transition navigator (TN) intervention in AYA with SCD. We developed a protocolized TN intervention that used ecological assessment and motivational interviewing to assess transition readiness, identify goals, and remove barriers to transition, and to provide disease and pain management education and skills to AYAs with SCD. Ninety-three percent (56/60) of enrolled individuals completed the intervention. Participation in the TN program was associated with significant improvement in mean transition readiness scores (3.58-4.15, P < .0001), disease knowledge scale (8.91-10.13, P < .0001), Adolescent Medication Barriers Scale (40.05-35.39, P = .003) and confidence in both disease (22.5-23.96, P = .048) and pain management (25.07-26.61, P = .003) for youth with SCD. The TN intervention was acceptable to youth with SCD, feasible to implement at an urban academic medical center, and addressed barriers to transition identified by the youth. Longer-term assessment is needed to determine if the TN intervention improved successful transfer to and retention in adult care.

Analysis of the redistribution of rs4977574-polymorphic variants of the ANRIL gen in patients with acute coronary syndrome of different sex

Annotation. The aim of the study was to analyze the distribution of rs4977574-polymorphic variants of the ANRIL gene in patients with acute coronary syndrome of different sex. The venous blood of 234 patients with acute coronary syndrome (ACS) and 195 people without cardiac pathology was used for the study. DNA was isolated from whole venous blood using the GeneJET Whole Blood Genomic DNA Purification Mini Kit (ThermoFisher Scientific, USA). rs4977574 ANRIL gene polymorphism was studied by real-time PCR reaction in the presence of TaqMan assay C_31720978_30. Statistical analysis of the study was performed using the SPSS program (version 17.0). A difference was found when comparing the frequencies of genotypes at the polymorphic site rs4977574 of the ANRIL gene in their distribution (p=0,035). According to the results of logistic regression, it was detected that in the recessive (p=0,015) and additive (p=0,012) inheritance models, carriers of the G/G genotype are approximately 2 times more likely to develop ACS than carriers of the A-allele. The reliability of the results was maintained after adjustments for gender, age, B&lt;I, smoking habits, diabetes and stress (p=0,049 for the recessive model; p=0,037 for the additive model). Thus, individuals with the rs4977574 G/G genotype polymorphism of the ANRIL long non-coding RNA gene have a 2 times higher risk of developing ACS than dominant allele carriers. Further research will focus on the association of ANRIL polymorphism with the risk of ACS depending on other risk factors.

Effect of vaginal antiseptic prior to caesarean section on the rate of post-caesarean complications: a blinded randomised controlled trial

BackgroundRates of caesarean section (CS) delivery are increasing worldwide. CS delivery is often complicated by post-surgical infection, estimated to have ten times higher risk of infections than that of vaginal delivery. While widespread use of prophylactic antibiotics with CS has reduced post-CS infection, incidence may be reduced further by cleansing the vagina with betadine antiseptic wash prior to CS. However, reports are not consistent, and different antiseptics have been practised variably. Therefore, in order to ensure that the risks to the mother are as minimal as possible, it is important to determine whether vaginal irrigation with antiseptic wash reduces post-CS infection rate, and if so, which antiseptic is paramount.MethodsWomen giving birth by elective or emergency CS will be assigned into either the intervention (1% povidone iodine (n = 125) or chlorhexidine (n = 125)) or the control (no-irrigation (n = 125)) group by using a block randomisation technique. Participants will receive vaginal cleansing with an intervention or no vaginal cleansing prior to CS. Follow-up will occur at day 14 and day 28 post-CS. A predeveloped questionnaire will be completed with patients’ socio-demographic characteristics and required clinical and pregnancy-related information. All the fever, infection and readmission-related information will be completed from either the patient’s or their record or at follow-up visits. Occurrence of post-CS infection, as measured by primary and secondary outcomes, will be compared between the groups.DiscussionThe results of this study may provide important data to define the future uniform use of vaginal antiseptic wash immediately prior to CS and to determine the best antiseptic wash details in reducing post-operative infections or complications.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620000971932p. Registered on 28 September 2020

Self-rated health may be a predictor for metabolic syndrome and high hs-CRP prevalences in healthy adults in South Korea: Based on the 2015 Korea National Health and Nutrition Examination Survey

