Ischemic Necrosis Research Articles

Recent advances in mesenchymal stem cell therapy for myocardial infarction.

Myocardial infarction refers to the ischemic necrosis of myocardium, characterized by a sharp reduction or interruption of blood flow in the coronary arteries due to the coronary artery occlusion, resulting in severe and prolonged ischemia in the corresponding myocardium and ultimately leading to ischemic necrosis of the myocardium. Given its high risk, it is considered as one of the most serious health threats today. In current clinical practice, multiple approaches have been explored to diminish myocardial oxygen consumption and alleviate symptoms, but notable success remains elusive. Accumulated clinical evidence has showed that the implantation of mesenchymal stem cell for treating myocardial infarction is both effective and safe. Nevertheless, there persists controversy and variability regarding the standardizing MSC transplantation protocols, optimizing dosage, and determining the most effective routes of administration. Addressing these remaining issues will pave the way of integration of MSCs as a feasible mainstream cardiac treatment.

Evaluation of Spermatic Cord Ligation as an Alternative Method of Castration in Dogs

The study evaluated open spermatic cord ligation as an alternative method of castration in dogs. Three Nigerian indigenous puppies were randomly selected (identified as SL1, SL2 and SL3) and used for the study. They underwent the same surgical procedure. Blood samples of the experimental puppies were taken daily for 3 days, pre-surgery. Additional blood sampling was at 24 hrs post-surgery, and, subsequently at 48 hrs interval for 3, 2, and 1 week(s) in SL1, SL2, SL3 respectively. Sera samples were harvested from the blood samples. At weeks 3, 2 and 1, the testicles of the puppies were harvested for macroscopic and microscopic evaluations. The puppies were physically examined daily throughout the study period. Serum testosterone concentration of the puppies was determined using ELISA kit. The pre-surgical values ranged from 0.1ng/mL-0.5ng/mL before the surgery and declined to 0ng/mL 24 hrs post-surgery. Gross appearance of the testicles showed atrophy of the testicles. Testicular histopathology showed distortion of germ and supporting cells due to ischaemic necrosis, which was more evident in SL1 followed by SL2, and then SL3. It was concluded from this study that the procedure was effective, minimally invasive, simple and fast.

Evaluation of the clinical efficacy of using an inverted triangular cannulated compression screw in combination with positive or negative buttress reduction for the healing of femoral neck fractures

ObjectiveWe aimed to compare the clinical efficacy of inverted triangular cannulated compression screws combined with Gotfried positive or negative buttress reduction in the healing of femoral neck fractures.MethodsBetween October 2017 and March 2021, 55 patients with femoral neck fractures underwent treatment using inverted triangular cannulated compression screws combined with Gotfried positive or negative buttress reduction. Among these patients, 29 received inverted triangular cannulated compression screws combined with Gotfried positive buttress reduction treatment. This group consisted of 16 males and 13 females, with an average age of 43.45 ± 8.23 years. Additionally, 26 patients received inverted triangular cannulated compression nails combined with Gotfried negative buttress reduction treatment. This group included 14 males and 12 females, with an average age of 41.96 ± 8.69 years. Postsurgery, various measurements were taken, including the degree of shortening of the femoral neck, degree of bone nonunion, degree of fixation failure, degree of ischemic necrosis of the femoral head, and Harris score of the hip joint.ResultsAll patients were followed up for a minimum of 18 months. The group that underwent treatment with an inverted triangular cannulated compression screw combined with Gotfried positive buttress reduction did not experience any cases of bone nonunion, fixation failure, or ischemic necrosis of the femoral head. In the group that received treatment with inverted triangle cannulated compression screws combined with Gotfried negative buttress reduction, there was one case of bone nonunion, three cases of early fixation failure, and one case of ischemic necrosis. Ultimately, five patients (19.23% of the total) underwent joint replacement surgery. The average shortening lengths in the vertical plane were 4.07 ± 1.98 mm and 8.08 ± 3.54 mm, respectively. In the horizontal plane, the average shortening lengths were 3.90 ± 1.57 mm and 7.77 ± 3.31 mm, respectively. At the last follow-up, the group that received Gotfried positive buttress reduction had a greater Harris hip joint score.ConclusionThe success rate of combining inverted triangular cannulated compression screws with Gotfried positive buttress reduction surgery is relatively high. This surgical approach effectively prevents femoral neck shortening and improves hip joint function. Moreover, it is crucial to avoid negative buttress reduction when managing femoral neck fractures.

