RESUMO
Several false positive low serum cryptococcal antigen (SCrAg) reports by lateral flow assay (LFA) were identified in late 2016 at our tertiary care hospital. After the recall and correction of the problem in the reagent, we studied the significance of SCrAg LFA ≤ 1:10 from January 2017 to October 2023. Of 20 patients with 31 samples of SCrAg LFA ≤1:10, 14 patients (70%) were classified as true positives, four (20%) were indeterminate, and only two (10%) patients were false positives. If a new SCrAg LFA ≤1:10 is detected, it should be repeated, and additional workup should be pursued.
We studied the significance of low serum cryptococcal antigen titer (SCrAg) LFA ≤ 1:10 from January 2017 to October 2023. Of 20 patients with SCrAg LFA ≤1:10, only two patients (10%) were false positives. If a new SCrAg ≤1:10 is detected, it should be repeated, and additional work up should be done.
RESUMO
BACKGROUND: Blastomycosis is an endemic fungal infection that causes pulmonary and systemic disease. It can occur irrespective of the patient's immune status. The risk factors associated with the severity of the disease are not well studied. METHODS: This is a retrospective study of patients admitted with blastomycosis at the University of Kentucky Hospital from 2004 to 2019. Logistic regression was used to identify variables associated with severe blastomycosis. RESULTS: A total of 76 patients were identified; 22 (28.9%) had at least one immunosuppressive condition. Pulmonary blastomycosis was reported in 49/76 (65%) of the patients and disseminated infection in 27/76 (35.5%). All diagnostic tests were not significantly different in diagnostic results in immunocompromised vs immunocompetent patients. Cultures and histopathology were positive in 56/61 (91.8%) and 54/63 (85.7%) respectively. Blastomyces or Histoplasma antigen test was positive in 13/17 (76.4%) in immunocompromised patients compared to 26/42 (61.9%) in immunocompetent patients. Immunocompromised patients were more likely to be admitted to the hospital and ICU compared to immunocompetent patients. In the multivariate analysis, pulmonary multilobar disease (RR 5.68; 95% CI 2.13-15.15), obesity (RR 2.39; 95% CI 1.26-4.51), diabetes mellitus (RR 3.50; 95% CI 1.38-8.90) and immunosuppression (RR 2.28; 95% CI 1.14-4.56) were significant independent risk factors for severe blastomycosis. Inpatient mortality proportion was higher in immunocompromised patients but not statistically significant. CONCLUSION: Pulmonary multilobar disease, obesity, diabetes mellitus and immunosuppression were risk factors associated with severe blastomycosis. Immunocompromised patients required more frequent hospitalisations compared to immunocompetent patients.
Assuntos
Blastomicose , Blastomyces , Blastomicose/diagnóstico , Blastomicose/epidemiologia , Diabetes Mellitus/epidemiologia , Humanos , Hospedeiro Imunocomprometido , Terapia de Imunossupressão/efeitos adversos , Pneumopatias/epidemiologia , Obesidade/epidemiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: Thrombocytopenia is associated with many viral infections suggesting virions interact with and affect platelets. Consistently, viral particles are seen inside platelets, and platelet activation markers are detected in viremic patients. In this article, we sought mechanistic insights into these virion/platelet interactions by examining how platelets endocytose, traffic, and are activated by a model virion. Approach and Results: Using fluorescently tagged HIV-1 pseudovirions, 3-dimensional structured illumination microscopy, and transgenic mouse models, we probed the interactions between platelets and virions. Mouse platelets used known endocytic machinery, that is, dynamin, VAMP (vesicle-associated membrane protein)-3, and Arf6 (ADP-ribosylation factor 6), to take up and traffic HIV-1 pseudovirions. Endocytosed HIV-1 pseudovirions trafficked through early (Rab4+) and late endosomes (Rab7+), and then to an LC3+ (microtubule-associated protein 1A/1B-light chain 3) compartment. Incubation with virions induced IRAK4 (interleukin 1 receptor-associated kinase 4), Akt (protein kinase B), and IKK (IκB kinase) activation, granule secretion, and platelet-leukocyte aggregate formation. This activation required TLRs (Toll-like receptors) and MyD88 (myeloid differentiation primary response protein 88) but was less extensive and slower than activation with thrombin. In vivo, HIV-1 pseudovirions injection led to virion uptake and platelet activation, as measured by IKK activation, platelet-leukocyte aggregate formation, and mild thrombocytopenia. All were decreased in VAMP-3-/- and, megakaryocyte/platelet-specific, Arf6-/- mice. Similar platelet activation profiles (increased platelet-leukocyte aggregates, plasma platelet factor 4, and phospho-IκBα) were detected in newly diagnosed and antiretroviral therapy-controlled HIV-1+ patients. CONCLUSIONS: Collectively, our data provide mechanistic insights into the cell biology of how platelets endocytose and process virions. We propose a mechanism by which platelets sample the circulation and respond to potential pathogens that they take up.
