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1.
Int J Mol Sci ; 25(5)2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38473721

RESUMO

Our study highlighted the immune changes by pro-inflammatory biomarkers in the gut-liver-axis-linked ROS-cell death mechanisms in chronic and acute inflammations when gut cells are exposed to endotoxins in patients with hepatic cirrhosis or steatosis. In duodenal tissue samples, gut immune barrier dysfunction was analyzed by pro-inflammatory biomarker expressions, oxidative stress, and cell death by flow cytometry methods. A significant innate and adaptative immune system reaction was observed as result of persistent endotoxin action in gut cells in chronic inflammation tissue samples recovered from hepatic cirrhosis with the A-B child stage. Instead, in patients with C child stage of HC, the endotoxin tolerance was installed in cells, characterized by T lymphocyte silent activation and increased Th1 cytokines expression. Interesting mechanisms of ROS-cell death were observed in chronic and acute inflammation samples when gut cells were exposed to endotoxins and immune changes in the gut-liver axis. Late apoptosis represents the chronic response to injury induction by the gut immune barrier dysfunction, oxidative stress, and liver-dysregulated barrier. Meanwhile, necrosis represents an acute and severe reply to endotoxin action on gut cells when the immune system reacts to pro-inflammatory Th1 and Th2 cytokines releasing, offering protection against PAMPs/DAMPs by monocytes and T lymphocyte activation. Flow cytometric analysis of pro-inflammatory biomarkers linked to oxidative stress-cell death mechanisms shown in our study recommends laboratory techniques in diagnostic fields.


Assuntos
Endotoxinas , Inflamação , Criança , Humanos , Endotoxinas/metabolismo , Espécies Reativas de Oxigênio , Cirrose Hepática , Apoptose , Citocinas , Biomarcadores
2.
Medicina (Kaunas) ; 57(6)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200527

RESUMO

The pathophysiology of accelerated atherosclerosis in people living with Human Immunofediciency virus (HIV) is complex. Coronary artery disease (CAD) has become an important cause of mortality in these patients. They often have atypical symptoms, leading to frequently missed diagnoses. We report a case of a 51-year-old male undergoing antiretroviral therapy who was admitted for acute coronary syndrome. He had severe coronary artery disease that involved difficult management.


Assuntos
Síndrome Coronariana Aguda , Doença da Artéria Coronariana , Infecções por HIV , Ponte de Artéria Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento
3.
Gastroenterology ; 146(2): 442-52.e1, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24126097

RESUMO

BACKGROUND & AIMS: Thrombocytopenia is common among patients with hepatitis C virus (HCV) infection and advanced fibrosis or cirrhosis, limiting initiation and dose of peginterferon-alfa (PEG) and ribavirin (RBV) therapy. The phase 3 randomized, controlled studies, Eltrombopag to Initiate and Maintain Interferon Antiviral Treatment to Benefit Subjects with Hepatitis C-Related Liver Disease (ENABLE)-1 and ENABLE-2, investigated the ability of eltrombopag to increase the number of platelets in patients, thereby allowing them to receive initiation or maintenance therapy with PEG and RBV. METHODS: Patients with HCV infection and thrombocytopenia (platelet count <75,000/µL) who participated in ENABLE-1 (n = 715) or ENABLE-2 (n = 805), from approximately 150 centers in 23 countries, received open-label eltrombopag (25-100 mg/day) for 9 weeks or fewer. Patients whose platelet counts reached the predefined minimal threshold for the initiation of PEG and RBV therapy (95% from ENABLE-1 and 94% from ENABLE-2) entered the antiviral treatment phase, and were assigned randomly (2:1) to groups that received eltrombopag or placebo along with antiviral therapy (24 or 48 weeks, depending on HCV genotype). The primary end point was sustained virologic response (SVR) 24 weeks after completion of antiviral therapy. RESULTS: More patients who received eltrombopag than placebo achieved SVRs (ENABLE-1: eltrombopag, 23%; placebo, 14%; P = .0064; ENABLE-2: eltrombopag, 19%; placebo, 13%; P = .0202). PEG was administered at higher doses, with fewer dose reductions, in the eltrombopag groups of each study compared with the placebo groups. More patients who received eltrombopag than placebo maintained platelet counts of 50,000/µL or higher throughout antiviral treatment (ENABLE-1, 69% vs 15%; ENABLE-2, 81% vs 23%). Adverse events were similar between groups, with the exception of hepatic decompensation (both studies: eltrombopag, 10%; placebo, 5%) and thromboembolic events, which were more common in the eltrombopag group of ENABLE-2. CONCLUSIONS: Eltrombopag increases platelet numbers in thrombocytopenic patients with HCV and advanced fibrosis and cirrhosis, allowing otherwise ineligible or marginal patients to begin and maintain antiviral therapy, leading to significantly increased rates of SVR. Clinical trial no: NCT00516321, NCT00529568.


