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.

The Predictive Value of Sepsis Scores for In-Hospital Mortality in Patients with Left-Sided Infective Endocarditis.

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.

Histoplasmosis in a fingolimod-treated patient: case report and scoping review.

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.

Cutaneous Naganishia albida (Cryptococcus albidus) infection: a case report and literature review.

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.

Challenges and insights in immunization in patients with demyelinating diseases: a bench-to-bedside and evidence-based review.

BACKGROUND: Infections are among the main causes of death in patients with demyelinating diseases of the central nervous system (CNSDD). Vaccines are effective methods in reducing hospitalization and death from infectious diseases, but they are challenging in patients with CNSDD because of autoimmunity and immunosuppression. OBJECTIVES: To summarize the pathophysiological rationale and main evidence for vaccine recommendations in patients with CNSDD. METHODS: Specialists with different backgrounds on the subject: a neurologist specialized in demyelinating diseases, an infectious diseases specialist and an immunologist, presented a critical narrative review of vaccination literature in patients with CNSDD, highlighting which vaccines should or should not be administered and the best time for it. RESULTS: Patients with DDSNC are at increased risk of vaccine-preventable viral and bacterial infections. Vaccines can prevent herpes zoster, hepatitis B reactivation, HPV-associated warts and tumors, viral and bacterial pneumonia, and meningitis. Live attenuated virus vaccines should not be used when the patient is on immunosuppression. Vaccines should be avoided during relapses. The greatest vaccine efficacy is given before treatment or at the end of medication. CONCLUSION: Patients with DDSNC need differentiated immunization in relation to additional vaccines, contraindicated vaccines and timing of vaccination.

Clinical and immunological features of laryngeal cryptococcosis.

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.

Cutaneous Naganishia albida (Cryptococcus albidus) infection: a case report and literature review

ABSTRACT 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.

Challenges and insights in immunization in patients with demyelinating diseases: a bench-to-bedside and evidence-based review / Desafios e insights na imunização de pacientes com doenças desmielinizantes: uma revisão da bancada à beira leito e baseada em evidências

ABSTRACT Background: Infections are among the main causes of death in patients with demyelinating diseases of the central nervous system (CNSDD). Vaccines are effective methods in reducing hospitalization and death from infectious diseases, but they are challenging in patients with CNSDD because of autoimmunity and immunosuppression. Objectives: To summarize the pathophysiological rationale and main evidence for vaccine recommendations in patients with CNSDD. Methods: Specialists with different backgrounds on the subject: a neurologist specialized in demyelinating diseases, an infectious diseases specialist and an immunologist, presented a critical narrative review of vaccination literature in patients with CNSDD, highlighting which vaccines should or should not be administered and the best time for it. Results: Patients with DDSNC are at increased risk of vaccine-preventable viral and bacterial infections. Vaccines can prevent herpes zoster, hepatitis B reactivation, HPV-associated warts and tumors, viral and bacterial pneumonia, and meningitis. Live attenuated virus vaccines should not be used when the patient is on immunosuppression. Vaccines should be avoided during relapses. The greatest vaccine efficacy is given before treatment or at the end of medication. Conclusion: Patients with DDSNC need differentiated immunization in relation to additional vaccines, contraindicated vaccines and timing of vaccination.

RESUMO Antecedentes: Infecções estão entre as principais causas de morte de pacientes com doenças desmielinizantes do sistema nervoso central (DDSNC). Vacinas são métodos eficazes para reduzir internação e morte por doenças infecciosas, porém são desafiadoras em pacientes com DDSNC tanto pela autoimunidade quanto pela imunossupressão. Objetivos: Resumir o racional fisiopatológico e as principais evidências para as recomendações de vacinas em pacientes com DDSNC. Métodos: Especialistas com diferentes formações no tema: um neurologista especialista em doenças desmielinizantes, um infectologista e um imunologista, apresentam uma revisão crítica narrativa da Literatura de vacinação em pacientes com DDSNC, com destaque a quais vacinas devem ou não ser administradas e o melhor momento para isso. Resultados: Pacientes com DDSNC têm risco aumentado para infecções imunopreveníveis virais e bacterianas. Vacinas podem prevenir herpes zooster, reativação de hepatite B, verrugas e tumores associados ao HPV, pneumonias virais e bacterianas, além de meningites. Vacinas de vírus vivos atenuados não devem ser usadas quando o paciente está em uso de imunossupressão. Vacinas devem ser evitadas durante surtos. A maior eficácia vacinal é dada antes do tratamento ou ao final de doses de medicações. Conclusão: Os pacientes com DDSNC necessitam de imunização diferenciada em relação a vacinas adicionais, vacinas contraindicadas e melhor momento de vacinação.

