RESUMO
PURPOSE: Colorectal cancer (CRC) is a very common malignancy of the digestive system. Despite a variety of treatments including surgery, chemotherapeutic and targeted drugs, the prognosis for patients with CRC is still unsatisfactory and the mortality remains high. Protein phosphorylation plays an essential role in tumorigenesis and progression and is also crucial for protein to act with proper functions. Ferroptosis is found widely involved in various diseases especially tumors as a newly identified programmed cell death. METHODS: In our study, we aimed at PPP2CA as a prospective target which may play a crucial role in CRC progression. In one hand, knockdown of PPP2CA significantly enhanced the malignant phenotype in HCT116. In the other hand, knockdown of PPP2CA significantly enhanced Erastin-induced ferroptosis as well. RESULTS: Specifically, knockdown of PPP2CA in HCT116 significantly increased the relative level of malondialdehyde (MDA), reactive oxygen species (ROS) and Fe2+, and decreased GSH/GSSG ratio after the treatment of certain concentration of Erastin. Besides, we found that the inhibition of PPP2CA further led to the suppression of SCD1 expression in CRC cells in a AMPK-dependent way. CONCLUSION: Ultimately, we conclude that PPP2CA may regulate Erastin-induced ferroptosis through AMPK/SCD1 signaling pathway.
Assuntos
Proteínas Quinases Ativadas por AMP , Neoplasias Colorretais , Ferroptose , Proteína Fosfatase 2 , Humanos , Ferroptose/efeitos dos fármacos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/tratamento farmacológico , Proteína Fosfatase 2/metabolismo , Proteína Fosfatase 2/genética , Células HCT116 , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Transdução de Sinais , Piperazinas/farmacologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: The present study aimed to evaluate the effect of early enteral nutrition (EEN) after definitive resection of anastomotic leakage (DRAL) resulting from a sigmoid colon or rectal cancer radical resection. METHODS: This was a prospective cohort study performed at our center. From January 2014 to May 2016, every patient received a standard postoperative nutritional protocol (SPNP) after DRAL and was included into SPNP group. From June 2016 to December 2018, all patients received an EEN after DRAL and were included into EEN group. The effect of postoperative EEN was evaluated. RESULTS: There were a final total of 133 patients enrolled in our study. There were 70 patients in the SPNP group, and 63 patients in the EEN group. There were 12 cases (19.05%) with a recurrent leakage in the EEN group, and 28 cases (40%) in the SPNP group. The recurrent rate was associated with EEN (HR = 0.417, 95% CI 0.196-0.890, p = 0.024). The median defecation time in the EEN group was 5(4-7) days, while in the SPNP group was 7(6-8.25) days. The defecation was associated with EEN (HR = 1.588, 95% CI 1.080-2.336, p = 0.019), as well. CONCLUSION: EEN could reduce the recurrent leakage rate and defecation time after definitive resection of anastomotic leakage resulting from sigmoid colon or rectal cancer radical resection.
Assuntos
Neoplasias Colorretais , Procedimentos Cirúrgicos do Sistema Digestório , Fístula Anastomótica/etiologia , Fístula Anastomótica/prevenção & controle , Neoplasias Colorretais/cirurgia , Nutrição Enteral , Humanos , Tempo de Internação , Complicações Pós-Operatórias/prevenção & controle , Estudos ProspectivosRESUMO
PURPOSE: The purpose of this study is to investigate the effects of different preoperative enteral nutrition feeding routes on the duration of gastrointestinal decompression after definitive surgery for small intestinal fistula. METHODS: From January 2015 to June 2019, patients with small intestinal fistula and receiving a definitive surgery were enrolled. According to the feeding route, patients were divided into a nasointestinal tube group and a nasogastric tube group. Clinical characteristics of the two groups were analyzed, and the influence of the two route on the recovery of gastrointestinal function was evaluated. RESULT: A total of 151 patients were enrolled in our study. There were 49 patients in the nasogastric tube group, and 102 patients in the nasointestinal tube group. Enteral nutrition via nasogastric feeding route had a positive effect on shortening the duration of gastrointestinal decompression (adjusted HR = 2.488, 95% CI: 1.692-3.659, P < 0.001). After propensity matching (PM), 44 patients were enrolled (22 vs 22). EN via nasogastric tube was a positive factor for getting rid of gastrointestinal decompression (adjusted HR = 3.563, 95% CI: 1.639-7.746, P = 0.001). CONCLUSION: Preoperative enteral nutrition via nasogastric route can reduce the duration of gastrointestinal decompression after definitive surgery for small intestinal fistula.
