Search

To compare the bone mineral density and the fracture risks in Saudi women with and without type 2 diabetes mellitus (T2DM).This cross-sectional study was carried out at Taibah Early Diagnostic Center, Al Madinah Al Munawarah, Saudi Arabia. A total of 465 women with and without T2DM aged ≥40 years who visited the center for a dual-energy X-ray absorptiometry scan between December 2020 and July 2021 were randomly selected. The 10-year probabilities of major osteoporotic fracture (MOF) and hip fracture (HF) were calculated using the Abu Dhabi Fracture Risk Assessment Tool (FRAX) with and without adjustment for T2DM. The adjustment was made by setting rheumatoid arthritis as the equivalent risk for T2DM in the FRAX. Bone mineral density values and the FRAX scores were compared between women with T2DM and non-diabetes.Of 465 women, 214 had T2DM, and 251 were non-diabetics. The mean age of women was 59.42±7.9 years. There were no significant differences in mean age, menopausal status, height, weight, and body mass index between T2DM and non-diabetic women. Bone mineral density values and the unadjusted FRAX scores were comparable between the 2 groups. However, after adjusting FRAX for T2DM, the FRAX for MOF and HF became significantly higher in T2DM women (In Saudi women with T2DM, unadjusted FRAX underestimated the risk of MOF and HF. Type 2 diabetes mellitus should be included as one of the clinical risk factors for fracture in future versions of the FRAX score.

This paper investigates a new approach to the rapid control of an upper limb exoskeleton actuator. We used a mathematical model and motion measurements of a human arm to estimate joint torque as a means to control the exoskeleton’s actuator. The proposed arm model is based on a two-pendulum configuration and is used to obtain instantaneous joint torques which are then passed into control law to regulate the actuator torque. Nine subjects volunteered to take part in the experimental protocol, in which inertial measurement units (IMUs) and a digital goniometer were used to measure and estimate the torque profiles. To validate the control law, a Simscape model was developed to simulate the arm model and control law in which measurement data from IMUs and a goniometer were fed into the suggested Simscape model. The arm torque profiles are key to the control approach and should be traced by torques produced by the exoskeleton actuators to provide comfort and flexibility for the subjects. A DC motor was used as an actuator for the exoskeleton, and its model was used in the physical Simscape model. To reduce the error in the driving torque compared with the reference arm torque, a PID controller was implemented. The results show the potential of our methodology for tracking and controlling the actuator’s torque, in which the mean square error was reduced to less than 0.2 - a significantly low value.

BackgroundThe impact of biologic therapies on body mass index (BMI) in patients with inflammatory bowel disease (IBD) is unclear. This study investigates any associations between BMI, type of IBD, and the type of medications taken among patients with IBD with varying weight categories.MethodsA cross sectional study was performed in an IBD tertiary care center. Data was obtained from patients with IBD attending outpatient clinics from January 1st, 2021 until November 1st, 2021. Adult patients, older than 18 years, with a diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) were recruited. The primary outcome was the association between BMI and medication used in IBD. The secondary outcome was the association between BMI and disease type and location in patients with IBD.ResultsThe study included a total of 528 patients of which, 66.5% have CD. Patients with normal weight comprises 55.9% of the participants, while those who are underweight, overweight or obese are 3.4, 28.2, and 12.5%, respectively. None of the underweight patients had UC. Among the normal weight, overweight and obese BMI categories, 34.6% vs. 36.2% vs. 31.8% had UC, respectively. Patients who are on tumor necrosis factor inhibitors (anti-TNF) with an immunomodulator (anti-TNF combination), are more likely to be overweight or obese than patients who are not on anti-TNF combination (OR 2.86, 95% CI 1.739–4.711, p < 0.001). Patients on vedolizumab are twice as likely to be overweight or obese than patients not on vedolizumab (OR 2.23, 95% CI 1.086–4.584, p < 0.05). Patients with ileocolonic CD are more likely to be overweight or obese compared to other subtypes of CD (OR 1.78, 95% CI 1.14–2.77, p = 0.01).ConclusionMany patients with IBD are either obese or overweight. Patients with IBD who are on anti-TNF combination therapy or vedolizumab monotherapy are more likely to be obese and overweight. In addition, patients will ileocolonic CD are more likely to be obese or overweight.

Background Several biologic therapies are currently available for the management of inflammatory bowel disease (IBD) rendering the choice and sequencing between them as a first line under question. In our study, we evaluated the effectiveness of biologic therapies in achieving important clinical and endoscopic outcomes in biologic naïve patients with IBD. Methods Electronic medical records of patients with moderate to severe IBD, who were previously naïve to biologics, were reviewed and evaluated retrospectively in a tertiary care gastroenterology center, Haya Alhabib Center. Patients who were on infliximab, adalimumab, ustekinumab and vedolizumab for 12 months were included. The primary end points were percentage of hospitalization, surgery, steroid free remission, and mucosal healing, defined as Mayo score less than 1 in ulcerative colitis and SES-CD score less than 3 in Crohn’s disease. Descriptive analysis was performed to measure outcomes. Results A total of 335 biologic naïve patients with IBD were included; 262 (78.2%) patients with ulcerative colitis and 73 (21.8%) patients with Crohn’s disease. Regarding hospitalization, 25 (14.7%) out of 170 on adalimumab,12 (10.7%) out of 112 on infliximab, and one (6.25%) on vedolizumab were hospitalized. None of the patients on ustekinumab were hospitalized. 9 out of 171 (4.7%) patients on adalimumab underwent surgery, while none of the patients on the other biologics underwent IBD related surgery. Regarding steroid free remission, 29 (16.9%) out of 171 patients on adalimumab received steroid courses, 15 (13.3%) out of 113 patients on infliximab, 4 (11.4%) out of 35 patients on ustekinumab, and 1 (6.3%) out of 16 patients on vedolizumab. A total of 159 out of 171 patients (93.0%) on adalimumab achieved mucosal healing. While 100 out of 113 patients (88.5%) on infliximab, 26 out of 35 patients (74.3%) on ustekinumab, and 7 out of 16 patients (43.8%) on vedolizumab achieved mucosal healing. Conclusion Adalimumab, infliximab, and ustekinumab and vedolizumab were all effective in inducing steroid free remission. However, patients on vedolizumab had numerically lower percentages of mucosal healing than other biologics. Percentage of hospitalizations and IBD related surgeries were higher in patients on infliximab and adalimumab. Future Larger prospective comparative studies are needed.

