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1.
Am J Hum Genet ; 109(10): 1894-1908, 2022 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-36206743

RESUMO

Individuals with cystic fibrosis (CF) develop complications of the gastrointestinal tract influenced by genetic variants outside of CFTR. Cystic fibrosis-related diabetes (CFRD) is a distinct form of diabetes with a variable age of onset that occurs frequently in individuals with CF, while meconium ileus (MI) is a severe neonatal intestinal obstruction affecting ∼20% of newborns with CF. CFRD and MI are slightly correlated traits with previous evidence of overlap in their genetic architectures. To better understand the genetic commonality between CFRD and MI, we used whole-genome-sequencing data from the CF Genome Project to perform genome-wide association. These analyses revealed variants at 11 loci (6 not previously identified) that associated with MI and at 12 loci (5 not previously identified) that associated with CFRD. Of these, variants at SLC26A9, CEBPB, and PRSS1 associated with both traits; variants at SLC26A9 and CEBPB increased risk for both traits, while variants at PRSS1, the higher-risk alleles for CFRD, conferred lower risk for MI. Furthermore, common and rare variants within the SLC26A9 locus associated with MI only or CFRD only. As expected, different loci modify risk of CFRD and MI; however, a subset exhibit pleiotropic effects indicating etiologic and mechanistic overlap between these two otherwise distinct complications of CF.


Assuntos
Fibrose Cística , Diabetes Mellitus , Doenças do Recém-Nascido , Obstrução Intestinal , Fibrose Cística/complicações , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Diabetes Mellitus/genética , Estudo de Associação Genômica Ampla , Humanos , Recém-Nascido , Obstrução Intestinal/complicações , Obstrução Intestinal/genética
2.
Physiol Genomics ; 56(3): 247-264, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38073491

RESUMO

Chronic intestinal inflammation is a poorly understood manifestation of cystic fibrosis (CF), which may be refractory to ion channel CF transmembrane conductance regulator (CFTR) modulator therapy. People with CF exhibit intestinal dysbiosis, which has the potential for stimulating intestinal and systemic inflammation. CFTR is expressed in organ epithelia, leukocytes, and other tissues. Here, we investigate the contribution of intestinal epithelium-specific loss of Cftr [iCftr knockout (KO)] to dysbiosis and inflammation in mice treated with either of two antiobstructive dietary regimens necessary to maintain CF mouse models [polyethylene glycol (PEG) laxative or a liquid diet (LiqD)]. Feces collected from iCftr KO mice and their wild-type (WT) sex-matched littermates were used to measure fecal calprotectin to evaluate inflammation and to perform 16S rRNA sequencing to characterize the gut microbiome. Fecal calprotectin was elevated in iCftr KO relative to WT mice that consumed either PEG or LiqD. PEG iCftr KO mice did not show a change in α diversity versus WT mice but demonstrated a significant difference in microbial composition (ß diversity) with included increases in the phylum Proteobacteria, the family Peptostreptococcaceae, four genera of Clostridia including C. innocuum, and the mucolytic genus Akkermansia. Fecal microbiome analysis of LiqD-fed iCftr KO mice showed both decreased α diversity and differences in microbial composition with increases in the Proteobacteria family Enterobacteriaceae, Firmicutes families Clostridiaceae and Peptostreptococcaceae, and enrichment of Clostridium perfringens, C. innocuum, C. difficile, mucolytic Ruminococcus gnavus, and reduction of Akkermansia. It was concluded that epithelium-specific loss of Cftr is a major driver of CF intestinal dysbiosis and inflammation with significant similarities to previous studies of pan Cftr KO mice.NEW & NOTEWORTHY Chronic intestinal inflammation is a manifestation of cystic fibrosis (CF), a disease caused by loss of the anion channel CF transmembrane conductance regulator (CFTR) that is expressed in many tissues. This study shows that intestinal epithelial cell-specific loss of CFTR [inducible Cftr knockout (KO)] in mice is sufficient to induce intestinal dysbiosis and inflammation. Experiments were performed on mice consuming two dietary regimens routinely used to prevent obstruction in CF mice.


Assuntos
Clostridioides difficile , Fibrose Cística , Obstrução Intestinal , Animais , Humanos , Camundongos , Clostridioides difficile/genética , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Disbiose/microbiologia , Expectorantes/uso terapêutico , Fezes , Inflamação , Complexo Antígeno L1 Leucocitário/uso terapêutico , Camundongos Endogâmicos CFTR , Camundongos Knockout , RNA Ribossômico 16S
3.
Ann Surg ; 279(4): 684-691, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37855681

