Faculty Publications (CoM)

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Carbapenem resistant Enterobacterales in the United Arab Emirates: a retrospective analysis from 2010 to 2021
(2023-12) Senok, Abiola
Abstract: Background: Carbapenem-resistant Enterobacterales (CRE) are spreading in the United Arab Emirates (UAE) where their dissemination is facilitated by international travel, trade, and tourism. The objective of this study is to describe the longitudinal changes of CRE as reported by the national AMR surveillance system of the UAE. Methods: In this study, we retrospectively describe CRE isolated from 317 surveillance sites, including 87 hospitals and 230 centers/clinics from 2010 to 2021. The associated clinical, demographic, and microbiological characteristics are presented by relying on the UAE national AMR surveillance program. Data was analyzed using WHONET microbiology laboratory database software (http://www.whonet.org). Results: A total of 14,593 carbapenem resistant Enterobacterales were analyzed, of which 48.1% were carbapenem resistant Klebsiella pneumoniae (CRKp), 25.1% carbapenem resistant Escherichia coli (CREc), and 26.8% represented 72 other carbapenem resistant species. Carbapenem resistant strains were mostly associated with adults and isolated from urine samples (36.9% of CRKp and 66.6% of CREc) followed by respiratory samples (26.95% for CRKp) and soft tissue samples (19.5% for CRKp). Over the studied period carbapenem resistance rates remained high, especially in K. pneumoniae, and in 2021 were equivalent to 67.6% for imipenem, 76.2% for meropenem, and 91.6% for ertapenem. Nevertheless, there was a statistically significant decreasing trend for imipenem and meropenem resistance in Klebsiella species (p < 0.01) while the decrease in ertapenem resistance was non-significant. Concerning E. coli, there was a statistically significant decreasing trend for meropenem and imipenem resistance over the 12 years, while ertapenem resistance increased significantly with 83.8% of E. coli exhibiting ertapenem resistance in 2021. Resistance rates to ceftazidime and cefotaxime remained higher than 90% (in 2021) for CRKp and cefotaxime rates increased to 90.5% in 2021 for CREc. Starting 2014, resistance to colistin and tigecycline was observed in carbapenem resistant Enterobacterales. CRE were associated with a higher mortality (RR: 6.3), admission to ICU (RR 3.9), and increased length of stay (LOS; 10 excess inpatient days per CRE case). Conclusion: This study supports the need to monitor CRE in the UAE and draws attention to the significant increase of ertapenem resistance in E. coli. Future surveillance analysis should include a genetic description of carbapenem resistance to provide new strategies.
Health literacy among pregnant women in the United Arab Emirates: The Mutaba'ah study
(2024-01) Loney, Tom
Abstract: Background: Health literacy is the degree to which individuals can obtain, process, understand, and communicate health-related information. Health literacy among pregnant women, in particular, may have a significant impact on maternal and child health. In the United Arab Emirates, no previous studies have been carried out to investigate the health literacy levels of pregnant women. Objective: This study aimed to investigate antenatal health literacy levels and identify associated factors among pregnant Emirati women in the United Arab Emirates. Design: This analysis was based on the baseline cross-sectional data for pregnant women participating in the prospective cohort Mutaba'ah Study, recruited between May 2017 and August 2022. Methods: Participants completed a self-administered questionnaire during their antenatal visits that collected sociodemographic and pregnancy-related information. Adequacy of health literacy was assessed using the BRIEF health literacy screening tool with adequate health literacy defined as a score ⩾ 17. Regression modeling investigated the association between the pregnant women characteristics with having adequate health literacy level (ability to read and comprehend most patient education materials). Results: A total of 2694 responses to the BRIEF health literacy screening tool were analyzed. Approximately, three-quarters (71.6%) of respondents showed adequate health literacy, followed by marginal (22.8%), and limited (5.6%) health literacy levels, respectively. Higher education levels (adjusted odds ratio (aOR) = 1.74, 95% confidence interval = 1.46-2.08), employment (adjusted odds ratio = 1.35, 95% confidence interval = 1.10-1.65), and adequate social support (adjusted odds ratio = 1.69, 95% confidence interval = 1.26-2.28) were associated with adequate health literacy levels. Participants who expressed worry about birth were less likely to have adequate literacy levels (adjusted odds ratio = 0.70, 95% confidence interval = 0.58-0.85). Conclusion: Nearly three-quarters of pregnant women have adequate health literacy. Nevertheless, measures including policies to sustain and enhance health literacy levels among all expectant mothers are required, with a specific focus on those having limited health literacy.
