Predictive factors for dose reduction and discontinuation of nintedanib in fibrotic interstitial lung diseases: Real life data.

Nintedanib, an intracellular inhibitor targeting multiple tyrosine kinases, has emerged as a standard treatment for various fibrotic lung diseases. Despite its efficacy, side effects such as nausea, diarrhea, and hepatotoxicity often lead to dose reduction or discontinuation. In this retrospective analysis at an university hospital's interstitial lung disease clinic, we aimed to identify baseline characteristics associated with dose adjustment or treatment discontinuation. Of the 58 patients included, 41.4% maintained the full nintedanib dose, while 31.0% required dosage reduction, and 27.6% discontinued treatment due to adverse events, predominantly gastrointestinal and hepatotoxic effects. Multivariate analysis revealed body surface area (BSA) as an independent and significant baseline risk factor (adjusted Odds Ratio [aOR] 0.22), suggesting a 78% decreased chance of requiring dose modification for every decimal point increase in BSA. A BSA cutoff of ≤1.73 m [2] exhibited a sensitivity of 73% and specificity of 91.7%, with significant impact on one-year survival under full-dose treatment (p < 0.001). Lower BSA was associated with early onset adverse effects, particularly gastrointestinal, supporting the need for regular clinical monitoring. The study emphasizes the importance of recognizing baseline factors to ensure the safety and tolerability of nintedanib, thereby preventing the progression of pulmonary fibrosis. These findings contribute to the evolving understanding of nintedanib management in fibrotic interstitial lung diseases, guiding clinicians in personalized treatment approaches.

Yellow Fever Virus Maintained by Sabethes Mosquitoes during the Dry Season in Cerrado, a Semiarid Region of Brazil, in 2021.

In recent decades, waves of yellow fever virus (YFV) from the Amazon Rainforest have spread and caused outbreaks in other regions of Brazil, including the Cerrado, a savannah-like biome through which YFV usually moves before arriving at the Atlantic Forest. To identify the vectors involved in the maintenance of the virus in semiarid environments, an entomological survey was conducted after confirmation of yellow fever (YF) epizootics at the peak of the dry season in the Cerrado areas of the state of Minas Gerais. In total, 917 mosquitoes from 13 taxa were collected and tested for the presence of YFV. Interestingly, mosquitoes of the Sabethes genus represented 95% of the diurnal captured specimens, displaying a peak of biting activity never previously recorded, between 4:30 and 5:30 p.m. Molecular analysis identified three YFV-positive pools, two from Sabethes chloropterus-from which near-complete genomes were generated-and one from Sa. albiprivus, whose low viral load prevented sequencing. Sa. chloropterus was considered the primary vector due to the high number of copies of YFV RNA and the high relative abundance detected. Its bionomic characteristics allow its survival in dry places and dry time periods. For the first time in Brazil, Sa. albiprivus was found to be naturally infected with YFV and may have played a role as a secondary vector. Despite its high relative abundance, fewer copies of viral RNA were found, as well as a lower Minimum Infection Rate (MIR). Genomic and phylogeographic analysis showed that the virus clustered in the sub-lineage YFVPA-MG, which circulated in Pará in 2017 and then spread into other regions of the country. The results reported here contribute to the understanding of the epidemiology and mechanisms of YFV dispersion and maintenance, especially in adverse weather conditions. The intense viral circulation, even outside the seasonal period, increases the importance of surveillance and YFV vaccination to protect human populations in affected areas.

Gut microbiota profile of COVID-19 patients: Prognosis and risk stratification (MicroCOVID-19 study).

