Introduction: Entero bacteria are mainly found in the gut of man and animals. The frequent acquisition of antibiotic resistance mechanisms explains why they are the bacteria most often implicated in human infectious p...Introduction: Entero bacteria are mainly found in the gut of man and animals. The frequent acquisition of antibiotic resistance mechanisms explains why they are the bacteria most often implicated in human infectious pathology. It is estimated to be involved in 50% of sepsis, 60% of enteritis, 70% of urinary tract infection case. Objective: To determine the prevalence of enterobacterial infections diagnosed at Fann Infectious Diseases Clinic, and describe their epidemiological, clinical, therapeutic and evolutionary aspects. Patients and Methods: This is a retrospective and descriptive study, on patients hospitalized from January 2013 to December 2014, at Fann Infectious Diseases Clinic, with bacteriological confirmation of an enterobacteria infection. Results: A total of 129 cases were collected during the study period. The average age was 41 years, and female were predominant (60%) with a sex ratio of 0.67. Comorbidity was found in 88.4% of the cases, most of which were HIV infection. The most common clinical signs were infectious syndrome (53.49%) and general impairment (40.31%). The main gateway was urinary (55.8%). Samples were monomicrobial in 76.7% of cases. Klebsiella and Escherichia were the most common and 68.7% of the subjects had probabilistic treatment. Most enterobacterial strains were resistant to third generation cephalosporins (C3G), aminoglycosides to ciprofloxacin and cotrimoxazole. Aside from 4% of them, all were sensitive to imipenem. Conclusion: The advent of antibiotics has brought hope in the treatment of enterobacterial infections. However, an increase in their resistance to the usual antibiotics has been noted in recent years. As a result, the fight against antibiotic resistance must be a priority.展开更多
Pseudomonas aeruginosa is one of the leading nosocomial pathogens worldwide, and their infections are difficult to treat due to acquired resistance to many antibiotics. This study aimed to detect class 1 and 2 integro...Pseudomonas aeruginosa is one of the leading nosocomial pathogens worldwide, and their infections are difficult to treat due to acquired resistance to many antibiotics. This study aimed to detect class 1 and 2 integrons and antibiotic susceptibility of clinical isolates of P. aeruginosa. Two hundred and five P. aeruginosa strains were collected from the seven general state hospitals in Turkey. They were characterized by antimicrobial susceptibility testing, screened for class 1 and class 2 integrons, and evaluated for the association between antibiotic resistance phenotypes and the presence of integrons. intI gene was amplified in 10 isolates (4.87%) by PCR and in seven isolates of them (70%) were found different gene cassettes. The aadA gene integrated into the class 1 integrons was most frequently found and it was followed by aac genes and blaOXA family genes. Sequence analysis of variable regions of the class 1 integrons showed five gene cassette arrays;aadA1(99%), aac(3)-Id(82%)-orf-aac(3”)-Ia(99%), aac(3)-Ie(83%)-blaoxa10(100%)- aadA1 (100%), aadA6(99%, 100%), aac(6’)-I(97%)-orf-aadA2(99%). No class 2 integron was detected. This study is the first multicenter study for class 1 integrons and it indicates the low rate of presence of class 1 gene cassette in P. aeruginosa.展开更多
BACKGROUND Nearly 290000 patients with chronic hepatitis C die annually from the most severe complications of the disease.One of them is liver cirrhosis,which occurs in about 20%of patients chronically infected with t...BACKGROUND Nearly 290000 patients with chronic hepatitis C die annually from the most severe complications of the disease.One of them is liver cirrhosis,which occurs in about 20%of patients chronically infected with the hepatitis C virus(HCV).Direct-acting antivirals(DAAs),which replaced interferon(IFN)-based regimens,significantly improved the prognosis of this group of patients,increasing HCV eradication rates and tolerability of therapy.Our study is the first to assess changes in patient profile,effectiveness,and safety in the HCV-infected cirrhotic population in the IFN-free era.AIM To document changes in patient characteristics and treatment regimens along with their effectiveness and safety profile over the years.METHODS The studied patients were selected from 14801 chronically HCV-infected individuals who started IFN-free therapy between July 2015 and December 2021 in 22 Polish hepatology centers.The retrospective analysis was conducted in real-world clinical practice based on the EpiTer-2 multicenter database.The measure of treatment effectiveness was the percentage of sustained virologic response(SVR)calculated after excluding patients lost to follow-up.Safety data collected during therapy and the 12-wk post-treatment period included information on adverse events,including serious ones,deaths,and treatment course.RESULTS The studied population(n=3577)was balanced in terms of gender in 2015-2017,while the following years showed the dominance of men.The decline in the median age from 63 in 2015-2016 to 61 years in 2021 was accompanied by a decrease in the percentage of patients with comorbidities and comedications.Treatment-experienced patients dominated in 2015-2016,while treatment-naive individuals gained an advantage in 2017 and reached 93.2%in 2021.Genotype(GT)-specific options were more prevalent in treatment in 2015-2018 and were supplanted by pangenotypic combinations in subsequent years.The effectiveness of the therapy was comparable regardless of the period analyzed,and patients achieved an overall response rate of 95%,with an SVR range of 72.9%-100%for the different therapeutic regimens.Male gender,GT3 infection,and prior treatment failure were identified as independent negative predictors of therapeutic success.CONCLUSION We have documented changes in the profile of HCV-infected cirrhotic patients over the years of accessibility to changing DAA regimens,confirming the high effectiveness of IFN-free therapy in all analyzed periods.展开更多
BACKGROUND It is estimated that 58 million people worldwide are infected with the hepatitis C virus(HCV).Patients with severe psychiatric disorders could not be treated with previously available interferon-based thera...BACKGROUND It is estimated that 58 million people worldwide are infected with the hepatitis C virus(HCV).Patients with severe psychiatric disorders could not be treated with previously available interferon-based therapies due to their unfavorable side effect profile.This has changed with the introduction of direct-acting antivirals(DAA),although their real-life tolerance and effectiveness in patients with different psychiatric disorders remain to be demonstrated.AIM To evaluate the effectiveness and safety of DAA in patients with various mental illnesses.METHODS This was a retrospective observational study encompassing 14272 patients treated with DAA for chronic hepatitis C in 22 Polish hepatology centers,including 942 individuals diagnosed with a mental disorder(anxiety disorder,bipolar affective disorder,depression,anxiety-depressive disorder,personality disorder,schizophrenia,sleep disorder,substance abuse disorder,and mental illness without a specific diagnosis).The safety and effectiveness of DAA in this group were compared to those in a group without psychiatric illness(n=13330).Antiviral therapy was considered successful if serum ribonucleic acid(RNA)of HCV was undetectable 12 wk after its completion[sustained virologic response(SVR)].Safety data,including the incidence of adverse events(AEs),serious AEs(SAEs),and deaths,and the frequency of treatment modification and discontinuation,were collected during therapy and up to 12 wk after treatment completion.The entire study population was included in the intent-to-treat(ITT)analysis.Per-protocol(PP)analysis concerned patients who underwent HCV RNA evaluation 12 wk after completing treatment.RESULTS Among patients with mental illness,there was a significantly higher percentage of men,treatmentnaive patients,obese,human immunodeficiency virus and hepatitis B virus-coinfected,patients with cirrhosis,and those infected with genotype 3(GT3)while infection with GT1b was more frequent in the population without psychiatric disorders.The cure rate calculated PP was not significantly different in the two groups analyzed,with a SVR of 96.9% and 97.7%,respectively.Although patients with bipolar disorder achieved a significantly lower SVR,the multivariate analysis excluded it as an independent predictor of treatment non-response.Male sex,GT3 infection,cirrhosis,and failure of previous therapy were identified as independent negative predictors.The percentage of patients who completed the planned therapy did not differ between groups with and without mental disorders.In six patients,symptoms of mental illness(depression,schizophrenia)worsened,of which two discontinued treatments for this reason.New episodes of sleep disorders occurred significantly more often in patients with mental disorders.Patients with mental illness were more frequently lost to follow-up(4.2%vs 2.5%).CONCLUSION DAA treatment is safe and effective in HCV-infected patients with mental disorders.No specific psychiatric diagnosis lowered the chance of successful antiviral treatment.展开更多
