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BACKGROUND: Progressive disseminated histoplasmosis is a significant issue in Latin America, particularly in Brazil, contributing to high mortality rates. OBJECTIVES: Our objectives were to comprehensively describe histoplasmosis treatment with various amphotericin B (AmB) formulations, including mortality rates, adverse effects and risk factors for mortality. METHODS: This multicentre retrospective cohort study (January 2014-December 2019) evaluated medical records of patients with proven or probable histoplasmosis treated with at least two doses of AmB in seven tertiary medical centres in Brazil. We assessed risk factors associated with death during hospitalization using univariate and multivariate analyses. RESULTS: The study included 215 patients, mostly male (nâ=â158, 73%) with HIV infection (nâ=â187, 87%), and a median age of 40 years. Only 11 (5%) patients initiated treatment with liposomal amphotericin B (L-AmB). Amphotericin B deoxycholate (D-AmB) was administered to 159 (74%) patients without changes in the treatment. The overall mortality during hospitalization was 23% (50/215). Variables independently associated with mortality were use of D-AmB (OR 4.93) and hospitalization in ICU (OR 9.46). There was a high incidence of anaemia (nâ=â19, 90%), acute kidney injury (nâ=â96, 59%), hypokalaemia (nâ=â73, 55%) and infusion reactions (nâ=â44, 20%) during treatment. CONCLUSIONS: We found that D-AmB was the main formulation, which was also associated with a higher mortality rate. Lipid formulations of AmB have become more readily available in the public health system in Brazil. Further studies to evaluate the effectiveness of L-AmB will likely show improvements in the treatment outcomes for patients with disseminated histoplasmosis.
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Anfotericina B , Antifúngicos , Histoplasmose , Humanos , Anfotericina B/uso terapêutico , Anfotericina B/efeitos adversos , Masculino , Histoplasmose/tratamento farmacológico , Histoplasmose/mortalidade , Feminino , Estudos Retrospectivos , Adulto , Antifúngicos/uso terapêutico , Antifúngicos/efeitos adversos , Pessoa de Meia-Idade , Brasil/epidemiologia , Ácido Desoxicólico/uso terapêutico , Ácido Desoxicólico/efeitos adversos , Fatores de Risco , Combinação de Medicamentos , Adulto Jovem , Hospitalização/estatística & dados numéricos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/mortalidade , Idoso , Hipopotassemia/induzido quimicamente , Hipopotassemia/mortalidadeRESUMO
Fingolimod is a sphingosine-1-phosphate receptor modulator used to treat multiple sclerosis. While fingolimod has been associated with an increased risk of cryptococcal meningitis, its correlation with other deep mycoses remains unclear. In this study, we conducted a scoping review of fingolimod associated with histoplasmosis, based on a case report, a literature review, and data from the FDA Adverse Events Reporting System (FAERS) as of January 24th, 2023. A 30-year-old Brazilian woman diagnosed with relapsing-remitting multiple sclerosis, receiving a daily dose of 0.5 mg of fingolimod, presented with a two-month history of fever and unintended weight loss, accompanied by lymphadenopathy, splenomegaly, and lung involvement was investigated. Biopsy of a lung nodule revealed fungal structures suggestive of Histoplasma sp. Additionally, serological testing yielded positive for Histoplasma capsulatum. Disseminated histoplasmosis should be considered in the differential diagnosis of febrile syndromes in patients undergoing fingolimod therapy for multiple sclerosis, particularly in the Americas, where this mycosis is endemic. Treatment with itraconazole and modification of immunotherapy can achieve excellent clinical outcomes.
