Spontaneous intracerebral hemorrhage - patients retrospectively consent to fibrinolytic surgery despite poor neurological outcome and reduced health-related quality of life.

Spontaneous intracerebral hemorrhage (ICH) might lead to devastating consequences. Nonetheless, subjective interpretation of life circumstances might vary. Recent data from ischemic stroke patients show that there might be a paradox between clinically rated neurological outcome and self-reported satisfaction with quality of life. Our hypothesis was that minimally invasive surgically treated ICH patients would still give their consent to stereotactic fibrinolysis despite experiencing relatively poor neurological outcome. In order to better understand the patients' perspective and to enhance insight beyond functional outcome, this is the first study assessing disease-specific health-related quality of life (hrQoL) in ICH after fibrinolytic therapy. We conducted a retrospective analysis of patients with spontaneous ICH treated minimally invasive by stereotactic fibrinolysis. Subsequently, using standardized telephone interviews, we evaluated functional outcome with the modified Rankin Scale (mRS), health-related Quality of Life with the Quality of life after Brain Injury Overall scale (QOLIBRI-OS), and assessed retrospectively if the patients would have given their consent to the treatment. To verify the primary hypothesis that fibrinolytic treated ICH patients would still retrospectively consent to fibrinolytic therapy despite a relatively poor neurological outcome, we conducted a chi-square test to compare good versus poor outcome (mRS) between consenters and non-consenters. To investigate the association between hrQoL (QOLIBRI-OS) and consent, we conducted a Mann-Whitney U-test. Moreover, we did a Spearman correlation to investigate the correlation between functional outcome (mRS) and hrQoL (QOLIBRI-OS). The analysis comprised 63 data sets (35 men, mean age: 66.9 ± 11.8 years, median Hemphill score: 3 [2-3]). Good neurological outcome (mRS 0-3) was achieved in 52% (33/63) of the patients. Patients would have given their consent to surgery retrospectively in 89.7% (52/58). These 52 consenting patients comprised all 33 patients (100%) who achieved good functional outcome and 19 of the 25 patients (76%) who achieved poor neurological outcome (mRS 4-6). The mean QOLIBRI-OS value was 49.55 ± 27.75. A significant association between hrQoL and retrospective consent was found (p = 0.004). This study supports fibrinolytic treatment of ICH even in cases when poor neurological outcome would have to be assumed since subjective perception of deficits could be in contrast with the objectively measured neurological outcome. HrQoL serves as a criterion for success of rtPa lysis therapy in ICH.

Establishing reliable selection criteria for performing fibrinolytic therapy in patients with intracerebral haemorrhage based on prognostic tools.

OBJECTIVES: Minimally invasive surgery combined with fibrinolytic therapy is a promising treatment option for patients with intracerebral haemorrhage (ICH), but a meticulous patient selection is required, because not every patient benefits from it. The ICH score facilitates a reliable patient selection for fibrinolytic therapy except for ICH-4. This study evaluated whether an additional use of other prognostic tools can overcome this limitation. MATERIALS AND METHODS: A consecutive ICH patient cohort treated with fibrinolytic therapy between 2010 and 2020 was retrospectively analysed. The following prognostic tools were calculated: APACHE II, ICH-GS, ICH-FUNC, and ICH score. The discrimination power of every score was determined by ROC-analysis. Primary outcome parameters regarding the benefit of fibrinolytic therapy were the in-hospital mortality and a poor outcome defined as modified Rankin scale (mRS) > 4. RESULTS: A total of 280 patients with a median age of 72 years were included. The mortality rates according to the ICH score were ICH-0 = 0 % (0/0), ICH-1 = 0 % (0/22), ICH-2 = 7.1 % (5/70), ICH-3 = 17.3 % (19/110), ICH-4 = 67.2 % (45/67), ICH-5 = 100 % (11/11). The APACHE II showed the best discrimination power for in-hospital mortality (AUC = 0.87, p < 0.0001) and for poor outcome (AUC = 0.79, p < 0.0001). In the subgroup with ICH-4, APACHE II with a cut-off of 24.5 showed a good discriminating power for in-hospital mortality (AUC = 0.83, p < 0.001) and for poor outcome (AUC = 0.87, p < 0.001). CONCLUSIONS: An additional application of APACHE II score increases the discriminating power of ICH score 4 enabling a more precise appraisal of in-hospital mortality and of functional outcome, which could support the patient selection for fibrinolytic therapy.

