RESUMO
BACKGROUND: Congenital CMV infection is the most common congenital infection worldwide and a major cause of neurological impairment and sensorineural hearing loss. Fetal CMV infection is confirmed by a positive PCR test in the amniotic fluid (amniocentesis performed after 18-20 weeks of gestation and at least 8 weeks after maternal infection). However, despite a negative antenatal CMV PCR result, some newborns can be tested positive at birth. Although not widely documented, the prognosis for these babies appears to be good. OBJECTIVES: The aim of this study is to evaluate the long-term prognosis of fetuses with a false-negative AFS for cCMV, with a minimum follow-up period of 6 years. STUDY DESIGN: This is a retrospective cohort study of false-negative amniocentesis reported at the CUB-Hôpital Erasme and Hôpital CHIREC in Brussels between 1985 and 2017. RESULTS: Of the 712 negative CMV PCR amniocenteses, 24 had a CMV PCR positive at birth. The false negative rate was 8.6 %. Of the 24 cases, 9 primary maternal infections occurred in the first trimester, 14 in the second trimester and 1 in the third trimester. Among the 24 children, 2 had symptoms at birth (hyperbilirubinemia and left paraventricular cysts), but all had normal follow-up (minimum 4 years, mean 16,6 years). DISCUSSION: Only 2 cases could be explained by early amniocentesis. Among the others, the false-negative results could be attributed to a low viral load, a delayed infection or, less likely, to a sample degradation. CONCLUSION: Despite the false-negative results, all 24 children had a normal long-term follow-up.
Assuntos
Amniocentese , Infecções por Citomegalovirus , Complicações Infecciosas na Gravidez , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/congênito , Reações Falso-Negativas , Recém-Nascido , Seguimentos , Complicações Infecciosas na Gravidez/virologia , Complicações Infecciosas na Gravidez/diagnóstico , Citomegalovirus/genética , Citomegalovirus/isolamento & purificação , Líquido Amniótico/virologia , Masculino , Adulto , Prognóstico , Transmissão Vertical de Doenças Infecciosas , Reação em Cadeia da Polimerase/métodosRESUMO
BACKGROUND: Adequate hand hygiene is considered as one of the most effective strategies in healthcare-related infection prevention. The potential negative effect of rings in hand disinfection and thus, in increased nosocomial infections rates is still controversial. Therefore, the present study was designed with the purpose of examining if rings frequently exposed to surgical scrubbing were associated or not with increased bacterial counts. METHODS: 32 volunteers were randomized into 4 groups: A (no rings), B (participants wore a ring), C (no rings and performed surgical scrubbing with chlorhexidine every 48 h) and D (participants wore a ring and performed surgical scrubbing every 48 h). Glove juice samples were obtained at day 0 (T0) and after a 90-min mock-surgery on day 14 (T1). Quantitative (number of UFC/mL) and qualitative data (microorganism type) were collected as study variables. RESULTS: All groups were comparable at T0. All ring carriers obtained negative cultures at T1. Ring presence was not associated with higher bacterial counts; comparisons between A vs B groups and C vs D groups showed no statistically significant differences (p = 0.076 and 1.000). T1 negative cultures were more frequent in participants performing surgical scrubbing every second day (93.8 % vs 75 %), although this difference did not reach statistical significance (p = 0.332). CONCLUSIONS: The presence of single plain ring does not seem to be associated with an increased hand bacterial load. Regular surgical scrubbing with chlorhexidine impregnated sponges reduces bacterial contamination of hands, even in the presence of plain rings.
