Matrix metalloproteinases are associated with severity of disease among COVID-19 patients: A possible pharmacological target.

COVID-19 is a devastating disease and imbalanced matrix metalloproteinase (MMP) activity may contribute to its pathophysiology. This exploratory study examined whether increased circulating concentrations of MMP-2 and MMP-9, and their endogenous inhibitors, the tissue inhibitors of MMP (TIMP)-1, TIMP-2, TIMP-3 and TIMP-4 are persistently found in patients 2 weeks after their recovery from severe or critical COVID-19 as compared with those in healthy controls. Subjects who had severe (n = 26) or critical (n = 25) PCR-confirmed COVID-19 and healthy controls (n = 21) had blood samples drawn 2 weeks after recovery and serum MMP-2, MMP-9, TIMP-1, TIMP-2, TIMP-3 and TIMP-4 were determined using two Human Luminex® Discovery Assays. Circulating MMP activity was also determined by gel zymography. Patients who had severe or critical COVID-19 had increased circulating MMP-9 and MMP-2 concentrations, with increased MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios indicating increased MMP activity, confirmed by gel zymography (all p < 0.05). Higher circulating MMP-9 (but not MMP-2) concentrations were found in critical versus severe COVID-19 (p < 0.05). We found increased circulating MMP-9 and MMP-2 concentrations and activity many days after recovery from the acute disease, with MMP-9 levels associated with disease severity. These biochemical alterations suggest that MMP-2 and MMP-9 may be important pharmacological targets in COVID-19.

Chylothorax and chylous ascites due to juvenile paracoccidioidomycosis: a case report.

Paracoccidioidomycosis (PCM) is a systemic fungal infection caused by Paracoccidioides species. Chylothorax is a rare complication of PCM. A 16-year-old adolescent presented daily fever, lymphadenomegaly, sweating, weight loss, ventilatory-dependent pain, and dysphagia, which confirmed PCM. During treatment, the patient developed chylothorax and chylous ascites. Chronic inflammatory and fibrotic lymphadenopathy may obstruct lymphatic vessels, resulting in the extravasation of lymph into the abdomen or pleural cavities. Chylothorax is one of several complications of PCM and can lead to respiratory insufficiency, even in patients undergoing antifungal therapy.

A contemporary investigation of burden and natural history of aspergillosis in people living with HIV/AIDS.

BACKGROUND: Untreated HIV infection can lead to profound immunosuppression and increase susceptibility of people living with HIV/AIDS (PLHA) to aspergillosis. OBJECTIVES: Reporting the burden and natural history of aspergillosis documented in PLHA admitted in five medical centres in Brazil. PATIENTS AND METHODS: Clinical, epidemiological and laboratory data were collected in all sequential cases of proven or probable aspergillosis documented in PLHA hospitalised in five medical centres between 2012 and 2020. RESULTS: We enrolled 25 patients ageing between 23 and 58 years (mean = 39) including 11 patients with invasive aspergillosis (IA) and 14 with chronic pulmonary aspergillosis (CPA). The prevalence rate of aspergillosis was 0.1% of 19.616 PLHA. Overall, 72.7% of patients with IA exhibited CD4 < 100 cells/mL and 42.8% of patients with CPA exhibited CD4 count >200 cells/mL. Most patients had a history of tuberculosis, especially those with CPA (85.7%). IA was documented after a mean of 16.5 days of hospitalisation, mainly in critically ill patients exposed to corticosteroids and broad-spectrum antibiotics. In the CPA group, a positive culture (71.4%) and radiological alterations were the most frequent findings supporting their diagnosis. Episodes of IA were mostly documented by tissue biopsies. Crude mortality rates were 72.7% and 42.8% in patients with IA and CPA, respectively. CONCLUSIONS: Despite being considered an unusual complication in PLHA (0.1%), IA should be considered in patients with profound immunosuppression and pneumonia refractory to conventional therapy. CPA should be investigated in PLHA with chronic deterioration of pulmonary function and previous diagnosis of tuberculosis.

Chylothorax and chylous ascites due to juvenile paracoccidioidomycosis: a case report

ABSTRACT Paracoccidioidomycosis (PCM) is a systemic fungal infection caused by Paracoccidioides species. Chylothorax is a rare complication of PCM. A 16-year-old adolescent presented daily fever, lymphadenomegaly, sweating, weight loss, ventilatory-dependent pain, and dysphagia, which confirmed PCM. During treatment, the patient developed chylothorax and chylous ascites. Chronic inflammatory and fibrotic lymphadenopathy may obstruct lymphatic vessels, resulting in the extravasation of lymph into the abdomen or pleural cavities. Chylothorax is one of several complications of PCM and can lead to respiratory insufficiency, even in patients undergoing antifungal therapy.