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Cloridrato de Fingolimode , Histoplasmose , Esclerose Múltipla Recidivante-Remitente , Humanos , Histoplasmose/tratamento farmacológico , Histoplasmose/diagnóstico , Cloridrato de Fingolimode/efeitos adversos , Feminino , Adulto , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Antifúngicos/efeitos adversos , Antifúngicos/uso terapêutico , Imunossupressores/efeitos adversos , HistoplasmaRESUMO
The literature holds few descriptions on immune response findings for laryngeal cryptococcosis. Immunology has been more extensively described in cases involving the central nervous system and the lungs, although many of these studies were conducted in animal models. We aimed to analyze the clinical and immunological characteristics of three patients with laryngeal cryptococcosis. We observed a weak participation of the innate immune response, whereas adaptive immunity showed the predominance of a Th2-type response over a Th1-type response. Most cases occur in male older adults with immunosuppressive conditions, of which HIV infection was absent. Hoarseness configured the main symptom. We found a disease that was restricted to the larynx and possibly the lungs by contiguity. Patients with hoarseness and lesions in nasal endoscopy should be investigated for cryptococcosis by a biopsy of the larynx, including with negative serum cryptococcal antigen. The immunological aspects of our findings of laryngeal involvement resembled those in the most commonly affected systems.
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Criptococose , Doenças da Laringe , Humanos , Criptococose/imunologia , Doenças da Laringe/imunologia , Doenças da Laringe/microbiologiaRESUMO
Congenital zika virus syndrome (CZS) has become a significant worldwide concern since the sudden rise of microcephaly related to zika virus (ZIKV) in Brazil. Primarily transmitted by Aedes mosquitoes, ZIKV shares serologic similarities with dengue virus (DENV), complicating the diagnosis and/or clinical management. The Angiotensin I-Converting Enzyme (ACE) was associated with either neuroprotective or anti-inflammatory properties in the central nervous system (CNS). The possible role(s) of ACE in these two flaviviruses infection remain largely unexplored. In this study, we evaluate ACE activity in the brain of ZIKV- or DENV-infected mice, both compared to MOCK, showing about 30 % increased ACE activity only in ZIKV-infected mice (p = 0.024), while no change was noticed in brain from DENV-infected animals (p = 0.888). In addition, the treatment with interferon beta (IFNß), under conditions previously demonstrated to rescue the normal size of microcephalic brains determined by ZIKV infection, also restored ACE activity in ZIKV-infected animals to levels close to that of the MOCK control group. Although inflammatory responses expected for either ZIKV or DENV infections, only ZIKV was associated with microcephaly, as well as with increased ACE activity and reversion by treatment with IFNß. Furthermore, this increase in ACE activity was observed only after intracerebroventricular (ICV) injection (F (2, 16) = 7.907, p = 0.004), but not for intraperitoneal (IP) administration of ZIKV (F (2, 26) = 1.996, p = 0.156), suggesting that the observed central ACE activity modulation may be associated with the presence of this specific flavivirus in the brain.
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BACKGROUND: The radiological manifestations of central nervous system (CNS) cryptococcosis are diverse and often subtle. There is heterogeneity on how different neuroimaging patterns impact prognosis. This study aims to assess the association between the neuroimaging and clinical outcomes of CNS cryptococcosis. METHODS: All patients with CNS cryptococcosis between July 2017 and April 2023 who underwent brain magnetic resonance imaging (MRI) were included. The primary outcome was mortality during hospitalisation. Secondary outcomes were readmission, ventricular shunting, duration of hospitalisation and time to the first negative cerebrospinal fluid culture. We compared the outcomes for each of the five main radiological findings on the brain MRI scan. RESULTS: We included 46 proven CNS cryptococcosis cases. The two main comorbidity groups were HIV infection (20, 43%) and solid organ transplantation (10, 22%), respectively. Thirty-nine patients exhibited at least one radiological abnormality (85%), with the most common being meningeal enhancement (34, 74%). The mortality rates occurred at 11% (5/46) during hospitalisation. We found no significant disparities in mortality related to distinct radiological patterns. The presence of pseudocysts was significantly associated with the need for readmission (p = .027). The ventricular shunting was significantly associated with the presence of pseudocysts (p = .005) and hydrocephalus (p = .044). CONCLUSION: In this study, there is no association between brain MRI findings and mortality. Larger studies are needed to evaluate this important issue.
