Microwave Thermal Ablation for Breast Cancer in Africa: A Pioneering Case Report Utilizing TATOpro.

The adoption of minimally invasive treatments for early-stage breast cancer is increasing. Microwave thermal ablation (MWA), a minimally invasive technique, has been studied for treating small breast cancer lesions. However, long-term evidence on its efficacy as a sole treatment is limited, as most studies combine MWA with other therapies and post-treatment surgical excision. This report details the case of an 83-year-old African patient who declined surgery and systemic therapies, opting for MWA using the TATOpro system as the sole treatment for contralateral breast cancer with axillary lymph node metastasis. The report includes a one-year follow-up, assessing disease recurrence with MRI and ultrasound. The findings highlight MWA's potential as an innovative and efficacious breast cancer treatment, emphasizing the need for adaptable strategies in oncology.

Using microfluidic shear to assess transfusion requirements in trauma patients.

Background: Viscoelastic assays have widely been used for evaluating coagulopathies but lack the addition of shear stress important to in vivo clot formation. Stasys technology subjects whole blood to shear forces over factor-coated surfaces. Microclot formation is analyzed to determine clot area (CA) and platelet contractile forces (PCFs). We hypothesize the CA and PCF from this novel assay will provide information that correlates with trauma-induced coagulopathy and transfusion requirements. Methods: Blood samples were collected on adult trauma patients from a single-institution prospective cohort study of high-level activations. Patient and injury characteristics, transfusion data, and outcomes were collected. Thromboelastography, coagulation studies, and Stasys assays were run on paired samples collected at admission. Stasys CA and PCFs were quantified as area under the curve calculations and maximum values. Normal ranges for Stasys assays were determined using healthy donors. Data were compared using Kruskal-Wallis tests and simple linear regression. Results: From March 2021 to January 2023, 108 samples were obtained. Median age was 37.5 (IQR 27.5-52) years; patients were 77% male. 71% suffered blunt trauma, 26% had an Injury Severity Score of ≥25. An elevated international normalized ratio significantly correlated with decreased cumulative PCF (p=0.05), maximum PCF (p=0.05) and CA (p=0.02). Lower cumulative PCF significantly correlated with transfusion of any products at 6 and 24 hours (p=0.04 and p=0.05) as well as packed red blood cells (pRBCs) at 6 and 24 hours (p=0.04 and p=0.03). A decreased maximum PCF showed significant correlation with receiving any transfusion at 6 (p=0.04) and 24 hours (p=0.02) as well as transfusion of pRBCs, fresh frozen plasma, and platelets in the first 6 hours (p=0.03, p=0.03, p=0.03, respectively). Conclusions: Assessing coagulopathy in real time remains challenging in trauma patients. In this pilot study, we demonstrated that microfluidic approaches incorporating shear stress could predict transfusion requirements at time of admission as well as requirements in the first 24 hours. Level of evidence: Level II.

Admission Viscoelastic Hemostatic Assay Parameters Predict Poor Long-Term Intracerebral Hemorrhage Outcomes.

BACKGROUND: Viscoelastic hemostatic assays (VHAs) provide more comprehensive assessments of coagulation compared with conventional coagulation assays. Although VHAs have enabled guided hemorrhage control therapies, improving clinical outcomes in life-threatening hemorrhage, the role of VHAs in intracerebral hemorrhage (ICH) is unclear. If VHAs can identify coagulation abnormalities relevant for ICH outcomes, this would support the need to investigate the role of VHAs in ICH treatment paradigms. Thus, we investigated whether VHA assessments of coagulation relate to long-term ICH outcomes. METHODS: Patients with spontaneous ICH enrolled into a single-center cohort study receiving admission Rotational Thromboelastometry (ROTEM) VHA testing between 2013 and 2020 were assessed. Patients with previous anticoagulant use or coagulopathy on conventional coagulation assays were excluded. Primary ROTEM exposure variables were coagulation kinetics and clot strength assessments. Poor long-term outcome was defined as modified Rankin Scale ≥ 4 at 6 months. Logistic regression analyses assessed associations of ROTEM parameters with clinical outcomes after adjusting for ICH severity and hemoglobin concentration. RESULTS: Of 44 patients analyzed, the mean age was 64 years, 57% were female, and the median ICH volume was 23 mL. Poor 6-month outcome was seen in 64% of patients. In our multivariable regression models, slower, prolonged coagulation kinetics (adjusted odds ratio for every second increase in clot formation time 1.04, 95% confidence interval 1.00-1.09, p = 0.04) and weaker clot strength (adjusted odds ratio for every millimeter increase of maximum clot firmness 0.84, 95% confidence interval 0.71-0.99, p = 0.03) were separately associated with poor long-term outcomes. CONCLUSIONS: Slower, prolonged coagulation kinetics and weaker clot strength on admission VHA ROTEM testing, not attributable to anticoagulant use, were associated with poor long-term outcomes after ICH. Further work is needed to clarify the generalizability and the underlying mechanisms of these VHA findings to assess whether VHA-guided treatments should be incorporated into ICH care.

