Areas Of Necrosis Research Articles

Clinicopathological and molecular characterization of astrocytoma

IntroductionAstrocytoma is a rare tumour of the central nervous system that often manifests with non-specific clinical symptoms and lacks distinct histological features. There is a pressing need for further understanding of the clinicopathological and molecular characteristics of astrocytoma. Identifying mutant genes can aid in reliable and early diagnosis, as well as provide insights for the development of targeted therapies.MethodsThis study aims to investigate the clinicopathologic and molecular characteristics of astroblastoma. A total of four patients diagnosed with astroblastoma were included in the analysis. Clinical features, histological findings, and immunohistochemistry results were reviewed and analyzed. Genetic alterations were identified using fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS), followed by patient follow-up.ResultsThe study included four female patients, ranging in age from 8 to 44 years. One patient had a tumour in the right parietal lobe, while the other three had tumours in the spinal cord. Histology is usually characterized by pseudorosettes of astroblasts and hyalinization of blood vessels. These tumors showed a growth pattern similar to traditional intracranial astroblastoma, and the histological manifestations of the four patients were all high-grade, showing features of high-density areas of tumor cells or necrosis. Immunohistochemical staining revealed that all four patients expressed OLIG2, EMA, and vimentin, while three patients also expressed GFAP and S-100. The Ki-67 positivity index was approximately 15% in three cases and 10% in one case. Fluorescence in situ hybridization (FISH) using break-apart probes showed EWRS1 breaks in three patients and MN1 breaks in one. Further DNA or RNA-targeted biallelic sequencing identified an EWSR1(Exon1-7)-BEND2(Exon2-14) fusion in case 1, and an EWSR1(Exon1-7)-BEND2(Intergenic) fusion in case 2. In case 3, an EWSR1(Exon1-7)-NUDT10(Intergenic) fusion was present, and in case 4, an MN1(Exon1)-BEND2(Exon2) fusion was identified. The EWSR1-NUDT10 gene fusion is a new fusion type in astroblastoma. The patients were followed up for 76.5, 17.6, 33.7, and 61.3 months, respectively. Three cases experienced tumour recurrences at the spinal cord site, with multiple recurrences in case 4.DiscussionOur study unveiled the distinctive clinicopathological and molecular mutational characteristics of astrocytoma, while also identifying rare mutated genes. Additionally, the detection of MN1 or EWSR1 gene fusion through FISH or next-generation sequencing can provide valuable insights into the molecular mechanisms and aid in the differential diagnosis of astrocytoma.

Evaluating CK20 and MCPyV Antibody Clones in Diagnosing Merkel Cell Carcinoma

Merkel cell carcinoma (MCC) is diagnosed through histopathological and immunohistochemical examination of biopsies from skin or other organs. Its distinguishing features include perinuclear dot-like staining with Cytokeratin 20 (CK20) and detection of Merkel cell polyomavirus (MCPyV) using various methods. However, CK20 and MCPyV negative MCC cases have been reported at varying rates. In this single center cross-sectional study, we aimed to determine which clones are more effective in diagnosing MCC by comparing the performance of CK20 antibody clones Ks20.8 and SP33, as well as MCPyV antibody clones Ab3 and CM2B4. Fifty-four patients diagnosed with MCC were included. Among these, 42 cases were primary cutaneous, and 12 cases were nodal MCC. Fifty-two (96.3%) cases were positive with both CK20 clones, while two cases were negative. Clone SP33 stained areas of necrosis, whereas Ks20.8 showed no aberrant staining. MCPyV was detected in 44 cases (81.5%) using clone Ab3 and 39 cases (72.2%) using clone CM2B4. Staining with MCPyV clone Ab3 was diffuse and strong in most cases, while approximately 30% of CM2B4-positive cases exhibited low percentages and/or weak staining, complicating the evaluation. The two CK20-negative cases were also negative with both MCPyV clones. Our data demonstrated that CK20 clone Ks20.8 may be preferred for MCC diagnosis due to its consistent performance and lack of aberrant staining. Similarly, MCPyV clone Ab3 appears superior to CM2B4 for identifying MCPyV-positive cases.