Assuntos
Plaquetas/metabolismo , Endocitose , Infecções por HIV/sangue , HIV-1/patogenicidade , Ativação Plaquetária , Trombocitopenia/sangue , Receptores Toll-Like/sangue , Vírion , Fator 6 de Ribosilação do ADP , Fatores de Ribosilação do ADP/sangue , Fatores de Ribosilação do ADP/genética , Animais , Antirretrovirais/uso terapêutico , Plaquetas/virologia , Agregação Celular , Células Cultivadas , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Quinase I-kappa B/sangue , Quinase I-kappa B/genética , Leucócitos/metabolismo , Leucócitos/virologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/sangue , Fator 88 de Diferenciação Mieloide/genética , Fator Plaquetário 4/sangue , Fator Plaquetário 4/genética , Trombocitopenia/diagnóstico , Trombocitopenia/virologia , Receptores Toll-Like/deficiência , Receptores Toll-Like/genética , Proteína 3 Associada à Membrana da Vesícula/sangue , Proteína 3 Associada à Membrana da Vesícula/genéticaRESUMO
BACKGROUND: Cryptococcosis is classically associated with the immunocompromised patients but there is a rising appreciation for its impact on the immunocompetent hosts. We sought to analyse the trends, diagnosis, treatment of different hosts and the effect of immunodeficiency and chronic liver disease on relapse and in-house mortality. METHODS: This is a retrospective study of 12 years of patients with cryptococcosis, divided into three different groups: HIV-infected, transplant and non-HIV non-transplant (NHNT). Data were analysed with Chi-square, unpaired parametric t test, simple and multivariate logistic regression analysis. RESULTS: Of 114 identified patients, 23 (20.2%) had HIV infection, 11 (9.6%) had transplant, 80 (70.2%) were NHNT patients. Overall, mortality was 28.1% (32/114) and relapse occurred in 10.5% (12/114) of patients. The mortality trend was higher (OR = 2.346, p = .287) in the transplant group (45.5%, 5/11) than in HIV (26.1%, 6/23) and NHNT groups (26.3%, 21/80). HIV was associated with relapse; 30.4% (7/23) for HIV-positive patients and 5.5% (5/91) for HIV-negative patients (OR = 7.525, p = .002). Chronic liver disease had a large and statistically significant association with mortality on multivariate analysis (OR = 3.583, p = .013) which was more pronounced than the HIV or transplant groups. It was independently associated with mortality by chi-square analysis (OR 3.137, p = .012). CONCLUSION: Chronic liver disease represented 30.7% (35/114) of all studied patients. It was a risk factor for in-hospital mortality. HIV infection and transplant were not statistically significant for mortality. Relapse was highest in the HIV-infected patients at 30.4% (7/23). These data highlight the effect of type and degree of immunocompromise on cryptococcosis.
