BACKGROUND: Sepsis is a life-threatening inflammatory condition in which the invading pathogen avoids the host's defense mechanisms and continuously stimulates and damages host cells. Consequently, many immune res...BACKGROUND: Sepsis is a life-threatening inflammatory condition in which the invading pathogen avoids the host's defense mechanisms and continuously stimulates and damages host cells. Consequently, many immune responses initially triggered for protection become harmful because of the failure to restore homeostasis, resulting in ongoing hyperinflammation and immunosuppression. METHODS: A literature review was conducted to address bacterial sepsis, describe advances in understanding complex immunological reactions, critically assess diagnostic approaches, and emphasize the importance of studying bacterial bottlenecks in the detection and treatment of sepsis.RESULTS: Diagnosing sepsis via a single laboratory test is not feasible;therefore, multiple key biomarkers are typically monitored, with a focus on trends rather than absolute values. The immediate interpretation of sepsis-associated clinical signs and symptoms, along with the use of specific and sensitive laboratory tests, is crucial for the survival of patients in the early stages. However, long-term mortality associated with sepsis is now recognized, and alongside the progression of this condition, there is an in vivo selection of adapted pathogens.CONCLUSION: Bacterial sepsis remains a significant cause of mortality across all ages and societies. While substantial progress has been made in understanding the immunological mechanisms underlying the inflammatory response, there is growing recognition that the ongoing host-pathogen interactions, including the emergence of adapted virulent strains, shape both the acute and long-term outcomes in sepsis. This underscores the urgent need for novel high-throughput diagnostic methods and a shift toward more pre-emptive, rather than reactive, treatment strategies in sepsis care.展开更多
Cardamonin is a natural chalcone that has been extensively investigated for its anticancer activity.However,its clinical relevance is still not explicit,limiting its progression into clinical trials and highlighting a...Cardamonin is a natural chalcone that has been extensively investigated for its anticancer activity.However,its clinical relevance is still not explicit,limiting its progression into clinical trials and highlighting a persistent gap between preclinical evidence and practical application.This review aims to assess the readiness of cardamonin to progress from laboratory research to clinical application as an anticancer agent by examining both scientific evidence and translational challenges.Preclinical pharmacokinetic and pharmacodynamic data suggest that cardamonin’s therapeutic potential as an anticancer agent is hindered by its poor oral bioavailability.Although its molecular targets remain undefined,evidence indicates that cardamonin can inhibit various signaling pathways,including nuclear factor kappa-light-chain-enhancer of activated B cells,mammalian target of rapamycin,signal transducer and activator of transcription 3,and Wnt/β-catenin.The lack of in vivo toxicity studies creates uncertainty regarding the balance between its therapeutic benefits and potential adverse effects when moving from laboratory research to human trials.Despite these limitations,cardamonin has,however,demonstrated antiproliferative,anti-metastatic,and chemosensitizing effects,mainly against breast,colorectal,and ovarian cancers.Nevertheless,exploring its combination with standard chemotherapeutic agents may offer a promising foundation for advancing cardamonin into clinical trials.展开更多
Even in cases where viral replication has been controlled by antiretroviral therapy for long periods of time, human immunodeficiency virus(HIV)-infected patients have several non-acquired immunodeficiency syndrome(AID...Even in cases where viral replication has been controlled by antiretroviral therapy for long periods of time, human immunodeficiency virus(HIV)-infected patients have several non-acquired immunodeficiency syndrome(AIDS) related co-morbidities, including liver disease, cardiovascular disease and neurocognitive decline, which have a clear impact on survival. It has been considered that persistent innate and acquired immune activation contributes to the pathogenesis of these non-AIDS related diseases. Immune activation has been related with several conditions, remarkably with the bacterial translocation related with the intestinal barrier damage by the HIV or by hepatitis C virus(HCV)-related liver cirrhosis. Consequently, increased morbidity and mortality must be expected in HIV-HCV coinfected patients. Disrupted gut barrier lead to an increased passage of microbial products and to an activation of the mucosal immune system and secretion of inflammatory mediators, which in turn might increase barrier dysfunction. In the present review, the intestinal barrier structure, measures of intestinal barrier dysfunction and the modifications of them in HIV monoinfection and in HIV-HCV coinfection will be considered. Both pathogenesis and the consequences for the progression of liver disease secondary to gut microbial fragment leakage and immune activation will be assessed.展开更多
BACKGROUND The World Health Organization defined long coronavirus disease 2019(COVID-19)as the continuation or development of new symptoms 3 months after the initial severe acute respiratory syndrome coronavirus 2 inf...BACKGROUND The World Health Organization defined long coronavirus disease 2019(COVID-19)as the continuation or development of new symptoms 3 months after the initial severe acute respiratory syndrome coronavirus 2 infection,with these symptoms lasting for at least 2 months with no other explanation.AIM To evaluate the potential laboratory and instrumental findings(short-term and long-term)resulting from COVID-19.METHODS This longitudinal observational COVID-19 cohort study(March 1,2020-March 1,2021)was carried out on patients≥18 years old who were admitted to the University Hospitals of Pisa,Siena and Careggi and the Azienda USL Toscana Nord Ovest,Sud Est and USL Centro Toscana and were subjected to follow-up.Follow-up was conducted between 0 day and 89 days,90 days and 179 days,180 days and 269 days,270 days and 359 days,and more than 360 days after hospitalization.RESULTS Of 2887 patients(58.5%males,average age 66.2 years)hospitalized in the study period(March 1,2020-March 1,2021)carrying out at least one follow-up examination within 12 months of discharge,a total of 1739 patients(705 males,average age 66 years)underwent laboratory tests,of whom 714 patients(470 males,average age 63 years)underwent spirometry.Some laboratory test results remained above the threshold even at follow-up beyond 360 days(C-reactive protein:36%,fibrin degradation fragment:48.8%,gamma-glutamyl transferase:16.8%),while others showed a return to normal range more quickly in almost all patients.Alterations in liver enzymes,hematocrit,hemoglobin,lymphocytes and neutrophils were associated with the risk of requiring oxygen therapy or forced expiratory volume in one second/forced vital capacity alterations at follow-up.CONCLUSION Alterations in liver enzymes,hematocrit or hemoglobin,lymphocytes and neutrophils were associated with risk outcomes(need for oxygen therapy or spirometry alterations).These imbalanced conditions may contribute to pulmonary dysfunction.展开更多
Introduction: The transmission of HIV from mother to child is reported from 30% to 40% without any intervention [1]. When all the measures for prevention are implemented, including treatment with HAART (Highly Active ...Introduction: The transmission of HIV from mother to child is reported from 30% to 40% without any intervention [1]. When all the measures for prevention are implemented, including treatment with HAART (Highly Active Antiretroviral Treatment), the rate of infection can be reduced between 1% and 2% [2]. In Guatemala, the statistics demonstrated an estimated of 20,000 women living with HIV virus infection during the period of 2009. In this scenario, mother to child HIV transmission is an important public health fact. In preliminary reports, there is strong evidence of the impact of preventing mother to child transmission with Lopinavir/Ritonavir in Guatemala is showing a small incidence of new HIV infections and good tolerance [3,4]. Objective: To evaluate the effect of HAART with Lopinavir/Ritonavir on the prevention of mother to child transmission (PMCT) in HIV-positive pregnant women at Roosevelt Hospital in Guatemala City. Methods: A retrospective cohort analysis study. The detection of pregnant HIV positive women and the follow up period was from January 2003 to December 2009, and a total of 219 women completed the follow up time. The HIV diagnosis and follow up for the child was made with molecular testing and antibody testing up to 18 months of age or until testing was negative. Adherence was quantified by pill counts. The interventions where offered to all the women in the cohort. Results: Regarding the pregnancy outcome, the study cohort gave a rate of abortion of 2.3%;10.6% of preterm births and 79.6% normal births. Of the 202/219 children born, there was a 1.4% rate of transmission (n = 3). The three infected children were born from mothers with high basal viral loads (xxx C/mL or higher). There were no serious adverse events related to antiretroviral therapy with Lopinavir/Ritonavir, with a 6.1% of non serious adverse events, most of them of gastrointestinal type, and anemia. Conclusions: The rate of transmission of HIV from mother to child was low in this population (1.4%), comparable to findings from similar studies [4]. Lopinavir/Ritonavir was well tolerated in this cohort and no serious adverse events in this population were reported.展开更多
