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Obstrucción Intestinal , Intestino Delgado , Necrosis , Tomografía Computarizada por Rayos X , Humanos , Obstrucción Intestinal/diagnóstico por imagen , Necrosis/diagnóstico por imagen , Intestino Delgado/diagnóstico por imagen , Intestino Delgado/patología , Masculino , Femenino , Tomografía Computarizada por Rayos X/métodos , Persona de Mediana Edad , Anciano , Adulto , Estudios Retrospectivos , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Catastrophic loss of the penis following post-circumcision necrosis is a rare and devastating complication. Treatment options are limited, and the process is highly challenging. This study aims to report the successful application of our combined treatment approach for a 6-year-old patient who experienced total penile loss due to progressive necrosis 1 year after circumcision. METHODS & RESULTS: Following penile degloving, proximal penile mobilisation and separation and reshaping of the corpora were performed. The penile shaft was covered with a tunnelled composite anterior-lateral inguinal skin flap. Glanuloplasty was performed using a left buccal mucosal graft, followed by 10 sessions of hyperbaric oxygen therapy. At 1.5 months postoperatively, urethral dilation was performed once because of minor voiding difficulties. At 10 months postoperatively, the patient had excellent voiding function and no additional complaints. The patient expressed high satisfaction with the outcome and is still under close follow up. CONCLUSIONS: A standard treatment for serious complications such as necrosis and total penile loss has not been established yet. Although scrotal skin flap is a straightforward technique, it was not preferred in our case because of fibrosis following scrotal necrosis and potential risk of hair growth. The developed approach could be an effective alternative to other techniques.
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Circuncisión Masculina , Oxigenoterapia Hiperbárica , Mucosa Bucal , Pene , Colgajos Quirúrgicos , Humanos , Masculino , Pene/cirugía , Mucosa Bucal/trasplante , Niño , Circuncisión Masculina/efectos adversos , Complicaciones Posoperatorias/terapia , Complicaciones Posoperatorias/etiología , Necrosis/etiología , Terapia CombinadaRESUMEN
In March 2023, our pediatric intensive care unit (PICU) retrospectively examined six cases of pediatric necrotizing tracheobronchitis (NTB), focusing on co-infections with influenza A virus (IAV) and Staphylococcus aureus (S. aureus). This study aimed to elucidate NTB's clinical characteristics, diagnostics, and therapeutic approaches. Diagnostics included symptom assessment, microbiological testing that confirmed all patients were positive for IAV H1N1 with a predominant S. aureus co-infection, and bronchoscopy. The patients predominantly exhibited fever, cough, and dyspnea. Laboratory analysis revealed decreased lymphocyte counts and elevated infection markers like C-reactive protein and procalcitonin. Chest computed tomography (CT) scans detected tracheobronchial obstructions in half of the cases, while bronchoscopy showed severe mucosal congestion, edema, necrosis, and purulent-hemorrhagic exudates. Treatments encompassed comprehensive strategies like oxygen therapy, intubation, bronchoscopic interventions, thoracentesis, oseltamivir, and a regimen of antibiotics. Our findings suggested potential correlations between clinical markers, notably lymphocyte count and procalcitonin, and clinical interventions such as the number of rescues and intensive care unit (ICU) duration. This research highlights the importance of early detection and the role of bronchoscopy and specific markers in assessing NTB, advocating for continued research in larger cohorts to better understand its clinical trajectory and refine treatment approaches for this challenging pediatric disease.
