Strong CD4+ T-Cell Responses to Ancestral and Variant Spike Proteins Are Established by NVX-CoV2373 Severe Acute Respiratory Syndrome Coronavirus 2 Primary Vaccination.

BACKGROUND: NVX-CoV2373 is an efficacious coronavirus disease 2019 (COVID-19) vaccine comprising full-length recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (rS) glycoprotein and Matrix-M adjuvant. Phase 2 of a randomized, placebo-controlled, phase 1/2 trial in healthy adults (18-84 years of age) previously reported good safety/tolerability and robust humoral immunogenicity. METHODS: Participants were randomized to placebo or 1 or 2 doses of 5-µg or 25-µg rS with 50 µg Matrix-M adjuvant 21 days apart. CD4+ T-cell responses to SARS-CoV-2 intact S or pooled peptide stimulation (with ancestral or variant S sequences) were measured via enzyme-linked immunosorbent spot assay and intracellular cytokine staining. RESULTS: A clearly discernable spike antigen-specific CD4+ T-cell response was induced after 1 dose, but markedly enhanced after 2 doses. Counts and fold increases in cells producing Th1 cytokines exceeded those secreting Th2 cytokines, although both phenotypes were clearly present. Interferon-γ responses to rS were detected in 93.5% of 2-dose 5-µg recipients. A polyfunctional CD4+ T-cell response was cross-reactive and of equivalent magnitude to all tested variants, including Omicron BA.1/BA.5. CONCLUSIONS: NVX-CoV2373 elicits a moderately Th1-biased CD4+ T-cell response that is cross-reactive with ancestral and variant S proteins after 2 doses. CLINICAL TRIALS REGISTRATION: NCT04368988.

Development of a New Measure of Housing Security: The REDD-CAT Housing Security Measure.

BACKGROUND: Housing security is a key social determinant of behavior related to health outcomes. OBJECTIVE: The purpose of this study was to develop a new patient-reported outcome measure that evaluates aspects of housing security for use in the Re-Engineered Discharge for Diabetes-Computer Adaptive Test (REDD-CAT) measurement system. DESIGN: Qualitative data, literature reviews, and cross-sectional survey study. PARTICIPANTS: A total of 225 people with T2DM provided responses to the items in this item pool. MAIN MEASURES: A new item pool that evaluates important aspects of housing security was developed using stakeholder data from focus groups of persons with T2DM. KEY RESULTS: For the Housing Affordability scale, factor analysis (both exploratory and confirmatory) supported the retention of six items. Of these items, none exhibited sparse cells or problems with monotonicity; no items were deleted due to low item-adjusted total score correlations. For the six affordability items, a constrained graded response model indicated no items exhibited misfit; thus, all were retained. No items indicated differential item functioning (examined for age, sex, education, race, and socioeconomic status). Thus, the final Affordability item bank comprised six items. A Housing Safety index (three items) and a Home Features index (eight items) were also developed. Reliability (i.e., internal consistency and test-retest reliability) and validity (i.e., convergent, discriminant, and known-groups) of the new measures were also supported. CONCLUSIONS: The REDD-CAT Housing Security Measure provides a reliable and valid assessment of housing affordability, safety, and home features in people with type 2 diabetes mellitus. Future work is needed to establish the clinical utility of this measure in other clinical populations.

Development and calibration data for the Illness Burden item bank: a new computer adaptive test for persons with type 2 diabetes mellitus.

PURPOSE: The purpose of this study was to develop a new measure, the Re-Engineered Discharge for Diabetes Computer Adaptive Test (REDD-CAT) Illness Burden item bank, to evaluate the impact that a chronic condition has on independent living, the ability to work (including working at home), social activities, and relationships. METHODS: Semi-structured interviews were used to inform the development of an item pool (47 items) that captured patients' beliefs about how a diagnosis of type 2 diabetes interferes with different aspects of their lives. The Illness Burden item bank was developed and tested in 225 people with type 2 diabetes mellitus. RESULTS: No items had sparse response option cells or problems with monotonicity; two items were deleted due to low item-rest correlations. Factor analyses supported the retention of 29 items. With those 29 remaining items, a constrained (common slope) graded response model fit assessment indicated that two items had misfit; they were excluded. No items displayed differential item functioning by age, sex, education, or socio-economic status. The final item bank is comprised of 27 items. Preliminary data supported the reliability (internal consistency and test-retest reliability) and validity (convergent, discriminant, and known-groups) of the new bank. CONCLUSION: The Illness Burden item bank can be administered as a computer adaptive test or a 6-item short form. This new measure captures patients' perceptions of the impact that having type 2 diabetes has on their daily lives; it can be used in conjunction with the REDD-CAT measurement system to evaluate important social determinants of health in persons with type 2 diabetes mellitus.