Assuntos
Clorexidina , Mãos , Humanos , Carga Bacteriana , Mãos/microbiologia , Bactérias , Pessoal de SaúdeRESUMO
BACKGROUND: To investigate the presence of genetic material of viral agents and the serum level of inflammatory cytokines in patients submitted to carotid endarterectomy having vulnerable versus stable atherosclerotic plaques. METHODS: Data of patients consecutively submitted to carotid endarterectomy for a significant stenosis from July 2019 to December 2019 were prospectively collected. The genetic material of Epstein-Barr (EBV), CitoMegalo (CMV), Herpes Simplex (HSV), Varicella-Zoster (VZV) and Influenza (IV) Viruses was searched in the patient's plaques, both in the "mid" of the plaque and in an adjacent lateral portion of no-plaque area. The serum levels of TNF-α, IL-1ß, IL-6, IL10 and CCL5 were determined. The obtained results were then correlated to the histologic vulnerability of the removed carotid plaque. P values < 0.05 were considered statistically significant. RESULTS: Data of 50 patients were analyzed. A vulnerable plaque was found in 31 patients (62%). The genome of CMV, HSV, VZV and IV was not found in any of the vascular samples, while the EBV genome was found in the "mid" of 2 vulnerable plaques, but not in their respective control area. Eighty-two percent of patients who did not receive anti-IV vaccination (23/28) had vulnerable carotid plaque, compared with 36% of vaccinated patients (8/22, P = 0.001). Serum levels of TNF-α and IL-6 were higher in patients with a vulnerable plaque compared to patients with a stable plaque (73.6 ± 238.2 vs. 3.9 ± 13.1 pg/ml, P= 0.01, and 45.9 ± 103.6 vs. 10.1 ± 25.3 pg/ml, P= 0.01, respectively), independent of comorbidities, viral exposure or flu vaccination. CONCLUSIONS: The EBV genome was found in the "core" of 2 vulnerable carotid plaques, but not in their respective adjacent control. Influenza vaccination was associated with a lower incidence of carotid plaque vulnerability. Serum levels of TNF-α and IL-6 were higher in patients with a vulnerable plaque compared to patients with a stable plaque.
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Estenose das Carótidas , Citocinas , Infecções por Citomegalovirus , Endarterectomia das Carótidas , Interleucina-6 , Placa Aterosclerótica , Fator de Necrose Tumoral alfa , Estenose das Carótidas/diagnóstico por imagem , Citocinas/sangue , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/genética , Endarterectomia das Carótidas/efeitos adversos , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/genética , Humanos , Inflamação/diagnóstico , Influenza Humana/diagnóstico , Influenza Humana/genética , Interleucina-6/sangue , Placa Aterosclerótica/genética , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangueRESUMO
The aim of this study was to investigate the effect of tobacco smoke exposure among severely pediatric ICU patients. A prospective epidemiological observational study was conducted among children with bronchiolitis younger than 2 years of age admitted to the Pediatric Intensive Care Unit of Children's University Hospital La Paz during the October 2017 to March 2018 outbreak. On admission, parents were asked whether they smoked. In children who required invasive mechanical ventilation, endotracheal aspirate was collected at the time of intubation. A total of 102 patients with bronchiolitis were studied. Among these, 14 (47%) of 30 infants whose parents smoked required invasive mechanical ventilation vs. 14 (19%) of 72 whose parents were nonsmokers (p = 0.007). Among patients on invasive mechanical ventilation, 10 (71%) of 14 infants with secondhand smoke exposure presented pulmonary bacterial superinfection vs. 3 (21%) of 14 in the unexposed (p = 0.012).Conclusion: Secondhand smoke exposure is an additional high risk for pulmonary bacterial superinfection and invasive mechanical ventilation in infants with severe acute bronchiolitis What is known: â¢Environmental tobacco smoke exposure is known to be an important risk factor for childhood lower respiratory tract infections. â¢Tobacco smoke makes structural changes in the respiratory tract and reduces the immune response. What in new: â¢Secondhand smoke exposure showed to be associated with the increased need and duration of invasive mechanical ventilation, and pediatric intensive care length of stay. â¢Tobacco smoke exposure is an additional risk factor for the presence of bacteria in the endotracheal aspirate.
