Essential metals, vitamins and antioxidant enzyme activities in COVID-19 patients and their potential associations with the disease severity.

The role of micronutrient deficiency in the pathogenesis of COVID-19 has been reviewed in the literature; however, the data are limited and conflicting. This study investigated the association between the status of essential metals, vitamins, and antioxidant enzyme activities in COVID-19 patients and disease severity. We recruited 155 patients, who were grouped into four classes based on the Adults guideline for the Management of Coronavirus Disease 2019 at King Faisal Specialist & Research Centre (KFSH&RC): asymptomatic (N = 16), mild (N = 49), moderate (N = 68), and severe (N = 22). We measured serum levels of copper (Cu), zinc (Zn), selenium (Se), vitamin D3, vitamin A, vitamin E, total antioxidant capacity, and superoxide dismutase (SOD). Among the patients, 30%, 25%, 37%, and 68% were deficient in Se (< 70.08 µg/L), Zn (< 0.693 µg/mL), vitamin A (< 0.343 µg/mL), and vitamin D3 (< 20.05 µg/L), respectively, and SOD activity was low. Among the patients, 28% had elevated Cu levels (> 1.401 µg/mL, KFSH&RC upper reference limit). Multiple regression analysis revealed an 18% decrease in Se levels in patients with severe symptoms, which increased to 30% after adjusting the model for inflammatory markers. Regardless of inflammation, Se was independently associated with COVID-19 severity. In contrast, a 50% increase in Cu levels was associated with disease severity only after adjusting for C-reactive protein, reflecting its possible inflammatory and pro-oxidant role in COVID-19 pathogenesis. We noted an imbalance in the ratio between Cu and Zn, with ~ 83% of patients having a Cu/Zn ratio > 1, which is an indicator of inflammation. Cu-to-Zn ratio increased to 45% in patients with mild symptoms and 34%-36% in patients with moderate symptoms compared to asymptomatic patients. These relationships were only obtained when one of the laboratory parameters (lymphocyte or monocyte) or inflammatory markers (neutrophil-to-lymphocyte ratio) was included in the regression model. These findings suggest that Cu/Zn might further exacerbate inflammation in COVID-19 patients and might be synergistically associated with disease severity. A 23% decrease in vitamin A was seen in patients with severe symptoms, which disappeared after adjusting for inflammatory markers. This finding may highlight the potential role of inflammation in mediating the relationship between COVID-19 severity and vitamin A levels. Despite our patients' low status of Zn, vitamin D3, and antioxidant enzyme (SOD), there is no evidence of their role in COVID-19 progression. Our findings reinforce that deficiency or excess of certain micronutrients plays a role in the pathogenesis of COVID-19. More studies are required to support our results.

Potential health risks of maternal phthalate exposure during the first trimester - The Saudi Early Autism and Environment Study (SEAES).

Phthalates are the most ubiquitous contaminants that we are exposed to daily due to their wide use as plasticizers in various consumer products. A few studies have suggested that in utero exposure to phthalates can disturb fetal growth and development in humans, because phthalates can interfere with endocrine function. We collected spot urine samples from 291 pregnant women in their first trimester (9.8 ± 2.3 gestational weeks) recruited in an ongoing prospective cohort study in Saudi Arabia. A second urine sample was collected within 1-7 d after enrollment. The aims of this study were to: (1) assess the extent of exposure to phthalates during the first trimester and (2) estimate the risk from single and cumulative exposures to phthalates. Most phthalate metabolites' urinary levels were high, several-fold higher than those reported in relevant studies from other countries. The highest median levels of monoethyl phthalate, mono-n-butyl phthalate (MnBP), mono-iso-butyl phthalate (MiBP), and mono-(2-ethylhexyl) phthalate (MEHP) in µg/l (µg/g creatinine) were 245.62 (197.23), 114.26 (99.45), 39.59 (34.02), and 23.51 (19.92), respectively. The MEHP levels were highest among three di (2-ethylhexyl) phthalate (DEHP) metabolites. %MEHP4, the ratio of MEHP to four di (2-ethylhexyl) phthalate metabolites (∑4DEHP), was 44%, indicating interindividual differences in metabolism and excretion. The hazard quotient (HQ) of individual phthalates estimated based on the reference dose (RfD) of the U.S. Environmental Protection Agency indicated that 58% (volume-based) and 37% (creatinine-based) of the women were at risk of exposure to ∑4DEHP (HQ > 1). Based on the tolerable daily intake (TDI) from the European Food Safety Authority, 35/12% (volume-/creatinine-based data) of the women were at risk of exposure to two dibutyl phthalate (∑DBP) metabolites (MiBP and MnBP). The cumulative risk was assessed using the hazard index (HI), the sum of HQs of all phthalates. The percentages of women (volume-/creatinine-based data) at health risks with an HI > 1 were 64/40% and 42/22% based on RfD and TDI, respectively. In view of these indices for assessing risk, our results for the anti-androgenic effects of exposing pregnant women to ∑4DEHP and ∑DBP early during pregnancy are alarming.