Efficacy of surgical treatments for the management of solitary rectal ulcer syndrome: a network meta-analysis.

AIM: Solitary rectal ulcer syndrome (SRUS) is a benign and poorly understood disorder with complex management. Typical symptoms include straining during defaecation, rectal bleeding, tenesmus, mucoid secretion, anal pain and a sense of incomplete evacuation. Diagnosis is based on characteristic clinical symptoms and endoscopic/histological findings. Several treatments have been reported in the literature with variable ulcer healing rates. This study aimed to evaluate the efficacy of different treatments for SRUS. MATERIALS AND METHODS: A systematic review and network meta-analysis were performed according to the PRISMA guidelines. Studies in English, French and Spanish languages were included. Papers written in other languages were excluded. Other exclusion criteria were reviews, case reports or clinical series enrolling less than five patients, study duplications, no clinical data of interest and no article available. A systematic literature search was conducted from January 2000 to March 2024 using the following databases: PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus. The biases of the studies were assessed using the Newcastle-Ottawa scale or the Jadad scale when appropriate. Types of treatment and their efficacy for the cure of SRUS were collected and critically assessed. The study's primary outcome was to estimate the rate of patients with ulcer healing. RESULTS: A total of 22 studies with 911 patients (men 361, women 550) diagnosed with SRUS were analysed in the final meta-analysis. The pooled effect estimates of treatment efficacy revealed that surgery showed the highest ulcer healing rate (70.5%; 95% CI 0.57-0.83). Surgery was superior in the cure of ulcers with respect to medical therapies and biofeedback (OR 0.09 and OR 0.14). CONCLUSION: Solitary rectal ulcer syndrome is a challenging clinical entity to manage. Proficient results have been reported with the surgical approach, suggesting its positive role in cases refractory to medical and biofeedback therapy. Further studies in homogeneous populations are required to evaluate the efficacy of surgery in this setting. (PROSPERO registration number CRD42022331422).

Clinical significance, molecular characterization, and immune microenvironment analysis of coagulation-related genes in clear cell renal cell carcinoma.

Background: Numerous studies have revealed a tight connection between tumor development and the coagulation system. However, the effects of coagulation on the prognosis and tumor microenvironment (TME) of clear cell renal cell carcinoma (ccRCC) remain poorly understood. Methods: We employed the consensus clustering method to characterize distinct molecular subtypes associated with coagulation patterns. Subsequently, we examined variations in the overall survival (OS), genomic profiles, and TME characteristics between these subtypes. To develop a prognostic coagulation-related risk score (CRRS) model, we utilized the least absolute shrinkage and selection operator Cox regression and stepwise multivariate Cox regression analyses. We also created a nomogram to aid in the clinical application of the risk score, evaluating the relationships between the CRRS and the immune microenvironment, responsiveness to immunotherapy, and targeted treatment. The clinical significance of PLAUR and its biological function in ccRCC were also further analyzed. Results: There were significant differences in clinical features, prognostic stratification, genomic variation, and TME characteristics between the two coagulation-related subtypes. We established and validated a CRRS using six coagulation-related genes that can be employed as an effective indicator of risk stratification and prognosis estimation for ccRCC patients. Significant variations in survival outcomes were observed between the high- and low-risk groups. The nomogram was proficient in predicting the 1-, 3-, and 5-year OS. Additionally, the CRRS emerged as a novel tool for evaluating the clinical effectiveness of immunotherapy and targeted treatments in ccRCC. Moreover, we confirmed upregulated PLAUR expression in ccRCC samples that was significantly correlated with poor patient prognosis. PLAUR knockdown notably inhibited ccRCC cell proliferation and migration. Conclusion: Our data suggested that CRRS may be employed as a reliable predictive biomarker that can provide therapeutic benefits for immunotherapy and targeted therapy in ccRCC.

Pilot Assessment of Platelet Thrombus Area and Contractile Force in Pediatric Congenital Heart Surgery Patients Using a Microfluidic Device.