Assuntos
Nutrição Enteral , Fístula Intestinal , Descompressão , Humanos , Intubação Gastrointestinal , Estado NutricionalRESUMO
BACKGROUND: To evaluate an innovative open necrosectomy strategy with continuous positive drainage and prophylactic diverting loop ileostomy for the management of late infected pancreatic necrosis (LIPN). METHODS: Consecutive patients were divided into open necrosectomy (ON) group (n = 23), open necrosectomy with colonic segment resection (ON+CSR) group (n = 8) and open necrosectomy with prophylactic diverting loop ileostomy (ON+PDLI) group (n = 11). Continuous positive drainage (CPD) via double-lumen irrigation-suction tube (DLIST) was performed in ON+PDLI group. The primary endpoints were duration of organ failure after surgery, postoperative complication, the rate of re-surgery and mortality. The secondary endpoints were duration of hospitalization, cost, time interval between open surgery and total enteral nutrition (TEN). RESULTS: The recovery time of organ function in ON+PDLI group was shorter than that in other two groups. Colonic complications occurred in 13 patients (56.5%) in the ON group and 3 patients (27.3%) in the ON+PDLI group (p = 0.11). The length of stay in the ON+PDLI group was shorter than the ON group (p = 0.001). The hospitalization cost in the ON+PDLI group was less than the ON group (p = 0.0052). CONCLUSION: ON+PDLI can avoid the intestinal dysfunction, re-ileostomy, the resection of innocent colon and reduce the intraoperative trauma. Despite being of colonic complications before or during operation, CPD + PDLI may show superior effectiveness, safety, and convenience in LIPN.
Assuntos
Infecções Intra-Abdominais , Pancreatite Necrosante Aguda , Drenagem , Humanos , Ileostomia/efeitos adversos , Pancreatite Necrosante Aguda/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: This study aimed to investigate the transcatheter arterial embolization (TAE) in treatment of abdominal bleeding in patients being treated with open abdomen due to duodenal fistula. METHODS: This was a retrospective study performed at our center. From January 2005 to November 2010, all patients with abdominal bleeding were treated with surgical hemostasis (SH) and included in SH group. From January 2012 to December 2018, all patients with a bleeding were treated with TAE and included in the TAE group. Clinical data were reviewed and compared between the two groups. The effect of TAE in the management of abdominal bleeding was evaluated. RESULTS: A total of 131 patients were enrolled, and there were 64 in the SH group and 67 in the TAE group. The success rate of hemostasis was higher in the TAE group (89.55% vs. 73.44%, adjusted OR = 4.065, 95% CI 1.336-12.336, P = 0.013). Moreover, the recognition rate of hemorrhagic vessels in the TAE group was higher (91.04 vs. 51.56; P < 0.001). The re-bleeding occurred in 20 patients, 7(11.67%) in the TAE group and 13(27.66%) in the SH group. The re-bleeding rate in SH group was higher (adjusted HR = 2.564, 95% CI 1.023-6.428, P = 0.045) CONCLUSIONS: TAE is an effective method in treatment of abdominal bleeding in patients being treated with open abdomen due to duodenal fistula.
Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Embolização Terapêutica , Hemostasia Cirúrgica , Fístula Intestinal/cirurgia , Cavidade Abdominal , Adulto , Feminino , Humanos , Fístula Intestinal/etiologia , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND Prevalence and associated risk factors for pressure ulcers (PU) vary in different body areas and diseases. Few studies have focused on PU in patients with enterocutaneous fistula (ECF). The aim of the present study was to investigate the prevalence and risk factors for PU in patients with ECF. MATERIAL AND METHODS From January 2016 to June 2016, medical records of 140 patients with ECF who were transferred to the Enterocutaneous Fistula Treatment Center, Jinling Hospital, were reviewed and analyzed. The prevalence of PU was investigated. To evaluate the risk factors for PU in patients with ECF, 5 patients with PU before admission were excluded, and the remaining 135 patients were divided into 2 groups: the PU group and the non-PU group. The risk factors for PU were confirmed by multivariate logistic regression analysis of characteristics on admission. RESULTS There were 42 cases with PU (5 cases with PU before admission, 37 cases with PU in the treatment after admission), and the prevalence of PU in patients with ECF was 30%. In addition, Braden risk score <19 (OR=9.33, CI: 2.80-31.08, p<0.001); underweight (BMI<18.5) (OR=5.21, CI: 1.65-16.39, p=0.005); onset of duodenal fistula (OR=4.86, CI: 1.33-17.78, p=0.017); diabetes (OR=4.95, CI: 1.03-23.85, p=0.046); and APACHE II score (OR=1.34, CI: 1.04-1.72, p=0.019) were associated with PU. CONCLUSIONS The PU prevalence was 30% in patients with ECF. Braden risk score <19, underweight, onset of duodenal fistula, diabetes, and APACHE II score were risk factors for PU in patients with ECF.
