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Aim: The coronavirus disease 2019 (COVID-19) pandemic has left negative spillover effects on the entire health care system. Previous studies have suggested significant declines in cases of acute coronary syndrome (ACS) and primary percutaneous coronary intervention (PCI) during the COVID-19 pandemic. Methods: We performed a quasi-experimental, retrospective cohort study of ACS hospitalisations by using a multi-institutional administrative claims database in Japan. We used interrupted time series analyses to ascertain impacts on cases, treatment approaches, and in-hospital mortality before and after Japan’s state of emergency to respond to COVID-19. The primary outcome was the change in ACS cases per week. Results: A total of 30, 198 ACS cases (including 21, 612 acute myocardial infarction and 8, 586 unstable angina) were confirmed between 1st July 2018 and 30th June 2020. After the state of emergency, an immediate decrease was observed in ACS cases per week (-18.3%; 95% confidence interval, -13.1 to -23.5%). No significant differences were found in the severity of Killip classification (P=0.51) or cases of fibrinolytic therapy (P=0.74). The impact of the COVID-19 pandemic on in-hospital mortality in ACS patients was no longer observed after adjustment for clinical characteristics (adjusted odds ratio, 0.93; 95% confidence interval, 0.78 to 1.12; P=0.49). Conclusions: We demonstrated the characteristics and trends of ACS cases in a Japanese population by applying interrupted time series analyses. Our findings provide significant insights into the association between COVID-19 and decreases in ACS hospitalisations during the pandemic.

The development of safe and efficacious enzyme-based human therapies has increased greatly in the last decades, thanks to remarkable advances in the understanding of the molecular mechanisms responsible for different diseases, and the characterization of the catalytic activity of relevant exogenous enzymes that may play a remedial effect in the treatment of such pathologies. Several enzyme-based biotherapeutics have been approved by FDA (the U.S. Food and Drug Administration) and EMA (the European Medicines Agency) and many are undergoing clinical trials. Apart from enzyme replacement therapy in human genetic diseases, which is not discussed in this review, approved enzymes for human therapy find applications in several fields, from cancer therapy to thrombolysis and the treatment, e.g., of clotting disorders, cystic fibrosis, lactose intolerance and collagen-based disorders. The majority of therapeutic enzymes are of microbial origin, the most convenient source due to fast, simple and cost-effective production and manipulation. The use of microbial recombinant enzymes has broadened prospects for human therapy but some hurdles such as high immunogenicity, protein instability, short half-life and low substrate affinity, still need to be tackled. Alternative sources of enzymes, with reduced side effects and improved activity, as well as genetic modification of the enzymes and novel delivery systems are constantly searched. Chemical modification strategies, targeted- and/or nanocarrier-mediated delivery, directed evolution and site-specific mutagenesis, fusion proteins generated by genetic manipulation are the most explored tools to reduce toxicity and improve bioavailability and cellular targeting. This review provides a description of exogenous enzymes that are presently employed for the therapeutic management of human diseases with their current FDA/EMA-approved status, along with those already experimented at the clinical level and potential promising candidates.

Background The incidence of acute empyema has increased in various countries; some elderly patients with acute empyema have contraindications for surgery under general anesthesia. Therefore, suitable management based on a patient’s clinical condition is required. Methods We evaluated the different surgical and nonsurgical therapeutic approaches available for patients with acute empyema. This was a retrospective study of 57 patients with acute empyema who received treatment in our department between May 2015 and February 2019. For patients who did not initially improve with drainage or drainage combined with fibrinolytic therapy, surgery, or additional percutaneous drainage was performed based on their general condition. We compared several clinical factors pertaining to the patients who underwent surgical versus nonsurgical treatment. Results Our study showed that the patients with a performance status of 0–2 and an American Society of Anesthesiologists physical status classification of class II or lower underwent surgery safely without major operative complications. The combination of repeated drainage of the pleural cavity and fibrinolytic therapy appeared to be a reasonable nonsurgical management option for patients in poor overall condition. Conclusion For an aging population, we think that the combination of repeated pleural cavity drainage procedures and fibrinolytic therapy is a reasonable nonsurgical strategy for the management of patients with acute empyema.

Despite routinely restoring epicardial coronary patency, with primary percutaneous coronary intervention (PCI), microvascular obstruction affects approximately half of patients and confers an adverse prognosis. There are no evidence-based treatments for microvascular obstruction. A key contributor to microvascular obstruction is distal embolisation and microvascular thrombi. Adjunctive intracoronary fibrinolytic therapy may reduce thrombotic burden, potentially reducing distal embolisation of atherothrombotic debris to the microcirculation. In this review, the evidence from published randomised trials on the effects of adjunctive intracoronary fibrinolytic therapy during primary PCI is critically appraised, the ongoing randomised trials are described, and conclusions are made from the available evidence. Clinical uncertainties, to be addressed by future research, are highlighted.

