Local Bleeding Research Articles

Impact of Kidney Disease in Patients Undergoing Catheter Directed Interventions for Intermediate to High-Risk Pulmonary Embolism.

Catheter-directed interventions (CDIs) for pulmonary embolism (PE) continue to evolve. However, due to the paucity of data, their use has been limited in patients with underlying kidney disease. The National Readmission Database (2016-2020) was utilized to identify intermediate to high-risk PE (IHR-PE) patients requiring CDI (thrombectomy, thrombolysis, and ultrasound-assisted thrombolysis). Cohorts were stratified based on the presence of CKD stage ≥3, including ESRD. A Propensity Score Matching (PSM) model was applied to compare outcomes. From 2016-2020, 20795 patients with IHR-PE underwent CDIs. Most were done in the non-CKD/ESRD population (N:18438, 88.7%), while only 2357 (11.3%) were done in the CKD/ESRD population. After propensity matching, the CKD/ESRD population had higher adverse events, including mortality (7.3% vs. 5.1%, p: 0.036), need for transfusions (52.6% vs. 44.7%, p<0.001), and acute bleeding (15.4% vs. 10.6%, p<0.001). CKD/ESRD population had a higher median LOS (5 vs. 4 days, p<0.001) and total cost ($32935 vs. $29805, p<0.001) in the index admission. Over the study period, total cost decreased in the CKD/ESRD population ($37829 to $31436, p-trend: 0.024) but remained the same in the non-CKD/ESRD population (p-trend>0.05). 180-day readmission rates were higher in the CKD/ESRD population (24.7% vs. 17.5%, p: 0.006). Our subgroup analysis, excluding ESRD patients, showed no significant difference in in-hospital mortality (6.5% vs. 7.3%, p>0.05), but the rates of thoracic or respiratory bleeding (4.5% vs. 2.6%, p:0.012), need for transfusions (52.4% vs.. 43.5%, p<0.001), and AKI (57.1% vs. 23.2%, p<0.001) were higher in patients with CKD undergoing CDIs for IHF-PE. CKD/ESRD patients requiring catheter-directed interventions for IHR-PE had higher periprocedural mortality and acute bleeding. The presence of ESRD mainly drove periprocedural mortality in our study, while the presence of non-dialyzed CKD was associated with higher rates of non-fatal localized hemorrhage.

Investigation of the Bifid Mandibular Canal Prevalence in the Central Anatolian Population: A Retrospective CBCT Study

Aim: This study aims to retrospectively examine cone beam computed tomography (CBCT) images obtained for various reasons to determine the prevalence of bifid mandibular canal (BMC) in the Central Anatolian population. Material and Method: A total of 518 mandibular canals (right and left sides evaluated separately) from 259 CBCT images (145 female, 114 male) that met the inclusion criteria were included in the study. BMCs were categorized as retromolar canal, forward canal, dental canal, and buccolingual canal. Individuals were grouped into age ranges of 15-34, 35-54, and 55-75 years. Statistical analysis was performed using IBM SPSS version 25.0. The data were then compared based on side (right/left), gender, and age. Results: BMC was observed in 35.9% of the total participants. The most common subtype was the forward canal (Type 3) at a rate of 41.9%, followed by the retromolar canal at 35.4%, the dental canal at 31.1%, and the buccolingual canal at 26.8%. While there was no significant difference in BMC prevalence by gender, the prevalence was found to be higher in the second age group. Conclusion: In conclusion, regardless of subtype, determining the presence of BMC in patients undergoing mandibular procedures is extremely important for informing the clinician, especially to avoid complications such as local anesthesia failure, postoperative paresthesia, or bleeding. If present, it should be noted in the CBCT report.

SPATEs promote the survival of Shigella to the plasma complement system upon local hemorrhage and bacteremia

Shigella spp. are the causative agents of shigellosis, which remains a leading cause of death in children under the age of 5. Symptoms of shigellosis include bloody diarrhea, associated to colon hemorrhage; in more severe cases, Shigella bacteremia is induced. These clinical features indicate that Shigella are exposed and survive exposure to plasma, locally and systemically, although this has not yet been studied at a molecular level. In this report, we confirmed in a guinea pig model of shigellosis that both S. flexneri 5a and S. sonnei induced local hemorrhages and we demonstrated that Shigella reached CD31+/CD34+ blood vessels located in the mucosa during the late stages of infection, and further disseminated in the bloodstream. These results confirmed the exposure of Shigella to plasma components during its virulence cycle. We demonstrated that all the tested Shigella strains survived plasma exposure in vitro, and we showed that Serine Protease Autotransporters of Enterobacteriaceae (SPATEs) contribute to Shigella dissemination within the colonic mucosa and in the bloodstream. We have confirmed that SPATEs are expressed and secreted in poorly oxygenated environments encountered by Shigella during late infection stages. We further demonstrated that SPATEs promoted Shigella survival in plasma, by cleaving complement component 3 (C3), thereby impairing the complement system activation. We have shown here that the ability of Shigella to survive plasma exposure is a key factor in its virulence, both within primary foci and systemically.

