Search

Thrombosis is a dangerous condition that can result in major damage. Fibrinolytic enzymes are significant therapeutic agents for thrombosis. This study focused on MsFE, a fibrinolytic protease from M. subtilissimus UCP1262, exploring its physicochemical traits and the impact of gamma radiation on its activity. Investigations included: fibrinogenolytic activity, effects of solvents and ions, gamma rays, enzyme shelf life, FTIR, CD, clotted times determination, and enzymatic kinetics. Notably, the major results obtained show the protease retained 90 % activity in organic solvents, FTIR indicated carbonyl functional groups and Circular dichroism spectroscopic studies indicated that the secondary structure (β-sheet) of enzyme remains mostly unaffected over pH 2.0–9.0, whereas considerable changes were observed in the tertiary structure. Kinetic analysis revealed altered parameters post-irradiation. Gamma radiation initially enhanced enzyme activity (10 kGy) but progressively decreased beyond 20 kGy. Metallic ions, especially magnesium, augmented irradiated enzyme activity. This study highlights gamma radiation's potential as a modulator for enhanced fibrinolytic activity, suggesting future biomedical applications. [Display omitted] • Mucor subtilissimus proves its significance as a producer of fibrinolytic proteases. • The protease degrades the α, β and γ chains of fibrinogen. • The 10 kGy radiation increased the activity of the enzyme by approximately 10 %. • Fe2+, Cu2+ and Mg2+ were able to increase the activity of the irradiated enzyme. • Produced enzymes can be a highly productive fibrinolytic for medical applications. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Study design: Retrospective. Background: In the 1980s, aneurysmal subarachnoid clot lysis with urokinase or alteplase (rtPA) was proven to effectively reduce vasospasm and neurological ischemic deficits, improving survival and clinical outcomes. This therapeutic option has been less commonly used since the introduction of endovascular treatment, but renewed interest has sparked in recent years. Aims: To investigate if single bolus cisternal urokinase subarachnoid clot lysis reduces vasospasm, neurological ischemic deficits, mortality, and permanent CSF diversion rates and improves outcomes. Additionally, we want to unveil which subgroup of patients benefit most. Material and methods: Study period January 2007–December 2019. 415 patients with saccular aneurysms and >1-year follow-up analyzed. Six groups created according to the treatment applied: no treatment (42), only external ventricular drain (16), endovascular treatment (155), clipping (53), clipping + 100,000UI urokinase (116), and incidental brain aneurysm (33). Results: The rates and severity of vasospasm, permanent CSF diversion, and mortality in Fisher grades ≥3 subarachnoid hemorrhages were higher with endovascular treatment than with surgical clipping with simultaneous cisternal urokinase administration. The best GOSE results on discharge and 6- and 12-month follow-ups happened in this latter group. The differences were more significant the higher the Fisher grade. We neither saw intraventricular, subarachnoid, subdural, or epidural hemorrhages nor systemic fibrinolysis or infections that could be related to the urokinase administration. Conclusions: Single bolus cisternal 100,000UI urokinase administration during emergency aneurysm clipping reduces vasospasm, mortality, and the need for permanent CSF diversion. It is not associated with a significant increase in intracranial hemorrhages or systemic fibrinolysis.

Background: Left-sided mechanical prosthetic heart valve thrombosis (PVT) occurs because of suboptimal anticoagulation and is common in low-resource settings. Urgent surgery and fibrinolytic therapy (FT) are the two treatment options available for this condition. Urgent surgery is a high-risk procedure but results in successful restoration of valve function more often and is the treatment of choice in developed countries. In low-resource countries, FT is used as the default treatment strategy, though it is associated with lower success rates and a higher rate of bleeding and embolic complications. There are no randomized trials comparing the two modalities. Methods: We performed a single center randomized controlled trial comparing urgent surgery (valve replacement or thrombectomy) with FT (low-dose, slow infusion tissue plasminogen activator, tPA) in patients with symptomatic left-sided PVT. The primary outcome was the occurrence of a complete clinical response, defined as discharge from hospital with completely restored valve function, in the absence of stroke, major bleeding or non-CNS systemic embolism. Outcome assessment was done by investigators blinded to treatment allocation. The principal safety outcome was the occurrence of a composite of in-hospital death, non-fatal stroke, non-fatal major bleed or non-CNS systemic embolism. Outcomes will be assessed both in the intention-to-treat, and in the as-treated population. We will also report outcomes at one year of follow-up. The trial has completed recruitment. Conclusion: This is the first randomized trial to compare urgent surgery with FT for the treatment of left-sided PVT. The results will provide evidence to help clinicians make treatment choices for these patients.(Clinical trial registration: CTRI/2017/10/010159).

