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Dania AlKhafaji,1 Reem Al Argan,1 Waleed Albaker,1 Abdulmohsen Al Elq,1 Mohammed Al-Hariri,2 Abir AlSaid,1 Abrar Alwaheed,1 Safi Alqatari,1 Alaa Alzaki,1 Sara Alwarthan,1 Fatimah AlRubaish,1 Haya AlGuaimi,1 Fatema Ismaeel,1 Nidaa Alsaeed,1 Zainab AlElq,1 Fatma Zainuddin3 1Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, King Fahd Hospital of the University, Khobar, Eastern Province, Saudi Arabia; 2Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Eastern Province, Saudi Arabia; 3Department of Medical Allied Services, Imam Abdulrahman Bin Faisal University, King Fahd Hospital of the University, Khobar, Eastern Province, Saudi ArabiaCorrespondence: Mohammed Al-Hariri Tel +966507275028Email mtalhariri@iau.edu.saPurpose: The world is experiencing a life-altering and extraordinary situation in response to the COVID-19 pandemic. There are limited data and controversies regarding the relationship between vitamin D (Vit D) status and COVID-19 disease. Thus, this study was designed to investigate the association between Vit D levels and the severity or outcomes of COVID-19 disease.Methods: A cross-sectional observational study was conducted in the Eastern province of Saudi Arabia from January to August 2021. All the admitted patients who were diagnosed with COVID-19 infection were distributed into three groups depending on their Vit D levels: normal, insufficiency, and deficiency. For the three groups, demographic data, and laboratory investigations as well as data regarding the severity of COVID-19 were collected and analysed.Results: A total of 203 diagnosed cases of COVID-19 were included in this study. The Vit D level was normal (> 30) in 31 (15.3%) cases, insufficient in 45 (22.2%) cases and deficient in 127 (62.6%) cases. Among the included cases, 58 (28.6%) were critical cases, 109 (53.7%) were severe and 36 (17.7%) had a mild-moderate COVID-19 infection. The most prevalent comorbidity of patients was diabetes mellitus 117 (57.6%), followed by hypertension 70 (34.5%), cardiac disease 24 (11.8%), chronic kidney disease 19 (9.4%) and chronic respiratory disease in 17 (8.4%) cases. Importantly, the current study did not detect any significant association between Vit D status and COVID-19 severity (p-value=0.371) or outcomes (hospital stay, intensive care units admission, ventilation, and mortality rate) (p-value > 0.05), even after adjusting the statistical model for the confounders.Conclusion: In hospital settings, Vit D levels are not associated with the severity or outcomes of COVID-19 disease. Further, well‐designed studies are required to determine whether Vit D status provides protective effects against worse COVID-19 outcomes.Keywords: vitamin D, COVID-19, severity, observational, Saudi Arabia

Previous evidence has shown an association between serum ferritin and bilirubin levels in the development of type 2 diabetes mellitus (T2DM) and glycemic control. However, the evidence is scarce in Saudi Arabia. In this study, we aimed to evaluate the association between serum ferritin and bilirubin levels with glycemic control in patients with T2DM. This was a cross-sectional study that involved 153 patients with T2DM recruited from outpatient diabetes clinics. Participants were categorized into two groups: well-controlled and uncontrolled T2DM, based on their glycemic status. We focused on comparing the iron profile and bilirubin levels between these two groups and examining the influence of antidiabetic medications on these parameters. A total of 153 patients with T2DM were included (58.2% women and 41.8% men). In both univariate and multivariate analyses, ferritin levels did not have a statistically significant association with glycemic control. However, patients with well-controlled T2DM had a significantly higher median level of total bilirubin and direct bilirubin than those with uncontrolled T2DM. Only direct bilirubin showed a statistically significant association with FBG less than 130 mg/dl and HbA1c level less than 7.0%. Ferritin level was not associated with glycemic control in patients with T2DM. On the other hand, direct bilirubin level was an independent predictor of better glycemic control. Monitoring direct bilirubin levels could aid in predicting glycemic control in T2DM and could be a potential target for developing antidiabetic medications., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s).)

