COVID-19 in patients with rheumatological diseases in the Eastern Province of Saudi Arabia.

The severity of the 2019 coronavirus disease (COVID-19) and its effects remain unpredictable. Certain factors, such as obesity, hypertension, and type 2 diabetes mellitus, may increase the severity of the disease. Rheumatology experts suggest that patients with active autoimmune conditions and controlled autoimmune diseases on immunosuppressive therapy may be at higher risk of developing severe COVID-19. In this retrospective observational study, we aimed to examine the patterns of COVID-19 in patients with underlying rheumatological diseases and their association with disease severity and hospital outcomes. A total of 34 patients with underlying rheumatological diseases who tested positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by polymerase chain reaction (PCR) were included between March 2020 and April 2021 at King Fahd Hospital of the University. The study population consisted of 76.47% female and 23.53% male patients, with a mean age ranging from 20 to 40 years. Female gender (p=0.0001) and younger age (p=0.004) were associated with milder disease. The most frequent rheumatological disease was systemic lupus erythematosus (SLE) (38.24%), which was associated with a milder infection (p=0.045). Patients treated with mycophenolate mofetil (MMF) had a milder disease course (p=0.0037). Hypertension was significantly associated with severe COVID-19 disease (p=0.037). There was no significant relationship between SLE and the need for ICU admission. Patients on hydroxychloroquine and MMF tended to develop milder disease, and there was no association between the severity of the infection and the treatment with steroids.

Construction of VSVΔ51M oncolytic virus expressing human interleukin-12.

The use of oncolytic viruses (OVs) in combination with cytokines, such as IL-12, is a promising approach for cancer treatment that addresses the limitations of current standard treatments and traditional cancer immunotherapies. IL-12, a proinflammatory cytokine, triggers intracellular signaling pathways that lead to increased apoptosis of tumor cells and enhanced antitumor activity of immune cells via IFN-γ induction, making this cytokine a promising candidate for cancer therapy. Targeted expression of IL-12 within tumors has been shown to play a crucial role in tumor eradication. The recent development of oncolytic viruses enables targeted delivery and expression of IL-12 at the tumor site, thereby addressing the systemic toxicities associated with traditional cancer therapy. In this study, we constructed an oncolytic virus, VSVΔ51M, based on the commercially available VSV wild-type backbone and further modified it to express human IL-12. Our preclinical data confirmed the safety and limited toxicity of the modified virus, VSV-Δ51M-hIL-12, supporting its potential use for clinical development.

Clinical outcome of pre-operative blood transfusion for sickle cell disease patients in post-operative complications.

BACKGROUND: Preoperative blood transfusion for patients with sickle cell disease is a debatable topic and it can be lifesaving. Sickle cell disease patients are at high risk for vaso-occlusive crisis due to the large concentration of sickle hemoglobin (HgbS) in their blood. Despite the current extensive research into this disease, there is still no consensus over whether blood transfusion is a preferable preoperative modality among patients undergoing elective surgical procedures. METHOD: A retrospective observational study, which enrolled 204 patients with Sickle cell disease who underwent surgery at King Fahad Hospital of the University (KFHU) over the last five years. The primary objective was to determine whether there is evidence that preoperative blood transfusion for SCD patients undergoing surgical procedures will reduce postoperative complications related to SCD. RESULTS: A total of 204 patients were included, of which 30% had preoperative blood transfusion. Majority of patient 44% had undergone cholecystectomy. On multivariate logistic regression analysis, patients who did not undergo blood transfusion had significantly higher risk to develop post-operative SCD complications (OR = 3.07, P value = 0.002). In addition, they had significantly prolonged hospitalization (OR = 2.22, P value = 0.08). In contrast, patients who received blood transfusion had lower risk for developing post-operative SCD-related complications (OR = 1.87, P value = 0.29), and decrease in the duration of hospitalization by (OR = 0.49, P value = 0.045). CONCLUSION: Our study showed that patients who had not undergone preoperative blood transfusion had higher risk to develop postoperative complications and prolonged hospital stay compared to those who underwent blood transfusion.

Delayed presentation of massive haemoptysis from aortic aneurysm after aortic coarctation repair (a case report).