Safety and tolerability of moxifloxacin for the treatment of disseminated BCGitis in children.

BACKGROUND AND OBJECTIVE: Disseminated BCGitis is a rare but serious complication of BCG vaccine in patients with underlying primary immunodeficiency. Fluoroquinolone antibiotics containing antimycobacterial regimen have been considered in the treatment of disseminated BCGitis, but there are limited data about the dosing, safety, and tolerability of fluoroquinolone such as moxifloxacin in children. The aim of this study was to report the experience with the dosing, safety, and tolerability of moxifloxacin in children with disseminated BCGitis. METHOD: This retrospective descriptive study included children who had been diagnosed with disseminated BCGitis and treated with an antimycobacterial regimen including moxifloxacin for more than two weeks from 2007 to 2017 at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. RESULT: Ten children were included: six (60.0%) were male and four (40.0%) were female. The primary diagnosis for five patients was Mendelian susceptibility to mycobacterial diseases (MSMD), four patients were diagnosed with severe combined immune deficiency (SCID), and the remaining patient had human immunodeficiency virus (HIV) infection. The overall mean duration of moxifloxacin treatment was 10.1 months. Liver toxicity was recorded in three patients. The most common medications used with moxifloxacin were ethambutol and clarithromycin. Moxifloxacin serum concentration level was determined in 5 patients. No musculoskeletal side effects were reported while the patient was on moxifloxacin. The treated patients showed a different response to an antimycobacterial regimen including moxifloxacin, with mortality in two patients. CONCLUSION: Our study suggests that moxifloxacin is generally tolerated in children and might be considered in disseminated BCGitis cases. Additionally, paying attention to side effects such as liver toxicity is recommended, particularly with the use of other antimycobacterial antibiotics, which could also be hepatotoxic. A moxifloxacin-containing regimen for disseminated BCGitis showed clinical improvement in some patients in this study, although the majority presented the same clinical condition.

ABO incompatible kidney transplantation: the Saudi experience.

Although the outcomes of ABO-incompatible (ABOi) kidney transplant recipients are quite favorable, these patients are at increased risk of early antibody-mediated rejection (AMR) and graft loss. Some studies have also shown high mortality in the ABOi group mainly due to increased risk of infections. The AMR rates have been reported anywhere from <10% to >50% in the literature. The outcomes of the ABOi kidney transplants in the Saudi population are not known. In this study, we aimed to determine the graft and patient survival in ABOi kidney transplant recipients in the Saudi population. We included all adult patients who underwent ABOi transplantation between 2007 and 2016. All patients received rituximab, therapeutic plasma exchange, thymoglobulin, intravenous antibiotics, and intravenous immunoglobulin. The maintenance immunosuppression was prednisone, mycophenolate mofetil, and tacrolimus. The data were collected from a prospectively maintained database. A total of 77 patients were included in the study. The most common blood group mismatch was A to O (44.2%), followed by B to O (26.0%) and A to B (16.9%). In the 1st year, 17% of patients developed acute cellular rejection and AMR occurred in 7.8% of patients. Two patients were diagnosed with BK nephropathy. In the 1st year, urinary tract infection occurred in 25 (32.5%) patients. No patient was diagnosed severe viral or fungal infection. In the 1st year, four grafts were lost (graft survival of 94.8%); all grafts were lost within two weeks, three due to AMR and one due to technical reason. One year patient survival was 100%. In this study of ABOi kidney transplant recipients, we observed low risks of infectious complications with excellent patient and graft survival. Our immunosuppressive protocol can be considered safe.

Benefits of adding coronary calcium score scan to stress myocardial perfusion positron emission tomography imaging.

