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1.
Plant Cell ; 36(5): 2000-2020, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38299379

RESUMO

The flower-infecting fungus Ustilaginoidea virens causes rice false smut, which is a severe emerging disease threatening rice (Oryza sativa) production worldwide. False smut not only reduces yield, but more importantly produces toxins on grains, posing a great threat to food safety. U. virens invades spikelets via the gap between the 2 bracts (lemma and palea) enclosing the floret and specifically infects the stamen and pistil. Molecular mechanisms for the U. virens-rice interaction are largely unknown. Here, we demonstrate that rice flowers predominantly employ chitin-triggered immunity against U. virens in the lemma and palea, rather than in the stamen and pistil. We identify a crucial U. virens virulence factor, named UvGH18.1, which carries glycoside hydrolase activity. Mechanistically, UvGH18.1 functions by binding to and hydrolyzing immune elicitor chitin and interacting with the chitin receptor CHITIN ELICITOR BINDING PROTEIN (OsCEBiP) and co-receptor CHITIN ELICITOR RECEPTOR KINASE1 (OsCERK1) to impair their chitin-induced dimerization, suppressing host immunity exerted at the lemma and palea for gaining access to the stamen and pistil. Conversely, pretreatment on spikelets with chitin induces a defense response in the lemma and palea, promoting resistance against U. virens. Collectively, our data uncover a mechanism for a U. virens virulence factor and the critical location of the host-pathogen interaction in flowers and provide a potential strategy to control rice false smut disease.


Assuntos
Quitina , Flores , Hypocreales , Oryza , Doenças das Plantas , Oryza/microbiologia , Oryza/metabolismo , Oryza/genética , Doenças das Plantas/microbiologia , Quitina/metabolismo , Flores/microbiologia , Hypocreales/patogenicidade , Hypocreales/genética , Hypocreales/metabolismo , Transdução de Sinais , Interações Hospedeiro-Patógeno , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Virulência , Fatores de Virulência/metabolismo , Fatores de Virulência/genética , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética
2.
Genomics ; 116(5): 110889, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38901654

RESUMO

Cholangiocarcinoma (CCA) is widely noted for its high degree of malignancy, rapid progression, and limited therapeutic options. This study was carried out on transcriptome data of 417 CCA samples from different anatomical locations. The effects of lipid metabolism related genes and immune related genes as CCA classifiers were compared. Key genes were derived from MVI subtypes and better molecular subtypes. Pathways such as epithelial mesenchymal transition (EMT) and cell cycle were significantly activated in MVI-positive group. CCA patients were classified into three (four) subtypes based on lipid metabolism (immune) related genes, with better prognosis observed in lipid metabolism-C1, immune-C2, and immune-C4. IPTW analysis found that the prognosis of lipid metabolism-C1 was significantly better than that of lipid metabolism-C2 + C3 before and after correction. KRT16 was finally selected as the key gene. And knockdown of KRT16 inhibited proliferation, migration and invasion of CCA cells.

3.
Dis Colon Rectum ; 67(7): 929-939, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38517090

RESUMO

BACKGROUND: A complete total mesorectal excision is the criterion standard in curative rectal cancer surgery. Ensuring quality is challenging in a narrow pelvis, and obesity amplifies technical difficulties. Pelvimetry is the measurement of pelvic dimensions, but its role in gauging preoperatively the difficulty of proctectomy is largely unexplored. OBJECTIVE: To determine pelvic structural factors associated with incomplete total mesorectal excision after curative proctectomy and build a predictive model for total mesorectal excision quality. DESIGN: Retrospective cohort study. SETTING: A quaternary referral center database of patients diagnosed with rectal adenocarcinoma (2009-2017). PATIENTS: Curative-intent proctectomy for rectal adenocarcinoma. INTERVENTIONS: All radiological measurements were obtained from preoperative CT images using validated imaging processing software tools. Completeness of total mesorectal excision was obtained from histology reports. MAIN OUTCOME MEASURES: Ability of radiological pelvimetry and obesity measurements to predict total mesorectal excision quality. RESULTS: Of the 410 cases meeting inclusion criteria, 362 underwent a complete total mesorectal excision (88%). Multivariable regression identified a deeper sacral curve (per 100 mm 2 [OR: 1.14; 95% CI, 1.06-1.23; p < 0.001]) and a greater transverse distance of the pelvic outlet (per 10 mm [OR:1.41, 95% CI, 1.08-1.84; p = 0.012]) to be independently associated with incomplete total mesorectal excision. An increased area of the pelvic inlet (per 10 cm 2 [OR: 0.85; 95% CI, 0.75-0.97; p = 0.02) was associated with a higher rate of complete mesorectal excision. No difference in visceral obesity ratio and visceral obesity (ratio >0.4 vs <0.4) between BMI (<30 vs ≥30) and sex was identified. A model was built to predict mesorectal quality using the following variables: depth of sacral curve, area of pelvic inlet, and transverse distance of the pelvic outlet. LIMITATIONS: Retrospective analysis is not controlled for the choice of surgical approach. CONCLUSIONS: Pelvimetry predicts total mesorectal excision quality in rectal cancer surgery and can alert surgeons preoperatively to cases of unusual difficulty. This predictive model may contribute to treatment strategy and aid in the comparison of outcomes between traditional and novel techniques of total mesorectal excision. See Video Abstract . USO DE MEDICIONES DE PELVIMETRA Y OBESIDAD VISCERAL BASADAS EN TC PARA PREDECIR LA CALIDAD DE TME EN PACIENTES SOMETIDOS A CIRUGA DE CNCER DE RECTO: ANTECEDENTES:Una escisión mesorrectal total y completa es el estándar de oro en la cirugía curativa del cáncer de recto. Garantizar la calidad es un desafío en una pelvis estrecha y la obesidad amplifica las dificultades técnicas. La pelvimetría es la medición de las dimensiones pélvicas, pero su papel para medir la dificultad preoperatoria de la proctectomía está en gran medida inexplorado.OBJETIVO:Determinar los factores estructurales pélvicos asociados con la escisión mesorrectal total incompleta después de una proctectomía curativa y construir un modelo predictivo para la calidad de la escisión mesorrectal total.DISEÑO:Estudio de cohorte retrospectivo.ÁMBITO:Base de datos de un centro de referencia cuaternario de pacientes diagnosticados con adenocarcinoma de recto (2009-2017).PACIENTES:Proctectomía con intención curativa para adenocarcinoma de recto.INTERVENCIONES:Todas las mediciones radiológicas se obtuvieron a partir de imágenes de TC preoperatorias utilizando herramientas de software de procesamiento de imágenes validadas. La integridad de la escisión mesorrectal total se obtuvo a partir de informes histológicos.PRINCIPALES MEDIDAS DE VALORACIÓN:Capacidad de la pelvimetría radiológica y las mediciones de obesidad para predecir la calidad total de la escisión mesorrectal.RESULTADOS:De los 410 casos que cumplieron los criterios de inclusión, 362 tuvieron una escisión mesorrectal total completa (88%). Una regresión multivariable identificó una curva sacra más profunda (por 100 mm2); OR:1,14,[IC95%:1,06-1,23,p<0,001], y mayor distancia transversal de salida pélvica (por 10mm); OR:1,41, [IC 95%:1,08-1,84,p=0,012] como asociación independiente con escisión mesorrectal total incompleta. Un área aumentada de entrada pélvica (por 10 cm2); OR:0,85, [IC95%:0,75-0,97,p=0,02] se asoció con una mayor tasa de escisión mesorrectal completa. No se identificaron diferencias en la proporción de obesidad visceral y la obesidad visceral (proporción>0,4 vs.<0,4) entre el índice de masa corporal (<30 vs.>=30) o el sexo. Se construyó un modelo para predecir la calidad mesorrectal utilizando variables: profundidad de la curva sacra, área de la entrada pélvica y distancia transversal de la salida pélvica.LIMITACIONES:Análisis retrospectivo no controlado por la elección del abordaje quirúrgico.CONCLUSIONES:La pelvimetría predice la calidad de la escisión mesorrectal total en la cirugía del cáncer de recto y puede alertar a los cirujanos preoperatoriamente sobre casos de dificultad inusual. Este modelo predictivo puede contribuir a la estrategia de tratamiento y ayudar en la comparación de resultados entre técnicas tradicionales y novedosas de escisión mesorrectal total. (Traducción- Dr. Ingrid Melo).


