Safety and efficacy of semaglutide in post kidney transplant patients with type 2 diabetes or Post-Transplant diabetes.

Objective: Type 2 diabetes mellitus (T2DM) and post-transplant diabetes mellitus (PTDM) are common in renal transplant recipients. Semaglutide has demonstrated efficacy and safety in patients with T2DM. To date, only a limited number of studies have investigated its use in renal transplant patients. This study assessed the safety and efficacy of semaglutide in post-renal transplant patients. Methods: A retrospective study was conducted at king Abdulaziz Medical City-Riyadh, Saudi Arabia. The subjects of the study were adults and adolescents (>14 years) who had undergone a kidney transplant and had pre-existing T2DM or PTDM. The study subjects were given semaglutide during the study period, from January 2018 to July 2022. The data were collected over a period of 18 months. Results: A total of 39 patients were included, 29 (74 %) of whom were male. A significant decrease in hemoglobin A1c (HbA1c) was observed during the follow-up period when compared to baseline (8.4 %±1.3 % at baseline vs. 7.4 %±1.0 % at 13-18 months (p < 0.001). A significant reduction in weight was also noted at follow-up as compared to baseline (99.5 kg ± 17.7 vs 90.7 kg ± 16.8 at 13-18 months (p < 0.001). No significant changes were found in renal graft function markers. Conclusion: Semaglutide was found to significantly reduce HbA1c levels and weight in post renal transplant patients with diabetes. No significant changes in markers of renal graft function were observed.

Predictors influencing dental clinic utilization in primary health care: A retrospective analysis of 233,069 patient records in Riyadh, Saudi Arabia.

Aim: This study aims to identify and address the predictors that promote or prevent the utilization of dental services in primary health care (PHC) centers located in Riyadh, Saudi Arabia, with an ultimate goal to increase the uptake of oral health care (OHC) services. Methodology: Registration data from 99 PHC centers was used. For each patient visiting a PHC center, information on the number of dental visits was captured. Continuous data was summarized as means, medians, and ranges, and categorical data as frequencies (%). The strength of association was reported as an incidence rate ratio (IRR) with 95% confidence interval (CI) and a p-value. Further analysis was conducted to illustrate the association between dental care visits and factors found independently significant in the final multivariate model using Karl Pearson correlation coefficient and t-test. All tests were two-sided and a p-value of p < 0.05 was considered significant. Results: The comorbidity profile of patients shows that 11,751(5%) were diabetic, while hypertension amounted to 10,712(4.6%). A statistically significant inverse correlation was observed between dental care visits and both age (r = -0.025, p < 0.001) and BMI (r = -0.013, p < 0.001). Mean dental care visits were significantly higher in patients without hypertension compared with those with hypertension (p < 0.001). Moreover, there was an approximate 4% increase in dental care visits among females compared to males, although this difference was not statistically significant. Conclusion: The study identified three predictors contributing to the low utilization of dental services in PHC centers in Riyadh. These include an inverse association between both age and body mass index (BMI) and the utilization of OHC. Additionally, the mean dental care visits were significantly higher for patients without hypertension in comparison to hypertensive patients.

Analysis of disease characteristics of a large patient cohort with congenital generalized lipodystrophy from the Middle East and North Africa.