The impact of targeted bleeding source treatment on the risk of recurrent bleeding after percutaneous coronary intervention among patients with a history of prior bleeding

Abstract Background Prior bleeding is one of the strongest predictors for bleeding after percutaneous coronary intervention (PCI). Whether targeted treatment of the prior bleeding site affects the risk of bleeding after PCI is unknown to date. Methods From an all-comers population undergoing PCI between 2009-2019, patients with BARC 2-4 bleeding prior to index PCI were identified. Among those, the recurrence of BARC 2-5 bleeding at the same bleeding site, any BARC 2-5 bleeding, and mortality were compared throughout 1 year after PCI between patients with vs. without targeted treatment at the prior bleeding site. Targeted treatment was defined as medical, interventional, or surgical therapy targeted to cure the cause of bleeding. Adjusted hazard ratios (HRadj) were extracted from Cox regressions. Inverse probability weights were computed from a logistic regression with targeted treatment as dependent variable, and the following covariates: ARC-HBR variables associated with ≥4% 1-year bleeding risk in this registry (including oral anticoagulation), aspirin, potent P2Y12 inhibitor treatment, and prior bleeding site. Results Out of 18’510 patients enrolled from 2009-2019, 845 (4.6%) had a history of prior BARC 2-4 bleeding before PCI. Mean age was 71.6 years, 25% were female, and 52% presented with acute coronary syndrome. Patients with targeted treatment were significantly younger (70.3 vs. 72.5 years, p=0.005) and had more frequently malignancies (25% vs. 18%, p=0.012). 26/344 (7.6%) of patients with targeted treatment vs. 31/501 (6.2%) of patients without targeted treatment experienced recurrent BARC 2-5 bleeding at the same bleeding site (HRadj 1.35, 95% CI 0.79-2.30, p=0.268). 45/344 (13.1%) of patients with targeted treatment vs. 59/501 (11.8%) of patients without targeted treatment experienced any recurrent BARC 2-5 bleeding (HRadj 1.16, 95% CI 0.78-1.72, p=0.473). The rate of mortality was also similar between the groups (targeted treatment 13.7% vs. no targeted treatment 12.4%, HRadj 1.13, 95% CI 0.76-1.67, p=0.549). Conclusions Among patients with a bleeding history before PCI, half of the recurrent bleeding events throughout 1-year after PCI occurred at the same bleeding site, regardless of whether the bleeding source underwent targeted treatment. These findings imply that targeted treatment is not protective for recurrent bleeding events after PCI and that prior bleeding represents rather a systemic than local bleeding risk.Frequency of bleeding sitesKaplan Meier curves

Clinical manifestations of alpine pit viper (Trimeresurus gracilis) bites

Introduction The alpine pit viper, Trimeresurus gracilis, is an endemic species in Taiwan. The incidence of human envenoming is rare. Case summaries We present three events in two patients bitten by Trimeresurus gracilis. In the first patient, envenoming inflicted pain, local bleeding, hemorrhagic bulla, and progressive swelling, leading to necrosis of the bite wound. In the second patient, the two snakebites caused pain and progressive swelling. There were no systemic effects such as organ damage or neurological deficits observed. A paraspecific antivenom against Trimeresurus stejnegeri and Protobothrops mucrosquamatus was used to treat both patients, with a favorable outcome in each. Discussion Combined with the clinical manifestations of two previously reported cases of Trimeresurus gracilis envenoming, the known effects of Trimeresurus gracilis venom in humans include local toxicities, severe soft-tissue damage, compartment syndrome, and coagulopathy without spontaneous systemic bleeding. The paraspecific antivenom, which has demonstrable cross-neutralization effects in animal studies, appeared to be effective against the local toxicities as the patients showed prompt cessation of the progression of their swelling. Conclusions The knowledge of clinical manifestations and management approaches to Trimeresurus gracilis envenoming is helpful for patient care. The use of the paraspecific antivenom should be considered in managing such envenoming.

