A multicentre study of amphotericin B treatment for histoplasmosis: assessing mortality rates and adverse events.

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 (n = 158, 73%) with HIV infection (n = 187, 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 (n = 19, 90%), acute kidney injury (n = 96, 59%), hypokalaemia (n = 73, 55%) and infusion reactions (n = 44, 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.

Association between neuroimaging and clinical outcomes in individuals with central nervous system cryptococcosis.

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.

Analysis of epidemiological and clinical aspects in cases of fungal osteomyelitis caused by non-Candida species.

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.

Mechanistic insights on the antibacterial action of the kyotorphin peptide derivatives revealed by in vitro studies and Galleria mellonella proteomic analysis.

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.

Paracoccidioidomycosis after eyebrow micropigmentation: Unusual reactivation or a new form of transmission by cutaneous inoculation?

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.

Clinical characteristics, diagnosis, and treatment of central nervous system sporotrichosis: Systematic review and meta-analysis.

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.

Metabolic profiling of Lomatozona artemisiifolia Baker plants grown in vitro and collected from nature using molecular networking and chemometric analysis.

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.

Itraconazole Serum Trough Concentrations Using Oral Capsules for the Treatment of Chronic Pulmonary Aspergillosis: What is the Target?

BACKGROUND: In regions where there is only itraconazole capsule as a therapeutic option for treatment of chronic pulmonary aspergillosis (CPA), measuring the serum concentrations becomes even more important for therapeutic success. OBJECTIVE: Evaluate the initial itraconazole serum trough concentrations after the administration of oral capsule of itraconazole for the treatment of CPA. METHODS: The measurement was performed at least 7-days after initiation of therapy. The standard treatment at our institution was a 200 mg capsule every 12 h. We defined that an adequate serum trough concentration of itraconazole during treatment was 1-4 mg/L. RESULTS: This study recruited 28 patients. The median value was 0.30 mg/L (IQR 0.01-0.70). Only 11% (n = 3) had adequate serum concentrations based on guideline recommendation. All patients with clinical deterioration had itraconazole serum levels ≤ 0.8 mg/L. CONCLUSION: The initial serum concentrations of itraconazole after capsule formulation administration were low. Increasing the dose should be considered when the itraconazole concentration is low, especially if it is ≤ 0.8 mg/L, and the patient presents with clinical deterioration. Larger studies are needed to evaluate the adequate concentrations recommended for CPA.

Systematic review and meta-analysis of galactomannan antigen testing in serum and bronchoalveolar lavage for the diagnosis of chronic pulmonary aspergillosis: defining a cutoff.

BACKGROUND: A clear cutoff value of galactomannan (GM) has not been established for chronic pulmonary aspergillosis (CPA) and is frequently extrapolated from invasive pulmonary aspergillosis. We performed a systematic review and meta-analysis to evaluate the diagnostic performance of serum and bronchoalveolar lavage (BAL) GM, and to propose a cutoff. METHODS: We extracted from the studies the cutoff of serum or/and BAL GM associated with true positives, false positives, true negatives, and false negatives. We performed a multi-cutoff model and a non-parametric random effect model. We estimated the optimal cutoff and the area under the curve (AUC) for GM in serum and BAL samples. RESULTS: Nine studies from 1999 to 2021 were included. Overall, the optimal cutoff of serum GM was 0.96 with a sensitivity of 0.29 (95%CI: 0.14-0.51); specificity of 0.88 (95%CI: 0.73-0.95); and AUC of 0.529 (with a CI: [0.415-0.682] [0.307-0.713]). The AUC for the non-parametric ROC model was 0.631. For BAL GM the cutoff was 0.67 with a sensitivity of 0.68 (95%CI: 0.51-0.82), specificity of 0.84 (95%CI: 0.70-0.92), and AUC of 0.814 (with a CI: [0.696-0.895] [0.733-0.881]). The AUC for the non-parametric model was 0.789. CONCLUSION: The diagnosis of CPA requires the assessment of a combination of mycological and serological factors, as no single serum and/or BAL GM antigen test is adequate. BAL GM performed better than serum, with better sensitivity and excellent accuracy.

Effects of lipodystrophy and physical exercise on bioimpedance parameters in people living with HIV: A cross-sectional study.