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Bronquitis , Coinfección , Gripe Humana , Infecciones Estafilocócicas , Staphylococcus aureus , Traqueítis , Humanos , Coinfección/diagnóstico , Masculino , Femenino , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/complicaciones , Gripe Humana/complicaciones , Gripe Humana/diagnóstico , Preescolar , Traqueítis/diagnóstico , Traqueítis/microbiología , Traqueítis/complicaciones , Bronquitis/diagnóstico , Bronquitis/microbiología , Bronquitis/complicaciones , Estudios Retrospectivos , Staphylococcus aureus/aislamiento & purificación , Lactante , Niño , Broncoscopía/métodos , Unidades de Cuidado Intensivo Pediátrico , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Necrosis , Virus de la Influenza A/aislamiento & purificaciónAsunto(s)
Necrosis , Pénfigo , Humanos , Pénfigo/patología , Pénfigo/diagnóstico , Femenino , Masculino , AdultoRESUMEN
Parkinson's Disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the Substantia nigra pars compacta (SNpc). Apoptosis is thought to play a critical role in the progression of PD, and thus understanding the effects of antiapoptotic strategies is crucial for developing potential therapies. In this study, we developed a unique genetic model to selectively delete Casp3, the gene encoding the apoptotic protein caspase-3, in dopaminergic neurons (TH-C3KO) and investigated its effects in response to a subacute regime of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration, which is known to trigger apoptotic loss of SNpc dopaminergic neurons. We found that Casp3 deletion did not protect the dopaminergic system in the long term. Instead, we observed a switch in the cell death pathway from apoptosis in wild-type mice to necrosis in TH-C3KO mice. Notably, we did not find any evidence of necroptosis in our model or in in vitro experiments using primary dopaminergic cultures exposed to 1-methyl-4-phenylpyridinium in the presence of pan-caspase/caspase-8 inhibitors. Furthermore, we detected an exacerbated microglial response in the ventral mesencephalon of TH-C3KO mice in response to MPTP, which mimicked the microglia neurodegenerative phenotype (MGnD). Under these conditions, it was evident the presence of numerous microglial phagocytic cups wrapping around apparently viable dopaminergic cell bodies that were inherently associated with galectin-3 expression. We provide evidence that microglia exhibit phagocytic activity towards both dead and stressed viable dopaminergic neurons through a galectin-3-dependent mechanism. Overall, our findings suggest that inhibiting apoptosis is not a beneficial strategy for treating PD. Instead, targeting galectin-3 and modulating microglial response may be more promising approaches for slowing PD progression.
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Apoptosis , Caspasa 3 , Neuronas Dopaminérgicas , Galectina 3 , Microglía , Necrosis , Fagocitosis , Animales , Neuronas Dopaminérgicas/metabolismo , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/patología , Microglía/metabolismo , Microglía/patología , Microglía/efectos de los fármacos , Apoptosis/efectos de los fármacos , Galectina 3/metabolismo , Galectina 3/genética , Caspasa 3/metabolismo , Ratones , Fagocitosis/efectos de los fármacos , Ratones Noqueados , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacología , Ratones Endogámicos C57BL , MasculinoRESUMEN
Necrotizing soft tissue infection (NSTI) is a life-threatening illness that can seriously harm a person. Over the last years the incidence of NSTI has increased. A rapid and thorough debridement is crucial to let patients survive. After this debridement, patients will often end up with large skin defects. A burn center is specialized in treating skin defects. Patients with large skin defects after the acute phase of NSTI can be referred to this for a multidisciplinary approach. In this article we describe the surgical treatment of the complex wounds of three referred patients with NSTI in our burn center.
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Desbridamiento , Infecciones de los Tejidos Blandos , Humanos , Infecciones de los Tejidos Blandos/terapia , Masculino , Resultado del Tratamiento , Necrosis , Persona de Mediana Edad , Fascitis Necrotizante/terapia , Fascitis Necrotizante/cirugía , Femenino , Adulto , Cicatrización de HeridasRESUMEN
OBJECTIVE: Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) autoantibodies are one of the myositis-specific antibodies which is associated with immune-mediated necrotizing myopathy (IMNM). However, the relationship between anti-HMGCR isotypes and prognosis has not yet been fully investigated. This study was conducted to gain insight into the association between anti-HMGCR isotypes and clinical, and prognosis in IMNM patients who were positive for anti-HMGCR antibodies. METHODS: Levels of anti-HMGCR isotypes (IgG, IgA and IgM) were assessed by enzyme-linked immunosorbent assay (ELISA) in 123 consecutive serum samples obtained from 71 patients who were positive for anti-HMGCR IgG at baseline. Disease activity was assessed by manual muscle testing (MMT) 8, Physician's Global Assessment (PGA) visual analog scale (VAS), and muscle VAS. RESULTS: Baseline anti-HMGCR IgG levels were correlated with PGA VAS (r = 0.24; p = 0.04), muscle VAS (r = 0.32; p < 0.01), and MMT8(r=-0.24; p = 0.04), and baseline anti-HMGCR IgM levels were positively correlated with PGA VAS (r = 0.27, p = 0.02), muscle VAS (r = 0.24, p = 0.04). Anti-HMGCR IgM positive patients had a lower age of onset [29(25,46) vs. 51(33,65), p = 0.006], and a higher proportion of neck weakness (63.5% vs. 34.6%, p = 0.031) compared with anti-HMGCR IgM negative patients. Longitudinal analysis showed that the changes in anti-HMGCR IgG levels were correlated with the changes in the PGA VAS (ß = 3.830; p < 0.0001), muscle VAS (ß = 2.893; p < 0.0001), MMT8 (ß=-19.368; p < 0.0001), and creatine kinase (CK) levels (ß = 3900.05, p < 0.0001). Anti-HMGCR IgM levels were weakly correlated with anti-HMGCR IgA levels at baseline (r = 0.33, p < 0.01), and the variations in anti-HMGCR IgA levels were correlated with the changes in anti-HMGCR IgM levels during follow-up (ß = 0.885; p < 0.0001). There were more patients with anti-HMGCR IgM who showed a refractory course than those who were with anti-HMGCR IgM negative (polycyclic course: 40% vs. 25%; chronic continuous course: 46.7% vs. 20.5%, p = 0.018). CONCLUSION: In anti-HMGCR IgG-positive IMNM patients, the levels of anti-HMGCR IgG are associated with disease activity, and anti-HMGCR IgM is associated with refractory outcome and poor prognosis.
