High rate of bleeding and arterial thrombosis in COVID-19: Saudi multicenter study.

BACKGROUND: Several observational studies have reported the rate of venous and arterial thrombotic events in patients infected with COVID-19, with conflicting results. The aim of this study was to estimate the rate of thrombotic and bleeding events in hospitalized patients diagnosed with Coronavirus disease 2019 (COVID-19). METHODS: This was a multicenter study of 636 patients admitted between 20 March 2020 and 31 May 2020 with confirmed COVID-19 in four hospitals. RESULTS: Over a median length of stay in the non-ICU group of 7 days and of 19 days in the ICU group, twelve patients were diagnosed with Venous thromboembolism (VTE) (1.8 %) (95 % CI, 1.1-3). The rate in the non-ICU group was 0.19 % (95 % CI, 0.04-0.84), and that in the ICU group was 10.3 % (95 % CI, 6.4-16.2). The overall rate of arterial event is 2.2 % (95 % CI, 1.4-3.3). The rates in the non-ICU and ICU groups were 0.94 % (95 % CI, 0.46-0.1.9) and 8.4 % (95 % CI, 5.0-14.0). The overall composite event rate was 2.9 % (95 % CI, 2.0-4.3). The composite event rates in the non-ICU and ICU groups were 0.94 % (95 % CI, 0.46-0.1.9) and 13.2 % (95 % CI, 8.7-19.5). The overall rate of bleeding is 1.7 % (95 % CI, 1.0-2.8). The bleeding rate in the non-ICU group was 0.19 % (95 % CI, 0.04-0.84), and that in the ICU group was 9.4 % (95 % CI, 5.7-15.1). The baseline D-dimer level was a significant risk factor for developing VTE (OR 1.31, 95 % CI, 1.08-1.57, p = 0.005) and composite events (OR 1.32, 95 % CI, 1.12-1.55, p = 0.0007). CONCLUSIONS: In this study, we found that the VTE rates in hospitalized patients with COVID-19 might not be higher than expected. In contrast to the risk of VTE, we found a high rate of arterial and bleeding complications in patients admitted to the ICU. An elevated D-dimer level at baseline could predict thrombotic complications in COVID-19 patients and may assist in the identification of these patients. Given the high rate of bleeding, the current study suggests that the intensification of anticoagulation therapy in COVID-19 patients beyond the standard of care be pursued with caution and would best be evaluated in a randomized controlled study.

Prospective comparative study between the effect of CIDEX® OPA and STERRAD NX on the durability of digital flexible ureteroscope.

PURPOSE: We compared the effect of chemical disinfection (CIDEX® OPA) and low-temperature hydrogen peroxide gas plasma (STERRAD NX) on two brand new digital flexible ureteroscope (DFU) (Flex-Xc) using subjective and objective parameters. METHODS: Over 11-month period, all flexible ureteroscopic procedures that fulfill the inclusion criteria were done by two brand new flexible ureteroscopes and were prospectively evaluated. Intraoperative data included total operative time, laser power and duration, stone criteria and subjective evaluation of the procedure as well as visibility and maneuverability scores were reported. The end point of the study was when the scope was deemed by the surgeon as unable to perform the procedure; when leak test is positive. RESULTS: A total of 88 patients were randomized either for the first flexible ureteroscope disinfected using Cidex® OPA (n = 59, 67%) or second ureteroscope sterilized with Sterrad NX (n = 29, 33%). Intraoperative, the first DFU was significantly used with a total operative time of approximately 49 h compared to the second one (p < 0.001). In the same context, laser power parameters were significantly different among the two groups (p = 0.003). The subjective evaluation of the procedure, maneuverability, visibility scores, laser duration, stone burden and post-operative infection rate were statistically insignificant between both groups. At the end point of the study, the deflection in up and downward directions for both DFU were measured. CONCLUSIONS: The durability and longevity of the DFU is strongly related to the sterilization method. Our findings suggest that CIDEX® OPA should prioritize Sterrad in sterilization of DFU.

HLA-A, B, C, DRB1 and DQB1 allele and haplotype frequencies in volunteer bone marrow donors from Eastern Region of Saudi Arabia.