Recognizing hepatic manifestations of COVID-19 and their impact on the severity and outcome is crucial in managing this emerging pandemic. However, we lack such reported data in Saudi Arabia regarding this clinical entity. This is a retrospective observational study conducted on 387 patients with COVID-19 disease who were hospitalized at King Fahad Hospital of the University from March-September 2020. The total cohort was divided into two groups: liver and non-liver involvement. Then, the frequency of hepatic manifestations was determined, followed by comparing severity and outcome among the two study groups. A total of 387 patients were included, of which 72.87% had hepatic manifestations. The most prevalent abnormalities were high LDH in 308 (79.58%) followed by AST 205 (52.97%), GGTP 124 (31.26%), ALT 74 (19.12%), PT/INR 66 (17.05%), direct bilirubin 51 (12.40%), total bilirubin 46 (11.88%), and low albumin 48 (12.4%). Univariate analyses showed that liver involvement was significantly associated with severe (31.91%) and critical (34.75%) presentation (P<0.001). Multivariate regression analysis showed that the presence of liver involvement was an independent risk factor for severe or critical COVID-19 disease (OR 2.44; P<0.001), longer hospitalization (OR 2.27; P=0.001), and ICU admission (OR 2.27; P=0.006). The current study showed that liver involvement is common in the setting of COVID-19 disease. Such patients had a higher disease severity and a worse clinical outcome., Competing Interests: The authors declare no conflict of interest., (©2022 JOURNAL of MEDICINE and LIFE.)

Worldwide incidence of obesity is increasing and impaired outcome in postoperative patients has been described. Antibiotic prescribing is complicated by different pharmacology in this population. This study evaluates mortality and morbidity of obese postoperative patients and explores possible relation to antibiotic therapy. Therefore, data obtained in a prospective study in 2009-2010 were analysed. Postoperative patients on 5 ICUs were included with >48h of ICU treatment and documented body-mass-index (BMI). Altogether 451 non-obese patients (BMI<30kg/m(2)) were compared with 130 obese patients including propensity score matching. There was significant heterogeneity of baseline characteristics. ICU-mortality was 7.5% in non-obese and 7.7% in obese patients (p>0.999), but 65.4% of obese patients required mechanical ventilation compared with only 53.2% of non-obese patients (p=0.016). These findings were validated in multivariate regression analyses (adjusted OR for ICU-mortality for obese patients 0.53, 95%-CI 0.188-1.321, p=0.197; adjusted OR for mechanical ventilation 1.841, 95%-CI 1.113-3.076, p=0.018). Results were confirmed by propensity score matching. Therapeutic drug monitoring for vancomycin (TDM) showed that underdosing and overdosing occurred more often in obese patients and sufficient TDM levels were less often achieved. In conclusion, obesity is associated with increased morbidity but ICU mortality is equal compared with a non-obese population. Pharmacological differences might explain observed differences in antibiotic therapy and in obese patients TDM might be especially of importance., (Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.)

Sunlight represents an exogenous factor stimulating formation of free radicals which can induce cell damage. To assess the effect of the different spectral solar regions on the development of free radicals in skin, in vivo electron paramagnetic resonance (EPR) investigations with human volunteers and ex vivo studies on excised human and porcine skin were carried out. For all skin probes, the ultraviolet (UV) spectral region stimulates the most intensive radical formation, followed by the visible (VIS) and the near infrared (NIR) regions. A comparison between the different skin models shows that for UV light, the fastest and highest production of free radicals could be detected in vivo, followed by excised porcine and human skin. The same distribution pattern was found for the VIS/NIR spectral regions, whereby the differences in radical formation between in vivo and ex vivo were less pronounced. An analysis of lipid composition in vivo before and after exposure to UV light clearly showed modifications in several skin lipid components; a decrease of ceramide subclass [AP2] and an increase of ceramide subclass [NP2], sodium cholesterol sulphate and squalene (SQ) were detectable. In contrast, VIS/NIR irradiation led to an increase of ceramides [AP2] and SCS, and a decrease of SQ. These results, which are largely comparable for the different skin models investigated in vivo and ex vivo, indicate that radiation exposure in different spectral regions strongly influences radical production in skin and also results in changes in skin lipid composition, which is essential for barrier function., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Recently, it has been demonstrated that calling of copy number alterations (CNAs) from amplicon sequencing (AS) data is feasible. Most approaches, however, require non-tumor (germline) DNA for data normalization. Here, we present the method Ioncopy for CNA detection which requires no normal controls and includes a significance assessment for each detected alteration.Ioncopy was evaluated in a cohort of 184 clinically annotated breast carcinomas. A total number of 252 amplifications were detected, of which 183 (72.6%) could be validated by a call of an additional amplicon interrogating the same gene. Moreover, a total number of 33 deletions were found, whereof 27 (81.8%) could be validated. Analyzing the 16 most frequently amplified genes, validation rates of over 89% could be achieved for 11 of these genes. 11 of the top 16 genes showed significant overexpression in the amplified tumors. 89.5% of the HER2-amplified tumors were GRB7 and STARD3 co-amplified, whereas 68.4% of the HER2-amplified tumors had additional MED1 amplifications. Correlations between CNAs measured by amplicons in HER2 exons 19, 20 and 21 were strong (all R > 0.93). AS based detection of HER2 amplifications had a sensitivity of 90.0% and a specificity of 98.8% compared to the gold standard of HER2 immunohistochemistry combined with in situ hybridization.In summary, we developed and validated a novel method for detection and significance assessment of CNAs in amplicon sequencing data. Using Ioncopy, AS offers a straightforward and efficient approach to simultaneously analyze gene amplifications and gene deletions together with simple somatic mutations in a single assay.