Self-rated health (SRH), affected by sociodemographic and health-related behavioral factors, is related to metabolic syndrome (MetS) and high-sensitivity C-reactive protein (hs-CRP) levels. We hypothesized that SRH would have an independent effect on MetS and high hs-CRP incidence in healthy adults after adjusting for sociodemographic and health-related behavioral confounding factors. Data of 1545 healthy participants (aged 19-65 years; 654 men), selected from the 2015 Korean National Health and Nutritional Examination Survey, were cross-sectionally analyzed. The SRH levels significantly increased with higher income (P < .05) and educational levels (P < .01) and were associated with sex, job, marital status, smoking, physical activity, perceived body image, and weight change (all P < .05). The percentage of participants with “very high or high” perceived stress were significantly lower in the “very healthy” group (18.5%) than in the “unhealthy” group (49.7%). Dietary protein, calcium, and phosphorus intakes were significantly higher with better SRH levels. MetS prevalence was related to sex, educational level, job, marital status, smoking, high-intensity exercise, and aerobic exercise (all P < .05), with a 2.776 times higher risk in the “unhealthy” than in the “very healthy” group after adjusting for these confounders. High hs-CRP levels were related to marital status, smoking, weekly walking, and aerobic exercise (all P < .05), with its risk being 2.093 times higher in the “unhealthy” than in the “very healthy” group after adjusting for these confounders. Thus, SRH may be an independent predictor of MetS and high hs-CRP levels and could be used for the development of a health promotion program in healthy adults.

Nutrition status and morbidity of Ethiopian children after recovery from severe acute malnutrition: Prospective matched cohort study.

After recovery, children with severe acute malnutrition (SAM) remain vulnerable to sub-optimal growth and malnutrition relapse. Although there is an increased interest in understanding these problems, data are scarce, and contextual factors can cause variability. We prospectively followed a cohort of Ethiopian children (215 post-SAM cases and 215 non-wasted controls), monthly for one year. The post-SAM cases were: age 6-59 months at admission into the community management of acute malnutrition (CMAM) program and being successfully discharged from CMAM (MUAC>11.0cm, weight gain of 20%, absence of oedema and clinically stable for two consecutive weeks). The controls were apparently healthy children from same village who had no history of an episode of AM and were matched 1:1 to a post-SAM child by age and sex. The primary outcomes were: cumulative incidence of acute malnutrition; growth trajectory; cumulative incidence of reported common morbidities, and cumulative proportion and incidence of deaths. The burden of common morbidities was higher among post-SAM than controls; post-SAM children had more frequent illness episodes (Incidence Rate Ratio of any illness 1.39, 95% CI: 1.14, 1.71; p<0.001). The prevalence of SAM was consistently higher among post-SAM cases than the control group, having a 14 times higher risk of developing SAM (Incidence Rate Ratio: 14.1; 95% CI: 3.5, 122.5; p<0.001). The divergence in weight and growth trajectory remained the same during the study period. Our results advocate for the design of post-discharge interventions that aim to prevent the reoccurrence of acute malnutrition, reduce morbidity and promote catch-up growth. Research is needed to define the appropriate package of post-discharge interventions.

Temporal Monitoring and Predicting of the Abundance of Malaria Vectors Using Time Series Analysis of Remote Sensing Data through Google Earth Engine.

In many studies regarding the field of malaria, environmental factors have been acquired in single-time, multi-time or a short-time series using remote sensing and meteorological data. Selecting the best periods of the year to monitor the habitats of Anopheles larvae can be effective in better and faster control of malaria outbreaks. In this article, high-risk times for three regions in Iran, including Qaleh-Ganj, Sarbaz and Bashagard counties with a history of malaria prevalence were estimated. For this purpose, a series of environmental factors affecting the growth and survival of Anopheles were used over a seven-year period through the Google Earth Engine. The results of this study indicated two high-risk times for Qaleh-Ganj and Bashagard counties and three high-risk times for Sarbaz county over the course of a year observing an increase in the abundance of Anopheles mosquitoes. Further evaluation of the results against the entomological data available in previous studies showed that the high-risk times predicted in this study were consistent with an increase in the abundance of Anopheles mosquitoes in the study areas. The proposed method is extremely useful for temporal prediction of the increase in abundance of Anopheles mosquitoes in addition to the use of optimal data aimed at monitoring the exact location of Anopheles habitats.

