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Objective: Our objective in this study is to determine the predictive factors of thromboembolic complications in patients with previous heart disease and severe covid-19 infection and the impact of previous use of antithrombotic drugs on protection against these complications. Method(s): We conducted a single-center retrospective study of 158 patients with heart disease admitted to an intensive care unit for severe SARS-COV-2 infection. To determine the predictive factors, we used a logistic regression analysis. Result(s): Out of 158 patients, 22 were complicated by a thromboembolic event, i.e. 13.9%, mean age of our population was 64.03 (SD = 15.27), with a male predominance of 98 (62%), For the predictive factors of thromboembolic complications, and after multivariate analysis, we find the duration of hospitalization with (OR=0.92 ;95%CI (0.863 - 0.983), p=0.014, previous use of anti-thrombotic drugs as a protective factor with ( OR=0.288, 95%CI (0.091 - 0.911), p=0.034 for anti-platelet agents ) and ( OR=0, 322, 95%CI (0.131 - 0.851), p=0.021) for anti-coagulants (Figure1), and finally thrombocytopenia at admission as a risk factor ( OR=4.58 95%CI (1.2 - 10.627), p=0.021). D-dimer was not detected as a risk factor, and this can be explained by the characteristics of our population. Although the previous use of anti-thrombotic drugs protects against thrombo-embolic complications during severe infection, there was no benefit in terms of mortality (Figure2). Conclusion(s): Prior use of antithrombotic drugs is a protective factor against thromboembolic complications in patients with a history of heart disease but has no effect on mortality.
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Objective: Adverse drug reactions increase morbidity and mortality, prolong hospital stay and increase healthcare costs. The primary objective of this study was to determine the prevalence of emergency department visits for adverse drug reactions and to describe their characteristics. The secondary objective was to determine the predictor variables of hospitalization for adverse drug reactions associated with emergency department visits. Method(s): Observational and retrospective study of adverse drug reactions registered in an emergency department, carried out from November 15th to December 15th, 2021. The demographic and clinical characteristics of the patients, the drugs involved and the adverse drug reactions were described. Logistic regression was performed to identify factors related to hospitalization for adverse drug reactions. Result(s): 10,799 patients visited the emergency department and 216 (2%) patients with adverse drug reactions were included. The mean age was 70 +/- 17.5 (18-98) years and 47.7% of the patients were male. A total of 54.6% of patients required hospitalization and 1.6% died from adverse drug reactions. The total number of drugs involved was 315 with 149 different drugs. The pharmacological group corresponding to the nervous system constituted the most representative group (n = 81). High-risk medications, such as antithrombotic agents (n = 53), were the subgroup of medications that caused the most emergency department visits and hospitalization. Acenocumarol (n = 20) was the main drug involved. Gastrointestinal (n = 62) disorders were the most common. Diarrhea (n = 16) was the most frequent adverse drug reaction, while gastrointestinal bleeding (n = 13) caused the highest number of hospitalizations. Charlson comorbidity index behaved as an independent risk factor for hospitalization (aOR 3.24, 95% CI: 1.47-7.13, p = 0.003, in Charlson comorbidity index 4-6;and aOR 20.07, 95% CI: 6.87-58.64, p = 0.000, in Charlson comorbidity index >= 10). Conclusion(s): The prevalence of emergency department visits for adverse drug reactions continues to be a non-negligible health problem. High-risk drugs such as antithrombotic agents were the main therapeutic subgroup involved. Charlson comorbidity index was an independent factor in hospitalization, while gastrointestinal bleeding was the adverse drug reaction with the highest number of hospital admissions.Copyright © 2022 Sociedad Espanola de Farmacia Hospitalaria (S.E.F.H)
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Spontaneous pneumomediastinum (SPM) is a decisive complication reported to be associated with COVID-19. Here, we present a case of SPM in a COVID-19positive patient that was not caused by any iatrogenic or known reasons. At the time of admission, the patient was COVID-positive and distressed. He was immediately subjected to hematological and radiological investigations (chest X-ray, HRCT), which confirmed pneumomediastinum. The patient was hypoxic and hypotensive even after receiving ionotropic support. Considering the patient's critical condition, a mediastinal pigtail catheterization was performed instead of a thoracotomy, and the catheter was in situ for nine days. Arterial blood gas was monitored during the hospital stay, and supplementary oxygen therapy was provided accordingly. The patient subsequently recovered and was discharged. Hence, SPM in this COVID patient was treated by pigtail catheterization, and major surgical interventions were avoided.Copyright © 2023 LookUs Scientific. All rights reserved.