Assuntos
Fístula Intestinal/complicações , Fístula Intestinal/fisiopatologia , Úlcera por Pressão/etiologia , Adolescente , Adulto , Idoso , Povo Asiático/genética , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND Abdominal bleeding is a severe complication of duodenal fistula, but few studies have focused on this problem. The purpose of the present study was to investigate the prevalence of and risk factors for intra-abdominal bleeding in patients with external duodenal fistula. MATERIAL AND METHODS From January 2014 to December 2016, medical records of 97 patients with external duodenal fistula were retrospectively reviewed and analyzed. The prevalence and risk factors for intra-abdominal bleeding were evaluated. RESULTS The prevalence of abdominal bleeding in patients with external duodenal fistula was 31.9% (95%CI: 22.5-41.4%). A total of 31 patients had intra-abdominal bleeding. Results revealed that acute kidney failure (OR: 8.462, 95% CI: 1.921-37.28, p=0.005) and retroperitoneal infection (OR: 5.373, 95% CI: 1.504-19.197, p=0.010) were associated with abdominal bleeding. CONCLUSIONS The prevalence of abdominal bleeding in patients with external duodenal fistula was 31.9%, and acute kidney failure and retroperitoneal infection were found to be risk factors for intra-abdominal bleeding.
Assuntos
Hemorragia/etiologia , Fístula Intestinal/complicações , Fístula Intestinal/etiologia , Abdome , Traumatismos Abdominais/etiologia , Injúria Renal Aguda , Adulto , Idoso , Fístula Cutânea/complicações , Fístula Cutânea/etiologia , Duodeno/fisiopatologia , Feminino , Humanos , Fístula Intestinal/sangue , Masculino , Metrorragia , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Monocyte subsets and monocyte-platelet aggregates (MPAs) play important roles in inflammation. AIM: To evaluate the association between the three human monocyte subsets and their contributions to MPAs and mortality among septic patients. METHODS: Consecutive septic patients were enrolled in. Age- and gender-matched nonseptic patients were recruited as control patients. Monocyte subsets and monocyte-platelet aggregates were determined by flow cytometric analysis. RESULTS: Elevated percentage of MPAs (MPAs%) was associated with an increased risk of mortality. CONCLUSIONS: This study demonstrated increased MPAs% enables the identification of a group of septic patients at high risk of death.
Assuntos
Monócitos/fisiologia , Sepse/sangue , Adulto , Estudos de Casos e Controles , Agregação Celular , Estado Terminal , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sepse/mortalidadeRESUMO
BACKGROUND: The nonthyroidal illness syndrome (NTIS) is prevalent among patients with enterocutaneous fistula and is associated with poor outcomes. The present study aimed to explore the role of enteral nutrition (EN) therapy on thyroid function among patients with enterocutaneous fistula and NTIS. METHODS: We conducted a retrospective observational study among patients with enterocutaneous fistula between January 2013 and April 2014. All enrolled patients received EN therapy. Thyroid function and other parameters were measured. RESULTS: After administration of 4 weeks of EN therapy, NTIS was resolved in 66 patients (Group A), while it persisted in 14 patients (Group B). The overall treatment success rate was 82.50 %. There were no significant differences between groups A and B at baseline for all parameters, except for the time from admission to start of EN therapy. The logistic analysis revealed that the time from admission to start of EN therapy was a significant independent indicator for achieving resolution of NTIS in our cohort. CONCLUSIONS: This retrospective observational cohort study demonstrated that EN therapy can aid in the resolution of NTIS among patients with enterocutaneous fistula. These findings confirm the benefit of EN in the treatment of enterocutaneous fistula.