Copyright of Revista Española de Cardiología (18855857) is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Latinoamericana de Hipertension is the property of Revista Latinoamericana de Hipertension and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

INTRODUCTION: Valvular heart disease presents a significant and escalating global health challenge. Prosthetic valve thrombosis (PVT) following surgical valve replacement is a primary cause of valve failure. The aim of this study was to ascertain the outcomes and complications of fibrinolytic therapy in patients diagnosed with PVT.METHOD: This cross-sectional study enrolled 81 patients diagnosed with PVT who underwent fibrinolytic therapy between 2008 and 2018. Streptokinase was administered to 87.6% of patients, while 12.4% received reteplase. All demographic and clinical data were gathered from the patients’ medical records. The incidence of successful recovery and complications were assessed.RESULTS: The records of 81 patients (43.2% male, mean age: 51.6 ± 13.9 years) were examined. The findings revealed that 59% and 35% of the patients had mitral and aortic PVT, respectively. While 12% of the patients experienced drug complications, 90% achieved successful recovery. Stroke and severe hemorrhage were complications frequently reported by the patients treated with streptokinase (8% and 4% respectively). The patients treated with reteplase demonstrated a 100% recovery rate. Conversely, 89% of the patients treated with streptokinase achieved successful recovery, and 7% of the patients experienced a partial recovery.CONCLUSION: Fibrinolytic agents can serve as an effective treatment with an excellent success rate for managing PVT in patients post-surgical valve replacement.

Among the high prevalence of cerebrovascular diseases nowadays, acute ischemic stroke stands out, representing a significant worldwide health issue with important socio-economic implications. Prompt diagnosis and intervention are important milestones for the management of this multifaceted pathology, making understanding the various stroke-onset symptoms crucial. A key role in acute ischemic stroke management is emphasizing the essential role of a multi-disciplinary team, therefore, increasing the efficiency of recognition and treatment. Neuroimaging and neuroradiology have evolved dramatically over the years, with multiple approaches that provide a higher understanding of the morphological aspects as well as timely recognition of cerebral artery occlusions for effective therapy planning. Regarding the treatment matter, the pharmacological approach, particularly fibrinolytic therapy, has its merits and challenges. Endovascular thrombectomy, a game-changer in stroke management, has witnessed significant advances, with technologies like stent retrievers and aspiration catheters playing pivotal roles. For select patients, combining pharmacological and endovascular strategies offers evidence-backed benefits. The aim of our comprehensive study on acute ischemic stroke is to efficiently compare the current therapies, recognize novel possibilities from the literature, and describe the state of the art in the interdisciplinary approach to acute ischemic stroke. As we aspire for holistic patient management, the emphasis is not just on medical intervention but also on physical therapy, mental health, and community engagement. The future holds promising innovations, with artificial intelligence poised to reshape stroke diagnostics and treatments. Bridging the gap between groundbreaking research and clinical practice remains a challenge, urging continuous collaboration and research. [ABSTRACT FROM AUTHOR]

Abstract 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.

Treatment for pediatric hydrocephalus aims not only to shrink the enlarged ventricle morphologically but also to create an intracranial environment that provides the best neurocognitive development and to deal with various treatment-related problems over a long period of time. Although the primary diseases that cause hydrocephalus are diverse, the ventricular peritoneal shunt has been introduced as the standard treatment for several decades. Nevertheless, complications such as shunt infection and shunt malfunction are unavoidable; the prognosis of neurological function is severely affected by such factors, especially in newborns and infants. In recent years, treatment concepts have been attempted to avoid shunting, mainly in the context of pediatric cases. In this review, the current role of neuroendoscopic third ventriculostomy for noncommunicating hydrocephalus is discussed and a new therapeutic concept for post intraventricular hemorrhagic hydrocephalus in preterm infants is documented. To avoid shunt placement and achieve good neurodevelopmental outcomes for pediatric hydrocephalus, treatment modalities must be developed.

The incidence of empyema is increasing and associated with a mortality rate of 20% in patients older than 65 years. Since 30% of patients with advanced empyema have contraindications to surgical treatment, novel, low-dose, pharmacological treatments are needed. A Streptococcus pneumoniae-induced rabbit model of chronic empyema recapitulates the progression, loculation, fibrotic repair, and pleural thickening of human disease. Treatment with single chain (sc) urokinase (scuPA) or tissue type (sctPA) plasminogen activators in doses 1.0–4.0 mg/kg were only partially effective in this model. Docking Site Peptide (DSP; 8.0 mg/kg), which decreased the dose of sctPA for successful fibrinolytic therapy in acute empyema model did not improve efficacy in combination with 2.0 mg/kg scuPA or sctPA. However, a two-fold increase in either sctPA or DSP (4.0 and 8.0 mg/kg or 2.0 and 16.0 mg/kg sctPA and DSP, respectively) resulted in 100% effective outcome. Thus, DSP-based Plasminogen Activator Inhibitor 1-Targeted Fibrinolytic Therapy (PAI-1-TFT) of chronic infectious pleural injury in rabbits increases the efficacy of alteplase rendering ineffective doses of sctPA effective. PAI-1-TFT represents a novel, well-tolerated treatment of empyema that is amenable to clinical introduction. The chronic empyema model recapitulates increased resistance of advanced human empyema to fibrinolytic therapy, thus allowing for studies of muti-injection treatments. [ABSTRACT FROM AUTHOR]

