EPAS1-related pheochromocytoma/paraganglioma.

In 2012, somatic EPAS1 pathogenic variants were found to cause a triad of pheochromocytoma/paragangliomas (PPGLs), polycythemia, and somatostatinoma. Since then, a limited number of studies on this subject have been reported, and data on the long-term outcome of metastatic disease are not available on this rare syndrome. We comprehensively reviewed EPAS1-related PPGL and describe an unusual patient who has been living with an EPAS1-related metastatic PPGL for 47 years. The results of this work show that EPAS1 pathogenic variants are rare, more in females and patients without pathogenic variants in other PPGL susceptibility genes. PPGLs are the most common manifestation followed by polycythemia and somatostatinoma. The EPAS1 pathogenic variants are often postzygotic, and the timing of their acquirement during embryonic development seems to correlate with the number and timing of development of the disease manifestations. Although recurrent and multifocal disease is common in EPAS1-related PPGL, distant metastases are uncommon and usually indolent. This is illustrated by a case of a man who was diagnosed at the age of 9 years and is currently 56 years old, alive, and well for 47 years with these metastases. He was found to have a somatic EPAS1 pathogenic variant (c.1592C>A, p.Pro531His) in bilateral pheochomocytoma and a pancreatic NET (somatostatinoma) but not in genomic DNA isolated from peripheral leukocytes. This and previous reports suggest that distant metastases are uncommon and less aggressive in EPAS1-related PPGLs compared to those found in other hereditary PPGLs.

Impact of Preoperative Serum Albumin Level on the Outcome of Colorectal Cancer Surgery.

Background Gastrointestinal malignancy surgeries are known to have a risk of postoperative complications. Preoperative nutritional status has been suggested as a potential predictor of postoperative outcomes, with low serum albumin levels utilized as a marker of malnutrition and increased risk of postoperative complications. This paper investigated the association between preoperative serum albumin levels and postoperative outcomes in patients undergoing colorectal cancer surgery. Methods This retrospective data-maintained study was based on all patients aged 18 years and above who underwent colorectal cancer surgery at King Abdulaziz Medical City, Riyadh, Saudi Arabia between 2015 and 2022. Results A total of 400 patients were included in the study. With an average age of 64.43 years. Males represented 254 (63%) of the patients, while females accounted for 146 (37%). Thirty percent of patients had hypoalbuminemia (i.e., albumin level below 35 g/L) before surgery. Among the sample, 112 (28%) experienced complications after surgery. The mean albumin level for patients who experienced postoperative complications was 30.46 g/L while patients without complications had a normal albumin level. As for the length of hospital stay, it was eight days for patients with a normal albumin level and 23 days for hypoalbuminemia patients. Conclusion In conclusion, preoperative hypoalbuminemia is associated with poor patient outcomes and can be utilized as a prognostic marker for patients in need of colorectal cancer surgery.

Germline Variants in Sporadic Pituitary Adenomas.

Context: Data on germline genetics of pituitary adenomas (PAs) using whole-exome sequencing (WES) are limited. Objective: This study investigated the germline genetic variants in patients with PAs using WES. Methods: We studied 134 consecutive functioning (80.6%) and nonfunctioning (19.4%) PAs in 61 female (45.5%) and 73 male patients (54.5%). Their median age was 34 years (range, 11-85 years) and 31 patients had microadenomas (23.0%) and 103 macroadenomas (77%). None of these patients had family history of PA or a known PA-associated syndrome. Peripheral blood DNA was isolated and whole-exome sequenced. We used American College of Medical Genetics and Genomics (ACMG) criteria and a number of in silico analysis tools to characterize genetic variant pathogenicity levels and focused on previously reported PA-associated genes. Results: We identified 35 variants of unknown significance (VUS) in 17 PA-associated genes occurring in 40 patients (29.8%). Although designated VUS by the strict ACGM criteria, they are predicted to be pathogenic by in silico analyses and their extremely low frequencies in 1000 genome, gnomAD, and the Saudi Genome Project databases. Further analysis of these variants by the Alpha Missense analysis tool yielded 8 likely pathogenic variants in 9 patients in the following genes: AIP:c.767C>T (p.S256F), CDH23:c.906G>C (p.E302D), CDH23:c.1096G>A (p.A366T), DICER1:c.620C>T (p.A207V), MLH1:c.955G>A (p.E319K), MSH2:c.148G>A (p.A50T), SDHA:c.869T>C (p.L290P) and USP48 (2 patients): c.2233G>A (p.V745M). Conclusion: This study suggests that about 6.7% of patients with apparently sporadic PAs carry likely pathogenic variants in PA-associated genes. These findings need further studies to confirm them.