Assuntos
Bronquiolite , Infecções por Vírus Respiratório Sincicial , Bronquiolite/epidemiologia , Bronquiolite/etiologia , Criança , Hábitos , Humanos , Lactente , Pais , Estudos Prospectivos , NicotianaRESUMO
BACKGROUND: In April 2012 our institution chose to switch from a two- step criteria for Gestational Diabetes Mellitus (GDM) screening, to the International Association of Diabetes in Pregnancy Study Group (IADSPG) criteria. This shift led to an increased prevalence of GDM in our pregnant population. We designed a study in order to estimate the magnitude of the increase in GDM prevalence before and after the switch in screening strategy. As a secondary objective we wanted to evaluate if there was a significant difference between the two periods in the percentage of maternal and neonatal complications such as gestational hypertensive disorders (GHD), primary cesarean section (pCS), preterm birth, large for gestational age (LGA) newborns, macrosomia, shoulder dystocia, 5' Apgar score less than to 7 at birth, neonatal intensive care unit (NICU) transfer and neonatal hypoglycemia. METHODS: We selected retrospectively 3496 patients who delivered between January 2009 and December 2011 who were screened with the two-step criteria (group A), and compared them to 2555 patients who delivered between January 2013 and December 2014 and who were screened with IADPSG criteria (Group B). We checked patients' electronic files to establish GDM status, baseline characteristics (age, body mass index, nationality, parity) and the presence of maternal and neonatal complications. RESULTS: GDM prevalence increased significantly from group A (3.4%; 95%CI 2.8-4.06%) to group B (16.28%; 95%CI 14.8 -17.7%). In group B there were significantly more non-Belgian and primiparous patients. There was no statistically significant difference in maternal and neonatal complications between the two groups, even after adjustment for nationality and parity. There was a non-significant reduction of the proportion of macrosomic and of LGA babies. CONCLUSIONS: In our population the introduction of IADPSG screening criteria has increased the prevalence of GDM without having a statistically significant impact on pregnancy outcomes.
Assuntos
Diabetes Gestacional , Programas de Triagem Diagnóstica , Doenças do Recém-Nascido/epidemiologia , Programas de Rastreamento , Complicações do Trabalho de Parto/epidemiologia , Adulto , Bélgica/epidemiologia , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiologia , Programas de Triagem Diagnóstica/normas , Programas de Triagem Diagnóstica/estatística & dados numéricos , Feminino , Humanos , Recém-Nascido , Doenças do Recém-Nascido/classificação , Masculino , Programas de Rastreamento/métodos , Programas de Rastreamento/organização & administração , Complicações do Trabalho de Parto/classificação , Gravidez , Resultado da Gravidez/epidemiologia , Cuidado Pré-Natal/métodos , Cuidado Pré-Natal/normas , Prevalência , Estudos RetrospectivosRESUMO
BACKGROUND: The human skin microbiome consists of colonizing and pathogen germs. The umbilical dimple is a humid environment prone to bacterial colonization and growth. In the laparoscopic era, the umbilicus has become the most common site of entrance into the peritoneum. The aim of this study was to describe the characteristics of umbilical microflora before antiseptic skin preparation. METHODS: Descriptive single-center study. A series of patients who underwent laparoscopic/open and elective/urgent abdominal surgery over a 2-month period were included. Patients were admitted the same day or the day before surgery. Before antiseptic skin preparation, microbiological samples were taken from the umbilicus, left upper abdominal quadrant, and nostril. A delayed referral time (>30 minutes) of the skin swabs to the microbiology laboratory was an exclusion criterion. RESULTS: Overall, 70 patients were included. The median age was 64 years (range 16-89) and a laparoscopic approach was used in 82.8% of cases. The most commonly performed operation was laparoscopic fundoplication for gastroesophageal reflux (25.8%). In the umbilicus, the most frequent colonizing bacteria were coagulase-negative Staphylococcus species and Corynebacterium. Opportunistic pathogens were found in 10 umbilical swabs compared with 8 in the left upper quadrant (14.2% versus 11.4%, p = .800). Overall, 50% of patients with umbilical opportunistic pathogens had a medium/high bacterial load compared with 62.5% in the left upper quadrant (p = .958). No postoperative surgical site infection was recorded in the study sample. CONCLUSIONS: Both the umbilicus and the left upper quadrant appear to be safe entry sites in laparoscopic surgery. Meticulous hygiene of these anatomical areas is strongly recommended before surgery regardless of the type of antiseptic solution and the short-term antibiotic prophylaxis. In-hospital preoperative showers may be unnecessary for well-educated patients.