There have been little and conflicting data regarding the relationship between coronary artery calcification score (CACS) and myocardial ischemia on positron emission tomography myocardial perfusion imaging (PET MPI). The aims of this study were to investigate the relationship between myocardial ischemia on PET MPI and CACS, the frequency and severity of CACS in patients with normal PET MPI, and to determine the optimal CACS cutoff point for abnormal PET. This retrospective study included 363 patients who underwent same-setting stress PET perfusion imaging and CACS scan because of clinically suspected coronary artery disease (CAD). Fifty-five (55%) of the 363 patients had abnormal PET perfusion. There was an association between sex, diabetes mellitus (DM), smoking, and CACS and PET perfusion abnormities with P = 0.003, 0.05, 0.005, and 0.001, respectively. However, there was no association between PET perfusion abnormalities with age, body mass index, hypertension, and hypercholesterolemia. There was association between CACS and age, sex, and DM with P = 0.000, 0.014, and 0.052, respectively, and stepwise increase in the frequency of myocardial ischemia and CACS groups. Receiver-operating characteristic analysis showed that a CACS ≥304 is the optimal cutoff for predicting perfusion abnormalities with sensitivity of 64% and specificity of 69%. In conclusion, the frequency of CAC in patients with normal PET MPI is 49%, it is highly recommended to combine CACS with PET MPI in patients without a history of CAD. PET MPI identifies myocardial ischemia and defines the need for coronary revascularization, but CAC reflects the anatomic burden of coronary atherosclerosis. Combining CACS to PET MPI allows better risk stratification and identifies high-risk patients with PET, and it may change future follow-up recommendations. CACS scan is readily available and easily acquired with modern PET-computed tomography (CT) and single-photon emission CT (SPECT)-CT with modest radiation exposure.

Association between breast arterial calcifications found on mammography and coronary artery calcifications in asymptomatic Saudi women.

BACKGROUND: Currently, there are no data on the prevalence of breast arterial calcification (BAC) in Saudi women. Furthermore, there are no data on the relationship between BAC and coronary artery calcium score (CACS) as a coronary artery disease (CAD) risk factor in Saudi women who undergo mammography. OBJECTIVE: Examine the role of BAC as a potential female-specific risk factor for CAD in Saudi women in order to investigate the relationship between BAC and CACS in women who undergo a screening mammography, and study the relationship between BAC and CAD risk factors, including age, diabetes mellitus, hypertension, chronic kidney disease (CKD), dyslipidemia, and family history of CAD. DESIGN: Retrospective, medical records review. SETTING: Single tertiary care center. PATIENTS AND METHODS: The study cohort included women who had mammograms and a CACS scan, and for whom data on CAD risk stratification and CAD risk factors had been collected within one year of each other from 2014 to 2017. Women with CAD were excluded from the study. MAIN OUTCOME MEASURES: Breast arterial calcification as a marker for coronary artery disease. SAMPLE SIZE: 307 Saudi women. RESULTS: BAC was found in 142 (46%) patients in the study population. BAC+ women were significantly older than the BAC- women (P=.001), and a strong association was found between BAC and CACS (P=.0001), diabetes (P=.0001), hypertension (P=.021), and CKD (P=.0031). However, no association was found between BAC and tobacco smoking, dyslipidemia, and family history of CAD. In addition, a strong correlation was found between CACS and the components of the BAC score (P less than .001). Multivariate linear regression analysis revealed that age, CAC, and CKD are the only strong predictors of BAC. CONCLUSIONS: The proportion of BAC in Saudi women is 46%, and there may be a strong association between BAC and CAC, age, hypertension, and CKD. A large-scale prospective research study is necessary to validate the role of BAC on screening mammography as a CAD risk stratification tool and before routine reporting of BAC on a mammography report. LIMITATIONS: Because this was a retrospective study, patient selection bias cannot be excluded. CONFLICT OF INTEREST: None.

Increases in Heart Rate Variability Signal Improved Outcomes in Rapid Response Team Consultations: A Cohort Study.

BACKGROUND: Reduced heart rate variability (HRV) indicates dominance of the sympathetic system and a state of "physiologic stress." We postulated that, in patients with critical illness, increases in HRV might signal successful resuscitation and improved prognosis. METHODS: We carried out a prospective observational study of HRV on all patients referred to the rapid response team (RRT) and correlated with serial vital signs, lactate clearance, ICU admission, and mortality. RESULTS: Ninety-one patients were studied. Significantly higher HRV was observed in patients who achieved physiological stability and did not need ICU admission: ASDNN 19 versus 34.5, p=0.032; rMSSD 13.5 versus 25, p=0.046; mean VLF 9.4 versus 17, p=0.021; mean LF 5.8 versus 12.4, p=0.018; and mean HF 4.7 versus 10.5, p=0.017. ROC curves confirmed the change in very low frequencies at 2 hours as a strong predictor for ICU admission with an AUC of 0.772 (95% CI 0.633, 0.911, p=0.001) and a cutoff value of -0.65 associated with a sensitivity of 78.6% and a specificity of 61%. CONCLUSIONS: Reduced HRV, specifically VLF, appears closely related to greater severity of critical illness, identifies unsuccessful resuscitation, and can be used to identify consultations that need early ICU admission.