Objective: To investigate the efficacy and safety of pharmacoinvasive (PI) strategy compared to primary percutaneous coronary intervention (PPCI) in the setting of a real-world ST-elevation myocardial infarction (STEMI) network where streptokinase (SK) is predominantly prescribed. Materials and Methods: The authors analyzed 325 STEMI patients who participated in The Siriraj STEMI network between July 2015 and October 2020. The primary efficacy endpoint was the incidence of cumulative major adverse cardiovascular and cerebrovascular events (MACCE) at one month, which were the composite of death, myocardial infarction, stroke, and non-coronary artery bypass graft (CABG)-related thrombolysis in myocardial infarction (TIMI) major or minor bleeding. The safety endpoint was non-CABG-related TIMI major or minor bleeding during the index hospitalization. Cox regression was performed for survival analysis. The authors applied propensity score matching to reduce the bias of the confounding variables. Results: Two hundred four patients received fibrinolytic therapy, 191 (93.6%) obtained SK, and 121 participants underwent PPCI. After propensity score matching analysis, the incidence of cumulative MACCE at one-month follow-up was not significantly different between the PI and the PPCI group (p=0.726) as well as the incidence of bleeding endpoint (p=0.446). In the subgroup analysis of the 191 patients who received SK (SK-PI), there was no statistical difference in the occurrence of cumulative MACCE compared to PPCI (p=0.136). Killip classification class III (hazard ratio [HR] 7.50, 95% confidence interval [CI] 3.25 to 17.31, p<0.001), and class IV (HR 9.78, 95% CI 4.31 to 22.21, p<0.001) were independent risk factors for developing MACCE. Conclusion: The streptokinase-based pharmacoinvasive strategy is non-statistically different in terms of efficacy and safety compared to PPCI. This evidence supports the utilization of the SK-PI approach in low- to middle-income countries where the availability of fibrin-specific fibrinolytic agents is often limited. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Arterial and venous thromboembolism is one of the most prevalent diseases and related to ischemic stroke, pulmonary embolism, and myocardial infarction leading to mortality or is morbidity. Fibrinolytic therapy is the most profound lifesaving therapy in these diseases. We aimed to evaluate the demographic features and post-tissue plasminogen activator (tPA) period of patients administered fibrinolytic in the emergency department (ED). Materials and Methods: This retrospective study was conducted with patients instituted fibrinolytic therapy in the ED between January 2018 and July 2021. Age and gender of the patients, vital signs, laboratory tests, comorbidities, drugs used, lifesaving therapies secondary to the present pathology, tPA complications, mortality and similar presentations within the six months period were recorded to the study form. Results: A total of 277 patients were included in the study. Ischemic stroke was the most prevalent disease entailing the institution of tPA (n=252; 91%). The study patients mostly used antihypertensives (n=155, 56%), followed by anti-aggregants (n=101, 36.5%). Intracranial hemorrhage (11.9%) was the most frequent complication secondary to tPA and the study patients had mostly undergone thrombectomy as a lifesaving therapy (n=34, 12.4%). The univariate analysis revealed that antiaggregant usage (n=21, 53.8% vs n=80, 33.6%; p=0.01), systolic blood pressure (160 mmHg, IQR: 138-190 vs 150 mmHg 130-169; p=0.02) and diastolic blood pressure (90 mmHg, IQR: 75-100 vs 83 mmHg, IQR: 72-94; p=0.03) differ between the patients with and without a post-tPA hemorrhage. Conclusion: According to the results of this study, ischemic stroke is the main pathology related to tPA administration in ED. Hypertension was the most seen comorbidity in study patients, mostly using anti-hypertensive and anti-aggregants. Intracranial hemorrhage was the most prevalent complication owing to tPA use, and systolic and diastolic blood pressures and anti-aggregant use pertain to post-tPA hemorrhages. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Endovascular coiling techniques have emerged as an alternative and effective approach for treating intracranial aneurysms. However, in some cases, previously coiled aneurysms may require secondary treatment with surgical clipping, presenting a more complex challenge compared with the initial intervention. 1,2 We present the case of a 39-year-old man with a residual class III Raymond-Roy occlusion partially coiled aneurysm at the left middle cerebral artery bifurcation (Video 1). Faced with the risks of rerupture, the patient underwent microsurgical treatment after providing consent. Despite successful initial microsurgical clipping, postoperative complications arose due to coil protrusion into the middle cerebral artery bifurcation, resulting in thrombotic occlusion of the frontal M2 branch. Emergency repeat microsurgical intervention and administration of a thrombolytic agent were performed to address complications, ultimately preserving blood flow. Subsequent endovascular placement of a flow-diverting stent 7 weeks after discharge confirmed complete occlusion of the aneurysm. The patient had no neurological deficit on follow-up. When planning microsurgical clipping of an aneurysm previously treated with coils, it is critical to consider coil placement, as there is a risk of prolapse if the coil is in the neck of the aneurysm. Thrombosis of the cerebral arteries is a potential complication of microsurgical clipping of partially coiled intracranial aneurysms, and injection of a fibrinolytic agent into thrombosed arterial branches may be an effective intraoperative method for treating intra-arterial thrombosis. 3 This case illustrates the challenges associated with treating partially coiled aneurysms, highlighting the significance of careful planning when considering microsurgical treatment. [ABSTRACT FROM AUTHOR]

