PD-L1 is highly expressed in ovarian cancer and associated with cancer stem cells populations expressing CD44 and other stem cell markers.

BACKGROUND: Immune checkpoint inhibitors, including PD-L1 (programmed death ligand-1) inhibitors have well documented anticancer therapeutic effect in most types of cancers but its use in the treatment of ovarian cancer is not yet proven. The aim of our study is to explore the predictive biomarkers in ovarian cancer and its association with the outcomes. We have investigated the role of PD-L1 expressions in the tumor microenvironment cells including immune cells and cancer stem cells in different types of ovarian cancer. METHODS: A total of 119 surgical archived ovarian cancer samples were collected from the pathology department at King Fahad Specialist Hospital, Dammam, Saudi Arabia that included serous carcinomas, clear cell carcinomas, mucinous carcinomas, endometrioid carcinomas, and granulosa cell tumors. Immunohistochemistry (IHC) staining was performed using (i) PD-L1 antibodies to detect PD-L1 expressions; (ii) CD8 and CD4 to detect Tumor Infiltrating Lymphocytes (TILs); and (iii) CD44, LGR5, and ALDH2 to detect stem cell markers. The clinicopathological data were collected from patients' medical record to investigate the association with PD-L1, TILs, and stem cells expressions. RESULTS: We report high PD-L1 expressions in 47.8% of ovarian cancer samples. PD-L1 expressions were detected in different types of epithelial ovarian cancer and were not associated with poor prognosis of ovarian cancer. However, determining the expression levels of TILs in the ovarian cancer tissues found that 81% (n = 97) of ovarian cancer samples have TILs that express both of CD8 and CD4 and significantly associated with high PD-L1 expressions. Interestingly, we have found that ovarian cancer tissues with high expressions of PD-L1 were associated with high expressions of stem cells expressing CD44 and LGR5. CONCLUSIONS: PD-L1 is highly expressed in the serous type of ovarian carcinomas and the overall expression of PD-L1 is not associated with poor survival rate. Furthermore, PD-L1 expressions are strongly associated with TILs and stem cell markers in ovarian cancer. Inhibiting the PD-L1 using immune checkpoint inhibitors might downregulate stem cell population that known to be associated with cancer recurrence.

Type and etiology of pediatric epilepsy in Jordan. A multi-center study.

OBJECTIVE: To study types and etiologies of epilepsy in Jordanian pediatric epileptic patients maintained on antiepileptic drugs using customized classification scheme of International League Against Epilepsy (ILAE) (2010) report. METHODS: This is a cross-sectional, multi-centre study on pediatric epileptic patients on antiepileptic drugs, who were managed in the pediatric neurology clinics at 6 teaching public hospitals in Jordan. RESULTS: Out of the 663 patients included in the study, (90.2%) had one seizure type, (53%) of this type were focal seizures followed by generalized seizures (41.5%) and spasms (5.5%). Distinctive constellations were found in 11/663 (1.7%) patients. Benign epilepsies with centrotemporal spikes were the most common electro clinical syndromes 60/221 (27.1%). Epilepsies attributed to structural-metabolic causes were documented in 278/663 (41.9%) patients, unknown causes 268/663(40.4%) and genetic causes in 117/663(17.7%). Most common causes of structural-metabolic group were due to perinatal insults (32%) and most common causes of the genetic group were the presumed genetic electro clinical syndromes (93.1%). CONCLUSION: Our study is on pediatric epilepsy, using customized classification scheme from the ILAE 2010 report which showed interesting results about type and etiology of epileptic seizures from developing country with potential impact on the international level.

Patterns of antiepileptic drugs use in epileptic pediatric patients in Jordan.

OBJECTIVE: To determine prescribing patterns of antiepileptic drugs (AEDs) in pediatric patients with confirmed diagnosis of epilepsy, and to provide knowledge of general practice of physicians. METHODS: The study was a multi-center crosssectional observational study, in specialized clinics for management of epilepsy in north, central and south Jordan. This study was conducted from January 2014 to July 2014. These were 3 from university tertiary care hospitals and 4 from governmental tertiary care hospitals. RESULTS: A total of 694 pediatric patients were included. Monotherapy AED use had the highest frequency 465 (67.0%), followed by dual therapy 162 (23.3%). The frequency of monotherapy in university hospitals was lower than governmental hospitals (p<0.05); however, Polytherapy was more frequent in younger children. Two old AEDs were most frequently prescribed as a monotherapy; Valproic acid 235 (50.5%) and carbamazepine 155 (33.3%). The most common combination in dual therapy was valproic acid with carbamazepine 28 (17.3%). The second most common combinations were carbamazepine with levetiracetam 21 (13.0%) or valproic acid with levetiracetam 20 (12.3%). CONCLUSION: Older AED remain first line drugs for use in both monotherapy and combination therapy for epileptic disorders. Polytherapy is associated with younger kids and being treated in a university hospital.