BACKGROUND: Congenital generalized lipodystrophy (CGL) is a rare inherited disease characterized by a near-total absence of adipose tissue and is associated with organ system abnormalities and severe metabolic complications. Here, we have analyzed the disease characteristics of the largest CGL cohort from the Middle East and North Africa (MENA) who have not received lipodystrophy-specific treatment. METHODS: CGL was diagnosed clinically by treating physicians through physical assessment and supported by genetic analysis, fat loss patterns, family history, and the presence of parental consanguinity. Data were obtained at the time of patient diagnosis and during leptin-replacement naïve follow-up visits as permitted by available medical records. RESULTS: Data from 43 patients with CGL (37 females, 86%) were collected from centers located in eight countries. The mean (median, range) age at diagnosis was 5.1 (1.0, at birth-37) years. Genetic analysis of the overall cohort showed that CGL1 (n = 14, 33%) and CGL2 (n = 18, 42%) were the predominant CGL subtypes followed by CGL4 (n = 10, 23%); a genetic diagnosis was unavailable for one patient (2%). There was a high prevalence of parental consanguinity (93%) and family history (67%) of lipodystrophy, with 64% (n = 25/39) and 51% (n = 20/39) of patients presenting with acromegaloid features and acanthosis nigricans, respectively. Eighty-one percent (n = 35/43) of patients had at least one organ abnormality; the most frequently affected organs were the liver (70%, n = 30/43), the cardiovascular system (37%, n = 16/43) and the spleen (33%, n = 14/43). Thirteen out of 28 (46%) patients had HbA1c > 5.7% and 20/33 (61%) had triglyceride levels > 2.26 mmol/L (200 mg/dl). Generally, patients diagnosed in adolescence or later had a greater severity of metabolic disease versus those diagnosed during childhood; however, metabolic and organ system abnormalities were observed in a subset of patients diagnosed before or at 1 year of age. CONCLUSIONS: This analysis suggests that in addition to the early onset of fat loss, family history and high consanguinity enable the identification of young patients with CGL in the MENA region. In patients with CGL who have not received lipodystrophy-specific treatment, severe metabolic disease and organ abnormalities can develop by late childhood and worsen with age.

The Effect of PCSK9 Inhibitors on LDL-C Target Achievement in Patients with Homozygous Familial Hypercholesterolemia: A Retrospective Cohort Analysis.

INTRODUCTION: Achieving target low-density lipoprotein-cholesterol (LDL-C) levels remains challenging when treating homozygous familial hypercholesterolemia (HoFH). Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are prescribed in addition to statins and ezetimibe, but patients' response varies and depends on residual low-density lipoprotein receptor (LDLR) function. METHODS: A multicenter, retrospective observational analysis evaluated LDL-C target achievement in response to PCSK9i treatment in 28 patients with HoFH from the Middle East/North Africa region. Effect of genotype was investigated. Demographic and clinical information was retrospectively obtained from medical records. Patient response to PCSK9i treatment was assessed by calculating percentage changes in lipid levels from pre-PCSK9i treatment baseline to most recent follow-up visit where patients were recorded as receiving PCSK9i on top of standard of care lipid-lowering therapies (LLTs; i.e., statins/ezetimibe) and assessing European Atherosclerosis Society (EAS) target achievement up to January 31, 2022. Lowest LDL-C level while receiving PCSK9i was identified. RESULTS: The cohort (n = 28) had a mean age (standard deviation; SD) of 22.8 (9.8) years (n = 28) and was 51% female (n = 27). Baseline LDL-C data were available in 24/28 (85.7%) patients (mean [SD] 14.0 [3.0] mmol/L). Median (interquartile range) duration of PCSK9i treatment was 12.0 months (4.0-19.1) months and mean (SD) % change in LDL-C after PCSK9i treatment was - 8.6% (12.1). LDL-C reduction from baseline was below 15% in 17/24 patients (70.8%). In the full cohort, mean (SD) minimum LDL-C during PCSK9i treatment was 11.9 (2.8; n = 28) mmol/L. No patient achieved EAS target LDL-C while receiving PCSK9i; genotype analysis suggested LDLR-null/null patients were most refractory to PCSK9i. CONCLUSION: Response to PCSK9i was minimal in this cohort of patients with HoFH. No patients achieved EAS LDL-C targets, and most failed to reach the EAS-recommended 15% LDL-C reduction for PCSK9i therapy continuation. These results suggest additional LLTs are necessary to achieve LDL-C targets in HoFH.

Lipidomics Profiling of Metformin-Induced Changes in Obesity and Type 2 Diabetes Mellitus: Insights and Biomarker Potential.