Understanding the mechanisms mediating cardi-renal benefit of empagliflozin in type 2 diabetes mellitus
(2023-11) Rizzo, Manfredi
Abstract: In a recently published, post-hoc analysis of the hallmark EMPA-REG OUTCOME trial, Kramer ¨ et al.1 assessed whether changes in cardiac and haemodynamic markers achieved with empagliflozin in subjects with type 2 diabetes mellitus (T2DM) may mediate its significant benefits across a number of surrogate cardiovascular and kidney outcomes. They have demonstrated that empagliflozin treatment resulted in a significant decrease in pulse pressure (PP), mean arterial pressure (MAP) and cardiac workload, compared with placebo; at week 12, placebo-adjusted mean changes from baseline were − 2.5 mmHg for PP, − 2.2 mmHg for MAP and − 315 mmHg x beats per minute (bpm) for cardiac workload (p < 0.0001 for all). They have also found that such benefits were present for both empagliflozin groups (10 mg and 25 mg) combined, while treatment differences were maintained throughout to week 164.1
Epidemiology and antimicrobial resistance trends of Acinetobacter species in the United Arab Emirates: a retrospective analysis of 12 years of national AMR surveillance data
(2023-12) Senok, Abiola
Abstract: Introduction: Acinetobacter spp., in particular A. baumannii, are opportunistic pathogens linked to nosocomial pneumonia (particularly ventilator-associated pneumonia), central-line catheter-associated blood stream infections, meningitis, urinary tract infections, surgical-site infections, and other types of wound infections. A. baumannii is able to acquire or upregulate various resistance determinants, making it frequently multidrug-resistant, and contributing to increased mortality and morbidity. Data on the epidemiology, levels, and trends of antimicrobial resistance of Acinetobacter spp. in clinical settings is scarce in the Gulf Cooperation Council (GCC) and Middle East and North Africa (MENA) regions. Methods: A retrospective 12-year analysis of 17,564 non-duplicate diagnostic Acinetobacter spp. isolates from the United Arab Emirates (UAE) was conducted. Data was generated at 317 surveillance sites by routine patient care during 2010-2021, collected by trained personnel and reported by participating surveillance sites to the UAE National AMR Surveillance program. Data analysis was conducted with WHONET. Results: Species belonging to the A. calcoaceticus-baumannii complex were mostly reported (86.7%). They were most commonly isolated from urine (32.9%), sputum (29.0%), and soft tissue (25.1%). Resistance trends to antibiotics from different classes during the surveillance period showed a decreasing trend. Specifically, there was a significant decrease in resistance to imipenem, meropenem, and amikacin. Resistance was lowest among Acinetobacter species to both colistin and tigecycline. The percentages of multidrug-resistant (MDR) and possibly extensively drug-resistant (XDR) isolates was reduced by almost half between the beginning of the study in 2010 and its culmination in 2021. Carbapenem-resistant Acinetobacter spp. (CRAB) was associated with a higher mortality (RR: 5.7), a higher admission to ICU (RR 3.3), and an increased length of stay (LOS; 13 excess inpatient days per CRAB case), as compared to Carbapenem-susceptible Acinetobacter spp. Conclusion: Carbapenem-resistant Acinetobacter spp. are associated with poorer clinical outcomes, and higher associated costs, as compared to carbapenem-susceptible Acinetobacter spp. A decreasing trend of MDR Acinetobacter spp., as well as resistance to all antibiotic classes under surveillance was observed during 2010 to 2021. Further studies are needed to explore the reasons and underlying factors leading to this remarkable decrease of resistance over time.
