Implementing remote triage in large health systems: A qualitative evidence synthesis.

Remote triage (RT) allows interprofessional teams (e.g., nurses and physicians) to assess patients and make clinical decisions remotely. RT use has developed widespread interest due to the COVID-19 pandemic, and has future potential to address the needs of a rapidly aging population, improve access to care, facilitate interprofessional team care, and ensure appropriate use of resources. However, despite rapid and increasing interest in implementation of RT, there is little research concerning practices for successful implementation. We conducted a systematic review and qualitative evidence synthesis of practices that impact the implementation of RT for adults seeking clinical care advice. We searched MEDLINE®, EMBASE, and CINAHL from inception through July 2018. We included 32 studies in this review. Our review identified four themes impacting the implementation of RT: characteristics of staff who use RT, influence of RT on staff, considerations in selecting RT tools, and environmental and contextual factors impacting RT. The findings of our systemic review underscore the need for a careful consideration of (a) organizational and stakeholder buy-in before launch, (b) physical and psychological workplace environment, (c) staff training and ongoing support, and (d) optimal metrics to assess the effectiveness and efficiency of implementation. Our findings indicate that preimplementation planning, as well as evaluating RT by collecting data during and after implementation, is essential to ensuring successful implementation and continued adoption of RT in a health care system.

Effectiveness of Acute Care Remote Triage Systems: a Systematic Review.

BACKGROUND: Technology-based systems can facilitate remote decision-making to triage patients to the appropriate level of care. Despite technologic advances, the effects of implementation of these systems on patient and utilization outcomes are unclear. We evaluated the effects of remote triage systems on healthcare utilization, case resolution, and patient safety outcomes. METHODS: English-language searches of MEDLINE (via PubMed), EMBASE, and CINAHL were performed from inception until July 2018. Randomized and nonrandomized comparative studies of remote triage services that reported healthcare utilization, case resolution, and patient safety outcomes were included. Two reviewers assessed study and intervention characteristics independently for study quality, strength of evidence, and risk of bias. RESULTS: The literature search identified 5026 articles, of which eight met eligibility criteria. Five randomized, two controlled before-and-after, and one interrupted time series study assessed 3 categories of remote triage services: mode of delivery, triage professional type, and system organizational level. No study evaluated any other delivery mode other than telephone and in-person. Meta-analyses were unable to be performed because of study design and outcome heterogeneity; therefore, we narratively synthesized data. Overall, most studies did not demonstrate a decrease in primary care (PC) or emergency department (ED) utilization, with some studies showing a significant increase. Evidence suggested local, practice-based triage systems have greater case resolution and refer fewer patients to PC or ED services than regional/national systems. No study identified statistically significant differences in safety outcomes. CONCLUSION: Our review found limited evidence that remote triage reduces the burden of PC or ED utilization. However, remote triage by telephone can produce a high rate of call resolution and appears to be safe. Further study of other remote triage modalities is needed to realize the promise of remote triage services in optimizing healthcare outcomes. PROTOCOL REGISTRATION: This study was registered and followed a published protocol (PROSPERO: CRD42019112262).

Evaluation of a point-of-care method for screening blood donors for sickle cell status.

BACKGROUND: Turbidity tests are commonly used for screening blood units for the presence of sickle cell trait (SCT) before transfusion to specific patient populations, based on recommendations of the AABB. In this pilot study, we evaluate a new method for screening blood donors and blood units for the presence of sickle hemoglobin. STUDY DESIGN AND METHODS: This study was based at King Abdulaziz University Hospital in Jeddah, Saudi Arabia. Study participants were approached consecutively between July 24, 2016, and August 8, 2016. Blood donors, control individuals, and known patients with sickle cell disease (SCD) were tested using both a point-of-care testing technology (Sickle SCAN, Biomedomics, Inc.) and hemoglobin capillary electrophoresis (HEP). Corresponding blood units were also tested using Sickle SCAN. RESULTS: A total of 200 donors, 13 blood units, and 57 patients and controls were included. Sensitivity and specificity of Sickle SCAN for detection of SCT and SCD was 100%, when compared to HEP as the gold standard. CONCLUSION: Sickle SCAN is a rapid test that shows high sensitivity and specificity for identification of hemoglobin S among blood donors and when used for testing blood units.