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Criptococose , Imageamento por Ressonância Magnética , Neuroimagem , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neuroimagem/métodos , Criptococose/diagnóstico por imagem , Criptococose/mortalidade , Criptococose/microbiologia , Adulto , Idoso , Estudos Retrospectivos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Infecções Fúngicas do Sistema Nervoso Central/diagnóstico por imagem , Infecções Fúngicas do Sistema Nervoso Central/mortalidade , Infecções Fúngicas do Sistema Nervoso Central/microbiologia , Prognóstico , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/mortalidade , Hospitalização , Infecções por HIV/complicaçõesRESUMO
Although TRPV1 receptors play an essential role in the adverse effects on the airways following captopril treatment, there is no available evidence of their involvement in treatment regimens involving repeated doses of captopril. Comparing the difference in these two treatment regimens is essential since captopril is a continuous-use medication. Thus, this study explored the role of the transient receptor potential vanilloid 1 (TRPV1) in the effects of captopril on rat airways using two treatment regimens. Airway resistance, bronchoalveolar lavage (BAL), and histological and immunohistochemical analyses were conducted in rats administered with single or repeated doses of captopril. This study showed that the hyperresponsiveness to bradykinin and capsaicin in captopril-treated rats was acute. Treatment with the selective B2 antagonist, HOE140 reduced bradykinin hyperresponsiveness and abolished capsaicin exacerbation in single-dose captopril-treated rats. Likewise, degeneration of TRPV1-positive neurones also reduced hyperresponsiveness to bradykinin. Single-dose captopril treatment increased leukocyte infiltration in the BAL when compared with the vehicle and this increase was reduced by TRPV1-positive neurone degeneration. However, when compared with the vehicle treatment, animals treated with repeated doses of captopril showed an increase in leukocyte influx as early as 1 h after the last captopril treatment, but this effect disappeared after 24 h. Additionally, an increase in TRPV1 expression occurred only in animals who received repeated captopril doses and the degeneration of TRPV1-positive neurones attenuated TRPV1 upregulation. In conclusion, these data strongly indicate that a treatment regimen involving multiple doses of captopril not only enhances sensitisation but also upregulates TRPV1 expression. Consequently, targeting TRPV1 could serve as a promising strategy to reduce the negative impact of captopril on the airways.
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Bradicinina , Líquido da Lavagem Broncoalveolar , Capsaicina , Captopril , Canais de Cátion TRPV , Animais , Captopril/farmacologia , Canais de Cátion TRPV/metabolismo , Ratos , Masculino , Bradicinina/farmacologia , Capsaicina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Ratos Sprague-Dawley , Resistência das Vias Respiratórias/efeitos dos fármacos , Antagonistas de Receptor B2 da Bradicinina/farmacologia , Relação Dose-Resposta a Droga , Hiper-Reatividade Brônquica/induzido quimicamente , Hiper-Reatividade Brônquica/tratamento farmacológico , Neurônios/efeitos dos fármacos , Neurônios/metabolismoRESUMO
Osteomyelitis caused by non-Candida species is rare and often neglected, and current recommendations are based on primarily clinical experience and expert opinion. The objective of this study was to describe a case series of non-Candida fungal osteomyelitis. This retrospective study included 10 patients with non-Candida fungal osteomyelitis. Patients with osteomyelitis and microbiologically confirmed non-Candida species from bone fragment cultures were selected from the institution Infection Control Board database. Fusarium spp. were the most commonly isolated fungus from bone fragment cultures in five patients (50%). The majority did not present immunosuppression. The most common etiology was post-traumatic (n = 7, 70%), particularly open fractures. All patients were treated with antifungals associated with surgery. The antifungals used were itraconazole in five patients (50%), and voriconazole in another five patients (50%), with a median duration of antifungal therapy of four weeks (range: 3-25). There were no observed deaths within 30 days and one year. An antifungal approach combined with surgical treatment demonstrated favorable clinical outcomes, including low mortality rates and effective remission.