RESUMO

OBJECTIVE: Many emergency general surgery (EGS) conditions can be managed operatively or nonoperatively, with outcomes that vary by diagnosis. We hypothesized that operative management would lead to higher in-hospital costs but to cost savings over time. BACKGROUND: EGS conditions account for $28 billion in health care costs in the United States annually. Compared with scheduled surgery, patients who undergo emergency surgery are at increased risk of complications, readmissions, and death, with accompanying costs of care that are up to 50% higher than elective surgery. Our prior work demonstrated that operative management had variable impacts on clinical outcomes depending on the EGS condition. METHODS: This was a nationwide, retrospective study using fee-for-service Medicare claims data. We included patients 65.5 years of age or older with a principal diagnosis for an EGS condition 7/1/2015-6/30/2018. EGS conditions were categorized as: colorectal, general abdominal, hepatopancreaticobiliary (HPB), intestinal obstruction, and upper gastrointestinal. We used near-far matching with a preference-based instrumental variable to adjust for confounding and selection bias. Outcomes included Medicare payments for the index hospitalization and at 30, 90, and 180 days. RESULTS: Of 507,677 patients, 30.6% received an operation. For HPB conditions, costs for operative management were initially higher but became equivalent at 90 and 180 days. For all others, operative management was associated with higher inpatient costs, which persisted, though narrowed, over time. Out-of-pocket costs were nearly equivalent for operative and nonoperative management. CONCLUSIONS: Compared with nonoperative management, costs were higher or equivalent for operative management of EGS conditions through 180 days, which could impact decision-making for clinicians, patients, and health systems in situations where clinical outcomes are similar.


Assuntos
Cirurgia Geral , Obstrução Intestinal , Procedimentos Cirúrgicos Operatórios , Humanos , Idoso , Estados Unidos , Estudos Retrospectivos , Cirurgia de Cuidados Críticos , Medicare , Hospitalização , Obstrução Intestinal/etiologia , Procedimentos Cirúrgicos Operatórios/efeitos adversos
4.
Ann Surg ; 279(4): 613-619, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37788345

RESUMO

OBJECTIVE: We aimed to compare outcomes of early and standard closure of diverting loop ileostomy (DLI) after proctectomy and determine risk factors for anastomotic leak (AL) and complications. BACKGROUND: Formation of DLI has been a routine practice after proctectomy to decrease the incidence and potential adverse sequela of AL. METHODS: PubMed, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) that compared outcomes of early versus standard closure of DLI after proctectomy. Main outcome measures were postoperative complications, AL, ileus, surgical site infection, reoperation, readmission, and hospital stay following DLI closure. RESULTS: Eleven RCTs (932 patients; 57% male) were included. Early closure group included 474 patients and standard closure 458 patients. Early closure was associated with higher odds of AL [odds ratio (OR): 2.315, P =0.013] and similar odds of complications (OR: 1.103, P =0.667), ileus (OR: 1.307, P =0.438), surgical site infection (OR: 1.668, P =0.079), reoperation (OR: 1.896, P =0.062), and readmission (OR: 3.431, P =0.206). Hospital stay was similar (weighted mean difference: 1.054, P =0.237). Early closure had higher odds of AL than standard closure when early closure was done ≤2 weeks (OR: 2.12, P =0.047) but not within 3 to 4 weeks (OR: 2.98, P =0.107). Factors significantly associated with complications after early closure were diabetes mellitus, smoking, and closure of DLI ≤2 weeks, whereas factors associated with AL were ≥ American Society of Anesthesiologists II classification and diabetes mellitus. CONCLUSIONS: Early closure of DLI after proctectomy has a higher risk of AL, particularly within 2 weeks of DLI formation. On the basis of this study, routine early ileostomy closure cannot be recommended.


Assuntos
Diabetes Mellitus , Íleus , Obstrução Intestinal , Protectomia , Neoplasias Retais , Masculino , Humanos , Feminino , Ileostomia/efeitos adversos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fístula Anastomótica , Protectomia/efeitos adversos , Obstrução Intestinal/etiologia , Íleus/epidemiologia , Íleus/etiologia , Diabetes Mellitus/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Neoplasias Retais/cirurgia
5.
Mol Genet Genomics ; 299(1): 44, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38625590

RESUMO

Megacystis-microcolon-hypoperistalsis-syndrome (MMIHS) is a rare and early-onset congenital disease characterized by massive abdominal distension due to a large non-obstructive bladder, a microcolon and decreased or absent intestinal peristalsis. While in most cases inheritance is autosomal dominant and associated with heterozygous variant in ACTG2 gene, an autosomal recessive transmission has also been described including pathogenic bialellic loss-of-function variants in MYH11. We report here a novel family with visceral myopathy related to MYH11 gene, confirmed by whole genome sequencing (WGS). WGS was performed in two siblings with unusual presentation of MMIHS and their two healthy parents. The 38 years-old brother had severe bladder dysfunction and intestinal obstruction, whereas the 30 years-old sister suffered from end-stage kidney disease with neurogenic bladder and recurrent sigmoid volvulus. WGS was completed by retrospective digestive pathological analyses. Compound heterozygous variants of MYH11 gene were identified, associating a deletion of 1.2 Mb encompassing MYH11 inherited from the father and an in-frame variant c.2578_2580del, p.Glu860del inherited from the mother. Pathology analyses of the colon and the rectum revealed structural changes which significance of which is discussed. Cardiac and vascular assessment of the mother was normal. This is the second report of a visceral myopathy corresponding to late-onset form of MMIHS related to compound heterozygosity in MYH11; with complete gene deletion and a hypomorphic allele in trans. The hypomorphic allele harbored by the mother raised the question of the risk of aortic disease in adults. This case shows the interest of WGS in deciphering complex phenotypes, allowing adapted diagnosis and genetic counselling.