Development and calibration data for the Medication Adherence Item Bank: a new computer adaptive test for persons with type 2 diabetes mellitus.

PURPOSE: To develop a new computer adaptive test that evaluates important aspects of medication adherence for persons with type 2 diabetes mellitus. METHODS: Two hundred and twenty-five people with type 2 diabetes mellitus completed 41 items related to medication adherence. RESULTS: Exploratory analysis supported the essential unidimensionality of the initial item pool. Five items were deleted due to low item-adjusted total score correlations (resulting in 36 items). Confirmatory factor analysis supported the retention of 27 items. A graded response model identified no items for exclusion, based on misfit. No items were flagged for meaningful differential item functioning (DIF). The final item bank is comprised of 27 items; an associated 6-item short form was constructed that balanced both psychometric factors (e.g., item information values) and clinical input. Initial analysis of the simulated CAT and static short form supported both the reliability (i.e., internal consistency and test-retest reliability) and validity (i.e., convergent, discriminant, and known groups) of both administration formats. CONCLUSIONS: The new medication adherence item bank provides a reliable and valid assessment of the ability to take medications accurately among people with T2DM; it will be available in early 2023 through healthmeasures.net.

Development and calibration data for the Healthcare Access Item Bank: a new computer adaptive test for persons with type 2 diabetes mellitus.

PURPOSE: The purpose of this study was to develop a new measure to evaluate the ability to receive medical services when needed among persons with type 2 diabetes mellitus. METHODS: The Healthcare Access measure was developed using data from 225 persons with type 2 diabetes mellitus who completed an item pool comprised of 54 questions pertaining to their experience accessing healthcare services. RESULTS: Exploratory and confirmatory factor analyses supported the retention of 45 items. In addition, a constrained graded response model (GRM), as well as analyses that examined item misfit and differential item functioning (investigated for age, sex, education, race, and socioeconomic status), supported the retention of 44 items in the final item bank. Expert review and GRM item calibration products were used to inform the selection of a 6-item static short form and to program the Healthcare Access computer adaptive test (CAT). Preliminary data supported the reliability (i.e., internal consistency and test-retest reliability) and validity (i.e., convergent, discriminant, and known-groups) of the new measure. CONCLUSIONS: The new Healthcare Access item bank can be used to examine the experiences that persons with type 2 diabetes mellitus have with healthcare access, to better target treatment improvements and mitigate disparities; it will be available as a part of the Neuro-Qol measurement system through healthmeasures.net and the PROMIS Application Programmable Interface (API) in early 2023.

Effectiveness of an Immersive Telemedicine Platform for Delivering Diabetes Medical Group Visits for African American, Black and Hispanic, or Latina Women With Uncontrolled Diabetes: The Women in Control 2.0 Noninferiority Randomized Clinical Trial.