Introduction: Herpes simplex virus is the most common etiology for life-threatening sporadic encephalitis worldwide. Antiviral therapy with acyclovir has been shown to reduce mortality and should be started promptly i...Introduction: Herpes simplex virus is the most common etiology for life-threatening sporadic encephalitis worldwide. Antiviral therapy with acyclovir has been shown to reduce mortality and should be started promptly in patients with clinically suspected viral encephalitis before serological confirmation of the diagnosis. Despite antiviral treatment, it is associated with significant mortality and a wide range of neurologic sequelae or neuropsychiatric disorders. Clinical presentation includes fever, headache, altered mental status, and focal or generalized seizures. In some cases, it can present with focal neurological deficits, such as an acute stroke. The aim of this study is to identify rare complications of HSVE. Presentation: We present a case of a 71-year-old female patient with herpes virus encephalitis and an ischemic cerebral accident. The findings of CT scan of the brain revealed an extensive right temporal hypodensity. CSF findings include an elevated protein level, normal glucose level and pleocytosis with lymphocyte predominance. The lumbar tap confirmed the presence of herpes simplex virus type 1 with polymerase chain reaction (PCR) in the CSF. Neurological manifestations include focal neurological deficit with left-sided hemiparesis and coma. After 40 days of complex therapy, an improvement in the mental state was observed. Conclusion: There are varying degrees of neurologic sequelae among survivors in children and adults despite the antiviral treatment. Herpes simplex encephalitis has significant morbidity and high mortality due to the lack of prophylactic treatment and preventable strategies.展开更多
Currently clinicians all around the world are experiencing a pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The clinical presentation of this pathology includes fever,dry cough,fatigue ...Currently clinicians all around the world are experiencing a pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The clinical presentation of this pathology includes fever,dry cough,fatigue and acute respiratory distress syndrome that can lead to death infected patients.Current studies on coronavirus disease 2019(COVID-19)continue to highlight the urgent need for an effective therapy.Numerous therapeutic strategies have been used until now but,to date,there is no specific effective treatment for SARS-CoV-2 infection.Elevated inflammatory cytokines have been reported in patients with COVID-19.Evidence suggests that elevated cytokine levels,reflecting a hyperinflammatory response secondary to SARS-CoV-2 infection,are responsible for multi-organ damage in patients with COVID-19.For these reason,numerous randomized clinical trials are currently underway to explore the effectiveness of biopharmaceutical drugs,such as,interleukin-1 blockers,interleukin-6 inhibitors,Janus kinase inhibitors,in COVID-19.The aim of the present paper is to briefly summarize the pathogenetic rationale and the state of the art of therapeutic strategy blocking hyperinflammation.展开更多
Objective:To investigate the antibiotic resistance genes inserted into class I and class 2integrons in Acinetobacler baumannii[A.baumannii)isolates obtained from nine different cities in Turkey.Methods:A collection of...Objective:To investigate the antibiotic resistance genes inserted into class I and class 2integrons in Acinetobacler baumannii[A.baumannii)isolates obtained from nine different cities in Turkey.Methods:A collection of 281 A.baumannii clinical isolates were collected from nine diferenl state hospitals in Turkey and were confirmed as A.baumannU by conventional biochemical,API testing and bla_(-OXA-51)specific PCR.The isolates were examined by PCR for existence of class I and2 integron gene cassettes.Results:They were characterized by antimicrobial susceptibility testing and the highest resistance rates were determined for piperacillin(90.03%),ciprofloxacin(87.54%),cefepime and trimethoprim/sulfamethoxazole(81.13%).The lowest resistance rates was for cefotaxime(3.55%).class 1 integrons were detected in 6.4%(18/281)of A.baumannii strains and no class 2 integron was detected.The gene casselles of class 1 inlegrons AacCI-AAC(3)l-aadAI,AacCI-aadA1,AAC(3)-I,AAC(3)-I-AAC(3)-I-aadA1,TEM-1.AAC(3)-I-aadA1-AAC(3)-I-AAC(3)-I,AAC(3)-I-AAC(3)-I-AAC(3)-I-aadA1,AAC(3)-I-aadA1,AAC(3)-I-AAC(3)-I,AAC(3)-I-aadA1-AAC(3)-I-aadA1,AAC(3)-I-AAC(3)-I-aadA1-AAC(3)-I-aadA1 were detected in eighteen strains.The aac genes family were most frequently found integrated into the class 1 inlegrons and it was followed by aadA genes and TEM-1 genes.Conclusions:This is an extensive study on the distribulion of class 1 integron among A.baumannii in Turkey.In addition to these,two new alleles were observed.Their percentage rates of similarity to other cassettes are 95%aadA1(TK A18)and 89%,aadA 1(ANKA3).展开更多
Objective: To investigate the association between IL-1 Ra variable number of tandem repeat(rs2234663), IL-6-597 GA(rs1800797), IL-6-572 GC(rs1800796) and the risk of CrimeanCongo hemorrhagic fever(CCHF) in the Turkish...Objective: To investigate the association between IL-1 Ra variable number of tandem repeat(rs2234663), IL-6-597 GA(rs1800797), IL-6-572 GC(rs1800796) and the risk of CrimeanCongo hemorrhagic fever(CCHF) in the Turkish patients. Methods: This study included 50 patients infected with CCHF and 50 healthy controls. These variants were genotyped using polymerase chain reaction and/or restriction fragment length polymorphism method. Results: The distribution of the IL-6-572 GC genotypes and alleles varied significantly between the patients and the controls. The subjects carrying IL-6-572 GC GG genotype and G allele had increased risk of developing CCHF compared to the control group(P=0.006, P=0.014, respectively). IL-6-572 GC GC genotype was higher in the controls than the patients(P=0.006). For the triple genotype combinations, the 1/2-GC-GG genotype combination was detected more frequently in the control group than CCHF patients(P=0.016). IL-6(-572/-597) GG-GG genotype was significantly higher in the patient group(P=0.015), while the GC-GG genotype was significantly lower in the patient group(P=0.005). Additionally, the G-G haplotype was significantly higher in the patient group(P=0.042), whereas C-G was found to be significantly lower in the patients than the control group(P=0.037). Conclusions: The results of this study suggest the IL-6-572 GC variant might be genetic markers of sensitivity to CCHF in the Turkish population and may facilitate greater protection against the disease.展开更多
Introducing PCR products into plasmids vectors is key for molecular techniques. Ideally cloning vectors are easy to construct, modify and propagate, neither require advanced techniques nor special equipment or reagent...Introducing PCR products into plasmids vectors is key for molecular techniques. Ideally cloning vectors are easy to construct, modify and propagate, neither require advanced techniques nor special equipment or reagents and efficiently incorporate PCR products at close to zero empty vector background. We provide an easy to engineer self-made cloning vector, neither requiring sophisticated tools or techniques nor advanced cloning knowledge. Through recombination we obtained the pUC18ccdB vector, carrying the ccdB suicide gene within the pUC18 backbone. When SmaI cleaved (within the ccdB) vector was T4 ligated with small (0.2 kbp) and intermediate (1.3 to 2.2 kbp) blunt end PCR-products and transformed into E. coli, the amount of clones with incorporated PCR product was comparable to commercial PCR-cloning kits and at a close to zero PCR product negative background. In conclusion we present a simple, versatile and cheap approach to an efficient “home made” PCR-cloning vector that allows integration of crude blunt end PCR products at close to zero background.展开更多
In solid organ transplant(SOT) recipients, Streptococcus pneumoniae can cause substantial morbidityand mortality ranging from non-invasive to invasive diseases, including pneumonia, bacteremia, and meningitis, with a ...In solid organ transplant(SOT) recipients, Streptococcus pneumoniae can cause substantial morbidityand mortality ranging from non-invasive to invasive diseases, including pneumonia, bacteremia, and meningitis, with a risk of invasive pneumococcal disease 12 times higher than that observed in non-immunocompromised patients. Moreover, pneumococcal infection has been related to graft dysfunction. Several factors have been involved in the risk of pneumococcal disease in SOT recipients, such as type of transplant, time since transplantation, influenza activity, and nasopharyngeal colonization. Pneumococcal vaccination is recommended for all SOT recipients with 23-valent pneumococcal polysaccharides vaccine. Although immunological rate response is appropriate, it is lower than in the rest of the population, decreases with time, and its clinical efficacy is variable. Booster strategy with 7-valent pneumococcal conjugate vaccine has not shown benefit in this population. Despite its relevance, there are few studies focused on invasive pneumococcal disease in SOT recipients. Further studies addressing clinical, microbiological, and epidemiological data of pneumococcal disease in the transplant setting as well as new strategies for improving the protection of SOT recipients are warranted.展开更多
