Nephrotic Syndrome and Statin Therapy: An Outcome Analysis.

Background and Objectives: Hypercholesterolemia in patients with nephrotic syndrome (NS) may predispose to cardiovascular events and alter kidney function. We aimed to evaluate statins efficiency in NS patients under immunosuppression using four endpoints: remission rate (RR), end-stage kidney disease (ESKD), major cardiovascular events (MACE), and thrombotic complications (VTE). Materials and Methods: We retrospectively examined the outcome at 24 months after diagnosis of 154 NS patients (age 53 (39-64) years, 64% male, estimated glomerular filtration rate (eGFR) 61.9 (45.2-81.0) mL/min). During the follow-up, the lipid profile was evaluated at 6 months and at 1 and 2 years. Results: The median cholesterol level was 319 mg/dL, and 83% of the patients received statins. Patients without statins (17%) had similar age, body mass index, comorbidities, blood lipids levels, NS severity, and kidney function. The most used statin was simvastatin (41%), followed by rosuvastatin (32%) and atorvastatin (27%). Overall, 79% of the patients reached a form of remission, 5% reached ESKD, 8% suffered MACE, and 11% had VTE. The mean time to VTE was longer in the statin group (22.6 (95%CI 21.7, 23.6) versus 20.0 (95%CI 16.5, 23.5) months, p 0.02). In multivariate analysis, statin therapy was not associated with better RR, kidney survival, or fewer MACE; however, the rate of VTE was lower in patients on statins (HR 2.83 (95%CI 1.02, 7.84)). Conclusions: Statins did not improve the remission rate and did not reduce the risk of MACE or ESKD in non-diabetic nephrotic patients. However, statins seemed to reduce the risk of VTE. Further randomized controlled studies are needed to establish statins' role in NS management.

Cardiovascular magnetic resonance for evaluation of cardiac involvement in COVID-19: recommendations by the Society for Cardiovascular Magnetic Resonance.

Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic that has affected nearly 600 million people to date across the world. While COVID-19 is primarily a respiratory illness, cardiac injury is also known to occur. Cardiovascular magnetic resonance (CMR) imaging is uniquely capable of characterizing myocardial tissue properties in-vivo, enabling insights into the pattern and degree of cardiac injury. The reported prevalence of myocardial involvement identified by CMR in the context of COVID-19 infection among previously hospitalized patients ranges from 26 to 60%. Variations in the reported prevalence of myocardial involvement may result from differing patient populations (e.g. differences in severity of illness) and the varying intervals between acute infection and CMR evaluation. Standardized methodologies in image acquisition, analysis, interpretation, and reporting of CMR abnormalities across would likely improve concordance between studies. This consensus document by the Society for Cardiovascular Magnetic Resonance (SCMR) provides recommendations on CMR imaging and reporting metrics towards the goal of improved standardization and uniform data acquisition and analytic approaches when performing CMR in patients with COVID-19 infection.

COVID-19 and SARS-CoV-2 Vaccines: A Cameo Role for Headache.

Headache is a very frequent symptom in COVID-19 and SARS-CoV-2 vaccination. Many studies have emphasized its clinical diagnostic and prognostic importance on the one hand, as in many cases these aspects have been completely ignored. It is therefore opportune to go back over these lines of research in order to gather what usefulness the headache symptom may or may not represent for the clinician dealing with COVID-19 or performing or following up on the clinical course following vaccination for SARS-CoV-2. The clinical evaluation of headache in COVID-19 is not fundamental in the diagnostic and prognostic process of the emergency departments; however, the risk of severe adverse events, although very rare, must be taken into account by the clinicians. For subjects presenting with severe, drug-resistant, and delayed-onset post-vaccination headache, it could represent a possible sign of central venous thrombosis or other thrombotic complications. Thus, a re-reading of the role of headache in COVID-19 and SARS-CoV-2 vaccination seems clinically useful.