Metformin is the first-line oral medication for treating type 2 diabetes mellitus (T2DM). In the current study, an untargeted lipidomic analytical approach was used to investigate the alterations in the serum lipidome of a cohort of 89 participants, including healthy lean controls and obese diabetic patients, and to examine the alterations associated with metformin administration. A total of 115 lipid molecules were significantly dysregulated (64 up-regulated and 51 down-regulated) in the obese compared to lean controls. However, the levels of 224 lipid molecules were significantly dysregulated (125 up-regulated and 99 down-regulated) in obese diabetic patients compared to the obese group. Metformin administration in obese diabetic patients was associated with significant dysregulation of 54 lipid molecule levels (20 up-regulated and 34 down-regulated). Levels of six molecules belonging to five lipid subclasses were simultaneously dysregulated by the effects of obesity, T2DM, and metformin. These include two putatively annotated triacylglycerols (TGs), one plasmenyl phosphatidylcholine (PC), one phosphatidylglycerol (PGs), one sterol lipid (ST), and one Mannosyl-phosphoinositol ceramide (MIPC). This study provides new insights into our understanding of the lipidomics alterations associated with obesity, T2DM, and metformin and offers a new platform for potential biomarkers for the progression of diabetes and treatment response in obese patients.

Effect Modification by Age and Gender in the Correlation Between Diabetes Mellitus, Hypertension, and Obesity.

BACKGROUND: Literature has reported differences in the epidemiology or natural history of non-communicable diseases among both the male and female sexes. Stratification of multimorbidity burden based on sex is crucial to identify and implement targeted prevention and control interventions for chronic diseases. OBJECTIVES: To determine the burden of hypertension, type-2 diabetes mellitus, and obesity; and to compare the related multimorbidity among male and female patients. METHODS: The study was a retrospective analysis of 375 802 medical records from primary care centers. Data was extracted from March 2022 to March 2023. A multivariate probit estimation methodology was employed using a 3-equations multivariate multiple probit model to jointly estimate the association of a person's sex with the diagnosis of the 3 chronic conditions: obesity, diabetes, and hypertension. A multinomial logistic regression analysis was conducted to allow each unique combination of these 3 chronic diseases. RESULTS: Females had a relatively higher proportion of obesity (58.1% vs 41.2%), obesity and diabetes only (58.9% vs 41.1%), obesity and hypertension (63.6% vs 36.4%), and joint diagnosis with 3 conditions (65.7% vs 34.3%). Females' participants consistently had a significantly higher likelihood of diagnosis compared with males except for diabetes (OR = 0.59, 95% CI: 0.56-0.62) and the combination of only diabetes and hypertension (OR = 0.67, 95% CI: 0.61-0.74). The likelihood of other combinations ranged from 1.04 (95% CI: 0.98-1.10) for only hypertension to 2.30 (95% CI: 2.10-2.53) for the joint diagnosis of all 3 conditions. An increased likelihood of a single or combined occurrence of 3 chronic conditions was observed with increased age. CONCLUSION: The multimorbidity distribution for diabetes mellitus, hypertension, and obesity differs significantly among male and female patients. The overall burden of morbidity, and mortality, however, tends to rise after 46 years of age, with the highest burden among individuals above 60 years of age.

Epidemiology of Glucose-6-Phosphate Dehydrogenase Deficiency in Arab Countries: Insights from a Systematic Review.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common metabolic disorder affecting more than 400 million individuals worldwide. Being an X-linked disorder, the disease is more common among males than females. Various Arab countries estimated the prevalence of G6PD deficiency; however, findings from different countries have not been synthesized collectively. Hence, a systematic review was undertaken to synthesize the findings on the epidemiology of G6PD deficiency in all Arab countries. We performed an electronic systematic literature search based on the eligibility criteria using databases, including MEDLINE, Embase, and CINHAL. The studies included in the review were primary and original research studies assessing the prevalence or incidence, risk factors, or determinants of G6PD deficiency, and published in the English language in a peer-reviewed scientific journal between 2000 and 2022. The systematic review was carried out with the help of an updated PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist. After the screening, 23 full texts were finalized for data extraction. The prevalence of G6PD deficiency ranged from 2 to 31% with a greater burden among high-risk populations like neonates with sickle cell anemia. The determinants included males, family history, consanguineous marriages, and geographic regions, which were all risk factors, except for body weight, which was a protective factor. The prevalence of G6PD deficiency varies across Arab countries, with a higher prevalence in males than females. Different regions of Arab countries need to revisit their screening and diagnostic guidelines to detect G6PD deficiency promptly and prevent unnecessary morbidity and mortality among their communities.