BACKGROUND: Medically underserved people with type 2 diabetes mellitus face limited access to group-based diabetes care, placing them at risk for poor disease control and complications. Immersive technology and telemedicine solutions could bridge this gap. OBJECTIVE: The purpose of this study was to compare the effectiveness of diabetes medical group visits (DMGVs) delivered in an immersive telemedicine platform versus an in-person (IP) setting and establish the noninferiority of the technology-enabled approach for changes in hemoglobin A1c (HbA1c) and physical activity (measured in metabolic equivalent of task [MET]) at 6 months. METHODS: This study is a noninferiority randomized controlled trial conducted from February 2017 to December 2019 at an urban safety net health system and community health center. We enrolled adult women (aged ≥18 years) who self-reported African American or Black race or Hispanic or Latina ethnicity and had type 2 diabetes mellitus and HbA1c ≥8%. Participants attended 8 weekly DMGVs, which included diabetes self-management education, peer support, and clinician counseling using a culturally adapted curriculum in English or Spanish. In-person participants convened in clinical settings, while virtual world (VW) participants met remotely via an avatar-driven, 3D VW linked to video teleconferencing. Follow-up occurred 6 months post enrollment. Primary outcomes were mean changes in HbA1c and physical activity at 6 months, with noninferiority margins of 0.7% and 12 MET-hours, respectively. Secondary outcomes included changes in diabetes distress and depressive symptoms. RESULTS: Of 309 female participants (mean age 55, SD 10.6 years; n=195, 63% African American or Black; n=105, 34% Hispanic or Latina; n=151 IP; and n=158 in VW), 207 (67%) met per-protocol criteria. In the intention-to-treat analysis, we confirmed noninferiority for primary outcomes. We found similar improvements in mean HbA1c by group at 6 months (IP: -0.8%, SD 1.9%; VW: -0.5%, SD 1.8%; mean difference 0.3, 97.5% CI -∞ to 0.3; P<.001). However, there were no detectable improvements in physical activity (IP: -6.5, SD 43.6; VW: -9.6, SD 44.8 MET-hours; mean difference -3.1, 97.5% CI -6.9 to ∞; P=.02). The proportion of participants with significant diabetes distress and depressive symptoms at 6 months decreased in both groups. CONCLUSIONS: In this noninferiority randomized controlled trial, immersive telemedicine was a noninferior platform for delivering diabetes care, eliciting comparable glycemic control improvement, and enhancing patient engagement, compared to IP DMGVs. TRIAL REGISTRATION: ClinicalTrials.gov NCT02726425; https://clinicaltrials.gov/ct2/show/NCT02726425.

Ferroptosis Involvement in Glioblastoma Treatment.

Glioblastoma multiforme (GBM) is one of the deadliest brain tumors. Current standard therapy includes tumor resection surgery followed by radiotherapy and chemotherapy. Due to the tumors invasive nature, recurrences are almost a certainty, giving the patients after diagnosis only a 12-15 months average survival time. Therefore, there is a dire need of finding new therapies that could potentially improve patient outcomes. Ferroptosis is a newly described form of cell death with several implications in cancer, among which GBM. Agents that target different molecules involved in ferroptosis and that stimulate this process have been described as potentially adjuvant anti-cancer treatment options. In GBM, ferroptosis stimulation inhibits tumor growth, improves patient survival, and increases the efficacy of radiation and chemotherapy. This review provides an overview of the current knowledge regarding ferroptosis modulation in GBM.

Preoperative Determination of Isocitrate Dehydrogenase Mutation in Gliomas Using Spectral Editing MRS: A Prospective Study.

BACKGROUND: The edited magnetic resonance spectroscopy (MRS) technique has not yet been formally evaluated for the in vivo detection of 2-hydroxyglutarate (2-HG) in patients with gliomas of various grades. PURPOSE: To evaluate the diagnostic accuracy of edited MRS in the preoperative identification of the isocitrate dehydrogenase (IDH) mutation status in patients with gliomas. STUDY TYPE: Prospective. POPULATION: Fifty-eight subjects (31 glioblastomas, 27 grade II and III gliomas). FIELD STRENGTH/SEQUENCE: Mescher-Garwood (MEGA)-PRESS and routine clinical brain tumor MR sequences were used at 3T. ASSESSMENT: Data were analyzed using an advanced method for accurate, robust, and efficient spectral fitting (AMARES) from jMRUI software. The amplitudes of the 2-HG, N-acetyl-aspartate (NAA), choline (Cho), and creatine/phosphocreatine (Cr) resonances were calculated with their associated Cramer-Rao lower bound (CRLB). The IDH1 R132H mutation status was assessed by immunohistochemistry for all patients. Patients with grades II and III gliomas with negative immunohistochemistry underwent DNA sequencing to further interrogate IDH mutation status. STATISTICAL TEST: The differences in 2-HG amplitudes, 2-HG/NAA, 2-HG/Cho, and 2-HG/Cr between IDH-mutant and IDH-wildtype gliomas were assessed using Mann-Whitney U-tests. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic accuracy of each parameter. RESULTS: The 2-HG amplitudes, 2-HG/NAA, and 2-HG/Cho were higher for IDH-mutant gliomas than IDH-wildtype gliomas (P < 0.007). Using a CRLB threshold <30%, a 2-HG cutoff greater than 0 had a sensitivity of 80% (95% confidence interval [CI]: 52-96%) and a specificity of 81% (95% CI: 54-96%) in identifying IDH-mutant gliomas. In the subset of patients with grades II and III gliomas, the sensitivity was 80% (95% CI: 52-96%) and specificity was 100% (95% CI: 40-100%). Among 2-HG ratios, the highest AUC for the identification of IDH mutant status was achieved using the 2-HG/NAA (AUC = 0.8, 95% CI 0.67-.89). DATA CONCLUSION: Preoperative edited MRS appears to be able to help identify IDH-mutant gliomas with high specificity. Level of Evidence 1 Technical Efficacy Stage 2 J. MAGN. RESON. IMAGING 2021;53:416-426.

