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1.
J Clin Med ; 10(8)2021 Apr 16.
Article in English | MEDLINE | ID: covidwho-1526841

ABSTRACT

Infection by SARS-CoV-2 is associated with a high risk of thrombosis. The laboratory documentation of hypercoagulability and impaired fibrinolysis remains a challenge. Our aim was to assess the potential usefulness of viscoelastometric testing (VET) to predict thrombotic events in COVID-19 patients according to the literature. We also (i) analyzed the impact of anticoagulation and the methods used to neutralize heparin, (ii) analyzed whether maximal clot mechanical strength brings more information than Clauss fibrinogen, and (iii) critically scrutinized the diagnosis of hypofibrinolysis. We performed a systematic search in PubMed and Scopus databases until 31st December 2020. VET methods and parameters, and patients' features and outcomes were extracted. VET was performed for 1063 patients (893 intensive care unit (ICU) and 170 non-ICU, 44 studies). There was extensive heterogeneity concerning study design, VET device used (ROTEM, TEG, Quantra and ClotPro) and reagents (with non-systematic use of heparin neutralization), timing of assay, and definition of hypercoagulable state. Notably, only 4 out of 25 studies using ROTEM reported data with heparinase (HEPTEM). The common findings were increased clot mechanical strength mainly due to excessive fibrinogen component and impaired to absent fibrinolysis, more conspicuous in the presence of an added plasminogen activator. Only 4 studies out of the 16 that addressed the point found an association of VETs with thrombotic events. So-called functional fibrinogen assessed by VETs showed a variable correlation with Clauss fibrinogen. Abnormal VET pattern, often evidenced despite standard prophylactic anticoagulation, tended to normalize after increased dosing. VET studies reported heterogeneity, and small sample sizes do not support an association between the poorly defined prothrombotic phenotype of COVID-19 and thrombotic events.

2.
JAMA Netw Open ; 4(6): e2111788, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1265353

ABSTRACT

Importance: Venous thromboembolism (VTE) is a common complication of COVID-19. It is not well understood how hospitals have managed VTE prevention and the effect of prevention strategies on mortality. Objective: To characterize frequency, variation across hospitals, and change over time in VTE prophylaxis and treatment-dose anticoagulation in patients hospitalized for COVID-19, as well as the association of anticoagulation strategies with in-hospital and 60-day mortality. Design, Setting, and Participants: This cohort study of adults hospitalized with COVID-19 used a pseudorandom sample from 30 US hospitals in the state of Michigan participating in a collaborative quality initiative. Data analyzed were from patients hospitalized between March 7, 2020, and June 17, 2020. Data were analyzed through March 2021. Exposures: Nonadherence to VTE prophylaxis (defined as missing ≥2 days of VTE prophylaxis) and receipt of treatment-dose or prophylactic-dose anticoagulants vs no anticoagulation during hospitalization. Main Outcomes and Measures: The effect of nonadherence and anticoagulation strategies on in-hospital and 60-day mortality was assessed using multinomial logit models with inverse probability of treatment weighting. Results: Of a total 1351 patients with COVID-19 included (median [IQR] age, 64 [52-75] years; 47.7% women, 48.9% Black patients), only 18 (1.3%) had a confirmed VTE, and 219 (16.2%) received treatment-dose anticoagulation. Use of treatment-dose anticoagulation without imaging ranged from 0% to 29% across hospitals and increased over time (adjusted odds ratio [aOR], 1.46; 95% CI, 1.31-1.61 per week). Of 1127 patients who ever received anticoagulation, 392 (34.8%) missed 2 or more days of prophylaxis. Missed prophylaxis varied from 11% to 61% across hospitals and decreased markedly over time (aOR, 0.89; 95% CI, 0.82-0.97 per week). VTE nonadherence was associated with higher 60-day (adjusted hazard ratio [aHR], 1.31; 95% CI, 1.03-1.67) but not in-hospital mortality (aHR, 0.97; 95% CI, 0.91-1.03). Receiving any dose of anticoagulation (vs no anticoagulation) was associated with lower in-hospital mortality (only prophylactic dose: aHR, 0.36; 95% CI, 0.26-0.52; any treatment dose: aHR, 0.38; 95% CI, 0.25-0.58). However, only the prophylactic dose of anticoagulation remained associated with lower mortality at 60 days (prophylactic dose: aHR, 0.71; 95% CI, 0.51-0.90; treatment dose: aHR, 0.92; 95% CI, 0.63-1.35). Conclusions and Relevance: This large, multicenter cohort of patients hospitalized with COVID-19, found evidence of rapid dissemination and implementation of anticoagulation strategies, including use of treatment-dose anticoagulation. As only prophylactic-dose anticoagulation was associated with lower 60-day mortality, prophylactic dosing strategies may be optimal for patients hospitalized with COVID-19.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/complications , Hospitalization/trends , SARS-CoV-2 , Venous Thromboembolism/prevention & control , Aged , COVID-19/epidemiology , Female , Hospital Mortality/trends , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Survival Rate/trends , United States/epidemiology , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology
3.
Neth Heart J ; 29(Suppl 1): 35-44, 2021 May.
Article in English | MEDLINE | ID: covidwho-1188200