Object: To analyze the clinical, epidemiological and laboratory characteristics of the cases with measles in the Plovdiv region, Bulgaria, in the period March-July 2017. Materials and Methods: The study included 139 h...Object: To analyze the clinical, epidemiological and laboratory characteristics of the cases with measles in the Plovdiv region, Bulgaria, in the period March-July 2017. Materials and Methods: The study included 139 hospitalized patients with measles, treated in the Clinic of Infectious Diseases, University Hospital “St. George”—Plovdiv, during the observed period. Diagnosis was verified by ELISA in 133 of the patients. The following methods were used: clinical and epidemiological analysis, laboratory, microbiological and imaging tests. Results: The age distribution of the patients was: infants below 1 year were 23.8%;1 - 3 years—24.5%;4 - 17 years—30.9%;and over 18 years —20.8%. Ethnicity: from Roma origin were 83.5% and Bulgarians—16.5%. Most of the patients (62%) reported contact with a measles patient. Ninety eight of the patients were over 13 months of age and they should have been immunized, as the vaccine in Bulgaria is applied on the 13 month. Of these 98 patients, 49% were immunized, 28% were not, and for 23% there were not data. The most common clinical symptoms were: fever—97.1%, cough—98.6% and runny nose—82.7%. Conjunctivitis was observed in 82%, asthenia in 46%, and diarrhea in 51.1%. The rash appeared average on the 4th day of the onset of complaints. Koplik’s spots were observed in 71.9%, cervical lymphadenopathy in 56.1%, hepatomegaly—in 25.2%, and splenomegaly—in 7.9%;auscultation data for bronchitis/pneumonia—in 33.1%. Laboratory tests: leucopenia in 32.4%, leukocytosis—2.2%, normal results—in the rest 65.4%. ESR was increased in 39.1% and CRP in 76.5% of the patients. X-ray of the lung was performed under indication and was positive in 28/46. The serological test—anti-measles IgM (ELISA) was positive in 95.7% (133/139). We observed the following complications: pneumonia—12.2%, bronchitis—15.1%, laryngitis—4.3%, otitis—1.4%, gastroenteritis—14.4% and stomatitis—6.5%. The outcome was fatal for one patient. Conclusions: Measles still prevails during the age of childhood, but 20.8% of the patients were adults. The analysis of the patient’s immunity showed that the lap of immunization was the main cause for periodical arising of epidemic outbreaks, although the programs for elimination of measles in Europe until 2020. The disease ran with typical course but we observed a higher rate of complications.展开更多
BACKGROUND The introduction of direct-acting antiviral drugs into clinical practice has revolutionized the treatment of chronic hepatitis C,making it highly effective and safe for patients.However,few researchers have...BACKGROUND The introduction of direct-acting antiviral drugs into clinical practice has revolutionized the treatment of chronic hepatitis C,making it highly effective and safe for patients.However,few researchers have analyzed the factors causing therapy failure in some patients.AIM To analyze factors influencing the failure of direct antiviral drugs in the large,multicenter EpiTer-2 cohort in a real-world setting.METHODS The study cohort consisted of patients with chronic hepatitis C treated at 22 Polish centers from 2016-2020.Data collected from the online EpiTer-2 database included the following:hepatitis C virus(HCV)genotype,stage of fibrosis,hematology and liver function parameters,Child-Turcotte-Pugh and Model for End-stage Liver Disease scores,prior antiviral therapy,concomitant diseases,and drugs used in relation to hepatitis B virus(HBV)and/or human immunodeficiency virus(HIV)coinfections.Adverse events observed during the treatment and follow-up period were reported.Both standard and machine learning methods were used for statistical analysis.RESULTS During analysis,12614 patients with chronic hepatitis C were registered,of which 11938(mean age:52 years)had available sustained virologic response(SVR)data[11629(97%)achieved SVR and 309(3%)did not].Most patients(78.1%)were infected with HCV genotype 1b.Liver cirrhosis was diagnosed in 2974 patients,while advanced fibrosis(F3)was diagnosed in 1717 patients.We included patients with features of hepatic failure at baseline[ascites in 142(1.2%)and encephalopathy in 68(0.6%)patients].The most important host factors negatively influencing treatment efficacy were liver cirrhosis,clinical and laboratory features of liver failure,history of hepatocellular carcinoma,and higher body mass index.Among viral factors,genotype 3 and viral load also exerted an influence on treatment efficacy.Classical statistical analysis revealed that treatment ineffectiveness seemed to be influenced by the male sex,which was not confirmed by the multivariate analysis using the machine learning algorithm(random forest).Coinfection with HBV(including patients with on-treatment reactivation of HBV infection)or HIV,extrahepatic manifestations,and renal failure did not significantly affect the treatment efficacy.CONCLUSION In patients with advanced liver disease,individualized therapy(testing for resistance-associated variants and response-guided treatment)should be considered to maximize the chance of achieving SVR.展开更多
Background Alzheimer’s disease(AD)is a progressive multifaceted neurodegenerative disorder for which no disease-modifying treatment exists.Neuroinflammation is central to the pathology progression,with evidence sugge...Background Alzheimer’s disease(AD)is a progressive multifaceted neurodegenerative disorder for which no disease-modifying treatment exists.Neuroinflammation is central to the pathology progression,with evidence suggesting that microglia-released galectin-3(gal3)plays a pivotal role by amplifying neuroinflammation in AD.However,the possible involvement of gal3 in the disruption of neuronal network oscillations typical of AD remains unknown.Methods Here,we investigated the functional implications of gal3 signaling on experimentally induced gamma oscillations ex vivo(20-80 Hz)by performing electrophysiological recordings in the hippocampal CA3 area of wild-type(WT)mice and of the 5×FAD mouse model of AD.In addition,the recorded slices from WT mice under acute gal3 application were analyzed with RT-qPCR to detect expression of some neuroinflammation-related genes,and amyloid-β(Aβ)plaque load was quantified by immunostaining in the CA3 area of 6-month-old 5×FAD mice with or without Gal3 knockout(KO).Results Gal3 application decreased gamma oscillation power and rhythmicity in an activity-dependent manner,which was accompanied by impairment of cellular dynamics in fast-spiking interneurons(FSNs)and pyramidal cells.We found that the gal3-induced disruption was mediated by the gal3 carbohydrate-recognition domain and prevented by the gal3 inhibitor TD139,which also prevented Aβ42-induced degradation of gamma oscillations.Further-more,the 5×FAD mice lacking gal3(5×FAD-Gal3KO)exhibited WT-like gamma network dynamics and decreased Aβplaque load.Conclusions We report for the first time that gal3 impairs neuronal network dynamics by spike-phase uncoupling of FSNs,inducing a network performance collapse.Moreover,our findings suggest gal3 inhibition as a potential therapeutic strategy to counteract the neuronal network instability typical of AD and other neurological disorders encompassing neuroinflammation and cognitive decline.展开更多
Helicobacter pylori(H.pylori)is one of the most common chronic bacterial infections in humans,affecting half of world’s population.Therapy for H.pylori infection has proven to be both effective and safe.The oneweek t...Helicobacter pylori(H.pylori)is one of the most common chronic bacterial infections in humans,affecting half of world’s population.Therapy for H.pylori infection has proven to be both effective and safe.The oneweek triple therapy including proton pump inhibitor,clarithromycin,and amoxicillin or metronidazole is still recommended as a first-line treatment to eradicate H.pylori infection in countries with low clarithromycin resistance.Generally,this therapy is well-tolerated,with only a few and usually minor side effects.However,rare but severe adverse effects such as pseudomembranous colitis have been reported,Clostridium difficile(C.difficile)infection being the main causative factor in all cases.We report the cases of two women who developed pseudomembranous colitis after a 1-wk triple therapy consisting of pantoprazole 20 mg bid,clarithromycin 500 mg bid,and amoxicillin 1 g bid to eradicate H.pylori infection.A limited colonoscopy showed typical appearance of pseudomembranous colitis,and the stool test for C.difficile toxins was positive.Rapid resolution of symptoms and negative C.difficile toxins were obtained in both patients with oral vancomycin.No relapse occurred during a four and eleven-month,respectively,follow up.These cases suggest that physicians should have a high index of suspicion for pseudomembranous colitis when evaluate patients with diarrhea following H.pylori eradication therapy.展开更多