OBJECTIVE: The aim of this study was to evaluate the effects of lipodystrophy and physical exercise on the parameters of bioimpedance spectroscopy (BIS) and bioimpedance vector analysis (BIVA) of people living with HIV (PLWHIV). METHODS: Seventy patients were divided into two groups: PLWHIV with lipodystrophy (PLWHIV-L) and PLWHIV without lipodystrophy (PLWHIV-NL). The phase angle (PhA) and the BIVA were determined from the values of resistance and reactance collected by the BIS. The percentage of fat mass and lean soft tissue (LST) were determined by dual-energy x-ray absorptiometry. For comparisons between the PLWHIV-L and PLWHIV-NL groups, the t test for independent samples or the Mann-Whitney test was used. From the BIVA, the average of the impedance vectors of the two groups was calculated with the 95% confidence ellipse, and the individual vectors of the patients divided by sex were also compared with the tolerance ellipses of 50%, 75%, and 95% of the healthy reference population. The relationships between the variables of interest were determined by the Pearson or Spearman correlation coefficient and the coefficient of determination. Analysis of covariance was used for comparisons between groups, adjusted for possible confounding variables. RESULTS: PLWIV-L showed better hydration conditions (P <0.01), higher LST (P <0.01), and lower percent of fat mass (P <0.01). No differences in PhA were observed between PLWHIV who practiced or did not practice physical exercise. There was a significant difference between the impedance vectors of the groups with and without lipodystrophy (T = 42.4 and P <0.01). Additionally, most of the patients who were positioned beyond the ellipse limits of 50% of tolerance fell into the areas of edema and cachexia. The extracellular to intracellular water ratio explained 81% of the PhA variations. When PhA was adjusted for height2, fat mass/height2 and LST, it was significantly different between groups of the female sex (PhA: P <0.01). CONCLUSION: Lipodystrophy and the practice of physical exercise do not present direct involvement in the PhA values, with sex, body composition, and hydration variables being the main influences on this variable. BIVA was able to show differences in the body composition of the groups even when the PhA values were similar.

A autonomia do adolescente em relação ao direto de imunização contra infecções sexualmente transmissíveis: revisão bibliográfica / La autonomía de los adolescentes en relación con la inmunización directa contra las infecciones de transmisión sexual: revisión bibliográfica / The autonomy of adolescents in relation to the direct of immunization against sexually transmitted infections: bibliographic review

O presente estudo trata-se de uma análise na literatura sobre o aspecto bioético da autonomia em relação a imunização contra Hepatite B e HPV na adolescência. Foi realizada uma revisão bibliográfica baseada no método prisma onde foram incluídos artigos em português e inglês os quais foram pesquisados nas plataformas Scientific Electronic Library Online (SciELO), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) e National Library of Medicine (PUBMED), utilizando os seguintes descritores Hepatitis B Vaccines, bioethics, Humans. Os resultados demostraram a eficiência dos profissionais de saúde no contato com o indivíduo e o convencimento deste através de um diálogo aberto e criação de vínculos. Evidenciou-se ainda o estudo evidenciou o direito a autonomia progressiva do paciente, no qual este ganha o direito a algumas escolhas como as imunizações de doenças sexualmente transmissíveis, como é o caso da Hepatite B e HPV, no entanto é necessário que o adolescente seja instruído sobre a imunização. Assim sendo, reconhece-se o direito a autonomia progressiva do adolescente, referente a escolha das imunizações contra a Hepatite B e HPV, entretanto, deve-se considerar que estes indivíduos sejam instruídos sobre os benefícios individuais e/ou coletivos da vacinação, contemplados por atividades de educação em saúde por profissionais qualificados, objetivando ampliar a cobertura global de imunização com doenças que caracterizam problemas de saúde pública.