OBJECTIVES: This work was designed to evaluate maximum platelet contractile force and thrombus area before and after cardiopulmonary bypass (CPB) in pediatric patients having congenital heart disease (CHD) surgery using a microfluidic device. DESIGN: A prospective cohort study was designed. SETTING: The work took place at an academic medical center. PARTICIPANTS: Twenty pediatric CHD patients ≤8 years of age with expected CPB time >30 minutes were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood was collected at baseline and post-CPB. Maximum platelet contractile force and thrombus area were evaluated in vitro using a microfluidic device (ATLAS PST). Post-CPB samples were supplemented with recombinant von Willebrand factor (rVWF) to explore the impact on contractile force and thrombus area. At baseline, the maximum thrombus area was 0.06 (0.05, 0.07), and the maximum force was 123.3 nN (68.4, 299.5). Linear mixed-effects regression models showed that the maximum thrombus area was larger post-CPB and post-CPB + rVWF compared with pre-CPB (estimated coefficient [Est] = 0.04, p = 0.002; Est = 0.09, p < 0.001, respectively). The maximum thrombus area was also larger post-CPB + rVWF compared with post-CPB (Est = 0.04, p = 0.001). Force was higher post-CPB + rVWF compared with pre-CPB (Est = 173.32, p = 0.044). CONCLUSIONS: In pediatric CHD patients, microfluidic testing demonstrated that platelet thrombus area increased slightly after CPB, while platelet contractile force did not change. In vitro addition of rVWF further increased thrombus area, suggesting augmentation of primary hemostasis. Microfluidic assessment of platelet contractile force and thrombus area in pediatric CHD patients appears feasible and can demonstrate changes after CPB. Further studies are needed to determine its accuracy, clinical utility, and normal values for pediatric patients.

EGFR-TKI-induced Factor V deficiency in a patient with advanced non-small cell lung cancer: The first case report.

Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is routinely prescribed as first-line therapy for advanced non-small cell lung cancer, regardless of the presence of the T790M resistance mutation. This study reports a rare case of Factor V inhibitor detection during osimertinib therapy in a patient with lung adenocarcinoma. These findings underscore the importance of vigilant monitoring for coagulation abnormalities during EGFR-TKI therapy.

Beta-2 Glycoprotein I IgA Isotype: An Important Consideration in Secondary Hypertension.

Anti-beta-2 glycoprotein I antibodies are an important player in hypercoagulable states, including those that lead to antiphospholipid syndrome. Traditionally, assays have only detected IgG and IgM isotypes of this antibody. However, newer assays also detect the IgA isotype. The problem lies in the largely unknown significance of this IgA isotype. This paper describes a middle-aged male who presented with hypertensive emergency and was later found to have IgA anti-beta-2 glycoprotein I antibodies. He was treated with multiple anti-hypertensives, aspirin, and statin therapy. In addition to the case, we discuss the implications of this IgA isotype and how it may relate to antiphospholipid syndrome, despite not currently being included in the laboratory diagnostic criteria for the disease.

The Influence of Preoperative Anticoagulant and Antiplatelet Therapy on Rebleeding Rates in Patients Suffering from Spinal Metastatic Cancer: A Retrospective Cohort Study.

INTRODUCTION: The age of patients requiring surgery for spinal metastasis, primarily those over 65, has risen due to improved cancer treatments. Surgical intervention targets acute neurological deficits and instability. Anticoagulants are increasingly used, especially in the elderly, but pose challenges in managing bleeding complications. The study examines the correlation between preoperative anticoagulant/antiplatelet use and bleeding risks in spinal metastasis surgery, which is crucial for optimizing patient outcomes. MATERIAL AND METHODS: In a retrospective study at our department from 2010 to 2023, spinal tumor surgery patients were analyzed. Data included demographics, neurological status, surgical procedure, preoperative anticoagulant/antiplatelet use, intra-/postoperative coagulation management, and the incidence of rebleeding. Coagulation management involved blood loss assessment, coagulation factor administration, and fluid balance monitoring post-surgery. Lab parameters were documented at admission, preop, postop, and discharge. RESULTS: A cohort of 290 patients underwent surgical treatment for spinal metastases, predominantly males (63.8%, n = 185) with a median age of 65 years. Preoperatively, 24.1% (n = 70) were on oral anticoagulants or antiplatelet therapy. Within 30 days, a rebleeding rate of 4.5% (n = 9) occurred, unrelated to preoperative anticoagulation status (p > 0.05). A correlation was found between preoperative neurologic deficits (p = 0.004) and rebleeding risk and the number of levels treated surgically, with fewer levels associated with a higher incidence of postoperative bleeding (p < 0.01). CONCLUSIONS: Surgical intervention for spinal metastatic cancer appears to be safe regardless of the patient's preoperative anticoagulation status. However, it remains imperative to customize preoperative planning and preparation for each patient, emphasizing meticulous risk-benefit analysis and optimizing perioperative care.