A Single Large Center Experience of Medically Treating Impending Compartment Syndrome of Tibia with Deflazacort

Abstract Background: Acute compartment syndrome (ACS) is a rare condition characterized by increased pressure in the closed compartments of the limbs resulting in ischemic tissue necrosis. Most of the patients present following limb fractures. Apart from surgical options such as fasciotomy, which has inherent complication of myonecrosis and severe infection, conservative management with corticosteroids hasshown to be useful. We conducted this study to understand the changes in intra-compartment pressures in ACS after regular monitoring following corticosteroids treatment. Materials and Methods: Consecutive patients of ACS following closed fractures lower limb fractures of tibia or fibula from June 2021 to February 2022 were included. The intra-compartment pressure was measured using a manometer at the time of presentation and after 3, 6, 12, 24, 48, 72, and 96 h of treatment with tab Deflazacort 6 mg × 1 Tablet × Tds. The efficacy of treatment was assessed on the basis of changes in intra-compartmental pressure and improvement in the clinical signs and symptoms of ACS. Results: The study included 60 patients, most (63.3%) suffering from fracture of proximal tibia or fibula (36.7%), presenting with ACS. The mean age was 32.4 ± 8.6 years and most (53%) were males. We observed a statistically significant change (P < 0.05) in the intra-compartment pressures from the baseline to 3 h, 24 h, 48 h, 72 h, and 96 h after corticosteroid treatment. None of these patients suffered from ischemic necrosis or any other complication of ACS. Conclusion: Our results suggest that the timely diagnosis of ACS in patients with lower limb fractures and early initiation of conservative management with corticosteroids can be a mainstay of treatment in these patients. This conservative approach can avoid surgical intervention and reduce the cost of management.

An Analysis of STEMI Cases in the Postgraduate Hospital in Khost, Afghanistan

Myocardial infarction, specifically ST elevation myocardial infarction (STEMI), involves the development of localized ischemic necrosis in the heart muscle due to an acute disruption of coronary blood flow. It clinically presents as burning, pressing, or squeezing chest pain that radiates to the left arm, collarbone, scapula, or jaw, along with symptoms such as shortness of breath, a feeling of fear, and cold sweat. Immediate hospitalization in a cardiac intensive care unit is crucial for patients with a developed myocardial infarction, as delays in treatment can be fatal. This study is a descriptive case series conducted in the year 1397 of the Islamic calendar. Out of 1602 inpatients admitted to Khost Postgraduate Hospital during this period, 50 patients were diagnosed with STEMI. The primary objectives of this research were to determine the frequency and pattern of STEMI cases at Khost Postgraduate Hospital during the year 1396 of the Islamic calendar.

Case Reports on Anatomical Variations of the Hepatic Arteries: Implications for Laparoscopic Cholecystectomy and Surgical Safety

A laparoscopic surgeon’s understanding of embryology, anatomy, and potential anatomical variations of the bile duct is crucial for safely performing gallbladder removal using this minimally invasive technique. In conducting two medical-legal autopsies, we identified a previously undocumented anatomical variant where the liver’s blood supply originates from the common hepatic artery, branching into a trident formation to form the right, left, and cystic hepatic arteries. Notably, the right hepatic artery is situated within Calot’s triangle, whereas the cystic artery is located anomalously outside the triangle. This anatomical anomaly poses significant surgical risks, including the potential for morbidity and mortality due to ischemic necrosis of the liver from vascular injury. The success of laparoscopic surgery under these circumstances relies heavily on the surgeon’s expertise in managing an atypical surgical field, adherence to a culture of safety, and a critical approach to safety in laparoscopic cholecystectomy.

