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Metabolites with high chemical reactivity serve important roles in chemical defenses of organisms. Formaldehyde, as a simple and highly reactive small molecule, can be produced by microorganisms, plants, and animals. Its toxicity is well known, but information about its other biological functions remains scarce. Here, we report that the natural product SEK34b produced by Streptomyces species can react nonenzymatically with formaldehyde in water to yield the methylene-bridged dimer phaeochromycin F. This process can eliminate the toxic substance formaldehyde produced by Staphylococcus aureus. Furthermore, there is a substantial inhibitory impact of phaeochromycin F on S. aureus. We hypothesize that these constitute an integrated system of defense and attack of Streptomyces species against competitors. Our study indicates that formaldehyde can react with vancomycin and tigecycline under mild conditions to generate the derivatives bearing an imidazolidin-4-one moiety, thereby reducing the antibacterial activity of these antibiotics. These data provide a possible chemical interaction mechanism of bacteria involving the nonenzymatic reactions of formaldehyde with highly reactive natural products.
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Ten undocumented carbazole derivatives (2-11) along with the reported analogue (1) were isolated from the mangrove-derived Streptomyces sp. OUCMDZ-5511, cultured with NaBr-supplemented liquid medium. Compounds 1-7 are brominated carbazoles, and 8, 10, and 11 feature an additional thiazole or 2,3-dihydro-1,4-oxathiine rings, respectively. Their structures were identified through spectroscopic techniques, computational chemistry, and X-ray crystallography. Notably, compounds 6 and 8 effectively inhibited immune cell migration, indicating anti-inflammatory activity in vivo, potentially via Myd88/Nf-κB pathways, as suggested for compound 6.
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Carbazoles , Streptomyces , Streptomyces/química , Carbazoles/química , Carbazoles/farmacología , Carbazoles/aislamiento & purificación , Estructura Molecular , Cristalografía por Rayos X , Bromo/química , Azufre/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Biología Marina , FN-kappa B/antagonistas & inhibidores , FN-kappa B/metabolismo , AnimalesRESUMEN
Crohn's disease (CD) is a refractory chronic inflammatory bowel disease (IBD) with unknown etiology. Transmural inflammation, involving the intestine and mesentery, represents a characteristic pathological feature of CD and serves as a critical contributor to its intractability. Here, this study describes an oral pyroptosis nanoinhibitor loaded with tumor necrosis factor-α (TNF-α) deoxyribozymes (DNAzymes) (DNAzymes@degradable silicon nanoparticles@Mannose, Dz@MDSN), which can target macrophages at the site of inflammation and respond to reactive oxygen species (ROS) to release drugs. Dz@MDSN can not only break the inflammatory cycle in macrophages by degrading TNF-α mRNA but also reduce the production of ROS mainly from macrophages. Moreover, Dz@MDSN inhibits excessive pyroptosis in epithelial cells through ROS clearance, thereby repairing the intestinal barrier and reducing the translocation of intestinal bacteria to the mesentery. Consequently, these combined actions synergistically contribute to the suppression of inflammation within both the intestine and the mesentery. This study likely represents the first successful attempt in the field of utilizing nanomaterials to achieve transmural healing for CD, which also provides a promising treatment strategy for CD patients.