Eficacia de la tromboprofilaxis con heparina de bajo peso molecular en pacientes críticos con COVID-19: estudio observacional, prospectivo y multicéntrico / Effectiveness of thromboprophylaxis with low molecular weight heparin in critically ill patients with COVID-19. An observational prospective, multicenter study

Introducción: Los pacientes COVID-19 presentan una coagulopatía caracterizada por una elevada incidencia de complicaciones tromboembólicas. Ante la controversia existente sobre el manejo de la tromboprofilaxis, se llevó a cabo un estudio con el objetivo de analizar el efecto de las diferentes dosis de heparina de bajo peso molecular (HBPM) utilizadas en los pacientes críticos con COVID-19. Material y métodos: Se evaluaron datos del Reg-COVID-19. Se compararon 2 grupos de pacientes según la dosis de HBPM administrada: profilaxis y tratamiento. El objetivo primario fue determinar si había relación de la dosis de HBPM con la mortalidad. Los objetivos secundarios incluyeron la incidencia de eventos trombóticos y hemorrágicos, la duración de la estancia en la UCI, la ventilación mecánica invasiva y los parámetros trombóticos e inflamatorios. Resultados: Se analizaron datos de 720 pacientes, 258 en el grupo de profilaxis y 462 en el de tratamiento. La proteína C reactiva, la ventilación mecánica invasiva y el tratamiento con tocilizumab o corticosteroides se relacionaron con la elección de la dosis de HBPM. La incidencia de complicaciones hemorrágicas (66/720, 9,2%) y trombóticas (69/720, 9,6%) fue similar en ambos grupos, al igual que el curso temporal de los eventos trombóticos, que ocurrieron antes que los hemorrágicos (9 [3-18] y 12 [6-19] días, respectivamente). La mortalidad fue menor en el grupo de profilaxis (25,2 frente al 35,1%), pero al aplicar un modelo de ponderación de probabilidad inversa, no se encontraron diferencias entre los grupos. Conclusión: No se encontraron efectos beneficiosos ni perjudiciales relacionados con la administración de dosis profilácticas o terapéuticas de HBPM en pacientes críticos COVID-19, con una tasa similar de complicaciones hemorrágicas o trombóticas. A partir de estos resultados, consideramos que son necesarios más estudios para determinar el protocolo óptimo de tromboprofilaxis en estos pacientes.(AU)

Introduction: COVID-19 induces coagulopathy associated with an increase of thromboembolic events. Due to the lack of agreement on recommendations for thromboprophylactic management, the aim of this study was to study the dosages of LMWH used in critically ill COVID-19 patients assessing the effect on their outcome. Metohds: We evaluated data of the Reg-COVID19. According to LMWH dose two groups were analyzed: prophylaxis and treatment. Primary outcome was the relationship of LMWH dosage with mortality. Secondary outcomes included the incidence of thrombotic and bleeding events, length of ICU stay, invasive mechanical ventilation, and thrombotic and inflammatory parameters. Results: Data of 720 patients were analyzed, 258 in the prophylaxis group and 462 in the treatment group. C Reactive Protein, invasive mechanical ventilation, tocilizumab and corticosteroid treatments were related with the choice of LMWH dose. Hemorrhagic events (66/720, 9.2%) and thrombotic complications (69/720, 9.6%) were similar in both groups (P=.819 and P=.265), as was the time course of the thrombotic events, earlier than hemorrhagic ones (9 [3-18] and 12 [6-19] days respectively). Mortality was lower in prophylaxis group (25.2% versus 35.1%), but once an inverse probability weighting model was applied, we found no effect of LMWH dose. Conclusion: We found no benefit or harm with the administration of therapeutic or prophylactic LMWH dose in COVID19 critically ill patients. With a similar rate of hemorrhagic or thrombotic events, the LMWH dose had no influence on mortality. More studies are needed to determine the optimal thromboprophylaxis protocol for critically ill patients.(AU)

Effectiveness of thromboprophylaxis with low molecular weight heparin in critically ill patients with COVID-19. An observational prospective, multicenter study.