IntroductionFew data exist regarding the immunogenicity of the third dose of BNT162b2 relative to the second dose in patients with inflammatory bowel disease (IBD) on different immunosuppressive therapies. We investigated the immunogenicity of BNT162b2 vaccine booster dose in patients with IBD on infliximab combination therapy.MethodThis is a prospective single-center observational study conducted from January 1, 2022 to February 28, 2022. Patients were recruited at the time of attendance at the infusion center. Eligibility criteria included patients with a confirmed diagnosis of IBD who are receiving infliximab with azathioprine or 6-mercaptopurine. Patients who received two doses of BNT162b2 vaccine (second dose group) were compared to patients who had received three doses of BNT162b2 vaccine [third dose (booster) group]. Patients were excluded if they were infected or had symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) previously since the start of the pandemic or received other vaccines than the BNT162b2. Our primary outcome was the concentrations of SARS-CoV-2 antibodies Immunoglobulin G (IgG) and neutralizing antibodies 40–45 weeks from the first dose of BNT162b2 vaccine in patients with IBD receiving infliximab combination therapy. Medians with interquartile range (IQR) were calculated.ResultsIn total, 162 patients with IBD and receiving infliximab combination therapy were recruited, and the number of patients in both the second dose group and third dose (booster) group was 81. Mean age was 35 years old in both groups. Median (IQR) SARS-CoV-2 IgG levels were significantly lower after the second dose [125 BAU/ml (43, 192)] compared to patients who received the third booster dose [207 BAU/ml (181, 234)] (P = 0.003). Neutralizing antibody levels were also lower after the second dose [80% (21, 95)] compared to patients who received the third booster dose [96% (93, 99)] (P ≤ 0.001). The percentage of patients who achieved positive SARS-CoV-2 IgG levels in the third (booster) dose group was 96.3%, whereas it was 86.4% in the second dose group. The percentage of participants who received the third (booster) dose and achieved a positive SARS-CoV-2-neutralizing antibody level was 100%, whereas it was 88.9% in the participants who received the second dose only.ConclusionMost patients with IBD on infliximab combination therapy had positive SARS-CoV-2 IgG and neutralizing antibody concentrations 40–45 weeks post BNT162b2 vaccination. However, SARS-CoV-2 IgG and neutralizing antibody concentrations were lower in patients who received two doses only compared to patients who received a third dose. A longer follow-up study is needed to evaluate decay in antibodies over time.

To study the impact of heavy metals especially tellurium, thallium, and osmium, in recurrent pregnancy loss (RPL) and to study their association with antioxidant status and DNA damage.This case-control study included women with RPL (n = 30) and healthy pregnant women as control (n = 30). Following blood collection, serum levels of thallium, tellurium, osmium, lead, mercury, and cadmium were estimated by inductively coupled plasma mass spectrophotometer.Women with RPL exhibited significantly higher levels of heavy metals (P 0.001) when compared with control women. Intriguingly, increased levels of serum thallium, tellurium, osmium, and lead were negatively correlated with total antioxidant status (P 0.05). Further, the RPL group demonstrated strong positive correlation between heavy metals (thallium, tellurium, osmium, lead) and DNA damage (P 0.05). No significant correlation between other heavy metals and markers of cellular damage was noted.Enhanced levels of heavy metals in women with RPL and correlation of thallium, tellurium, osmium, and lead with markers of cellular damage reflect the role of heavy metal poisoning, especially thallium, tellurium, and osmium, as potential risk factor in the etiology underlying recurrent miscarriage.

To compare Saudi Arabia with other countries regarding patient attitudes towards fasting Ramadan and complications related to fasting during the COVID-19 pandemic.Data collected from Saudi Arabia and 12 other mostly Muslim majority countries, via physician administered questionnaire within post Ramadan 2020.1485 Type1 diabetes (T1DM) patients analyzed; 705 (47.5%) from Saudi Arabia vs. 780 (52.5%) from other countries. 1056 (71.1%) fasted Ramadan; 636 (90.2%) of Saudi patients vs. 420 (53.8%) of other countries. Experiencing Ramadan during the COVID-19 pandemic did not affect the Saudi T1DM patients' decision to fast while it significantly influenced their decision in other countries (1.4 vs 9.9%, P 0.001). More Saudi patients needed to break the fast due to a diabetes related complication compared to other countries (67.4% vs. 46.8%, p=0.001). The mean number of days fasted in Saudi and other countries was 24 ± 7 and 23 ± 8 days respectively. Hypoglycemic events were more common among Saudi patients during Ramadan compared to other countries 72% and 43.6% (p 0.001) respectively. There was a significant difference in timing; the largest peak for Saudi Arabia patients was after dawn (35% vs 7%, p 0.001), while it was pre-sunset for the other countries (23 vs 54%, p = 0.595). Day time-hyperglycemia was also more common among Saudi patients (48.6% vs. 39%, p 0.001), however it was a less likely cause to break the fast (25.6% vs 38.3%, p 0.001).Observing the fast of Ramadan is extremely common among Saudi T1DM patients compared to other Muslim countries and was not affected by the COVID-19 pandemic. However, it was associated with higher frequency of hypoglycemic and hyperglycemic episodes.

الملخص: ورم القواتم هو ورم نادر يفرز هرمونات الكاتيكولامين ويحدث في حوالي ٠.١-٠.٥٪ من مرضى ارتفاع ضغط الدم. تشمل علامات ورم القواتم وأعراضه عادة ارتفاع ضغط الدم ونوبات من الصداع والتعرق والخفقان. في حالات نادرة قد يشكو المريض من أعراض وعلامات أقل شيوعا من الأعراض التقليدية لورم القواتم.في هذا التقرير نناقش حالة سيدة كانت أعراض شكواها الأساسية فشل القلب الاحتقاني وجلطة في الأوردة العميقة لليد اليمنى، ثم تم تشخيصها بورم القواتم. مع العلاج الطبي والجراحي تم شفاء اعتلال عضلة القلب بالكامل وتم علاج الجلطة بأدوية منع تخثر الدم.يعتبر ورم القواتم أحد العلل المسببة لفشل القلب المفاجئ وغير المبرر و/أو سبب لجلطة الأوردة العميقة.يمكن شفاء اعتلال عضلة القلب الناجم عن ورم القواتم بالعلاج الطبي والجراحي. Abstract: Pheochromocytomas are rare catecholamine-secreting neoplasms, occurring in approximately 0.1–0.5% of the patients with hypertension. Typically, a pheochromocytoma presents with hypertension, a paroxysm of headaches, sweating, and palpitation. However, patients may also present with atypical clinical manifestations on rare occasions. This report presents a case involving a young woman who presented with two rare manifestations of pheochromocytomas: congestive heart failure and right upper extremity deep vein thrombosis (DVT). Her cardiomyopathy was completely resolved by surgical and medical therapy, while DVT was resolved with anticoagulation. Pheochromocytoma should be considered in case of sudden and unexplained cardiac failure and/or DVT. Pheochromocytoma-induced cardiomyopathy can be reversed with medical and/or surgical therapy for pheochromocytomas.

IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination has been effective in protecting against severe COVID-19 infections and related mortality. It is recommended for all individuals including patients with inflammatory bowel disease (IBD). However, safety data are lacking in this group of patients. Therefore, we aim to evaluate the short- and long-term vaccine related adverse events (AEs) in patients with IBD.MethodsThis is a prospective, observational cohort study investigating short- and long-term AEs related to the BNT162b2 vaccine in patients with IBD (study group) after the first and second dose compared to healthy participants (control group). Patients were recruited at the time of attendance to the clinic or infusion rooms. Short term (via questionnaire. Follow-up phone-based survey was made to collect data on long term (up to 24 weeks) AEs.ResultsA total of 408 patients answered the questionnaires, 204 patients in each group, the study and control group. No serious adverse events were reported in either the study or the control group after the first or the second dose. Participants in the control group reported more frequent pain at the injection site than those in the study group after the first dose [58 (57%) vs. 38 (37%) respectively, P = 0.005]. After the second dose, tiredness was reported more frequently in the control group [49 (48%)] compared to the study group [25 (24%) (P < 0.001)]. At 20–24 weeks post vaccination, 386 out of 408 (94.6%) patients were willing to participate in the follow-up phone based questionnaire [196 (96.1%) in the study group vs. 190 (93.1%) in the control group]. In both groups, none of the patients reported local, systemic, or severe adverse events (0 out of 386) at week 20–24 post second dose.ConclusionThe BNT162b2 vaccine is safe in patients with IBD. No severe or long-term adverse events were reported in our study. The frequency of local and systemic adverse events after the second dose was generally higher among healthy participants compared to patients with IBD. Further studies including a larger cohort with a longer follow-up duration are needed to assess for possible rare adverse events.