ABSTRACT

BACKGROUND: In patients hospitalised with COVID-19, an increased incidence of thromboembolic events, such as pulmonary embolism, deep vein thrombosis and stroke, has been reported. It is unknown whether anticoagulation can prevent these complications and improve outcome. METHODS: A systematic literature search was performed to answer the question: What is the effect of (prophylactic and therapeutic dose) anticoagulation therapy in COVID-19 patients on cardiovascular and thromboembolic complications and clinical outcome? Relevant outcome measures were mortality (crucial), hospital admission, length of stay, thromboembolic complications (pulmonary embolism, stroke, transient ischaemic attack), need for mechanical ventilation, acute kidney injury and use of renal replacement therapy. Medline and Embase databases were searched with relevant search terms until 17 July 2020. After systematic analysis, eight studies were included. Analysis was stratified for the start of anticoagulation before or during hospital admission. RESULTS: There was insufficient evidence that therapeutic anticoagulation could improve the outcome in patients hospitalised with COVID-19. None of the studies demonstrated improved mortality, except for one very small Italian study. Furthermore, none of the studies showed a positive effect of anticoagulation on other outcome measures in COVID-19, such as ICU admission, length of hospital stay, thromboembolic complications, need for mechanical ventilation, acute kidney failure or need for renal replacement therapy, except for two studies demonstrating an association between anticoagulation and a lower incidence of pulmonary embolism. However, the level of evidence of all studies varied from 'low' to 'very low', according to the GRADE methodology. CONCLUSION: Analysis of the literature showed that there was insufficient evidence to answer our objective on the effect of anticoagulation on outcome in COVID-19 patients, especially due to the low scientific quality of the described studies. Randomised controlled studies are needed to answer this question.

4.
Case Rep Vasc Med ; 2021: 8832638, 2021.
Article in English | MEDLINE | ID: covidwho-1138465

ABSTRACT

The COVID-19 pandemic has created an unprecedented global health care crisis. COVID-19 patients are found to have increased thrombotic risk. Despite being on prophylactic anticoagulation, many develop serious arterial and venous thromboembolic events. Emerging reports indicate COVID-19 may be considered a novel risk factor for portal vein thrombosis. Although, intra-abdominal infections are identified as risk factors, clostridium difficile colitis has not been typically seen as a risk factor for PVT. We report a case of an elderly female with a recent diagnosis of COVID-19 and no prior history of cirrhosis or malignancy who presented with diarrhea due to clostridium difficile infection. She developed sudden onset severe abdominal pain during the course of hospitalization. Acute portal vein thrombosis was identified on CT imaging of the abdomen, and she improved well with therapeutic anticoagulation. Acute portal vein thrombosis usually results from a combination of local and systemic prothrombotic risk factors. The combination of local infection by clostridium difficile and COVID-19 coagulopathy led to development of portal vein thrombosis in our patient. To the best of our knowledge, this is the first case of portal vein thrombosis reported in a patient with clostridium difficile infection in the setting of COVID-19 coagulopathy. During the current pandemic, clinicians should strongly consider abdominal imaging in patients presenting with abdominal pain due to clostridium difficile infection in the setting of COVID-19 to rule out complications such as portal vein thrombosis. Early diagnosis and treatment of portal vein thrombosis prevent complications of portal hypertension and intestinal infarctions.