AIM: To determine the incidence, etiology, risk factors and outcome of ventilator-associated pneumonia(VAP) in patients undergoing orthotopic liver transplantation(OLT).METHODS: This retrospective study considered 242...AIM: To determine the incidence, etiology, risk factors and outcome of ventilator-associated pneumonia(VAP) in patients undergoing orthotopic liver transplantation(OLT).METHODS: This retrospective study considered 242 patients undergoing deceased donor OLT. VAP was diagnosed according to clinical and microbiological criteria. RESULTS: VAP occurred in 18(7.4%) patients, with an incidence of 10 per 1000 d of mechanical ventilation(MV). Isolated bacterial etiologic agents were mainly Enterobacteriaceae(79%). Univariate logistic analysis showed that model for end-stage liver disease(MELD) score, pre-operative hospitalization, treatment with terlipressin, Child-Turcotte-Pugh score, days of MV and red cell transfusion were risk factors for VAP. Multivariateanalysis, considering significant risk factors in univariate analysis, demonstrated that pneumonia was strongly associated with terlipressin usage, pre-operative hospitalization, days of MV and red cell transfusion. Mortality rate was 22% in the VAP group vs 4% in the group without VAP. CONCLUSION: Our data suggest that VAP is an important cause of nosocomial infection during postoperative period in OLT patients. MELD score was a significant risk factor in univariate analysis. Multiple transfusions, treatment with terlipressin, preoperative hospitalization rather than called to the hospital while at home and days of MV constitute important risk factors for VAP development.展开更多
AIM:To investigate the serovirological prevalence and clinical features of hepatitis E virus(HEV) infection in end-stage renal failure patients and in the healthy population.METHODS:HEV infection is a viral disease th...AIM:To investigate the serovirological prevalence and clinical features of hepatitis E virus(HEV) infection in end-stage renal failure patients and in the healthy population.METHODS:HEV infection is a viral disease that can cause sporadic and epidemic hepatitis.Previous studies unexpectedly showed a high prevalence of HEV antibodies in immunosuppressed subjects,including hemodialysis(HD)patients and patients who had undergone kidney transplant.A cohort/case-control study was carried out from January 2012 to August 2013 in two hospitals in southern Italy(Foggia and S.Giovanni Rotondo,Apulia).The seroprevalence of HEV was determined in 801 subjects;231 HD patients,120 renal transplant recipients,and450 health individuals.All HD patients and the recipients of renal transplants were attending the Departments of Nephrology and Dialysis at two hospitals located in Southern Italy,and were included progressively in this study.Serum samples were tested for HEV antibodies(Ig G/Ig M);in the case of positivity they were confirmed by a Western blot assay and were also tested for HEV-RNA,and the HEV genotypes were determined.RESULTS:A total of 30/801(3.7%)patients were positive for anti-HEV Ig(Ig G and/or Ig M)and by Western blot.The healthy population presented with a prevalence of 2.7%,HD patients had a prevalence of 6.0%,and transplant recipients had a prevalence of 3.3%.The overall combined HEV-positive prevalence in the two groups with chronic renal failure was 5.1%.The rates of exposure to HEV(positivity of HEV-Ig G/M in the early samples)were lower in the healthy controls,but the difference among the three groups was not statistically significant(P>0.05).Positivity for anti-HEV/Ig M was detected in 4/30(13.33%)anti-HEV Ig positive individuals,in 2/14 HD patients,in1/4 transplant individuals,and in 1/12 of the healthy population.The relative risk of being HEV-Ig M-positive was significantly higher among transplant recipients compared to the other two groups(OR=65.4,95%CI:7.2-592.7,P<0.001),but the subjects with HEV-Ig M positivity were numerically too few to calculate a significant difference.No patient presented with chronic hepatitis from HEV infection alone.CONCLUSION:This study indicated a higher,but not significant,circulation of HEV in hemodialysis patients vs the healthy population.Chronic hepatitis due to the HEV virus was not observed.展开更多
AIM: To check the safety and efficacy of boceprevir/telaprevir with peginterferon/ribavirin for hepatitis C virus(HCV) genotype 1 in the real-world settings. METHODS: This study was a non-randomized, observational, pr...AIM: To check the safety and efficacy of boceprevir/telaprevir with peginterferon/ribavirin for hepatitis C virus(HCV) genotype 1 in the real-world settings. METHODS: This study was a non-randomized, observational, prospective, multicenter. This study involved 47 centers in Italy. A database was prepared for the homogenous collection of the data, was used by all of the centers for data collection, and was updated continuously. All of the patients enrolled in this study were older than 18 years of age and were diagnosed with chronic infection due to HCV genotype 1. The HCV RNA testing was performed using COBAS-Taq Man2.0(Roche, LLQ 25 IU/m L). RESULTS: All consecutively treated patients were included. Forty-seven centers enrolled 834 patients as follows: Male 64%; median age 57(range 18-78), of whom 18.3% were over 65; mean body mass index 25.6(range 16-39); genotype 1b(79.4%); diagnosis of cirrhosis(38.2%); and fibrosis F3/4(71.2%). The following drugs were used: Telaprevir(66.2%) and PEG-IFN-alpha2a(67.6%). Patients were na?ve(24.4%), relapsers(30.5%), partial responders(14.8%) and null responders(30.3%). Overall, adverse events(AEs) occurred in 617 patients(73.9%) during the treatment. Anemia was the most frequent AE(52.9% of cases), especially in cirrhotic. The therapy was stopped for 14.6% of the patients because of adverse events or virological failure(15%). Sustained virological response was achieved in 62.7% of the cases, but was 43.8% in cirrhotic patients over 65 years of age. CONCLUSION: In everyday practice, triple therapy is safe but has moderate efficacy, especially for patients over 65 years of age, with advanced fibrosis, nonresponders to peginterferon + ribavirin.展开更多
Human toxocariasis is a widespread parasitic disease caused by ingestion of Toxocara canis or catis larvae or eggs. Parasitic diseases are uncommon in industrialized countries, yet this problem has not disappeared. Pa...Human toxocariasis is a widespread parasitic disease caused by ingestion of Toxocara canis or catis larvae or eggs. Parasitic diseases are uncommon in industrialized countries, yet this problem has not disappeared. Parasitic diseases can cause different syndrome (visceral larva migrans, ocular larva migrans) and the clinical features can be confusing. Severe organ involvement affecting the liver, lungs, nervous central system and eyes can lead to serious damage. We present a case of toxocariasis presenting with fever, desaturation and cholestatic hepatitis. Only the subsequent appearance of eosinophilia helped us to arrive at the correct diagnosis. Prompt diagnosis allowed specific therapy avoiding permanent complications.展开更多
Background/Aims: Interferon (IFN) monotherapy significantly reduces the chron icity rate of acute hepatitis C (AHC) but optimal regimen and treatment timing r emain undefined. The aim of this study was to assess the e...Background/Aims: Interferon (IFN) monotherapy significantly reduces the chron icity rate of acute hepatitis C (AHC) but optimal regimen and treatment timing r emain undefined. The aim of this study was to assess the efficacy of a 6- month course of pegylated IFN (PEG- IFN) α - 2b monotherapy in AHC patients and to investigate if IFN treatment initiated after 12 weeks from clinical presentatio n, still achieved a high response rate. Methods: Sixteen AHC patients still vire mic after 12 weeks from the onset were treated with PEG- IFN α - 2b (1.5 mcg/ kg once weekly) for 6 months and followed for at least 12 months. Response to th erapy was defined as normal ALT values and undetectable HCV RNA (< 50 IU/ml) at the end of therapy, after 6 (sustained r esponse) and 12 months follow- up (long- term response). Results: At the end o f treatment, HCV RNA was undetectable in 15/16 patients while ALT normalized in 14/16 patients. After 6 and 12 months follow- up, 15/16 patients (94% ) showed virological and biochemical response. Conclusions: A 6- month course of PEG- IFN α - 2b is effective in inducing resolution of AHC in 94% of patients. Ou r results provide a rationale for delaying treatment for 12 weeks, targeting onl y patients who fail to clear the virus spontaneously and truly requiring therapy without loss of efficacy.展开更多
BACKGROUND The revolution in treatment of patients with chronic hepatitis C virus(HCV)infection dates back to the introduction of direct-acting antivirals(DAAs).The increase in efficacy was most pronounced in patients...BACKGROUND The revolution in treatment of patients with chronic hepatitis C virus(HCV)infection dates back to the introduction of direct-acting antivirals(DAAs).The increase in efficacy was most pronounced in patients infected with genotype(GT)1b,as this was the most poorly responsive population to treatment during the interferon era.AIM To identify the most effective interferon-free therapy for GT1b-infected patients and to determine positive and negative predictors of virological response.METHODS This real-world retrospective analysis included patients chronically infected with GT1b HCV whose data were obtained from the multicenter observational EpiTer-2 database.Treatment effectiveness was evaluated for each therapeutic regimen as the percentage of sustained virological responses(SVR).Assessment of the safety was based on the evaluation of the course of therapy,the occurrence of adverse events including serious ones,deaths during treatment and in the post 12-wk follow-up period.RESULTS The studied population consisted of 11385 patients with a mean age of 53±14.8 years and a female predominance(53.4%).The majority of them were treatment-naïve(74.6%)and patients with cirrhosis accounted for 24.3%.Of the DAA regimens used,76.9%were GT-specific with ombitasvir/paritaprevir/ritonavir+dasabuvir±ribavirin being the most used option(32.4%).A total of 10903 patients responded to treatment resulting in a 98.1%in the per-protocol analysis after excluding 273 patients without SVR data.The effectiveness of all regimens exceeded 90%and the highest SVR of 98.9%was achieved in patients treated with a combination of glecaprevir/pibrentasvir.Logistic regression analyses showed that the virologic response was independently associated with female sex[odds ratio(OR)=1.67],absence of decompensated cirrhosis at baseline(OR=2.42)and higher baseline platelets(OR=1.004 per 1000/μL increase),while the presence of human immunodeficiency virus(HIV)coinfection significantly decreased the odds of response(OR=0.39).About 95%-100%of patients completed therapy irrespective of the drug regimen.At least one adverse effect occurred in 10.9%-36.3%and most of them were mild.No treatment related deaths have been reported.CONCLUSION We documented very high effectiveness and a good safety profile across all DAA regimens.Positive predictors of SVR were female sex,absence of decompensated cirrhosis at baseline and higher platelet count while HIV coinfection reduced the effectiveness.展开更多