SW033291 promotes liver regeneration after acetaminophen-induced liver injury in mice.

Acetaminophen (APAP) is a commonly utilized antipyretic and analgesic drug. Overdose of APAP is a primary contributor to drug-induced liver injury and acute liver failure (ALF). SW033291 has been shown to play a role in tissue regeneration in various diseases; however, its potential to facilitate liver regeneration following APAP-induced hepatic injury remains unexamined. Thus, this study focused on exploring the therapeutic impacts and mechanisms of SW033291 on liver damage by establishing models of APAP-induced acute liver injury in mice. The results showed that treatment with SW033291 reduces serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, decreases the area of hepatic necrosis, increases glutathione (GSH) levels, and decreases tissue malondialdehyde (MDA) content, as well as the expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in mice with liver injury. It could also promote hepatocyte proliferation and inhibit apoptosis by increasing tissue prostaglandin E2 (PGE2) levels. In conclusion, SW033291 demonstrates the capacity to ameliorate APAP-induced hepatic injury in mice by fostering liver regeneration, attenuating oxidative stress, and modulating inflammatory responses, thereby presenting itself as a promising candidate for the development of therapeutic interventions targeting acute liver failure.

Primary breast sarcoma in a male patient

Primary sarcoma of the breast is an extremely rare tumor in men. Furthermore, only a few cases of undifferentiated/unclassified sarcoma of the male breast have been reported in the literature. We report a case of primary undifferentiated sarcoma occurring in the male breast. A 66-year-old male patient presented with a rapidly growing ulcerative left breast lump. A large partially circumscribed, dense mass was noted on mammography which involved the overlying skin with contour bulge. Sonographic evaluation revealed a large hypervascular heteroechoic mass showing areas of internal necrosis. An initial core-needle biopsy suggested malignant phyllodes tumor, but final histopathology revealed a high-grade primary sarcoma with immunohistochemistry suggesting uncertain differentiation. A review of the literature is presented with focus on imaging and treatment of these unusual neoplasms.

ATF3 triggers M2 macrophage polarization to protect against pulp inflammation through WNT4 regulation.

Pulpitis is a common inflammatory oral disease that can lead to pulp necrosis. The aim of this study is to investigate the expression and regulatory mechanisms of ATF3, a potential therapeutic marker, in pulpitis. A mouse pulpitis model with different degrees of inflammation is established, and the expression of ATF3 in pulpitis is explored. The histological features of healthy pulp and pulpitis are analyzed by HE staining, and classical inflammatory factors are detected by immunohistochemistry (IHC). In an in vitro study, we investigate the role of ATF3 in the regulation of WNT4 transcription and explore the effects of the ATF3/WNT4 axis on the polarization of RAW264.7 macrophages, the inflammatory response and the osteogenic differentiation of human dental pulp stem/stromal cells (hDPSCs). Our results show that ATF3 is expressed at low levels in inflamed pulp tissues; overexpression of ATF3 reduces the area of pulp necrosis, decreases the level of pro-inflammatory factors, and promotes macrophage polarization toward the M2 type. Furthermore, we reveal that ATF3 binds to the WNT4 promoter region and positively regulates the expression of WNT4 and that ATF3 downregulates M1 markers and increases the expression of M2 markers by regulating WNT4 expression. In addition, ATF3 promotes the osteogenic differentiation of dental pulp stem cells. In summary, this study reveals that ATF3 promotes M2 macrophage polarization by regulating WNT4, which in turn inhibits pulpal inflammatory responses and promotes the osteogenic differentiation of dental pulp stem cells. These findings suggest that ATF3 may be a potential target for pulpitis treatment.

Evaluation of a potential bidirectional influence of metabolic syndrome and apical periodontitis: An animal-based study.