INTRODUCTION: COVID-19 induces coagulopathy associated with an increase of thromboembolic events. Due to the lack of agreement on recommendations for thromboprophylactic management, the aim of this study was to study the dosages of LMWH used in critically ill COVID-19 patients assessing the effect on their outcome. METHODS: We evaluated data of the Reg-COVID19. According to LMWH dose two groups were analyzed: prophylaxis and treatment. Primary outcome was the relationship of LMWH dosage with mortality. Secondary outcomes included the incidence of thrombotic and bleeding events, length of ICU stay, invasive mechanical ventilation, and thrombotic and inflammatory parameters. RESULTS: Data of 720 patients were analyzed, 258 in the prophylaxis group and 462 in the treatment group. C Reactive Protein, invasive mechanical ventilation, tocilizumab and corticosteroid treatments were related with the choice of LMWH dose. Hemorrhagic events (66/720, 9.2%) and thrombotic complications (69/720, 9.6%) were similar in both groups (p = .819 and p = .265), as was the time course of the thrombotic events, earlier than hemorrhagic ones (9 [3-18] and 12 [6-19] days respectively). Mortality was lower in prophylaxis group (25.2% versus 35.1%), but once an inverse probability weighting model was applied, we found no effect of LMWH dose. CONCLUSION: We found no benefit or harm with the administration of therapeutic or prophylactic LMWH dose in COVID19 critically ill patients. With a similar rate of hemorrhagic or thrombotic events, the LMWH dose had no influence on mortality. More studies are needed to determine the optimal thromboprophylaxis protocol for critically ill patients.

Severe COVID-19-A Review of Suggested Mechanisms Based on the Role of Extracellular Matrix Stiffness.

The severity of COVID-19 commonly depends on age-related tissue stiffness. The aim was to review publications that explain the effect of microenvironmental extracellular matrix stiffness on cellular processes. Platelets and endothelial cells are mechanosensitive. Increased tissue stiffness can trigger cytokine storm with the upregulated expression of pro-inflammatory cytokines, such as tumor necrosis factor alpha and interleukin IL-6, and tissue integrity disruption, leading to enhanced virus entry and disease severity. Increased tissue stiffness in critically ill COVID-19 patients triggers platelet activation and initiates plague formation and thrombosis development. Cholesterol content in cell membrane increases with aging and further enhances tissue stiffness. Membrane cholesterol depletion decreases virus entry to host cells. Membrane cholesterol lowering drugs, such as statins or novel chitosan derivatives, have to be further developed for application in COVID-19 treatment. Statins are also known to decrease arterial stiffness mitigating cardiovascular diseases. Sulfated chitosan derivatives can be further developed for potential use in future as anticoagulants in prevention of severe COVID-19. Anti-TNF-α therapies as well as destiffening therapies have been suggested to combat severe COVID-19. The inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells pathway must be considered as a therapeutic target in the treatment of severe COVID-19 patients. The activation of mechanosensitive platelets by higher matrix stiffness increases their adhesion and the risk of thrombus formation, thus enhancing the severity of COVID-19.

Severe COVID-19-A Review of Suggested Mechanisms Based on the Role of Extracellular Matrix Stiffness.

The severity of COVID-19 commonly depends on age-related tissue stiffness. The aim was to review publications that explain the effect of microenvironmental extracellular matrix stiffness on cellular processes. Platelets and endothelial cells are mechanosensitive. Increased tissue stiffness can trigger cytokine storm with the upregulated expression of pro-inflammatory cytokines, such as tumor necrosis factor alpha and interleukin IL-6, and tissue integrity disruption, leading to enhanced virus entry and disease severity. Increased tissue stiffness in critically ill COVID-19 patients triggers platelet activation and initiates plague formation and thrombosis development. Cholesterol content in cell membrane increases with aging and further enhances tissue stiffness. Membrane cholesterol depletion decreases virus entry to host cells. Membrane cholesterol lowering drugs, such as statins or novel chitosan derivatives, have to be further developed for application in COVID-19 treatment. Statins are also known to decrease arterial stiffness mitigating cardiovascular diseases. Sulfated chitosan derivatives can be further developed for potential use in future as anticoagulants in prevention of severe COVID-19. Anti-TNF-α therapies as well as destiffening therapies have been suggested to combat severe COVID-19. The inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells pathway must be considered as a therapeutic target in the treatment of severe COVID-19 patients. The activation of mechanosensitive platelets by higher matrix stiffness increases their adhesion and the risk of thrombus formation, thus enhancing the severity of COVID-19.