Risk adjusted EWMA control chart based on support vector machine with application to cardiac surgery data.

In the current study, we demonstrate the use of a quality framework to review the process for improving the quality and safety of the patient in the health care department. The researchers paid attention to assessing the performance of the health care service, where the data is usually heterogeneous to patient's health conditions. In our study, the support vector machine (SVM) regression model is used to handle the challenge of adjusting the risk factors attached to the patients. Further, the design of exponentially weighted moving average (EWMA) control charts is proposed based on the residuals obtained through SVM regression model. Analyzing real cardiac surgery patient data, we employed the SVM method to gauge patient condition. The resulting SVM-EWMA chart, fashioned via SVM modeling, revealed superior shift detection capabilities and demonstrated enhanced efficacy compared to the risk-adjusted EWMA control chart.

LncRNA GAS8-AS1 dinucleotide genetic variantn.713A>G, n.714T>C is associated with early-stage disease, lymph node, and distant metastasis in differentiated thyroid cancer.

PURPOSE: Long noncoding RNAs (lncRNAs) play an essential role in the epigenetic regulation of various key genes involved in vital cellular functions. A somatic dinucleotide mutation in the lncRNA GAS8-AS1 was reported in Chinese papillary thyroid cancer. However, GAS8-AS1 dinucleotide alteration and its impact have never been explored in differentiated thyroid cancers and other populations. METHODS: We extracted genomic DNA from 265 DTCs and 97 normal healthy subjects, PCR amplified and Sanger sequenced to examine the GAS8-AS1 dinucleotide alteration. Calculated genotype/allele frequency to test Hardy-Weinberg Equilibrium (HWE) and performed a genetic model of inheritance to determine its association with DTC risk. Correlated the GAS8-AS1 dinucleotide variant distribution with clinical characteristics to find the association. Predicted GAS8-AS1 RNA secondary structure for wild type and variant using RemuRNA and RNAfold to assess the conformational changes. RESULTS: GAS8-AS1 dinucleotide alteration (n.713A > G, rs55742939; n.714T > C, rs61118444) identified in DTCs is a germline variant not somatic. The GAS8-AS1 genotype and allele frequency significantly deviated for HWE in DTCs (χ2 = 37.954; p = 0.0001) though not associated with its risk. Dinucleotide variant distribution was remarkably associated with early-stage disease (p = 0.002), lymph node (p = 0.01), and distant metastasis (p = 0.01) in DTCs. The GAS8-AS1 bearing dinucleotide variant markedly showed conformational change compared to that of its wild type. CONCLUSIONS: These findings indicate that GAS8-AS1 is genetically deregulated and implicated in several stages of DTC tumorigenesis suggesting it could be a promising prognostic biomarker in DTCs.

Awareness of Medication-Related Osteonecrosis of the Jaws Amongst Patients on Antiresorptive and Antiangiogenic Medications.