Does hydroxychloroquine improve patient reported outcomes in patients with lupus?

BACKGROUND: Hydroxychloroquine (HCQ) use is associated with less disease activity, flares, damage and improved survival in Systemic Lupus Erythematosus (SLE). However, its effect on patient reported health outcomes (PROs) such as quality of life (QOL) is not known. METHODS: International data from Study on Outcomes of Lupus (SOUL) from 2,161 SLE patients were compared by HCQ use. Disease activity and damage were assessed using SELENA-SLEDAI and SLICC-ACR/SDI. QOL was evaluated using LupusPRO and Lupus Impact Tracker (LIT). Linear regression analyses were performed with LupusPRO summary scores health related HRQOL, non-health related NHRQOL and LIT as dependent and HCQ use as independent variable. Analyses were undertaken to test mediation of effects of HCQ use on QOL through disease activity. RESULTS: Mean age was 40.5 ± 12.8 years, 93% were women. Sixty-three (1363/2161) percent were on HCQ. On univariate analysis, HCQ use was associated with (a) better QOL (LupusPRO-HRQOL: ß 6.19, 95% CI 4.15, 8.24, P ≤ 0.001, LupusPRO NHRQOL: ß 5.83, 95% CI 4.02, 7.64, P ≤ 0.001) and less impact on daily life (LIT: ß -9.37, 95% CI -12.24, -6.50, P ≤ 0.001). On multivariate and mediational analyses, the effects of HCQ on QOL were indirectly and completely mediated through disease activity. CONCLUSIONS: HCQ use in SLE is associated with better patient reported health outcomes (LupusPRO-HRQOL and NHRQOL and impact on daily life), and the effects are mediated through disease activity. This information can facilitate patients and physician's communication with decision-making regarding the use of HCQ for SLE management.

Higher atypical enteropathogenic Escherichia coli (a-EPEC) bacterial loads in children with diarrhea are associated with PCR detection of the EHEC factor for adherence 1/lymphocyte inhibitory factor A (efa1/lifa) gene.

BACKGROUND: Typical enteropathogenic Escherichia coli (t-EPEC) are known to cause diarrhea in children but it is uncertain whether atypical EPEC (a-EPEC) do, since a-EPEC lack the bundle-forming pilus (bfp) gene that encodes a key adherence factor in t-EPEC. In culture-based studies of a-EPEC, the presence of another adherence factor, called EHEC factor for adherence/lymphocyte activation inhibitor (efa1/lifA), was strongly associated with diarrhea. Since a-EPEC culture is not feasible in clinical laboratories, we designed an efa1/lifA quantitative PCR assay and examined whether the presence of efa1/lifA was associated with higher a-EPEC bacterial loads in pediatric diarrheal stool samples. METHODS: Fecal samples from children with diarrhea were tested by qPCR for EPEC (presence of eae gene) and for shiga toxin genes to exclude enterohemorrhagic E. coli, which also contain the eae gene. EPEC containing samples were then tested for the bundle-forming pilus gene found in t-EPEC and efa1/lifA. The eae gene quantity in efa1/lifA-positive and negative samples was compared. RESULTS: Thirty-nine of 320 (12%) fecal samples tested positive for EPEC and 38/39 (97%) contained a-EPEC. The efa1/lifA gene was detected in 16/38 (42%) a-EPEC samples. The median eae concentration for efa1/lifA positive samples was significantly higher than for efa1/lifA negative samples (median 16,745 vs. 1183 copies/µL, respectively, p = 0.006). CONCLUSIONS: Atypical enteropathogenic E. coli-positive diarrheal stool samples containing the efa1/lifA gene had significantly higher bacterial loads than samples lacking this gene. This supports the idea that efa1/lifA contributes to diarrheal pathogenesis and suggests that, in EPEC-positive samples, efa/lifA may be a useful additional molecular biomarker.

How frequently are predicted peptides actually recognized by CD8 cells?