Abstract P192: Disparities In Stroke And Mortality In Children With Congenital Heart Defects

Background: Critical congenital heart defects (CCHD) are a subset of cyanotic lesions that require intervention within the first days to weeks of life for survival. For children born with CCHD, the neonatal period is considered the time of highest risk for stroke and overall poor outcomes. Prior studies have identified racial differences in neonatal outcomes among children with CCHD. Whether these differences persist throughout childhood is unclear. Methods: Using the National Inpatient Sample database, we analyzed all children with CCHD ≤ 18 years hospitalized from 2005-2018. Primary outcome was a composite of incident stroke (ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage) and all-cause mortality within strata of ages and years and over the 14-year period of observation. Chi-square tests and multivariable regression were used to assess differences in outcomes. Trends were analyzed adjusting for sex, insurance, and hospital features. Results: A total of 59,438 children with CCHD were hospitalized during the study period: 58% were White (W), 15% Black (B), and 27% Hispanic (H). Overall rate of stroke or death was 4.7% in White children, 6.6% in Black, and 5.6% in Hispanic. Disparities were most pronounced in infancy (Figure; relative differences (RD) compared to White children: 27% (B) and 20% (H), P=0.000) and in early childhood (Figure; RD: 42% (B) and 9% (H), P=0.002). Black and Hispanic children with CCHD had higher rates of stroke and death from 2005-2009 (Figure; RD compared to White children: 24% (B), 22% (H); P = 0.001) and in 2015-2018 (Figure; RD: 21% (B), 18% (H); P = 0.000). These disparities did not change significantly over time in crude or adjusted models (P=0.07, P=0.06). Conclusion: Racial and ethnic disparities in stroke and death among children with CCHD persist after the neonatal period with only modest change in these differences in recent years. Further work identifying the mediators of these disparities is necessary to improve outcomes in this vulnerable pediatric population.

Clinical Management of Opioid Withdrawal.

Appropriate clinical management of opioid withdrawal is a crucial bridge to long-term treatment for opioid use disorder (OUD), because it is a high-risk time for potential opioid overdose and relapse. We provide a narrative review of evidence-based opioid withdrawal management strategies applicable to a variety of treatment settings and geographies. The goals of opioid withdrawal management include relieving suffering associated with withdrawal, providing appropriate diagnosis and screening, engaging patients in initiation of OUD treatment, and using harm reduction strategies, all guided by a patient-centered approach to care. In addition, we discuss complex cases, relapse prevention strategies, and new developments in opioid withdrawal management.

Factors Associated with the Need for a Primary Endodontic Treatment after Single-Unit Crown Cementation: A Retrospective Case-Control Study

IntroductionThis case-control study aimed to identify factors associated with an increased risk for endodontic treatment after single-unit crown cementation and to describe the timeline of such events. MethodsAfter evaluating the electronic records of all single-unit crowns placed on nonendodontically treated teeth between 1999 and 2019 and excluding teeth with preexisting questionable or confirmed endodontic disease, “cases” were identified as teeth requiring primary endodontic treatment after crown cementation. This was not examined in the current study because the cases and controls were matched by tooth type. ResultsOverall, 69 teeth without any suspected or confirmed past endodontic disease required an endodontic intervention after crown cementation. The mean number ± standard deviation of restorations in a tooth before crown cementation was significantly higher among the cases than the matched controls (2.16 ± 0.99 vs 0.78 ± 0.78, P < .05). Teeth with ≥2 and ≥3 previous restorations had an almost 4 (odds ratio = 3.81; 95% confidence interval, 1.56–9.29; P < .05) and almost 6 (odds ratio = 5.97; 95% confidence interval, 1.230–28.95; P < .05) times higher risk, respectively, for endodontic treatment after crown cementation compared with teeth with ≤1 restoration present before crown cementation. The majority (65%, n = 45) of teeth in the cases group required endodontic treatment during the first 3 years after crown cementation. ConclusionsThe presence of multiple restorations at the time of crown cementation was identified as a significant predictive factor for the need for endodontic treatment after crown cementation in teeth with no preexisting questionable or confirmed endodontic disease. Therefore, clinicians should be aware and inform patients about the increased risk of primary endodontic treatment in teeth with a history of more than 1 restoration, especially during the first 3 years after permanent crown cementation.