BACKGROUND Ventilator-associated pneumonia(VAP)is defined as pneumonia that occurs two calendar days following endotracheal intubation or after that.It is the most common infection encountered among intubated patients...BACKGROUND Ventilator-associated pneumonia(VAP)is defined as pneumonia that occurs two calendar days following endotracheal intubation or after that.It is the most common infection encountered among intubated patients.VAP incidence showed wide variability between countries.AIM To define the VAP incidence in the intensive care unit(ICU)in the central gove-rnment hospital in Bahrain and review the risk factors and the predominant bacterial pathogens with their antimicrobial susceptibility pattern.METHODS The research was a prospective cross-sectional observational study over six months from November 2019 to June 2020.It included adult and adolescent patients(>14 years old)admitted to the ICU and required intubation and mechanical ventilation.VAP was diagnosed when it occurred after 48 h after endotracheal intubation using the clinical pulmonary infection score,which considers the clinical,laboratory,microbiological,and radiographic evidence.RESULTS The total number of adult patients admitted to the ICU who required intubation and mechanical ventilation during the study period was 155.Forty-six patients developed VAP during their ICU stay(29.7%).The calculated VAP rate was 22.14 events per 1000 ventilator days during the study period,with a mean age of 52 years±20.Most VAP cases had late-onset VAP with a mean number of ICU days before the development of VAP of 9.96±6.55.Gram-negative contributed to most VAP cases in our unit,with multidrug-resistant Acinetobacter being the most identified pathogen.CONCLUSION The reported VAP rate in our ICU was relatively high compared to the international benchmark,which should trigger a vital action plan for reinforcing the implementation of the VAP prevention bundle.展开更多
The risk of reactivation in patients with chronic or past/resolved hepatitis B virus(HBV)infection receiving chemotherapy or immunosuppressive drugs is a wellknown possibility.The indication of antiviral prophylaxis w...The risk of reactivation in patients with chronic or past/resolved hepatitis B virus(HBV)infection receiving chemotherapy or immunosuppressive drugs is a wellknown possibility.The indication of antiviral prophylaxis with nucleo(t)side analogue is given according to the risk of HBV reactivation of the prescribed therapy.Though the advent of new drugs is occurring in all the field of medicine,in the setting of hematologic malignancies the last few years have been characterized by several drug classes and innovative cellular treatment.As novel therapies,there are few data about the rate of HBV reactivation and the decision of starting or not an antiviral prophylaxis could be challenging.Moreover,patients are often treated with a combination of different drugs,so evaluating the actual role of these new therapies in increasing the risk of HBV reactivation is difficult.First results are now available,but further studies are still needed.Patients with chronic HBV infection[hepatitis B surface antigen(HBsAg)positive]are reasonably all treated.Past/resolved HBV patients(HBsAg negative)are the actual area of uncertainty where it could be difficult choosing between prophylaxis and pre-emptive strategy.展开更多
Hepatitis C virus(HCV)/human immunodeficiency virus(HIV)co-infection still involves 2.3 million patients worldwide of the estimated 37.7 million living with HIV,according to World Health Organization.People living wit...Hepatitis C virus(HCV)/human immunodeficiency virus(HIV)co-infection still involves 2.3 million patients worldwide of the estimated 37.7 million living with HIV,according to World Health Organization.People living with HIV(PLWH)are six times greater affected by HCV,compared to HIV negative ones;the greater prevalence is encountered among people who inject drugs and men who have sex with men:the risk of HCV transmission through sexual contact in this setting can be increased by HIV infection.These patients experience a high rate of chronic hepatitis,which if left untreated progresses to end-stage liver disease and hepato-cellular carcinoma(HCC)HIV infection increases the risk of mother to child vertical transmission of HCV.No vaccination against both infections is still available.There is an interplay between HIV and HCV infections.Treatment of HCV is nowadays based on direct acting antivirals(DAAs),HCV treatment plays a key role in limiting the progression of liver disease and reducing the risk of HCC development in mono-and coinfected individuals,especially when used at an early stage of fibrosis,reducing liver disease mortality and morbidity.Since the sustained virological response at week 12 rates were observed in PLWH after HCV eradication,the AASLD has revised its simplified HCV treatment algorithm to also include individuals living with HIV.HCV eradication can determine dyslipidemia,since HCV promotes changes in serum lipid profiles and may influence lipid metabolism.In addition to these apparent detrimental effects on the lipid profile,the efficacy of DAA in HCV/HIV patients needs to be considered in light of its effects on glucose metabolism mediated by improvements in liver function.The aim of the present editorial is to describe the advancement in HCV treatment among PLWH.展开更多
Background Stigma experienced by people with infectious diseases impedes access to care,leading to adverse psychosocial consequences.Community-based interventions could prevent or mitigate these consequences but lack ...Background Stigma experienced by people with infectious diseases impedes access to care,leading to adverse psychosocial consequences.Community-based interventions could prevent or mitigate these consequences but lack robust evidence.This scoping review aimed to identify and critically appraise community-based psychosocial support interventions to reduce stigma and improve mental health for people affected by stigmatizing infectious diseases including tuberculosis(TB),HIV/AIDS,and leprosy.Methods This was a scoping review of literature indexed in PubMed,Web of Science,Elton B.Stephens Company(EBSCO)database,as well as reports in the World Health Organization repository,published from January 2000 to June 2023.We included research articles and reports addressing stigma and mental health disorders among indi-viduals with TB,HIV/AIDS,or leprosy and/or their household members in low-and middle-income and/or high TB burden countries.We extracted information regarding types of psychosocial interventions and their reported impact on health and psychosocial indicators.Results Thirty studies were included in this review:21(70%)related to HIV/AIDS,seven(23%)leprosy,and two(7%)TB.Of these,eleven were quantitative studies,nine qualitative,and ten mixed-methods.Eleven community-based interventions were reported to reduce infectious disease-related stigma,predominantly internalized and enacted stigma,and improve adherence to medication,quality of life,health-related knowledge,depression symptoms,and psychosocial wellbeing.Most studies involved lay people in the community as supporters of those affected.The predominant reported mechanism of intervention effect was the ability of supporters to enable those affected to feel seen and listened to,to accept their diagnosis,to improve their self-esteem,and to facilitate continuation of their daily lives,and thereby reducing anticipated stigma,self-stigma,and mental illness.Adequate training for lay people was reported to be essential to ensure success of interventions.Conclusions This review identified a paucity of high-quality evidence relating to community-based interven-tions to reduce stigma for infectious diseases.However,such interventions have been reported to reduce stigma and improve mental health among people with HIV/AIDS,leprosy,and TB.Engaging affected communities and peers,through the conception,planning,training,implementation,and evaluation phases,was reported to be essential to optimise intervention uptake,impact,and sustainability.展开更多