A 48-year-old man presented with gradually worsening dyspnea three days after testing positive for COVID-19. He was admitted to the intensive care unit on maximum high flow nasal cannula settings and subsequently intubated for hypoxic respiratory failure due to COVID-19 pneumonia. Two weeks into the patient's hospital course, he unexpectedly developed worsening hypotension with multiple vasopressor requirements. Labs revealed an unexpected hemoglobin drop from 12.5 to 7.9 g/dL. Chest radiograph showed near complete opacification of the right hemithorax concerning for hemothorax. This case presentation describes a rare phenomenon of spontaneous hemothorax in a patient with COVID-19.

OBJECTIVES: This study investigated the current status of acute ischemic stroke (AIS) management in an Iranian emergency department (ED). METHODS: A descriptive study using a retrospective chart review was conducted on medical records of 270 patients with AIS who presented to the ED of a tertiary university hospital in the northeast of Iran from March 22 to September 22, 2019. The steps of this review process included instrument identification, medical records retrieval, data extraction, and data verification. RESULTS: Of patients with AIS, 88.9% (n = 240) did not receive stroke code activation. For the 11.1% of patients (n = 30) who received activation, 7% of codes (n = 19) were canceled by the acute stroke team and IV recombinant tissue plasminogen activator (r-tPA) was only administered for 4.1% of patients (n = 11). ED arrival outside 4.5 h from symptom onset was the main barrier to IV r-tPA administration for 83.8% of potentially eligible patients with AIS (n = 217). The median door-to-needle time was 70 min (interquartile range: 47-90 min). CONCLUSIONS: There was a better clinical performance in terms of critical time goals in potentially eligible patients with AIS if managed with stroke team activation compared to no stroke team activation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective., Background: In the 1980s, aneurysmal subarachnoid clot lysis with urokinase or alteplase (rtPA) was proven to effectively reduce vasospasm and neurological ischemic deficits, improving survival and clinical outcomes. This therapeutic option has been less commonly used since the introduction of endovascular treatment, but renewed interest has sparked in recent years., Aims: To investigate if single bolus cisternal urokinase subarachnoid clot lysis reduces vasospasm, neurological ischemic deficits, mortality, and permanent CSF diversion rates and improves outcomes. Additionally, we want to unveil which subgroup of patients benefit most., Material and Methods: Study period January 2007-December 2019. 415 patients with saccular aneurysms and >1-year follow-up analyzed. Six groups created according to the treatment applied: no treatment (42), only external ventricular drain (16), endovascular treatment (155), clipping (53), clipping + 100,000UI urokinase (116), and incidental brain aneurysm (33)., Results: The rates and severity of vasospasm, permanent CSF diversion, and mortality in Fisher grades ≥3 subarachnoid hemorrhages were higher with endovascular treatment than with surgical clipping with simultaneous cisternal urokinase administration. The best GOSE results on discharge and 6- and 12-month follow-ups happened in this latter group. The differences were more significant the higher the Fisher grade. We neither saw intraventricular, subarachnoid, subdural, or epidural hemorrhages nor systemic fibrinolysis or infections that could be related to the urokinase administration., Conclusions: Single bolus cisternal 100,000UI urokinase administration during emergency aneurysm clipping reduces vasospasm, mortality, and the need for permanent CSF diversion. It is not associated with a significant increase in intracranial hemorrhages or systemic fibrinolysis., Competing Interests: The authors declare that they have no competing financial interests of personal relationships that could have apperared to influence the work reported in this paper., (© 2024 The Authors.)