Mild-to-severe traumatic brain injury in children: altered cytokines reflect severity

BackgroundPaediatric traumatic brain injury (TBI) is recognised to have significant longer-term neurocognitive effects. Childhood is a time of high risk for head injury. Functional recovery is variable with a combination of any or all of physical, cognitive and emotional impairment. Immune activation and alteration in cytokine levels are present following TBI which may differ from adults.MethodsPro- and anti-inflammatory cytokines including Interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, IL-17A, Tumor Necrosis Factor (TNF)-α and Interferon (IFN)-γ were examined at baseline and following in vitro treatment with endotoxin of whole blood, in the following children: severe TBI (sTBI: initial Glasgow coma scale(GCS) ≤ 8), mild TBI (mTBI; GCS 14/15) at 0-4d and at 10-14d post-TBI and compared to healthy age-matched controls.ResultsThe study enrolled 208 children, including 110 with TBI cohort (n = 104 mild; 6 severe) and controls (n = 98). At baseline all children with TBI had increased IL-6. The mTBI group had significantly increased IFN-γ versus controls. In sTBI at baseline, IFN-γ was decreased compared to controls. At baseline IL-8, IL-10, IL-17A, and TNF-α were decreased in mTBI compared to controls. This persisted at 2 week post-mTBI. The AUC for detecting mTBI was 0.801 CI (0.73–086) using IL6/IL10 ratio. mTBI showed a greater fold change in IL-8 and TNF-α in response to endotoxin stimulation, a response that persisted at 2 weeks. Children with sTBI did not have a significant IL-6 response to endotoxin, but did show an increase in IL-17A.ConclusionChildren with all TBI including mTBI show altered cytokine profiles and altered endotoxin responses. Although cytokines increased in sTBI especially in response to endotoxin, suppressed responses were found in mTBI coupled with persistent immune dysfunction post-injury.

Abstract TP169: Post-Neonatal Stroke In Children With Critical Congenital Heart Defects

Background: Critical congenital heart defects (CCHD) are a subset of mostly cyanotic lesions that require intervention within the first days to weeks of life for survival. For children born with CCHD, the neonatal period is considered the time of highest risk for brain injury as abnormalities in fetal circulation can lead to vulnerabilities in cerebral perfusion prior to corrective cardiac procedures. The prevalence and timing of cerebrovascular events associated with CCHD after the neonatal period is less clear. Methods: We performed a cross-sectional analysis using the National Inpatient Sample database from 2012-2018. We included all children aged 1-18 years hospitalized with either ischemic stroke (IS), intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH). We created multivariable linear and logistic regression models to assess differences in age at stroke onset and mortality after stroke. Results: We identified 4,647 pediatric strokes, 162 (3.5%) of which were associated with CCHD. Adjusting for demographic and clinical covariates, the median age at time of stroke was lower in CCHD patients across all stroke subtypes (Figure). Children with CCHD experienced a higher proportion of IS compared to children without CCHD (75.3% vs 49.5%, P&lt;0.001); and a lower proportion of ICH and SAH (10.5% vs 25.7% and 14.2% vs 24.9%; both P = 0.002). In-hospital mortality for the entire sample following stroke was 10.4% for IS, 14.5% for ICH, and 13.4% for SAH. Adjusting for demographics and confounders, presence of CCHD doubled the odds of death following stroke (OR 2.05; 95% CI 1.35-3.11). Conclusion: Beyond the first year of life, children with CCHD have earlier age at stroke onset and higher post-stroke mortality compared to children without CCHD. Continued vigilance and monitoring of potential neurological complications is warranted in children with CCHD.

Prevalence and associated risk factors of hypertension and pre-hypertension among the adult population: findings from the Dubai Household Survey, 2019