Our institution, Sultan Qaboos University Hospital, has set a protocol for vaccinating elderly > 65 years and eligible adult groups of patients against seasonal influenza and Streptococcus pneumoniae when admitted ...Our institution, Sultan Qaboos University Hospital, has set a protocol for vaccinating elderly > 65 years and eligible adult groups of patients against seasonal influenza and Streptococcus pneumoniae when admitted as inpatients or seen at outpatient clinics. Here, I assess the compliance of various medical teams with this policy. Background: Methods: electronic records of admitted patients in adult general medical words were reviewed for vaccination from 28 January 2024 until 28 February 2024. Results: Among 203 patients at presentation, 45 patients were new with unknown immunization status. At presentation, only seven and eleven of 158 patients (4.4% and 7%) had been vaccinated in the previous admission for influenza and Pneumococcus respectively. Upon discharge only four and six patients (2.12% and 3.24%) were given seasonal influenza and pneumococcal vaccines respectively. Discharge summaries and referral letters mentioned vaccination status of patients in two cases only. Conclusion: Rates of vaccination against influenza and S pneumoniae are very low in the elderly and adult patients with chronic medical conditions. A surveillance system needs to be set in place to monitor this.展开更多
AIM: To investigate a possible association between serum vitamin D levels and spontaneous hepatitis B surface antigen (HBsAg) seroclearance. METHODS: Fifty-three patients diagnosed with chronic inactive hepatitis B an...AIM: To investigate a possible association between serum vitamin D levels and spontaneous hepatitis B surface antigen (HBsAg) seroclearance. METHODS: Fifty-three patients diagnosed with chronic inactive hepatitis B and spontaneous HBsAg seroclearance were followed up in two Israeli liver units between 2007 and 2012. This retrospective study reviewed medical charts of all the patients, extracting demographic, serological and vitamin D rates in the serum, as well as medical conditions and current medical therapy. Spontaneous HBsAg seroclearance was defined as the loss of serum HBsAg indefinitely. Vitamin D levels were compared to all patients who underwent spontaneousHBsAg seroclearance.HBsAg seroclearance. RESULTS: Out of the 53 patients who underwent hepatitis B antigen seroclearance, 44 patients (83%) had normal levels of 25-hydroxyvitamin vitamin D compared to 9 patients (17%) who had below normal levels. Multivariate analysis showed that age (>35 years) OR = 1.7 (95%CI: 1.25-2.8, P=0.05), serum vitamin D levels (>20 ng/mL) OR = 2.6 (95%CI: 2.4-3.2, P=0.02), hepatitis B e antigen negativity OR = 2.1 (95%CI: 2.2-3.1, P=0.02), low viral load (hepatitis B virus DNA < 100 IU/mL) OR = 3 (95%CI: 2.6-4.2, P = 0.01) and duration of HBsAg seropositivity (> 8 years) OR = 1.6 (95%CI: 1.15-2.6, P=0.04) were also associated with spontaneous HBsAg seroclearance. CONCLUSION: We found a strong correlation between normal vitamin D levels and spontaneous HBsAg seroclearance.展开更多
AIM: To review gastrointestinal and liver infections in children undergoing antineoplastic chemotherapy. To look at gut microflora features in oncology children.METHODS: We selected studies published after year 2000, ...AIM: To review gastrointestinal and liver infections in children undergoing antineoplastic chemotherapy. To look at gut microflora features in oncology children.METHODS: We selected studies published after year 2000, excluding trials on transplanted pediatric patients. We searched English language publications in MEDLINE using the keywords: "gastrointestinal infection AND antineoplastic chemotherapy AND children", "gastrointestinal infection AND oncology AND children", "liver infection AND antineoplastic chemotherapy AND children", "liver abscess AND chemotherapy AND child", "neutropenic enterocolitis AND chemotherapy AND children", "thyphlitis AND chemotherapy AND children", "infectious diarrhea AND children AND oncology", "abdominal pain AND infection AND children AND oncology", "perianal sepsis AND children AND oncology", "colonic pseudo-obstruction A N D o n c o l o g y A N D c h i l d A N D c h e m o t h e r a p y ", "microflora AND children AND malignancy", "microbiota AND children AND malignancy", "fungal flora AND children AND malignancy". We also analysed evidence from several articles and book references.RESULTS: Gastrointestinal and liver infections represent a major cause of morbidity and mortality in children undergoing antineoplastic chemotherapy. Antineoplastic drugs cause immunosuppression in addition to direct toxicity, predisposing to infections, although the specific risk is variable according to disease and host features. Common pathogens potentially induce severe diseases whereas opportunistic microorganisms may attack vulnerable hosts. Clinical manifestations can be subtle and not specific. In addition, several conditions are rare and diagnostic process and treatments are not standardized. Diagnosis may be challenging, however early diagnosis is needed for quick and appropriate interventions. Interestingly, the source of infectionin those children can be exogenous or endogenous. Indeed, mucosal damage may allow the penetrance of endogenous microbes towards the bowel wall and their translocation into the bloodstream. However, only limited knowledge of intestinal dysbiosis in oncology children is available. CONCLUSION: The diagnostic work-up requires a multimodal approach and should be implemented(also by further studies on new biomarkers) for a prompt and individualized therapy.展开更多
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(CD...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.展开更多
Invasive infections are a major complication before liver transplantation(LT)and in the early phase after surgery.There has been an increasing prevalence of invasive fungal disease(IFD),especially among the sickest pa...Invasive infections are a major complication before liver transplantation(LT)and in the early phase after surgery.There has been an increasing prevalence of invasive fungal disease(IFD),especially among the sickest patients with decompensated cirrhosis and acute-on-chronic liver failure,who suffer from a profound state of immune dysfunction and receive intensive care management.In such patients,who are listed for LT,development of an IFD often worsens hepatic and extra-hepatic organ dysfunction,requiring a careful evaluation before surgery.In the post-transplant setting,the burden of IFD has been reduced after the clinical advent of antifungal prophylaxis,even if several major issues still remain,such as duration,target population and drug type(s).Nevertheless,the development of IFD in the early phase after surgery significantly impairs graft and patient survival.This review outlines presentation,prophylactic and therapeutic strategies,and outcomes of IFD in LT candidates and recipients,providing specific considerations for clinical practice.展开更多
Liver disease in human immunodeficiency virus(HIV)-infected individuals encompasses the spectrum from abnormal liver function tests,liver decompensation,with and without evidence of cirrhosis on biopsy,to non-alcoholi...Liver disease in human immunodeficiency virus(HIV)-infected individuals encompasses the spectrum from abnormal liver function tests,liver decompensation,with and without evidence of cirrhosis on biopsy,to non-alcoholic liver disease and its more severe form,non-alcoholic steatohepatitis and hepatocellular cancer.HIV can infect multiple cells in the liver,leading to enhanced intrahepatic apoptosis,activation and fibrosis.HIV can also alter gastro-intestinal tract permeability,leading to increased levels of circulating lipopolysaccharide that may have an impact on liver function.This review focuses on recent changes in the epidemiology,pathogenesis and clinical presentation of liver disease in HIV-infected patients,in the absence of co-infection with hepatitis B virus or hepatitis C virus,with a specific focus on issues relevant to low and middle income countries.展开更多