Background Medication-related osteonecrosis of the jaws (MRONJ) is a rare but severe condition that has garnered increasing attention in recent years. It primarily affects individuals undergoing treatment with antiresorptive and antiangiogenic medications, such as bisphosphonates and denosumab, commonly prescribed for osteoporosis and cancer-related bone metastases. Therefore, the present study aimed to assess awareness and understanding of MRONJ among patients receiving antiresorptive and antiangiogenic medications. Methods A cross-sectional survey was conducted among 110 patients receiving antiresorptive and antiangiogenic medications in a clinical setting. Participants were given a structured questionnaire to assess their awareness of MRONJ. The questionnaire covered aspects such as MRONJ, bisphosphonate usage, and awareness of the condition's potential complications. Demographic information was also collected. Chi-square and Fisher's tests were performed using SPSS statistical software. Results In terms of gender distribution, 63.6% of the participants were female. Concerning age distribution, the majority (43.6%) fell within the 21 to 40 age group, whereas only 5.5% were aged over 60. Regarding educational attainment, a substantial majority (58.2%) of the participants held a bachelor's degree. The study findings reveal that a considerable proportion (35.5%) of participants possess awareness regarding jaw osteonecrosis, and this association is statistically significant (p=0.002). A substantial number of participants administered the medication orally (30.9%), while others utilized various administration routes, including injection (IV and others) (40%), and this difference was also statistically significant (p=0.001). Most participants took bisphosphonates for osteoporosis (41.8%) or cancer (13.6%), both statistically significant (p<0.01). Gender had no significant impact (p>0.01), but age showed potential associations (p=0.07 for awareness, p=0.003 for medication use). Educational backgrounds had no significant link, except for bisphosphonate usage (p<0.01) and side effects reporting (p<0.01). Conclusion Notably, a small percentage of participants demonstrated awareness of this condition, indicating a need for continued education and awareness campaigns. Further research and interventions may be warranted to address the specific needs of different age groups and educational backgrounds in promoting safe and effective medication management.

Revitalizing oncology medications access in Saudi Arabia: Current challenges and recommendations by the Saudi Oncology Pharmacy Assembly.

BACKGROUND: Cancer care is posing immense challenges to healthcare systems globally. Advances in screening, monitoring, and treating cancer improved patient outcomes and survival rates yet amplified the disease burden. Multiple barriers might impede early access to innovative therapies. We thoroughly examined the current challenges in oncology medication access in Saudi Arabia and provided consensus recommendations to revitalize the process. METHODS: A focus group discussion was conducted. Expert healthcare providers (pharmacists and physicians) were invited to participate based on prespecified criteria. The research team conducted a qualitative analysis of the discussion to identify themes and formulate recommendations. RESULTS: Fourteen experts were equally distributed into two groups, limiting the number in each group to 7. Pharmacists were 12 (∼86%), and physicians were 2 (∼14%). Ten were practicing in governmental hospitals, four representing different sectors; regulatory bodies, including Ministry of Health, National Unified Procurement Company, and Saudi Food and Drug Authority. Five themes were identified: national cancer burden, local data availability, pharmacoeconomic evaluation, patients reported outcomes, administration, and procurement. Consensus recommendations were formulated to optimize the formulary management process, enabling informed decision-making and facilitating early medication access for cancer patients. CONCLUSIONS: The formulary management process can be enhanced by addressing the national cancer burden, promoting local data availability, conducting pharmacoeconomic evaluations, focusing on patient outcomes, and improving administration and procurement procedures. Implementing these recommendations can improve access to oncology medications and improve patient care outcomes in Saudi Arabia.

Ultrasonographic predictors of thyroid cancer in Bethesda III and IV thyroid nodules.