Background: Gut microbiota is intrinsically associated with the immune system and can promote or suppress infectious diseases, especially viral infections. This study aims to characterize and compare the microbiota profile of infected patients with SARS-CoV-2 (milder or severe symptoms), non-infected people, and recovered patients. This is a national, transversal, observational, multicenter, and case-control study that analyzed the microbiota of COVID-19 patients with mild or severe symptoms at home, at the hospital, or in the intensive care unit, patients already recovered, and healthy volunteers cohabiting with COVID-19 patients. DNA was isolated from stool samples and sequenced in a NGS platform. A demographic questionnaire was also applied. Statistical analysis was performed in SPSS. Results: Firmicutes/Bacteroidetes ratios were found to be significantly lower in infected patients (1.61 and 2.57) compared to healthy volunteers (3.23) and recovered patients (3.89). Furthermore, the microbiota composition differed significantly between healthy volunteers, mild and severe COVID-19 patients, and recovered patients. Furthermore, Escherichia coli, Actinomyces naeslundii, and Dorea longicatena were shown to be more frequent in severe cases. The most common COVID-19 symptoms were linked to certain microbiome groups. Conclusion: We can conclude that microbiota composition is significantly affected by SARS-CoV-2 infection and may be used to predict COVID-19 clinical evolution. Therefore, it will be possible to better allocate healthcare resources and better tackle future pandemics.

Granulomatosis With Polyangiitis: Remissions in a Thiopurine Fast Metabolizer Over 20 Years.

A 35-year-old Maori man presented with lethargy, nasal congestion, scleritis, epistaxis, progressive shortness of breath, myalgia, and pleuritic pain. His CT scan showed bilateral pulmonary infiltrates and a corneal biopsy confirmed granulomatosis with polyangiitis (GPA).  Remission was achieved with cyclophosphamide-based regimen. Maintaining remission proved difficult because of treatment side effects or relapses on cyclophosphamide, methotrexate, or azathioprine maintenance regimes. Overall, he needed six courses of pulse cyclophosphamide / IV methylprednisolone therapy in his first 10 years of treatment. He was identified to be an azathioprine fast metabolizer producing little active metabolite at usual doses. The combination of low dose azathioprine / allopurinol achieved therapeutic level of 6-thioguanine nucleotides (TGNs) to achieve long-term remission. Low dose azathioprine / allopurinol at levels to control inflammatory bowel disease achieve long-term remission of GPA. He has been in remission for 10 years without side effects or relapses.

Spindle cell sarcoma: a rare cause of a spontaneous pneumothorax.

Secondary spontaneous pneumothoraces are associated with a variety of lung disorders. Malignancy is a rare cause of a pneumothorax and rarely the presenting feature. Cavitating primary tumours are less frequent causes of pneumothoraces than secondary tumours. We present the case of an asymptomatic spontaneous pneumothorax in a 71-year-old never-smoking woman. Her right apical pneumothorax was diagnosed by chance on a chest radiograph for a fall. Her final diagnosis was a primary spindle cell sarcoma of the pleura. This case demonstrates the need to explore the underlying causes of a non-resolving pneumothorax. The early diagnosis of her sarcoma allowed curative treatment.

Palliative Care in Heart Failure: Challenging Prognostication.

Heart failure (HF) is a chronic progressive disease with high morbimortality and poor quality of life (QoL). Palliative care significantly improves clinical outcomes but few patients receive it, in part due to challenging decisions about prognosis. This retrospective study, included all patients consecutively discharged from an Acute Heart Failure Unit over a period of one year, aiming to assess the accuracy of the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score in predicting mortality. Additionally, predictors of death at one and three years were explored using a multivariate regression model. The MAGGIC score was useful in predicting mortality, without significant difference between mortality observed at three-years follow-up compared with a mortality given by the score (p=0.115). Selected variables were statistically compared showing that poor functional status, high New York Heart Association (NYHA) at discharge, psychopharmacs use, and high creatininemia were associated with higher mortality (p<0.05). The multivariate regression model identified three predictors of one-year mortality: psychopharmacs baseline use (OR=4.110; p=0.014), angiotensin-converting enzyme inhibitors/angiotensin receptor blocker (ACEI/ARB) medication at discharge (OR=0.297; p=0.033), and higher admission's creatinine (OR=2.473; p=0.028). For three-year mortality outcome, two variables were strong independent predictors: psychopharmacs (OR=3.330; p=0.022) and medication with ACEI/ARB at discharge (OR=0.285; p=0.018). Models' adjustment was assessed through the receiver operating characteristic (ROC) curve. The best model was the one-year mortality (area under the curve, AUC 81%), corresponding to a good discrimination power. Despite prognostication, when setting goals of care an individualised patient-centred approach is imperative, based on the patient's objectives and needs. Risk factors related to poorer outcomes should be considered, in particular, higher NYHA at discharge which also represents symptom burden. Hospitalisation is an opportunity to optimize global care for heart failure patients including palliative care.