This study aimed to explore the possible bidirectional interrelations between fructose-induced metabolic syndrome (MS) and apical periodontitis (AP). Twenty-eight male Wistar rats were distributed into four groups (n = 7, per group): Control (C), AP, Fructose Consumption (FRUT) and Fructose Consumption and AP (FRUT+AP). The rats in groups C and AP received filtered water, while those in groups FRUT and FRUT+AP received a 20% fructose solution mixed with water to induce MS. The groups AP and FRUT+AP had the pulp of their right mandibular first molar exposed to induce AP. Food consumption, murinometric measurements, blood glucose levels and glucose tolerance were monitored. Fifty-six days after the start of the experiment, the animals were euthanized, and serum samples were collected for metabolomic analysis. Mandibles, livers and right kidneys were also collected. The area and volume of the periapical lesions were calculated using micro-computed tomography. Histopathological evaluation was performed. Kruskal-Wallis followed by the Student-Newman-Keuls or Mann-Whitney tests and one-way anova followed by Tukey's or Independent t-test were used for non-parametric and parametric data, respectively (p < .05). Multivariate analysis and variable importance in projection score were applied to assess metabolite profile differences among groups (p < .05). FRUT and FRUT+AP groups showed significantly increased fluid intake, body mass, abdominal circumference, blood glucose levels, liver weight and visceral fat weight (p < .05), indicating the development of MS. The analyses of the metabolite profile suggest increasing glucose, histidine, lactate, fatty acid and phenylalanine in the FRUT+AP group. There were no significant differences in volume and area of periapical lesions in micro-CT analyses (p = .1048 and p = .7494, respectively). Histopathological analysis of the hemimandibles demonstrated areas of inflammatory response, necrosis and microabscess in the periapical region. Hepatic histopathological observations indicated notable differences in cell appearance, with the FRUT and FRUT+AP groups showing signs of microsteatosis. Kidney analysis revealed Bowman's space dilation in the FRUT and AP groups, while the FRUT+AP group exhibited retracted Bowman's space, suggesting a possible alteration in renal filtration capacity. MS had no impact on the progression of AP in rats. However, AP exacerbated the systemic state affected by MS, with changes in liver and kidney tissues and metabolite levels.

Synthesis and Biological Evaluation of a New Biphenyl-Based Organogold(III) Complex with In Vitro and In Vivo Anticancer Activity.

Despite recent advances in cancer treatment, there is still a need for novel compounds with antineoplastic activity. Among 11 biphenyl-based organogold(III) N-heterocyclic carbene (NHC) (BGC) complexes of general formula [(C^C)Au(NHC-pyr)X], where (C^C) = 4,4'-ditertbutylbiphenyl, X = Cl or phenylacetylide, and (NHC-pyr) is a pyridyl-substituted NHC ligand, the complex BGC4 bearing a 4-CF3-pyridyl substituent and a chloride ligand showed promising antineoplastic activity on the triple negative breast cancer cell line. BGC4 was able to induce cell apoptosis but had no effect on the cell cycle. In vivo, BGC4 reduced the tumor growth rate by increasing the necrosis area and decreasing the mitotic activity. Repeated injections of BGC4 did not induce common side effects. The present investigation shows that BGC4 is a promising antineoplastic candidate. Its potential as a future chemotherapy for the treatment of cancer will be strengthened by evaluating its efficacy in combined treatment with current chemotherapy.

Evaluation of lithium chloride safety and toxicokinetics for injection in minipigs