The effect of sodium-glucose co-transporter-2 inhibitors on markers of subclinical atherosclerosis
(2023-12) Rizzo, Manfredi
Abstract: Background: Despite the widespread use of classical cholesterol-lowering drugs to mitigate the adverse impacts of dyslipidaemia on atherosclerosis, many patients still face a substantial residual risk of developing atherosclerotic cardiovascular disease (CVD). This risk is partially attributed to non-traditional pathophysiological pathways. Latest evidence suggests that sodium glucose co-transporter-2 (SGLT2) inhibitors are beneficial for patients suffering from type 2 diabetes mellitus (T2DM) or established CVD by reducing morbidity and mortality. However, the underlying mechanisms of this benefit have not been clearly elucidated. It has been hypothesized that one possible mechanism could be the attenuation of subclinical atherosclerosis (SA) progression. Aim: The objective of this narrative review is to examine the present evidence concerning the impact of SGLT2 inhibitors on markers of SA. Results: The current evidence on the efficacy of SGLT2 on SA, endothelial function and arterial stiffness remains controversial. Findings from observational and randomized studies are quite heterogeneous; however, they converge that the antiatherosclerotic activity of SGLT2 inhibitors is not strong enough to be widely used for prevention of atherosclerosis progression in patients with or without T2DM. Conclusions: Further research is needed to investigate the underlying mechanisms and the possible beneficial impact of SGLT2i on primary and secondary CVD prevention through attenuation of premature atherosclerosis progression.
Anticoagulation-Associated Bleeding in Patients Screened for Atrial Fibrillation versus Usual Care-A Post Hoc Analysis from the LOOP Study
(2023-12) Krieger, Derk
Abstract: Background: Atrial fibrillation (AF) prevalence is rising; however, data on the bleeding risks associated with the detection of subclinical AF are needed. Objective Our objective was to determine the bleeding increment associated with implantable loop recorder (ILR) screening for subclinical AF and subsequent anticoagulation initiation compared with usual care. Methods This post hoc study utilized LOOP trial data from 6,004 elderly patients with stroke risks randomized to either ILR ( n = 1,503) or usual care ( n = 4,503). The mean follow-up time was 64.5 months, and none were lost to follow-up. The primary exposure was the initiation of oral anticoagulation, and the main outcome was the risk of major bleeding events following initiation of oral anticoagulants (OACs), determined by time-dependent cox regression. Second, we investigated antithrombotic prescription patterns and major bleeding events after antiplatelet treatment and in subgroups. Results OAC was initiated in 1,019 participants with a mean age (years) of 78.8 (± 4.67) in control versus 77.0 (± 4.84) in ILR, p < 0.0001. Altogether did 202 participants end or pause OAC treatment. Among AF patients (n = 910) had 40 (28%) completely ended OAC and 105 (72%) temporarily paused OAC during follow-up. Major bleeding events totaled 221 (3.7%). Forty-seven major bleeding events followed an OAC initiation in 1,019 participants (4.6%); 26 versus 21 events in the control and ILR groups, respectively. The hazard ratio (HR) for major bleeding after OAC initiation compared with before initiation was 2.08 (1.50-2.90) p < 0.0001 overall, 2.81 (1.82-4.34) p < 0.0001 for control and 1.32 (0.78-2.23) p = 0.31 for the ILR group ( p = 0.07 for interaction). Antiplatelet treatment resulted in an overall adjusted HR of 1.3 (0.96-1.75) p = 0.09. For OAC users aged ≥75 years in the ILR group, the rate of major bleeding was 1.73 (0.92-2.96) compared with 0.84 (0.36-1.66) for an age <75 years, and the rate of the corresponding control subgroup aged ≥75 years was 2.20 (1.23-3.63) compared with 1.64 (0.82-2.93) for an age <75 years. Conclusion The individual risk of major bleeding increased twofold after initiation of oral anticoagulation for all patients in this study. However, the patients screened for subclinical AF did not have a higher bleeding risk after initiation of anticoagulation compared with those in usual care. Trial Registration: The LOOP study is registered at ClinicalTrials.gov, identifier: NCT020364 50.
Overexpression and nonsynonymous mutations of UDP-glycosyltransferases are potentially associated with pyrethroid resistance in Anopheles funestus
(2023-12) Al-Yazeedi, Talal
Abstract: UDP-glycosyltransferases (UGTs) enzymes are pivotal in insecticide resistance by transforming hydrophobic substrates into more hydrophilic forms for efficient cell elimination. This study provides the first comprehensive investigation of Anopheles funestus UGT genes, their evolution, and their association with pyrethroid resistance. We employed a genome-wide association study using pooled sequencing (GWAS-PoolSeq) and transcriptomics on pyrethroid-resistant An. funestus, along with deep-targeted sequencing of UGTs in 80 mosquitoes Africa-wide. UGT310B2 was consistently overexpressed Africa-wide and significant gene-wise Fst differentiation was observed between resistant and susceptible populations: UGT301C2 and UGT302A3 in Malawi, and UGT306C2 in Uganda. Additionally, nonsynonymous mutations in UGT genes were identified. Gene-wise Tajima's D density curves provide insights into population structures within populations across these countries, supporting previous observations. These findings have important implications for current An. funestus control strategies facilitating the prediction of cross-resistance to other UGT-metabolised polar insecticides, thereby guiding more effective and targeted insecticide resistance management efforts.