Perioperative prothrombin complex concentrate and fibrinogen administration are associated with thrombotic complications after liver transplant.

Background: Use of intraoperative prothrombin complex concentrates (PCC) and fibrinogen concentrate administration has been linked to thrombotic events. However, it is unknown if its use is associated with thrombotic events after liver transplant. Methods and analysis: We conducted a post hoc analysis of a prospectively conducted registry database study on patients who underwent liver transplant between 2004 and 2017 at Heidelberg University Hospital, Heidelberg, Germany. Univariate and multivariate analyses were used to determine the association between PCC and fibrinogen concentrate administration and thrombotic complications. Results: Data from 939 transplantations were included in the analysis. Perioperative PCC or fibrinogen administration was independently associated with the primary composite endpoint Hepatic artery thrombosis (HAT), Portal vein thrombosis (PVT), and inferior vena cava thrombosis [adjusted HR: 2.018 (1.174; 3.468), p = 0.011]. PCC or fibrinogen administration was associated with the secondary endpoints 30-day mortality (OR 4.225, p < 0.001), graft failure (OR 3.093, p < 0.001), intraoperative blood loss, red blood cell concentrate, fresh frozen plasma and platelet transfusion, longer hospitalization, and longer length of stay in intensive care units (ICUs) (all p < 0.001). PCC or fibrinogen administration were not associated with pulmonary embolism, myocardial infarction, stroke, or deep vein thrombosis within 30 days after surgery. Conclusion: A critical review of established strategies in coagulation management during liver transplantation is warranted. Perioperative caregivers should exercise caution when administering coagulation factor concentrate during liver transplant surgery. Prospective randomized controlled trials are needed to establish causality for the relationship between coagulation factors and thrombotic events in liver transplantation. Further studies should be tailored to identify patient subgroups that will likely benefit from PCC or fibrinogen administration.

COVID-19 Co-Infection May Promote Development of Sinusitis Complication in Children.

BACKGROUND: The olfactory dysfunction that occurs during a COVID-19 infection has sparked much debate about its similarity to sinusitis. Up to 65% of COVID-19 pediatric patients may be asymptomatic; however, when symptoms are observed, fever and cough are the most common. Nasal congestion and discharge as well as headaches can also be seen, which makes both entities, i.e., COVID-19 and sinusitis, similar to each other. METHODS: In this review, we present the clinical case of a teenager with a history of acute sinusitis and COVID-19 co-infection followed by purulent meningoencephalitis. We aim to summarize available findings on the association between COVID-19, sinusitis, and possible common complications of both diseases. RESULTS: Differentiating between COVID-19 and sinusitis can be confusing because presented symptoms may overlap or mimic each other. Increased risk of complications, especially in patients with bacterial sinusitis co-infected with SARS-CoV-2, should prompt physicians to monitor young patients and inform parents about disturbing symptoms and possible complications. CONCLUSIONS: Acute sinusitis and COVID-19 co-infection may lead to numerous complications and should be included among the factors predisposing to worse prognosis. It is especially related to patients with high risk factors and even more important in children as they often pass the infection asymptomatically and its complications can lead to loss of health or life.

SCUBE1 is associated with thrombotic complications, disease severity, and in-hospital mortality in COVID-19 patients.