Assuntos
Antivirais/uso terapêutico , Benzoatos/uso terapêutico , Fármacos Hematológicos/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hidrazinas/uso terapêutico , Cirrose Hepática/complicações , Pirazóis/uso terapêutico , Trombocitopenia/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Esquema de Medicação , Feminino , Seguimentos , Hepatite C Crônica/sangue , Hepatite C Crônica/complicações , Humanos , Quimioterapia de Indução , Análise de Intenção de Tratamento , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Cirrose Hepática/sangue , Cirrose Hepática/virologia , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêutico , Trombocitopenia/sangue , Trombocitopenia/virologia , Resultado do Tratamento , Adulto Jovem
4.
Germs ; 13(1): 10-19, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38023954

RESUMO

Introduction: This study aimed to identify isolates from colonization and assess the risk factors for bacterial colonization and the risk of death in patients admitted to the intensive care unit (ICU) of the Constanta County Infectious Diseases Hospital between September 2017 and September 2019. Methods: This was a retrospective case-control study in a single center that included all patients admitted to the ICU in Constanta, Romania, who underwent bacteriological screening upon admission and 7 days after admission, between September 2017 and September 2019. In total, 253 patients were included in this study. The nasal exudate, pharyngeal exudate, and rectal swab samples were screened. Results: In this study, 253 patients were screened bacteriologically, of which 53 had bacterial colonization and 200 did not. Among the bacterial strains, Klebsiella spp. (43.39%) was the most frequently isolated. The predominant resistance mechanism detected in the bacterial isolates was extended-spectrum ß-lactamase (ESBL). Multivariate analysis identified a Carmeli score of 3 as an independent risk factor for acquiring bacterial colonization in the ICU. The mortality rate of patients with bacterial colonization was 11.32% and 6% for the patients without colonization (p>0.05). Conclusions: Our study revealed an increased prevalence of Enterobacterales colonization in the ICU. Risk factors for acquiring bacterial colonization differed depending on the type of bacterial colonization, such as ESBL, carbapenemases, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE). An independent risk factor for acquiring bacterial colonization was the Carmeli score of 3.

5.
Diagnostics (Basel) ; 13(16)2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37627941

RESUMO

People living with HIV infection are at high risk for cardiovascular events due to inflammation and atherosclerosis. Also, some antiretroviral therapies may contribute to the risk of cardiovascular complications. Immune status is highly dependent on the level of lymphocyte T helper CD4+. There are data suggesting that immune status and CD4+ cell count may be involved in the development of cardiovascular complications in these patients. Our study is longitudinal and retrospective and included a total number of 50 patients with HIV infection associated with acute coronary syndrome, divided into two subgroups based on the nadir of CD4+ cells. This study analyzes the relationship between the immune status of HIV patients, assessed by the nadir of the CD4+ T-cell count, and the outcome of these patients. Also, secondary endpoints were the assessment of the magnitude of coronary lesions and of thrombotic and bleeding risk assessed by specific scores. Clinical and biological parameters and also the extension and complexity of coronary lesions were assessed. Although patients with poor immune status had more complex coronary lesions and increased operative risk and bleeding risk at one year, this was not associated with significant differences in major adverse cardiac and cerebrovascular events at the 30-day and 1-year outcomes.