Assuntos
Anormalidades Múltiplas , Colo , Duodeno , Doenças Fetais , Obstrução Intestinal , Pseudo-Obstrução Intestinal , Bexiga Urinária , Adulto , Humanos , Masculino , Colo/anormalidades , Duodeno/anormalidades , Pseudo-Obstrução Intestinal/genética , Cadeias Pesadas de Miosina/genética , Estudos Retrospectivos , Bexiga Urinária/anormalidades , Feminino
6.
Radiology ; 310(2): e231710, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38319165

RESUMO

Background Preoperative recognition of irreversible bowel necrosis is important, as it provides valuable guidance for surgical strategy selection but also may inform perioperative risk assessment and communication. Few studies have focused on the association between CT signs and bowel necrosis. Purpose To assess the diagnostic accuracy of CT signs to predict bowel necrosis in patients with closed-loop small bowel obstruction (CL-SBO). Materials and Methods This retrospective single-center study included patients who were surgically confirmed to have CL-SBO caused by adhesion or internal hernia between January 2016 and May 2022. Necrosis was determined based on surgical exploration and postoperative pathologic examination. Two radiologists independently reviewed CT signs by both subjective visual assessment and objective measurement. Disagreements were resolved in consensus with a third gastrointestinal radiologist. Univariable and multivariable analyses were used to assess the association between CT signs and bowel necrosis, and Cohen κ was used to assess interobserver agreement. Sensitivity and specificity were calculated for each CT sign. Results This study included 145 patients: 61 (42.1%) in the necrotic group (median age, 62 years [IQR, 51-71.5 years]; 37 [60.7%] women) and 84 (57.9%) in the nonnecrotic group (median age, 61.5 years [IQR, 51-68.8 years]; 51 [60.7%] women). Univariable analysis and multivariable analysis showed that increased attenuation of intestinal contents and increased attenuation of intestinal wall were independent predictors for bowel necrosis (odds ratio = 45.3 and 15.1; P = .001 and P < .001, respectively). Increased attenuation of intestinal contents and increased attenuation of intestinal wall had similar sensitivity (64% and 67%, respectively) and specificity (99% and 92%, respectively) for predicting bowel necrosis. However, interobserver agreement was better for assessing the contents than the wall (κ = 0.84 and 0.59, respectively). Conclusion Increased attenuation of intestinal contents was a highly specific CT sign with good reproducibility to predict bowel necrosis in CL-SBO. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Taourel and Zins in this issue.


Assuntos
Conteúdo Gastrointestinal , Obstrução Intestinal , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Reprodutibilidade dos Testes , Estudos Retrospectivos , Obstrução Intestinal/diagnóstico por imagem , Obstrução Intestinal/cirurgia , Necrose/diagnóstico por imagem , Tomografia Computadorizada por Raios X
7.
Ann Surg Oncol ; 31(5): 3212-3221, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38349564

RESUMO

BACKGROUND: Traditionally, surgical treatment is recommended for right-sided colonic cancer obstruction (RCCO); however, the literature comparing surgical or non-surgical procedures is lacking. METHODS: Patients included in this study were divided into two groups: one group received elective surgery after self-expanding metal stent (SEMS) placement, i.e., the bridge to surgery (BTS) group, and one group received emergency surgery (ES). RESULTS: Thirty-five patients were included in the BTS group and 60 patients underwent ES. The technical and clinical success rates for SEMS placement were 100% and 88.6%, respectively, while the short-term complication rates were 51.4% and 33.3% for the BTS and ES groups, respectively (p = 0.082). Overall, 2.9% and 3.3% of postoperative deaths occurred in the BTS and ES groups (p = 1.000). The 1-year overall survival (OS) rates were 91.4% and 88.3% (p = 0.840), 3-year OS rates were 85.7% and 81.7% (p = 0.860), and 5-year OS rates were 82.9% and 76.7% (p = 0.620) in the BTS and ES groups, respectively. No tumor recurrence was found in the BTS group but seven recurrences were found in the ES group (11.7%) [p = 0.091]. Laparoscopic surgery was chosen by 42.9% of patients in the BTS group and 26.7% of patients in the ES group (p = 0.104); however, the length of hospital stay (p = 0.001) was longer in the BTS group. CONCLUSIONS: In the two groups, no differences were found in terms of postoperative complications and mortality as well as OS. The BTS group preferred to perform laparoscopic surgery and the technical success rate of stenting was high, therefore SEMS for RCCO was considered safe and feasible.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Obstrução Intestinal , Stents Metálicos Autoexpansíveis , Humanos , Neoplasias Colorretais/patologia , Stents Metálicos Autoexpansíveis/efeitos adversos , Recidiva Local de Neoplasia/complicações , Neoplasias do Colo/complicações , Neoplasias do Colo/cirurgia , Stents/efeitos adversos , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Resultado do Tratamento , Estudos Retrospectivos
8.
Dis Colon Rectum ; 67(7): 878-894, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557484