Assuntos
Fístula Cutânea/terapia , Nutrição Enteral , Síndromes do Eutireóideo Doente/terapia , Fístula Intestinal/terapia , Fístula Cutânea/patologia , Síndromes do Eutireóideo Doente/fisiopatologia , Feminino , Humanos , Fístula Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND AND AIM: The open abdomen (OA) is associated with significant morbidity and mortality, and its management poses a formidable challenge. Inability to achieve primary closure of the abdominal wall is one of the most severe complications of this technique. Factors influencing primary fascial closure, however, are unknown. This study aims to explore the influence of fluid volume overload on the application of vacuum-assisted and mesh-mediated fascial traction (VAWCM) in OA treatment. METHODS: A review of patients undergoing OA management using VAWCM technique from January 2006 to November 2011 was performed. Patients with aged <18 y OA treatment for fewer than 5 d and abdominal wall hernia before OA treatment were excluded. RESULTS: Average age was 45 ± 10.1 y and average OA treatment time was 31 ± 6.8 d. The complete fascial closure rate was 60%. The overall mean bodyweight-based fluid overload was 7.2 kg (range: -8.0 to +21.6 kg), representing a mean percent weight gain of 11.5% (range: -9.5% to +27%). Patients with fluid-related weight gain ≥10% had a lower primary facial closure rate than those with <10% (39% versus 77%). And primary facial closure rate seems to further decrease with fluid-related weight gain ≥20%, suggesting a dose-response effect of progressive fluid accumulation. CONCLUSIONS: The VAWCM method provided a high primary fascial closure rate after long-term treatment of OA. Fluid volume overload negatively influences delayed primary facial closure. Judicious intravenous fluid resuscitation should be advocated in the therapy of critically ill patients.
Assuntos
Técnicas de Fechamento de Ferimentos Abdominais , Fasciotomia , Hidratação/efeitos adversos , Hérnia Ventral/cirurgia , Tratamento de Ferimentos com Pressão Negativa , Desequilíbrio Hidroeletrolítico/complicações , Cicatrização/fisiologia , APACHE , Abdome/cirurgia , Adulto , Fáscia/fisiologia , Feminino , Hérnia Ventral/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/mortalidade , Pancreatite/cirurgia , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/terapia , Estudos Retrospectivos , Telas Cirúrgicas , Desequilíbrio Hidroeletrolítico/mortalidadeRESUMO
BACKGROUND/AIMS: Long intestinal tube splinting (LITS) is a strategy that helps to reduce the recurrence of adhesive small bowel obstruction (ASBO) by fixing the bowel to ensure a favorable lie. Even though anterograde LITS is favored by most surgeons, its postoperative complications are noteworthy. Retrograde LITS was hardly reported in previous studies. METHODOLOGY: A retrospective analysis was performed on all patients who had retrograde LITS for postoperative ASBO between December 2001 and 2008 at our unit. Medical records were reviewed. Patients were followed up by telephone to identify recurrent ASBO. RESULTS: There were 162 patients received retrograde LITS. The overall complication rate was 8%, and the tube splinting complication rate was 0.6%. The average length of follow-up was 75±28.1 months (from 5 to 131 months). The incidence of recurrent ASBO was 5.4%. CONCLUSIONS: The results show that retrograde LITS is an effective method for preventing recurrent ASBO. Its overall complication rate and tube splinting rate are lower than anterograde LITS.
Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Obstrução Intestinal/cirurgia , Intestino Delgado/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/instrumentação , Desenho de Equipamento , Feminino , Humanos , Obstrução Intestinal/diagnóstico , Intestino Delgado/patologia , Masculino , Pessoa de Meia-Idade , Recidiva , Reoperação , Estudos Retrospectivos , Contenções , Fatores de Tempo , Aderências Teciduais , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Intra-abdominal abscess is a common complication in Crohn's disease (CD). Traditional percutaneous catheter drainage (PCD) and surgical intervention could not obtain satisfactory results in some cases. We herein demonstrate a novel management option and compare it with traditional strategies. METHODS: A total of 77 patients were retrospectively collected into 3 groups. Postoperative complication, postoperative recurrence of abscess, subsequent surgery, ultimate stoma creation rate, and survival rate were analyzed. RESULTS: Patients were divided into the trocar group (n = 21), PCD group (n = 25), and surgery group (n = 31). The incidences of postoperative complication as well as the incidence of recurrent abscess were lowest in trocar group, and ultimate stoma creation rate was highest in the surgery group. Subsequent surgery after initial intervention and survival rate during the follow-up period were similar among the 3 groups. CONCLUSIONS: Trocar puncture with sump drain had lower incidence of postoperative complication, postoperative recurrence of abscess, and ultimate stoma creation compared with conventional PCD and surgical interventions. This novel technique might be an optimal option in the management of intra-abdominal abscesses in CD.
Assuntos
Abscesso Abdominal/etiologia , Abscesso Abdominal/cirurgia , Doença de Crohn/complicações , Drenagem/métodos , Adolescente , Adulto , Drenagem/efeitos adversos , Drenagem/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Instrumentos Cirúrgicos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: This study was designed to develop and validate a nomogram for predicting intolerable early enteral nutrition (EEN) following definitive surgery (DS) for small intestinal fistula. METHODS: A total of 377 patients, recruited from January 2016 to September 2023, was randomly allocated into development (n=251) and validation (n=126) groups in a 2:1 ratio. Risk factors were identified using the nomogram. Its performance was assessed based on calibration, discrimination, and clinical utility, with validation confirming its effectiveness. RESULTS: Of the 377 patients, 87 (23.1%) were intolerant to EEN, including 59 (23.1%) in the development cohort and 28 (22.1%) in the validation cohort (P=0.84). Four factors were identified as predictive of intolerable EEN: severe abdominal adhesion, deciliter of blood loss during DS, human serum albumin (Alb) input >40 g during and within 48 hours post-DS, and the visceral fat area (VFA)/total abdominal muscle area index (TAMAI) ratio. The model demonstrated excellent discrimination, with a C-index of 0.79 (95% CI, 0.74-0.87, including internal validation) and robust calibration. In the validation cohort, the nomogram showed strong discrimination (C-index=0.77; 95% CI, 0.64-0.87) and solid calibration. Decision curve analysis affirmed the nomogram's clinical utility. CONCLUSION: This research introduces a nomogram that enables the individualized prediction of intolerable EEN following DS for small intestinal fistula, demonstrating a possible clinical utility.
RESUMO
Abdominal adhesions manifests following abdominal infections triggered by intestinal fistulas. The severity of such adhesions depends on the extent of fiber deposition and peritoneal fibrinolysis following peritoneal injury, which may be influenced by sustained inflammation within the abdominal cavity. In this regard, the visceral-to-subcutaneous fat area (VFA/SFA) ratio has been implicated as a potential marker of inflammation. This study aimed to explore the relationship between VFA/SFA and abdominal adhesions. This multicenter study was conducted across four tertiary institutions and involved patients who had undergone definitive surgery (DS) for intestinal fistula from January 2009 and October 2023. The presence of abdominal adhesions was determined intraoperatively. VFA/SFA was investigated as a potential risk factor for severe adhesions. The study comprised 414 patients with a median age of 50 [interquartile range (IQR) 35-66] years and a median body mass index of 20.0 (IQR 19.2-22.4) kg/m2, including 231 males with a median VFA/SFA of 1.0 (IQR 0.7-1.2) and 183 females a median VFA/SFA of 0.8 (0.6-1.1). VFA/SFA was associated with severe abdominal adhesions in males [odds ratio (OR) = 3.34, 95% CI 1.14-9.80, p = 0.03] and females (OR = 2.99, 95% CI 1.05-8.53, p = 0.04). J-shaped association between VFA/SFA ratio and severe adhesions was revealed in both sex. The increasing trend can be revealed when OR more than 0.8, and 0.6 in males and females respectively. Preoperative VFA/SFA demonstrates predictive value for statues of severe abdominal adhesions in DS for anastomotic fistula after small intestine resection.
