Itaconate inhibits SYK through alkylation and suppresses inflammation against hvKP induced intestinal dysbiosis.

Hypervirulent Klebsiella pneumoniae (hvKP) is a highly lethal opportunistic pathogen that elicits more severe inflammatory responses compared to classical Klebsiella pneumoniae (cKP). In this study, we investigated the interaction between hvKP infection and the anti-inflammatory immune response gene 1 (IRG1)-itaconate axis. Firstly, we demonstrated the activation of the IRG1-itaconate axis induced by hvKP, with a dependency on SYK signaling rather than STING. Importantly, we discovered that exogenous supplementation of itaconate effectively inhibited excessive inflammation by directly inhibiting SYK kinase at the 593 site through alkylation. Furthermore, our study revealed that itaconate effectively suppressed the classical activation phenotype (M1 phenotype) and macrophage cell death induced by hvKP. In vivo experiments demonstrated that itaconate administration mitigated hvKP-induced disturbances in intestinal immunopathology and homeostasis, including the restoration of intestinal barrier integrity and alleviation of dysbiosis in the gut microbiota, ultimately preventing fatal injury. Overall, our study expands the current understanding of the IRG1-itaconate axis in hvKP infection, providing a promising foundation for the development of innovative therapeutic strategies utilizing itaconate for the treatment of hvKP infections.

Identification of Risk Factors and Phenotypes of Surgical Site Infection in Patients After Abdominal Surgery.

OBJECTIVES: We aimed to determine the current incidence rate and risk factors for surgical site infection (SSI) after abdominal surgery in China and to further demonstrate the clinical features of patients with SSI. BACKGROUND: Contemporary epidemiology and clinical features of SSI after abdominal surgery remain poorly characterized. METHODS: A prospective multicenter cohort study was conducted from March 2021 to February 2022; the study included patients who underwent abdominal surgery at 42 hospitals in China. Multivariable logistic regression analysis was performed to identify risk factors for SSI. Latent class analysis (LCA) was used to explore the population characteristics of SSI. RESULTS: In total, 23,982 patients were included in the study, of whom 1.8% developed SSI. There was a higher SSI incidence in open surgery (5.0%) than in laparoscopic or robotic surgeries (0.9%). Multivariable logistic regression indicated that the independent risk factors for SSI after abdominal surgery were older age, chronic liver disease, mechanical bowel preparation, oral antibiotic bowel preparation, colon or pancreas surgery, contaminated or dirty wounds, open surgery, and colostomy/ileostomy. LCA revealed 4 subphenotypes in patients undergoing abdominal surgery. Types α and ß were mild subclasses with a lower SSI incidence; whereas types γ and δ were the critical subgroups with a higher SSI incidence, but their clinical features were different. CONCLUSIONS: LCA identified 4 subphenotypes in patients who underwent abdominal surgery. Types γ and δ were critical subgroups with a higher SSI incidence. This phenotype classification can be used to predict SSI after abdominal surgery.

Host stimulator of interferon genes is essential for the efficacy of anti-programmed cell death protein 1 inhibitors in non-small cell lung cancer.

The stimulator of interferon genes (STING) pathway is important for anticancer immune responses. However, the relative contributions of host and tumour STING in anti-programmed cell death protein 1 (anti-PD-1) inhibitor responses in non-small cell lung cancer (NSCLC) are unknown. STING expression in tumour and blood was associated with anti-PD-1 therapy in NSCLC patients; Moreover, loss of PD-1 inhibitor therapeutic potency was demonstrated in STING KO (knock out) splenocytes and STING KO mice. STING knock-down in tumour cells had no effect. STING on CD8+ T cells and host cells, not tumour cells, correlated with clinical effect of anti-PD-1 therapy in NSCLC patients. Finally, adoptive transfer of CD8+ T cells restored PD-1 inhibitor anticancer effects. STING in host cells but not in tumour cells mediates anti-PD-1 inhibitor responses in cancer immunotherapy and could be used to select advantageous NSCLC patients from immunotherapy.

Hypertonic saccharide solution delays pyroptosis in murine macrophages regardless of the membrane binding of gasdermin D N-terminal.