RESUMO

BACKGROUND: The optimal treatment strategy for left-sided malignant colonic obstruction remains controversial. Emergency colonic resection has been the standard of care; however, self-expanding metallic stenting as a bridge to surgery may offer short-term advantages, although oncological concerns exist. Decompressing stoma may provide a valid alternative, with limited evidence. OBJECTIVE: To perform a systematic review and Bayesian arm random-effects model network meta-analysis comparing the approaches for management of malignant left-sided colonic obstruction. DATA SOURCES: A systematic review of PubMed, Embase, Cochrane Library, and Google Scholar databases was conducted from inception to August 22, 2023. STUDY SELECTION: Randomized controlled trials and propensity score-matched studies. INTERVENTIONS: Emergency colonic resection, self-expanding metallic stent, and decompressing stoma. MAIN OUTCOME MEASURES: Oncologic efficacy, morbidity, successful minimally invasive surgery, primary anastomosis, and permanent stoma rates. RESULTS: Nineteen of 5225 articles identified met our inclusion criteria. Stenting (risk ratio 0.57; 95% credible interval, 0.33-0.79) and decompressing stomas (risk ratio 0.46, 95% credible interval: 0.18-0.92) resulted in a significant reduction in the permanent stoma rate. Stenting facilitated minimally invasive surgery more frequently (risk ratio 4.10; 95% credible interval, 1.45-13.13) and had lower overall morbidity (risk ratio 0.58; 95% credible interval, 0.35-0.86). A pairwise analysis of primary anastomosis rates showed increased stenting (risk ratio 1.40; 95% credible interval, 1.31-1.49) compared with emergency resection. There was a significant decrease in the 90-day mortality with stenting (risk ratio 0.63; 95% credible interval, 0.41-0.95) compared with resection. There were no differences in disease-free and overall survival rates, respectively. LIMITATIONS: There is a lack of randomized controlled trials and propensity score matching data comparing short-term and long-term outcomes for diverting stomas compared to self-expanding metallic stents. Two trials compared self-expanding metallic stents and diverting stomas in left-sided malignant colonic obstruction. CONCLUSIONS: This study provides high-level evidence that a bridge-to-surgery strategy is safe for the management of left-sided malignant colonic obstruction and may facilitate minimally invasive surgery, increase primary anastomosis rates, and reduce permanent stoma rates and postoperative morbidity compared with emergency colonic resection.


Assuntos
Neoplasias do Colo , Obstrução Intestinal , Metanálise em Rede , Pontuação de Propensão , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Obstrução Intestinal/cirurgia , Obstrução Intestinal/etiologia , Obstrução Intestinal/terapia , Neoplasias do Colo/complicações , Neoplasias do Colo/cirurgia , Colectomia/métodos , Stents Metálicos Autoexpansíveis , Descompressão Cirúrgica/métodos , Stents , Colostomia/métodos
9.
J Surg Res ; 297: 71-82, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38447338

RESUMO

INTRODUCTION: Studies identifying predictors of postoperative outcomes in adhesive small bowel obstruction are limited. This study investigates the efficacy of the modified frailty index (mFI)to predict postoperative morbidity and mortality among patients undergoing surgery for adhesive small bowel obstruction. METHODS: A multicentre retrospective cohort study including patients undergoing surgery for adhesive small bowel obstruction after failed trial of nonoperative management between January 2015 and December 2020 was performed. Impact of frailty status using the mFI, stratified as frail (≥0.27) and robust (<0.27), on postoperative morbidity, mortality, length of stay, and discharge destination was evaluated using multiple logistic regression. RESULTS: Ninety-two robust patients (mean age 62.4 y, 68% female) and 41 frail patients (mean age 81.7 y, 63% female) were included. On simple stratification, frail patients had significantly increased 30-d morbidity (overall morbidity 80% versus 49%) and need for higher level of care on discharge (41% versus 9%). However, on multiple regression, functional dependence but not the mFI, was independently associated with worse 30-d overall morbidity (odds ratio [OR] 3.97, confidence interval [CI] 1.29-12.19) and lower likelihood of returning to preoperative disposition (OR 0.21, CI 0.05-0.91). The delay in operation beyond 5 d was independently associated with worse 30-d outcomes including overall morbidity and mortality (OR 7.54, CI 2.13-26.73) and decreased return to preoperative disposition (OR 0.14, CI 0.04-0.56). CONCLUSIONS: The mFI, although promising, was not independently predictive of outcomes following surgery for adhesive small bowel obstruction. Further adequately powered studies are required.


Assuntos
Fragilidade , Obstrução Intestinal , Humanos , Feminino , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Masculino , Estudos Retrospectivos , Obstrução Intestinal/cirurgia , Morbidade , Complicações Pós-Operatórias , Fatores de Risco , Medição de Risco
10.
J Surg Res ; 293: 239-247, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37802018