Assuntos
Fístula Intestinal , Intestino Delgado , Gordura Intra-Abdominal , Gordura Subcutânea , Humanos , Masculino , Feminino , Aderências Teciduais/etiologia , Aderências Teciduais/patologia , Pessoa de Meia-Idade , Idoso , Adulto , Intestino Delgado/cirurgia , Intestino Delgado/patologia , Gordura Subcutânea/patologia , Fístula Intestinal/etiologia , Fístula Intestinal/cirurgia , Complicações Pós-Operatórias/etiologia , Fatores de RiscoRESUMO
BACKGROUND: Gut barrier failure caused by endotoxemia is a life-threatening problem. The present study aimed to determine whether any specific intestinal site is highly correlated with gut barrier failure, and whether recombinant human growth hormone (rhGH) can ameliorate gut barrier failure in a rat model of endotoxemia. METHODS: Enterostomy tubes were surgically placed in adult male Sprague-Dawley rats three days before induction of endotoxemia by lipopolysaccharide (LPS) injection. Controls received no LPS. Rats were then randomly assigned to receive subcutaneous injections of rhGH (experimental, n = 30) or 0.9 % saline (control, n = 15) at 24, 48, or 72 h after LPS injection. Escherichia coli labeled with green fluorescent protein (GFP) were injected into the intestinal segment of all rats through the enterostomy tubes. The number of GFP-labeled E. coli detected in mesenteric lymph nodes was examined after 96 h. Apoptosis and proliferation rates of intestinal epithelial cells, and intestinal permeability were measured. RESULTS: Endotoxemia led to high mortality, compared with the control group, and rhGH treatment did not improve survival. Intestinal permeability, reflected by translocation rates of GFP-labeled E. coli, and apoptosis rates in the LPS-induced endotoxemia group were higher than those in the non-endotoxemia control group, and the endotoxemia ileum group had the highest rates of both bacterial translocation and apoptosis. The LPS+GH group had less bacterial translocation and apoptosis than the LPS-induced endotoxemia group. In contrast, the proliferation rates were lower in the LPS group compared to the LPS+GH group. CONCLUSIONS: Endotoxemia can induce gut barrier failure in rats, and the ileum is the site of greatest risk. The GH can reduce the incidence of endotoxemia-induced gut barrier failure, but not the associated mortality.
Assuntos
Endotoxemia/tratamento farmacológico , Infecções por Escherichia coli/tratamento farmacológico , Hormônio do Crescimento Humano/uso terapêutico , Intestinos/efeitos dos fármacos , Animais , Apoptose , Translocação Bacteriana , Endotoxemia/metabolismo , Endotoxemia/microbiologia , Endotoxemia/patologia , Escherichia coli/fisiologia , Infecções por Escherichia coli/metabolismo , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/patologia , Hormônio do Crescimento Humano/farmacologia , Mucosa Intestinal/metabolismo , Intestinos/microbiologia , Intestinos/patologia , Lipopolissacarídeos , Linfonodos/microbiologia , Masculino , Permeabilidade/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêuticoRESUMO
BACKGROUND: Omega-3 fatty acid (ω-3 FA) lipid emulsion has been reported to inhibit nitric oxide (NO) production and alter inducible nitric oxide synthase (iNOS) protein expression in lipopolysaccharide (LPS)-stimulated murine macrophages. However, the role of cellular uptake of l-arginine and iNOS transcription in ω-3 FA emulsion-induced inhibition of NO has not been explored. In addition, cationic amino acid transporter-2 (CAT-2) can regulate iNOS activity. The effect of ω-3 FA emulsion on CAT-2 expression is unknown. In the present study, we hypothesized that ω-3 FA emulsion pretreatment would decrease the production of NO in LPS-stimulated macrophages and that this effect would occur through alterations in the cellular uptake of l-arginine and CAT-2 expression, in addition to iNOS expression. METHODS: Confluent immortalized murine macrophages (RAW264.7cells) were incubated with Dulbecco's modiï¬ed Eagle's medium, ω-3 FA emulsion, or an isoenergetic ω-6 lipid emulsion for 4 h. The cells were washed and then stimulated with LPS (1 µg/mL) or media alone for 12 or 24 h before harvesting. Greiss reagent was used to assess NO production of plate well supernatants. Cellular uptake of l-arginine was assessed through [(3)H]-l-arginine. The expression of iNOS and CAT-2 mRNA in harvested RAW264.7 was quantified by reverse transcriptase-polymerase chain reaction. RESULTS: NO production of unstimulated RAW264.7 cells was similar in all groups. After LPS stimulation, ω-3 FA pretreatment at 12 and 24 h produced significantly less NO (P < 0.05) compared with ω-6 FA or media only. ω-3 FA pretreatment at 12 and 24 h resulted in less l-arginine uptake. iNOS and CAT-2 mRNA was significantly decreased with ω-3 FA pretreatment compared with ω-6 FA or media-only treatment (P < 0.05). CONCLUSIONS: These experiments demonstrated that, in addition to other anti-inflammatory effects, ω-3 FA lipid emulsion also significantly lowers NO production and l-arginine transport through altered expression of iNOS and CAT-2 in LPS-stimulated RAW264.7 macrophage cells.
