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Ingen søgeord valgt.
45 emner vises.
Yawei Wang, Min Wang, Renlong Bao, Ligui Wang, Xinying Du, Shaofu Qiu, Chaojie Yang, Hongbin Song
Journal of Medical Virology, 15.08.2023
Tilføjet 15.08.2023
Journal of Infectious Diseases, 15.08.2023
Tilføjet 15.08.2023
AbstractEbola virus (EBOV) induces cell death not only in infected permissive cells but also in non-permissive, bystander cells by employing different mechanisms. Hydroxycarboxylic Acid Receptor 2 (HCAR2) has been reported to be involved in apoptotic cell death. We previously reported an increase in the expression of HCAR2-specific mRNA in EBOV-infected individuals with fatal outcomes. Here, we report that infection with an EBOV lacking the VP30 gene (EBOVΔVP30) results in the upregulation of HCAR2 mRNA expression in human hepatocyte Huh7.0 cells stably expressing VP30. Transient overexpression of HCAR2 reduced the viability of Huh7.0 cells and human embryonic kidney cells. Phosphatidylserine externalization and cell membrane permeabilization by HCAR2 overexpression was also observed. Interestingly, co-expression of HCAR2 with EBOV VP40 further reduced cell viability in transfected cells compared to HCAR2 co-expression with other viral proteins. Our data suggests that HCAR2 may contribute to EBOV-induced cell death.
Læs mere Tjek på PubMedO’Gara, Brian P.; Tung, Matthew G.; Kennedy, Kevin F.; Espinosa-Leon, Juan P.; Shaefi, Shahzad; Gluck, Jason; Raz, Yuval; Seethala, Raghu; Reich, John A.; Faugno, Anthony J.; Brodie, Daniel; Garan, A. Reshad; Grandin, E. Wilson
Critical Care Medicine, 15.08.2023
Tilføjet 15.08.2023
OBJECTIVES: To determine whether multisite versus single-site dual-lumen (SSDL) cannulation is associated with outcomes for COVID-19 patients requiring venovenous extracorporeal membrane oxygenation (VV-ECMO). DESIGN: Retrospective analysis of the Extracorporeal Life Support Organization Registry. Propensity score matching (2:1 multisite vs SSDL) was used to control for confounders. PATIENTS: The matched cohort included 2,628 patients (1,752 multisite, 876 SSDL) from 170 centers. The mean (sd) age in the entire cohort was 48 (11) years, and 3,909 (71%) were male. Patients were supported with mechanical ventilation for a median (interquartile range) of 79 (113) hours before VV-ECMO support. INTERVENTIONS: None. MEASUREMENTS: The primary outcome was 90-day survival. Secondary outcomes included survival to hospital discharge, duration of ECMO support, days free of ECMO support at 90 days, and complication rates. MAIN RESULTS: There was no difference in 90-day survival (49.4 vs 48.9%, p = 0.66), survival to hospital discharge (49.8 vs 48.2%, p = 0.44), duration of ECMO support (17.9 vs 17.1 d, p = 0.82), or hospital length of stay after cannulation (28 vs 27.4 d, p = 0.37) between multisite and SSDL groups. More SSDL patients were extubated within 24 hours (4% vs 1.9%, p = 0.001). Multisite patients had higher ECMO flows at 24 hours (4.5 vs 4.1 L/min, p < 0.001) and more ECMO-free days at 90 days (3.1 vs 2.0 d, p = 0.02). SSDL patients had higher rates of pneumothorax (13.9% vs 11%, p = 0.03). Cannula site bleeding (6.4% vs 4.7%, p = 0.03), oxygenator failure (16.7 vs 13.4%, p = 0.03), and circuit clots (5.5% vs 3.4%, p = 0.02) were more frequent in multisite patients. CONCLUSIONS: In this retrospective study of COVID-19 patients requiring VV-ECMO, 90-day survival did not differ between patients treated with a multisite versus SSDL cannulation strategy and there were only modest differences in major complication rates. These findings do not support the superiority of either cannulation strategy in this setting.
Læs mere Tjek på PubMedCummings, Matthew J.; Bakamutumaho, Barnabas; Tomoiaga, Alin S.; Owor, Nicholas; Jain, Komal; Price, Adam; Kayiwa, John; Namulondo, Joyce; Byaruhanga, Timothy; Muwanga, Moses; Nsereko, Christopher; Nayiga, Irene; Kyebambe, Stephen; Sameroff, Stephen; Che, Xiaoyu; Lutwama, Julius J.; Lipkin, W. Ian; O’Donnell, Max R.