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Background and Importance Nirmatrelvir/ritonavir (PAXLOVID) is a recently approved drug to prevent progression in high-risk COVID-19-infected patients. Aim and Objectives To evaluate prescribing and dispensing of PAXLOVID and the proportion of patients with hospitalisation or death from any cause at 28 day. Material and Methods Descriptive, retrospective, observational study carried out between May and August 2022 in a secondlevel hospital. All patients with PAXLOVID prescription were selected. Sources of information were: electronic medical records and the prescription programme. The Variables analysed were: sex, age, risk factors, indications, interactions, dispensation (yes/no) and final treatment received. Risk factors were evaluated with our country's drug regulatory agency (DRA) recommendations to assesed the indication. Efficacy was assessed by the proportion of patients admitted to hospital and 28-day mortality. Results PAXLOVID was prescribed to 34 patients, 14 (41.2%) were women. The median age was 76.3 years old [RIQ 25.4]. Main indications for PAXLOVID were: to be undergoing treatment with myelotoxic chemotherapy (32.3%), corticosteroids or other immunosuppressants (29.4%);being over 80 years of age and presenting specific Risk factors (14.7%) and primary immunodeficiency (5.8%). 21 patients (61.8%) had some relevant interaction with their usual medication. The most frequent interactions were with statins (23.5%), analgesics (20.6%), oral anticoagulants (12%), antiarrhythmics (8.8%), antiplatelet drugs (5.8%), antidepressants (5.8%) and antidiarrhoeals (5.8%). After Validation by the Pharmacy Service, 11 patients (32.4%) did not receive PAXLOVID, 5 because they did not meet DRA criteria, 2 because their glomerular filtration rate was less than 30 ml/min and 4 because they had incompatible interactions. 4 patients finally received 3 days-remdesivir. Among patients who received PAXLOVID, 82.26% received full doses, with 4 patients (11.76%) requiring adjustment for renal impairment. 3 patients (13%) were hospitalised in the first month, none died. Conclusion and Relevance The main indications for which PAXLOVID was prescribed were patients undergoing chemotherapy and/or immunosuppressive treatments. Interactions with PAXLOVID were frequent and in some cases limited treatment. Validation by Pharmacy Service prevented a considerable number of patients from receiving PAXLOVID when it was no-indicated or when they had insurmountable interactions, also allowed patients to receive the dose adjusted for renal impairment. PAXLOVID was effective in avoiding hospital admission and mortality in the majority of patients.
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Background: COVID-19 is a respiratory disease that results in a prothrombotic state manifesting as thrombotic, microthrombotic and thromboembolic events. As a result, several antithrombotic modalities have been implicated in the treatment of this disease. Purpose(s): Currently, prophylactic dose anticoagulation is considered the standard of care antithrombotic regimen in hospitalised patients with COVID-19. However, high-quality data about the subject is unavailable. This study aimed to identify if therapeutic anticoagulation (TAC) or concurrent use of antiplatelet and anticoagulants was associated with an improved outcome in this patient population. Method(s): A retrospective observational cohort study of adult patients admitted to a single university hospital for COVID-19 infection was performed. The primary outcome was a composite of in-hospital mortality, intensive care unit (ICU) admission or the need for mechanical ventilation. The secondary outcomes were each of the components of the primary outcome, in-hospital mortality, ICU admission, or the need for mechanical ventilation. Result(s): 242 patients were included in the study and divided into four subgroups: Therapeutic anticoagulation (TAC), prophylactic anticoagulation+ antiplatelet (PACAP), TAC+antiplatelet (TACAP) and prophylactic anticoagulation (PAC) which was the reference for comparison. Multivariable Cox regression analysis and propensity matching were done and showed when compared with PAC, TACAP and TAC were associated with less inhospital all-cause mortality with an adjusted HR (aHR) of 0.113 (95% CI 0.028 to 0.449) and 0.126 (95% CI 0.028 to 0.528), respectively. The number needed to treat in both subgroups was 11. Furthermore, PACAP was associated with a reduced risk of invasive mechanical ventilation with an aHR of 0.07 (95% CI 0.014 to 0.351). However, the was no statistically significant difference in the occurrence of major or minor bleeds, ICU admission or the composite outcome of in-hospital mortality, ICU admission or the need for mechanical ventilation. Conclusion(s): The use of combined anticoagulant and antiplatelet agents or TAC alone in hospitalised patients with COVID-19 was associated with a better outcome in comparison to PAC alone without an increase in the risk of major and minor bleeds. Sufficiently powered randomised controlled trials are needed to further evaluate the safety and efficacy of combining antiplatelet and anticoagulants agents or using TAC in the management of patients with COVID-19 infection.
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Background and aim: In Veneto region, rates of hospitalization (2.4 per 10,000) and 30-day mortality (4.3%) for non-variceal upper gastrointestinal bleeding (NVUGIB) were stable during 2012-2019. The COVID-19 pandemic has caused a global health emergency and the aim of this study was to evaluate COVID-19 impact on hospitalizations and mortality for NVUGIB in Veneto region. Material(s) and Method(s): This is a retrospective study based on administrative databasescarried out to compare NVUGIB hospitalizations and 30-day mortality after hospital admission before (2018- 2019) and duringthe COVID-19 pandemic (2020-2021).The indicator proposed by the National Outcomes Evaluation Programme was adopted,includingall NVUGIB hospitalizations of patients over 18 years old, residing in Veneto, excluding conditions with indication of anticoagulant or antiplatelet therapy, trauma, cardiovascular surgeries, cancer, cirrhosis. The crude and standardized hospitalization rates (sHR,direct standardization method),and 30-day mortality were calculated. Chi-square, Mann Whitney test, ORand adjusted OR (aOR), estimated throughlogistic regression analysis were used to compare the two periods. Result(s): 3,436 eligible admissions for NVUGIB were identified, 1,872 before COVID-19and 1,564 during the pandemic: 815 in 2020 and 749 in 2021. The distribution by age and sex in the two periods was comparable: 42% females, above 60% patients aged >70 years;females were older (p<.0001) (median age: males 72 (IQR:57-81), females 81 (IQR:70-87)). sHR were significantly higher in the pre- COVID-19 period (2.34 per 10,000 population 95% CI 2.23-2.45 Vs. 1.90 95% CI 1.80-1.99) and comparable between 2020 and 2021 (1.99;95% CI:1.85-2.12Vs. 1.81;95% CI:1.68-1.94 p-value=0.0644). Rates increased with age and were higher for patients over 80. Rates were also higher among males for both periods and for all age groups. Crude 30-day mortality was significantly higher for females in both periods(F:M risk ratio: pre-COVID-19: 1.57 - p-value: 0.0355;during covid: 1.49 - p-value: 0.0316) and was higher during the pandemic both for males (3.75% vs 6.11%) and females (5.9%vs 9.12%) also after adjusting for age (aOR males: 1.71;95% CI:1.13-2.61;females: 1.56;95% CI:1.04-2.33). Conclusion(s): COVID-19 pandemic has caused a global reduction of access to care with an important decrease also of NVUGIB hospitalization rate (- 19%) and a concomitant rise of 30-day mortality (+58%).Copyright © 2023. Editrice Gastroenterologica Italiana S.r.l.