6.
Diagnostics (Basel) ; 13(9)2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37174918

RESUMO

People living with human immunodeficiency virus have increased cardiovascular risk due to a higher prevalence of traditional and particular risk factors such as chronic inflammation, immune dysregulation, endothelial dysfunction, coagulation abnormalities and antiretroviral therapy. In developed countries, coronary artery disease has become the most frequent cardiovascular disease and an important cause of mortality in these patients. The symptomatology of an acute coronary syndrome can be atypical, and the prevalence of each type of acute coronary syndrome is reported differently. Regarding coronary artery disease severity in people living with HIV, the literature data indicates that the presence of single-vessel disease is akin to that of HIV-negative patients, and their short-term prognosis is unclear. This study aims to assess the clinical characteristics, biological parameters, angiographical features and short-term prognosis of acute coronary syndrome in a cohort of Romanian people living with human immunodeficiency virus.

7.
Diagnostics (Basel) ; 12(12)2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36553155

RESUMO

People living with human immunodeficiency virus have an increased cardiovascular risk due to higher prevalence of traditional risk factors, such as smoking, dyslipidemia, hypertension, diabetes, or obesity, and particular risk factors, such as inflammation, endothelial dysfunction, and antiretroviral therapy. Thus, people living with human immunodeficiency virus can develop accelerated atherosclerosis. The incidence of coronary artery disease in these patients may be twice as high compared with that of HIV-negative individuals with similar characteristics. "Porcelain aorta" is a term used to describe extensive circumferential calcification of the thoracic aorta. The pathophysiology of porcelain aorta is not fully understood. We present a case of a young man who was a smoker and living with HIV since childhood, without other traditional cardiovascular risk factors, who presented to the emergency room with a positive stress test for myocardial ischemia. Transthoracic echocardiography revealed normal regional and global myocardial wall motion, ascending aorta ectasia, and moderate aortic regurgitation. Coronary angiography showed a critical calcified proximal left anterior descending artery stenosis and an important calcification of the thoracic aorta. Therefore, the most important challenge was the management of coronary syndrome in a young person living with HIV, with associated porcelain aorta and aortic regurgitation.

8.
Exp Ther Med ; 23(2): 186, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35069867

RESUMO

Infective endocarditis represents a rare complication among patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2); it is often a nosocomial infection and the symptomatology can be masked by respiratory failure symptoms from SARS-CoV-2 bronchopneumonia. Management of patients with severe forms of SARS-COV-2 infection who also have associated infective endocarditis is very difficult, especially in mono-specialty hospitals (such as infectious diseases hospitals) where access to cardiological investigations is limited. The current study presents the case of a 73-year-old woman with increased cardiovascular risk (high blood pressure, diabetes mellitus and obesity), with uninvestigated ischaemic heart disease, who was admitted to the Department of Infectious Diseases in the Clinical Infectious Diseases Hospital (Constanta, Romania) due to SARS-CoV-2. Although the evolution was initially favorable, the condition of the patient significantly deteriorated on the 14th day of hospitalization due to the development of Enterococcus faecium infective endocarditis. Despite the therapy, the evolution was fulminant. Infection with coronavirus disease 2019 can result in numerous comorbidities, which cause higher mortality rates than in the general population.

9.
J Int Med Res ; 50(10): 3000605221129154, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36259133

RESUMO

OBJECTIVE: To identify carbapenem-resistant Enterobacteriaceae (CRE) in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) and to determine whether they had different risk factors for the acquisition of CRE than patients without COVID-19. METHODS: This retrospective single-centre, case-control study enrolled patients with and without COVID-19. The demographic, clinical, infection, colonization and mortality data were compared between the two groups. RESULTS: A total of 38 patients with COVID-19 and 26 patients without COVID-19 were enrolled. The majority of isolates detected in COVID-19 patients were Klebsiella spp. Leukopenia at admission (odds ratio [OR] 4.70; 95% confidence interval [CI] 1.37, 16.10), invasive mechanical ventilation (OR 5.74; 95% CI 1.07, 30.63), carbapenem treatment (OR 5.09; 95% CI 1.21, 21.27) and corticosteroid treatment (OR 7.06; 95% CI 1.53, 32.39) were independent risk factors for CRE acquisition in COVID-19 patients. Intensive care unit (ICU) mortality was significantly higher in COVID-19 patients compared with patients without COVID-19 (OR 20.62; 95% CI 5.50, 77.23). Length of ICU stay increased the risk of death in patients with COVID-19 (subdistribution hazard ratio 3.81; 95% CI 1.33, 10.92). CONCLUSION: CRE strains were more common in patients with COVID-19 and they had different risks for CRE compared with patients without COVID-19.