文摘Introduction: Entero bacteria are mainly found in the gut of man and animals. The frequent acquisition of antibiotic resistance mechanisms explains why they are the bacteria most often implicated in human infectious pathology. It is estimated to be involved in 50% of sepsis, 60% of enteritis, 70% of urinary tract infection case. Objective: To determine the prevalence of enterobacterial infections diagnosed at Fann Infectious Diseases Clinic, and describe their epidemiological, clinical, therapeutic and evolutionary aspects. Patients and Methods: This is a retrospective and descriptive study, on patients hospitalized from January 2013 to December 2014, at Fann Infectious Diseases Clinic, with bacteriological confirmation of an enterobacteria infection. Results: A total of 129 cases were collected during the study period. The average age was 41 years, and female were predominant (60%) with a sex ratio of 0.67. Comorbidity was found in 88.4% of the cases, most of which were HIV infection. The most common clinical signs were infectious syndrome (53.49%) and general impairment (40.31%). The main gateway was urinary (55.8%). Samples were monomicrobial in 76.7% of cases. Klebsiella and Escherichia were the most common and 68.7% of the subjects had probabilistic treatment. Most enterobacterial strains were resistant to third generation cephalosporins (C3G), aminoglycosides to ciprofloxacin and cotrimoxazole. Aside from 4% of them, all were sensitive to imipenem. Conclusion: The advent of antibiotics has brought hope in the treatment of enterobacterial infections. However, an increase in their resistance to the usual antibiotics has been noted in recent years. As a result, the fight against antibiotic resistance must be a priority.
基金supported by Recep Tayyip Erdogan University Research Fund Grants BAP-2013.102.03.12 and BAP-2013.102.03.13.
文摘Pseudomonas aeruginosa is one of the leading nosocomial pathogens worldwide, and their infections are difficult to treat due to acquired resistance to many antibiotics. This study aimed to detect class 1 and 2 integrons and antibiotic susceptibility of clinical isolates of P. aeruginosa. Two hundred and five P. aeruginosa strains were collected from the seven general state hospitals in Turkey. They were characterized by antimicrobial susceptibility testing, screened for class 1 and class 2 integrons, and evaluated for the association between antibiotic resistance phenotypes and the presence of integrons. intI gene was amplified in 10 isolates (4.87%) by PCR and in seven isolates of them (70%) were found different gene cassettes. The aadA gene integrated into the class 1 integrons was most frequently found and it was followed by aac genes and blaOXA family genes. Sequence analysis of variable regions of the class 1 integrons showed five gene cassette arrays;aadA1(99%), aac(3)-Id(82%)-orf-aac(3”)-Ia(99%), aac(3)-Ie(83%)-blaoxa10(100%)- aadA1 (100%), aadA6(99%, 100%), aac(6’)-I(97%)-orf-aadA2(99%). No class 2 integron was detected. This study is the first multicenter study for class 1 integrons and it indicates the low rate of presence of class 1 gene cassette in P. aeruginosa.
文摘BACKGROUND Nearly 290000 patients with chronic hepatitis C die annually from the most severe complications of the disease.One of them is liver cirrhosis,which occurs in about 20%of patients chronically infected with the hepatitis C virus(HCV).Direct-acting antivirals(DAAs),which replaced interferon(IFN)-based regimens,significantly improved the prognosis of this group of patients,increasing HCV eradication rates and tolerability of therapy.Our study is the first to assess changes in patient profile,effectiveness,and safety in the HCV-infected cirrhotic population in the IFN-free era.AIM To document changes in patient characteristics and treatment regimens along with their effectiveness and safety profile over the years.METHODS The studied patients were selected from 14801 chronically HCV-infected individuals who started IFN-free therapy between July 2015 and December 2021 in 22 Polish hepatology centers.The retrospective analysis was conducted in real-world clinical practice based on the EpiTer-2 multicenter database.The measure of treatment effectiveness was the percentage of sustained virologic response(SVR)calculated after excluding patients lost to follow-up.Safety data collected during therapy and the 12-wk post-treatment period included information on adverse events,including serious ones,deaths,and treatment course.RESULTS The studied population(n=3577)was balanced in terms of gender in 2015-2017,while the following years showed the dominance of men.The decline in the median age from 63 in 2015-2016 to 61 years in 2021 was accompanied by a decrease in the percentage of patients with comorbidities and comedications.Treatment-experienced patients dominated in 2015-2016,while treatment-naive individuals gained an advantage in 2017 and reached 93.2%in 2021.Genotype(GT)-specific options were more prevalent in treatment in 2015-2018 and were supplanted by pangenotypic combinations in subsequent years.The effectiveness of the therapy was comparable regardless of the period analyzed,and patients achieved an overall response rate of 95%,with an SVR range of 72.9%-100%for the different therapeutic regimens.Male gender,GT3 infection,and prior treatment failure were identified as independent negative predictors of therapeutic success.CONCLUSION We have documented changes in the profile of HCV-infected cirrhotic patients over the years of accessibility to changing DAA regimens,confirming the high effectiveness of IFN-free therapy in all analyzed periods.
文摘BACKGROUND It is estimated that 58 million people worldwide are infected with the hepatitis C virus(HCV).Patients with severe psychiatric disorders could not be treated with previously available interferon-based therapies due to their unfavorable side effect profile.This has changed with the introduction of direct-acting antivirals(DAA),although their real-life tolerance and effectiveness in patients with different psychiatric disorders remain to be demonstrated.AIM To evaluate the effectiveness and safety of DAA in patients with various mental illnesses.METHODS This was a retrospective observational study encompassing 14272 patients treated with DAA for chronic hepatitis C in 22 Polish hepatology centers,including 942 individuals diagnosed with a mental disorder(anxiety disorder,bipolar affective disorder,depression,anxiety-depressive disorder,personality disorder,schizophrenia,sleep disorder,substance abuse disorder,and mental illness without a specific diagnosis).The safety and effectiveness of DAA in this group were compared to those in a group without psychiatric illness(n=13330).Antiviral therapy was considered successful if serum ribonucleic acid(RNA)of HCV was undetectable 12 wk after its completion[sustained virologic response(SVR)].Safety data,including the incidence of adverse events(AEs),serious AEs(SAEs),and deaths,and the frequency of treatment modification and discontinuation,were collected during therapy and up to 12 wk after treatment completion.The entire study population was included in the intent-to-treat(ITT)analysis.Per-protocol(PP)analysis concerned patients who underwent HCV RNA evaluation 12 wk after completing treatment.RESULTS Among patients with mental illness,there was a significantly higher percentage of men,treatmentnaive patients,obese,human immunodeficiency virus and hepatitis B virus-coinfected,patients with cirrhosis,and those infected with genotype 3(GT3)while infection with GT1b was more frequent in the population without psychiatric disorders.The cure rate calculated PP was not significantly different in the two groups analyzed,with a SVR of 96.9% and 97.7%,respectively.Although patients with bipolar disorder achieved a significantly lower SVR,the multivariate analysis excluded it as an independent predictor of treatment non-response.Male sex,GT3 infection,cirrhosis,and failure of previous therapy were identified as independent negative predictors.The percentage of patients who completed the planned therapy did not differ between groups with and without mental disorders.In six patients,symptoms of mental illness(depression,schizophrenia)worsened,of which two discontinued treatments for this reason.New episodes of sleep disorders occurred significantly more often in patients with mental disorders.Patients with mental illness were more frequently lost to follow-up(4.2%vs 2.5%).CONCLUSION DAA treatment is safe and effective in HCV-infected patients with mental disorders.No specific psychiatric diagnosis lowered the chance of successful antiviral treatment.