Drip-and-ship toward mothership model for mechanical thrombectomy during COVID-19 pandemic: a retrospective analysis.

INTRODUCTION: During the first wave of the COVID-19 pandemic in spring 2020, our stroke network shifted from a drip-and-ship strategy (transport of acute ischemic stroke patients to the nearest primary stroke centers) toward a mothership model (direct transportation to the Comprehensive Stroke Center). We retrospectively analyzed stroke network performances comparing the two models. PATIENTS AND METHODS: All spoke-district patients treated with endovascular thrombectomy (EVT) between 15th March-15th June 2019 (drip-and-ship) and 2020 (mothership) were considered. We compared onset-to-groin time (OGT) and onset-to-needle time (ONT) between the two periods. Secondarily, we investigated other performances parameters (percentage of IV thrombolysis, timing of diagnostic and treatment) and clinical outcome (3-month modified Rankin Scale). RESULTS: Twenty-four spoke-district patients in 2019 (drip-and-ship) and 26 in 2020 (mothership) underwent EVT. The groups did not differ for age, sex, risk factors, pre-stroke mRS 0-1, NIHSS, and ASPECTS distribution. The MS model showed a significant decrease of the OGT (162.5 min vs 269 min, p = 0.001) without significantly affecting the ONT (140.5 min vs 136 min, p = 0.853), ensuring a higher number of IV thrombolysis in combination with EVT (p = 0.030). The mothership model showed longer call-to-door time (median + 23 min, p < 0.005), but shorter door-to-needle (median - 31 min, p = 0.001), and door-to-groin time (- 82.5 min, p < 0.001). We found no effects of the stroke network model on the 3-month mRS (ordinal shift analysis, p = 0.753). CONCLUSIONS: The shift to the mothership model during the COVID-19 pandemic guaranteed quicker EVT without significantly delaying IVT.

Impact of COVID-19 on Acute Myocardial Infarction Care.

The global health crisis caused by the COVID-19 pandemic has evolved rapidly to overburden health care organizations around the world and has resulted in significant morbidity and mortality. Many countries have reported a substantial and rapid reduction in hospital admissions for acute coronary syndromes and percutaneous coronary intervention. The reasons for such abrupt changes in health care delivery are multifactorial and include lockdowns, reduction in outpatient services, reluctance to seek medical attention for fear of contracting the virus, and restrictive visitation policies adopted during the pandemic. This review discusses the impact of COVID-19 on important aspects of acute MI care.

A Novel Technique of SMA Massage with Systemic Fibrinolytic Therapy in Ischemic Midgut Volvulus: As a Lifesaving Last Expedient.

Purpose: Midgut volvulus is a surgical emergency requiring immediate intervention. Intestinal ischemia of the midgut as a consequence of volvulus from malrotation is a fateful event with high mortality and significant morbidity even in survivors. Derotation followed by correction of malrotation is the procedure of choice though has significant morbidity if intestinal reperfusion was not successful. A combined treatment to restore intestinal perfusion based on the digital massage of the superior mesenteric artery after derotation and systemic infusion of fibrinolytic has been previously reported with success but underused. Here, we report three such cases of midgut malrotation with severe intestinal ischemia due to volvulus. Materials and Methods: A retrospective analysis of three confirmed cases of midgut malrotation with volvulus managed with emergency laparotomy, derotation, and Superior Mesenteric Artery (SMA) massage with systemic fibrinolytic therapy, followed by correction of malrotation was evaluated. Results: There was dramatic improvement in intestinal perfusion noted in all three patients inspite of delayed presentation. 2 out of 3 patients on follow up are doing well with adequate weight gain while 1 patient succumbed due to sepsis. Conclusion: Critical intestinal ischemia due to mesenteric thrombosis can persist after derotation of midgut volvulus and can lead to devastating consequences. The use of digital massage of SMA to disrupt the thrombus along with fibrinolytic therapy though reported is underutilized. Hence, awareness of this management and usage needs to be re-emphasized.

Tissue plasminogen activator with prolonged dwell time effectively evacuates pleural effusions.