INTRODUCTION: COVID-19 disease, which has recently become an important cause of mortality and morbidity all over the world, is remarkably associated with thrombotic complications. Although many factors are responsible for these increased thrombotic complications in COVID-19 disease, its relationship with a marker that increases the risk of thrombosis such as Signal peptide-CUB-EGF domain-containing protein 1 (SCUBE1) has not yet been clarified. This is the first study to examine the potential diagnostic and prognostic value of SCUBE1 levels in patients with COVID-19. In this study, we aimed to clarify the relationship between the increased risk of thrombosis and SCUBE1 in the course of COVID-19 disease. MATERIALS AND METHODS: 553 patients with COVID-19 and 553 healthy controls were compared in terms of SCUBE1 levels. Additionally, patients with COVID-19 were divided into two groups according to their SCUBE1 levels and compared in terms of severity of disease, thrombotic complications and in-hospital mortality. RESULTS: SCUBE1 levels were significantly higher in patients with COVID-19 compared to the control group (p < 0.001). Plasma SCUBE1 levels were significantly higher in patients with severe disease and thrombotic complications, those with mild to moderate disease, and those without thrombotic complications (p < 0.001, for both). In addition, SCUBE1 was found to be an independent predictor of in-hospital mortality (p < 0.001). CONCLUSIONS: SCUBE1 may be one of the major determinants of thrombotic complications, which is an increased cause of mortality and morbidity in COVID-19 patients so inhibition of this peptide may be among the therapeutic targets in patients with COVID-19.

Extensive Cerebral Venous Thrombosis as an Isolated Presentation in a COVID-19-Positive Young Adult.

Due to the increase in the number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases globally, more medical case reports are being published showing the different complications of coronavirus disease 2019 (COVID-19). One of the important complications is thrombotic events that occur as a sequela of COVID-19. Here we present a case of a previously healthy male patient in his 30s who presented to the emergency unit experiencing headaches, vomiting, and weakness in his left arm. On examination, he was vitally stable, and fully oriented, but noted to have jerky movements of the left arm; therefore, he was sent for a CT brain scan. Shortly after, he developed a generalized tonic-clonic seizure. After stabilizing the patient, CT brain with cerebral venography was done, which revealed extensive thrombosis of the superior sagittal sinus and bilateral superficial cortical veins. The patient's blood test showed a high D-dimer (4.90 ug/ml), and the COVID-19 polymerase chain reaction (PCR) swab test was positive. It is commonly known that COVID-19 infection presents with fever and respiratory symptoms; however, our case illustrates the thrombotic complication of SARS-CoV-2 infection with no pneumonia or respiratory symptoms with a high level of d-dimer.

[Biochemical markers of thrombotic complications in the acute period of ischemic stroke].

AIM: To study the profile of biochemical markers of the hemostasis system, to clarify their role and relationships in the pathogenesis of the development of thrombotic complications (TC) of ischemic stroke (IS) and the associated assessment of the possibilities of their diagnostic application. MATERIALS AND METHODS: The study group included 302 patients (164 men, 138 women) who were admitted to the hospital with a diagnosis of IS within 24 hours of the onset of the disease. The diagnosis was confirmed by computed tomography. The average age of patients was 69 (5088) years. Blood was taken from all patients on the 1st day of the disease to determine the profile of analytes presumably associated with the pathogenesis of TC. Levels of homocysteine, protein C inhibitor, thrombomodulin, plasminogen, tissue plasminogen activator, urokinase, plasminogen activator type 1 inhibitor, t-PA/PAI-1 complex, vitronectin, plasmin-2-antiplasmin complex, D-dimer, fibronectin were determined in blood serum by ELISA. RESULTS: TC in the acute period of IS (up to 21 days) were recorded in 32 (10.6%, 95% CI 7.3714.3) patients, of which pulmonary embolism was observed in 27 (8.94%, 95% CI 5.9812.4) patients, deep vein thrombosis in 5 (1.66%, 95% CI 0.473.47) patients. The results of the study of a panel of specific proteins involved in pathogenetic processes accompanying necrosis of brain tissue in IS demonstrated that of the entire list of markers of the hemostasis system activation selected for the study, the most significant are: the concentration of fibronectin in the prognosis of the absence of TC with a threshold value of more than 61 mkg/ml and OR 4.4 (95% CI 1.512.9, p=0.011), and the concentration of the t-PA/PAI-1 complex in the prognosis of the development of TC with a threshold value of more than 14 ng/ml and OR 11.3 (95% CI 1.18109.3, p=0.03). CONCLUSION: The significance of the t-PA/PAI-1 complex and fibronectin as markers of TC in IS may be due to a violation of the activation processes of the fibrinolytic link of hemostasis and the accumulation of non-deposited compounds that damage the vascular wall.

Plasminogen activator inhibitor 1 and gestational diabetes: the causal relationship.