Purpose: Transatlantic guidelines endorse quality metrics for timely reperfusion in patients with ST-elevation myocardial infarction (STEMI). Compliance in low- and middle-income countries (LMICs) is largely unknown., Study Design: We prospectively evaluated 2928 STEMI patients in Kerala, India, across 16 PCI-capable hospitals who received reperfusion with either primary percutaneous coronary intervention (PPCI) or fibrinolysis. Primary endpoint was a major adverse cardiovascular event (MACE) composite of death, non-fatal myocardial infarction, stroke or readmission for heart failure at 1-year., Results: Among reperfused STEMI patients, 320 (10.9%) received timely reperfusion with either PPCI or fibrinolysis, 1985 (67.8%) received delayed PPCI, and 623 (21.3%) received delayed fibrinolysis. Timely reperfusion had lower unadjusted MACE rates than delayed PCI or fibrinolysis (timely reperfusion: 11.9%, delayed PPCI: 13.6%, delayed fibrinolysis: 23.9%, P < 0.001). Mortality was lowest in the timely reperfusion group (timely reperfusion: 6.3%, delayed PPCI: 7.8%, delayed fibrinolysis 18.8%, P < 0.001). After multivariate analysis, delayed fibrinolysis had a higher MACE rate (HR 1.52 95% CI 1.04-2.21) and mortality (HR 1.97, 95% CI 1.18-3.25) compared to timely reperfusion. Total ischemic time > 3 h and delayed first medical contact-to-needle time predicted MACE at 1 year., Conclusions: Among STEMI patients in Kerala, India, only one in 10 eligible patients received timely reperfusion. Longer total ischemic times and delayed fibrinolysis were associated with 1-year MACE. Improving timely reperfusion is critical to enhancing STEMI outcomes in LMICs. What is already known on this topic Given the established link between delay to reperfusion and worse major adverse cardiac events (MACE), global efforts have concentrated on minimizing different components of the total ischemic time to improve ST-elevation myocardial infarction (STEMI) outcomes. Compliance in low- and middle-income countries (LMICs) is largely unknown. What this study adds In this cohort of STEMI patients in Kerala, India, total ischemic time and first medical contact-to-needle time correlated with long-term MACE rates, whereas other timeliness indicators did not. How this study might affect research, practice or policy Our study highlights the significant barriers to accessing STEMI care that are prevalent in LMICs despite incremental growth in the number of PCI-capable hospitals. The pre-hospital phase within total ischemic time is the most important quality improvement metric of STEMI care in LMICs, especially for patients chosen for fibrinolysis., (© The Author(s) 2024. Published by Oxford University Press on behalf of Fellowship of Postgraduate Medicine.)

Summary: Background: Due to limited access to primary percutaneous coronary intervention for the management of ST-segment elevation myocardial infarction (STEMI) in low-to-middle-income countries (LMICs), fibrinolysis serves as a vital alternative reperfusion therapy. Among fibrinolytic agents, the cost-effectiveness of tenecteplase (TNK) in LMICs as compared to streptokinase (SK) for STEMI management remains unknown. Methods: Cost-effectiveness was analyzed using a hybrid model consisting of short-term analysis (30-days decision tree model) and long-term analysis (Markov model). Both health care provider and societal perspectives over a lifetime horizon with 3% discount rate were considered. Input parameters were obtained from Thailand's national health database, a network meta-analysis and literature review. Outcome measure was an incremental cost-effectiveness ratio (ICER) determined by an incremental cost per quality-adjusted life years (QALY) gain. An ICER of less than $5,590 per QALY gain is considered cost-effective. Series of sensitivity analyses were also performed. Findings: From the societal perspective, TNK increases cost by $827 and increases QALY by 0·173. Thus, the ICER is $4,777 per QALY gained. Similarly, the ICER from health care provider perspective is $4,664 per QALY gained. In the probabilistic sensitivity analysis, using 5,590 USD per QALY as threshold, the probability of TNK being cost-effective was 83% from both perspectives. The most influential parameters were risk ratio of death for treatment with TNK compared to SK and drug cost of TNK. Interpretation: In a resource-limited country like Thailand, tenecteplase is a cost-effective fibrinolytic drug for treatment of STEMI compared to streptokinase. Funding: None.

• Widespread microthrombosis is considered as an etiology for impaired oxygenation in patients with COVID-19 with ARDS. • Systemic thrombolytic versus prophylactic- and therapeutic-dose anticoagulation were compared in present study. • Systematic thrombolytic therapy did not improve oxygenation in critically ill patients with COVID-19. [ABSTRACT FROM AUTHOR]

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

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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

Here, we reported a 32-year-old male presenting to the emergency department with respiratory symptoms and coronavirus disease 2019 (COVID-19) diagnosis. Multiple thrombi were detected in his heart and inferior vena cava, probably due to former deep-vein thrombosis. The presence of patent foramen ovale and high pressure of the right heart caused the clots to enter the heart's left side. He received fibrinolytics, and his condition improved with no need for surgery. Hence, patients with impending paradoxical embolism may take advantage of medical treatment, such as fibrinolytics. Moreover, COVID-19 appears to be associated with a strong thrombotic tendency, and anticoagulants might be helpful.

