Levels of soluble TNF receptors (sTNFR1 and sTNFR2) increase with clinical worsening of patients and are related to COVID-19 mortality.

The present study aimed to inspect the serum levels of the soluble receptors, sTNFR1 and sTNFR2, in patients with COVID-19. The large production of inflammatory cytokines is an essential process in the pathogenesis of COVID-19. TNF is a multifaceted proinflammatory cytokine which has soluble and membrane receptors. Thus, knowing the role of these receptors will help better understand this disease's immunopathogenesis. We included 131 patients confirmed for SARS-CoV-2, separated into three groups: ward patients without O2 support, group A (n = 14); ward patients with O2 support, group B (n = 85), and patients in an intensive care unit (ICU), group C (n = 32), making up the receptors dosed by flow cytometry. The results showed that sTNFR1 and sTNFR2 are associated with disease severity, being higher in group C when compared to group A. As for the levels of receptors and their relationship with the degree of lung involvement, we found higher values of sTNFR1 in patients in group 1 (pulmonary involvement < 25%), suggesting that inflammatory processes related to TNF are not necessarily associated with the primary site of infection. When we analysed the patients who passed away compared to those who recovered, both receptors significantly increased the mortality numbers. These findings suggest a relevant influence of soluble receptors in the inflammatory processes involved in the pathogenesis of COVID-19. Wherefore, we suggest using these receptors as biomarkers of severity and mortality of the disease.

Fungal esophagitis associated with tuberculous pericarditis in an human immunodeficiency virus-positive patient: a case report.

BACKGROUND: Opportunistic infections are frequent in people living with the human immunodeficiency virus who either do not have access to antiretroviral therapy (ART) or use it irregularly. Tuberculosis is the most frequent infectious disease in PLHIV and can predispose patients to severe fungal infections with dire consequences. CASE PRESENTATION: We describe the case of a 35-year-old Brazilian man living with human immunodeficiency virus (HIV) for 10 years. He reported no adherence to ART and a history of histoplasmosis with hospitalization for 1 month in a public hospital in Natal, Brazil. The diagnosis was disseminated Mycobacterium tuberculosis infection. He was transferred to the health service in Recife, Brazil, with a worsening condition characterized by daily fevers, dyspnea, pain in the upper and lower limbs, cough, dysphagia, and painful oral lesions suggestive of candidiasis. Lymphocytopenia and high viral loads were found. After screening for infections, the patient was diagnosed with tuberculous pericarditis and esophageal candidiasis caused by Candida tropicalis. The isolated yeasts were identified using the VITEK 2 automated system and matrix-assisted laser desorption/ionization time-of-flight-mass spectrometry. Antifungal microdilution broth tests showed sensitivity to fluconazole, voriconazole, anidulafungin, caspofungin, micafungin, and amphotericin B, with resistance to fluconazole and voriconazole. The patient was treated with COXCIP-4 and amphotericin deoxycholate. At 12 days after admission, the patient developed sepsis of a pulmonary focus with worsening of his respiratory status. Combined therapy with meropenem, vancomycin, and itraconazole was started, with fever recurrence, and he changed to ART and tuberculostatic therapy. The patient remained clinically stable and was discharged with clinical improvement after 30 days of hospitalization. CONCLUSION: Fungal infections should be considered in patients with acquired immunodeficiency syndrome as they contribute to worsening health status. When mycoses are diagnosed early and treated with the appropriate drugs, favorable therapeutic outcomes can be achieved.

Proximal tubular dysfunction related to tenofovir in people living with HIV/AIDS: a pharmacogenetic study.