Management of anticoagulant-related soft tissue bleeding

Spontaneous, severe, and life-threatening soft tissue bleeding (STB) in patients taking anticoagulants is associated with high morbidity and mortality due to the substantial blood loss and nonspecific clinical symptoms. The optimal management of these predominantly older patients with multiple comorbidities has not yet been unanimously clarified. This work comprises aliterature search and analysis of the pertinent retrospective studies and case series. Structured diagnostic workup with contrast-enhanced computed tomography (CT) is essential for planning transarterial embolization (TAE). Contrast agent extravasation, the signal flare phenomenon, and the hematocrit effect are all indicative of active bleeding or an anticoagulant-related hematoma. For TAE, coils, particles, and liquid embolic agents can be used alone or in combination. Aback door/front door embolization should be strived for. Transarterial embolization is the method of choice for managing anticoagulant-related localized or diffuse spontaneous soft tissue bleeding in the context of hemodynamic stabilization of the patient.

Analysis of risk factors for bleeding as a complication of ultrasound-guided percutaneous liver biopsy examination

Objective: To explore the independent risk factors for bleeding in patients following percutaneous liver biopsy examination. Methods: The clinicopathological data of patients who underwent percutaneous liver biopsy examination at Nanjing Second Hospital from January 2012 to December 2021 were retrospectively collected. Univariate and multivariate logistic regression analysis were used to investigate the effect of age, gender, lesion type (diffuse liver parenchymal lesions, focal liver lesions), number of biopsies, tissue length, presence or absence of cirrhosis, presence or absence of portosystemic shunt, erythrocytes, white blood cells, hemoglobin, platelets, prothrombin time, fibrinogen, international normalized ratio, and liver biochemical indicators on bleeding following liver biopsy, as well as to screen independent risk factors. Results: A total of 3 331 patients were examined by percutaneous liver biopsy, and 3 060 cases were actually included by excluding 271 cases who took consultation from other hospitals. The overall postoperative hemorrhagic rate was 1.6% (49/3 060). Of which, forty-four cases (1.4%) had overt bleeding (hemodynamic changes or hemoglobin decreased by more than 20 g/L), five cases (0.2%) had minor bleeding, three cases had subcapsular hepatic hemaotma, and two cases had local bleeding from liver biopsy. Among the overt bleeding cases, two cases were in the off-label group (platelet<50×109/L or international normalized ratio>1.5), and the rest were in the non-off-label group. The results of univariate analysis showed that factors such as focal liver lesions, portosystemic shunt, prolonged prothrombin time, increased international normalized ratio, bilirubin, and alkaline phosphatase were associated with bleeding after liver biopsy in the non-off-label group. The multivariate collinearity diagnosis revealed statistically significant differences for the indicators. Multivariate logistic regression analysis finally included factors such as lesion type, portosystemic shunt, international normalized ratio, total bilirubin, and alkaline phosphatase. The results showed that patients with focal liver lesions were more prone to bleed after surgery than patients with diffuse liver parenchymal lesions (OR=3.396, P=0.002, 95%CI: 1.596-7.228). Patients with portosystemic shunt were more prone to bleed than those without portosystemic shunt (OR=3.301, P=0.018, 95%CI: 1.232-8.845). Patients were more likely to experience bleeding following liver biopsy when their total bilirubin levels were elevated (OR=1.006, P<0.001, 95%CI:1.003-1.008). Conclusion: Focal liver lesions, portosystemic shunts, and elevated total bilirubin are independent risk factors for bleeding after percutaneous liver biopsy.

Convexity subarachnoid hemorrhage revealed contralateral internal carotid artery dissection due to Eagle syndrome: a case report

BackgroundAtraumatic localized convexity subarachnoid hemorrhage (cSAH) is an uncommon form of nonaneurysmal subarachnoid hemorrhage characterized by bleeding limited to the cerebral convexities. Ipsilateral cSAH can result from a variety of causes, such as internal carotid artery stenosis, obstruction, and dissection, although concomitant contralateral cSAH is exceptionally rare. In this case, the initial findings of cSAH led us to discovering contralateral internal carotid artery dissection (ICAD) and an elongated styloid process (ESP). ESP is recognized as a risk factor for ICAD, which is a hallmark of Eagle syndrome. This sequence of findings led to the diagnosis of Eagle syndrome, illustrating a complex and intriguing interplay between cerebrovascular conditions and anatomical variations.Case presentationA 47-year-old Japanese woman experienced acute onset of headache radiating to her neck, reaching its zenith approximately two hours after onset. Given the intractable nature of the headache and its persistence for three days, she presented to the emergency department. Neurological examination revealed no abnormalities, and the coagulation screening parameters were within normal ranges. Brain computed tomography (CT) revealed right parietal cSAH, while CT angiography (CTA) revealed ICAD and an ESP measuring 30.1 mm on the left side, positioned only 1.4 mm from the dissected artery. The unusual occurrence of contralateral cSAH prompted extensive and repeated imaging reviews that excluded reversible cerebral vasoconstriction syndrome (RCVS), leading to a diagnosis of left ICAD secondary to Eagle syndrome. The patient underwent conservative management, and the dissected ICA spontaneously resolved. The patient has remained recurrence-free for two and a half years.ConclusionsManaging cSAH requires diligent investigation for ICAD, extending beyond its identification to explore underlying causes. Recognizing Eagle syndrome, though rare, as a potential etiology of ICAD necessitates the importance of evaluating ESPs. The method for preventing recurrent cervical artery dissection due to Eagle syndrome is controversial; however, conservative management is a viable option.