El presente estudio es un análisis de la literatura sobre el aspecto bioético de la autonomía en relación con la inmunización contra la Hepatitis B y el VPH en la adolescencia. Se realizó una revisión bibliográfica basada en el método del prisma, que incluyó artículos en portugués e inglés que fueron buscados en la Biblioteca Científica Electrónica en Línea (SciELO), Literatura Latinoamericana y del Caribe en Ciencias de la Salud (LILACS) y la Biblioteca Nacional de Medicina (PUBMED), utilizando los siguientes descriptores Vacunas Hepatitis B, bioética, Humanos. Los resultados demostraron la eficiencia de los profesionales de la salud en contactar al individuo y convencerlo a través de un diálogo abierto y creación de vínculos. También se evidenció que el estudio evidenció el derecho del paciente a la autonomía progresiva, en la que adquiere el derecho a algunas opciones como las inmunizaciones de enfermedades de transmisión sexual, como la Hepatitis B y el VPH, sin embargo, es necesario que el adolescente sea educado sobre la inmunización. Por lo tanto, se reconoce el derecho del adolescente a la autonomía progresiva, en cuanto a la elección de las vacunas contra la Hepatitis B y el VPH, sin embargo, se debe considerar que estos individuos sean educados sobre los beneficios individuales y/o colectivos de la vacunación, contemplados por las actividades de educación en salud por profesionales calificados, con el objetivo de ampliar la cobertura mundial de inmunización con enfermedades que caracterizan los problemas de salud pública.

The present study is an analysis of the literature on the bioethical aspect of autonomy in relation to immunization against Hepatitis B and HPV in adolescence. A bibliographic review was carried out based on the prism method, which included articles in Portuguese and English which were searched on the Scientific Electronic Library Online (SCIELO), Latin American and Caribbean Literature on Health Sciences (LILACS) and the National Library of Medicine (PUBMED), using the following descriptors Hepatitis B Vaccines, bioethics, Humans. The results demonstrated the efficiency of health professionals in contacting the individual and convincing him/her through an open dialogue and creation of bonds. It was also evidenced the study evidenced the patient's right to progressive autonomy, in which he gains the right to some choices such as immunizations of sexually transmitted diseases, such as Hepatitis B and HPV, however it is necessary for the adolescent to be educated about immunization. Therefore, the adolescent's right to progressive autonomy is recognized, regarding the choice of immunizations against Hepatitis B and HPV, however, it must be considered that these individuals are instructed on the individual and/or collective benefits of vaccination, contemplated by health education activities by qualified professionals, aiming to expand the global coverage of immunization with diseases that characterize public health problems.

Abordagem epidemiológica e considerações bioéticas sobre a infecção pelo vírus da hepatite b em crianças e adolescentes no estado do acre, Brasil / Enfoque epidemiológico y consideraciones bioéticas sobre la infección por el virus de la hepatitis b en niños y adolescentes en el estado de Acre, Brasil / Epidemiological approach and bioethical considerations on hepatitis b virus infection in children and adolescents in the state of Acre, Brazi

O estudo investiga os aspectos epidemiológicos da hepatite B em crianças e adolescentes, discutindo os resultados encontrados à luz dos princípios da bioética. Trata-se de um estudo transversal, retrospectivo, com base em uma série temporal de casos, cujos dados de notificação foram extraídos do Sistema de Informação de Agravos de Notificação (SINAN) e dados de vacinação do Sistema de Informação do Programa Nacional de Imunizações - SIPNI, no período de 2011 a 2020. Foram notificados 889 casos de hepatite B na população de estudo. A maioria dos participantes encontravam-se na faixa etária de 15 a 19 anos 738 (83%), do sexo feminino 549 (62%), cor da pele parda 637 (72%) residentes na zona urbana 490 (55%) e com ensino fundamental incompleto 279 (31%). A provável fonte de infecção foi por via sexual 450 (51%). A forma clínica mais comum foi a Hepatite Crônica 496 (56%). A maioria dos contaminados com Hepatite B foram indivíduos não vacinados 298 (34%). A luz da bioética os resultados demostram que a prática da vacinação pode contemplar os princípios bioéticos, já que o grau de autonomia depende de um tipo de intervenção planejada e quanto maior a relação entre benefício e ônus, tendo em conta os princípios de beneficência e não maleficência, menos decisiva é essa autonomia.