Assuntos
COVID-19 , Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Enterobacteriaceae , Humanos , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/epidemiologia , Estudos de Casos e Controles , Estudos Retrospectivos , Antibacterianos/uso terapêutico , SARS-CoV-2 , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Unidades de Terapia Intensiva , Fatores de Risco
10.
N Engl J Med ; 358(6): 568-79, 2008 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-18256392

RESUMO

BACKGROUND: Hypersensitivity reaction to abacavir is strongly associated with the presence of the HLA-B*5701 allele. This study was designed to establish the effectiveness of prospective HLA-B*5701 screening to prevent the hypersensitivity reaction to abacavir. METHODS: This double-blind, prospective, randomized study involved 1956 patients from 19 countries, who were infected with human immunodeficiency virus type 1 and who had not previously received abacavir. We randomly assigned patients to undergo prospective HLA-B*5701 screening, with exclusion of HLA-B*5701-positive patients from abacavir treatment (prospective-screening group), or to undergo a standard-of-care approach of abacavir use without prospective HLA-B*5701 screening (control group). All patients who started abacavir were observed for 6 weeks. To immunologically confirm, and enhance the specificity of, the clinical diagnosis of hypersensitivity reaction to abacavir, we performed epicutaneous patch testing with the use of abacavir. RESULTS: The prevalence of HLA-B*5701 was 5.6% (109 of 1956 patients). Of the patients receiving abacavir, 72% were men, 84% were white, and 18% had not previously received antiretroviral therapy. Screening eliminated immunologically confirmed hypersensitivity reaction (0% in the prospective-screening group vs. 2.7% in the control group, P<0.001), with a negative predictive value of 100% and a positive predictive value of 47.9%. Hypersensitivity reaction was clinically diagnosed in 93 patients, with a significantly lower incidence in the prospective-screening group (3.4%) than in the control group (7.8%) (P<0.001). CONCLUSIONS: HLA-B*5701 screening reduced the risk of hypersensitivity reaction to abacavir. In predominantly white populations, similar to the one in this study, 94% of patients do not carry the HLA-B*5701 allele and are at low risk for hypersensitivity reaction to abacavir. Our results show that a pharmacogenetic test can be used to prevent a specific toxic effect of a drug. (ClinicalTrials.gov number, NCT00340080.)


Assuntos
Didesoxinucleosídeos/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Testes Genéticos , Antígenos HLA-B/genética , Testes do Emplastro , Inibidores da Transcriptase Reversa/efeitos adversos , Adolescente , Adulto , Idoso , Didesoxinucleosídeos/uso terapêutico , Método Duplo-Cego , Hipersensibilidade a Drogas/genética , Hipersensibilidade a Drogas/prevenção & controle , Feminino , Marcadores Genéticos , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , HIV-1 , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Transcriptase Reversa/uso terapêutico
11.
Germs ; 11(2): 319-323, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34422703

RESUMO

INTRODUCTION: Thrombocytopenia is common in SARS-COV-2 infection, and about a quarter of cases have moderate thrombocytopenia. Severe thrombocytopenia is less common and is associated with severe forms of COVID-19. The pathogenesis of this thrombocytopenia appears to be complex, the immune mechanism being incriminated. Immune thrombocytopenic purpura (ITP) is one of the severe complications of COVID-19 and has an increased risk of mucosal or cutaneous bleeding. CASE REPORT: We present the case of a 72-year-old woman admitted to the hospital with moderate COVID-19 who developed severe thrombocytopenia 13 days after the onset of COVID symptoms. Nine days after admission, her platelets decreased from 149×109/L to 3×109/L and numerous patches appeared on the skin and mucous membranes. She was responsive to corticosteroids and platelet transfusion, after five days, the platelet level returned to normal. CONCLUSIONS: Close hematological monitoring of patients with COVID is necessary to prevent severe complications. Even if this patient did not receive immunoglobulins, corticosteroid therapy and platelet administration led to a favorable outcome.