Assuntos
Adenocarcinoma , Obesidade Abdominal , Pelvimetria , Protectomia , Neoplasias Retais , Tomografia Computadorizada por Raios X , Humanos , Neoplasias Retais/cirurgia , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Masculino , Feminino , Estudos Retrospectivos , Protectomia/métodos , Pessoa de Meia-Idade , Idoso , Pelvimetria/métodos , Adenocarcinoma/cirurgia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Tomografia Computadorizada por Raios X/métodos , Obesidade Abdominal/diagnóstico por imagem , Pelve/diagnóstico por imagem , Reto/cirurgia , Reto/diagnóstico por imagem
4.
Arch Virol ; 169(3): 42, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38332318

RESUMO

Beauveria bassiana Vuillemin is an entomopathogenic fungus that has been developed as a biological insecticide. B. bassiana can be infected by single or multiple mycoviruses, most of which are double-stranded RNA (dsRNA) viruses, while infections with single-stranded RNA (ssRNA) viruses, especially negative single-stranded RNA (-ssRNA) viruses, have been observed less frequently. In the present study, we sequenced and analyzed the complete genomes of two new different mycoviruses coinfecting a single B. bassiana strain: a -ssRNA virus which we have named "Beauveria bassiana negative-strand RNA virus 1" (BbNSRV1), and a dsRNA virus, which we have named "Beauveria bassiana orthocurvulavirus 1" (BbOCuV1). The genome of BbNSRV1 consists of a single segment of negative-sense, single-stranded RNA with a length of 6169 nt, containing a single open reading frame (ORF) encoding a putative RNA-dependent RNA polymerase (RdRp) with 1949 aa (220.1 kDa). BLASTx analysis showed that the RdRp had the highest sequence similarity (59.79%) to that of Plasmopara viticola lesion associated mononegaambi virus 2, a member of the family Mymonaviridae. This is the first report of a -ssRNA mycovirus infecting B. bassiana. The genome of BbOCuV1 consists of two dsRNA segments, 2164 bp and 1765 bp in length, respectively, with dsRNA1 encoding a protein with conserved RdRp motifs and 70.75% sequence identity to the putative RdRp of the taxonomically unassigned mycovirus Fusarium graminearum virus 5 (FgV5), and the dsRNA2 encoding a putative coat protein with sequence identity 64.26% to the corresponding protein of the FgV5. Phylogenetic analysis indicated that BbOCuV1 belongs to a taxonomically unassigned group of dsRNA mycoviruses related to members of the families Curvulaviridae and Partitiviridae. Hence, it might be the member of a new family that remains to be named and formally recognized.


Assuntos
Beauveria , Micovírus , Vírus de RNA , Vírus , Humanos , Beauveria/genética , RNA de Cadeia Dupla/genética , Filogenia , Genoma Viral , Vírus de RNA/genética , Vírus/genética , Vírus de RNA de Cadeia Dupla/genética , Micovírus/genética , RNA Polimerase Dependente de RNA/genética , RNA Viral/genética , Fases de Leitura Aberta
5.
Colorectal Dis ; 26(5): 886-898, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38594838

RESUMO

AIM: Restorative proctocolectomy with transabdominal ileal pouch-anal anastomosis (abd-IPAA) has become the standard surgical treatment for medically refractory ulcerative colitis (UC). However, it requires a technically difficult distal anorectal dissection and anastomosis due to the bony confines of the deep pelvis. To address these challenges, the transanal IPAA approach (ta-IPAA) was developed. This novel approach may offer increased visibility and range of motion compared with abd-IPAA, although its postoperative benefits remain unclear. The aim of this work was to perform a systematic review and meta-analysis to compare and inform the frequency of postoperative outcomes between ta-IPAA and abd-IPAA for patients with UC. METHOD: Several databases were searched from inception until May 2022 for studies reporting postoperative outcomes of patients undergoing ta-IPAA. Reviewers, working independently and in duplicate, evaluated studies for inclusion and graded the risk of bias. Odds ratios (OR), mean differences (MD) and prevalence ratio (PR) and their corresponding 95% confidence intervals (CIs) were calculated using random-effects models. Sensitivity analysis was performed. RESULTS: Ten retrospective studies comprising 284 patients with ta-IPAA were included. Total mesorectal excision was performed in 61.8% of cases and close rectal dissection in 27.9%. There was no difference in the odds of Clavien-Dindo (CD) I-II complications, CD III-IV and anastomotic leak (OR 0.96, 95% CI 0.27-3.40; OR 1.18, 95% CI 0.65-2.16; OR 1.37, 95% CI 0.58-3.23; respectively) between ta-IPAA and abd-IPAA. The ta-IPAA pooled CD I-II complication rate was 18% (95% CI 5%-35%) and for CD III-IV 10% (95% CI 5%-17%), and the anastomotic leak rate was 6% (95% CI 2%-10%). There were no deaths reported. CONCLUSIONS: This meta-analysis compared the novel ta-IPAA procedure with abd-IPAA and found no difference in postoperative outcomes. While the need for randomized controlled trails and comparison of functional outcomes between both approaches remains, this evidence should assist colorectal surgeons to decide if ta-IPAA is a viable alternative.