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Autoanticuerpos , Hidroximetilglutaril-CoA Reductasas , Inmunoglobulina M , Humanos , Masculino , Femenino , Inmunoglobulina M/sangre , Inmunoglobulina M/inmunología , Persona de Mediana Edad , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Hidroximetilglutaril-CoA Reductasas/inmunología , Adulto , Anciano , Miositis/inmunología , Miositis/sangre , Necrosis/inmunología , Ensayo de Inmunoadsorción Enzimática , Enfermedades Musculares/inmunología , Enfermedades Musculares/sangre , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunologíaRESUMEN
Background: Cerebral radiation necrosis (RN), a severe complication of stereotactic radiotherapy (SRT), has been shown to significantly decrease patient survival time and quality of life. The purpose of this study was to analyze whether bevacizumab can prevent or reduce the occurrence of SRT-induced cerebral RN in non-small cell lung cancer (NSCLC) patients with brain metastases. Materials and methods: We retrospectively reviewed the clinical records of NSCLC patients with brain metastases from March 2013 to June 2023 who were treated with SRT. Patients were divided into two groups: those in the bevacizumab group received SRT with four cycles of bevacizumab, and patients in the control group received SRT only. Inverse probability of treatment weighting (IPTW) was performed based on a multinomial propensity score model to balance the baseline characteristics. The chi-square test was used. A Cox model was used to evaluate overall survival (OS). Results: A total of 80 patients were enrolled, namely, 28 patients in the bevacizumab group and 52 patients in the control group. The possibility of developing cerebral RN and/or symptomatic edema (RN/SE) was significantly decreased in patients treated with bevacizumab compared to those who did not receive bevacizumab before IPTW (p=0.036) and after IPTW (p=0.015) according to chi-square analysis. The IPTW-adjusted median OS was 47.7 months (95% CI 27.4-80.8) for patients in the bevacizumab group and 44.1 months (95% CI 36.7-68.0) (p=0.364) for patients in the control group. Conclusion: The application of bevacizumab concurrent with SRT may prevent or reduce the occurrence of cerebral RN in NSCLC patients with brain metastases.
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Bevacizumab , Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Necrosis , Traumatismos por Radiación , Radiocirugia , Humanos , Carcinoma de Pulmón de Células no Pequeñas/terapia , Bevacizumab/uso terapéutico , Bevacizumab/administración & dosificación , Masculino , Femenino , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/terapia , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Persona de Mediana Edad , Radiocirugia/efectos adversos , Anciano , Estudios Retrospectivos , Traumatismos por Radiación/etiología , Traumatismos por Radiación/prevención & control , Antineoplásicos Inmunológicos/uso terapéuticoRESUMEN
PURPOSE: To evaluate exogenous hyaluronic acid (HA) derived from bacterial fermentation through enteral and parenteral routes in ischemic skin flaps induced in rats, using clinical and histological exams; and interleukins (IL) as tissue inflammatory biomarkers. METHODS: Sixty-four male adults Wistar rats with ischemic skin flaps on the dorsum were randomized into four groups, based on the treatment protocol: subcutaneous administration of saline solution (0.9%) (GI); oral administration of distilled water (GII); subcutaneous administration of HA (0.3%) (GIII); and oral administration of HA (1%) (GIV). Flaps of all groups were comparable regarding clinical and macroscopic evaluation, histological examination, pro-inflammatory cytokines (IL-1ß, IL-6, and tumor necrosis factor-α) and anti-inflammatory cytokine IL-10. RESULTS: A lower percentage of necrosis was identified in flaps treated with subcutaneous administration of HA (0.3%). The pro- and anti-inflammatory cytokines, epidermis thickness, blood vessels, and inflammatory cells showed statistically significant inter-group and intra-group differences (p < 0.05). CONCLUSIONS: High molecular HA (1,400 ~ 2,000 kDa) administrated by subcutaneous or oral route exhibited beneficial effects in ischemic skin flaps of rats. However, subcutaneous administration of HA (0.3%) showed better results in terms of the percentage of necrosis and epithelialization.