Concise Review: Getting to the Core of Inherited Bone Marrow Failures.

Bone marrow failure syndromes (BMFS) are a group of disorders with complex pathophysiology characterized by a common phenotype of peripheral cytopenia and/or hypoplastic bone marrow. Understanding genetic factors contributing to the pathophysiology of BMFS has enabled the identification of causative genes and development of diagnostic tests. To date more than 40 mutations in genes involved in maintenance of genomic stability, DNA repair, ribosome and telomere biology have been identified. In addition, pathophysiological studies have provided insights into several biological pathways leading to the characterization of genotype/phenotype correlations as well as the development of diagnostic approaches and management strategies. Recent developments in bone marrow transplant techniques and the choice of conditioning regimens have helped improve transplant outcomes. However, current morbidity and mortality remain unacceptable underlining the need for further research in this area. Studies in mice have largely been unable to mimic disease phenotype in humans due to difficulties in fully replicating the human mutations and the differences between mouse and human cells with regard to telomere length regulation, processing of reactive oxygen species and lifespan. Recent advances in induced pluripotency have provided novel insights into disease pathogenesis and have generated excellent platforms for identifying signaling pathways and functional mapping of haplo-insufficient genes involved in large-scale chromosomal deletions-associated disorders. In this review, we have summarized the current state of knowledge in the field of BMFS with specific focus on modeling the inherited forms and how to best utilize these models for the development of targeted therapies. Stem Cells 2017;35:284-298.

Markers of endothelial dysfunction and leucocyte activation in Saudi and non-Saudi haplotypes of sickle cell disease.

Sickle cell disease (SCD) is an autosomal recessive inherited hemoglobinopathy, characterized by chronic hemolysis and recurrent vaso-occlusive crisis (VOC). This study investigates changes in leucocyte subsets and the relationship between cell adhesion molecule expression and disease manifestations in patients during steady state and acute VOC. We compared soluble E-selectin and P-selectin levels in 84 SCD patients, in steady state and during VOC to 84 healthy controls. Using immunophenotyping, we also compared lymphocyte subsets in these three groups. Further, we compared E-selectin and P-selectin levels in patients of Saudi ethnicity to non-Saudi patients, in all three groups. Lymphocyte subsets showed high percentages of total T lymphocytes, T helper and suppressor lymphocytes, B lymphocytes as well as NK cells in patients with SCD during steady state, while B lymphocytes and NK cells were significantly higher during acute VOC crisis. High levels of both soluble E-selectin (sE-selectin) and soluble P-selectin (sP-selectin) markers were demonstrated in the serum of patients with SCD during both steady state and acute VOC. Levels of selectins were significantly higher in acute VOC. The immunophenotypic expression of L-selectin, on leucocytes, was high in SCD both during steady state and during acute VOC in comparison to normal control subjects. There was no significant difference in all three study groups between Saudi and non-Saudi patients. These findings suggest that patients with SCD have increased expression of adhesion molecules: E-selectin and P-selectin, which play an important role in the pathogenesis of VOC. Despite the distinct phenotype of Saudi patients with SCD, there was no significant difference in levels of soluble E-selectin and soluble P-selectin between Saudi and non-Saudi patients in all three groups. While sickle cell disease is a well-recognized state of chronic inflammation, the role of specific adhesion molecules is steadily unraveling. Studies are underway to investigate the potential role of selectin antagonists, for prevention and reversal of acute vascular occlusions in SCD patients.

Plasmapheresis in severe methemoglobinemia following occupational exposure.

Ferrous iron can be converted to ferric iron by oxidative stress which results in the formation of methemoglobin. Consequently, the oxygen dissociation curve is shifted to the left, which leads to tissue hypoxia and ultimately may cause death. Acquired methemoglobinemia can be due to a host of offending agents and chemicals including nitrites, local anesthetics, aniline and antimalarial drugs. There are several approaches to the management of methemoglobinemia. The first step is to stop the offending agent and initiate supportive measures. Methylene blue can be used successfully provided the patient has no evidence of glucose 6 phosphate deficiency. Hyperbaric oxygen and intravenous ascorbic acid are other treatment options. We present a case of unusually severe methemoglobinemia (82% methemoglobin) secondary to occupational exposure that failed to respond to several lines of management including methylene blue, red cell exchange, intravenous ascorbic acid, and hyperbaric oxygen. However, the patient responded swiftly to plasmapheresis started upon suspicion of concomitant thrombotic thrombocytopenic purpura, and he subsequently recovered completely. Thus, plasmapheresis may have a role in severe methemoglonbinemia unresponsive to standard treatment options.