Lithium salts are known to treat bipolar disorder. Their high potential as neuroprotective agents in cerebral ischemia determines relevance for preclinical studies for the registration of new drugs based on them. Aim of the study was to investigate the toxic properties and local tolerability with an assessment of the toxicokinetics of the developed lithium chloride preparation for injection in dwarf pigs with repeated intravenous administration. Material and methods. Lithium chloride (solution, for intravenous administration 4.2 %) has been administered to minipigs (control and 3 experimental groups of animals of 3 males and 3 females) for 28 days at doses of 12.6; 29.4 and 63 mg/kg. General toxicity, local irritation, and basic pharmacokinetic parameters (Cmax, AUC0-24, MRT, T1/2, Vss, and Cl) were evaluated. Serum lithium ion concentration was estimated colorimetrically using quinizarin. Results and discussion. Toxic properties of the test drug were revealed, expressed in a change in the clinical state (vomiting after administration, inhibition of behavior and feed refusal), body weight negative dynamics, clinical and laboratory changes, shortening of the “QT” interval, accompanied by abnormalities according to the pathomorphological study results (focal infiltration with single renal tubular necrosis areas, kidneys fibrosis, replacement of thyroid tissue with adipose tissue). There were no signs of locally irritating effects of the test product. To evaluate toxicokinetic parameters, a bioanalytical assay (calibration range – from 0.17 to 5.45 μg/mL) was developed and validated, which is not inferior by its characteristics to the commercial reagent kits. According to the results of biomaterial analysis no lithium accumulation in the pig’s body was found with repeated use of the test drug. Doses of the drug that provide toxic concentrations of lithium (above 3 μg/ml) in the minipig’s serum were identified. The NOAEL was 12.6 mg/kg and the LOAEL was 29.4 mg/kg. Conclusions. The comprehensive approach to the consideration of toxic manifestations and toxicokinetics, including its analytical component of studies of this kind, was noted. The obtained results should be taken into account to assess the benefit/risk ratio in the clinical use of lithium chloride injection.

Pancreatic tuberculosis revealed by a mass with neoplastic appearance: a case report

Introduction. Pancreatic tuberculosis is an extremely rare form of extrapulmonary tuberculosis. This condition can be challenging to diagnose due to its rarity, nonspecific symptoms and radiological features that may mimic a neoplastic origin. Case report. A 46-year-old immunocompetent patient with no past history of tuberculosis exposure presented with spontaneously resolving jaundice over the past month, accompanied by nonspecific fever episodes and general fatigue with no other associated digestive symptoms. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) scans revealed a poorly defined, partially necrotic mass in the pancreatic head with heterogeneous hypodensity and enhancement after contrast injection. Additionally, there were nodal and hilar macro-nodal lesions with necrotic appearances, as well as peripancreatic lymphadenopathy. The patient was scheduled for an endoscopic ultrasound (EUS) examination, which revealed the presence of a heterogeneous lesion with areas of necrosis in the posterosuperior aspect of the head and isthmus of the pancreas, accompanied by perilesional and coeliac lymphadenopathies with necrotic centres. EUS-guided tissue sampling allowed the diagnosis of pancreatic tuberculosis, with both histological examination and GeneXpert MTB/RIF testing rapidly positive for Mycobacterium tuberculosis, followed by culture on solid Loewenstein–Jensen medium. The patient responded well to antitubercular chemotherapy. Conclusion. Pancreatic tuberculosis, though rare, should be considered in cases of pancreatic masses, especially in endemic regions. Tissue samples with necrosis should be tested for M. tuberculosis using GeneXpert and Loewenstein–Jensen culture. This work highlights the GeneXpert MTB/RIF test as highly sensitive, specific and fast, making it ideal for diagnosing extrapulmonary tuberculosis, particularly when smear results are negative.

Conidiobolomicose com comprometimento neurológico em ovino no Pará, Brasil

ABSTRACT: The study was conducted on a 3-year-old female Santa Inês sheep from a property located in the municipality of Santo Antônio de Tauá, west of Pará. The affected animal had a history of exophthalmos in the left eye, nasal discharge, and breathing difficulty for more than three months. On physical examination, the animal had a low body score, apathy, unilateral facial asymmetry, moderate unilateral left exophthalmos, mixed dyspnea and unilateral profuse serosanguinous nasal discharge. At necropsy, a large nasal mass was observed, predominantly yellowish-white with blackish-red areas, with an irregular, finely granular, moist, and friable surface. The mass invaded from the mucocutaneous junction of the left nostril to the choanae, infiltrated the frontal sinuses, the cribiform plate, and reached the meninges and the frontal portion of the brain. Microscopy of the surface of the nasal epithelium showed severe destruction of the turbinates and epithelia, evidenced by extensive areas of necrosis with a large amount of cellular debris, ulceration, and secondary bacterial infection. In the central nervous system there was pyogranulomatous meningitis with marked vessel congestion, as well as foci of necrosis and granulomatous inflammation. Immunohistochemistry showed intense staining of numerous intralesional hyphae for antibodies against Conidiobolus lamprauges. The diagnosis of granulomatous rhinitis of mycotic origin associated with the Conidiobolus lamprauges was based on epidemiological, clinical-pathological, and immunohistochemical data.