SARS-CoV-2 infects neurons, astrocytes, choroid plexus epithelial cells and pericytes of the human central nervous system in vitro.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with neurological sequelae including haemorrhage, thrombosis and ischaemic necrosis and encephalitis. However, the mechanism by which this occurs is unclear. Neurological disease associated with COVID-19 has been proposed to occur following direct infection of the central nervous system and/or indirectly by local or systemic immune activation. We evaluated the expression of angiotensin-converting enzyme-2 and transmembrane protease, serine 2 (TMPRSS2) in brain tissue from five healthy human donors and observed low-level expression of these proteins in cells morphologically consistent with astrocytes, neurons and choroidal ependymal cells within the frontal cortex and medulla oblongata. Primary human astrocytes, neurons, choroid plexus epithelial cells and pericytes supported productive SARS-CoV-2 infection with ancestral, Alpha, Delta and Omicron variants. Infected cells supported the full viral life cycle, releasing infectious virus particles. In contrast, primary brain microvascular endothelial cells and microglia were refractory to SARS-CoV-2 infection. These data support a model whereby SARS-CoV-2 can infect human brain cells, and the mechanism of viral entry warrants further investigation.

Diagnosis and Treatment of Hepatic Hematoma After Liver Transplantation in a Timely Manner

ObjectiveHematomas of the liver graft, that is, postintervention, subcapsular or intrahepatic are rare yet potentially fatal complications following liver transplantation (LT), necessitating immediate diagnosis and management to avert devastating outcomes. This study was aimed to introduce our approach to manage graft hematoma subsequent to LT. MethodsAmong 131 orthotopic liver transplantations (OLT) conducted at our institution between January 2017 and May 2023, 3 cases of intrahepatic (n = 2) and extrahepatic (n = 1) hematoma were confirmed through computed tomography (CT) within 10 days after LT. The clinical outcomes of various treatment modalities for these three cases were analyzed. ResultsThree out of 131 (2.3%) LT recipients developed graft hematoma. Patient 1 developed a spontaneous intrahepatic hematoma, without evident predisposing factors, while patient 2 developed an intrahepatic hematoma following endoscopic retrograde cholangiopancreatography (ERCP). The third case that is extrahepatic hematoma was speculated to be a result of minor hepatic parenchymal injury stemming from compressive and volume-reducing manipulation of a large graft, or secondary to focal ischemic necrosis of the liver. Our management protocol was summarized as follows: (1). Immediate ultrasound and CT, particularly enhanced CT; (2). Puncture and percutaneous drainage (PD) of the hematoma; (3). Arterial embolization if the origin could be identified as a ruptured vessel; (4). Surgical evacuation of the hematoma in the presence of bile leakage, to avoid a compartment respectably secondary infection. All three patients responded favorably to treatment and remained alive to date. ConclusionPrompt diagnosis and sequential individualized management can successfully deal with intra-/extrahepatic graft hematoma after LT. Our results underscored that an individualized management considering potential future complications into account.

Diabetic myonecrosis complicated by emphysematous pyomyositis and abscess caused by Escherichia coli: a case report