OBJECTIVES: The purpose of this case-control study was to verify the association between single nucleotide polymorphisms (SNPs) in genes encoding drug transporters related to tenofovir disoproxil fumarate (TDF) and proximal renal tubular dysfunction (PRTD), and the association between PRTD and clinical characteristics. METHODS: The 'cases' met the diagnostic criteria for PRTD, determined by the presence of two or more of the following abnormalities: non-diabetic glycosuria, metabolic acidosis, increased uric acid and phosphorus excretion, decreased tubular phosphorus reabsorption and ß2-microglobulinuria. We analyzed eight SNPs in ABCC2, ABCC4, ABCC10 and SLC28A2 genes. Genotyping was performed using real-time PCR. RESULTS: Of the 204 people living with HIV, 38 (18.6%) met the criteria for diagnosis of PRTD and 131 were male (64.2%), with a mean age of 49 years and a history of previous antiretroviral therapy for an average of 5 years. In the multivariate analysis, older individuals, TDF use, protease inhibitor, antihypertensives and anticonvulsants were associated with a risk of developing PRTD. Increased excretion of ß2microglobulin was associated with the A/G genotype of rsCC8187710 from ABCC2 ( P = 0.003) and the following genotypes of ABCC4 SNPs: A/G from rs1059751 ( P = 0.023), G/G from rs1059751 ( P = 0.030) and C/C of rs3742106 ( P = 0.041). The increase in the fraction of excreted phosphorus was associated with the C/T genotype of SNCC rsP40037 from ABCC2 ( P = 0.0041). CONCLUSIONS: The results indicate an important relationship between SNPs associated with these markers and changes in proximal renal tubule function, and thus support their use as biomarkers for the early detection of PRTD risk.

Occurrence of qnrB1 and qnrB12 genes, mutation in gyrA and ramR, and expression of efflux pumps in isolates of Klebsiella pneumoniae carriers of blaKPC-2.

PURPOSE: The occurrence of quinolone-resistance genes (qnrA, qnrB and qnrS), the presence of mutations in gyrA, gyrB and parC, as well as the expression of efflux pumps (acrB and acrF) and mutations in the gene ramR. METHODOLOGY: Were investigated in 30 blaKPC-2-positive isolates of Klebsiella pneumoniae taken from infection and colonization in hospital patients from Recife-PE, Brazil. The detection of the qnr, acrB and acrF genes and analysis of the mutations in ramR and the quinolone-resistance-determining regions of gyrA, gyrB and parC were performed by PCR followed by DNA sequencing. RESULTS: Among the isolates analysed, 73.3 % (n=22) presented the qnrB gene. For the DNA sequencing, six isolates (K3-A2, K12-A2, K25-A2, K27-A2, K19-A2 and K3-C2) were selected and the qnrB1 and qnrB12 variants were detected. This is the first ever report, to the best of our knowledge, of the presence of qnrB12 in K. pneumoniae. This is also the first report, to the best of our knowledge, of the presence of qnrB1 or qnrB12 with blaKPC-2 in K. pneumoniae in Brazil. Mutations were observed in gyrA S83 and in ramR. All isolates presented genes for the acrB and acrF efflux pumps and the reverse transcription PCR performed showed that the pumps were being expressed. CONCLUSION: KPC-2-positive isolates colonizing patients, which also showed qnrB, mutation in gyrA and efflux pumps, may be important reservoirs for disseminating these resistance mechanisms in the hospital environment.

Multifocal skeletal tuberculosis in an immunocompetent patient: a case report.

BACKGROUND: The occurrence of multifocal skeletal involvement in immunocompetent patients is rare, even in countries where tuberculosis is endemic. Multifocal skeletal lesions may occur as a result of hematogenous dissemination from another primary focus such as cervical lymph nodes, lungs, tonsils or gastrointestinal tract. CASE PRESENTATION: We present a 59 year-old man with a history of intermittent and disabling pain in his left knee for 2 years. The patient in this case presented with lung infection with bilateral skeletal dissemination in the knees and femurs. Immunological examination for the HIV was negative. CONCLUSIONS: Diagnosis of this condition is not always easy because of the disease's insidious character, and it can be confused with other diseases such as osteoarthritis, especially in middle-aged individuals.