Inflammatory bowel disease is thought to be caused by an aberrant immune response to gut bacteria in a genetically susceptible host. The gut microbiota plays an important role in the pathogenesis and complications of ...Inflammatory bowel disease is thought to be caused by an aberrant immune response to gut bacteria in a genetically susceptible host. The gut microbiota plays an important role in the pathogenesis and complications of the two main inflammatory bowel diseases: Crohn's disease(CD) and ulcerative colitis. Alterations in gut microbiota, and specifically reduced intestinal microbial diversity, have been found to be associated with chronic gut inflammation in these disorders. Specific bacterial pathogens, such as virulent Escherichia coli strains, Bacteroides spp, and Mycobacterium avium subspecies paratuberculosis, have been linked to the pathogenesis of inflammatory bowel disease. Antibiotics may influence the course of these diseases by decreasing concentrations of bacteria in the gut lumen and altering the composition of intestinal microbiota. Different antibiotics, including ciprofloxacin, metronidazole, the combination of both, rifaximin, and anti-tuberculous regimens have been evaluated in clinical trials for the treatment of inflammatory bowel disease. For the treatment of active luminal CD, antibiotics may have a modest effect in decreasing disease activity and achieving remission, and are more effective in patients with disease involving the colon. Rifamixin, a non absorbable rifamycin has shown promising results. Treatment of suppurative complications of CD such as abscesses and fistulas, includes drainage and antibiotic therapy, most often ciprofloxacin, metronidazole, or a combination of both. Antibiotics might also play a role in maintenance of remission and prevention of post operative recurrence of CD. Data is more sparse for ulcerative colitis, and mostly consists of small trials evaluating ciprofloxacin, metronidazole and rifaximin. Most trials did not show a benefit for the treatment of active ulcerative colitis with antibiotics, though 2 meta-analyses concluded that antibiotic therapy is associated with a modest improvement in clinical symptoms. Antibiotics show a clinical benefit when used for the treatment of pouchitis. The downsides of antibiotic treatment, especially with recurrent or prolonged courses such as used in inflammatory bowel disease, are significant side effects that often cause intolerance to treatment, Clostridium dificile infection, and increasing antibiotic resistance. More studies are needed to define the exact role of antibiotics in inflammatory bowel diseases.展开更多
AIM: To evaluate the long-term eradication of hepatitis C virus (HCV) infection and liver-related complications in chronically infected patients that have achieved sustained virological response. METHODS: One hundred ...AIM: To evaluate the long-term eradication of hepatitis C virus (HCV) infection and liver-related complications in chronically infected patients that have achieved sustained virological response. METHODS: One hundred and fifty subjects with chronic hepatitis C (CHC) or cirrhosis and sustained virological response (SVR) between the years of 1989 and 2008 were enrolled in a long-term clinical follow-up study at the Gastrointestinal and Liver Unit of the University Hospital of Naples "Federico Ⅱ". At the beginning of the study, the diagnosis of HCV infection was made on the basis of serum positivity for antibodies to HCV and detection of HCV RNA transcripts, while a diagnosis of chronic hepatitis was formulated using imaging techniques and/or a liver biopsy. SVR was achieved by interferon-based therapy, both conventional and pegylated, with and without ribavirin treatment. The patients were evaluated for follow-up at a median length of 8.6 years, but ranged from 2-19.9 years. Among them, 137 patients had pre-treatment CHC and 13 had cirrhosis. The patients were followed with clinical, biochemical, virological, and ultrasound assessments on a given schedule. Finally, a group of 27 patients underwent a liver biopsy at the beginning of the study and transient elastography at their final visit to evaluate changes in liver fibrosis. RESULTS: The median follow-up was 8.6 years (range 2-19.9 years). HCV RNA remained undetectable in all patients, even in patients who eventually developed liver-related complications, indicating no risk of HCV recurrence. Three liver-related complications were observed: two cases of hepatocellular carcinoma and one case of bleeding from esophageal varices resulting in an incidence rate of 0.23%/person per year. Further, all three complications took place in patients diagnosed with cirrhosis before treatment began. Only one death due to liver-related causes occurred, resulting in a mortality rate of 0.077% person per year. This amounts to a 99.33% survival rate in our cohort of patients after therapy for HCV infection. Finally, of the 27 patients who underwent a liver biopsy at the beginning of the study, a reduction in liver fibrosis was observed in 70.3% of the cases; only three cases registering values of liver stiffness indicative of significant fibrosis. CONCLUSION: Patients with CHC and SVR show an excellent prognosis with no risk of recurrence and a very low rate of mortality. Our data indicate that viruseradication following interferon treatment can last up to 20 years.展开更多
Hepatitis B virus (HBV) reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents. In particular, the risk ofHBV reactivation is heightened by the use monoclonala...Hepatitis B virus (HBV) reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents. In particular, the risk ofHBV reactivation is heightened by the use monoclonalantibodies, such as rituximab (anti-CD20) and alemtuzumab (anti-CD52) that cause profound and longlasting immunosuppression. Emerging data indicatethat HBV reactivation could also develop following theuse of other biologic agents, such as tumor necrosis factor (TNF)-α inhibitors. When HBV reactivation is di-agnosed, it is mandatory to suspend biologic treatmentand start antiviral agents immediately. However, preemptive antiviral therapy prior to monoclonal antibodyadministration is crucial in preventing HBV reactivationand its clinical consequences. Several lines of evidencehave shown that risk of HBV reactivation is greatlyreduced by the identifi cation of high-risk patients andthe use of prophylactic antiviral therapy. In this article, we discuss current trends in the management of HBV reactivation in immunosuppressed patients receiving biologic therapy, such as rituximab, alemtuzumab and TNF-α antagonists.展开更多
Background: A new rapid Immunochromatographic test (ICT) kit (MPT64 TB Ag Kit) for detection of MPT64 Antigen in M. tuberculosis (MTB) isolates used for rapid identification of MTB isolates developed by SD (Standard D...Background: A new rapid Immunochromatographic test (ICT) kit (MPT64 TB Ag Kit) for detection of MPT64 Antigen in M. tuberculosis (MTB) isolates used for rapid identification of MTB isolates developed by SD (Standard Diagnostics) Bio line, South Korea was evaluated. The ICT is a rapid, reliable and cheaper method that can be used instead of conventional biochemical tests for confirming MTB in culture isolates in resource limited laboratories. The study also evaluated the ability of ICT to detect MPT64-Antigen before the micro MGIT could signal positive. Material/Methods: A total of 450 sputum samples of individual patients were used for the study. 152 isolates of Mycobacteria were recovered from solid and liquid media. These strains were tested for the detection of MPT64-antigen. H37Rv strain was served as the positive reference control and also used for early detection of Antigen experiment. Findings: The development of bands on both test and sample region when H37Rv strain was tested were seen (MPT64 antigen positive). When 138 MTB isolates were tested, it showed a similar banding pattern indicating 100% sensitivity. MPT64 band formation was not detected in any of the 14 isolates indicating 100% specificity. Both PPV & NPV were 100%. All the isolates negative for MPT64 Ag were confirmed as MOTT by conventional bio-chemical PNBA. The H37Rv strain showed a faint band from the 2nd day onwards from inoculation till 3rd day in the earlier Antigen detection experiment. Conclusion: Rapid identification of MTB culture isolate is a pressing need for diagnosis and proceeding to perform drug susceptibility testing. MPT64 TB Ag detection ICT kit is a rapid, reliable method, good substitute for molecular identification methods, and conventional biochemical test which is time-consuming and technically demanding. The early detection of Antigen can be used as an effective tool in diagnosis.展开更多
