Low-risk Population Research Articles

Construction and validation of a nomogram to predict left ventricular hypertrophy in low-risk patients with hypertension.

Electrocardiography (ECG) is an accessible diagnostic tool for screening patients with hypertensive left ventricular hypertrophy (LVH). However, its diagnostic sensitivity is low, with a high probability of false-negatives. Thus, this study aimed to establish a clinically useful nomogram to supplement the assessment of LVH in patients with hypertension and without ECG-LVH based on Cornell product criteria (low-risk hypertensive population). A cross-sectional dataset was used for model construction and divided into development (n=2906) and verification (n=1447) datasets. A multivariable logistic regression risk model and nomogram were developed after screening for risk factors. Of the 4353 low-risk hypertensive patients, 673 (15.4%) had LVH diagnosed by echocardiography (Echo-LVH). Eleven risk factors were identified: hypertension awareness, duration of hypertension, age, sex, high waist-hip ratio, education level, tea consumption, hypochloremia, and other ECG-LVH diagnostic criteria (including Sokolow-Lyon, Sokolow-Lyon products, and Peguero-Lo Presti). For the development and validation datasets, the areas under the curve were 0.724 (sensitivity=0.606) and 0.700 (sensitivity=0.663), respectively. After including blood pressure, the areas under the curve were 0.735 (sensitivity=0.734) and 0.716 (sensitivity=0.718), respectively. This novel nomogram had a good predictive ability and may be used to assess the Echo-LVH risk in patients with hypertension and without ECG-LVH based on Cornell product criteria.

A novel anoikis-related gene signature predicts prognosis in patients with sepsis and reveals immune infiltration

Sepsis is a common acute and severe medical condition with a high mortality rate. Anoikis, an emerging form of cell death, plays a significant role in various diseases. However, the role of anoikis in sepsis remains poorly understood. Based on the datasets from Gene Expression Omnibus and anoikis-related genes from GeneCards, the differentially expressed anoikis-related genes (DEARGs) were identified. Based on hub genes of DEARGs, a novel prognostic risk model was constructed, and the pattern of immune infiltration was investigated by CIBERSORT algorithm. And small molecule compounds targeting anoikis in sepsis were analyzed using Autodock. Of 23 DEARGs, CXCL8, CFLAR, FASLG and TP53 were significantly associated with the prognosis of sepsis (P < 0.05). Based on the prognostic risk model constructed with these four genes, high-risk population of septic patients had significant lower survival probability than low-risk population (HR = 3.30, P < 0.001). And the level of CFLAR was significantly correlated with the number of neutrophils in septic patients (r = 0.54, P < 0.001). Moreover, tozasertib had low binding energy with CXCL8, CFLAR, FASLG and TP53, and would be a potential compound for sepsis. Conclusively, our results identified a new prognostic model and potential therapeutic molecular for sepsis, providing new insights on mechanism and treatment of sepsis.

P604 Exploring the role of chest X-ray in latent tuberculosis screening in Inflammatory Bowel Disease