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Enfermedad de Crohn , ADN Catalítico , Piroptosis , Factor de Necrosis Tumoral alfa , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/patología , Enfermedad de Crohn/metabolismo , Piroptosis/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Humanos , Animales , Administración Oral , Ratones , ADN Catalítico/química , ADN Catalítico/metabolismo , ADN Catalítico/farmacología , Nanopartículas/química , Especies Reactivas de Oxígeno/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Silicio/química , Silicio/farmacología , Manosa/química , Manosa/farmacología , Células RAW 264.7 , MasculinoRESUMEN
Importance: Hepatitis C can be cured with direct-acting antivirals (DAAs), but Medicaid programs have implemented fibrosis, sobriety, and prescriber restrictions to control costs. Although restrictions are easing, understanding their association with hepatitis C treatment rates is crucial to inform policies that increase access to lifesaving treatment. Objective: To estimate the association of jurisdictional (50 states and Washington, DC) DAA restrictions and Medicaid expansion with the number of Medicaid recipients with filled prescriptions for DAAs. Design, Setting, and Participants: This cross-sectional study used publicly available Medicaid documents and claims data from January 1, 2014, to December 31, 2021, to compare the number of unique Medicaid recipients treated with DAAs in each jurisdiction year with Medicaid expansion status and categories of fibrosis, sobriety, and prescriber restrictions. Medicaid recipients from all 50 states and Washington, DC, during the study period were included. Multilevel Poisson regression was used to estimate the association between Medicaid expansion and DAA restrictive policies on jurisdictional Medicaid DAA prescription fills. Data were analyzed initially from August 15 to November 15, 2023, and subsequently from April 15 to May 9, 2024. Exposures: Jurisdictional Medicaid expansion status and fibrosis, sobriety, and prescriber DAA restrictions. Main Outcomes and Measures: Number of people treated with DAAs per 100â¯000 Medicaid recipients per year. Results: A total of 381â¯373 Medicaid recipients filled DAA prescriptions during the study period (57.3% aged 45-64 years; 58.7% men; 15.2% non-Hispanic Black and 52.2% non-Hispanic White). Medicaid nonexpansion jurisdictions had fewer filled DAA prescriptions per 100â¯000 Medicaid recipients per year than expansion jurisdictions (38.6 vs 86.6; adjusted relative risk [ARR], 0.56 [95% CI, 0.52-0.61]). Jurisdictions with F3 to F4 (34.0 per 100â¯000 Medicaid recipients per year; ARR, 0.39 [95% CI, 0.37-0.66]) or F1 to F2 fibrosis restrictions (61.9 per 100â¯000 Medicaid recipients per year; ARR, 0.62 [95% CI, 0.59-0.66]) had lower treatment rates than jurisdictions without fibrosis restrictions (94.8 per 100â¯000 Medicaid recipients per year). Compared with no sobriety restrictions (113.5 per 100â¯000 Medicaid recipients per year), 6 to 12 months of sobriety (38.3 per 100â¯000 Medicaid recipients per year; ARR, 0.65 [95% CI, 0.61-0.71]) and screening and counseling requirements (84.7 per 100â¯000 Medicaid recipients per year; ARR, 0.87 [95% CI, 0.83-0.92]) were associated with reduced treatment rates, while 1 to 5 months of sobriety was not statistically significantly different. Compared with no prescriber restrictions (97.8 per 100â¯000 Medicaid recipients per year), specialist consult restrictions was associated with increased treatment (66.2 per 100â¯000 Medicaid recipients per year; ARR, 1.05 [95% CI, 1.00-1.10]), while specialist required restrictions were not statistically significant. Conclusions and Relevance: In this cross-sectional study, Medicaid nonexpansion status, fibrosis, and sobriety restrictions were associated with a reduction in the number of people with Medicaid who were treated for hepatitis C. Removing DAA restrictions might facilitate treatment of more people diagnosed with hepatitis C.