12.
Genes (Basel) ; 12(7)2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34356086

RESUMO

Emery-Dreifuss muscular dystrophy (EDMD) is a rare genetic disease that affects the musculoskeletal system, including the heart, causing rhythm disorders and cardiomyopathy, sometimes requiring an implantable cardioverter-defibrillator (ICD) or heart transplantation due to severe heart damage. The case described herein concerns a 16-year-old girl, with grade II obesity, without other known pathological antecedents or cardiac pathology diagnosis given an annual history of cardiological investigations. She was admitted to the Infectious Diseases Department with SARS-CoV-2 virus infection. The anamnesis showed that the cardiological investigations performed in the past were completed due to the medical history antecedents of her sister, who had been diagnosed with dilated cardiomyopathy, having undergone the placement of an ICD and a heart transplant. Numerous investigations were performed during hospitalization, which revealed high levels of high-sensitive cardiac troponin I (hs-cTnI), creatine kinase (CK) and N-terminal pro b-type natriuretic peptide (NT-proBNP). Dynamic electrocardiographic evaluations showed ventricular extrasystoles, without clinical manifestations. The patient presented stage 2 arterial hypertension (AHT) during hospitalization. A cardiac ultrasound was also performed, which revealed suspected mild subacute viral myocarditis with cardiomyopathy, and antihypertensive medication was initiated. A heart MRI was performed, and the patient was diagnosed with dilated cardiomyopathy, refuting the suspicion of viral subacute myocarditis. After discharge, as the patient developed gait disorders with an impossible heel strike upon walking and limitation of the extension of the arms and ankles, was hospitalized in the Neurology Department. Electrocardiograms (ECGs) were dynamically performed, and because the rhythm disorders persisted, the patient was transferred to the Cardiology Department. On Holter monitoring, non-sustained ventricular tachycardia (NSVT) was detected, so antiarrhythmic treatment was initiated, and placement of an ICD was subsequently decided and was diagnosed with EDMD. Genetic tests were also performed, and a mutation of the lamin A/C gene was detected (LMNA gene exon 2, variant c448A > C (p.Thr150pro), heterozygous form, AD).


Assuntos
COVID-19 , Cardiomiopatia Dilatada , Distrofia Muscular de Emery-Dreifuss , SARS-CoV-2/metabolismo , Adolescente , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/fisiopatologia , COVID-19/terapia , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Dilatada/terapia , Feminino , Humanos , Distrofia Muscular de Emery-Dreifuss/sangue , Distrofia Muscular de Emery-Dreifuss/diagnóstico por imagem , Distrofia Muscular de Emery-Dreifuss/fisiopatologia , Distrofia Muscular de Emery-Dreifuss/terapia
13.
Antibiotics (Basel) ; 10(5)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34065029

RESUMO

Infections with carbapenem-resistant Enterobacteriaceae are emerging as an important challenge in healthcare settings. Currently, carbapenem-resistant Klebsiella pneumoniae (CRKP) are the species of CRE most commonly encountered in hospitals. CRKP is resistant to almost all available antimicrobial agents, and infections with CRKP have been associated with high rates of morbidity and mortality, particularly among persons with prolonged hospitalization exposed to invasive devices. We report nine patients hospitalized in an intensive care unit (ICU) with severe coronavirus disease 2019 (COVID-19) who developed invasive infections due to carbapenemase-producing Klebsiella pneumoniae (CP-Kp), KPC and OXA-48, strains that have not been previously identified in our hospital. Despite ceftazidime/avibactam therapy, five patients died. Coinfections can contribute to a poor prognosis for patients with COVID-19, especially for high-risk populations such as elderly patients. Therefore, it is crucial to establish a rigorous program of antibiotic administration in intensive care units.