文摘Introduction: Herpes simplex virus is the most common etiology for life-threatening sporadic encephalitis worldwide. Antiviral therapy with acyclovir has been shown to reduce mortality and should be started promptly in patients with clinically suspected viral encephalitis before serological confirmation of the diagnosis. Despite antiviral treatment, it is associated with significant mortality and a wide range of neurologic sequelae or neuropsychiatric disorders. Clinical presentation includes fever, headache, altered mental status, and focal or generalized seizures. In some cases, it can present with focal neurological deficits, such as an acute stroke. The aim of this study is to identify rare complications of HSVE. Presentation: We present a case of a 71-year-old female patient with herpes virus encephalitis and an ischemic cerebral accident. The findings of CT scan of the brain revealed an extensive right temporal hypodensity. CSF findings include an elevated protein level, normal glucose level and pleocytosis with lymphocyte predominance. The lumbar tap confirmed the presence of herpes simplex virus type 1 with polymerase chain reaction (PCR) in the CSF. Neurological manifestations include focal neurological deficit with left-sided hemiparesis and coma. After 40 days of complex therapy, an improvement in the mental state was observed. Conclusion: There are varying degrees of neurologic sequelae among survivors in children and adults despite the antiviral treatment. Herpes simplex encephalitis has significant morbidity and high mortality due to the lack of prophylactic treatment and preventable strategies.
文摘Currently clinicians all around the world are experiencing a pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The clinical presentation of this pathology includes fever,dry cough,fatigue and acute respiratory distress syndrome that can lead to death infected patients.Current studies on coronavirus disease 2019(COVID-19)continue to highlight the urgent need for an effective therapy.Numerous therapeutic strategies have been used until now but,to date,there is no specific effective treatment for SARS-CoV-2 infection.Elevated inflammatory cytokines have been reported in patients with COVID-19.Evidence suggests that elevated cytokine levels,reflecting a hyperinflammatory response secondary to SARS-CoV-2 infection,are responsible for multi-organ damage in patients with COVID-19.For these reason,numerous randomized clinical trials are currently underway to explore the effectiveness of biopharmaceutical drugs,such as,interleukin-1 blockers,interleukin-6 inhibitors,Janus kinase inhibitors,in COVID-19.The aim of the present paper is to briefly summarize the pathogenetic rationale and the state of the art of therapeutic strategy blocking hyperinflammation.
基金Supported by Recep Tayyip Erdogan University(Grant No.BAP2012.102.03.4.and BAP-2013.102.03.4)
文摘Objective:To investigate the antibiotic resistance genes inserted into class I and class 2integrons in Acinetobacler baumannii[A.baumannii)isolates obtained from nine different cities in Turkey.Methods:A collection of 281 A.baumannii clinical isolates were collected from nine diferenl state hospitals in Turkey and were confirmed as A.baumannU by conventional biochemical,API testing and bla_(-OXA-51)specific PCR.The isolates were examined by PCR for existence of class I and2 integron gene cassettes.Results:They were characterized by antimicrobial susceptibility testing and the highest resistance rates were determined for piperacillin(90.03%),ciprofloxacin(87.54%),cefepime and trimethoprim/sulfamethoxazole(81.13%).The lowest resistance rates was for cefotaxime(3.55%).class 1 integrons were detected in 6.4%(18/281)of A.baumannii strains and no class 2 integron was detected.The gene casselles of class 1 inlegrons AacCI-AAC(3)l-aadAI,AacCI-aadA1,AAC(3)-I,AAC(3)-I-AAC(3)-I-aadA1,TEM-1.AAC(3)-I-aadA1-AAC(3)-I-AAC(3)-I,AAC(3)-I-AAC(3)-I-AAC(3)-I-aadA1,AAC(3)-I-aadA1,AAC(3)-I-AAC(3)-I,AAC(3)-I-aadA1-AAC(3)-I-aadA1,AAC(3)-I-AAC(3)-I-aadA1-AAC(3)-I-aadA1 were detected in eighteen strains.The aac genes family were most frequently found integrated into the class 1 inlegrons and it was followed by aadA genes and TEM-1 genes.Conclusions:This is an extensive study on the distribulion of class 1 integron among A.baumannii in Turkey.In addition to these,two new alleles were observed.Their percentage rates of similarity to other cassettes are 95%aadA1(TK A18)and 89%,aadA 1(ANKA3).
文摘Objective: To investigate the association between IL-1 Ra variable number of tandem repeat(rs2234663), IL-6-597 GA(rs1800797), IL-6-572 GC(rs1800796) and the risk of CrimeanCongo hemorrhagic fever(CCHF) in the Turkish patients. Methods: This study included 50 patients infected with CCHF and 50 healthy controls. These variants were genotyped using polymerase chain reaction and/or restriction fragment length polymorphism method. Results: The distribution of the IL-6-572 GC genotypes and alleles varied significantly between the patients and the controls. The subjects carrying IL-6-572 GC GG genotype and G allele had increased risk of developing CCHF compared to the control group(P=0.006, P=0.014, respectively). IL-6-572 GC GC genotype was higher in the controls than the patients(P=0.006). For the triple genotype combinations, the 1/2-GC-GG genotype combination was detected more frequently in the control group than CCHF patients(P=0.016). IL-6(-572/-597) GG-GG genotype was significantly higher in the patient group(P=0.015), while the GC-GG genotype was significantly lower in the patient group(P=0.005). Additionally, the G-G haplotype was significantly higher in the patient group(P=0.042), whereas C-G was found to be significantly lower in the patients than the control group(P=0.037). Conclusions: The results of this study suggest the IL-6-572 GC variant might be genetic markers of sensitivity to CCHF in the Turkish population and may facilitate greater protection against the disease.
文摘Introducing PCR products into plasmids vectors is key for molecular techniques. Ideally cloning vectors are easy to construct, modify and propagate, neither require advanced techniques nor special equipment or reagents and efficiently incorporate PCR products at close to zero empty vector background. We provide an easy to engineer self-made cloning vector, neither requiring sophisticated tools or techniques nor advanced cloning knowledge. Through recombination we obtained the pUC18ccdB vector, carrying the ccdB suicide gene within the pUC18 backbone. When SmaI cleaved (within the ccdB) vector was T4 ligated with small (0.2 kbp) and intermediate (1.3 to 2.2 kbp) blunt end PCR-products and transformed into E. coli, the amount of clones with incorporated PCR product was comparable to commercial PCR-cloning kits and at a close to zero PCR product negative background. In conclusion we present a simple, versatile and cheap approach to an efficient “home made” PCR-cloning vector that allows integration of crude blunt end PCR products at close to zero background.
基金Supported by Ministerio de Economíay Competitividad,Instituto de Salud CarlosⅢ-co-financed by the European Development Regional Fund"A way to achieve Europe"ERDF,and the Spanish Network for the Research in Infectious Diseases,No.REIPI RD12/00015/0001
文摘In solid organ transplant(SOT) recipients, Streptococcus pneumoniae can cause substantial morbidityand mortality ranging from non-invasive to invasive diseases, including pneumonia, bacteremia, and meningitis, with a risk of invasive pneumococcal disease 12 times higher than that observed in non-immunocompromised patients. Moreover, pneumococcal infection has been related to graft dysfunction. Several factors have been involved in the risk of pneumococcal disease in SOT recipients, such as type of transplant, time since transplantation, influenza activity, and nasopharyngeal colonization. Pneumococcal vaccination is recommended for all SOT recipients with 23-valent pneumococcal polysaccharides vaccine. Although immunological rate response is appropriate, it is lower than in the rest of the population, decreases with time, and its clinical efficacy is variable. Booster strategy with 7-valent pneumococcal conjugate vaccine has not shown benefit in this population. Despite its relevance, there are few studies focused on invasive pneumococcal disease in SOT recipients. Further studies addressing clinical, microbiological, and epidemiological data of pneumococcal disease in the transplant setting as well as new strategies for improving the protection of SOT recipients are warranted.