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Background Patients with hypoplastic left heart syndrome (HLHS) undergo a Fontan procedure as part of single ventricle surgical palliation. Post-Fontan, sluggish blood flow and an imbalance in coagulant factor proteins may predispose to thrombus formation. Other risk factors may include chylothorax as well as acute and chronic inflammation. Currently, there is no standardized surveillance strategy to detect thrombus in Fontan patients. Case A 34-month old male with HLHS underwent an extracardiac non-fenestrated Fontan complicated by chylothorax treated with 5 days of IV steroids and diuretics. He was on therapeutic aspirin. After progressive worsening of right pleural effusion, a chest tube was placed three weeks post-Fontan with continued chylous output. Stool alpha 1 antitrypsin was negative. Decision-making Given persistent chylothorax, a repeat echocardiogram was performed revealing a large mass in the Fontan circuit less than one month post-op. Cardiac CT showed occlusive thrombus filling the entirety of the Fontan conduit extending into hepatic veins and bilateral pulmonary arteries. He underwent extensive surgical thrombectomy and Fontan conduit revision. Hypercoagulable work-up revealed elevated factor 8 and von Willebrand factor activity which persisted more than one month post-op. Patient's history was also significant for COVID-19 infection 6 months prior. He was initially anticoagulated with bivalirudin with tirofiban initiated for antiplatelet therapy. He was ultimately transitioned to rivaroxaban, pentoxifylline and aspirin with chylothorax resolution over one month without thrombus recurrence. Conclusion Development of risk stratification tools to identify patients at higher risk for thrombi formation post-Fontan may facilitate patient selection for more aggressive anticoagulation. Consideration of elevated factor 8 as well as persistent or recurrent chylothorax may be beneficial, as increased thrombosis risk has been reported for both conditions in Fontan patients.Copyright © 2023 American College of Cardiology Foundation
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Background: Modalities of use of androgen deprivation therapy (ADT), like triptorelin, in real life, at the era of new strategies in advanced stages, lack of recent data. Our purpose here was to describe main reasons of choice of formulation and route (F&R) of triptorelin treatment (Tt) declared by the physician. Patient comorbidities, cancer aggressiveness and physician habits may influence their choices. Method(s): Initiated in 2020, a prospective, multicenter, non-interventional study is ongoing in France (TALISMAN, NCT04593420). Patients with histologically confirmed PCa, eligible for >= 12-month triptorelin Tt within its label were enrolled. Interim analysis of baseline data was planned when 50% of 786 planned patients were enrolled. Modalities of use, including F&R of triptorelin prescribed [monthly intramuscular (1mIM), every 3 months subcutaneous (3mSC) or intramuscular (3mIM), every 6 months intramuscular (6mIM)], were described. Result(s): 509 patients were included in the interim analysis. Overall population was presented at ASCO-GU22. Subgroups of F&R are presented here. Main F&R prescribed was 3mSC (70.7%). Main baseline parameters in F&R subgroups are presented (except for 1mIM, 4 patients (0.8%)). 31 patients had missing F&R data and were not included in subgroups. 62.1% of patients overall received at least one concomitant systemic Tt for comorbidity at baseline (58.2% in 3mIM, 61.7% in 3mSC and 6mIM). 18.6% and 13.0% of patients overall received, respectively, platelet aggregation inhibitor and anticoagulant;they were 20.9% and 13.8% in 3mSC, 7.3% and 5.5% in 3mIM, 18.5% and 11.1% in 6mIM. Conclusion(s): Main reason of choice of F&R of triptorelin was physician preferred F&R (47.7%);noticeable reasons included anticoagulants for the choice of 3mSC, planned total duration of Tt for 3mIM and 6mIM, and potential impact on compliance for 6mIM. As the covid pandemic may change the management of patients with prostate cancer, longer acting formulations may become more attractive.