14.
Antivir Ther ; 24(6): 425-435, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31355775

RESUMO

BACKGROUND: The safety and efficacy of doravirine were compared with that of efavirenz as initial treatment of adults living with HIV-1 infection (NCT01632345). METHODS: A Phase IIb double-blind trial with participants stratified by screening HIV-1 RNA (≤ or >100,000 copies/ml) and randomized 1:1:1:1:1 to receive once-daily doravirine (25, 50, 100 or 200 mg) or efavirenz 600 mg (Part I) for up to 96 weeks, with open-label tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg (TDF/FTC). After dose selection at week 24, doravirine 100 mg was provided to participants receiving the other doses of doravirine and additional participants were randomized 1:1 to receive once-daily doravirine 100 mg or efavirenz 600 mg for 96 weeks with TDF/FTC (Part II). Primary outcomes were the proportion of participants with HIV-1 RNA <40 copies/ml at week 24, and central nervous system (CNS) adverse events (AEs) by weeks 8 and 24 (Parts I+II combined). RESULTS: 210 and 132 participants were randomized in Parts I and II, respectively, and 216 (108 on doravirine 100 mg, 108 on efavirenz) were evaluable for Parts I+II combined. At week 24, the proportion of participants with HIV-1 RNA <40 copies/ml was 72.9% for doravirine 100 mg and 73.1% for efavirenz (difference -0.5 [95% CI -12.3, 11.2]). In addition, CNS AEs were reported by 26.9% and 47.2% of doravirine and efavirenz recipients, respectively (difference -20.4 [95% CI -32.6, -7.5]; P=0.002). CONCLUSIONS: Doravirine 100 mg with TDF/FTC demonstrated similar antiretroviral activity and superior CNS safety compared with efavirenz 600 mg with TDF/FTC.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Benzoxazinas/administração & dosagem , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Piridonas/administração & dosagem , Triazóis/administração & dosagem , Adulto , Idoso , Alcinos , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade , Benzoxazinas/efeitos adversos , Ciclopropanos , Feminino , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Piridonas/efeitos adversos , Resultado do Tratamento , Triazóis/efeitos adversos , Carga Viral , Adulto Jovem
15.
HIV Clin Trials ; 9(6): 375-86, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19203903

RESUMO

PURPOSE: Treatment-related toxicities frequently limit antiretroviral therapy for patients with HIV-1 infection. This study evaluated the changes in treatment-limiting toxicities when the primary toxicity-causing agent was replaced with enfuvirtide. METHOD: Adult patients with HIV-1 infection (N = 91) with antiretroviral treatment-limiting toxicities were enrolled in this multicenter, open-label, single-arm, 24-week study. Enfuvirtide 90 mg bid was administered instead of a single toxicity-causing component of the previous antiretroviral regimen. Changes in severity of antiretroviral toxicity, safety, tolerability, and maintenance of efficacy of the enfuvirtide regimen were evaluated at baseline and at 4, 8, 12, and 24 weeks. RESULTS: Eighty-four percent of participants completed the study. Injection site reactions with enfuvirtide caused premature withdrawal in 5 participants (5%); a further 10 participants (11%) also withdrew early. Overall antiretroviral-related, treatment-limiting toxicities improved or resolved in 53% of participants switching to enfuvirtide, remained unchanged in 43%, and worsened in 3%. At Week 24, 66% of participants (60/91; intent-to-treat population) maintained or improved their viral load category and 73% of participants (66/91) maintained or improved their CD4 cell counts. CONCLUSION: Replacing a toxicity-causing antiretroviral with enfuvirtide may reduce toxicity without compromising the efficacy of different antiretroviral regimens.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Proteína gp41 do Envelope de HIV , Inibidores da Fusão de HIV , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , HIV-1/efeitos dos fármacos , Fragmentos de Peptídeos , Inibidores da Transcriptase Reversa/efeitos adversos , Adulto , Idoso , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Esquema de Medicação , Quimioterapia Combinada , Enfuvirtida , Feminino , Proteína gp41 do Envelope de HIV/administração & dosagem , Proteína gp41 do Envelope de HIV/efeitos adversos , Proteína gp41 do Envelope de HIV/uso terapêutico , Inibidores da Fusão de HIV/administração & dosagem , Inibidores da Fusão de HIV/efeitos adversos , Inibidores da Fusão de HIV/uso terapêutico , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/efeitos adversos , Fragmentos de Peptídeos/uso terapêutico , Qualidade de Vida , RNA Viral/sangue , Resultado do Tratamento , Carga Viral , Adulto Jovem
16.
J Crit Care Med (Targu Mures) ; 3(1): 39-44, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29967870