ImportanceAlthough patients with acute stroke are routinely evaluated for potential treatment (ie, treatability of the stroke), preventability of the presenting stroke is generally not seriously considered.ObjectiveTo systematically analyze stroke preventability.Design, setting, and participantsWe evaluated medical records of 274 consecutive patients discharged with a diagnosis of ischemic stroke between December 2, 2010, and June 11, 2012, at the University of California Irvine Medical Center. Mean (SE) patient age was 67.2 (0.8) years. Data analysis was conducted from July 3, 2014, to August 4, 2015.ExposuresMedical records were systematically examined for demographic information, stroke risk factors, stroke severity, and acute stroke treatment.Main outcomes and measuresWe defined stroke preventability as the degree to which the patient's presenting stroke was preventable. Using variables easily determined at onset of stroke, we developed a 10-point scale (0, not preventable; 10, most preventable) to classify the degree of stroke preventability. Our focus was effectiveness of treatment of hypertension (0-2 points), hyperlipidemia (0-2 points), and atrial fibrillation (0-4 points), as well as use of antithrombotic treatment for known prior cerebrovascular and cardiovascular disease (0-2 points).ResultsTotal risk scores ranged from 0 to 8 (mean [SE], 2.2 [0.1]), with 207 patients (75.5%) exhibiting some degree of preventability (score of 1 or higher). Seventy-one patients (25.9%) had scores of 4 or higher, indicating that the stroke was highly preventable. Severity of stroke as determined by the National Institutes of Health Stroke Scale score was not related to preventability of stroke. However, 21 of 71 patients (29.6%) whose stroke was highly preventable were treated with intravenous or intra-arterial acute stroke therapy while these treatments were provided for only 13 of 67 patients (19.4%) with scores of 0 (no preventability) and 19 of 136 patients (14.0%) with scores of 1 to 3 (low preventability) (P = .03).Conclusions and relevanceMost patients with acute stroke exhibited some degree of preventability. Preventability and treatment of stroke were significantly associated, indicating that the most preventable strokes paradoxically were more likely to receive acute treatment.

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. [ABSTRACT FROM AUTHOR]

Empyema, a severe complication of pneumonia, trauma, and surgery is characterized by fibrinopurulent effusions and loculations that can result in lung restriction and resistance to drainage. For decades, efforts have been focused on finding a universal treatment that could be applied to all patients with practice recommendations varying between intrapleural fibrinolytic therapy (IPFT) and surgical drainage. However, despite medical advances, the incidence of empyema has increased, suggesting a gap in our understanding of the pathophysiology of this disease and insufficient crosstalk between clinical practice and preclinical research, which slows the development of innovative, personalized therapies. The recent trend towards less invasive treatments in advanced stage empyema opens new opportunities for pharmacological interventions. Its remarkable efficacy in pediatric empyema makes IPFT the first line treatment. Unfortunately, treatment approaches used in pediatrics cannot be extrapolated to empyema in adults, where there is a high level of failure in IPFT when treating advanced stage disease. The risk of bleeding complications and lack of effective low dose IPFT for patients with contraindications to surgery (up to 30%) promote a debate regarding the choice of fibrinolysin, its dosage and schedule. These challenges, which together with a lack of point of care diagnostics to personalize treatment of empyema, contribute to high (up to 20%) mortality in empyema in adults and should be addressed preclinically using validated animal models. Modern preclinical studies are delivering innovative solutions for evaluation and treatment of empyema in clinical practice: low dose, targeted treatments, novel biomarkers to predict IPFT success or failure, novel delivery methods such as encapsulating fibrinolysin in echogenic liposomal carriers to increase the half-life of plasminogen activator. Translational research focused on understanding the pathophysiological mechanisms that control 1) the transition from acute to advanced-stage, chronic empyema, and 2) differences in outcomes of IPFT between pediatric and adult patients, will identify new molecular targets in empyema. We believe that seamless bidirectional communication between those working at the bedside and the bench would result in novel personalized approaches to improve pharmacological treatment outcomes, thus widening the window for use of IPFT in adult patients with advanced stage empyema. [ABSTRACT FROM AUTHOR]

Abstract 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.

Abstract 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.