BackgroundMinimal data is available on the prevalence and correlates of hypertension and prehypertension in Dubai. The study aims to measure the prevalence of hypertension and pre-hypertension and the associated socio-demographic characteristics, behavioral risk factors and comorbidities among the adult population of Dubai.MethodsThis study used data from the Dubai Household Health Survey, 2019. A cross-sectional population survey based on a complex stratified cluster random design. The total eligible sample included 2530 adults (18+). Sociodemographic and behavioral factors were considered as independent covariates. The main study outcome variables, pre-hypertension and hypertension, were ordinal, with normotension as the reference group.ResultsThe overall prevalence of hypertension in adults was 32.5% (38.37% in males and 16.66% in females). Prehypertension was prevalent in 29.8% of adults in Dubai (28.85% in males and 32.31% in females). The multivariate logistic regression analysis revealed that age groups, gender, occupation, and high Body Mass Index were significantly associated with a higher risk of hypertension at the level of P < 0.05. No clear trend toward a higher correlation of hypertension was noted with the increase in age, except after the age of 50 years. Males were five- times more likely to be hypertensive than females. Participants enrolled in skilled and service works had a five times higher risk of hypertension, compared with the reference group (professionals). Obese subjects had a 5.47-times greater correlation of hypertension compared with normal-weight subjects. Physically active individuals were less likely to develop hypertension. For the correlates with prehypertension in the present analysis, skilled and service workers and those working in elementary jobs had a higher risk of prehypertension, compared with the reference group (professionals) Individuals with a status of overweight were associated with a higher prevalence of prehypertension compared with people of normal weight.ConclusionsThis study showed a high prevalence of prehypertension and hypertension among adults in Dubai. Some socio-demographic and behavioral risk factors were correlated with prehypertension and hypertension among the studied population. Interventions aiming at increasing public awareness about such risk factors are essential.

Trajectories of suicidal ideation following separation from military service: Overall trends and group differences.

Although the transition out of military service is a high-risk time for suicidal ideation (SI), a paucity of research examines the development of SI during this transition process and veteran subgroups at risk for SI as they readjust to civilian life. A population-based, longitudinal post-9/11 veteran cohort reported SI frequency at 3, 9, 15, 21, and 27months post-separation using the Patient Health Questionnaire-9. We identified distinct trajectories of SI over time (i.e., classes) using latent class growth analysis and examined demographic and military service predictors of class membership overall and by gender using multinomial logistic regression. Four SI trajectories that were similar across genders were identified: resilient (90.1%), delayed onset (5.0%), remitting (2.7%), and chronic (2.2%). Younger age, minority race/ethnicity, medical and other (vs. honorable) separation types, and Veterans Health Administration service utilization were associated with increased odds of assignment to a higher-risk trajectory (delayed onset, remitting, and/or chronic vs. resilient), whereas continued service in the National Guard/Reserves and officer rank was associated with lower odds of assignment to a higher-risk trajectory. Findings regarding veterans at greatest risk for SI following military separation can inform targeted assessment and early intervention efforts.

Associations Between Diabetic Retinopathy and Parkinson's Disease: Results From the Catalonian Primary Care Cohort Study.

The purpose of this study was to assess the risk of occurrence of Parkinson's disease (PD) among subjects with type 2 diabetes and diabetic retinopathy (DR) in our large primary health care database from Catalonia (Spain). A retrospective cohort study with pseudo-anonymized routinely collected health data from SIDIAP was conducted from 2008 to 2016. We calculated the number of events, time to event, cumulative incidence, and incidence rates of PD for subjects with and without DR and for different stages of DR. The proportional hazards regression analysis was done to assess the probability of occurrence between DR and PD. In total, 26,453 type 2 diabetic subjects with DR were identified in the database, and 216,250 subjects without DR at inclusion. During the follow-up period, 1,748 PD events occurred. PD incidence rate and cumulative incidence were higher among subjects with DR (16.95 per 10,000 person-years and 0.83%, respectively). In the unadjusted analysis, subjects with DR were at 1.25 times higher risk (hazard ratio: 1.22, 95% confidence interval: 1.06; 1.41) of developing PD during the study period. However, we did not find any statistically significant HR for DR in any models after adjusting for different risk factors (age, sex, duration of diabetes, smoking, body mass index, glycosylated hemoglobin, comorbidities). In conclusion, in our primary health care population database, DR was not associated with an increased risk of PD after adjusting for different risk factors. In our retrospective cohort study, age, male sex, and diabetes duration were independent risk factors for developing PD.

"Will I Need a Brace?": likelihood of curve progression to bracing range in adolescent idiopathic scoliosis.