Assuntos
Colite Ulcerativa , Complicações Pós-Operatórias , Proctocolectomia Restauradora , Humanos , Proctocolectomia Restauradora/métodos , Proctocolectomia Restauradora/efeitos adversos , Colite Ulcerativa/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Bolsas Cólicas/efeitos adversos , Canal Anal/cirurgia , Feminino , Masculino , Adulto , Estudos Retrospectivos , Pessoa de Meia-Idade , Anastomose Cirúrgica/métodos , Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/etiologia , Fístula Anastomótica/epidemiologia , Cirurgia Endoscópica Transanal/métodos , Cirurgia Endoscópica Transanal/efeitos adversos , Doenças Inflamatórias Intestinais/cirurgia
6.
Int J Mol Sci ; 25(5)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38473754

RESUMO

Muscle formation directly determines meat production and quality. The non-SMC condensin I complex subunit G (NCAPG) is strongly linked to the growth features of domestic animals because it is essential in controlling muscle growth and development. This study aims to elucidate the tissue expression level of the bovine NCAPG gene, and determine the key transcription factors for regulating the bovine NCAPG gene. In this study, we observed that the bovine NCAPG gene exhibited high expression levels in longissimus dorsi and spleen tissues. Subsequently, we cloned and characterized the promoter region of the bovine NCAPG gene, consisting of a 2039 bp sequence, through constructing the deletion fragment double-luciferase reporter vector and site-directed mutation-identifying core promoter region with its key transcription factor binding site. In addition, the key transcription factors of the core promoter sequence of the bovine NCAPG gene were analyzed and predicted using online software. Furthermore, by integrating overexpression experiments and the electrophoretic mobility shift assay (EMSA), we have shown that cAMP response element binding protein 1 (CREB1) and myogenic differentiation 1 (MYOD1) bind to the core promoter region (-598/+87), activating transcription activity in the bovine NCAPG gene. In conclusion, these findings shed important light on the regulatory network mechanism that underlies the expression of the NCAPG gene throughout the development of the muscles in beef cattle.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Regulação da Expressão Gênica , Bovinos , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Regiões Promotoras Genéticas , Mioblastos
7.
Int J Mol Sci ; 25(11)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38892214

RESUMO

Jeryak is the F1 generation of the cross between Gannan yak and Jersey cattle, which has the advantages of fast growth and high adaptability. The growth and development of skeletal muscle is closely linked to meat production and the quality of meat. However, the molecular regulatory mechanisms of muscle growth differences between Gannan yak and Jeryak analyzed from the perspective of chromatin opening have not been reported. In this study, ATAC-seq was used to analyze the difference of chromatin openness in longissimus muscle of Gannan yak and Jeryak. It was found that chromatin accessibility was more enriched in Jeryak compared to Gannan yak, especially in the range of the transcription start site (TSS) ± 2 kb. GO and KEGG enrichment analysis indicate that differential peak-associated genes are involved in the negative regulation of muscle adaptation and the Hippo signaling pathway. Integration analysis of ATAC-seq and RNA-seq revealed overlapping genes were significantly enriched during skeletal muscle cell differentiation and muscle organ morphogenesis. At the same time, we screened FOXO1, ZBED6, CRY2 and CFL2 for possible involvement in skeletal muscle development, constructed a genes and transcription factors network map, and found that some transcription factors (TFs), including YY1, KLF4, KLF5 and Bach1, were involved in skeletal muscle development. Overall, we have gained a comprehensive understanding of the key factors that impact skeletal muscle development in various breeds of cattle, providing new insights for future analysis of the molecular regulatory mechanisms involved in muscle growth and development.


Assuntos
Músculo Esquelético , RNA-Seq , Animais , Bovinos/genética , Músculo Esquelético/metabolismo , Músculo Esquelético/crescimento & desenvolvimento , Sequenciamento de Cromatina por Imunoprecipitação , Desenvolvimento Muscular/genética , Cromatina/genética , Cromatina/metabolismo , Carne/análise , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
8.
Pak J Pharm Sci ; 37(2(Special)): 435-442, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38822547

RESUMO

Depression is a common non-motor symptom of Parkinson's disease. Previous studies demonstrated that hydroxysafflor yellow A had properties of improving motor symptoms of Parkinson's disease. The effect of hydroxysafflor yellow A on depression in Parkinson's disease mice is investigated in this study. To induce Parkinson's disease model, male Swiss mice were exposed to rotenone (30 mg/kg) for 6 weeks. The chronic unpredictable mild stress was employed to induce depression from week 3 to week 6. Sucrose preference, tail suspension, and forced swimming tests were conducted. Golgi and Nissl staining of hippocampus were carried out. The levels of dopamine, 5-hydroxytryptamine and the expression of postsynaptic density protein 95, brain-derived neurotrophic factor in hippocampus were assayed. It showed that HSYA improved the depression-like behaviors of Parkinson's disease mice. Hydroxysafflor yellow A attenuated the injury of nerve and elevated contents of dopamine, 5-hydroxytryptamine in hippocampus. Treatment with hydroxysafflor yellow A also augmented the expression of postsynaptic density protein 95 and brain-derived neurotrophic factor. These findings suggest that hydroxysafflor yellow A ameliorates depression-like behavior in Parkinson's disease mice through regulating the contents of postsynaptic density protein 95 and brain-derived neurotrophic factor, therefore protecting neurons and neuronal dendrites of the hippocampus.


Assuntos
Comportamento Animal , Fator Neurotrófico Derivado do Encéfalo , Chalcona , Depressão , Hipocampo , Quinonas , Serotonina , Animais , Quinonas/farmacologia , Quinonas/uso terapêutico , Chalcona/análogos & derivados , Chalcona/farmacologia , Chalcona/uso terapêutico , Masculino , Camundongos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/tratamento farmacológico , Depressão/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Comportamento Animal/efeitos dos fármacos , Serotonina/metabolismo , Dopamina/metabolismo , Rotenona/farmacologia , Modelos Animais de Doenças , Proteína 4 Homóloga a Disks-Large/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Doença de Parkinson/psicologia
9.
Virol J ; 20(1): 237, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37848986

RESUMO

BACKGROUND: Aspirin is widely used to treat various clinical symptoms. Evidence suggests that aspirin has antiviral properties, but little is known about its specific effect against rotavirus. METHODS: MA104, Caco-2, and CV-1 cells were infected with rotavirus, and aspirin was added after 12 h. Viral mRNA and titer levels were measured by qRT-PCR and immunofluorescence assays. For in vivo validation, forty specific-pathogen-free SD rats were randomly divided into oral aspirin (ASP) groups and control (NC) groups. 16 S rRNA gene sequencing was performed to identify gut microbiota. After 6 months of continuous ASP/NC administration, the rats were infected with rotavirus. Fecal samples were collected over a 30-day time course, and viral levels were quantified. Proinflammatory cytokines/chemokine levels were measured by ELISA. RESULTS: Aspirin inhibited rotavirus infection in cell lines and in rats. The effects of aspirin on viral replication were associated with the alteration of gut microbiota composition by aspirin, including increased abundance of Firmicutes and decreased abundance of Bacteroidetes after aspirin treatment. Mechanistically, aspirin reduced IL-2 and IL-10 levels, and increased IRF-1 and COX-2 levels. Aspirin blocked rotavirus replication in vitro and in vivo, which might be related to effects on IRF-1, COX-2, chemokines, and gut microbial composition. CONCLUSION: These results indicate that long-term oral aspirin administration reduces rotavirus infection. Intestinal virus infection may be suppressed in elderly patients who take aspirin for a long time. The change of their Gut microbiota may lead to functional disorder of the intestinal tract, which may provide some reference for clinical adjuvant probiotics treatment.