Tuberculosis and Sarcoidosis Overlap: A Clinical Challenge From Diagnosis to Treatment.

Tuberculosis (TB) and sarcoidosis have clinical, immunologic, and radiologic similarities and the differential diagnosis is often a challenge. Some cases are described in which patients have both diseases concomitantly. There is a hypothesis that posits TB and sarcoidosis as being along the spectrum of the same disease. This has important implications for treatment decisions, since immunosuppression, which is a treatment for sarcoidosis, is undesirable in TB patients. We are going to describe a clinical case of a TB patient who developed more severe symptoms during the course of TB treatment and, after excluding TB progression or resistance, he was diagnosed as probable sarcoidosis. He was started on immunosuppression, with great improvement, finishing the TB treatment completely asymptomatic.

Drug-Induced Liver Injury Caused by Amoxicillin/Clavulanate.

Drug-induced liver injury (DILI) has a relatively low incidence, and as it is a diagnosis of exclusion, it can become quite a challenge for the clinician. Amoxicillin/clavulanate continues to be one of the most prescribed antibiotics and only rarely causes liver injury. We report a case of DILI associated with this antibiotic to bring attention to a rare side effect of a very commonly prescribed drug. This is the case of a 71-year-old man, with no relevant past medical history, who presented to the Emergency Department due to jaundice in the previous two weeks, with no immediate identifiable cause. The patient was admitted to our Internal Medicine Ward, and after getting a detailed clinical history and excluding other common and severe causes of liver injury, the diagnosis was made that liver injury was due to amoxicillin/clavulanate intake, thus demonstrating the importance of an in-depth history.

Immune Thrombocytopenic Purpura - Different Presentations in Two COVID-19 Patients.

Immune thrombocytopenic purpura (ITP) is a rare acquired autoimmune disease, resulting from platelet destruction and impaired platelet production. It has been described as associated with either genetic or environmental risk factors, such as viral infections, and in a few cases has been reported to be associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although steroid treatment is the most widely used first-line treatment of ITP, in the early days of coronavirus disease 2019 (COVID-19) it was controversial, but it has since become approved in treatment for COVID-19. The authors report two different cases of COVID-19-associated ITP, with special emphasis on the timing of presentation, severity, and treatment decisions. Remarkably, one of the patients who suffered severe thrombocytopenia was safely treated with corticosteroids in the late phase of COVID-19 infection.

Derivation and external validation of the SHIeLD score for predicting outcome in normotensive pulmonary embolism.

BACKGROUND: Identifying patients with normotensive pulmonary embolism (PE) who may benefit from thrombolysis remains challenging. We sought to develop and validate a score to predict 30-days PE-related mortality and/or rescue thrombolysis. METHODS: We retrospectively assessed 554 patients with normotensive PE. Independent predictors of the studied endpoint were identified from variables available at admission in the emergency department and were used to create a score. The model was validated in 308 patients from a separate hospital. RESULTS: A total of 64 patients died or needed rescue thrombolysis (44 in the derivation cohort). Four independent prognostic factors were identified: Shock index ≥ 1.0 (OR 3.33; 95% CI 1.40-7.93; P = 0.006), HypoxaemIa by the PaO2/FiO2 ratio (OR 0.92 per 10 units; 95% CI 0.88-0.97; P < 0.001), Lactate (OR 1.38 per mmol/L; 95% CI 1.09-1.75; P = 0.008) and cardiovascular Dysfunction (OR 5.67; 95% CI 2.60-12.33; P < 0.001) - SHIeLD score. In the development cohort, event rates for each risk tercile were 0.0%, 2.2%, and 21.6%. In the validation cohort, corresponding rates were 0.0%, 1.9%, and 14.3%. The C-statistic was 0.90 (95% CI 0.86-0.94, P < 0.001) in the derivation cohort and 0.82 (95% CI 0.75-0.89, P < 0.001) in the validation cohort. Decision curve analysis showed that the SHIeLD score is able to accurately identify more true positive cases than the European Society of Cardiology decision criteria. CONCLUSIONS: A risk score to predict 30-days PE-related mortality and/or rescue thrombolysis in patients with normotensive PE was developed and validated. This score may assist physicians in selecting patients for closer monitoring or aggressive treatment strategy.