Plasminogen activator inhibitor 1 (PAI-1) also known as serpin E1 or endothelial plasminogen activator inhibitor, is produced from endothelial cells and adipose tissue. PAI-1 inhibits tissue plasminogen activator (tPA) and urokinase (uPA) preventing activation of plasminogen and fibrinolysis. Gestational diabetes mellitus (GDM) is defined as glucose intolerance and hyperglycemia during pregnancy. The underlying mechanism of GDM is due to the reduction of insulin secretion or the development of insulin resistance (IR). Normal PAI-1 is a crucial mediator for maintaining pregnancy, though aberrantly high PAI-1 promotes inflammation and thrombosis with increased risk of pregnancy loss. Increasing PAI-1 level had been shown to be an early feature of cardio-metabolic derangement in women with GDM. As well, GDM is regarded as an independent predictor for increasing PAI-1 levels compared to normal pregnancy. Taken together, GDM seems to be the causal factor in the increase of PAI-1 via induction of IR, hyperglycemia and hypertriglyceridemia. In conclusion, GDM triggers expression and release of PAI-1 which linked with GDM severity due to exaggerated pro-inflammatory and inflammatory cytokines with the development of IR. High PAI-1 levels in GDM may induce hypofibrinolysis and thrombotic complications.

Use of rotational thromboelastometry to predict the outcome of COVID-19 patients: A retrospective observational study.

Background and Aims: The hypercoagulability occurring in COVID-19 patients is detected only by Rotational thromboelastometry (ROTEM). However, the benefit of performing ROTEM in the management of disease and predicting the outcome of COVID-19 patients is yet to be established. Material and Methods: The data of 23 critically ill and 11 stable COVID-19 adult patients were extracted from the hospital information system admitted between July and August 2020 and patient charts and analyzed retrospectively. The critically ill patients were divided as a survivor and non-survivor groups. The Intrinsic pathway part of ROTEM (INTEM) and Fibrinogen part of ROTEM (FIBTEM) were performed on day 0 for both critically ill and stable patients, and on day 10 for critically ill patients. The statistical package for social science (SPSS) version 26 was used for statistical analysis. Results: The median FIBTEM amplitude at 5 min (A5) and maximum clot firmness (MCF) were elevated in both stable and critically ill patients (24 vs 27 mm, P = 0.46 and 27.5 vs 40 mm, P = 0.011) with a significant difference in FIBTEM MCF. But there was no significant difference between number of survivors and non-survivors with FIBTEM MCF >25 at day 0 and day 10. Conclusion: The Hypercoagulability state as detected by ROTEM parameters at day 0 and day 10 had no association with the outcome (mortality) of critically ill COVID-19 patients. Hence it cannot be used as a prognostic test. The increasing age, comorbidities and D-dimer values were associated with a poor prognosis in COVID-19 patients.

Characterizing Thrombotic Complication Risk Factors Associated With COVID-19 via Heterogeneous Patient Data: Retrospective Observational Study.