Abstract Background Patients being treated with biologics or JAK inhibitors have an increased reactivation risk of latent tuberculosis infection (LTBI), and this is associated with a more severe infective course. Current ECCO guidance recommends the screening for LTBI by a combination of patient clinical data and epidemiological factors, chest X-ray (CXR), and tuberculin skin test or interferon-gamma release assay (IGRA) prior to starting immunosuppressive treatment. The evidence supporting CXR is categorized at evidence level 5, and information on its use in screening for LTBI originates from two decades ago. Apart from radiation exposure, a single posterior-anterior view has limited diagnostic capabilities. This study aims to determine the relation between CXR findings and IGRA test results in patients undergoing LTBI screening before commencing immunosuppressive therapy for Inflammatory bowel disease (IBD) patients in a low-risk population. Methods This is a retrospective analysis whereby IBD patients (≥16 years) on biologics or JAK inhibitors were identified from our local database. The clinical data, epidemiological, CXR and IGRA result were then analysed from the electronic case records. The IGRA test used was the QuantiFERON-TB Gold. Results A total of 356 patients were included in the study, with 58.7% (n=209) being male. Among these patients, the majority had Crohn's disease (66.6%, n=236), 30.1% (n=109) had ulcerative colitis, and the remaining 2.8% were classified as having IBD-unclassified. Most patients (97.1%) had been exposed to anti-TNF alpha medications and 13.2% were exposed to multiple biologicals. The mean age of IBD diagnosis was 30.3 years (SD+/-15.7). None of the patients had any clinical suggestion nor any evidence for exposure to TB. None of the CXRs performed revealed any radiological signs of prior TB infection. 93.8% (n=334) of the IGRA results were negative and 4.2% (n=15) were categorized as indeterminate. Among those with indeterminate results, 66.7% (n=10) were undergoing corticosteroid treatment for active disease. The remaining 2.0% (n=7) had a positive IGRA test and were treated for LTBI.None of these patients had TB reactivation when then treated with biologicals. Conclusion This research highlights that performing routinely a CXR in individuals with a negative IGRA offers little to no benefit, and subjects patients to unnecessary radiation. It also demonstrates the importance of conducting the IGRA test early, before initiating any immunosuppressive treatment. Furthermore, in patients with a negative IGRA, if chest imaging is required for screening purposes, opting for an ultra-low dose CT might be more prudent than a CXR, as it visualises the lungs better and the radiation exposure is not substantially different.

Knowledge of non-contraceptive benefits of and willingness to consider taking oral contraceptive pills among a low-risk female population: a cross-sectional study

Background In addition to its widely-appreciated contraceptive applications, the oral contraceptive pill (OCP) conveys both oncological and non-oncological benefits. Oncological benefits include a decreased risk of endometrial, ovarian, and colorectal cancer. Non-oncological benefits include reducing androgenic effects and alleviating menstruation-related problems. This study aimed to ascertain knowledge levels of non-contraceptive benefits and risks of OCP use among participants without contraindications to OCPs. This study also assessed factors associated with participants being more likely to consider taking OCPs. Methods 263 women aged 21 to 40 years old with no contraindications for OCP usage participated in this study. An anonymous questionnaire collected sociodemographic information and assessed participants’ knowledge of the non-contraceptive benefits and risks associated with OCP use. Multivariate linear regression was used to assess factors associated with knowledge levels. Multivariate logistic regression was used to investigate factors associated with being more likely to consider taking OCPs among women who did not presently take them. Results Multivariate logistic regression revealed that participants who were more knowledgeable overall about the non-contraceptive benefits of OCPs were more likely to consider taking OCPs (coefficient = 0.184, p-value = 0.00). Knowledge of both oncological and non-oncological benefits of OCP use was relatively poor, especially among older women. Current OCP users were found to be more knowledgeable about their benefits. Conclusions As women with greater knowledge of non-contraceptive benefits of OCPs are more likely to consider taking them, knowledge gaps regarding OCPs should be filled, so that more women may reap the non-contraceptive benefits of OCPs.

High-Grade Serous Ovarian Cancer-A Risk Factor Puzzle and Screening Fugitive.

High-grade serous ovarian cancer (HGSOC) is the most lethal tumor of the female genital tract. Despite extensive studies and the identification of some precursor lesions like serous tubal intraepithelial cancer (STIC) or the deviated mutational status of the patients (BRCA germinal mutation), the pathophysiology of HGSOC and the existence of particular risk factors is still a puzzle. Moreover, a lack of screening programs results in delayed diagnosis, which is accompanied by a secondary chemo-resistance of the tumor and usually results in a high recurrence rate after the primary therapy. Therefore, there is an urgent need to identify the substantial risk factors for both predisposed and low-risk populations of women, as well as to create an economically and clinically justified screening program. This paper reviews the classic and novel risk factors for HGSOC and methods of diagnosis and prediction, including serum biomarkers, the liquid biopsy of circulating tumor cells or circulating tumor DNA, epigenetic markers, exosomes, and genomic and proteomic biomarkers. The novel future complex approach to ovarian cancer diagnosis should be devised based on these findings, and the general outcome of such an approach is proposed and discussed in the paper.

