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
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
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
Objective:To describe the clinical features and outcomes of arboviral infections in solid organ transplant recipients(SOTRs).Methods:This study included SOTRs identified from a passive surveillance cohort of 1466 pati...Objective:To describe the clinical features and outcomes of arboviral infections in solid organ transplant recipients(SOTRs).Methods:This study included SOTRs identified from a passive surveillance cohort of 1466 patients with acute undifferentiated febrile illness between 2012 and 2019.Diagnosis of arboviral infection was confirmed using RT-PCR and/or serological testing.Clinical,laboratory,and outcome data were extracted and analyzed descriptively.Results:Eleven SOTRs(10 kidney,1 heart transplant recipient)were diagnosed with arboviral infections:8 with dengue(DENV),2 with chikungunya virus(CHIKV),and 1 with Zika virus(ZIKV)infection.The median time from transplantation to symptom onset was 35.0 days(IQR 28.5-111.0).DENV infection was associated with severe disease,including dengue shock syndrome(50%,4/8)and dengue hemorrhagic fever(25%,2/8).Six patients(75%,6/8)required ICU admission.Common laboratory abnormalities in dengue patients included leukopenia(100%,8/8),thrombocytopenia(100%,8/8),elevated transaminases(87.5%,7/8),and acute kidney injury(50%,4/8).CHIKV and ZIKV cases presented as mild,self-limiting febrile illnesses without complications.All patients recovered without long-term morbidity.Conclusions:DENV infection in SOTRs is associated with significant morbidity,particularly early post-transplant,and requires heightened clinical vigilance.In contrast,CHIKV and ZIKV infections tend to follow a benign course.Enhanced vector control,early diagnostic testing,supportive management,and consideration of dengue vaccination in appropriate candidates are essential to mitigate the impact of arboviral infections in transplant recipients in endemic areas.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
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
BACKGROUND Hepatitis delta virus(HDV)infection is the most severe form of chronic viral hepatitis,yet sex-based clinical differences remain poorly defined.Understanding these differences may inform disease management ...BACKGROUND Hepatitis delta virus(HDV)infection is the most severe form of chronic viral hepatitis,yet sex-based clinical differences remain poorly defined.Understanding these differences may inform disease management and guide research.AIM To investigate sex-related differences in demographic and clinical characteristics of patients with chronic HDV infection in a nationwide,real-world Italian setting.METHODS We analyzed demographic,clinical,and virological data from 513 hepatitis B surface antigen/anti-HDV-positive patients,consecutively enrolled between 2019 and 2024,across 58 liver clinics in the Italian PITER HDV cohort.A propensity score-weighted logistic regression model evaluated the association between sex and cirrhosis and/or hepatocellular carcinoma.RESULTS Among 513 patients(61.6%male),median age(56.0 years)and age distribution were similar by sex(P=0.41).Cirrhosis was frequent:73.4%vs 66.0%(anti-HDV-positive)and 77.8%vs 74.2%(HDV RNA-positive)in males and females,respectively.HDV RNA levels were comparable(P=0.93).The highest proportion of females with cirrhosis(33.8%)was in the 56-60-year group,similar to males(34.9%).Among patients with cirrhosis aged≤40 years,females,(80.9%of whom of non-Italian origin),were more represented than males(16.1%vs 6.5%respectively,P<0.05).Male sex was associated with cirrhosis(odds ratio=1.85;95%confidence interval:1.004-3.40).Among HDV RNA-positive patients,males more often had hepatocellular carcinoma,elevated gammaglutamyl transpeptidase,alcohol use,diabetes,hypertension,steatotic liver disease,and hepatitis C virus/human immunodeficiency virus coinfection.Interferon eligibility was similar.CONCLUSION HDV-infected females develop cirrhosis earlier,without liver disease cofactors,while males show advanced liver disease with multiple cofactors.Tailored care for young migrant women and cofactor-guided management for men may improve HDV outcomes,promoting equity.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
Stem cells can be obtained from women's menstrual blood derived from the endometrium.The cells display stem cell markers such as Oct-4,SSEA-4,Nanog,and c-kit(CD117),and have the potent ability to differentiate int...Stem cells can be obtained from women's menstrual blood derived from the endometrium.The cells display stem cell markers such as Oct-4,SSEA-4,Nanog,and c-kit(CD117),and have the potent ability to differentiate into various cell types,including the heart,nerve,bone,cartilage,and fat.There has been no evidence of teratoma,ectopic formation,or any immune response after transplantation into an animal model.These cells quickly regenerate after menstruation and secrete many growth factors to display recurrent angiogenesis.The plasticity and safety of the acquired cells have been demonstrated in many studies.Menstrual blood-derived stem cells(MenSCs) provide an alternative source of adult stem cells for research and application in regenerative medicine.Here we summarize the multipotent properties and the plasticities of MenSCs and other endometrial stem cells from recent studies conducted both in vitro and in vivo.展开更多
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.