Critical Care Medicine, 15.08.2023
Tilføjet 15.08.2023
OBJECTIVES: In high-income countries (HICs), sepsis endotypes defined by distinct pathobiological mechanisms, mortality risks, and responses to corticosteroid treatment have been identified using blood transcriptomics. The generalizability of these endotypes to low-income and middle-income countries (LMICs), where the global sepsis burden is concentrated, is unknown. We sought to determine the prevalence, prognostic relevance, and immunopathological features of HIC-derived transcriptomic sepsis endotypes in sub-Saharan Africa. DESIGN: Prospective cohort study. SETTING: Public referral hospital in Uganda. PATIENTS: Adults (n = 128) hospitalized with suspected sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Using whole-blood RNA sequencing data, we applied 19-gene and 7-gene classifiers derived and validated in HICs (SepstratifieR) to assign patients to one of three sepsis response signatures (SRS). The 19-gene classifier assigned 30 (23.4%), 92 (71.9%), and 6 (4.7%) patients to SRS-1, SRS-2, and SRS-3, respectively, the latter of which is designed to capture individuals transcriptionally closest to health. SRS-1 was defined biologically by proinflammatory innate immune activation and suppressed natural killer-cell, T-cell, and B-cell immunity, whereas SRS-2 was characterized by dampened innate immune activation, preserved lymphocyte immunity, and suppressed transcriptional responses to corticosteroids. Patients assigned to SRS-1 were predominantly (80.0% [24/30]) persons living with HIV with advanced immunosuppression and frequent tuberculosis. Mortality at 30-days differed significantly by endotype and was highest (48.1%) in SRS-1. Agreement between 19-gene and 7-gene SRS assignments was poor (Cohen’s kappa 0.11). Patient stratification was suboptimal using the 7-gene classifier with 15.1% (8/53) of individuals assigned to SRS-3 deceased at 30-days. CONCLUSIONS: Sepsis endotypes derived in HICs share biological and clinical features with those identified in sub-Saharan Africa, with major differences in host–pathogen profiles. Our findings highlight the importance of context-specific sepsis endotyping, the generalizability of conserved biological signatures of critical illness across disparate settings, and opportunities to develop more pathobiologically informed sepsis treatment strategies in LMICs.
Læs mere Tjek på PubMedJessica Pope
Lancet Infectious Diseases, 15.08.2023
Tilføjet 15.08.2023
As the COVID-19 pandemic slowly begins to loosen its grip on humanity and international health care, several questions are emerging. Two, however, occur repeatedly, and are perhaps the most crucial: where did SARS-CoV-2 come from, and how do we prevent another pandemic? With evidence indicating that SARS-CoV-2 might have emerged from the area of Huanan Seafood market where live wild animals were sold, scientists postulate that the virus might have been transmitted from animals to humans. A pathogenic jump from animals to humans has been at the heart of several historical pandemics.
Læs mere Tjek på PubMedPriscila F P S Pinto, Camila S S Teixeira, Maria Yury Ichihara, Davide Rasella, Joilda S Nery, Samila O L Sena, Elizabeth B Brickley, Maurício L Barreto, Mauro N Sanchez, Julia M Pescarini
Lancet Infectious Diseases, 15.08.2023
Tilføjet 15.08.2023
The high and sustained risk of tuberculosis among contacts reinforces the need to systematically expand and strengthen contact tracing and preventive treatment policies in Brazil in order to achieve national and international targets for tuberculosis elimination.