Defensive medicine is widespread and practiced the world over, with serious consequences for patients, doctors, and healthcare costs. Even students and resi-dents are exposed to defensive medicine practices and taught...Defensive medicine is widespread and practiced the world over, with serious consequences for patients, doctors, and healthcare costs. Even students and resi-dents are exposed to defensive medicine practices and taught to take malpractice liability into consideration when making clinical decisions. Defensive medicine is generally thought to stem from physicians' perception that they can easily be sued by patients or their relatives who seek compensation for presumed medical errors. However, in our view the growth of defensive medicine should be seen in the context of larger changes in the conception of medicine that have taken place in the last few decades, undermining the patient–physician trust, which has traditionally been the main source of professional satisfaction for physicians. These changes include the following: time directly spent with patients has been overtaken by time devoted to electronic health records and desk work; family doctors have played a progressively less central role; clinical reasoning is being replaced by guidelines and algorithms; the public at large and a number of young physicians tend to believe that medicine is a perfect science rather than an imperfect art, as it continues to be; and modern societies do not tolerate the inevitable morbidity and mortality. To finally reduce the increasing defensive behavior of doctors around the world, the decriminalization of medical errors and the assurance that they can be dealt with in civil courts or by medical organizations in all countries could help but it would not suffice. Physicians and surgeons should be allowed to spend the time they need with their patients and should give clinical reasoning the importance it deserves. The institutions should support the doctors who have experienced adverse patient events, and the media should stop reporting with excessive evidence presumed medical errors and subject physicians to "public trials" before they are eventually judged in court.展开更多
基金funded by the Deanship of Scientific Research (DSR) at King Abdulaziz UniversityJeddah+1 种基金Saudi Arabiaunder grant number G-150-248-1443。
文摘BACKGROUND: Sepsis is a life-threatening inflammatory condition in which the invading pathogen avoids the host's defense mechanisms and continuously stimulates and damages host cells. Consequently, many immune responses initially triggered for protection become harmful because of the failure to restore homeostasis, resulting in ongoing hyperinflammation and immunosuppression. METHODS: A literature review was conducted to address bacterial sepsis, describe advances in understanding complex immunological reactions, critically assess diagnostic approaches, and emphasize the importance of studying bacterial bottlenecks in the detection and treatment of sepsis.RESULTS: Diagnosing sepsis via a single laboratory test is not feasible;therefore, multiple key biomarkers are typically monitored, with a focus on trends rather than absolute values. The immediate interpretation of sepsis-associated clinical signs and symptoms, along with the use of specific and sensitive laboratory tests, is crucial for the survival of patients in the early stages. However, long-term mortality associated with sepsis is now recognized, and alongside the progression of this condition, there is an in vivo selection of adapted pathogens.CONCLUSION: Bacterial sepsis remains a significant cause of mortality across all ages and societies. While substantial progress has been made in understanding the immunological mechanisms underlying the inflammatory response, there is growing recognition that the ongoing host-pathogen interactions, including the emergence of adapted virulent strains, shape both the acute and long-term outcomes in sepsis. This underscores the urgent need for novel high-throughput diagnostic methods and a shift toward more pre-emptive, rather than reactive, treatment strategies in sepsis care.
基金Supported by Malaysian Ministry of Higher Education through the Fundamental Research Grant Scheme,No.FP103-2019.
文摘Cardamonin is a natural chalcone that has been extensively investigated for its anticancer activity.However,its clinical relevance is still not explicit,limiting its progression into clinical trials and highlighting a persistent gap between preclinical evidence and practical application.This review aims to assess the readiness of cardamonin to progress from laboratory research to clinical application as an anticancer agent by examining both scientific evidence and translational challenges.Preclinical pharmacokinetic and pharmacodynamic data suggest that cardamonin’s therapeutic potential as an anticancer agent is hindered by its poor oral bioavailability.Although its molecular targets remain undefined,evidence indicates that cardamonin can inhibit various signaling pathways,including nuclear factor kappa-light-chain-enhancer of activated B cells,mammalian target of rapamycin,signal transducer and activator of transcription 3,and Wnt/β-catenin.The lack of in vivo toxicity studies creates uncertainty regarding the balance between its therapeutic benefits and potential adverse effects when moving from laboratory research to human trials.Despite these limitations,cardamonin has,however,demonstrated antiproliferative,anti-metastatic,and chemosensitizing effects,mainly against breast,colorectal,and ovarian cancers.Nevertheless,exploring its combination with standard chemotherapeutic agents may offer a promising foundation for advancing cardamonin into clinical trials.
基金Supported by Instituto de Salud Carlos III,Plan Nacional de I+D+I 2008-2011No.PI11/00605 and Plan Estatal de I+D+I 2013-2016+1 种基金No.PI14/01779Co-financed by FEDER(Fondo Europeo de Desarrollo Regional)
文摘Even in cases where viral replication has been controlled by antiretroviral therapy for long periods of time, human immunodeficiency virus(HIV)-infected patients have several non-acquired immunodeficiency syndrome(AIDS) related co-morbidities, including liver disease, cardiovascular disease and neurocognitive decline, which have a clear impact on survival. It has been considered that persistent innate and acquired immune activation contributes to the pathogenesis of these non-AIDS related diseases. Immune activation has been related with several conditions, remarkably with the bacterial translocation related with the intestinal barrier damage by the HIV or by hepatitis C virus(HCV)-related liver cirrhosis. Consequently, increased morbidity and mortality must be expected in HIV-HCV coinfected patients. Disrupted gut barrier lead to an increased passage of microbial products and to an activation of the mucosal immune system and secretion of inflammatory mediators, which in turn might increase barrier dysfunction. In the present review, the intestinal barrier structure, measures of intestinal barrier dysfunction and the modifications of them in HIV monoinfection and in HIV-HCV coinfection will be considered. Both pathogenesis and the consequences for the progression of liver disease secondary to gut microbial fragment leakage and immune activation will be assessed.
基金Supported by Regione Toscana,No.D55H20000210002.
文摘BACKGROUND The World Health Organization defined long coronavirus disease 2019(COVID-19)as the continuation or development of new symptoms 3 months after the initial severe acute respiratory syndrome coronavirus 2 infection,with these symptoms lasting for at least 2 months with no other explanation.AIM To evaluate the potential laboratory and instrumental findings(short-term and long-term)resulting from COVID-19.METHODS This longitudinal observational COVID-19 cohort study(March 1,2020-March 1,2021)was carried out on patients≥18 years old who were admitted to the University Hospitals of Pisa,Siena and Careggi and the Azienda USL Toscana Nord Ovest,Sud Est and USL Centro Toscana and were subjected to follow-up.Follow-up was conducted between 0 day and 89 days,90 days and 179 days,180 days and 269 days,270 days and 359 days,and more than 360 days after hospitalization.RESULTS Of 2887 patients(58.5%males,average age 66.2 years)hospitalized in the study period(March 1,2020-March 1,2021)carrying out at least one follow-up examination within 12 months of discharge,a total of 1739 patients(705 males,average age 66 years)underwent laboratory tests,of whom 714 patients(470 males,average age 63 years)underwent spirometry.Some laboratory test results remained above the threshold even at follow-up beyond 360 days(C-reactive protein:36%,fibrin degradation fragment:48.8%,gamma-glutamyl transferase:16.8%),while others showed a return to normal range more quickly in almost all patients.Alterations in liver enzymes,hematocrit,hemoglobin,lymphocytes and neutrophils were associated with the risk of requiring oxygen therapy or forced expiratory volume in one second/forced vital capacity alterations at follow-up.CONCLUSION Alterations in liver enzymes,hematocrit or hemoglobin,lymphocytes and neutrophils were associated with risk outcomes(need for oxygen therapy or spirometry alterations).These imbalanced conditions may contribute to pulmonary dysfunction.
