PMN-MDSC:A Culprit Behind Immunosenescence and Increased Susceptibility to Clostridioides difficile Infection During Aging

Susceptibility to pathogens in the elderly is heightened with age,largely because of immunosenescence.As an immune regulatory organ,bone marrow creates immune cells that move to other organs and tis-sues through the blood.Despite the significance of this process of this organ,there is limited research on changes in immune cell generation in the bone marrow and their effects on immunosenescence.In this study,the compositions of immune cells in bone marrow from young(three months)and old(24+months)mice were compared by means of mass cytometry,with further validation obtained through the reanalysis of single-cell RNA sequencing data and cell sorting via flow cytometry.The effects of differential immune cells on immunosenescence in old mice were evaluated using the Clostridium difficile(C.difficile)infection model.Our results showed that aged mice presented with a reduction in bone tra-beculae structure,which was accompanied by a notable increase in polymorphonuclear(PMN)-myeloid-derived suppressor cell(MDSC)abundance.Through bulk-seq and reverse transcription quantitative polymerase chain reaction(RT-qPCR)analysis,we identified differential genes associated with the immune response—specifically,the Th17 cell differentiation pathway.Furthermore,the increase in exported PMN-MDSCs to the large intestine resulted in increased gut permeability and inflammatory damage to the colon following C.difficile infection.After clearing the PMN-MDSCs in old mice using the anti-Gr-1 antibody,the symptoms induced by C.difficile were significantly relieved,as evidenced by an inhibited IL-17 pathway in the colon and reduced gut permeability.In conclusion,aging increases the number of PMN-MDSCs in both the generated bone marrow and the outputted intestine,which con-tributes to susceptibility to C.difficile infection.This study provides a novel target for anti-aging therapy for immunosenescence,which is beneficial for improving immune function in elders.

Clostridium difficile infection following colon subtotal resection in a patient with gallstones: A case report and review of literature

BACKGROUND Clostridium difficile(C.difficile)infection(CDI)is a rare clinical disease caused by changes in the intestinal microenvironment,which has a variety of causes and a poor prognosis,and for which there is no standardized clinical treatment.CASE SUMMARY A patient experienced recurrent difficulty in bowel movements over the past decade.Recently,symptoms worsened within the last ten days,leading to a clinic visit due to constipation.The patient was subsequently referred to our depart-ment.Preoperatively,the patient was diagnosed with obstructed colon accom-panied by gallstones.Empirical antibiotics were administered both before and after surgery to prevent infection.On the fourth day post-surgery,symptoms of CDI emerged.Stool cultures confirmed the presence of C.difficile DNA.Treatment involved a combination of vancomycin and linezolid,resulting in the patient's successful recovery upon discharge.However,the patient failed to adhere to the prescribed medication after discharge and was discovered deceased during a follow-up two months later.CONCLUSION CDI is the leading cause of nosocomial post-operative care,with limited clinical cases and poor patient prognosis,and comprehensive clinical treatment guidelines are still lacking.This infection can be triggered by a variety of factors,including intestinal hypoxia,inappropriate antibiotic use,and bile acid circulation disorders.In patients with chronic bowel disease and related etiologies,prompt preoperative attention to possible CDI and preoperative bowel preparation is critical.Adequate and prolonged medication should be maintained in the treatment of CDI to prevent recurrence of the disease.

Therapeutics involved in managing initial and recurrent Clostridium difficile infection:An updated literature review

Clostridium difficile infection(CDI)has been increasing due to the effect of recurrent hospitalizations.The use of antibiotics has been shown to alter the gut microbiome and lead to CDIs.The treatment is limited to three major antibiotics;however,the incidence of recurrent CDIs has been increasing and drug resistance is a major concern.This aspect is a growing concern in modern medicine especially in the elderly population,critical care patients,and immunocompromised individuals who are at high risk of developing CDIs.Clostridium difficile can lead to various complications including septic shock and fulminant colitis that could prove to be lethal in these patients.Newer modalities of treatment have been developed including bezlotoxumab,a monoclonal antibody and fecal microbiota transplant.There have been studies showing asymptomatic carriers and drug resistance posing a major threat to the healthcare system.Newer treatment options are being studied to treat and prevent CDIs.This review will provide an insight into the current treatment modalities,prevention and newer modalities of treatment and challenges faced in the treatment of CDIs.