ANODYNE study: A double-blind randomized trial of greater occipital nerve block of methylprednisolone and lignocaine versus placebo as a transitional preventive treatment for episodic cluster headache.

There is inadequate evidence of the efficacy of greater occipital nerve block (GONB) for the preventive treatment of cluster headaches. We assessed the efficacy and tolerability of GONB injections as a transitional preventive treatment for episodic cluster headaches (ECH). This randomized, double-blind, placebo-controlled, parallel-group trial conducted at GB Pant Institute of Postgraduate Medical Education and Research, New Delhi, India, included ECH patients diagnosed by ICHD-3 criteria, aged 18-65, with one or more attacks per 24 h for seven days before randomization (baseline). ECH patients were either not on preventive medications or on stable doses for at least three months. ECH patients were randomized to receive active GONB (2 ml methylprednisolone (80 mg) and 2 ml lignocaine (2%)) and placebo (4 ml saline injections). Before giving GONB, lignocaine jelly was applied topically to mask the effect of numbness following the GONB. The primary efficacy endpoint was the mean change in weekly attack frequency from baseline to Week 4. Efficacy analyses were performed in a modified intention-to-treat population that included all patients who received at least one injection of GONB and had a follow-up for one week following GONB. The safety analysis included treatment-emergent adverse effects (TEAE) in all patients who received at least one dose of investigational product. The trial was registered with the Clinical Trials Registry of India (CTRI/2021/21/038397). Forty ECH patients were randomized between December 2021 and January 2023. Thirty-nine patients (19 in the active and 20 in the placebo groups) were available for efficacy analysis. The change in weekly attack frequency from baseline to Week 4 was -11.1 (95% CI: -8.5 to -4.4) for the active group compared to -7.7 (95% CI: -11.8 to -9.8) for placebo (mean difference -3.4 (95% CI: -5.2 to -1.7, p < 0.001). We noted TEAE in 18 (90%) of 20 patients who received the active drug and in 18 (90%) of 20 patients who received a placebo (p = 0.38). The common TEAE were local site bleeding and pain, which were mild and transient. No serious adverse events were reported. This study found that GONB with methylprednisolone and lignocaine significantly reduced the weekly attack frequency from baseline to Week 1 through Week 4 in ECH patients compared to a placebo. GONB was well tolerated.

Clinical Outcomes of Talus Bone Marrow Edema: Comparing Plaster Cast, Crutches, and Walking Boot Treatments.

BACKGROUND Bone marrow edema (BME) basically involves localized hemorrhage and subtle compression fracture within the bone. We compared outcomes of 70 patients with traumatic BME of the talus, treated with a plaster cast, crutches, or walking boot. MATERIAL AND METHODS MRIs diagnosed 70 patients with talus BME who were randomly assigned into 3 groups of different treatments: Group 1 (n=33) patients were treated with plaster cast's Group 2 (n=21) patients used crutches, and Group 3 (n=16) patients used walking boots. The outcome variables were AOFAS and VAS scores. RESULTS No significant difference was demonstrated in the pre-treatment AOFAS scores between the groups (P>0.05). The AOFAS scores differed significantly after treatment, with Group 2 had the greatest increase in scores (P=0.002) and significantly higher AOFAS scores compared to Group 1 (100 [79-100] vs 94 [75-100], P=0.001). No significant difference was found in pre-treatment VAS scores between the groups (P=0.007). The post-treatment VAS scores were significantly reduced, especially for Group 2. Within-group analysis demonstrated a significant decrease of VAS scores for all groups (P<0.001). CONCLUSIONS Use of non-weight-bearing crutches for 3 weeks had better clinical results than use of a plaster cast when treating talus traumatic bone marrow edema. This was reflected in higher AOFAS and VAS, suggesting use of crutches is associated with better pain management and improved function.