OBJECTIVES: Fibrinolytic therapy can be effective for management of complex pleural effusions. Tissue plasminogen activator (tPA, 10 mg) and deoxyribonuclease (DNAse) every 12 h with a dwell time of one hour is a common strategy based on published data. We used a simpler protocol of tPA (4 mg) without DNAse but with a longer dwell time of 12 h, repeated daily. We reviewed our results. METHODS: Charts were reviewed and demographics, clinical data and treatment information were abstracted. Outcomes were assessed based on radiographic findings and need for surgery. RESULTS: Two hundred and fifteen effusions in 207 patients (8 bilateral) were identified. 85% were either infectious or malignant. Two hundred and forty nine chest tubes were used: 84% were 10 Fr or 12 Fr and 7% were PleurX®. Five hundred and thirty one doses of tPA were given. The median number of doses per effusion was 2 (range 1-10), and 84% of effusions were treated with three or fewer doses. There were no significant bleeding complications. Median time to chest tube removal was 6 days (range 1 to 98, IQR 4 to 10). Drainage was considered complete for 78% of effusions, while 6% required decortication. CONCLUSIONS: Low dose tPA daily with a 12 h dwell time may be as effective as the standard regimen of tPA and DNAse twice daily with one hour dwell. For most patients only three doses were required, and small pigtail catheters were sufficient. This regimen uses less medication and is logistically much easier than the current standard.

The role of blood product removal in intraventricular hemorrhage of prematurity: a meta-analysis of the clinical evidence.

INTRODUCTION: Premature neonates have a high risk of intraventricular hemorrhage (IVH) at birth, the blood products of which activate inflammatory cascades that can cause hydrocephalus and long-term neurological morbidities and sequelae. However, there is no consensus for one treatment strategy. While the mainstay of treatment involves CSF diversion to reduce intracranial pressure, a number of interventions focus on blood product removal at various stages including extraventricular drains (EVD), intra-ventricular thrombolytics, drainage-irrigation-fibrinolytic therapy (DRIFT), and neuroendoscopic lavage (NEL). METHODS: We performed a systematic review and meta-analysis to compare the risks and benefits commonly associated with active blood product removal treatment strategies. We searched MEDLINE, Embase, Scopus, Cochrane Library, and CINAHL databases through Dec 2020 for articles reporting on outcomes of EVDs, thrombolytics, DRIFT, and NEL. Outcomes of interest were rate of conversion to ventriculoperitoneal shunt (VPS), infection, mortality, secondary hemorrhage, and cognitive disability. RESULTS: Of the 10,398 articles identified in the search, 23 full-text articles representing 22 cohorts and 530 patients were included for meta-analysis. These articles included retrospective, prospective, and randomized controlled studies on the use of EVDs (n = 7), thrombolytics (n = 8), DRIFT therapy (n = 3), and NEL (n = 5). Pooled rates of reported outcomes for EVD, thrombolytics, DRIFT, and NEL for ventriculoperitoneal shunt (VPS) placement were 51.1%, 43.3%, 34.3%, and 54.8%; for infection, 15.4%, 12.5%, 4.7%, and 11.0%; for mortality, 20.0%, 11.6%, 6.0%, and 4.9%; for secondary hemorrhage, 5.8%, 7.8%, 20.0%, and 6.9%; for cognitive impairment, 52.6%, 50.0%, 53.7%, and 50.9%. Meta-regression using type of treatment as a categorical covariate showed no effect of treatment modality on rate of VPS conversion or cognitive disability. CONCLUSION: There was a significant effect of treatment modality on secondary hemorrhage and mortality; however, mortality was no longer significant after adjusting for year of publication. Re-hemorrhage rate was significantly higher for DRIFT (p < 0.001) but did not differ among the other modalities. NEL also had lower mortality relative to EVD (p < 0.001) and thrombolytics (p = 0.013), which was no longer significant after adjusting for year of publication. Thus, NEL appears to be safer than DRIFT in terms of risk of hemorrhage, and not different than other blood-product removal strategies in terms of mortality. Outcomes-in terms of shunting and cognitive impairment-did not differ. Later year of publication was predictive of lower rates of mortality, but not the other outcome variables. Further prospective and randomized studies will be necessary to directly compare NEL with other temporizing procedures.

Comparison between surgery and fibrinolytic therapy in prosthetic valve thrombosis: A systematic review and meta-analysis.