Impact of Socioeconomic Characteristics on Metabolic Control in Children with Type 1 Diabetes in a Developing Country

Objective: Adequate glycemic control in children with type 1 diabetes reduces the risk of future complications. Identifying factors affecting haemoglobin A1c (HbA1c) is crucial to management of metabolic control. We aimed to identify possible socioeconomic predictors of poor metabolic control this patient group in Jordan, a developing country with limited resources. Methods: Medical charts of children with type 1 diabetes attending the pediatric endocrine clinics in two major diabetes centers were reviewed. HbA1c ≥7.5% (58 mmol/mol) was considered to reflect poor metabolic control. Logistic regression analysis was performed to identify predictors of poor glycemic control. The association between socioeconomic characteristics and metabolic control was evaluated using multiple correspondence analysis (MCA). Results: Two hundred and fifty-nine children were enrolled in the study. One fifth of the patients (20.5%) achieved HbA1c <7.5%. Patients with dietary non-compliance [odds ratio (OR): 3.533, confidence interval (CI): 1.803 - 6.926; p<0.001], and those who were overweight (OR: 3.869, CI: 1.218 - 12.294; p=0.022) were more likely to have poor metabolic control. Children whose mothers had a bachelor's degree or higher were less likely to have poor metabolic control compared to children whose mothers had only elementary education (OR: 0.241, CI: 0.079 - 0.734; p=0.012). MCA revealed an association between low socioeconomic status and poor metabolic control. Children with deceased mothers had significantly higher HbA1c of 10.6±1.86% compared to an average of 8.7±1.45% for the rest of participants (p=0.005). Conclusion: Low socioeconomic status, lower levels of maternal education and maternal death were associated with poor metabolic control. Identifying children with these risk factors might play an important role in optimizing metabolic control and provide better diabetes care.

Personal and Clinical Predictors of Poor Metabolic Control in Children with Type 1 Diabetes in Jordan.

BACKGROUND: Achieving adequate metabolic control in children with type 1 diabetes is important in slowing the progression of future microvascular and macrovascular complications, but still it is a universal challenge. We aim to investigate possible factors associated with poor metabolic outcomes in Jordan as an example of a country with limited resources. METHODS: This is a retrospective chart review study of children with type 1 diabetes. Several clinical and personal characteristics were tested for association with metabolic control reflected by HbA1c levels. Linear logistic regression analysis was used to evaluate possible predictors of metabolic control. One-way ANOVA analysis was used to detect significant differences in HbA1c between categories. RESULTS: Significant predictors of metabolic control were found. A one-year increase in age led to an increase in HbA1c by 0.053% (P = 0.044). A decline in HbA1c levels was predicted in children who have precise amount of carbohydrates or who are receiving insulin at school (-0.46% (P = 0.014) and -0.82% (P = 0.004), respectively). When family members other than mothers decided the insulin dose, the HbA1c level increased by 0.74% (P = 0.005). CONCLUSION: Poor metabolic control was associated with age, dietary noncompliance, not receiving insulin at school, and absence of direct mother care. Our study is one of the few studies from Middle East evaluating predictors of metabolic control. Global research studies help in giving universal insight towards developing more effective multidisciplinary team approach for diabetes care and education.

Prevalence of celiac disease and celiac-related antibody status in pediatric patients with type 1 diabetes in Jordan

OBJECTIVE: Scientific findings regarding the prevalence of celiac disease (CD) in pediatric patients with type 1 diabetes (T1D) in the Arab world are scarce. We aimed to determine the prevalence of biopsy-proven celiac disease (BPCD) among pediatric patients with T1D from Jordan. We also assessed the possible predictors for developing CD in this cohort of patients and we compared T1D patients who developed BPCD with those who had positive CD serology but negative histology and/or fluctuating CD serology. METHODS: Celiac serology and duodenal biopsy results from 2012 to 2017 were collected from patients with T1D. The outcome of positive celiac serology and the risk factors for CD in T1D patients were investigated. RESULTS: A total of 538 children of which 278 boys (51.7%) were included in the study. The prevalence of positive serology and the diagnosis of BPCD in this cohort of T1D patients were 16.6 and 9.1% respectively. Eighty percent of those with BPCD were asymptomatic and 47% were diagnosed with CD at onset of T1D. Spontaneous normalization of celiac serology occurred in 23.6% of those with positive serology. CONCLUSION: CD is prevalent in T1D pediatric patients from Jordan (9.1%). It is often asymptomatic and the majority of cases were diagnosed at onset or within 5 years of T1D diagnosis. Spontaneous normalization of CD serology occurred in some patients with T1D. Hence, a watchful follow-up is recommended in such patients.

Predictors of type 1 diabetes mellitus outcomes in young adults after transition from pediatric care.

