A Saudi multicenter experience on therapeutic plasma exchange for patients with thrombotic thrombocytopenic purpura: A call for national registry.

BACKGROUND: The improvement in the clinical care for patients with thrombotic thrombocytopenic purpura (TTP) is evolving, and many efforts are being put to standardize it. Here, we aimed to assess the provided care at a national level and identify deficiencies. METHODS: A national Saudi retrospective descriptive study was carried out at six tertiary referral centers and included all patients who underwent therapeutic plasma exchange (TPE) for the diagnosis of TTP between May 2005, and July 2022. Collected information included demographic data, clinical features on presentation, and the results of laboratory investigations at admission and discharge. In addition, the number of TPE sessions, days till the first session of TPE, usage of immunological agents, and clinical outcomes were all collected. RESULTS: One hundred patients were enrolled, predominantly female (56%). The mean age was 36.8 years. At diagnosis, 53% of patients showed neurological involvement. The mean platelet count at presentation was 21 × 109 /L. All patients had anemia (mean hematocrit 24.2%). Schistocytes were present in the peripheral blood film of all patients. The mean number of TPE rounds was 13 ± 9.3, and the mean days to start TPE since admission for the first episode was 2.5 days. ADAMTS13 level was measured in 48% of patients and was significantly low in 77% of them. Assessing for clinical TTP scores, 83%, 1000%, 64% of eligible patients had an intermediate/high PLASMIC, FRENCH, and Bentley scores, respectively. Caplacizumab was used on only one patient, and rituximab was administered to 37% of patients. A complete response for the first episode was achieved in 78% of patients. The overall mortality rate was 25%. Neither time to TPE, the use of rituximab or steroid affected survival. CONCLUSIONS: Our study shows an excellent response to TPE with a survival rate approximate to the reported international literature. We observed a deficiency in using validated scoring systems in addition to confirming the disease by ADAMTS13 testing. This emphasizes the need for a national registry to facilitate proper diagnosis and management of this rare disorder.

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.

IMPORTANCE trial: a provisional study-design of a single-center, phase II, double-blinded, placebo-controlled, randomized, 4-week study to compare the efficacy and safety of intranasal esketamine in chronic opioid refractory pain.

Background:  Cancer is the second leading cause of death globally. Up to 86% of advanced cancer patients experience significant pain, while 10-20% live in chronic pain. Besides, increasing prescription of opioids resulted in 33,000 deaths in the US in 2015. Both reduce patients' functional status and quality of life. While cancer survival rates are increasing, therapeutic options for chronic opioid refractory pain are still limited. Esketamine is the s-enantiomer of ketamine, with superior analgesic effect and less psychotomimetic side effects. Intranasal esketamine was approved by the FDA for treatment-resistant depression. However, its use in chronic cancer pain has never been tested. Therefore, we propose a phase II, randomized, placebo-controlled trial to evaluate the efficacy and safety of intranasal esketamine in chronic opioid refractory cancer pain. Methods and analysis: We will recruit 120 subjects with chronic opioid refractory pain, defined as pain lasting more than 3 months despite optimal therapy with high dose opioids (>60 mg morphine equivalent dose/day) and optimal adjuvant therapy. Subjects will be randomized into two groups: intranasal esketamine (56mg) and placebo. Treatment will be administered twice a week for four consecutive weeks. The primary outcome is defined as reduction in the Numeric Pain Rating Scale (NPRS) after first application. Secondary outcomes include NPRS reduction after four weeks, the number of daily morphine rescue doses, functional status and satisfaction, and depression. Conclusion: This study may extend therapeutic options in patients with chronic pain, thus improving their quality of life and reducing opioid use. Trial registration: Clinical Trials.gov, NCT04666623. Registered on 14 December 2020.