Multimodal data fusion using sparse canonical correlation analysis and cooperative learning: a COVID-19 cohort study.

Through technological innovations, patient cohorts can be examined from multiple views with high-dimensional, multiscale biomedical data to classify clinical phenotypes and predict outcomes. Here, we aim to present our approach for analyzing multimodal data using unsupervised and supervised sparse linear methods in a COVID-19 patient cohort. This prospective cohort study of 149 adult patients was conducted in a tertiary care academic center. First, we used sparse canonical correlation analysis (CCA) to identify and quantify relationships across different data modalities, including viral genome sequencing, imaging, clinical data, and laboratory results. Then, we used cooperative learning to predict the clinical outcome of COVID-19 patients: Intensive care unit admission. We show that serum biomarkers representing severe disease and acute phase response correlate with original and wavelet radiomics features in the LLL frequency channel (cor(Xu1, Zv1) = 0.596, p value < 0.001). Among radiomics features, histogram-based first-order features reporting the skewness, kurtosis, and uniformity have the lowest negative, whereas entropy-related features have the highest positive coefficients. Moreover, unsupervised analysis of clinical data and laboratory results gives insights into distinct clinical phenotypes. Leveraging the availability of global viral genome databases, we demonstrate that the Word2Vec natural language processing model can be used for viral genome encoding. It not only separates major SARS-CoV-2 variants but also allows the preservation of phylogenetic relationships among them. Our quadruple model using Word2Vec encoding achieves better prediction results in the supervised task. The model yields area under the curve (AUC) and accuracy values of 0.87 and 0.77, respectively. Our study illustrates that sparse CCA analysis and cooperative learning are powerful techniques for handling high-dimensional, multimodal data to investigate multivariate associations in unsupervised and supervised tasks.

Compliance with guideline recommendations in the management of patients with hospitalized community-acquired pneumonia.

Compliance with guidelines in the empirical treatment for community-acquired pneumonia (CAP) is very important to increase treatment success and reduce mortality. This study aimed to determine compliance with guideline recommendations for CAP and define the role of the clinical pharmacist (CP). Patients diagnosed with CAP were evaluated retrospectively between January 2018 and January 2020 and prospectively between February 2020 and February 2021. Compliance with guidelines was evaluated according to the local, national (Turkish Thoracic Society), and international (American Thoracic Society and Infectious Disease Society of America, European Society of Clinical Microbiology and Infectious Diseases) guidelines. A total of 751 patients (423 in the retrospective and 328 in the prospective period) were included. It was determined that the 30-day mortality and length of stay were higher in patients who were not treated according to the guidelines. The compliance for empirical treatments was 16.3%-59.1% and 7.8%-30.1% in retrospective and prospective periods, respectively. During the prospective period, a total of 603 recommendations were made by CP, and 578 (95.9%) were accepted and implemented. In the prospective period, treatment duration was shortened, inappropriate fluoroquinolone use was decreased, the switch to oral treatment was increased, and the number of potential drug-drug interactions was decreased (p < 0.001). Compliance with guidelines is essential to be improved to reduce mortality, shorten the length of stay, determine the appropriate antimicrobial duration, and reduce the use of fluoroquinolones and broad-spectrum antibiotics unless necessary. CP intervention contributes to the rational selection of antimicrobials, limiting drug-drug interactions, avoiding toxicities, and compliance with guidelines.

Invasive fungal rhinosinusitis by Fusarium proliferatum/annulatum in a patient with acute myeloid leukemia: A case report and review of the literature.

Antifungal prophylaxis with a mold-effective agent has led to a substantial decrease in invasive infections caused by Aspergillus spp. in the management of patients with acute myeloid leukemia undergoing induction chemotherapy. However, difficult-to-treat infections caused by other molds, such as Fusarium, Lomentospora, and Scedosporium species may still complicate the neutropenic period. Here, we present a case of a 23-year-old woman with acute myeloid leukemia who developed a breakthrough invasive fungal rhinosinusitis caused by Fusarium proliferatum/annulatum on posaconazole prophylaxis. The infection was diagnosed using clinical, microbiological, and radiological criteria and the isolate was identified using Matrix Assisted Lazer Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) and sequencing. We searched Pubmed with "Fusarium proliferatum", "Fusarium annulatum", "immunosuppression AND fusariosis", "rhinosinusitis AND Fusarium proliferatum" and summarized the English literature for similar rhinosinusitis cases infected with the same pathogen.