BACKGROUND: COVID-19 has been observed to be associated with venous and arterial thrombosis. The inflammatory disease prolongs hospitalization, and preexisting comorbidities can intensity the thrombotic burden in patients with COVID-19. However, venous thromboembolism, arterial thrombosis, and other vascular complications may go unnoticed in critical care settings. Early risk stratification is paramount in the COVID-19 patient population for proactive monitoring of thrombotic complications. OBJECTIVE: The aim of this exploratory research was to characterize thrombotic complication risk factors associated with COVID-19 using information from electronic health record (EHR) and insurance claims databases. The goal is to develop an approach for analysis using real-world data evidence that can be generalized to characterize thrombotic complications and additional conditions in other clinical settings as well, such as pneumonia or acute respiratory distress syndrome in COVID-19 patients or in the intensive care unit. METHODS: We extracted deidentified patient data from the insurance claims database IBM MarketScan, and formulated hypotheses on thrombotic complications in patients with COVID-19 with respect to patient demographic and clinical factors using logistic regression. The hypotheses were then verified with analysis of deidentified patient data from the Research Patient Data Registry (RPDR) Mass General Brigham (MGB) patient EHR database. Data were analyzed according to odds ratios, 95% CIs, and P values. RESULTS: The analysis identified significant predictors (P<.001) for thrombotic complications in 184,831 COVID-19 patients out of the millions of records from IBM MarketScan and the MGB RPDR. With respect to age groups, patients 60 years and older had higher odds (4.866 in MarketScan and 6.357 in RPDR) to have thrombotic complications than those under 60 years old. In terms of gender, men were more likely (odds ratio of 1.245 in MarketScan and 1.693 in RPDR) to have thrombotic complications than women. Among the preexisting comorbidities, patients with heart disease, cerebrovascular diseases, hypertension, and personal history of thrombosis all had significantly higher odds of developing a thrombotic complication. Cancer and obesity were also associated with odds>1. The results from RPDR validated the IBM MarketScan findings, as they were largely consistent and afford mutual enrichment. CONCLUSIONS: The analysis approach adopted in this study can work across heterogeneous databases from diverse organizations and thus facilitates collaboration. Searching through millions of patient records, the analysis helped to identify factors influencing a phenotype. Use of thrombotic complications in COVID-19 patients represents only a case study; however, the same design can be used across other disease areas by extracting corresponding disease-specific patient data from available databases.

Effect of Intraoperative Tranexamic Acid on Perioperative Major Hemorrhage Requiring Transfusion in Patients Undergoing Elective Spine Surgery: A Propensity Score-Matched Analysis Using a National Inpatient Database.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: This study aimed to examine whether the use of intravenous TXA in elective spine surgery is associated with reduced perioperative massive hemorrhage requiring transfusion. METHODS: We extracted all patients who underwent decompression with or without fusion surgery for the cervical, thoracic, and lumbar spine between April 2012 and March 2019. The primary outcome was the occurrence of massive hemorrhage requiring transfusion, defined as at least 560 mL of blood transfusion within 2 days of spine surgery or the requirement of additional blood transfusion from 3-7 days postoperatively. Secondary outcomes were the occurrence of thrombotic complications (pulmonary embolism, acute coronary syndrome, and stroke) and postoperative hematoma requiring additional surgery. RESULTS: We identified 83,821 eligible patients, with 9747 (12%) patients in the TXA group. Overall, massive hemorrhage requiring transfusion occurred in 781 (.9%) patients. Propensity score matching yielded 8394 pairs. In the matched cohort, the TXA group had a lower proportion of massive hemorrhage requiring transfusion than the control group (.7% vs 1.1%; P = .002). There was no significant difference in the occurrence of thrombotic complications and postoperative hematoma requiring additional surgery between both groups. The multivariable regression analysis also showed that the use of TXA was associated with significantly lower proportions of massive hemorrhage requiring transfusion (odds ratio, .62; 95% confidence interval, .43-.90; P = .012). CONCLUSIONS: In this analysis using real-world data, TXA use in elective spinal surgery was associated with reduced perioperative massive hemorrhage requiring transfusion without increasing thrombotic complications. LEVEL OF EVIDENCE: Prognostic Level Ⅲ.

Heparin-induced thrombocytopenia in patients readmitted after open cardiac surgical procedures: A case series.

Objectives: Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication that occurs in a small percentage of patients exposed to heparin. Concerns of HIT are particularly high in patients undergoing cardiac procedures requiring cardiopulmonary bypass, as they are exposed to high doses of heparin intraoperatively. Our aim was to identify and assess the hospital courses of patients who were diagnosed with HIT during readmission following cardiac surgery. Methods: A retrospective review of patients who underwent open cardiac surgical procedures from June 2017 through October 2019 was performed. Of these, we identified patients who were newly diagnosed with HIT upon readmission. HIT positivity was defined as a positive anti-PF4 antibody screening test, plus a positive serotonin release assay. Results: Of the 2496 patients identified, 13 patients were HIT positive on index admission and were excluded. Of the remaining 2483 patients, 351 were readmitted within 30 days. Six were newly diagnosed with HIT during readmission, 5 of whom presented with thrombotic complications. One patient was readmitted with thrombocytopenia and was started on argatroban; the remaining 5 did not have a significantly lower platelet count on readmission. Of the 12 patients readmitted for venous thromboembolism, 4 tested positive for HIT. Conclusions: HIT can have a delayed appearance following open heart surgery. Venous thromboembolism appears to be a significant indicator for HIT during readmission, even in the absence of thrombocytopenia. This may support the use of non-heparin anticoagulation for cardiac surgery patients readmitted with thromboembolism until HIT status is determined.