Quality of Life Outcomes in a Pediatric Thalassemia Population in Egypt.

Thalassemia is a disorder of hemoglobin (Hb) synthesis characterized by chronic hemolysis. In ß-thalassemias major (ß-TM), patients require regular transfusion at an early age due to severe anemia. Subsequently, intensive chelation therapy is initiated to mitigate the effects of the resultant iron overload. Clinical disease burden and the demanding treatment can affect health-related quality of life (HRQoL) outcomes in this population. The aim of this study was to assess HRQoL outcomes in Egyptian pediatric thalassemia patients. Patients were enrolled simultaneously from the hematology clinic at the National Research Institute in Cairo, Egypt. The Arabic version of SF36 tool was used to assess HRQoL outcomes. Socioeconomic data were collected by patient and parent interviews. Clinical data were collected by review of medical records. One hundred and thirty patients and 60 controls were enrolled, with a mean age of 5.4 ± 3.2 years and 6.3 ± 3.0, respectively. The HRQoL outcome scores were lower in all domains in the thalassemia group compared to the control group (p = 0.0001). Transfusion-dependent (TD) patients had lower HRQoL scores compared to nontransfusion-dependent (NTD) patients (p = 0.0001). Patient education and maternal education were independently associated with better HRQoL scores (p = 0.007, p = 0.028, respectively). Residents of rural areas reported lower scores compared to urban residents (p = 0.026). Thalassemia was associated with lower HRQoL scores, in all domains, compared to HRQoL in unaffected controls. Chronic transfusion independence, patient education, and maternal education were all associated with higher HRQoL scores. Psychological, social, and economic support for families with thalassemia are all essential tools to improve HRQoL outcomes.

Effectiveness of Intermittent Pneumatic Compression Devices for Venous Thromboembolism Prophylaxis in High-Risk Surgical Patients: A Systematic Review.

BACKGROUND: Thromboprophylaxis regimens include pharmacologic and mechanical options such as intermittent pneumatic compression devices (IPCDs). There are a wide variety of IPCDs available, but it is uncertain if they vary in effectiveness or ease of use. This is a systematic review of the comparative effectiveness of IPCDs for selected outcomes (mortality, venous thromboembolism [VTE], symptomatic or asymptomatic deep vein thrombosis, major bleeding, ease of use, and adherence) in postoperative surgical patients. METHODS: We searched MEDLINE (via PubMed), Embase, CINAHL, and Cochrane CENTRAL from January 1, 1995, to October 30, 2014, for randomized controlled trials, as well as relevant observational studies on ease of use and adherence. RESULTS: We identified 14 eligible randomized controlled trials (2633 subjects) and 3 eligible observational studies (1724 subjects); most were conducted in joint arthroplasty patients. Intermittent pneumatic compression devices were comparable to anticoagulation for major clinical outcomes (VTE: risk ratio, 1.39; 95% confidence interval, 0.73-2.64). Limited data suggest that concurrent use of anticoagulation with IPCD may lower VTE risk compared with anticoagulation alone, and that IPCD compared with anticoagulation may lower major bleeding risk. Subgroup analyses did not show significant differences by device location, mode of inflation, or risk of bias elements. There were no consistent associations between IPCDs and ease of use or adherence. CONCLUSIONS: Intermittent pneumatic compression devices are appropriate for VTE thromboprophylaxis when used in accordance with current clinical guidelines. The current evidence base to guide selection of a specific device or type of device is limited.

Coagulation activation in sickle cell trait: an exploratory study.