There has been growing interest and insight into the histological composition of retrieved stroke emboli. One of the main focuses of the stroke clot analysis literature has been the implications of clot composition on mechanical thrombectomy procedures. However, the holy grail of clot analysis may not be in the field of clot–device interaction, but rather, in understanding mechanisms of fibrinolysis resistance. The mechanisms underlying the low response to fibrinolytic therapy, even with the newer, more powerful agents, remain poorly understood. While factors such as embolus size, location and collateral status influence alteplase delivery and recanalisation rates; compositional analyses focused on histological and ultrastructural characteristics offer unique insights into mechanisms of alteplase resistance. In this review, we strive to provide comprehensive review of current knowledge on clot composition and ultrastructural analyses that help explain resistance to fibrinolysis.

Coronavirus disease 2019 (COVID-19) may predispose patients to venous thromboembolism (VTE). Limited data are available on the utilization of the Pulmonary Embolism Response Team (PERT) in the setting of the COVID-19 global pandemic. We performed a single-center study to evaluate treatment, mortality, and bleeding outcomes in patients who received PERT consultations in March and April 2020, compared to historical controls from the same period in 2019. Clinical data were abstracted from the electronic medical record. The primary study endpoints were inpatient mortality and GUSTO moderate-to-severe bleeding. The frequency of PERT utilization was nearly threefold higher during March and April 2020 ( n = 74) compared to the same period in 2019 ( n = 26). During the COVID-19 pandemic, there was significantly less PERT-guided invasive treatment (5.5% vs 23.1%, p = 0.02) with a numerical but not statistically significant trend toward an increase in the use of systemic fibrinolytic therapy (13.5% vs 3.9%, p = 0.3). There were nonsignificant trends toward higher in-hospital mortality or moderate-to-severe bleeding in patients receiving PERT consultations during the COVID-19 period compared to historical controls (mortality 14.9% vs 3.9%, p = 0.18 and moderate-to-severe bleeding 35.1% vs 19.2%, p = 0.13). In conclusion, PERT utilization was nearly threefold higher during the COVID-19 pandemic than during the historical control period. Among patients evaluated by PERT, in-hospital mortality or moderate-to-severe bleeding were not significantly different, despite being numerically higher, while invasive therapy was utilized less frequently during the COVID-19 pandemic.

Malignant pleural effusion (MPE) is common in lung cancer. We report a case of highly viscous recurrent MPE associated with lung cancer. The viscosity prohibited gravity-dependent drainage initially with a 6-Fr aspiration catheter and subsequently with a 12-Fr intercostal drain. The effusion was eventually evacuated after a single dose of intrapleural fibrinolytic therapy. This process was repeated a total of 13 times over a 12-month period in an ambulatory setting. No bleeding complications were observed. This case highlights the feasibility and safety of repeated intrapleural fibrinolysis in the management of highly viscous recurrent MPE in an ambulatory setting.

Spontaneous intracerebral hemorrhage (ICH), a devastating neurological emergency, is characterized by a high mortality and mobility due to cerebrovascular rupture and hematoma formation. Here we describe a 52-year-old woman with a 34 ml left external capsule hemorrhage who developed unconsciousness and right hemiplegia. Minimally invasive puncture was subsequently performed followed by thrombolysis therapy for hematoma evacuation. At day 4 after symptom onset, surgery for hematoma evacuation was performed. Specifically, CT imaging was utilized to establish a trajectory for the YL-1 type puncture needle. Once access was established, the hematoma was evacuated through thrombolysis and drainage. After the clot was evacuated, the patient achieved a favorable outcome. The successful outcome achieved in this specific case, suggests that minimally invasive puncture and thrombolysis after intracerebral hemorrhage may be a promising treatment option for hematoma evacuation.

Background Primary fibrinolysis for pediatric empyema has become standard of care at our institution. Early study of our protocol revealed a 16% thoracoscopic decortication rate after primary fibrinolysis. We now report the frequency with which children progress to operation with maturation of the protocol. Methods A database of patients diagnosed with empyema between September 2014 and March 2019 was examined. Patients who underwent tissue plasminogen activator (tPA) therapy with or without subsequent video-assisted thoracoscopic (VATS) decortication were included. Patients with additional indications for tube thoracostomy or VATS were excluded. Results Forty-eight patients were included. Median age was 4.5 years [IQR 2–9.3]. Median length of stay (LOS) was 8 days [IQR 6–11]. No patients underwent primary VATS. Median days with a chest tube was 5 [IQR 5–6] and median number of doses of tPA was 3 [IQR 3–3]. Seven patients (14.6%) had a chest tube replaced without undergoing VATS. The VATS rate was 4.2% in the first half of this study but 0% in the last 33 months. Conclusion Thoracoscopic decortication is rarely necessary in children with empyema. Raising the threshold for surgical intervention and utilizing further nonoperative measures can avoid an operation in most children without increasing in-hospital length of stay. Level of evidence IV