RESUMO

INTRODUCTION: Toxic megacolon is a life-threatening disease and is one of the most serious complications of Clostridium difficile infection (CDI), usually needing prompt surgical intervention. Early diagnosis and adequate medical treatment are mandatory. CASES PRESENTATION: In the last two years, three Caucasian female patients have been diagnosed with toxic megacolon and treated in the Clinical Infectious Diseases Hospital, Constanta. All patients had been hospitalized for nonrelated conditions. The first patient was in chemotherapy for non-Hodgkin's lymphoma, the second patient had undergone surgery for colon cancer, and the third patient had surgery for disc herniation. In all cases the toxin test (A+B) was positive and ribotype 027 was present. Abdominal CT examination, both native and after intravenous contrast, showed significant colon dilation, with marked thickening of the wall. Resolution of the condition did not occur using the standard treatment of metronidazole and oral vancomycin, therefore the therapy was altered in two cases using intracolonic administration of vancomycin and intravenous tigecycline. CONCLUSIONS: In these three cases of CDI, the risk factors for severe evolution were: concurrent malignancy, renal failure, obesity, and immune deficiencies. Ribotype 027, a marker for a virulent strain of CD, was found in all three cases complicated by toxic megacolon. The intracolonic administration of vancomycin, and intravenous tigecycline was successful when prior standard therapy had failed, and surgery was avoided.

17.
Germs ; 5(2): 44-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26097834

RESUMO

INTRODUCTION: The objective of the study was to determine the association of host human leukocyte antigen (HLA) class II genotype DRB1 alleles with the response to interferon therapy, viral loads and extent of liver fibrosis in a group of Romanian patients diagnosed with chronic hepatitis C, with different clinical outcomes. Class II HLA genes, particularly the HLA-DRB1 and DQB1 genes, have been shown to have an important role in self-limiting or persistent viral infection, in different genetic populations. In chronic hepatitis C both susceptible and protective alleles have been described, influencing the development of autoimmunity and progression to cirrhosis and hepatocellular carcinoma. METHODS: The study included 54 patients diagnosed with chronic hepatitis C, registered and monitored from January 2014 to January 2015 at the Clinical Hospital of Infectious Diseases, Constanta, Romania. The selected patients were positive for anti-HCV antibodies and HCV-RNA, with screening laboratory results indicating HCV genotype 1b. The method used for the assignment of alleles at HLA-DRB1 and DQB1 loci was molecular genotyping, by the sequence specific oligonucleotide (SSO) hybridization method, and when required, by the sequence specific primers method (SSP). The presence of different alleles in patients has been analyzed for statistical significance. RESULTS: The presence of HLA-DRB1*0301 had a high frequency (14.8%) in null-responders (NR) while alleles DRB1*0701 (11.1%), DRB1*11# (22.2%) and DRB1*0101 (16.7%) were prevalent in sustained virologic responders (SVR). No significant correlation was found between the presence of HLA-DRB1* alleles and viral loads or liver fibrosis with p values not statistically significant after the Bonferroni correction. CONCLUSION: The presented data suggest that in this group of Romanian patients, certain HLA alleles influence the therapeutic response in HCV infection and genetic predisposition may play a role in hepatitis C virus infection in those patients.