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Ácido Hialurónico , Isquemia , Distribución Aleatoria , Ratas Wistar , Colgajos Quirúrgicos , Animales , Masculino , Ácido Hialurónico/administración & dosificación , Colgajos Quirúrgicos/irrigación sanguínea , Colgajos Quirúrgicos/patología , Piel/efectos de los fármacos , Piel/patología , Método Doble Ciego , Citocinas/análisis , Citocinas/metabolismo , Necrosis , Ratas , Administración Oral , Modelos Animales de Enfermedad , Reproducibilidad de los ResultadosRESUMEN
Cell death is a fundamental process in health and disease. Emerging research shows the existence of numerous distinct cell death modalities with similar and intertwined signaling pathways, but resulting in different cellular outcomes, raising the need to understand the decision-making steps during cell death signaling. Paracetamol (Acetaminophen, APAP)-induced hepatocyte death includes several apoptotic processes but eventually is executed by oncotic necrosis without any caspase activation. Here, we studied this paradoxical form of cell death and revealed that APAP not only fails to activate caspases but also strongly impedes their activation upon classical apoptosis induction, thereby shifting apoptosis to necrosis. While APAP intoxication results in massive drop in mitochondrial respiration, low cellular ATP levels could be excluded as an underlying cause of missing apoptosome formation and caspase activation. In contrast, we identified oxidative stress as a key factor in APAP-induced caspase inhibition. Importantly, caspase inhibition and the associated switch from apoptotic to necrotic cell death was reversible through the administration of antioxidants. Thus, exemplified by APAP-induced cell death, our study stresses that cellular redox status is a critical component in the decision-making between apoptotic and necrotic cell death, as it directly affects caspase activity.
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Acetaminofén , Apoptosis , Caspasas , Hepatocitos , Estrés Oxidativo , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Acetaminofén/farmacología , Caspasas/metabolismo , Animales , Humanos , Necrosis , Ratones , Activación Enzimática/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Adenosina Trifosfato/metabolismo , Masculino , Transducción de Señal/efectos de los fármacosAsunto(s)
Arteritis de Células Gigantes , Labio , Necrosis , Cuero Cabelludo , Lengua , Humanos , Arteritis de Células Gigantes/diagnóstico por imagen , Arteritis de Células Gigantes/complicaciones , Cuero Cabelludo/diagnóstico por imagen , Cuero Cabelludo/patología , Lengua/diagnóstico por imagen , Lengua/patología , Necrosis/diagnóstico por imagen , Labio/diagnóstico por imagen , Labio/patología , Estudios de Casos y Controles , Francia , Arterias Temporales/diagnóstico por imagen , Arterias Temporales/patologíaRESUMEN
BACKGROUND AND OBJECTIVES: Immune-mediated necrotizing myopathy (IMNM) caused by antibodies against 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is an inflammatory myopathy that has been epidemiologically correlated with previous statin exposure. We characterized in detail a series of 11 young statin-naïve patients experiencing a chronic disease course mimicking a limb-girdle muscular dystrophy. With the hypothesis that HMGCR upregulation may increase immunogenicity and trigger the production of autoantibodies, our aim was to expand pathophysiologic knowledge of this distinct phenotype. METHODS: Clinical and epidemiologic data, autoantibody titers, creatine kinase (CK) levels, response to treatment, muscle imaging, and muscle biopsies were assessed. HMGCR expression in patients' muscle was assessed by incubating sections of affected patients with purified anti-HMGCR+ serum. Whole-exome sequencing (WES) with a special focus on cholesterol biosynthesis-related genes and high-resolution human leukocyte antigen (HLA) typing were performed. RESULTS: Patients, aged 3-25 years and mostly female (90.9%), presented with subacute proximal weakness progressing over many years and high CK levels (>1,000 U/L). Diagnostic delay ranged from 3 to 27 years. WES did not reveal any pathogenic variants. HLA-DRB1*11:01 carrier frequency was 60%, a significantly higher proportion than in the control population. No upregulation or mislocalization of the enzyme in statin-exposed or statin-naïve anti-HMGCR+ patients was observed, compared with controls. DISCUSSION: WES of a cohort of patients with dystrophy-like anti-HMGCR IMNM did not reveal any common rare variants of any gene, including cholesterol biosynthesis-related genes. HLA analysis showed a strong association with HLA-DRB1*11:01, previously mostly described in statin-exposed adult patients; consequently, a common immunogenic predisposition should be suspected, irrespective of statin exposure. Moreover, we were unable to conclusively demonstrate muscle upregulation/mislocalization of HMGCR in IMNM, whether or not driven by statins.