Retraction Note: SNPs in genes implicated in radiation response are associated with radiotoxicity and evoke roles as predictive and prognostic biomarkers.

The authors are retracting this article [1] because the data have already been published in [2] making this a redundant publication. Ghazi Alsbeih, Najla Al-Harbi, Khaled Al-Hadyan, Mohamed Shoukri and Nasser Al-Rajhi agree with this retraction. Medhat El-Sebaie did not respond to our correspondence.

Use of beta blockers is associated with hearing loss.

OBJECTIVE: This study was conducted to investigate the hypothesis that patients using ß-blockers will develop hearing loss. DESIGN: A cross-sectional study. STUDY SAMPLE: A total of 125 patients completed the study. A total of 63 patients were on ß-blockers and 62 were not on ß-blockers. RESULTS: Carvedilol was significantly associated with hearing loss. Other beta-blockers including metoprolol and atenolol showed no association with hearing loss. Linear multiple regression analysis was run including variables of gender, age, ischaemic heart disease, cardiac failure/dilated cardiomyopathy, frusemide and carvedilol use as predictors for total hearing loss severity at all frequencies. Age and gender, as well as carvedilol, were found to be the only statistically significant predictors for hearing loss severity. CONCLUSION: Chronic use of carvedilol was associated with significant hearing loss. This may need to be taken into account when prescribing the drug. Further randomised controlled studies with baseline audiometric hearing tests before starting treatment, and periodic follow-up tests, would provide a better assessment of the effect of carvedilol on hearing.

Prevalence and predictors of myocardial ischemia by preoperative myocardial perfusion single photon emission computed tomography in patients undergoing noncardiac surgery.

BACKGROUND: The prevalence and predictors of myocardial ischemia before noncardiac surgery are unknown. In addition the predictive value of myocardial perfusion single-photon emission computed tomography (SPECT) before noncardiac in individual patients is uncertain. OBJECTIVE: Evaluate the prevalence and predictors of myocardial ischemia before noncardiac surgery, and determine the postoperative cardiac outcome based on results of myocardial perfusion SPECT. DESIGN: Retrospective. SETTING: Single tertiary care center. PATIENTS AND METHODS: We reviewed the records of adult patients diagnosed with myocardial ischemia by myocardial perfusion SPECT who were undergoing noncardiac surgery. Myocardial perfusion SPECT had been performed within 4 weeks prior to noncardiac surgery requiring general anesthesia. MAIN OUTCOME MEASURES: Prevalence of abnormal myocardial perfusion SPECT results on preoperative evaluation; abnormal myocardial perfusion SPECT results as a predictor for postoperative cardiac events such as cardiac death, nonfatal myocardial infarction, and unstable angina. RESULTS: Of 131 patients who underwent noncardiac surgery from February 2015 to April 2016, 84 (64%) patients were female and the mean (SD) age was 64.1 (13.6) years. The prevalence of abnormal myocardial perfusion SPECT was 18% (24 of 131). Normal myocardial perfusion SPECT was highly predictive (up to 100%), but a positive myocardial perfusion SPECT had low positive predictive value (4%). Variables associated with an abnormal myocardial perfusion SPECT included ischemic heart disease, congestive heart failure, ASA score of 3 or more, limited exercise capacity (less than 4 METs), male sex, hypercholesterolemia, hypertension, smoking, and abnormal ECG. In a multivariable analysis, history of ischemic heart disease and history of smoking were significant predictors of abnormal myocardial perfusion SPECT (P=.001, and .029, respectively). CONCLUSIONS: Because of the low positive predictive value of myocardial perfusion SPECT, utilization of the technique in the workup of cardiac patients undergoing noncardiac surgery has been inappropriate. Myocardial perfusion SPECT should be restricted to only clearly defined appropriate use criteria. LIMITATIONS: Relatively small number of patients and retrospective design.

Genetic Predisposition to Cervical Cancer and the Association With XRCC1 and TGFB1 Polymorphisms.