Clostridium difficile的中文翻译商讨

＂艰难梭菌＂是近几年来备受关注的专业词。但是,在大量资料上也有＂难辨梭菌＂一词,其使用频率似乎更高。两者均无英文对照,谈及内容极相似。原来两者均是Clostridium difficile的译名。

Comparison of pediatric and adult antibiotic-associated diarrhea and Clostridium difficile infections

Antibiotic-associated diarrhea(AAD) and Clostridum difficile infections(CDI) have been well studied for adult cases, but not as well in the pediatric population. Whether the disease process or response to treatments differs between pediatric and adult patients is an important clinical concern when following global guidelines based largely on adult patients. A systematic review of the literature using databases Pub Med(June 3, 1978-2015) was conducted to compare AAD and CDI in pediatric and adult populations and determine significant differences and similarities that might impact clinical decisions. In general, pediatric AAD and CDI have a more rapid onset of symptoms, a shorter duration of disease and fewer CDI complications(required surgeries and extended hospitalizations) than in adults. Children experience more community-associated CDI and are associated with smaller outbreaks than adult cases of CDI. The ribotype NAP1/027/BI is more common in adults than children. Children and adults share some similar risk factors, but adults have more complex risk factor profiles associated with more co-morbidities, types of disruptive factors and a wider range of exposures to C. difficile in the healthcare environment. The treatment of pediatric and adult AAD is similar(discontinuing or switching the inciting antibiotic), but other treatment strategies for AAD have not been established. Pediatric CDI responds better to metronidazole, while adult CDI responds better to vancomycin. Recurrent CDI is not commonly reported for children. Prevention for both pediatric and adult AAD and CDI relies upon integrated infection control programs, antibiotic stewardship and may include the use of adjunctive probiotics. Clinical presentation of pediatric AAD and CDI are different than adult AAD and CDI symptoms. These differences should be taken into account when rating severity of disease and prescribing antibiotics.

基于CX3CL1/CX3CR1信号通路探讨加味补阳还五汤对卒中后抑郁大鼠神经可塑性的影响

目的探究加味补阳还五汤对卒中后抑郁(PSD)大鼠神经可塑性的影响。方法60只大鼠随机分为假手术组、模型组、氟西汀组及加味补阳还五汤低、中、高剂量组,采用复合方法制备PSD模型,加味补阳还五汤低、中、高剂量组给予不同剂量加味补阳还五汤(6.7、13.4、26.8 g/kg)灌胃,氟西汀组给予氟西汀(1.8 mg/kg)灌胃,假手术组和模型组给予等体积蒸馏水灌胃,连续21 d。给药结束后,进行神经功能、行为学评分,HE、尼氏染色观察脑组织病理变化,免疫荧光染色观察神经元(Neun)和小胶质细胞(Iba1)之间相互作用,Western blot法检测神经趋化因子(CX3CL1)、CX3CR1、磷脂酰肌醇3激酶(PI3K)、苏氨酸激酶(Akt)蛋白表达。结果与模型组比较,各给药组神经功能缺损评分降低(P<0.05,P<0.01),旷场活动总距离和进入中央区域频次增加(P<0.05,P<0.01),不动时间缩短(P<0.05);加味补阳还五汤中、高剂量组和氟西汀组新奇摄食潜伏期缩短(P<0.01),缺血侧海马细胞排列整齐,细胞水肿减轻,细胞基本正常,尼氏小体增多,CX3CL1/Neun、CX3CR1/Iba1荧光强度增强(P<0.05),CX3CL1、CX3CR1、PI3K、p-Akt蛋白表达升高(P<0.05,P<0.01)。结论加味补阳还五汤对PSD大鼠具有抗抑郁、神经保护作用,其机制可能与调控CX3CL1/CX3CR1信号通路关键因子、增强神经可塑性有关。

Clostridium difficile infection and inflammatory bowel disease:Understanding the evolving relationship