Cardio-Metabolic Health of Offspring Exposed in Utero to Human Immuno-Deficiency Virus and Anti-Retroviral Treatment: A Systematic Review
(2023-12) Goswami, Nandu
Abstract: Background: Antiretroviral treatment (ART) use during pregnancy continues to rise as it is known to decrease the likelihood of HIV transmission from mother to child. However, it is still unknown whether foetal exposure to (ART) may affect the foetal environment, predisposing the offspring to cardiometabolic risk. Therefore, the aim of this study was to systematically review the cardio-metabolic effects of in utero exposure to HIV/ART on offspring. Methods: We carried out a systematic review and obtained literature from the Google scholar, PubMed, ProQuest, Web of Science, and Scopus databases. Two independent reviewers evaluated the titles, abstracts, and full-length English contents. Data from the eligible studies were included. Results: The search yielded 7596 records. After assessing all of these records, 35 of the full-length articles were included in this systematic review. Several studies showed that low birth weight, small head circumference, and altered mitochondrial content were more common among HIV-exposed uninfected (HEU) children compared to HIV-unexposed uninfected children (HUU). A few studies demonstrated elevated triglyceride levels, lower levels of insulin, and increased blood pressure, oxidative stress, vascular dysfunction, cardiac damage, and myocardial dysfunction among HEU children compared with HUU children. Conclusion: Most findings showed that there were cardio-metabolic health risk factors among HEU children, indicating that maternal exposure to HIV and ART may negatively affect foetal health, which may lead to cardio-metabolic morbidity later in life.
Epicardial adipose tissue and subclinical incident atrial fibrillation as detected by continuous monitoring: a cardiac magnetic resonance imaging study
(2023-12) Krieger, Derk
Abstract: Epicardial adipose tissue (EAT) has endocrine and paracrine functions and has been associated with metabolic and cardiovascular disease. This study aimed to investigate the association between EAT, determined by cardiac magnetic resonance imaging (CMR), and incident atrial fibrillation (AF) following long-term continuous heart rhythm monitoring by implantable loop recorder (ILR). This study is a sub-study of the LOOP study. In total, 203 participants without a history of AF received an ILR and underwent advanced CMR. All participants were at least 70 years of age at inclusion and had at least one of the following conditions: hypertension, diabetes, previous stroke, or heart failure. Volumetric measurements of atrial- and ventricular EAT were derived from CMR and the time to incident AF was subsequently determined. A total of 78 participants (38%) were diagnosed with subclinical AF during a median of 40 (37-42) months of continuous monitoring. In multivariable Cox regression analyses adjusted for age, sex, and various comorbidities, we found EAT indexed to body surface area to be independently associated with the time to AF with hazard ratios (95% confidence intervals) up to 2.93 (1.36-6.34); p = 0.01 when analyzing the risk of new-onset AF episodes lasting ≥ 24 h. Atrial EAT assessed by volumetric measurements on CMR images was significantly associated with the incident AF episodes as detected by ILR.
The Effect of Sodium-Glucose Cotransporter Inhibitors on Renal Function as Adjunctive to Insulin in Adults with Type 1 Diabetes: An Updated Multilevel Meta-analysis of Randomized Controlled Trials
(2024-01) Rizzo, Manfredi
Abstract: Introduction: This systematic review aimed to summarize the existing evidence from published randomized controlled trials (RCTs) on the impact of sodium-glucose cotransporter (SGLT) inhibitors on albuminuria levels and renal function in patients with type 1 diabetes mellitus (T1D). Methods: The literature search was performed through Medline (via PubMed), Cochrane Library, and Scopus until November 11, 2023. Double-independent study selection, data extraction, and quality assessment were performed. Evidence was pooled with three-level mixed-effects meta-analysis. Results: In total, 5221 participants with T1D among 11 RCTs were analyzed. All RCTs had low risk of bias according to the Cochrane Collaboration tool (RoB 2). SGLT inhibitors were associated with a significantly greater reduction in urine albumin-to-creatinine ratio (UACR) compared to controls (MD = - 23.13%; 95% CI = [- 33.69, - 12.57]; P < 0.001; level of evidence high). On the basis of subgroup analysis, this effect was consistent across all available SGLT inhibitors, irrespective of the dosage. Finally, a neutral class effect was observed on the estimated glomerular filtration rate (eGFR, MD = - 1.03 mL/min/1.73 m2; 95% CI = [- 2.26, 0.19]; P = 0.1; level of evidence moderate). Only empagliflozin was associated with a significant reduction in eGFR compared to placebo (MD = - 2.23 mL/min/1.73 m2; 95% CI = [- 3.62, - 0.84]; P = 0.002). Conclusion: Our findings suggest that adjunctive therapy with SGLT inhibitors results in a significant reduction in albuminuria, while their use is associated with a neutral effect on creatinine clearance, as a measure of renal function. Future renal outcome trials are needed to assess SGLT inhibitors' role in the pharmacological armamentarium against diabetic nephropathy in T1D.