This study assessed a functional protocol to identify myocarditis or myocardial involvement in competitive athletes following SARS-CoV2 infection.We prospectively evaluated competitive athletes (n = 174) for myocarditis or myocardial involvement using the Multidisciplinary Inquiry of Athletes in Miami (MIAMI) protocol, a median of 18.5 (IQR 16-25) days following diagnosis of COVID-19 infection. The protocol included biomarker analysis, ECG, cardiopulmonary stress echocardiography testing with global longitudinal strain (GLS), and targeted cardiac MRI for athletes with abnormal findings. Patients were followed for median of 148 days.We evaluated 52 females and 122 males, with median age 21 (IQR: 19, 22) years. Five (2.9%) had evidence of myocardial involvement, including definite or probable myocarditis (n = 2). Three of the 5 athletes with myocarditis or myocardial involvement had clinically significant abnormalities during stress testing including ventricular ectopy, wall motion abnormalities and/or elevated VE/VCO2, while the other two athletes had resting ECG abnormalities. VO2Screening protocols that include exercise testing may enhance the sensitivity of detecting COVID-19 related myocardial involvement following recovery from SARS-CoV2 infection.

IntroductionAnti-drug antibodies to infliximab (ATI) and adalimumab (ATA) are associated with loss of response to tumor necrosis factor antagonist (anti-TNF) therapy in inflammatory bowel disease (IBD). We evaluated the relationship between patient sex and serum TNF antagonist drug and antibody concentrations in inflammatory bowel disease. MethodsA nationwide multicenter retrospective cohort study was conducted by evaluating patient charts from July 2018 until February 2021. The effect of patient sex on anti-drug antibodies and serum drug concentration in patients with IBD across 7 hospitals was investigated. A subgroup analysis also investigated the effect of anti-TNF combination therapy. ResultsIn the total study sample (n = 1093), males receiving infliximab had higher anti-drug antibody concentrations (38.3 vs. 22.3 AU/ml; aRoGM = 1.72, 95% CI: 1.30-2.27, p-value

Nephronophthisis (NPHP) is a group of rare inherited ciliopathy disorders characterized by the multicystic dysplastic kidney, oligohydramnios, and tubulointerstitial nephritis that progresses to end-stage renal disease (ESRD). NPHP is a clinically and genetically heterogeneous disorder with extrarenal symptoms including skeletal deformities, nervous system anomalies, and ophthalmologic features. Three clinical subtypes, infantile, juvenile, and adolescent, have been recognized based on age of onset of ESRD. Infantile nephronophthisis with asphyxiating thoracic dystrophy is a very rare association. Here, we investigated a consanguineous family having two neonates with a clinical phenotype of lethal infantile NPHP associated with asphyxiating thoracic dystrophy. Whole exome sequence data analysis identified a splice acceptor site variant (Chr3-132408107-CCT-C; NM_153240.4: c.2694-2_2694-1del) in the NPHP3 gene. The segregation of a variant in the family was confirmed by Sanger sequencing. The lethal phenotype in our case might be due to respiratory insufficiency secondary to a severely restricted thoracic cage. Present work is an exclusive depiction of lethal infantile NPHP phenotype in association with asphyxiating thoracic dystrophy that has not been reported before in families segregating NPHP3 mutations. Moreover, this work expands the phenotypic spectrum of NPHP3 variants. Overall, our findings add to the increasing body of evidence that mutations in ciliary genes/proteins show pleiotropic effects with phenotypic overlap between related disorders and apparently unrelated clinical entities.

Background Anti-drug antibodies to infliximab (ATI) and adalimumab (ATA) are associated with loss of response to tumor necrosis factor antagonist (anti-TNF) therapy in inflammatory bowel disease (IBD). We evaluated the relationship between patient sex and serum TNF antagonist drug and antibody concentrations in inflammatory bowel disease Methods A nationwide multicenter retrospective cohort study was conducted by evaluating patients’ charts from July 2018 until September 2021. The effect of patient sex on anti-drug antibodies and serum drug concentration in patients with IBD across 7 hospitals was investigated. A subgroup analysis also investigated the effect of anti-TNF combination therapy. Geometric means were calculated, and multiple linear regression was used to estimate the adjusted ratio of geometric means (RoGM) and their 95% confidence intervals (CI). Results In the total study sample (n = 1093), males receiving infliximab had higher anti-drug antibody concentrations (38.3 vs. 22.3 AU/ml; aRoGM = 1.72, 95% CI: 1.30–2.27, p-value Conclusion In patients receiving infliximab, anti-drug antibodies were higher in males than females. Consistent with this, serum drug concentrations were lower in males than females on infliximab. There was no difference in anti-drug antibody and serum drug concentrations among males and females on adalimumab. In addition, no difference in anti-drug antibodies between males and females receiving anti-TNF combination therapy was observed

Background: Iron deficiency (ID) and ID anemia (IDA) are common in the member states of the Gulf Cooperation Council (GCC). The unique genetic and lifestyle factors of the patient population in the region have necessitated the development of recommendations to help educate health-care professionals on appropriate diagnosis and management of ID/IDA. Methods: A panel of regional experts, including gastroenterologists and hematologists with expertise in the treatment of IDA, was convened to develop regional practice recommendations for ID/IDA. After reviewing the regional and international literature, the expert panel developed consensus recommendations for screening, diagnosis, and treatment of patients with IDA in the GCC region. Results: The recommendations proposed were customized to the patient population keeping in view the increasingly recognized burden of coeliac disease, high fertility and obesity rates, high prevalence of alpha- and beta-thalassemia traits, and poor tolerance and low treatment compliance with oral iron therapy. Conclusions: This consensus statement proposes recommendations for screening, diagnosis, and treatment of IDA in the GCC region.

Recent studies have shown the role of mitochondrial DNA (mtDNA) variants in the pathogenesis of both psoriasis (Ps) and type 2 diabetes (T2D) amongst different ethnicities. However, no studies have investigated the mtDNA variants present in patients with Ps, T2D, and both Ps and T2D (Ps-T2D) in the Arab population. The entire mitochondrial genomes of Kuwaiti subjects with Ps, T2D, Ps-T2D and healthy controls were sequenced using Ion Torrent next-generation sequencing. A total of 36 novel mutations and 51 previously reported mutations were identified in the patient groups that were absent in the controls. Amongst the novel mutations, eight were non-synonymous and exhibited amino acid changes. Of these, two missense mutations (G5262A and A12397G) in the ND genes were detected in the Ps group and a C15735T missense mutation in the CYB gene was detected in Ps-T2D. Other known sequence variations were seen more frequently in all or certain patient groups compared with the controls (P

OBJECTIVES: The DaR Global survey was conducted to determine the impact of the COVID-19 pandemic on the intentions to fast and the outcomes of fasting in

Objective: Published data show a clear link between psoriasis (Ps) and the increasing prevalence of comorbid conditions, such as diabetes mellitus type 2 (DM2). The role of the mitochondrial genomic haplogroup in the potential coexistence of Ps and DM2 comorbidity is the subject of this study. Material and Methods: Ninety-eight Kuwaiti individuals were recruited in 4 cohorts (20 healthy controls, 15 with DM2, 34 with Ps, and 29 with Ps and diabetes mellitus). An Ion Torrent S5XL was used to sequence mitochondrial DNA (mtDNA). χ2 test was used to assess differences in the distribution of each haplogroup between cases and controls (p < 0.05). The Bonferroni correction was applied (p < 0.004). The mtDNA haplogroups were analyzed by HaploGrep. Results: Haplogroups R0, U, J, T, N, L3, M, H, X, HV, R, and K were detected in the studied population. Haplogroup M had a high risk for Ps (odds ratio (OR) 4.0, p = 0.003). Haplogroup R0 and J had decreased the risk of DM2 (OR 0.28, p = 0.007). Conclusion: Our results indicated that mtDNA haplogroups have a potential contribution to the pathogenesis of Ps and DM2 comorbidity. We show for the first time that the comorbidity of diabetes in Ps may be related to mitochondrial dysfunction.