Clostridium difficile(C.difficile)infection(CDI)is the leading identifiable cause of antibiotic-associated diarrhea.While there is an alarming trend of increasing incidence and severity of CDI in the United States and Europe,superimposed CDI in patients with inflammatory bowel disease(IBD)has drawn considerable attention in the gastrointestinal community.The majority of IBD patients appear to contract CDI as outpatients.C.difficile affects disease course of IBD in several ways,including triggering disease flares,sustaining activity,and in some cases,acting as an"innocent"bystander.Despite its wide spectrum of presentations,CDI has been reported to be associated with a longer duration of hospitalization and a higher mortality in IBD patients.IBD patients with restorative proctocolectomy or with diverting ileostomy are not immune to CDI of the small bowel or ileal pouch.Whether immunomodulator or corticosteroid therapy for IBD should be continued in patients with superimposed CDI is controversial.It appears that more adverse outcomes was observed among patients treated by a combination of immunomodulators and antibiotics than those treated by antibiotics alone.The use of biologic agents does not appear to increase the risk of acquisition of CDI.For CDI in the setting of underlying IBD,vancomycin appears to be more efficacious than metronidazole.Randomized controlled trials are required to clearly define the appropriate management for CDI in patients with IBD.

Antibiotic prophylaxis in variceal hemorrhage:Timing,effectiveness and Clostridium difficile rates

AIM:To investigate if antibiotics administered within 8 h of endoscopy reduce mortality or increase the incidence of Clostridium difficile infection(CDI).METHODS:A 2-year retrospective analysis of all patients who presented with first variceal hemorrhage was undertaken.The primary outcome measure was 28-d mortality.Secondary outcome measures were 28-d rebleeding rates and 28-d incidence of CDI.All patients were admitted to a tertiary liver unit with a consultantled,24-h endoscopy service.Patients received standard care including terlipressin therapy.Data collection included:primary and secondary outcome measures,timing of first administration of intravenous antibiotics,eti-ology of liver disease,demographics,endoscopy details and complications.A prospective study was undertaken to determine the incidence of CDI in the study population and general medical inpatients admitted for antibiotic therapy of at least 5 d duration.Statistical analysis was undertaken using univariate,non-parametric tests and multivariate logistic regression analysis.RESULTS:There were 70 first presentations of variceal hemorrhage during the study period.Seventy percent of cases were male and 65.7% were due to chronic alcoholic liver disease.In total,64/70(91.4%) patients received antibiotics as prophylaxis during their admission.Specifically,53/70(75.7%) received antibiotics either before endoscopy or within 8 h of endoscopy [peri-endoscopy(8 h) group],whereas 17/70(24.3%) received antibiotics at > 8 h after endoscopy or not at all(non peri-endoscopy group).Overall mortality and rebleeding rates were 13/70(18.6%) and 14/70(20%),respectively.The periendoscopy(8 h) group was significantly less likely to die compared with the non peri-endoscopy group [13.2% vs 35.3%,P = 0.04,odds ratio(OR) = 0.28(0.078-0.997)] and showed a trend towards reduced rebleeding [17.0% vs 29.4%,P = 0.27,OR = 0.49(0.14-1.74)].On univariate analysis,the non peri-endoscopy group [P = 0.02,OR = 3.58(1.00-12.81)],higher model for end-stage liver disease(MELD) score(P = 0.02),presence of hepatorenal syndrome [P < 0.01,OR = 11.25(2.24-56.42)] and suffering a clinical episode of sepsis [P = 0.03,OR = 4.03(1.11-14.58)] were significant predictors of death at 28 d.On multivariate logistic regression analysis,lower MELD score [P = 0.01,OR = 1.16(1.04-1.28)] and periendoscopy(8 h) group [P = 0.01,OR = 0.15(0.03-0.68)] were independent predictors of survival at 28 d.The CDI incidence(5.7%) was comparable to that in the general medical population(5%).CONCLUSION:Antibiotics administered up to 8 h following endoscopy were associated with improved survival at 28 d.CDI incidence was comparable to that in other patient groups.

Clostridium difficile infections in China

Clostridium difficile （C.difficile） infection has become one of the major hospital-associated infections in Western countries in the last two decades.However,there is limited information on the status of C.difficile infection in Chinese healthcare settings.Given the large and increasing elderly population and the well-recognized problem of over-prescribing of broad spectrum antibiotics in China,it is critical to understand the epidemiology and potential risk factors that may contribute to C.difficile infection in China.A literature review of available published studies,including those in Chinese language-based journals,was conducted.A review of the currently available literature suggested the presence of C.difficile infections in China,but also suggested that these infections were not particularly endemic.This finding should lead to better designed and greatly expanded studies to provide a more reliable epidemiologically-based conclusion on the actual status of C.difficile infection in China,including the identification of any associated risk factors.Such information is ultimately valuable to develop appropriate strategies to prevent C.difficile infection and the vast negative impact of such infections in China and other developing countries.