RESUMO

INTRODUCTION: Small bowel obstruction (SBO) is one of the most common causes for hospital admission in Ethiopia. The use of water-soluble contrast agents (WSCAs) such as Gastrografin to manage adhesive SBO can predict nonoperative resolution of SBO and reduce decision time to surgery and length of hospital stay. However, nothing is known about practice patterns and Gastrografin use in low-income settings. We sought to characterize current management practices, including use of WSCAs, as well as outcomes for patients with SBO in Addis Ababa, Ethiopia. METHODS: We conducted a mixed-methods study consisting of a survey of surgeons throughout Ethiopia and a retrospective record review at five public, tertiary care-level teaching hospitals in Addis Ababa. RESULTS: Of the 76 surgeons who completed the survey, 63% had heard of the use of WSCAs for SBO and only 11% used oral agents for its management. Chart review of 149 patients admitted with SBO showed the most common etiology was adhesion (39.6% of admissions), followed by small bowel volvulus (20.8%). Most patients (83.2%) underwent surgery during their admission. The most common diagnosis in patients who did not require surgery was also adhesion (68.0%), as well as for those who had surgery (33.9%), followed by small bowel volvulus (24.2%). CONCLUSIONS: The etiology of SBO in Ethiopia may be changing, with postoperative adhesions becoming more common than other historically more prevalent causes. Although a Gastrografin protocol as a diagnostic and potentially therapeutic aid for SBO is feasible in this population and setting, challenges can be anticipated, and future studies of protocol implementation and effectiveness are needed to further inform its utility in Ethiopia and other low-income and middle-income countries.


Assuntos
Obstrução Intestinal , Volvo Intestinal , Humanos , Diatrizoato de Meglumina/uso terapêutico , Volvo Intestinal/complicações , Estudos Retrospectivos , Estudos de Viabilidade , Etiópia , Obstrução Intestinal/etiologia , Obstrução Intestinal/terapia , Meios de Contraste , Aderências Teciduais/complicações , Aderências Teciduais/diagnóstico
11.
Rapid Commun Mass Spectrom ; 38(2): e9664, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38124169

RESUMO

RATIONALE: TongFu XieXia Decoction (TFXXD), a formulation rooted in traditional Chinese medicine and optimized through clinical practice, serves as an advanced version of the classic Da Cheng Qi decoction used for treating intestinal obstruction (IO), demonstrating significant therapeutic efficacy. However, due to the intricate nature of herbal compositions, the principal constituents and potential mechanisms of TFXXD have yet to be clarified. Accordingly, this study seeks to identify the active compounds and molecular targets of TFXXD, as well as to elucidate its anti-IO mechanisms. METHODS: Qualitative identification of the principal constituents of TFXXD was accomplished using ultra-high preformance liquid chromatography-quadrupole-orbitrap mass spectrometry (UPLC-Q-Orbitrap-MS/MS) analysis. PharmMapper facilitated the prediction of potential molecular targets, whereas protein-protein interaction analysis was conducted using STRING 11.0. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the Metascape database. A "compounds-target-pathway" network was meticulously constructed within Cytoscape 3.8.2. Finally, molecular docking studies were performed to investigate the interactions between the core target and the crucial compound. RESULTS: UPLC-Q-Orbitrap-MS/MS analysis identified 65 components with high precision and sensitivity. Furthermore, 64 potential targets were identified as integral to TFXXD bioactivity in IO treatment. Gene Ontology enrichment analysis revealed 995 distinct biological functions, while the Kyoto Encyclopedia of Genes and Genomes enrichment analysis identified 143 intricate signaling pathways. CONCLUSION: Molecular docking studies substantiated the substantial affinity between the TFXXD bioactive constituents and their corresponding targets in the context of IO. TFXXD exerts its therapeutic efficacy in IO through a multifaceted interplay between multiple compounds, targets, and pathways. The integration of network pharmacology with UPLC-Q-Orbitrap-MS/MS has emerged as a promising strategy to unravel the intricate web of molecular interactions underlying herbal medicine. However, it is imperative to emphasize the necessity for further in vivo and in vitro experiments.


Assuntos
Medicamentos de Ervas Chinesas , Obstrução Intestinal , Humanos , Farmacologia em Rede , Cromatografia Líquida de Alta Pressão , Simulação de Acoplamento Molecular , Espectrometria de Massas em Tandem , Obstrução Intestinal/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
12.
Scand J Gastroenterol ; 59(1): 108-111, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37694882

RESUMO

OBJECTIVES: Stenting of malignant colon obstruction is used as a bridge to surgery or as an alternative to surgical colostomy in a palliative setting. Current guidelines recommend stent placement as the first line of treatment in colonic obstruction in both curative and palliative settings. However, it is unclear whether the location of the malignant obstruction influences the outcome of the stenting procedure. The goal of this study was to compare the outcomes of colonic stents between proximal and distal colonic strictures with regard to technical and clinical success and the risk of adverse events. METHODS: A multi-center retrospective cohort was composed of patients who underwent a colonic stent placement at two tertiary hospitals between 2013 and 2021. The technical and clinical outcome, stent type used, duration of post-procedural hospital stay and complications were noted. RESULTS: A total of 148 patients who underwent colonic stenting were identified. 41 patients underwent stent placement in the proximal colon and 107 patients underwent a distal stent placement. There was no difference in technical success (100% vs 96.3%, p = 0.209), clinical success (97.0% vs 89.6%, p = 0.199) or complications (24.4% vs 37.4%, p = 0,135). CONCLUSION: Technical success and clinical success rates are high and do not differ between stent locations. There is no significant difference in complication rates between proximal and distal colonic stents.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Obstrução Intestinal , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Stents/efeitos adversos , Obstrução Intestinal/cirurgia , Obstrução Intestinal/complicações , Colostomia , Cuidados Paliativos , Neoplasias Colorretais/cirurgia , Neoplasias do Colo/complicações , Neoplasias do Colo/cirurgia
13.
Scand J Gastroenterol ; 59(1): 39-45, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37622924