Prevalence of Hepatitis B in Canadian First-Time Blood Donors: Association with Social Determinants of Health.

Hepatitis B is transmitted sexually, by blood contact, and vertically from mother to child. Chronic hepatitis B is often seen in immigrants from higher-prevalence countries and their Canadian-born children. We assessed the relationship between hepatitis B and social determinants of health. Included were 1,539,869 first-time Canadian blood donors from April 2005 to December 2022. All donations were tested for hepatitis B markers. Logistic regression was fit with chronic hepatitis B as the dependent variable and age, sex, year, and ethnocultural composition and material deprivation quintiles as independent variables. Chronic hepatitis B prevalence was 47.5/100,000 (95% CI 41.5-53.5, years 2017-2022). Chronic hepatitis B prevalence was elevated in males, older age groups, and those living in more materially deprived and higher ethnocultural neighbourhoods. Of 212,518 donors from 2020 to 2022 with race/ethnicity data, chronic hepatitis B prevalence was highest in East Asians. The findings are consistent with infections in immigrants, acquired in their country of origin, in their Canadian-born children and in those with other risks. As blood donors are a low-risk population unaware of their infection and unlikely to seek testing, our results highlight the ongoing public health challenges of diagnosing chronic hepatitis B and treating it when appropriate.

Mitochondrial DNA Haplogroups and SNPs: Risk Factors in Multiple Cancers Based on a Cross-Tumor Analysis in Chinese Population.

Mitochondrial DNA's (mtDNA) haplogroups and SNPs were associated with the risk of different cancer. However, there is no evidence that the same haplogroup or mitochondrial SNP (mtSNP) exhibits the pleiotropic effect on multiple cancers. We recruited 2,489 participants, including patients with colorectal, hepatocellular, lung, ovarian, bladder, breast, pancreatic, and renal cell carcinoma. In addition, 715 healthy individuals from Northern China served as controls. Next, cross-tumor analysis was performed to determine whether mtDNA variation is associated with multiple cancers. Our results revealed a significant decrease in the occurrence risk of multiple cancers among individuals belonging to haplogroup A [OR = 0.553, 95% confidence interval (CI) = 0.375-0.815, P = 0.003]. Furthermore, we identified 11 mtSNPs associated with multiple cancers and divided the population into high-risk and low-risk groups. Low-risk groups showed a significantly reduced risk of occurrence compared with high-risk groups (OR = 0.614, 95% CI = 0.507-0.744, P < 0.001). Furthermore, using interaction analysis, we identified a special group of individuals belonging to haplogroup A/M7 and the low-risk population, who exhibit a lower risk of multiple cancers compared with other populations (OR = 0.195, 95% CI = 0.106-0.359, P < 0.001). Finally, gene set enrichment analysis confirmed that haplogroup A/M7 patients had lower expression levels of cancer-related pathway genes compared with haplogroup D patients. We found that specific mtDNA haplogroups and mtSNPs may play a role in predicting multiple cancer predisposition in Chinese populations. This may provide a potential tool for early screening in clinical settings for individuals in the Chinese population.

Impact of vaccination and high-risk group awareness on the mpox epidemic in the United States, 2022–2023: a modelling study