The hepatitis C virus (HCV) is estimated to affect 71 million people worldwide. In 2016, the World Health Organization adopted the first global health sector strategy to eliminate viral hepatitis as a public health threat by 2030. In December 2018, the European Association for the Study of the Liver, International Liver Foundation convened an expert panel to address the elimination of HCV in Kuwait. Several steps have already been taken to eliminate HCV in Kuwait, including free HCV treatment for Kuwait's citizens, high blood safety standards, and the implementation of screening and awareness programs. The expert panel made several recommendations aimed at accelerating the elimination of HCV in Kuwait: The development of a national strategy and action plan to guide all HCV elimination activities; the formation of a coordination mechanism to support collaboration between hepatitis working committees; the prioritization of micro-elimination at primary, secondary or tertiary facilities, in prisons and rehabilitation centers; and ensuring the involvement of multiple stakeholders - including relevant civil society groups - in all activities. Enhanced screening and linkage to care should be prioritized in Kuwait, with the expansion of the prescriber base to primary healthcare providers and nurse practitioners to be considered. Raising awareness and educating people about HCV infection also remain essential to achieve the goal of HCV elimination. Lastly, a national HCV registry should be developed to help monitor the implementation of viral hepatitis plans and progress towards achieving national and international targets.

Background: Vaccination is a promising strategy to protect vulnerable groups like inflammatory bowel disease (IBD) patients against COVID-19 and associated severe outcomes. COVID-19 vaccine clinical trials excluded IBD patients taking infliximab with azathioprine or 6-mercaptopurine (infliximab combination). Therefore, we sought to evaluate serologic responses to COVID-19 vaccination with the mRNA vaccine, BNT162b2, in patients with IBD receiving infliximab combination therapy compared with healthy participants. Method: This was a multicenter prospective study. Patients with IBD were recruited at the time of attendance at infusion center between 1 August 2021, and 15 September 2021. Our primary outcome were the concentrations of SARS-CoV-2 antibodies 4–10 weeks after vaccination with two doses of BNT162b2 vaccine in patients with IBD taking infliximab combination therapy (study group) compared with a healthy participants group (control group). Both study and control groups were matched for age, sex, and time-since-last-vaccine-dose using optimal pair-matching method. Results: In total, 116 participants were recruited in the study, 58 patients in the study group and 58 in the control group. Median (IQR) IgG concentrations were lower in the study group (99 BAU/mL (40, 177)) than the control group (139 BAU/mL (120, 188)) following vaccination (p = 0.0032). Neutralizing antibodies were also lower in the study group compared with the control group (64% (23, 94) vs. 91% (85, 94), p &lt, 0.001). The median IgA levels in the study group were also significantly lower when compared with the control group (6 U/mL (3, 34) vs. 13 U/mL (7, 30), p = 0.0097). In the study group, the percentages of patients who achieved positive IgG, neutralizing antibody and IgA levels were 81%, 75%, and 40%, respectively. In the control group, all participants (100%) had positive IgG and neutralizing antibody levels while 62% had positive IgA levels. Conclusion: In patients with IBD receiving infliximab combination therapy, SARS-CoV2 IgG, IgA, and neutralizing antibody levels after BNT162b2 vaccination were lower compared with healthy participants. However, most patients treated with infliximab combination therapy seroconverted after two doses of the vaccine.

Objectives: To determine the optimal cutoff value for neck circumference (NC) that define overweight/obesity and assess its predictive potential for cardiometabolic risks (CMR) among Saudi subjects. Methods: A cross sectional study of 785 adults recruited from a public health awareness campaign in Medina, Saudi Arabia during June 2015. Waist circumference (WC), NC, body mass index (BMI), blood pressure (BP), and random blood glucose (RBG) were assessed, and the presence of CMR were collected by a questionnaire. Pearson’s correlation coefficients were used to evaluate the associations of NC with other anthropometric indices and CMR. The optimal cutoff value for NC to identify overweight/obesity was determined by receiver operating characteristic (ROC) curves. Results: There were significant correlations between NC and BMI, weight, WC, age, RBG, and BP. The area under the curve for NC and WC in the ROC analysis was 0.86 for men and 0.77 for women, and NC ≥39.25 cm for men and ≥34.75 cm for women were the best cutoff levels for identifying subjects with central obesity with an 89% sensitivity and a 71% specificity for men and an 80% sensitivity and a 65% specificity for women. These cutoff levels for NC were associated with a significantly increased risk for diabetes, dyslipidemia, and hypertension. Conclusion: Neck circumference is positively correlated with BMI and WC, and can be used to identify overweight/obesity and predict CMR in Saudi individuals. Saudi Med J 2017; Vol. 38 (12): 1219-1223 doi: 10.15537/smj.2017.12.20926 How to cite this article: Alfadhli EM, Sandokji AA, Zahid BN, Makkawi MA, Alshenaifi RF, Thani TS, Habeeb HA.Neck circumference as a marker of obesity and a predictor of cardiometabolic risk among Saudi subjects. Saudi Med J . 2017 Dec;38(12):1219-1223. doi: 10.15537/smj.2017.12.20926.

The purpose of our study was to identify the currently lacking molecular mechanism that accounts for the co-occurrence of two seemingly disparate diseases: psoriasis and type II diabetes. We aimed to investigate a panel of 84 genes related to the diabetic regulatory network in psoriasis (Ps), psoriasis type II diabetes (Ps-T2D), type II diabetes (T2D) and healthy control (HC). We hypothesize that such attempts would provide novel diagnostic markers and/or insights into pathogenesis of the disease. A quantitative Real Time-PCR Human Diabetes RT2 Profiler PCR Array was chosen to explore the expression profile 84 diabetic genes in study subjects. Statistical analysis was carried out using appropriate software. The analysis revealed three candidate genes GSK3B, PTPN1, STX4 that are differentially expressed in study subjects. GSK3B was highly significant in Ps-T2D (P = 0.00018, FR = − 26.6), followed by Ps (P = 0.0028, FR = − 14.5) and T2D groups (P = 0.032, FR = − 5.9). PTPN1 showed significant association only with PS-T2D (P = 0.00027, FR = − 8.5). STX4 showed significant association with both Ps (P = 0.0002, FR = − 20) and Ps-T2D (P = 0.0016, FR = − 11.2). ACE represents an additional marker that showed suggestive association with Ps (P = 0.0079, FR = − 9.37). Our study highlights the complex genetics of Ps-T2D and present biomarkers for the development of T2D in Ps cases.