Objetivo: avaliar as habilidades dos enfermeiros, no uso terapêutico do Alteplase, como terapia fibrinolítica, em pacientes com diagnóstico de infarto agudo do miocárdio. Método: A pesquisa foi realizada por meio de um estudo descritivo transversal, quantitativo, realizado por meio de questionário como instrumento de coleta, contendo 10 questões de múltipla escolha elaboradas pelo autor. A amostra foi constituída por 24 enfermeiros. A coleta de dados foi realizada em julho de 2019, com CAAE n° 13159219.7.0000.5493. Os dados foram analisados e tratados por meio da análise descritiva. Resultado: Os resultados mostraram que os participantes da pesquisa possuem habilidades para o manuseio e aplicabilidade da terapia fibrinolítica, Alteplase, em pacientes acometidos por infarto agudo do miocárdio. Conclusão:Os resultados obtidos demonstram que os enfermeiros possuem habilidade para o manuseio, administração, aplicabilidade do Alteplase, bem como na avaliação dos sintomas e contraindicações do medicamento em pacientes acometidos por Infarto Agudo do Miocárdio. Entretanto, foi identificado uma porcentagem que apresentam dificuldades na execução de todas as atividades. Portanto, o estudo contribuirá na elaboração de protocolos aos profissionais da área da saúde envolvidos de modo direto ou indireto aos cuidados aos pacientes que necessitam desta intervenção farmacológica como tratamento.

Rationale: Pleural infection is frequently encountered in clinical practice and is associated with high morbidity and mortality. Limited evidence exists regarding the optimal treatment. Although bo...

Objective The use of intrapleural tissue plasminogen activator (tPA) and dornase alfa (DNase) is common in the management of pleural space infection. We review our experience with the efficacy and safety of this therapy. We performed a single center, retrospective study of consecutive patients with complicated parapneumonic effusion or empyema who received tPA/DNase therapy. Treatment success was defined as radiographic and clinical improvement in pleural space infection that precluded the need for surgical intervention, and the absence of mortality related to pleural infection. Results Fifty-six patients received concurrent once daily tPA/DNase therapy (median 3 days) from July 2014 to July 2019. Fifty-two patients (92.9%) had treatment success. Median duration of chest tube therapy was 10 days and length of stay was 15 days. Significant pleural bleeding requiring transfusion therapy occurred in five patients (8.9%). Of these, three patients (5.4%) required operative intervention. Concurrent once daily administration of tPA/DNase in patients with pleural infection yielded comparable rates of treatment success as compared to twice daily concurrent or sequential administration. However, adverse events highlight potential safety concerns with using once daily concurrent administration of tPA/DNAse.

The pivotal studies that led to the recommendations for emergent reperfusion therapy for ST-elevation myocardial infarction (STEMI) were conducted for the most part over 25 years ago. At that time, contemporary standard treatments including aspirin, statin, and even anticoagulation were not commonly used. The 2013 American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) guidelines and the 2017 European Society of Cardiology guidelines give a class I recommendation (with the level of evidence A) for primary percutaneous coronary intervention (pPCI) in patients with STEMI and ischemic symptoms of less than 12 h. However, if the patient presents to a hospital without pPCI capacity, and it is anticipated that pPCI cannot be performed within 120 min of first medical contact, fibrinolytic therapy is indicated (if there are no contraindications) (class I indication, level of evidence A). Our review of the pertinent literature shows that the current recommendation for inferior STEMI is based on the level of evidence lower than A. We can consider level B even C, supporting the recommendation for fibrinolytic therapy if pPCI is not available for inferior STEMI.

Background Studies have shown that the primary causes of death in patients with acute coronary syndrome are arrhythmias and heart failure. The aim of this study is to evaluate the short-term prognosis of fragmented QRS (f-QRS) in patients with acute myocardial infarction (MI). Methods This study was a prospective and longitudinal analytic study performed on all patients with acute MI admitted to Rasht Heshmat Hospital Emergency during 2018–2019. Serial Electrocardiography (ECG) was performed in the emergency room after patient admission and was repeated 24 h after percutaneous coronary intervention and fibrinolytic therapy, as well as at the time of patient discharge. Short-term prognosis of f-QRS in patients was evaluated by a cardiologist within admission, 40 days after hospitalization and three months later again. Results In this study, 453 patients with MI were evaluated in two treatment methods of fibrinolytic and invasive with and without f-QRS. Based on the data of this study, the four study groups had no statistically significant difference in arrhythmia (p = 0.196). In addition, the effect of study groups on left ventricular ejection fraction index was not statistically significant (p = 0.597). The probability of adverse outcomes occurrence was not statistically significant among the four groups (p = 0.07). Conclusion The final results of this study showed that there was no significant difference between the four study groups and arrhythmia status. Therefore, f-QRS was not introduced as an independent predictor of arrhythmia in patients with acute MI.

The incidence of pleural infection is increasing, and there remain many challenges to managing this condition. This review provides a synthesised overview of the current state of knowledge and identifies key areas for future research. Recent studies have broadened our understanding of pleural microbiology and the natural history of pleural infection. The development and evolution of intrapleural fibrinolytic therapy have established three separate treatment options in pleural infection. This has led to the development of new management algorithms and re-examined the role of surgery. Similarly, the uptake of bedside thoracic ultrasound has improved assessment and ensured safer and more accurate procedures. There have been major advances in our understanding of pleural infection over the last few years. Patients have more treatment options, and modern management algorithms can limit the need for surgical intervention. Outcomes from pleural infection have remained largely unchanged over decades, which suggest that the time for a paradigm shift may be approaching. However, key questions remain unanswered.