OBJECTIVE: Cervical carcinoma (CC), a multifactorial cancer, is assumed to have a host genetic predisposition component that modulates its susceptibility in various populations. We investigated the association between CC risk in Saudi women and 6 single-nucleotide polymorphisms (SNPs) in hypothesis-driven candidate genes. METHODS: A total of 545 females were included, comprising 232 CC patients and 313 age-/sex-matched control subjects. Six SNPs (CDKN1A C31A, ATM G1853A, HDM2 T309G, TGFB1 T10C, XRCC1 G399A, and XRCC3 C241T) were genotyped by direct sequencing. RESULTS: Of the 6 SNPs studied, TGFB1 T10C (odds ratio, 0.74; 95% confidence interval, 0.57-0.94) and XRCC1 G399A (odds ratio, 1.45; 95% confidence interval, 1.11-1.90) displayed different frequencies in cancer patients and control subjects and showed statistically significant association in univariate (P = 0.017, P = 0.005, respectively) analysis. The Cochran-Armitage trend test had confirmed the results (P = 0.027 and P = 0.006, respectively), indicating an ordering in the effect of the risk alleles in CC patients. The 2 SNPs, TGFB1 T10C and XRCC1 G399A, showed also degrees of deviation from Hardy-Weinberg equilibrium in cancer patients (P = 0.001 and P = 0.083, respectively) but not in the control subjects. Furthermore, correction for multiple testing using multivariate logistic regression to assess the joint effect of all SNPs has sustained significant statistical association (P = 0.025 and P = 0.009, respectively). CONCLUSIONS: TGFB1 T10C and XRCC1 G399A SNPs were associated with CC risk in univariate and multivariate analysis and displayed allele-dosage effects and coselection in cancer patients. Patients harboring the majority allele TGFB1 T10 (Leu) or the variant allele XRCC1 399A (Gln) have approximately 1.5-fold increased risk to develop CC. Host SNPs genotyping may provide relevant biomarkers for CC risk assessment in personalized preventive medicine.

High prevalence of coronary artery calcification in Saudi patients with normal myocardial perfusion.

BACKGROUND: Normal single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) has a high negative predictive value for ischemic heart disease. Thus, the presence of subclinical coronary atherosclerosis detected by coronary artery calcification (CAC) score in patients who have under-gone SPECT MPI is unknown. OBJECTIVES: Determine the prevalence of coronary artery calcification (CAC) in patients with normal SPECT MPI and examine the association of CAC with conventional coronary artery disease (CAD) risk factors. DESIGN: Cross-sectional analytical study using medical records from February 2010 to April 2016. SETTINGS: Single tertiary-care center. PATIENTS AND METHODS: We studied patients referred from the outpatient clinical services for clinically indicated noninvasive CAD diagnosis with MPI SPECT. CAC scoring was subsequently performed within 3 months after a normal MPI. We excluded patients with chest pain or decompensated heart failure or patients with a history of CAD. The study population was divided into three groups: patients with a CAC score of 0, a CAC score from 1 to 300, and a CAC score more than 300. The groups were analyzed by age and other demographic and clinical characteristics. MAIN OUTCOME MEASURE(S): Prevalence of CAC in patients with normal MPI. RESULTS: The prevalence of CAC was 55% (n=114) in 207 patients with a mean (SD) age of 57.1 (10.4) years. Twelve percent had severe coronary atherosclerosis (CAC score > 300). All patients had a normal MPI SPECT. CAC scores were 0 for 93 patients (45%), 1 to 300 for 89 (43%), and more than 300 for 24 (12%). There was a strong association between CAC score and age (P < .0001), male sex (P < .0001), and diabetes mellitus (P=.042), but no association between CAC score and hypertension (P=.153), family history of CAD (P=.23), obesity (P=.31), hypercholesterolemia (P=.071), or smoking (P=.308). CONCLUSIONS: The prevalence of CAC is high in this study population of patients with normal SPECT MPI. Age, male sex and diabetes were risk factors associated with CAC. LIMITATIONS: Single center and small study population.

Mycobacterium tuberculosis in solid organ transplantation: incidence before and after expanded isoniazid prophylaxis.