RESUMO

BACKGROUND: Few studies have compared endoscopic balloon dilation (EBD) and surgery in the treatment of duodenal stricture in patients with Crohn's disease (CD). METHODS: We performed a retrospective study to compare the efficacy and safety among patients with CD-associated duodenal stricture treated with EBD or surgery from October 2013 to December 2021. Univariate and multivariate analyses were performed to evaluate factors associated with recurrence-free or surgery-free survival. RESULTS: A total of 48 eligible patients were included, including 30 patients treated with EBD only and 18 patients treated with surgery. Patients treated with surgery experienced more symptomatic improvement (100% vs. 63.33%, p = 0.003) and significantly longer recurrence-free survival (6.31 [IQR: 3.00-8.39] years vs. 2.96 [IQR: 1.06-5.42] years, p = 0.01) but suffered more postprocedural adverse events (16.67% vs. 0.74% per procedure, p = 0.001). In patients initially treated with EBD (n = 41), a total of 11 (26.83%) required subsequent surgical intervention. Younger age at CD diagnosis (HR = 0.90, 95% CI: 0.81-1.00, p = 0.04) was associated with a higher risk for subsequent surgery. CONCLUSIONS: Surgery for CD-associated duodenal strictures was associated with a longer recurrence-free survival. EBD was safe and effective with minimal postprocedural adverse events but led to a high frequency of recurrence.


Assuntos
Doença de Crohn , Obstrução Intestinal , Humanos , Doença de Crohn/cirurgia , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Estudos Retrospectivos , Dilatação/efeitos adversos , Obstrução Intestinal/etiologia , Resultado do Tratamento , Endoscopia Gastrointestinal/métodos
14.
BMC Infect Dis ; 24(1): 201, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355443

RESUMO

Histoplasmosis is a fungal infection most frequently seen in immunocompromised patients. It is endemic in Central and South America and in Africa. The infection is usually asymptomatic in a healthy individual. Extrapulmonary dissemination can be seen in immunocompromised hosts. Gastrointestinal manifestations frequently involve the terminal ileum and cecum, mimicking Crohn's disease or malignancy. We describe the case of a 36-year-old healthy man from Cameroon, living in Switzerland for 13 years and without any medical nor surgical history, who presented peritonitis not responding to antibiotics. CT-scan showed bowel obstruction and signs of peritonitis. We opted for an explorative laparoscopy, which was converted to laparotomy with extensive adhesiolysis. Diagnostic of histoplasmosis was confirmed by histology and PCR analysis on biopsy. To our knowledge, this is the first described case of peritonitis as main outcome of a disseminated histoplasmosis involving the peritoneum in an immunocompetent patient.


Assuntos
Doença de Crohn , Histoplasmose , Obstrução Intestinal , Peritonite , Masculino , Humanos , Adulto , Histoplasmose/complicações , Doença de Crohn/complicações , Peritonite/diagnóstico , Peritonite/complicações , Camarões
15.
BMC Infect Dis ; 24(1): 365, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561696

RESUMO

BACKGROUND: Cytomegalovirus infection manifests varying clinical characteristics and severity in diverse populations with different immune statuses. The signs and symptoms of gastrointestinal involvement are nonspecific. Here, we present a case of cytomegalovirus colitis in an immunocompetent adolescent, which manifested as intestinal pseud-obstruction. CASE PRESENTATION: A 15-year-old man who had contracted novel coronavirus infection one month earlier was admitted to our hospital with fever, abdominal pain, and hematochezia. His abdomen was distended, and laboratory evaluation revealed a decrease in the blood count, an increase in inflammatory indicators and hepatic impairment. Imaging shows bowel wall thickening and dilatation of the colon. A diagnosis of intestinal infection combined with acute intestinal pseud-obstruction was made. Diarrhea persisted despite conservative treatment with empirical antibiotics. A colonoscopy was performed. Pathology confirmed cytomegalovirus infection. Ganciclovir therapy was initiated, and subsequent review showed a good recovery. CONCLUSIONS: The case was diagnosed as cytomegalovirus colitis. We reviewed the reports of 9 cases of bowel obstruction, including our own, and found that the majority of the adult patients were elderly with underlying disease. Clinical and endoscopic manifestations are typically nonspecific, and imaging shows typical signs of intestinal obstruction. The final diagnosis was confirmed by pathology. Most of them have a good prognosis. We suggest that cytomegalovirus colitis can also lead to intestinal obstruction and that viral reactivation in immunocompetent individuals may be associated with inflammatory conditions and viral coinfection, particularly with the novel coronavirus.