Background: The efficacy of ticagrelor in the long-term post–ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain.Objectives: The purpose o...

Imtinene Ben Mrad,1 Melek Ben Mrad,2 Zeineb Oumaya,1 Ihsen Zairi,1 Boutheina Besbes,1 Khalil Ouaghlani,1 Sofien kamoun,1 Sobhi Mleyhi,2 Rim Miri,2 khadija Mzoughi,1 Sondos Kraiem1 1Cardiology Department, Habib Thameur Hospital, Tunis, Tunisia; 2Cardiovascular Surgery Department, Rabta Hospital, Tunis, TunisiaCorrespondence: Imtinene Ben MradCardiology Department, Habib Thameur Hospital, App 2b, Bloc 12, cite Olympique, Tunis, 1003, TunisiaTel +011 216 20156852Email imtinenebenmrad12@gmail.comAbstract: Alveolar hemorrhage (AH) is a heterogeneous clinical syndrome with a high mortality rate, characterized by extensive bleeding into the alveolar spaces. AH secondary to systemic thrombolysis treatment in the setting of acute myocardial infarction is an uncommon complication, but potentially fatal and can lead to acute respiratory failure. This entity is rarely reported in the literature. We report two cases of acute AH after intravenous thrombolysis for acute myocardial infarction, which could contribute to the literature on the subject, and discuss the risk factors as well as the clinical and radiological findings supporting the diagnosis. We overview also the rare previous published case reports in this context, and we contrast our findings with those reported in the literature.Keywords: hemoptysis, alveolar hemorrhage, myocardial infarction, fibrinolytic therapy, streptokinase

Fibrinolytic agents provide an important alternative therapeutic strategy in individuals presenting with ST-elevation myocardial infarction (STEMI). Ultimately, primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for most patients with STEMI, including elderly patients and patients with coronavirus disease 2019 (COVID-19) infection. Fibrinolytic therapy should always be considered when timely primary PCI cannot be delivered appropriately. Clinicians should promptly recognize the signs of fibrinolytic therapy failure and consider rescue PCI. When fibrinolytics are used, coronary angiography and revascularization should not be conducted within the initial 3 hours after fibrinolytic administration.

Intraventricular hemorrhage (IVH) is a devastating neurosurgical condition associated with high rates of morbidity and mortality. It can occur as the result of several pathologies and typically presents with mental status changes, neurologic deficits, seizures, headaches, and decreased Glasgow Coma Scale score. These patients are often treated with placement of an external ventricular drain, which helps decrease the clot burden; however, they commonly clot off leading to multiple exchanges. We present a case in which drainage, irrigation, and fibrinolytic (DRIFT) therapy using IRRAflow® (IRRAS) irrigating catheter was used to treat a patient with severe IVH secondary to aneurysmal subarachnoid hemorrhage.

Plasminogen activator inhibitor‐1 (PAI‐1) is an endogenous irreversible inhibitor of tissue‐type (tPA) and urokinase (uPA) plasminogen activators. PAI‐1‐targeted fibrinolytic therapy (PAI‐1‐TFT) is designed to decrease the therapeutic dose of tPA and uPA, attenuating the risk of bleeding and other complications. Docking site peptide (DSP) mimics the part of the PAI‐1 reactive center loop that interacts with plasminogen activators, thereby affecting the PAI‐1 mechanism. We used DSP for PAI‐1‐TFT in two rabbit models: chemically induced pleural injury and Streptococcus pneumoniae induced empyema. These models feature different levels of inflammation and PAI‐1 expression. PAI‐1‐TFT with DSP (2.0 mg/kg) converted ineffective doses of single chain (sc) tPA (72.5 µg/kg) and scuPA (62.5 µg/kg) into effective ones in chemically induced pleural injury. DSP (2.0 mg/kg) was ineffective in S. pneumoniae empyema, where the level of PAI‐1 is an order of magnitude higher. DSP dose escalation to 8.0 mg/kg resulted in effective PAI‐1‐TFT with 0.25 mg/kg sctPA (1/8th of the effective dose of sctPA alone) in empyema. There was no increase in the efficacy of scuPA. PAI‐1‐TFT with DSP increases the efficacy of fibrinolytic therapy up to 8‐fold in chemically induced (sctPA and scuPA) and infectious (sctPA) pleural injury in rabbits. PAI‐1 is a valid molecular target in our model of S. pneumoniae empyema in rabbits, which closely recapitulates key characteristics of empyema in humans. Low‐dose PAI‐1‐TFT is a novel interventional strategy that offers the potential to improve fibrinolytic therapy for empyema in clinical practice., Empyema remains an important clinical problem with high mortality among patients 65 years and older. Targeting plasminogen activator inhibitor 1 (PAI‐1) in two rabbit models of pleural injury resulted in to up to eight‐fold increases in the efficacy of fibrinolytic therapy (decrease in dose needed for effective treatment). Low‐dose PAI‐1‐targeting fibrinolytic therapy would expand the population of patients that could benefit from treatment and improve therapeutic outcomes.

