The rs11684747 and rs55790676 SNPs of ADAM17 influence tuberculosis susceptibility and plasma levels of TNF, TNFR1, and TNFR2.

Introduction: The proteolytic activity of A Disintegrin and Metalloproteinase 17 (ADAM17) regulates the release of tumor necrosis factor (TNF) and TNF receptors (TNFRs) from cell surfaces. These molecules play important roles in tuberculosis (TB) shaping innate immune reactions and granuloma formation. Methods: Here, we investigated whether single nucleotide polymorphisms (SNPs) of ADAM17 influence TNF and TNFRs levels in 224 patients with active TB (ATB) and 118 healthy close contacts. Also, we looked for significant associations between SNPs of ADAM17 and ATB status. TNF, TNFR1, and TNFR2 levels were measured in plasma samples by ELISA. Four SNPs of ADAM17 (rs12692386, rs1524668, rs11684747, and rs55790676) were analyzed in DNA isolated from peripheral blood leucocytes. The association between ATB status, genotype, and cytokines was analyzed by multiple regression models. Results: Our results showed a higher frequency of rs11684747 and rs55790676 in close contacts than ATB patients. Coincidentally, heterozygous to these SNPs of ADAM17 showed higher plasma levels of TNF compared to homozygous to their respective ancestral alleles. Strikingly, the levels of TNF and TNFRs distinguished participant groups, with ATB patients displaying lower TNF and higher TNFR1/TNFR2 levels compared to their close contacts. Conclusion: These findings suggest a role for SNPs of ADAM17 in genetic susceptibility to ATB.

Dysbiosis and structural disruption of the respiratory microbiota in COVID-19 patients with severe and fatal outcomes.

The COVID-19 outbreak has caused over three million deaths worldwide. Understanding the pathology of the disease and the factors that drive severe and fatal clinical outcomes is of special relevance. Studying the role of the respiratory microbiota in COVID-19 is especially important as the respiratory microbiota is known to interact with the host immune system, contributing to clinical outcomes in chronic and acute respiratory diseases. Here, we characterized the microbiota in the respiratory tract of patients with mild, severe, or fatal COVID-19, and compared it to healthy controls and patients with non-COVID-19-pneumonia. We comparatively studied the microbial composition, diversity, and microbiota structure between the study groups and correlated the results with clinical data. We found differences in the microbial composition for COVID-19 patients, healthy controls, and non-COVID-19 pneumonia controls. In particular, we detected a high number of potentially opportunistic pathogens associated with severe and fatal levels of the disease. Also, we found higher levels of dysbiosis in the respiratory microbiota of patients with COVID-19 compared to the healthy controls. In addition, we detected differences in diversity structure between the microbiota of patients with mild, severe, and fatal COVID-19, as well as the presence of specific bacteria that correlated with clinical variables associated with increased risk of mortality. In summary, our results demonstrate that increased dysbiosis of the respiratory tract microbiota in patients with COVID-19 along with a continuous loss of microbial complexity structure found in mild to fatal COVID-19 cases may potentially alter clinical outcomes in patients. Taken together, our findings identify the respiratory microbiota as a factor potentially associated with the severity of COVID-19.

Clinicopathologic and immunohistochemical study of choroid plexus tumors: single-institution experience in Mexican population.

In recent years, few studies have specifically focused on only histological features in choroid plexus tumors. We retrospectively reviewed the clinicopathologic and histological features in 37 patients with choroid plexus tumors and correlated these with glial fibrillary acidic protein (GFAP) expression and proliferation cell nuclear antigen (PCNA), p53, p21, and Rb labeling indexes, with special attention to tumor recurrence/regrowth. The study included 24 choroid plexus papillomas (CPPs), 4 atypical choroid plexus papillomas (ACPPs), and 9 choroid plexus carcinomas (CPCs). Patient age ranged from 15 to 70 years (mean 44 years). Most of the choroid plexus tumors were located in the IV ventricle. Recurrence was observed in 21 (52%) cases, 14 of which were CPP and 7 of which were CPC (P = 0.032). Histologic findings included major necrosis, fibrosis and psammoma bodies, amyloid deposits, inflammation, and thick vessels in recurrent tumors. The PCNA labeling index was 52.04 + or - 13.92 in CPPs, 76.50 + or - 17 in ACPPs, and 95.22 + or - 21.34 in CPCs (P = 0.009), and 67.43 + or - 28 in recurrent tumors. Similar values were found for p53, p21, and Rb. Furthermore, we observed that these presented more histological changes, adding, than nonrecurrent tumors, as well as a higher proliferation index of cell-cycle markers, and these were dependent predictor factors of survival. Recurrent tumors showed a different biological behavior than nonrecurrent tumors, but histological observations showed no mitotic features in order to consider them as grade II.