Emergence of highly resistant Candida auris in the United Arab Emirates: a retrospective analysis of evolving national trends
(2024-01) Senok, Abiola
Abstract: Introduction: The Centers for Disease Prevention and Control lists Candida auris, given its global emergence, multidrug resistance, high mortality, and persistent transmissions in health care settings as one of five urgent threats. As a new threat, the need for surveillance of C. auris is critical. This is particularly important for a cosmopolitan setting and global hub such as the United Arab Emirates (UAE) where continued introduction and emergence of resistant variant strains is a major concern. Methods: The United Arab Emirates has carried out a 12 years of antimicrobial resistance surveillance (2010-2021) across the country, spanning all seven Emirates. A retrospective analysis of C. auris emergence from 2018-2021 was undertaken, utilising the demographic and microbiological data collected via a unified WHONET platform for AMR surveillance. Results: Nine hundred eight non-duplicate C. auris isolates were reported from 2018-2021. An exponential upward trend of cases was found. Most isolates were isolated from urine, blood, skin and soft tissue, and the respiratory tract. UAE nationals nationals comprised 29% (n = 186 of 632) of all patients; the remainder were from 34 other nations. Almost all isolates were from inpatient settings (89.0%, n = 809). The cases show widespread distribution across all reporting sites in the country. C. auris resistance levels remained consistently high across all classes of antifungals used. C. auris in this population remains highly resistant to azoles (fluconazole, 72.6% in 2021) and amphotericin. Echinocandin resistance has now emerged and is increasing annually. There was no statistically significant difference in mortality between Candida auris and Candida spp. (non-auris) patients (p-value: 0.8179), however Candida auris patients had a higher intensive care unit (ICU) admission rate (p-value <0.0001) and longer hospital stay (p < 0.0001) compared to Candida spp. (non-auris) patients. Conclusion: The increasing trend of C. auris detection and associated multidrug resistant phenotypes in the UAE is alarming. Continued C. auris circulation in hospitals requires enhanced infection control measures to prevent continued dissemination.
Unraveling the developmental dynamic of visual exploration of social interactions in autism
(2023-12) Jan, Reem Kais
Abstract: Atypical deployment of social gaze is present early on in toddlers with autism spectrum disorders (ASDs). Yet, studies characterizing the developmental dynamic behind it are scarce. Here, we used a data-driven method to delineate the developmental change in visual exploration of social interaction over childhood years in autism. Longitudinal eye-tracking data were acquired as children with ASD and their typically developing (TD) peers freely explored a short cartoon movie. We found divergent moment-to-moment gaze patterns in children with ASD compared to their TD peers. This divergence was particularly evident in sequences that displayed social interactions between characters and even more so in children with lower developmental and functional levels. The basic visual properties of the animated scene did not account for the enhanced divergence. Over childhood years, these differences dramatically increased to become more idiosyncratic. These findings suggest that social attention should be targeted early in clinical treatments.
Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs
(2023-12) Uddin, Mohammed
Abstract: Life-threatening "breakthrough" cases of critical COVID-19 are attributed to poor or waning antibody (Ab) response to SARS-CoV-2 vaccines in individuals already at risk. Preexisting auto-Abs neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; their contribution to hypoxemic breakthrough cases in vaccinated people is unknown. We studied a cohort of 48 individuals (aged 20 to 86 years) who received two doses of a messenger RNA (mRNA) vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Ab levels to the vaccine, neutralization of the virus, and auto-Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal Ab response to the vaccine. Among them, 10 (24%) had auto-Abs neutralizing type I IFNs (aged 43 to 86 years). Eight of these 10 patients had auto-Abs neutralizing both IFN-α2 and IFN-ω, whereas two neutralized IFN-ω only. No patient neutralized IFN-β. Seven neutralized type I IFNs at 10 ng/ml and three at 100 pg/ml only. Seven patients neutralized SARS-CoV-2 D614G and Delta efficiently, whereas one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only type I IFNs at 100 pg/ml neutralized both D614G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating Abs capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a notable proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population.
Oligogenic inheritance in severe adult obesity
(2024-01) Almansoori, Sumaya
Abstract: Background/objective: The genetic architecture of extreme non-syndromic obesity in adults remains to be elucidated. A range of genes are known to cause monogenic obesity, but even when pathogenic mutations are present, there may be variable penetrance. Methods: Whole-exome sequencing (WES) was carried out on a 15-year-old male proband of Pakistani ancestry who had severe obesity. This was followed by family segregation analysis, using Sanger sequencing. We also undertook re-analysis of WES data from 91 unrelated adults with severe obesity (86% white European ancestry) from the Personalised Medicine for Morbid Obesity (PMMO) cohort, recruited from the UK National Health Service. Results: We identified an oligogenic mode of inheritance of obesity in the proband's family-this provided the impetus to reanalyze existing sequence data in a separate dataset. Analysis of PMMO participant data revealed two further patients who carried more than one rare, predicted-deleterious mutation in a known monogenic obesity gene. In all three cases, the genes involved had known autosomal dominant inheritance, with incomplete penetrance. Conclusion: Oligogenic inheritance may explain some of the variable penetrance in Mendelian forms of obesity. We caution clinicians and researchers to avoid confining sequence analysis to individual genes and, in particular, not to stop looking when the first potentially-causative mutation is found.
Evaluating the Effectiveness of Triiodothyronine Suppression and Withdrawal Versus Thyrogen Injections in Thyroid Cancer Assessments
(2023-12) Abdulhameed, Nada M.
Abstract: Objective: This study aimed to evaluate the specificity and effectiveness of triiodothyronine (T3) suppression and withdrawal, as compared to the conventional diagnostic approach using Thyrogen recombinant thyroid-stimulating hormone (TSH) injections, in the assessment of thyroid cancer patients post-thyroidectomy. Methods In this retrospective study, 18 patients diagnosed with thyroid cancer at a tertiary care hospital (Mediclinic City Hospital) in Dubai were included. The patients underwent total thyroidectomy, iodine ablation, and neck ultrasound. The cohort's clinical characteristics were analyzed, and histopathological examination of thyroid nodules was performed. In this study, paired T-tests were applied to evaluate the before-and-after impact of T3 and Thyrogen treatments on TSH and thyroglobulin (TG) levels in individual patients. To further analyze the effectiveness of these treatments, independent T-tests were conducted, allowing for a comparison of TSH and TG levels between different treatment groups within the patient cohort. This approach provided a comprehensive assessment of the treatments' effects on key thyroid indicators. Additionally, the diagnostic accuracy of T3 withdrawal and Thyrogen post-test on TG levels was assessed using statistical measures including sensitivity, specificity, and predictive values. Results The cohort had a mean age of 42.1 years and a female predominance. Distinct clinical profiles were observed across different thyroid cancer subtypes. Histopathological analysis confirmed typical features of papillary carcinoma variants. Significant changes in TSH levels post-treatment were noted, with T3 treatments showing a marked increase in TSH and TG levels, although changes in TG levels were not always statistically significant. Diagnostic test evaluation showed a sensitivity of 77.78%, a specificity of 83.33%, and an overall accuracy of 80.00% for T3 withdrawal and Thyrogen post-test on TG. Conclusion The study provides comprehensive insights into the clinical profiles and treatment responses in thyroid cancer patients post-thyroidectomy. The effectiveness of T3 and Thyrogen treatments in altering TSH and TG levels was established, with significant implications for patient management. The diagnostic tests for T3 withdrawal and Thyrogen post-test on TG demonstrated high accuracy, underlining their clinical utility in the post-treatment evaluation of thyroid cancer patients.