Predictors of Severity of Influenza-Related Hospitalizations: Results From the Global Influenza Hospital Surveillance Network (GIHSN).

BACKGROUND: The Global Influenza Hospital Surveillance Network (GIHSN) has since 2012 provided patient-level data on severe influenza-like-illnesses from >100 participating clinical sites worldwide based on a core protocol and consistent case definitions. METHODS: We used multivariable logistic regression to assess the risk of intensive care unit admission, mechanical ventilation, and in-hospital death among hospitalized patients with influenza and explored the role of patient-level covariates and country income level. RESULTS: The data set included 73 121 patients hospitalized with respiratory illness in 22 countries, including 15 660 with laboratory-confirmed influenza. After adjusting for patient-level covariates we found a 7-fold increase in the risk of influenza-related intensive care unit admission in lower middle-income countries (LMICs), compared with high-income countries (P = .01). The risk of mechanical ventilation and in-hospital death also increased by 4-fold in LMICs, though these differences were not statistically significant. We also find that influenza mortality increased significantly with older age and number of comorbid conditions. Across all severity outcomes studied and after controlling for patient characteristics, infection with influenza A/H1N1pdm09 was more severe than with A/H3N2. CONCLUSIONS: Our study provides new information on influenza severity in underresourced populations, particularly those in LMICs.

Multimodal Biomedical Data Fusion Using Sparse Canonical Correlation Analysis and Cooperative Learning: A Cohort Study on COVID-19.

Through technological innovations, patient cohorts can be examined from multiple views with high-dimensional, multiscale biomedical data to classify clinical phenotypes and predict outcomes. Here, we aim to present our approach for analyzing multimodal data using unsupervised and supervised sparse linear methods in a COVID-19 patient cohort. This prospective cohort study of 149 adult patients was conducted in a tertiary care academic center. First, we used sparse canonical correlation analysis (CCA) to identify and quantify relationships across different data modalities, including viral genome sequencing, imaging, clinical data, and laboratory results. Then, we used cooperative learning to predict the clinical outcome of COVID-19 patients. We show that serum biomarkers representing severe disease and acute phase response correlate with original and wavelet radiomics features in the LLL frequency channel (corr(Xu1, Zv1) = 0.596, p-value < 0.001). Among radiomics features, histogram-based first-order features reporting the skewness, kurtosis, and uniformity have the lowest negative, whereas entropy-related features have the highest positive coefficients. Moreover, unsupervised analysis of clinical data and laboratory results gives insights into distinct clinical phenotypes. Leveraging the availability of global viral genome databases, we demonstrate that the Word2Vec natural language processing model can be used for viral genome encoding. It not only separates major SARS-CoV-2 variants but also allows the preservation of phylogenetic relationships among them. Our quadruple model using Word2Vec encoding achieves better prediction results in the supervised task. The model yields area under the curve (AUC) and accuracy values of 0.87 and 0.77, respectively. Our study illustrates that sparse CCA analysis and cooperative learning are powerful techniques for handling high-dimensional, multimodal data to investigate multivariate associations in unsupervised and supervised tasks.

Cessation of Rectal Screening for Vancomycin-Resistant Enterococci: Experience from a Tertiary Care Hospital from Türkiye.

OBJECTIVE: Here, we compared the impact of different polices on the epidemiology of Vancomycin-resistant Enterococcus faecium bloodstream infections (VRE-BSIs) in a tertiary care hospital including two hospital buildings (oncology and adult hospitals) in the same campus. MATERIAL AND METHODS: All patients who were hospitalized in high-risk units were screened weekly for VRE colonization via rectal swab between January 2006 and January 2013. After January 2013, VRE screening was only performed in cases of suspicion of VRE outbreak and during point prevalence studies to evaluate the epidemiology of VRE colonization. Contact precautions were in place for all VRE-positive patients. The incidence density rates of hospital-acquired (HA)-VRE-BSIs were compared between two periods. RESULTS: While the rate of VRE colonization was higher in the second period (5% vs. 9.5% (p < 0.01) for the adult hospital, and 6.4% vs. 12% (p = 0.02 for the oncology hospital), there was no increase in the incidence rate HA-VRE BSIs after the cessation of routine rectal screening in either of the hospitals. CONCLUSION: Screening policies should be dynamic and individualized according to the epidemiology of VRE as well as the workforce and cost. Periodical rectal screening of VRE can be discontinued if suspicion of an outbreak can be carefully monitored.