6.
Chest ; 159(6): 2417-2427, 2021 06.
Article in English | MEDLINE | ID: covidwho-1131172

ABSTRACT

BACKGROUND: Because of the high risk of thrombotic complications (TCs) during SARS-CoV-2 infection, several scientific societies have proposed to increase the dose of preventive anticoagulation, although arguments in favor of this strategy are inconsistent. RESEARCH QUESTION: What is the incidence of TC in critically ill patients with COVID-19 and what is the relationship between the dose of anticoagulant therapy and the incidence of TC? STUDY DESIGN AND METHODS: All consecutive patients referred to eight French ICUs for COVID-19 were included in this observational study. Clinical and laboratory data were collected from ICU admission to day 14, including anticoagulation status and thrombotic and hemorrhagic events. The effect of high-dose prophylactic anticoagulation (either at intermediate or equivalent to therapeutic dose), defined using a standardized protocol of classification, was assessed using a time-varying exposure model using inverse probability of treatment weight. RESULTS: Of 538 patients included, 104 patients experienced a total of 122 TCs with an incidence of 22.7% (95% CI, 19.2%-26.3%). Pulmonary embolism accounted for 52% of the recorded TCs. High-dose prophylactic anticoagulation was associated with a significant reduced risk of TC (hazard ratio, 0.81; 95% CI, 0.66-0.99) without increasing the risk of bleeding (HR, 1.11; 95% CI, 0.70-1.75). INTERPRETATION: High-dose prophylactic anticoagulation is associated with a reduction in thrombotic complications in critically ill patients with COVID-19 without an increased risk of hemorrhage. Randomized controlled trials comparing prophylaxis with higher doses of anticoagulants are needed to confirm these results. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04405869; URL: www.clinicaltrials.gov.


Subject(s)
Anticoagulants/administration & dosage , COVID-19/complications , COVID-19/therapy , Critical Care , Thrombosis/epidemiology , Thrombosis/prevention & control , Aged , Female , France , Humans , Incidence , Male , Middle Aged , Pulmonary Embolism/epidemiology , Retrospective Studies , Venous Thromboembolism/epidemiology
7.
Int J Infect Dis ; 100: 34-41, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-943159

ABSTRACT

BACKGROUND: The incidence of venous thromboembolic events (VTE) in patients with COVID-19 is generally high but varies markedly. However, the relationship between anticoagulation and mortality in patients with COVID-19 is still unclear. METHODS: We performed a systematic review and meta-analysis to determine the incidence of VTE and evaluate the role of anticoagulation in patients with COVID-19. Random effects models were used to determine overall pooled estimates and 95% confidence intervals (CIs). RESULTS: After a database search, 25 observational studies (20 on VTE incidence and 5 on the relationship between anticoagulation and mortality) were included. The pooled incidence rates of VTE, pulmonary embolism (PE), and deep vein thrombosis (DVT) in hospitalised COVID-19 patients were 21% (95% CI 15-27%), 15% (95% CI 10-20%), and 27% (95% CI 19-36%), respectively. A meta-analysis of five studies found that anticoagulation was not associated with an increased risk of mortality in hospitalised COVID-19 patients (RR = 0.86, 95% CI, 0.69-1.09, P = 0.218; I2 = 47.4%). CONCLUSIONS: In conclusion, the incidence of VTE among hospitalised COVID-19 patients was high. Clinical trials are urgently needed to evaluate the roles of prophylactic and therapeutic anticoagulation in COVID-19.