The expression of interferon inducible genes are reported to be heightened in systemic lupus erythematosus (SLE); nevertheless, not much is known regarding the genetic variants underlying these genes and their role in the pathogenesis of disease. Herein, we aim to explore the potential association and contribution of polymorphisms in MX1 gene (i) promoter with part of exon 1 (ii) intron 6, and (iii) their resulting haplotypes, with susceptibility to SLE. A total of 306 subjects, 152 SLE and 154 healthy controls (HC), were screened by direct sequencing method. Statistical analysis was carried out using appropriate software. The screening region of interest in MX1 revealed the existence of promoter (-123C/A, -88G/T, -20 A/C) and intron 6 (+9862G/A, +10190G/A, +9901C/G, +9920C/A, +9959C/T, +10047A/G) variants in SLE and HC. A significant association was observed between MX1 -88G/T SNP and susceptibility to SLE (χ (2) = 4.18, p = 0.04, OR = 1.89, 95 % CI 1.03-3.5). Haplotype analysis also revealed increased risk of SLE among individuals carrying CTA haplotype (-123 C, -88 T, -20 A) (χ (2) = 5.74, p = 0.017, OR = 4.28, 95 % CI 1.30-14.06). None of the other tested variants showed any significant association with SLE. The present study is the first to reveal the influence of genetic variation in MX1 gene in susceptibility to SLE.

The complement system anchors the innate inflammatory response by triggering both cell-mediated and antibody-mediated immune responses against pathogens. The complement system also plays a critical role in sterile tissue injury by responding to damage-associated molecular patterns. The degree and duration of complement activation may be a critical variable controlling the balance between regenerative and destructive inflammation following sterile injury. Recent studies in kidney transplantation suggest that aberrant complement activation may play a significant role in delayed graft function following transplantation, confirming results obtained from rodent models of renal ischemia/reperfusion (I/R) injury. Deactivating the complement cascade through targeting anaphylatoxins (C3a/C5a) might be an effective clinical strategy to dampen reperfusion injury and reduce delayed graft function in liver transplantation. Targeting the complement cascade may be critical in donor livers with mild to moderate steatosis, where elevated lipid burden amplifies stress responses and increases hepatocyte turnover. Steatosis-driven complement activation in the donor liver may also have implications in rejection and thrombolytic complications following transplantation. This review focuses on the roles of complement activation in liver I/R injury, strategies to target complement activation in liver I/R, and potential opportunities to translate these strategies to transplanting donor livers with mild to moderate steatosis.

BACKGROUND AND OBJECTIVES: Use of the criteria of the International Association of Diabetes and Pregnancy Study Group (IADPSG) identifies additional cases of gestational diabetes mellitus (GDM) that have a lesser degree of hyperglycemia. The objective of this study was to compare the clinical characteristics and the pregnancy outcomes of GDM cases identified by IADPSG versus those identified by the former American Diabetes Association (ADA) criteria. DESIGN AND SETTING: Prospective cohort study of Saudi women conducted at the Maternity and Children Hospital, Madinah, Saudi Arabia from October 2011 to August 2012. PATIENTS AND METHODS: Consecutive pregnant women treated in the antenatal service performed oral glucose tolerance tests between 24 to 28 weeks of gestation. GDM was diagnosed according to IADPSG and the former ADA criteria. The women were divided into three groups by GDM diagnosed by both criteria, additional GDM identified by the IADPSG criteria, and cases with normal glucose tolerance (NGT). Clinical characteristics and pregnancy outcomes were compared. RESULTS: Of 277 women who underwent OGTT, 47 (16.9%) were diagnosed by the former ADA criteria and 115 (41.5%) by the IADPSG criteria. The IADPSG criteria identified all women with GDM by the former ADA criteria and an additional 68 cases. The additional GDM cases had the same clinical characteristics as cases diagnosed by both criteria except for lower blood pressure and less frequent glycosuria. On the other hand, they were older, heavier and had a higher frequency of past GDM and history of recurrent abortions than the NGT group. In addition, they had significantly more cesarean deliveries, neonatal hypoglycemia, and a lower Apgar score than the NGT group. LIMITATIONS: Relatively small numbers of subjects, which could limit the power of statistical findings. CONCLUSIONS: The IADPSG criteria increased GDM frequency. The additional GDM cases identified by IADPSG have the same clinical characteristics and adverse pregnancy outcomes as cases with GDM identified by the older criteria.

Systemic lupus erythematosus (lupus) is a genetically heterogeneous autoimmune disorder with an obscure etiology. With 92-94% of human genes exhibiting alternative splicing, gaining insights to such events may lead to better diagnostics. Herein, we explored the genome-wide peripheral blood transcriptome of lupus and its severe form lupus-nephritis (LN) compared to healthy controls (HC). Age/gender/ethnically-matched Arab females were tested using high-density arrays and statistical analysis was carried out using appropriate software. Analysis revealed 15 splice variants that are differentially expressed between lupus/HC and 99 variants between LN/HC (p ≤ 0.05, SI> or ≤ 0.5, Benjamin Hochberg-False discovery rate correction). Comparison between LN/lupus revealed 7 variants that significantly differed in expression. Pathway analysis of differentially spliced-genes postulated 11 significant pathways in lupus and 12 in LN (p

BACKGROUND AND OBJECTIVES: The prevalence of gestational diabetes (GDM) has increased recently worldwide, mainly due to adoption of the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria. The objectives of this study were to determine the prevalence of GDM in Saudi women and to assess risk factors and pregnancy outcomes using the IADPSG criteria. DESIGN AND SETTING: A prospective descriptive study of pregnant Saudi women presenting at the Maternity and Children Hospital, Medina, Saudi Arabia, between October 2011 and June 2014. METHODS: Fasting plasma glucose, glycated hemoglobin, and random plasma glucose concentrations were obtained for all participants at the first antenatal visit. In women with normal results, screening for GDM was performed at 24 to 28 weeks of gestation, with a 75-g oral glucose tolerance test (OGTT). Women who had GDM were treated with diet, exercise, and insulin as needed. Pregnancy outcomes were recorded after delivery. Multiple logistic regression was used to assess possible risk factors for GDM. RESULTS: Early screenings showed abnormal glucose in 211 of 954 women (22.1%). In 445 women, the OGTT showed GDM in 183 women (39.4%). GDM cases identified by OGTT and by early screening increased the rate of GDM to 51% (292 women). Older maternal age, higher body mass index, higher blood pressure, past GDM, history of delivering a malformed child, and family history of diabetes were the main risk factors for GDM. GDM increased the risk of neonatal hypoglycemia (OR 9.353), low Apgar score (OR 5.546), and induction of labor (OR 2.33). The newborns of GDM mothers had a higher birth weight: 3043 g vs. 2890 g in the non-GDM group (P=.004). Other maternal and neonatal outcomes were not significantly different between the two groups. CONCLUSION: The prevalence of GDM is high among Saudi women. Timely and effective treatment reduces perinatal morbidity and improves outcomes.