PULP REVASCULARIZATION IN LOWER MOLARS

Objective: The aim of this study was to report a pulp revascularization case report performed on a lower molar. Methodology: The searches were carried out on Web of Science, PUBMED Central, BVS/BIREME, Scielo, Brazilian CAPES as well as Google academic portal. Twenty four articles were researched concerning the revascularization process to reach apical finalization. Knowledge from books and periodicals were also consulted, constituting the gray literature to give reliable information for this paper. In order to reinforce the basis of this study, it was decided to use the protocols of Yin (2001) and Pereira et al. (2008). Results: During the reporting process, supported by literature review, it is possible to note that for pulp revascularization to occur successfully, infection control, stimulation of local bleeding and cell activation are necessary steps. Furthermore, factors such as age, clinical cure and nutritional conditions directly influence the success rate of each case.

The Role of Tissue Factor In Signaling Pathways of Pathological Conditions and Angiogenesis.

Tissue factor (TF) is an integral transmembrane protein associated with the extrinsic coagulation pathway. TF gene expression is regulated in response to inflammatory cytokines, bacterial lipopolysaccharides, and mechanical injuries. TF activity may be affected by phosphorylation of its cytoplasmic domain and alternative splicing. TF acts as the primary initiator of physiological hemostasis, which prevents local bleeding at the injury site. However, aberrant expression of TF, accompanied by the severity of diseases and infections under various pathological conditions, triggers multiple signaling pathways that support thrombosis, angiogenesis, inflammation, and metastasis. Protease-activated receptors (PARs) are central in the downstream signaling pathways of TF. In this study, we have reviewed the TF signaling pathways in different pathological conditions, such as wound injury, asthma, cardiovascular diseases (CVDs), viral infections, cancer and pathological angiogenesis. Angiogenic activities of TF are critical in the repair of wound injuries and aggressive behavior of tumors, which are mainly performed by the actions of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1 (HIF1-α). Pro-inflammatory effects of TF have been reported in asthma, CVDs and viral infections, including COVID-19, which result in tissue hypertrophy, inflammation, and thrombosis. TF-FVII induces angiogenesis via clotting-dependent and -independent mechanisms. Clottingdependent angiogenesis is induced via the generation of thrombin and cross-linked fibrin network, which facilitate vessel infiltration and also act as a reservoir for endothelial cells (ECs) growth factors. Expression of TF in tumor cells and ECs triggers clotting-independent angiogenesis through induction of VEGF, urokinase-type plasminogen activator (uPAR), early growth response 1 (EGR1), IL8, and cysteine-rich angiogenic inducer 61 (Cyr61).

Tremendous and infrequently adenoid cystic carcinoma of the breast without any metastasis for more than 20 years: A case report.

Breast adenoid cystic carcinoma is an extremely rare tumor that is incompletely understood, accounting for less than <0.1% of all breast cancers, with an average diameter of 3 cm, and it is extremely rare to see a large, non-metastatic breast adenoid cystic carcinoma with a diameter of about 30 cm. Since this disease is extremely rare, there are few reports in the literature and limited data on clinical diagnosis and treatment. We present a case of a 71-year-old woman with a large, non-metastatic adenoid cystic carcinoma of the left breast and share our opinion on the diagnosis and treatment of this case. A 71-year-old woman with a 20-year-old left breast mass with local bleeding and rupture for 1 hour presented to our hospital for further diagnosis and treatment. A computed tomography scan showed a large soft tissue mass shadow in the left breast and malignancy was considered. Subsequently, tissue aspiration pathology was performed and the results confirmed adenoid cystic carcinoma of the breast. Intraoperative pathology results of radical mastectomy for left breast cancer diagnosed adenoid cystic carcinoma of the breast and immunohistochemistry results of triple-negative breast cancer. Treatment of adenoid cystic carcinoma of the breast included neoadjuvant chemotherapy for breast cancer, radical mastectomy of the left breast, and postoperative chemotherapy. Initially, neoadjuvant chemotherapy for breast cancer was performed, and the TAC regimen was used to successfully reduce the size of the tumor and gain access to surgical treatment for breast cancer. The patient has recovered well after the surgery, with no wound infection or ulceration, and is now waiting for the patient's physical function to recover for postoperative chemotherapy, with no obvious discomfort. Adenoid cystic carcinoma tumors are usually around 3 cm; such a huge 30 cm adenoid cystic carcinoma of the breast is extremely rare, and it is extremely rare to find a breast malignancy that has not developed regional lymph node and distant metastases for more than 20 years. Clinicians must remain vigilant for early breast malignancies at a high age of incidence and conduct further research for diagnosis to avoid delays.