Feasibility of rabbit auricular VX2 tumor model as an experimental model for intra-arterial embolization.

This study aimed to evaluate the feasibility of VX2 tumor in rabbit auricles as an experimental model for intra-arterial embolization. This study was approved by our Institutional Animal Care and Use Committee. VX2 tumors were implanted in both auricles of 12 New Zealand White Rabbits. To investigate the angiographic and pathologic characteristics, angiography, ultrasonography, and thermography were performed 1-2 weeks after inoculation, and image analysis was performed. The animals were sacrificed thereafter, and histologic analysis was conducted by a pathologist. Tumors did not grow in 3/24 auricles of 12 rabbits used in the experiment, and one rabbit died during anesthesia for an ultrasonographic examination. Therefore, images were obtained from a total of 19 auricles. Angiography was successfully performed in 11 rabbits, and hypervascularity and tumor feeding vessels were clearly observed in all tumors. The enhancement effect increased significantly as the volume increased. In histologic evaluation, the average area of necrosis was 27%. In conclusion, a rabbit auricular VX2 tumor model is easy to create, and its features can be conveniently observed on visual inspection. Moreover, it appears hypervascular on angiography, and the tumor feeding vessel is easy to approach. Thus, it is useful for studying intra-arterial embolization.

ГЕПАТОПРОТЕКТОРНАЯ АКТИВНОСТЬ МАГНИЯ БИС-АЦЕТАМИНОЭТАНСУЛЬФОНАТА ПРИ КЕТАТОКОНАЗОЛОВОМ ЛЕКАРСТВЕННОМ ПОРАЖЕНИИ ПЕЧЕНИ (ЭКСПЕРИМЕНТАЛЬНОЕ ИССЛЕДОВАНИЕ)

The hepatoprotective activity of magnesium bis-acetaminoethanesulfonate with the laboratory code LBK-527 was studied in ketoconazole-induced liver injury. Drug-induced liver injury was modeled by intragastric administration of ketoconazole at a dose of 100 mg for 3 days. LBK-527 and the comparison drug heptral were administered to animals at a dose of 100 mg / kg / day and 60 mg / kg / day intraperitoneally 1 hour before the introduction of hepatotoxin for 14 days. Biochemical blood parameters characterizing the functional activity of the liver were studied, its histological picture of the liver was assessed, and macro- and micromorphometry of the organ was performed on the 7th and 14th days. The substance LBK-527 prevents the cytotoxic effect of ketoconazole on the functional activity of the liver. There is a decrease in ketoconazole-induced cytolysis, normalization of the level of total bilirubin in the blood plasma of animals. The appearance of the liver, its relative and absolute weight in animals with drug-induced hepatitis treated with LKB-527 were comparable with intact rats. On histological preparations stained with hematoxylin and eosin, a decrease in the area of necrosis of the liver parenchyma was observed, the beam structure of the tissue was preserved. The area of the cytoplasm, nucleus and nuclear-cytoplasmic ratio approached the values of the intact group. The appearance of multinucleated hepatocytes indicated the activation of the synthetic activity of the liver and the launch of regeneration mechanisms. Thus, it can be concluded that the substance under study has a hepatoprotective effect.

Case study of disseminated leiomyomatosis with urological and colorectal involvement and a literature review