Læs mere Tjek på PubMedJun An Kang, Swarnalee Dutta, Yong Hoon Lee
PLoS One Infectious Diseases, 15.08.2023
Tilføjet 15.08.2023
by Jun An Kang, Swarnalee Dutta, Yong Hoon Lee Burkholderia glumae causes bacterial panicle blight (BPB) and bacterial seedling rot (BSR) which are difficult to control in rice plants. Seed disinfection using microbes and eco-friendly materials is an efficient alternative practice for managing BPB and BSR. In this study, we applied Cytobacillus firmus JBRS159 (JBRS159) in combination with silicon dioxide (SiO2) nanoparticle or potassium silicate (K2SiO3) solution to control BSR. JBRS159, SiO2 nanoparticle, and K2SiO3 independently suppressed the BSR disease and promoted growths of rice and Arabidopsis. Population of B. glumae in the treated rice seeds was suppressed by the application of JBRS159 via competitions for nutrients and niches. The mixture of JBRS159 and each Si compound (SiO2 nanoparticle or K2SiO3) was complementary for disease-suppressing and growth-promoting activities of individual treatment. The results of this study indicate that mixture of JBRS159 with each Si compound can be harnessed for disease control and growth promotion as efficient alternatives to chemical pesticides and synthetic fertilizers. The efficacy of JBRS159 and Si compounds in the control of BSR and BPB in the field remains to be evaluated.
Læs mere Tjek på PubMedStefanie Mueller, Johanna Bialas, Stella Ryu, Nicola Catone, Annette Aichem
PLoS One Infectious Diseases, 15.08.2023
Tilføjet 15.08.2023
by Stefanie Mueller, Johanna Bialas, Stella Ryu, Nicola Catone, Annette Aichem The ubiquitin-like modifier FAT10 is highly upregulated under inflammatory conditions and targets its conjugation substrates to the degradation by the 26S proteasome. This process termed FAT10ylation is mediated by an enzymatic cascade and includes the E1 activating enzyme ubiquitin-like modifier activating enzyme 6 (UBA6), the E2 conjugating enzyme UBA6-specific E2 enzyme 1 (USE1) and E3 ligases, such as Parkin. In this study, the function of the HECT-type ubiquitin E3 ligase HUWE1 was investigated as a putative E3 ligase and/or conjugation substrate of FAT10. Our data provide strong evidence that HUWE1 is FAT10ylated in a UBA6 and FAT10 diglycine-dependent manner in vitro and in cellulo and that the HUWE1-FAT10 conjugate is targeted to proteasomal degradation. Since the mutation of all relevant cysteine residues within the HUWE1 HECT domain did not abolish FAT10 conjugation, a role of HUWE1 as E3 ligase for FAT10ylation is rather unlikely. Moreover, we have identified the autophagy-related protein AMBRA1 as a new FAT10 interaction partner. We show that the HUWE1-FAT10 conjugate formation is diminished in presence of AMBRA1, while the interaction between AMBRA1 and HUWE1 is strengthened in presence of FAT10. This implies a putative interplay of all three proteins in cellular processes such as mitophagy.
Læs mere Tjek på PubMedIwona Hawryluk, Swapnil Mishra, Seth Flaxman, Samir Bhatt, Thomas A. Mellan
PLoS One Infectious Diseases, 15.08.2023
Tilføjet 15.08.2023
by Iwona Hawryluk, Swapnil Mishra, Seth Flaxman, Samir Bhatt, Thomas A. Mellan Evaluating normalising constants is important across a range of topics in statistical learning, notably Bayesian model selection. However, in many realistic problems this involves the integration of analytically intractable, high-dimensional distributions, and therefore requires the use of stochastic methods such as thermodynamic integration (TI). In this paper we apply a simple but under-appreciated variation of the TI method, here referred to as referenced TI, which computes a single model’s normalising constant in an efficient way by using a judiciously chosen reference density. The advantages of the approach and theoretical considerations are set out, along with pedagogical 1 and 2D examples. The approach is shown to be useful in practice when applied to a real problem —to perform model selection for a semi-mechanistic hierarchical Bayesian model of COVID-19 transmission in South Korea involving the integration of a 200D density.