Proteomic Profiling Identifies Distinct Regulation of Proteins in Obese Diabetic Patients Treated with Metformin.

Background: Obesity and type 2 diabetes mellitus (T2DM) are characterized by underlying low-grade chronic inflammation. Metformin has been used as the first line of therapy in T2DM as it decreases hepatic glucose production and glucose intestinal absorption, enhances insulin sensitivity and weight loss, and is known to ameliorate inflammation. The mechanisms through which metformin exerts its effect remain unclear. Proteomics has emerged as a unique approach to explore the biological changes associated with diseases, including T2DM. It provides insight into the circulating biomarkers/mediators which could be utilized for disease screening, diagnosis, and prognosis. Methods: This study evaluated the proteomic changes in obese (Ob), obese diabetics (OD), and obese diabetic patients on metformin (ODM) using a 2D DIGE MALDI-TOF mass spectrometric approach. Results: Significant changes in sixteen plasma proteins (15 up and 1 down, ANOVA, p ≤ 0.05; fold change ≥ 1.5) were observed in the ODM group when compared to the Ob and OD groups. Bioinformatic network pathway analysis revealed that the majority of these altered plasma proteins are involved in distinct pathways involving acute-phase response, inflammation, and oxidative response and were centered around HNF4A, ERK, JNK, and insulin signaling pathways. Conclusions: Our study provides important information about the possible biomarkers altered by metformin treatment in obese patients with and without T2DM. These altered plasma proteins are involved in distinct pathways involving acute-phase response, inflammation, and oxidative response and were centered around HNF4A, ERK, JNK, and insulin signaling pathways. The presented proteomic profiling approach may help in identifying potential biomarkers/mediators affected by metformin treatment in T2DM and inform the understanding of metformin's mechanisms of action.

Primary leiomyosarcoma of the thyroid with concurrent papillary thyroid cancer: a rare case report and a review of literature.

BACKGROUND: Leiomyosarcoma (LMS) is a soft tissue malignant tumor that has a predilection to the abdominopelvic and limb smooth muscles. LMS of the thyroid is exceptionally rare. Papillary thyroid cancer (PTC) is the most common thyroid malignancy and originates from the thyroid epithelial layer. To our knowledge, the presence of both tumors in the same patient has not been reported previously. CASE PRESENTATION & LITERATURE REVIEW: A 42-year-old woman presented with a progressively enlarging neck mass for a few months. She underwent left thyroid lobectomy, and the histology showed high-grade primary LMS of the thyroid. She subsequently underwent a complete thyroidectomy, which identified a classical PTC on her right lobe. Our comprehensive literature review identified 39 published cases of primary LMS of the thyroid. The average tumor size was 5.88 cm and occurred more in women. The most common presentation was neck mass, followed by compressive symptoms. Recurrence and metastasis were uncommon at 15% and 10-25%, respectively. CONCLUSION: Thyroid LMS is a rare malignancy with a worse prognosis than PTC. A thorough workup must be done to rule out metastasis before labeling it as primary thyroid cancer.

Gene Expression Profiling of Peripheral Blood Mononuclear Cells in Type 2 Diabetes: An Exploratory Study.