Proton pump inhibitors therapy and risk of Clostridium difficile infection: Systematic review and meta-analysis

AIM To perform a systematic review and meta-analysis on proton pump inhibitors(PPIs) therapy and the risk of Clostridium difficile infection(CDI). METHODS We conducted a systematic search of MEDLINE/Pub Med and seven other databases through January 1990 to March 2017 for published studies that evaluated the association between PPIs and CDI. Adult case-control and cohort studies providing information on the association between PPI therapy and the development of CDI were included. Pooled odds ratios(ORs) estimates with 95% confidence intervals(CIs) were calculated using the random effect. Heterogeneity was assessed by I^2 test and Cochran's Q statistic.Potential publication bias was evaluated via funnel plot, and quality of studies by the Newcastle-Otawa Quality Assessment Scale(NOS). RESULTS Fifty-six studies(40 case-control and 16 cohort) involving 356683 patients met the inclusion criteria and were analyzed. Both the overall pooled estimates and subgroup analyses showed increased risk for CDI despite substantial statistical heterogeneity among studies. Meta-analysis of all studies combined showed a significant association between PPI users and the risk of CDI(pooled OR = 1.99, CI: 1.73-2.30, P < 0.001) as compared with non-users. The association remained significant in subgroup analyses: by design-case-control(OR = 2.00, CI: 1.68-2.38, P < 0.0001), and cohort(OR = 1.98, CI: 1.51-2.59, P < 0.0001); adjusted(OR = 1.95, CI: 1.67-2.27, P < 0.0001) and unadjusted(OR = 2.02, CI: 1.41-2.91, P < 0.0001); unicenter(OR = 2.18, CI: 1.72-2.75, P < 0.0001) and multicenter(OR = 1.82, CI: 1.51-2.19, P < 0.0001); age ≥ 65 years(OR = 1.93, CI: 1.40-2.68, P < 0.0001) and < 65 years(OR = 2.06, CI: 1.11-3.81, P < 0.01). No significant differences were found in subgroup analyses(test for heterogeneity): P = 0.93 for case-control vs cohort, P = 0.85 for adjusted vs unadjusted, P = 0.24 for unicenter vs multicenter, P = 0.86 for age ≥ 65 years and < 65 years. There was significant heterogeneity across studies(I^2 = 85.4%, P < 0.001) as well as evidence of publication bias(funnel plot asymmetry test, P = 0.002). CONCLUSION This meta-analysis provides further evidence that PPI use is associated with an increased risk for development of CDI. Further high-quality, prospective studies are needed to assess whether this association is causal.

Clostridium difficile and inflammatory bowel disease: Role in pathogenesis and implications in treatment

Clostridium difficile(C.difficile)is the leading cause of antibiotic associated colitis and nosocomial diarrhea.Patients with inflammatory bowel disease(IBD)are at increased risk of developing C.difficile infection(CDI),have worse outcomes of CDI-including higher rates of colectomy and death,and experience higher rates of recurrence.However,it is still not clear whether C.difficile is a cause of IBD or a consequence of the inflammatory state in the intestinal environment.The burden of CDI has increased dramatically over the past decade,with severe outbreaks described in many countries,which have been attributed to a new and more virulent strain.A parallel rise in the incidence of CDI has been noted in patients with IBD.IBD patients with CDI tend be younger,have less prior antibiotic exposure,and most cases of CDI in these patients represent outpatient acquired infections.The clinical presentation of CDI in these patients can be unique-including diversion colitis,enteritis and pouchitis,and typical findings on colonoscopy are often absent.Due to the high prevalence of CDI in patients hospitalized with an IBD exacerbation,and the prognostic implications of CDI in these patients,it is recommended to test all IBD patients hospitalized with a disease flare for C.difficile.Treatment includes general measures such as supportive care and infection control measures.Antibiotic therapy with either oral metronidazole,vancomycin,or the novel antibiotic-fidaxomicin,should be initiated as soon as possible.Fecal macrobiota transplantation constitutes another optional treatment for severe/recurrent CDI.The aim of this paper is to review recent data on CDI in IBD:role in pathogenesis,diagnostic methods,optional treatments,and outcomes of these patients.