Wei-Yi Ye,1,2 Jia Li,2 Xiang Li,2 Xue-Zhi Yang,2 Yi-Yun Weng,2 Wei-Wei Xiang,3 Ou Zhang,2 Bo-Xi Ke,4,* Xu Zhang2,* 1Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Zhejiang, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 3School of Mental Health, Wenzhou Medical University, Wenzhou, People’s Republic of China; 4Taizhou Central Hospital (Taizhou University Hospital), Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xu ZhangDepartment of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of ChinaTel +86 577 5557 9372Fax +86 577 5557 9318Email 1102805261@qq.comBo-Xi KeTaizhou Central Hospital (Taizhou University Hospital), Zhejiang 318000, People’s Republic of ChinaTel +86 139 5769 8220Email keboxi@163.comPurpose: Red blood cell (RBC) distribution width (RDW) is known to reflect the heterogeneity of RBC volume, which may be associated with cardiovascular events or mortality after myocardial infarction. However, the association between RDW and stroke, especially regarding endpoints such as death, remains ambiguous. This study aimed to explore the prognostic value of RDW and its effect on mortality among patients with acute ischemic stroke (AIS) undergoing intravenous thrombolysis (IVT) after one year.Patients and Methods: We retrospectively reviewed patients with AIS treated with IVT between January 2016 and March 2018. We grouped the patients according to modified ranking scale (MRS) scores as follows:0– 2, favorable functional outcome group; and 3– 6, unfavorable functional outcome. Predictors were determined using multivariate logistic regression (MVLR). The area under receiver-operating characteristic curve (AUC) was used to evaluate the predictive capability of variables. Furthermore, the Cox proportional hazard model was used to assess the contribution of risk factors to the outcome of death at one year later.Results: MVLR analysis showed that RDW (odds ratio [OR], 1.179; 95% confidence interval [CI], 0.900– 1.545; p = 0.232) was not an independent predictor of unfavorable functional outcome, but it (OR 1.371; 95% CI 1.109– 1.696; p = 0.004) was an independent biomarker for all-cause mortality. The optimal RDW cut-off value to predict mortality was 14.65% (sensitivity: 42%, specificity: 88.3%, AUC: 0.649, p < 0.001). Furthermore, higher RDW (hazard ratio, 2.860; 95% CI, 1.724– 4.745; p < 0.001) indicated a greater risk of death.Conclusion: The baseline RDW is a potential predictor of mortality in patients with AIS undergoing IVT, but RDW might not be associated with worse survival function among stroke survivors, which will help us to improve treatments and the management of patients with AIS.Keywords: red blood cells, death, inflammatory, cerebrovascular accident, fibrinolytic therapy, predictor

Empyema, a severe complication of pneumonia, trauma, and surgery is characterized by fibrinopurulent effusions and loculations that can result in lung restriction and resistance to drainage. For decades, efforts have been focused on finding a universal treatment that could be applied to all patients with practice recommendations varying between intrapleural fibrinolytic therapy (IPFT) and surgical drainage. However, despite medical advances, the incidence of empyema has increased, suggesting a gap in our understanding of the pathophysiology of this disease and insufficient crosstalk between clinical practice and preclinical research, which slows the development of innovative, personalized therapies. The recent trend towards less invasive treatments in advanced stage empyema opens new opportunities for pharmacological interventions. Its remarkable efficacy in pediatric empyema makes IPFT the first line treatment. Unfortunately, treatment approaches used in pediatrics cannot be extrapolated to empyema in adults, where there is a high level of failure in IPFT when treating advanced stage disease. The risk of bleeding complications and lack of effective low dose IPFT for patients with contraindications to surgery (up to 30%) promote a debate regarding the choice of fibrinolysin, its dosage and schedule. These challenges, which together with a lack of point of care diagnostics to personalize treatment of empyema, contribute to high (up to 20%) mortality in empyema in adults and should be addressed preclinically using validated animal models. Modern preclinical studies are delivering innovative solutions for evaluation and treatment of empyema in clinical practice: low dose, targeted treatments, novel biomarkers to predict IPFT success or failure, novel delivery methods such as encapsulating fibrinolysin in echogenic liposomal carriers to increase the half-life of plasminogen activator. Translational research focused on understanding the pathophysiological mechanisms that control 1) the transition from acute to advanced-stage, chronic empyema, and 2) differences in outcomes of IPFT between pediatric and adult patients, will identify new molecular targets in empyema. We believe that seamless bidirectional communication between those working at the bedside and the bench would result in novel personalized approaches to improve pharmacological treatment outcomes, thus widening the window for use of IPFT in adult patients with advanced stage empyema.

Here, we reported a 32-year-old male presenting to the emergency department with respiratory symptoms and coronavirus disease 2019 (COVID-19) diagnosis. Multiple thrombi were detected in his heart and inferior vena cava, probably due to former deep-vein thrombosis. The presence of patent foramen ovale and high pressure of the right heart caused the clots to enter the heart's left side. He received fibrinolytics, and his condition improved with no need for surgery. Hence, patients with impending paradoxical embolism may take advantage of medical treatment, such as fibrinolytics. Moreover, COVID-19 appears to be associated with a strong thrombotic tendency, and anticoagulants might be helpful. [ABSTRACT FROM AUTHOR]