Disseminated peritoneal leiomyomatosis (DPL), also known as diffuse peritoneal leiomyomatosis, is a rare disease characterized by a sub peritoneal proliferation of benign nodules, mainly composed of benign smooth muscle cells, macroscopically mimicking peritoneal carcinosis. We report the case of a 60-year-old patient, with hypertension under treatment, being followed for the management of pauci-symptomatic abdominopelvic masses, evolving in a context of conservation of the general state, who underwent hysterectomy with adnexectomy by laparotomy for uterine myoma. Imaging revealed three masses, extending from the perigastric to the pelvic region, with areas of necrosis, moderate peritoneal effusion and lumbo-aortic and primitive iliac lymph nodes with small infracentimetric axes. The management consisted of a complete cytoreduction. Postoperative management was straightforward. LPD is a rare condition, with around 200 cases published in the literature. Its incidence is estimated at around 1/10,000,000, given the generally asymptomatic nature of the disease. The etiopathogenesis of this condition remains poorly elucidated, although several causal theories have been described in the literature, including hormonal, iatrogenic and congenital or hereditary. The management of LPD is not currently standardized, but surgery remains the gold standard. LPD is a rare, benign condition characterized by sub peritoneal proliferation of smooth muscle cells. It occurs most frequently in women of childbearing age, but can also occur in postmenopausal women and men. Treatments for LPD are not standardized, and further studies are required in the near future.

Discrepancy between radiography and magnetic resonance imaging in Japanese Investigation Committee classification type C osteonecrosis of the femoral head

PurposeThe Japanese Investigation Committee (JIC) classification for osteonecrosis of the femoral head (ONFH) is based on the necrotic area relative to the weight-bearing surface on anteroposterior (AP) radiographs or central coronal MRI. Discrepancies exist between these methods, potentially related to the AP necrosis area. This study evaluated these discrepancies and the extent of AP necrotic lesions.MethodsWe retrospectively reviewed 139 patients (188 hips) with nontraumatic ONFH, JIC type C1 or C2 on radiography, and collapse < 3 mm. Cases with and without discrepancies between radiography and MRI were designated as discrepancy and consistent groups, respectively. We assessed the proportion of patients in the discrepancy group and survival rates in both groups, with femoral head collapse > 3 mm as the endpoint. The cutoff value for AP necrotic regions on lateral radiographs identifying discrepancies was calculated using ROC curve analysis.ResultsThe discrepancy group comprised 28 hips (14.9%) vs. 160 hips in the consistent group. Five-year survival rates were 73.3% vs. 31.9% (P < 0.01), and AP necrotic region extent was 61.2 vs. 73.8 mm (P < 0.001) in discrepancy vs. consistent groups. The cutoff value for necrotic region extent revealing discrepancies was 66.9% (AUC 0.833, sensitivity 83.8%, specificity 82.4%).ConclusionPatients with AP necrotic regions < 66.9% were more likely to show discrepancies between radiography and MRI in type classification. This study can help improve accuracy in assessing ONFH severity and prognosis.

Reconstruction Using Negative Pressure Wound Therapy with a Cotton Filler for Fixation of Male Genital Skin Grafts in Cases of Fournier&apos;s Gangrene

The reliable engraftment of skin grafts into areas with complex shapes can be challenging. Here, we report a case of successful fixation of a genital skin graft using negative pressure wound therapy (NPWT) with RENASYS® Cotton Filler. A 44-year-old male with no relevant medical history underwent split-thickness skin grafting for a genital skin defect caused by Fournier's gangrene. A 0.4-mm sheet graft was applied for the penile skin defect, while 0.4-mm 1.5 times mesh grafting was applied for the testis and spermatic cord. NPWT with a cotton filler was used for seven days of fixation. No postoperative pain or stool contamination was observed. Although a small area of partial necrosis developed, the lesion healed with conservative treatment. Six months after surgery, there was no scar contracture, urination disorder, or pain during erection. Cotton fillers are highly malleable and adaptable, allowing for simple and reliable fixation of skin grafts in complex areas. Moreover, NPWT for genital graft fixation avoids contamination from stools. Therefore, we recommend fixation using NPWT with a cotton filler for genital skin grafting.