Assuntos
Arginina/metabolismo , Transportador 2 de Aminoácidos Catiônicos/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Óxido Nítrico/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Transporte Biológico/fisiologia , Linhagem Celular , Emulsões , Ácidos Graxos Ômega-6/farmacologia , Macrófagos/citologia , Camundongos , Óxido Nítrico Sintase Tipo II/metabolismo , RNA Mensageiro/metabolismoRESUMO
PTGS2 genetic 3' untranslated region (3'UTR) miRNA binding sites variants are significantly associated with cancer risk; however, the roles of genetic variants in PTGS2 gene 3'UTR and post-transcriptional regulation have not been elucidated. We report that rs689470 and rs5275 in the PTGS2 3'UTR have potential miRNA-binding sites by using bioinformatics analysis. However, only the rs689470 was significantly associated with PTGS2 mRNA expression in lymphoblastoid cell lines (P = 0.026), but not for rs5275 (P = 0.626). rs689470 might be putative variants mediating the post-transcriptional regulation of target PTGS2 gene. Better understanding of how 3'UTR variants regulate PTGS2 activity will pave the way to targeting the PTGS2 pathway in cancer therapy.
Assuntos
Ciclo-Oxigenase 2/genética , RNA Mensageiro/metabolismo , Regiões 3' não Traduzidas , Sítios de Ligação , Linhagem Celular Tumoral , Biologia Computacional , Ciclo-Oxigenase 2/metabolismo , Bases de Dados Factuais , Feminino , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , MicroRNAs/metabolismo , Fenótipo , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologiaRESUMO
GOALS: This study was designed to investigate the clinical features of nonthyroidal illness syndrome (NTIS) compared with euthyroid patients in Crohn's disease (CD), to explore the etiology of NTIS in CD, to evaluate the clinical outcomes of NTIS patients, and to inspect the correlation of clinical variables and NTIS, and their ability of differentiating NTIS from euthyroid patients. BACKGROUND: NTIS has been described for more than 30 years. However, only few studies focused on the relationship between NTIS and CD. The incidence, underlying pathogenesis, clinical outcomes, and correlation with other inflammatory disease severity and nutritional variables of NTIS in CD have not been completely established. METHODS: Prospectively, 44 CD patients were enrolled. Medical records and various laboratory values (including thyroidal, nutritional, and inflammatory variables) were collected in all participants. RESULTS: The incidence of NTIS in CD was 36.4%. Albumin, Acute Physiology and Chronic Health Evaluation II score, and Crohn's Disease Activity Index score in NTIS group were statistically different from those in euthyroid group. A decreased sum activity of deiodinases and a reduced ratio of TT4/FT4 were observed in NTIS group. Duration of hospitalization was significantly longer for NTIS patients than euthyroid patients. Albumin was confirmed as a protective factor of NTIS in CD. Receiver operating characteristic curve analysis demonstrated the differentiating capacity of albumin, suggesting 37.6 g/L as optimal cut-off value with sensitivity and specificity of 81.3% and 79.2%, respectively. CONCLUSIONS: NTIS was a common complication in CD. NTIS patients showed worse nutrition status and clinical outcome, and more critical disease activity and severity compared with euthyroid patients. A hypodeiodination condition and a potential thyroid-hormone-binding dysfunction may play a role in the etiology of NTIS in CD. Albumin was a meaningful protective and distinguishing marker of NTIS in CD.