Detection of antigen-specific CD8 cells frequently relies on the use of peptides that are predicted to bind to HLA Class I molecules or have been shown to induce immune responses. There is extensive knowledge on individual HLA alleles' peptide-binding requirements, and immunogenic peptides for many antigens have been defined. The 32 individual peptides that comprise the CEF peptide pool represent such well-defined peptide determinants for Cytomegalo-, Epstein-barr-, and Influenza virus. We tested the accuracy of these peptide recognition predictions on 42 healthy human donors that have been high-resolution HLA-typed. According to the predictions, 241 recall responses should have been detected in these donors. Actual testing showed that 36 (15 %) of the predicted CD8 cell responses occurred in the high frequency range, 41 (17 %) in mid-frequencies, and 45 (19 %) were at the detection limit. In 119 instances (49 %), the predicted peptides were not targeted by CD8 cells detectably. The individual CEF peptides were recognized in an unpredicted fashion in 57 test cases. Moreover, the frequency of CD8 cells responding to a single peptide did not reflect on the number of CD8 cells targeting other determinants on the same antigen. Thus, reliance on one or a few predicted peptides provides a rather inaccurate assessment of antigen-specific CD8 cell immunity, strongly arguing for the use of peptide pools for immune monitoring.

Differences in mouse and human nonmemory B cell pools.

Identifying cross-species similarities and differences in immune development and function is critical for maximizing the translational potential of animal models. Coexpression of CD21 and CD24 distinguishes transitional and mature B cell subsets in mice. In this study, we validate these markers for identifying analogous subsets in humans and use them to compare the nonmemory B cell pools in mice and humans, across tissues, and during fetal/neonatal and adult life. Among human CD19(+)IgM(+) B cells, the CD21/CD24 schema identifies distinct populations that correspond to transitional 1 (T1), transitional 2 (T2), follicular mature, and marginal zone subsets identified in mice. Markers specific to human B cell development validate the identity of marginal zone cells and the maturation status of human CD21/CD24 nonmemory B cell subsets. A comparison of the nonmemory B cell pools in bone marrow, blood, and spleen in mice and humans shows that transitional B cells comprise a much smaller fraction in adult humans than mice. T1 cells are a major contributor to the nonmemory B cell pool in mouse bone marrow, in which their frequency is more than twice that in humans. Conversely, in spleen, the T1:T2 ratio shows that T2 cells are proportionally ∼ 8-fold higher in humans than in mice. Despite the relatively small contribution of transitional B cells to the human nonmemory pool, the number of naive follicular mature cells produced per transitional B cell is 3- to 6-fold higher across tissues than in mice. These data suggest differing dynamics or mechanisms produce the nonmemory B cell compartments in mice and humans.

Polymerase chain reaction detection of Kingella kingae in children with culture-negative septic arthritis in eastern Ontario.

BACKGROUND: The bacterium Kingella kingae may be an under-recognized cause of septic arthritis in Canadian children because it is difficult to grow in culture and best detected using molecular methods. OBJECTIVES: To determine whether K kingae is present in culture-negative joint fluid specimens from children in eastern Ontario using polymerase chain reaction (PCR) detection methods. METHODS: K kingae PCR testing was performed using residual bacterial culture-negative joint fluid collected from 2010 to 2013 at a children's hospital in Ottawa, Ontario. The clinical features of children with infections caused by K kingae were compared with those of children with infections caused by the 'typical' septic arthritis bacteria, Staphylococcus aureus and Streptococcus pyogenes. RESULTS: A total of 50 joint fluid specimens were submitted over the study period. Ten were culture-positive, eight for S aureus and two for S pyogenes. Residual joint fluid was available for 27 of the 40 culture-negative specimens and K kingae was detected using PCR in seven (25.93%) of these samples. Children with K kingae were significantly younger (median age 1.7 versus 11.3 years; P=0.01) and had lower C-reactive protein levels (median 23.8 mg/L versus 117.6. mg/L; P=0.01) than those infected with other bacteria. CONCLUSIONS: K kingae was frequently detected using PCR in culture-negative joint fluid specimens from children in eastern Ontario. K kingae PCR testing of culture-negative joint samples in children appears to be warranted.