Assuntos
Criptococose , Doença Hepática Terminal , Infecções por HIV , Criptococose/epidemiologia , Criptococose/mortalidade , Doença Hepática Terminal/epidemiologia , Infecções por HIV/epidemiologia , Humanos , Recidiva , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção TerciáriaRESUMO
Several case reports and cohort studies have examined the use of (1,3)-beta-d-glucan measurement with cerebrospinal fluid to diagnose fungal meningitis. This systematic review aims to characterize the evidence regarding cerebrospinal fluid (1,3)-beta-d-glucan measurement to detect fungal meningitis. We searched PubMed for (1,3)-beta-d-glucan and each of several distinct fungi, cerebrospinal fluid, and meningitis. Summary data including diagnostic performance (where applicable) were recorded. A total of 939 records were examined via a PubMed search. One hundred eighteen records remained after duplicates were removed, and 104 records were excluded, as they did not examine cerebrospinal fluid, included animals, or focused on nonfungal infections. Fourteen studies were included in this systematic review. A variety of fungi, including species of Candida, Aspergillus, Exserohilum, Cryptococcus, Histoplasma, and Coccidioides, were studied, although most were case reports. Diagnostic accuracy was examined in 5 studies. Cerebrospinal fluid (CSF) (1,3)-beta-d-glucan measurement showed >95% sensitivity in the corticosteroid injection-related outbreak of Exserohilum rostratum One study in Histoplasma meningitis found 53% (53/87) sensitivity and 87% (133/153) specificity, while another study of Cryptococcus meningitis found 89% (69/78) sensitivity and 85% (33/39) specificity. CSF (1,3)-beta-d-glucan testing may be useful, primarily as a nonspecific marker of fungal meningitis. Although the FDA black box warning states that Cryptococcus spp. do not make (1,3)-beta-d-glucan, the current evidence shows that (1,3)-beta-d-glucan is detectable in cryptococcal meningitis. Organism-specific testing should be used in conjunction with (1,3)-beta-d-glucan measurement.
Assuntos
Meningite Criptocócica , Meningite Fúngica , Ascomicetos , Líquido Cefalorraquidiano , Testes Diagnósticos de Rotina , Glucanos , Histoplasma , Humanos , Meningite Criptocócica/diagnóstico , Meningite Fúngica/diagnósticoRESUMO
Background: Central nervous system (CNS) histoplasmosis is a life-threatening condition and represents a diagnostic and therapeutic challenge. Isolation of Histoplasma capsulatum from cerebrospinal fluid (CSF) or brain tissue is diagnostic; however, culture is insensitive and slow growth may result in significant treatment delay. We performed a retrospective multicenter study to evaluate the sensitivity and specificity of a new anti-Histoplasma antibody enzyme immunoassay (EIA) for the detection of IgG and IgM antibody in the CSF for diagnosis of CNS histoplasmosis, the primary objective of the study. The secondary objective was to determine the effect of improvements in the Histoplasma galactomannan antigen detection EIA on the diagnosis of Histoplasma meningitis. Methods: Residual CSF specimens from patients with Histoplasma meningitis and controls were tested for Histoplasma antigen and anti-Histoplasma immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody using assays developed at MiraVista Diagnostics. Results: A total of 50 cases and 157 controls were evaluated. Fifty percent of patients with CNS histoplasmosis were immunocompromised, 14% had other medical conditions, and 36% were healthy. Histoplasma antigen was detected in CSF in 78% of cases and the specificity was 97%. Anti-Histoplasma IgG or IgM antibody was detected in 82% of cases and the specificity was 93%. The sensitivity of detection of antibody by currently available serologic testing including immunodiffusion and complement fixation was 51% and the specificity was 96%. Testing for both CSF antigen and antibody by EIA was the most sensitive approach, detecting 98% of cases. Conclusions: Testing CSF for anti-Histoplasma IgG and IgM antibody complements antigen detection and improves the sensitivity for diagnosis of Histoplasma meningitis.