Pulmonary embolism (PE) is a common and potentially fatal condition. Despite advances in diagnostic procedures, late detection and non-detection of this condition is also not uncommon. In patients with PE, recurrent embolisms and death can be prevented with prompt diagnosis and adequate treatment. Due to presentation with a non-specific clinical picture and symptomatology, unfortunately almost one third of the patients remain undiagnosed and untreated. We know that there is a large difference in outcome between treated and untreated patients with PE (25-30% mortality in untreated and 2-8% in treated patients). We present a case of PE in the era of the COVID-19 pandemic in an adult patient with acute dyspnea, vomiting, presyncope, chest pain, and shock. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Pediatric Infection / Çocuk Enfeksiyon Dergisi is the property of Journal of Pediatric Infection / Cocuk Enfeksiyon Dergisi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction/Objective. Patients with submassive (intermediate risk) pulmonary embolism (PE) represent a very heterogeneous group, whose therapeutic strategy still questions whether some groups of patients would have net clinical benefit from fibrinolytic therapy (FT). Methods. From the institutional pulmonary embolism registry, 116 patients with submassive PE were identified, and the relation of their outcome to FT was analyzed using the propensity score (PS) adjustment. The primary endpoint was the composite of death, in-hospital cardiopulmonary deterioration, or recurrence of PE. Safety outcomes were updated TIMI non-CABG related major and minor bleeding. Results. According to Cox regression analysis, the incidence of composite endpoint was significantly lower in patients treated with FT compared to anticoagulant therapy (AT) only (PS adjusted HR 0.22; 95% CI 0.05–0.89; p = 0.039). But, when patients were stratified into four PS quartiles, only patients in the highest PS quartile that received fibrinolysis, had significantly lower composite event rate than patients treated with AT (HR 0.20; 95% CI 0.01–0.56; p = 0.016). The overall mortality of the study group was 5.2% and there was no significant difference between the treatment groups. Total bleeding was significantly more frequent in FT patients (HR 3.07; 95% CI 1.02–13.29; p = 0.047), but not the major one. Conclusion. The use of FT was associated with a better outcome compared to AT in patients with submassive PE, but the benefit was mainly driven from those with highest values of PS, i.e. with the highest baseline risk. The rate of major bleeding was not significantly increased by FT.

Background: Pulmonary embolism (PE) is a lethal clinical condition requiring immediate systemic thrombolysis to decrease mortality. Reteplase has been extensively used in acute myocardial infarction but studies in massive PE are rare. We have presented here efficacy and safety of reteplase in patients with high risk PE diagnosed on basis of bedside transthoracic echocardiography. Methods: This was retrospective study including 20 patients of massive PE undergoing thrombolysis with reteplase. Bedside TTE was used to evaluate presence of RV dysfunction and thrombi in these patients with hemodynamic compromise. Safety and efficacy outcomes were analysed till three months of follow up. Results: 12 patients (60%) included in the study were males and mean age was 41 ± 19 years. The dyspnoea, chest pain and haemoptysis improved in all patients after thrombolysis. At discharge, RV dilatation normalised, systolic pulmonary artery pressure decreased, systolic blood pressure significantly increased and hypoxemia had completely corrected. Two patients had minor self-limiting bleeding episodes in form of mild haematuria and oral bleeding. During the follow up period of 3 months all patients were clinically stable and there were no bleeding episodes or death. Moreover, there was no recurrence of PE and/or DVT. Conclusion: Reteplase is highly efficacious in massive pulmonary embolism and results in rapid clinical improvement. Moreover, it can be safely used without increased risk of significant bleeding or mortality. Although limited by retrospective nature, reteplase appears to be an attractive option for massive PE but large prospective studies are further required.

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.

Abstract 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.

Abstract Antithrombotic therapy has long been a trade‐off between antithrombotic effects and hemorrhagic risk. With the aid of nanotechnology, antithrombotic drugs have realized and will further realize highly controllable targeting, disease microenvironment responsive release, imaging‐guided treatment, and reversal agents’ development in parallel with novel antithrombotics. Preclinical studies have indicated that intelligent antithrombotic nanomedicines show potential in preventing hemorrhagic risk, evading the balancing act of current antithrombotic treatments. However, none of these nanomedicines have come into clinical trials. In this review, we present a strategic summary of the field of nanoantithrombotics, which is needed to guide the design and application of the next generation of antithrombotic nanomedicines. Herein, we present the recent progress in the preclinical studies of this field, which can be divided into three categories: fibrinolytic, anticoagulant, and antiplatelet therapies. In addition, we provide an outlook on how future antithrombotic nanomedicine design can better overcome the current translational challenges for clinical use.

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.

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. [ABSTRACT FROM AUTHOR]

Antithrombotic therapy has long been a trade‐off between antithrombotic effects and hemorrhagic risk. With the aid of nanotechnology, antithrombotic drugs have realized and will further realize highly controllable targeting, disease microenvironment responsive release, imaging‐guided treatment, and reversal agents' development in parallel with novel antithrombotics. Preclinical studies have indicated that intelligent antithrombotic nanomedicines show potential in preventing hemorrhagic risk, evading the balancing act of current antithrombotic treatments. However, none of these nanomedicines have come into clinical trials. In this review, we present a strategic summary of the field of nanoantithrombotics, which is needed to guide the design and application of the next generation of antithrombotic nanomedicines. Herein, we present the recent progress in the preclinical studies of this field, which can be divided into three categories: fibrinolytic, anticoagulant, and antiplatelet therapies. In addition, we provide an outlook on how future antithrombotic nanomedicine design can better overcome the current translational challenges for clinical use. [ABSTRACT FROM AUTHOR]