Possibilities of Managing Waste Iron Sorbent FFH after CO2 Capture as an Element of a Circular Economy.

With a growing need to reduce greenhouse gas emissions, innovative carbon dioxide sorbents are being sought. One of the sorbents being tested is nanoparticle ferric hydrosol (FFH). In parallel with sorbent testing, it is also necessary to test the used sorbent after carbon dioxide capture (FFHCO2) and to develop an optimal method for its processing and management. The research described in this article evaluated the potential use of FFHCO2 in dewatering, coagulation and bioleaching processes. The research results indicate that the basic strategy for dealing with waste FFHCO2 sorbent should be to minimize the amount of waste by volume reduction-dewatering. Recycling of FFHCO2 as an iron waste coagulant or its processing products by bioleaching had no technological justification. It is only proposed to recover the material-iron compounds-if it is environmentally and economically justified.

Global coagulation assays detect an early prothrombotic state in children with acute lymphoblastic leukemia.

BACKGROUND: Pediatric patients with acute lymphoblastic leukemia (ALL) are at highest risk of venous thromboembolism (VTE) during the induction phase of treatment (IT). These events are not predictable by conventional coagulation assays. OBJECTIVES: To investigate the utility of global coagulation assays (GCA) for assessing the hemostatic state in children with ALL during IT. METHODS: We included children with ALL (n=15) and healthy controls (n=15). Analyses were performed at different time points during IT of the AIEOP-BFM protocols. In addition to prothrombotic biomarkers, natural anticoagulants proteins and in vivo thrombin generation (TG) markers, ex vivo TG was measured using the gold-standard Calibrated-Automated-Thrombogram method (CAT), the automated-ST Genesia (STG), and Thrombodynamics-analyzer (TD). The latter also provided measurement of fibrin clot formation (FCF). RESULTS: Differently from conventional coagulation assays and in vivo TG markers, ex vivo GCA, detected increasing prothrombotic changes during IT. Particularly, TG measured with TD as expressed by endogenous thrombin potential (ETP) was significantly elevated already at d8-12 (p<0.01) and continued to increase during IT as compared to prior to treatment beginning, indicating a very early shift towards a procoagulant state. A similar pattern was observed for the rate of FCF (V:p<0.01 at d8-12). Remarkably, in patients developing thrombotic complications (n=5), both GCA, STG and TD, showed a significantly higher ETP very early (already at d8-12, p<0.05), well before clinical manifestation. CONCLUSION: GCA capture prothrombotic changes early during IT in ALL pediatric patients. If confirmed, this approach will allow tailoring thromboprophylaxis in children with ALL at highest risk for VTE.

Factor XIII in major burns coagulation.

BACKGROUND: In the days following a burn injury, major burn patients (MBP) present a multifactorial coagulation disorder known as acute burn-induced coagulopathy. Several studies have investigated coagulation in MBPs; however, Factor XIII (FXIII), which converts fibrin monomers into a stable clot and promotes wound healing, has not yet been studied. OBJECTIVE: To determine the kinetics of FXIII and other coagulation factors and cofactors in MBPs in order to clarify coagulopathy in these patients and its potential relationship with surgical bleeding. METHODS: Prospective observational pilot study of the kinetics of FXIII and other coagulation factors and cofactors in MBPs during the first 30 days of burn injury. RESULTS: FXIII levels show a significant decline of 75.10% in the interval between the burn injury and surgery, and a decline of 87.70% in the 24 h following surgery. Patients undergo surgery with a median antigenic FXIII of 32%. Plasma levels of most factors decrease significantly 24 h after the burn injury. CONCLUSION: MBPs experience a significant decrease in plasma levels of FXIII from the time of admission up to 24 h after surgery. Abnormally low levels were observed at the time of surgery that could not be detected by other coagulation tests. The decrease in most factors at 24 h seems to be associated with dilution due to intensive fluid resuscitation.

Treatment experience for different risk groups of Kaposiform hemangioendothelioma.