HISTORIQUE: La bactérie Kingella kingae peut être une cause sousdiagnostiquée d'arthrite septique chez les enfants canadiens, car elle est difficile à développer en culture et qu'elle est plus facile à déceler à l'aide de méthodes moléculaires. OBJECTIFS: Déterminer si le K kingae est présent dans des prélèvements de liquide articulaire à bactériologie négative provenant d'enfants de l'est de l'Ontario, à l'aide des méthodes de détection par amplification en chaîne par polymérase (PCR). MÉTHODOLOGIE: Les chercheurs ont réalisé la PCR du K kingae dans le liquide articulaire à bactériologie négative résiduel prélevé entre 2010 et 2013 dans un hôpital pour enfants d'Ottawa, en Ontario. Ils ont comparé les caractéristiques cliniques des enfants atteints d'une infection causée par le K kingae à celles d'enfants infectés par les bactéries habituellement responsables de l'arthrite septique, soit le Staphylococcus aureus et le Streptococcus pyogenes. RÉSULTATS: Au total, 50 prélèvements de liquide articulaire ont été soumis pendant la période de l'étude. Dix étaient à bactériologie positive, soit huit au S aureus et deux au S pyogenes. Il y avait du liquide articulaire résiduel pour 27 des 40 prélèvements à bactériologie négative, et le K kingae a été décelé par PCR dans sept d'entre eux (25,93 %). Les enfants infectés par le K kingae étaient beaucoup plus jeunes (âge médian de 1,7 an plutôt que de 11,3 ans; P=0,01) et avaient un taux de protéine C-réactive plus faible (médiane de 23,8 mg/L plutôt que de 117,6 mg/L; P=0,01) que ceux infectés par d'autres bactéries. CONCLUSIONS: Le K kingae était souvent décelé par PCR dans les prélèvements de liquide articulaire à bactériologie négative réalisés chez des enfants de l'est de l'Ontario. Il semble justifié d'effectuer une PCR du K kingae dans les prélèvements articulaires à bactériologie négative réalisés chez les enfants.

Direct Streptococcus pneumoniae real-time PCR serotyping from pediatric parapneumonic effusions.

BACKGROUND: To determine the serotypes of Streptococcus pneumoniae responsible for pneumonia complicated by parapneumonic effusion in children, we performed real-time PCR based pneumococcal "serotyping" directly on parapneumonic fluid samples. METHODS: Specimens were collected at two children's hospitals in Ontario, Canada from 2009 to 2011. Samples in which S. pneumoniae was detected by PCR were tested with serotype-specific 5'exonuclease PCR assays for the 13 serotypes contained in the 13-serotype pneumococcal vaccine. RESULTS: Thirty-five S. pneumoniae PCR-positive pleural samples were studied. Pneumococcal serotyping PCR assays were positive for 34 of 35 (97%). Serotype 3 was detected most frequently, in 19/35 (54%), followed by serotype 19A in 9/35 (26%), serotype 7 F/A in 4/35 (11%), serotype 1 in 1/35 (3%), and serotype 6A also in 1/35 (3%). CONCLUSIONS: PCR testing demonstrated that the vast majority (97%) of S. pneumoniae parapneumonic effusions were caused by serotypes present in the 13-serotype vaccine that were not present in the original 7 serotype vaccine. This suggests that use of the 13-serotype vaccine could potentially prevent many S. pneumoniae pneumonias complicated by parapneumonic effusion in our region, provided serotype replacement does not occur.

Real-time polymerase chain reaction for microbiological diagnosis of parapneumonic effusions in Canadian children.

BACKGROUND: Community-acquired pneumonia (CAP) complicated by parapneumonic effusion/empyema is an infectious syndrome commonly encountered by physicians caring for children in Canada. OBJECTIVE: To investigate the incremental benefit of novel molecular testing for the microbiological diagnosis of pediatric CAP complicated by parapneumonic effusion/empyema in Canada. METHODS: A convenience sample of pleural fluid from 56 children who had been admitted to hospital in Ontario with CAP complicated by parapneumonic effusion between 2009 and 2011 was examined. Multiple uniplex real-time polymerase chain reaction (PCR) testing was performed on these pleural fluids and compared with traditional culture-based testing of blood and pleural fluid samples. RESULTS: Molecular methods detected a pathogen in 82% of cases, whereas traditional cultures of blood and pleural fluids detected a pathogen in only 25%. The majority of parapneumonic effusions were associated with pneumococcal infection; Streptococcus pneumoniae was detected in 62% of the samples using molecular methods but in only 14% of samples using culture-based methods. Streptococcus pyogenes, detected in 16% of samples using PCR, was the second most common pathogen found. No patients were found to have empyema caused by Staphylococcus aureus. DISCUSSION: The results showed that multiple uniplex real-time PCR performed substantially better than traditional culture methods for microbiological diagnosis of CAP complicated by effusion/ empyema. S pneumoniae and S pyogenes were found to be responsible for the majority of infections. The approach detected pathogens in a similar proportion of pleural fluid samples as previously reported nested PCR assays; furthermore, the real-time closed-well approach also minimized the risk of nonspecificity due to cross-contamination relative to nested PCR. CONCLUSIONS: Real-time PCR for the detection of bacterial DNA in pleural fluids has the potential to better define the microbiological cause of pediatric CAP. This approach could help clinicians provide targeted antimicrobial therapy.