To stop or not to stop novel oral anticoagulants prior to performing joint interventional maneuvers? Evidence from a prospective study that the therapy can be maintained.

Anticoagulation is common in patients undergoing routine musculoskeletal interventional maneuvers. Previous retrospective studies have established the safety of continuing anticoagulation with novel oral anticoagulants (NOACs) when performing this kind of interventions. Indeed, ultrasound (US)-guided interventional maneuvers have shown a superior safety profile compared to blind anatomical maneuvers. To evaluate prospectively the periprocedural bleeding events in NOAC-anticoagulated patients undergoing interventional articular or periarticular procedures. Consecutive patients diagnosed with inflammatory or degenerative rheumatologic pathology requiring interventional maneuvers were prospectively recruited. Group 1 was treated with NOACs, group 2 was treated with vitamin K antagonists, and group 3 was not anticoagulated. Prior to the international maneuver, NOAC therapy was continuously administered, in regimens dictated by the underlying anticoagulation indication. Demographics, comorbidities, laboratory parameters, locally administered medication (corticosteroids or viscosupplementation), interventional maneuver location, needle size, and local bleeding events were recorded. Post-procedural control was performed at 30 min, 48 h, and 7 days. No articular/periarticular bleeding event occurred in patients treated with NOACs, regardless of their type and dosage, locally administered medication, needle size, location, and number of interventions per individual. Several patients in all groups developed small superficial ecchymoses at the injection site. Our results suggest that NOACs are safe to be used in a continuous regimen prior to US-guided injections, even as dual antithrombotic therapy (in combination with aspirin). The use of lower gauge needles, chosen for viscosupplementation therapy, was not burdened with adverse effects on the procedural outcome. Key Points • Currently, no prospective studies have been performed to establish the safety of continuous NOAC anticoagulation when performing routine intra- or periarticular interventional maneuvers. • The study offers an extensive view on a wide spectrum of intra- and periarticular interventional maneuvers including anatomic targets and needle sizes that were not previously assessed. • The study offers a perspective into performing repetitive maneuvers in the same patient, both over a short time and at longer intervals. • The zero periprocedural bleeding risk observed in our study may reassure practitioners and suggest that US-guided interventional therapeutic interventions are safe in patients treated with a continuous regimen of different NOACs.

Tracheostomy Complications Over 5 Years: Decannulation Analysis.

Tracheostomy is a life-saving surgical intervention commonly performed in patients requiring prolonged mechanical ventilation. However, the decannulation process is associated with various complications that can affect patient outcomes. This study aimed to assess complications and their management during decannulation in a cohort of tracheostomy patients at a tertiary care hospital, considering the complexities introduced by prior intubation. A retrospective cohort study was conducted involving 450 patients who underwent tracheostomy during a stipulated timeframe. Data regarding demographic characteristics, complications, and management strategies during decannulation were analysed. Special attention was given to distinguishing between complications directly related to the tracheostomy procedure and those potentially influenced by previous intubation. Out of the 450 patients, 250 experienced minor complications such as localized bleeding, oxygen desaturation, and minor infections. Another 40 faced major complications including severe haemorrhage, tracheal damage, and stenosis. Increasing age and tracheostomy duration were identified as significant predictors of complications. Pharmacological treatments, surgical interventions, and respiratory therapy were among the management strategies employed. The differentiation between complications arising from tracheostomy and prior intubation highlighted the need for comprehensive patient evaluation. Complications associated with decannulation occur frequently with varying severity. Efficient recognition and management of these complications are vital for improving patient outcomes. The study provides important insights into the challenges experienced during the decannulation process and highlights the necessity of considering prior intubation history in the management of tracheostomy decannulation to refine patient care protocols.

Using organ-on-a-chip technology to study haemorrhagic activities of snake venoms on endothelial tubules

Snakebite envenomation is a major public health issue which causes severe morbidity and mortality, affecting millions of people annually. Of a diverse range of clinical manifestations, local and systemic haemorrhage are of particular relevance, as this may result in ischemia, organ failure and even cardiovascular shock. Thus far, in vitro studies have failed to recapitulate the haemorrhagic effects observed in vivo. Here, we present an organ-on-a-chip approach to investigate the effects of four different snake venoms on a perfused microfluidic blood vessel model. We assess the effect of the venoms of four snake species on epithelial barrier function, cell viability, and contraction/delamination. Our findings reveal two different mechanisms by which the microvasculature is being affected, either by disruption of the endothelial cell membrane or by delamination of the endothelial cell monolayer from its matrix. The use of our blood vessel model may shed light on the key mechanisms by which tissue-damaging venoms exert their effects on the capillary vessels, which could be helpful for the development of effective treatments against snakebites.