El estudio investiga los aspectos epidemiológicos de la hepatitis B en niños y adolescentes, discutiendo los resultados encontrados a la luz de los principios bioéticos. Se trata de un estudio transversal, retrospectivo, basado en una serie temporal de casos, cuyos datos de notificación fueron extraídos del Sistema de Información de Enfermedades de Declaración Obligatoria (SINAN) y datos de vacunación del Sistema de Información del Programa Nacional de Inmunizaciones SIPNI, desde 2011 hasta 2020. Se informaron 889 casos de hepatitis B en la población de estudio. La mayoría de los participantes tenían entre 15 y 19 años 738 (83 %), sexo femenino 549 (62 %), color de piel morena 637 (72 %), residentes en zona urbana 490 (55 ) y con educación primaria incompleta 279 (31 %). La fuente probable de infección fue a través de relaciones sexuales 450 (51%). La forma clínica más frecuente fue la Hepatitis Crónica 496 (56%). La mayoría de los infectados con Hepatitis B eran individuos no vacunados 298 (34%). A la luz de la bioética, los resultados muestran que la práctica de la vacunación puede contemplar principios bioéticos, ya que el grado de autonomía depende de un tipo de intervención planificada y mayor la relación entre beneficio y carga, teniendo en cuenta los principios de beneficencia y no maleficencia, menos decisiva es esta autonomía.

The study investigates the epidemiological aspects of hepatitis B in children and adolescents, discussing the results found in the light of bioethical principles. This is a cross-sectional, retrospective study, based on a time series of cases, whose notification data were extracted from the Notifiable Diseases Information System (SINAN) and vaccination data from the National Immunization Program Information System SIPNI, from 2011 to 2020. 889 cases of hepatitis B were reported in the study population. Most participants were aged between 15 and 19 years old 738 (83%), female 549 (62%), brown skin color 637 (72%) living in the urban area 490 (55%) and with incomplete elementary education 279 (31%). The probable source of infection was through sexual intercourse 450 (51%). The most common clinical form was Chronic Hepatitis 496 (56%). Most of those infected with Hepatitis B were unvaccinated individuals 298 (34%). In the light of bioethics, the results show that the practice of vaccination can contemplate bioethical principles, since the degree of autonomy depends on a type of planned intervention and the greater the relationship between benefit and burden, taking into account the principles of beneficence and not maleficence, the less decisive is this autonomy.

Clinical, radiological and laboratory characteristics of central nervous system histoplasmosis: A systematic review of a severe disease.

BACKGROUND: The knowledge of central nervous system (CNS) histoplasmosis is limited to case reports and series. OBJECTIVES: Our objective was to synthesise clinical, radiological and laboratory characteristics of CNS histoplasmosis to improve our understanding of this rare disease. METHODS: We performed a systematic review using Pubmed/MEDLINE, Embase and LILACS databases accessed on March 2023 without publication date restrictions. Inclusion criteria comprised: (1) histopathological, microbiological, antigen or serological evidence of histoplasmosis; (2) CNS involvement based on cerebrospinal fluid pleocytosis or neuroimaging abnormalities. We classified the certainty of the diagnosis in proven (CNS microbiological and histopathological confirmation), probable (CNS serological and antigen confirmation) or possible (non-CNS evidence of histoplasmosis). Metaproportion was used to provide a summary measure with 95% confidence intervals for the clinical, radiological and laboratory characteristics. Chi-squared test was used to compare mortality between pairs of antifungal drugs. RESULTS: We included 108 studies with 298 patients. The median age was 31 years, predominantly male, and only 23% were immunocompromised (134/276, 95%CI: 3-71), mainly due to HIV infection. The most common CNS symptom was headache (130/236, 55%, 95%CI: 49-61), with a duration predominantly of weeks or months. Radiological presentation included histoplasmoma (79/185, 34%, 95%CI: 14-61), meningitis (29/185, 14%, 95%CI: 7-25), hydrocephalus (41/185, 37%, 95%CI: 7-83) and vasculitis (18/185, 6%, 95%CI: 1-22). There were 124 proven cases, 112 probable cases and 40 possible cases. The majority of patients presented positive results in CNS pathology (90%), serology (CSF: 72%; serum: 70%) or CSF antigen (74%). Mortality was high (28%, 56/198), but lower in patients who used liposomal amphotericin B and itraconazole. Relapse occurred in 13% (23/179), particularly in HIV patients, but less frequently in patients who used itraconazole. CONCLUSION: Central nervous system histoplasmosis usually presents subacute-to-chronic symptoms in young adults. Neuroimaging patterns included not only focal lesions but also hydrocephalus, meningitis and vasculitis. Positive results were commonly found in CSF antigen and serology. Mortality was high, and treatment with liposomal amphotericin B followed by itraconazole may decrease mortality.