The unprecedented global outbreak of mpox in 2022 posed a public health challenge. In addition to the mpox vaccine campaign in the United States (US), community organisations and public health agencies initiated educational efforts to promote sexual risk reduction. This modelling study estimated the impact of the two-dose vaccination campaign and sexual behaviour changes coincident with high-risk group awareness on the mpox epidemic in the US. We fitted a deterministic, risk-structured SEIARV model to the epidemic curve of reported mpox cases in the US between May 22, 2022 and December 22, 2022. We evaluated the putative effects of the two preventive responses in the US -- vaccination and sexual risk reduction -- at the population-level, by calculating the prevention percentages of cumulative cases compared to the counterfactual scenario without interventions. We performed sensitivity analyses with four parameters: case reporting fidelity, vaccine effectiveness, proportion of asymptomatic cases, and assortative mixing. Model fitting revealed a basic reproduction number of 3.88 and 0.39 for the high-risk and low-risk populations, respectively, with 71.8% of mpox cases estimated from the high-risk population. A two-dose vaccination campaign, solely, could prevent 21.2% (10.2%-24.1%) of cases, while behaviour changes due to high-risk group awareness alone could prevent 15.4% (14.3%-20.6%). The combination of both measures were synergistic, with the model suggesting that 64.0% (43.8%-69.0%) of US cases were averted that would have otherwise occurred. Our models suggest that the 2022-2023 mpox epidemic in the US was controlled by a combination of two-dose mpox vaccination campaign and high-risk group awareness and sexual risk reduction. Taiwan Ministry of Education grant #NTU-112L9004, Taiwan National Science and Technology Council grant #MOST-109-2314-B-002-147-MY3 and grant #NSC-112-2314-B-002-216-MY3. SHV was supported, in part, by US National Institutes of Health grant #P30MH062294.

Multisystem Inflammatory Syndrome in Children during the COVID-19 Pandemic: A Review of Clinical Manifestations, Cardiac Complications and Medical Management.

The SARS-CoV-2 pandemic has led to widespread research on associated clinical syndromes. While pediatric patients were initially deemed as a low-risk population for severe COVID-related disease, an increasing number of case reports have revealed a rare but potentially life-threatening syndrome, multisystem inflammatory syndrome in children (MIS-C). MIS-C is hypothesized to be due to hyperactivation of the immune system via a cytokine storm which leads to end-organ damage via endothelial dysfunction and changes in vascular permeability. Laboratory studies have displayed increased inflammatory markers such as C-reactive protein, erythrocyte sedimentation rate, D-dimer, tumor necrosis factor-alpha, and various interleukins. Studies have reported a wide range of clinical manifestations, including but not limited to fever, hypotension, shock, rash, coagulopathy, and gastrointestinal distress. Cardiac imaging and screening tests have revealed several complications, such as left ventricular failure, arrhythmias, and pericardial effusions. Medical management of MIS-C and cardiac sequelae have included supportive care, intravenous immunoglobulins, and corticosteroids, as well as immunomodulators, monoclonal antibodies, aspirin, and therapeutic anticoagulation, which have prevented serious outcomes in the majority of pediatric patients. Future multicenter and large-scale research is required for precise risk-stratification of MIS-C as well as long-term monitoring of sequelae. In this review, we aim to (1) outline the laboratory findings and clinical manifestations of MIS-C, and (2) describe cardiac complications and medical management of MIS-C.

Evaluation of the efficacy of labor induction with vaginal misoprostol in a low-risk pregnant women population.

The aim of this study was to evaluate the success rate and predictors of labor induction using vaginal misoprostol in a low-risk pregnant women population. A prospective cohort study was carried out with 196 pregnant women. Groups 2 and 4 of the Robson Classification admitted for induction of labor with vaginal misoprostol (25 μg tablets every 6 h, up to 4 tablets, for a maximum of 24 h). The success of labor induction was considered the achievement of vaginal delivery. Binary logistic regression was used to determine the best predictors of successful induction of labor with vaginal misoprostol. Of all the pregnant women analyzed, 140 (71.4%) were successful and 56 (28.6%) were unsuccessful. Pregnant women who achieved successful induction had a higher number of pregnancies (1.69 vs. 1.36, p=0.023), a higher number of deliveries (0.57 vs. 0.19, p<0.001), a higher Bishop score (2.0 vs. 1.38, p=0.002), and lower misoprostol 25 μg tablets (2.18 vs. 2.57, p=0.031). No previous deliveries [x2(1)=3.14, odds ratio (OR): 0.24, 95% confidence interval (CI): 0.10-0.57, R2 Nagelkerke: 0.91, p=0.001] and the presence of one previous delivery [x2(1)=6.0, OR: 3.40, 95% CI: 1.13-10.16, R2 Nagelkerke: 0.043, p=0.029] were significant predictors of successful induction of labor with vaginal misoprostol. A high rate of labor induction success using vaginal misoprostol in a low-risk population was observed, mainly in multiparous and with gestational age>41 weeks. No previous delivery decreased the success of labor induction, while one previous delivery increased the success of labor induction.