A unique immune signature of serum cytokine and chemokine dynamics in patients with Zika virus infection from a tropical region in Southern Mexico.

OBJECTIVES: To describe the kinetics of circulating cytokines and chemokines in humans with ZIKAV infection. METHODS: Serum levels of different immune mediators in patients with ZIKAV infection were measured at distinct stages of the disease, as well as in culture supernatants from human monocytes infected with a clinical ZIKAV isolate. We also looked for clinical features associated with specific immune signatures among symptomatic patients. RESULTS: We evaluated 23 ZIKAV-infected patients. Their mean age was 32 ± 8.3 years and 65% were female. ZIKAV patients showed elevated IL-9, IL-17A, and CXCL10 levels at acute stages of the disease. At day 28, levels of CCL4 and CCL5 were increased, whereas IL-1RA, CXCL8 and CCL2 were decreased. At baseline, IL-7 was increased among patients with headache, whereas CCL2, and CCL3 were decreased in patients with bleeding and rash, respectively. Our clinical ZIKAV isolate induced a broad immune response in monocytes that did not resemble the signature observed in ZIKAV patients. CONCLUSIONS: We showed a unique immune signature in our cohort of ZIKAV-infected patients. Our study may provide valuable evidence helpful to identify immune correlates of protection against ZIKAV.

High performance of rapid influenza diagnostic test and variable effectiveness of influenza vaccines in Mexico.

OBJECTIVES: To evaluate the performance of rapid influenza diagnostic tests (RIDT) and influenza vaccines' effectiveness (VE) during an outbreak setting. METHODS: We compared the performance of a RIDT with RT-PCR for influenza virus detection in influenza-like illness (ILI) patients enrolled during the 2016/17 season in Mexico City. Using the test-negative design, we estimated influenza VE in all participants and stratified by age, virus subtype, and vaccine type (trivalent vs quadrivalent inactivated vaccines). The protective value of some clinical variables was evaluated by regression analyses. RESULTS: We enrolled 592 patients. RT-PCR detected 93 cases of influenza A(H1N1)pdm09, 55 of AH3N2, 141 of B, and 13 A/B virus infections. RIDT showed 90.7% sensitivity and 95.7% specificity for influenza A virus detection, and 91.5% sensitivity and 95.3% specificity for influenza B virus detection. Overall VE was 33.2% (95% CI: 3.0-54.0; p = 0.02) against any laboratory-confirmed influenza infection. VE estimates against influenza B were higher for the quadrivalent vaccine. Immunization and occupational exposure were protective factors against influenza. CONCLUSIONS: The RIDT was useful to detect influenza cases during an outbreak setting. Effectiveness of 2016/17 influenza vaccines administered in Mexico was low but significant. Our data should be considered for future local epidemiological policies.

A New Method to Quantify Ifosfamide Blood Levels Using Dried Blood Spots and UPLC-MS/MS in Paediatric Patients with Embryonic Solid Tumours.

Ifosfamide blood concentrations are necessary to monitor its therapeutic response, avoiding any adverse effect. We developed and validated an analytical method by UPLC-MS/MS to quantify ifosfamide in dried blood spots (DBS). Blood samples were collected on Whatman 903® filter paper cards. Five 3 mm disks were punched out from each dried blood spot. Acetonitrile and ethyl acetate were used for drug extraction. Chromatographic separation was carried out in an Acquity UPLC equipment with a BEH-C18 column, 2.1 x 100 mm, 1.7 µm (Waters®). The mobile phase consisted in 5 mM ammonium formate and methanol:acetonitrile (40:48:12 v/v/v) at 0.2 mL/min. LC-MS/MS detection was done by ESI+ and multiple reaction mode monitoring, ionic transitions were m/z1+ 260.99 > 91.63 for ifosfamide and 261.00 > 139.90 for cyclophosphamide (internal standard). This method was linear within a 100-10000 ng/mL range and it was accurate, precise and selective. Ifosfamide samples in DBS were stable for up to 52 days at -80°C. The procedure was tested in 14 patients, ages 1 month to 17 years (9 males and 5 females), with embryonic tumours treated with ifosfamide, alone or combined, at a public tertiary referral hospital. Ifosfamide blood levels ranged from 11.1 to 39.7 µmol/L at 12 hours after the last infusion, while 24-hour levels ranged from 0.7-19.7 µmol/L. The median at 12 hours was 19.5 µmol/L (Q25 14.4-Q75 29.0) and 3.8 µmol/L (Q25 1.5-Q75 9.9) at 24 hours, p<0.001. This method is feasible to determine ifosfamide plasma levels in paediatric patients.

Potentially-toxic and essential elements profile of AH1N1 patients in Mexico City.