INTRODUCTION: Massive haemoptysis refers to coughing and losing a huge amount of blood in a 24-hour period. It's a life-threatening condition with high mortality rate. CASE PRESENTATION: We report a rare case of massive haemoptysis in a 60-year-old female patient who had aortic coarctation repair 30 years ago. Her Computed tomography (CT) angiography showed huge aneurysmal dilatation and dissection of the descending thoracic aorta at the site of the repair. Thoracic endovascular aortic repair (TEVAR) was done, but the patient had recurrent massive haemoptysis due to extension of the aneurysm to the aortic arch. The patient then underwent one stage surgical right to left carotid artery shunt followed by TEVAR to the aortic arch covering the left common carotid artery. The procedure was successful, and haemoptysis was controlled without any complications. DISCUSSION: In this case the high index of suspicion for thoracic aortic aneurysm in patients presenting with haemoptysis and prior history of coarctation repair were demonstrated. CONCLUSION: massive haemoptysis in patients who had aortic coarctation repair is an alarming sign, and surgical intervention is required. TEVAR has become one of the best approaches for managing aortic aneurysm and has replaced open repair.

Gene therapy for spinal muscular atrophy: the Qatari experience.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by hypotonia, progressive muscle weakness, and wasting. Onasemnogene abeparvovec (Zolgensma®) is a novel gene therapy medicine, FDA-approved in May 2019 for the treatment of SMA. This study aimed to describe Qatari experience with onasemnogene abeparvovec by reviewing the clinical outcomes of 9 SMA children (7 SMA type 1 and 2 with SMA type 2) aged 4‒23 months treated between November 2019 and July 2020. Children <2 years with 5q SMA with a bi-allelic mutation in the SMN1 gene were eligible for gene therapy. Liver function (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and total bilirubin), platelet count, coagulation profile, troponin-I levels, and motor scores (Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders [CHOP INTEND]), were regularly monitored following gene therapy. All patients experienced elevated AST or ALT, two experienced high prothrombin time, and one experienced elevated bilirubin; all of these patients were asymptomatic. Furthermore, one event of vomiting after infusion was reported in one patient. Significant improvements in CHOP INTEND scores were observed following therapy. This study describes the short-term outcomes and safety of onasemnogene abeparvovec, which is well tolerated and shows promise for early efficacy.

DNA Based Vaccine Expressing SARS-CoV-2 Spike-CD40L Fusion Protein Confers Protection Against Challenge in a Syrian Hamster Model.

SARS-CoV-2 infections present a tremendous threat to public health. Safe and efficacious vaccines are the most effective means in preventing the infections. A variety of vaccines have demonstrated excellent efficacy and safety around the globe. Yet, development of alternative forms of vaccines remains beneficial, particularly those with simpler production processes, less stringent storage conditions, and the capability of being used in heterologous prime/boost regimens which have shown improved efficacy against many diseases. Here we reported a novel DNA vaccine comprised of the SARS-CoV-2 spike protein fused with CD40 ligand (CD40L) serving as both a targeting ligand and molecular adjuvant. A single intramuscular injection in Syrian hamsters induced significant neutralizing antibodies 3-weeks after vaccination, with a boost substantially improving immune responses. Moreover, the vaccine also reduced weight loss and suppressed viral replication in the lungs and nasal turbinates of challenged animals. Finally, the incorporation of CD40L into the DNA vaccine was shown to reduce lung pathology more effectively than the DNA vaccine devoid of CD40L. These results collectively indicate that this DNA vaccine candidate could be further explored because of its efficacy and known safety profile.

Cancer genetics program: Follow-up on clinical genetics and genomic medicine in Qatar.

This article presents an overview of the cancer genetics program in Qatar. In addition to summarizing clinical, research, educational, and other aspects, data related to testing outcomes (over the course of approximately 5.5 years) are presented.

Depression, Hopelessness and Social Support among Breast Cancer Patients: in Highly Endogamous Population