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Case Report: Purpose: Milrinone is an inodilator that is used in the treatment of cardiogenic dysfunction and shock. It causes increased cardiac output by stimulating myocardial contractility, enhancing cardiac relaxation, and reducing afterload via phosphodiesterase III inhibition, preventing cyclic adenosine monophosphate (cAMP) degradation. Increased cAMP concentrations are known to inhibit platelet aggregation. Veno-arterial-extracorporeal membrane oxygenation (VA-ECMO) is an extracorporeal treatment option for inotrope-refractory cardiogenic shock and is often used in conjunction with inodilators. Often, patients supported on ECMO require systemic anticoagulation to prevent clotting complications. Therefore, thromboelastography (TEG) with platelet mapping is used to help gauge a patient's clotting status and gives clinicians information about the degree of platelet inhibition present. We present the case of two patients, both supported on VA-ECMO, who developed platelet inhibition with clinically significant bleeding while on milrinone, requiring the cessation of the milrinone infusion. Cases: First, we present an adult female in her fourth decade of life who required VA-ECMO for Covid-19 ARDS and cardiogenic shock. TEG platelet mapping was obtained for clinically significant bleeding from her trachea and gastrointestinal tract. Ten days after starting milrinone, adenosine-5'-diphosphate (ADP) inhibition was elevated at 67.4% and arachidonic acid (AA) inhibition normal at 1.8%. Twenty days after starting milrinone, ADP inhibition was 93.3% and AA inhibition was 76.4%. Milrinone discontinued and repeat TEG platelet mapping (10 days after discontinuation) showed ADP inhibition of 76.8% and AA inhibition of 0%. Her lowest ADP inhibition was 41.9%, approximately 1 month after milrinone discontinuation. Milrinone again attempted and ADP inhibition was 87.9% and AA inhibition 89.2% within 24 hours of initiation. No data available for platelet inhibition prior to starting milrinone. Next, we present a 9 year old female with acute myeloid leukemia who required VA-ECMO for septic shock. Initial TEG platelet mapping, obtained 2 days after milrinone initiation, showed ADP inhibition of 43.6% and AA inhibition of 98.7%. Two days after discontinuation of milrinone, her ADP inhibition was 19.6% but AA inhibition remained elevated at 91.9%. However, after 4 days off milrinone, her ADP inhibition was normal at 15.5% and AA inhibition mildly elevated at 33.6%. No data available for platelet inhibition prior to starting milrinone. Conclusion(s): Milrinone is a known platelet inhibitor due to increased intracellular cAMP concentrations. For patients on ECMO and milrinone, care should be given to the degree of platelet inhibition and potential risk of clinically significant bleeding. Further studies are needed to further investigate the correlation between milrinone, platelet inhibition, and clinically significant bleeding in ECMO patients. Copyright © 2023 Southern Society for Clinical Investigation.
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Background: Neutrophil extracellular traps (NETs) release is the one of the main mechanisms behind hypercoagulability and disease severity in severe acute respiratory syndromes. The identification of drugs capable of inhibiting this pathological mechanism is mandatory. Aim(s): Neutrophil extracellular traps (NETs) release is the one of the main mechanisms behind hypercoagulability and disease severity in severe acute respiratory syndromes. The identification of drugs capable of inhibiting this pathological mechanism is mandatory. Method(s): Healthy neutrophils (20 x 103/well) were stimulated with phorbol myristate acetate (PMA) or sera from severe COVID-19 patients (n = 16) in the presence or absence of dipyridamole (10 muM), aspirin (1 mM) and heparin (50 mug/mL). Neutrophils nuclei were stained with nuclear red and incubated with a medium containing the non-permeable cell membrane marker Sytox Green. Cell images were obtained using IncuCyte ZOOM and the number of cells that suffered netosis was monitored over time. NETs release was determined after 1 h of incubation and the percentage of NETs was calculated dividing the number of green cells by the total number of cells per well. Result(s): COVID-19 induced NETs was lower in neutrophils pretreated with heparin (median 2.6%, IQR 2.6-2.9) than in non-treated neutrophils (median 3.6%, IQR 3.2-4.0, p < 0.0001). Pretreatment with dipyridamole and aspirin did not change the effect of COVID-19 sera in inducing NETs. A similar pattern of inhibition was observed with PMA stimulation, in which heparin decreased NETs by 3 times (NETs after PMA 43.2% and NETs after PMA and heparin 14.8%) while dipyridamole and aspirin did not significantly affect the release of PMA-induced NETs (Figure 1). Figure 2 illustrates the identification of NETs. Conclusion(s): Heparin was capable of inhibiting in vitro NETs release induced by COVID-19, while dipyridamole and aspirin had no significant effect on this process. Such findings are in line with evidence that heparin use can improve COVID-19 prognosis. (Figure Presented).