Clinical Presentation and Integrated Management of Pressure Injuries in the Emergency Hospital Setting: A Plastic Surgeon’s Perspective

Background: Pressure injuries are localized areas of tissue damage or necrosis that occur when pressure is applied to the skin for prolonged periods, often over bony prominences, often the sacrum, heels, ischial tuberosities, and greater trochanters. The pathophysiology is complex, involving a combination of mechanical forces, ischemia, and tissue hypoxia. Methods: We conducted a 2-year retrospective study aiming to assess the clinical characteristics, risk factors, and management of pressure injuries in patients admitted to an emergency hospital who underwent a plastic surgery examination. Results: This study included 176 patients with clinically diagnosed pressure ulcers, with findings showing 28.52% of cases as stage III and 35.57% as stage IV. Common sites included the sacrum (40.94%), ischium (15.1%), and heel (14.43%). The median patient age was 76 years, with 47.15% between 60 and 80 years and 36.93% ≥ 80 years, often presenting with comorbidities increasing the risk of pressure injuries, such as cardiovascular disease (71.59%), diabetes (18.18%) and obesity (9.66%). Important risk factors included neurological diseases (46.02%), spinal cord injuries (14.7%), and nutritional deficiencies, as indicated by anemia (10.43g/dL; 95% CI [10.04; 10.82]), low serum albumin (2.56 g/dL; 95% CI [2.43; 2.69]) and proteins (5.54 g/dL; 95% CI [5.34; 5.73]). Mortality was significant, at 36.93%, with 23.3% occurring within the first 7 days of hospitalization due to the patients’ critical condition. Decision-making for surgical intervention considered the patient's general status, comorbidities, and ulcer severity. Surgical treatment consisted of seriate debridement, negative pressure vacuum therapy, and/or coverage using skin grafting, local advancement, or rotation flaps. Conclusions: The key question for a plastic surgeon to consider is how pressure ulcers should be managed. Various debridement and covering techniques should be tailored to the wound’s characteristics, considering patient comorbidities and general health condition.

A Death Too Fast - Suxamethonium Chloride Poisoning: A Case Report

Introduction: Suxamethonium chloride (SUX) is a short acting depolarizing muscle relaxant commonly used for medical procedures to induce respiratory paralysis. The case report aims to highlight the important postmortem findings associated with SUX poisoning. Case report: A female adult health-care worker in her thirties was found dead in her bedroom at home. There were two empty ampoules of IV/IM Suxamethonium Chloride 100 mg/2 ml found next to the body. Results: The autopsy revealed an adult female with multiple needle injection marks. Gross examination of the lungs showed markedly congested lungs and froth in the airways. The liver showed foci of petechial haemorrhages and confluent haemorrhages. Other internal organs showed diffuse vascular congestion. Microscopically, significant pathological changes were seen in the lungs and kidneys with areas of pulmonary infarction and acute tubular necrosis. SUX was not detected from the toxicological analysis. Correlating the circumstantial evidence at the scene of death, autopsy and microscopic findings, the cause of death was certified as SUX poisoning. Conclusions: We wished to demonstrate the autopsy and histopathological findings associated with acute SUX poisoning culminating in death due to respiratory paralysis.

Oral Toxicity of Magnesium Oxide Nanoparticles, MgO NPs on Liver in Male Rats

Nanotechnology is an emerging technology that has led to the nanomedicine development, which involves nanoparticles that exist in the natural world. Nanoparticle is an ultrafine unit with dimensions measured in nanometers. They are created as a result of human activities, and have recently been used in various biomedical applications, consumer products, and commercially, etc. Magnesium oxide nanoparticles (MgO NPs), among the known metal oxides, have attracted a vast scientific interest. Therefore, human health can be at risk of continuous exposure. However, the toxic effects of MgO NPs should be assessed with their increased applications. The present study aimed to investigate the physiological and histological, alterations induced by the MgO nanoparticles in hepatocytes of male rats through oral route with (250, and 1000) mg/kg for (14, 28, and 56) days. Fifty-four male mature rats, (2.5 - 3 months old) were divided randomly into nine groups of six rats each, gavaged with MgO NPs (which were purchased from US Research Nanomaterials, Inc). The results obtained revealed highly significant increase (p&lt;0.01) in aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and total bilirubin. The histopathological examinations showed sinusoidal dilatation, atrophy of hepatocytes, depletion of glycoprotein, focal area of necrosis, inflammatory cells infiltration and apoptosis. MgO NPs demonstrated potential harm to liver tissue, and human health.