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Antifúngicos , Osteomielite , Humanos , Osteomielite/microbiologia , Osteomielite/epidemiologia , Osteomielite/tratamento farmacológico , Antifúngicos/uso terapêutico , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Feminino , Adulto , Adulto Jovem , Idoso , Adolescente , Micoses/microbiologia , Micoses/epidemiologia , Micoses/tratamento farmacológico , Micoses/mortalidade , Fungos/isolamento & purificação , Fungos/classificação , Fungos/efeitos dos fármacos , Fungos/genética , CriançaRESUMO
PURPOSE: This study investigated the pharmacological effects of topical trans-anethole, a natural compound found in anise, star anise, and fennel essential oils, and its relationship with the transient receptor potential of ankyrin 1 (TRPA1). METHODS: The effects of topical anethole were assessed by eye wiping, nociceptive behaviour, and ear oedema in mice. Histological evaluations were performed on the ears of the animals topically treated with anethole. RESULTS: Anethole caused less eye irritation than capsaicin (a TRPV1 agonist) and allyl isothiocyanate (a TRPA1 agonist). Anethole (250 and 500 nmol/20 µL/paw) promoted neurogenic nociception in the paw (20.89 ± 3.53 s and 47.56 ± 8.46 s, respectively) compared with the vehicle (0.88 ± 0.38 s). HC030031 (56.1 nmol/20 µL/paw), a TRPA1 antagonist, abolished this nociceptive response. Anethole (4, 10, and 20 µmol/20 µL/ear) induced ear oedema (30.25 ± 4.78 µm, 78.00 ± 3.74 µm, and 127.50 ± 27.19 µm, respectively) compared with the vehicle (5.00 ± 0.5 µm). HC030031 (56.1 nmol/20 µL/ear) inhibited the oedema induced by anethole (10 µmol/20 µL/ear). Ears pre-treated with anethole or allyl isothiocyanate on the first day and re-exposed to these compounds on the third day showed a reduction in oedema (68.16 ± 6.04% and 38.81 ± 8.98.9%, respectively). Cross-desensitisation between anethole and allyl isothiocyanate was observed. Histological analysis confirmed the beneficial effects of anethol. CONCLUSION: As repeated topical applications of anethole induce the desensitisation of TRPA1, we suggest its clinical application as a topical formulation for treating skin diseases or managing pain associated with this receptor. Anethole may also have advantages over capsaicin and allyl isothiocyanate because of its low pungency and pleasant aroma.
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O rápido envelhecimento populacional impulsiona iniciativas com o objetivo de otimizar a saúde da população idosa em todo o mundo. Recentemente, no Brasil, foi publicado pelo Conselho Nacional dos Secretários de Saúde (CONASS) o Manual de Avaliação Multidimensional da Pessoa Idosa, que propõe a adoção combinada e em larga escala da ferramenta de triagem do ICOPE da Organização Mundial da Saúde (OMS) e do instrumento Índice de Vulnerabilidade Clínico-Funcional-20 (IVCF-20) para definir linhas de cuidado à pessoa idosa. Embora iniciativas dessa natureza sejam prementes, os instrumentos propostos ainda não têm validação adequada na população brasileira, e a sua utilização com o objetivo de balizar diretrizes em saúde em todo o território nacional parece precipitada e arriscada. Diante disso, propõe-se um debate amplo e urgente entre os especialistas da área, com o objetivo de planejar políticas de saúde pública eficazes e seguras para a população idosa brasileira. (AU)
Rapid population aging is driving initiatives aimed at optimizing the health of older populations worldwide. In Brazil, the National Council of State Secretaries of Health (CONASS) recently published the Handbook for Multidimensional Geriatric Assessment in Primary Care, which proposes the combined, large-scale adoption of the World Health Organization (WHO) ICOPE screening tool and the Clinical-Functional Vulnerability Index-20 (IVCF-20) instrument to define care pathways for older people. Although there is a pressing need for initiatives of this nature, the proposed instruments have not yet been adequately validated in the Brazilian population, and their use for the purpose of establishing countrywide health guidelines appears hasty and risky. Therefore, we propose a broad, urgent debate among experts in the field with the aim of planning effective and safe public health policies for the Brazilian older population. (AU)
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Humanos , Idoso , Idoso de 80 Anos ou mais , Atenção Primária à Saúde , Política de Saúde , Qualidade de Vida , Organização Mundial da SaúdeRESUMO
