Liver Hemorrhage Research Articles

Pembrolizumab or placebo plus chemotherapy for advanced HER2-negative gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: An updated analysis of KEYNOTE-859 for patients enrolled in Asia.

464 Background: After a median follow-up of 41.6 months, data from the global phase 3 KEYNOTE-859 study (NCT03675737; N = 1579) continued to show that use of pembrolizumab (pembro) plus chemotherapy (chemo) improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR), with manageable safety, versus placebo (pbo) plus chemo for patients (pts) with advanced HER2-negative G/GEJ adenocarcinoma. Here, we report updated results from the subgroup analysis of pts enrolled in Asia after an additional 11 months of follow-up from the first interim analysis. Methods: Eligible pts aged ≥18 years with locally advanced unresectable or metastatic HER2-negative G/GEJ adenocarcinoma, an ECOG performance status (PS) of 0 or 1, and measurable disease per RECIST v1.1 were randomly assigned 1:1 to receive pembro 200 mg or pbo IV Q3W for ≤35 cycles; all pts received investigator’s choice of chemo (FP or CAPOX). The primary end point was OS. Secondary end points included PFS, ORR, and DOR per RECIST v1.1 by blinded independent central review, and safety. Efficacy end points were evaluated in all randomly assigned pts (intention to treat). Results: A total of 525 pts (263, pembro plus chemo; 262, pbo plus chemo) were enrolled in KEYNOTE-859 in Asia. The median time from randomization to database cutoff (August 22, 2023) was 39.2 months (range, 26.0-56.8). The median OS was 17.3 months (95% CI, 14.8-19.5) for pembro plus chemo versus 13.0 months (95% CI, 11.8-14.4) for pbo plus chemo (HR, 0.75; 95% CI, 0.62-0.91). The median PFS was 8.4 months (95% CI, 7.1-9.6) for pembro plus chemo versus 5.8 months (95% CI, 5.6-6.9) for pbo plus chemo (HR, 0.72; 95% CI, 0.58-0.89). The ORR was 61.2% (95% CI, 55.0-67.1; 36, complete response [CR]; 125, partial response [PR]) for pembro plus chemo and 48.5% (95% CI, 42.3-54.7; 24, CR; 103, PR;) for pbo plus chemo. The median DOR was 10.0 months (range, 1.2+ to 50.8+) for pembro plus chemo and 5.8 months (range, 1.3+ to 44.3+) for pbo plus chemo; 28.9% and 23.3% of pts, respectively, had a response lasting ≥24 months. Grade 3-5 treatment-related adverse events (AEs) occurred in 155 pts (59.2%) in the pembro plus chemo group and 119 pts (45.4%) in the pbo plus chemo group. Treatment-related AEs led to death in 1 pt (0.4%) in the pembro plus chemo group (unknown cause) and 2 pts (0.8%) in the pbo plus chemo group (cerebral hemorrhage and abnormal liver function). Immune-mediated AEs and infusion reactions occurred in 85 pts (32.4%) in the pembro plus chemo group and 35 pts (13.4%) in the pbo plus chemo group. Conclusions: The addition of pembro to chemo improved OS, PFS, and ORR in pts with advanced HER2-negative G/GEJ adenocarcinoma from Asia enrolled in KEYNOTE-859, with no new safety signals. These results further support first-line pembro plus chemo as a treatment option for this population. Clinical trial information: NCT03675737 .

Examining the etiology and pregnancy outcomes of 152 critically ill pregnant patients in the Intensive Care Unit