Background and Objectives: Visceral obesity is associated with chronic low-grade inflammation that predisposes to metabolic syndrome. Indeed, infiltration of adipose tissue with immune-inflammatory cells, including 'classical' inflammatory M1 and anti-inflammatory 'alternative' M2 macrophages, causes the release of a variety of bioactive molecules, resulting in the metabolic complications of obesity. This study examined the relative expression of macrophage phenotypic surface markers, cholesterol efflux proteins, scavenger receptors, and adenosine receptors in human circulating peripheral blood mononuclear cells (PBMCs), isolated from patients with type 2 diabetes mellitus (T2DM), with the aim to phenotypically characterize and identify biomarkers for these ill-defined cells. Materials and Methodology: PBMCs were isolated from four groups of adults: Normal-weight non-diabetic, obese non-diabetic, newly diagnosed with T2DM, and T2DM on metformin. The mRNA expression levels of macrophage phenotypic surface markers (interleukin-12 (IL-12), C-X-C motif chemokine ligand 10 (CXCL10), C-C motif chemokine ligand 17 (CCL17), and C-C motif receptor 7 (CCR7)), cholesterol efflux proteins (ATP-binding cassette transporter-1 (ABCA1), ATP binding cassette subfamily G member 1 (ABCG1), and sterol 27-hydroxylase (CYP27A)), scavenger receptors (scavenger receptor-A (SR-A), C-X-C motif ligand 16 (CXCL16), and lectin-like oxidized LDL receptor-1 (LOX-1)), and adenosine receptors (adenosine A2A receptor (A2AR) and adenosine A3 receptor (A3R)) were measured using qRT-PCR. Results: In PBMCs from T2DM patients, the expression of IL-12, CCR7, ABCA1, and SR-A1 was increased, whereas the expression of CXCL10, CCL17, ABCG1,27-hydroxylase, LOX-1, A2AR and A3R was decreased. On the other hand, treatment with the antidiabetic drug, metformin, reduced the expression of IL-12 and increased the expression of 27-hydroxylase, LOX-1, CXCL16 and A2AR. Conclusions: PBMCs in the circulation of patients with T2DM express phenotypic markers that are different from those typically present in adipose tissue M1 and M2 macrophages and could be representative of metabolically activated macrophages (MMe)-like cells. Our findings suggest that metformin alters phenotypic markers of MMe-like cells in circulation.

The Prevalence and Pattern of Using Complementary and Alternative Medicine in Saudi Patients With Diabetes: A Cross-Sectional Study.

Background Diabetes mellitus is a common disease in Saudi Arabia. Patients with chronic diseases, such as diabetes, tend to use complementary and alternative medicine (CAM) either as an addition or alternative to their medical therapy. Many studies have evaluated the CAM herbal products used by patients with diabetes; however, there have been few and inconsistent studies on other types of CAM, and most studies on CAM have focused on their use in type 2 diabetes. Objective This study aimed to determine the prevalence and patterns of CAM use among patients with type 1 or type 2 diabetes in Riyadh, Kingdom of Saudi Arabia. Methods This cross-sectional study was conducted in an adult Saudi population at King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia. Data were collected from December 2019 to February 2020 using a data collection form and patient interviews. Results We included 332 patients, 43% of whom had type 1 diabetes; 26% of the patients had previously used one or more types of CAM. Approximately 53% of CAM users had glycated hemoglobin (HbA1c) level of ≥9%. Among CAM users, 51% mentioned that their blood sugar readings were improved with CAM treatments. Mind-body therapy was the most commonly used CAM (54%), followed by biologically based CAM, including herbs (46%). The most commonly used herbal supplements were black cumin (42%), followed by fenugreek (28%), myrrh (24%), frankincense (22%), cinnamon (15%), garlic (15%), and onion (15%). Older age and employment status were predictors of CAM use in Saudi patients with diabetes. The main sources of knowledge about CAM were from family and friends. Conclusions CAM use is common among Saudi Arabian patients with diabetes. Patients with diabetes who are aged >65 years and employment status were the main predictor of CAM use. Assessing CAM use is an important aspect of clinical encounters with Saudi patients, especially patients with type 1 diabetes.

A Pattern of Lipid Profile Among Saudi Adults With Type 1 Diabetes Mellitus in a Tertiary Hospital: A Retrospective Study.