Recent epidemiologic data suggest that sickle cell trait (HbAS; AS) is a risk factor for venous thromboembolism. We conducted an exploratory study of healthy subjects with AS under baseline conditions to determine whether a chronic basal hyperactivation of coagulation exists, and if so, what mechanism(s) contribute to this state. Eighteen healthy AS individuals were compared to 22 African-American controls with a normal haemoglobin profile (HbAA; AA) and 17 patients with sickle cell disease (HbSS; SS). Plasma thrombin-antithrombin complexes and D-dimer levels were elevated in AS relative to AA patients (P = 0·0385 and P = 0·017, respectively), and as expected, were much higher in SSversusAA (P < 0·0001 for both). Thrombin generation in platelet poor plasma was indistinguishable between AA and AS subjects, whereas a paradoxical decrease in endogenous thrombin potential was observed in SS (P ≤ 0·0001). Whole blood tissue factor was elevated in SS compared to AA (P = 0·005), but did not differ between AA and AS. Plasma microparticle tissue factor activity was non-significantly elevated in AS (P = 0·051), but was clearly elevated in SS patients (P = 0·004) when compared to AA controls. Further studies in larger cohorts of subjects with sickle cell trait are needed to confirm the results of this preliminary investigation.

Comparative effectiveness of new oral anticoagulants and standard thromboprophylaxis in patients having total hip or knee replacement: a systematic review.

BACKGROUND: Pharmacologic thromboprophylaxis reduces the risk for venous thromboembolism after total hip replacement (THR) or total knee replacement (TKR). New oral anticoagulants (NOACs), including direct thrombin inhibitors and factor Xa inhibitors, are emerging options for thromboprophylaxis after these procedures. PURPOSE: To compare the benefits and risks of NOACs versus standard thromboprophylaxis for adults having THR or TKR. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews from January 2009 through March 2013. STUDY SELECTION: English-language systematic reviews. DATA EXTRACTION: Two independent reviewers abstracted data and rated study quality and strength of evidence. DATA SYNTHESIS: Six good-quality systematic reviews compared NOACs with low-molecular-weight heparin (LMWH) for thromboprophylaxis after THR or TKR. Risk for symptomatic deep venous thrombosis, but not risk for death or nonfatal pulmonary embolism, was reduced with factor Xa inhibitors compared with LMWH (4 fewer events per 1000 patients). Conversely, the risk for major bleeding increased (2 more events per 1000 patients). Outcomes of dabigatran did not significantly differ from those of LMWH. Indirect evaluation of NOACs by common comparison with LMWH showed nonsignificantly reduced risks for venous thromboembolism with rivaroxaban compared with dabigatran (risk ratio [RR], 0.68 [95% CI, 0.21 to 2.23]) and apixaban (RR, 0.59 [CI, 0.26 to 1.33]) but increased major bleeding. New oral anticoagulants have not been compared with warfarin, aspirin, or unfractionated heparin. LIMITATIONS: Head-to-head comparisons among NOACs were not available. Efficacy is uncertain in routine clinical practice. CONCLUSION: New oral anticoagulants are effective for thromboprophylaxis after THR and TKR. Their clinical benefits over LMWH are marginal and offset by increased risk for major bleeding. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs.

Impact of sickle hemoglobinopathies on pregnancy-related venous thromboembolism.

OBJECTIVE: The aim of the study is to examine the relationship between sickle cell trait (Hb AS) and other sickle hemoglobinopathies and the risk of thromboembolism during pregnancy or the puerperium. STUDY DESIGN: Retrospective cohort study of African American women receiving prenatal care from 1991 to 2006. Sickle cell status was ascertained by routine hemoglobin electrophoresis. Venous thromboembolism (VTE) was defined as one or more episodes of deep venous and/or pulmonary thromboembolism during pregnancy or the puerperium according to discharge diagnoses based on International Classification of Diseases, Ninth Revision codes. RESULTS: Among 22,140 women with hemoglobin (Hb) AA status, 20 women (0.09%) experienced pregnancy-related VTE compared with 3 women (0.15%) of 2,037 women with Hb AS; relative risk (RR) for the association with AS status = 1.6; 95% confidence interval (CI) 0.5 to 5.5. Of 103 women, 3 women (2.9%) with sickle cell disease conditions (Hb SS, Hb SC, or Hb S,beta-thalassemia) experienced thromboembolism. Compared with women with Hb AA status, the RR = 32.2, 95% CI 9.7 to 107. CONCLUSION: Sickle cell trait may be associated with a modest increase in VTE in the setting of pregnancy; sickle cell disease conditions are strongly associated with this rare but potentially fatal outcome.