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Antivirales , Medicaid , Humanos , Medicaid/estadística & datos numéricos , Estados Unidos , Estudios Transversales , Antivirales/uso terapéutico , Antivirales/economía , Masculino , Femenino , Persona de Mediana Edad , Hepatitis C/tratamiento farmacológico , Adulto , Política de Salud/legislación & jurisprudencia , Accesibilidad a los Servicios de Salud/estadística & datos numéricosRESUMEN
Achieving optimal nutritional status in patients with penetrating Crohn's disease is crucial in preparing for surgical resection. However, there is a dearth of literature comparing the efficacy of total parenteral nutrition (TPN) v. exclusive enteral nutrition (EEN) in optimising postoperative outcomes. Hence, we conducted a case-matched study to assess the impact of preoperative EEN v. TPN on the incidence of postoperative adverse outcomes, encompassing overall postoperative morbidity and stoma formation, among penetrating Crohn's disease patients undergoing bowel surgery. From 1 December 2012 to 1 December 2021, a retrospective study was conducted at a tertiary centre to enrol consecutive patients with penetrating Crohn's disease who underwent surgical resection. Propensity score matching was utilised to compare the incidence of postoperative adverse outcomes. Furthermore, univariate and multivariate logistic regression analyses were conducted to identify the risk factors associated with adverse outcomes. The study included 510 patients meeting the criteria. Among them, 101 patients in the TPN group showed significant improvements in laboratory indicators at the time of surgery compared with pre-optimisation levels. After matching, TPN increased the occurrence of postoperative adverse outcomes (92·2 % v. 64·1 %, P = 0·001) when compared with the EEN group. In the multivariate analysis, TPN showed a significantly higher OR for adverse outcomes than EEN (OR = 4·241; 95 % CI 1·567-11·478; P = 0·004). The study revealed that penetrating Crohn's disease patients who were able to fulfil their nutritional requirements through EEN exhibited superior nutritional and surgical outcomes in comparison with those who received TPN.
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BACKGROUND: Temporary stoma formation is common in Crohn's disease (CD), while stoma reversal is associated with postoperative morbidity. This study aimed to evaluate the postoperative outcomes of split stoma reversal, SSR (i.e., exteriorization of proximal and distal ends of the stoma through a small common opening) and end stoma closure, ESC (i.e., the proximal stump externalized, and distal end localized abdominally. METHODS: Patients with CD who underwent stoma reversal surgeries between January 2017 and December 2021 were included. Demographic, clinical, and postoperative data were collected and analyzed to evaluate outcomes of reversal surgery. RESULTS: A total of 255 patients who underwent stoma reversal surgeries met the inclusion criteria. SSR was superior to ESC in terms of operative time (80.0 vs. 120.0, p = 0.0004), intraoperative blood loss volume (20.0 vs. 100.0, p = 0.0002), incision length (3.0 vs. 15.0, p < 0.0001), surgical wound classification (0 vs. 8.3%, p = 0.04), postoperative hospital stay (7.0 vs. 9.0, p = 0.0007), hospital expense (45.6 vs. 54.2, p = 0.0003), and postoperative complications (23.8% vs. 44.3%, p = 0.0040). Although patients in the ESC group experienced more surgical recurrence than those in the SSR group (8.3% vs. 3.2%) during the follow-up, the Kaplan-Meier curve analysis revealed no statistical difference (p = 0.29). CONCLUSIONS: The split stoma can be recommended when stoma construction is indicated in patients with Crohn's disease.
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Enfermedad de Crohn , Complicaciones Posoperatorias , Reoperación , Estomas Quirúrgicos , Humanos , Enfermedad de Crohn/cirugía , Femenino , Masculino , Adulto , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos , Estomas Quirúrgicos/efectos adversos , Persona de Mediana Edad , Reoperación/estadística & datos numéricos , Resultado del Tratamiento , Adulto Joven , Tiempo de Internación/estadística & datos numéricos , Tempo Operativo , Ileostomía/efectos adversos , Ileostomía/métodosRESUMEN
There is a paucity of data on the surgical or medical treatment for abscess/fistula complicating Crohn's disease after successful nonsurgical management. We conducted a cohort study to investigate the long-term outcomes and the risk factors for the requirement of subsequent surgical intervention in Crohn's disease patients with complicating fistulas/abscess following successful nonsurgical management. Data were collected on penetrating Crohn's disease experiencing successful nonsurgical treatment between December 2012 and December 2021. Long-term outcomes and risk factors of surgery were assessed by univariate and multivariate analysis, and subgroup analysis was performed based on penetrating phenotype including abscess, fistula, and phlegmon. A total of 523 penetrating Crohn's disease patients; there were 390, 125, and 60 patients complicated with fistulas, abscess, and phlegmon, respectively. Long-term outcomes showed that BMIâ <â 18.5 (kg/m 2 ), the recurrent abscess, and stricture were independent risk factors of surgery. Biologics and resolution of abscess were independent protective factors of surgery. Furthermore, in 399 patients undergoing early surgery, stricture and BMIâ <â 18.5 (kg/m 2 ) were independent risk factors, and biologics and abscess resolution were protective of the early surgery. Subgroup analysis based on fistula, abscess, and phlegmon phenotype also demonstrated that concomitant stricture was an independent risk factor and the use of biologics was protective of surgical resection. Our data indicate that biologics can delay the requirement of surgery and may be given to patients with penetrating complicating Crohn's disease who have been successfully treated nonoperatively, but surgical resection should be considered in the setting of malnutrition and stenosis formation.