OBJECTIVE: Dyslipidemia is prevalent in adults living with type 1 diabetes, and it can worsen the presentation of microvascular complications such as retinopathy. This study aims to identify the pattern coupled with the frequency of dyslipidemia in diabetic adults who followed up at different clinics in King Abdulaziz Medical City, Riyadh, and evaluate the associations with demographic and clinical characteristics. METHODS: A cross-sectional, retrospective chart review study of 514 adults with type 1 diabetes was conducted in a tertiary health care facility in the central region of Saudi Arabia. Demographics were retrieved by using the implemented electronic medical records. Fasting lipid profile, glycated hemoglobin (HbA1c), and thyroid-stimulating hormone (TSH) levels were checked for all subjects. RESULTS: Five hundred and fourteen (514) subjects aged 18-65 years were studied (mean age: 26.1 ± 7.1 years). There were 318 (62%) females in the sample, and their mean age was significantly different from the mean age of males (p = 0.01). The mean duration of having diabetes was 12.8 ± 6.9 years. The prevalence of lipid abnormalities included abnormal low-density lipoprotein (LDL) (70%), hypercholesterolemia (23%), abnormal high-density lipoprotein (HDL) (8%), and hypertriglyceridemia (5%). Abnormal HDL was significantly higher in males than in females (p=<0.001). There were no statistically significant differences in the prevalence of other lipid abnormalities between the two genders and the age group < or ≥ 25 years. There was no statistically significant difference in the mean of the tested lipids levels between the two genders. One hundred and forty-three (143) (27.8%) patients had more than one abnormal lipid condition. A statistically significant difference was observed in the mean HbA1c between males and females (p=0.001). Otherwise, there was no significant association of lipid abnormalities with gender, age, diabetes duration, and weight. CONCLUSION: The most prevalent lipid abnormality was high LDL cholesterol. Nearly a third of the tested individuals had more than one lipid abnormality. Furthermore, poor glycemic control was linked to abnormal lipid profiles. Consequently, local programs must aim to screen and intervene early to delay and prevent future severe vascular complications related to non-treated dyslipidemia.

Prevalence of Associated Endocrine Diseases in Patients with Neurofibromatosis Type 1.

Background Neurofibromatosis type 1 (NF-1) is an autosomal dominant neurocutaneous disorder that increases the risk of developing benign and malignant tumors. Several associated endocrine diseases in NF-1 patients have been explained in the literature. Thus, this study aims to assess the endocrine manifestations as there no previous local data have discussed this association. Methods A retrospective cross-sectional study was conducted at KAMC and KASCH, Riyadh, Saudi Arabia by including all patients genetically confirmed with NF1 from 2004 until 2019 using a consecutive non-probability sampling technique. The included data were demographics, consanguinity, genetic variant mutations as well as associated endocrine diseases. Results The prevalence of patients with associated endocrine diseases was estimated to be 19.4%. Short stature showed the highest frequency of associated endocrine diseases followed by subclinical hypothyroidism. Positive consanguinity, sporadic mutation, and pathogenic variant showed high frequencies. Conclusion The coexistence of endocrine diseases was found in NF-1 patients. Therefore, screening for endocrine abnormality in patients with NF-1 by comprehensive history and physical exam as well as investigations to minimize complications and the late presentation should be considered; however, further studies are necessary to address the need.

The Prediction of Malignancy Risk in Thyroid Nodules Classified as Bethesda System Category III (AUS/FLUS) and the Role of Ultrasound Finding for Prediction of Malignancy Risk.

Objective To predict the risk of malignancy in category III of the Bethesda System for Reporting Thyroid Cytopathology "Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance (AUS/FLUS)" at King Abdulaziz Medical City, Riyadh, Saudi Arabia. It also intends to determine other possible contributing predictors of malignancy in thyroid nodules such as age, sex, and ultrasound (US) findings. Method This retrospectively designed study included 187 patients (mean age, 43.9 ± 14.1 years) with thyroid nodules, which were diagnosed as AUS/FLUS and all patients included had total thyroidectomy or lobectomy between January 2013 and December 2018 at King Abdulaziz Medical City in Riyadh, Saudi Arabia. The electronic medical records, US images, and final cytopathology and histopathology reports were reviewed and analyzed. Result The overall incidence of AUS/FLUS was (46.5%). Multivariate analysis of US features revealed that malignancy was significantly associated with nodules with irregular margins, microcalcification, multiple numbers (P < 0.001), and hypoechogenicity (P 0.04). Conclusion Despite the high rate of malignancy of nodules AUS/FLUS, it is still consistent with previously reported studies. The highly suspicious ultrasound features (irregular margins, microcalcification, multiple nodules, and hypoechogenicity) could be helpful in the diagnosis of thyroid cancer.

Medical Students' Insights Towards Patient Safety.