Macrolides for better resolution of community-acquired pneumonia: A global meta-analysis of clinical outcomes with focus on microbial aetiology.

OBJECTIVES: This meta-analysis examined the effect of macrolides on resolution of community-acquired pneumonia (CAP) and interpretation of clinical benefit according to microbiology; emphasis is given to data under-reported countries (URCs). METHODS: This meta-analysis included 47 publications published between 1994 and 2022. Publications were analysed for 30-d mortality (58 759 patients) and resolution of CAP (6465 patients). A separate meta-analysis was done for the prevalence of respiratory pathogens in URCs. RESULTS: Mortality after 30 d was reduced by the addition of macrolides (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.51-0.82). The OR for CAP resolution when macrolides were added to the treatment regimen was 1.23 (95% CI 1.00-1.52). In the CAP resolution analysis, the most prevalent pathogen was Streptococcus pneumoniae (12.68%; 95% CI 9.36-16.95%). Analysis of the pathogen epidemiology from the URCs included 12 publications. The most prevalent pathogens were S. pneumoniae (24.91%) and Klebsiella pneumoniae (12.90%). CONCLUSION: The addition of macrolides to the treatment regimen led to 35% relative decrease of 30-d mortality and to 23% relative increase in resolution of CAP.

Comparison of Maternal and Perinatal Outcomes Associated with Delta (B.1.617.2) and Other Variants of Severe Acute Respiratory Syndrome-Coronavirus 2.

OBJECTIVE: To compare the frequency of adverse maternal and perinatal outcomes associated with delta (B.1.617.2) and other variants of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). STUDY DESIGN: An observational study. Place and Duration of the Study: Bursa City Hospital, Bursa, Turkey, from March 2020 to February 2022. METHODOLOGY: The study included 423 pregnant women diagnosed with COVID-19 based on real-time reverse transcriptase-polymerase chain reaction (RT-PCR) testing. The patients were divided into the delta variant (n=135) and other variants (n=288) (alpha, beta, gamma) groups, and maternal and perinatal outcomes were compared between the groups. Data including symptoms, laboratory findings, radiological findings, hospital and intensive care unit (ICU) stay, delivery outcomes, and mortality rates were recorded. RESULTS: The delta variant group demonstrated higher rates of moderate and severe pneumonia than the other variant group (p=0.005). According to the World Health Organization (WHO) classification, 49.6% and 18.5% of patients experienced moderate and severe disease, respectively in the delta variant group, compared to 38.5% and 10.1%, respectively in the other variant group (p=0.001). A total of 20.0% of the patients in the delta variant group and 8.3% of the patients in the other variant group required ICU stay. The length of ICU stay was significantly longer in the delta variant group (p=0.001). CONCLUSION: The rates of maternal morbidity and mortality increased in the pregnant population with low rates of vaccination in the period of the fourth wave which was associated with the delta variant. No significant difference was observed in perinatal morbidity between the delta and other variants. KEY WORDS: COVID-19, Delta variant, Maternal morbidity, Perinatal outcomes, Adverse pregnancy outcomes.

Evaluation of Histopathologic Alterations in First-trimester COVID-19-positive Pregnancies Ending in Abortion.

This study aims to evaluate histopathologic alterations and the presence of chronic histiocytic intervillositis in first-trimester coronavirus-2019 (COVID-19)-positive pregnancies ending in abortion, compared with those at a similar gestational week and undergoing curettage before the pandemic. This retrospective case-control study consisted of 9 patients who were infected with COVID-19 and undergoing curettage for abortion between April 2020 and January 2021. The control group consisted of 34 patients with a similar gestational age who underwent curettage for abortion before August 2019. Demographic and clinical data were recorded. A histopathologic examination of the placental specimens was performed. The CD68 immunostaining was performed to detect intravillous and intervillous histiocytes. At the time of diagnosis of COVID 19, 7 patients (77.8%) of COVID-19-positive women had symptoms with the most common symptoms of fatigue (66.7%) and cough (55.6%). Histopathologic examination revealed that the rate of intravillous and intervillous calcification, intervillous fibrinoid deposition, hydropic villi and acute lymphocytic villitis, and fetal and maternal thrombi was significantly higher in the COVID-19-positive patients than the control group ( P =0.049, 0.002, 0.049, 0.014, 0.008, 0.001, and 0.014, respectively). There was a significant difference in the CD68 staining of the intravillous and intervillous histiocytes between the groups ( P =0.001). This study showed a significant increase in the intervillous fibrinoid deposition, thrombi formation in the maternal and fetal vascular structures, acute lymphocytic villitis, and an increase of CD68 + stained histiocytes in the intravillous and intervillous spaces in women infected with COVID-19 during the first trimester of pregnancy.