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SESSION TITLE: Problems in the Pleura Case Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (Btk), approved for treatment of a variety of B-cell malignancies, including chronic lymphocytic leukemia (CLL). There is an association of increased risk of bleeding with ibrutinib due to platelet dysfunction caused by the medication. Bleeding is usually non-life threating such as subcutaneous or mucosal bleeding, epistaxis, and ecchymosis. But major bleeding has been reported such as intracranial hemorrhage and gastrointestinal hemorrhage. Thoracic complications from ibrutinib are rare. Below is a case report discussing a hemorrhagic pleural effusion thought to be caused by Ibrutinib. CASE PRESENTATION: Patient is a 78-year-old male initially diagnosed with CLL on flow cytometry showing a low-grade B cell lymphoproliferative process. Patient was monitored by Hematology and when kappa light chain numbers began to rise, a bone marrow biopsy was performed showing 90% infiltration of the marrow with lymphoid cells. Patient was started on Ibrutinib therapy and responded well to treatment. A year after starting therapy, patient presented to the emergency room with increased shortness of breath and fatigue. Patient was found to be COVID-19 positive and chest x-ray showed a large right sided pleural effusion. Thoracentesis was performed draining 1650cc of bloody fluid. Fluid studies revealed a lymphocytic effusion with RBC count 1,185375, WBC of 1751. Cultures and cytology were negative. On further history, patient was without recent trauma or surgery, CTA chest was negative for pulmonary embolism. QuantiFERON Gold test was negative, indicating low likelihood of tuberculosis. Patient was not on any antiplatelet or systemic anticoagulation medications. Ibrutinib therapy was held during hospitalization and pleural effusion did not reaccumulate. Patient passed away during hospital stay secondary to respiratory failure due to COVID-19. DISCUSSION: Ibrutinib is an orally bioavailable bruton tyrosine kinase inhibitor (BTKi) and forms an irreversible covalent bound to BTK at the Cysteine-481 residue. Ibrutinib predisposes to bleeding by inhibiting BTK and Tec, which play a role in the inhibitory signaling pathway of platelet collagen receptors such as glycoprotein VI (GP VI) and C-type lectin-like receptor 2 (CLEC-2). Our patient had no other risk factors for developing a hemorrhagic effusion. CLL itself can cause malignant effusions, one study found the incidence of malignant effusions among patients with CLL to be 9%, but the effusion was noted to be serous or serosanguinous and there was pleural involvement in all patients which was not the case in our patient. CONCLUSIONS: There is currently a minimal amount of data to guide clinicians regarding the use of ibrutinib in patients at high risk of bleeding or on anticoagulant or antiplatelet therapy. It is important to realize bleeding complications related to ibrutinib therapy can occur. Reference #1: Shatzel JJ, Olson SR, Tao DL, McCarty OJT, Danilov AV, DeLoughery TG. Ibrutinib-associated bleeding: pathogenesis, management and risk reduction strategies. J Thromb Haemost. 2017;15(5):835-847. doi:10.1111/jth.13651 Reference #2: Burger JA, Tedeschi A, Barr PM, et al. Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia. N Engl J Med. 2015;373(25):2425-2437. doi:10.1056/NEJMoa1509388 Reference #3: Paydas S. Management of adverse effects/toxicity of ibrutinib. Crit Rev Oncol Hematol. 2019;136:56-63. doi:10.1016/j.critrevonc.2019.02.001 DISCLOSURES: No relevant relationships by fatima ali No relevant relationships by Joan Wiley
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Background: Arterial thrombotic events (ATE) are important cause of noncancer-related deaths among patients with cancer. It is estimated that the prevalence of ATE among those patients is between 2-5%. However, data regarding acute myeloid leukemia (AML) related ATE are scarce and far less available than those related to venous thrombotic events. Aims: To determine the incidence of ATE in nonM3-AML patients and to underline the potential risk factors for ATE development. Methods: The single center, retrospective, cohort study was carried out in University Clinical Center of Serbia. Adult patients, who were diagnosed with nonM3-AML between January 2009. and December 2021. were included. In all patients the occurrence of ATE (e.g. a heart attack, a stroke, critical limb ischemia) was assessed during the active treatment and the three months following the last chemotherapy session. Diagnosis of ATE was established using clinical, laboratory and radiological methods. Patients who experienced venous thromboembolism during the treatment period were excluded. Demographic data, presence of obesity, smoking status, history of thrombosis, baseline laboratory findings (complete blood count, fibrinogen, D-dimer, PT, aPTT, LDH), leukemia-related parameters (cytogenetics (including ELN risk stratification), flow cytometry), Khorana score, ECOG PS, HCT CI score, concurrent COVID-19 were collected from patients' health records. The methods of descriptive (mean ± standard deviation, median (range), frequency (%)) and analytic statistics (Student's t-test, chi-squared test) were used. Results: A total of 545 patients (293 males (53.8%)) were included in the study. Median age of the study population was 58 (range: 18-81) years. ATE was noted in 18/545 (3.3%) subjects with following distribution: ischemic stroke 12/18 (66.7%), myocardial infarction 5/18 (27.8%), and acute lower extremity arterial thrombosis 1/18 (5.5%). ATE was diagnosed most commonly during the induction (8 (44.4%) patients), reinduction (3 (16.7%) patients) and consolidation (4 (22.2%) patients) cycles. However, cases of ATE were noted at diagnosis (1 (5.6%) patient), after transplantation (1 (5.6%) patient) or at relapse (1 (5.6%) patient) as well. ATE were significantly more frequent among patients with previous history of thromboembolic events (p = 0.016). Moreover, ATE were more common in patients with adverse cytogenetic abnormalities (p < 0.001). Other examined parameters did not significantly differ between those with and without ATE. Summary/Conclusion: The incidence of arterial thrombosis in our group was 3.3% which is in accordance with the previously published studies. Since the great number of already known risk factors for the arterial thrombosis are modifiable (e.g. smoking, diet, physical activity, excessive drinking?) it is important to actively work on the reduction on those risk factors, especially if the patient has the history of previous thromboembolic event and/or suffer from high risk AML. Prophylactic therapy with antiplatelet agents is aggravated due to the lack of firmer evidences and the presence of thrombocytopenia. Therefore further studies regarding this issue are needed.