BACKGROUND: The risk of tuberculosis is increased in solid organ transplantation. Rates remain high in developed and developing countries. We developed protocols to better identify transplant recipients at risk of tuberculosis and initiate interventions to prevent tuberculosis. OBJECTIVES: Report tuberculosis incidence in solid-organ transplant recipients and the results of expanded isoniazid prophylaxis in deceased-donor renal transplantation. DESIGN: Retrospective cohort study, comparing two time periods. SETTING: Large transplantation center in a WHO-medium endemicity country for tuberculosis. METHODS: In a cohort of all solid-organ transplant recipients performed between 2003 and 2012, tuberculosis-free transplantation follow-up is used for incidence calculation. Rates of tuberculosis in renal transplant recipients are compared before and after implementation of expanded isoniazid prophylaxis. MAIN OUTCOME MEASURE(S): Active tuberculosis post-transplantation. RESULTS: Of 1966 solid-organ transplant recipients (kidney: 1391, liver: 426, heart: 114, lung: 35), 20 recipients (1.02%) developed tuberculosis. Twelve cases (60%) developed tuberculosis within one year of transplantation. The incidence was 248 cases per 100 000 transplant-years. The proportion of transplant recipients (incidence of tuberculosis per 100 000 transplant-years) for specific organs were kidney 0.58% (127), liver 1.88% (594), heart: 1.75% (570), and lung 5.71% (4750). In the survival analysis, lung transplant recipients had significantly higher rates of tuberculosis compared to recipients of kidneys from living donors (P=.0001) with a rate ratio of 45.3 (95% CI: 7-313). Mortality was 5% among tuberculosis patients. After implementing expanded isoniazid prophylaxis among deceased-donor kidney recipients, no tuberculosis occurred in 177 recipients, compared to 3 out of 155 (2%) recipients before implementation. CONCLUSIONS: Rates of tuberculosis among our solid transplant recipients are decreasing. Universal iso-niazid prophylaxis in transplant recipients could reduce transplant-associated tuberculosis in endemic areas. LIMITATIONS: Donor data on tuberculosis exposure and prevention and tuberculosis prevention efforts before referral to our center are not available for all patients.

Reduced rate of human papillomavirus infection and genetic overtransmission of TP53 72C polymorphic variant lower cervical cancer incidence.

BACKGROUND: Cervical cancer is a predominantly human papillomavirus (HPV)-driven disease worldwide. However, its incidence is unexplainably low in western Asia, including Saudi Arabia. Using this paradigm, we investigated the role of HPV infection rate and host genetic predisposition in TP53 G72C single nucleotide polymorphism (SNP) presumed to affect cancer incidence. METHODS: Patients treated between 1990 and 2012 were reviewed, and a series of 232 invasive cervical cancer cases were studied and compared with 313 matched controls without cancer. SNP was genotyped by way of direct sequencing. HPV linear array analysis was used to detect and genotype HPV in tumor samples. RESULTS: The incidence of cervical cancer revealed bimodal peaks at 42.5 years, with a slighter rebound at 60.8 years. Among all cases, 77% were HPV-positive and 16 HPV genotypes were detected-mostly genotypes 16 (75%) and 18 (9%)-with no difference by age, histology, or geographical region. Although the TP53 G72C genotype was not associated with overall cervical cancer risk, it was significantly associated with HPV positivity (odds ratio, 0.57; 95% confidence interval, 0.36-0.90; P = .016). Furthermore, the variant C allele was significantly overtransmitted in the population (P < .0003). CONCLUSION: Cervical cancer incidence displays bimodal curve peaking at a young age with secondary rebound at older age. The combination of relative low HPV infection and variant TP53 72C allele overtransmission provide a plausible explanation for the low incidence of cervical cancer in our population. Therefore, HPV screening and host SNP genotyping may provide more relevant biomarkers to gauge the risk of developing cervical cancer. Cancer 2017;123:2459-66. © 2017 American Cancer Society.

Validation of an Arabic Questionnaire for Symptom Assessment.

BACKGROUND: Impeccable assessment of symptoms is central to palliative care (PC) practice. OBJECTIVES: The study objectives are (1) to test the validity of the Arabic Questionnaire for Symptom Assessment (AQSA) as a self-administered (SA) tool for assessing the severity of the listed symptoms among PC patients and (2) to test the validity of AQSA when completed by a proxy. METHODS: The AQSA is a tool for assessing the severity of 11 symptoms in addition to the overall suffering experience on a 0 to 10 numeric scale. Symptom scores on the SA AQSA were compared to scores obtained through interviews with patients. The same procedure was repeated with patients' sitters to explore the validity of using the tool for symptom assessment by proxy. RESULTS: The study involved 107 pairs (a patient and a sitter, each) with a mean age of 46.3 years (females 59.8%) for patients and 35.9 years (females 65.7%) for sitters. The correlation coefficient ( r) for agreement between SA and interview-based (IB) scores for patients ranged from .65 ( P < .0001) for drowsiness to .86 ( P < .0001) for pain. The SA AQSA showed positive correlation between sitters' and patients' scores, with r ranging from .28 ( P = .004) for depression to .62 ( P ≤ .0001) for vomiting. CONCLUSIONS: The strong positive correlation between SA and IB AQSA indicates that the former is a valid tool. When the SA AQSA is used by proxy, it showed moderate to strong positive correlation with patients' actual scores for most of the symptoms.