BACKGROUND: Type 1 diabetes (T1D) is a common chronic disease. Poor health outcomes are often noted after transfer to adult health care. It is important to determine the predictors of such outcomes to decrease morbidity and mortality. METHODS: The present retrospective study included patients followed for ≥1 year before and ≥1 year after transfer to adult care in a Canadian tertiary diabetes center. Data including demographics, education, comorbidity and pediatric diabetes management-related factors were analyzed as possible independent predictors of adult HbA1c, number of adult diabetes-related hospitalizations, and clinic visits. RESULTS: In all, 102 youths were followed to a mean (±SD) age of 21.8 ± 1.5 years. Predictors of mean adult HbA1c using linear regression were the presence of any comorbidity (0.71%; 95% confidence interval [CI] 0.15-1.27; P = 0.01) and pediatric HbA1c (0.67% per 1% increase in HbA1c; 95% CI 0.51-0.84; P < 0.001). Predictors of hospitalization for hyperglycemia were a history of pediatric hospitalization for hyperglycemia (incidence rate ratio [IRR] 1.20; 95% CI 1.02-1.41; P = 0.029) and high school vs university education (IRR 3.13; 95% CI 1.12-8.73; P = 0.030). CONCLUSION: Young adults with complicated health histories and less education are more likely to experience poor diabetes outcomes in the years after transfer to adult care. These features may highlight youth requiring closer attention or may be targets for intervention.

Evaluation of venous thromboembolism prophylaxis in a major hospital in a developing country.

Background Venous thromboembolism is the most common preventable cause of hospital death. Despite that, there is still a large gap between what we know about venous thromboembolism prophylaxis and what is happening in current practice. Objective To evaluate VTE prophylaxis in Al-Basheer hospital and assess the extent of agreement of physicians' practice with the guidelines. Setting Al-Basheer governmental hospital in Jordan between January 2016 and June 2016. Method In this cross-sectional observational study, patients were randomly selected from medical and surgical wards. The need for venous thromboembolism prophylaxis was assessed according to the American College of Chest Physicians guideline (9th edition) for men and non-pregnant women, and the Royal College of Obstetricians and Gynecologists guidelines for pregnant women. MAIN OUTCOME MEASURE: rate of agreement of venous thromboembolism prophylaxis with the guidelines. Results The total number of patients was 1030, Patients in the medical wards constituted most of the participants. The rate of concordance with the guidelines was 718/1030 (69.7%) in the total number of patients When the patients were divided into groups: those that required venous thromboembolism prophylaxis and those that did not, the rate of agreement with guidelines in the subgroup that needed prophylaxis 160/456 (35.1%) was lower than the rate in the subgroup that did not need prophylaxis 558/574 (97.2%), p value <0.001. Conclusion venous thromboembolism prophylaxis in Al-Basheer hospital is not appropriate and underused, this might be attributed to the absence of an institutional guideline.

Evaluation of VTE Prophylaxis in an Educational Hospital: Comparison Between the Institutional Guideline (Caprini 2006) and the ACCP Guideline (Ninth Edition).

Venous thromboembolism (VTE) is the most common preventable cause of hospital death; the burden of VTE includes the management of the acute event (deep vein thrombosis [DVT]/pulmonary embolism) and the chronic subsequents such as postthrombotic syndrome and recurrent DVT. All experts agree that despite the abundance of knowledge available on VTE and how to prevent it, it is still underused, and since the first step in prophylaxis is to identify those who are at high risk of VTE, several risk assessment models have been developed to identify these patients and provide appropriate prophylaxis. In our study, the institutional guideline in a tertiary educational hospital is the Caprini score (2006), a comparison was conducted between the institutional guideline and the American College of Chest Physicians guideline (ACCP ninth edition [ACCP-9]) in terms of the degree of agreement of the actual prophylaxis with the institutional guideline and the ACCP-9 and the differences in risk levels. The concordance with the ACCP-9 guideline was higher than with the institutional guideline, specifically in those patients receiving prophylaxis, and there was an overestimation of the risk levels in the institutional guideline, especially in medical patients. The replacement of the existing Caprini-2006 with the ACCP-9 is prudent, since it agrees with the physicians' clinical judgment and may result in reduced use of pharmacologic prophylaxis which could lead to lower costs and fewer adverse effects.

Evaluation of venous thromboembolism prophylaxis after the introduction of an institutional guideline: Extent of application and implementation of its recommendations.

Venous thromboembolism (VTE) includes deep vein thrombosis and pulmonary embolism. Although much is known about risk factors for VTE, there is failure in administration of appropriate prophylaxis to patients who are at risk for VTE. A paper-based reminder system is considered to be among the most effective methods of improving VTE prophylaxis in hospitalized patients. However, their success relies on choosing an evidence-based institutional guideline and implementation of its recommendations. This study was carried out to detect the extent of application of the institutional guideline (Caprini score risk assessment sheet). The study was carried out in the Jordan University Hospital; 354 patients were enrolled in the study and distributed among the following wards: nonorthopedic surgical (n = 119), medical (n = 220), and surgical orthopedic wards (n = 15). The risk assessment sheet was present in only 47.2% of the patient's' files, and the scores in the files were estimated correctly in only 52.1% of cases. Prophylaxis received by patients matched the recommendation of the Caprini score in 67.1% of the patients. The degree of concordance of the VTE prophylaxis with the Caprini score was 59.9%. This study showed that the institutional guideline was poorly implemented in the hospital.