Identification of prognostic RNA editing profiles for clear cell renal carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cancer and currently lacks effective biomarkers. This research aims to analyze and identify RNA editing profile associated with ccRCC prognosis through bioinformatics and in vitro experiments. Transcriptome data and clinical information for ccRCC were retrieved from the TCGA database, and RNA editing files were obtained from the Synapse database. Prognostic models were screened, developed, and assessed using consistency index analysis and independent prognostic analysis, etc. Internal validation models were also constructed for further evaluation. Differential genes were investigated using GO, KEGG, and GSEA enrichment analyses. Furthermore, qPCR was performed to determine gene expression in human renal tubular epithelial cells HK-2 and ccRCC cells A-498, 786-O, and Caki-2. An RNA editing-based risk score, that effectively distinguishes between high and low-risk populations, has been identified. It includes CHD3| chr17:7815229, MYO19| chr17:34853704, OIP5-AS1| chr15:41590962, MRI1| chr19:13883962, GBP4| chr1:89649327, APOL1| chr22:36662830, FCF1| chr14:75203040 edited sites or genes and could serve as an independent prognostic factor for ccRCC patients. qPCR results showed significant up-regulation of CHD3, MYO19, MRI1, APOL1, and FCF1 in A-498, 786-O, and Caki-2 cells, while the expression of OIP5-AS1 and GBP4 was significantly down-regulated. RNA editing site-based prognostic models are valuable in differentiating between high and low-risk populations. The seven identified RNA editing sites may be utilized as potential biomarkers for ccRCC.

Deep-learning model for prenatal congenital heart disease screening generalizes to community setting and outperforms clinical detection.

Despite nearly universal prenatal ultrasound screening programs, congenital heart defects (CHD) are still missed, which may result in severe morbidity or even death. Deep machine learning (DL) can automate image recognition from ultrasound. The main aim of this study was to assess the performance of a previously developed DL model, trained on images from a tertiary center, using fetal ultrasound images obtained during the second-trimester standard anomaly scan in a low-risk population. A secondary aim was to compare initial screening diagnosis, which made use of live imaging at the point-of-care, with diagnosis by clinicians evaluating only stored images. All pregnancies with isolated severe CHD in the Northwestern region of The Netherlands between 2015 and 2016 with available stored images were evaluated, as well as a sample of normal fetuses' examinations from the same region and time period. We compared the accuracy of the initial clinical diagnosis (made in real time with access to live imaging) with that of the model (which had only stored imaging available) and with the performance of three blinded human experts who had access only to the stored images (like the model). We analyzed performance according to ultrasound study characteristics, such as duration and quality (scored independently by investigators), number of stored images and availability of screening views. A total of 42 normal fetuses and 66 cases of isolated CHD at birth were analyzed. Of the abnormal cases, 31 were missed and 35 were detected at the time of the clinical anatomy scan (sensitivity, 53%). Model sensitivity and specificity were 91% and 78%, respectively. Blinded human experts (n = 3) achieved mean ± SD sensitivity and specificity of 55 ± 10% (range, 47-67%) and 71 ± 13% (range, 57-83%), respectively. There was a statistically significant difference in model correctness according to expert-graded image quality (P = 0.03). The abnormal cases included 19 lesions that the model had not encountered during its training; the model's performance in these cases (16/19 correct) was not statistically significantly different from that for previously encountered lesions (P = 0.41). A previously trained DL algorithm had higher sensitivity than initial clinical assessment in detecting CHD in a cohort in which over 50% of CHD cases were initially missed clinically. Notably, the DL algorithm performed well on community-acquired images in a low-risk population, including lesions to which it had not been exposed previously. Furthermore, when both the model and blinded human experts had access to only stored images and not the full range of images available to a clinician during a live scan, the model outperformed the human experts. Together, these findings support the proposition that use of DL models can improve prenatal detection of CHD. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Addition of High-Sensitivity Troponin to Perioperative Risk Assessment Improves the Predictive Ability of Death in Non-Cardiac Surgery Patients.