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Background: Coronavirus-19 disease (COVID-19) has been responsible, to date, for more than 5 million of deaths. Immunothrombosis may be a major factor contributing to mortality in COVID-19 and pulmonary arterial tree involvement that mimics multiple pulmonary embolism could be a major contributor to disease course. Immunomodulatory drugs are of some beneft but mechanism not completely clear. We investigated pulmonary arterial tree clots to better appreciate their immunothrombotic nature, in contrast to the pathological characteristics of non-infammatory thrombi (1). Objectives: The primary objective was to study in depth the arterial thrombosis in COVID-19, by characterizing the immunohistochemical nature of thrombi, performing macroscopic and microscopic analyses, and by comparing clinical, laboratory and anatomical-pathological data of these patients with other patients died for COVID-19 but without evidence of pulmonary arterial thrombosis. Methods: Autopsies were performed in patients (cases) who died for COVID-19 with evidence of pulmonary arterial thrombosis at autopsy fnding but without pathological signs of bronchopneumonia or peripheral venous thrombosis. COVID-19 positive patients without pulmonary arterial thrombosis were selected as control group. Hematoxylin and eosin stained slides were reviewed choosing those with visible pulmonary thrombi. Further histochemical and immunohisto-chemical staining were performed in selected paraffin blocks. Each component of the thrombus was evaluated with the software application QuPath in terms of fbrin, red blood cells, platelets and immune cells percentage after scanning the slides with Aperio System. Laboratory tests were recorded at 2 points: at hospital admission and at Intensive Care Unit transfer. Results: We included 13 patients (cases) and 14 controls, matched for age, gender and time from diagnosis to death. Twenty arterial thrombi were studied. By immuno-histochemistry, arterial thrombi were composed by white blood cells (WBC) [median, IQR range: 10% (5-12.25)], mainly neutrophils [58% (35.2-64.5)], red blood cells [12%, (6-34.25)], fbrin [19% (14.5-42.25)], platelets [39%, (31.75-48)] (Figure 1). Three cases had a history of previous thrombosis. All cases had received anticoagulant treatment during hospitalization, low molecular weight heparin in 12/13 (therapeutic regimen in 4/12, prophylactic in 8/12) while 1/13 continued oral anticoagulants for comorbidity. By comparing laboratory fndings between cases and controls, cases showed signifcantly higher levels of platelet count [median, IQR range: 195000/mmc (157750-274500) vs 143500 (113000-175250), p=0.011], LDH [854 U/l (731-1315) vs 539 (391.5-660), p=0.003)] at hospital admission, and D-dimer at ICU transfer [25072 FEU (6951-50531) vs 1024 (620-5501), p=0.003)]. Conclusion: Pulmonary arterial thrombosis in COVID-19 is a type of immune-mediated infammatory thrombosis, since the amount of WBC is 6-times more than normal value seen in non-infammatory thrombi. Some markers of infammation, necrosis and coagulation are much more increased in this subset of patients. Chest CT angiography rather than simple CT scan at hospital admission could be more useful in this setting, and treatments with antiplatelet agents or anticoagulants, eventually in combination with immunotherapy, might positively affect the outcome.
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Background: In winter, you can usually see a picture of Perniosis and/or chilblains. Painful, often itchy, red-to-purple lesions that affect the acrid surfaces of the fngers and toes after contact with the cold, resembling vasculitis, characterize them. Chilblains can be idiopathic and self-limiting or associated with systemic diseases. The diagnosis is usually clinical, but in some circumstances, analytical and microscopic studies of a biopsy sample may be necessary. We present a series of 19 consecutive cases of Pseudoperniosis associated with probable past INFECTION by SARS-CoV-2. Methods: During the winter 2020-21, an unexpected number of cases referred as 'acute arthritis/vasculitis' have been received in our rheumatology section and associated consultations. In the pathochrony of patients, exposure to cold was referred to as the main triggering factor. Initially qualifed as PERNIOSIS. Given the appearance in the current situation of Pandemic by covid-19, we began to request the serology SARS2-COVID19 IgG/IgM. Appreciating an approximate rate of 70% of IgG+ positivity in which it was performed. Results: Characteristics of the clinical data collected evolutionarily in the 19 patients: These are preferably young people, without any other pathology, although there are also people of all ages, with a clinical picture of edema of soft parts preferably of the hands, but also in the feet, with pain and some hemorrhage infusions, including ulcerations in the areas of the knuckles or pressure (PHOTO1-2-3). Despite the overwhelming nature of the picture, they do not associate any other symptoms and the analyses are normal, including acute phase reactants (ESR and PCR), and serological markers of autoimmune disease. Approximately 1/4 of them reported having passed clinical compatible with the covid19 infection and/or having been isolated with some minor symptom, but they had not been performed PCR. The others did not report any symptoms associated with COD19 infection. From the initial diagnosis, about 40 days passed on average. Many of them were being treated with corticosteroids/NSAIDs without improvement. In the ultrasounds performed, only edema of periarticular and paratendinous tissue is appreciated, such as that which can occur after a momentary ischemic picture. All evolved favorably avoiding cold (probable triggering factor), and with antiplatelet agent (infant aspirin). Conclusion: This picture of Pseudoperniosis lacks the typical pruritus of perniosis and the main problem is pain along with edema of the tissues of the hand that leads to make it impossible to use. Similarly, asymmetric lesions similar to perniosis were observed in patients who presented skin manifestations of SARS-CoV-2 infection in a study conducted in Spain (1). We are following these patients to assess if there is any relationship with any other factor that facilitates this unusual incidence, and at the same time indicate the transience of the clinical picture that evolves favorably in a few weeks.