Assuntos
Abdome/cirurgia , Laparoscopia/métodos , Microbiota , Umbigo/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Desinfecção/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Umbigo/cirurgia , Adulto JovemRESUMO
BACKGROUND: Plasma concentrations of natriuretic peptides have been shown to predict prognosis in heart failure (HF) patients with left ventricle (LV) dysfunction. It is still unclear if measurements after cardiac surgery are associated with any effect on the outcome. We aimed to prospectively investigate the longitudinal profile of serial evaluations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in ischemic HF patients undergoing Surgical Ventricular Reconstruction (SVR) and how NT-proBNP levels at different time-points are associated with the outcome. METHODS: One hundred and forty-three patients (122 men, 64⯱â¯9â¯years old) with post-infarction LV remodeling referred to our Center for SVR had an assessment of NT-proBNP levels before surgery and 6, 12 and 18â¯months after surgery. The analysis was performed using the logarithm of the biomarker and joint modeling of serial measurements through mixed models together with Cox regression to analyze time to event data. RESULTS: The average level of the biomarker decreased by about 50% during the first year after the operation. Time-varying NT-proBNP levels were associated with the hazard of: 1% increase in NT-proBNP during the follow-up was associated with 1.5% increase of the risk of the composite event (95% CI: 1.0%, 2.6%) and with 4.2% increase of the risk of death (95% CI: 2.2%, 8.2%). CONCLUSIONS: Serial profiles (either in increasing or in decreasing) at different time points are associated with a modulation of the risk of adverse events and, therefore, are important indicators for monitoring the evolution of the disease, even after cardiac surgery.
Assuntos
Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/cirurgia , Ventrículos do Coração/cirurgia , Revascularização Miocárdica/tendências , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Procedimentos de Cirurgia Plástica/tendências , Idoso , Biomarcadores/sangue , Feminino , Seguimentos , Insuficiência Cardíaca/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica , Estudos ProspectivosRESUMO
BACKGROUND: Early detection of anastomotic leakage after esophagectomy has the potential to reduce morbidity and mortality. Prompt suspicion of leak may help to exclude patients from fast-track protocols, thereby avoiding early oral feeding and early hospital discharge which could aggravate the prognosis of a clinically occult leak. PATIENTS AND METHODS: Observational retrospective cohort study. Patients with diagnosis of esophageal cancer who underwent elective minimally invasive esophagectomy were included. The following data were collected: age, gender, BMI, comorbidities, ASA score, tumor histology, TNM staging, use of neo-adjuvant therapy, type of operation, operative time, morbidity, and 90-day mortality. A panel of biomarkers including C-reactive protein (CRP), procalcitonin (PCT), white blood cells (WBC), and percentage of neutrophils (PN) were measured at baseline and on postoperative days 3, 5, and 7. RESULTS: Two hundred forty-three patients operated between 2012 and 2017 were included in the study. Anastomotic leakage occurred in 29 patients. There was a statistical association over time between anastomotic leakage and CRP (p < 0.001), PCT (p < 0.001), WBC (p = 0.019), and PN (p = 0.007). The cut-off value of CRP on POD 5 was 8.3 mg/dL, AUC = 0.818, negative LR = 0.176. CONCLUSIONS: Increased serum CRP, PCT, WBC, and PN after minimally invasive esophagectomy are associated with anastomotic leakage. A CRP value lower than 8.3 mg/dL, combined with reassuring clinical and radiological signs, may be useful to exclude leakage on postoperative day 5.
Assuntos
Fístula Anastomótica/sangue , Biomarcadores Tumorais/sangue , Proteína C-Reativa/análise , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Idoso , Idoso de 80 Anos ou mais , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/fisiopatologia , Área Sob a Curva , Distribuição de Qui-Quadrado , Estudos de Coortes , Intervalo Livre de Doença , Procedimentos Cirúrgicos Eletivos/métodos , Procedimentos Cirúrgicos Eletivos/mortalidade , Neoplasias Esofágicas/mortalidade , Esofagectomia/mortalidade , Esofagoscopia/efeitos adversos , Esofagoscopia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Estatísticas não Paramétricas , Análise de Sobrevida , Resultado do TratamentoRESUMO
INTRODUCTION: Acute kidney injury (AKI) occurs frequently after abdominal aortic surgery and there is currently no effective marker able to detect early onset. The aim of this study is to evaluate the ability of neutrophil gelatinase-associated lipocalin (NGAL) to early identify the development of acute renal damage in patients undergoing endovascular aneurysm repair (EVAR) or open aortic repair (OAR). MATERIALS AND METHODS: Serial samples of blood and urine were obtained from 25 patients undergoing both EVAR and OAR. Seven male subjects with AKI and 18 subjects with no-AKI (17 males, 1 female) were included in the study. We determined concentrations of serum creatinine (sCr) and urinary, serum and whole blood NGAL (uNGAL, sNGAL, bNGAL) collected at baseline, and after 4 and 18 hours. AKI was defined according to the RIFLE criteria (risk, injury, failure, loss of kidney function, and end-stage kidney disease): increase by 50% in sCr or reduction of at least 25% of estimated glomerular filtration rate (eGFR) from baseline. RESULTS: Seven patients developed AKI in the stage Risk. There was no significant difference in sNGAL concentrations in the AKI group as compared to no-AKI group. However, the uNGAL/uCreatinine ratio and bNGAL concentrations were significantly higher after 18 hours in the AKI group (no-AKI 1.69 (0.91 - 2.47) vs AKI 3.2 (2.08 - 5.92) ng/mg for uNGAL/uCreatinine ratio, P = 0.036; and no-AKI 83 (59 - 131) vs AKI 164 (126 - 263) ng/mL for bNGAL, P = 0.029). CONCLUSIONS: Our results suggest that uNGAL, sNGAL and bNGAL, after abdominal aortic surgery, are not suitable as early biomarkers of AKI.