Background Circulating Sex hormone binding globulin (SHBG) levels are inversely associated with insulin resistance. This study was conducted to compare maternal serum SHBG level between pregnant women with normal glucose tolerance and those with gestational diabetes (GDM) and to investigate the roll of SHBG in GDM diagnosis. Methods This was a case controlled study of 90 pregnant women, 45 women with GDM and 45 matched controls, attending obstetrics clinic at Ohud Hospital, Madina, Saudi Arabia between April 2014 and March 2015. Measurement of serum SHBG levels by Enzyme-linked immunosorbent assay (ELISA) method were done between 24 and 28 weeks of gestation. The best cut-off point of SHBG to diagnose GDM was calculated in receiver operating characteristic curve. Results Compared with the control group, SHBG concentrations were significantly lower in the GDM group; median 23 nmol/L (18–30) vs. 78 nmol/L (65–96), p

The purpose of this study was to analyze the effect of the HumDN1 VNTR polymorphism on DNASE1 mRNA expression and enzyme activity in lupus (SLE) and rheumatoid arthritis (RA) compared to healthy control (HC). Kuwait subjects (n = 500) matched by age/gender/ethnicity were genotyped by fragment-analysis. DNASE1 expression was analysed using quantitative Real-Time-PCR and sera from subjects were screened for DNase1 reduction activity by ELISA. Allele and genotype distribution of HumDN1 VNTR revealed a significant association with susceptibility to SLE and RA (p0.05, OR1). Relative expression analysis revealed a significant increase in DNASE1 mRNA in SLE (p = 0.0001) and RA (p = 0.002) compared to HC. Stratification of subjects revealed, increased DNASE1 expression in SLE with 5/5 (p = 0.0001), 3/4 (p = 0.0001) and 3/5 genotype (p = 0.01). A reduction in DNASE1 expression was specifically observed in SLE with 4,4 genotype (p = 0.0004). RA patients with 3/4 genotype (p = 0.02) showed a significant increase in DNASE1 expression. Similarly a significant association was observed between DNase1 reduction activity and SLE (p = 0.0001). SLE patients with 3,4 (p = 0.0001) and 5,5 genotype (p = 0.0001) showed increased DNase1 reduction activity, while a lack of association was observed with RA. The present study is the first to reveal the effect of HumDN1 VNTR on DNASE1 expression in SLE and RA.

The present study was aimed to explore the effect of two selected polymorphisms from interleukin-1β (IL-1β) gene [SNPs -511 and +3953] and a variable number of tandem repeat (VNTR) from interleukin-1 receptor antagonist (IL-1RN) on the susceptibility and severity of alopecia areata (AA) in Kuwaiti subjects. IL-1β SNPs C-511T, C+3953T, and IL-1RN VNTR were screened in 96 alopecia patients classified clinically, according to the disease severity as patchy (P), semiuniversalis (SU), and universalis (U), and in 100 ethnically matched healthy controls. Polymerase chain reaction followed by restriction fragment length polymorphism and direct DNA sequencing were employed for genotyping. Comparing the stratified AA cases based on severity, IL-β SNP C-511T showed a significant association (genotype and allelotype levels p = 0.03 and p = 0.028, respectively). Genotype CC was 50 % more frequent in U cases than in P or SU. When P and SU were grouped and tested against U, a significant difference was observed (genotype and allelotype levels p = 0.006 and p = 0.008, respectively). Compared to genotype CT, carriers of IL-1β -511 CC genotype showed an increased risk to develop severe AA (p = 0.004, OR = 4.14, 95 % CI = 1.61-10.69). Four alleles and genotypes (1/1, 1/3, 1/4, and 2/2) of IL-1RN VNTR were detected in AA patients while only two (1/1 and 1/3) in controls. IL-1RN VNTR showed genotype and allelotype association with AA (p = 0.05 and p = 0.025, respectively). Our results showed that IL-1β and IL-1RN VNTR are significantly associated with the susceptibility to alopecia areata. Allele C of the IL-β C-511T SNP is linked to the severe form of AA.

Aim: To explore the potential genetic association of CTLA-4 Exon1 +49A/G and 3′UTR (AT)n to susceptibility to systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and overlapping (OP) autoimmunity; affected with more than one autoimmune disease. Expression of two major CTLA-4 isoforms; full length (mCTLA-4) and soluble (sCTLA-4) were explored in all subjects. A total of 680-age/gender/ethnically matched Kuwaitis were recruited and polymerase chain reaction (PCR)-fragment analysis was employed for genotyping both markers. mCTLA-4 and sCTLA-4 mRNA expression were analyzed using quantitative real time-PCR. The enzyme-linked immunosorbent assay (ELISA) was used to screen sCTLA-4 in all subjects' sera. Results: Only two CTLA-4 3′UTR (AT)n allelotypes; (AT)15 and (AT)6 were detected. The heterozygous (AT)15/6 genotype confers protectivity rather than susceptibility to SLE (p=0.01, odds ratio=0.43, and confidence interval=0.21–0.86). No significant association was observed between Exon 1 +49A/G and any of the tested diseases. A consistently high serum sCTLA-4 level was observed in RA (6.8 ng/mL, p=0.005), SLE (6.34 ng/mL, p=0.007), and OP (8.75 ng/mL, p=0.012) compared to healthy control. A significant increase in the expression of sCTLA-4 mRNA was observed in OP (p=0.05) and SLE (p=0.047), while a significant increase in the expression of mCTLA-4 (p=0.01) was observed only in OP. Conclusion: The present study is the first to report a statistically significant association between OP and serum sCTLA-4. The novelty of our study is the significance of CTLA-4 in the pathogenesis of OP besides SLE and RA.

The purpose of this study was to analyse the effect of the T-786C polymorphism and intron 4 27 bp variable number tandem repeat(VNTR) eNOS markers for their potential association with Systemic Lupus Erythematosus(SLE), Hashimotos thyroiditis(HT) and Rheumatoid arthritis(RA) as well as to explore their effect on eNOS mRNA expression and nitrate production(NOx). Kuwaitis (n= 383) matched by age, gender and ethnicity were genotyped by fluorescent-labelled-restriction fragment length polymorphism (RFLP) and fragment analysis. Expression of eNOS mRNA was analysed using RT-PCR and sera from subjects were screened for NOx using ELISA. Analysis of the allelic frequency revealed a significant association of the 4b allele with susceptibility to SLE (p = 0.0092,OR = 1.76). The 4bb genotype was found to be associated with SLE (p = 0.0076,OR = 1.97) and HT (p = 0.05,OR = 1.81). Allelic and genotypic distribution did not differ between RA patients and healthy control subjects. The 4bb genotype resulted in reduced expression of eNOS mRNA in SLE, RA and HT, but only the reduction in HT was significant (p= 0.05). The 4ab genotype revealed a significant association with increased eNOS expression in HT (p= 0.03) and RA (p= 0.014) patients, and elevated NOx levels were detected in the autoimmune disease cohorts (p< 0.05) when compared to healthy control subjects. The T-786C SNP failed to show a significant association (p> 0.05) with SLE, HT, and RA patients. This study is the first to reveal a significant association between the 4bb genotype of the 27 bp VNTR and susceptibility to HT. The expression of eNOS is related to the number of 27 bp repeats, with heterozygous 4bb repeats showing a decrease in eNOS expression. eNOS – endothelial nitric oxide synthase.