Bracing treatment for adolescent idiopathic scoliosis (AIS) is typically initiated in skeletally immature patients with primary curves greater than 25°. The goal of this study was to develop a model predicting a patient's likelihood of progressing to bracing treatment. All patients with AIS presenting to a large pediatric spine center with a primary curve below 25° and skeletally immature (Sanders stage 1-6) were included. A patient was considered to have progressed into the bracing range if their primary curve reached a 25° threshold prior to skeletal maturity. Binary logistic regression analysis was performed to predict the likelihood of curve progression into bracing range. A total of 180 patients (71% female) were included in this study with an average presenting age of 13.2 ± 1.4years. At presentation, 31 (17%) were pre-peak height velocity, 62 (34%) were at their peak height velocity, and 87 (48%) were in the late adolescent growth stage. The high-risk patient group was defined as Sanders 1-2 and curve size > 10 and < 25° or Sanders 3-6 and curve size > 20 but < 25°. Those in the high-risk group demonstrated an over 5 times higher risk of progression to bracing range when accounting for age, sex, and curve location (OR: 5.168, 95% CI: 2.212-12.071, p < 0.001). Patient's curve magnitude and skeletal maturity can be used to predict their likelihood of curve progression to greater than 25° and thus require bracing treatment. Orthopaedic providers can consider earlier treatment interventions or stricter follow-up adherence for patients at high risk for progression. 3-retrospective cohort study.

Gender Differences Associated with Hyper-Inflammatory Conditions in COVID-19 Patients.

COVID-19 has been associated with various hyper-inflammatory conditions (HICs) such as macrophage activation, hematological dysfunction, cytokinaemia, coagulopathy, and liver inflammation. However, it is not clear if the differences in the disease severity and mortality shown by male and female COVID-19 patients are associated with these HICs. Here, we review the literature and present supporting laboratory data on the gender differences associated with various HICs in COVID-19 patients. We measured plasma/serum levels of various HIC specific clinical markers in severe male (N=132) and severe female (N=78) COVID-19 patients. The result revealed that all clinical markers were highly elevated above the normal in both male and female COVID-19 patients. However, a comparison of AUROC (area under the receiving operative characteristics) of specific clinical markers revealed that elevation in serum ferritin (marker for macrophage activation), and neutrophil to lymphocyte (N/L) ration (marker for hematological dysfunction) was much higher in male compared to the female COVD-19 patients. Further, univariate regression analyses revealed that male COVID-19 patients had two times higher risks than female patients for developing macrophage activation (OR 2.36, P=0.004)), hematological dysfunctions (OR 2.23, P=0.01), coagulopathy (OR 2.10, P=0.01), and cytokinaemia (OR 2.31, P=0.01). Similar results were obtained in bivariate analyses. Survival curve analysis showed that male COVID-19 patients had relatively short survival duration than female COVID-19 patients (hazard ratio 2.0, 95% CI 1.3-3.7, P=0.01). The above findings suggest that the high mortality rate in male COVID-19 patients compared to the female could be due to higher prevalence and severity of various HICs.

Preceding anti-spike IgG levels predicted risk and severity of COVID-19 during the Omicron-dominant wave in Santa Fe city, Argentina.

The SARS-CoV-2 Omicron variant has increased infectivity and immune escape compared with previous variants, and caused the surge of massive COVID-19 waves globally. Despite a vast majority (~90%) of the population of Santa Fe city, Argentina had been vaccinated and/or had been infected by SARS-CoV-2 when Omicron emerged, the epidemic wave that followed its arrival was by far the largest one experienced in the city. A serosurvey conducted prior to the arrival of Omicron allowed to assess the acquired humoral defences preceding the wave and to conduct a longitudinal study to provide individual-level real-world data linking antibody levels and protection against COVID-19 during the wave. A very large proportion of 1455 sampled individuals had immunological memory against COVID-19 at the arrival of Omicron (almost 90%), and about half (48.9%) had high anti-spike immunoglobulin G levels (>200 UI/ml). However, the antibody titres varied greatly among the participants, and such variability depended mainly on the vaccine platform received, on having had COVID-19 previously and on the number of days elapsed since last antigen exposure (vaccine shot or natural infection). A follow-up of 514 participants provided real-world evidence of antibody-mediated protection against COVID-19 during a period of high risk of exposure to an immune-escaping highly transmissible variant. Pre-wave antibody titres were strongly negatively associated with COVID-19 incidence and severity of symptoms during the wave. Also, receiving a vaccine shot during the follow-up period reduced the COVID-19 risk drastically (15-fold). These results highlight the importance of maintaining high defences through vaccination at times of high risk of exposure to immune-escaping variants.