Risk stratification is an important step in perioperative evaluation. However, the main risk scores do not incorporate biomarkers in their set of variables. Evaluate the incremental power of troponin to the usual risk stratification. A total of 2,230 patients admitted to the intensive care unit after non-cardiac surgery were classified according to three types of risk: cardiovascular risk (CVR), Revised Cardiac Risk Index (RCRI); and inherent risk of surgery (IRS). The main outcome was all-cause mortality. Cox regression was used as well as c-statistics before and after addition of high-sensitivity troponin (at least one measurement up to three days after surgery). Finally, net reclassification index and integrated discrimination improvement were used to assess the incremental power of troponin for risk stratification. Significance level was set at 0.05. Mean age of patients was 63.8 years and 55.6% were women. The prevalence of myocardial injury after non-cardiac surgery (MINS) was 9.4%. High CVR-patients had a higher occurrence of MINS (40.1 x 24.8%, p<0.001), as well as high IRS-patients (21.3 x 13.9%, p=0.004) and those with a RCRI≥3 (3.0 x 0.7%, p=0.009). Patients without MINS, regardless of the assessed risk, had similar mortality rate. The addition of troponin to the risk assessment improved the predictive ability of death at 30 days and at 1 year in all risk assessments. The prevalence of MINS is higher in the high-risk population. However, its prevalence in lower-risk population is not negligible and causes a higher risk of death. The addition of high-sensitivity troponin increased the predictive ability of risk assessment in all groups.

Adição da Troponina Ultrassensível à Avaliação de Risco Perioperatório Melhora a Capacidade Preditiva de Morte em Pacientes Submetidos à Cirurgia Não Cardíaca

Abstract Background Risk stratification is an important step in perioperative evaluation. However, the main risk scores do not incorporate biomarkers in their set of variables. Objective Evaluate the incremental power of troponin to the usual risk stratification Methods A total of 2,230 patients admitted to the intensive care unit after non-cardiac surgery were classified according to three types of risk: cardiovascular risk (CVR), Revised Cardiac Risk Index (RCRI); and inherent risk of surgery (IRS). The main outcome was all-cause mortality. Cox regression was used as well as c-statistics before and after addition of high-sensitivity troponin (at least one measurement up to three days after surgery). Finally, net reclassification index and integrated discrimination improvement were used to assess the incremental power of troponin for risk stratification. Significance level was set at 0.05. Results Mean age of patients was 63.8 years and 55.6% were women. The prevalence of myocardial injury after non-cardiac surgery (MINS) was 9.4%. High CVR-patients had a higher occurrence of MINS (40.1 x 24.8%, p&lt;0.001), as well as high IRS-patients (21.3 x 13.9%, p=0.004) and those with a RCRI≥3 (3.0 x 0.7%, p=0.009). Patients without MINS, regardless of the assessed risk, had similar mortality rate. The addition of troponin to the risk assessment improved the predictive ability of death at 30 days and at 1 year in all risk assessments. Conclusion The prevalence of MINS is higher in the high-risk population. However, its prevalence in lower-risk population is not negligible and causes a higher risk of death. The addition of high-sensitivity troponin increased the predictive ability of risk assessment in all groups.

Cardiovascular Risk Scales Association with Cerebrospinal Fluid Alzheimer's Disease Biomarkers in Cardiovascular Low Cardiovascular Risk Regions.