Background: Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor with a high risk of mortality. Few studies with large samples of KHE have been reported. KHE may develop into the Kasabach-Merritt phenomenon (KMP), which is characterized by thrombocytopenia and consumptive coagulopathy. The features of severe symptomatic anemia and life-threatening low platelets make the management of KHE associated with KMP challenging. Objective: The aim of this study was to examine the clinical characteristics of patients with KHE and discuss the treatment experience for different risk groups of KHE. Methods: Through a retrospective review of 70 patients diagnosed with KHE between 2017 and 2022 in our center, we classify lesions into three clinicopathological stages based on the tumor involving depth, and divided the severity of KHE into three levels by estimating clinicopathological stages and severity of thrombocytopenia. Treatments of different severity groups were estimated with sufficient data. Results: In our cohort, 27% were neonates, and KHE lesion occurred at birth in 84% of patients. There was a slight male predominance (32 girls and 38 boys). Common clinical characteristics included associated coagulation disorder (100%), locally aggressive cutaneous blue-purple mass (89%), thrombocytopenia (78%), and local pain or joint dysfunction (20%). The lower extremities were the dominant location (35%), followed by the trunk (29%), the maxillofacial region and neck (24%), and the upper extremities (10%). Of the total cohort, 78% developed KMP; the median age at which thrombocytopenia occurred was 27.8 days. The median platelet count of patients who were associated with KMP was 24,000/µL in our cohort. Ninety-two percent of patients were given surgery treatment and 89% of these patients were given high-dose methylprednisolone (5-6 mg/kg daily) before surgery. In 55 patients with KMP, 36% were sensitive to high-dose corticosteroid therapy. Patients from the low-risk group (eight cases) underwent operation, all of whom recovered without recurrence after a maximum follow-up of 5 years. Out of 26 patients from the high-risk group, 25 underwent surgery treatment, with 1 case undergoing secondary surgery after recurrence and 1 case taking sirolimus. Out of 36 cases from the extremely high-risk group, 32 underwent surgery (including 2 cases who underwent external carotid artery ligation and catheterization), 3 of whom underwent secondary operation after recurrence, and the remaining 4 cases took medicine. The mean length of having sirolimus was 21 months; two cases stopped taking sirolimus due to severe pneumonia. Two cases died at 1 and 3 months after discharge. Conclusions: Our study describes the largest assessment of high-risk patients with KHE who have undergone an operation to date, with 5 years of follow-up to track recovery, which provides invaluable knowledge for the future treatment of patients with KHE and KMP from different risk groups: Early surgical intervention may be the most definitive treatment option for most patients with KHE; multimodality treatment is the best choice for the extremely high-risk group.

Outcomes of slow coagulation transscleral cyclophotocoagulation in a predominantly African American glaucoma population.

Purpose: To evaluate outcomes of slow coagulation transscleral cyclophotocoagulation (SC-TSCPC) in a primarily African American patient population with glaucoma. Methods: A retrospective chart review was performed for 104 consecutive cases of SC-TSCPC by a single surgeon between November 6, 2019-September 7, 2023. Power ranged from 1150 to 1500 mW, duration was 4 s, and number of spots ranged from 10 to 25. Exclusion criteria were diagnosis of neovascular glaucoma, prior CPC, visual acuity (VA) of no light perception or unable to be assessed due to patient's mental status, aphakia, or follow-up <3 months. The primary outcome measure was surgical success defined as an intraocular pressure (IOP) of 6-21 mmHg with a ≥20 % reduction from baseline, no glaucoma re-operation, and no loss of light-perception. Secondary outcome measures included VA, glaucoma medication use, and post-surgical complications. Analysis was also stratified by lens status as literature suggests a greater IOP-lowering effect in pseudophakic eyes after CPC. Results: There were 28 eligible patients (6 phakic, 22 pseudophakic) included in this analysis. Mean follow-up was 11.6 ± 8.3 months, and 14 patients had postoperative year 1 data available. The mean age was 75.2 ± 13.9 years, 42.9 % were female, and 92.9 % were African American, reflective of the demographics of the local community. The cumulative success rate was 68.5 % at 1 year and did not differ significantly between phakic and pseudophakic patients. Mean VA worsened from 20/600 preoperatively to 20/1050 at last follow-up (P = 0.04) and was marginally worse in the phakic group (P = 0.15). Mean IOP decreased from 31.1 ± 13.2 mmHg on 4.0 ± 1.5 medications preoperatively to 13.8 ± 7.1 mmHg on 2.6 ± 1.5 medications at last follow-up (P < 0.001; P < 0.01), with a more pronounced effect among pseudophakic patients. 85.7 % of patients had prolonged anterior chamber (AC) inflammation beyond 1 month, which persisted in 10.7 % at last follow-up. The cystoid macular edema (CME) rate was 21.4 %, with 10.7 % persistent at last follow-up. Conclusions: SC-TSCPC is an effective, non-incisional IOP-lowering procedure in phakic and pseudophakic eyes that may not otherwise be ideal candidates for incisional glaucoma surgery. Pseudophakic eyes may experience larger reductions in IOP, however, laser settings can be titrated on a case-by-case basis depending on individual patients' goals. There was a higher incidence of prolonged AC inflammation and CME in our cohort compared to similar studies which report rates of 12.7 % and 2.7 %, respectively. Although the significance of such complications may differ based on the visual potential of each patient, these findings support existing literature that African American patients can have greater incidence of inflammation and subsequent sequalae after ocular surgery.