HISTORIQUE: La pneumonie d'origine non nosocomiale (PONN) compliquée par un épanchement parapneumonique ou un empyème est un syndrome infectieux qu'observent souvent les médecins qui soignent des enfants au Canada. OBJECTIF: Examiner les avantages incrémentiels de nouveaux tests moléculaires pour poser un diagnostic microbiologique de PONN pédiatrique compliquée par un épanchement parapneumonique ou un empyème au Canada. MÉTHODOLOGIE: Les chercheurs ont examiné un échantillon de commodité de liquide pleural prélevé chez 56 enfants hospitalisés en Ontario à cause d'une PONN compliquée par un épanchement parapneumonique entre 2009 et 2011. Ils ont effectué de multiples tests de réaction en chaîne de la polymérase (PCR) uniplexe en temps réel sur ce liquide pleural et les ont comparés aux examens classiques des cultures de sang et de liquide pleural. RÉSULTATS: Les méthodes moléculaires ont permis de déceler un pathogène dans 82 % des cas, tandis que les cultures classiques de sang et de liquide pleural n'ont permis d'en déceler que dans 25 % des cas. La majorité des épanchements parapneumoniques s'associait à une infection pneumococcique. En effet, les chercheurs ont décelé un Streptococcus pneumoniae dans 62 % des échantillons au moyen des méthodes moléculaires, mais seulement dans 14 % des échantillons au moyen des méthodes de culture. Le Streptococcus pyogenes, décelé dans 16 % des échantillons par PCR, était le deuxième pathogène en importance à avoir été décelé. Aucun patient n'avait d'empyème causé par le Staphylococcus aureus. EXPOSÉ: Les résultats ont démontré que de multiples tests de PCR uniplexe en temps réel donnaient des résultats beaucoup plus précis que les cultures classiques pour poser un diagnostic microbiologique de PONN compliquée par un épanchement ou un empyème. Le S pneumoniae et le S pyogenes étaient responsables de la majorité des infections. Cette méthode permet de déceler des pathogène dans une proportion similaire d'échantillons de liquide pleural que les PCR nichées déclarées antérieurement. De plus, la technique en temps réel par système fermé réduisait le risque de non-spécificité attribuable à la contamination croisée observée en cas de PCR nichée. CONCLUSIONS: La PRC en temps réel pour déceler l'ADN bactérien dans le liquide pleural définit peut-être mieux la cause microbiologique de la PONN pédiatrique. Cette approche pourrait aider les cliniciens à proposer un traitement antimicrobien ciblé.

Cerebral vasospasm as a consequence of pituitary apoplexy: illustrative case.

BACKGROUND: Cerebral vasospasm is a rare but devastating complication following pituitary apoplexy. Cerebral vasospasm is often associated with subarachnoid hemorrhage (SAH), and early detection is crucial for proper management. OBSERVATIONS: The authors present a case of cerebral vasospasm after endoscopic endonasal transsphenoid surgery (EETS) in a patient with pituitary apoplexy secondary to pituitary adenoma. They also present a literature review of all similar cases published to date. The patient is a 62-year-old male who presented with headache, nausea, vomiting, weakness, and fatigue. He was diagnosed with pituitary adenoma with hemorrhage, for which he underwent EETS. Pre- and postoperative scans showed SAH. On postoperative day 11, he presented with confusion, aphasia, arm weakness, and unsteady gait. Magnetic resonance imaging and computed tomography scans were consistent with cerebral vasospasm. The patient underwent endovascular treatment of acute intracranial vasospasm and was responsive to intra-arterial milrinone and verapamil infusion of the bilateral internal carotid arteries. There were no further complications. LESSONS: Cerebral vasospasm is a severe complication that can occur after pituitary apoplexy. It is essential to assess the risk factors linked to the cerebral vasospasm. In addition, a high index of suspicion will allow neurosurgeons to diagnose cerebral vasospasm after EETS early and take the necessary measures to manage it accordingly.