Cardiovascular risk factors are associated with Alzheimer's Disease (AD) development. However, few studies compare the overall cardiovascular risk with AD biomarkers, and when done, they are mainly performed in moderate cardiovascular risk regions. To determine whether cardiovascular risk in older adults is associated with pathological cerebrospinal fluid (CSF) biomarkers of AD in a low cardiovascular risk population. This is a cross-sectional study performed between 2017 and 2020. The present work included patients between 50 and 75 years old who were negative for CSF AD biomarkers and had minimum cognitive alterations (controls) and patients with positive CSF AD biomarkers and in early stages of AD (cases). CSF biomarkers included total tau, phosphorylated tau 181 and amyloid ß42 (Aß42). Analytical variables were obtained. ERICE, SCORE2 and Framingham scales were used to calculate the overall patient's cardiovascular risk. The Aß42/Aß40 ratio and neurofilaments were explored when available. Two hundred and thirty-three patients were included. Nearly 76% of the sample had AD. AD patients had higher cardiovascular risk than controls (p-value < 0.05). ERICE and SCORE2 were associated with AD presence. Framingham was not. A correlation between elevated cardiovascular risk and higher total tau and NfL levels was observed when adjusted by age. Cardiovascular risk assessment may be helpful in neurodegenerative disorders detection, as it is associated with CSF total tau and NfL. ERICE and SCORE2 may be useful scales in low cardiovascular risk regions to improve cardiovascular control and prevent neurodegenerative pathologies.

A Different Perspective of COVID-19 Pandemic: Efficacy and Safety of mRNA Vaccines in Immunocompetent and Immunocompromised Individuals (Part 3).

Shortly after the declaration of the pandemic, several anti-SARS-CoV-2 vaccines entered phase 3 clinical trials. One year later, Pfizer-BioNTech and Moderna published their initial trial results, encompassing a 2-month follow-up. The studies were only designed to test whether the vaccines were effective and safe on the short-term.The vaccine's efficacy in the 2 trials was defined as relative risk reduction instead of absolute risk reduction, a more accurate determinant of vaccine effectiveness in the real world. These studies were not designed to assess viraltransmission, disease severity, and death as primary outcomes.Vulnerable subgroups of individuals were excluded from the studies. No correlate of immunity against the SARS-CoV2 was identified.Vaccine-induced immunity declined shortly after vaccination and was not protective against new variants. Vaccination and boosting effectiveness were suboptimal in immunocompromised patients. In contrast, in recovered COVID-19 patients, natural immunity was shown to be protective, lasting longer and being more effective against new variants. Findings from subsequent scientific reports questioned the effectiveness of these vaccines in providing protective immunity despite boosting in infection-naïve and infection-experienced individuals. Reports also raised concerns on their safety in relation to cardiovascular pathology, sudden death, and acquired autoimmunity mainly in the low-risk young population. With the doubtful accuracy of the polymerase chain reaction testing in relation to case definition and diagnosis, the inability of the vaccines to stop viral transmission, the uncertain effectiveness of these vaccines, and serious adverse events of these vaccines lead us to question the validity ofthe vaccine mandate in public and private domains.

Exploring Biomarkers in Gestational Diabetes Mellitus: A Comprehensive Review

Gestational Diabetes Mellitus (GDM) is a common complication during pregnancy, typically diagnosed in the second or third trimester. Factors such as advanced maternal age, obesity and a sedentary lifestyle contribute to its prevalence. The pathophysiology involves insulin resistance, β-cell dysfunction, gluconeogenesis, adipose tissue dysfunction, gut microbiota dysbiosis and oxidative stress. GDM is associated with maternal and neonatal complications, both short-term and long-term. Managing GDM requires interventions such as medication, dietary adjustments and regular physical activity. However, early detection in low-risk populations remains challenging. The Oral Glucose Tolerance Test (OGTT) is the gold standard for diagnosis but is limited by its inconvenience and reliance on multiple blood samples. The present review focuses on novel biomarkers for early and accurate GDM diagnosis. It discusses emerging biomarkers such as vitamin D, vitamin B9, vitamin B12, preptin, angiopoietin-like protein 8, adiponectin, chemerin, omentin-1, leptin, Interleukin-6 (IL-6), homocysteine, C-peptide, irisin, adropin, nesfatin-1, Afamin, fetuin A, amylin, galectin, osteocalcin, resistin, visfatin and Fatty Acid-binding Protein 4 (FABP4). The review explores the pathophysiology of these biomarkers in GDM and presents preliminary study findings.