[Investigation of the Frequency of Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis and Mycoplasma genitalium in Men Living with HIV in Terms of Sociodemographic Characteristics and Behavioral Risk Factors]. / HIV ile Yasayan Erkeklerde Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis ve Mycoplasma genitalium Sikliginin Sosyodemografik Özellikler ve Davranissal Risk Faktörleri ile Birlikte Arastirilmasi.

The aim of this study was to investigate the frequency of Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis and Mycoplasma genitalium in men living with HIV in terms of sociodemographic characteristics and behavioral risk factors. In this cross-sectional, single center study, all HIV-infected male patients, aged ≥ 18 years, including those being followed-up (n= 142) and the new admissions (n= 16) at Hacettepe University, Department of Infectious Diseases between March 1st, 2017 and May 1st, 2018 were included. After obtaining the informed consent form; age, follow-up days in STI-clinic, marital status, education, employment status; STI-related sign and symptoms, prior STI diagnosis, multiple sexual partners during the last year, exchanging sex for money, sexual orientation, drug use, condom use with regular and casual partner and also risk factors regarding partners were inquired as behavioural risk factors. A sample of first-voided urine of each participant was tested for the presence of Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis and Mycoplasma genitalium by using nucleic acid amplification test (NAAT) (BD-MAX system, BD Diagnostics, USA) and BD MAX Mycoplasma-Ureaplasma-OSR for BioGX, (BD Diagnostics, The Netherlands). All participants living with HIV, men who have sex with men (MSM) and heterosexual men were grouped as STI-positive and STI-negative and compared. For all statistical analysis, SPSS 24 software was used. During the period of 14 months; the data was determined as follows: median follow-up time was 1138 (IQR= 159.5- 1494.5) days, median age was 35 (IQR= 28-42) years, 73.3% were single, 68.3% were at least college graduates or had higher educational attainment, 78.1% were currently employed. Of the participants, 26.9% reported STI-related sign and symptoms, 50.0% at least one STI episode in the past. Nine (5.6%) M.genitalium, five (3.1%) N.gonorrhoeae, and four (2.5%) C.trachomatis were detected in the urine samples of 17 (10.7%) individuals. N.gonorrhoeae and C.trachomatis were detected simultaneously in only one patient's urine sample. STI-positive patients (n= 17) were determined to be younger compared to STI-negative group [(p= 0.02; 27 years (IQR= 24-37) vs 35 years (IQR= 28-42)], had prominent STI-related signs and symptoms (p< 0.001) and had more multiple sexual partners (p= 0.03). The median CD4+ T lymphocyte count were relatively lower (p= 0.03) in STI-positive patients and plasma HIV RNA level was higher compared to the STI-negative participants (p= 0.05). STI-positive MSM group were younger [p= 0.01; 26 years (IQR= 23.5-29) vs 33 years, (IQR= 28-40)], STI-related signs and symptoms were more prominent (p= 0.02), the frequency of exchanging sex for money/drugs among their partners (p= 0.03) was higher compared to their STI-negative counterparts. Among STI-positive heterosexual patients, the presence of STI-related signs and symptoms (p= 0.04), drug use among their partners (p= 0.04) and plasma HIV RNA level (p<0.01) were significantly higher. STI was identified as an important health problem in this series of men living with HIV, 63.0% of whom had MSM and had a relatively high education level and socioeconomic status. Young age, having multiple partners, drug use, exchanging sex for money/drugs were prominent among the participants and their partners. Public health studies should focus on preventing STIs in young people living with HIV who have behavioral risk factors.