Objective: This study was undertaken to determine the prevalence of congenital cytomegalovirus (CMV) infection in pregnant women at the end of pregnancy in Kuwait using cord blood and maternal urine. Subjects and Methods: Urine samples were collected prior to childbirth, and cord blood was collected immediately after delivery from 983 women. Anti-CMV IgG and IgM antibodies were determined using ELISA; CMV DNA was detected using nested PCR, and viral load was calculated using real-time PCR. CMV concentration in samples was categorized as low when the viral load ≤103 copies/µl, intermediate when the viral load = 103–104 copies/µl, and high when the viral load >104 copies/µl. The cord blood serology outcome was compared to cord blood PCR, cord blood viral load, maternal urine PCR and viral load analyses. Results: Serology showed that of the 983 cord blood samples, 89 (9%) were positive for anti-CMV IgM antibodies; PCR test showed 44 (4.5%) contained CMV DNA, and there was a high viral load in all. Maternal urine PCR showed that 9 (10.11%) women had CMV DNA, and there was a high viral load in 7 (78%). The kappa test for measures of agreement showed a reasonable agreement (0.45) between cord blood PCR and urine PCR. Conclusion: This study showed that CMV infection in the cord blood sera of pregnant women is common in Kuwait and highlights the need for more clinically based studies to follow up newborns with congenital CMV infection.

arginine and molecular oxygen in vascular endothelial cells (Kincl et al.2009). Angiotensin-converting enzyme (ACE), present on the surface of vascularendothelial cells, generates the potent vasoconstrictor angiotensin II from angio-tensin I and inactivates the vasodilator bradykinin (Erdo¨s 1990). Angiotensin IImodulates NO synthesis in cardiovascular tissue, and NO modulates the action ofangiotensin II (Dubey et al. 1995; Nakagami et al. 1999). Many polymorphismslocated in the ACE and NOS3 genes have been reported to play a major role in thepathogenesis of coronary artery disease (CAD) and related outcomes (Cambienet al. 1992; Yoshimura et al. 2000; Bor-Kucukatay et al. 2010; Hamelin et al. 2011).The -T786C polymorphism in the NOS3 gene causes a reduction of promoteractivity and has been reported as a risk factor for coronary spasm in a Japanesepopulation (Nakayama et al. 1999). The Glu298Asp polymorphism has been

Eur J Clin Invest 2011; 41 (10): 1105–1112 Abstract Background High-density lipoprotein cholesterol (HDL-C) levels are low in Iranians. Low HDL-C is the most frequent phenotype in metabolic syndrome (MetS) among the Iranian population (32%). This has been claimed to be related to genetic factors. Materials and methods To investigate possible genes linked to this disorder, 12 microsatellite markers were selected. They were used in 107 families with MetS and low HDL-C to analyse relevant association and linkage signals. Result Family-based association tests under the biallelic mode gave many positive association signals. Higher association – after correction for multiple testing – was found to be linked with marker D8S1743 and D11S1304 (P

Homozygous beta-thalassemia is a common genetic disorder in the Arabian Peninsula and an important cause of morbidity in Kuwait. The anemia is so severe that chronic blood transfusions, and the resulting iron overload, cause a shift in immunoregulatory balances and a deficiency in zinc. It was reported that individual immunological profile of CD8+ T-lymphocytes may have a modifying effect on the severity of iron overload in HFE homozygous hemochromatosis patients, with low numbers being negatively correlated with the total amount of body iron stores. This has not been tested in thalassemia major patients. This study was designed to utilize flow cytometric immunophenotyping to characterize effects of regular blood transfusion, and high serum ferritin levels because of irregular use of iron chelation therapy on T lymphocytes (CD2, CD3, CD4 and CD8), B lymphocytes (CD19) and natural killer cells (CD56) and zinc levels in the blood of patients with thalassemia major (n = 49) and healthy normal controls (n = 60) in Kuwait. None of the patients had active infections. T-cell markers' percentage levels were comparable between patients and controls (P > 0.05), while B cell marker (CD19) was significantly higher in patients (P = 0.007). Patients had lower percentage levels of CD56 cells (P = 0.007) and normal serum zinc. All patients had high serum ferritin levels with no significant correlation to CD8+ T lymphocytes (P > 0.05). High iron stores did not have an effect on T lymphocytes' profile, with normal zinc levels perhaps related to non compliance with chelation therapy. The high B cell marker may be indicative of stimulation of antibody producing cells as a result of regular blood transfusions.

Introduction: Patients with thalassemia major often present with a hypercoagulable state, the pathogenesis of which is still not understood. Materials and Methods: This study evaluates the risk factors for hypercoagulability in 50 β-thalassemia major patients and 50 healthy controls. Fasting total homocysteine, protein C (PC), protein S (PS), antithrombin (AT), activated protein C resistance (APCR) and lupus anticoagulant (LA) were assessed. MTHFR C677T mutation was determined. Results: Significant reductions in PC, PS and AT were noted in patients. Only 4% of the patients had hyperhomocysteinemia. Thirty-two percent of the patients were heterozygous and 4% were homozygous for MTHFR C677T mutation. Conclusion: The natural coagulation inhibitors PC, PS and AT were significantly reduced in patients with β-thalassemia major and were thus important risk factors for the hypercoagulable state, but hyperhomocysteinemia and MTHFR mutation do not seem to be significant risk factors for thromboembolic events.

A woman with isolated ACTH deficiency and empty sella in a background of primary antiphospholipid syndrome (APS) is described. A 24-year-old woman was admitted for premature delivery at 30 weeks of gestation and was found to have severe pulmonary hypertension and right sided heart failure. A few hours after delivery, without excessive blood loss, she suddenly lost consciousness, and was found to be hypotensive and hypoglycemic. The findings on hormonal evaluation were consistent with isolated secondary adrenal insufficiency as both ACTH and cortisol levels were very low. Magnetic resonance imaging of the pituitary fossa showed an empty sella. Her severe cor pulmonale was found to be due to primary APS. The patient was given replacement of glucocorticoid and treated with frusemide, spironolactone, warfarin, sildenafil and inhaled iloprost for her pulmonary hypertension, after which her clinical status improved substantially. Follow-up tests of the hypothalamic-pituitary axis found normal serum LH, FSH, TSH, FT4 and prolactin secretion; serum ACTH and plasma cortisol levels remained low.

Objectives: We aimed to investigate germline mutation in another extended von Hippel-Lindau (VHL) family in Kuwait with Arabian and Persian genetic admixture. Materials andMethod: Polymerase chain reaction (PCR) followed by single-strand conformation polymorphism (SSCP) and direct sequencing of the PCR amplicons, that showed clear band shift, were used to screen the VHL gene in the index patient, 20 members of her family and 55 healthy controls of matching ethnicity. Result: The clinical history of all patients revealed multiple hemangioblastomas in various organs without pheochromocytomas. SSCP showed a clear band shift in 2 PCR amplicons, which were then sequenced. One was in the promoter region revealing a polymorphic site (A–123G) found as heterozygous in 40% of the healthy control subjects of the same ethnicity. The second band shift was in exon 2 seen in all clinically diagnosed VHL cases but not in the healthy members of the family or the screened healthy population. Direct sequencing revealed it was a heterozygous missense mutation G564T (Trp117Cys). Tracking the mutation in the family pedigree showed its origin from the Persian side. Conclusion: This is a second missense G564T mutation in another VHL patient from Kuwait that will help expand our knowledge of the VHL gene mutation spectrum in this region of the world.

Objectives: This study aimed at determining the effects of cigarette smoking based on gender, on several hematological parameters and von Willebrand factor protein in the asymptomatic Arab population of Kuwait. Subjects and Methods: Ninety-two subjects participated in this study: 55 males (31 smokers and 24 nonsmokers) and 37 females (18 smokers and 19 nonsmokers). Complete blood count results were obtained using Beckman Coulter Hematology Analyzer. Von Willebrand factor functional activity was determined using an enzyme-linked immunoassay-based test in which anti-von Willebrand factor IgG monoclonal antibody was used that recognizes a functional epitope of the protein. The coagulation profile was obtained using ACL® 9000 coagulation analyzer. Results: Male smokers had significantly higher levels of white blood cell count (p = 0.03) and von Willebrand factor protein levels (p = 0.029), and a significantly shorter thrombin time (p = 0.019) than nonsmokers. Smoking did not appear to affect any of the parameters analyzed in females as no significant difference was found between smokers and nonsmokers (p > 0.05). Conclusion: Our results showed that smoking affected white blood cell count and von Willebrand factor levels in males and not in females, and as such could be potential markers for smoking-induced endothelial damage in asymptomatic Arab male smokers.