Chronic lymphocytic leukaemia and spontaneous rupture of spleen.

Pathological or spontaneous splenic rupture is a rare but well-recognised complication of haematological malignancies. The authors present a clinical report of a 78-year-old woman with known clinical history of chronic lymphocytic leukaemia and atrial fibrillation under anticoagulation with apixaban which has spontaneous splenic rupture. Pathological examination revealed lymph node and splenic infiltration due to chronic lymphocytic leukaemia. The diagnosis of splenic rupture must be considered in all patients with haematological malignancies who experience acute abdomen. Given the severity, it requires a correct and timely diagnosis.

A Reflection on the Use of Enoxaparin Based on Three Case Reports.

Enoxaparin is indicated for the treatment or prevention of many clinical disorders including deep vein thromboembolism, atrial fibrillation and mechanical valve thrombosis. It is one of the most commonly prescribed drugs in hospitals. However, haemorrhagic complications can occur, particularly in the elderly, patients with renal function impairment and patients with a very high or very low body weight. The authors describe the cases of three patients who had one or more risk factors for haemorrhagic complications, such as abdominal haematomas. The clinical presentation was similar in all three cases, with sudden-onset abdominal pain, an altered state of consciousness and hypotension. In all cases, investigation showed acute anaemia and large abdominal haematomas on imaging studies. A conservative approach was taken in the three patients, with suspension and reversal of anticoagulation, fluid resuscitation and red blood cell transfusion. Haemodynamic stability was achieved in two of the patients, but the third patient died. The authors consider it is important to present these case reports because of the widespread use of enoxaparin, and the need for rigorous dose adjustment for renal function variations and body weight. We hope this article raises awareness of haemorrhagic complications in high-risk groups and propose protocols are introduced for dose adjustment and monitoring the efficacy of enoxaparin. LEARNING POINTS: Clinicians should consider the possibility of enoxaparin-associated haemorrhagic complications in high-risk groups.Prompt identification and treatment of the haemorrhagic disorder can improve outcome.Correct dosing with anti-Xa in high-risk populations, such as the elderly, those with abnormal renal function and those with extremely high or low body weight, may be helpful in patients anticoagulated with enoxaparin.

Autologous platelet-rich plasma action on skin autografts in horses / Ação do plasma rico em plaquetas autólogo em autoenxertos de pele em equinos

ABSTRACT: This study evaluated the action of autologous platelet-rich plasma (PRP) on cutaneous wounds, containing skin autografts, in the gluteal region of horses. Seven healthy horses were used. Two 6 x 6cm cutaneous wounds were produced on each side of the gluteal region. Eight days after wound induction, grafts were performed with skin fragments harvested from the neck, as well as the application of PRP, prepared by double-centrifugation protocol. Wounds with autografts on the left side received PRP (group T), and those with autografts on the right side did not receive treatment (group C). Macroscopic and microscopic evaluations were performed, considering the integration of autografts and retraction of wound edges, as well as neovascularization, inflammatory infiltrate, young fibroblasts, collagenization, reepithelization and autografts integration. There was no difference between the groups (P > 0.05) in relation to most macroscopic and microscopic variables. However, neovascularization was significantly greater (p = 0.0191) in group T, on the 14th day after grafting. It is concluded that PRP favors the process of skin repair with autografts in horses, since it increases the neovascularization in the initial phase of wound healing. Furthermore, the PRP seems to positively influence the integration of the skin autografts and the retraction of the wound edges.