Background: Bethesda III and IV thyroid nodules continue to be difficult to manage. Although molecular testing may assist in decision-making, it is expensive, not widely available, and not without pitfalls. The objective of this study is to assess whether certain thyroid ultrasonographic features may predict the risk of thyroid cancer in patients with Bethesda III and IV thyroid nodules and be used as additional decision-making tools to complement cytopathological results in deciding on diagnostic thyroidectomy. Methods: We retrospectively evaluated the ultrasonographic features of Bethesda categories III and IV thyroid nodules in patients who underwent subsequent thyroidectomy. We used the final histopathological examination of the surgical specimens as the gold-standard test and analyzed individual preoperative ultrasonographic features as predictors of malignancy. Results: Of the 278 patients who were diagnosed with Bethesda III and IV thyroid nodules on fine needle aspiration cytology (FNAC), 111 (39.9%) had thyroid cancer, and 167 (59.9%) exhibited benign nodules. The malignancy rate was higher in patients with Bethesda IV nodules (28/50, 56%) than those with Bethesda III nodules (83/228, 36.4%; p=0.016). In univariate analysis, hypoechogenicity (55.6% in malignant vs. 35.3% in benign, p=0.006) and calcifications (54.5 in malignant vs. 35.4% in benign, p=0.008) were significantly different between the benign and malignant pathology groups, whereas the size of the dominant nodule, number of nodules, irregular borders, taller-than-wide shape, and the presence of lymph nodes were comparable between the two groups. These two ultrasonographic features (hypoechogenicity and calcifications) remained significantly associated with the risk of malignancy in multivariate logistic regression analysis (for hypoechogenicity, p=0.014, odds ratio: 2.1, 95% CI:1.0-3.7 and for calcifications, p=0.019, odds ratio: 1.98, 95% CI:1.12-3.50). The sensitivity, specificity, positive and negative predictive values, and accuracy were 31.5%, 83%, 55.6%,64.7%, and 62.6%, for hypoechogenicity, respectively and 32.4%, 82%, 54.5%, 67.8%, and 62%, for calcification, respectively. Conclusions: Hypoechogenicity and calcifications in Bethesda III and IV thyroid nodules are strong predictors of thyroid cancer and associated with a two-fold increased risk of malignancy.

An aggressive cabergoline-resistant, temozolomide-responsive macroprolactinoma due to a germline SDHB pathogenic variant in the absence of paraganglioma or pheochromocytoma.

Context: Germline succinate dehydrogenase subunit B (SDHB) pathogenic variants are characteristic of familial paraganglioma (PGL) syndrome type 4. This syndrome frequently presents with abdominal PGL and has high tendency for locally aggressive behavior and distant metastasis. The vast majority of pituitary adenomas (PAs) are sporadic. However, PAs can be part of a number of familial tumor syndromes such as multiple endocrine neoplasia type 1 (MEN 1) or more rarely in association with pheochromocytoma and PGL (referred to as 3P syndrome). Only a limited number of PAs in association with SDHB-related PGL has been reported and the vast majority occurred subsequently or simultaneously with pheochromocytoma/PGL (collectively abbreviated as PPGL). In this report, we describe a young patient who had a giant pituitary macroprolactinoma resistant to large doses of cabergoline (CBG) and external beam radiotherapy (XRT). The patient did not have personal history of PPGL but was found to carry a germline SDHB pathogenic variant. Case report: A 38-year-old woman presented with headache, visual disturbances and galactorrhea and was found to have a 34-mm macroprolactinoma. She was treated with CBG 3-4 mg per week but PA continued to grow and caused significant cranial pressure symptoms. She underwent two transsphenoidal surgeries with rapid tumor recurrence after each one. She received XRT but PA continued to grow. She was finally treated with temozolomide with excellent response. Whole exome and subsequent Sanger sequencing confirmed that she has a pathogenic monoallelic SDHB mutation (NM_003000:c.C343T, p.R115*). PA tissue showed loss of heterozygosity for the same mutation and absent SDHB immunostaining confirming the pathogenic role of this SDHB mutation. Conclusion: Germline SDHB mutations can rarely cause PA in the absence of PPGL. They should be considered as a possible cause of aggressiveness and resistance to dopamine agonists in similar cases.

Coincidental Occurrence of Multiple Endocrine Neoplasia Type 1 and Breast Cancer in a Young Saudi Girl: A Case Study and Genetic Analysis.

Multiple Endocrine Neoplasia Type 1 (MEN-1) is an autosomal dominant familial disorder associated with tumors in both endocrine and non-endocrine organs. It is uncommon for MEN-1 to coincide with breast cancer. We present a case of a 15-year-old Saudi girl who exhibited the classic symptoms of MEN-1 and subsequently developed breast cancer. The patient's breast cancer was diagnosed using ultrasonography and core biopsy, and she was treated with surgical interventions. Despite these treatments, her cancer progressed to a metastatic stage, and her overall health deteriorated, leading to cardiopulmonary arrest at a young age. Although the simultaneous appearance of MEN-1 and breast cancer in our patient may suggest a potential link, our comprehensive genetic analysis found no relationship between her MEN-1 mutation and the onset of breast cancer. This suggests that, in this case, the two conditions co-occurred by chance. Nonetheless, additional research is needed to explore potential associations between MEN-1 and breast cancer.