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Enfermedad de Crohn , Fístula Intestinal , Humanos , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/terapia , Masculino , Femenino , Adulto , Factores de Riesgo , Fístula Intestinal/etiología , Fístula Intestinal/terapia , Resultado del Tratamiento , Recurrencia , Adulto Joven , Persona de Mediana Edad , Constricción Patológica/etiología , Productos Biológicos/uso terapéutico , Absceso Abdominal/etiología , Absceso Abdominal/terapia , Absceso Abdominal/cirugía , Factores de Tiempo , Celulitis (Flemón)/etiología , Celulitis (Flemón)/terapia , Estudios Retrospectivos , Índice de Masa Corporal , Procedimientos Quirúrgicos del Sistema Digestivo , AdolescenteRESUMEN
Psychrophilic fungus Pseudogymnoascus sp. OUCMDZ-4032 derived from Antarctica was cultivated under 16 °C to produce a new glucolipid compound (1). Its structure was elucidated by analysis of detailed spectroscopic data, acid hydrolysis and 1-phenyl-3-methyl-5-pyrazolone precolumn derivatization, and 13C NMR quantum chemical calculations. Though compound 1 did not show inhibitory activity against bacteria, it can reduce the minimum inhibitory concentration (MIC) of ciprofloxacin against Gram-negative bacteria Pseudomonas aeruginosa, Escherichia coli, and Salmonella paratyphi by 1024, 256 and 256-fold. Compound 1 showed potential as a synergistically inhibiting adjuvant in co-administration with antibiotic to enhance antibacterial activities.
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Antibacterianos , Ciprofloxacina , Bacterias Gramnegativas , Pruebas de Sensibilidad Microbiana , Ciprofloxacina/farmacología , Ciprofloxacina/química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Bacterias Gramnegativas/efectos de los fármacos , Sinergismo Farmacológico , Estructura MolecularRESUMEN
Purpose: In the realm of pain management, traditional Chinese medicine, specifically acupuncture, has garnered increasing attention. This meta-analysis pioneers the evaluation of acupuncture's effectiveness in treating insomnia among hypertensive patients. Methods: We conducted a comprehensive search across several databases-PubMed, Web of Science, Cochrane Library, WANFANG, China National Knowledge Infrastructure (CNKI), Sinomed, and the Chinese Journal of Science and Technology (VIP). Additionally, forward and backward articles of studies published from the inception of these databases until 10 September 2023, were reviewed. This systematic review and meta-analysis included all randomized controlled trials (RCTs) focusing on acupuncture for insomnia in hypertensive patients, without imposing language or date restrictions. We rigorously assessed all outcome measures reported in these trials. The evidence was synthesized by calculating the difference between mean differences (MD) in symptom change. The quality of the evidence was determined using the Cochrane Risk of Bias tool. This study is registered with PROSPERO under number CRD42023461760. Results: Our analysis included 16 RCTs, comprising 1,309 patients. The findings revealed that acupuncture was significantly more effective than the control group in reducing insomnia symptoms, as indicated by a greater decrease in the PSQI score (MD = -3.1, 95% CI [-3.77 to -2.62], p < 0.00001). Additionally, improvements in both systolic and diastolic blood pressure were more pronounced in the acupuncture group compared to the control group (SBP: MD = -10.31, 95% CI [-16.98 to -3.64], p = 0.002; DBP: MD = -5.71, 95% CI [-8.19 to -3.23], p < 0.00001). These results suggest that acupuncture not only improves sleep quality but also lowers blood pressure in patients suffering from hypertension and insomnia. Further research is warranted to elucidate optimal acupuncture points and the duration of treatment for maximized therapeutic effect.Systematic review registration:https://www.crd.york.ac.uk/prospero, CRD42023461760.