RESUMO: Este estudo avaliou a ação do plasma rico em plaquetas (PRP) autólogo em feridas cutâneas, contendo autoenxertos de pele em equinos. Foram utilizados sete equinos hígidos, nos quais foram produzidas duas feridas cutâneas de 6 x 6cm, em cada um dos lados da região glútea. Oito dias após a indução das feridas, foram realizados enxertos com fragmentos de pele colhidos do pescoço, assim como a aplicação do PRP, preparado através de protocolo de dupla centrifugação. As feridas com autoenxertos do lado esquerdo receberam PRP (grupo T), e as com autoenxertos do lado direito não receberam tratamento (grupo C). Foram realizadas avaliações macroscópica e microscópica, considerando as variáveis integração dos autoenxertos e retração das bordas da ferida, além de neovascularização, infiltrado inflamatório, fibroblastos jovens, colagenização, reepitelização e integração dos autoenxertos. Não houve diferença entre os grupos (p > 0,05) em relação à maioria das variáveis macroscópicas e microscópicas. Contudo, a neovascularização foi significativamente maior (P = 0,0191) no grupo T, no 14º dia após a realização da enxertia. Conclui-se que o PRP favorece o processo de reparo da pele com autoenxertos em equinos, já que aumenta a neovascularização na fase inicial da cicatrização da ferida. Ainda, o PRP parece influenciar positivamente a integração dos autoenxertos de pele e a retração das bordas da ferida.

Isolation of syringaldehyde from Mikania laevigata medicinal extract and its influence on the fatty acid profile of mice / Extrato medicinal de Mikania laevigata: influência no perfil de ácidos graxos em camundongos e isolamento de siringaldeído por CLAE semipreparativa

The Mikania genus is widely known as "guaco" and is used to treat fever, rheumatism, flu and respiratory diseases. Our previous work evidenced the synergism among M. laevigata extract components to produce desirable effects, and included the coumarin precursor, o-coumaric acid as marker. Many Mikania species are producers of ent-kaurene diterpenes which presented antiespasmodic and relaxant activities on smooth muscle. Seeking to standardize the guaco extract, which is registered in the Brazilian Pharmacopoea, this paper deals with the determination of kaurenoic acid through LC-PDA and the isolation through LC of syringaldehyde. Kaurenoic acid was not found in the extract, and syringaldehyde is one of the major compounds of pharmacopoeal extract, together with coumarin and o-coumaric acid. Samples from the lung and liver of Balb-C isogenic allergic pneumonitis bearing mice, treated with the same extract, were analyzed through GC-FID, and the fatty acid content was determined and analyzed. The results obtained by measuring the arachidonic acid (ARA) and docosahexaenoic acid (DHA) in the liver and lung of treated animals demonstrated that the fatty acid composition is distinct in both tissues, and that in the liver, only the DHA was altered as a result of the treatments. DHA is absent in the lung and in both organs, no significant difference in ARA production was observed. The aqueous extract, coumarin and o-coumaric acid stimulated DHA synthesis in the liver (p < 0.05).

O gênero Mikania é popularmente conhecido como "guaco" e é utilizado para tratar febre, reumatismo, resfriados e afecções respiratórias. Em trabalho prévio demonstramos sinergismo entre os componentes do extrato de M. laevigata para produzir os efeitos farmacológicos esperados, incluindo a cumarina e seu precursor ácido o-cumárico como marcadores. Muitas espécies de Mikania são produtoras de diterpenos ent-caurenos que apresentam atividade antispasmódica e relaxante da musculatura lisa. Buscando a padronização do extrato medicinal de guaco (preparado segundo a farmacopéia brasileira 1ª edição), este trabalho visou determinar a presença de ácido caurenóico através de CLAE-DAD e isolou siringaldeído através de CLAE semipreparativa, sendo que o primeiro não foi encontrado no extrato e o siringaldeído é um dos seus componentes majoritários. Camundongos isogênicos Balb-C portadores de pneumonite alérgica foram tratados com este extrato, e amostras de pulmão e fígado foram analisadas por CG-DIC quanto ao seu conteúdo de ácidos graxos. A quantidade de ácido araquidônico (ARA) e de ácido docosahexaenóico (DHA) encontrada demonstrou que a composição é distinta em ambos tecidos, e apenas a concentração de DHA hepático foi alterado em função do tratamento, o qual não foi encontrado no pulmão. Não foi detectada diferença significativa na produção de ARA. Tanto o extrato aquoso, quanto a cumarina e o ácido o-cumárico, estimularam a síntese de DHA no fígado (p < 0.05).