BackgroundNecrotizing myopathies and muscle necrosis can be caused by immune-mediated mechanisms, drugs, ischemia, and infections, and differential diagnosis may be challenging.Case presentationWe describe a case of diabetic myonecrosis complicated by pyomyositis and abscess caused by Escherichia coli. A white woman in her late forties was admitted to the hospital with a 1.5 week history of bilateral swelling, weakness, and mild pain of the lower extremities and inability to walk. She had a history of type 1 diabetes complicated by diabetic retinopathy, neuropathy, nephropathy, and end-stage renal disease. C-reactive protein was 203 mg/l, while creatinine kinase was only mildly elevated to 700 IU/l. Magnetic resonance imaging of her lower limb muscles showed extensive edema, and muscle biopsy was suggestive of necrotizing myopathy with mild inflammation. No myositis-associated or myositis-specific antibodies were detected. Initially, she was suspected to have seronegative immune-mediated necrotizing myopathy, but later her condition was considered to be explained better by diabetic myonecrosis with multifocal involvement. Her symptoms alleviated without any immunosuppressive treatment. After a month, she developed new-onset and more severe symptoms in her right posterior thigh. She was diagnosed with emphysematous urinary tract infection and emphysematous myositis and abscess of the right hamstring muscle. Bacterial cultures of drained pus from abscess and urine were positive for Escherichia coli. In addition to abscess drainage, she received two 3–4-week courses of intravenous antibiotics. In the discussion, we compare the symptoms and findings typically found in pyomyositis, immune-mediated necrotizing myopathy, and diabetic myonecrosis (spontaneous ischemic necrosis of skeletal muscle among people with diabetes). All of these diseases may cause muscle weakness and pain, muscle edema in imaging, and muscle necrosis. However, many differences exist in their clinical presentation, imaging, histology, and extramuscular symptoms, which can be useful in determining diagnosis. As pyomyositis often occurs in muscles with pre-existing pathologies, the ischemic muscle has likely served as a favorable breeding ground for the E. coli in our case.ConclusionsIdentifying the etiology of necrotizing myopathy is a diagnostic challenge and often requires a multidisciplinary assessment of internists, pathologists, and radiologists. Moreover, the presence of two rare conditions concomitantly is possible in cases with atypical features.

Single-center experience of intraoperative ligation of the splenic artery for prevention of splenic artery steal syndrome in patients after living donor liver transplant

Background. Living donor liver transplant is an effective method of treatment in patients with different types of endstage liver diseases. Unfortunately, patients undergoing such a complex treatment sometimes develop various vascular complications. Splenic artery steal syndrome has emerged as a cause of graft ischemia in living donor liver transplant recipients and may lead to high liver enzyme levels, cholestasis, hepatic artery thrombosis, and even a graft loss in some severe cases.Objective. Evaluation of the first results in the experience of our center with a routine intraoperative ligation of the splenic artery during the procedure of right lobe living donor liver transplantation in adult recipients for the prevention of the steal syndrome development in the postoperative period.Material and methods. Living donor liver transplant recipients with known hepatic arterial flow impairment were retrospectively studied. Patients were allocated into groups with regard whether the splenic artery had been ligated or not during the transplant procedure. Arterial complications were reviewed in both groups.Results. None of 30 patients with ligated splenic artery developed splenic artery steal syndrome after living donor liver transplant. splenic artery steal syndrome occurred in 60% patients with non-ligated splenic artery. Surgical technique of performing arterial anastomosis was not related to the splenic artery steal syndrome development (p<0.01 There was no local ischemic necrosis noted in the spleen in patients with the ligated splenic artery.Conclusion. Based on the analysis of our own experience and literature data, the splenic artery ligation appears to be an effective and safe method for preventing a splenic artery steal syndrome in patients following right lobe liver transplantation, with a minimal risk of ischemic complications for the spleen. However, further studies with larger sample sizes are needed to obtain more reliable results. Ultrasound examination and endovascular intervention are the primary tools for an early detection of abnormalities and rapid restoration of arterial blood flow in the hepatic artery of the graft.

Oversized Surgical Preparation of the Implant Site: Systematic Review and Meta-analysis of Preclinical Studies.