Background Coronavirus disease 2019 (COVID-19) predisposes patients to a prothrombotic state with demonstrated microvascular involvement. The degree of hypercoagulability appears to correlate with outcomes, however optimal criteria to assess for the highest risk patients for thrombotic events remain unclear; we hypothesized that deranged thromboelastography (TEG) measurements of coagulation would correlate with thromboembolic events. Methods Patients admitted to an intensive care unit with COVID-19 diagnoses that had TEG analyses performed were studied. Conventional coagulation assays, D-dimer levels, and viscoelastic parameters were analyzed using a receiver operating characteristic curve to predict thromboembolic outcomes and new onset renal failure. Results Forty-four patients with COVID-19 were included in the analysis. Derangements in coagulation laboratory values including elevated D-Dimer, fibrinogen, PT, and PTT were confirmed; viscoelastic parameters showed an elevated maximum amplitude and low lysis at 30 minutes. A complete lack of lysis of clot at 30 minutes was seen in 57% of patients and predicted VTE with an AUROC of .742 (p=0.021). A D-Dimer cutoff of 2600 ng/ml predicted need for dialysis with an AUROC of .779 (p=0.005). Overall, patients with no lysis of clot at 30 minutes and a D-Dimer of greater than 2600 ng/ml had a rate of VTE of 50% compared to 0% for patients with neither risk factor (p=0.008) and had a hemodialysis rate of 80% compared to 14% (p=0.004). Conclusions Fibrinolysis shutdown, as evidenced by elevated D-Dimer and complete failure of clot lysis at 30 minutes on thromboelastography, predicts thromboembolic events and need for hemodialysis in critically ill patients with COVID-19. Further clinical trials are required to ascertain the need for early therapeutic anticoagulation or fibrinolytic therapy to address this state of fibrinolysis shutdown., Graphical abstract, COVID-19 ICU patients are hypercoagulable. Fibrinolysis shutdown as demonstrated by complete lack of clot lysis at 30 minutes on thromboelastography combined with elevated D-Dimer levels predicts thromboembolic complications and new onset kidney failure.

The impact of diabetes mellitus (DM) on clinical outcomes of acute ST-segment elevation myocardial infarction (STEMI) following fibrinolytic therapy remains uncertain. We queried the National Inpatient Sample (NIS) for STEMI patients who received fibrinolytic therapy. Categorical and continuous variables were compared using the unadjusted odds ratio (uOR) and t-test analysis, respectively. A binary logistic regression model was used to control the outcomes for patient demographics, procedural characteristics, and baseline comorbidities. A total of 111,155 (no-DM 84,146, DM 27,009) were included. The unadjusted odds of in-hospital mortality (8.4% vs. 6.8%, uOR 1.25, 95% CI 1.19-1.31, P = 0.0001) and cardiogenic shock (7.7% vs. 6.2%, uOR 1.26, 95% CI 1.20-1.33, P = 0.0001) were significantly higher in patients with DM compared to those with no DM, respectively. The odds for major bleeding and cardiopulmonary arrest were significantly lower for in diabetes. The adjusted pooled estimates mirrored the unadjusted findings. Diabetic patients receiving fibrinolytic therapy for STEMI might have higher odds of all-cause mortality and cardiogenic shock compared to non-diabetic patients.

Indwelling Pleural Catheters (IPC) are increasingly being used for management of recurrent pleural effusions (RPEs). Use of IPC for management of both malignant and non-malignant recurrent pleural effusions has been associated with complications such as dysfunctional or nonfunctioning IPCs. Alteplase, a tissue plasminogen activator (tPA) is often used to restore flow of non-draining IPC in symptomatic patients. We present a case of a sixty-eight-year old patient with life-threatening pleural hemorrhage following intrapleural catheter instillation of tPA that was managed successfully by thoracotomy. Our case describe the importance of individualizing the fibrinolytic dose, frequency and the indwelling time in high risk patients. We have reviewed the current literature and recommendations for use of fibrinolytic therapy for IPC in high risk patients on anticoagulation.

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/). Georg Thieme Verlag KG, Introduction: Criticisms have been raised against the sole use of p-value in interpreting results from randomized controlled trials (RCTs). Additional tools have been suggested, like the fragility index (FI), a measure of a trial’s robustness/fragility, and derivative measures. The FI is the minimum number of patients who would have to be converted from nonevents to events, in the group with the least events, for a result to lose statistical significance. Objective: This study aimed to evaluate RCT supporting European Society of Cardiology (ESC) guidelines regarding antithrombotics, using the FI and FI-related measures. Methods FI, fragility quotient (FQ), and FI minus LTF lost to follow-up (FI LTF) were calculated for the RCT underpinning recommendations regarding antithrombotic therapy from the updated ESC guidelines. LTF was compared with FI. Results were calculated for the total group of studies, as per guideline and as per recommendation type. Results Overall, 61 studies were included. The median FI was 24.5 (interquartile range [IQR]: 9.0–60.0) and median FQ was 0.0035 (IQR: 0.0019–0.0056). Median FI LTF was 2.0 (IQR: 0.0–38.0). Twenty (32.8%) of the studies had one primary or main safety outcome with LTF exceeding FI. Peripheral arterial disease guideline and chronic coronary syndrome guideline had the lowest (2.5; IQR: 1.8–3.3) and the highest (48.5; IQR: 23.8–73.0) FI, respectively. Conclusion: The median FI suggests robustness of clinical trials evaluating antithrombotic drugs cited in the guidelines, but about one-third of them had LTF larger than FI. This emphasizes the need for assessing trials’ robustness when constructing guidelines.