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Six new 9H-carbazole derivatives (1-6) and nine previously reported compounds (7-15) were isolated from a fermented solid medium of the Thailand mangrove-derived Streptomyces strain, OUCMDZ-5511, under fluoride stress. Compounds 2-5, 12, and 15 were exclusively present in the fluoride-supplemented fermentation medium, while compounds 7-9, 13, and 14 were newly discovered natural products. The molecular structures of the compounds were identified by a spectroscopic analysis. The new compound 2 displayed antiquorum sensing activity against Chromobacterium violaceum ATCC 12472 by reducing the violacein production and inhibiting the biofilm formation in a concentration-dependent manner. The study revealed that compound 2 could be a novel potential inhibitor of quorum sensing.
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Fluoruros , Streptomyces , Fluoruros/farmacología , Antibacterianos/farmacología , Percepción de Quorum , Carbazoles/farmacología , BiopelículasRESUMEN
JOURNAL/nrgr/04.03/01300535-202410000-00031/figure1/v/2024-02-06T055622Z/r/image-tiff Glutamate excitotoxicity has been shown to play an important role in glaucoma, and glutamate can induce ferroptosis. The p38 mitogen-activated protein kinase (MAPK) pathway inhibitor SB202190 has a potential ability to suppress ferroptosis, and its downstream targets, such as p53, have been shown to be associated with ferroptosis. However, whether ferroptosis also occurs in retinal ganglion cells in response to glutamate excitotoxicity and whether inhibition of ferroptosis reduces the loss of retinal ganglion cells induced by glutamate excitotoxicity remain unclear. This study investigated ferroptosis in a glutamate-induced glaucoma rat model and explored the effects and molecular mechanisms of SB202190 on retinal ganglion cells. A glutamate-induced excitotoxicity model in R28 cells and an N-methyl-D-aspartate-induced glaucoma model in rats were used. In vitro experiments showed that glutamate induced the accumulation of iron and lipid peroxide and morphological changes of mitochondria in R28 cells, and SB202190 inhibited these changes. Glutamate induced the levels of p-p38 MAPK/p38 MAPK and SAT1 and decreased the expression levels of ferritin light chain, SLC7A11, and GPX4. SB202190 inhibited the expression of iron death-related proteins induced by glutamate. In vivo experiments showed that SB202190 attenuated N-methyl-D-aspartate-induced damage to rat retinal ganglion cells and improved visual function. These results suggest that SB202190 can inhibit ferroptosis and protect retinal ganglion cells by regulating ferritin light chain, SAT1, and SLC7A11/Gpx4 pathways and may represent a potential retina protectant.
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Neurodegenerative diseases refer to a battery of medical conditions that affect the survival and function of neurons in the brain, which are mainly presented with progressive loss of cognitive and/or motor function. Acupuncture showed benign effects in improving neurological deficits, especially on movement and cognitive function impairment. Here, we reviewed the therapeutic mechanisms of acupuncture at the neural circuit level in movement and cognition disorders, summarizing the influence of acupuncture in the dopaminergic system, glutamatergic system, γ-amino butyric acid-ergic (GABAergic) system, serotonergic system, cholinergic system, and glial cells at the circuit and synaptic levels. These findings can provide targets for clinical treatment and perspectives for further studies.