Presence of fimH, mrkD, and irp2 virulence genes in KPC-2-producing Klebsiella pneumoniae isolates in Recife-PE, Brazil.

Klebsiella pneumoniae strains can produce different virulence factors, such as fimbrial adhesins and siderophores, which are important in the colonization and development of the infection. The aims of this study were to determine the occurrence of fimH, mrkD, and irp2 virulence genes in 22 KPC-2-producing K. pneumoniae isolates as well as 22 not producing-KPC isolates, from patients from different hospitals in Recife-PE, Brazil, and also to analyze the clonal relationship of the isolates by enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR). The genes were detected by PCR and DNA sequencing. The bla KPC-2 gene was identified in 22 KPC-positive isolates. On analyzing the antimicrobial susceptibility profile of the isolates, it was detected that polymyxin and amikacin were the antimicrobials of best activity against K. pneumoniae. On the other hand, five isolates exhibited resistance to polymyxin. In the KPC-positive group, was observed a high rate of resistance to cephalosporins, followed by carbapenems. Molecular typing by ERIC-PCR detected 38 genetic profiles, demonstrating a multiclonal spread of the isolates analyzed. It was observed that the virulence genes irp2, mrkD, and fimH were seen to have together a higher frequency in the KPC-positive group. The accumulation of virulence genes of KPC-positive K. pneumoniae isolates, observed in this study, along with the multi-resistance impose significant therapeutic limitations on the treatment of infections caused by K. pneumoniae.

Frequency and risk factors for HIV-associated neurocognitive disorder and depression in older individuals with HIV in northeastern Brazil.

BACKGROUND: The study was undertaken to describe the frequency of HIV-associated neurocognitive disorders (HAND) and depressive symptoms in an older population with human immunodeficiency virus (HIV). METHODS: A cross-sectional analysis of patients aged 50 years or older infected with HIV was carried out in an outpatient setting in Brazil from March to November 2008. Patients selected were submitted to cognitive evaluation using the Mini-Mental State Examination and International HIV Dementia Scale, and also to functional and depression evaluations. RESULTS: Among the 52 patients evaluated, the frequency of neurocognitive disorder was 36.5%, while for dementia the frequency was 13.5%. No risk factors were identified. Among the patients with cognitive impairment, 73.7% had cortical impairment. The frequency of depressive symptoms was of 34.6%. The female gender was identified as a risk factor (p = 0.018) and patients with depressive symptoms had greater functional impairment (p < 0.001). CONCLUSION: HAND and depressive symptoms are common in an older population. Patients with cognitive impairment achieved lower scores on the cortical assessment scales. Depressive symptoms are a stronger factor for functional impairment.

Prevalence of hyperapolipoprotein B and associations with other cardiovascular risk factors among human immunodeficiency virus-infected patients in Pernambuco, Brazil.

BACKGROUND: Hypertriglyceridemia associated with low high-density lipoprotein (HDL) levels and hypercholesterolemia is the most common metabolic disorder among human immunodeficiency virus (HIV)-infected patients using antiretroviral therapy. This atherogenic profile is associated with increased cardiovascular risk among these patients. Apolipoprotein B (apoB) is a better parameter than low-density lipoprotein (LDL) for evaluating lipids and cardiovascular risk among patients with diabetes and metabolic syndrome, but studies of apoB among HIV-infected patients are scarce. METHODS: A cross-sectional study was conducted to estimate hyperapolipoprotein B (hyperapoB) prevalence and its association with other factors among HIV-infected patients attended in Recife, Pernambuco, Brazil. RESULTS: The prevalence of hyperapoB was 32.4% among 256 patients (62.1% male), with 90 mg/dL as the cutoff point. It was associated with prolonged use (>3 years) of antiretroviral therapy [odds ratio (OR), 3.63; 95% confidence interval (CI), 1.24-10.6], hypertriglyceridemia (OR, 2.45; 95% CI, 1.22-4.91), insulin resistance according to homeostasis model assessment of insulin resistance (HOMA-IR) (OR, 2.12; 95% CI, 1.03-4.35), past history of diabetes (OR, 3.58; 95% CI, 1.0-12.7), and hypertension (OR, 1.98; 95% CI, 0.92-4.28). It was not associated with low HDL levels or self-report lipodystrophy. ApoB was higher in patients with metabolic syndrome according to the National Cholesterol Education Program (NCEP) criteria and in those with higher Framingham scores. CONCLUSIONS: ApoB is a good parameter for evaluating lipid levels in HIV-infected patients with hypertriglyceridemia, among whom LDL measurements may not be appropriate. ApoB might be useful for diagnosing and treating hypertriglyceridemia in this population. The association between hyperapoB and hypertriglyceridemia and diseases relating to insulin resistance among HIV-infected patients suggests that this group of patients presents higher cardiovascular risk.