BACKGROUND: Prosthetic valve thrombosis (PVT) is a rare but life-threatening complication. Surgery and fibrinolytic therapy (FT) are the two main treatment options for PVT. The choice between surgery and FT has always been a matter of debate. Previous studies have shown that although the mortality rate is higher in surgery, complications are less frequent than in FT. We aimed to perform a systematic review and meta-analysis to compare the results of surgery and FT in PVT. METHODS: A systematic review of the literature was performed through Medline, Embase, Scopus, and Web of Science, encompassing all studies comparing surgery and FT in PVT. The rate of each complication and risk ratio (RR) of complications in surgery and FT were assessed using random-effects models. RESULTS: Fifteen studies with 1235 patients were included in the meta-analysis. The pooled risk of the mortality was not significantly different between FT and surgery in patients with PVT (pooled RR = 0.78, 95% confidence interval [CI]: 0.38-1.60, I² = 61.4%). The pooled risks of thromboembolic events (pooled RR = 4.70, 95% CI: 1.83-12.07, I² = 49.6%) and major bleeding (pooled RR = 2.45, 95% CI: 1.09-5.50, I² = 41.1%) and PVT recurrence (pooled RR = 2.06 95% CI: 1.29-3.27, I² = 0.0%) were significantly higher in patients who received FT. CONCLUSION: Surgery may be safer and with fewer complications than FT for PVT treatment. However, randomized clinical trials are needed to determine the proper treatment for PVT.

Update on Novel Targeted Therapy for Pleural Organization and Fibrosis.

Pleural injury and subsequent loculation is characterized by acute injury, sustained inflammation and, when severe, pathologic tissue reorganization. While fibrin deposition is a normal part of the injury response, disordered fibrin turnover can promote pleural loculation and, when unresolved, fibrosis of the affected area. Within this review, we present a brief discussion of the current IPFT therapies, including scuPA, for the treatment of pathologic fibrin deposition and empyema. We also discuss endogenously expressed PAI-1 and how it may affect the efficacy of IPFT therapies. We further delineate the role of pleural mesothelial cells in the progression of pleural injury and subsequent pleural remodeling resulting from matrix deposition. We also describe how pleural mesothelial cells promote pleural fibrosis as myofibroblasts via mesomesenchymal transition. Finally, we discuss novel therapeutic targets which focus on blocking and/or reversing the myofibroblast differentiation of pleural mesothelial cells for the treatment of pleural fibrosis.

Bridging a Century-Old Problem: The Pathophysiology and Molecular Mechanisms of HA Filler-Induced Vascular Occlusion (FIVO)-Implications for Therapeutic Interventions.

Biocompatible hyaluronic acid (HA, hyaluronan) gel implants have altered the therapeutic landscape of surgery and medicine, fostering an array of innovative products that include viscosurgical aids, synovial supplements, and drug-eluting nanomaterials. However, it is perhaps the explosive growth in the cosmetic applications of injectable dermal fillers that has captured the brightest spotlight, emerging as the dominant modality in plastic surgery and aesthetic medicine. The popularity surge with which injectable HA fillers have risen to in vogue status has also brought a concomitant increase in the incidence of once-rare iatrogenic vaso-occlusive injuries ranging from disfiguring facial skin necrosis to disabling neuro-ophthalmological sequelae. As our understanding of the pathophysiology of these injuries has evolved, supplemented by more than a century of astute observations, the formulation of novel therapeutic and preventative strategies has permitted the amelioration of this burdensome complication. In this special issue article, we review the relevant mechanisms underlying HA filler-induced vascular occlusion (FIVO), with particular emphasis on the rheo-mechanical aspects of vascular blockade; the thromboembolic potential of HA mixtures; and the tissue-specific ischemic susceptibility of microvascular networks, which leads to underperfusion, hypoxia, and ultimate injury. In addition, recent therapeutic advances and novel considerations on the prevention and management of muco-cutaneous and neuro-ophthalmological complications are examined.

Efficacy and safety of intraventricular fibrinolytic therapy for post-intraventricular hemorrhagic hydrocephalus in extreme low birth weight infants: a preliminary clinical study.