Retained haemothorax is a common sequela of traumatic haemothorax and refers to blood that cannot be drained from the pleural cavity. We report a case of trapped lung secondary to retained haemothorax in a patient who sustained a penetrating chest injury. Initial chest computed tomography (CT) showed a large haemothorax that was managed with an intercostal drain insertion (ICD). Repeat chest CT and thoracic ultrasonography performed after ICD removal showed an organized pleural space resembling haematoma. ICD was reinserted with administration of intrapleural fibrinolytic therapy (IPFT). Subsequent chest CT showed the development of a pleural rind and trapped lung. A second ICD was inserted, and further IPFT were administered together with aggressive negative pressure suction. Haemoglobin remained stable. The patient made a full recovery and imaging performed two weeks later showed minor blunting of the costophrenic angle. This case highlights the feasibility and safety of IPFT in the management of trapped lung associated with traumatic retained haemothorax as an alternative to surgery.

During the ongoing COVID-19 pandemic, national societies have suggested various levels of reliance on fibrinolytic therapy because of anticipated delays in primary percutaneous coronary intervention (PPCI), resource limitations, and hazards to health care workers ([1][1]). Studies examining

A high rate of thrombotic complications, such as pulmonary embolism, has been linked to mortality in COVID-19, and appropriate treatment of thrombosis is important for lifesaving. Although heparin is frequently used to treat thrombotic pathology in COVID-19, pulmonary embolism is still seen in severe cases. Although systemic fibrinolytic therapy is a focus of attention because a thrombotic pathology is the cause of death in severe COVID-19, it should be kept in mind that fibrinolytic therapy might be harmful at advanced stage of COVID-19 where the status of disseminated intravascular coagulation (DIC) has been transmitted from suppressed-fibrinolytic to enhanced-fibrinolytic in disease progression of COVID-19. In this respect, inhalation therapy with fibrinolytic substances might be a safe and promising treatment.

Background: Management of septated/loculated pleural effusion with failed tube drainage is limited to VATS or IPFT (Intra Pleural Fibrinolytic Therapy). VATS is an expensive modality with limited availability and an invasive procedure. IPFT is affordable, easily available therapy with good results and requires less skill as compared to VATS. Aim: To study the role of IPFT in Septated/Loculated pleural effusion with failed tube drainage. Methods: A 1-year case-control study done in India with 50 patients with failed tube drainage ( Results: Total number of STK doses were 6 in 84%(n= 21) and 4 in 16% (n=4). In our study, among cases and control mean pleural fluid drained after IPFT was 1298.00 ± 571.58 ml and 155.60±23.43 ml respectively. In cases and controls outcome was successful in 80% (n=20), 16% (n=4), partial response in 16%(n=4), 64% (n=16) and failure were 4% (n=1), 20% (n=5) respectively. ICD removal achieved at discharge in 60% (n=15) cases and 32% (n=8) among control group. 12% (n=3) of cases 28% (n=7) of controls were referred for VATS. Conclusions: IPFT is an effective, very safe and affordable option in septated/loculated pleural effusion with failed tube drainage, where VATS is not readily accessible. A multi-centric study should be done to make guidelines for IPFT use.

The ongoing coronavirus disease 2019 pandemic has resulted in additional challenges for systems designed to perform expeditious primary percutaneous coronary intervention for patients presenting with ST-segment–elevation myocardial infarction. There are 2 important considerations: the guideline-recommended time goals were difficult to achieve for many patients in high-income countries even before the pandemic, and there is a steep increase in mortality when primary percutaneous coronary intervention cannot be delivered in a timely fashion. Although the use of fibrinolytic therapy has progressively decreased over the last several decades in high-income countries, in circumstances when delays in timely delivery of primary percutaneous coronary intervention are expected, a modern fibrinolytic-based pharmacoinvasive strategy may need to be considered. The purpose of this review is to systematically discuss the contemporary role of an evidence-based fibrinolytic reperfusion strategy as part of a pharmacoinvasive approach, in the context of the emerging coronavirus disease 2019 pandemic.

Objective Talc slurry pleurodesis (TSP) can lead to permanent small loculations. Intrapleural tissue plasminogen activator (tPA) breaks down loculations, and therefore may improve results but may also inhibit pleurodesis. tPA was given with and after talc slurry to promote more uniform talc distribution and eliminate loculations. Methods Charts were reviewed for patients treated with TSP with or without tPA. Chest x-rays after TSP were compared to chest x-rays before and graded as "worse", "same", or "better". Incidence of need for repeat TSP was recorded. Results There were 52 patients, eight with bilateral effusions, for a study cohort of 60 effusions. One-third of the effusions were malignant. No patients experienced significant bleeding. Results were better than baseline for 14 (26%) patients given tPA, but not for patients that never received tPA. The addition of tPA 4-6 mg with talc slurry resulted in no patients requiring repeat TSP. When tPA was given after talc slurry, a delay of three days was associated with the lowest incidence of repeat TSP (3/14, 21%). Conclusions There were no significant complications from tPA use to supplement TSP, and tPA may improve results without interfering with pleurodesis. A prospective trial is warranted.