Assuntos
Anticorpos Antifúngicos/líquido cefalorraquidiano , Antígenos de Fungos/líquido cefalorraquidiano , Histoplasmose/diagnóstico , Técnicas Imunoenzimáticas/métodos , Imunoglobulina G/líquido cefalorraquidiano , Imunoglobulina M/líquido cefalorraquidiano , Meningite Fúngica/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Líquido Cefalorraquidiano/imunologia , Líquido Cefalorraquidiano/microbiologia , Criança , Pré-Escolar , Testes Diagnósticos de Rotina/métodos , Feminino , Galactose/análogos & derivados , Humanos , Lactente , Masculino , Mananas/líquido cefalorraquidiano , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto JovemRESUMO
The diagnosis of central nervous system (CNS) histoplasmosis is often difficult. Although cerebrospinal fluid (CSF) (1,3)-ß-d-glucan (BDG) is available as a biological marker for the diagnosis of fungal meningitis, there are limited data on its use for the diagnosis of Histoplasma meningitis. We evaluated CSF BDG detection, using the Fungitell assay, in patients with CNS histoplasmosis and controls. A total of 47 cases and 153 controls were identified. The control group included 13 patients with a CNS fungal infection other than histoplasmosis. Forty-nine percent of patients with CNS histoplasmosis and 43.8% of controls were immunocompromised. The median CSF BDG level was 85 pg/ml for cases, compared to <31 pg/ml for all controls (P < 0.05) and 82 pg/ml for controls with other causes of fungal meningitis (P = 0.27). The sensitivity for detection of BDG in CSF was 53.2%, whereas the specificity was 86.9% versus all controls and 46% versus other CNS fungal infections. CSF BDG levels of ≥80 pg/ml are neither sensitive nor specific to support a diagnosis of Histoplasma meningitis.
Assuntos
Técnicas de Laboratório Clínico/métodos , Histoplasmose/diagnóstico , beta-Glucanas/líquido cefalorraquidiano , Adulto , Biomarcadores/líquido cefalorraquidiano , Histoplasma/isolamento & purificação , Histoplasma/metabolismo , Histoplasmose/líquido cefalorraquidiano , Humanos , Meningite Fúngica/líquido cefalorraquidiano , Meningite Fúngica/diagnóstico , Meningite Fúngica/microbiologia , Proteoglicanas , Curva ROC , Kit de Reagentes para DiagnósticoRESUMO
BACKGROUND: Histoplasmosis may complicate tumor necrosis factor (TNF)-α blocker therapy. Published case series provide limited guidance on disease management. We sought to determine the need for long-term antifungal therapy and the safety of resuming TNF-α blocker therapy after successful treatment of histoplasmosis. METHODS: We conducted a multicenter retrospective review of 98 patients diagnosed with histoplasmosis between January 2000 and June 2011. Multivariate logistic regression was used to evaluate risk factors for severe disease. RESULTS: The most commonly used biologic agent was infliximab (67.3%). Concomitant corticosteroid use (odds ratio [OR], 3.94 [95% confidence interval {CI}, 1.06-14.60]) and higher urine Histoplasma antigen levels (OR, 1.14 [95% CI, 1.03-1.25]) were found to be independent predictors of severe disease. Forty-six (47.4%) patients were initially treated with an amphotericin B formulation for a median duration of 2 weeks. Azole treatment was given for a median of 12 months. TNF-α blocker therapy was initially discontinued in 95 of 98 (96.9%) patients and later resumed in 25 of 74 (33.8%) patients at a median of 12 months (range, 1-69 months). The recurrence rate was 3.2% at a median follow-up period of 32 months. Of the 3 patients with recurrence, 2 had restarted TNF-α blocker therapy, 1 of whom died. Mortality rate was 3.2%. CONCLUSIONS: In this study, disease outcomes were generally favorable. Discontinuation of antifungal treatment after clinical response and an appropriate duration of therapy, probably at least 12 months, appears safe if pharmacologic immunosuppression has been held. Resumption of TNF-α blocker therapy also appears safe, assuming that the initial antifungal therapy was administered for 12 months.
Assuntos
Anti-Inflamatórios/efeitos adversos , Histoplasmose/complicações , Infliximab/efeitos adversos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/efeitos adversos , Adalimumab/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/uso terapêutico , Antifúngicos/uso terapêutico , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Criança , Etanercepte/efeitos adversos , Etanercepte/uso terapêutico , Feminino , Histoplasmose/tratamento farmacológico , Humanos , Síndrome Inflamatória da Reconstituição Imune , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: To improve our understanding of risk factors, management, diagnosis, and outcomes associated with histoplasmosis after solid organ transplant (SOT), we report a large series of histoplasmosis occurring after SOT. METHODS: All cases of histoplasmosis in SOT recipients diagnosed between 1 January 2003 and 31 December 2010 at 24 institutions were identified. Demographic, clinical, and laboratory data were collected. RESULTS: One hundred fifty-two cases were identified: kidney (51%), liver (16%), kidney/pancreas (14%), heart (9%), lung (5%), pancreas (2%), and other (2%). The median time from transplant to diagnosis was 27 months, but 34% were diagnosed in the first year after transplant. Twenty-eight percent of patients had severe disease (requiring intensive care unit admission); 81% had disseminated disease. Urine Histoplasma antigen detection was the most sensitive diagnostic method, positive in 132 of 142 patients (93%). An amphotericin formulation was administered initially to 73% of patients for a median duration of 2 weeks; step-down therapy with an azole was continued for a median duration of 12 months. Ten percent of patients died due to histoplasmosis with 72% of deaths occurring in the first month after diagnosis; older age and severe disease were risk factors for death from histoplasmosis. Relapse occurred in 6% of patients. CONCLUSIONS: Although late cases occur, the first year after SOT is the period of highest risk for histoplasmosis. In patients who survive the first month after diagnosis, treatment with an amphotericin formulation followed by an azole for 12 months is usually successful, with only rare relapse.