Alkaloids from Siparuna (Siparunaceae) are predicted as the inhibitors of proteolysis and plasma coagulation caused by snake venom and potentially counteract phospholipase A2 activity of Bothrops jararaca

Ethnopharmacological relevanceSnakebite envenomation (SBE) is the world's most lethal neglected tropical disease. Bothrops jararaca is the species that causes the greatest number of SBEs in the South and Southeastern of Brazil. The main symptoms are local (inflammation, edema, hemorrhage, and myonecrosis) and systemic (hemorrhage, hemostatic alterations with consumptive coagulopathy, and death) effects. Species of the genus Siparuna, Siparunaceae, are used in folk and traditional medicine to treat SBE. However, limited information is available concerning Brazilian Siparuna species against SBE. Aim of the studyTo investigate the correlation between the compounds present in the extracts of five Siparuna species as potential agents against proteolytic activity, plasma coagulation, and phospholipase A2 (PLA2) activity caused by B. jararaca venom, using data obtained by UHPLC-MS/MS, biological activity, and multivariate statistics. Materials and methodsThe ethanol extracts from leaves of S. ficoides, S. decipiens, S. glycycarpa, S. reginae, and S. cymosa were fractionated by liquid-liquid extraction using different solvents of increasing polarity (hexane, dichloromethane, ethyl acetate, and n-butanol), affording their respective extracts, totaling 25 samples that were assayed through in vitro plasma coagulation and proteolytic activity assays. Moreover, the extracts were analyzed by UHPLC-MS/MS, using electrospray ionization (ESI) and atmospheric-pressure chemical ionization (APCI) in negative and positive ionization modes. The data was processed in MZmine v. 2.53 and evaluated by multivariate statistical tests (PLS) using the software UnscramblerX v. 10.4. These data were also used to build molecular networks (GNPS), and some ions of interest could be annotated using the library of molecules on the GNPS platform. ResultsA total of 19 extracts inhibited B. jararaca-induced plasma coagulation, with emphasis on S. cymosa and S. reginae (800 s). The inhibition of the proteolytic activity was also promising, ranging from 16% (S. glycycarpa) to 99% (S. cymosa, S. decipiens, and S. reginae). In addition, most extracts from S. cymosa and S. reginae inhibited 70–90% of PLA2 activity. Based on data from positive mode APCI analyses, it was possible to obtain a statistic model with reliable predictive capacity which exhibited an average R2 of 0.95 and a Q2 of 0.88, indicating a robust fit. This process revealed five ions, identified as the alkaloids: coclaurine (1), stepholidine (2) O-methylisopiline (3), nornantenine (4) and laurolitsine (5). This is the first study to evidence the potential antivenom of alkaloids from Siparuna species. ConclusionsAltogether, our results give support to the popular use of Siparuna extracts in SBE accidents, suggesting their potential as an alternative or complementary strategy against envenoming by B. jararaca venom. The predicted ions in the chemometric analysis for the assayed activities can also be correlated with the blocking activity and encourage the continuation of this study for possible isolation and testing of individual compounds on the used models.

Tranexamic acid loaded in a physically crosslinked trilaminate dressing for local hemorrhage control: Preparation, characterization, and in-vivo assessment using two different animal models

This work aimed at formulating a trilaminate dressing loaded with tranexamic acid. It consisted of a layer of 3 % sodium hyaluronate to initiate hemostasis. It was followed by a mixed porous layer of 5 % polyvinyl alcohol and 2 % kappa–carrageenan. This layer acted as a drug reservoir that controlled its release. The third layer was 5 % ethyl cellulose backing layer for unidirectional release of tranexamic acid towards the wound. The 3 layers were physically crosslinked by hydrogen bonding as confirmed by Infrared spectroscopy. Swelling and release studies were performed, and results proposed that increasing number of layers decreased swelling properties and sustained release of tranexamic acid for 8 h. In vitro blood coagulation study was performed using human blood and showed that the dressing significantly decreased coagulation time by 70.5 % compared to the negative control. In vivo hemostatic activity was evaluated using tail amputation model in Wistar rats. Statistical analysis showed the dressing could stop bleeding in a punctured artery of the rat tail faster than the negative control by 59 %. Cranial bone defect model in New Zealand rabbits was performed to check for bone hemostasis and showed significant decrease in the hemostatic time by 80 % compared to the control.