OBJECTIVES: This study aimed to explore Saudi Arabian medical students' perceptions of patient safety. METHODS: A cross-sectional descriptive study was conducted in the College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia, in September 2019. The Attitudes to Patient Safety Questionnaire (APSQ III) was used to explore undergraduate medical students' attitudes towards and knowledge of PS. The main outcomes measured were the APSQ III's nine domains. Data were analysed using Statistical Package for the Social Sciences and students' attitudes were communicated as mean scores ± standard deviations. RESULTS: A total of 301 participants were included in this study (response rate: 85.75%). Six domains reflected a positive attitude while three domains showed a neutral attitude. The domain of 'team functioning' had the highest mean score (5.8) followed by 'working hours as a cause of error' (5.6) and 'error inevitability' (5.4). There was a significant difference between gender in the domain 'patient involvement in reducing error' (P = 0.012) and 'importance of patient safety (PS) in the curriculum' (P = 0.001). In addition, the 'importance of PS in the curriculum' domain was significantly different across different age groups (P = 0.039). CONCLUSION: Medical students were highly interested in PS and recommended implementing a comprehensive undergraduate PS programme to fulfil their educational needs.

Assessment of normal reference values for thyroid uptake of technetium-99m pertechnetate in a Saudi population.

BACKGROUND: Thyrotoxicosis is a common medical problem. Thyroid nuclear imaging with either I123 or technetium-99m (Tc-99m) pertechnetate are used to determine the cause. Although I123 has been the standard technique, Tc-99m pertechnetate is now commonly used, acceptable and easier to perform. The commonly used normal value of Tc-99m pertechnetate is 1-4%, but lower normal values have been reported in different populations. OBJECTIVE: Determine normal reference range of Tc-99m pertechne-tate thyroid uptake for thyroid scintigraphy in Saudi Arabia. DESIGN: Retrospective, cross-sectional. SETTING: Nuclear medicine service at tertiary care center in Riyadh. PATIENTS AND METHODS: We used data from biochemically euthyroid patients who underwent a thyroid Tc-99m pertechnetate scan while having parathyroid scintigraphy for hyperparathyroidism between April 2009 to April 2019. Medical records and biochemical thyroid function tests were reviewed and Tc-99m pertechnetate thyroid uptake values were determined for each patient. MAIN OUTCOME MEASURES: Thyroid uptake of Tc-99m pertechne-tate in euthyroid patients. SAMPLE SIZE: 167 RESULTS: The mean and median uptake of Tc-99m pertechnetate in euthyroid patients were 0.86% and 1.0%, respectively, and the inter-quartile range was 0.0-1.0%. The normal reference range in the study population was 0.2-2%. Thyroid uptake inversely correlated with age in females (r=-0.37, P<.001), males (r=-0.46, P=.001), and for all patients (r=?0.39, P<.0001). CONCLUSION: The range for normal thyroid Tc-99m pertechnetate was lower than the standard 1-4% range. Moreover, uptake decreased with age. Further studies are needed to establish the normal age-adjusted uptake for the thyroid Tc-99m pertechnetate scan. LIMITATIONS: Single center and retrospective. CONFLICT OF INTEREST: None.

Effect of Monthly and Bi-Monthly 50,000 International Units (IU) Maintenance Therapy With Vitamin D3 on Serum Level of 25-Hydroxyvitamin D in Adults: A Randomized Controlled Trial.