IFITM1 aggravates ConA-Induced autoimmune hepatitis by promoting NKT cell activation through increased AMPK-Dependent mitochondrial function

Although interferon-induced transmembrane 1 (IFITM1) is known for its crucial role in antiviral immunity, its involvement in autoimmune hepatitis (AIH) remains largely unexplored. In this study, we observed that IFITM1 expression is markedly upregulated in a Concanavalin A (ConA)-induced AIH model, with particularly high and markedly elevated expression in natural killer T (NKT) cells. To further understand the role of IFITM1, we examined the responses of IFITM1−/− mice in a model of ConA-induced liver injury. In comparison to wild-type mice, IFITM1−/− mice exhibited reduced sensitivity in this model, as evidenced by significantly ameliorated necrosis areas, lower serum aminotransferase levels, a reduced number of intrahepatic NKT cells, and decreased expression of inflammatory factors, such as IL-1β, IL-6, IFN-γ and TNF-α. Notably, by using IFITM1-GFP mice and IFITM1−/− mice, we demonstrated that IFITM1 expression in NKT cells is crucial for their proliferation, proinflammatory cytokine production, and cytotoxic functions. Furthermore, analysis of single-cell RNA sequencingdata revealed that IFITM1 is essential for mitochondrial function, which is mediated by the AMP-activated protein kinase (AMPK) pathway. We also validated the importance of IFITM1 for the AMPK pathway and mitochondrial ATP synthesis in vivo. Together, our findings elucidate that IFITM1 could regulate NKT cell activation and survival by promoting mitochondrial function during AIH.

The Importance of the Skin Syndrome in the Primary Diagnosis of Connective Tissue Diseases in Children: Case Report

Background. Timely verification of the clinical diagnosis of connective tissue diseases in children based on the onset of the earliest symptoms, including skin manifestations, and timely initiation of treatment can prevent the development of irreversible complications, increase the life expectancy of patients and its quality.The aim of the study. To analyze the nature of skin manifestations as a marker of the onset connective tissue disorders, such as systemic lupus erythematosus (SLE), localized scleroderma (morphea), juvenile dermatomyositis (JDM), juvenile polyarteritis nodosa (PAN), systemic juvenile idiopathic arthritis (SJIA), and the timing of the main clinical diagnosis from the moment of manifestation of connective tissue disorders. To clearly demonstrate the importance of skin syndrome in the timeliness of clinical diagnosis, a clinical case is presented.Methods. Analysis of medical records and prospective observation of 47 patients aged up to 17 years 11 months with an established diagnosis of connective tissue diseases and the presence of skin syndrome at the onset of the disease.Results. Among patients with SLE, only 20.0% of children had skin syndrome only in the form of butterfly rash, and other skin manifestations were noted in 80.0% of patients. The period from the onset of skin syndrome to diagnosis was 8.0 ± 2.1 months. In 57.2% of patients with morphea, skin syndrome was detected exclusively in the form of single or multiple elements, and in 42.8% there was a combination of a pathognomonic morphological element with alopecia and scleroderma. The average time to make a clinical diagnosis of morphea from the onset of the skin syndrome was 11.0 ± 1.9 months. In all patients with JDM, skin manifestations were characterized by polymorphism (papules and Gottron’s sign, heliotrope rash, palmar capillaritis, livedo reticularis, cheilitis). The diagnosis was made 14.0 ± 3.2 months from the onset of skin syndrome. In patients with documented PAN, skin manifestations debuted in the form of erythema, areas of necrosis, palmar capillaritis, livedo reticularis, and cheilitis. The period from the onset of skin syndrome to clinical diagnosis was 6.0 ± 2.4 months. Among patients with SJIA, skin syndrome was represented by a maculopapular rash associated with fever and its regression when body temperature normalized. The period until clinical diagnosis was made from the onset of the skin syndrome was 2.0 ± 1.1 months.Conclusion. In most cases, the skin syndrome in patients at the onset of the disease was characterized by polymorphism and diversity of elements with the involvement of the vascular component. At the same time, the time from the debut of connective tissue disease in the form of the appearance of skin syndrome to the clinical diagnosis varied in the range from 2 to 14 months.