文摘Introduction: The transmission of HIV from mother to child is reported from 30% to 40% without any intervention [1]. When all the measures for prevention are implemented, including treatment with HAART (Highly Active Antiretroviral Treatment), the rate of infection can be reduced between 1% and 2% [2]. In Guatemala, the statistics demonstrated an estimated of 20,000 women living with HIV virus infection during the period of 2009. In this scenario, mother to child HIV transmission is an important public health fact. In preliminary reports, there is strong evidence of the impact of preventing mother to child transmission with Lopinavir/Ritonavir in Guatemala is showing a small incidence of new HIV infections and good tolerance [3,4]. Objective: To evaluate the effect of HAART with Lopinavir/Ritonavir on the prevention of mother to child transmission (PMCT) in HIV-positive pregnant women at Roosevelt Hospital in Guatemala City. Methods: A retrospective cohort analysis study. The detection of pregnant HIV positive women and the follow up period was from January 2003 to December 2009, and a total of 219 women completed the follow up time. The HIV diagnosis and follow up for the child was made with molecular testing and antibody testing up to 18 months of age or until testing was negative. Adherence was quantified by pill counts. The interventions where offered to all the women in the cohort. Results: Regarding the pregnancy outcome, the study cohort gave a rate of abortion of 2.3%;10.6% of preterm births and 79.6% normal births. Of the 202/219 children born, there was a 1.4% rate of transmission (n = 3). The three infected children were born from mothers with high basal viral loads (xxx C/mL or higher). There were no serious adverse events related to antiretroviral therapy with Lopinavir/Ritonavir, with a 6.1% of non serious adverse events, most of them of gastrointestinal type, and anemia. Conclusions: The rate of transmission of HIV from mother to child was low in this population (1.4%), comparable to findings from similar studies [4]. Lopinavir/Ritonavir was well tolerated in this cohort and no serious adverse events in this population were reported.
文摘BACKGROUND Ventilator-associated pneumonia(VAP)is defined as pneumonia that occurs two calendar days following endotracheal intubation or after that.It is the most common infection encountered among intubated patients.VAP incidence showed wide variability between countries.AIM To define the VAP incidence in the intensive care unit(ICU)in the central gove-rnment hospital in Bahrain and review the risk factors and the predominant bacterial pathogens with their antimicrobial susceptibility pattern.METHODS The research was a prospective cross-sectional observational study over six months from November 2019 to June 2020.It included adult and adolescent patients(>14 years old)admitted to the ICU and required intubation and mechanical ventilation.VAP was diagnosed when it occurred after 48 h after endotracheal intubation using the clinical pulmonary infection score,which considers the clinical,laboratory,microbiological,and radiographic evidence.RESULTS The total number of adult patients admitted to the ICU who required intubation and mechanical ventilation during the study period was 155.Forty-six patients developed VAP during their ICU stay(29.7%).The calculated VAP rate was 22.14 events per 1000 ventilator days during the study period,with a mean age of 52 years±20.Most VAP cases had late-onset VAP with a mean number of ICU days before the development of VAP of 9.96±6.55.Gram-negative contributed to most VAP cases in our unit,with multidrug-resistant Acinetobacter being the most identified pathogen.CONCLUSION The reported VAP rate in our ICU was relatively high compared to the international benchmark,which should trigger a vital action plan for reinforcing the implementation of the VAP prevention bundle.
文摘The risk of reactivation in patients with chronic or past/resolved hepatitis B virus(HBV)infection receiving chemotherapy or immunosuppressive drugs is a wellknown possibility.The indication of antiviral prophylaxis with nucleo(t)side analogue is given according to the risk of HBV reactivation of the prescribed therapy.Though the advent of new drugs is occurring in all the field of medicine,in the setting of hematologic malignancies the last few years have been characterized by several drug classes and innovative cellular treatment.As novel therapies,there are few data about the rate of HBV reactivation and the decision of starting or not an antiviral prophylaxis could be challenging.Moreover,patients are often treated with a combination of different drugs,so evaluating the actual role of these new therapies in increasing the risk of HBV reactivation is difficult.First results are now available,but further studies are still needed.Patients with chronic HBV infection[hepatitis B surface antigen(HBsAg)positive]are reasonably all treated.Past/resolved HBV patients(HBsAg negative)are the actual area of uncertainty where it could be difficult choosing between prophylaxis and pre-emptive strategy.
文摘Hepatitis C virus(HCV)/human immunodeficiency virus(HIV)co-infection still involves 2.3 million patients worldwide of the estimated 37.7 million living with HIV,according to World Health Organization.People living with HIV(PLWH)are six times greater affected by HCV,compared to HIV negative ones;the greater prevalence is encountered among people who inject drugs and men who have sex with men:the risk of HCV transmission through sexual contact in this setting can be increased by HIV infection.These patients experience a high rate of chronic hepatitis,which if left untreated progresses to end-stage liver disease and hepato-cellular carcinoma(HCC)HIV infection increases the risk of mother to child vertical transmission of HCV.No vaccination against both infections is still available.There is an interplay between HIV and HCV infections.Treatment of HCV is nowadays based on direct acting antivirals(DAAs),HCV treatment plays a key role in limiting the progression of liver disease and reducing the risk of HCC development in mono-and coinfected individuals,especially when used at an early stage of fibrosis,reducing liver disease mortality and morbidity.Since the sustained virological response at week 12 rates were observed in PLWH after HCV eradication,the AASLD has revised its simplified HCV treatment algorithm to also include individuals living with HIV.HCV eradication can determine dyslipidemia,since HCV promotes changes in serum lipid profiles and may influence lipid metabolism.In addition to these apparent detrimental effects on the lipid profile,the efficacy of DAA in HCV/HIV patients needs to be considered in light of its effects on glucose metabolism mediated by improvements in liver function.The aim of the present editorial is to describe the advancement in HCV treatment among PLWH.
基金funded by grant MR/Y503216/1 from the Medical Research Council Public Health Intervention Development(PHIND)UK.TW is also supported by grants from the Wellcome Trust,UK(209075/Z/17/Z)+2 种基金the Medical Research Council,Department for International Development,and Wellcome Trust(Joint Global Health Trials,MR/V004832/1)a Dorothy Temple Cross Tuberculosis International Collaboration Grant from the Medical Research Foundation(MRF-131-0006-RG-KHOS-C0942)UK.AF is also supported by PUTI Q1 grant(NKB-230/UN2.RST/HKP.05.00/2024)by Universitas Indonesia.All funders had no involvement in data collection,analysis,report writing and decision to submission.
文摘Background Stigma experienced by people with infectious diseases impedes access to care,leading to adverse psychosocial consequences.Community-based interventions could prevent or mitigate these consequences but lack robust evidence.This scoping review aimed to identify and critically appraise community-based psychosocial support interventions to reduce stigma and improve mental health for people affected by stigmatizing infectious diseases including tuberculosis(TB),HIV/AIDS,and leprosy.Methods This was a scoping review of literature indexed in PubMed,Web of Science,Elton B.Stephens Company(EBSCO)database,as well as reports in the World Health Organization repository,published from January 2000 to June 2023.We included research articles and reports addressing stigma and mental health disorders among indi-viduals with TB,HIV/AIDS,or leprosy and/or their household members in low-and middle-income and/or high TB burden countries.We extracted information regarding types of psychosocial interventions and their reported impact on health and psychosocial indicators.Results Thirty studies were included in this review:21(70%)related to HIV/AIDS,seven(23%)leprosy,and two(7%)TB.Of these,eleven were quantitative studies,nine qualitative,and ten mixed-methods.Eleven community-based interventions were reported to reduce infectious disease-related stigma,predominantly internalized and enacted stigma,and improve adherence to medication,quality of life,health-related knowledge,depression symptoms,and psychosocial wellbeing.Most studies involved lay people in the community as supporters of those affected.The predominant reported mechanism of intervention effect was the ability of supporters to enable those affected to feel seen and listened to,to accept their diagnosis,to improve their self-esteem,and to facilitate continuation of their daily lives,and thereby reducing anticipated stigma,self-stigma,and mental illness.Adequate training for lay people was reported to be essential to ensure success of interventions.Conclusions This review identified a paucity of high-quality evidence relating to community-based interven-tions to reduce stigma for infectious diseases.However,such interventions have been reported to reduce stigma and improve mental health among people with HIV/AIDS,leprosy,and TB.Engaging affected communities and peers,through the conception,planning,training,implementation,and evaluation phases,was reported to be essential to optimise intervention uptake,impact,and sustainability.