BackgroundCollaborative multidisciplinary approaches in obstetrics, particularly in conjunction with Intensive Care Units (ICUs), offer innovative treatment strategies for critically ill pregnant women. This study aimed to assess pregnancy outcomes and mortality in critically ill pregnant women in the Intensive Care Unit (ICU) and to provide valuable clinical insights for improving the management of obstetric emergency care, reducing maternal and neonatal adverse outcomes, and improving the level of obstetric care.MethodsThis study retrospectively included 152 critically ill pregnant women admitted to the ICU. They were grouped according to the main reason for ICU admission as well as the variety of diseases present at the time of admission. Then their clinical data were evaluated.ResultsThe results showed that the main obstetric factors leading to ICU admission were pregnancy-related hypertensive disease, postpartum hemorrhage, and acute fatty liver of pregnancy; the non-obstetric factors included either pregnancy complicated by heart disease, sepsis, or malignant tumors. The maternal mortality rate was higher in the non-obstetric direct factor group than in the obstetric direct factor group (22.12% vs. 6.25%, p = 0.016). As for the pregnancy outcome, the cesarean section rate in the group affected by obstetric factors was significantly higher than that in the group affected by non-obstetric factors (p = 0.008). Furthermore, the incidence of pregnancy termination and induced abortion before 28 weeks in the group affected by non-obstetric factors was significantly higher than that in the group affected by obstetric factors (all p < 0.05). There was a statistically significant difference in mortality among the three groups of patients with different SOFA scores (p = 0.000), suggesting that the mortality of critically ill pregnant women with higher SOFA scores increased, making it a valuable tool for evaluating prognosis.ConclusionNon-obstetric factors were the primary contributors for ICU admission of expecting mothers. Therefore, utilizing modalities that successfully analyze these factors can aid in understanding the characteristics of critically ill pregnant women, and advancing perinatal healthcare technologies to reduce maternal mortality rates.

Safety and Efficacy of Portal Vein Recanalization with Creation of Intrahepatic Portosystemic Shunt (PVR-TIPS) to Treat Chronic Portal Vein Thrombosis in Non-cirrhotic Patients.

This study assesses the efficacy and safety of Portal Vein Recanalization with Intrahepatic Portosystemic Shunt (PVR-TIPS) in non-cirrhotic patients with chronic portal vein occlusion (CPVO), cavernomatous transformation, and symptomatic portal hypertension (PH) and/or portal vein thrombotic progression. Medical records of 21 non-cirrhotic patients with CPVO and portal cavernoma undergoing PVR-TIPS were analyzed. Hemodynamic (intraprocedural reduction in portosystemic pressure gradient), clinical (data on gastrointestinal bleeding, abdominal pain, ascites, and presence of esophageal varices from imaging exams) and technical success (PVR-TIPS) assessed efficacy. Safety was determined through complications classified according to the CIRSE Classification System. PVR-TIPS was successfully performed in all patients, resulting in a significant reduction in portal pressure gradient by 10mmHg (21.475 ± 9.7mmHg - 11.454 ± 5,4mmHg, p < 0.001), alleviating portal hypertension symptoms without thrombotic progression. Clinical success included resolution or reduction of ascites (p = 0.016), gastroesophageal varices (p = 0.004), abdominal pain (p = 0.0021), and cessation of gastrointestinal bleeding (p = 0.021). Complications occurred in 33% of patients, including six grade III events (1 perioperative liver bleeding, 5 delayed stent occlusions) and one grade VI event resulting in death (4.8%). Primary patency rate was 76% (21.3months, range:0.2-82), secondary patency 100% (4months, range:3.8-40.8). Survival at follow-up was 90.4%, with one unrelated death. One patient underwent liver transplantation, three became eligible post-recanalization. PVR-TIPS proves effective and safe in reducing portal pressure gradient, thereby alleviating PH symptoms without evidence of portal thrombosis progression in non-cirrhotic patients with CPVO and portal cavernoma. It expands therapeutic options, including liver transplantation.

Laparoscopic liver resection utilizing the ventral avascular area of the inferior vena cava: A retrospective cohort study.