Assuntos
Microbioma Gastrointestinal , Infecções por Rotavirus , Rotavirus , Humanos , Ratos , Animais , Idoso , Rotavirus/genética , Infecções por Rotavirus/tratamento farmacológico , Células CACO-2 , Ciclo-Oxigenase 2 , Ratos Sprague-Dawley , Aspirina/farmacologia , RNA Ribossômico 16S/genética
10.
Dis Colon Rectum ; 66(12): 1532-1538, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37493224

RESUMO

BACKGROUND: Patients with familial adenomatous polyposis who have undergone restorative proctocolectomy can develop adenomas in the pouch. OBJECTIVE: To review experience with pouch surveillance and create a classification system for polyposis severity. DESIGN: A retrospective review of patients undergoing IPAA and follow-up at 1 institution. SETTING: A center for hereditary colorectal cancer within a quaternary referral center. PATIENTS: All patients undergoing IPAA and followed endoscopically after surgery by the center. INTERVENTIONS: Yearly pouchoscopy and treatment of polyps as required. MAIN OUTCOME MEASURES: Primary outcome measure was incidence and severity of pouch neoplasia and its changes with time. METHODS: A retrospective study of patients who had a restorative proctocolectomy for familial adenomatous polyposis at Cleveland Clinic. Severity of polyposis was classified on the basis of size, number, and histology. RESULTS: One hundred sixty-five patients were analyzed. The median age at IPAA was 31 years and 52% were male. The median follow-up was 10.1 years; the median number of pouchoscopies per patient was 4. The median interval between pouchoscopies was 21.9 months. Overall, the incidence of pouch adenomas was found in 47 patients (28.5%). The median time from pouch to first pouch adenoma diagnosis was 10.3 years. The estimated cumulative incidence rates of pouch adenoma at 5, 10, 15, 20, and 30 years after IPAA were 5.9%, 21.7%, 40%, 54.8%, and 69.9%, respectively. At the first diagnosis of pouch adenoma, 25 patients had stage 1, 10 had stage 2, 8 had stage 3, and 4 had stage 4. Twenty of 47 patients progressed to a higher stage. No patient developed cancer. LIMITATIONS: Genotype was not available for all patients. CONCLUSIONS: There is an increasing incidence of pouch neoplasia after restorative proctocolectomy, reaching a plateau at 25 years. The polyposis is usually mild but sometimes increases in severity. LA INCIDENCIA ACUMULADA Y LA PROGRESIN DE LOS ADENOMAS DE LA BOLSA ILEAL EN PACIENTES CON POLIPOSIS ADENOMATOSA FAMILIAR: ANTECEDENTES:Los pacientes con poliposis adenomatosa familiar que se han sometido a una proctocolectomía restauradora pueden desarrollar adenomas en la bolsa.OBJETIVO:Revisamos nuestra experiencia con la vigilancia de la bolsa y creamos un sistema de clasificación para la gravedad de la poliposis.DISEÑO:Una revisión retrospectiva de pacientes sometidos a anastomosis de bolsa ileoanal y seguimiento en una institución.ESCENARIO:Un centro para el cáncer colorrectal hereditario dentro de un centro de referencia cuaternarioPACIENTES:Todos los pacientes sometidos a anastomosis reservorio ileoanal y seguidos por vía endoscópica tras la cirugía por el centro.INTERVENCIONES:Bolsascopia anual y tratamiento de pólipos según sea necesarioPRINCIPALES MEDIDAS DE RESULTADO:Primaria: Incidencia y gravedad de la neoplasia del reservorio y sus cambios con el tiempo.MÉTODOS:Un estudio retrospectivo de pacientes que se sometieron a una proctocolectomía restauradora por poliposis adenomatosa familiar en la Clínica Cleveland. La gravedad de la poliposis se clasificó según el tamaño, el número y la histología.RESULTADOS:Se analizaron 165 pacientes. La mediana de edad del IPAA fue de 31 años y el 52% eran hombres. La mediana de seguimiento fue de 10,1 años; número medio de reservorioscopias por paciente = 4. El intervalo medio entre reservorioscopias fue de 21,9 meses. Incidencia global de adenomas de reservorio = 47/165 (28,5%). Tiempo mediano desde el reservorio hasta el primer diagnóstico de adenoma en reservorio = 10,3 años. La tasa de incidencia acumulada estimada de adenoma de bolsa a los 5, 10, 15, 20, y 30 años después de la IPAA es del 5,9%, 21,7%, 40%, 54,8%, y 69,9%, respectivamente. En el primer diagnóstico de adenoma de la bolsa, 25 pacientes tenían estadio 1, 10 estadio 2, 8 estadio 3 y 4 estadio 4. 20/47 pacientes progresaron a un estadio superior Ningún paciente desarrolló cáncer.LIMITACIONES:Genotipo no disponible para todos los pacientesCONCLUSIONES:Hay una incidencia creciente de neoplasia de la bolsa después de la proctocolectomía restauradora, alcanzando una meseta a los 25 años. La poliposis suele ser leve, pero a veces aumenta en severidad. (Traducción-Dr. Yesenia Rojas-Khalil ).


Assuntos
Polipose Adenomatosa do Colo , Bolsas Cólicas , Neoplasias Colorretais , Proctocolectomia Restauradora , Feminino , Humanos , Masculino , Polipose Adenomatosa do Colo/epidemiologia , Polipose Adenomatosa do Colo/cirurgia , Neoplasias Colorretais/epidemiologia , Incidência , Proctocolectomia Restauradora/efeitos adversos , Estudos Retrospectivos , Adulto
11.
Dis Colon Rectum ; 66(10): 1359-1372, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36602511