Subcutaneous Implantable Cardioverter Defibrillators Implantation Without Defibrillation Threshold Testing: A Single Center Experience.

BACKGROUND: Subcutaneous implantable cardioverter defibrillator (S-ICD) system has been proven to be an effective therapy for prevention of sudden cardiac death (SCD) in selected patients. Although the Shockless IMPLant Evaluation (SIMPLE) trial has shown that defibrillation threshold (DFT) testing is not necessary for transvenous ICD (TV-ICD) systems, it is still recommended for S-ICD systems. We aimed to study the efficacy and safety of S-ICD implantation without DFT in our Heart Center with the comparison of S-ICD patients' outcome to those with a single chamber TV-ICD without DFT in the same period. METHODS: A retrospective analysis of patients underwent S-ICD without DFT from December 2014 to May 2016 with the comparison to single chamber TV-ICD patients implanted during the same period. RESULTS: Thirty consecutive patients (23 males (76.7%); mean age 41 ± 13 years; mean left ventricular ejection fraction 30±12%) received a S-ICD for primary (25 patients, 83.3%) or secondary prevention (five patients, 16.7%) of SCD. During a mean follow-up of 710.6 ± 190 days, three patients received 38 appropriate ICD shocks (90.5%), and two patients received four inappropriate shocks (9.5%). There were two mortalities (6.7%): one cardiac and one non-cardiac. When compared to 30 consecutive who received a single chamber TV-ICD during the same period, there was no significant difference in mortality. CONCLUSIONS: Implantation of S-ICD using intermuscular approach without DFT seems to be safe and effective. Data from large S-ICD registries with long-term follow-up, and preferably randomized controlled studies, are needed to confirm this finding.

Thromboembolic events in patients with inflammatory bowel disease.

BACKGROUND/AIMS: Inflammatory bowel disease (ulcerative colitis and Crohn's disease) is characterized by a chronic inflammatory condition, and is accompanied by abnormalities in coagulation and a hyper-coagulable state. This study was conducted to examine the risk factors for developing Thromboembolic Events in Inflammatory Bowel Disease (IBD) in a population with prevalent consanguinity. PATIENTS AND METHODS: Patients with a definitive diagnosis of IBD who were seen in the gastroenterology clinic of King Khalid University Hospital (Riyadh, Saudi Arabia) from 2010- to 2012, were asked to participate in this prospective cohort study, and were followed for one 1 year. Data was collected using specifically designed case report forms (CRF) by trained research personnel. RESULTS: A total of 100 Saudi patients with IBD were studied. There were 51 (51%) women and the mean ± standard deviation (SD) age of the group was 31.24 ± 10.78 years. Those with Crohn's disease constituted 72% of the patients, and 28% had ulcerative colitis. Eight patients (8%) had at least one Thrombotic Event ([six deep venous thrombosis (DVT), and two pulmonary embolism (PE)]. Family history of deep venous thrombosis was present in 5%, and family history of pulmonary embolism (PE) in 4% of the patients. After adjusting for age and gender, a family history of Thrombotic event was identified as to be the only statistically significant predictor of thrombosis in IBD patients (RR = 9.22, 95% CI: 2.10--40.43). CONCLUSION: In a population with high consanguinity, Thromboembolic events (DVT and PE) had a prevalence of 8% among IBD patients, positive family history of pulmonary embolism was a predictor of thrombosis. Further studies are needed to explore the role of genetic factors in this population.

New-onset diabetes after kidney transplantation: Incidence, risk factors, and outcomes.