Pyroptosis is a type of programmed lytic cell death that could be activated by either the canonical or noncanonical inflammasome pathway. In this study, we aimed to examine the effect of hypertonic solution on noncanonical pyroptosis in macrophage. We found that although hypertonic solution had a general inhibitory effect on noncanonical pyroptosis, the underlying mechanism varied by the solute causing hypertonicity. Specifically, hypertonic NaCl or KCl solution inhibited the cleavage of gasdermin D, the pore-forming protein in pyroptosis, whereas hypertonic saccharide solution did not affect the cleavage or membrane binding of gasdermin D. In this case, nevertheless, pyroptosis was still inhibited as evidenced by the preserved mitochondria activity and cell membrane permeability.

Negative pressure wound therapy for surgical site infections: A systematic review and meta-analysis.

OBJECTIVE: Negative pressure wound therapy is one of the most common treatments for infected wounds. The aim of this meta-analysis was to compare the efficacy of negative pressure wound therapy with conventional treatment methods in the treatment of surgical site infection. DESIGN: This study is registered with International Prospective Register of Systematic Reviews. DATA SOURCES: The Pubmed, Embase and the Cochrane Central Register of Controlled Trials databases were searched. METHODS: The systematic review was searched by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method. All trials reporting the use of negative pressure wound therapy for surgical site infection treatment were included regardless of surgery type. The primary outcome measure was wound healing. Secondary outcomes were length of hospital stay, medical costs, adverse events, and reoperation rates. Results are presented with 95% confidence intervals and report estimates as odds ratios. Heterogeneity was determined through the I2 test, with I2  > 50% indicating substantial heterogeneity and p < .10 significance. The search was performed on 10 March 2020. RESULTS: We identified 13 eligible trial comparisons, of which 2 were randomized controlled trials and 11 cohort study. Negative pressure wound therapy in surgical site infection (SSI) patients significantly increased wound healing rate, accelerated wound healing time, increased daily wound healing area, reduced hospital stay, and reduced adverse events. However, negative pressure wound therapy was associated with increased medical costs. CONCLUSION: Negative pressure wound therapy may be more effective for the treatment of surgical site infection relative to conventional debridement, dressings and other treatments. However, further high-quality randomized controlled trials are needed to determine the most optimal application of negative pressure wound therapy. IMPACT: Negative pressure wound therapy is the best treatment strategy for surgical site infection. This study can improve medical practitioners' awareness of negative pressure wound therapy for surgical site infection, promoting the development of relevant randomized controlled trials.

Diagnosis and Management of Intraabdominal Infection: Guidelines by the Chinese Society of Surgical Infection and Intensive Care and the Chinese College of Gastrointestinal Fistula Surgeons.

The Chinese guidelines for IAI presented here were developed by a panel that included experts from the fields of surgery, critical care, microbiology, infection control, pharmacology, and evidence-based medicine. All questions were structured in population, intervention, comparison, and outcomes format, and evidence profiles were generated. Recommendations were generated following the principles of the Grading of Recommendations Assessment, Development, and Evaluation system or Best Practice Statement (BPS), when applicable. The final guidelines include 45 graded recommendations and 17 BPSs, including the classification of disease severity, diagnosis, source control, antimicrobial therapy, microbiologic evaluation, nutritional therapy, other supportive therapies, diagnosis and management of specific IAIs, and recognition and management of source control failure. Recommendations on fluid resuscitation and organ support therapy could not be formulated and thus were not included. Accordingly, additional high-quality clinical studies should be performed in the future to address the clinicians' concerns.

Incidence and risk factors of surgical site infection following colorectal surgery in China: a national cross-sectional study.