Introduction: The World Health Organization (WHO) has proposed to monitor intrinsic capacity (IC) in the older population as a public health strategy through the Integrated Care for Older People (ICOPE) program. Although the program has been developed based on solid concepts, scientific evidence on its practical applicability is still scarce. Objectives: To evaluate IC in Brazilian older adults, its progress over time, and its association with sociodemographic and health factors and outcomes. To evaluate the psychometric properties of the WHO/ICOPE screening tool. Methods: This is a prospective multicenter cohort study with a 36-month follow-up. We will recruit 3838 people aged ≥60 years, registered in the health care units included in the study by the participating centers. We will collect sociodemographic and health data and will administer tools to assess IC domains, both those provided for in the ICOPE screening tool and the sequence of confirmatory assessments provided for in the program. Participants will be reassessed every 6 months for 36 months. Expected results: To establish the profile of IC in the study population and to understand its progress and the variables associated with the clinical outcomes of interest. To reveal the diagnostic and psychometric properties of the WHO/ICOPE screening tool. The project is funded by the Brazilian National Council for Scientific and Technological Development (CNPq). Relevance: Understanding the potential use of the ICOPE public health strategy proposed by the WHO within the scope of the Brazilian Unified Health System (SUS) by integrating several research centers in the field of Geriatrics and Gerontology throughout Brazil. (AU)
Introdução: A Organização Mundial da Saúde (OMS) propõe o monitoramento da capacidade intrínseca (CI) da população idosa como estratégia de saúde pública por meio do Programa ICOPE (Integrated Care for Older People). Embora construído com base em conceitos sólidos, a evidência científica sobre a aplicabilidade prática da proposta ainda é escassa. Objetivo: Avaliar a capacidade intrínseca da população idosa brasileira, sua trajetória e sua associação com variáveis sociodemográficas, de saúde e desfechos. Avaliar as propriedades psicométricas da ferramenta de triagem da estratégia ICOPE da OMS. Metodologia: Coorte multicêntrica prospectiva com seguimento de 36 meses. Serão recrutadas 3.838 pessoas com 60 anos ou mais, cadastradas nas unidades de saúde incluídas no estudo pelos centros participantes. Serão coletados dados sociodemográficos e de saúde e aplicados instrumentos para avaliação dos domínios da CI, tanto aqueles previstos no instrumento de triagem do ICOPE quanto a sequência de avaliações confirmatórias previstas no programa. Os participantes serão acompanhados semestralmente ao longo de 36 meses. Resultados esperados: Estabelecer o perfil da CI na população estudada, entender a sua trajetória e as variáveis associadas aos desfechos clínicos avaliados. Revelar as propriedades diagnósticas e o perfil psicométrico da ferramenta de triagem do ICOPE da OMS. O projeto tem financiamento do Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). Relevância: Compreensão sobre o potencial de utilização da estratégia ICOPE de saúde pública proposta pela OMS no âmbito do Sistema Único de Saúde (SUS) pela integração de diversos centros de pesquisa científica na área de Geriatria e Gerontologia de todo o Brasil. (AU)
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Humanos , Idoso , Idoso de 80 Anos ou maisRESUMO
Objective: To investigate the association between diet quality, nutritional status, and sarcopenia in a sample of the oldest old. Methods: Using a cross-sectional design, individuals aged ≥ 80 years were enrolled. To determine their energy and macronutrient intake, 24-hour dietary recall was used to calculate the Healthy Eating Index. Nutritional status was categorized based on Mini Nutritional Assessment (MNA) scores. Sarcopenia was diagnosed using both the 2010 and 2018 EWGSOP criteria. Electrical bioimpedance was used to calculate the muscle mass index. Muscle strength was measured through handgrip dynamometry, and muscle performance was determined with a 4-m gait speed test. To test the association between the HEI with sarcopenia, means of HEI scores were compared between sarcopenic and non-sarcopenic participants using indendent t-tests. Prevalence rate ratios were calculated using a Poisson Regression model with robust estimation of standard errors. Results: The study population consisted of 119 participants, predominantly women (n = 67; 56.3%), with a mean age of 83.4 (SD, 3.0) years. The prevalence of sarcopenia varied significantly according to the classification criteria, being higher according to EWGSOP 2010 than EWGSOP 2018 criteria (46.7 vs. 17.6%), as expected. Female participants and those categorized as malnourished presented higher prevalence of sarcopenia. Nutrition quality, estimated by the Healthy Eating Index, was not associated with the outcome. Reduced total energy and high protein intake were independently associated with both sarcopenia and severe sarcopenia, regardless of the diagnostic criteria. Conclusions: The Health Eating Index was not associated with sarcopenia in this sample of older adults ≥80 years. Sarcopenia prevalence, as defined by the EWGSOP 2018 criteria, was higher in those with MNA≤24 and with reduced daily total energy comsumption independently of age, sex and education attainment. Higher protein intake, oposed to expected, was indenpendently associated with sarcopenia, possibly due to protopathic bias. Large longitudinal studies are still required to investigate the relationship between nutrition quality and Sarcopenia in 80+ aged adults. (AU)