To answer the following focus question: In preclinical in vivo experimental models, do oral implants placed in overdimensioned (OD) sites present greater biomechanical properties and histomorphometric parameters of osseointegration compared to implants placed in standard or undersized implant sockets? Online databases were searched for controlled animal studies reporting on OD sites up to February 2023. The relative implant- final drill discrepancy (IDD) was used to categorize the control and test groups according to surgical drilling protocol: (1) control: undersized (IDD > 0.5 mm) or standard (IDD = 0.2 to 0.5 mm); and (2) test OD: stress-free oversized (IDD = 0.0 to -0.1 mm); test GAP: friction-free oversized (IDD ≤ -0.1 mm). Random-effects meta-analyses were performed for the outcomes of insertion and removal torque values (ITV and RTV, respectively), bone-to-implant contact (%BIC), and bone density (%BD) for short- (0 to 2 weeks), intermediate- (3 to 4 weeks), and long-term (≥ 5 weeks) healing periods. Of the 527 records identified, 13 studies met the eligibility criteria. Histologically, the OD and GAP groups prevented ischemic necrosis and extensive bone resorption at the bone-implant interface in both the marginal cortical layer and the trabeculae. Faster and increased rates of bone formation, characterized by primary osteons and highly vascularized tissue, took place in OD sites between 1 and 5 weeks of healing. Meta-analyses indicated statistically significant benefits in favor of (1) control vs OD for short-term healing in extraoral sites, with pooled estimates (weighted mean difference) of ITV = 25.35 Ncm, %BIC = 2.10%, and %BD = 26.19%; (2) control vs OD for long-term healing in intraoral sites, with %BD = 11.69%; (3) control vs GAP for intermediate-term healing in extraoral sites, with %BD = 3.03%; and (4) control vs GAP for long-term healing in extraoral sites, with RTV = 5.57 Ncm. Oversized surgical preparation of the implant site does not seem to provide any additional benefit compared to standard or undersized sites regarding quantitative parameters of osseointegration. However, it does minimize marginal bone resorption and yields better-quality bone healing, despite the comparable results among different experimental animal models in the late postoperative period.

Digital ischemic necrosis in a patient with systematic lupus erythematosus patient after severe acute respiratory syndrome coronavirus 2 infection: a case report

BackgroundPatients with coronavirus disease 2019 have a high incidence of thrombosis that decreases after recovery. When coronavirus disease 2019 is accompanied by diseases prone to thrombosis, risk of post-infection thrombotic events may increase.Case presentationWe report a case of digital ischemic gangrene in a 24-year-old Chinese female with systemic lupus erythematosus after recovery from coronavirus disease 2019. The pathogenesis was related to clinical characteristics of systemic lupus erythematosus, hypercoagulability caused by coronavirus disease 2019, and second-hit due to viral infection.ConclusionPatients with autoimmune diseases should remain alert to autoimmune system disorders induced by severe acute respiratory syndrome coronavirus 2 and other viruses. Treatment for these patients should be strictly standardized, and appropriate anticoagulation methods should be selected to prevent thrombosis.

Clinical Presentation, Bacteriologic Findings and Possible Risk Factors for Ischemic Teat Necrosis in Cattle-A Case Series.

Ischemic teat necrosis (ITN) is a growing problem in the dairy industry characterized by teat lesions, necrosis, pruritus and automutilation. Despite the economic and welfare consequences, there is no treatment, and the etiology of the disease remains poorly understood. The aim of this study was to investigate ITN by analyzing its clinical presentation, potential risk factors and microbial involvement. Methods included collection of milk and swab samples from affected cows over a period of one-and-a-half years and completion of questionnaires by veterinarians and farmers. Microbial testing included PCR testing for Treponema spp. and cultural testing by anaerobic and aerobic incubation on blood agar. The results showed a high and significant prevalence of Treponema spp. and Staphylococcus aureus in affected teats compared to non-ITN-affected control teats, indicating their potential role in the development of ITN. Other factors such as edema and milking practices also appear to contribute to the tissue damage. First-lactation and early-lactation heifers are particularly at risk. In conclusion, ITN appears to have a multifactorial etiology with both infectious and non-infectious factors playing a role. Further research is needed to better understand the complex interplay of these factors and to develop effective prevention and management strategies.