We analyzed HLA allele and haplotype frequencies from donors from the Eastern region of Saudi Arabia. A cross-sectional study was performed on 2405 bone marrow donors from the Eastern region. HLA typing was carried out by sequencing. The most common HLA allele groups were HLA-A*02:01:01G (11.08%), A*01:01:01G (10.40%), HLA-B*52:01:01G (8.79%), B*18:01:01G (8.07%), HLA-C*04:01:01G (17.88%), C*12:03:01G (10.23%), HLA-DRB1*10:01 (14.89%), DRB1*03:01:01G (14.10%), HLA-DQB1*02:01:01G (24.53%) and DQB1*05:01:01G (20.17%). The most frequent HLA-A~ C~ B~ DRB1~ DQB1 haplotypes were HLA-A*01:03~ C*15:05:01G~ B*73:01~ DRB1*10:01:01~ DQB1*05:01:01G (3.11%) and HLA-A*01:01:01G~ C*12:02:01G~ B*52:01:01G~ DRB1*15:02:01~ DQB1*06:01:01G (2.25%). When comparing the allele and haplotype frequencies of the Eastern regions' population to those from the Central region we found significant differences in several allele frequencies including A*01:01:01G (P ≤ 0.0001), B*52:01:01G (P ≤ 0.0001), B*18:01:01G (P = 0.0001), C*12:03:01G (P < 0.0001), DRB1*10:01:01 (P < 0.0001) and DQB1*05:01:01G (P < 0.0001). Our data confirms genetic heterogeneity among the Saudi population.

Splenectomy vs. rituximab as a second-line therapy in immune thrombocytopenic purpura: a single center experience.

Immune thrombocytopenic purpura (ITP) is a common hematological disease treated primarily by corticosteroids. The aim of the present study was to compare response rate between patients, underwent splenectomy vs. rituximab as second-line therapy. Adult patients diagnosed with ITP who did not respond to corticosteroids or relapsed during the period 1990-2014 were included in a quasi-experimental study. Categorical variables were compared using Fisher exact test. Response to treatment was compared using logistic regression. Data were analyzed using SAS V9.2. One-hundred and forty-three patients with ITP were identified through medical records. Of 62 patients treated, 30 (48.38%) required second-line therapy. 19 (63%) patients received rituximab, and 11 (37%) underwent splenectomy. Platelets at diagnosis were not different between study groups (p = 0.062). Splenectomy group patients were younger (p = 0.011). Response to second-line therapy showed no significant difference between two groups (OR 2.03, 95% CI (0.21-22.09), p = 0.549). Results did not show a statistically significant difference in platelet counts over time between treatment groups (p = 0.101). When used exclusively as a second-line therapy for steroid-refractory ITP, the response rate was not statistically different between rituximab and splenectomy. However, further large studies are needed to assess the response rates for these treatment modalities as a second-line therapy.

Isolation and characterization of a new naturally immortalized human breast carcinoma cell line, KAIMRC1.

BACKGROUND: Breast cancer is one of the most common cancer and a leading cause of death in women. Up to date the most commonly used breast cancer cell lines are originating from Caucasians or Afro-Americans but rarely cells are being derived from other ethnic groups. Here we describe for the first time the establishment of a naturally transformed breast cancer cell line, KAIMRC1 from an Arab woman of age 62 suffering from stage IIB breast cancer (T2N1M0). Moreover, we have characterized these cells for the biological and molecular markers, induction of MAPK pathways as well as its response to different commercially available drugs and compounds. METHODS: Breast cancer tissue sections were minced and cultured in media for several weeks. KAIMRC1 cells were successfully isolated from one of the primary breast tumor tissue cultures without any enzymatic digestion. To study the growth characteristics of the cells, wound healing assay, clonogenic assay, cell proliferation assays and live cell time-lapse microscopy was performed. Karyotyping, Immunophenotyping and molecular pathway specific compound treatment was also performed. A selective breast cancer gene expression panel was used to identify genes involved in the signal transduction dysregulation and malfunction of normal biological processes during breast carcinogenesis. RESULTS: These cells are ER/PR-positive and HER2-negative. The epithelial nature of these cells was confirmed by flow cytometry analysis using epithelial cell markers. They are cuboidal in shape and relatively smaller in size as compared to established cell lines, MCF-7, MDA MB-231 and the normal breast cell line, MCF-10A. In normal cell culture conditions these cells showed the capability of growing both in monolayer as well as in 3-D conformation. They showed a doubling time in vitro of approximately 24 h. They exhibit a modal karyotype of 58-63,X with abnormalities in a couple of chromosomes. KAIMRC1 cells were found to be more responsive to drug treatment in vitro in comparison to the established MDA MB-231 and MCF-7 cell lines. CONCLUSIONS: In conclusion we have isolated and characterized a new naturally immortalized breast cell line, KAIMRC1 with a potential to play a key role in opening up novel avenues towards the understanding of breast carcinoma.