Challenges, Characteristics, and Outcomes of Chronic Pulmonary Aspergillosis: A 11-Year Experience in A Middle-Income Country.

OBJECTIVES: Chronic pulmonary aspergillosis (CPA) is a research priority in fungal diseases with a need for new studies to reduce misdiagnosis with more common diseases, discuss improvement in diagnostic methods and better characterize gaps in antifungal and surgical treatments to improve clinical outcomes. METHODS: In this retrospective study, we reviewed medical records of patients diagnosed with CPA from January 2010 to June 2021 at University of São Paulo, São Paulo, Brazil. We evaluated clinical characteristics, radiological findings, serology, treatment, and outcomes. RESULTS: The study included 91 participants, with 43 (47.3%) patients who underwent surgery and 69 (75.8%) received antifungal therapy. We found a predominance of middle-aged adults (median 51 years), males (n = 58, 64%) with lower BMI (median 21.3 kg/m2). The most common underlying lung disease was pulmonary tuberculosis (n = 70, 76.9%). The commonest symptoms were cough (n = 67, 74%), haemoptysis, and dyspnea (n = 63, 70%). The most common chest computerized tomography abnormalities were cavity (n = 86, 94.5%), with a predominance of mycetomas (n = 78, 91%). The serology was positive in 81% (61/75). The one-year mortality was low (3.3%). Clinical improvement and stability occurred in 89% of participants for constitucional symptoms and 86% for pulmonary symptoms. While serological improvement and stability occurred in 71%. Radiological improvement and stability occurred in 75%. CONCLUSION: We observed a good outcome after 1-year follow-up, in which the majority had improvement or stability of pulmonary and constitutional symptoms, decrease in CIE titers and low mortality.

Systematic review of neuroparacoccidioidomycosis: The contribution of neuroimaging.

BACKGROUND: Advanced neuroimaging demonstrated that neurological involvement occurs in up to 30% of paracoccidioidomycosis (PCM) cases. Current knowledge of neuroparacoccidioidomycosis (NPCM) is based on a 2009 systematic review. However, in the last decade, several new cases have been published, with modern neuroimaging techniques. OBJECTIVES: We believe a new systematic review is needed to summarise these advances. METHODS: We searched PubMed/MEDLINE, Embase and LILACS for studies from January 2010 to May 2022. Case series and case reports of NPCM were included. We performed a metaproportion to estimate a summary proportion with 95% confidence intervals (CI). RESULTS: Thirty-four studies including 104 patients were evaluated. We combined our data with the results from the previous review that included 257 cases, totalling 361 patients. We found no new important demographic, clinical or laboratory characteristics. On magnetic resonance imaging (MRI), we found that 72% (95%CI: 38-91) had hyperintensity on T1-weighted image; 84% (95%CI: 71%-92%) had hypointensity on T2-weighted image; 80% (95%CI: 66-89) had contrast enhancement with the classical ring-enhancing pattern. All 8 patients undergoing spectroscopy presented lipid peaks. We found a 16% mortality, lower than in the previous review (44%). CONCLUSION: NPCM presents a characteristic pattern on MRI that may help to differentiate it from other causes of single or multiple brain lesions. Albeit there is a frequent pattern, it is not specific, as other granulomatous diseases may show similar findings. Advances in neuroimaging with early diagnosis and appropriate management of the disease may have contributed to reducing its mortality.

Sensitivity of Antigen, Serology, and Microbiology Assays for Diagnosis of the Subtypes of Chronic Pulmonary Aspergillosis at a Teaching Hospital in São Paulo, Brazil.