文摘Our institution, Sultan Qaboos University Hospital, has set a protocol for vaccinating elderly > 65 years and eligible adult groups of patients against seasonal influenza and Streptococcus pneumoniae when admitted as inpatients or seen at outpatient clinics. Here, I assess the compliance of various medical teams with this policy. Background: Methods: electronic records of admitted patients in adult general medical words were reviewed for vaccination from 28 January 2024 until 28 February 2024. Results: Among 203 patients at presentation, 45 patients were new with unknown immunization status. At presentation, only seven and eleven of 158 patients (4.4% and 7%) had been vaccinated in the previous admission for influenza and Pneumococcus respectively. Upon discharge only four and six patients (2.12% and 3.24%) were given seasonal influenza and pneumococcal vaccines respectively. Discharge summaries and referral letters mentioned vaccination status of patients in two cases only. Conclusion: Rates of vaccination against influenza and S pneumoniae are very low in the elderly and adult patients with chronic medical conditions. A surveillance system needs to be set in place to monitor this.
文摘AIM: To investigate a possible association between serum vitamin D levels and spontaneous hepatitis B surface antigen (HBsAg) seroclearance. METHODS: Fifty-three patients diagnosed with chronic inactive hepatitis B and spontaneous HBsAg seroclearance were followed up in two Israeli liver units between 2007 and 2012. This retrospective study reviewed medical charts of all the patients, extracting demographic, serological and vitamin D rates in the serum, as well as medical conditions and current medical therapy. Spontaneous HBsAg seroclearance was defined as the loss of serum HBsAg indefinitely. Vitamin D levels were compared to all patients who underwent spontaneousHBsAg seroclearance.HBsAg seroclearance. RESULTS: Out of the 53 patients who underwent hepatitis B antigen seroclearance, 44 patients (83%) had normal levels of 25-hydroxyvitamin vitamin D compared to 9 patients (17%) who had below normal levels. Multivariate analysis showed that age (>35 years) OR = 1.7 (95%CI: 1.25-2.8, P=0.05), serum vitamin D levels (>20 ng/mL) OR = 2.6 (95%CI: 2.4-3.2, P=0.02), hepatitis B e antigen negativity OR = 2.1 (95%CI: 2.2-3.1, P=0.02), low viral load (hepatitis B virus DNA < 100 IU/mL) OR = 3 (95%CI: 2.6-4.2, P = 0.01) and duration of HBsAg seropositivity (> 8 years) OR = 1.6 (95%CI: 1.15-2.6, P=0.04) were also associated with spontaneous HBsAg seroclearance. CONCLUSION: We found a strong correlation between normal vitamin D levels and spontaneous HBsAg seroclearance.
文摘AIM: To review gastrointestinal and liver infections in children undergoing antineoplastic chemotherapy. To look at gut microflora features in oncology children.METHODS: We selected studies published after year 2000, excluding trials on transplanted pediatric patients. We searched English language publications in MEDLINE using the keywords: "gastrointestinal infection AND antineoplastic chemotherapy AND children", "gastrointestinal infection AND oncology AND children", "liver infection AND antineoplastic chemotherapy AND children", "liver abscess AND chemotherapy AND child", "neutropenic enterocolitis AND chemotherapy AND children", "thyphlitis AND chemotherapy AND children", "infectious diarrhea AND children AND oncology", "abdominal pain AND infection AND children AND oncology", "perianal sepsis AND children AND oncology", "colonic pseudo-obstruction A N D o n c o l o g y A N D c h i l d A N D c h e m o t h e r a p y ", "microflora AND children AND malignancy", "microbiota AND children AND malignancy", "fungal flora AND children AND malignancy". We also analysed evidence from several articles and book references.RESULTS: Gastrointestinal and liver infections represent a major cause of morbidity and mortality in children undergoing antineoplastic chemotherapy. Antineoplastic drugs cause immunosuppression in addition to direct toxicity, predisposing to infections, although the specific risk is variable according to disease and host features. Common pathogens potentially induce severe diseases whereas opportunistic microorganisms may attack vulnerable hosts. Clinical manifestations can be subtle and not specific. In addition, several conditions are rare and diagnostic process and treatments are not standardized. Diagnosis may be challenging, however early diagnosis is needed for quick and appropriate interventions. Interestingly, the source of infectionin those children can be exogenous or endogenous. Indeed, mucosal damage may allow the penetrance of endogenous microbes towards the bowel wall and their translocation into the bloodstream. However, only limited knowledge of intestinal dysbiosis in oncology children is available. CONCLUSION: The diagnostic work-up requires a multimodal approach and should be implemented(also by further studies on new biomarkers) for a prompt and individualized therapy.
文摘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.
文摘Invasive infections are a major complication before liver transplantation(LT)and in the early phase after surgery.There has been an increasing prevalence of invasive fungal disease(IFD),especially among the sickest patients with decompensated cirrhosis and acute-on-chronic liver failure,who suffer from a profound state of immune dysfunction and receive intensive care management.In such patients,who are listed for LT,development of an IFD often worsens hepatic and extra-hepatic organ dysfunction,requiring a careful evaluation before surgery.In the post-transplant setting,the burden of IFD has been reduced after the clinical advent of antifungal prophylaxis,even if several major issues still remain,such as duration,target population and drug type(s).Nevertheless,the development of IFD in the early phase after surgery significantly impairs graft and patient survival.This review outlines presentation,prophylactic and therapeutic strategies,and outcomes of IFD in LT candidates and recipients,providing specific considerations for clinical practice.
基金Supported by An NHMRC Practitioner Fellowship to Lewin SRan am FAR Mathilde Krim Fellowship in Basic Biomedical Science to Crane Man NHMRC postgraduate scholarship to Iser D
文摘Liver disease in human immunodeficiency virus(HIV)-infected individuals encompasses the spectrum from abnormal liver function tests,liver decompensation,with and without evidence of cirrhosis on biopsy,to non-alcoholic liver disease and its more severe form,non-alcoholic steatohepatitis and hepatocellular cancer.HIV can infect multiple cells in the liver,leading to enhanced intrahepatic apoptosis,activation and fibrosis.HIV can also alter gastro-intestinal tract permeability,leading to increased levels of circulating lipopolysaccharide that may have an impact on liver function.This review focuses on recent changes in the epidemiology,pathogenesis and clinical presentation of liver disease in HIV-infected patients,in the absence of co-infection with hepatitis B virus or hepatitis C virus,with a specific focus on issues relevant to low and middle income countries.