Stem cell research and regenerative medicine at King Abdullah International Medical Research Center.

Translation of stem cell research from bench to bedside opens up exciting new therapeutic options for patients. Although stem cell research has progressed rapidly, its clinical applications have not kept pace. We report on the establishment of a stem cell research and regenerative medicine program at King Abdullah International Medical Research Center (KAIMRC). The purpose of this unit is to coordinate advanced stem cell research and translational outcomes with the goal of treating chronic human diseases, such as cancer, diabetes, cardiovascular, neurological, immunological, and liver diseases. Our first step in achieving this goal was to integrate the stem cells and regenerative medicine unit with our umbilical cord blood bank and bone marrow registry. This organizational structure will provide different sources for stem cells for research and clinical purposes, and facilitate our stem cell research and stem cell transplantation program. We are at an early and exciting stage in our program, but we believe that our progress to the international stage will be rapid and have a significant impact.

Clinico-pathological pattern of extranodal non-Hodgkin's lymphoma in Saudi Arabia.

OBJECTIVES: The incidence of primary extranodal non-Hodgkin's lymphoma (NHL) is variable in different regions of world but there is a paucity of literature on various demographic aspects of extranodal NHL as a group. This study was conducted to evaluate the clinico-pathological pattern of extranodal NHL in Saudi patients. METHODS: We retrospectively studied a cohort of 855 NHL patients in four tertiary care centres in Riyadh, Saudi Arabia over a period of 5 years. RESULTS: Extranodal NHL constituted 41.4% of the total. The mean age of affected patients was 55∓18 years and a male to female ratio of 1.5:1.0. Most presented in the age range of 41-60 years. NHL of gastro-intestinal (GI) tract was the most common extranodal variety, followed by head and neck NHL (18%), primary cutaneous lymphoma (14.4%), primary CNS lymphoma (5.6%), and primary bone, thyroid and soft tissue lymphoma (4.5% each). In the GI tract, stomach was the most common site involved, accounting for more than 81% of GI NHL. Diffuse large B-cell lymphoma was the most common histologic type, comprising around 72% of all extranodal lymphomas. CONCLUSIONS: Extranodal NHL is common in Saudi Arabia and diffuse large B cell lymphoma is the most common histologic subtype. We found significant differences in the pattern of extranodal NHL in Saudi patients compared to those reported from other parts of the world. Further studies focused on the risk factors and treatment outcome are needed to better understand the biology of a disease common in this population.

Recombinant activated factor VII treatment of retroperitoneal hematoma in a patient with renal failure receiving enoxaparin and clopidogrel.

Enoxaparin is a low-molecular-weight heparin that has pharmacokinetic and therapeutic advantages over unfractionated heparin in certain clinical conditions. However, its administration is not without risk. We describe the case of a 70-year-old woman with numerous medical problems who developed severe retroperitoneal bleeding after receiving several therapeutic doses of subcutaneous enoxaparin that inadvertently were not adjusted for her renal function until day 14 of therapy. She had severe bleeding with hemodynamic instability and required massive transfusions of blood products. Her bleeding could be controlled only by administration of four doses of recombinant activated factor VII (factor VIIa) in addition to embolization of the bleeding sites through angiographic microcoiling. The patient's hemodynamic status improved, and her hemoglobin level stabilized. This case report provides evidence of the clinical effectiveness of factor VIIa use as part of the management of refractory enoxaparin-induced retroperitoneal bleeding. However, further studies are needed to validate the dose-response relationship and further support the clinical utility of factor VIIa in this life-threatening situation.