PURPOSES: Surgical site infection (SSI) after colorectal surgery is a frequent complication associated with the increase in morbidity, medical expenses, and mortality. To date, there is no nationwide large-scale database of SSI after colorectal surgery in China. The aim of this study was to determine the incidence of SSI after colorectal surgery in China and to further evaluate the related risk factors. METHODS: Two multicenter, prospective, cross-sectional studies covering 55 hospitals in China and enrolling adult patients undergoing colorectal surgery were conducted from May 1 to June 30 of 2018 and the same time of 2019. The demographic and perioperative characteristics were collected, and the main outcome was SSI within postoperative 30 days. Multivariable logistic regressions were conducted to predict risk factors of SSI after colorectal surgery. RESULTS: In total, 1046 patients were enrolled and SSI occurred in 74 patients (7.1%). In the multivariate analysis with adjustments, significant factors associated with SSI were the prior diagnosis of hypertension (OR, 1.903; 95% confidence interval [CI], 1.088-3.327, P = 0.025), national nosocomial infection surveillance risk index score of 2 or 3 (OR, 3.840; 95% CI, 1.926-7.658, P < 0.001), laparoscopic or robotic surgery (OR, 0.363; 95% CI, 0.200-0.659, P < 0.001), and adhesive incise drapes (OR, 0.400; 95% CI, 0.187-0.855, P = 0.018). In addition, SSI group had remarkably increased length of postoperative stays (median, 15.0 d versus 9.0d, P < 0.001), medical expenses (median, 74,620 yuan versus 57,827 yuan, P < 0.001), and the mortality (4.1% versus 0.3%, P = 0.006), compared with those of non-SSI group. CONCLUSION: This study provides the newest data of SSI after colorectal surgery in China and finds some predictors of SSI. The data presented in our study can be a tool to develop optimal preventive measures and improve surgical quality in China.

Current progress of source control in the management of intra-abdominal infections.

Intra-abdominal infection (IAI) is a deadly condition in which the outcome is associated with urgent diagnosis, assessment and management, including fluid resuscitation, antibiotic administration while obtaining further laboratory results, attaining precise measurements of hemodynamic status, and pursuing source control. This last item makes abdominal sepsis a unique treatment challenge. Delayed or inadequate source control is an independent predictor of poor outcomes and recognizing source control failure is often difficult or impossible. Further complicating issue in the debate is surrounding the timing, adequacy, and procedures of source control. This review evaluated and summarized the current approach and challenges in IAI management, which are the future research directions.

Surgical Site Infection After Gastrointestinal Surgery in China: A Multicenter Prospective Study.

BACKGROUND: There is no nationwide database of information on surgical site infection (SSI) after gastrointestinal surgery in China. This study aimed to determine the incidence of SSI after gastrointestinal surgery in China and evaluate the related risk factors. MATERIALS AND METHODS: The multicenter, prospective, observational study enrolled adult patients who underwent gastrointestinal surgery from May 1, 2018 to June 30, 2018 in 30 hospitals in China. The demographic and perioperative characteristics were collected, and the primary outcome was 30-d SSI. Predictors of SSI were determined by multivariable logistic regressions. Subgroup analysis was performed to determine the predictors of SSI in different surgeries. RESULTS: A total of 1290 patients were enrolled and SSI occurred in 68 patients (5.2%). Multivariate analysis with adjustments revealed that normal body mass index, normal blood glucose level, low national nosocomial infection surveillance risk index score, noncolon surgery, laparoscopic or robotic surgery, and use of mechanical bowel preparation were associated with reduced SSI in gastrointestinal surgery. Subgroup analysis revealed diverse predictors of SSI in diverse surgeries. National nosocomial infection surveillance risk index score of 2 and a high blood glucose level increased the incidence of SSI in colorectal and noncolorectal surgery, respectively. Besides, mechanical bowel preparation and laparoscopic or robotic surgery were protective factors for SSI in colorectal and noncolorectal surgery, respectively. CONCLUSIONS: This study provides the newest data of SSI after gastrointestinal surgery in China and revealed some predictors of SSI in diverse surgeries, which can be a tool to look for areas to target quality improvement initiatives.

Clinical parameters and outcomes of necrotizing soft tissue infections secondary to gastrointestinal fistulas.