Detection of Non-Alcoholic Fatty Liver Disease with Non-invasive Tools in Turkish People Living with HIV and with Apparently Normal Liver Function.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become a significant cause of mortality and morbidity in people living with HIV. OBJECTIVE: We aimed to investigate NAFLD presence by magnetic resonance imaging (MRI) methods, including MRI-derived proton density fat fraction (MRI-PDFF) and MRE, and ultrasound elastography among Turkish people living with HIV (PLWH), and identify factors correlated with fatty liver. METHODS: We included 57 PLWH attending outpatient clinics on antiretroviral therapy (ART) for more than six months, without HBV/HCV co-infection, significant alcohol consumption, active opportunistic infection, previously diagnosed hepatobiliary disease, T2DM, and hyperlipidemia. We performed MRI, MRE, and US elastography on all participants. RESULTS: The mean age of the participants (M/F, 47/10) was 41.7± 12 years. The median duration of HIV infection was 3 (0.5-19 years) years. The mean MRI-PDFF was 4.4 ± 3.8 %, and 11 had fatty liver. The mean MRE value was 2.27 ± 0.6 kPa, inflammation was present in 16, and 4 participants had values consistent with fibrosis. The mean US elastography of the study population was 4.1±2.4 kPa. The mean right and left CCA intima-media of the study population was 0.65± 0.23 mm and 0.66± 0.25 mm; 16 had increased intima-media thickness. In patients with fatty liver, a significant positive correlation was present between MRE and CCA intima-media thickness (rs=0.82, p:0.006 for MRE-left CCA; r=0.68, p=0.042 for MRE-right CCA). CONCLUSION: We demonstrated that even a significant proportion of PLWH individuals with normal transaminase levels have fatty liver. Future prospective trials are warranted to understand and mitigate the risk factors, course of NAFLD, and accurate non-invasive tests, predicting fibrosis in people living with HIV.

Modeling the future of HIV in Turkey: Cost-effectiveness analysis of improving testing and diagnosis.

AIMS: This study aimed to determine HIV incidence and prevalence in Turkey and to estimate the cost-effectiveness of improving testing and diagnosis in the next 20 years. BACKGROUND: HIV incidence in Turkey has been rapidly increasing in the last decade with a particularly high rate of infection for younger populations, which underscores the urgent need for a robust prevention program and improved testing capacity for HIV. METHODS: We developed a dynamic compartmental model of HIV transmission and progression among the Turkish population aged 15-64 and assessed the effect of improving testing and diagnosis. The model generated the number of new HIV cases by transmission risk and CD4 level, HIV diagnoses, HIV prevalence, continuum of care, the number of HIV-related deaths, and the expected number of infections prevented from 2020 to 2040. We also explored the cost impact of HIV and the cost-effectiveness of improving testing and diagnosis. RESULTS: Under the base case scenario, the model estimated an HIV incidence of 13,462 cases in 2020, with 63% undiagnosed. The number of infections was estimated to increase by 27% by 2040, with HIV incidence in 2040 reaching 376,889 and HIV prevalence 2,414,965 cases. Improving testing and diagnosis to 50%, 70%, and 90%, would prevent 782,789, 2,059,399, and 2,336,564 infections-32%, 85%, and 97% reduction in 20 years, respectively. Improved testing and diagnosis would reduce spending between $1.8 and $8.8 billion. CONCLUSIONS: In the case of no improvement in the current continuum of care, HIV incidence and prevalence will significantly increase over the next 20 years, placing a significant burden on the Turkish healthcare system. However, improving testing and diagnosis could substantially reduce the number of infections, ameliorating the public health and disease burden aspects.

Diagnostic stewardship in infectious diseases: a continuum of antimicrobial stewardship in the fight against antimicrobial resistance.

Antimicrobial resistance (AMR) has been exacerbated by the inappropriate use of diagnostics, leading to excessive prescription of antimicrobials, and is an imminent threat to global health. Diagnostic stewardship (DS) is an auxiliary to antimicrobial stewardship (AMS) and comprises ordering the right tests, for the right patient, at the right time. It also promotes the judicious use of rapid and novel molecular diagnostic tools to enable the initiation of proper antibiotic therapy, while avoiding excessive use of broad-spectrum antibiotics. Proper interpretation of test results is crucial to avoid overdiagnosis and excessive healthcare costs. Although many rapid diagnostic tools have been developed with a high diagnostic yield, they are often limited by accessibility, cost, and lack of knowledge regarding their use. Careful consideration of clinical signs and symptoms with knowledge of the local epidemiology are essential for DS. This enables appropriate interpretation of microbiological results. Multidisciplinary teams that include well trained professionals should cooperate to promote DS. Challenges and barriers to the implementation of DS are mostly caused by scarcity of resources and lack of trained personnel and, most importantly, lack of knowledge. The lack of resources is often due to absence of awareness of the impact that good medical microbiology diagnostic facilities and expertise can have on the proper use of antibiotics.