Uninterrupted Continuation of VV-ECMO Without Anticoagulation for 44 Days in COVID-19 ARDS: A Precarious Quandary.

Venovenous extracorporeal membrane oxygenation (VV-ECMO) has become a mainstay treatment modality for a select patient population who do not respond to conventional medical therapy suffering from severe acute respiratory distress syndrome (ARDS) due to COVID-19. This therapy necessitates the utilization of anticoagulation, whether unfractionated heparin or bivalirudin, to prevent thrombotic complications. Scarce are reports of VV-ECMO implementation leading to acute hemorrhage mandating cessation of anticoagulation in a patient suffering from COVID-19 ARDS. Herein, the authors report a case of a successful outcome in a COVID-19 ARDS patient who suffered an acute hemorrhagic complication leading to pre-emptive termination of systemic anticoagulation. The authors believe this to be one of the first such cases in the literature.

A Rare Case of Recurrent Arterial Thrombosis Secondary to Iron Deficiency Anemia.

Iron deficiency anemia is the leading cause of anemia all over the world. Iron deficiency is known to cause reactive thrombocytosis. However, arterial thrombosis secondary to reactive thrombocytosis is a rare entity. In this article, we present a case of a 37-year-old female with recurrent arterial thrombosis due to severe thrombocytosis caused by iron deficiency anemia. The patient developed spleen and kidney infractions, as well as abdominal aortic thrombosis. She was subsequently treated with iron and aspirin with an improvement of the anemia and thrombocytosis, with no further thrombotic complications. Arterial thrombosis is a very serious condition as the thrombus can embolize to carotid arteries leading to stroke or to peripheral blood vessels causing peripheral ischemia and gangrene. Iron deficiency anemia is a reversible cause of thrombocytosis that can be treated very easily to avoid thrombotic complications.

Subclavian versus femoral arterial cannulations during extracorporeal membrane oxygenation: A propensity-matched comparison.

BACKGROUND: During peripheral extracorporeal veno-arterial membrane oxygenation (VA-ECMO) support, subclavian arterial cannulation provides, in comparison to femoral arterial cannulation, an anterograde flow which may prevent from left ventricular (LV) distention and improve outcomes. We aimed to compare the effectiveness of subclavian cannulation to femoral cannulation in reducing LV overdistension consequences, hemostatic complications and mortality. METHODS: This retrospective study conducted in two intensive care units of the Lille academic hospitals from January 2013 to December 2019 included 372 non-moribund adult patients supported by VA-ECMO. The primary endpoint was a new onset of pulmonary edema (PO) or LV unloading. Secondary endpoints were myocardial recovery, serious bleeding (according to Extracorporeal Life Support Organization definition), thrombotic complications (a composite of stroke, cannulated limb or mesenteric ischemia, intracardiac or aortic-root thrombosis) and 28 day mortality. Differences in outcomes were analyzed using propensity score matching (PSM) and inverse probability of treatment weighting adjustment (IPTW). RESULTS: As compared to femoral cannulation (n = 320 patients), subclavian cannulation (n = 52 patients) did not reduce the occurrence of new onset of PO or LV unloading after PSM [HR 0.99 (95% CI 0.51-1.91)]. There was no other difference in outcomes in PSM cohort. In IPTW adjustment cohort, subclavian cannulation was associated with reduced recovery and increased serious bleeding with four accidental decannulations observed. CONCLUSION: Subclavian artery cannulation was not associated with reduced LV distension related complications, thrombotic complications and 28 day mortality. Rather, it may increase serious bleeding and accidental decannulations, and reduce recovery. Therefore, subclavian cannulation should be limited to vascular accessibility issues.