Association of race and ethnicity in cesarean rates in a diverse low-risk populationAssociation of race and ethnicity in cesarean rates in a diverse low-risk population

Objective To evaluate racial disparities in cesarean delivery rates in an ethnically diverse nulliparous, term, singleton, vertex (NTSV) population at an inner-city tertiary care center. Methods This is a retrospective cohort study evaluating cesarean delivery rates by race and ethnicity in an ethnically diverse NTSV population with approximately equal numbers of Hispanic, non-Hispanic Black and non-Hispanic White participants from January 1st through December 31st, 2020. The primary outcome was cesarean delivery rate. The secondary outcome was urgency of cesarean delivery categorized as emergent, unscheduled or elective. Univariable analysis was utilized to evaluate the association of maternal clinical characteristics and the primary and secondary outcomes. Multivariable analysis was performed for variables significant in univariable analysis (p &lt;0.05). Results A total of 872 patients were included in the study. 290 were non-Hispanic White (33.3%), 258 were non-Hispanic Black (29.6%), 245 were Hispanic (28.1%), and 79 were Asian (9.1%). The overall cesarean rate was 32.5%. The cesarean delivery rates for non-Hispanic White, non-Hispanic Black, Hispanic, and Asian patients were 26.6%, 40.7%, 31.4%, and 30.4%, respectively. Non-Hispanic Black patients had significantly higher odds of cesarean delivery when compared to non-Hispanic White patients (OR 1.96, 95% CI: 1.37-2.81). This increased risk persisted in the multivariable analysis (aOR 1.83, 95% CI: 1.13-2.97). The risk of emergent cesarean delivery for non-Hispanic Black patients was also significantly increased (OR 3.69, 95% CI: 2.28-5.75), (aOR 3.39, 95% CI: 1.90-6.05). Conclusion Non-Hispanic Black patients had significantly higher risk of cesarean delivery and emergent cesarean delivery when compared to non-Hispanic White patients in an NTSV population at an inner-city tertiary care center.

Transcatheter Aortic Valve Implantation Access Sites: Same Goals, Distinct Aspects, Various Merits and Demerits.

Transcatheter aortic valve implantation (TAVI) has been established as a safe and efficacious treatment for patients with severe symptomatic aortic stenosis (AS). Despite being initially developed and indicated for high-surgical-risk patients, it is now offered to low-risk populations based on the results of large randomized controlled trials. The most common access sites in the vast majority of patients undergoing TAVI are the common femoral arteries; however, 10-20% of the patients treated with TAVI require an alternative access route, mainly due to peripheral atherosclerotic disease or complex anatomy. Hence, to achieve successful delivery and implantation of the valve, several arterial approaches have been studied, including transcarotid (TCr), axillary/subclavian (A/Sc), transapical (TAp), transaortic (TAo), suprasternal-brachiocephalic (S-B), and transcaval (TCv). This review aims to concisely summarize the most recent literature data and current guidelines as well as evaluate the various access routes for TAVI, focusing on the indications, the various special patient groups, and the advantages and disadvantages of each technique, as well as their adverse events.

A three-gene signature reveals changes in the tumor immune microenvironment in the progression from NAFLD to HCC

Hepatocellular carcinoma (HCC) is one of the most dangerous malignant tumors. The incidence rates of obesity related NAFLD and NASH are increasing year by year, and they are the main risk factors for HCC at present. Finding the mechanism of malignant transformation of NAFLD and NASH is helpful for early prevention and diagnosis. In this study, we performed differential analysis using NAFLD data, NASH data, and HCC data to identify crossover differential genes. Then, using the clinical data of TCGA, a prognostic risk prediction model of three genes (TEAD4, SOCS2, CIT) was constructed, and survival analysis and receiver operating characteristic curves were drawn. The prognostic model was validated using ICGC, GSE116174 and GSE54236 datasets. In addition, we assessed immune status and function in high- and low-risk populations using a prognostic model. Moreover, we assessed the expression of CIT in clinical samples and HCC cell lines and validated its role in HCC development. Our study elucidates the important role of the tumor immune microenvironment in the development of NAFLD/NASH to HCC, deepens the understanding of the pathogenesis of NAFLD/NASH development to HCC, and is helpful for clinical management and decision-making.