Potential role for statins in sickle cell disease.

The complex pathophysiology of sickle cell disease (SCD) is remarkably similar to that observed in other chronic vascular diseases and involves multiple biologic pathways triggered by ischemia reperfusion injury, coagulation activation, and inflammation. Statins are potent lipid-lowering agents commonly used to reduce the risk of cardiovascular disease. Independent of their lipid lowering effect, statins have been shown to down-regulate inflammatory mediators and endothelial adhesion molecules, reduce tissue factor expression and restore nitric oxide bioavailability. The pleiotropic effects of statins make these agents attractive therapeutic candidates for SCD. This article reviews available evidence for the potential role of statins in SCD.

Comparative effectiveness of warfarin and new oral anticoagulants for the management of atrial fibrillation and venous thromboembolism: a systematic review.

BACKGROUND: New oral anticoagulants (NOACs), including direct thrombin inhibitors (DTIs) and factor Xa (FXa) inhibitors, are emerging alternatives for prophylaxis and treatment of atrial fibrillation (AF) and venous thromboembolism (VTE). PURPOSE: To compare the benefits and harms of NOACs versus warfarin for AF and VTE. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews from January 2001 through July 2012; U.S. Food and Drug Administration (FDA) database for adverse event reports. STUDY SELECTION: English-language, randomized, controlled trials (RCTs) comparing NOACs with warfarin for management of AF or VTE and observational studies and FDA reports on adverse effects. DATA EXTRACTION: Two independent reviewers abstracted data and rated study quality and strength of evidence. DATA SYNTHESIS: Six good-quality RCTs compared NOACs (2 DTI studies, 4 FXa inhibitor studies) with warfarin. In AF, NOACs decreased all-cause mortality (risk ratio [RR], 0.88 [95% CI, 0.82 to 0.96]); in VTE, NOACs did not differ for mortality or VTE outcomes. Across indications, adverse effects of NOACs compared with warfarin were fatal bleeding (RR, 0.60 [CI, 0.46 to 0.77]), major bleeding (RR, 0.80 [CI, 0.63 to 1.01]), gastrointestinal bleeding (RR, 1.30 [CI, 0.97 to 1.73]), and discontinuation due to adverse events (RR, 1.23 [CI, 1.05 to 1.44]). Subgroup analyses suggest a higher risk for myocardial infarction with DTIs than with FXa inhibitors. Bleeding risk for NOACs may be increased in persons older than 75 years or those receiving warfarin who have good control. LIMITATION: There were no head-to-head comparisons of NOACs and limited data on harms. CONCLUSION: New oral anticoagulants are a viable option for patients receiving long-term anticoagulation. Treatment benefits compared with warfarin are small and vary depending on the control achieved by warfarin treatment. PRIMARY FUNDING SOURCE: Department of Veterans Affairs.

Machine Learning-Based Prediction of COVID-19 Prognosis Using Clinical and Hematologic Data.

The coronavirus disease 2019 (COVID-19) pandemic is challenging healthcare systems worldwide. The prediction of disease prognosis has a critical role in confronting the burden of COVID-19. We aimed to investigate the feasibility of predicting COVID-19 patient outcomes and disease severity based on clinical and hematological parameters using machine learning techniques. This multicenter retrospective study analyzed records of 485 patients with COVID-19, including demographic information, symptoms, hematological variables, treatment information, and clinical outcomes. Different machine learning approaches, including random forest, multilayer perceptron, and support vector machine, were examined in this study. All models showed a comparable performance, yielding the best area under the curve of 0.96, in predicting the severity of disease and clinical outcome. We also identified the most relevant features in predicting COVID-19 patient outcomes, and we concluded that hematological parameters (neutrophils, lymphocytes, D-dimer, and monocytes) are the most predictive features of severity and patient outcome.

D-dimer antigen: current concepts and future prospects.