Editorial: Occupation and cancer: new insights into burden, risk factors, and prevention
(2023-12) Loney, Tom
Abstract: Occupational cancers (OC) are the result of exposure to carcinogenic agents at the workplace. The most frequent types of OC are lung cancer, mesothelioma, bladder cancer, and non-melanoma skin cancers (NMSC) (1, 2). More than 40 years ago, Doll and Peto (3) estimated, with a relatively large degree of uncertainty, that ~4% of all cancer cases were attributable to occupational exposures. Although job characteristics and occupational exposures have changed considerably during the past four decades, this estimation is still widely accepted with the caveat that updated estimates are urgently needed. Nevertheless, only a fraction of OCs are recognized and recorded in most countries. With the possible exception of mesothelioma, all the other OCs are largely under-reported as occupational diseases to the national health authorities. Indeed, many countries, especially developing countries, where exposures to occupational carcinogens may be higher, have not yet established cancer registries that collect data on occupational history. An additional challenge of discovering occupational etiology relates to the fact that cancer is a disease with a long preclinical phase and many OCs are diagnosed after retirement. Hence, this Research Topic aimed to deepen and widen knowledge on OC, in order to raise awareness among all interested stakeholders, including workers, occupational health and safety (OHS) professionals, and policymakers, with the overall goal of preventing these occupational diseases.
A Rare Presentation of a Branchial Cleft Cyst: Can It Cause Syncope in a Pediatric Patient?
(2023-12) Akbarpoor, Fatemeh; Alshehhi, Asma; Aakef, Khadeeja
Abstract: Branchial cleft cysts (BCCs) are a congenital malformation most commonly seen in children and adolescents. BCCs are usually incidental findings and are benign in nature. In this report, we present a case of a 13-year-old female with syncope as a rare complication of a fluid-filled second BCC. The patient initially presented with a unilateral non-tender swelling on the right side of the neck and submandibular region, which was suspicious of an inflammatory process. After initial lab investigations came back negative, imaging studies of the neck with computed tomography (CT) with intravenous contrast revealed a hypodense lesion with a uniform density, which lay beneath the sternocleidomastoid muscle and abutted the carotid sheath. The cyst was surgically excised, and histopathological studies of the cyst wall and the analysis of the fluid contained within the cyst confirmed that it was indeed a branchial cleft cyst. We propose that the syncopal episodes she experienced most likely occurred due to the proximity of the cyst wall to the carotid sheath, which caused a mass effect leading to carotid sinus syndrome (CSS). This is the first case of CSS due to a BCC to be reported in the pediatric population.
Serum multi-omics analysis in hindlimb unloading mice model: Insights into systemic molecular changes and potential diagnostic and therapeutic biomarkers
(2023-12) Giddey, Alexander D.
Abstract: Microgravity, in space travel and prolonged bed rest conditions, induces cardiovascular deconditioning along with skeletal muscle mass loss and weakness. The findings of microgravity research may also aid in the understanding and treatment of human health conditions on Earth such as muscle atrophy, and cardiovascular diseases. Due to the paucity of biomarkers and the unknown underlying mechanisms of cardiovascular and skeletal muscle deconditioning in these environments, there are insufficient diagnostic and preventative measures. In this study, we employed hindlimb unloading (HU) mouse model, which mimics astronauts in space and bedridden patients, to first evaluate cardiovascular and skeletal muscle function, followed by proteomics and metabolomics LC-MS/MS-based analysis using serum samples. Three weeks of unloading caused changes in the function of the cardiovascular system in c57/Bl6 mice, as seen by a decrease in mean arterial pressure and heart weight. Unloading for three weeks also changed skeletal muscle function, causing a loss in grip strength in HU mice and atrophy of skeletal muscle indicated by a reduction in muscle mass. These modifications were partially reversed by a two-week recovery period of reloading condition, emphasizing the significance of the recovery process. Proteomics analysis revealed 12 dysregulated proteins among the groups, such as phospholipid transfer protein, Carbonic anhydrase 3, Parvalbumin alpha, Major urinary protein 20 (Mup20), Thrombospondin-1, and Apolipoprotein C-IV. On the other hand, metabolomics analysis showed altered metabolites among the groups such as inosine, hypoxanthine, xanthosine, sphinganine, l-valine, 3,4-Dihydroxyphenylglycol, and l-Glutamic acid. The joint data analysis revealed that HU conditions mainly impacted pathways such as ABC transporters, complement and coagulation cascades, nitrogen metabolism, and purine metabolism. Overall, our results indicate that microgravity environment induces significant alterations in the function, proteins, and metabolites of these mice. These observations suggest the potential utilization of these proteins and metabolites as novel biomarkers for assessing and mitigating cardiovascular and skeletal muscle deconditioning associated with such conditions.