Laparoscopic liver resection (LLR) can be challenging due to the difficulty of establishing a retrohepatic tunnel under laparoscopy. Dissecting the third hepatic hilum before parenchymal transection often leads to significant liver mobilization, tumor compression, and bleeding from the short hepatic veins (SHVs). This study introduces a novel technique utilizing the ventral avascular area of the inferior vena cava (IVC), allowing SHVs to be addressed after parenchymal transection, thereby reducing surgical complexity and improving outcomes in in situ LLR. To introduce and evaluate a novel LLR technique using the ventral avascular area of the IVC and compare its short-term outcomes with conventional methods. The clinical cohort data of patients with pathologically confirmed hepatocellular carcinoma or intrahepatic cholangiocarcinoma who underwent conventional LLR and novel LLR between July 2021 and July 2023 at the First Affiliated Hospital of Chongqing Medical University were retrospectively analyzed. In novel LLR, we initially separated the caudate lobe from the IVC using dissecting forceps along the ventral avascular area of the IVC. Then, we transected the parenchyma of the left and right caudate lobes from the caudal side to the cephalic side using the avascular area as a marker. Subsequently, we addressed the SHVs and finally dissected the root of the right hepatic vein or left hepatic vein. The short-term postoperative outcomes and oncological results of the two approaches were evaluated and compared. A total of 256 patients were included, with 150 (58.59%) undergoing conventional LLR and 106 (41.41%) undergoing novel LLR. The novel technique resulted in significantly larger tumor resections (6.47 ± 2.96 cm vs 4.01 ± 2.33 cm, P < 0.001), shorter operative times (199.57 ± 60.37 minutes vs 262.33 ± 83.90 minutes, P < 0.001), less intraoperative blood loss (206.92 ± 37.09 mL vs 363.34 ± 131.27 mL, P < 0.001), and greater resection volume (345.11 ± 31.40 mL vs 264.38 ± 31.98 mL, P < 0.001) compared to conventional LLR. This novel technique enhances liver resection outcomes by reducing intraoperative complications such as bleeding and tumor compression. It facilitates a safer, in situ removal of complex liver tumors, even in challenging anatomical locations. Compared to conventional methods, this technique offers significant advantages, including reduced operative time, blood loss, and improved overall surgical efficiency.

Goose Deoxycholic Acid Ameliorates Liver Injury in Laying Hens with Fatty Liver Hemorrhage Syndrome by Inhibiting the Inflammatory Response

Fatty liver hemorrhagic syndrome (FLHS) in laying hens is a nutritional and metabolic disease involving liver enlargement, hepatic steatosis, and hepatic hemorrhage as the primary symptoms. The syndrome is prone to occur during the peak laying period of laying hens, which has resulted in significant economic losses in the laying hen breeding industry; however, the specific pathogenesis of FLHS remains unclear. Our group and previous studies have shown that bile acid levels are significantly decreased during the development of fatty liver and that targeted activation of bile acid–related signaling pathways is beneficial for preventing and treating fatty liver. In this study, we generated a FLHS laying hen model by feeding hens a high-energy, low-protein diet, with goose deoxycholic acid (CDCA) given as an intervention. HE staining, fluorescence quantitative PCR, and ELISA were used to evaluate the effects of CDCA on pathological changes and inflammatory responses in the liver. The results showed that hepatic hemorrhage in FLHS laying hens was reduced after CDCA treatment. Furthermore, fat vacuoles and transaminase levels decreased significantly. In addition, expression levels of M1-type macrophage markers and polarization products were significantly reduced, and the expression of pro-inflammatory regulatory factors related to the JAK-STAT signaling pathway, LPS-TLR4-Myd88–NF-kB signaling pathway, and NLRP3 inflammasomes decreased significantly as well. Expression levels of M2-type macrophage markers and polarization products increased significantly, as did the expression of anti-inflammatory regulators related to the JAK-STAT signaling pathway. These results suggest that CDCA ameliorates liver injury in laying hens with FLHS by inhibiting macrophage M1-type polarization and the resulting pro-inflammatory response, thereby promoting M2-type macrophage polarization and an anti-inflammatory response.

Chitosan oligosaccharide alleviates DON-induced liver injury via suppressing ferroptosis in mice.

Chitosan oligosaccharide (COS), a water-soluble derivative of chitin, has been recognized for its diverse biological properties. Deoxynivalenol (DON) is a prevalent mycotoxin, causing extreme liver damage. However, the mechanism whereby COS alleviates DON-induced liver injury remains unclear. In the present study, C57BL/6 mice were randomly divided into four groups: control (CON), DON (1.0 mg/d/kg BW DON), COS (200 mg/d/kg BW COS), and COS+DON (200 mg/d/kg BW COS + 1.0 mg/d/kg BW DON), with a period of 28 days. The results indicated that COS effectively reversed DON-induced weight loss, elevated liver index, and liver hemorrhage and swelling in mice. Moreover, COS significantly reduced liver reactive oxygen species (ROS) levels, malondialdehyde (MDA) content, and lactate dehydrogenase (LDH) release in DON-exposed mice, while restoring the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and total antioxidant capacity (T-AOC). Further investigations revealed that COS modulated the expressions of pro-inflammatory cytokines and anti-apoptotic proteins through stimulation of the Nrf2/HO-1 signaling pathway and suppression of the NF-κB signaling pathway. Additionally, COS inhibited ferroptosis by modulating the SLC7A11/GSH/GPX4 pathway and the expression of FTH1 and FLC proteins, thereby reducing lipid peroxidation accumulation and iron overload. In summary, this research showed that COS mitigated DON-induced liver injury in mice by alleviating DON-induced oxidative stress, inflammation, apoptosis, and ferroptosis via modulating the Nrf2/HO-1/NF-κB and GPX4 signaling pathways. These results offer a theoretical basis for the development and application of COS as a novel liver protectant and propose innovative therapeutic strategies for combating DON-induced liver damage.