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.
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.
文摘Objective:To describe the clinical features and outcomes of arboviral infections in solid organ transplant recipients(SOTRs).Methods:This study included SOTRs identified from a passive surveillance cohort of 1466 patients with acute undifferentiated febrile illness between 2012 and 2019.Diagnosis of arboviral infection was confirmed using RT-PCR and/or serological testing.Clinical,laboratory,and outcome data were extracted and analyzed descriptively.Results:Eleven SOTRs(10 kidney,1 heart transplant recipient)were diagnosed with arboviral infections:8 with dengue(DENV),2 with chikungunya virus(CHIKV),and 1 with Zika virus(ZIKV)infection.The median time from transplantation to symptom onset was 35.0 days(IQR 28.5-111.0).DENV infection was associated with severe disease,including dengue shock syndrome(50%,4/8)and dengue hemorrhagic fever(25%,2/8).Six patients(75%,6/8)required ICU admission.Common laboratory abnormalities in dengue patients included leukopenia(100%,8/8),thrombocytopenia(100%,8/8),elevated transaminases(87.5%,7/8),and acute kidney injury(50%,4/8).CHIKV and ZIKV cases presented as mild,self-limiting febrile illnesses without complications.All patients recovered without long-term morbidity.Conclusions:DENV infection in SOTRs is associated with significant morbidity,particularly early post-transplant,and requires heightened clinical vigilance.In contrast,CHIKV and ZIKV infections tend to follow a benign course.Enhanced vector control,early diagnostic testing,supportive management,and consideration of dengue vaccination in appropriate candidates are essential to mitigate the impact of arboviral infections in transplant recipients in endemic areas.
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 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.
基金Supported by the Investigator Sponsored Research Grant from Gilead Sciences,No.IN-IT-980-6816the Fondazione Italiana per la Ricerca sul Cancro(AIRC),No.IG 2020 ID 24858.
文摘BACKGROUND Hepatitis delta virus(HDV)infection is the most severe form of chronic viral hepatitis,yet sex-based clinical differences remain poorly defined.Understanding these differences may inform disease management and guide research.AIM To investigate sex-related differences in demographic and clinical characteristics of patients with chronic HDV infection in a nationwide,real-world Italian setting.METHODS We analyzed demographic,clinical,and virological data from 513 hepatitis B surface antigen/anti-HDV-positive patients,consecutively enrolled between 2019 and 2024,across 58 liver clinics in the Italian PITER HDV cohort.A propensity score-weighted logistic regression model evaluated the association between sex and cirrhosis and/or hepatocellular carcinoma.RESULTS Among 513 patients(61.6%male),median age(56.0 years)and age distribution were similar by sex(P=0.41).Cirrhosis was frequent:73.4%vs 66.0%(anti-HDV-positive)and 77.8%vs 74.2%(HDV RNA-positive)in males and females,respectively.HDV RNA levels were comparable(P=0.93).The highest proportion of females with cirrhosis(33.8%)was in the 56-60-year group,similar to males(34.9%).Among patients with cirrhosis aged≤40 years,females,(80.9%of whom of non-Italian origin),were more represented than males(16.1%vs 6.5%respectively,P<0.05).Male sex was associated with cirrhosis(odds ratio=1.85;95%confidence interval:1.004-3.40).Among HDV RNA-positive patients,males more often had hepatocellular carcinoma,elevated gammaglutamyl transpeptidase,alcohol use,diabetes,hypertension,steatotic liver disease,and hepatitis C virus/human immunodeficiency virus coinfection.Interferon eligibility was similar.CONCLUSION HDV-infected females develop cirrhosis earlier,without liver disease cofactors,while males show advanced liver disease with multiple cofactors.Tailored care for young migrant women and cofactor-guided management for men may improve HDV outcomes,promoting equity.
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.
基金Project supported by the National Science and Technology Major Project of China (No. 2008ZX10002-009)the National Basic Research Program (973) of China (No. 2007CB513001)
文摘Stem cells can be obtained from women's menstrual blood derived from the endometrium.The cells display stem cell markers such as Oct-4,SSEA-4,Nanog,and c-kit(CD117),and have the potent ability to differentiate into various cell types,including the heart,nerve,bone,cartilage,and fat.There has been no evidence of teratoma,ectopic formation,or any immune response after transplantation into an animal model.These cells quickly regenerate after menstruation and secrete many growth factors to display recurrent angiogenesis.The plasticity and safety of the acquired cells have been demonstrated in many studies.Menstrual blood-derived stem cells(MenSCs) provide an alternative source of adult stem cells for research and application in regenerative medicine.Here we summarize the multipotent properties and the plasticities of MenSCs and other endometrial stem cells from recent studies conducted both in vitro and in vivo.