RESUMO

BACKGROUND: Mesenchymal stem cells have been used for the treatment of perianal Crohn's fistulizing disease by direct injection. However, no studies to date have included patients with proctitis, anal canal involvement, and multiple branching tracts. OBJECTIVE: This study aimed to determine safety and efficacy of mesenchymal stem cells for refractory perianal Crohn's disease. DESIGN: Phase IB/IIA randomized controlled trial. SETTINGS: Tertiary IBD referral center. PATIENTS: Adult Crohn's disease patients with perianal fistulizing disease. INTERVENTION: Seventy-five million mesenchymal stem cells were administered with a 22-G needle by direct injection after curettage and primary closure of the fistula tract. A repeat injection of 75 million mesenchymal stem cells at 3 months was given if complete clinical and radiographic healing were not achieved. MAIN OUTCOMES MEASURES: Adverse and serious adverse events occurred at postprocedure day 1, week 2, week 6, month 3, month 6, and month 12. Clinical healing, radiographic healing per MRI, and patient-reported outcomes were collected at the same time points. RESULTS: A total of 23 patients were enrolled and treated; 18 were treatment patients and 5 were control. There were no adverse or serious adverse events reported related to mesenchymal stem cell therapy. At 6 months, 83% of the treatment group and 40% of the control group had complete clinical and radiographic healing. The perianal Crohn's disease activity index, Wexner incontinence score, and VanAssche score had all significantly decreased in treatment patients at 6 months; none significantly decreased in the control group. LIMITATIONS: Single institution and single blinded. CONCLUSIONS: Bone marrow-derived mesenchymal stem cells offer a safe and effective alternative treatment approach for severe perianal fistulizing Crohn's disease. See Video Abstract at http://links.lww.com/DCR/C128 . UN ESTUDIO DE FASE IB/IIA DE CLULAS MADRE MESENQUIMALES DERIVADAS DE MDULA SEA ALOGNICA EXPANDIDA EX VIVO PARA EL TRATAMIENTO DE LA ENFERMEDAD DE CROHN FISTULIZANTE PERIANAL: ANTECEDENTES:Las células madre mesenquimales se han utilizado para el tratamiento de la enfermedad fistulizante de Crohn perianal mediante inyección dirigida. Sin embargo, ningún estudio hasta la fecha ha incluido pacientes con proctitis, afectación del canal anal y vías de ramificación múltiples.OBJETIVO:Determinar la seguridad y eficacia de las células madre mesenquimales para la enfermedad de Crohn perianal refractaria.DISEÑO:Ensayo de control aleatorizado de fase IB/IIA.AJUSTES:Centro de referencia de enfermedad inflamatoria intestinal terciaria.PACIENTES:Pacientes adultos con enfermedad de Crohn con enfermedad fistulizante perianal.INTERVENCIÓN:Se administraron 75 millones de células madre mesenquimales con una aguja 22G mediante inyección directa después del legrado y cierre primario del trayecto de la fístula. Se administró una inyección repetida de 75 millones de células madre mesenquimales a los 3 meses si no se lograba una curación clínica y radiográfica completa.PRINCIPALES MEDIDAS DE RESULTADOS:eventos adversos y adversos graves en el día 1, la semana 2, la semana 6, el mes 3, el mes 6 y el mes 12 después del procedimiento. Curación clínica, curación radiográfica por imagen de resonancia magnética y resultados informados por el paciente en los mismos puntos de tiempo.RESULTADOS:Un total de 23 pacientes fueron reclutados y tratados; 18 fueron de tratamiento y 5 de control. No se informaron eventos adversos o adversos graves relacionados con la terapia con células madre mesenquimales. A los seis meses, el 83 % del grupo de tratamiento y el 40 % del control tenían una curación clínica y radiográfica completa. El índice de actividad de la enfermedad de Crohn perianal, la puntuación de incontinencia de Wexner y la puntuación de VanAssche habían disminuido significativamente en los pacientes de tratamiento a los seis meses; ninguno disminuyó significativamente en el grupo de control.LIMITACIONES:Institución única y simple ciego.CONCLUSIONES:Las células madre mesenquimales derivadas de la médula ósea ofrecen un d tratamiento alternativo seguro y eficaz para la enfermedad de Crohn fistulizante perianal grave. Consulte Video Resumen en http://links.lww.com/DCR/C128 . (Traducción-Dr Yolanda Colorado ).


Assuntos
Doença de Crohn , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Fístula Retal , Adulto , Humanos , Medula Óssea , Doença de Crohn/complicações , Doença de Crohn/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Fístula Retal/etiologia , Fístula Retal/terapia , Resultado do Tratamento
12.
Dis Colon Rectum ; 66(10): 1373-1382, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36649183

RESUMO

BACKGROUND: Redo ileocolic resection for recurrent Crohn's disease is associated with increased technical complexity and higher complication rates compared to primary resection. Literature concerning redo surgery for recurrent Crohn's disease is scarce and it is controversial whether a redo is a risk factor for postoperative anastomotic leak. OBJECTIVE: This study aimed to hypothesized that redo ileocolic resection for Crohn's disease is an independent risk factor for anastomotic leak. DESIGN: Retrospective, case-control study from 1994 to 2019 with multivariate analysis and propensity score weighting. SETTING: Quaternary, IBD-referral center. PATIENTS: Adult patients aged >18 years were included in the study. INTERVENTIONS: Primary or redo ileocolic resection with an anastomosis, with or without diverting ileostomy. MAIN OUTCOME MEASURES: Thirty-day anastomotic leak rate. RESULTS: A total of 991 patients (56% primary and 44% redo ileocolic resections) were included. Patients who underwent redo resection were significantly older with more comorbidities, fewer medications, and less fistulizing disease compared to the primary group. On univariate analysis, patients who underwent redo resection had more overall complications (50.5% vs 36.2%, p < 0.001), and the cumulative number of prior ileocolic resections was significantly associated with increased risk for overall morbidity ( p < 0.001). There were 31 (3%) anastomotic leaks; leak rates did not differ between groups ( p = 0.60). Multivariable analysis indicated that extensive adhesiolysis ( p < 0.001), ileostomy omission ( p = 0.009), and intraoperative abscess/fistula ( p = 0.02) were independently associated with leaks but not redo resection ( p = 0.27). Patients with 0, 1, 2, or 3 of these risk factors had observed leak rates of 1.1%, 1.3%, 6.0%, and 11.6.% ( p = 0.03), respectively. LIMITATIONS: The limitations of this study were selection bias, referral bias, and single quaternary center. CONCLUSIONS: Compared to primary procedures, redo ileocolic resection for recurrent Crohn's disease is associated with increased overall morbidity but not anastomotic leak. See Video Abstract at http://links.lww.com/DCR/C132 . LA RESECCIN ILEOCLICA REHECHA NO ES UN FACTOR DE RIESGO INDEPENDIENTE DE FUGA ANASTOMTICA EN LA ENFERMEDAD DE CROHN RECURRENTE: ANTECEDENTES:La resección ileocólica para la enfermedad de Crohn recurrente se asocia con una mayor complejidad técnica y mayores tasas de complicaciones en comparación con la resección primaria. La literatura sobre la reintervención quirúrgica para la enfermedad de Crohn recurrente es escasa y es controvertido si una redo es un factor de riesgo para la fuga anastomótica posoperatoria.OBJETIVO:Tenemos la hipótesis de que rehacer la resección ileocólica para la enfermedad de Crohn es un factor de riesgo independiente para la fuga anastomótica.DISEÑO:Estudio retrospectivo de casos y controles de 1994 a 2019 con análisis multivariado y ponderación de puntuación de propensión.AJUSTE:Centro de referencia de enfermedad inflamatoria intestinal de cuarto nivel.PACIENTES:Pacientes adultos >18 años.INTERVENCIONES:Resección ileocólica primaria o rehecha con una anastomosis, con o sin derivación de ileostomía.PRINCIPALES MEDIDAS DE RESULTADO:Tasa de fuga anastomótica a los 30 días.RESULTADOS:Se incluyeron un total de 991 pacientes (56% resecciones primarias y 44% resecciones ileocólicas rehechas). Los pacientes de reintervención eran significativamente mayores con más comorbilidades, menos medicamentos y menos enfermedad fistulizante en comparación con el grupo primario. En el análisis univariado, los pacientes reoperados tuvieron más complicaciones generales (50,5% frente a 36,2%, p < 0,001) y el número acumulado de resecciones ileocólicas previas se asoció significativamente con un mayor riesgo de morbilidad general ( p < 0,001). Hubo 31 (3%) fugas anastomóticas; las tasas de fuga no difirieron entre los grupos ( p = 0,6). El análisis multivariado indicó que la adhesiolisis extensa ( p < 0,001), la omisión de ileostomía ( p = 0,009) y el absceso/fístula intraoperatorios ( p = 0,02) se asociaron de forma independiente con fugas, pero no con nueva resección ( p = 0,27). Los pacientes con 0, 1, 2 o 3 de estos factores de riesgo observaron tasas de fuga del 1,1%, 1,3%, 6,0% y 11,6% ( p = 0,03), respectivamente.LIMITACIONES:Sesgo de selección, Sesgo de referencia, un centro de cuarto nivelCONCLUSIÓN:En comparación con los procedimientos primarios, la resección ileocólica para la enfermedad de Crohn recurrente se asocia con una mayor morbilidad general, pero no con una fuga anastomótica. Consulte Video Resumen en http://links.lww.com/DCR/C132 . (Traducción-Dr. Mauricio Santamaria ).