Photodynamic hemostatic silk fibroin film with photo-controllable modulation of macrophages for bacteria-infected wound healing.

Massive hemorrhage and chronic wounds caused by bacterial infections after trauma are significant challenges in clinical practice. An ideal hemostatic wound dressing should simultaneously manage bleeding and prevent bacterial infections and also hold excellent biocompatibility and bioactivities to successfully modulate immune microenvironments to promote wound healing. In this study, a silk fibroin-based light-responsive film was demonstrated to possess effective capacity of light-induced non-compressible hemostasis on liver hemorrhage and tail bleeding in vivo by binding with blood platelets to promote the clotting cascade. The blood loss of the rats was significantly less after C-MASiF films were applied, which were 1223.33 ± 347.9 mg (liver trauma) and 363.33 ± 60.28 mg (tail trimming). Importantly, the films exhibited photo-controllable modulation activity on macrophages through repeated near-infrared irradiation to regulate the immune microenvironment to enhance photodynamic antibacterial therapy. Moreover, the light-responsive silk fibroin film effectively promoted Staphylococcus aureus infected burn wound healing in vivo. The quantity of residual bacteria in the wound sites of mice in the C-MASiF films group (0.05 ± 0.0047 × 108 CFU mL-1) was considerably less than that in the control group (3.18 ± 0.75 × 108 CFU mL-1), and the wound area in the C-MASiF group (78.03% ± 4.12%) was considerably smaller than that in the control group (60.33% ± 8.81%) after 14 days. Overall, this light-responsive silk fibroin film can provide a powerful strategy for wound healing of burns.

The role of the nurse in the care of a post-operative cesarean patient with HELLP syndrome in the gynecology and obstetrics service of a National Hospital, 2022

Pregnancy with hellp syndrome is life-threatening, it appears in 5-9 out of every 1000 pregnancies and in 10-20% of cases with severe preeclampsia, it causes the breakdown of red blood cells, causing liver problems , bleeding and blood pressure. The objective of this study is to manage nursing care for a patient with síndrome of hellp and hemoperitoneum with pelvic hematoma in the obstetrics-gynecology service. The present study is a research with a qualitative approach, clinical case type, study subject female, 21 years old. The nursing care process was used as a method, the assessment guide of Marjorie Gordon's 11 functional patterns was applied, by which altered patterns were found, formulating the nursing diagnoses: Decreased cardiac output, Acute Pain and CP: Shock hypovolemic. The activities were executed in a timely manner, the evaluation was through the difference in baseline and final scores of the indicators. We can conclude that hellp syndrome is a hypertensive disorder of pregnancy, however, the complication of this post-cesarean patient is hemoperitoneum with pelvic hematoma, timely nursing care against this was the main axis in the patient's restoration. It is concluded that, according to the problems identified in the patient, the nursing care process was managed in its five stages, improving the patient's health status, but the survival and success of the treatment provided depends on the timely identification of the problems and appropriate choice of treatment

A Recombinant Human Collagen and RADA-16 Fusion Protein Promotes Hemostasis and Rapid Wound Healing.