Assuntos
Injúria Renal Aguda/diagnóstico , Procedimentos Endovasculares/métodos , Lipocalina-2/análise , Injúria Renal Aguda/complicações , Área Sob a Curva , Creatinina/sangue , Creatinina/urina , Estudos Transversais , Feminino , Humanos , Lipocalina-2/sangue , Lipocalina-2/urina , Masculino , Projetos Piloto , Curva ROCRESUMO
BACKGROUND: Patients with congenital heart defects are frequently hospitalized before surgery. This exposes them to a high risk for pathogen colonization. There are limited data on colonization prevalence in the pediatric cardiac population, and limited data concerning its potential role in the risk of developing infections after cardiac surgery. AIM: This study aimed to verify the impact of preoperative colonization on postoperative infections in a population of pediatric cardiac surgery patients coming from Italy and developing countries. METHODS: This was a retrospective study conducted in all the patients aged ≤18 years who underwent pediatric open-heart surgery in the year 2015. Clinical data were retrieved from the institutional database for cardiac surgery patients. Data on swab cultures were retrieved from the laboratory database. Swab colonization was tested for association with infection and other outcomes. RESULTS: Among 169 children who performed the screening for pathogen colonization, 50% had at least one positive swab. Italian patients were (P=.001) less likely to be colonized with respect to foreign patients (relative risk 0.17, 95% CI 0.09-0.35). Postoperative infections in colonized patients occurred at a similar rate as in noncolonized patients (relative risk 1.24, 95% CI 0.64-2.39; P=.532). Colonized patients had a preoperative stay (P=.021) longer than noncolonized patients (mean difference 2 days, 95% CI 0.3-3.8 days). CONCLUSION: The results of our study suggest that the impact of preoperative colonization on outcome and postoperative infections may be negligible; larger series are required to clearly define this issue.
Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Cardiopatias Congênitas/microbiologia , Cardiopatias Congênitas/cirurgia , Infecção da Ferida Cirúrgica/microbiologia , Criança , Pré-Escolar , Cuidados Críticos , Países em Desenvolvimento , Farmacorresistência Bacteriana , Enterobacteriaceae/efeitos dos fármacos , Feminino , Humanos , Lactente , Recém-Nascido , Itália/epidemiologia , Tempo de Internação , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Cavidade Nasal/microbiologia , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/epidemiologiaRESUMO
Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are the most common adult form of muscular dystrophy, characterized by autosomal dominant progressive myopathy, myotonia, and multiorgan involvement. The onset and symptoms of the myotonic dystrophies are diverse, complicating their diagnoses and limiting a comprehensive approach to their clinical care. Diagnostic delay in DM2 is due not only to the heterogeneous phenotype and the aspecific onset but also to the unfamiliarity with the disorder by most clinicians. Moreover, the DM2 diagnostic odyssey is complicated by the difficulties to develop an accurate, robust, and cost-effective method for a routine molecular assay. The aim of this review is to underline by challenging approach the diagnostic limits and pitfalls that could results in failure to recognize the presence of DM2 disease. Understanding and preventing delays in DM2 diagnosis may facilitate family planning, improve symptom management in the short term, and facilitate more specific treatment in the long term.