Assuntos
Infecções por Citomegalovirus , Enterocolite , Obstrução Intestinal , Infecções Intra-Abdominais , Adolescente , Humanos , Masculino , Colonoscopia , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Enterocolite/complicações , Ganciclovir/uso terapêutico , Infecções Intra-Abdominais/tratamento farmacológico
16.
Int J Colorectal Dis ; 39(1): 79, 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38797803

RESUMO

BACKGROUND: Empty Pelvis Syndrome, subsequent to the removal of pelvic organs, results in the descent of the small bowel into an inflamed pelvic cavity, leading to the formation of adhesions and subsequent small bowel obstruction. However, no effective measures have been previously described. OBJECTIVE: Describe a simple and autologous solution to prevent "Empty Pelvis Syndrome," small bowel obstruction, and adhesions by utilizing the cecum to occlude the pelvis. DESIGN: Mobilization of the right colon to lower the cecum into the pelvic cavity to occlude the superior pelvic ring to some degree and changing the direction of the terminal ileum. SETTINGS: Hospital Universitario Fundación Jiménez Díaz, Department of General Surgery, Colorectal Service. PATIENTS: Eight anonymized patients were included in this study, each with varying colorectal pathologies. Patients were above 18 years old. MAIN OUTCOME MEASURES: Percent of blockage of the superior pelvic ring produced by the descended cecum recorded in percentage; the amount of small intestine descended past the superior pelvic ring recorded in cm. RESULTS: The mobilization of the cecum achieved partial occlusion of the superior pelvic ring. The descent of the small bowel beyond this landmark ranged from 0 to 4.9 cm. LIMITATIONS: Given the small number of patients included in this study, these results cannot be generalized to the whole of the population. A bladder emptying protocol prior to CT scans was not implemented, resulting in variations in measurements among patients. CONCLUSION: The cecum-to-pelvis technique is a simple method that can serve as an autologous solution to EPS (enteropelvic fistula) and help reduce postoperative complications such as SBO (small bowel obstruction) and adhesions. It is not essential to completely occlude the superior pelvic ring to achieve successful outcomes.


Assuntos
Ceco , Pelve , Complicações Pós-Operatórias , Humanos , Ceco/cirurgia , Pelve/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Feminino , Masculino , Pessoa de Meia-Idade , Aderências Teciduais/prevenção & controle , Aderências Teciduais/etiologia , Adulto , Obstrução Intestinal/prevenção & controle , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Idoso
17.
J Gastroenterol Hepatol ; 39(2): 337-345, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37842961

RESUMO

BACKGROUND AND AIM: The PillCam patency capsule (PC) without a radio frequency identification tag was released to preclude retention of the small bowel capsule endoscope (CE) in Japan in 2012. We conducted a multicenter study to determine tag-less PC-related adverse events (AEs). METHODS: We first conducted a retrospective survey using a standardized data collection sheet for the clinical characteristics of PC-related AEs among 1096 patients collected in a prospective survey conducted between January 2013 and May 2014 (Cohort 1). Next, we retrospectively investigated additional AEs that occurred before and after Cohort 1 within the period June 2012 and December 2014 among 1482 patients (Cohort 2). RESULTS: Of the 2578 patients who underwent PC examinations from both cohorts, 74 AEs occurred among 61 patients (2.37%). The main AEs were residual parylene coating in 25 events (0.97%), PC-induced small bowel obstruction, suspicious of impaction, in 23 events (0.89%), and CE retention even after patency confirmation in 10 events (0.39%). Residual parylene coating was significantly associated with Crohn's disease (P < 0.01). Small bowel obstruction was significantly associated with physicians with less than 1 year of experience handling the PC and previous history of postprandial abdominal pain (P < 0.01 and P < 0.03, respectively). CE retention was ascribed to erroneous judgment of PC localization in all cases. CONCLUSIONS: This large-scale multicenter study provides evidence supporting the safety and efficiency of a PC to preclude CE retention. Accurate PC localization in patients without excretion and confirmation of previous history of postprandial abdominal pain before PC examinations is warranted (UMIN000010513).


Assuntos
Endoscopia por Cápsula , Obstrução Intestinal , Polímeros , Xilenos , Humanos , Estudos Retrospectivos , Endoscopia por Cápsula/efeitos adversos , Estudos Prospectivos , Obstrução Intestinal/epidemiologia , Obstrução Intestinal/etiologia , Dor Abdominal/etiologia
18.
J Gastroenterol Hepatol ; 39(2): 353-359, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37897304

RESUMO

BACKGROUND AND AIM: Resection for Crohn's disease (CD) related strictures is definitive but carries risk of morbidity, recurrence, and short bowel syndrome. On the contrary, the durability of endotherapy (ET) for CD-related strictures is questionable. Prospective comparative studies are limited. We aimed to prospectively compare the outcomes of ET in CD strictures with a case-matched surgical therapy (ST) cohort. METHODS: Patients undergoing ET or resection for primary CD strictures (symptomatic, non-traversable, < 5 cm length, n ≤ 3) between January 2021 and March 2022 in a high-volume tertiary center were compared with regard to recurrent symptoms, escalation of therapy, re-intervention, and re-operation based on propensity matched analysis. RESULTS: Fifty-nine patients [49% ET, 57.6% male, median (years): 34 (15-74)] had ≥ 12 months of follow up. Before propensity matching, cumulative re-intervention rate was significantly higher with ET [34.5% (10/29) vs 3.3% (1/30) ST, P = 0.002]. Recurrent symptoms (34.5% vs 26.7%, P = 0.42), escalation of medical therapy (27.5% vs 23.3%, P = 0.64), and re-operation (7.4% vs 3.1%, P = 0.55) were comparable. In propensity matched analysis adjusted for demographics, disease, and stricture characteristics [n = 42, 21 each, 62% male, median (years): 32 (15-60)], cumulative probability of re-intervention rates was higher in ET (28.6% vs 4.8%, P = 0.042). The cumulative probability of recurrent symptoms (ET: 33.3% vs surgery 33.3%, P = 0.93), therapy escalation (ET: 23.8% vs surgery 28.6%, P = 0.75), and re-operation (ET: 9.5% vs surgery 4.8%, P = 0.57) was similar. CONCLUSIONS: ET for CD strictures require higher re-interventions compared with resection although re-operation could be avoided in the majority with comparable symptom free survival at 1 year.