Subject(s)
Anticoagulants/therapeutic use , Betacoronavirus , Coronavirus Infections/complications , Pneumonia, Viral/complications , Venous Thromboembolism/epidemiology , COVID-19 , Coronavirus Infections/mortality , Humans , Incidence , Pandemics , Pneumonia, Viral/mortality , SARS-CoV-2 , Venous Thromboembolism/prevention & control
8.
J Med Case Rep ; 14(1): 188, 2020 Oct 15.
Article in English | MEDLINE | ID: covidwho-863352

ABSTRACT

BACKGROUND: Currently, there is minimal data available highlighting the prevalence of venous thromboembolism in patients infected with coronavirus disease 2019 (COVID-19). This case report with a literature review emphasizes a unique presentation of COVID-19 that is highly important for health care providers to consider when treating their patients. CASE REPORT: A 65-year-old Caucasian male patient presented to the emergency department with a 2-day history of dyspnea on exertion after his wife's recent diagnosis of COVID-19. He additionally had experienced a couple of episodes of self-resolving diarrhea a few days before presentation. Based on the patient's clinical presentation and the laboratory workup identifying an elevated D-dimer, a computed tomography angiogram of the chest was obtained, which was significant for moderately large, bilateral pulmonary emboli with a saddle embolus, and an associated small, left lower lobe, pulmonary infarct. Ultrasound of the lower extremity showed non-occlusive deep vein thrombosis at the distal left femoral vein to the left popliteal vein. The patient was additionally diagnosed with COVID-19 when the results of the COVID-19 polymerase chain reaction test returned as positive. The patient was admitted to the COVID unit, and he was started on an intravenously administered, unfractionated heparin drip for management of his bilateral pulmonary emboli and deep vein thrombosis. The patient's clinical condition improved significantly with anticoagulation, and he was observed in the hospital for 3 days, after which he was discharged home on the enoxaparin bridge with warfarin. Post-discharge telephone calls at day 10 and week 4 revealed that the patient was appropriately responding to anticoagulation treatment and had no recurrence of his symptoms related to venous thromboembolism and COVID-19. CONCLUSION: As COVID-19 continues to lead to significant mortality, more data is emerging that is exposing its perplexing pathogenicity. Meanwhile, the presentation of venous thromboembolism in patients with COVID-19 remains an unusual finding. It is imperative for health care providers to be mindful of this unique association to make necessary diagnostic evaluations and provide appropriate treatment for the patients.


Subject(s)
Coronavirus Infections , Enoxaparin/administration & dosage , Femoral Vein/diagnostic imaging , Heparin/administration & dosage , Pandemics , Pneumonia, Viral , Pulmonary Embolism , Venous Thromboembolism , Warfarin/administration & dosage , Aged , Anticoagulants/administration & dosage , Betacoronavirus/isolation & purification , COVID-19 , Computed Tomography Angiography/methods , Coronavirus Infections/blood , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Fibrin Fibrinogen Degradation Products/analysis , Hospitalization , Humans , Lung/diagnostic imaging , Male , Pneumonia, Viral/blood , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pulmonary Embolism/diagnosis , Pulmonary Embolism/etiology , Pulmonary Embolism/therapy , SARS-CoV-2 , Treatment Outcome , Ultrasonography/methods , Venous Thromboembolism/diagnosis , Venous Thromboembolism/etiology , Venous Thromboembolism/therapy
9.
Thromb Res ; 196: 375-378, 2020 12.
Article in English | MEDLINE | ID: covidwho-786322

ABSTRACT

BACKGROUND: SARS-CoV-2 infection has noted derangements in coagulation markers along with significant thrombotic complications. Post-mortem examinations show severe endothelial injury and widespread thrombotic microangiopathy in the pulmonary vasculature. Early reports describing the use of prophylactic anticoagulation demonstrated improved survival, leading to the adoption of prophylactic and therapeutic anticoagulation guided by D-dimer levels. The clinical usefulness of D-dimer values, trends, and more intensive anticoagulation remains an area of clinical interest. OBJECTIVES: Assess the outcomes and laboratory trends in COVID-19 patients stratified by intensity of anticoagulation at time of admission. PATIENTS AND METHODS: Retrospectively review the differences in clinical outcomes and laboratory trends in patients hospitalized with COVID-19 in the Lifespan Health System. RESULTS: Between 27 February and 24 April 2020, 468 patients were hospitalized. Initial use of high-intensity thromboprophylaxis was associated with improved 30-day mortality (adjusted RR 0.26; 95% confidence interval [CI], 0.07-0.97; p = 0.045) without a significant increased rate of bleeding (p = 0.11). In severe COVID-19, D-dimer significantly increased during hospitalization with standard thromboprophylaxis (p < 0.001) but remained stable or decreased with high-intensity prophylaxis or therapeutic anticoagulation. CONCLUSION: Patients who received high-intensity prophylactic anticoagulation had a downtrend in D-dimer levels and improved 30-day mortality. This suggests a role in anticoagulation in mitigating adverse outcomes associated with COVID-19; however, further randomized, prospective studies are needed.