In this study, we designed a fusion protein, rhCR, by combining human collagen with the self-assembling peptide RADA-16 using genetic engineering technology. The rhCR protein was successfully expressed in Pichia pastoris. The rhCR can self-assemble into a three-dimensional nanofiber network under physiological conditions. The lyophilized rhCR sponge exhibited high elasticity modulus and stable swelling properties. In vitro experiments confirmed that the rhCR had good biocompatibility and could significantly promote the adhesion, proliferation, and migration of fibroblasts (L929), upregulating the expression of genes such as Vim, Fgf, Vegf, and Tgf-β3 in L929 cells. When applied to a mouse liver hemorrhage model, rhCR hemostatic sponges rapidly formed nanofibers on the ruptured liver surface, activated platelet CD62P, and significantly reduced blood loss and bleeding duration compared to the recombinant human collagen (rhCol) alone. Furthermore, the rhCR application markedly accelerated wound healing in a mouse full-thickness skin defect model, with the wound healing rate in the rhCR group being 2.6 times that of the untreated group and 1.7 times that of the rhCol group on day 6 postinjury. Histological and immunofluorescence analyses revealed that the rhCR promoted collagen deposition and epidermal regeneration and improved the quality of skin tissue repair by stimulating tissue cells to produce cytokines, growth factors, and immune factors through immunological regulation. The rhCR fusion protein combines the advantages of collagen and RADA-16, overcoming the limitations of their separate use in hemostatic and tissue engineering applications. This biomaterial and its design idea hold promise for a variety of regenerative applications.

Computer-Aided Construction and Evaluation of Poly-L-Lysine/Hyodeoxycholic Acid Nanoparticles for Hemorrhage and Infection Therapy.

Background: Traumatic hemorrhage and infection are major causes of mortality in wounds caused by battlefield injuries, hospital procedures, and traffic accidents. Developing a multifunctional nano-drug capable of simultaneously controlling bleeding, preventing infection, and promoting wound healing is critical. This study aimed to design and evaluate a nanoparticle-based solution to address these challenges effectively. Methods: Using a one-pot assembly approach, we prepared a series of nanoparticles composed of poly-L-lysine and hyodeoxycholic acid (PLL-HDCA NPs). Theoretical simulations and experimental studies were combined to optimize their structure and functionality. In vitro platelet aggregation, antibacterial assays, cytotoxicity tests, and hemolysis evaluations were performed. In vivo efficacy was assessed in various hemorrhage models, a full-thickness skin defect model, and a skin irritation test. Results: PLL-HDCA NPs demonstrated effective induction of platelet aggregation and significantly reduced bleeding time and blood loss in mouse models, including tail vein, femoral vein, artery, and liver bleeding. Antibacterial assays revealed strong activity against E. coli and S. aureus. Wound healing studies showed that PLL-HDCA NPs promoted tissue repair in a full-thickness skin defect model. Cytotoxicity and hemolysis tests indicated minimal impact on human cells and significantly reduced hemolysis rates compared to PLL alone. Skin irritation tests confirmed the safety of PLL-HDCA NPs for external application. Conclusions: PLL-HDCA NPs represent a safe, efficient, and multifunctional nano-drug suitable for topical applications to control bleeding, combat infection, and facilitate wound healing, making them promising candidates for use in battlefield and hospital settings.

Nanofiber-based Multifunctional Microspheres for Rapid Hemostasis and Microorganism Removal of Water.

Constructing hemostats capable of effectively controlling severe hemorrhage from irregular wounds presents significant challenges and imperatives. In this study, a novel approach is introduced using nanofibrous chitin microspheres (NCM) that are compressed to 60% strain (NCM-60%) to amplify their water-initiated expansion performance. This unique capacity allows NCM-60% to efficiently conform to and fill irregular bleeding cavities, even those of varying depths and curvatures, thereby promoting rapid blood coagulation at deep hemorrhage sites. NCM-60% exhibits effective control of severe femoral artery and "J"-shaped liver hemorrhages in 151 ± 6 s and 68 ± 15 s, respectively, revealing its exceptional hemostatic efficacy. Furthermore, NCM-60% exhibited promising capabilities in removing microbes from water, achieving removal rates of over 96% of bacteria. Blood compatibility assessments and cytotoxicity tests further confirmed the favorable biocompatibility of NCM-60%. Importantly, NCM-60% is found to biodegrade and be absorbed in vivo within 12 weeks. This study represents the first instance of leveraging chitin nanofiber-based biomaterials to design water-initiated expansion micro-hemostat, and integrate hemostatic functions with waterborne microorganism removal, thereby expanding the potential applications of micro-nanostructural materials in emergency first-aid scenarios.

Application of Intraoperative Ultrasound in Laparoscopic Liver Resection with Pringle Maneuver: A Comparative Study with the Pringle Maneuver.