Introduction Published trials of intrapleural therapy for complex pleural effusions rely on fibrinolytics and deoxyribonuclease (DNase) with dwell times of less than six hours and frequent dosing. We reviewed our experience with fibrinolytics alone but with a longer dwell time (12 hours). Methods Tissue plasminogen activator (tPA, 1-6 mg per dose) was given through pigtail catheters placed using image guidance. Planned treatment was for a dwell time of 12 hours with repeat dosing daily for three days or until drainage was less than 100 cc or grossly bloody. Chest x-ray and/or computed tomography (CT) were used to determine completeness of pleural drainage. Results Forty-six patients presenting with 47 complex pleural effusions were given 131 doses of tPA. Doses of 4, 5, and 6 mg were most common (n=17, 70, and 33, respectively). Dwell time ranged from five to 14 hours with 12 hours being most common (n=115). Additional chest tubes were placed in 18 effusions. Ten effusions (21%) required decortication: seven for trapped lung and three for incomplete drainage. Drainage was considered complete in 33/40 (82.5%) effusions without trapped lung. Median chest tube duration was seven days (range three to 28 days). tPA therapy was discontinued in two patients for bleeding, but neither experienced hemodynamic instability. Conclusions tPA with a 12-hour dwell time is effective and safe for management of complex pleural effusions, although chest tube duration was prolonged. tPA alone is less expensive and easier than when combined with DNase, and this strategy warrants a prospective evaluation.

Objective To evaluate characteristics and outcomes of patients presenting with mechanical prosthetic valve thrombosis in a tertiary cardiac center in Pakistan. Methods This was a prospective and interventional study conducted at Rawalpindi Institute of Cardiology over a period of two years. The clinical characteristics of patients presenting with clinical suspicion of prosthetic valve thrombosis were recorded. They were, then, subjected to streptokinase, redo surgery and heparin based on their hemodynamic stability, thrombus burden and surgical risk. The patients were then followed for the outcomes of the study. Results Out of 576 patients with mechanical valve replacement during the study period, 70 patients had developed prosthetic valve thrombosis. Out of 70 patients, there were 41 female (58.50%) and 29 male (41.50%) participants. The mean age of the participants was 48.40±15.00 years. The overall incidence of mechanical prosthetic valve thrombosis was 12.15%. There were 30 patients (42.80%) with a suboptimal international normalized ratio (INR) and 28 patients (40.00%) were non-compliant to warfarin therapy. The overall incidence of adverse clinical outcome was 18.00%, while the overall mortality rate was 10.00%. The mortality was higher for patients who underwent redo surgery (16.60%) as compared to patients who had received fibrinolytic therapy (9.60%). Conclusion Poor compliance with warfarin and suboptimal INR are the important factors causing mechanical prosthetic valve. Because of lower mortality rate, fibrinolysis with streptokinase is a reasonable treatment option for mechanical prosthetic valve thrombosis.

The current coronavirus disease 2019 (COVID-19) outbreak is a significant health crisis that impacts every healthcare system worldwide, and has led to a dramatic change in dealing with different diseases during the pandemic. Interventional cardiologists are frontline workers who deal with many cardiovascular emergencies, either in patients with proven COVID-19 or in suspected cases. Many heart associations worldwide are currently setting appropriate recommendations for the management of emergency cardiac interventions. In this expert opinion, the authors highlight the essential requirements in the cardiac catheterisation laboratory during the COVID-19 pandemic.

Background We systematically reviewed trials comparing different reperfusion strategies for ST‐segment–elevation myocardial infarction and used multivariate network meta‐analysis to compare outcomes across these strategies. Methods and Results We identified 31 contemporary trials in which patients with ST‐segment–elevation myocardial infarction were randomized to ≥2 of the following strategies: fibrinolytic therapy (n=4212), primary percutaneous coronary intervention ( PCI ) (n=6139), or fibrinolysis followed by routine early PCI (n=5006). We categorized the last approach as “facilitated PCI ” when the median time interval between fibrinolysis to PCI was PCI was associated with the lowest risk of mortality, nonfatal reinfarction, and stroke. For mortality, primary PCI had an odds ratio of 0.73 (95% CI , 0.61–0.89) when compared with fibrinolytic therapy. Of the remaining strategies, the pharmacoinvasive approach was the next most favorable with an odds ratio for death of 0.79 (95% CI , 0.59–1.08) compared with fibrinolytic therapy. The Bayesian model indicated that when the 2 strategies examining routine early invasive therapy following fibrinolysis were directly compared, the probability of adverse outcomes was lower for the pharmacoinvasive approach relative to facilitated PCI . Conclusions A pharmacoinvasive approach is safer and more effective than facilitated PCI and fibrinolytic therapy alone. This has significant implications for ST‐segment–elevation myocardial infarction care in settings where timely access to primary PCI , the preferred treatment for ST‐segment–elevation myocardial infarction , is not available.