Subject(s)
Betacoronavirus , COVID-19 , Coronavirus Infections , Pneumonia, Viral , Venous Thromboembolism , Anticoagulants/therapeutic use , China , Humans , Pandemics , Patients , Prospective Studies , Retrospective Studies , SARS-CoV-2
10.
Trials ; 21(1): 769, 2020 Sep 07.
Article in English | MEDLINE | ID: covidwho-748922

ABSTRACT

OBJECTIVES: To assess the effect of anticoagulation with bivalirudin administered intravenously on gas-exchange in patients with COVID-19 and respiratory failure using invasive mechanical ventilation. TRIAL DESIGN: This is a single centre parallel group, superiority, randomized (1:1 allocation ratio) controlled trial. PARTICIPANTS: All patients admitted to the Hamad Medical Corporation -ICU in Qatar for COVID-19 associated respiratory distress and in need of mechanical ventilation are screened for eligibility. INCLUSION CRITERIA: all adult patients admitted to the ICU who test positive for COVID-19 by PCR-test and in need for mechanical ventilation are eligible for inclusion. Upon crossing the limit of D-dimers (1.2 mg/L) these patients are routinely treated with an increased dose of anticoagulant according to our local protocol. This will be the start of randomization. EXCLUSION CRITERIA: pregnancy, allergic to the drug, inherited coagulation abnormalities, no informed consent. INTERVENTION AND COMPARATOR: The intervention group will receive the anticoagulant bivalirudin intravenously with a target aPTT of 45-70 sec for three days while the control group will stay on the standard treatment with low-molecular-weight heparins /unfractionated heparin subcutaneously (see scheme in Additional file 1). All other treatment will be unchanged and left to the attending physicians. MAIN OUTCOMES: As a surrogate parameter for clinical improvement and primary outcome we will use the PaO2/FiO2 (P/F) ratio. RANDOMISATION: After inclusion, the patients will be randomized using a closed envelope method into the conventional treatment group, which uses the standard strategy and the experimental group which receives anticoagulation treatment with bivalirudin using an allocation ratio of 1:1. BLINDING (MASKING): Due to logistical and safety reasons (assessment of aPTT to titrate the study drug) only the data-analyst will be blinded to the groups. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): We performed a sample size calculation and assumed the data for P/F ratio (according to literature) is normally distributed and used the mean which would be: 160 and SD is 80. We expect the treatment will improve this by 30%. In order to reach a power of 80% we would need 44 patients per group (in total 88 patients). Taking approximately 10% of dropout into account we will include 100 patients (50 in each group). TRIAL STATUS: The local registration number is MRC-05-082 with the protocol version number 2. The date of approval is 18th June 2020. Recruitment started on 28th June and is expected to end in November 2020. TRIAL REGISTRATION: The protocol is registered before starting subject recruitment under the title: "Anticoagulation in patients suffering from COVID-19 disease. The ANTI-CO Trial" in ClinicalTrials.org with the registration number: NCT04445935 . Registered on 24 June 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 2). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
Antithrombins/therapeutic use , Coronavirus Infections/drug therapy , Peptide Fragments/therapeutic use , Pneumonia, Viral/drug therapy , Respiration, Artificial , Respiratory Distress Syndrome/therapy , Anticoagulants/therapeutic use , Betacoronavirus , COVID-19 , Coronavirus Infections/blood , Critical Illness , Fibrin Fibrinogen Degradation Products/metabolism , Heparin/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Hirudins , Humans , Pandemics , Partial Thromboplastin Time , Pneumonia, Viral/blood , Qatar , Recombinant Proteins/therapeutic use , SARS-CoV-2
11.
J Community Hosp Intern Med Perspect ; 10(4): 306-309, 2020 Aug 02.
Article in English | MEDLINE | ID: covidwho-725436