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Aim and objective: During the recent COVID-19 pandemic various vaccines have been developed and approved for emergency use, including adenovirus vector-based ChAdOx1 nCov-19. There are few reports of serious adverse events following immunization (AEFI). Materials and methods: Here, we report two cases of serious AEFI who required ICU admission. Results: Case 1: A 55-y-m hospitalized with complaints of giddiness for 4 days and onset of weakness of all four limbs with altered sensorium for 1 day. He had no history of any comorbidity, non-smoker and non-alcoholic, and no previous episodes of transient ischemic attacks. He was vaccinated with a second dose of adenoviral vector-based ChAdOx1 nCov-19 vaccine (8 days before the onset of first symptoms). After hospitalization, immediate intubation was done for airway protection. His neurological examination revealed blinking of eyes spontaneously, motor power of 0/5 in all four limbs, deep tendon reflex of +2, and mute plantar. MRI Brain was done on the next day (day of illness, DOI-4), which revealed acute infarct in the pons and bilateral cerebellar hemisphere. He was referred to our ICU on DOI-12. Repeat MRI Brain on DOI-16 showed subacute infarcts in the pons, bilateral middle cerebellar peduncles, and left cerebral hemisphere with thrombosed basilar artery. Lipid profile, homocysteine levels, auto-immune work-up were normal. Echocardiography showed normal LV function with no evidence of LA clot. Carotid Doppler showed normal carotid vessels. In view of ischemic stroke and basilar artery thrombosis anti-platelet agent and therapeutic anticoagulation continued. Over the next 3 weeks, he showed gradual improvement in motor power (3/5 in upper limbs and 2/5 in lower limbs) and weaned off from mechanical ventilation. Case 2: A 19-y-m hospitalized with complaints of acute onset paraesthesia and progressive weakness in both lower limbs for 4 days and difficulty in speech and swallowing for 1 day. He had no history of any comorbidity, and no history of preceding viral/bacterial infection except that he had received the first dose of the adenoviral vector-based ChAdOx1 nCov-19 vaccine (16 days before the onset of first symptoms). After hospitalization, he required intubation in view of pooling of oral secretions and respiratory distress. Clinical examination revealed bifacial weakness, severe neck muscle weakness, and flaccid areflexic quadriparesis with prominent proximal upper and lower limb weakness. Pin-prick sensation was distally reduced in both lower limbs with associated autonomic instability in the form of tachycardia and hypertension. MRI Brain was normal in the study. In further work, Guillain-Barré syndrome (GBS) was diagnosed. CSF showed albumin-cytologic dissociation (protein 1.14 g/L and nil cell), and bilateral motor nerve axonal neuropathy on nerve conduction study. Immunoglobulin (IVIG) therapy was started on DOI-6. He did not show significant improvement and was referred to our ICU for further management. During the 5th week of illness, the IVIG dose was repeated without any improvement and continuing requirement of mechanical ventilation. Conclusion: Though vaccination is one of the important public health interventions implemented to tackle the COVID-19 pandemic, there are known and unknown serious AEFI being reported. Both cases presented quadriparesis with different diagnoses, who received vaccination for COVID-19.
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Since the spread of the novel coronavirus infection, most researchers have noted a low proportion of sick children in general pediatric cohort compared to adults, who had a mild disease course and rare complications. The most frequent clinical manifestations of the disease are respiratory and, some less frequently diarrheal syndromes. The disease has predominantly mild or asymptomatic course. The risk of adverse outcomes in children, similar to adults, clearly correlate with the presence of background chronic pathology. The need for respiratory support prevails in children with a severe premorbid burden. Here, a clinical case of ongoing novel coronavirus infection in adolescent patient comorbid with chronic kidney pathology is described. In adolescence, the patient was diagnosed with mesangioproliferative glomerulonephritis (IgA-nephropathy), and further registered at the dispensary receiving a combination therapy with angiotensin converting enzyme inhibitors and disaggregation drugs. The epidemiological history contained no established contacts with infectious patients. The clinical manifestations of COVID-19 in the patient are represented by catarrhal and diarrheal syndromes, transient renal dysfunction in the acute period of the disease. The onset of coronavirus infection was clinically characterized by symptoms of damaged gastrointestinal tract and was considered as acute gastroenteritis of infectious etiology. Empirically prescribed antibacterial therapy in combination with antiplatelet agents and symptomatic drugs had no effect. The diagnosis of the novel coronavirus infection was verified only on day 4 of hospitalization, clinical and laboratory signs of lung damage emerged. The inflammatory process developed in the patient lungs was secondary to the main pathology. The severity of the patient’s condition was determined by the presence of respiratory and renal insufficiency. Lung damage with minimal severity complaints and clinical data had a bimodal pattern and required respiratory support. A comprehensive approach to treatment, including respiratory, antiviral, enterosorption, anticoagulation, anti-inflammatory, antihypertensive, hepatoprotective, symptomatic therapy with change in antibacterial drugs allowed to achieve positive dynamics. On day 12 of the illness, the patient required no respiratory support. The presence of symptoms of gastrointestinal tract damage in COVID-19 necessitates the mandatory inclusion of PCR assay for SARS-CoV-2 into diagnostic protocol in patients with diarrheal syndrome to perform etiological disease interpretation.
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These days, anticoagulants are in great demand. They are used as a prophylaxis for thromboembolic complications in various diseases and conditions in general therapeutic practice, cardiology, neurology, as well as obstetrics to manage high-risk pregnancies. The relevance of anticoagulants competent use has come to the fore in connection with the emergence of a new disease – COVID-19 and its serious complications such as developing thrombotic storm, in which the timely applied anticoagulant therapy is the key to the success of therapy. The risk of bleeding should be considered when using any anticoagulant. Age, impaired renal function and concomitant use of antiplatelet agents are common risk factors for bleeding. Moreover, only vitamin K antagonists and heparin have specific antidotes – vitamin K and protamine, respectively. Inhibitors of other anticoagulants are universal presented as inactivated or activated prothrombin complex concentrate and recombinant factor VIIa. Hemodialysis effectively reduces dabigatran concentration, activated charcoal is effective in the case of recent oral administration of lipophilic drugs. Research on new antidotes of currently available anticoagulants is under way, similar to testing of new types of anticoagulants that are sufficiently effective in preventing and treating thromboembolic complications with minimal risk of hemorrhagic. The main contraindication to anticoagulants use is the doctor's ignorance of the mechanisms of drug action and opportunities for suppressing its effect.