How do BRAFV600E and TERT promoter mutations interact with the ATA and TNM staging systems in thyroid cancer?

Context: The American Thyroid Association risk stratification (ATA) and the American Joint Committee on Cancer Tumor Node Metastases (TNM) predict recurrence and mortality of differentiated thyroid cancer (DTC). BRAFV600E and TERT promoter mutations have been shown to correlate with the histopathological features and outcome of DTC. Our objectives were to study the correlation of these molecular markers with these clinicopathological-staging systems. Patients and methods: We studied 296 unselected patients, 214 females and 82 males with a median age of 36 years (IQR 23.3-49.0). BRAFV600E and TERT promoter mutations were tested by PCR-based Sanger sequencing. Data were extracted from medical records and analysed using Chi-Square and Fisher Exact tests and Kaplan Meier analysis. Results: Of 296 patients tested, 137 (46.3%) had BRAFV600E-positive tumors and 72 (24.3%) were positive for TERT promoter mutations. The BRAFV600E mutation did not correlate with the ATA and TNM staging, being non-significantly different in various stages of these systems and did not predict the development of persistent disease (PD) (P 0.12). Unlike BRAFV600E, TERT promoter mutations were more frequent in the ATA high-risk than in intermediate- or low-risk tumors (P 0.006) and in TNM stages III and IV than lower stages (P <0.0001). TERT promoter mutations also predicted the outcome, being present in 37.2% of patients with PD compared to only 15.4% in those without evidence of disease (P <0.0001). The same pattern was also seen when BRAFV600E and TERT promoter mutations were combined. Conclusion: TERT promoter mutations alone or in combination with BRAFV600E mutation, but not BRAFV600E mutation alone, correlated well with the ATA and TNM staging and predicted development of PD, especially in higher stages of these systems.

Migrated intrauterine device: Case series report.

INTRODUCTION AND IMPORTANCE: Implantation of an intrauterine device (IUD) is a common method of contraception in Saudi Arabia. Although rare, IUD migration and colon perforation have been reported. The current report presented three cases of IUD migration into the colon and recto-uterine pouch. METHODS AND OUTCOMES: The study included a series of three cases of migrated IUDs. The first case was a 25-year-old female, Gravida 2, Para 2 + 0, at 28 week-gestation, who presented with abdominal pain with a history of IUD placement that had not been removed or imaged before. The patient submitted to the caesarian section (CS), where IUD was found in the sigmoid colon. Elective laparoscopic removal of IUD with resection and primary repair of sigmoid colon was done later. The second case was a 37-year-old female, Gravida 1, Para 1 + 0, non-pregnant hypothyroidism, and a history of IUD placement. The patient got pregnant and gave birth through CS. She was then presented with abdominal pain and requested the removal of the IUD. On colonoscopy, IUD was seen in the pouch of Douglas with no evidence of a fistulous tract. IUD was removed through laparoscopy. The third case was a 47-year-old female, Gravida 14, Para 14 + 0, with a history of previous CS presented with a missing IUD that had been inserted 20 years ago after she had five pregnancies and subsequent deliveries. On colonoscopy, IUD was embedded on the wall of the transverse colon, and through abdominal surgery, IUD was removed by cutting through the colon and primary repair was done. CLINICAL DISCUSSION: the presentation of IUD migration cases was foundto vary according to the site of migration and type of IUD.however the cases are usually present with abdominal pain. An abdominal pelvic imaging with CT in these patients are essential in diagnosis. Retrival of migrating IUDs may be done through colonoscopy, laparoscopy, and in some cases with adhesion laparotomy is the solution. CONCLUSION: Abdominal and pelvic CT scan are very important in the diagnosis and the localization of IUD. Elective colonoscopy and laparoscopy are successful management approaches for these cases.