ABSTRACT

We present three patients with COVID-19 who developed acute renal failure during hospitalization and were seen to have an improvement in their kidney function after being started on therapeutic anticoagulation with heparin (Target PTT 58-93 seconds) for varying indications (atrial fibrillation, popliteal vein thrombosis and a pulmonary embolism). Their kidney functions improved significantly following anticoagulation with a clear temporal relationship between the former and latter. Anticoagulation was held for one patient due to concern of gastrointestinal bleeding and his kidney functions worsened a day after stopping anticoagulation. D-dimer levels also improved with anticoagulation but the trend of other inflammatory markers remained unpredictable.

12.
Kardiol Pol ; 78(6): 642-646, 2020 06 25.
Article in English | MEDLINE | ID: covidwho-701600

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic affects anticoagulation not only in those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but also in most patients who require daily anticoagulant therapy and are facing substantial limitations in medical care these days. Concomitant venous thromboembolism (VTE), a potential cause of unexplained deaths, has frequently been reported in patients with COVID-19, but its management is still challenging due to the complexity between antithrombotic therapy and hematological alterations. In the era of COVID-19 pandemic, it is highly recommended for patients who require chronic anticoagulation to continue therapy to prevent thromboembolic events. To avoid regular and frequent blood tests and unnecessary exposure to SARS-CoV-2 during contacts with medical personnel, direct oral anticoagulants should be strongly preferred whenever possible. Current evidence is insufficient to recommend routine pharmacological antithrombotic prophylaxis in all hospitalized patients with COVID-19. In patients with COVID-19 who are suspected of VTE or in whom the diagnosis is confirmed, parenteral therapy with low-molecular-weight heparin should be initiated in the absence of contraindications. If heparin-induced thrombocytopenia is suspected, nonheparin anticoagulants should be used such as bivalirudin or fondaparinux. In case of confirmed acute pulmonary embolism, treatment should be guided by risk stratification as defined in the current guidelines.


Subject(s)
Anticoagulants/therapeutic use , Coronavirus Infections/complications , Expert Testimony , Pneumonia, Viral/complications , Practice Guidelines as Topic , Venous Thromboembolism/drug therapy , Betacoronavirus , Blood Coagulation , COVID-19 , Coronavirus Infections/therapy , Hospitalization/statistics & numerical data , Humans , Pandemics , Pneumonia, Viral/therapy , Poland , Pulmonary Embolism/complications , Risk Factors , SARS-CoV-2 , Societies, Medical
13.
Int J Infect Dis ; 97: 299-302, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-597963

ABSTRACT

Severe coronavirus disease 2019 (COVID-19) is known to be associated with a heightened risk of thromboembolism. However, the risk associated with mild and moderate illness from COVID-19 is unknown, and there is no current recommendation for prophylaxis against thromboembolism in patients after hospital treatment, unless there are established thrombophilic risk factors. We report the case of a 52-year-old woman who presented with massive saddle pulmonary embolism 1 week after initial hospital discharge, which was treated successfully with thrombolysis. This case raises the question of whether extended prophylactic anticoagulation should be considered even in low-risk COVID-19 cases.


Subject(s)
Coronavirus Infections/complications , Heart Failure/drug therapy , Pneumonia, Viral/complications , Pulmonary Embolism/drug therapy , Pulmonary Heart Disease/drug therapy , Anticoagulants/therapeutic use , Betacoronavirus , Blood Coagulation , COVID-19 , Female , Heart Failure/virology , Humans , Middle Aged , Pandemics , Pulmonary Embolism/virology , Pulmonary Heart Disease/virology , Risk Factors , SARS-CoV-2 , Thrombolytic Therapy
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