Many patients develop new-onset diabetes after kidney transplantation (NODAT). Its incidence and epidemiology are unknown in the Saudi population. We aimed to study the incidence, epidemiology, and outcomes of kidney transplant recipients who developed NODAT. This is a retrospective study of all adults who received kidney transplant between January 2003 and December 2009. NODAT was defined according to the criteria outlined in the 2003 International Consensus guidelines. A total of 500 patients were included in this study, 54% were male patients. One hundred thirty-six patients (27%) developed diabetes (NODAT group). In the univariate analysis, patients were older in the NODAT group (P <0.001), were of higher weight (P = 0.006), and had positive family history of diabetes (P = 0.002). Similarly, more patients in this group had impaired glucose tolerance before transplant (P = 0.01) and history of hepatitis C infection (P = 0.005). In the multivariate analysis, older age [odds ratio (OR) 1.06], family history of diabetes (OR 1.09), hepatitis C infection (OR 1.92), and impaired fasting glucose (OR 1.79) were significant risk factors for the development of NODAT. Mortality was 6% in the NODAT group and 0.5% in the non-diabetic group had died (P <0.001). Graft survival was not different between the groups (P = 0.35). In conclusion, there is a significant risk of developing diabetes after renal transplantation. Patients are at higher risk if they are older, have a family history of diabetes, pre-transplant impaired fasting/random glucose, and hepatitis C virus infection.

Pulmonary hydatid cysts: the naturally occurring models for rupture.

BACKGROUND: Pulmonary hydatid cysts are recognized to have high rate of rupture compared to those in other affected organs. To identify risk factors associated with endobronchial rupture, we prospectively assessed 32 patients with hydatid cysts. There were 21 males and 11 females, with a mean age of 32 ± 15 years (range 9 to 65 years). METHODS: All patients undergoing thoracotomies for hydatid cysts were included. Demographic data, site, size, and whether cysts were ruptured or intact, were reviewed. Intraoperatively, bronchial fistula diameters were measured. A stepwise multiple logistic regression model was used to analyze the results. RESULTS: Seventeen (53.1%) patients presented with ruptured cysts (group 1) and 15 with intact cysts (group 2). There was a significant difference in mean fistula diameter between groups: 6.16 ± 2 mm in group 1 vs. 0.34 ± 0.19 mm in group 2 (p ≤ 0.0001), which was identified as the only significant risk factor associated with cyst rupture. CONCLUSION: At the fistula site, the intracystic pressure is unopposed, leading to herniation of the endocyst membrane, disruption of its integrity, and rupture. Therefore, we postulate that this scenario in combination with other coexisting factors could be the possible mechanism for cyst rupture in group 1. This concept may also explain the pathogenesis of the high rate of rupture of pulmonary hydatid cysts. Accordingly, we consider these cysts a naturally occurring model for rupture, which should be treated surgically as soon as the diagnosis is made, to avoid complications.

Systematic Analysis of AU-Rich Element Expression in Cancer Reveals Common Functional Clusters Regulated by Key RNA-Binding Proteins.

Defects in AU-rich elements (ARE)-mediated posttranscriptional control can lead to several abnormal processes that underlie carcinogenesis. Here, we performed a systematic analysis of ARE-mRNA expression across multiple cancer types. First, the ARE database (ARED) was intersected with The Cancer Genome Atlas databases and others. A large set of ARE-mRNAs was over-represented in cancer and, unlike non-ARE-mRNAs, correlated with the reversed balance in the expression of the RNA-binding proteins tristetraprolin (TTP, ZFP36) and HuR (ELAVL1). Serial statistical and functional enrichment clustering identified a cluster of 11 overexpressed ARE-mRNAs (CDC6, KIF11, PRC1, NEK2, NCAPG, CENPA, NUF2, KIF18A, CENPE, PBK, TOP2A) that negatively correlated with TTP/HuR mRNA ratios and was involved in the mitotic cell cycle. This cluster was upregulated in a number of solid cancers. Experimentally, we demonstrated that the ARE-mRNA cluster is upregulated in a number of tumor breast cell lines when compared with noninvasive and normal-like breast cancer cells. RNA-IP demonstrated the association of the ARE-mRNAs with TTP and HuR. Experimental modulation of TTP or HuR expression led to changes in the mitosis ARE-mRNAs. Posttranscriptional reporter assays confirmed the functionality of AREs. Moreover, TTP augmented mitotic cell-cycle arrest as demonstrated by flow cytometry and histone H3 phosphorylation. We found that poor breast cancer patient survival was significantly associated with low TTP/HuR mRNA ratios and correlated with high levels of the mitotic ARE-mRNA signature. These results significantly broaden the role of AREs and their binding proteins in cancer, and demonstrate that TTP induces an antimitotic pathway that is diminished in cancer. Cancer Res; 76(14); 4068-80. ©2016 AACR.