Impact of Clostridium difficile infection on inflammatory bowel disease outcome: A review

Although a considerable number of studies support a substantial increase in incidence, severity, and healthcare costs for Clostridium difficile infection (CDI) in inflammatory bowel disease (IBD), only few evaluate its impact on IBD outcome. Medline and several other electronic databases from January 1993 to October 2013 were searched in order to identify potentially relevant literature. Most of the studies showed that IBD patients with CDI present a greater proportion of worse outcomes than those without CDI. These patients have longer length of hospital stay, higher rates of colectomies, and increased mortality. Patients with ulcerative colitis are more susceptible to CDI and have more severe outcomes than those with Crohn&#x02019;s disease. However, studies reported variable results in both short- and long-term outcomes. Contrasting results were also found between studies using nationwide data and those reporting from single-center, or between some North-American and European studies. An important limitation of all studies analyzed was their retrospective design. Due to contrasting data often provided by retrospective studies, further prospective multi-center studies are necessary to evaluate CDI impact on IBD outcome. Until then, a rapid diagnosis and adequate therapy of infection are of paramount importance to improve IBD patients&#x02019; outcome. The aim of this article is to provide up to date information regarding CDI impact on outcome in IBD patients.

Proton pump inhibitors as a risk factor for recurrence of Clostridium-difficile-associated diarrhea

AIM:To investigate the risk factors for Clostridiumdifficile-associated diarrhea(CDAD)recurrence,and its relationship with proton pump inhibitors(PPIs). METHODS:Retrospective data of 125 consecutive hospitalized patients diagnosed with CDAD between January 2006 and December 2007 were collected by medical chart review.Collected data included patient characteristics at baseline,underlying medical disease, antibiotic history before receiving a diagnosis of CDAD, duration of hospital stay,severity of CDAD,concurrenttreatment with PPIs,laboratory parameters,response to CDAD therapy,and recurrence of disease within 90 d of successful treatment.Various clinical and laboratory parameters were compared in patients in whom CDAD did or did not recur. RESULTS:Of the 125 patients(mean age,67.6± 13.9 years)that developed CDAD,98(78.4%)did not experience recurrence(non-recurrent group)and 27 (21.6%)experienced one or more recurrences(recurrent group).Prior to the development of CDAD,96% of the 125 patients were prescribed antibiotics,and 56(44.8%)of the patients received PPIs.Age older than 65 years(P=0.021),feeding via nasogastric tube(NGT)(P=0.045),low serum albumin level(P =0.025),and concurrent use of PPIs(P=0.014) were found to be risk factors for CDAD recurrence by univariate analysis.However,sex,length of hospital stay,duration and type of antibiotics used,severity of disease,leukocyte count and C-reactive protein(CRP) were not associated with risk of CDAD recurrence.On multivariate analysis,the important risk factors were advanced age(>65 years,adjusted OR:1.32,95% CI:1.12-3.87,P=0.031),low serum albumin level(< 2.5 g/dL,adjusted OR:1.85,95%CI:1.35-4.91,P= 0.028),and concurrent use of PPIs(adjusted OR:3.48, 95%CI:1.64-7.69,P=0.016). CONCLUSION:Advanced age,serum albumin level< 2.5 g/dL,and concomitant use of PPIs were found to be significant risk factors for CDAD recurrence.

Burden of Clostridium difficile infection between 2010 and 2013:Trends and outcomes from an academic center in Eastern Europe

AIM:To analyze the incidence and possible risk factors in hospitalized patients treated with Clostridium difficile infection(CDI).METHODS:A total of 11751 patients were admitted to our clinic between 1 January 2010 and 1 May2013.Two hundred and forty-seven inpatients were prospectively diagnosed with CDI.For the risk analysis a 1:3 matching was used.Data of 732 patients matched for age,sex,and inpatient care period and unit were compared to those of the CDI population.Inpatient records were collected from an electronic hospital database and comprehensively reviewed.RESULTS:Incidence of CDI was 21.0/1000 admissions(2.1%of all-cause hospitalizations and 4.45%of total inpatient days).The incidence of severe CDI was 12.6%(2.63/1000 of all-cause hospitalizations).Distribution of CDI cases was different according to the unit type,with highest incidence rates in hematology,gastroenterology and nephrology units(32.9,25 and24.6/1000 admissions,respectively) and lowest rates in 1.4%(33/2312) in endocrinology and general internal medicine(14.2 and 16.9/1000 admissions)units.Recurrence of CDI was 11.3%within 12 wk after discharge.Duration of hospital stay was longer in patients with CDI compared to controls(17.6 ± 10.8d vs 12.4 ± 7.71 d).CDI accounted for 6.3%of allinpatient deaths,and 30-d mortality rate was 21.9%(54/247 cases).Risk factors for CDI were antibiotic therapy[including third-generation cephalosporins or fluoroquinolones,odds ratio(OR) = 4.559;P < 0.001],use of proton pump inhibitors(OR = 2.082,P< 0.001),previous hospitaiization within 12 mo(OR = 3.167,P < 0.001),previous CDI(OR = 15.32;P < 0.001),while presence of diabetes mellitus was associated with a decreased risk for CDI(OR = 0.484;P< 0.001).Treatment of recurrent cases was significantly different from primary infections with more frequent use of vancomycin alone or in combination(P < 0.001),and antibiotic therapy duration was longer(P < 0.02).Severity,mortality and outcome of primary infections and relapsing cases did not significantly differ.CONCLUSION:CDI was accounted for significant burden with longer hospitaiization and adverse outcomes.Antibiotic,PPI therapy and previous hospitaiization or CDI were risk factors for CDI.