Assuntos
Histoplasmose/epidemiologia , Transplante de Órgãos/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/uso terapêutico , Criança , Pré-Escolar , Feminino , Histoplasmose/diagnóstico , Histoplasmose/tratamento farmacológico , Histoplasmose/imunologia , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto JovemAssuntos
Gerenciamento Clínico , Refluxo Gastroesofágico , Saúde Global , Qualidade de Vida , Diagnóstico Diferencial , Refluxo Gastroesofágico/epidemiologia , Refluxo Gastroesofágico/fisiopatologia , Refluxo Gastroesofágico/psicologia , Refluxo Gastroesofágico/terapia , Humanos , Estilo de Vida , Prognóstico , Fatores de RiscoRESUMO
A 16-year-old patient presented with acute myocarditis after gastroenteritis. His ECGs showed STEMI-like evolutionary changes. Serial troponin measurement was maximum on 3rd day. Echocardiography showed a mildly reduced ejection fraction (45%). He made an uneventful recovery after appropriate treatment. After one-month follow-up, his ECG and echo returned to normal.
RESUMO
BACKGROUND: HIV-1 infection is associated with multiple procoagulant changes and increased thrombotic risk. Possible mechanisms for this risk include heigthened expression of procoagulant tissue factor (TF) on circulating monocytes, extracellular vesicles, and viral particles and/or acquired deficiency of protein S (PS), a critical cofactor for the anticoagulant protein C (PC). PS deficiency occurs in up to 76% of people living with HIV-1 (PLWH). As increased ex vivo plasma thrombin generation is a strong predictor of mortality, we investigated whether PS and plasma TF are associated with plasma thrombin generation. METHODS: We analyzed plasma samples from 9 healthy controls, 17 PLWH on first diagnosis (naive), and 13 PLWH on antiretroviral therapy (ART). Plasma thrombin generation, total and free PS, PC, C4b-binding protein, and TF activity were measured. RESULTS: We determined that the plasma thrombin generation assay is insensitive to PS, because of a lack of PC activation, and developed a modified PS-sensitive assay. Total plasma PS was reduced in 58% of the naive and 38% of the ART-treated PLWH samples and correlated with increased thrombin generation in the modified assay. Conversely, plasma TF was not increased in our patient population, suggesting that it does not significantly contribute to ex vivo plasma thrombin generation. CONCLUSION: These data suggest that reduced total plasma PS contributes to the thrombotic risk associated with HIV-1 infection and can serve as a prothrombotic biomarker. In addition, our refined thrombin generation assay offers a more sensitive tool to assess the functional consequences of acquired PS deficiency in PLWH.