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Background: Arterial hypertension has been described as one of the main risk factors for poor prognosis in Covid-19. In this context, the role of angiotensin-converting enzyme 2 (ACE2) in this infection has been studied, with studies showing how this enzyme acts as a functional receptor for SARS-CoV-2, favoring the penetration of the virus into the cell. The main objective of this work is to study the impact of chronic antihypertensive treatment in a cohort of SARS-CoV-2 positive patients with arterial hypertension, as well as clinical outcomes during hospitalization. Method: Single-center observational retrospective cohort study conducted at a tertiary level university hospital from 1st March 2020 to 31st May 2020. All adult patients admitted with a diagnosis of COVID-19 and a history of arterial hypertension on chronic treatment with an antihypertensive drug during the three months prior to contracting the infection were included. For the analysis, patients were divided into three groups according to the chronic antihypertensive treatment they were receiving: angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin II receptor antagonists (ARB) or other treatment, excluding those patients who during the three months prior to the start of the study had been on concomitant treatment with ACE inhibitors and ARB, as well as those on treatment with more than four antihypertensive drugs. Results: A total of 475 cases with positive PCR for SARS-CoV-2 cases had hypertension as an associated comorbidity on antihypertensive treatment in the three months prior to admission. The mean age of this cohort of patients was 77.05 (SD 10.95) years, most of them male (56.8%) Regarding the prolonged length of stay variable, 127 patients (26.7%) were admitted for 14 days or more, with no statistically significant differences between the three groups. For patients admitted to the Intensive Care Unit (ICU) (29 patients, 6.1%) no differences were observed between the three study groups either.Regarding the outcome variable, all-cause in-hospital mortality, no statistically significant differences were observed between the groups (p = 0.836). Conclusions: Patients admitted with SARS-CoV2 respiratory infection with a diagnosis of hypertension and pre-admission treatment with an antihypertensive drug showed no statistically significant differences in mortality between those hypertensive patients who received renin-angiotensin-aldosterone system (RAAS) inhibitor antihypertensive drugs and those who received other antihypertensive treatments.
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Background and aims: Optimal management of carotid artery freefloating thrombus (CAFFT) and CAFFT-related strokes remains unclear. We sought to examine the clinical characteristics, treatment strategies and patient outcomes for CAFFT-related ischaemic strokes. Methods: We conducted a single-centre retrospective observational study by extracting data from electronic patient records. We included consecutive patients admitted between 2016-2021 with ischaemic stroke and CAFFT on initial CT/MR angiogram. Results: We included 59 patients (mean age 63, 66% male). Vascular risk factors included hypertension (42%), diabetes (19%), dyslipidaemia (27%), previous stroke (10%), smoking history (56%) and alcohol excess (14%). 6 patients (10%) were COVID-19 positive. Median modified Rankin score was 0 and mean NIHSS was 11. On admission, 42% were taking antiplatelet agents, 10% were on anticoagulant, 34% had CRP >10mg/L, and 14% had eGFR <50 ml/min/1.73m2. On arrival, 27% received IV thrombolysis and 19% underwent mechanical thrombectomy. Acute antithrombotic strategies included IV heparin (49%), low molecular weight heparin (47%), oral anticoagulation (15%), and antiplatelet agents (63%). 24 patients (41%) were referred to vascular surgery, of whom 9 (38%, 15% of total) received emergency carotid endarterectomy. Neurological deterioration (<7 days) occurred in 14%. In-hospital mortality was 8% overall, but 67% for COVID-positive patients. At 6 months, recurrent stroke occurred in 12% and mortality was 3%. Conclusions: CAFFT-related ischaemic stroke is associated with significant mortality and neurological morbidity. The use of different acute antithrombotic strategies and emergency carotid endarterectomy varied significantly between patients. These major treatment options should be subjects of future clinical trials.
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Introduction: Antifibrotic drugs, including nintedanib and pirfenidone, are approved for the treatment of idiopathic pulmonary fibrosis (IPF). Pirfenidone blocks the synthesis of TGF-beta and does appear to increase the risk of CV or bleeding events. Nintedanib is a Vascular Endothelial Growth Factor Receptors (VEGFR) inhibitor and may increase the risk of bleeding. Bleeding events were reported in 10% of patients in clinical trials (despite excluding patients at risk of bleeding including those on con-current anticoagulation (AC) or antiplatelet (AP) therapy. Consequently, nintedanib is relatively contraindicated for patients with IPF on anticoagulation or antiplatelet therapy. However, results from real-life data demonstrate that 17.8% of our patients with IPF are on anticoagulation or antiplatelet therapy. The overall incident of bleeding events in those patients taking either or with nintedanib is similar to that reported for Nintedanib alone. We describe two patients with antifibrotic and anticoagulation therapy to highlight how to manage these patients. Case 1. A 67-year-old female with history of acute pulmonary embolism secondary to COVID-19 on anticoagulation therapy presents for workup of acute respiratory distress syndrome or suspected exacerbation of underlying IPF-usual interstitial pneumonia. Patient treated as IPF with pirfenidione. Case 2. A 69-year-old man with a history of atrial fibrillation on anticoagulation therapy presents for follow-up of progressive fibrosing interstitial lung disease secondary to hypersensitivity pneumonitis. Nintedanib initiated for progressive fibrosing lung disease. Discussion: Concomitant use of anticoagulation and/or antiplatelet therapy with antifibrotics doesn't increase bleeding risk. Conclusion. Anticoagulation and/or antiplatelet therapy should not be a reason to withhold antifibrotic therapy in patients with IPF.