PURPOSE: To evaluate the efficacy and safety of our unique therapy for treating post-intraventricular hemorrhagic hydrocephalus (PIVHH) in low birth weight infants (LBWls) through an early stage fibrinolytic therapeutic strategy involving urokinase (UK) injection into the lateral ventricle, called the "Ventricular Lavage (VL) therapy." METHODS: Overall, 43 consecutive infants with PIVHH were included. Most were extremely LBWIs (n = 39). Other cases included very LBWIs (n = 2) and full-term infants (n = 2). VL therapy involved continuous external ventricular drainage (EVD) management using a very fine catheter and intermittent slow injection of 6000 IU of UK every 3-6 h to actively dissolve hematomas. RESULTS: Early EVD management (within 3 weeks of IVH onset) was performed in 25 infants, with combination VL therapy in 21 infants. Five initiated late EVD management (≥ 3 weeks after IVH onset); the remaining 13 were treated conservatively for several weeks, delaying surgical intervention. Eighteen of 21 (86%) infants who received VL therapy did not require permanent shunt surgery. There were no serious complications, including the absence of secondary hemorrhage and infection. Two-thirds of the infants treated in the late stages required permanent shunt, and various shunt-related complications frequently occurred. A good outcome occurred in 13/17 infants in the early treatment group, despite most subjects having an IVH grade IV, and in 6/15 in the late treatment group. CONCLUSIONS: Permanent shunt surgery needs were dramatically reduced following early VL therapy, and functional outcomes were favorable. VL therapy might be a promising strategy that could lead to the development of new treatments for PIVHH.

Multimodal treatment for acute empyema based on the patient's condition, including patients who are bedridden: A single center retrospective study.

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.

Contraindications to intravenous thrombolysis in prehospital triage of thrombectomy candidates.

BACKGROUND AND PURPOSE: The existence of contraindications to intravenous thrombolysis (IVT) is considered a criterion for direct transfer of patients with suspected acute stroke to thrombectomy-capable centers in the prehospital setting. Our aim was to assess the utility of this criterion in a setting where routing protocols are defined by the Madrid - Direct Referral to Endovascular Center (M-DIRECT) prehospital scale. METHODS: This was a post hoc analysis of the M-DIRECT study. Reported contraindications to IVT were retrospectively collected from emergency medical services reports and categorized into late window, anticoagulant treatment and other contraindications. Final diagnosis and treatment rates were compared between patients with and without reported IVT contraindications and according to anticoagulant treatment or late window categories. RESULTS: The M-DIRECT study included 541 patients. Reported IVT contraindications were present in 227 (42.0%) patients. Regarding final diagnosis no significant differences were found between patients with or without reported IVT contraindications: ischaemic stroke (any) 65.6% vs. 62.1%, ischaemic stroke with large vessel occlusion (LVO) 32.2% vs. 28.3%, hemorrhagic stroke 15.4% vs. 15.6%, stroke mimic 18.9% vs. 22.3% respectively. Amongst patients with LVO, endovascular thrombectomy (EVT) was performed less often in the presence of IVT contraindications (56.2% vs. 74.2%). M-DIRECT-positive patients had higher rates of LVO and EVT compared with M-DIRECT-negative patients independent of reported IVT contraindications. CONCLUSIONS: Reported IVT contraindications alone do not increase EVT likelihood and should not be considered to determine routing in urban stroke networks.

Inferior ST-Elevation Myocardial Infarction Presenting When Urgent Primary Percutaneous Coronary Intervention Is Unavailable: Should We Adhere to Current Guidelines?

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.

Intrahematomal catheter placement with connection to the ventricular system allows more effective thrombolysis of combined intracerebral and intraventricular hematomas.

Intracerebral hematomas (ICH) with intraventricular hemorrhage (IVH) are associated with high morbidity. Catheter-based thrombolysis with recombinant tissue plasminogen activator (rtPA) allows a faster hematoma resolution compared to conservative treatment. However, simultaneous thrombolysis of ICH and IVH is not achievable because the ependyma hinders ICH-lysis if rtPA is given into the ventricles and inversely. We evaluated if the thrombolysis efficacy is enhanced by placing an intrahematomal catheter reaching the ventricle. Patients with ICH plus IVH treated with catheter-based thrombolysis were retrospectively analyzed. Group 1 included patients with an intrahematomal catheter reaching the ventricles and group 2 patients with a catheter placed exclusively in the ICH. The relative hematoma volume reduction (RVR) of ICH and IVH within 3 days was calculated. Furthermore, the patients' outcome, the hydrocephalus incidence, and the infection rate were evaluated. A total of 74 patients were analyzed, of whom 49% had a catheter reaching the ventricle. The mean ICH-RVR (68% vs. 58%, p = 0.0001) and IVH-RVR were significantly higher in group 1 compared to group 2. In group 1, infections occurred more often compared to group 2 (31% vs. 6%, p = 0.005). There was no difference in outcome and in hydrocephalus incidence between both groups. The catheter reaching the ventricles allows simultaneous and more effective thrombolysis of ICH and IVH. We assume that the fibrinolytic property of cerebrospinal fluid itself and a washout effect contribute to these findings. In patients with ICH plus IVH, catheter positioning through the hematoma into the ventricle, and subsequent fibrinolytic therapy should be considered.