Comparison of assays measuring extracellular vesicle-tissue factor in plasma samples: Communication from the ISTH SSC Subcommittee on Vascular Biology.

BACKGROUND: Scientific and clinical interest in extracellular vesicles (EVs) is growing. EVs that expose tissue factor (TF) bind factor VII/VIIa and can trigger coagulation. Highly procoagulant TF-exposing EVs are detectable in the circulation in various diseases, such as sepsis, COVID-19 or cancer. Many in-house and commercially available assays have been developed to measure EV-TF activity and antigen but only a few studies have compared some of these assays. The ISTH SSC Subcommittee on Vascular Biology initiated a multicenter study to compare the sensitivity, specificity and reproducibility of these assays. MATERIALS AND METHODS: Platelet-depleted plasma samples were prepared from blood of healthy donors. The plasma samples were spiked either with EVs from human milk, or EVs from TF-positive and TF-negative cell lines. Plasma was also prepared from whole human blood with or without LPS stimulation. Twenty-one laboratories measured EV-TF activity and antigen in the prepared samples using their own assays representing 18 functional and 9 antigenic assays. RESULTS: There was a large variability in the absolute values for the different EV-TF activity and antigen assays. Activity assays had higher specificity and sensitivity compared to antigen assays. In addition, there was a large intra-assay and inter-assay variability. Functional assays that used a blocking anti-TF antibody or immunocapture were the most specific and sensitive. Activity assays that used immunocapture had a lower coefficient of variation compared to assays that isolated EVs by high-speed centrifugation. CONCLUSION: Based on this multicenter study, we recommend measuring EV-TF using a functional assay in the presence of an anti-TF antibody.

Laparoscopic liver resection for a patient of hepatocellular carcinoma with von Willebrand disease: a case report.

BACKGROUND: The safety of laparoscopic hepatectomy for inherited coagulation disorders is unclear; however, the safety of open hepatectomy has been reported in several studies. Herein, we report the first case of a laparoscopic hepatectomy for a patient with von Willebrand Disease (VWD). CASE PRESENTATION: A 76-year-old male with a history of chronic hepatitis C and VWD type 2B was advised surgical resection of a 4 cm hepatocellular carcinoma in segment 7 of the liver. The patient was diagnosed with VWD in his 40 s due to gastrointestinal bleeding caused by gastric erosion. The von Willebrand factor (VWF) ristocetin cofactor activity was 30%, and VWF large multimer deficiency and increased ristocetin-induced platelet agglutination were observed. The preoperative platelet count was reduced to 3.5 × 104/µL; however, preoperative imaging findings had no evidence of liver cirrhosis, such as any collateral formations and splenomegaly. The indocyanine green retention rate at 15 min was 10%, and his Child-Pugh score was 5 (classification A). Perioperatively, VWF/factor VIII was administered in accordance with our institutional protocol. A laparoscopic partial hepatectomy of the right posterior segment was performed. The most bleeding during surgery occurred during the mobilization of the right lobe of the liver due to inflammatory adhesion between the retroperitoneum and the tumor. Bleeding during parenchymal transection was controlable. The duration of hepatic inflow occlusion was 65 min. The surgical duration was 349 min, and the estimated blood loss was 2150 ml. Four units of red blood cells and fresh frozen plasma were transfused at the initiation of parenchymal transection, and 10 units of platelets were transfused at the end of the parenchymal transection. On postoperative day 1, the transection surface drainage fluid became hemorrhagic, and emergency contrast-enhanced computed tomography showed extravasation in the greater omentum. Percutaneous transcatheter arterial embolization of the omental branch of the right gastroepiploic artery was performed. No further postoperative interventions were required. The patient was discharged on postoperative day 14. CONCLUSION: The indications for laparoscopic hepatectomy in patients with VWD should be carefully considered, and an open approach may still be the standard approach for patients with VWD.

Temperature effect on coagulation function in mild hypothermic patients undergoing thoracic surgeries: thromboelastography (TEG) versus standard tests.