Evaluating the pro-survival potential of apoptotic bodies derived from 2D- and 3D- cultured adipose stem cells in ischaemic flaps

In the realm of large-area trauma flap transplantation, averting ischaemic necrosis emerges as a pivotal concern. Several key mechanisms, including the promotion of angiogenesis, the inhibition of oxidative stress, the suppression of cell death, and the mitigation of inflammation, are crucial for enhancing skin flap survival. Apoptotic bodies (ABs), arising from cell apoptosis, have recently emerged as significant contributors to these functions. This study engineered three-dimensional (3D)-ABs using tissue-like mouse adipose-derived stem cells (mADSCs) cultured in a 3D environment to compare their superior biological effects against 2D-ABs in bolstering skin flap survival. The findings reveal that 3D-ABs (85.74 ± 4.51) % outperform 2D-ABs (76.48 ± 5.04) % in enhancing the survival rate of ischaemic skin flaps (60.45 ± 8.95) % (all p < 0.05). Mechanistically, they stimulated angiogenesis, mitigated oxidative stress, suppressed apoptosis, and facilitated the transition of macrophages from M1 to M2 polarization (all p < 0.05). A comparative analysis of microRNA (miRNA) profiles in 3D- and 2D-ABs identified several specific miRNAs (miR-423-5p-up, miR30b-5p-down, etc.) with pertinent roles. In summary, ABs derived from mADSCs cultured in a 3D spheroid-like arrangement exhibit heightened biological activity compared to those from 2D-cultured mADSCs and are more effective in promoting ischaemic skin flap survival. These effects are attributed to their influence on specific miRNAs.

A Co-MOF encapsulated microneedle patch activates hypoxia induction factor-1 to pre-protect transplanted flaps from distal ischemic necrosis

Avoiding ischemic necrosis after flap transplantation remains a significant clinical challenge. Developing an effective pretreatment method to promote flap survival postoperatively is crucial. Cobalt chloride (CoCl2) can increase cell tolerance to ischemia and hypoxia condition by stimulating hypoxia-inducible factor-1 (HIF-1) expression. However, the considerable toxic effects severely limit the clinical application of CoCl2. In this study, cobalt-based metal-organic frameworks (Co-MOF) encapsulated in a microneedle patch (Co-MOF@MN) was developed to facilitate the transdermal sustained release of Co2+ for rapid, minimally invasive rapid pretreatment of flap transplantation. The MN patch was composed of a fully methanol-based two-component cross-linked polymer formula, with a pyramid structure and high mechanical strength, which satisfied the purpose of penetrating the skin stratum corneum of rat back to achieve subcutaneous vascular area administration. Benefiting from the water-triggered disintegration of Co-MOF and the transdermal delivery via the MN patch, preoperative damage and side effects were effectively mitigated. Moreover, in both the oxygen-glucose deprivation/recovery (OGD/R) cell model and the rat dorsal perforator flap model, Co-MOF@MN activated the HIF-1α pathway and its associated downstream proteins, which reduced reperfusion oxidative damage, improved blood supply in choke areas, and increased flap survival rates post-transplantation. This preprotection strategy, combining MOF nanoparticles and the MN patch, meets the clinical demands for trauma minimization and uniform administration in flap transplantation. Statement of significanceCobalt chloride (CoCl2) can stimulate the expression of hypoxia-inducible factor (HIF-1) and improve the tolerance of cells to ischemia and hypoxia conditions. However, the toxicity and narrow therapeutic window of CoCl2 severely limit its clinical application. Herein, we explored the role of Co-MOF as a biocompatible nanocage for sustained release of Co2+, showing the protective effect on vascular endothelial cells in the stress model of oxygen-glucose deprivation. To fit the clinical needs of minimal trauma in flap transplantation, a Co-MOF@MN system was developed to achieve local transdermal delivery at the choke area, significantly improving blood supply opening and flap survival rate. This strategy of two-step delivery of Co2+ realized the enhancement of biological functions while ensuring the biosafety.

Experimental study of slow-released Angiogenin by silicon micro-needle in improving blood support to multiple-territory perforator flaps in rats.

