Impact of Subsyndromal Delirium Occurrence and Its Trajectory during ICU Stay

Funding Information: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Publisher Copyright: © 2022 by the authors.Despite recent advances in the field, the association between subsyndromal delirium (SSD) in the ICU and poor outcomes is not entirely clear. We performed a retrospective multicentric observational study analyzing mental status during the first 72 h of ICU stay. Of the 681 patients included, SSD occurred in 22.7%. Considering the worst cognitive assessment during the first 72 h, 233 (34%) patients had normal mental status, 124 (18%) patients had SSD and 324 (48%) patients had delirium or coma. SSD was not independently associated with an increased risk of death when compared with normal mental status (OR 95%IC 1.0 vs. 1.35 [0.73–1.49], p = 0.340), but was associated with a longer ICU LOS (7.0 (4–12) vs. 4 (3–8) days, p 23 points. Our findings support the association of SSD with increased ICU LOS, but not with ICU mortality. Monitoring the trajectory of SSD early at ICU admission can help to identify patients with increased risk of conversion from SSD to delirium or coma.publishersversionpublishe

Cell-cycle and suppressor proteins expression in uterine cervix in HIV/HPV co-infection: comparative study by tissue micro-array (TMA)

<p>Abstract</p> <p>Background</p> <p>The oncoproteins of human papillomavirus (HPVs) directly effect cell-cycle control. We hypothesize that regulatory and cell cycle protein expression might be additionally modified in the cervix of HIV/HPV co-infected women.</p> <p>Methods</p> <p>We analyzed the expression of Rb, p27, VEGF and Elf-1 transcriptor factor by immunohistochemistry in 163 paraffin-embeded cervical samples using Tissue Micro-Array (TMA) and correlated this to HIV-1 and HPV infection.</p> <p>Results</p> <p>HIV/HPV co-infection was associated with a significant increase in expression (p < 0.001) of VEGF and p27 in both low and high grade CIN when compared to the cervices of women infected by HPV alone. Decreased Rb expression was evident with increased CIN grade in the cervices of women infected with HPV alone (p = 0.003 average of cells/mm²in CIN I: 17.9, CIN II/III: 4.8, and tumor 3.9). Rb expression increased 3-fold for both low and high grade CIN with HPV/HIV-1 co-infection compared to HPV infection alone but did not reach statistical significance. There was a significant increase in Elf-1 expression in HPV+/HIV- women with CIN II/III and tumor (average of cells/mm²in CIN I: 63.8; CIN II/III: 115.7 and tumor: 112.0, p = 0.005), in comparison to controls.</p> <p>Conclusion</p> <p>Co-infection of HPV and HIV leads to significant increase in the VEGF and p27 expression when compared to HPV+/HIV-negative infection that could facilitate viral persistence and invasive tumor development.</p

Phenotypes of lung mononuclear phagocytes in HIV seronegative tuberculosis patients: evidence for new recruitment and cell activation

Mycobacterium tuberculosis preferentially resides in mononuclear phagocytes. The mechanisms by which mononuclear phagocytes keep M. tuberculosis in check or by which the microbe evades control to cause disease remain poorly understood. As an initial effort to delineate these mechanisms, we examined by immunostaining the phenotype of mononuclear phagocytes obtained from lungs of patients with active tuberculosis. From August 1994 to March 1995, consecutive patients who had an abnormal chest X-ray, no demostrable acid-fast bacilli in sputum specimens and required a diagnostic bronchoalveolar lavage (BAL) were enrolled. Of the 39 patients enrolled, 21 had microbiologically diagnosed tuberculosis. Thirteen of the 21 tuberculosis patients were either HIV seronegative (n = 12) or had no risk factor for HIV and constituted the tuberculosis group. For comparison, M. tuberculosis negative patients who had BAL samples taken during this time (n = 9) or normal healthy volunteers (n = 3) served as control group. Compared to the control group, the tuberculosis group had significantly higher proportion of cells expressing markers of young monocytes (UCHM1) and RFD7, a marker for phagocytic cells, and increased expression of HLA-DR, a marker of cell activation. In addition, tuberculosis group had significantly higher proportion of cells expressing dendritic cell marker (RFD1) and epithelioid cell marker (RFD9). These data suggest that despite recruitment of monocytes probably from the peripheral blood and local cell activation, host defense of the resident lung cells is insufficient to control M. tuberculosis