Background We systematically reviewed trials comparing different reperfusion strategies for ST‐segment–elevation myocardial infarction and used multivariate network meta‐analysis to compare outcomes across these strategies. Methods and Results We identified 31 contemporary trials in which patients with ST‐segment–elevation myocardial infarction were randomized to ≥2 of the following strategies: fibrinolytic therapy (n=4212), primary percutaneous coronary intervention (PCI) (n=6139), or fibrinolysis followed by routine early PCI (n=5006). We categorized the last approach as “facilitated PCI” when the median time interval between fibrinolysis to PCI was

Accumulating evidence suggests that influenza and influenza-like illnesses can act as a trigger for acute myocardial infarction. Despite these unprecedented times providers should not overlook acute coronary syndrome (ACS) guidelines, but may choose to modify the recommended approach in situations with confirmed or suspected COVID-19 disease. In this document, we suggest recommendations as to how to triage patients diagnosed with ACSs and provide with algorithms of how to manage the patients and decide the appropriate treatment options in the era of COVID-19 pandemic. We also address the inpatient logistics and discharge to follow-up considerations for the function of already established ACS network during the pandemic. Accumulating evidence suggests that influenza and influenza-like illnesses can act as a trigger for acute myocardial infarction.1, 2, 3, 4 In this document, we suggest recommendations as to how to triage patients diagnosed with acute coronary syndromes (ACSs) and provide with algorithms of how to manage the patients and decide the appropriate treatment options in the era of COVID-19 pandemic. We also address the inpatient logistics and discharge to follow-up considerations for the function of already established ACS network during the pandemic. Definitions To minimize the misunderstanding in COVID-19 case definitions between healthcare workers we recommend adopting the World Health Organization guidelines on case definitions as following:• Confirmed case (COVID-19 +) – a patient with laboratory confirmation of COVID-19 infection, irrespective of clinical signs and symptoms. • Suspected case (COVID-19 +/-) – a patient with acute respiratory illness (fever and at least one sign/symptom of respiratory disease, e.g., cough, shortness of breath), OR a patient with acute respiratory illness (fever and at least one sign/symptom of respiratory disease, e.g., cough, shortness of breath), AND ...[...].

The authors describe a case of a patient admitted with a pre-syncopal episode and precordial discomfort, and whose cardiac ultrasound performed in the Emergency Room was suggestive of Pulmonary Embolism. The patient was submitted to fibrinolytic therapy after cardiac arrest. The computerized tomography done after this episode not only confirmed the presence of pulmonary embolism but had also shown a Stanford Type B Aortic Dissection. The option was to maintain the therapeutic anticoagulation, having the patient evolved favourably. Resumo: Os autores descrevem um caso de uma doente admitida após episódio pré-sincopal associado a precordialgia e cujo ecocardiograma sumário feito no Serviço de Urgência demonstrou alterações compatíveis com tromboembolismo pulmonar, tendo a doente sido submetida a terapêutica fibrinolítica, após episódio de paragem cardiorrespiratória. Na angiotomografia de tórax feita posteriormente para confirmação diagnóstica demonstra-se a presença não só de trombos no nível da artéria pulmonar, mas também de disseção da aorta Stanford B, tendo-se optado pela manutenção de anticoagulação terapêutica e a doente evoluído de forma favorável.

Coronavirus disease 2019 (COVID-19), currently a worldwide pandemic, is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The suspected contribution of thrombotic events to morbidity and mortality in COVID-19 patients has prompted a search for novel potential options for preventing COVID-19-associated thrombotic disease. In this article by the Global COVID-19 Thrombosis Collaborative Group, we describe novel dosing approaches for commonly used antithrombotic agents (especially heparin-based regimens) and the potential use of less widely used antithrombotic drugs in the absence of confirmed thrombosis. Although these therapies may have direct antithrombotic effects, other mechanisms of action, including anti-inflammatory or antiviral effects, have been postulated. Based on survey results from this group of authors, we suggest research priorities for specific agents and subgroups of patients with COVID-19. Further, we review other agents, including immunomodulators, that may have antithrombotic properties. It is our hope that the present document will encourage and stimulate future prospective studies and randomized trials to study the safety, efficacy, and optimal use of these agents for prevention or management of thrombosis in COVID-19.

Cardiovascular diseases (CVD) like myocardial infraction (MI) is still becoming the leading cause of morbidity and mortality and major problem in our healthcare system. Nowadays, revolution in high-tech medical treatment alongside with well-trained staff could decrease adverse event in ST elevation myocardial infarction (STEMI) patient. However, in developing country like Indonesia, those still become a challenge. Fibrinolytic therapy is still common practice even though primary percutaneous coronary intervention (PPCI) preferred. Intracranial bleeding is one of the most unfavorable effect after fibrinolytic therapy. Clinical should aware with clinical deterioration. Here we present case series of deadly intracranial haemorrhage in STEMI patient after fibrinolytic therapy.