Læs mere Tjek på PubMedTagyedeen H. Shoaib, Walaa Ibraheem, Mohammed Abdelrahman, Wadah Osman, Asmaa E. Sherif, Ahmed Ashour, Sabrin R. M. Ibrahim, Kholoud F. Ghazawi, Samar F. Miski, Sara A. Almadani, Duaa Fahad ALsiyud, Gamal A. Mohamed, Abdulrahim A. Alzain
PLoS One Infectious Diseases, 15.08.2023
Tilføjet 15.08.2023
by Tagyedeen H. Shoaib, Walaa Ibraheem, Mohammed Abdelrahman, Wadah Osman, Asmaa E. Sherif, Ahmed Ashour, Sabrin R. M. Ibrahim, Kholoud F. Ghazawi, Samar F. Miski, Sara A. Almadani, Duaa Fahad ALsiyud, Gamal A. Mohamed, Abdulrahim A. Alzain Triple-negative breast cancer (TNBC) is an aggressive malignancy that requires effective targeted drug therapy. In this study, we employed in silico methods to evaluate the efficacy of seven approved drugs against human ck2 alpha kinase, a significant modulator of TNBC metastasis and invasiveness. Molecular docking revealed that the co-crystallized reference inhibitor 108600 achieved a docking score of (-7.390 kcal/mol). Notably, among the seven approved drugs tested, sunitinib, bazedoxifene, and etravirine exhibited superior docking scores compared to the reference inhibitor. Specifically, their respective docking scores were -10.401, -7.937, and -7.743 kcal/mol. Further analysis using MM/GBSA demonstrated that these three top-ranked drugs possessed better binding energies than the reference ligand. Subsequent molecular dynamics simulations identified etravirine, an FDA-approved antiviral drug, as the only repurposed drug that demonstrated a stable and reliable binding mode with the human ck2 alpha protein, based on various analysis measures including RMSD, RMSF, and radius of gyration. Principal component analysis indicated that etravirine exhibited comparable stability of motion as a complex with human ck2 alpha protein, similar to the co-crystallized inhibitor. Additionally, Density functional theory (DFT) calculations were performed on a complex of etravirine and a representative gold atom positioned at different sites relative to the heteroatoms of etravirine. The results of the DFT calculations revealed low-energy complexes that could potentially serve as guides for experimental trials involving gold nanocarriers of etravirine, enhancing its delivery to malignant cells and introducing a new drug delivery route. Based on the results obtained in this research study, etravirine shows promise as a potential antitumor agent targeting TNBC, warranting further investigation through experimental and clinical assessments.
Læs mere Tjek på PubMedShakera Ahmed, Anwarul Karim, Tanvir Kabir Chowdhury, Orindom Shing Pulock, Nowrin Tamanna, Mastura Akter, Puja Biswas, Fahmida Afroz, Susmita Dey Pinky, Anika Nahrin Alabbi, Tasnuba Raisa Jamil, Zarin Tasnim, Dipa Dev, Mraching Marma, Tasmiah Tahera Aziz, Hafiz Ahmed Nazmul Hakim, A. K. M. Khairul Basher, Nur Hossain Bhuiyan Shahin, Tahmina Banu
PLoS One Infectious Diseases, 15.08.2023
Tilføjet 15.08.2023
by Shakera Ahmed, Anwarul Karim, Tanvir Kabir Chowdhury, Orindom Shing Pulock, Nowrin Tamanna, Mastura Akter, Puja Biswas, Fahmida Afroz, Susmita Dey Pinky, Anika Nahrin Alabbi, Tasnuba Raisa Jamil, Zarin Tasnim, Dipa Dev, Mraching Marma, Tasmiah Tahera Aziz, Hafiz Ahmed Nazmul Hakim, A. K. M. Khairul Basher, Nur Hossain Bhuiyan Shahin, Tahmina Banu Background The COVID-19 pandemic has significantly impacted the surgical practice throughout the world, including elective surgical care. This study investigated the characteristics of patients undergoing elective surgery, the prevalence of COVID-19 infection, the surgical procedures performed, and 30-day mortality in general and pediatric surgical settings in selected tertiary-level hospitals in Bangladesh from November 2020 to August 2021. Methods This serial cross-sectional study included 264 patients scheduled for elective surgeries during the study period. All patients underwent COVID-19 real-time polymerase chain reaction (RT-PCR) testing within 24 hours before surgery. Data on age, sex, common comorbidities, surgical procedures, and 30-day mortality were collected and analyzed. Furthermore, comparisons were made between COVID-19 positive and negative patients. Results The prevalence of COVID-19 infection among patients was 10.6%. Older age, a history of major surgery within the last three months, hypertension, and diabetes mellitus were significantly associated with COVID-19 infection. All COVID-19-negative patients underwent surgery, while only 46.4% of COVID-19-positive patients underwent surgery. The most common surgical procedures were related to the digestive system, breast, and urinary system. Only one patient (0.4%) died within 30 days after surgery among the COVID-19-negative patients, whereas two patients (7.1%) died among the COVID-19-positive patients: one before surgery and one after surgery. Conclusions This study provides valuable insights into the characteristics, burden of COVID-19 infection, and 30-day mortality of patients undergoing elective surgery in tertiary care centers in Bangladesh during the pandemic.