Outcomes of fibrinolytic therapy for patients with metastatic cancer and acute pulmonary embolism.

INTRODUCTION: Malignancy is a common cause of morbidity and mortality in the United States and around the world and the second leading cause of death in the United States. There is little data on the impact of metastatic cancer on the risk of hemorrhagic stroke or mortality among patients undergoing fibrinolytic therapy (FT) for acute PE. METHODS: Using the National Inpatient Sample (NIS) database, we extracted admissions with a primary diagnosis of acute pulmonary embolism that underwent FT from 2010 to 2014. We performed a case control matched analysis between patients with and without metastatic cancer. Our primary outcome of interest was Mortality and our secondary outcome of interest was hemorrhagic stroke (HS). RESULTS: Of the 883,183 patients with a primary diagnosis of acute PE between 2010 and 12014, 23,690 patients (2.7%) underwent FT. After exclusion, 22,592 patients were included in the analysis. Of these, 941 patients (4.2%) were reported to have metastatic cancer. There was a higher incidence of cerebrovascular accidents and intubation/mechanical ventilation in the metastatic cancer arm. Mortality was significantly higher in the metastatic cancer arm with no difference in the incidence of HS. In multivariate regression analysis, among all patients that underwent FT for acute PE, metastatic cancer was associated with a significant odds for mortality (OR 1.91, 95% CI 1.11-5.82, p < .001). CONCLUSION: The presence of metastatic cancer in patients undergoing fibrinolytic therapy for acute pulmonary embolism is associated with increase mortality.

Intracerebral Hemorrhage-Score Allows a Reliable Prediction of Mortality in Patients with Spontaneous Intracerebral Hemorrhage Managed by Fibrinolytic Therapy.

OBJECTIVE: Intracerebral hemorrhage (ICH) is associated with high morbidity and mortality. Prognosis estimation would be helpful for the treatment decision making in ICH patients. The ICH-score was published in 2001 to estimate the 30-day mortality in conservatively treated patients with ICH. We evaluated the reproducibility of the ICH-score in ICH patients undergoing fibrinolytic therapy. METHODS: We performed a retrospective analysis of patients with supratentorial ICH managed by fibrinolytic therapy and evaluated the 30-day mortality. The ICH-score was then applied to match the mortality in our patients with the mortality predicted by the ICH-score. The ICH-score is based on parameters available at admission: age, hematoma volume, intraventricular expansion, and clinical status according to the Glasgow Coma Scale. RESULTS: A total of 233 patients were analyzed. The 30-day mortality rate was 30% (70/233). An age of ≥80 years was associated with a significantly higher mortality rate (OR 2.26, chi-square test p = 0.01). A hematoma volume of ≥30 mL led significantly more often to 30-day mortality (OR 3.72, chi-square test p = 0.01). The mortality was significantly higher in the patients with intraventricular hemorrhage (2.97, chi-square test p = 0.003). The ICH-score showed a significant correlation with mortality (chi-square test, p < 0.0001). The following mortality rates were estimated using the ICH-score in our cohort: 1 = 0% (0/13), 2 = 0% (0/51), 3 = 1.3% (1/82), 4 = 43% (13/31), 5 = 100% (56/56). CONCLUSION: The ICH-score not only allows a reliable estimation of the 30-day mortality in patients with ICH treated conservatively but also treated by clot lysis. Compared to conservative treatment, the fibrinolytic therapy reduced the 30-day mortality in the patients with ICH-scores 1-4. Patients with ICH-score 5 do not have a benefit of fibrinolytic therapy and should no longer be considered to be candidates for fibrinolytic therapy.

Usefulness of Tp-Te interval and Tp-Te/QT ratio in the prediction of ventricular arrhythmias and mortality in acute STEMI patients undergoing fibrinolytic therapy.