文摘Inflammatory bowel disease is thought to be caused by an aberrant immune response to gut bacteria in a genetically susceptible host. The gut microbiota plays an important role in the pathogenesis and complications of the two main inflammatory bowel diseases: Crohn's disease(CD) and ulcerative colitis. Alterations in gut microbiota, and specifically reduced intestinal microbial diversity, have been found to be associated with chronic gut inflammation in these disorders. Specific bacterial pathogens, such as virulent Escherichia coli strains, Bacteroides spp, and Mycobacterium avium subspecies paratuberculosis, have been linked to the pathogenesis of inflammatory bowel disease. Antibiotics may influence the course of these diseases by decreasing concentrations of bacteria in the gut lumen and altering the composition of intestinal microbiota. Different antibiotics, including ciprofloxacin, metronidazole, the combination of both, rifaximin, and anti-tuberculous regimens have been evaluated in clinical trials for the treatment of inflammatory bowel disease. For the treatment of active luminal CD, antibiotics may have a modest effect in decreasing disease activity and achieving remission, and are more effective in patients with disease involving the colon. Rifamixin, a non absorbable rifamycin has shown promising results. Treatment of suppurative complications of CD such as abscesses and fistulas, includes drainage and antibiotic therapy, most often ciprofloxacin, metronidazole, or a combination of both. Antibiotics might also play a role in maintenance of remission and prevention of post operative recurrence of CD. Data is more sparse for ulcerative colitis, and mostly consists of small trials evaluating ciprofloxacin, metronidazole and rifaximin. Most trials did not show a benefit for the treatment of active ulcerative colitis with antibiotics, though 2 meta-analyses concluded that antibiotic therapy is associated with a modest improvement in clinical symptoms. Antibiotics show a clinical benefit when used for the treatment of pouchitis. The downsides of antibiotic treatment, especially with recurrent or prolonged courses such as used in inflammatory bowel disease, are significant side effects that often cause intolerance to treatment, Clostridium dificile infection, and increasing antibiotic resistance. More studies are needed to define the exact role of antibiotics in inflammatory bowel diseases.
文摘AIM: To evaluate the long-term eradication of hepatitis C virus (HCV) infection and liver-related complications in chronically infected patients that have achieved sustained virological response. METHODS: One hundred and fifty subjects with chronic hepatitis C (CHC) or cirrhosis and sustained virological response (SVR) between the years of 1989 and 2008 were enrolled in a long-term clinical follow-up study at the Gastrointestinal and Liver Unit of the University Hospital of Naples "Federico Ⅱ". At the beginning of the study, the diagnosis of HCV infection was made on the basis of serum positivity for antibodies to HCV and detection of HCV RNA transcripts, while a diagnosis of chronic hepatitis was formulated using imaging techniques and/or a liver biopsy. SVR was achieved by interferon-based therapy, both conventional and pegylated, with and without ribavirin treatment. The patients were evaluated for follow-up at a median length of 8.6 years, but ranged from 2-19.9 years. Among them, 137 patients had pre-treatment CHC and 13 had cirrhosis. The patients were followed with clinical, biochemical, virological, and ultrasound assessments on a given schedule. Finally, a group of 27 patients underwent a liver biopsy at the beginning of the study and transient elastography at their final visit to evaluate changes in liver fibrosis. RESULTS: The median follow-up was 8.6 years (range 2-19.9 years). HCV RNA remained undetectable in all patients, even in patients who eventually developed liver-related complications, indicating no risk of HCV recurrence. Three liver-related complications were observed: two cases of hepatocellular carcinoma and one case of bleeding from esophageal varices resulting in an incidence rate of 0.23%/person per year. Further, all three complications took place in patients diagnosed with cirrhosis before treatment began. Only one death due to liver-related causes occurred, resulting in a mortality rate of 0.077% person per year. This amounts to a 99.33% survival rate in our cohort of patients after therapy for HCV infection. Finally, of the 27 patients who underwent a liver biopsy at the beginning of the study, a reduction in liver fibrosis was observed in 70.3% of the cases; only three cases registering values of liver stiffness indicative of significant fibrosis. CONCLUSION: Patients with CHC and SVR show an excellent prognosis with no risk of recurrence and a very low rate of mortality. Our data indicate that viruseradication following interferon treatment can last up to 20 years.
文摘Hepatitis B virus (HBV) reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents. In particular, the risk ofHBV reactivation is heightened by the use monoclonalantibodies, such as rituximab (anti-CD20) and alemtuzumab (anti-CD52) that cause profound and longlasting immunosuppression. Emerging data indicatethat HBV reactivation could also develop following theuse of other biologic agents, such as tumor necrosis factor (TNF)-α inhibitors. When HBV reactivation is di-agnosed, it is mandatory to suspend biologic treatmentand start antiviral agents immediately. However, preemptive antiviral therapy prior to monoclonal antibodyadministration is crucial in preventing HBV reactivationand its clinical consequences. Several lines of evidencehave shown that risk of HBV reactivation is greatlyreduced by the identifi cation of high-risk patients andthe use of prophylactic antiviral therapy. In this article, we discuss current trends in the management of HBV reactivation in immunosuppressed patients receiving biologic therapy, such as rituximab, alemtuzumab and TNF-α antagonists.
文摘Background: A new rapid Immunochromatographic test (ICT) kit (MPT64 TB Ag Kit) for detection of MPT64 Antigen in M. tuberculosis (MTB) isolates used for rapid identification of MTB isolates developed by SD (Standard Diagnostics) Bio line, South Korea was evaluated. The ICT is a rapid, reliable and cheaper method that can be used instead of conventional biochemical tests for confirming MTB in culture isolates in resource limited laboratories. The study also evaluated the ability of ICT to detect MPT64-Antigen before the micro MGIT could signal positive. Material/Methods: A total of 450 sputum samples of individual patients were used for the study. 152 isolates of Mycobacteria were recovered from solid and liquid media. These strains were tested for the detection of MPT64-antigen. H37Rv strain was served as the positive reference control and also used for early detection of Antigen experiment. Findings: The development of bands on both test and sample region when H37Rv strain was tested were seen (MPT64 antigen positive). When 138 MTB isolates were tested, it showed a similar banding pattern indicating 100% sensitivity. MPT64 band formation was not detected in any of the 14 isolates indicating 100% specificity. Both PPV & NPV were 100%. All the isolates negative for MPT64 Ag were confirmed as MOTT by conventional bio-chemical PNBA. The H37Rv strain showed a faint band from the 2nd day onwards from inoculation till 3rd day in the earlier Antigen detection experiment. Conclusion: Rapid identification of MTB culture isolate is a pressing need for diagnosis and proceeding to perform drug susceptibility testing. MPT64 TB Ag detection ICT kit is a rapid, reliable method, good substitute for molecular identification methods, and conventional biochemical test which is time-consuming and technically demanding. The early detection of Antigen can be used as an effective tool in diagnosis.
文摘Defensive medicine is widespread and practiced the world over, with serious consequences for patients, doctors, and healthcare costs. Even students and resi-dents are exposed to defensive medicine practices and taught to take malpractice liability into consideration when making clinical decisions. Defensive medicine is generally thought to stem from physicians' perception that they can easily be sued by patients or their relatives who seek compensation for presumed medical errors. However, in our view the growth of defensive medicine should be seen in the context of larger changes in the conception of medicine that have taken place in the last few decades, undermining the patient–physician trust, which has traditionally been the main source of professional satisfaction for physicians. These changes include the following: time directly spent with patients has been overtaken by time devoted to electronic health records and desk work; family doctors have played a progressively less central role; clinical reasoning is being replaced by guidelines and algorithms; the public at large and a number of young physicians tend to believe that medicine is a perfect science rather than an imperfect art, as it continues to be; and modern societies do not tolerate the inevitable morbidity and mortality. To finally reduce the increasing defensive behavior of doctors around the world, the decriminalization of medical errors and the assurance that they can be dealt with in civil courts or by medical organizations in all countries could help but it would not suffice. Physicians and surgeons should be allowed to spend the time they need with their patients and should give clinical reasoning the importance it deserves. The institutions should support the doctors who have experienced adverse patient events, and the media should stop reporting with excessive evidence presumed medical errors and subject physicians to "public trials" before they are eventually judged in court.