Assuntos
Doença de Crohn , Fístula , Adulto , Humanos , Doença de Crohn/complicações , Estudos Retrospectivos , Estudos de Casos e Controles , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Fatores de Risco , Fístula/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
13.
Dis Colon Rectum ; 66(3): 410-418, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35333791

RESUMO

BACKGROUND: Recommendations regarding venous thromboembolism prophylaxis in patients admitted to the hospital for IBD continue to evolve. OBJECTIVE: This study aimed to determine the 90-day rate and risk factors of deep venous thromboembolism and pulmonary embolism in cohorts of patients with IBD admitted to medical and surgical services. DESIGN: This was a retrospective review. SETTING: The study was conducted at a quaternary IBD referral center. PATIENTS: The study included adult patients ( > 18 y of age) with a known diagnosis of either ulcerative colitis or Crohn's disease who had an inpatient hospital admission for IBD between January 1, 2002, and January 1, 2020. MAIN OUTCOME MEASURES: The primary outcome measures were 90-day rate of deep venous thromboembolism and pulmonary embolism among admitted patients. RESULTS: A total of 86,276 hospital admissions from 16,551 patients with IBD occurred between January 1, 2002, and January 1, 2020. A total of 35,992 patients (41.7%) were given subcutaneous heparin for venous thromboembolism prophylaxis, and 8188 patients (9.49%) were given enoxaparin for venous thromboembolism prophylaxis during the inpatient hospital admission. From the date of hospital admission, the 90-day rate of deep venous thromboembolism was 4.3% (n = 3664); of these, 1731 patients (47%) were diagnosed during the admission and 1933 patients (53%) were diagnosed after discharge. From the date of hospital admission, the 90-day rate of pulmonary embolism was 2.4% (n = 2040); of these, 960 patients (47%) were diagnosed during admission and 1080 patients (53%) were diagnosed after discharge. LIMITATIONS: The study was limited by its retrospective nature and unmeasured severity of the disease. CONCLUSIONS: Patients admitted for IBD had a 90-day deep venous thromboembolism event rate of 4.3% and pulmonary embolism event rate of 2.4%. More than half of the events occurred after discharge, and venous thromboembolism events were higher among patients with IBD admitted to a medical service than those admitted to a surgical service. See Video Abstract at http://links.lww.com/DCR/B947 . TROMBOEMBOLIA VENOSA EN PACIENTES INGRESADOS CON ENFERMEDAD INFLAMATORIA INTESTINAL UNA EXPERIENCIA EN TODA LA EMPRESA DE ENCUENTROS HOSPITALARIOS: ANTECEDENTES:Recomendaciones sobre la profilaxis de tromboembolia venosa en pacientes ingresados con enfermedad inflamatoria intestinal (EII) continúa evolucionando.OBJETIVO:Determinar la tasa a 90 días y los factores de riesgo de tromboembolia venosa profunda y embolia pulmonar en cohortes de pacientes ingresados con EII médico y quirúrgico.DISEÑO:Esta fue una revisión retrospectiva.AJUSTE:El estudio se llevó a cabo en un centro cuaternario de derivación de EII.PACIENTES:Se incluyeron pacientes adultos (> 18 años) con diagnóstico conocido de colitis ulcerosa o enfermedad de Crohn que fueron hospitalizados por EII entre el 1 de Enero de 2002 y el 1 de Enero de 2020.PRINCIPALES MEDIDAS DE RESULTADOS:Las medidas principales fueron la tasa de tromboembolia venosa profunda a 90 días y la embolia pulmonar entre los pacientes ingresados.RESULTADOS:Un total de 86.276 ingresos hospitalarios de 16.551 pacientes con EII ocurrieron entre el 1 de Enero de 2002 y el 1 de Enero de 2020. A un total de 35.992 (41,7%) se les administró heparina subcutánea para profilaxis de tromboembolia venosa y a 8.188 (9,49%) se les administró enoxaparina para profilaxis de tromboembolia venosa durante el ingreso hospitalario. A partir de la fecha de ingreso hospitalario, la tasa de tromboembolia venosa profunda a 90 días fue del 4,3% (n = 3.664); de estos 1.731 (47%) se diagnosticaron durante el ingreso y 1.933 (53%) se diagnosticaron después del alta. Desde la fecha de ingreso hospitalario, la tasa de embolia pulmonar a los 90 días fue de 2,4% (n = 2.040); De estos, 960 (47%) fueron diagnosticados durante el ingreso y 1.080 (53%) fueron diagnosticados después del alta.LIMITACIONES:El estudio fue retrospectivo y no se midió la gravedad de la enfermedad.CONCLUSIÓNES:Los pacientes ingresados por EII tuvieron una tasa de tromboembolia venosa profunda y de eventos de embolia pulmonar de 4,3% y 2,4%, respectivamente, a 90 días. Más de la mitad de los eventos ocurrieron después del alta y los eventos de TEV fueron más altos entre los pacientes de EII médicos que quirúrgicos. Consulte Video Resumen en http://links.lww.com/DCR/B947 . (Traducción- Dr. Yesenia Rojas-Khalil ).


Assuntos
Colite Ulcerativa , Doença de Crohn , Embolia Pulmonar , Tromboembolia Venosa , Adulto , Humanos , Estudos Retrospectivos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Doença de Crohn/complicações , Doença de Crohn/epidemiologia , Doença de Crohn/terapia , Colite Ulcerativa/complicações , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/terapia , Anticoagulantes/uso terapêutico , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/etiologia , Hospitais
14.
Dis Colon Rectum ; 66(2): 306-313, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35358097