Assuntos
Distrofia Miotônica/diagnóstico , Humanos , Distrofia Miotônica/genética , Distrofia Miotônica/patologiaRESUMO
Background. Anaemia is common in inflammatory bowel disease (IBD), frequently resulting from a combination of iron deficiency and of anaemia of chronic disease (ACD). ACD is characterized by macrophage iron retention induced by proinflammatory cytokines. Hepcidin is the master inducer of iron accumulation during ACD, and its production is mainly regulated by IL-6 and the novel erythroid hormone erythroferrone (ERFE). This study evaluates whether anti-TNF monoclonal antibodies therapy modurates hepcidin production and the levels of its main regulators, leading to a restoration of iron homeostasis. Methods. Sera were collected from 21 IBD patients, before each anti-TNF administration, for the first 6 weeks of therapy. Prohepcidin, erythropoietin, erythroferrone, C reactive protein, interleukin-6, iron markers, and haemoglobin levels were measured and clinical activity indexes were evaluated. Results. Serum prohepcidin, IL-6, CRP, and ferritin were significantly reduced after 6-week treatment; an increase in serum iron and total transferrin was observed. No changes in the EPO-ERFE axis were found. Remarkably, haemoglobin was significantly increased. Conclusions. Anti-TNF therapy improves iron metabolism and, subsequently, anaemia in IBD. This effect appears to be related to the modulation of the cytokine network and specifically IL-6 leading to a relevant decrease of hepcidin, a master regulator of ACD.
Assuntos
Adalimumab/uso terapêutico , Anemia/sangue , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Eritropoetina/sangue , Hepcidinas/sangue , Infliximab/uso terapêutico , Interleucina-6/imunologia , Hormônios Peptídicos/sangue , Adolescente , Adulto , Anemia/complicações , Anemia/imunologia , Proteína C-Reativa/imunologia , Doença Crônica , Colite Ulcerativa/sangue , Colite Ulcerativa/complicações , Colite Ulcerativa/imunologia , Doença de Crohn/sangue , Doença de Crohn/complicações , Doença de Crohn/imunologia , Feminino , Ferritinas/sangue , Hemoglobinas , Humanos , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/imunologia , Ferro/sangue , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto JovemRESUMO
To explore the relationship between innate immunity and hepatitis C Virus (HCV) in determining the risk of cirrhosis (CIR), hepatocellular carcinoma (HCC), mixed cryoglobulinemia syndrome (MCS) and non-Hodgkin lymphoma (NHL), we investigated the impact of the toll-like receptor-2 (TLR2) and interleukin-28B (IL28B) genetic variants. TLR2 -174 del variant was associated with TLR2 expression and with specific downstream molecules that drive the expression of different interleukins; rs12979860 Il28B was important in response to interferon-treatment and in spontaneous clearance of HCV. The risk for liver and lymphoproliferative diseases in HCV progression was clarified by stratifying 862 HCV-positive patients into groups based on liver (CIR, HCC) and lymphoproliferative HCV-related diseases (MCS, NHL) and compared with chronic HCV (CHC) infection. Analysis of TLR2-IL28B haplotypes showed an association of wild type haplotype with the lymphoproliferative diseases (OR 1.77, p = 0.029) and a slight increase in HCV viral load (HR 1.38, p = 0.054). Wild type haplotype (TLR2 ins/ins- IL28B C/C) was also found associated with older age in patients with an hepatic diseases (in CIR and in HCC p = 0.038 and p = 0.020, respectively) supporting an effect of innate immunity in the liver disease progression. TLR2 and IL28B polymorphisms in combination showed a role in the control of HCV viral load and different HCV disease progression.
Assuntos
Hepacivirus/isolamento & purificação , Hepatite C Crônica/genética , Interleucinas/genética , Transtornos Linfoproliferativos/genética , Transtornos Linfoproliferativos/virologia , Receptor 2 Toll-Like/genética , Adulto , Idoso , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Humanos , Interferons , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Transtornos Linfoproliferativos/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Survival of children with combined immunodeficiency is strongly related to patient's age and clinical situation at the time of hematopoietic stem cell transplantation (HSCT). We describe the clinical features before HSCT or enzyme replacement therapy (ERT) in a cohort of children treated in a National Reference Unit. METHODS: A retrospective study of children with CIDs treated in our Hospital during a 20-year period (1995-2014) was performed, analyzing their clinical situation before HSCT/ERT. RESULTS: Thirty-one children were included. Risk factors such as family history or consanguinity were present in 35% of cases, but only 3 children (9%) were initially studied because of family history. Median ages at clinical onset, diagnosis and HSCT/ERT were 3.3, 5.6 and 8.1 months, respectively. All patients had lymphopenia before HSCT/ERT. At the time of admission to our unit, 68% of cases had abnormal lung auscultation, 72% were malnourished, 45% reported chronic gastroenteritis and 35% had hepatosplenomegaly. Before HSCT/ERT, respiratory infections and sepsis episodes were documented in 80% and 42% of cases, respectively. In 23% of children, a viral systemic infection was confirmed. The mortality rate was 35%, and 72% of children who died had Gram-negative bacterial sepsis or a viral infection. CONCLUSIONS: The present study shows the characteristics and outcome of children with CIDs in the absence of neonatal screening. Although all our patients had lymphopenia and most of them had suffered relevant infections or had a positive family history, these factors were not identified early. Respiratory and systemic viral infections were the main source of infection with important implications in clinical outcome. Our results highlight the importance of the implementation of neonatal screening, to improve survival rates.