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Humanos , Idoso de 80 Anos ou mais , Idoso , Estado Nutricional , Sarcopenia , Alimentos, Dieta e NutriçãoRESUMO
OBJECTIVES: The selected kyotorphin derivatives were tested to improve their antimicrobial and antibiofilm activity. The antimicrobial screening of the KTP derivatives were ascertained in the representative strains of bacteria, including Streptococcus pneumoniae, Streptococcus pyogenes, Escherichia coli and Pseudomonas aeruginosa. METHODS: Kyotorphin derivatives, KTP-NH2, KTP-NH2-DL, IbKTP, IbKTP-NH2, MetKTP-DL, MetKTP-LD, were designed and synthesized to improve lipophilicity and resistance to enzymatic degradation. Peptides were synthesized by standard solution or solid-phase peptide synthesis and purified using RP-HPLC, which resulted in >95 % purity, and were fully characterized by mass spectrometry and 1H NMR. The minimum inhibitory concentrations (MIC) determined for bacterial strains were between 20 and 419 µM. The direct effect of IbKTP-NH2 on bacterial cells was imaged using scanning electron microscopy. The absence of toxicity, high survival after infection and an increase in the hemocytes count was evaluated by injections of derivatives in Galleria mellonella larvae. Proteomics analyses of G. mellonella hemolymph were performed to investigate the underlying mechanism of antibacterial activity of IbKTP-NH2 at MIC. RESULTS: IbKTP-NH2 induces morphological changes in bacterial cell, many differentially expressed proteins involved in DNA replication, synthesis of cell wall, and virulence were up-regulated after the treatment of G. mellonella with IbKTP-NH2. CONCLUSION: We suggest that this derivative, in addition to its physical activity on the bacterial membranes, can elicit a cellular and humoral immune response, therefore, it could be considered for biomedical applications.
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Anti-Infecciosos , Endorfinas , Mariposas , Animais , Proteômica , Mariposas/microbiologia , Antibacterianos/farmacologia , Larva , PeptídeosRESUMO
We report a case of unusual paracoccidioidomycosis reactivation after eyebrow micropigmentation in a Brazilian patient. The cutaneous lesion was the only clinical manifestation. Direct cutaneous inoculation in dermal tissues with Paracoccidioides sp. is extremely rare, explaining why paracoccidioidomycosis is not classically considered a cutaneous implantation mycosis.
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BACKGROUND: The clinical features of central nervous system (CNS) sporotrichosis are derived from case reports and a limited series of cases. Our objective was to carry out a systematic review and meta-analysis of CNS sporotrichosis. METHODS: We searched PubMed/MEDLINE, Embase, Scopus, and LILACS on 9 September 2023. Our inclusion criteria were documentation of Sporothrix and demonstrated CNS involvement. A metaproportion or metamean analysis was performed to estimate a summary proportion with 95% confidence intervals. RESULTS: We included 52 cases of CNS sporotrichosis published from 1966 to 2023. Forty-six patients were male (88%, 95% CI: 77-95), and the mean age was 39 years (95% CI: 36-43). Close contact with cats was reported in 55% of cases (95% CI: 37-72). Thirty-two (61.5%) patients were from Brazil, 18 patients from the United State of America (34.6%). Only two Sporothrix species were reported: S. schenckii (26/41, 63%), and S. brasiliensis (15/41, 37%). The most common neurological symptom was headache. Meningitis was chronic in approximately 80% of cases. A significant majority of the patients were immunocompromised. HIV infection was the primary cause of immunosuppression (85%, 95% CI: 61-95). Overall mortality was 56% (22/39). The comparison of Kaplan-Meier survival curve showed a higher mortality with a statistically significant difference in immunosuppressed patients (p = .019). CONCLUSION: CNS sporotrichosis represents a notable cause of chronic meningitis, especially in individuals living in the Americas with HIV infection and concurrent skin lesions.