During spring of 2009, a new influenza virus AH1N1 spread in the world causing acute respiratory illness and death, resulting in the first influenza pandemic since 1968. Blood levels of potentially-toxic and essential elements of 40 pneumonia and confirmed AH1N1 were evaluated against two different groups of controls, both not infected with the pandemic strain. Significant concentrations of potentially-toxic elements (lead, mercury, cadmium, chromium, arsenic) along with deficiency of selenium or increased Zn/Cu ratios characterized AH1N1 cases under study when evaluated versus controlled cases. Deficiency of selenium is progressively observed from controls I (influenza like illness) through controls II (pneumonia) and finally pneumonia-AH1N1 infected patients. Cases with blood Se levels greater than the recommended for an optimal cut-off to activate glutathione peroxidase (12.5 µg/dL) recovered from illness and survived. Evaluation of this essential element in critical pneumonia patients at the National Institutes is under evaluation as a clinical trial.

Motivos de hospitalización en pacientes con tuberculosis pulmonar en un hospital de referencia / Reasons for medical admission in patients with pulmonary tuberculosis in a referral institute

Objetivo: Determinar la prevaíencia de complicaciones torácicas en pacientes con tuberculosis pulmonar hospitalizados en el Instituto Nacional de Enfermedades Respiratorias (INER). Lugar del estudio: INER, centro de tercer nivel y referencia dedicado a la atención médica especializada, docencia e investigación de enfermedades respiratorias. Material y métodos: Se realizó un estudio retrospectivo con la revisión de los expedientes clínicos de pacientes con tuberculosis pulmonar ingresados al INER, en un período que comprendió del 1 de julio al 31 de diciembre de 2003. Resultados: De los 124 pacientes con tuberculosis pulmonar que acudieron al INER durante el período de estudio, 62.9% (78/124) fueron hospitalizados; 44.9% (35/78) del sexo masculino; mediana de edad, 44.5 años (rango 16-78); el diagnóstico bacteriológico se hizo por baciloscopía en 51.3% (40/78); sólo por cultivo, 5.1% (4/78) y por baciloscopía y cultivo, 43.6% (34/78). Del total de pacientes, 66.6% (52/78) se clasificaron en la categoría I de la Organización Mundial de la Salud. La prevaíencia de diabetes mellitus fue 43.7% (31/78). Los motivos de hospitalización fueron: 46.2% (36/78) para diagnóstico; hemoptisis, 34.6% (27/78); infecciones, 5.2% (4/78) y otros motivos, 14.0% (11/78). Presentaron bronquiectasias, 85.7% (66/78); neumonía, 6.4% (5/78); neumonía por Mycobacterium tuberculosis, 5.1% (4/78); empierna, 5.1% (4/78); fístula broncopleural, 3.9% (3/78); aspergiloma, 2.6% (2/78); compresión tráqueo-bronquial, 1.3% (l/78) y fibrotórax, 12.8% (10/78). Conclusiones: Los pacientes hospitalizados en el INER por tuberculosis pulmonar manifestaron una elevada frecuencia de complicaciones, especialmente de bronquiectasias y hemoptisis. Casi 44% de los pacientes presentó diabetes mellitus; uno de cada dos fue hospitalizado para diagnóstico.

Purpose: To determine the prevalence of thoracic complications in hospitalized patients with pulmonary tuberculosis. Setting: National referral hospital for the care, teaching and investigation of respiratory diseases. Material and methods: This study is based on the retrospective analysis of pulmonary tuberculosis patients admitted from July 1 to December 31, 2003 and was conducted at The National Institute of Respiratory Diseases (INER), Mexico. Results: Seventy eight patients with pulmonary tuberculosis were included in the six month period; 35 (44.9%) were male; the bacteriological diagnosis was done by sputum smear in 51.3% (40/78), culture in 5.1% (4/78) and sputum smear and culture in 43.6% (34/78). Patients were classified as WHO category I in 66.7% (52/78); 43.7% had diabetes mellitus (31/78). Admission causes: for diagnosis in 46.2% (36/78); hemoptysis in 34.6% (27/78); infection in 5.2% (4/78); other causes in 14.0% (11/78); bronchiectasis were present in 85.7% (66/ 77); pneumonia in 6.4% (5/78); Mycobacterium tuberculosis pneumonia in 5.1% (4/78); empyema in 5.1% (4/78); bronchopleural fistula in 3.9% (3/ 78); aspergilloma in 2.6% (2/78); tracheobronchial obstruction in 1.3% (1/78); fibrothorax in 12.8% (10/78). Conclusions: Hospitalized pulmonary tuberculosis patients show an elevated rate of pulmonary complications. Almost half had diabetes mellitus; almost half were hospitalized for diagnosis.