BACKGROUND: Necrotizing soft tissue infections (NSTIs) is severe surgical infections which can occur following trauma or abdominal surgery. NSTIs secondary to gastrointestinal (GI) fistula is a rare but severe complication. METHODS: A retrospective cohort study was performed on all subjects presenting with GI fistulas associated NSTIs were included. Clinical characteristics, microbiological profile, operations performed, and outcomes of patients were analyzed. RESULTS: Between 2014 and 2017, 39 patients were finally enrolled. The mean age were 46.9 years and male were the dominant. For the etiology of fistula, 25 (64.1%) of the patients was due to trauma. Overall, in-hospital death occurred in 15 (38.5%) patients. Microbiologic findings were obtained from 31 patients and Klebsiella pneumoniae was the most common species (41.0%). Eight patients were treated with an open abdomen; negative pressure wound therapy was used in 33 patients and only 2 patients received hyperbaric oxygen therapy. Younger age and delayed abdominal wall reconstruction repair were more common in trauma than in non-trauma. Non-survivors had higher APACHE II score, less source control< 48 h and lower platelet count on admission than survivors. Multiple organ dysfunction syndrome, multidrug-resistant organisms and source control failure were the main cause of in-hospital mortality. CONCLUSIONS: Trauma is the main cause of GI fistulas associated NSTIs. Sepsis continues to be the most important factor related to mortality. Our data may assist providing enlightenment for quality improvement in these special populations.

Hybrid material for open abdomen: saving the wound from intestinal fistula.

Treatment of an open abdomen (OA) wound combined with an intestinal fistula is a challenge in the clinic. Here, inspired by the antibacterial activity of graphene (G) and its derivatives, we present a hybrid patch based on the ability of graphene and polycaprolactone (PCL) to kill bacteria and save the cells in a wound. Benefiting from the antibacterial ability of graphene oxide (GO), cells could survive in the presence of bacteria. With the increased ability to protect cells, this patch accelerated wound healing in an OA and intestinal fistula wound model. Additionally, the sub-acute toxicity score showed no extra damage to organs. In conclusion, the employment of the hybrid material for an OA and an intestinal fistula wound healing is encouraging. A hybrid patch based on graphene oxide and polycaprolactone electrospun was generated for open abdomen and fistula wound. The application of the hybrid patch could save the cells from bacteria which contribute to accelerating wound healing.

Risk factors and clinical outcomes of hypervirulent Klebsiella pneumoniae induced bloodstream infections.

The prevalence of hypervirulent Klebsiella pneumoniae (hvKP) is high in China, but clinical characteristics and outcomes of hvKP induced bloodstream infections (BSIs) are not clear. The purpose of the present study was to determine the risk factors and clinical outcomes of hvKP-BSIs in populations admitted in a teaching hospital of Nanjing, China. The genetic characteristics and antibiotic resistance patterns of the hvKP strains were further analyzed. A retrospective study was conducted in 143 patients with K. pneumoniae BSIs at Jinling Hospital in China from September 2015 to December 2016. A positive polymerase chain reaction (PCR) amplification of the plasmid-borne rmpA (p-rmpA) and aerobactin (iucA) was identified as hvKP. Overall, 24.5% (35/143) of K. pneumoniae isolates were hvKP. Multivariate analysis implicated diabetes mellitus (OR = 3.356) and community-acquired BSIs (OR = 4.898) as independent risk factors for hvKP-BSIs. The 30-day mortality rate of the hvKP-BSIs group was 37.1% (13/35) compared with 40.7% (44/108) in the cKP-BSIs control group (P = 0.706). The KPC-producing isolates (OR = 2.851), underlying disease with gastrointestinal fistula (OR = 3.054), APACHE II score ≥ 15 (OR = 6.694) and Pitt bacteremia score ≥ 2 (OR = 6.232) at infection onset were independent predictors for 30-day mortality of K. pneumoniae bacteremia patients. A high percentage (57.1%, 20/35) of KPC-producing isolates was observed among hvKP strains and ST11 was dominant in hvKP strains (17/35, 48.6%). KPC-producing hvKP is emerging, indicating the importance of epidemiologic surveillance and clinical awareness of this pathogen.

A Randomized Control Trial of Preoperative Oral Antibiotics as Adjunct Therapy to Systemic Antibiotics for Preventing Surgical Site Infection in Clean Contaminated, Contaminated, and Dirty Type of Colorectal Surgeries.