Læs mere Tjek på PubMedTushar Garg, Bareng Aletta Sanny Nonyane, Mbali Mohlamonyane, Limakatso Lebina, Neil A. Martinson, David W. Dowdy, Colleen F. Hanrahan
PLoS One Infectious Diseases, 15.08.2023
Tilføjet 15.08.2023
by Tushar Garg, Bareng Aletta Sanny Nonyane, Mbali Mohlamonyane, Limakatso Lebina, Neil A. Martinson, David W. Dowdy, Colleen F. Hanrahan People with tuberculosis (TB) are often lost to follow-up during treatment transition to another facility. These losses may result in substantial morbidity and mortality but are rarely recorded. We conducted a record review on adults diagnosed with TB at 11 hospitals in Limpopo, South Africa, who were subsequently transferred to a local clinic to initiate or continue treatment. We then performed in-depth record reviews at the primary care clinic to which they were referred and called participants who could not be identified as starting treatment. Between August 2017 and April 2018, we reviewed records of 778 individuals diagnosed with TB in-hospital and later referred to local clinics for treatment. Of the 778, 88 (11%) did not link to care, and an additional 43 (5.5%) died. Compared to people without cough, those with cough had higher odds of linking to care (aOR = 2.01, 95% CI: 1.26–3.25, p = 0.005) and were also linked more quickly [adjusted Time Ratio (aTR) = 0.53, 95% CI:0.36–0.79, p
Læs mere Tjek på PubMedMalaria Journal, 15.08.2023
Tilføjet 15.08.2023
Abstract Background Population suppression gene drive is currently being evaluated, including via environmental risk assessment (ERA), for malaria vector control. One such gene drive involves the dsxFCRISPRh transgene encoding (i) hCas9 endonuclease, (ii) T1 guide RNA (gRNA) targeting the doublesex locus, and (iii) DsRed fluorescent marker protein, in genetically-modified mosquitoes (GMMs). Problem formulation, the first stage of ERA, for environmental releases of dsxFCRISPRh previously identified nine potential harms to the environment or health that could occur, should expressed products of the transgene cause allergenicity or toxicity. Methods Amino acid sequences of hCas9 and DsRed were interrogated against those of toxins or allergens from NCBI, UniProt, COMPARE and AllergenOnline bioinformatic databases and the gRNA was compared with microRNAs from the miRBase database for potential impacts on gene expression associated with toxicity or allergenicity. PubMed was also searched for any evidence of toxicity or allergenicity of Cas9 or DsRed, or of the donor organisms from which these products were originally derived. Results While Cas9 nuclease activity can be toxic to some cell types in vitro and hCas9 was found to share homology with the prokaryotic toxin VapC, there was no evidence from previous studies of a risk of toxicity to humans and other animals from hCas9. Although hCas9 did contain an 8-mer epitope found in the latex allergen Hev b 9, the full amino acid sequence of hCas9 was not homologous to any known allergens. Combined with a lack of evidence in the literature of Cas9 allergenicity, this indicated negligible risk to humans of allergenicity from hCas9. No matches were found between the gRNA and microRNAs from either Anopheles or humans. Moreover, potential exposure to dsxFCRISPRh transgenic proteins from environmental releases was assessed as negligible. Conclusions Bioinformatic and literature assessments found no convincing evidence to suggest that transgenic products expressed from dsxFCRISPRh were allergens or toxins, indicating that environmental releases of this population suppression gene drive for malaria vector control should not result in any increased allergenicity or toxicity in humans or animals. These results should also inform evaluations of other GMMs being developed for vector control and in vivo clinical applications of CRISPR-Cas9.