Assuntos
Doença de Crohn , Obstrução Intestinal , Humanos , Masculino , Feminino , Doença de Crohn/complicações , Doença de Crohn/cirurgia , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Estudos Prospectivos , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Resultado do Tratamento , Dilatação , Estudos Retrospectivos , Endoscopia Gastrointestinal
19.
J Pediatr Gastroenterol Nutr ; 78(6): 1261-1272, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38651614

RESUMO

OBJECTIVES: Previous studies have shown rates of surgical resection of up to 41% in stricturing pediatric Crohn's disease (CD). In this retrospective multicenter study, our aims were to identify clinical risk factors and magnetic resonance enterography (MRE) features of small bowel strictures associated with surgery. METHODS: Pediatric patients with symptomatic stricturing small bowel CD (defined as obstructive symptoms or proximal dilatation on MRE) confirmed by MRE between 2010 and 2020 were recruited from 12 French tertiary hospitals. Patient characteristics were compared by surgical outcome multivariable Cox regression. RESULTS: Fifty-six patients (61% boys) aged 12.2 ± 2.7 years at diagnosis of CD were included. Median duration of CD before diagnosis of stricture was 11.7 months (interquartile range [IQR]: 25-75: 1.2-29.9). Nineteen (34%) patients had stricturing phenotype (B2) at baseline. Treatments received  before stricture diagnosis included MODULEN-IBD (n = 31), corticosteroids (n = 35), antibiotics (n = 10), anti-TNF (n = 27), immunosuppressants (n = 28). Thirty-six patients (64%) required surgery, within 4.8 months (IQR: 25-75: 1.8-17.3) after stricture diagnosis. Parameters associated with surgical resection were antibiotic exposure before stricture diagnosis (adjusted odds ratio [aOR]: 15.62 [3.35-72.73], p = 0.0005), Crohn's disease obstructive symptoms score (CDOS) > 4 (aOR: 3.04 [1.15-8.03], p = 0.02) and dilation proximal to stricture >28 mm (aOR: 3.62 [1.17-11.20], p = 0.03). CONCLUSION: In this study, antibiotic treatment before stricture diagnosis, intensity of obstructive symptoms, and diameter of dilation proximal to small bowel stricture on MRE were associated with risk for surgical resection.


Assuntos
Doença de Crohn , Intestino Delgado , Humanos , Doença de Crohn/cirurgia , Doença de Crohn/complicações , Masculino , Estudos Retrospectivos , Feminino , Fatores de Risco , Criança , Intestino Delgado/cirurgia , Intestino Delgado/patologia , Adolescente , Constrição Patológica/etiologia , França , Imageamento por Ressonância Magnética , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia
20.
Colorectal Dis ; 26(5): 851-870, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38609340

RESUMO

AIM: Reporting of participant descriptors in studies of adhesive small bowel obstruction (ASBO) can help identify characteristics associated with favourable outcomes and allow comparison with other studies and real-world clinical populations. The aim was to identify the pattern of participant descriptors reported in studies assessing interventions for ASBO. METHOD: This systematic review was registered with PROSPERO (CRD42021281031) and reported in line with the PRISMA checklist. Systematic searches of Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were undertaken to identify studies assessing operative and non-operative interventions for adults with ASBO. Studies were dual screened for inclusion. Descriptors were categorised into conceptual domains by the research team. RESULTS: Searches identified 2648 studies, of which 73 were included. A total of 156 unique descriptors were identified. On average, studies reported 12 descriptors. The most frequently reported descriptors were sex, age, SBO aetiology, history of abdominal surgery, BMI and ASA classification. The highest number of descriptors in a single study was 34, compared to the lowest number of descriptors which was one. Pathway factors were the least frequently described domain. Overall, 37 descriptors were reported in just one study. CONCLUSION: There is a lack of consistency in participant descriptors reported in studies of SBO. Furthermore, a significant proportion of the descriptors were used infrequently. This makes it challenging to assess whether study participants are representative of the wider population. Further work is required to develop a Core Descriptor Set to standardise the reporting of patient characteristics and reduce heterogeneity between studies.


Assuntos
Obstrução Intestinal , Intestino Delgado , Humanos , Obstrução Intestinal/etiologia , Aderências Teciduais/complicações , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Idoso
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