Aim: The aim of this study was to assess the relationship between different demographic variables, hopelessness, depression and social support of Breast cancer patients in Qatari's population. Design: This is an observational cohort hospital based study. Subjects and Methods: The study included 678 breast cancer patients. The questionnaires included a demographic questionnaire, the Beck Hopelessness Scale (BHS), Back Depression Scale (BDS) and Multidimensional Scale of Perceived Social Support (MSPSS). The demographic questionnaire was used to assess patients' basic information including gender, age, marital status, education, family size, and place of residence. Medical information regarding cancer stage, the time passed since diagnosis, treatment, and duration of disease were recorded. Results: The mean age of the studied women was 47.7±10.2 years. Among the studied patients, 34.7% were Qataris and 65.3% were Arab expatriates. Nearly 39.2% of the patients were in pre-menopausal status and 60.8% in post-menopausal status. 86.1% of women were married. 14.6% were illiterate women, 20.9% were university graduates and 37.2% were housewives. Smoking habit was less common in studied Arab women (9.1%), but, sheesha smoking was more common, 17.7%. Daily physical activity indicated 25.7% were walking 30 minutes per-day and 14% were walking 60 minutes per day. 30.4% of them had consanguineous parents. Breast feeding was practiced among 67.7% of women and over 73% were considered overweight and obese. Furthermore, over 75% of breast cancer women were at the Stage 3 (40.9%) and Stage 4 (35.8%) of cancer. The percentage of patients who underwent mastectomy and lumpectomy were 49.3 % and 50.7%, respectively. It was observed that 27.7% of BDI patients had moderate depression and 19.5% of the BDI patients had severe depression and with mean and standard deviation 25.1±7.7. Also, the mean and SD of BDI for consanguineous has showed statistically significant 28.4±5.7 than non- consanguineous 23.2± 8.0 (p<0.001). All socio-demographic variables showed statistically significant differences with the total BHS score. The highest score belongs to the family sub-dimension. Conclusion: The present study indicates that hopelessness of the patients with breast cancer decreased with the increase in their social support. Therefore, activating patient social support systems is of importance in increasing their levels of hope. The present study revealed the coexistence of the socio-demographic, physical, psychological, and cognitive problems faced by patients with cancer.

An assessment of reliability and validity of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 among breast cancer patients in Qatar.

INTRODUCTION: Breast cancer has been the most common cancer type that affects women worldwide and subsequent treatment is often associated with considerable psychological and quality of life (QoL). AIM: This study aimed to assess psychometric properties of the Arabic version of the European Organization for Research and Treatment of Cancer (EORTC) general QoL questionnaire (QLQ-C30) for breast cancer patients in Qatar. MATERIALS AND METHODS: This is a cross-sectional hospital-based study conducted on 678 breast cancer patients using Arabic version of the EORTC QLQ-C30 tool. RESULTS: The mean age of women was 47.7 ± 10.2 years and 33.4% of women had consanguineous parents. Six subscales out of the nine met the standards of reliability with coefficients ranging from 0.55 to 0.89. The mean score of all functioning scales was high >55. Advanced breast cancer stages of III-IV had higher symptomatic scores significantly than those in early stages for the physical function, cognitive, fatigue, insomnia, appetite loss, constipation, and financial difficulties. Correlation coefficients between each item ranged from -0.113 to 0.960, and item 21 (tense) and item 23 (irritable) had strongest negative correlations with their corresponding emotional functioning subscale, whereas items 29 (physical condition) and 30 (overall QoL) had the strongest positive correlation with Global Health/QoL subscale. Item 6 (limited work) showed a higher correlation with fatigue (r = 0.749). Likewise, item 19 (pain interfered with daily activities) of the pain subscale had higher correlations with physical functioning, role functioning, and fatigue subscales. CONCLUSION: Qatari Arabic version of the EORTC QLQ-C30 showed acceptable psychometric properties, which is a reliable and valid instrument, that can be used by oncologists.

Two Qatari siblings with cystic fibrosis and apparent mineralocorticoid excess.

Cystic fibrosis (CF) and apparent mineralocorticoid excess (AME) syndrome are both autosomal recessive disorders that result from mutations of specific identified genes for each condition. CF is caused by defects in the Cystic fibrosis trans membrane conductance regulator (CFTR) gene which encodes for a protein that functions as a chloride channel and regulates the flow of other ions across the apical surface of epithelial cells. AME is due to the deficiency of 11ß-hydroxysteroid dehydrogenase type 2 enzyme (11ßHSD2), which is responsible for the peripheral inactivation of cortisol to cortisone. Cortisol excess stimulates the mineralocoritoid receptors (MR) resulting in intense sodium retention, hypokalemia and hypertension. We report on a consanguineous Arab family, in which two sibs inherited both CF and AME. Gene testing for AME revealed previously unreported mutation in the 11ßHSD2 gene. This report draws attention to the importance of recognizing the possibility of two recessive disorders in the same child in complex consanguineous families. Moreover, it provides a unique opportunity to highlight the implications of the coexistence of two genetic disorders on patient care and genetic counseling of the family.