BACKGROUND AND AIM: Acute ST-elevation myocardial infarction (STEMI) is associated with fatal and non-fatal ventricular arrhythmic events (VAE). Although primary percutaneous intervention (PCI) is first-line treatment in STEMI, fibrinolytic therapy (FT) is still widely used in many countries. Tp-Te interval; Tp-Te/QT ratio and QT dispersion (QTd) are novel markers of ventricular repolarization (VR) and associate with VAE and mortality. Hereby, we assessed Tp-Te, QTd and Tp-Te/QT in acute STEMI patients undergoing FT and analyzed their relationship with post-FT VAE, and arrhythmic and overall deaths. METHODS: A total of 207 consecutive STEMI patients treated with FT were retrospectively evaluated. Patients were divided in Group 1 (non-VAE group) and Group 2 (VAE group). ECG, clinical and demographic data were noted. Relationship between the pre-FT electrocardiographic parameters of VR and post-FT VAE, arrhythmic and overall death was evaluated. RESULTS: Tp-Te, Tp-Te/QT and QTd were significantly higher in Group 2 compared to Group 1 (p < 0.05). Tp-Te, Tp-Te/QT, QTd, QTc and left ventricular ejection fraction (LVEF) predicted VAE. Tp-Te/QT and LVEF predicted arrhythmic death (1.05; 95% CI 1.01-1.08; p = 0.031 and 0.87; 95% CI 0.72-0.96; p = 0.040; respectively). In ROC analysis, cut-off for Tp-Te/QT to predict VAE was >0.305 with 87.5% sensitivity and 60.1% specificity (AUC: 0.90; 95% CI: 0.85-0.95; p < 0.001), and to predict arrhythmic death was >0.315 with 83.3% sensitivity and 62% specificity (AUC: 0.70; 95% CI: 0.60-0.81; p = 0.018). CONCLUSION: Tp-Te, Tp-Te/QT, QTc, QTd and LVEF are independent predictors of post-FT VAE in acute STEMI. Tp-Te/QT ratio is associated with VA-related deaths.

Intrapleural alteplase therapy: what are the knowns and unknowns?

In pneumology, enzymatic properties of plasmin are used to disrupt fibrin adhesions and septations formed during pathological conditions of the pleural cavity. In that case, fibrinolytics are administrated locally via a chest tube in the pleural cavity to evacuate pathological effusion. Although the first intrapleural administration of fibrinolytic occurred seventy years ago, there has been no consensus on dosing or a uniform procedure of their application. The aim of the article is to summarize current knowledge of alteplase usage in pneumology and discuss practical aspects of its intrapleural application regarding specific possibilities in the Czech Republic.

Targeting plasminogen activator inhibitor-1 in tetracycline-induced pleural injury in rabbits.

Elevated active plasminogen activator inhibitor-1 (PAI-1) has an adverse effect on the outcomes of intrapleural fibrinolytic therapy (IPFT) in tetracycline-induced pleural injury in rabbits. To enhance IPFT with prourokinase (scuPA), two mechanistically distinct approaches to targeting PAI-1 were tested: slowing its reaction with urokinase (uPA) and monoclonal antibody (mAb)-mediated PAI-1 inactivation. Removing positively charged residues at the "PAI-1 docking site" (179RHRGGS184→179AAAAAA184) of uPA results in a 60-fold decrease in the rate of inhibition by PAI-1. Mutant prourokinase (0.0625-0.5 mg/kg; n = 12) showed efficacy comparable to wild-type scuPA and did not change IPFT outcomes ( P > 0.05). Notably, the rate of PAI-1-independent intrapleural inactivation of mutant uPA was 2 times higher ( P < 0.05) than that of the wild-type enzyme. Trapping PAI-1 in a "molecular sandwich"-type complex with catalytically inactive two-chain urokinase with Ser195Ala substitution (S195A-tcuPA; 0.1 and 0.5 mg/kg) did not improve the efficacy of IPFT with scuPA (0.0625-0.5 mg/kg; n = 11). IPFT failed in the presence of MA-56A7C10 (0.5 mg/kg; n = 2), which forms a stable intrapleural molecular sandwich complex, allowing active PAI-1 to accumulate by blocking its transition to a latent form. In contrast, inactivation of PAI-1 by accelerating the active-to-latent transition mediated by mAb MA-33B8 (0.5 mg/kg; n = 2) improved the efficacy of IPFT with scuPA (0.25 mg/kg). Thus, under conditions of slow (4-8 h) fibrinolysis in tetracycline-induced pleural injury in rabbits, only the inactivation of PAI-1, but not a decrease in the rate of its reaction with uPA, enhances IPFT. Therefore the rate of fibrinolysis, which varies in different pathologic states, could affect the selection of PAI-1 inhibitors to enhance fibrinolytic therapy.