Conhecimento da doença em pacientes com insuficiência cardíaca / Disease knowledge of patients with heart failure

Uma das maiores dificuldades na adesão ao tratamento de portadoresde insuficiência cardíaca (IC) é a falta de conhecimentosobre a doença e seu tratamento. Este estudo teve como objetivoavaliar o conhecimento do paciente com IC em relação à suadoença. Estudo de natureza descritiva e exploratória realizado noambulatório de Cardiologia de um hospital terciário no interiordo Estado de São Paulo. O conhecimento foi avaliado por meiodo questionário de avaliação do conhecimento e autocuidado daIC. Fizeram parte desta amostra 32 pacientes com idade médiade 61 (± 12) anos. Os pacientes apresentaram média de acertosde 11,4% (± 7), sendo que 44% conheciam sobre a afecção, 25%souberam relatar os sintomas de IC, 31% responderam corretamentea ação do IECA e 28% da digoxina; entretanto, pequenaparcela soube informar os efeitos adversos desses medicamentos.Referente ao tratamento não farmacológico, 16% dos pacientesresponderam corretamente sobre o consumo de bebidas alcoólicas,34% sobre os alimentos que contribuem na soma de líquidosingeridos por dia e 31% entendem a importância do controlede peso. Este estudo revelou que os pacientes portadores de ICapresentaram baixa média de acertos sobre o conhecimento,tratamento e autocuidado. A ampliação do conhecimento dospacientes, com implementação de novas estratégias, constituiaspecto relevante para a mudança do seu comportamento e,consequentemente, melhora do autocuidado.

A major difficulty with treatment adherence in patients withheart failure (HF) is the lack of knowledge about the diseaseand its treatment. This study aimed to assess the knowledgeof patients with HF in relation to their disease. Study of descriptiveand exploratory nature performed in cardiology clinicof a tertiary hospital in the countryside of the state of SãoPaulo. The knowledge was assessed through a questionnaireevaluating knowledge and self-care of HF. This questionnairewas applied in a sample of 32 patients with a mean age of 61years old (± 12). Patients had mean score correct of 11.4%(± 7), 44% knew about the disease, 25% were able to reportthe symptoms of HF, 31% answered correctly the action ofACE inhibitors and 28% knew about the action of digoxin.A small part, however, could inform the adverse effects ofthese drugs. Referring to non-pharmacological treatment,16% of patients answered about the consumption of alcoholicbeverages, 34% about foods that contribute to add to theliquid ingested per day and 31% understood the importanceof weight control. This study showed that patients with HFhad low score correct on knowledge, treatment and self-care.Broadening knowledge of patients with implementation ofnew strategies is a relevant aspect to change their behaviorand therefore improve self-care.

Monitoramento e avaliação de eventos adversos: a experiência do Hospital de Clínicas de Porto Alegre / Monitoring and evaluation of adverse events: the experience at Hospital de Clínicas de Porto Alegre

A proteção dos participantes nas pesquisas que envolvem seres humanos é uma das atribuições fundamentais dos Comitês de Ética em Pesquisa (CEPs), estando regulamentada em âmbito nacional e internacional. Segundo esses documentos, cabe aos CEPs não só revisar todos os protocolos de pesquisa submetidos a ele, mas também monitorar a ocorrência dos eventos adversos (EA) encaminhados pelo pesquisador no transcorrer da pesquisa. Esse monitoramento deve ser ágil e crítico, orientando sua ação em observância à relação dano/benefício de cada estudo, com o objetivo de proteger os participantes de pesquisa. O Grupo de Pesquisa e Pós-Graduação do Hospital de Clínicas de Porto Alegre (HCPA) implantou, em 2001, o Programa de Monitoramento de Riscos e Eventos Adversos, que atualmente é desenvolvido pelo Laboratório de Pesquisa em Bioética e Ética na Ciência

Based on national and international regulations, one of the the Research Ethics Committees (REC) have the attribution to protect human beings involved in research. According to these documents, REC should not only review all the research protocols, but also monitor adverse events (AE) reported by the investigator. This monitoring activities must be agile and critical, guiding its actions by evaluation of risk/benefit associated to each study. The Grupo de Pesquisa e Pós-Graduação of the Hospital de Clínicas de Porto Alegre (HCPA) introduced, in 2001, the Program of Monitoring of Risks and Adverse Events, developed by the Laboratório de Pesquisa em Bioética e Ética na Ciência