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Cadenas HLA-DRB1 , Hidroximetilglutaril-CoA Reductasas , Humanos , Hidroximetilglutaril-CoA Reductasas/genética , Hidroximetilglutaril-CoA Reductasas/inmunología , Femenino , Masculino , Adulto , Cadenas HLA-DRB1/genética , Adulto Joven , Niño , Adolescente , Preescolar , Mutación , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Necrosis , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Miositis/inmunología , Miositis/genéticaRESUMEN
Respiratory diseases are a growing concern in public health because of their potential to endanger the global community. Cell death contributes critically to the pathophysiology of respiratory diseases. Recent evidence indicates that necroptosis, a unique form of programmed cell death (PCD), plays a vital role in the molecular mechanisms underlying respiratory diseases, distinguishing it from apoptosis and conventional necrosis. Necroptosis is a type of inflammatory cell death governed by receptor-interacting serine/threonine protein kinase 1 (RIPK1), RIPK3, and mixed-lineage kinase domain-like protein (MLKL), resulting in the release of intracellular contents and inflammatory factors capable of initiating an inflammatory response in adjacent tissues. These necroinflammatory conditions can result in significant organ dysfunction and long-lasting tissue damage within the lungs. Despite evidence linking necroptosis to various respiratory diseases, there are currently no specific alternative treatments that target this mechanism. This review provides a comprehensive overview of the most recent advancements in understanding the significance and mechanisms of necroptosis. Specifically, this review emphasizes the intricate association between necroptosis and respiratory diseases, highlighting the potential use of necroptosis as an innovative therapeutic approach for treating these conditions.
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Necroptosis , Humanos , Animales , Enfermedades Respiratorias/patología , Enfermedades Respiratorias/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , NecrosisRESUMEN
Hypertrophic cardiomyopathy (HCM) is a heart muscle disease associated with an increased risk for sudden cardiac death (SCD). Cytokeratin 18-based proteins, such as M30 and M65 antigens, are known cell-death biomarkers. M30 antigen is released from cells during apoptosis, and M65 antigen is released during cell death from any cause, such as apoptosis or necrosis. We aimed to study the expression of M30 and M65 antigens in peripheral blood obtained by 46 HCM patients and compare with 27 age- and sex-matched patients without HCM. We also investigated the CK18 expression in myocardium from postmortem HCM hearts. M30 and M65 antigens were significantly increased in the HCM vs. non-HCM group (Μ30: 338 ± 197 U/uL vs. 206 ± 166 U/uL, p = 0.003; M65: 428 ± 224 U/uL vs. 246 ± 214 U/uL, p = 0.001), and HCM patients with a higher expression of these markers (M30: 417 ± 208 vs. 271 ± 162 U/uL, p = 0.011; M65: 518 ± 242 vs. 351 ± 178 U/uL, p = 0.011) had a higher risk for SCD. In HCM, both apoptosis and necrosis are increased, but particularly necrosis (M30/M65 ratio: 0.75 ± 0.09 vs. 0.85 ± 0.02, p < 0.001). CK18 is expressed in the HCM myocardium (1.767 ± 0.412 vs. 0.537 ± 0.383, % of area, p = 0.0058). Therefore, M30 and M65 antigens may be novel biomarkers in HCM.