Chronic pulmonary aspergillosis (CPA) is divided into five subtypes. The diagnosis of CPA is complicated due to poor sensitivity of the laboratory tests. Diagnostic performance of different antigen, serological, and microbiological methods in subtypes of CPA is unknown. The purpose of this study was to evaluate the diagnostic performance in different subtypes of CPA. A total of 91 participants with CPA were included, and the study was performed at Hospital das Clínicas of University of São Paulo. Bronchoalveolar lavage galactomannan (73%, 11/15), serology by immunodiffusion test (81%, 61/75), and histology (78%, 39/50) had the best sensitivity. The counterimmunoelectrophoresis (CIE) titers had a significant statistical difference between the CPA subtypes (P < 0.001), in which the forms chronic fibrosing pulmonary aspergillosis (CFPA) and subacute invasive aspergillosis (SAIA) had higher titers: 1/64 (interquartile range [IQR]: 1/32-1/256) and 1/64 (1/32-1/128). C-reactive protein generally presented lower values (median 15 mg/L, IQR: 6-33), with higher values in SAIA and lower values for Aspergillus nodule. Overall, we found a low diagnostic sensitivity of current tests. Regarding the CPA subtypes, we did not find great differences in the performance of the tests, but it is observed that the inflammatory markers and CIE titers tend to be higher in forms of the more extensive lung parenchyma involvement, such as SAIA and CFPA.

Characterization of Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant Shedding and Predictors of Viral Culture Positivity on Vaccinated Healthcare Workers With Mild Coronavirus Disease 2019.

In this prospective cohort of 30 vaccinated healthcare workers with mild Omicron variant infection, we evaluated viral culture, rapid antigen test (RAT), and real-time reverse-transcription polymerase chain reaction (RT-PCR) of respiratory samples at days 5, 7, 10, and 14. Viral culture was positive in 46% (11/24) and 20% (6/30) of samples at days 5 and 7, respectively. RAT and RT-PCR (Ct ≤35) showed 100% negative predictive value (NPV), with positive predictive values (PPVs) of 32% and 17%, respectively, for predicting viral culture positivity. A lower RT-PCR threshold (Ct ≤24) improved culture prediction (PPV = 39%; NPV = 100%). Vaccinated persons with mild Omicron infection are potentially transmissible up to day 7. RAT and RT-PCR might be useful tools for shortening the isolation period.

Orthopedic infections due to Trichosporon species: Case series and literature review.

Reports of orthopedic fungal infections caused by Trichosporon species are extremely scarce, thus we aimed to describe a case series and review the cases published in the literature. Patients were retrospectively included if a previous culture of bone, joint, or soft tissues had resulted positive for Trichosporon species along with a clinical diagnosis of an orthopedic infection. Eight patients were included with diverse orthopedic conditions, most of them cases of osteomyelitis. The main isolated species was Trichosporon asahii. All patients were treated with antifungals, mainly voriconazole, and surgical management, resulting in high rates of clinical improvement and low associated mortality.

Reports of orthopedic infections caused by Trichosporon species are scarce. We described a case series of orthopedic infections caused by Trichosporon species and reviewed the previous published cases in the literature. We observed a high rate of clinical improvement and a low associated mortality.

Establishment of suitable reference genes for studying relative gene expression during the transition from trophozoites to cyst-like stages and first evidences of stress-induced expression of meiotic genes in Trichomonas vaginalis.

Trichomonas vaginalis is a parasite of the human urogenital tract and the causative agent of trichomoniasis, a sexually transmitted disease of worldwide importance. This parasite is usually found as a motile flagellated trophozoite. However, when subjected to stressful microenvironmental conditions, T. vaginalis trophozoites can differentiate into peculiar cyst-like stages, which exhibit notable physiological resistance to unfavourable conditions. Although well documented in morphological and proteomic terms, patterns of gene expression changes involved in the cellular differentiation into cyst-like stages are mostly unknown. The real-time reverse transcription polymerase chain reaction (RT-qPCR) is recognized as a sensitive and accurate method for quantification of gene expression, providing fluorescence-based data that are proportional to the amount of a target RNA. However, the reliability of relative expression studies depends on the validation of suitable reference genes, which RNAs exhibit a minimum of variation between tested conditions. Here, we attempt to determine suitable reference genes to be used as controls of invariant expression during cold-induced in vitro differentiation of T. vaginalis trophozoites into cyst-like forms. Furthermore, we reveal that the mRNA from the meiotic recombinase Dmc1 is upregulated during this process, indicating that cryptic sexual events may take place in cyst-like stages of T. vaginalis.