Læs mere Tjek på PubMedMalaria Journal, 15.08.2023
Tilføjet 15.08.2023
Abstract Background Urbanization generally improves health outcomes of residents and is one of the potential factors that might contribute to reducing malaria transmission. However, the expansion of Anopheles stephensi, an urban malaria vector, poses a threat for malaria control and elimination efforts in Africa. In this paper, malaria trends in urban settings in Ethiopia from 2014 to 2019 are reported with a focus on towns and cities where An. stephensi surveys were conducted. Methods A retrospective study was conducted to determine malaria trends in urban districts using passive surveillance data collected at health facilities from 2014 to 2019. Data from 25 towns surveyed for An. stephensi were used in malaria trend analysis. Robust linear models were used to identify outliers and impute missing and anomalous data. The seasonal Mann-Kendal test was used to test for monotonic increasing or decreasing trends. Results A total of 9,468,970 malaria cases were reported between 2014 and 2019 through the Public Health Emergency Management (PHEM) system. Of these, 1.45 million (15.3%) cases were reported from urban settings. The incidence of malaria declined by 62% between 2014 and 2018. In 2019, the incidence increased to 15 per 1000 population from 11 to 1000 in 2018. Both confirmed (microscopy or RDT) Plasmodium falciparum (67%) and Plasmodium vivax (28%) were reported with a higher proportion of P. vivax infections in urban areas. In 2019, An. stephensi was detected in 17 towns where more than 19,804 malaria cases were reported, with most of the cases (56%) being P. falciparum. Trend analysis revealed that malaria cases increased in five towns in Afar and Somali administrative regions, decreased in nine towns, and had no obvious trend in the remaining three towns. Conclusion The contribution of malaria in urban settings is not negligible in Ethiopia. With the rapid expansion of An. stephensi in the country, the receptivity is likely to be higher for malaria. Although the evidence presented in this study does not demonstrate a direct linkage between An. stephensi detection and an increase in urban malaria throughout the country, An. stephensi might contribute to an increase in malaria unless control measures are implemented as soon as possible. Targeted surveillance and effective response are needed to assess the contribution of this vector to malaria transmission and curb potential outbreaks.
Læs mere Tjek på PubMedRamatoulie E. Janha, Alasana Bah, Hawanatu Jah, Fatima Touray, Yahaya Idris, Saikou Keita, Yassin Gaye, Samba Jallow, Tisbeh Faye-Joof, Baboucarr Njie, Rachel Craik, Nuredin I. Mohammed, Peter von Dadelszen, Umberto D'Alessandro, Anna Roca, the PRECISE Network
International Journal of Infectious Diseases, 15.08.2023
Tilføjet 15.08.2023
SARS-CoV-2, the causative agent of the coronavirus disease 2019 (COVID-19), was first identified in December 2019 in Wuhan, China [1]. SARS-CoV-2 was rapidly transmitted globally, disrupting structures and systems; and causing millions of deaths. Globally, there were 278.7M COVID-19 cases and 5.39M attributable deaths by December 2021 [2], 21 months after the World Health Organization (WHO) declared COVID-19 a pandemic [3]. Nigeria reported the first case in Sub-Saharan Africa (SSA) on 28 January 2020 [4].
Læs mere Tjek på PubMedAtsushi Senda, Akira Endo, Kiyohide Fushimi, Yasuhiro Otomo
International Journal of Infectious Diseases, 15.08.2023
Tilføjet 15.08.2023
Group A Streptococcus (GAS) is a Gram-positive, beta-hemolytic coccus. It can cause various diseases, ranging from mild illnesses (such as pharyngitis and impetigo) to severe illnesses (such as necrotizing fasciitis and streptococcal toxic shock syndrome (STSS)). Invasive group A Streptococcus infection (iGAS) is defined as the isolation of GAS from sterile sites including the blood, pleura, and cerebrospinal fluid [1].
Læs mere Tjek på PubMedClinical & Experimental Immunology, 15.08.2023
Tilføjet 15.08.2023
AbstractPrimary adrenal insufficiency (PAI) is most often caused by an autoimmune destruction of the adrenal cortex resulting in failure to produce cortisol and aldosterone. The aetiology is thought to be a combination of genetic and environmental risk factors, leading to breakdown of immunological tolerance. Regulatory T cells (Tregs) are deficient in many autoimmune disorders, but it is not known whether they contribute to development of PAI. We aimed to investigate the frequency and function of naïve and expanded Tregs from patients with PAI and polyendocrine syndromes compared to age- and gender-matched healthy controls. Flow cytometry was used to assess the frequency and characterise functional markers of blood Tregs in PAI (N=15). Expanded Treg suppressive abilities were assessed with a flow cytometry based suppression assay (N=20), while bulk RNA-sequencing was used to examine transcriptomic differences (N=16) and oxygen consumption rate was measured by a Seahorse cell metabolic assay (N=11). Our results showed that Treg frequency and suppressive capacity was similar between patients and control. An increased expression of killer-cell leptin-like receptors and mitochondrial genes was revealed in PAI patients, but their expanded Tregs did not display signs of mitochondrial dysfunction. Our findings do not support a clear role for Tregs in the contribution of PAI development.