Background: Appropriate surgical techniques for controlling bleeding and preserving residual liver function are key to the success of laparoscopic liver resection. This study aims to evaluate the application effect of intraoperative ultrasound in the Pringle maneuver of laparoscopic liver resection. Materials and Methods: Between January 2022 and June 2023, 100 patients underwent laparoscopic liver resection and were randomly allocated to receive application of intraoperative ultrasound for Pringle maneuver (intraoperative ultrasound group, n = 50) or conventional Pringle maneuver (conventional group, n = 50). Intraoperative blood loss, blood transfusion, operation time, hepatic portal block time, complications (bile leakage, hemorrhage, ascites, and posthepatectomy liver failure), and hospital stay were compared between groups, along with the alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TB) levels at postoperative days 1, 3, and 7. Results: The operation time, postoperative ALT, AST, and TB levels on postoperative days 1, 3, and 7, complications (bile leakage, hemorrhage, ascites, and posthepatectomy liver failures), and hospital stay were comparable between groups. Compared with the conventional group, the intraoperative ultrasound group had significantly less intraoperative blood loss (P = .015), lower blood transfusion rate (P = .035), and less hepatic portal block time (P = .012). Conclusions: Applying intraoperative ultrasound in laparoscopic liver resection for hepatic pedicle occlusion is a safe, simple, and effective method.

TWEAK is an activator of Hippo-YAP signaling protecting against hepatic Ischemia/ reperfusion injury

Hepatic ischemia–reperfusion injury (IRI) represents a formidable complication commonly linked with hemorrhagic shock, liver resection, and transplantation. This study aims to elucidate the role of Tumor Necrosis Factor-like Weak Inducer of Apoptosis (TWEAK) in the pathogenesis of hepatic I/R injury and to delineate the underlying mechanisms involved. Utilizing a hypoxia-reoxygenation model in human liver organoids (HLOs) alongside a murine model of warm ischemia–reperfusion injury, we systematically investigated the interplay between TWEAK, its receptor Fn14, and the HIPPO signaling pathway. Our findings indicate that TWEAK pretreatment significantly mitigates IRI in murine livers as well as hypoxia/reoxygenation injury in HLOs. Notably, administration of adeno-associated virus (AAV) to knock down Fn14 abrogated the protective effects of TWEAK in the murine model. Transcriptome sequencing analysis revealed that the interaction between TWEAK and Fn14 enhances cellular resistance to IRI by activating the HIPPO signaling pathway. Overall, TWEAK emerges as a promising therapeutic target for mitigating hepatic I/R injury, potentially improving outcomes in liver transplantation.

Self-gelling, tunable adhesion, antibacterial and biocompatible quaternized cellulose/tannic acid/polyethylene glycol/montmorillonite composite powder for quick hemostasis

Hemostatic powders are widely used in incompressible or irregularly shaped bleeding wounds, but traditional hemostatic powders exhibit low adhesion, unsatisfactory hemostatic effect, limited infection control, and are not suitable for clinical or emergency situations. This study developed a novel self-gelling hemostatic powder (QTPM) consisting of quaternized cellulose (QC)/ tannic acid (TA)/ polyethylene glycol (PEG)/ montmorillonite (MMT). QTPM could absorb interfacial liquid hydrating to a stable hydrogel which form a switchable adhesion to tissues. Moreover, QTPM exhibits excellent antibacterial property by the synergistic effect of QC and TA. Furthermore, QTPM directly activate intrinsic and extrinsic coagulation hemostatic pathways to enhance hemostasis, and it concentrate coagulation factors. In vivo hemostasis study results show that QTPM significantly accelerated hemostasis and reduced blood loss compared with the blank group (>75 % reduction in hemostatic time, >85 % reduction in blood loss) in liver bleeding model (hemostasis time of 71.67 ± 7.09 s, blood loss of 19.23 ± 2.60 mg) and tail amputation model (hemostasis time of 91.03 ± 12.05 s, blood loss of 15.24 ± 1.77 mg). Therefore, the advantages of QTPM including rapid and effective hemostasis, easy usage, easy storability and adaptability make it a potential biomaterial for rapid hemostasis direction in the clinical setting.