Assuntos
Terapia de Reposição de Enzimas/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Síndromes de Imunodeficiência/terapia , Bacteriemia/imunologia , Terapia de Reposição de Enzimas/efeitos adversos , Feminino , Infecções por Bactérias Gram-Negativas/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Síndromes de Imunodeficiência/complicações , Lactente , Masculino , Infecções Respiratórias/imunologia , Estudos Retrospectivos , Fatores de Risco , Espanha , Resultado do Tratamento , Viroses/imunologiaRESUMO
By derivatizing the purely competitive CK2 inhibitor N1-(4,5,6,7-tetrabromo-1H-benzimidazol-2-yl)-propane-1,3-diamine (K137) at its 3-amino position with a peptidic fragment composed of three or four glutamic or aspartic acid residues, a new family of bisubstrate inhibitors has been generated whose ability to simultaneously interact with both the ATP and the phosphoacceptor substrate-binding sites has been probed by running mixed competition kinetics and by mutational mapping of the kinase residues implicated in substrate recognition. The most effective bisubstrate inhibitor, K137-E4, interacts with three functional regions of the kinase: the hydrophobic pocket close to the ATP-binding site, the basic residues of the p+1 loop that recognizes the acidic determinant at position n+1 and the basic residues of α-helixC that recognize the acidic determinant at position n+3. Compared with the parent inhibitor (K137), K137-E4 is severalfold more potent (IC50 25 compared with 130 nM) and more selective, failing to inhibit any other kinase as drastically as CK2 out of 140 enzymes, whereas 35 kinases are inhibited more potently than CK2 by K137. K137-E4 is unable to penetrate the cell and to inhibit endogenous CK2, its pro-apoptotic efficacy being negligible compared with cell-permeant inhibitors; however, it readily inhibits ecto-CK2 on the outer cell surface, reducing the phosphorylation of several external phosphoproteins. Inhibition of ecto-CK2 by K137-E4 is accompanied by a slower migration of cancer cells as judged by wound healing assays. On the basis of the cellular responses to K137-E4, we conclude that ecto-CK2 is implicated in cell motility, whereas its contribution to the pro-survival role of CK2 is negligible.
Assuntos
Benzimidazóis/química , Inibidores de Proteínas Quinases/química , Proteínas Quinases/química , Estrutura Secundária de Proteína/efeitos dos fármacos , Trifosfato de Adenosina/química , Trifosfato de Adenosina/metabolismo , Benzimidazóis/farmacologia , Sítios de Ligação , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Humanos , Cinética , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteínas Quinases/efeitos dos fármacos , Proteínas Quinases/metabolismoRESUMO
Frequent use of carbapenems has contributed to the increase to K. pneumoniae strains resistant to this class of antibiotics (CRKP), causing a problem in the clinical treatment of patients. This investigation reports the epidemiology, genetic diversity, and clinical implication of the resistance to drugs mediated by CRKP in our hospital. A total of 280 K. pneumoniae strains were collected; in particular 98/280 (35%) were CRKP. Sequencing analysis of CRKP isolated strains showed that 9/98 of MBL-producing strains carried the bla VIM-1 gene and 89/98 of the isolates were positive for bla KPC-2. Antimicrobial susceptibility tests revealed a complete resistance to third-generation cephalosporins and a moderate resistance to tigecycline, gentamicin, and fluoroquinolones with percentages of resistance of 61%, 64%, and 98%, respectively. A resistance of 31% was shown towards trimethoprim-sulfamethoxazole. Colistin was the most active agent against CRKP with 99% of susceptibility. Clonality was evaluated by PFGE and MLST: MLST showed the same clonal type, ST258, while PFGE analysis indicated the presence of a major clone, namely, pulsotype A. This finding indicates that the prevalent resistant isolates were genetically related, suggesting that the spread of these genes could be due to clonal dissemination as well as to genetic exchange between different clones.