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Antifúngicos , Sporothrix , Esporotricose , Esporotricose/tratamento farmacológico , Esporotricose/diagnóstico , Humanos , Sporothrix/isolamento & purificação , Antifúngicos/uso terapêutico , Gatos , Masculino , Adulto , Feminino , Animais , Brasil/epidemiologia , Infecções Fúngicas do Sistema Nervoso Central/tratamento farmacológico , Infecções Fúngicas do Sistema Nervoso Central/microbiologia , Infecções Fúngicas do Sistema Nervoso Central/diagnóstico , Infecções Fúngicas do Sistema Nervoso Central/mortalidade , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: As infective endocarditis has particular characteristics compared to other infectious diseases, it is not clear if sepsis scores are reported with good accuracy in these patients. The aim of this study is to evaluate the accuracy of the qSOFA and SOFA scores to predict mortality in patients with infective endocarditis. METHODS: Between January 2010 and June 2019, 867 patients with suspected left-sided endocarditis were evaluated; 517 were included with left-sided infective endocarditis defined as "possible" or "definite" endocarditis, according to the Modified Duke Criteria. ROC curves were constructed to assess the accuracy of qSOFA and SOFA sepsis scores for the prediction of in-hospital mortality. RESULTS: The median age was 57 years, 65% were male, 435 (84%) had pre-existing heart valve disease, and the overall mortality was 28%. The most frequent etiologies were Streptococcus spp. (36%), Enterococcus spp. (10%), and Staphylococcus aureus (9%). The sepsis scores from the ROC curves used to predict in-hospital mortality were qSOFA 0.601 (CI95% 0.522-0.681) and SOFA score 0.679 (CI95% 0.602-0.756). A sub-group analysis in patients with and without pre-existing valve disease for SOFA ≥ 2 showed ROC curves of 0.627 (CI95% 0.563-0.690) and 0.775 (CI95% 0.594-0.956), respectively. CONCLUSIONS: qSOFA and SOFA scores were associated with increased in-hospital mortality in patients with infective endocarditis. However, as accuracy was relatively lower compared to other sites of bacterial infections, we believe that this score may have lower accuracy when predicting the prognosis of patients with IE, because, in this disease, the patient's death may be more frequently linked to valvular and cardiac dysfunction, as well as embolic events, and less frequently directly associated with sepsis.
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ABSTRACT Fingolimod is a sphingosine-1-phosphate receptor modulator used to treat multiple sclerosis. While fingolimod has been associated with an increased risk of cryptococcal meningitis, its correlation with other deep mycoses remains unclear. In this study, we conducted a scoping review of fingolimod associated with histoplasmosis, based on a case report, a literature review, and data from the FDA Adverse Events Reporting System (FAERS) as of January 24th, 2023. A 30-year-old Brazilian woman diagnosed with relapsing-remitting multiple sclerosis, receiving a daily dose of 0.5 mg of fingolimod, presented with a two-month history of fever and unintended weight loss, accompanied by lymphadenopathy, splenomegaly, and lung involvement was investigated. Biopsy of a lung nodule revealed fungal structures suggestive of Histoplasma sp. Additionally, serological testing yielded positive for Histoplasma capsulatum. Disseminated histoplasmosis should be considered in the differential diagnosis of febrile syndromes in patients undergoing fingolimod therapy for multiple sclerosis, particularly in the Americas, where this mycosis is endemic. Treatment with itraconazole and modification of immunotherapy can achieve excellent clinical outcomes.
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ABSTRACT The literature holds few descriptions on immune response findings for laryngeal cryptococcosis. Immunology has been more extensively described in cases involving the central nervous system and the lungs, although many of these studies were conducted in animal models. We aimed to analyze the clinical and immunological characteristics of three patients with laryngeal cryptococcosis. We observed a weak participation of the innate immune response, whereas adaptive immunity showed the predominance of a Th2-type response over a Th1-type response. Most cases occur in male older adults with immunosuppressive conditions, of which HIV infection was absent. Hoarseness configured the main symptom. We found a disease that was restricted to the larynx and possibly the lungs by contiguity. Patients with hoarseness and lesions in nasal endoscopy should be investigated for cryptococcosis by a biopsy of the larynx, including with negative serum cryptococcal antigen. The immunological aspects of our findings of laryngeal involvement resembled those in the most commonly affected systems.