Assuntos
Infecções por HIV , Proteína S , Biomarcadores , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Trombina/metabolismo , TromboplastinaRESUMO
BACKGROUND: Accurate and timely methods for the diagnosis of histoplasmosis in resource-limited countries are lacking. Histoplasma antigen detection by enzyme immunoassay (EIA) is widely used in the United States (US) but not in resource-limited countries, leading to missed or delayed diagnoses and poor outcomes. Lateral flow assays (LFAs) can be used in this setting. METHODS: Frozen urine specimens were submitted to MiraVista diagnostics for antigen testing from 3 medical centers in endemic areas of the US. They were blinded and tested for the MVista Histoplasma LFA. Patients were classified as controls or cases of histoplasmosis. Cases were divided into proven or probable; pulmonary or disseminated; immunocompetent or immunosuppressed; and mild, moderate, or severe. RESULTS: Three hundred fifty-two subjects were enrolled, including 66 cases (44 proven, 22 probable) and 286 controls. Most of the cases were immunocompromised (71%), and 46 had disseminated and 20 had pulmonary histoplasmosis. Four cases were mild, 42 moderate, and 20 severe. LFA and EIA were highly concordant (κ = 0.84). Sensitivity and specificity of the LFA were 78.8% and 99.3%, respectively. LFA sensitivity was higher in proven cases (93.2%), patients with disseminated (91.3%), moderate (78.6%), and severe disease (80%), and those with galactomannan levels >1.8 ng/mL (97.8%). Specificity was 99.3% in proven cases, 99.3% in patients with moderate or severe disease, and 96.8% in those with galactomannan levels >1.8 ng/mL. Cross-reactivity was noted with other endemic mycoses. CONCLUSIONS: The MVista Histoplasma LFA meets the need for accurate rapid diagnosis of histoplasmosis in resource-limited countries, especially in patients with high disease burden, potentially reducing morbidity and mortality.
RESUMO
Cadmium is an environmental toxic metal and its exposure has become a worldwide public health threat. We aimed to evaluate the exposure assessment of cadmium in people living in Ta Zin Yae Kyaw village of Nyaung Don Township in Ayeyarwady Division, Myanmar and adverse effects of cadmium on the kidneys. Subjects (18-40 years) residing in this village were selected as the exposed group (n = 65) and those living in Kamayut Township in Yangon Division, Myanmar as the control group (n = 65). Spot urine samples were taken for determination of urinary cadmium concentration using graphite-furnace atomic absorption spectrometry (GFAAS) method and adjusted to the concentration of creatinine in urine. To assess the kidney function, urinary ß2-microglobulin level was determined by ELISA, serum creatinine was measured by colorimetric Jaffe method and estimated glomerular filtration rate (eGFR) was calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Urine cadmium concentrations were significantly higher in the exposed group (median (Interquartile range): 0.96 (0.19-1.77) µg/g Creatinine) compared to the control (p = 0.036). Urinary ß2-microglobulin levels were significantly higher (p = 0.000) and eGFR was significantly lower in the exposed group (p = 0.013) compared to the control. In addition, urine cadmium level showed significant positive correlation with urinary ß2-microglobulin in all study population (p < 0.01). Positive correlation becomes stronger (p < 0.01) in the exposed group only. For eGFR, significant negative correlation was found in all study population (p < 0.01) and exposed group (p < 0.01). Our findings suggested that environmental cadmium exposure can induce renal dysfunction in both tubular and glomerular functions in apparently healthy human adults.
Assuntos
Cádmio/toxicidade , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/toxicidade , Nefropatias/induzido quimicamente , Glomérulos Renais/efeitos dos fármacos , Túbulos Renais/efeitos dos fármacos , Adolescente , Adulto , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Mianmar , Adulto JovemRESUMO
BACKGROUND/AIM: Although inflammatory bowel disease (IBD) incidence has increased over the past two decades in Asia, data on extraintestinal manifestations (EIMs) of IBD in Asian patients are limited. We aimed to evaluate the prevalence and clinical characteristics of EIMs in Asian IBD patients. METHODS: In total, 1,764 patients (1,130 with ulcerative colitis [UC] and 634 with Crohn's disease [CD]) were recruited from 10 tertiary centers in Asia. The medical records of IBD patients were retrospectively reviewed for the presence, clinical characteristics, chronological order, and therapeutic management of EIMs. RESULTS: EIMs were reported in 199 (11.3%) patients, of which 17 (1.0%) patients had multiple EIMs. EIMs were more prevalent in CD patients (Pâ¯=â¯0.02). Multiple logistic regression analysis revealed that female sex (odds ratio [OR] 2.02, 95% confidence interval [CI] 1.15-3.55), stricture (OR 2.49, 95% CI 1.41-4.39) and female sex (OR 2.57, 95% CI 1.52-4.34), extensive colitis (OR 2.63, 95% CI 1.57-4.41) were associated with EIMs in CD and UC patients respectively. EIMs appeared in 8% of patients before IBD diagnosis; 95% of cases with EIM could be managed via first-line therapy. CONCLUSION: EIM prevalence is lower among Asian IBD patients than among patients from Western countries; however, the risk factors for EIM were similar between both populations.