文摘Object: To analyze the clinical, epidemiological and laboratory characteristics of the cases with measles in the Plovdiv region, Bulgaria, in the period March-July 2017. Materials and Methods: The study included 139 hospitalized patients with measles, treated in the Clinic of Infectious Diseases, University Hospital “St. George”—Plovdiv, during the observed period. Diagnosis was verified by ELISA in 133 of the patients. The following methods were used: clinical and epidemiological analysis, laboratory, microbiological and imaging tests. Results: The age distribution of the patients was: infants below 1 year were 23.8%;1 - 3 years—24.5%;4 - 17 years—30.9%;and over 18 years —20.8%. Ethnicity: from Roma origin were 83.5% and Bulgarians—16.5%. Most of the patients (62%) reported contact with a measles patient. Ninety eight of the patients were over 13 months of age and they should have been immunized, as the vaccine in Bulgaria is applied on the 13 month. Of these 98 patients, 49% were immunized, 28% were not, and for 23% there were not data. The most common clinical symptoms were: fever—97.1%, cough—98.6% and runny nose—82.7%. Conjunctivitis was observed in 82%, asthenia in 46%, and diarrhea in 51.1%. The rash appeared average on the 4th day of the onset of complaints. Koplik’s spots were observed in 71.9%, cervical lymphadenopathy in 56.1%, hepatomegaly—in 25.2%, and splenomegaly—in 7.9%;auscultation data for bronchitis/pneumonia—in 33.1%. Laboratory tests: leucopenia in 32.4%, leukocytosis—2.2%, normal results—in the rest 65.4%. ESR was increased in 39.1% and CRP in 76.5% of the patients. X-ray of the lung was performed under indication and was positive in 28/46. The serological test—anti-measles IgM (ELISA) was positive in 95.7% (133/139). We observed the following complications: pneumonia—12.2%, bronchitis—15.1%, laryngitis—4.3%, otitis—1.4%, gastroenteritis—14.4% and stomatitis—6.5%. The outcome was fatal for one patient. Conclusions: Measles still prevails during the age of childhood, but 20.8% of the patients were adults. The analysis of the patient’s immunity showed that the lap of immunization was the main cause for periodical arising of epidemic outbreaks, although the programs for elimination of measles in Europe until 2020. The disease ran with typical course but we observed a higher rate of complications.
文摘BACKGROUND The introduction of direct-acting antiviral drugs into clinical practice has revolutionized the treatment of chronic hepatitis C,making it highly effective and safe for patients.However,few researchers have analyzed the factors causing therapy failure in some patients.AIM To analyze factors influencing the failure of direct antiviral drugs in the large,multicenter EpiTer-2 cohort in a real-world setting.METHODS The study cohort consisted of patients with chronic hepatitis C treated at 22 Polish centers from 2016-2020.Data collected from the online EpiTer-2 database included the following:hepatitis C virus(HCV)genotype,stage of fibrosis,hematology and liver function parameters,Child-Turcotte-Pugh and Model for End-stage Liver Disease scores,prior antiviral therapy,concomitant diseases,and drugs used in relation to hepatitis B virus(HBV)and/or human immunodeficiency virus(HIV)coinfections.Adverse events observed during the treatment and follow-up period were reported.Both standard and machine learning methods were used for statistical analysis.RESULTS During analysis,12614 patients with chronic hepatitis C were registered,of which 11938(mean age:52 years)had available sustained virologic response(SVR)data[11629(97%)achieved SVR and 309(3%)did not].Most patients(78.1%)were infected with HCV genotype 1b.Liver cirrhosis was diagnosed in 2974 patients,while advanced fibrosis(F3)was diagnosed in 1717 patients.We included patients with features of hepatic failure at baseline[ascites in 142(1.2%)and encephalopathy in 68(0.6%)patients].The most important host factors negatively influencing treatment efficacy were liver cirrhosis,clinical and laboratory features of liver failure,history of hepatocellular carcinoma,and higher body mass index.Among viral factors,genotype 3 and viral load also exerted an influence on treatment efficacy.Classical statistical analysis revealed that treatment ineffectiveness seemed to be influenced by the male sex,which was not confirmed by the multivariate analysis using the machine learning algorithm(random forest).Coinfection with HBV(including patients with on-treatment reactivation of HBV infection)or HIV,extrahepatic manifestations,and renal failure did not significantly affect the treatment efficacy.CONCLUSION In patients with advanced liver disease,individualized therapy(testing for resistance-associated variants and response-guided treatment)should be considered to maximize the chance of achieving SVR.
基金funding provided by Karolinska Institute.This work was supported by the Swedish Research Council,the Swedish Brain Foundation,the Swedish Alzheimer Foundation,theÅhlén Foundation(AF),the Berger Foundation(TD),the Olle Engkvist Foundation(TD),G&K Kock Foundation(TD),the Strategic Research Area MultiPark at Lund University(TD),the Foundation for Geriatric Diseases at Karolinska Institutet,theÅhlén Foundation(YAT),Consejo Nacional de Ciencia y Tecnología(CONACYT)postdoctoral fellowships and StratNeuro program at Karolinska Institutet(LEAG),Lindhés Advokabyra AB Grant and Stohnes Stiftelse(LEAG,YAT)the Spanish Ministerio de Ciencia e Innovación(MICIN/AEI/FEDER:PID2019-107677 GB-I00,ARM).
文摘Background Alzheimer’s disease(AD)is a progressive multifaceted neurodegenerative disorder for which no disease-modifying treatment exists.Neuroinflammation is central to the pathology progression,with evidence suggesting that microglia-released galectin-3(gal3)plays a pivotal role by amplifying neuroinflammation in AD.However,the possible involvement of gal3 in the disruption of neuronal network oscillations typical of AD remains unknown.Methods Here,we investigated the functional implications of gal3 signaling on experimentally induced gamma oscillations ex vivo(20-80 Hz)by performing electrophysiological recordings in the hippocampal CA3 area of wild-type(WT)mice and of the 5×FAD mouse model of AD.In addition,the recorded slices from WT mice under acute gal3 application were analyzed with RT-qPCR to detect expression of some neuroinflammation-related genes,and amyloid-β(Aβ)plaque load was quantified by immunostaining in the CA3 area of 6-month-old 5×FAD mice with or without Gal3 knockout(KO).Results Gal3 application decreased gamma oscillation power and rhythmicity in an activity-dependent manner,which was accompanied by impairment of cellular dynamics in fast-spiking interneurons(FSNs)and pyramidal cells.We found that the gal3-induced disruption was mediated by the gal3 carbohydrate-recognition domain and prevented by the gal3 inhibitor TD139,which also prevented Aβ42-induced degradation of gamma oscillations.Further-more,the 5×FAD mice lacking gal3(5×FAD-Gal3KO)exhibited WT-like gamma network dynamics and decreased Aβplaque load.Conclusions We report for the first time that gal3 impairs neuronal network dynamics by spike-phase uncoupling of FSNs,inducing a network performance collapse.Moreover,our findings suggest gal3 inhibition as a potential therapeutic strategy to counteract the neuronal network instability typical of AD and other neurological disorders encompassing neuroinflammation and cognitive decline.
文摘Helicobacter pylori(H.pylori)is one of the most common chronic bacterial infections in humans,affecting half of world’s population.Therapy for H.pylori infection has proven to be both effective and safe.The oneweek triple therapy including proton pump inhibitor,clarithromycin,and amoxicillin or metronidazole is still recommended as a first-line treatment to eradicate H.pylori infection in countries with low clarithromycin resistance.Generally,this therapy is well-tolerated,with only a few and usually minor side effects.However,rare but severe adverse effects such as pseudomembranous colitis have been reported,Clostridium difficile(C.difficile)infection being the main causative factor in all cases.We report the cases of two women who developed pseudomembranous colitis after a 1-wk triple therapy consisting of pantoprazole 20 mg bid,clarithromycin 500 mg bid,and amoxicillin 1 g bid to eradicate H.pylori infection.A limited colonoscopy showed typical appearance of pseudomembranous colitis,and the stool test for C.difficile toxins was positive.Rapid resolution of symptoms and negative C.difficile toxins were obtained in both patients with oral vancomycin.No relapse occurred during a four and eleven-month,respectively,follow up.These cases suggest that physicians should have a high index of suspicion for pseudomembranous colitis when evaluate patients with diarrhea following H.pylori eradication therapy.
文摘AIM: To determine the incidence, etiology, risk factors and outcome of ventilator-associated pneumonia(VAP) in patients undergoing orthotopic liver transplantation(OLT).METHODS: This retrospective study considered 242 patients undergoing deceased donor OLT. VAP was diagnosed according to clinical and microbiological criteria. RESULTS: VAP occurred in 18(7.4%) patients, with an incidence of 10 per 1000 d of mechanical ventilation(MV). Isolated bacterial etiologic agents were mainly Enterobacteriaceae(79%). Univariate logistic analysis showed that model for end-stage liver disease(MELD) score, pre-operative hospitalization, treatment with terlipressin, Child-Turcotte-Pugh score, days of MV and red cell transfusion were risk factors for VAP. Multivariateanalysis, considering significant risk factors in univariate analysis, demonstrated that pneumonia was strongly associated with terlipressin usage, pre-operative hospitalization, days of MV and red cell transfusion. Mortality rate was 22% in the VAP group vs 4% in the group without VAP. CONCLUSION: Our data suggest that VAP is an important cause of nosocomial infection during postoperative period in OLT patients. MELD score was a significant risk factor in univariate analysis. Multiple transfusions, treatment with terlipressin, preoperative hospitalization rather than called to the hospital while at home and days of MV constitute important risk factors for VAP development.