Multifunctional injectable oxidized sodium alginate/carboxymethyl chitosan hydrogel for rapid hemostasis

Uncontrolled bleeding from incompressible or irregularly shaped wounds is a major factor in the death of people in the battlefield or surgery process. Ideal rapid hemostatic materials should have the performance of rapid hemostasis and at the same time can be applied to a variety of complex wound trauma types, in addition, excellent antimicrobial properties, adhesion, biocompatibility, degradation, and the non-toxicity of degradation products are also necessary, but there are fewer hemostatic materials that meet these requirements. Herein, we prepared an injectable hemostatic hydrogel based on the natural products sodium alginate (SA) and carboxymethyl chitosan (CMC). Oxidized sodium alginate (OSA) was prepared by the oxidation reaction of NaIO4 with SA, and OSA with aldehyde group was mixed with CMC with amino group to rapidly form an in situ injectable hemostatic hydrogel (OSA/CMC) by the Schiff base reaction. OSA/CMC hydrogel exhibited excellent antimicrobial and adhesion properties by the Schiff base reaction. In addition, OSA/CMC hydrogel directly activate the endogenous coagulation pathway through the synergistic effect of OSA, CMC to enhance the hemostatic effect. The results of in vivo hemostasis study showed that OSA/CMC hydrogel significantly accelerated hemostasis and reduced blood loss in liver hemorrhage model and tail amputation model. Therefore, OSA/CMC hydrogel is expected to be a potential material in the direction of rapid clinical hemostasis due to its good adhesion properties, antimicrobial properties, biocompatibility, blood compatibility, and efficient rapid hemostasis.

A self-gelling alginate/chitosan based powder containing bioactive nanoparticles for non-compressible bleeding control and promoting wound healing

The challenge remains in developing hemostatic dressings that can fulfill both hemostatic and repair functions to meet clinical demands worldwide. Herein, the biodegradable powders composed of benzeneboronic acid-modified sodium alginate/catechol-modified quaternized chitosan hydrogel (SBQCC) networks and bioactive cerium oxide nanoparticles (CNPs), were prepared for hemostasis and promoting wound healing. The SBQCC/CNPs powders had good self-gelation ability, water absorption ratio, tissue adhesiveness and biocompatibility. The SBQCC/CNPs powders could not only rapidly absorb a large amount of blood to concentrate coagulation factors when applied on bleeding wounds, but also formed an adhesive hydrogel physical barrier to control bleeding in situ. Meanwhile, the aggregation and activation of red blood cells and platelets induced by the SBQCC/CNPs powders can initiate the forming of internal blood clot with fibrin to further enhance the hemostatic effect. The SBQCC/CNPs powders demonstrated excellent hemostatic performance in non-compressible rat tail vein bleeding and rabbit liver bleeding models. In addition, SBQCC/CNPs powder-derived hydrogels had antibacterial activity and multiple biological activities, including antioxidant, anti-inflammatory and promoting angiogenesis for accelerating wound healing. Therefore, the SBQCC/CNPs powders can accelerate wound healing while achieving effective hemostasis, which will be a promising hemostatic dressing.

New Onset of Acute and Chronic Hepatic Diseases Post-COVID-19 Infection: A Systematic Review.

The SARS-CoV-2 virus caused a pandemic in the 2020s, which affected almost every aspect of life. As the world is recovering from the effect of the coronavirus, the concept of post-COVID-19 syndrome has emerged. Multiple organ systems have been implicated, including the liver. We aim to identify and analyze the reported cases of severe and long-term parenchymal liver injury post-COVID-19 infection. Several databases were used to conduct a comprehensive literature search to target studies reporting cases of severe and long-term parenchymal liver injury post-COVID-19 infection. Screening, data extraction, and cross checking were performed by two independent reviewers. Only 22 studies met our inclusion criteria. Our results revealed that liver steatosis, non-alcoholic fatty liver disease (NAFLD), and cirrhosis were the most reported liver associated complications post-COVID-19 infection. Moreover, complications like acute liver failure, hepatitis, and liver hemorrhage were also reported. The mechanism of liver injury post-COVID-19 infection is not fully understood. The leading proposed mechanisms include the involvement of the angiotensin-converting enzyme-2 (ACE-2) receptor expressed in the liver and the overall inflammatory state caused by COVID-19 infection. Future studies should incorporate longer follow-up periods, spanning several years, for better insight into the progression and management of such diseases.

Calcium Ion-Coupled Polyphosphates with Different Degrees of Polymerization for Bleeding Control.