Machine-Learning-Assisted Cyclostationary Spectral Analysis for Joint Signal Classification and Jammer Detection at the Physical Layer of Cognitive Radio.

Cognitive radio technology was introduced as a possible solution for spectrum scarcity by exploiting dynamic spectrum access. In the last two decades, most researchers focused on enabling cognitive radios for managing the spectrum. However, due to their intelligent nature, cognitive radios can scan the radio frequency environment and change their transmission parameters accordingly on-the-fly. Such capabilities make it suitable for the design of both advanced jamming and anti-jamming systems. In this context, our work presents a novel, robust algorithm for spectrum characterisation in wideband radios. The proposed algorithm considers that a wideband spectrum is sensed by a cognitive radio terminal. The wideband is constituted of different narrowband signals that could either be licit signals or signals jammed by stealthy jammers. Cyclostationary feature detection is adopted to measure the spectral correlation density function of each narrowband signal. Then, cyclic and angular frequency profiles are obtained from the spectral correlation density function, concatenated, and used as the feature sets for the artificial neural network, which characterise each narrowband signal as a licit signal with a particular modulation scheme or a signal jammed by a specific stealthy jammer. The algorithm is tested under both multi-tone and modulated stealthy jamming attacks. Results show that the classification accuracy of our novel algorithm is superior when compared with recently proposed signal classifications and jamming detection algorithms. The applications of the algorithm can be found in both commercial and military communication systems.

ß-catenin attenuation leads to up-regulation of activating NKG2D ligands and tumor regression in BrafV600E-driven thyroid cancer cells.

Introduction: BRAFV600E mutations frequently occur in papillary thyroid cancer (PTC). ß-catenin, encoded by CTNNB1, is a key downstream component of the canonical Wnt signaling pathway and is often overexpressed in PTC. BRAFV600E-driven PTC tumors rely on Wnt/ß-catenin signaling to sustain growth and progression. Methods: In the present study, we investigated the tumorigenicity of thyroid cancer cells derived from BRAFV600E PTC mice following Ctnnb1 ablation (BVE-Ctnnb1null). Results: Remarkably, the tumorigenic potential of BVE-Ctnnb1null tumor cells was lost in nude mice. Global gene expression analysis of BVE-Ctnnb1null tumor cells showed up-regulation of NKG2D receptor activating ligands (H60a, H60b, H60c, Raet1a, Raet1b, Raet1c, Raet1d, Raet1e, and Ulbp1) and down-regulation of inhibitory MHC class I molecules H-2L and H-2K2 in BVE-Ctnnb1null tumor cells. In vitro cytotoxicity assay demonstrated that BVE-Ctnnb1wt tumor cells were resistant to NK cell-mediated cytotoxicity, whereas BVE-Ctnnb1null tumor cells were sensitive to NK cell-mediated killing. Furthermore, the overexpression of any one of these NKG2D ligands in the BVE-Ctnnb1wt cell line resulted in a significant reduction of tumor growth in nude mice. Conclusions: Our results indicate that active ß-catenin signaling inhibits NK cell-mediated immune responses against thyroid cancer cells. Targeting the ß-catenin signaling pathway may have significant therapeutic benefits for BRAF-mutant thyroid cancer by not only inhibiting tumor growth but also enhancing host immune surveillance.

Awareness and utilization of smoking cessation clinics in Saudi Arabia, findings from the 2019 Global Adult Tobacco Survey.