18.
Germs ; 4(1): 16-21, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24639957

RESUMO

INTRODUCTION: The purpose of our study was to evaluate clinical and pathological characteristics as well as treatment outcomes in HIV-infected patients with disseminated tuberculosis from the Regional HIV/AIDS Center Constanta, Romania, and to determine associated risk factors. METHODS: We analyzed HIV-infected adults diagnosed with disseminated tuberculosis (TB) over the past two years, monitored in the Regional HIV/AIDS Center Constanta. RESULTS: Out of a total number of 956 HIV-infected patients, 42 had been diagnosed with tuberculosis over the past two years (2011-2013) (4.39%) and 16 of them developed disseminated TB (38%). At the time of diagnosis, we recorded abnormal chest X-rays in 8 (50%), and positive sputum cultures in 4 (25%) of them. The median CD4 count was 40 cells/µL with a range of 5-85 cells/µL; HIV-RNA was detectable in all cases. Multidrug-resistant tuberculosis (MDR-TB) was identified in 6 cases. The outcome was unfavorable in 15 patients. CONCLUSION: In our study, disseminated tuberculosis appeared to be a common pattern of evolution of HIV-TB co-infection (38%). Sputum smear positivity was low and chest X-ray images did not follow a typical pattern. HIV-TB co-infected patients with CD4 lymphocyte cell count <50 cells/µL were more likely to have disseminated TB. The severity of cases, proved by a high mortality rate, requires consideration of this diagnosis early in patients with advanced AIDS, even if laboratory investigations are not suggestive.

19.
J Gastrointestin Liver Dis ; 23(1): 95-8, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24689104

RESUMO

The simultaneous occurrence of two rare conditions in a single patient is uncommon. We report the case of a patient with rectal actinomycosis covering an anorectal melanoma (both infrequent conditions), the last one being later recognized, only after surgical excision. We underline here the role of thinking "outside the box" when an unusual situation is experienced.


Assuntos
Actinomicose/complicações , Melanoma/complicações , Neoplasias Retais/complicações , Actinomicose/diagnóstico , Colonoscopia , Feminino , Humanos , Imageamento por Ressonância Magnética , Melanoma/diagnóstico , Melanoma/cirurgia , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Doenças Raras/diagnóstico , Doenças Raras/cirurgia , Neoplasias Retais/diagnóstico , Neoplasias Retais/cirurgia , Tomografia Computadorizada por Raios X
20.
Germs ; 4(2): 30-40, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24967217

RESUMO

INTRODUCTION: Rotavirus (RV) is a leading cause of acute gastroenteritis (AGE), affecting 95% of children below five years of age. METHODS: In this prospective, multi-center study, children below five years of age who were hospitalized or those who visited the emergency room (ER) due to AGE or who developed AGE at least 48 hours after hospitalization (nosocomial infection) and had a RV-positive stool sample were included (n=1,222). RV-positive samples were genotyped by reverse-transcriptase polymerase chain reaction. RESULTS: RV test results were available for 1,212 children (hospitalizations [n=677], ER visits [n=398] and nosocomial AGE cases [n=137]). Proportions of rotavirus gastroenteritis (RVGE) hospitalizations and ER visits were 51.70% (350/677; 95%CI: 47.86-55.52) and 36.18% (144/398; 95%CI: 31.45-41.12), respectively. Overall, 45.95% (494/1075) of all community-acquired AGE cases were due to RV. High numbers of RVGE cases were recorded between January and March. Most common genotypes were G9P[8] (34.27%) followed by G4P[8] (25.83%) and G1P[8] (23.02%). Of all community-acquired RVGE cases, the highest number of cases was observed in children aged 12-23 months. Median duration of hospitalization among RV-positive subjects was six days (range: 2-31 days). Incidence of nosocomial RVGE was 0.52 (95%CI: 0.45-0.60) cases per 1,000 child-days hospitalization. Median duration for additional hospitalization due to nosocomial RVGE was five days (range: 1-10). The highest burden of nosocomial RVGE was observed in children aged 12-23 months (42.34%, 58/137). Our findings confirm a high burden of acute RVGE disease in Romania and provide useful data to support the implementation of RV vaccination in Romania. TRIAL REGISTRATION: NCT01253967.

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