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Penicillium citrinum GZWMJZ-836 is an endophytic fungus from Drynaria roosii Nakaike. Five previously undescribed citrinin derivatives (1-5) and six intermediates related to their biosynthesis (6-11) were obtained from the extract of this strain's solid fermentation using multiple column chromatography separations, including high-performance liquid chromatography. The structures of these compounds were determined through comprehensive spectroscopic analyses, primarily using NMR and HRESIMS data. The stereochemistry was mainly confirmed by ECD calculations, and the configurations of C-7' in compounds 4 and 5 were determined using 13C NMR calculations. Compounds 4-5 and 8 showed antibacterial activity against five strains, with minimum inhibitory concentration values ranging from 7.8 to 125 µM. Compounds 4 and 7 exhibited inhibitions against three plant pathogenic fungi, with IC50 values ranging from 66.6 to 152.1 µM. Additionally, a putative biosynthetic pathway for compounds 1-5 derived from citrinin was proposed.
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Citrinina , Penicillium , Citrinina/farmacología , Citrinina/química , Estructura Molecular , Penicillium/química , Hongos , Espectroscopía de Resonancia MagnéticaRESUMEN
BACKGROUND: Prophylactic intraoperative drains have been shown not superior for patients underwent intestinal surgery. However, for patients with Crohn's disease (CD), this needs further exploration. METHODS: In this pilot study, CD patients were randomly assigned to drain (n = 50) and no-drain (n = 50) groups. The primary endpoint was the rate of postoperative prolonged ileus (PPOI). The secondary endpoints were postoperative abdominal ascites, postoperative systemic inflammatory response syndrome (SIRS) and C-reactive protein (CRP) levels. RESULTS: The incidences of PPOI and postoperative abdominal ascites were significantly lower in the drain group (12% vs 44%; 0% vs 24%, both P < .05). Postoperative SIRS incidence and CRP levels were significantly increased in the no-drain group [36% vs 10%; 54.9 vs 34.3 mg/L, both P < .05]. In multivariate analysis, prophylactic drainage was the independent protective factor for PPOI and postoperative LOS. CONCLUSIONS: Prophylactic drainage may be associated with improved clinical outcomes in CD patients.
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Ascitis , Enfermedad de Crohn , Humanos , Ascitis/complicaciones , Enfermedad de Crohn/cirugía , Enfermedad de Crohn/complicaciones , Proyectos Piloto , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Drenaje , Síndrome de Respuesta Inflamatoria Sistémica/complicacionesRESUMEN
Glaucoma is a prevalent cause of blindness globally, characterized by the progressive degeneration of retinal ganglion cells (RGCs). Among various factors, glutamate excitotoxicity stands out as a significant contributor of RGCs loss in glaucoma. Our study focused on Ripa-56 and its protective effect against NMDA-induced retinal damage in mice, aiming to delve into the potential underlying mechanism. The R28 cells were categorized into four groups: glutamate (Glu), Glu + Ripa-56, Ripa-56 and Control group. After 24 h of treatment, cell death was assessed by PI / Hoechst staining. Mitochondrial membrane potential changes, apoptosis and reactive oxygen species (ROS) production were analyzed using flow cytometry. The alterations in the expression of RIP-1, p-MLKL, Bcl-2, BAX, Caspase-3, Gpx4 and SLC7A11 were examined using western blot analysis. C57BL/6j mice were randomly divided into NMDA, NMDA + Ripa-56, Ripa-56 and control groups. Histological changes in the retina were evaluated using hematoxylin and eosin (H&E) staining. RGCs survival and the protein expression changes of RIP-1, Caspase-3, Bcl-2, Gpx4 and SLC7A11 were observed using immunofluorescence. Ripa-56 exhibited a significant reduction in the levels of RIP-1, p-MLKL, Caspase-3, and BAX induced by glutamate, while promoting the expression of Bcl-2, Gpx-4, and SLC7A1 in the Ripa-56-treated group. In our study, using an NMDA-induced normal tension glaucoma mice model, we employed immunofluorescence and H&E staining to observe that Ripa-56 treatment effectively ameliorated retinal ganglion cell loss, mitigating the decrease in retinal ganglion cell layer and bipolar cell layer thickness caused by NMDA. In this study, we have observed that Ripa-56 possesses remarkable anti- necroptotic, anti-apoptotic and anti-ferroptosis properties. It demonstrates the ability to combat not only glutamate-induced excitotoxicity in R28 cells, but also NMDA-induced retinal excitotoxicity in mice. Therefore, Ripa-56 could be used as a potential retinal protective agent.