The D-dimer antigen is a unique marker of fibrin degradation that is formed by the sequential action of 3 enzymes: thrombin, factor XIIIa, and plasmin. First, thrombin cleaves fibrinogen producing fibrin monomers, which polymerize and serve as a template for factor XIIIa and plasmin formation. Second, thrombin activates plasma factor XIII bound to fibrin polymers to produce the active transglutaminase, factor XIIIa. Factor XIIIa catalyzes the formation of covalent bonds between D-domains in the polymerized fibrin. Finally, plasmin degrades the crosslinked fibrin to release fibrin degradation products and expose the D-dimer antigen. D-dimer antigen can exist on fibrin degradation products derived from soluble fibrin before its incorporation into a fibrin gel, or after the fibrin clot has been degraded by plasmin. The clinical utility of D-dimer measurement has been established in some scenarios, most notably for the exclusion of VTE. This article consists of 2 sections: in the first, the dynamics of D-dimer antigen formation is discussed and an overview of commercially available D-dimer assays is provided. The second section reviews available evidence for the clinical utilization of D-dimer antigen measurement in VTE, as well as emerging areas of D-dimer utilization as a marker of coagulation activation in other clinical settings.

Thromboprophylaxis for orthopedic surgery; An updated meta-analysis.

BACKGROUND: Venous thromboembolism (VTE) is a serious complication of orthopedic surgery. Low molecular weight heparin (LMWH) has been the standard of care for thromboprophylaxis in this population. However, direct oral anticoagulants (DOACs) are increasingly being used as alternatives. OBJECTIVE: To assess the efficacy and safety of DOACs versus LMWH for thromboprophylaxis in orthopedic surgery. METHODS: We searched MEDLINE, Embase, and the Cochrane Collaboration Central Register of Controlled Trials from inception until April 2020, for randomized controlled trials (RCTs) comparing DOACs with LMWH for thromboprophylaxis in orthopedic surgery. RESULTS: Twenty-five RCTs met inclusion criteria, including 40,438 patients, with a mean age of 68 years and 50% were males. Compared to LMWH, DOACs were associated with a significant reduction of major VTE; defined as the composite events of proximal deep vein thrombosis (DVT), pulmonary embolism (PE), and VTE-related mortality (RR 0.33; 95% CI: 0.20-0.53; P<0.01), and total DVT (RR: 0.59; 95% CI: 0.48-0.73; P<0.01), but not PE (RR 0.81; 95% CI: 0.49-1.34; P=0.42). There was no statistically significant difference between both groups on the incidence of major bleeding (RR 0.99; 95% CI: 0.77-1.27; P=0.92), clinically relevant non-major bleeding (RR 1.04; 95% CI: 0.92-1.17; P=0.52), all-cause mortality (RR 1.06; 95% CI: 0.64-1.76; P=0.83), VTE-related mortality (RR 0.84; 95% CI: 0.40-1.74; P=0.64) and bleeding-related mortality (RR 1.24; 95% CI: 0.30-5.18; P=0.77). CONCLUSION: For patients undergoing orthopedic surgery, thromboprophylaxis with DOACs is associated with a significant reduction of major VTE and DVT, compared to LMWH. Safety outcomes were not significantly different between both treatment groups.

Clinical and hematologic presentations of adults with COVID-19 patients in Jeddah: A case control study.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), is associated with significant morbidity and mortality. The clinical features of COVID-19 were mentioned in previous studies. However, risk factors for COVID-19 are not fully recognized. The aim of this study is to characterize risk factors and clinical features of COVID-19 disease in Jeddah, Saudi Arabia. METHODS: A retrospective, chart-review, case-control study was conducted at King Abdulaziz University, Jeddah, Saudi Arabia. Demographic, clinical, radiological, and laboratory data on patients diagnosed between March 18 and May 18, 2020 were collected and analyzed. RESULTS: We reviewed medical records on 297 suspected cases of COVID-19. Of these, 175 (59%) tested positive for COVID-19 by polymerase chain reaction (PCR) and considered as cases, while 122 (41%) tested negative and considered as control. COVID-19 positive cases were more likely to be males, and non-health care providers. Hypertension (15%), diabetes (10%) and two or more concurrent comorbidities (54.4%) were more prevalent among COVID-19 patients. Patients presented with fever, cough, and loss of taste/smell were more likely to test positive for COVID-19 (P = 0.001, 0.008, 0.008; respectively). Radiological evidence of pneumonia was associated with confirmed COVID-19 disease (P = 0.001). Shortness of breath and gastrointestinal symptoms were not associated with the risk of COVID-19 at presentation. On admission, white blood cells, neutrophils, lymphocytes, eosinophils, basophils, and platelets were significantly lower among COVID-19 patients compared with controls. Surprisingly, D-Dimer levels were lower among COVID-19 positive patients when compared with controls. CONCLUSION: Male gender, hypertension, and diabetes are the most commonly observed risk factors associated with COVID-19 disease in Jeddah, Saudi Arabia. COVID-19 patient had significantly lower lymphocyte and neutrophil counts.