Evaluation of MCM-2 Expression in TMA Cervical Specimens

Background:Minichromosome maintenance proteins (MCM) are highly expressed in actively replicating cells. The need for biological markers for cervical carcinoma and its precursor lesions is emerging. Our main aim was to determine the immunohistochemical expression of MCM-2 in HIV-positive and -negative dysplastic cervical specimens. Methods:Immunohistochemical analysis of MCM-2 was performed in a total of 352 cervical TMA specimens of normal control, low-grade CIN, high-grade CIN and invasive tumor. 38 specimens were from HIV-positive women. A receiver operating characteristic (ROC) curve was constructed to determine the best cutoff to diagnose high-grade CIN and invasive cervical cancer. Results:In the progression from normal epithelium to high-grade CIN and invasive tumor we found significant differences in the MCM-2 expression (p,0.05). Based on the ROC curve of 80% with an area under the curve (AUC) of 0.78, expression of MCM-2 to diagnose high-grade CIN and invasive tumor resulted in sensitivity of 81%, specificity of 66%, a positive predictive value (PPV) of 86% and a negative predictive value (NPV) of 57%. HIV-positive cervices revealed a decreasing expression of MCM-2 in both LGCIN and HGCIN compared with HIV-negative specimens (p,0.0001). Conclusions:The present study suggests that immunohistochemical MCM-2 may not be a promising biomarker for diagnosing high-grade CIN and invasive cance

Clonal expansion across the seas as seen through CPLP-TB database: A joint effort in cataloguing Mycobacterium tuberculosis genetic diversity in Portuguese-speaking countries.

Tuberculosis (TB) remains a major health problem within the Community of Portuguese Language Speaking Countries (CPLP). Despite the marked variation in TB incidence across its member-states and continued human migratory flux between countries, a considerable gap in the knowledge on the Mycobacterium tuberculosis population structure and strain circulation between the countries still exists. To address this, we have assembled and analysed the largest CPLP M. tuberculosis molecular and drug susceptibility dataset, comprised by a total of 1447 clinical isolates, including 423 multidrug-resistant isolates, from five CPLP countries. The data herein presented reinforces Latin American and Mediterranean (LAM) strains as the hallmark of M. tuberculosis populational structure in the CPLP coupled with country-specific differential prevalence of minor clades. Moreover, using high-resolution typing by 24-loci MIRU-VNTR, six cross-border genetic clusters were detected, thus supporting recent clonal expansion across the Lusophone space. To make this data available to the scientific community and public health authorities we developed CPLP-TB (available at http://cplp-tb.ff.ulisboa.pt), an online database coupled with web-based tools for exploratory data analysis. As a public health tool, it is expected to contribute to improved knowledge on the M. tuberculosis population structure and strain circulation within the CPLP, thus supporting the risk assessment of strain-specific trends

uma nova ferramenta de vigilância transnacional da tuberculose no espaço lusófono

A Tuberculose (TB) permanece um grave problema de saúde pública na Comunidade dos Países de Língua Portuguesa (CPLP). Apesar da ampla variância da incidência da TB nos seus estados-membro e de um fluxo migratório contínuo entre os países que integram este grupo, existe uma enorme lacuna no que diz respeito ao conhecimento da estrutura populacional conjunta do Mycobacterium tuberculosis e circulação de estirpes entre estes países. Para fazer face a esta necessidade, foi agregado e analisado o maior conjunto de dados respeitante à diversidade genotípica e resistência fenotípica na CPLP que compreende um total de 1447 isolados clínicos, incluindo 423 isolados multirresistentes de cinco países da CPLP. Por forma a tornar estes dados disponíveis para a comunidade científica e autoridades de saúde pública, foi desenvolvida a CPLP-TB (disponível em http://cplp-tb.ff.ulisboa.pt), uma base de dados disponível online e provida de aplicativos para análise exploratória do conteúdo. Como ferramenta de saúde pública, espera-se que venha a contribuir para um conhecimento mais aprofundado da estrutura populacional do M. tuberculosis e circulação de estirpes na CPLP de forma a apoiar a avaliação de risco e tendências específicas para diversos clones. Tuberculosis (TB) remains a major health problem within the Community of Portuguese Language Speaking Countries (CPLP). Despite the marked variation in TB incidence across its member-states and continued human migratory flux between countries, a considerable gap in the knowledge on the Mycobacterium tuberculosis population structure and strain circulation between the countries still exists. To address this, we have assembled and analyzed the largest CPLP M . tuberculosis molecular and drug susceptibility dataset, comprised by a total of 1447 clinical isolates, including 423 multidrug-resistant isolates, from five CPLP countries. To make this data available to the scientific community and public health authorities we developed CPLP-TB (available at http://cplp-tb.ff.ulisboa.pt), an online database coupled with web-based tools for exploratory data analysis. As a public health tool, it is expected to contribute to improved knowledge on the M. tuberculosis population structure and strain circulation within the CPLP, thus supporting the risk assessment of strain-specific trends.publishersversionpublishe