Examining the Role of Histaminergic, Orexinergic, and Cannabinergic Systems in Redox Regulation in Gastric Adenocarcinoma.

Histaminergic, orexinergic, and cannabinoid systems play a role in both physiologic and oncogenic mechanisms in digestive tissues. These three systems are important mediators of tumor transformation, as they are associated with redox alterations, which are key aspects in oncological disorders. The three systems are known to promote alterations in the gastric epithelium through intracellular signaling pathways, such as oxidative phosphorylation, mitochondrial dysfunction, and increased Akt, which might promote tumorigenesis. Histamine promotes cell transformation through redox-mediated alterations in the cell cycle, DNA repair, and immunological response. The increase in histamine and oxidative stress generates angiogenic and metastatic signals through the VEGF receptor and H2R-cAMP-PKA pathway. Immunosuppression in the presence of histamine and ROS is linked to a decrease in dendritic and myeloid cells in gastric tissue. These effects are counteracted by histamine receptor antagonists, such as cimetidine. Regarding orexins, overexpression of the Orexin 1 Receptor (OX1R) induces tumor regression through the activation of MAPK-dependent caspases and src-tyrosine. OX1R agonists are candidates for the treatment of gastric cancer by stimulating apoptosis and adhesive interactions. Lastly, cannabinoid type 2 (CB2) receptor agonists increase ROS, leading to the activation of apoptotic pathways. In contrast, cannabinoid type 1 (CB1) receptor agonists decrease ROS formation and inflammation in gastric tumors exposed to cisplatin. Overall, the repercussion of ROS modulation through these three systems on tumor activity in gastric cancer depends on intracellular and/or nuclear signals associated with proliferation, metastasis, angiogenesis, and cell death. Here, we review the role of these modulatory systems and redox alterations in gastric cancer.

Lung transplantation for interstitial lung disease in idiopathic inflammatory myositis: A cohort study.

In patients with interstitial lung disease (ILD) complicating classical or amyopathic idiopathic inflammatory myopathy (IIM), lung transplantation outcomes might be affected by the disease and treatments. Here, our objective was to assess survival and prognostic factors in lung transplant recipients with IIM-ILD. We retrospectively reviewed data for 64 patients who underwent lung transplantation between 2009 and 2021 at 19 European centers. Patient survival was the primary outcome. At transplantation, the median age was 53 [46-59] years, 35 (55%) patients were male, 31 (48%) had classical IIM, 25 (39%) had rapidly progressive ILD, and 21 (33%) were in a high-priority transplant allocation program. Survival rates after 1, 3, and 5 years were 78%, 73%, and 70%, respectively. During follow-up (median, 33 [7-63] months), 23% of patients developed chronic lung allograft dysfunction. Compared to amyopathic IIM, classical IIM was characterized by longer disease duration, higher-intensity immunosuppression before transplantation, and significantly worse posttransplantation survival. Five (8%) patients had a clinical IIM relapse, with mild manifestations. No patient experienced ILD recurrence in the allograft. Posttransplantation survival in IIM-ILD was similar to that in international all-cause-transplantation registries. The main factor associated with worse survival was a history of muscle involvement (classical IIM). In lung transplant recipients with idiopathic inflammatory myopathy, survival was similar to that in all-cause transplantation and was worse in patients with muscle involvement compared to those with the amyopathic disease.

Double-Lung Transplantation in a Patient with Pulmonary Type B Niemann-Pick Disease: A Valid Treatment Option.

Niemann-Pick disease is a rare autosomal recessive disease characterized by an abnormal intracellular lipid accumulation. Type B is later in onset and a less severe form of the disease, so affected people may survive in adulthood. Storage of sphingomyelin in pulmonary macrophages can lead to interstitial lung disease. There are very few published cases of lung transplantation in patients with Niemann-Pick disease, all of them described in the last 2 years. We present here one case of a 57-year-old man successfully treated with a double-lung transplant.

Classification of maternal morbidity and mortality using an organic dysfunction scale. / Clasificación de morbilidad y mortalidad materna mediante una escala de disfunción orgánica.

BACKGROUND: The patient with high-risk pregnancy and organic dysfunction is called "critically ill" or "near miss" by the World Health Organization (WHO), generally requiring an intensive care unit (ICU) to avoid death. The WHO establishes its identification through the maternal severity index (MSI). However, this index and other rating scales only detect very high mortality, and not all categories. In order to fully assess the obstetric patient, taking into account different models, gestational parameters, the spectrum of maternal morbidity and treatment, a new scale is proposed to correctly detect and classify maternal morbidity and mortality. OBJECTIVE: To classify maternal morbidity and mortality using an organic dysfunction scale. METHOD: Diagnostic and prognostic test validation study. Selection of 80 obstetric patients admitted to the ICU, in a period of 1 year. Scale application by 5 phases: scoring system, detection of multi-organ dysfunction syndrome (MODS), validation of diagnostic test compared to MSI; morbidity and mortality classification. Association, reproducibility and validity tests are performed to determine reliability. RESULTS: 2596 observations were made. The tests support detecting MODS (t Student, P < 0.01) and favor the utility of the scale (sensibility 93%, specificity 65%). The correlation coefficient of the scoring system is positive (0.5274), having >12 points (>50%) emits the highest risk. CONCLUSIONS: The new scale adequately detects the MODS and allows an objective classification of the degree of maternal morbidity and mortality.

INTRODUCCIÓN: La paciente con embarazo de alto riesgo y disfunción orgánica se denomina «críticamente enferma¼ o «near miss¼ por la Organización Mundial de la Salud (OMS), y generalmente requiere ingreso en la unidad de cuidados intensivos (UCI) para evitar su muerte. La OMS establece su identificación mediante el índice de severidad materna (ISM). Sin embargo, este índice y las demás escalas de valoración solo detectan mortalidad muy alta, y no todas las categorías. Con el fin de valorar integralmente a la paciente obstétrica, tomando en cuenta diferentes modelos, parámetros gestacionales, espectro de morbilidad materna y tratamientos, se propone una nueva escala que permita detectar y clasificar correctamente la morbilidad y la mortalidad maternas. OBJETIVO: Clasificar la morbilidad y la mortalidad maternas mediante una escala de disfunción orgánica. MÉTODO: Estudio de validación de prueba diagnóstica y pronóstica. Selección de 80 pacientes obstétricas con ingreso a UCI, en un periodo de 1 año. Aplicación de la escala por cinco fases: sistema de puntuación, detección del síndrome de disfunción multiorgánica (SDMO), validación de prueba diagnóstica comparada con ISM, clasificación de morbilidad y mortalidad. Se realizan pruebas de asociación, reproducibilidad y validez para determinar la confiabilidad. RESULTADOS: Se hicieron 2596 observaciones. Las pruebas avalan detectar SDMO (t de Student, P < 0.01) y favorecen la utilidad de la escala (sensibilidad del 93% y especificidad del 65%). El coeficiente de correlación del sistema de puntuación es positivo (0.5274); tener >12 puntos (>50%) indica el mayor riesgo. CONCLUSIONES: La nueva escala detecta adecuadamente el SDMO y permite clasificar de manera objetiva el grado de morbilidad y la mortalidad materna.