BACKGROUND: Tobacco use remains a leading cause of premature death. To combat tobacco use, the Ministry of Health (MOH) improved access to smoking cessation clinics (SCCs) by developing fixed SCCs and mobile SCCs, which move based on demand across locations. The goal of this study was to investigate awareness and utilization of SCCs among tobacco users in Saudi Arabia and the factors that influence their awareness and utilization. METHOD: This cross-sectional study used the 2019 Global Adult Tobacco Survey. Three outcome variables were employed, including tobacco users' awareness of fixed SCCs, mobile SCCs, and utilization of fixed SCCs. Several independent variables were examined, including sociodemographic characteristics and tobacco use. Multivariable logistic regression analyses were performed. RESULTS: One thousand six hundred sixty-seven tobacco users were included in this study. There were 60%, 26%, and 9% of tobacco users who were aware of fixed SCCs, aware of mobile SCCs, and visited fixed SCCs, respectively. The likelihood of being aware of SCCs increased among users residing in urban areas (fixed SCCs: OR = 1.88; 95% CI = 1.31-2.68; mobile SCCs: OR = 2.09; CI = 1.37-3.17) while it decreased among those reported self-employed (fixed SCCs: OR = 0.31; CI = 0.17-0.56; mobile SCCs: OR = 0.42; CI = 0.20-0.89). The likelihood of visiting fixed SCCs increased among educated tobacco users aged 25-34 (OR = 5.61; CI = 1.73-18.21) and 35-44 (OR = 4.22; CI = 1.07-16.64) while the odds of visiting SCCs decreased among those who were working in the private sector (OR = 0.26; CI = 0.09-0.73). CONCLUSION: The decision to quit smoking must be supported by an effective healthcare system that provides accessible and affordable smoking cessation services. Knowing the factors that influence the awareness and utilization of SCCs would help policymakers dedicate efforts targeting those who desire to quit smoking yet face limitations in using SCCs.

Lifestyle Assessment of Primary Healthcare Physicians in Taif, Saudi Arabia in the Year 2022.

Objective This study aims to evaluate primary healthcare physicians' lifestyles to promote their well-being and improve care quality for the general population. Methods This cross-sectional quantitative study was conducted on primary healthcare physicians in Taif, Kingdom of Saudi Arabia (KSA), using self-administered questionnaires. Results We included 206 participants aged 26-66. Most participants were 35 years old or younger (67%), male (62.1%), and residents (52.4%). Of all participants, 49.5% held a Bachelor's degree, 40.8% had completed their board certificate or Ph.D., and 69.9% had at least 10 years of experience. Of all participants, 16.5% and less than 9% reported having hypercholesterolemia and other comorbidities, respectively. More than 50% were physically inactive, 26.2% were moderately inactive, and 17.4% were moderately active or active individuals. Physical activity was significantly associated with job titles (p < 0.018). The qualification was associated with dietary score (p = 0.034), and 42.7% of participants were in need of diet change. About a quarter (25.2%) were smokers, and 92.3% of them smoked daily. Male participants were associated with a greater likelihood of smoking (p < 0.001). Overall, 41.7% were overweight, and 25.7% were obese. Increased BMI was associated with older age and male gender (p < 0.001 and p < 0.002, respectively), as well as the title of the physician and years of experience (p < 0.001 and p < 0.002, respectively). Conclusion Participants' unhealthy lifestyles indicate the need to establish measures to promote healthy lifestyles among physicians.

Clinical use of Molecular Data in Thyroid Nodules and Cancer.

Over the past 3 decades, advances in the molecular genetics of thyroid cancer (TC) have been translated into diagnostic tests, prognostic markers, and therapeutic agents. The main drivers in differentiated TC pathogenesis are single-point mutations and gene fusions in components of the Mitogen-activated protein kinase (MAPK) and phosphoinositide-3-kinase-protein kinase B/Akt (PI3K/Akt) pathways. Other important genetic alterations in the more advanced types of TC include TERT promoter, TP53, EIF1AX, and epigenetic alterations. Using this knowledge, several molecular tests have been developed for cytologically indeterminate thyroid nodules. Currently, 3 commercially available tests are in use including a DNA/RNA-based test (ThyroSeq v.3), an RNA-based test (Afirma Gene Sequencing Classifier), and a hybrid DNA/miRNA test, ThyGeNEXT/ThyraMIR. These tests are mostly used to rule out malignancy in Bethesda III and IV thyroid nodules because they all have high sensitivities and negative predictive values. Their common use, predominantly in the United States, has resulted in a significant reduction in unnecessary thyroid surgeries for benign nodules. Some of these tests also provide information on the underlying molecular drivers of TC; this may support decision making in initial TC management planning, although this practice has not yet been widely adopted. More importantly, molecular testing is essential in patients with advanced disease before using specific mono-kinase inhibitors (eg, selpercatinib for RET-altered TC) because these drugs are ineffective in the absence of a specific molecular target. This mini-review discusses the utilization of molecular data in the clinical management of patients with thyroid nodules and TC in these different clinical situations.