Short histological kaleidoscope - recent findings in histology. Part III.

The paper provides an overview of the current understanding of different cells' biology (e.g., keratinocytes, Paneth cells, myoepithelial cells, myofibroblasts, chondroclasts, monocytes, atrial cardiomyocytes), including their origin, structure, function, and role in disease pathogenesis, and of the latest findings in the medical literature concerning the brown adipose tissue and the juxtaoral organ of Chievitz.

The Physical Activity Assessment of Adults With Type 2 Diabetes Using Accelerometer-Based Cut Points: Scoping Review.

BACKGROUND: Incorporating physical activity into lifestyle routines is recommended for individuals with type 2 diabetes. Accelerometers offer a promising method for objectively measuring physical activity and for assessing interventions. However, the existing literature for accelerometer-measured physical activity among middle-aged and older adults with type 2 diabetes is lacking. OBJECTIVE: This study aims to identify research studies in which accelerometer-based cut points were used to classify the physical activity intensity of middle-aged to older adults with type 2 diabetes as sedentary, light, moderate, vigorous, and very vigorous, and to determine if validated accelerometer cut points specifically for this population exist. METHODS: We followed the Joanna Briggs Institute methodology for scoping reviews. Between June 23 and July 12, 2020, two reviewers independently screened records from four databases (PubMed, Web of Science, Embase, Engineering Village) and the ActiGraph Corp web site for eligible studies that included patients with type 2 diabetes with a sample mean age ≥50 years, used research-grade accelerometers, applied cut points to categorize objectively measured physical activity, and were available in English. We excluded studies reporting exclusively steps or step counts measured by accelerometers or pedometers and conference abstracts or other sources that did not have a full text available. Data extraction was completed using Microsoft Excel. Data for the following variables were tabulated based on frequency distributions: study design, accelerometer type, device placement, epoch length, total wear time, and cut points used. Study aims and participant demographic data were summarized. RESULTS: A total of 748 records were screened at the abstract level, and 88 full-text articles were assessed for eligibility. Ultimately, 46 articles were retained and analyzed. Participants' mean ages ranged from 50 to 79.9 years. The ActiGraph accelerometer and the Freedson et al and Troiano et al counts-per-minute cut points were the most frequently used across the literature. Freedson et al and Troiano et al counts-per-minute cut points for light, moderate, and vigorous activity correspond to <1952, 1952-5724, and ≥5725, and 100-2019, 2020-5998, and ≥5999, respectively. The Lopes et al cut points were developed by calibrating the ActiGraph in middle-aged and older adults with overweight/obesity and type 2 diabetes. These counts-per-minute thresholds are ≥200 (light), ≥1240 (moderate), and ≥2400 (vigorous), and were applied in 1 interventional study. CONCLUSIONS: An assortment of accelerometer cut points have been used by researchers to categorize physical activity intensity for middle-aged and older adults with diabetes. Only one set of cut points was validated and calibrated in our population of interest. Additional research is warranted to address the need for diabetes-specific cut points to inform public health recommendations. This includes confirmation that the Lopes et al cut points reflect clinically meaningful changes in physical activity for adults with diabetes who have comorbidities other than overweight/obesity and the development of relative intensity cut points that may be more suitable for those with suboptimal physical functioning.

Short histological kaleidoscope - recent findings in histology. Part II.

This article focuses on the latest histological knowledge in the field regarding the peripheral lymphoid system [mucosa-associated lymphoid tissue (MALT), bronchus-associated lymphoid tissue (BALT), gut-associated lymphoid tissue (GALT)], the thymus stroma, some of the various corpuscles of the human body (Hassall's corpuscles in thymus, arenaceous corpuscles in pineal gland, corpora amylacea in prostate and other locations) and Fañanas glial cells in the cerebellum.

Short histological kaleidoscope - recent findings in histology. Part I.

This article is a review of new advances in histology, concerning either classification or structure of different tissular elements (basement membrane, hemidesmosomes, urothelium, glandular epithelia, adipose tissue, astrocytes), and various organs' constituents (blood-brain barrier, human dental cementum, tubarial salivary glands, hepatic stellate cells, pineal gland, fibroblasts of renal interstitium, Leydig testicular cells, ovarian hilar cells), as well as novel biotechnological techniques (tissue engineering in angiogenesis), recently introduced.