UV irradiation is one of the most harmful exogenous factors for the human skin. In addition to the development of erythema, free radicals, that is reactive oxygen species (ROS), are induced under its influence and promote the development of oxidative stress in the skin. Several techniques are available for determining the effect of UV irradiation. Resonance Raman spectroscopy (RRS) measures the reduction of the carotenoid concentration, while electron paramagnetic resonance (EPR) spectroscopy enables the analysis of the production of free radicals. Depending on the method, the skin parameters are analysed in vivo or ex vivo. This study provides a critical comparison between in vivo and ex vivo investigations on the ROS formation and carotenoid depletion caused by UV irradiation in human skin. The oxygen content of tissue was also determined. It was shown that the antioxidant status measured in the skin samples in vivo and ex vivo was different. The depletion in the carotenoid concentration in vivo exceeded the value determined ex vivo by a factor of about 1.5, and the radical formation after UV irradiation was significantly greater in vivo by a factor of 3.5 than that measured in excised human skin, which can be explained by the lack of oxygen ex vivo., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Sacropexy is a generally applied treatment of prolapse, yet there are known possible complications of it. An essential need exists for better alloplastic materials., Methods: Between April 2013 and June 2014, we performed a modified laparoscopic bilateral sacropexy (MLBS) in 10 patients using a MRI-visible PVDF mesh implant. Selected patients had prolapse POP-Q stages II-III and concomitant OAB. We studied surgery-related morbidity, anatomical and functional outcome, and mesh-visibility in MRI. Mean follow-up was 7.4 months., Results: Concomitant colporrhaphy was conducted in 1/10 patients. Anatomical success was defined as POP-Q stage 0-I. Apical success rate was 100% and remained stable. A recurrent cystocele was seen in 1/10 patients during follow-up without need for intervention. Out of 6 (6/10) patients with preoperative SUI, 5/6 were healed and 1/6 persisted. De-novo SUI was seen in 1/10 patients. Complications requiring a relaparoscopy were seen in 2/10 patients. 8/10 patients with OAB were relieved postoperatively. The first in-human magnetic resonance visualization of a prolapse mesh implant was performed and showed good quality of visualization., Conclusion: MLBS is a feasible and safe procedure with favorable anatomical and functional outcome and good concomitant healing rates of SUI and OAB. Prospective data and larger samples are required.

Changes in lipid metabolism are an important but not well-characterized hallmark of cancer. On the basis of our recent findings of lipidomic changes in breast cancer, we investigated glycerol-3-phosphate acyltransferase (GPAM), a key enzyme in the lipid biosynthesis of triacylglycerols and phospholipids. GPAM protein expression was evaluated and linked to metabolomic and lipidomic profiles in a cohort of human breast carcinomas. In addition, GPAM mRNA expression was analyzed using the GeneSapiens in silico transcriptiomics database. High cytoplasmic GPAM expression was associated with hormone receptor negative status (p = 0.013). On the protein (p = 0.048) and mRNA (p = 0.001) levels, increased GPAM expression was associated with a better overall survival. Metabolomic analysis by GC-MS showed that sn-glycerol-3-phosphate, the substrate of GPAM, was elevated in breast cancer compared to normal breast tissue. LC-MS based lipidomic analysis identified significantly higher levels of phospholipids, especially phosphatidylcholines in GPAM protein positive tumors. In conclusion, our results suggest that GPAM is expressed in human breast cancer with associated changes in the cellular metabolism, in particular an increased synthesis of phospholipids, the major structural component of cellular membranes.

Background: Platinum resistance constitutes a therapeutic challenge in the treatment of ovarian cancer, with overall unsatisfactory response rates to standard chemotherapy and correspondingly low survival. Regional abdominal hyperthermia and bevacizumab are treatment options that have both shown the capacity to improve the results of standard chemotherapy in the platinum-resistant situation, when added to the treatment schedule., Case Report: We report on a 29-year-old patient with primary platinum-refractory ovarian cancer, who was treated with a combination of pegylated liposomal doxorubicin, regional abdominal hyperthermia and bevacizumab in a four-week cycle over a long-term period of 38 months. Due to an excellent clinical and radiologic response resulting in stable disease, with a concomitant mild toxicity profile consisting only of intermitted diarrhoea and mild fatigue [corrected] , the treatment was continued in an ambulatory setting., Discussion: To our knowledge we describe the first experience with combination treatment of pegylated liposomal doxorubicin with regional abdominal hyperthermia and bevacizumab in a long term setting of almost 2 years. Excellent response with comparably low toxicity was demonstrated. Further evaluation as a therapeutic option in this heavily pretreated and highly palliative patient population is warranted.