BACKGROUND: Preoperative bowel preparation with or without oral antibiotics is controversial in terms of postoperative surgical site infections. OBJECTIVE: This study aimed to evaluate the efficacy of oral antibiotics as adjunct therapy to systemic antibiotics with mechanical bowel preparation for preventing surgical site infections in clean contaminated, contaminated, and dirty colorectal procedures. DESIGN: This was a single-center, prospective randomized study. SETTING: This study was conducted at the General Surgery Department at Jinling Hospital, Nanjing University, China, from July 15, 2014 to January 20, 2016. PATIENTS: Patients aged ≥18 years scheduled for abdominal surgery with clean-contaminated, contaminated, and dirty wounds were selected. INTERVENTIONS: Patients were randomly assigned to receive preoperative mechanical bowel preparation or mechanical bowel preparation with oral antibiotics. MAIN OUTCOMES: The primary outcome was the rate of surgical site infections. The secondary outcomes were extra-abdominal complications, duration of postoperative ileus, and readmission rate. RESULTS: Ninety-five patients were allocated to each group. Eight and 26 surgical site infections (8.42% vs 27.3 %, p = 0.004) occurred in the mechanical bowel preparation with oral antibiotics and mechanical bowel preparation groups. Thirteen extra-abdominal complications were reported: 6 in the mechanical bowel preparation with oral antibiotics group and 7 in the mechanical bowel preparation group (6.3% vs 7.3%, p = 0.77). Postoperative ileus duration did not differ between groups (p = 0.23). There were 4 readmissions in the mechanical bowel preparation group and none in the mechanical bowel preparation with oral antibiotics group (p = 0.04). On multivariable analysis, blood loss ≥500 mL (OR, 5.1; 95% CI, 1.27-20.4; p = 0.02), ASA score ≥3 (OR, 3.9; 95% CI, 1.2-12.5; p = 0.01), contaminated types (OR, 3.6; 95% CI, 1.5-8.6; p = 0.01), and administration of preoperative oral antibiotics (OR, 0.20; 95% CI, 0.06-0.60; p = 0.005) independently affected the incidence of surgical site infections. LIMITATIONS: This was a single-center study. CONCLUSION: Preoperative oral antibiotics, as adjunct therapy to systemic antibiotics and mechanical bowel preparation, significantly reduced surgical site infections and minimized the readmission rates in clean contaminated, contaminated, and dirty types of colorectal surgery. See Video Abstract at http://links.lww.com/DCR/A437.

Shifting trends in bacteriology and antimicrobial resistance among gastrointestinal fistula patients in China: an eight-year review in a tertiary-care hospital.

BACKGROUND: The purpose of this study was to determine the shifting trends in bacteriology and antimicrobial resistance of infectious specimens isolated from gastrointestinal (GI) fistula patients over eight years in China. METHODS: We retrospectively reviewed the microbial records of intra-abdominal specimens at a teaching hospital from 2008 to 2015. Study period was divided into the first half (2008-2011) and the second half (2012-2015). All isolates underwent antibiotic susceptibility testing by the micro dilution method. RESULTS: A total of 874 intra-abdominal isolates were consecutively collected from 502 GI fistula patients (mean age, 46.5 years, 71.1% male) during the study period. Patients in the second study period (2012-2015) were older (>65 years) and more likely to have experienced cancer. Over the entire study period, most infections were caused by E. coli (24.2%) and K. pneumonia (14.1%). There was a significant decrease in the proportion E. coli isolates that were extended- spectrum beta-lactamase (ESBL)-positive (P = 0.026). The proportion of E. coli resistant to imipenem increased from 14.3% in 2008-2011 to 25.9% in 2012-2015 (P = 0.037). Imipenem resistance prevalence was higher in ESBL-negative bacteria than ESBL-positive bacteria for both E. coli and K. pneumonia (P < 0.001). In Enterococcus, significant increase in resistance to ampicillin (P = 0.01) and moxifloxacin (P = 0.02) over time were observed. In Staphylococcus and fungi, rates of antibiotic resistance did not significantly change over the study period. CONCLUSIONS: Gram-negative bacteria predominated as causative agents of intra-abdominal infections in GI fistula patients, and there was an increase in levels of resistance to certain antibiotics, particularly carbapenems. Infection control and source control are important tools available to surgeons to prevent the emergence of antibiotic-resistant pathogens.