Risk factors in human immunodeficiency virus/acquired immunodeficiency syndrome patients undergoing antiretroviral therapy in the state of Pernambuco, Brazil: a case-control study.

BACKGROUND: Although human immunodeficiency virus (HIV)-associated lipodystrophy has been reported for more than a decade, there is still considerable uncertainty regarding the mechanisms involved in its pathogenesis. METHODS: A case-control study was performed that aimed to identify the risk factors for lipodystrophy in HIV/acquired immunodeficiency syndrome (AIDS) patients undergoing antiretroviral therapy in Pernambuco, Brazil. RESULTS: Between July and November, 2007, a total of 332 patients were enrolled in the study: 182 cases and 150 controls. The following factors were independently associated with lipodystrophy: Use of stavudine [odds ratio (OR), 4.0; 95% confidence interval (CI), 2.3-6.9], use of didanosine (OR, 1.8; 95% CI, 1.0-3.4), use of lopinavir/ritonavir for less than 3 years (OR, 0.5; 95% CI, 0.2-1.0) and use of nucleoside/nucleotide analogue reverse transcriptase inhibitors (NTRIs) for more than 3 years (OR, 2.9; 95% CI, 1.6-5.2). Other associated factors were: duration of antiretroviral therapy (OR, 4.3; 95% CI, 2.4-7.9) and duration of HIV infection (OR, 2.9; 95% CI, 1.8-4.7). There was no association with the use of protease inhibitor when it was adjusted for the use of NRTIs. CONCLUSION: In this study, factors related to antiretroviral therapy were the main risk factors for lipodystrophy, corroborating the literature, but the findings also point to the need for further exploration into some of these associations, especially with the use of didanosine and lopinavir/ritonavir, which are less frequently reported. Future studies with a larger number of patients and a prospective design could provide valuable information for understanding this disorder.

Characteristics of pulmonary tuberculosis in HIV seropositive and seronegative patients in a Northeastern region of Brazil.

The aim of this study was to analyse the clinical, epidemiological and bacteriological features present in 60 pulmonary tuberculosis patients who were also infected with human immunodeficiency virus (HIV) and to compare these with 120 TB patients who were not infected with HIV. The patients with pulmonary tuberculosis and HIV coinfection were mostly male (p = 0.001), showed a higher frequency of weight loss >10 kilos (p <0.001), had a higher rate of non-reaction result to the tuberculin skin test (p <0.001), a higher frequency of negative sputum smear examination for acid-fast bacilli (p = 0.001) and negative sputum culture for Mycobacterium tuberculosis (p = 0.001). Treatment failure was more common in those who were HIV positive (p <0.000). No higher frequency of resistance to antituberculosis drugs was found to be associated with TB/HIV coinfection (p = 0.407). Association between extrapulmonary and pulmonary tuberculosis was more frequent in those seropositive to HIV than those without HIV virus, 30% and 1.6% respectively. These findings showed a predominance of atypical clinical laboratory features in co-infected patients, and suggest that health care personnel should consider the possibility this diagnosis.