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Glaucoma , Células Ganglionares de la Retina , Animales , Ratones , Células Ganglionares de la Retina/patología , Caspasa 3/metabolismo , N-Metilaspartato/metabolismo , Ácido Glutámico/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Ratones Endogámicos C57BL , Retina/patología , Apoptosis , Glaucoma/patologíaRESUMEN
BACKGROUNDS: The decision to perform a stoma during surgical resection of penetrating Crohn's disease (CD) is a critical consideration. The objective of this study was to identify factors that influence stoma creation and develop a predictive nomogram model to assist surgeons in making optimal surgical decisions. METHODS: A retrospective study was conducted at a tertiary center from December 1, 2012, to December 1, 2021, involving consecutive patients with penetrating CD who underwent elective surgical resection. The LASSO regression method was used to select preoperative predictors, and a nomogram was constructed using multivariate logistic regression. The performance of the nomogram was validated in an internal cohort by assessing its discrimination, calibration, and clinical usefulness. RESULTS: The study included 405 cases in the training group and 135 cases in the validation group. Nine risk factors for stoma formation were identified, including disease location, fistula resulted from previous anastomosis, absence of preoperative exclusive enteral nutrition support, albumin levels below 35 g/L, C-reactive protein levels above 10 mg/L, hemoglobin levels below 100 g/L, perianal disease, internal fistula, and surgical approach. These risk factors were selected using the LASSO regression method, and a nomogram was developed based on them. The area under the curve and the coefficient of determination (R2) of the nomogram were 0.821 and 0.394, respectively. And the nomogram demonstrated good performance in the validation cohort. CONCLUSIONS: The nomogram exhibited good predictive ability for stoma formation during elective surgical resection for penetrating CD, which can assist surgeons in making informed clinical decisions.
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Enfermedad de Crohn , Procedimientos Quirúrgicos Electivos , Nomogramas , Estomas Quirúrgicos , Humanos , Enfermedad de Crohn/cirugía , Masculino , Estudios Retrospectivos , Femenino , Adulto , Procedimientos Quirúrgicos Electivos/métodos , Factores de Riesgo , Persona de Mediana EdadRESUMEN
Twelve new polyenic macrolactams, cyclamenols G-R (1 and 3-13), together with the known analogue cyclamenol A (2), were isolated from Streptomyces sp. OUCMDZ-4348. Their structures were elucidated by spectroscopic analysis, quantum chemical calculations, chemical derivatizations, and Mosher's methods. The sequenced genome of OUCMDZ-4348 revealed the putative biosynthetic gene cluster of cyclamenols. It was proposed that the polycyclic natural products, cyclamenols H-R, might be formed from cyclamenols A and G through nonenzymatic intramolecular cycloadditions and oxidative cyclizations.