Recurrent Clostridium difficile infections:The importance of the intestinal microbiota

Clostridium difficile infections(CDI)are a leading cause of antibiotic-associated and nosocomial diarrhea.Despite effective antibiotic treatments,recurrent infections are common.With the recent emergence of hypervirulent isolates of C.difficile,CDI is a growing epidemic with higher rates of recurrence,increasing severity and mortality.Fecal microbiota transplantation(FMT)is an alternative treatment for recurrent CDI.A better understanding of intestinal microbiota and its role in CDI has opened the door to this promising therapeutic approach.FMT is thought to resolve dysbiosis by restoring gut microbiota diversity thereby breaking the cycle of recurrent CDI.Since the first reported use of FMT for recurrent CDI in 1958,systematic reviews of case series and case report have shown its effectiveness with high resolution rates compared to standard antibiotic treatment.This article focuses on current guidelines for CDI treatment,the role of intestinal microbiota in CDI recurrence and current evidence about FMT efficacy,adverse effects and acceptability.

Complicated fecal microbiota transplantation in a tetraplegic patient with severe Clostridium difficile infection

A 65-year-old male suffering from acute spinal cord injury leading to incomplete tetraplegia presented with severe recurrent Clostridium difficile(C. difficile) infection subsequent to antibiotic treatment for pneumonia. After a history of ineffective antimicrobial therapies, including metronidazole, vancomycin, fidaxomicin, rifaximin and tigecycline, leading to several relapses, the patient underwent colonoscopic fecal microbiota transplantation from his healthy son. Four days subsequent to the procedure, the patient showed a systemic inflammation response syndrome. Without detecting an infectious cause, the patient received antimicrobial treatment, including tigecycline, metronidazole, vancomycin via polyethylene glycol and an additional enema for a period of seven days, leading to a prompt recovery and no reported C. difficile infection relapse during a 12 wk follow up.

Fulminant Clostridium difficile infection: An association with prior appendectomy?

AIM: To examine if fulminant Clostridium difficile infections(CDI) resulting in colectomy was associated with a prior appendectomy and whether any association affected the severity of the disease.METHODS: A retrospective chart review was performed on patients who underwent colectomy for CDI between 2001 and 2011.The appendectomy rate was calculated based on the absence of an appendix on the surgical pathology report.This was compared to an established lifetime risk of appendectomy in the general population.A chart review was performed for mortality and traditional markers of CDI disease severity.Fisher’s exact test was used to calculate the likelihood of association between prior appendectomy,mortality,and clinical markers of severity of infection.RESULTS: Fifty-five specimens were identified with pseudomembranous colitis consistent with CDI.All patients had a clinical history consistent with CDI and 45 of 55(81.8%) specimens also had microbiological confirmation of CDI.Appendectomy was observed in 24 of 55 specimens(0.436,99%CI: 0.280-0.606).This was compared to the lifetime incidence of appendectomy of 17.6%.The rate of appendectomy in our sample was significantly higher than would be expected in the general population(43.6% vs 17.6%,P 【 0.01).Disease severity did not differ based on presence or absence of an appendix and no association was detected between prior appendectomy and mortality(OR = 0.588,95%CI: 0.174-1.970).CONCLUSION: The rate of appendectomy in the patients whose CDI led to colectomy,was significantly higher than the calculated lifetime risk,suggesting an association of appendectomy and severe CDI resulting in colectomy.Larger prospective studies are needed to assess any potential causal relationships affecting fulminant CDI.