Human pulmonary dirofilariasis with secondary myocarditis.

Dirofilariasis is a little-known zoonosis, with dogs and cats as definitive hosts. It is caused by nematodes and transmitted by mosquito bites. We report the case of a 67-year-old man with a consumptive syndrome with two subpleural pulmonary opacities. A transthoracic lung biopsy revealed a Dirofilaria worm. Myocardial nuclear magnetic resonance (NMR) demonstrated dilated cardiomyopathy after myocarditis related to dirofilariasis. Human infection is rare and occurs accidentally. The most common radiological alteration is a mainly subpleural coin lesion. Dirofilariasis is a neglected emergent disease and knowledge about it is important for differential diagnoses from neoplastic pulmonary nodules.

Human pulmonary dirofilariasis with secondary myocarditis

Abstract Dirofilariasis is a little-known zoonosis, with dogs and cats as definitive hosts. It is caused by nematodes and transmitted by mosquito bites. We report the case of a 67-year-old man with a consumptive syndrome with two subpleural pulmonary opacities. A transthoracic lung biopsy revealed a Dirofilaria worm. Myocardial nuclear magnetic resonance (NMR) demonstrated dilated cardiomyopathy after myocarditis related to dirofilariasis. Human infection is rare and occurs accidentally. The most common radiological alteration is a mainly subpleural coin lesion. Dirofilariasis is a neglected emergent disease and knowledge about it is important for differential diagnoses from neoplastic pulmonary nodules.

HIV-negative pulmonary disease caused by nontuberculous mycobacteria in Southern Brazil: clinical and microbiological characterization.

BACKGROUND: Nontuberculous mycobacteria (NTM) have been identified with increasing frequency in the clinical practice. The aim of this study was to characterize NTM isolates in respiratory specimens from patients with pulmonary disease and to correlate this with clinical/radiological findings, decision to start treatment and outcomes. METHODS: A cross-sectional descriptive study was performed and included all patients who had at least one NTM isolated in respiratory specimens between 2011 and 2014. NTM culture was performed in liquid medium followed by immunochromatographic identification (anti-MPT64). Species identification was based on nucleic acid amplification followed by restriction analysis of a 441 bp fragment of the hsp65 gene (hsp65 PRA) and patients' records were reviewed. RESULTS: From 14,394 cultures in 4 years, 590 (4.10%) grew NTM and 305 (51.7%) isolates were characterized till species level, representing 290 patients including those with and without human immunodeficiency virus (HIV) infection. Two hundred and eleven non-HIV patients had NTM isolated from respiratory specimens, 49 (23.2%) had criteria for active disease based on the American Thoracic Society (ATS) 2007. The majority was men above 51 years old and M. intracellulare was detected in 59.2% (29/49), followed by M. avium 14.3% (7/49), and M. abscessus 12.2% (6/49). CONCLUSIONS: Old age, nodular and nodular/bronchiectasis radiographic pattern, previous tuberculosis (TB) treatment and M. intracellulare were more frequent among NTM-disease patients compared to those only colonized. Positive culture and maintenance of clinical symptoms (poor outcome) was a rule when M. abscessus caused NTM-disease. Positive acid-fast smear in respiratory specimen is a strong predictor of disease.

A DECADE TREND OF MULTIDRUG RESISTANT TUBERCULOSIS IN SÃO PAULO STATE, BRAZIL.

The aim of this retrospective study was to review all the notified cases of multidrug-resistant tuberculosis (MDR-TB) in São Paulo State (Brazil), as well as to describe and discuss the clinical, microbiological and radiologic aspects in a single reference center, within the same state, from 2000 to 2012. There were 1,097 notifications of MDR-TB in São Paulo State over this period, 70% affecting men aged on average 38 years (10-77). There was a significant fall in the MDR-TB mortality rate from 30% to 8% (2000-2003 versus 2009-2012). The same trend was observed in the cases studied at the reference center. The number of notified cases increased and death rate reduced from 37.5% (2000-2005) to 3.4% (2006-2012). Among the 48 drug-resistant TB cases, 17 non-tuberculous Mycobacteria were isolated in the sputum culture of nine patients, without any clinical significance. TB and fungus co-infection was diagnosed in 15% (7/48) of these cases: three with confirmed chronic pulmonary aspergillosis and four with positive serological markers for paracoccidioidomycosis. Overall, the reports show that MDR-TB diagnosis and cure rates have increased, while the mortality rate has decreased significantly in São Paulo State including in the studied reference center.