Impact of pharmacist-led educational intervention on pneumococcal vaccination rates in cancer patients: a randomized controlled study.

PURPOSE: This study aimed to evaluate clinical pharmacist's contribution to the pneumococcal vaccination rate by providing education to cancer patients in hospital settings. METHODS: This study was conducted in 2 tertiary-care hospitals' medical oncology outpatient clinics. Patients over 18 years of age and diagnosed with cancer for less than 2 years, in remission stage, and have not previously received the pneumococcal vaccine were included. Patients were randomized to intervention and control groups. The intervention group was provided vaccination education and recommended to receive the PCV13 vaccine. The control group received routine care. Patients' knowledge about pneumonia/pneumococcal vaccine, Vaccine Attitude Examination Scale (VAX) score, and vaccination rates were evaluated at baseline and 3 months after the education. RESULTS: A total of 235 patients (intervention: 117, control: 118) were included. The mean age ± SD was 57.86 ± 11.88 years in the control and 60.68 ± 11.18 years in the intervention groups. The numbers of correct answers about pneumonia/pneumococcal vaccine (p = 0.482) and VAX scores (p = 0.244) of the groups were similar at baseline. After the intervention, the median (IQR) number of correct answers in intervention group [10(3)] was higher than control group [8(4)] (p < 0.001). After the education, the total VAX score (mean ± SD) was less in intervention group (33.09 ± 7.018) than the control group (36.07 ± 6.548) (p = 0.007). Three months after the education, 20.2% of the patients in the intervention and 6.1% in the control groups were vaccinated with pneumococcal vaccine (p = 0.003). CONCLUSIONS: The pneumococcal vaccination rate in cancer patients has increased significantly by the education provided by a clinical pharmacist in hospital settings.

Human memory T cell dynamics after aluminum-adjuvanted inactivated whole-virion SARS-CoV-2 vaccination.

This study evaluates the functional capacity of CD4+ and CD8+ terminally-differentiated effector (TEMRA), central memory (TCM), and effector memory (TEM) cells obtained from the volunteers vaccinated with an aluminum-adjuvanted inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac). The volunteers were followed for T cell immune responses following the termination of a randomized phase III clinical trial. Seven days and four months after the second dose of the vaccine, the memory T cell subsets were collected and stimulated by autologous monocyte-derived dendritic cells (mDCs) loaded with SARS-CoV-2 spike glycoprotein S1. Compared to the placebo group, memory T cells from the vaccinated individuals significantly proliferated in response to S1-loaded mDCs. CD4+ and CD8+ memory T cell proliferation was detected in 86% and 78% of the vaccinated individuals, respectively. More than 73% (after a short-term) and 62% (after an intermediate-term) of the vaccinated individuals harbored TCM and/or TEM cells that responded to S1-loaded mDCs by secreting IFN-γ. The expression of CD25, CD38, 4-1BB, PD-1, and CD107a indicated a modulation in the memory T cell subsets. Especially on day 120, PD-1 was upregulated on CD4+ TEMRA and TCM, and on CD8+ TEM and TCM cells; accordingly, proliferation and IFN-γ secretion capacities tended to decline after 4 months. In conclusion, the combination of inactivated whole-virion particles with aluminum adjuvants possesses capacities to induce functional T cell responses.

Does marking as sterile mean really sterile? Stenotrophomonas maltophilia outbreak caused by a blood-gas injector containing liquid heparin.

An outbreak investigation was initiated after detecting an increase in the number of patients with Stenotrophomonas maltophilia bloodstream infections (SM-BSIs) througout the hospital. S. maltophilia was isolated from the cultures of blood-gas injectors containing liquid heparin. The incidence density of SM-BSIs decreased significantly after prohibiting the use of those injectors.

Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial.

BACKGROUND: Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants. METHODS: Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures. RESULTS: Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modified intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49-69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute difference and 95% CI - 0.1% [- 8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (- 3.2% [- 9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a significant interaction between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated participants were on average 11 years older, with more comorbidities. CONCLUSION: This clinical trial was prematurely stopped for external evidence and therefore underpowered to conclude on a potential survival benefit of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these findings warrant further investigation in other trials and real-world studies. Trial registration Bari-SolidAct is registered at NCT04891133 (registered May 18, 2021) and EUClinicalTrials.eu ( 2022-500385-99-00 ).