PURPOSE: Our previous research has revealed that mild hypothermia leads to excessive bleeding in thoracic surgeries, while the underlying mechanism stayed unrevealed by the standard coagulation tests. The research question in this study was as follows: "How does mild hypothermia impair the hemostatic function in patients receiving thoracic surgeries?". The purpose was to detect the disturbed coagulation processes by comparing the TEG parameters in patients receiving active vs. passive warming during thoracic surgeries. METHODS: Standard coagulation tests and thromboelastography (TEG) were adopted to compare the hemostatic functions in patients receiving active vs. passive warming during thoracic surgeries. Furthermore, blood samples from passive warming group were retested for TEG at actual core body temperatures. RESULTS: Sixty-four eligible patients were included in this study. TEG revealed that mild hypothermia significantly disturbed coagulation by decreasing MA (59.4 ± 4.5 mm vs. 64.2 ± 5.7 mm, p = 0.04) and α angle (70.4 ± 5.2° vs. 74.9 ± 4.4°, p = 0.05) and prolonging ACT (122.2 ± 19.3 s vs. 117.3 ± 15.2 s, p = 0.01) and K time (1.9 ± 1.0 s vs. 1.3 ± 0.4 min, p = 0.02). TEGs conducted under core body temperatures revealed more impaired coagulation than those incubated at 37 °C. Furthermore, postoperative shivering and waking time were significantly increased in mild hypothermic patients. CONCLUSION: Mild hypothermia significantly impaired coagulation function in patients receiving thoracic surgeries, which could be detected by TEGs other than the standard coagulation tests. Temperature-adjusted TEGs may provide a preferable method of hemostatic monitoring and transfusion guidance in thoracic surgeries, which warrants further clinical investigations.

Coagulation and fibrinolytic markers offer utility when distinguishing between benign and malignant gallbladder tumors: A cross-sectional study.

BACKGROUND: The metabolic or proliferative abnormalities that are characteristic of tumor cells can lead to abnormal fibrinolysis or coagulation system activity, with certain tumors exhibiting hypercoagulability or existing in a fibrinolytic state. However, the utility of biomarkers of coagulation and fibrinolysis when seeking to differentiate between benign gallbladder disease and malignant gallbladder tumors remains uncertain. METHODS: This study included a total of 81 patients with benign gallbladder polyps and 94 patients with malignant gallbladder tumors. Pre-biopsy or pretreatment levels of PT, APTT, FIB, D-dimer, FDP, PLT, PIC, TAT, TM, and t-PAIC from these patients were compared using Mann-Whitney tests. The baseline data of the patients were analyzed using chi-square tests, and the diagnostic utility of these biomarkers in distinguishing between benign and malignant gallbladder lesions was evaluated using ROC curves, and Spearman correlation analysis was employed to assess the correlation between these indicators and tumor parameters. RESULTS: The average age of malignant gallbladder tumor group was higher than benign gallbladder polyp group. And the base line analysis showed that there was a statistic difference in age, history of smoking, drinking, biliary tract disease, BMI of over weight between these two groups. In patients with malignant gallbladder tumors, FIB, D-dimer, FDP, PIC, TAT, TM, and t-PAIC levels were significantly elevated relative to those in patients affected by benign gallbladder polyp. The AUC for FIB, D-dimer, and FDP was 0.8469, 0.6514, 0.5950, while for PIC, TAT, TM, t-PAIC and four biomarker combined diagnosed was 0.8455, 0.6554, 0.7130, 0.6806, and 0.8859. Among these, TM was associated with the vascular invasion of tumor patients; TAT and t-PAIC were associated with neural invasion; D-dimer and FDP were related to the maximum tumor diameter; and FDP had a certain correlation with the tumor stage. CONCLUSIONS: In gallbladder tumor patients, conventional coagulation metrics like FIB, D-dimer, and FDP, as well as newer thrombotic indicators such as PIC, TAT, TM, and t-PAIC, were obviously increased. Correlations with tumor parameters suggested their potential as biomarkers to distinguish benign from malignant gallbladder growths.

Gas-propelled nanomotors alleviate colitis through the regulation of intestinal immunoenvironment-hematopexis-microbiota circuits.