Urinary albumin excretion is associated with pulmonary hypertension in sickle cell disease: potential role of soluble fms-like tyrosine kinase-1.

BACKGROUND: Pulmonary hypertension (PHT) is reported to be associated with measures of renal function in patients with sickle cell disease (SCD). The purpose of this exploratory study was to determine the relationship between albuminuria and both clinical and laboratory variables in SCD. DESIGN AND METHODS: This cross-sectional study was performed using a cohort of adult patients with SCD and control subjects without SCD. Spot urine for microalbumin/creatinine ratio, measures of hemolysis, inflammation and other laboratory studies were obtained. Pulmonary artery systolic pressure was determined by Doppler echocardiography, and the diagnosis of PHT was defined using age-, sex- and body mass index-adjusted reference ranges. RESULTS: Seventy-three patients with SCD and 21 healthy, race-matched control subjects were evaluated. In patients with SCD, normoalbuminuria was observed in 34 patients (46.6%), microalbuminuria in 24 patients (32.9%) and macroalbuminuria in 15 patients (20.5%). There was a significant correlation between urine albumin excretion and age. In patients with HbSS and Sbeta(0) thalassemia, the levels of sFLT-1, soluble VCAM and NT pro-BNP were significantly higher in those with macroalbuminuria, compared to patients with microalbuminuria and normoalbuminura, but no significant differences were observed in the levels of laboratory measures of hemolysis. Urine albumin excretion was associated with PHT and a history of stroke. CONCLUSIONS: Our study confirms the high prevalence of albuminuria in SCD. The association of urine albumin excretion with sFLT-1 suggests that this vascular endothelial growth factor receptor family member may contribute to the development of albuminuria in SCD. By inducing endothelial activation and endothelial dysfunction, sFLT-1 appears to be a link between glomerulopathy and PHT in SCD.

Synonymous Mutation in DKC1 Causes Telomerase RNA Insufficiency Manifesting as Familial Pulmonary Fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most common of short telomere phenotypes. Familial clustering of IPF is common, but the genetic basis remains unknown in more than one-half of cases. We identified a 65-year-old man with familial IPF, short telomere length, and low telomerase RNA levels. He was diagnosed with a short telomere syndrome after developing hematologic complications post-lung transplantation, but no mutations were identified in a clinical testing pipeline. RESEARCH QUESTION: What is the molecular basis underlying the familial IPF and low telomerase RNA levels in this patient? STUDY DESIGN AND METHODS: We analyzed whole-genome sequence data and performed functional molecular studies on cells derived from the patient and his family. RESULTS: We identified a previously unreported synonymous variant c.942G>A p.K314K in DKC1, the gene encoding the dyskerin ribonucleoprotein, which is required for telomerase RNA biogenesis. The mutation created a competing de novo exonic splicing enhancer, and the misspliced product was degraded by nonsense-mediated decay causing an overall dyskerin deficiency in mutation carriers. In silico tools identified other rare silent DKC1 variants that warrant functional evaluation if found in patients with short telomere-mediated disease. INTERPRETATION: Our data point to silent mutation in telomere maintenance genes as a mechanism of familial pulmonary fibrosis. In contrast to DKC1 missense mutations, which primarily manifest in children as dyskeratosis congenita, hypomorphic mutations affecting dyskerin levels likely have a predilection to presenting in adults as pulmonary fibrosis.