RESUMO

BACKGROUND: Colorectal resections have relatively high rates of surgical site infections causing significant morbidity. Incisional negative pressure wound therapy was introduced to improve wound healing of closed surgical incisions and to prevent surgical site infections. OBJECTIVE: This randomized controlled trial aimed to investigate the effect of incisional NPWT on superficial surgical site infections in high-risk, open, reoperative colorectal surgery. DESIGN: This was a single-center randomized controlled trial conducted between July 2015-October 2020. Patients were randomly assigned to incisional negative pressure wound therapy or standard gauze dressing with a 1:1 ratio. A total of 298 patients were included. SETTINGS: This study was conducted at the colorectal surgery department of a tertiary-level hospital. PATIENTS: This study included patients older than 18 years who underwent elective reoperative open colorectal resections. Patients were excluded who had open surgery within the past 3 months, who had active surgical site infection, and who underwent laparoscopic procedures. MAIN OUTCOME MEASURES: The primary outcome was superficial surgical site infection within 30 days. Secondary outcomes were deep and organ-space surgical site infections within 7 days and 30 days, postoperative complications, and length of hospital stay. RESULTS: A total of 149 patients were included in each arm. The mean age was 51 years, and 49.5% were women. Demographics, preoperative comorbidities, and preoperative albumin levels were comparable between the groups. Overall, most surgeries were performed for IBD, and 77% of the patients had an ostomy fashioned during the surgery. No significant difference was found between the groups in 30-day superficial surgical site infection rate (14.1% in control versus 9.4% in incisional negative pressure wound therapy; p = 0.28). Deep and organ-space surgical site infections rates at 7 and 30 days were also comparable between the groups. Postoperative length of stay and complication rates (Clavien-Dindo grade) were also comparable between the groups. LIMITATIONS: The patient population included in the trial consisted of a selected group of high-risk patients. CONCLUSIONS: Incisional negative pressure wound therapy was not associated with reduced superficial surgical site infection or overall complication rates in patients undergoing high-risk reoperative colorectal resections. See Video Abstract at http://links.lww.com/DCR/B956 . EFECTO DE LA TERAPIA DE HERIDA INSICIONAL CON PRESIN NEGATIVA EN INFECCIONES DEL SITIO QUIRRGICO EN CIRUGA COLORRECTAL REOPERATORIA DE ALTO RIESGO UN ENSAYO CONTROLADO ALEATORIZADO: ANTECEDENTES:Las resecciones colorrectales tienen tasas relativamente altas de infecciones del sitio quirúrgico que causan una morbilidad significativa. La terapia de heridas incisionales con presión negativa se introdujo para mejorar la cicatrización de las heridas de incisiones quirúrgicas cerradas y para prevenir infecciones del sitio quirúrgico.OBJETIVO:El objetivo de este ensayo controlado y aleatorizado fue investigar el efecto de la terapia de herida incisional con presión negativa en infecciones superficiales del sitio quirúrgico en cirugía colorrectal re operatoria, abierta y de alto riesgo.DISEÑO:Ensayo controlado y aleatorizado de un solo centro entre julio de 2015 y octubre de 2020. Los pacientes fueron aleatorizados para recibir tratamiento para heridas incisionales con presión negativa o vendaje de gasa estándar en una proporción de 1:1. Se incluyeron un total de 298 pacientes.AJUSTE:Este estudio se realizó en el departamento de cirugía colorrectal de un hospital de tercer nivel.PACIENTES:Se incluyeron pacientes mayores de 18 años que se fueron sometidos a resecciones colorrectales abiertas, re operatorias y electivas. Se excluyeron aquellos pacientes que tuvieron cirugía abierta en los últimos 3 meses, con infección activa del sitio quirúrgico y que fueron sometidos a procedimientos laparoscópicos.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue infección superficial del sitio quirúrgico dentro de los 30 días. Los resultados secundarios fueron infecciones del sitio quirúrgico profundas y del espacio orgánico dentro de los 7 y 30 días, las complicaciones posoperatorias y la duración de la estancia hospitalaria.RESULTADOS:Se incluyeron un total de 149 pacientes en cada brazo. La edad media fue de 51 años y el 49,5% fueron mujeres. La demografía, las comorbilidades preoperatorias y los niveles de albúmina preoperatoria fueron comparables entre los grupos. En general, la mayoría de las cirugías fueron realizadas por enfermedad inflamatoria intestinal y al 77 % de los pacientes se les confecciono una ostomía durante la cirugía. No hubo diferencias significativas entre los grupos en la tasa de infección del sitio quirúrgico superficial a los 30 días (14,1 % en el control frente a 9,4 % en el tratamiento de herida incisional con presión negativa, p = 0,28). Las tasas de infecciones del sitio quirúrgico profundas y del espacio orgánico a los 7 y 30 días también fueron comparables entre los grupos. La duración de la estancia postoperatoria y las tasas de complicaciones (Clavien-Dindo Graduacion) también fueron comparables entre los grupos.LIMITACIONES:La población de pacientes incluida en el ensayo consistió en un grupo seleccionado de pacientes de alto riesgo.CONCLUSIONES:Video Resumen en http://links.lww.com/DCR/B956 . (Traducción-Dr. Osvaldo Gauto ).


Assuntos
Cirurgia Colorretal , Tratamento de Ferimentos com Pressão Negativa , Infecção da Ferida Cirúrgica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Colectomia/métodos , Cirurgia Colorretal/efeitos adversos , Estudos Retrospectivos , Ferida Cirúrgica , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/prevenção & controle
15.
Inorg Chem ; 62(12): 4971-4979, 2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-36922906

RESUMO

In order to develop efficient protocols for CO2 reduction with less expensive and more convenient hydrogen sources, the catalytic reactivities of group 10 metal hydride complexes supported by a PNCNP pincer ligand, [2,6-(tBu2PNH)2C6H3]MH (M = Ni, 1a; Pd, 1b; Pt, 1c), against the hydroboration of CO2 with NH3·BH3 and NaBH4 have been explored. Both 1a and 1b readily react with CO2 at room temperature to form the corresponding formato complexes, [2,6-(tBu2PNH)2C6H3]MOC(O)H (M = Ni, 2a; Pd, 2b), in nearly quantitative yields. Treatment of NH3·BH3 with CO2 (1 atm) in 1,4-dioxane or THF at room temperature in the presence of 0.05-1.0 mol % of 1b followed by hydrolysis of the resulting mixtures produces formic acid in 105-186% yields, and initial turnover frequencies of up to 2000 h-1 are observed. In the presence of 1.0 mol % of 1b, NaBH4 reacts with CO2 (1 atm) in THF at room temperature to form NaB[OC(O)H]4 (3) in 87% isolated yield. In situ NMR spectroscopy indicates that the reactions proceed through the insertion of the C═O bond in CO2 into the Pd-H bond in 1b to form 2b, which sequentially reacts with the hydrides in NH3·BH3 or NaBH4 to produce boron formato species and regenerate 1b. This work represents one of the rare examples of catalytic transfer hydrogenation of CO2 with NH3·BH3 to the formic acid level under very mild conditions without any additives and also the first example of 4 equiv of CO2 uptake by NaBH4 in a reaction.

16.
Org Biomol Chem ; 21(25): 5288-5296, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37318055

RESUMO

A catalytic protocol for the Cp*RhIII-promoted C6-selective N-heteroarylation of 2-pyridones with N-heterocyclic boronates has been successfully developed utilizing a removable pyridine auxiliary. This system features high efficiency with mild conditions and also tolerates ortho- and meta-substituted pyridines, pyrazoles, pyrimidine, non-substituted quinolines, thiophene and furan well. The easy synthetic approach could potentially be applied to construct heterocyclic drug molecules bearing 2-pyridone-heteroaryl motifs.