This research aimed to investigate the effect of slow-released angiogenin by silicon micro-needle on angiogenesis in the Choke zone of dorsal multiple-territory perforator flap in rats, as well as its mechanism. Thirty-six adult Sprague-Dawley (SD) rats were randomly divided into control group, model group, and four experimental groups. In model group, slow-release saline through a silicon micro-needle was placed in choke II zone of the flap 7 days before the operation. For rats in four experimental groups, angiogenin was released via micro-needle in the choke I and choke II zones of the cross-zone flap 7 days before and 3 days before flap surgery, respectively. A 12 cm × 3 cm cross-zone perforator flap model was made on the back of all five groups. The flap survival rate in slow-release angiopoietin group was statistically higher than that in model group (P<0.05). Angiogenin in choke zone of the flap was increased in slow-release angiogenin group (P<0.05). In slow-release angiogenin group, the micro-vessel density was increased and the arteriovenous diameter was decreased, while the arteriovenous diameter was increased in model group (P<0.05). The levels of vascularendothelialgrowthfactorA (VEGF-A) and angiotensin 1 (ANG-1) in choke zone were both elevated in slow-release angiogenin group (P<0.05). The expression of CD31 was significantly elevated in flaps of experimental groups (P<0.05). Micro-needle to slow release Angiogenin can increase the drug concentration in the tissues of the choke zone, promote the vascularization of rat dorsal crossover area perforator flap, reduce the possibility of flap ischemic necrosis, and improve the flap survival rate.

Research progress of neurovascular units involved in ischemic stroke

AbstractIschemic stroke is the most prevalent cerebrovascular disorder in the clinical setting. It results in associated neurological abnormalities due to a variety of factors, including disruption of cerebral arterial blood flow, hypoxia, and ischemic necrosis of local brain tissues. The neurovascular unit (NVU) is a dynamic structural complex that consists of neurons, glial cells, pericytes, vascular endothelial cells, and the extracellular matrix. Many cells work together to preserve the integrity of the central nervous system (CNS) under physiological conditions. However, following ischemic stroke, NVU homeostasis is disrupted along with the development of tissue ischemia and hypoxia, as well as impaired interactions between various components of the NVU. Collectively, the changes result in increased blood–brain barrier permeability, neuronal dysfunction, and functional destruction of nerve conduction bundles, ultimately leading to the clinical manifestation of neurological deficits including motor, cognitive, and speech impairments that hinder the rehabilitation process. In recent years, with continuously expanding research on ischemic cerebrovascular disease, the role of interconnections between different cells in the NVU in ischemic stroke has received increasing attention. To describe new concepts for the prevention and treatment of ischemic cerebrovascular illnesses, this article reviews the interplay between NVU in the pathogenesis of ischemic stroke.