Background Vitamin D deficiency is a prevalent condition worldwide. Identification of optimal supplementation approaches for maintaining normal vitamin D level in healthy adults is still required. It has been clearly established that sun exposure and diet do not provide the recommended daily amount of vitamin D, and that vitamin D supplementation is needed to maintain normal levels in the Saudi population. The aim of this study was to compare the efficacy of two regimens, monthly and bimonthly doses of 50,000 International Units (IU) cholecalciferol (vitamin D3), in maintaining normal serum levels of 25-hydroxyvitamin D in Saudi adults. Methods This study was a randomized controlled trial conducted to compare the efficacy of three regimens in maintaining a normal level of vitamin D in adult individuals. The study took place at three primary healthcare centers in King Abdul-Aziz Medical City, Riyadh, Saudi Arabia. A total of 65 participants were enrolled and randomly divided into two intervention groups and one control group. All participants were contacted by researchers and followed up at their corresponding primary health care center for two successive visits. Results All 65 participants completed the study. The participants were mostly females (49; 75.4%); the mean age was 42.1 years (±13.5). The difference in vitamin D levels after three months of the trial was statistically significant among the three groups. A decrease in vitamin D level was recorded in the control group and in the once monthly intake of 50,000 IU group. The bimonthly intake of 50,000 IU group maintained statistically significant vitamin D levels > 75. Conclusion Bimonthly vitamin D3 supplementation appears to be an efficient regimen for maintaining a normal level of 25(OH)D, regardless of the amount of vitamin D obtained from diet and sun exposure.

Gene Expression Profiling of Apoptotic Proteins in Circulating Peripheral Blood Mononuclear Cells in Type II Diabetes Mellitus and Modulation by Metformin.

INTRODUCTION: Insulin resistance in obesity and type 2 diabetes mellitus (T2DM) is associated with cardiovascular complications such as atherosclerosis. On the other hand, the reduction of apoptosis in macrophages has been linked with accelerated atherosclerosis. Apoptosis is controlled by a different family of proteins including Bcl-2 and caspases. METHODS: To examine apoptosis in insulin resistance, we assessed the mRNA expression by qRT-PCR of several Bcl-2 family members, as well as caspase-3, -7, -8, and -9 in peripheral blood mononuclear cells (PBMCs) isolated from lean, obese, diabetic, and diabetic on metformin individuals. RESULTS: PBMCs of diabetic individuals exhibited reduced expression of caspase-7 and increased expression of Bcl-10, Bad, Bax, Bid, and caspase-3. T2DM on metformin group had significantly higher Bad, Bax, and caspase-7 expression. DISCUSSION: The moderate up-regulation of pro-apoptotic Bcl-10, Bax, Bad, Bid, and the effector caspase-3 coupled with inhibition of caspase-7 in circulating PBMCs of T2DM could be the result of increased inflammation in T2DM. Metformin treatment significantly inhibited the expression of Bcl-10, Bid, and caspase-3 and upregulated Bad/Bax/caspase-7 pathway suggesting the activation of Bad/Bax/caspase-7 apoptotic pathway. Further studies are warranted to elicit the underlying apoptotic pathways of PBMCs in T2DM and following metformin treatment.

Metformin alters peripheral blood mononuclear cells (PBMC) senescence biomarkers gene expression in type 2 diabetic patients.

BACKGROUND: Although there is increasing evidence showing that cell senescence is increased in circulating PBMC in type 2 diabetes mellitus (T2DM), the data are contradictory. This study examined several senescence biomarkers, including LMNA/C transcript variants, p16INK4a, p53, and p21Cip1/WAF, in PBMC of T2DM patients and the effect of Metformin on these senescence markers. METHODS: Blood samples were obtained from 30 lean, 30 obese, 20 newly diagnosed type 2 diabetes mellitus (T2DM), and 30 T2DM on Metformin. PBMC were isolated and mRNA expression of the senescence biomarkers were quantified by RT-qPCR. The effect of ectopic expression of LMNA and LMNC in human monocytic cells lines (THP-1 and U937) on several inflammatory mediators were also examined. RESULTS: LMNA expression was significantly higher in PBMC of obese and T2DM patients. LMNC expression was significantly inhibited in T2DM patients. LMNAΔ10 and Progerin mRNA expression was not detected in PBMC of all groups. Expression of p16INK4a, p21Cip1/WAF and p53 were inhibited significantly in T2DM. Metformin treatment reverted LMNA, LMNC, and p53 expression levels to normal levels. Upregulation of LMNA in monocytic THP-1 and U937 cell lines induced CD68, TNFα, CCL2, IL-6 and NOS2. CONCLUSIONS: These data support the notion that LMNA may mediate senescence in PBMCs of T2DM by upregulating inflammatory pathways. Metformin may exert its anti-inflammatory property by modulation of senescence mediator LMNA.