The development of efficient hemostatic materials is crucial for achieving rapid hemorrhage control and effective wound healing. Inorganic polyphosphate (polyP) is recognized as an effective modulator of the blood coagulation process. However, the specific effect of polyP chain length on coagulation is not yet fully understood. Furthermore, calcium ions (Ca2+) are essential for the coagulation process, promoting multiple enzyme-catalyzed reactions within the coagulation cascade. Hence, calcium ion-coupled polyphosphate powders with three different degrees of polymerization (CaPP-n, n = 20, 50, and 1500) are synthesized by an ion-exchange reaction. CaPP exhibits a crystalline phase at a low polymerization degree and transitions to an amorphous phase as the polymerization degree increases. Notably, the addition of Ca2+ enhances the wettability of polyP, and CaPP promotes hemostasis, with varying degrees of effectiveness related to chain length. CaPP-50 exhibits the most promising hemostatic performance, with the lowest blood clotting index (BCI, 12.1 ± 0.7%) and the shortest clotting time (302.0 ± 10.5 s). By combining Ca2+ with polyP of medium-chain length, CaPP-50 demonstrates an enhanced ability to accelerate the adhesion and activation of blood cells, initiate the intrinsic coagulation cascade, and form a stable blood clot, outperforming both CaPP-20 and CaPP-1500. The hemostatic efficacy of CaPP-50 is further validated using rat liver bleeding and femoral artery puncture models. CaPP-50 is proven to possess hemostatic properties comparable to those of commercial calcium-based zeolite hemostatic powder and superior to kaolin. In addition, CaPP-50 exhibits excellent biocompatibility and long-term storage stability. These results suggest that CaPP-50 has significant clinical and commercial potential as an active inorganic hemostatic agent for rapid control of bleeding.

Novel Flowable Hemostatic Agent ActiClot: Efficacy and Safety Assessment in Rat and Porcine Models.

Background/Objectives: This study evaluated the hemostatic performance and safety of ActiClot (ATC), a new flowable hemostatic agent, through in vivo tests. Methods: ATC was compared with the commercially available FLOSEAL®. ATC consists of carboxymethyl starch, thrombin, and sorbitol powders in Syringe I, and a calcium chloride solution in Syringe II. In vivo evaluation used rat liver bleeding and porcine heart bleeding models. Safety was assessed using a rat subcutaneous implantation model. Results: ATC significantly reduced hemostasis time (70.00 ± 7.35 s) compared to gauze control (240.63 ± 32.31 s) in the rat liver model, showing a 70% reduction. There was no significant difference between ATC and FLOSEAL® (58.75 ± 13.42 s). In the porcine heart model, both agents achieved 100% hemostasis within 3 min, with no significant difference in success rates within 2 min (ATC 87.5%, FLOSEAL® 75%). The gauze control group failed in all tests. The rat subcutaneous implantation model showed no visual ATC observation after 48 h, indicating biocompatibility, with no inflammation observed. Conclusions: ATC demonstrated effective hemostatic performance similar to FLOSEAL® in two in vivo models, with faster hemostasis in the rat liver model. It also showed excellent safety and biocompatibility, indicating its potential for surgical and emergency bleeding control.

Enhanced specific surface area and mechanical property of silk nanofibers aerogel for potential hemostasis applications

Biopolymer aerogel is a new type of material with potential applications in the biomedical field. Silk fibroin is of particular interest as a raw material with good biocompatibility and degradable. However, the low mechanical strength and small specific surface area of silk fibroin aerogels limit its further development. Herein, a fast water absorption, highly specific surface area and mechanically strong of aerogels were prepared using low crystal silk fibroin nanofibers (SNF), sol-gel process, solvent exchange and supercritical carbon dioxide (CO2) drying method. The resulting Aero-Sc displayed highly specific surface area (251 m2/g), porosity (97.6 %) and water absorption capacity (1200 %). Furthermore, with rapid water absorption and stronger erythrocyte adhesion, the Aero-Sc showed highly effective hemostasis in vitro. In vivo, animal experiments on rat liver hemorrhage model confirmed that SNF aerogels have a less blood loss (312 ± 29 mg) and faster hemostatic time (92 ± 13 s) than commercially gelatin sponge (p < 0.05). The unique properties of silk fibroin nanofibers aerogel developed in this study has great potential to be a safe and effective hemostatic medical device.