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Streptomyces , Lactamas Macrocíclicas/química , Streptomyces/genética , Streptomyces/química , Regiones Antárticas , Estructura MolecularRESUMEN
BACKGROUND: Azathioprine [AZA] effectively prevents postoperative endoscopic recurrence [ER] in Crohn's disease [CD]. However, the efficacy of AZA emerges after 3 months. Exclusive enteral nutrition [EEN] can maintain remission in CD. The present trial investigates whether AZA plus postoperative 3-month EEN is superior to AZA alone in preventing ER of CD. METHODS: In total, 84 high-risk CD patients undergoing intestinal resection received AZA alone or AZA plus 3 months of EEN [AZAâ +â EEN] postoperatively. The primary endpoint was the rate of ER at 12 months. Secondary endpoints included the rate of ER at 3 months, clinical recurrence [CR], CD activity index [CDAI] scores, faecal calprotectin [FC], and C-reactive protein [CRP]. Quality of life was assessed using Short Form-36 [SF-36] and the Inflammatory Bowel Disease Questionnaire [IBDQ]. RESULTS: Patients in the AZAâ +â EEN group exhibited significantly lower rates of ER compared to the AZA group at both 12 months (33.3% [13/39] vs 63.2% [24/38], Pâ =â 0.009) and 3 months (8.6% [3/35] vs 28.1% [9/32], Pâ =â 0.037) post-surgery. The rates of CR between the two groups at 3 and 12 months were similar. CDAI scores, FC, albumin level, and CRP were all comparable between the two groups. Quality of life was significantly higher in the AZA group than in the AZAâ +â EEN group at 3 months but became comparable from 5 to 12 months postoperatively. CONCLUSION: In high-risk CD patients, combining AZA with postoperative 3-month EEN reduces 1-year ER but may temporarily impact quality of life. Further large-scale, long-term studies are warranted. TRIAL NUMBER: NCT05214430.
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Azatioprina , Enfermedad de Crohn , Nutrición Enteral , Inmunosupresores , Calidad de Vida , Prevención Secundaria , Humanos , Enfermedad de Crohn/terapia , Enfermedad de Crohn/cirugía , Enfermedad de Crohn/prevención & control , Azatioprina/uso terapéutico , Masculino , Femenino , Adulto , Nutrición Enteral/métodos , Prevención Secundaria/métodos , Inmunosupresores/uso terapéutico , Persona de Mediana Edad , Proteína C-Reactiva/análisis , Recurrencia , Complejo de Antígeno L1 de Leucocito/análisis , Terapia Combinada , Adulto JovenRESUMEN
Ileostomy creation is a common procedure to mitigate postoperative complications in Crohn's disease (CD) patients. However, the optimal timing for ileostomy closure remains controversial. This study aims to investigate whether delayed ileostomy closure (> 6 months post formation) affects postoperative complications compared to early closure (≤ 6 months post formation). Consecutive CD patients who underwent ileostomy reversal at a tertiary care center between January 1, 2013, and December 1, 2021, were included. The study compared patients who underwent early ileostomy closure to matched patients undergoing delayed ileostomy closure. The 90-day postoperative complications were compared between the two groups. The study included 352 eligible patients for ileostomy reversion. Our data showed that patients undergoing delayed ileostomy closure had higher incidence of ileostomy-related infectious complications (12% vs. 4%, p = 0.008), a longer postoperative hospital stay (10 days with an IQR of 7-12 days versus 8 days with an IQR of 7-11 days, p = 0.024), and increased rate of ileus (28% versus 15%, p = 0.003). There were 256 patients included after 1:1 propensity score matching. The results revealed no significant differences in postoperative hospital stay, infectious or non-infectious complications except for a statistically significant increase in the incidence of ileus in the delayed closure group (p = 0.01). Patients undergoing delayed ileostomy closure has similar outcomes to early closure in terms of postoperative complications, except for a higher incidence of ileus.
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An efficient and convenient method for the synthesis of oxalamides by the reaction of ß-ketoamides with tertiary amines and TBHP was developed. A variety of ß-ketoamides and tertiary amines substrates were well-tolerated in this transformation. Based on the control experiments, a plausible mechanism for this reaction was proposed that involved the tandem oxidation/amination process. In addition, α,ß-epoxy amides could be obtained by adjusting the reaction conditions.