Immunogenicity of two doses of inactive COVID-19 vaccine and third booster dose mRNA vaccine in patients with cancer receiving active systemic therapy.

We aimed to evaluate the seroconversion rates after two doses of inactive COVID-19 vaccine (CoronaVac) and the benefit of a third dose mRNA vaccine booster in patients with cancer receiving active treatment. Patients with solid tumors receiving active treatment (n = 101) and patients with no-cancer (n = 48) as the control group were included in the study. All the patients and controls had received two doses of CoronaVac and a third booster dose of the mRNA vaccine (Bnt162b2). Anti-SARS-CoV-2 Spike Receptor Binding Domain IgG antibody levels after the second and third dose were measured with quantitative ELISA. The median age of the patients was 66 (IQR 60-71). 79% of the patients were receiving chemotherapy, and 21% were receiving immunotherapy at the time of vaccination. Antibody levels measured after two doses of CoronaVac were significantly lower in patients with cancer than in the control group (median 0 µg/ml [IQR 0-1.17 µg/ml] vs median 0.91 µg/ml [IQR 0-2.24 µg/ml], respectively, P = .002). Seropositivity rates were 46.5% in patients with cancer and 72.9% in the control group (P = .002). Antibody measurement was performed in 26 patients after the third dose. Seroconversion rate increased from 46.5% to 88.5% (P < .001), and the antibody titers significantly increased with the third-dose booster (median 0 µg/ml [IQR 0-1.17 µg/ml] after two doses vs 12.6 µg/ml [IQR 1.8-69.1 µg/ml] after third booster dose, P < .001). Immunogenicity of CoronaVac is low in patients with cancer receiving active treatment, and administering a third dose of an mRNA vaccine is effective in terms of improving seroconversion rates.

Prevalence of Common Human Coronaviruses (NL63, 229E, and OC43) in Adults before the COVID-19 Pandemic: a Single-Center Study from Turkey, 2015-2020.

Common Human Coronaviruses (HCoVs), such as NL63, HKU1, 229E, and OC43, induce respiratory tract infections worldwide. Epidemiological studies of HCoVs are of paramount importance because the disease burden and trajectory (in years) have not been well addressed in adults. Here, we aimed to describe the burden of HCoVs in a hospital setting over five years before the coronavirus disease 2019 pandemic. This was a retrospective study of patients (>18 years) between January 1, 2015, and January 1, 2020, whose respiratory specimens were tested by multiplex real-time polymerase chain reaction. In total, 7,861 respiratory samples (4,540 patients) were included, 38% of which tested positive for any respiratory virus. Of these, 212 (12.2%) samples were positive for HCoVs, and their co-infection with other respiratory viruses was 30.6%. Rhinovirus (27.6%) was the most common co-infection among all three HCoVs. The overall prevalence of HCoVs tended to be the highest in the winter (40.9%). Patients aged ≥60 years had the highest prevalence of overall HCoVs (39.7%). Given the duration and large sample size, this study from Turkey is one of the largest to date among adults in the literature. These epidemiological data and molecular surveillance of HCoVs have important implications for the control and prevention of respiratory infections.

Clinical Validation and Evaluation of a Colorimetric SARS-CoV-2 RT-LAMP Assay Against RT-PCR.

Objective: Reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) is one of the time-saving, accurate, and cost-effective alternative methods to real-time polymerase chain reaction (RT-PCR). This study aimed to identify the robustness of a colorimetric RT-LAMP assay kit that we developed, detecting SARS-COV-2 viral RNA within 30 minutes using a primer set special to the N gene against RT-PCR, the gold standard. Materials and Methods: Both symptomatic and asymptomatic subjects were included from a single university hospital and the status of both RT-PCR and RT-LAMP assay results were compared, and the consistency of these two assays was analyzed. Results: We showed that the RT-LAMP and RT-PCR assay results confirmed 90% consistency. When we consider the epidemiologic, clinical, and radiologic evaluation, the consistency reached 97%. Conclusion: The results revealed that the colorimetric RT-LAMP assay was efficient, robust, and rapid to be used as in vitro diagnostic tool to display competitiveness compared with RT-PCR.