Assuntos
Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/terapia , Adolescente , Adulto , Ásia/epidemiologia , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia confers considerable morbidity and mortality. Although vancomycin or daptomycin monotherapy is usually curative, prolonged bacteremia necessitating supplemental ceftaroline has occurred. The practice has led to the question of whether to continue with ceftaroline following bacteremia resolution. METHODS: Adult patients hospitalized with MRSA bacteremia at the University of Kentucky Medical Center between January 2015 and December 2017 were retrospectively reviewed. Study subjects required supplemental ceftaroline due to 4 or more days of bacteremia despite vancomycin or daptomycin. They additionally had accompanying native valve infective endocarditis, osteomyelitis, or brain abscess. Patients were divided into two cohorts. One group continued with ceftaroline plus vancomycin or daptomycin following bacteremia resolution (combination therapy group). The other group received vancomycin or daptomycin alone (monotherapy group). All involved received 6-8 weeks of therapy. Patients' Pitt bacteremia score (PBS) and Charlson comorbidity index (CCI) values were calculated. Treatment outcomes of inpatient mortality, recurrence of bacteremia, 30-day readmission, acute kidney injury, and leukopenia were recorded and compared. RESULTS: A total of 30 patients comprised the study population. 15 patients were assigned to each cohort. The median PBS value of the combination therapy group was 2, compared with 1 among the monotherapy group. The median CCI score of both groups was 0. No statistically significant difference in the aforementioned treatment outcomes was seen between the two groups. CONCLUSION: In subjects with complicated and prolonged MRSA bacteremia requiring supplemental ceftaroline, clinical outcomes did not differ among patients prescribed vancomycin or daptomycin alone following bacteremia resolution versus patients who continued combination therapy.
RESUMO
Histoplasmosis is an endemic mycosis caused by Histoplasma capsulatum. Infection develops by inhalation of microconidia from environmental sites inhabited by birds and bats. Disseminated disease is the usual presentation due to impaired cellular immunity. Common clinical manifestations include fever, fatigue, malaise, anorexia, weight loss, and respiratory symptoms. Histoplasma antigen detection is the most sensitive method for diagnosis. The sensitivity of the MVista® Quantitative Histoplasma antigen enzyme immunoassay is 95-100% in urine, over 90% in serum and bronchoalveolar lavage (BAL) antigen and 78% in cerebral spinal fluid (CSF). A proven diagnosis can be established by culture or pathology with sensitivities between 70% and 80%. The sensitivity of antibody detection by immunodiffusion or complement fixation was between 60% and 70%. Diagnosis using molecular methods has not been adequately validated for implementation and FDA cleared assays are unavailable. Liposomal amphotericin B should be used for 1-2 weeks followed by itraconazole for at least one year until CD4 counts are above 150 cells/mm3, HIV viral load is below 400 copies/mL and Histoplasma urine antigen is negative. Serum itraconazole level should be monitored to avoid drug toxicity. Antigen should be measured periodically to establish that treatment is effective and to assist in identifying relapse. The incidence of immune reconstitution inflammatory syndrome is low but it must be considered in patients who are thought to be failing antifungal treatment as it does not respond to changing antifungal agents but rather to initiation of corticosteroid therapy. In this review, we discuss pathogenesis, clinical manifestations, diagnosis and treatment based on personal experience and relevant publications.