Left ventricular unloading during venoarterial extracorporeal membrane oxygenation implantation: benefits or complications?

Abstract Funding Acknowledgements None. Introduction Peripheral venoarterial extracorporeal membrane oxygenation (VA ECMO) is a therapeutic option for refractory cardiogenic shock (CS). However, the retrograde flow increases afterload, leading to pulmonary edema, blood stasis in the left ventricle (LV) and formation of thrombi. Several strategies try to reduce LV pressure, including the percutaneous transvalvular microaxial pump (p-MCS) and intra-aortic balloon pump (IABP). However, these interventions are associated to complications, such as limb ischemia, embolism, bleeding and hemolysis. Purpose This study aims to investigate whether simultaneous LV unloading at ECMO implant yields clinical benefits or complications compared to ECMO implantat alone. Methods Consecutive patients (pts) with CS requiring peripheral VA ECMO from January 2020 to August 2023 were prospectively included, comparing the group that received LV unloading through IABP or p-MCS to the group that received ECMO only. Standard statistical methods were used. Results A total of 38 pts required VA ECMO. 18 of them received LV unloading since cannulation (8 with IABP and 10 with p-MCS). In the group without initial LV-unloading (20), 3 pts required IABP and 1 p-MCS during support and 1 was changed to VAV ECMO. Change to axillar configuration was perfomed in 1 pts in the unloaded group and in 2 in the only-ECMO group. A higher prevalence of SCAI E (72.2%) was observed in the unloaded-ECMO, compared to the only-ECMO, where SCAI D was more prevalent (60%) (p=0.024). In the LV unloaded group, acute myocardial infarction (AMI) was the leading cause of CS, while myocarditis was the predominant one in the other group (p=0.01). The simultaneous support had a higher rate of intubation (94.4% vs 50% p=0.004) and more acute pulmonary edema (44.4% vs 10% p=0.027). In the ECMO-only 2 pts required intubation during support and LV stasis was observed in 1, whereas no cases were reported in the LV-unloaded group (p=0.036). The mean PaO2/FiO2 during support were higher in the not unloaded group (284.54 vs 200.50 mmHg p=0.036), necessitating lower FiO2 levels (40.89 vs 61.47% p=0.003). In terms of complications, we included the 4 patients from the ECMO-only group who eventually required LV unloading in the unloaded-ECMO. There were no significant differences in the duration of support, in-hospital mortality, stroke, embolism, systemic and local bleeding, or hemolysis. Conclusions Pts with ECMO and LV unloading since cannulation debuted with more severe CS, more AMI as the underlying cause, higher rates of acute pulmonary edema, and intubation. Despite these challenges, they did not experience worse outcomes in terms of in-hospital mortality or ischemic and hemorrhagic events. Notably, 4 patients initially managed with ECMO eventually required subsequent LV unloading. Consequently, the simultaneous implantation of ECMO and a LV unloading device appears to be a reasonable alternative for select patients with a higher risk profile.

Same-day discharge after large-bore access in percutaneous coronary intervention of chronic total coronary occlusions.

Same-day discharge (SDD) in patients undergoing percutaneous coronary intervention (PCI) of a chronic total occlusion (CTO) is appealing because of the increased patient comfort. However, data on SDD following large-bore vascular access are scarce. We investigated the feasibility and safety of SDD in patients undergoing large-bore CTO PCI. Between 2013 and 2023, 948 patients were prospectively enrolled in a single-centre CTO registry and underwent CTO PCI. SDD was pursued in all patients. Large-bore access was defined as the use of ≥7 French (Fr) sheaths in ≥1 access site. A logistic regression analysis was used to identify predictors for non-SDD. Clinical follow-up was obtained at 30 days. SDD was observed in 62% of patients. Large-bore access was applied in 99% of the cohort. SDD patients were younger and more often male, with lower rates of renal insufficiency and prior coronary artery bypass grafting. Local access site bleeding (odds ratio [OR] 8.53, 95% confidence interval [CI]: 5.24-13.87) and vascular access complications (OR 7.23, 95% CI: 1.98-26.32) made hospitalisation more likely, with vascular access complications occurring in 3%. At 30 days, the hospital readmission rate was low in both SDD and non-SDD patients (5% vs 7%; p=non-significant). Finally, SDD was not a predictor for major adverse cardiovascular events (MACE) at follow-up. Same-day discharge can be achieved in the majority of patients undergoing CTO PCI with large-bore (≥7 Fr) access. Similar low hospital readmission and MACE rates between SDD and non-SDD patients at 30 days demonstrate the feasibility and safety of SDD.