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Biomarcadores , Cardiomiopatía Hipertrófica , Queratina-18 , Humanos , Cardiomiopatía Hipertrófica/metabolismo , Cardiomiopatía Hipertrófica/sangre , Queratina-18/metabolismo , Queratina-18/sangre , Masculino , Biomarcadores/metabolismo , Biomarcadores/sangre , Femenino , Persona de Mediana Edad , Necrosis , Miocardio/metabolismo , Miocardio/patología , Apoptosis , Adulto , Anciano , Muerte Súbita Cardíaca , Fragmentos de PéptidosRESUMEN
Tracking cell death in vivo can enable a better understanding of the biological mechanisms underlying tissue homeostasis and disease. Unfortunately, existing cell death labeling methods lack compatibility with in vivo applications or suffer from low sensitivity, poor tissue penetration, and limited temporal resolution. Here, we fluorescently labeled dead cells in vivo with Trypan Blue (TBlue) to detect single scattered dead cells or to generate whole-mount three-dimensional maps of large areas of necrotic tissue during organ regeneration. TBlue effectively marked different types of cell death, including necrosis induced by CCl4 intoxication in the liver, necrosis caused by ischemia-reperfusion in the skin, and apoptosis triggered by BAX overexpression in hepatocytes. Moreover, due to its short circulating lifespan in blood, TBlue labeling allowed in vivo "pulse and chase" tracking of two temporally spaced populations of dying hepatocytes in regenerating mouse livers. Additionally, upon treatment with cisplatin, TBlue labeled dead cancer cells in livers with cholangiocarcinoma and dead thymocytes due to chemotherapy-induced toxicity, showcasing its utility in assessing anticancer therapies in preclinical models. Thus, TBlue is a sensitive and selective cell death marker for in vivo applications, facilitating the understanding of the fundamental role of cell death in normal biological processes and its implications in disease.
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Muerte Celular , Azul de Tripano , Animales , Ratones , Muerte Celular/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Hepatocitos/patología , Hepatocitos/metabolismo , Humanos , Neoplasias/patología , Ratones Endogámicos C57BL , Regeneración Hepática/efectos de los fármacos , Hígado/patología , Hígado/efectos de los fármacos , Rastreo Celular/métodos , Apoptosis/efectos de los fármacos , Imagenología Tridimensional , Regeneración/efectos de los fármacos , Necrosis , MasculinoRESUMEN
Necrotizing soft tissue infections are a heterogeneous group of severe infections of the skin, connective tissue and muscles in which necrotic destruction of the tissue occurs at the site of infection. Various bacteria are known as "typical" triggering pathogens and the infection can occur on the entire surface of the body. Necrotizing soft tissue infections are always a time-sensitive emergency associated with high mortality. Many affected patients are critically ill and require treatment in an intensive care unit. The rapid and radical surgical treatment is an essential part of management and in addition an adequate and timely antimicrobial treatment is of great importance. The health consequences for surviving patients are often severe, as extensive soft tissue damage leads to functional impairments. In many cases extensive plastic surgery follow-up is necessary. Therefore, necrotizing soft tissue infections are "complicated" in every phase of the disease and require interprofessional treatment. This review article provides a current overview of various aspects of the diagnostics, treatment and aftercare of necrotizing soft tissue infections.
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Necrosis , Infecciones de los Tejidos Blandos , Humanos , Infecciones de los Tejidos Blandos/terapia , Infecciones de los Tejidos Blandos/diagnóstico , Infecciones de los Tejidos Blandos/microbiología , Infecciones de los Tejidos Blandos/patología , Necrosis/microbiología , Fascitis Necrotizante/diagnóstico , Fascitis Necrotizante/terapia , Fascitis Necrotizante/microbiología , Fascitis Necrotizante/patología , Antibacterianos/uso terapéuticoRESUMEN
ABSTRACT: The study aimed to investigate the pathogenesis of sepsis-induced cardiomyopathy, a leading cause of mortality in septic patients. Transcriptome data from cecal ligation and puncture-induced septic mice were analyzed at different time points (24, 48, and 72 hours) using GSE171546 data. Through weighted gene co-expression network analysis, time series, and differential expression analyses, key time-series differentially expressed genes were identified. In addition, single-cell sequencing data (GSE207363) were used for both differential and pseudotime analyses to pinpoint differentially expressed genes specific to endothelial cells. The study highlighted Spock2, S100a9, S100a8, and Xdh as differential genes specific to endothelial cells in a time-dependent manner. Immunofluorescence validation confirmed the increased expression of SPOCK2 in the endothelial cells of cecal ligation and puncture-induced septic mice. Furthermore, in vitrostudies showed that deletion of Spock2 significantly increased LPS-induced apoptosis and necrosis in human umbilical vein endothelial cells. In conclusion, SPOCK2 expression was increased in septic cardiac endothelial cells and LPS-induced human umbilical vein endothelial cells and may play a protective role.