#855 Cyclophilin D in cholesterol crystal-induced acute kidney injury

Abstract Background and Aims Cholesterol crystal embolism (CCE) occurs when cholesterol crystal (CC) clots move from an atherosclerotic plaque in a large artery to a smaller artery, leading to obstruction, ischemia, and organ failure. CCE directly impairs blood flow by provoking a local inflammatory response and triggering arterial thrombus formation, consisting of collagen and fibrin mesh, platelet and neutrophil activation, and extracellular DNA trap formation. Activated platelets form a procoagulant surface that supports adhesion to collagen and fibrin mesh, promoting thrombus growth and the recruitment of immune cells. CCE often targets kidney tissue, leading to thrombotic angiopathy, acute loss of glomerular filtration rate (GFR), and necrosis in tubular cells. Cyclophilin D (CypD) plays a central role in regulating platelet procoagulant activity by triggering calcium bursts and mitochondrial depolarization. While the increased number of procoagulant platelets contributes to thrombosis, CypD-mediated procoagulant pathomechanisms in the kidney during CCE remain unknown. In our study presented here, we hypothesized that CypD deficiency might attenuate procoagulant platelet activity, thereby inhibiting CCE-induced kidney infarction and organ injury. Method 6-week-old wild-type (WT) and CypD-/- mice were administered 10 mg/kg CC through injections into the left kidney arteries in vivo. Kidneys were collected 24 hours later, and kidney function, infarct size, necroinflammation and kidney injury were evaluated using GFR measurements, TTC colorimetric assay, immunohistochemistry, and immunofluorescence microscopy. For in vitro studies, whole blood samples were isolated from WT and CypD-/- mice and perfused on a collagen-coated surface in the presence or absence of CC under arterial shear conditions of 1000s-1. Results After CC injection in mice, CypD deficiency ameliorated immunothrombosis, acute kidney injury, and organ failure. CypD-/- mice were protected from the sudden drop in GFR, i.e., acute kidney injury, which resulted from the reduced number of arteries obstructed by crystal clots. Kidney infarct size consistently decreased in CypD-/- mice. CypD-/- mice displayed reduced neutrophil recruitment to thrombotic microangiopathic lesions, indicating diminished immunothrombosis. Preemptive injection of the CypD inhibitor cyclosporin A could prevent CC-mediated vessel obstruction and infarct size, thereby improving kidney function. Interestingly, WT platelets showed increased platelet adhesion and phosphatidylserine (PS) exposure on a collagen-coated surface in the presence of CC under shear conditions in whole blood, suggesting increased procoagulant activity, which was strongly reduced in CypD-/- platelets. Conclusion During CCE-mediated kidney injury, CypD-mediated platelet activation and consequent procoagulant activity accelerate ischemic tissue necrosis and the recruitment of neutrophils. Inhibition of CypD-mediated signaling could be a potential therapeutic approach to inhibit acute kidney injury in patients with CCE.

Molecular Screening for Digital Dermatitis-Associated Treponemes in Bovine Ischaemic Teat Necrosis Lesions and Milk in Dairy Cattle

Bovine ischaemic teat necrosis (ITN) is a disease affecting the skin of the teats of dairy cows with an unknown aetiopathogenesis. Digital dermatitis (DD)-associated treponemes have previously been suggested as a potential aetiological agent in ITN, although the sample size was small. The current study, using established PCR techniques, aimed to examine the association with the presence of DD-associated treponemes in a large number of ITN samples from a wider geographical area, and surveyed the potential of milk as an infection reservoir. From 95 ITN lesions, 35.8% (n = 34) were positive for at least one DD-associated treponeme compared with only 5.6% (n = 1) of 18 non-lesioned teats from cows with ITN lesions on a different teat using a nested PCR approach. All 10 age- and production-matched control cows were negative for DD-associated treponemes via PCR. No DD-associated treponemes could be detected from foremilk of cows with (n = 19) and without (n = 31) a DD lesion on the hind feet. DD-associated treponemes could be detected via PCR after incubation in milk for up to 2 h. Therefore, milk does not appear to be a competent reservoir for transmission of DD-associated treponemes. Moreover, in the current study DD-associated treponemes were only detected in a subset of ITN samples, so it is unlikely these opportunistic skin-associated pathogens are the major or sole agent of ITN.

The Role of CT scan in the Diagnosis of Ileosigmoid Knot: A Case Report and Literature Review

The ileosigmoid knot, although rare, represents a complex surgical emergency requiring rapid and precise man agement. Imaging, particularly computed tomography (CT), plays a crucial role in diagnosis by highlighting specific features such as the "spiral sign" and signs of necrosis. Early detection through these imaging modalities allows for prompt surgical intervention, minimizing the risks of severe complications associated with intestinal torsion. The speed of surgical intervention is crucial to prevent progression to ischemic necrosis, reduce the risks of intestinal perforation, peritonitis, and other serious complications. Various surgical modalities, such as colonic diversion, detorsion, segmental resection, or extended resection in case of necrosis, must be tailored to the clinical presentation and intraoperative findings. Ultimately, the combination of advanced radiological imaging and swift surgical intervention is the key to successful management of the ileosigmoid knot. Emphasizing awareness among healthcare professionals of this rare condition and educating patients to recognize symptoms promptly will contribute to the early and effective management of this infrequent surgical l emergency.