17.
Colorectal Dis ; 25(6): 1187-1193, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36992540

RESUMO

AIM: Diverting loop ileostomy reversal (DLI-R) is routinely performed from 2-6 months following ileal pouch-anal anastomosis (IPAA). The safety of delayed reversal after IPAA is not well-defined. The aim of this study was to determine if prolonged diversion is associated with adverse outcomes compared to routine closure. METHODS: Adult patients undergoing primary IPAA with DLI from 2000 to 2021 were included in this retrospective cohort study from our institutional database. Patients were stratified into tertiles based on timing of reversal: Routine (56-116 days), Delayed (117-180 days), or Prolonged (>6 months). Univariate analysis compared categorical variables between groups. Patients reversed at <8 weeks were excluded. RESULTS: In total, 2615 patients underwent DLI-R following IPAA (3-stage 61%, 2-stage 39%; mean age 39.9 years). DLI-R was performed as Routine, Delayed and Prolonged in 1908 (72.9%), 426 (16.4%) and 281 (10.8%), respectively. Overall, DLI-R related complications occurred in 12.4% (n = 324). The complication rate in the Routine group was 11% (n = 210), in the Delayed group was 12.2% (n = 52) and in the Prolonged group was 22.1% (n = 62). Reasons for prolonged diversion in the Prolonged group were complications at the time of IPAA in 207 (73.9%) or patient preference/scheduling in 73 (26.1%). DLI-R >6 months after IPAA due to complications had higher rates of overall complications following ileostomy reversal (OR 2.6, 95% CI 1.85-3.72, p < 0.001) whereas when DLI-R was delayed due to preference/scheduling outcomes were not different than the Routine group (p = 0.28). CONCLUSION: Prolonged time to ileostomy reversal after IPAA is probably safe without increased risk of complications when due to patient preference.


Assuntos
Colite Ulcerativa , Bolsas Cólicas , Proctocolectomia Restauradora , Adulto , Humanos , Estudos Retrospectivos , Colite Ulcerativa/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Proctocolectomia Restauradora/efeitos adversos , Ileostomia/efeitos adversos , Anastomose Cirúrgica , Bolsas Cólicas/efeitos adversos , Resultado do Tratamento
18.
Acta Pharmacol Sin ; 44(1): 92-104, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35794374

RESUMO

Promoting adult neurogenesis in the enteric nervous system (ENS) may be a potential therapeutic approach to cure enteric neuropathies. Enteric glial cells (EGCs) are the most abundant glial cells in the ENS. Accumulating evidence suggests that EGCs can be a complementary source to supply new neurons during adult neurogenesis in the ENS. In the brain, astrocytes have been intensively studied for their neuronal conversion properties, and small molecules have been successfully used to induce the astrocyte-to-neuron transition. However, research on glia-to-neuron conversion in the ENS is still lacking. In this study, we used GFAP-Cre:Rosa-tdTomato mice to trace glia-to-neuron transdifferentiation in the ENS in vivo and in vitro. We showed that GFAP promoter-driven tdTomato exclusively labelled EGCs and was a suitable marker to trace EGCs and their progeny cells in the ENS of adult mice. Interestingly, we discovered that RepSox or other ALK5 inhibitors alone induced efficient transdifferentiation of EGCs into neurons in vitro. Knockdown of ALK5 further confirmed that the TGFßR-1/ALK5 signalling pathway played an essential role in the transition of EGCs to neurons. RepSox-induced neurons were Calbindin- and nNOS-positive and displayed typical neuronal electrophysiological properties. Finally, we showed that administration of RepSox (3, 10 mg· kg-1 ·d-1, i.g.) for 2 weeks significantly promoted the conversion of EGCs to neurons in the ENS and influenced gastrointestinal motility in adult mice. This study provides a method for efficiently converting adult mouse EGCs into neurons by small-molecule compounds, which might be a promising therapeutic strategy for gastrointestinal neuropathy.


Assuntos
Neuroglia , Neurônios , Camundongos , Animais , Neuroglia/metabolismo , Neurônios/metabolismo , Piridinas/metabolismo , Motilidade Gastrointestinal
19.
Surg Endosc ; 37(5): 4065-4074, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36952049

RESUMO

BACKGROUND: Total abdominal colectomy with end ileostomy is the first stage of the three-stage surgical treatment of medically refractory ulcerative colitis. Laparoscopic surgery is a safe approach offering several benefits. Single-incision laparoscopic surgery is an alternative minimally invasive approach providing excellent cosmetic results. Literature on single-incision laparoscopic clockwise continuous total abdominal colectomy in the treatment of ulcerative colitis is limited. Aim of the study is to describe our surgical technique and report the outcomes. METHODS: Medically refractory ulcerative colitis patients who underwent single-incision laparoscopic clockwise continuous total abdominal colectomy with end ileostomy by a single surgeon between January 2013 and December 2020 at our tertiary care center are included. Patient charts were reviewed retrospectively. RESULTS: 52 patients were included in the final analysis. 51.9% patients were male with the median age of 31.5 years and body mass index of 22.2 kg/m2. Median duration of operation was 100 min with estimated blood loss of 50 ml. There were no intraoperative complications, conversions to conventional laparoscopy or open surgery. Postoperative complications were reported in 13 (25%) patients with most common being ileus (17.3%). 3 patients had surgical site infections. 2 patients had postoperative bleeding requiring blood transfusion. 2 patients had reoperation within postoperative 30 days. Median length of hospital stay was 2 days. No mortalities were reported. CONCLUSION: Single-incision laparoscopic clockwise continuous approach is safe and effective in ulcerative colitis patients undergoing total abdominal colectomy with end ileostomy. Further prospective randomized studies are warranted.


Assuntos
Colite Ulcerativa , Laparoscopia , Humanos , Masculino , Adulto , Feminino , Colite Ulcerativa/cirurgia , Ileostomia/métodos , Estudos Retrospectivos , Resultado do Tratamento , Colectomia/métodos , Laparoscopia/métodos , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia
20.
J Chem Phys ; 158(12): 124705, 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-37003787

RESUMO

Due to conversion equilibrium between solvent and H- and O-containing adsorbates, the true surface state of a catalyst under a particular electrochemical condition is often overlooked in electrocatalysis research. Herein, by using surface Pourbaix analysis, we show that many electrocatalytically active transition metal X-ides (e.g., oxides, nitrides, carbides, and hydroxides) tend to possess the surface states different from their pristine stoichiometric forms under the pH and potential of interest due to water dissociation or generation. Summarizing the density functional theory calculated surface Pourbaix diagrams of 14 conditionally stable transition metal X-ide materials, we found that some of these surfaces tend to be covered by O-containing adsorbates at a moderate or high potential, while vacancies or H-covered surfaces may form at a low potential. These results suggest the possibility of poisoning or creation of surface sites beyond the pristine surface, implying that the surface state under reaction conditions (pH and potentials) needs to be considered before the identification and analysis of active sites of a transition metal X-ide catalyst. In addition, we provide an explanation of the observed theory and experiment discrepancy that some transition metal X-ides are "more stable in experiment than in theory." Based on our findings, we conclude that analyzing the surface state of transition metal X-ide electrocatalysts by theoretical calculations (e.g., surface Pourbaix diagram analysis), in situ/operando and post-reaction experiments are indispensable to accurately understand the underlying catalytic mechanisms.

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