Risk factors of surgical site infections in patients with Crohn's disease complicated with gastrointestinal fistula.

PURPOSE: Surgical site infection (SSI) is the most common complication following surgical procedures. This study aimed to determine risk factors associated with SSI in patients with Crohn's disease (CD) complicated with gastrointestinal fistula. METHODS: This was a retrospective review of patients who underwent surgical resection in gastrointestinal fistula patients with CD between January 2013 and January 2015, identified from a prospectively maintained gastrointestinal fistula database. Demographic information, preoperative medication, intraoperative findings, and postoperative outcome data were collected. Univariate and multivariate analysis was carried out to assess possible risk factors for SSI. RESULTS: A total of 118 patients were identified, of whom 75.4% were men, the average age of the patients was 34.1 years, and the average body mass index (BMI) was 18.8 kg/m2. The rate of SSI was 31.4%. On multivariate analysis, preoperative anemia (P = 0.001, OR 7.698, 95% CI 2.273-26.075), preoperative bacteria present in fistula tract (P = 0.029, OR 3.399, 95% CI 1.131-10.220), and preoperative enteral nutrition (EN) <3 months (P < 0.001, OR 11.531, 95% CI 3.086-43.079) were predictors of SSI. Notably, preoperative percutaneous abscess drainage was shown to exert protection against SSI in fistulizing CD (P = 0.037, OR 0.258, 95% CI 0.073-0.920). CONCLUSION: Preoperative anemia, bacteria present in fistula tract, and preoperative EN <3 months significantly increased the risk of postoperative SSI in gastrointestinal fistula complicated with CD. Preoperative identification of these risk factors may assist in risk assessment and then to optimize preoperative preparation and perioperative care.

The Impact of Obesity on the Clinical Course of Inflammatory Bowel Disease: A Meta-Analysis.

BACKGROUND Obesity has been linked with a pro-inflammatory state and the development of inflammatory diseases, including inflammatory bowel disease (IBD). However, there is some controversy regarding whether obesity is associated with an adverse clinical course in patients with IBD. The aim of this meta-analysis was to assess the association between obesity and clinical outcomes in IBD patients. MATERIAL AND METHODS Electronic databases (PubMed, Embase, Cochrane Library, and Web of Science) were systematically searched for studies investigating the association between obesity and clinical outcomes in patients with IBD. A meta-analysis was performed using Review Manager software. RESULTS Among the 4,798 articles identified, seven met the inclusion criteria for our meta-analysis. The pooled data revealed that obese patients were significantly less likely to undergo IBD-related surgery, receive hormone therapy, and experience hospitalization compared with non-obese patients. However, no statistically significant difference was observed in perianal disease, anti-TNF use, and immunomodulator use between the two groups. CONCLUSIONS Our meta-analysis indicated that clinical outcomes were significantly different in obese versus non-obese patients with IBD. We found that obesity was associated with a less severe disease course of IBD. Future prospective studies are needed to confirm the relationship between obesity and the clinical course of IBD.

Association Between Diabetes Mellitus and Outcomes of Patients with Sepsis: A Meta-Analysis.

BACKGROUND Diabetes mellitus (DM) is a critical medical problem that can make people more likely to develop infectious complications, even sepsis. However, the influence of DM on the outcomes of septic patients is still controversial. Thus, we conducted the present meta-analysis to investigate whether DM worsens outcomes of septic patients. MATERIAL AND METHODS We searched studies from PubMed, Embase, and Cochrane Library databases from 1966 to July 1, 2016. The primary outcome we chose was 28-day or 30-day mortality or in-hospital mortality. RESULTS Our meta-analysis of 10 enrolled studies performed between 2000 and 2016 shows that the mortality rate of septic patients with DM was slightly lower than that of non-diabetic patients (risk ratio [RR]=0.97, 95% confidence interval [CI]: 0.96 to 0.98, P<0.00001). On the other hand, septic patients with DM had a shorter hospital stay (weighted mean difference (WMD)=-2.27, 95% CI: -4.11 to -0.44, P=0.01), a higher incidence rate of AKI (RR=1.56, 95% CI: 1.25 to 1.95, P<0.001), and a similar incidence of respiratory dysfunction (RR=0.86, 95% CI: 0.71 to 1.04, P=0.11) compared with those without DM. CONCLUSIONS The results from the meta-analysis suggest that DM does not impair the outcome of patients with sepsis, and the incidence of acute kidney injury increases dramatically in septic patients with DM. Due to the limitations of the analysis, more well-designed trials are still necessary.