文摘AIM:To investigate the serovirological prevalence and clinical features of hepatitis E virus(HEV) infection in end-stage renal failure patients and in the healthy population.METHODS:HEV infection is a viral disease that can cause sporadic and epidemic hepatitis.Previous studies unexpectedly showed a high prevalence of HEV antibodies in immunosuppressed subjects,including hemodialysis(HD)patients and patients who had undergone kidney transplant.A cohort/case-control study was carried out from January 2012 to August 2013 in two hospitals in southern Italy(Foggia and S.Giovanni Rotondo,Apulia).The seroprevalence of HEV was determined in 801 subjects;231 HD patients,120 renal transplant recipients,and450 health individuals.All HD patients and the recipients of renal transplants were attending the Departments of Nephrology and Dialysis at two hospitals located in Southern Italy,and were included progressively in this study.Serum samples were tested for HEV antibodies(Ig G/Ig M);in the case of positivity they were confirmed by a Western blot assay and were also tested for HEV-RNA,and the HEV genotypes were determined.RESULTS:A total of 30/801(3.7%)patients were positive for anti-HEV Ig(Ig G and/or Ig M)and by Western blot.The healthy population presented with a prevalence of 2.7%,HD patients had a prevalence of 6.0%,and transplant recipients had a prevalence of 3.3%.The overall combined HEV-positive prevalence in the two groups with chronic renal failure was 5.1%.The rates of exposure to HEV(positivity of HEV-Ig G/M in the early samples)were lower in the healthy controls,but the difference among the three groups was not statistically significant(P>0.05).Positivity for anti-HEV/Ig M was detected in 4/30(13.33%)anti-HEV Ig positive individuals,in 2/14 HD patients,in1/4 transplant individuals,and in 1/12 of the healthy population.The relative risk of being HEV-Ig M-positive was significantly higher among transplant recipients compared to the other two groups(OR=65.4,95%CI:7.2-592.7,P<0.001),but the subjects with HEV-Ig M positivity were numerically too few to calculate a significant difference.No patient presented with chronic hepatitis from HEV infection alone.CONCLUSION:This study indicated a higher,but not significant,circulation of HEV in hemodialysis patients vs the healthy population.Chronic hepatitis due to the HEV virus was not observed.
文摘AIM: To check the safety and efficacy of boceprevir/telaprevir with peginterferon/ribavirin for hepatitis C virus(HCV) genotype 1 in the real-world settings. METHODS: This study was a non-randomized, observational, prospective, multicenter. This study involved 47 centers in Italy. A database was prepared for the homogenous collection of the data, was used by all of the centers for data collection, and was updated continuously. All of the patients enrolled in this study were older than 18 years of age and were diagnosed with chronic infection due to HCV genotype 1. The HCV RNA testing was performed using COBAS-Taq Man2.0(Roche, LLQ 25 IU/m L). RESULTS: All consecutively treated patients were included. Forty-seven centers enrolled 834 patients as follows: Male 64%; median age 57(range 18-78), of whom 18.3% were over 65; mean body mass index 25.6(range 16-39); genotype 1b(79.4%); diagnosis of cirrhosis(38.2%); and fibrosis F3/4(71.2%). The following drugs were used: Telaprevir(66.2%) and PEG-IFN-alpha2a(67.6%). Patients were na?ve(24.4%), relapsers(30.5%), partial responders(14.8%) and null responders(30.3%). Overall, adverse events(AEs) occurred in 617 patients(73.9%) during the treatment. Anemia was the most frequent AE(52.9% of cases), especially in cirrhotic. The therapy was stopped for 14.6% of the patients because of adverse events or virological failure(15%). Sustained virological response was achieved in 62.7% of the cases, but was 43.8% in cirrhotic patients over 65 years of age. CONCLUSION: In everyday practice, triple therapy is safe but has moderate efficacy, especially for patients over 65 years of age, with advanced fibrosis, nonresponders to peginterferon + ribavirin.
文摘Human toxocariasis is a widespread parasitic disease caused by ingestion of Toxocara canis or catis larvae or eggs. Parasitic diseases are uncommon in industrialized countries, yet this problem has not disappeared. Parasitic diseases can cause different syndrome (visceral larva migrans, ocular larva migrans) and the clinical features can be confusing. Severe organ involvement affecting the liver, lungs, nervous central system and eyes can lead to serious damage. We present a case of toxocariasis presenting with fever, desaturation and cholestatic hepatitis. Only the subsequent appearance of eosinophilia helped us to arrive at the correct diagnosis. Prompt diagnosis allowed specific therapy avoiding permanent complications.
文摘Background/Aims: Interferon (IFN) monotherapy significantly reduces the chron icity rate of acute hepatitis C (AHC) but optimal regimen and treatment timing r emain undefined. The aim of this study was to assess the efficacy of a 6- month course of pegylated IFN (PEG- IFN) α - 2b monotherapy in AHC patients and to investigate if IFN treatment initiated after 12 weeks from clinical presentatio n, still achieved a high response rate. Methods: Sixteen AHC patients still vire mic after 12 weeks from the onset were treated with PEG- IFN α - 2b (1.5 mcg/ kg once weekly) for 6 months and followed for at least 12 months. Response to th erapy was defined as normal ALT values and undetectable HCV RNA (< 50 IU/ml) at the end of therapy, after 6 (sustained r esponse) and 12 months follow- up (long- term response). Results: At the end o f treatment, HCV RNA was undetectable in 15/16 patients while ALT normalized in 14/16 patients. After 6 and 12 months follow- up, 15/16 patients (94% ) showed virological and biochemical response. Conclusions: A 6- month course of PEG- IFN α - 2b is effective in inducing resolution of AHC in 94% of patients. Ou r results provide a rationale for delaying treatment for 12 weeks, targeting onl y patients who fail to clear the virus spontaneously and truly requiring therapy without loss of efficacy.
文摘BACKGROUND The revolution in treatment of patients with chronic hepatitis C virus(HCV)infection dates back to the introduction of direct-acting antivirals(DAAs).The increase in efficacy was most pronounced in patients infected with genotype(GT)1b,as this was the most poorly responsive population to treatment during the interferon era.AIM To identify the most effective interferon-free therapy for GT1b-infected patients and to determine positive and negative predictors of virological response.METHODS This real-world retrospective analysis included patients chronically infected with GT1b HCV whose data were obtained from the multicenter observational EpiTer-2 database.Treatment effectiveness was evaluated for each therapeutic regimen as the percentage of sustained virological responses(SVR).Assessment of the safety was based on the evaluation of the course of therapy,the occurrence of adverse events including serious ones,deaths during treatment and in the post 12-wk follow-up period.RESULTS The studied population consisted of 11385 patients with a mean age of 53±14.8 years and a female predominance(53.4%).The majority of them were treatment-naïve(74.6%)and patients with cirrhosis accounted for 24.3%.Of the DAA regimens used,76.9%were GT-specific with ombitasvir/paritaprevir/ritonavir+dasabuvir±ribavirin being the most used option(32.4%).A total of 10903 patients responded to treatment resulting in a 98.1%in the per-protocol analysis after excluding 273 patients without SVR data.The effectiveness of all regimens exceeded 90%and the highest SVR of 98.9%was achieved in patients treated with a combination of glecaprevir/pibrentasvir.Logistic regression analyses showed that the virologic response was independently associated with female sex[odds ratio(OR)=1.67],absence of decompensated cirrhosis at baseline(OR=2.42)and higher baseline platelets(OR=1.004 per 1000/μL increase),while the presence of human immunodeficiency virus(HIV)coinfection significantly decreased the odds of response(OR=0.39).About 95%-100%of patients completed therapy irrespective of the drug regimen.At least one adverse effect occurred in 10.9%-36.3%and most of them were mild.No treatment related deaths have been reported.CONCLUSION We documented very high effectiveness and a good safety profile across all DAA regimens.Positive predictors of SVR were female sex,absence of decompensated cirrhosis at baseline and higher platelet count while HIV coinfection reduced the effectiveness.