Evaluating the potential of Vitamin D and curcumin to alleviate inflammation and mitigate the progression of osteoarthritis through their effects on human chondrocytes: A proof-of-concept investigation
(2023-12) Patnaik, Rajashree; Riaz, Sumbal; Sivani, Bala Mohan; Faisal, Shemima; Naidoo, Nerissa; Banerjee, Yajnavalka
Abstract: Osteoarthritis (OA) is a chronic degenerative joint disorder primarily affecting the elderly, characterized by a prominent inflammatory component. The long-term side effects associated with current therapeutic approaches necessitate the development of safer and more efficacious alternatives. Nutraceuticals, such as Vitamin D and curcumin, present promising therapeutic potentials due to their safety, efficacy, and cost-effectiveness. In this study, we utilized a proinflammatory human chondrocyte model of OA to assess the anti-inflammatory properties of Vitamin D and curcumin, with a particular focus on the Protease-Activated Receptor-2 (PAR-2) mediated inflammatory pathway. Employing a robust siRNA approach, we effectively modulated the expression of PAR-2 to understand its role in the inflammatory process. Our results reveal that both Vitamin D and curcumin attenuate the expression of PAR-2, leading to a reduction in the downstream proinflammatory cytokines, such as Tumor Necrosis Factor-alpha (TNF-α), Interleukin 6 (IL-6), and Interleukin 8 (IL-8), implicated in the OA pathogenesis. Concurrently, these compounds suppressed the expression of Receptor Activator of Nuclear Factor kappa-Β Ligand (RANKL) and its receptor RANK, which are associated with PAR-2 mediated TNF-α stimulation. Additionally, Vitamin D and curcumin downregulated the expression of Interferon gamma (IFN-γ), known to elevate RANKL levels, underscoring their potential therapeutic implications in OA. This study, for the first time, provides evidence of the mitigating effect of Vitamin D and curcumin on PAR-2 mediated inflammation, employing an siRNA approach in OA. Thus, our findings pave the way for future research and the development of novel, safer, and more effective therapeutic strategies for managing OA.
Unveiling the dynamics of antimicrobial utilization and resistance in a large hospital network over five years: Insights from health record data analysis
(2023-12) Senok, Abiola; Alsuwaidi, Hanan; Alsheikh Ali, Alawi
Abstract: Antimicrobial Resistance (AMR) presents a pressing public health challenge globally which has been compounded by the COVID-19 pandemic. Elucidation of the impact of the pandemic on AMR evolution using population-level data that integrates clinical, laboratory and prescription data remains lacking. Data was extracted from the centralized electronic platform which captures the health records of 60,551 patients with a confirmed infection across the network of public healthcare facilities in Dubai, United Arab Emirates. For all inpatients and outpatients diagnosed with bacterial infection between 01/01/2017 and 31/05/2022, structured and unstructured Electronic Health Record data, microbiological laboratory data including antibiogram, molecular typing and COVID-19 testing information as well as antibiotic prescribing data were extracted curated and linked. Various analytical methods, including time-series analysis, natural language processing (NLP) and unsupervised clustering algorithms, were employed to investigate the trends of antimicrobial usage and resistance over time, assess the impact of prescription practices on resistance rates, and explore the effects of COVID-19 on antimicrobial usage and resistance. Our findings identified a significant impact of COVID-19 on antimicrobial prescription practices, with short-term and long-lasting over-prescription of these drugs. Resistance to antimicrobials increased the odds ratio of all mortality to an average of 2.18 (95% CI: 1.87-2.49) for the most commonly prescribed antimicrobials. Moreover, the effects of antimicrobial prescription practices on resistance were observed within one week of initiation. Significant trends in antimicrobial resistance, exhibiting fluctuations for various drugs and organisms, with an overall increasing trend in resistance levels, particularly post-COVID-19 were identified. This study provides a population-level insight into the evolution of AMR in the context of COVID-19 pandemic. The findings emphasize the impact of COVID-19 on the AMR crisis, which remained evident even two years after the onset of the pandemic. This underscores the necessity for enhanced antimicrobial stewardship to address the evolution of AMR.

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