Delayed Diagnosis is Associated with Early and Emergency Need for First Crohn's Disease-Related Intestinal Surgery.

BACKGROUND Increasing evidence suggests that delayed diagnosis in Crohn's disease is associated with a complicated disease course. The aim of this study was to explore the association between delayed diagnosis and the timing of the first Crohn's disease-related intestinal surgery. MATERIAL AND METHODS A retrospective study included 215 Crohn's disease patients with previous surgical history in the Department of General Surgery of Jinling Hospital, China, between January 2013 and March 2016. Data were collected on demographics, clinical characteristics, medication history, and operation history. RESULTS The time from the first appearance of Crohn's disease-related symptoms to the first intestinal surgery in the delayed diagnosis group was obviously shorter than in the non-delayed diagnosis group (26.4±28.7 months vs. 42.6±58.4 months, respectively, p=0.032). Patients in the delayed diagnosis group tended to receive more ileal resections (47.8% vs. 26.4%, respectively, p=0.002) and less ileocecal resections (22.4% vs. 37.2%, respectively, p=0.032). More patients in the delayed diagnosis group received the first Crohn's disease-related intestinal surgery as an emergency one (20.9% vs. 4.7%, respectively, p=0.001). CONCLUSIONS Delayed diagnosis is associated with early and emergency need for the first Crohn's disease-related intestinal surgery.

Association between the -159C/T polymorphism in the promoter region of the CD14 gene and sepsis: a meta-analysis.

BACKGROUND: The association between CD14-159C/T polymorphism and sepsis has been assessed but results of current studies appeared conflicting and inconstant. This analysis was aimed to determine whether the CD14-159C/T polymorphism confers susceptibility to sepsis or is associated with increased risk of death from sepsis. METHOD: The authors conducted a comprehensive search of PubMed, EMBASE, ISI Web of Science, Cochrane library, ScienceDirect, Wiley Online Library and CNKI databases according to a prespecified protocol. Language limits were restricted to English and Chinese. Two reviewers independently selected the articles and extracted relevant data onto standardized forms. Disagreements were settled by discussion and suggestions from senior consultants. The strength of association were evaluated by odds ratio (OR) and 95% confidence interval (CI). Studies failed to fit the Hardy-Weinberg-Equilibrium were excluded. RESULTS: The research identified a total of 2317 full-text articles of which 14 articles met the predefined inclusion criteria. Meta-analysis was performed for allele frequency of C versus T, as well as genotypes CC + CT versus TT (dominant model), CC versus TT + CT (recessive model), CT versus TT and CC versus TT (additive model). All control samples were in Hardy-Weinberg proportion. No significant association between CD14-159C/T polymorphism and sepsis susceptibility or mortality were detected in the overall population. Nonetheless, subgroup analysis of Asian ethnicity revealed significant association between the CD14-159C/T polymorphism and susceptibility to sepsis in additive model (CC versus TT: OR = 0.52, 95% CI 0.29-0.92, p = 0.03) and recessive model (CC versus CT + TT: OR = 0.50, 95% CI 0.30-0.84, p = 0.009). Of note, three out of the five papers included in the subgroup focused exclusively on burn ICU patients. CONCLUSIONS: This meta-analysis demonstrated that CD14-159C/T polymorphism is likely to be associated with susceptibility to sepsis in Asian population, especially for the TT genotype. However, bias may rise for etiologic reasons because the majority of subjects in the subgroup came from burn ICU. CD14-159C/T polymorphism is not relevant to sepsis mortality in any genetic models, regardless of the ethnicities. Due to the exploratory nature of the study, no adjustment for multiple testing was adopted, and therefore the results should be interpreted with precaution. Well-designed studies with larger sample size and more ethnic groups are required to further validate the results.