The progression of ulcerative colitis (UC) is associated with immunologic derangement, intestinal hemorrhage, and microbiota imbalance. While traditional medications mainly focus on mitigating inflammation, it remains challenging to address multiple symptoms. Here, a versatile gas-propelled nanomotor was constructed by mild fusion of post-ultrasonic CaO2 nanospheres with Cu2O nanoblocks. The resulting CaO2-Cu2O possessed a desirable diameter (291.3 nm) and a uniform size distribution. It could be efficiently internalized by colonic epithelial cells and macrophages, scavenge intracellular reactive oxygen/nitrogen species, and alleviate immune reactions by pro-polarizing macrophages to the anti-inflammatory M2 phenotype. This nanomotor was found to penetrate through the mucus barrier and accumulate in the colitis mucosa due to the driving force of the generated oxygen bubbles. Rectal administration of CaO2-Cu2O could stanch the bleeding, repair the disrupted colonic epithelial layer, and reduce the inflammatory responses through its interaction with the genes relevant to blood coagulation, anti-oxidation, wound healing, and anti-inflammation. Impressively, it restored intestinal microbiota balance by elevating the proportions of beneficial bacteria (e.g., Odoribacter and Bifidobacterium) and decreasing the abundances of harmful bacteria (e.g., Prevotellaceae and Helicobacter). Our gas-driven CaO2-Cu2O offers a promising therapeutic platform for robust treatment of UC via the rectal route.

Experimental Verification of Erchen Decoction Plus Huiyanzhuyu Decoction in the Treatment of Laryngeal Squamous Cell Carcinoma Based on Network Pharmacology.

BACKGROUND: The prescription of Chinese herbal medicine (CHM) consists of multiple herbs that exhibit synergistic effects due to the presence of multiple components targeting various pathways. In clinical practice, the combination of Erchen decoction and Huiyanzhuyu decoction (EHD) has shown promising outcomes in treating patients with laryngeal squamous cell carcinoma (LSCC). However, the underlying mechanism by which EHD exerts its therapeutic effects in LSCC remains unknown. METHODS: Online databases were utilized for the analysis and prediction of the active constituents, targets, and key pathways associated with EHD in the treatment of LSCC. The protein-protein interaction (PPI) network of common targets was constructed and visualized using Cytoscape 3.8.1 software. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the functional roles of core targets within the PPI network. Protein clustering was conducted utilizing the MCODE plug-in. The obtained results highlight the principal targets and pathways involved. Subsequently, clinical samples were collected to validate alterations in the levels of these main targets through Western blotting (WB) and immunohistochemistry (IHC). Furthermore, both in vivo and in vitro experiments were conducted to investigate the therapeutic effects of EHD on healing LSCC and elucidate its underlying mechanism. Additionally, to ensure experimental reliability and reproducibility, quality control measures utilizing HPLC were implemented for EHD herbal medicine. RESULTS: The retrieval and analysis of databases in EHD medicine and LSCC disease yielded a total of 116 overlapping targets. The MCODE plug-in methods were utilized to acquire 8 distinct protein clusters through protein clustering. The findings indicated that both the first and second clusters exhibited a size greater than 6 scores, with key genes PI3K and ErbB occupying central positions, while the third and fourth clusters were associated with proteins in the PI3K, STAT3, and Foxo pathways. GO functional analysis reported that these targets had associations mainly with the pathway of p53 mediated DNA damage and negative regulation of cell cycle in terms of biological function; the death-induced signaling complex in terms of cell function; transcription factor binding and protein kinase activity in terms of molecular function. The KEGG enrichment analysis demonstrated that these targets were correlated with several signaling pathways, including PI3K-Akt, FoxO, and ErbB2 signaling pathway. On one hand, we observed higher levels of key genes such as P-STAT3, P-PDK1, P-Akt, PI3K, and ErbB2 in LSCC tumor tissues compared to adjacent tissues. Conversely, FOXO3a expression was lower in LSCC tumor tissues. On the other hand, the key genes mentioned above were also highly expressed in both LSCC xenograft nude mice tumors and LSCC cell lines, while FOXO3a was underexpressed. In LSCC xenograft nude mice models, EHD treatment resulted in downregulation of P-STAT3, P-PDK1, PI3K, P-AKT, and ErbB2 protein levels but upregulated FOXO3a protein level. EHD also affected the levels of P-STAT3, P-PDK1, PI3K, P-AKT, FOXO3a, and ErbB2 proteins in vitro: it inhibited P-STAT3, P-AKT, and ErbB2, while promoting FOXO3a; however, it had no effect on PDK1 protein. In addition, HPLC identified twelve compounds accounting for more than 30% within EHD. The findings from this study can serve as valuable guidance for future experimental investigations. CONCLUSION: The possible mechanism of EHD medicine action on LSCC disease is speculated to be closely associated with the ErbB2/PI3K/AKT/FOXO3a signaling pathway.