Assuntos
Infecções por Klebsiella/genética , Klebsiella pneumoniae/genética , beta-Lactamases/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carbapenêmicos/uso terapêutico , Criança , Pré-Escolar , Colistina/administração & dosagem , Farmacorresistência Bacteriana/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/patogenicidade , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: Despite the recent innovations, complications of prostate biopsy can occur. The aim of this study was a prospective monitoring of major septic complications occurring after transrectal prostate biopsy, to describe their causing agents, to report the clinical course of these patients, and to give guidelines based on our personal experience. METHODS: This prospective study was carried out between January 2009 and September 2010. Complications were evaluated by telephone interviews. RESULTS: Between January 2009 and September 2010, 447 (96.5%) completed the telephone interview. Urosepsis occurred in ten patients (2.2%) and in three cases evolved into septic shock. Of these ten patients, nine had a positive blood culture, of whom eight for Escherichia coli and one for Aeromonas hydrophila, Aeromonas caviae, and Aeromonas sobria. In seven cases, the E. coli isolated were resistant to fluoroquinolone and six produced an extended spectrum beta-lactamase. Six E. coli were classified as multidrug-resistant organisms. Of the 10 patients, one died after the onset of multiorgan failure. For the other nine, the mean time spent in the hospital was 9 days (range, 6-15 days). CONCLUSIONS: Escherichia coli are developing new drug resistances. Early recognition of patients who harbor MDRO E. coli in their rectum or in the urine could be an important strategy for preventing sepsis. If a patient who has recently undergone transrectal prostate biopsy shows clinical signs of sepsis in the 48 h, a multiresistant E. coli infection must be suspected. The patient must be admitted urgently to the hospital, and carbapenem antibiotic therapy should be started.
Assuntos
Biópsia por Agulha/efeitos adversos , Infecções por Escherichia coli/etiologia , Escherichia coli/isolamento & purificação , Próstata/patologia , Sepse/etiologia , Idoso , Antibacterianos/uso terapêutico , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias da Próstata/diagnóstico , Sepse/tratamento farmacológico , Sepse/microbiologiaRESUMO
AIMS: Elevated homocysteinaemia is associated not only with an increased risk for cardiovascular disease but also for increased morbidity and mortality in patients with established coronary artery or cerebrovascular disease. Whether elevated homocysteine further increases the morbidity and mortality in patients undergoing cardiac surgery on cardiopulmonary bypass (CPB) (a prothrombotic state itself) remains less known. METHODS AND RESULTS: Accordingly, we conducted a prospective observational study with pre-operative measurement of plasma homocysteine levels in 531 consecutive patients undergoing cardiac operations on CPB. The association of pre-operative plasma homocysteine levels with post-operative morbidity and hospital mortality was evaluated. Elevated homocysteine levels (>15 micromol/L) were observed in 209 patients (39.4%), and homocysteinaemia was associated with a higher mortality and perioperative morbidity (major morbidity, low cardiac output, acute renal failure, mesenteric infarction, and thrombo-embolic events). Even after accounting for the differences in baseline clinical features, EuroSCORE, and CPB time, pre-operative homocysteine levels remained independently associated with hospital mortality [odds ratio (OR) 1.06, 95% confidence interval (CI) 1.03-1.11], major morbidity (OR 1.04, 95% CI 1.01-1.07), low cardiac output (OR 1.04, 95% CI 1.02-1.08), mesenteric infarction (OR 1.06, 95% CI 1.01-1.11), and thrombo-embolic events (OR 1.09, 95% CI 1.04-1.13). This association of homocysteine with increased risk of morbidity and mortality was observed particularly in CABG patients. CONCLUSION: Elevated pre-operative homocysteine level is independently associated with increased morbidity and mortality, particularly in patients undergoing CABG. Specific post-operative antithrombotic strategies may be advisable in hyperhomocysteinaemic patients.