BACKGROUND: Chronic radiation proctopathy (CRP) is a troublesome complication of radiotherapy to the pelvis for which current treatment modalities are suboptimal. Currently, the application of formalin to the rectal mucosa (AFR) and thermal ablation with argon plasma coagulation (APC) are the most promising options.OBJECTIVE: To compare the efficacy and safety of AFR with APC for CRP.PATIENTS AND METHODS: Records of 22 patients (male to female ratio, 19:3; mean age, 74 years) who received either APC or AFR for chronic hematochezia caused by CRP, and who were evaluated and treated between May 1998 and April 2002, were reviewed. Complete evaluations were made three months after completion of each therapeutic modality. Patients were considered to be responders if there was a 10% increase in hemoglobin from baseline or complete normalization of hemoglobin (male patients, higher than 130 g/L; female patients, higher than 115 g/L) without the requirement for blood transfusion.RESULTS: The mean hemoglobin level before therapy was 107 g/L. Patients received an average of 1.78 sessions for APC and 1.81 sessions for AFR. Eleven patients (50%) were treated with APC alone, eight patients (36%) with AFR alone and three (14%) with both modalities (two with AFR followed by APC, and one with APC followed by AFR). Eleven of 14 patients (79%) in the APC group were responders, compared with three of 11 patients (27%) in the AFR group (P=0.017). In the APC group, seven of 11 responders required only a single session, while in the AFR group, only one patient responded after a single session. Adverse events (nausea, vomiting, flushing, abdominal cramps, rectal pain and fever) occurred in two patients after APC and in nine patients after AFR (P=0.001). In the APC group, the mean hemoglobin level increase was 20 g/L at three months follow-up, compared with 14 g/L in the AFR group.CONCLUSION: This retrospective study suggests that APC is more effective and safe than topical AFR to control hematochezia caused by CRP. Further studies are needed to confirm this observation.

Objective: To examine the concordance between lifestyle practices and beliefs of people living in Kuwait, and between their lifestyle practices and established evidence-informed recommendations for health. Subjects and Methods: A cross-sectional interview questionnaire study was conducted using a convenience sample of 100 adults living in Kuwait (age range 19-75 years). The interview included sections on demographics, and lifestyle-related practices and beliefs related to smoking, diet/nutrition, physical activity/exercise, sleep, and stress. Diet/nutrition and physical activity/exercise benchmarks were based on international standards. Analyses included descriptive statistics and the χ2 test. Results: Beliefs about the importance of nutrition in lifestyle-related conditions were limited, and this was apparent in participants' dietary habits, e.g., low consumption of fruit/vegetables and multigrains: 16 (16%) and 9 (9%) met the recommended guidelines, respectively. Ninety-nine (99%) believed physical activity/exercise affects health overall, and 44 (44%) exercised regularly. Of the sample of 100, 20 (20%) exercised in accordance with evidence-based recommendations for maximal health. Compared with beliefs about other lifestyle-related behaviors/attributes, respondents believed nutrition contributed more than stress to heart disease, cancer, and stroke, and stress contributed more than nutrition to hypertension and diabetes. Conclusion: In this study, our findings showed a discrepancy between lifestyle-related practices and beliefs, and between each of these and evidence-based recommendations for maximal health, i.e., not smoking, several servings of fruit and vegetables and whole-grain foods daily, healthy weight, restorative sleep, and low-to-moderate stress levels.

Gestational diabetes mellitus (GDM) is the most common medical complication of pregnancy. It is associated with maternal and neonatal adverse outcomes. Maintaining adequate blood glucose levels in GDM reduces morbidity for both mother and baby. There is a lack of uniform strategies for screening and diagnosing GDM globally. This review covers the latest update in the diagnosis and management of GDM. The initial treatment of GDM consists of diet and exercise. If these measures fail to achieve glycemic goals, insulin should be initiated. Insulin analogs are more physiological than human insulin, and are associated with less risk of hypoglycemia, and may provide better glycemic control. Insulin lispro, aspart, and detemir are approved to be used in pregnancy. Insulin glargine is not approved in pregnancy, but the existing studies did not show any contraindications. The use of oral hypoglycemic agents; glyburide and metformin seems to be safe and effective in pregnancy. Saudi Med J 2015; Vol. 36 (4): 399-406 doi: 10.15537/smj.2015.4.10307

Objectives: To compare the performance of SEDIsystemTM, a fully automated analyzer for the measurement of the erythrocyte sedimentation rate (ESR), with the manual Westergren method. Materials and Methods: Both methods were applied to 150 randomly selected subjects. The linear regression and Bland and Altman data analysis methods were used to measure the agreement between the automated and manual methods. Results: The regression analysis showed a good correlation between the two methods (r = 0.91). The Bland and Altman data analysis showed no systematic bias (95% confidence interval for mean difference); however, limits of agreement were between 11.52 and –37.88. This indicates that ESR values measured by the SEDIsystem may be 11.52 mm/h above or 37.88 mm/h below the reference method. A greater scatter of data was also observed with abnormally high (>25 mm/h) ESR results (mean of difference = –21.4 and limits of agreement = –45.2 and 2.26) compared with normal (Conclusion: The Bland and Altman statistical analysis showed a wide degree of scatter between results obtained by the two ESR techniques that was not clearly demonstrated using the linear regression analysis. The automated system was found to underestimate ESR with the Bland and Altman statistical analysis, and therefore a correction factor is recommended.

Context: Diet and nutrition are important factors in the promotion and maintenance of good health. Physicians are involved in medical nutrition therapy of their patients; however, little is known on how physicians are personally adherent to good nutrition. The aim of the study was to assess the nutritional practices of Saudi physicians. Subjects and Methods: This is a pilot study that included 48 healthy Saudi physicians, of both genders, randomly selected from King Fahad Hospital, Madina, Saudi Arabia from June 2013 to December 2013. Self-reported dietary intake over 24 h was assessed. The adequacy of nutrient intake was evaluated by comparing the physicians’ intake to the dietary reference intakes (DRI). Results: The mean age of physicians was 41.6 ± 10 years, weight was 78 ± 20.2 kg, and body mass index was 27.76 ± 5.37 kg/m2. They reported adequate daily consumption of food energy with high intake of carbohydrate (178.5 ± 46.4%) of DRI and high fat and protein intake from animal sources with low fiber intake (34.9 ± 25.1%) of DRI. Daily intakes for most of the micronutrients were lower than recommended with the exception of phosphorus, Vitamin E, and Vitamin B12 with no significant difference between males and females, except for lower intake of iron and Vitamin D by females. Vitamin D was the most severe deficient vitamin; 46.1 ± 53.9% of DRI. Conclusions: Nutritional practices of the sampled group of Saudi Physicians were not optimal. They have a high prevalence of micronutrients deficiencies. In addition, they tend to consume less fiber, more carbohydrate, and food from animal sources. Actions are needed to control nutrition status in Saudi Arabia, including the adoption of healthy eating pattern early in life, extensive nutrition and health education, and intervention strategies.