Læs mere Tjek på PubMedClinical & Experimental Immunology, 15.08.2023
Tilføjet 15.08.2023
AbstractThe mucosal immune system is implicated in the etiology and progression of inflammatory bowel diseases. The lamina propria and epithelium of the gut mucosa constitute two separate compartments, containing distinct T cell populations. Human CD4 T cell programming and regulation of lamina propria and epithelium CD4 T cells, especially during inflammation, remains incompletely understood. We performed flow cytometry, bulk and single-cell RNA-sequencing to profile ileal lamina propria and intraepithelial CD4 T cells (CD4CD8αα, regulatory T cells (Tregs), CD69 - and CD69 high Trm T cells) in controls and Crohn’s disease (CD) patients (paired non-inflamed and inflamed). Inflammation results in alterations of the CD4 T cell population with a pronounced increase in Tregs and migrating/infiltrating cells. On a transcriptional level, inflammation within the epithelium induced T cell activation, increased IFNγ responses and an effector Treg profile. Conversely, few transcriptional changes within the lamina propria were observed. Key regulators including the chromatin remodelers ARID4B and SATB1 were found to drive compartment-specific transcriptional programming of CD4 T(reg) cells. In summary, inflammation in CD patients primarily induces changes within the epithelium and not the lamina propria. Additionally, there is compartment-specific CD4 T cell imprinting, driven by shared regulators, between the lamina propria and the epithelium. The main consequence of intraepithelial adaptation, irrespective of inflammation, seems to be an overall dampening of broad (pro-inflammatory) responses and tight regulation of lifespan. These data suggest differential regulation of the lamina propria and epithelium, with a specific regulatory role in the inflamed epithelium.
Læs mere Tjek på PubMedShields, M., Tonmyr, L., Gonzalez, A., Atkinson, L., Blair, D.-L., Hovdestad, W., MacMillan, H.
BMJ Open, 15.08.2023
Tilføjet 15.08.2023
ObjectivesDepression is associated with problems in functioning in many aspects of life, including parenting. COVID-19 has increased risk factors for depression. We investigated the prevalence of depression among parents during the pandemic and the association with dysfunctional parenting. DesignCanadian nationwide cross-sectional study. Setting and participantsThe 2020 and 2021 Surveys on COVID-19 and Mental Health (SCMH) and the Canadian Community Health Survey (CCHS) (2015-2019). Responding sample sizes for parents were 3121 for the 2020-SCMH; 1574 for the 2021-SCMH and 6076 for the CCHS. Primary outcome measuresAll three surveys collected information on symptoms of major depressive disorder (MDD). The SCMH measured harsh parenting. ResultsBased on data from the 2021-SCMH collected during wave 3 of COVID-19, 14.4% of fathers and 21.2% of mothers screened positive for MDD. These prevalence estimates were similar to those from the 2020-SCMH during wave 2, but at least two times higher than pre-COVID-19 estimates from the CCHS. Multivariate analyses revealed a linear association between MDD and harsh parenting. COVID-19-related stressors were associated with harsh parenting. Among mothers, feeling lonely or isolated because of COVID-19 was a risk factor for harsh parenting; among fathers, being a front-line worker was a risk factor. Meditation was a protective factor for mothers. ConclusionsAfter years of stability, the prevalence of MDD increased substantially among Canadian parents during the pandemic. Ongoing monitoring is vital to determine if elevated levels of depression persist because chronic depression increases the likelihood of negative child outcomes. Programmes aimed at addressing depression and bolstering parenting skills are needed as families continue to face stressors associated with COVID-19.
Læs mere Tjek på PubMedKhoury, J. E., Atkinson, L., Jack, S., Bennett, T., Raha, S., Duku, E., Gonzalez, A.