RESUMO
OBJECTIVE: The aim of the study was to investigate the association between single nucleotide polymorphisms (SNP) at rs 1501299 (SNP+276 G>T) of the adiponectin gene and plasma adiponectin levels in type 2 diabetes mellitus (T2DM) patients in Myanmar. METHODOLOGY: One hundred T2DM patients and 104 non-diabetic subjects were included in this cross-sectional analytical study. Genotype frequencies were determined by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) method. Plasma adiponectin level was measured by enzyme-linked immunosorbent assay (ELISA). RESULT: Genotype frequencies (GG, GT, TT) of SNP+276 in diabetic patients were 39%, 48% and 13%, respectively. The GT and TT genotypes were more frequent in T2DM patients (OR 1.98, 95% CI, 1.10-3.55; p=0.02 and OR 4.07, 95% CI, 1.34-12.3; p=0.01), respectively. The T allele of SNP+276 was significantly associated with T2DM (OR 1.96, 95% CI, 1.27-3.01; p=0.002). Mean plasma adiponectin level was significantly lower than in T2DM patients (27.41±16.7 µg/mL) compared to non-diabetic subjects (37.19±26.77 µg/mL) (p=0.002). CONCLUSION: SNP+276 at rs 1501299 of the adiponectin gene was associated with type 2 diabetes and low plasma adiponectin levels in this Myanmar population.
RESUMO
BACKGROUND/AIMS: Differences in the Helicobacter pylori infection rate are not sufficient to clarify the dissimilarity of gastric cancer incidence between Myanmar and its neighboring countries. To better understand this trend, the H. pylori virulence gene cagA was characterized in Myanmar. METHODS: Glutamate-proline-isoleucine-tyrosine-alanine (EPIYA) patterns and CagA multimerization (CM) motifs of cagA genotypes were examined by performing polymerase chain reactions and DNA sequencing. RESULTS: Of 69 tested H. pylori strains, cagA-positive patients had significantly more severe histological scores in their antrum than cagA-negative patients. Sequence analysis revealed that 94.1% of strains had Western-type cagA containing an EPIYA motif (92.6%) or EPIYT motif (6.4%). The intestinal metaplasia scores in the antral of patients infected with the ABC and ABCC types of cagA were significantly higher than those of patients with AB-type cagA. Interestingly, in patients infected with H. pylori, 46.3% of strains with three EPIYA motifs contained two identical Western-typical CM motifs, and these patients showed significantly higher antrum inflammation scores than patients infected with two identical nontypical-CM motif strains (p=0.02). CONCLUSIONS: In Myanmarese strains, Western-type cagA was predominant. The presence of CM motifs and the proportion of multiple EPIYA-C segments might partially explain the intermediate gastric cancer risk found in Myanmar.
Assuntos
Antígenos de Bactérias/análise , Proteínas de Bactérias/análise , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Intestinos/patologia , Região 3'-Flanqueadora/genética , Adulto , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Feminino , Gastrite/microbiologia , Infecções por Helicobacter/epidemiologia , Humanos , Incidência , Intestinos/microbiologia , Masculino , Metaplasia , Pessoa de Meia-Idade , Mianmar/epidemiologia , Reação em Cadeia da Polimerase , Antro Pilórico/microbiologia , Análise de Sequência de DNA , Neoplasias Gástricas/microbiologiaRESUMO
Central nervous system (CNS) involvement occurs in 5 to 10% of individuals with disseminated histoplasmosis. Most experience has been derived from small single center case series, or case report literature reviews. Therefore, a larger study of central nervous system (CNS) histoplasmosis is needed in order to guide the approach to diagnosis, and treatment.A convenience sample of 77 patients with histoplasmosis infection of the CNS was evaluated. Data was collected that focused on recognition of infection, diagnostic techniques, and outcomes of treatment.Twenty nine percent of patients were not immunosuppressed. Histoplasma antigen, or anti-Histoplasma antibodies were detected in the cerebrospinal fluid (CSF) in 75% of patients. One year survival was 75% among patients treated initially with amphotericin B, and was highest with liposomal, or deoxycholate formulations. Mortality was higher in immunocompromised patients, and patients 54 years of age, or older. Six percent of patients relapsed, all of whom had the acquired immunodeficiency syndrome (AIDS), and were poorly adherent with treatment.While CNS histoplasmosis occurred most often in immunocompromised individuals, a significant proportion of patients were previously, healthy. The diagnosis can be established by antigen, and antibody testing of the CSF, and serum, and antigen testing of the urine in most patients. Treatment with liposomal amphotericin B (AMB-L) for at least 1 month; followed by itraconazole for at least 1 year, results in survival among the majority of individuals. Patients should be followed for relapse for at least 1 year, after stopping therapy.