Thyroid Cancer, Neuroendocrine Tumor, Adrenal Adenoma, and Other Tumors in a Patient With a Germline PMS1 Mutation.

Context: Multiple tumors in the same patient suggest a genetic predisposition. Here, we report a patient who presented with several unusual types of malignant and benign tumors, presumably due to a pathogenic germline PMS1 mutation. Case: A 69-year-old woman presented with a 2-year history of abdominal pain and diarrhea. A computed tomography scan of the abdomen revealed a gastrointestinal neuroendocrine tumor (GiNET) with liver metastases and a nonfunctional benign adrenal adenoma. Bilateral large lung nodules were thought to be also metastases from the GiNET but turned out to be differentiated thyroid cancer metastases, which later progressed to anaplastic thyroid cancer (ATC) and led to the patient's demise. A right sphenoid wing meningioma causing partial hypopituitarism was diagnosed during her evaluation. A mammogram and a breast ultrasound revealed a 0.3-cm left breast nodule. Due to the multiplicity of her tumors, whole exome sequencing was performed. This revealed a previously described PMS1 deletion mutation causing a frameshift and truncation (NM_000534c.1258delC, p.His420Ilefs*22) but no other pathogenic variant in other cancer genes. DNA isolated from the ATC tumor tissue showed loss of heterozygosity of the same mutation, highly suggestive of its pathogenic role in thyroid cancer and presumably other tumors. Conclusion: This case reports several tumors including thyroid cancer, GiNET, adrenal adenoma, meningioma, and breast nodule, likely due to the PMS1 mutation found in this patient.

Factors associated with the desire to quit tobacco smoking in Saudi Arabia: Evidence from the 2019 Global Adult Tobacco Survey.

INTRODUCTION: Saudi Arabia is expected to witness a slight reduction in tobacco use. The Saudi government offers free-of-charge smoking cessation services. Yet, factors influencing the desire to quit smoking are not comprehensively investigated in Saudi Arabia. This study examines the factors influencing the desire to quit among smoking adults in Saudi Arabia and investigates whether using alternative tobacco products, such as e-cigarettes, is associated with the desire to quit smoking. METHODS: Data from the 2019 nationally representative Global Adults Tobacco Survey (GATS) was used. GATS utilized a face-to-face household cross-sectional survey that collected data from adults aged ≥15 years. Several factors including, sociodemographic characteristics, use of alternative tobacco products, attitude toward tobacco control, and awareness of smoking cessation clinics (SCCs), were examined to predict the desire to quit. Logistic regression analysis was conducted. RESULTS: A total of 11381 individuals completed the survey. Of the total sample, 1667 participants were tobacco smokers. The majority of the tobacco smokers were interested in quitting smoking (82.4%); 58% of cigarette smokers and 17.1% of waterpipe smokers were interested in quitting smoking. The desire to quit smoking was positively associated with the awareness of SCCs (AOR=3; 95% CI: 1.8-5), attitude toward raising tobacco taxes (AOR=2.3; 95% CI: 1.4-3.8), and a strict rule of smoking inside the home (AOR=2; 95% CI: 1.1-3.9). No statistical association was found between the desire to quit smoking and the use of e-cigarettes. CONCLUSIONS: The desire to quit tobacco smoking among Saudi smokers increased with awareness of SCCs, favoring taxes on tobacco products, and implementing strict rules of smoking inside the home. The study reveals valuable insights into the main factors that could inform the development of more effective policy interventions targeting smokers in Saudi Arabia.