Sarcoma de Kaposi associado à SIDA: relato de caso / Kaposis's sarcoma associated with AIDS: case report

Sarcoma de Kaposi (SK) é uma neoplasia angioproliferativa multifocal de etiologia viral e patogênese multifatorial, com a presença de múltiplos nódulos hiperpigmentados e elevados, podendo acometer pele e tecido subcutâneo. Relatamos paciente infectado pelo Vírus da Imunodeficiência Humana (HIV) há 10 anos, de transmissão ignorada, com lesões em membros inferiores (MMII) de cor violácea, nodulares, não pruriginosas, indolores; diagnosticadas como SK por estudo anatomopatológico e imunohistoquímico. Realizado screening para doença disseminada com endoscopia digestiva alta (EDA), radiografias de tórax e ósseas nos membros acometidos, ultrassonografia (USG) de abdome total e a videolaringoscopia, que não demostraram lesão inicial. Paciente durante a internação teve avaliação dos Serviços de Proctologia, Urologia e Otorrinolaringologia. A terapêutica empregada com base na introdução da terapia antirretroviral (TARV) teve sucesso na regressão das lesões em MMII, sem necessidade de quimioterapia ou radioterapia.

Kaposi's Sarcoma (KS) is a multifocal angioproliferative neoplasm of viral etiology and multifactorial pathogenesis, with the presence of multiple hyperpigmented and elevated nodules, which can affect skin and subcutaneous tissue. We reported a patient who was infected by the Human Immunodeficiency Virus (HIV) 10 years ago and had unknown the way of transmission, with lesions in the lower limbs (LMW) of violet color, nodular, not pruritic, painless; diagnosed as Kaposi's sarcoma by anatomopathological and immunohistochemical study. Screening for disseminated disease with upper digestive endoscopy (UDE), chest and bony radiographs on affected limbs, total abdomen ultrasonography (USG) and videolaryngoscopy, which did not show an initial lesion. Patient had been evaluated by Proctology, Urology and Otorhinolaryngology medical specialties. The treatment was based on the introduction of antiretroviral therapy which allowed in the regression of lesions and effectiveness without the need for chemotherapy or radiotherapy.

Glicogenoses: uma revisão geral / Glycogenoses: an overeview

Compreender o metabolismo dos diferentes tipos de glicogênio no organismo humano torna-se de suma importância, pois além da sua relevância no fornecimento energético e no controle da glicemia, o glicogênio pode estar relacionado com diversos tipos de doenças que comprometem a saúde do ser humano, especialmente pela deficiência em enzimas de vias anabólicas e catabólicas. Em um contexto de avanços no desenvolvimento de pesquisas relacionadas às áreas da saúde, uma série de estudos busca entender fisiologicamente os caminhos do glicogênio em situações de exercício, repouso, jejum, dentre outras, além de analisar os mais variados transtornos decorrentes da deficiência no metabolismo desse polissacarídeo. Um exemplo são as glicogenoses, doenças hereditárias, em sua maioria de caráter recessivo, relacionadas com o armazenamento de glicogênio. Dentre alguns dos treze tipos de glicogenoses podemos citar a glicogenose tipo 0, uma doença rara que se desenvolve na infância e implica na produção defeituosa da enzima glicogênio sintase; e a glicogenose tipo I, também conhecida como Doença de Von Gierke, que se caracteriza pela deficiência no complexo enzimático glicose-6-fosfatase, responsável pela catalisação da hidrólise de glicose-6-fosfato na metabolização do glicogênio. Apesar de todas essas doenças serem caracterizadas por glicogenoses, elas possuem diferenças quanto ao órgão afetado, à gravidade de suas manifestações, o perfil etário que cada uma atinge e no efeito enzimático. Por isso, a necessidade de estudos que correlacionam as principais causas e sintomas, e visam proporcionar uma visão global dessas desordens de hereditariedade.

The comprehension of the metabolism of different types of glycogen in the human organism becomes extremely important since, other than its relevance in providing energy and controlling glycemia, glycogen can be related to many types of diseases that compromise the human health, especially when it comes to the deficiency in enzyme anabolic and catabolic pathways. In the context of advances in the development of researches related of health area, many studies inquire a physiological understanding of the glycogen pathways exercising, resting, fasting and other conditions, as well as analyzing the most varied disorders arising from hereditary deficiencies in the carbohydrate metabolism, in polysaccharide specially. The glycogenoses are hereditary disorders, which present mainly recessive feature, related with the glycogen storage. Among the thirteen types of glycogenoses, type 0 is a rare disease that develops in early stages of life and implies in the production of defective glycogen synthase enzyme; and type I is characterized by the deficiency of the glucose-6-phosphatase enzyme complex, responsible for catalyzing the hydrolysis of glucose-6- phosphate in glycogen metabolism. Although all these diseases are characterized as being glycogenoses, they possess differences as to the organ affected, the gravity of their manifestations, the age it begins to manifest, and in which way it affects enzymatic properties. Therefore, there is a necessity of studies that correlates the main causes and symptoms, and aim to provide a global vision of these hereditary disorders.