Assuntos
Doença de Crohn/complicações , Síndromes do Eutireóideo Doente/etiologia , APACHE , Adulto , Biomarcadores/sangue , Distribuição de Qui-Quadrado , China , Cuidados Críticos , Doença de Crohn/sangue , Doença de Crohn/diagnóstico , Doença de Crohn/fisiopatologia , Doença de Crohn/terapia , Progressão da Doença , Síndromes do Eutireóideo Doente/sangue , Síndromes do Eutireóideo Doente/diagnóstico , Síndromes do Eutireóideo Doente/fisiopatologia , Síndromes do Eutireóideo Doente/terapia , Feminino , Hospitalização , Humanos , Incidência , Tempo de Internação , Modelos Logísticos , Masculino , Estado Nutricional , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Curva ROC , Respiração Artificial , Fatores de Risco , Sensibilidade e Especificidade , Albumina Sérica/análise , Albumina Sérica Humana , Índice de Gravidade de Doença , Hormônios Tireóideos/sangue , Fatores de TempoRESUMO
BACKGROUND: In patients diagnosed with sarcopenia, the presence of chronic preoperative inflammation, assessed by the ratio of the visceral fat area (VFA) to the total abdominal muscle area index (TAMAI) (VFA/TAMAI), has been found to adversely affect wound healing. An elevated VFA/TAMAI may contribute to a higher incidence of postoperative recurrent fistulas (RFs) following definitive surgery (DS) for small intestinal fistulas accompanied by diffuse extensive abdominal adhesions. The objective of this study was to evaluate the predictive value of VFA/TAMAI for postoperative RFs. METHODS: The study enrolled 183 sarcopenic patients, with a median age of 51 years [interquartile range (IQR): 38-61 years), a median body mass index of 19.6 kg/m 2 (IQR: 18.9-21.0 kg/m 2 ) who underwent DS for small intestinal fistulas between January 2018 and October 2022 were included in the multicenter study. The outcomes assessed were RFs and postoperative length of stay (LOS). VFA/TAMAI was examined as a potential risk factor for each outcome. RESULTS: Out of the 183 patients, 20.2% ( n =37) developed RFs. The multivariate regression analysis identified VFA/TAMAI as the sole factor associated with RFs [odds ratio=1.78, 95% confidence interval (CI): 1.09-2.87, P =0.02]. The multivariable Cox regression analysis demonstrated that an elevated VFA/TAMAI was linked to a reduced postoperative LOS (hazard ratio=0.69, 95% CI: 0.59-0.81, P <0.001). CONCLUSION: In sarcopenic patients, a high VFA/TAMAI predicated the occurrence of RFs after DS for small intestinal fistulas in the presence of diffuse extensive abdominal adhesions.
Assuntos
Fístula Intestinal , Sarcopenia , Humanos , Pessoa de Meia-Idade , Estudos de Coortes , Sarcopenia/complicações , Gordura Intra-Abdominal/cirurgia , Gordura Intra-Abdominal/patologia , Estudos Retrospectivos , Fatores de Risco , Complicações Pós-Operatórias/epidemiologia , Índice de Massa Corporal , Músculos Abdominais , Fístula Intestinal/etiologia , Fístula Intestinal/cirurgiaRESUMO
OBJECTIVE: To explore the surgical approaches and clinical outcomes of chronic radiation intestinal injury (CRII). METHODS: From January 1, 2001 to December 31, 2010, at Department of Surgery, Nanjing General Hospital of Nanjing Command a consecutive series of 206 CRII patients undergoing surgical interventions was reviewed retrospectively. There were 64 males and 142 females with an age range of (50 ± 11) years old. The indications, surgical approaches, surgical complications and mortality were analyzed. RESULTS: 206 CRII patients received 229 surgical treatment, 31 patients underwent two or more operations. The course of surgical interventions included intestinal obstruction (n = 142), intestinal fistula (n = 56), proctitis (n = 12), bleeding (n = 6) and others (n = 13). They underwent 229 laparotomies including intestinal resection and primary anastomosis (n = 142), intestinal resection and enterostomy (n = 57), exclusion of radiation-related gastrointestinal diseases (n = 14) and other procedures (n = 16). The occurrence rate of postoperative intestinal complications was 25.7% (53/206). Five patients (2.4%) died within the postoperative 28 days. CONCLUSION: Surgery is often required for patients with chronic radiation-induced intestinal obstruction, fistula, hemorrhage and perforation, etc. Resection and primary anastomosis with undamaged segments may be performed safely in selected patients. And a judicious use of stoma can reduce the rates of major surgical mortality and morbidity.