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Apoptosis , Cardiomiopatías , Modelos Animales de Enfermedad , Células Endoteliales de la Vena Umbilical Humana , Ratones Endogámicos C57BL , Sepsis , Animales , Sepsis/metabolismo , Sepsis/genética , Sepsis/complicaciones , Humanos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/patología , Cardiomiopatías/metabolismo , Cardiomiopatías/genética , Cardiomiopatías/patología , Masculino , Factores de Tiempo , Transcriptoma , Células Cultivadas , Ratones Noqueados , Células Endoteliales/metabolismo , Células Endoteliales/patología , Redes Reguladoras de Genes , Necrosis , Bases de Datos Genéticas , Transducción de Señal , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Lipopolisacáridos/farmacología , Regulación hacia Arriba , Análisis de la Célula Individual , Ratones , Calgranulina BRESUMEN
Free flap reconstruction for postoperative tissue defects in oral and maxillofacial tumors is a critical component of reconstructive surgery. Identifying risk factors for flap necrosis is essential for improving surgical outcomes and patient quality of life. A retrospective study was conducted on patients who underwent free flap reconstruction between January 2020 and December 2023. Patients were included if they had comprehensive medical records and at least a six-month follow-up. We excluded those with a history of flap necrosis, uncontrolled systemic diseases, non-adherence to postoperative care, or concurrent malignancy treatments. Data on demographics, comorbidities, flap characteristics, and operative details were collected and analyzed using univariate analysis and logistic regression tests. Univariate analysis did not find a significant correlation between flap necrosis and factors such as hyperlipidemia, lymph node metastasis, or flap type. However, diabetes mellitus, oral infections, and albumin levels below 35 g/L were significantly associated with flap necrosis. Multivariate logistic regression showed diabetes mellitus increased the odds of flap necrosis by approximately ninefold, and oral infection increased it by over tenfold. Diabetes mellitus, oral infection, and low albumin levels are significant risk factors for flap necrosis in free flap reconstruction after oral and maxillofacial surgery. Prompt identification and management of these factors are crucial to mitigate the risk of flap necrosis.
Asunto(s)
Colgajos Tisulares Libres , Necrosis , Procedimientos de Cirugía Plástica , Humanos , Masculino , Femenino , Persona de Mediana Edad , Factores de Riesgo , Procedimientos de Cirugía Plástica/métodos , Procedimientos de Cirugía Plástica/efectos adversos , Estudios Retrospectivos , Anciano , Complicaciones Posoperatorias/etiología , Adulto , Neoplasias de la Boca/cirugía , Neoplasias de la Boca/patologíaRESUMEN
PURPOSE: The treatment of amoebic infections is often problematic, largely due to delayed diagnosis, amoebae transformation into resistant cyst form, and lack of availability of effective chemotherapeutic agents. Herein, we determined anti-Acanthamoeba castellanii properties of three metal oxide nanoparticles (TiO2, ZrO2, and Al2O3). METHODS: Amoebicidal assays were performed to determine whether metal oxide nanoparticles inhibit amoebae viability. Encystation assays were performed to test whether metal oxide nanoparticles inhibit cyst formation. By measuring lactate dehydrogenase release, cytotoxicity assays were performed to determine human cell damage. Hoechst 33342/PI staining was performed to determine programmed cell death (apoptosis) and necrosis in A. castellanii. RESULTS: TiO2-NPs significantly inhibited amoebae viability as observed through amoebicidal assays, as well as inhibited their phenotypic transformation as evident using encystation assays, and showed limited human cell damage as observed by measuring lactate dehydrogenase assays. Furthermore, TiO2-NPs altered parasite membranes and resulted in necrotic cell death as determined using double staining cell death assays with Hoechst33342/Propidium iodide (PI) observed through chromatin condensation. These findings suggest that TiO2-NPs offers a potential viable avenue in the rationale development of therapeutic interventions against Acanthamoeba infections.