Stool therapy may become a preferred treatment of recurrent Clostridium difficile?

Fecal enemas were first reported to successfully treat life threatening enterocolitis in 1958, but fecal therapy to treat Clostridium difficile (C. difficile ) infection has remained esoteric and not well investigated until recently. In the past few years, systematic reviews of case series and case reports of fecal microbiota transplant for recurrent C. difficile infection have become available and validate use of fecal transplant for C. difficile enterocolitis. Methods of fecal transplant reported in the literature include: nasogastric tube, gastroscope, duodenal tube, colonoscopy, rectal tube, and fecal enemas administered at home; no method has been shown to be superior. A recent randomized study published in New England Journal of Medicine found fecal transplant to be superior to oral vancomycin alone in treatment of recurrent C. difficile enterocolitis. The significance of this trial cannot be underestimated as it lends credibility to the idea of intentionally using microbes to combat disease, providing an alternative to the older paradigm of disease eradication through use of antimicrobials.

Risk factors for Clostridium difficile infection in cirrhotic patients

Background: Cirrhotic patients are susceptible to Clostridium difficile infection(CDI), however, the high risk factors are not clear. The present study aimed to identify the risk factors in cirrhotic patients with CDI. Methods: A total of 526 cirrhotic patients admitted to our hospital between May 2015 and October 2015 were included in this study. Stool samples were collected upon admission for the detection of CDI and toxin. CDI was monitored during the hospital stay. In total, 34 cases showed CDI. Then we analyzed the effects of age, sex, C. difficile colonization(CDC), multiple hospitalization, extended hospital stay, elevation of total bilirubin(TBIL), creatinine(Cr), Child-Pugh grade C, hepatic encephalopathy, hepatorenal syndrome, upper gastrointestinal hemorrhage, and exposure of antibiotics and proton pump inhibitor(PPI) on the CDI in cirrhotic patients. Results: Patients in the CDI group had more frequent CDC, multiple hospitalization, and extended hospital stay compared to those in the non-C. difficile infection(NCDI) group. Patients in the CDI group had higher TBIL and Cr, and higher frequency of Child-Pugh grade C, hepatic encephalopathy, upper gastrointestinal hemorrhage compared with those in the NCDI group. Multiple logistic regression analysis indicated that age > 60 years(OR = 1.689;95% CI: 1.135–3.128), multiple hospitalization(OR = 3.346;95% CI: 1.392–8.043), length of hospital stay > 20 days(OR = 1.564;95% CI: 1.113–2.563), hypoproteinemia(OR = 4.962;95% CI: 2.053–11.996), CDC(OR = 18.410;95% CI: 6.898–49.136), hepatic encephalopathy(OR = 1.357;95% CI: 1.154–2.368), and exposure of antibiotics(OR = 1.865;95% CI: 1.213–2.863) and PPI(OR = 3.125;95% CI: 1.818–7.548) were risk factors of CDI. Conclusions: Age > 60 years, multiple hospitalization, length of hospital stay > 20 days, hypoproteinemia, CDC, hepatic encephalopathy, and exposure of antibiotics and PPI were risk factors for CDI in cirrhotic patients. These may contribute to the early diagnosis and monitoring of CDI in clinical practice.

Appendectomy and Clostridium difficile colitis:Relationships revealed by clinical observations and immunology

Advances in understanding the interaction between the human immune system and the microbiome have led to an improved understanding of the function of the vermiform appendix as a safe-house for beneficial bacteria in the colon.These advances have been made despite long standing clinical observations that the appendectomy is a safe and effective procedure.However,more recent clinical data show that an appendectomy puts patients at increased risk for recurrent Clostridium difficile(C.difficile)-associated colitis,and probably other diseases associated with an altered microbiome.At the same time,appendectomy does not apparently put patients at risk for an initial onset of C.difficile-associated colitis.These clinical observations point toward the idea that the vermiform appendix might not effectively protect the microbiome in the face of broad spectrum antibiotics,the use of which precedes the initial onset of C.difficile-associated colitis.Further,these observations point to the idea that historically important threats to the microbiome such as infectious gastrointestinal pathogens have been supplanted by other threats,particularly the use of broad spectrum antibiotics.