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Naganishia albida (Cryptococcus albidus) is considered saprophytic fungi, and is rarely reported as a human pathogen. Cutaneous infections caused by non-neoformans cryptococcus are rare. We describe a case of an immunocompetent older male with cutaneous cryptococcosis caused by Naganishia albida following skin trauma, and conduct a literature review in PubMed, Lilacs, and Embase. Only six previous similar reports were found. The seven cases (including ours) were widely distributed geographically (Brazil, the US, the UK, Hungary, South Korea, and Iran), all males, and their ages varied, ranging from 14 to 86 years. Four individuals had underlying skin diseases (Sezary Syndrome, psoriasis, and skin rash without etiology) plus potentially immunosuppressive underlying conditions (diabetes mellitus, kidney transplantation, and the use of etanercept, adalimumab, and methylprednisolone). Cutaneous presentation was polymorphic, with lesions characterized as warts, ulcers, plaques, and even macules. Two patients presented disseminated disease. Serum cryptococcal antigen was negative in six patients, and diagnosis was made by fungal culture in all. There is a lack of data on optimal antifungal treatment and outcomes.
Assuntos
Basidiomycota , Criptococose , Cryptococcus neoformans , Cryptococcus , Humanos , Masculino , Antifúngicos/uso terapêutico , Criptococose/diagnósticoRESUMO
Brazilian Cerrado is recognised as a biodiversity hotspot due to the presence of endemic species with great biological potential. Particularly, Lomatozona artemisiifolia, is a rare species found in the Cerrado region in midwestern Brazil. Efforts have been made for its conservation in the Cerrado, such as the use of in vitro micropropagation, demanding a comparative analysis between grown plants and those collected from nature. For this purpose, we performed the chemical study of L. artemisiifolia by LC-ESI-MS/MS and molecular networking analysis in the Global Natural Products Social Molecular Networking (GNPS) with in silico annotation using Network Annotation Propagation (NAP), which led to the observation of labdane diterpenes and flavonoid subclasses as the most representative specialised metabolites of this plant. In addition, molecular networking and chemometric analysis were correlated, allowing the metabolite profile emerging from field growth and micropropagation conditions to be observed.
RESUMO
Ndel1 oligopeptidase activity shows promise as a potential biomarker for diagnosing schizophrenia (SCZ) and monitoring early-stage pharmacotherapy. Ndel1 plays a pivotal role in critical aspects of brain development, such as neurite outgrowth, neuronal migration, and embryonic brain formation, making it particularly relevant to neurodevelopmental disorders like SCZ. Currently, the most specific inhibitor for Ndel1 is the polyclonal anti-Ndel1 antibody (NOAb), known for its high specificity and efficient anti-catalytic activity. NOAb has been vital in measuring Ndel1 activity in humans and animal models, enabling the prediction of pharmacological responses to antipsychotics in studies with patients and animals. To advance our understanding of in vivo Ndel1 function and develop drugs for mental disorders, identifying small chemical compounds capable of specifically inhibiting Ndel1 oligopeptidase is crucial, including within living cells. Due to challenges in obtaining Ndel1's three-dimensional structure and its promiscuous substrate recognition, we conducted a high-throughput screening (HTS) of 2,400 small molecules. Nine compounds with IC50-values ranging from 7 to 56 µM were identified as potent Ndel1 inhibitors. Notably, one compound showed similar efficacy to NOAb and inhibited Ndel1 within living cells, although its in vivo use may pose toxicity concerns. Despite this, all identified compounds hold promise as candidates for further refinement through rational drug design, aiming to enhance their inhibitory efficacy, specificity, stability, and biodistribution. Our ultimate goal is to develop druggable Ndel1 inhibitors that can improve the treatment and support the diagnosis of psychiatric disorders like SCZ.