BMJ Open, 15.08.2023
Tilføjet 15.08.2023
IntroductionThe COVID-19 pandemic has had a unique impact on the mental health and well-being of pregnant individuals and parents of young children. However, the impact of COVID-19-related stress during pregnancy on early child biopsychosocial development, remains unclear. The COVID-19 Wellbeing and Stress Study will: (1) investigate the impact of different forms of prenatal stress experienced during the pandemic (including objective hardship, perceived psychological distress and biological stress) on child stress biology, (2) examine the association between child stress biology and child developmental outcomes, (3) determine whether child stress biology acts as a mechanism linking prenatal stress to adverse child developmental outcomes and (4) assess whether gestational age at the onset of the COVID-19 pandemic or child sex, moderate these associations. Methods and analysesThe COVID-19 Wellbeing and Stress Study is a prospective longitudinal study, consisting of six time points, spanning from pregnancy to 3 years postpartum. The study began in June 2020, consisting of 304 pregnant people from Ontario, Canada. This multimethod study is composed of questionnaires, biological samples, behavioural observations and developmental assessments Ethics and disseminationThis study was approved by the Hamilton Integrated Research Ethics Board (#11034) and the Mount Saint Vincent University Research Ethics Board (#2020-187, #2021-075, #2022-008). Findings will be disseminated through peer-reviewed presentations and publications, community presentations, and electronic forums (social media, newsletters and website postings).
Læs mere Tjek på PubMedBMJ Open, 15.08.2023
Tilføjet 15.08.2023
Catsis S, Champneys AR, Hoyle R, et al. Process modelling of NHS cardiovascular waiting lists in response to the COVID-19 pandemic. BMJ Open 2023;13:e065622. doi:10.1136/bmjopen-2022-065622 The authors want to alert the readers that a typographical error noticed on page 7 first paragraph in third line ‘5000’ has been corrected to ‘50,000’.
Læs mere Tjek på PubMedBMC Infectious Diseases, 15.08.2023
Tilføjet 15.08.2023
Abstract Introduction Psittacosis can cause severe community-acquired pneumonia (CAP). The clinical manifestations of psittacosis range from subclinical to fulminant psittacosis with multi-organ failure. It is essential to summarize the clinical characteristic of patients with severe psittacosis accompanied by acute hypoxic respiratory failure (AHRF). Methods This retrospective study included patients with severe psittacosis caused CAP accompanied by AHRF from 19 tertiary hospitals of China. We recorded the clinical data, antimicrobial therapy, respiratory support, complications, and outcomes. Chlamydia psittaci was detected on the basis of metagenomic next-generation sequencing performed on bronchoalveolar lavage fluid samples. Patient outcomes were compared between the treatment methods. Results This study included 45 patients with severe CAP and AHRF caused by psittacosis from April 2018 to May 2021. The highest incidence of these infections was between September and April. There was a history of poultry contact in 64.4% of the patients. The median PaO2/FiO2 of the patients was 119.8 (interquartile range, 73.2 to 183.6) mmHg. Four of 45 patients (8.9%) died in the ICU, and the median ICU duration was 12 days (interquartile range, 8 to 21) days. There were no significant differences between patients treated with fluoroquinolone initially and continued after the diagnosis, fluoroquinolone initially followed by tetracycline, and fluoroquinolone combined with tetracycline. Conclusion Psittacosis caused severe CAP seems not rare, especially in the patients with the history of exposure to poultry or birds. Empirical treatment that covers atypical pathogens may benefit such patients, which fluoroquinolones might be considered as an alternative.
Læs mere Tjek på PubMedBMC Infectious Diseases, 15.08.2023
Tilføjet 15.08.2023
Abstract Background The World Health Organization’s (WHO) 2030 goal of eradicating Hepatitis B and C viruses must also include HIV co-infected children. However, data on the prevalence of this condition are lacking in the Democratic Republic of Congo (DRC), which is considered as one of the countries with high-prevalence of these viruses. The need to assess the extent of this co-infection in the children of this country is therefore important in order to capitalize on efforts to improve prevention and management of both infections. Methodology This is a comparative cross-sectional study conducted from February 04, 2015 to September 03, 2019 at 14 General Reference Hospitals with a pediatric HIV management programme in South Kivu province. The study compared the frequency of hepatitis B (HBV) and C (HCV) markers and factors associated with these two viruses in two equal groups: HIV-positive and HIV-negative children. The data were analyzed using the SPSS version 20.0 software and the significance level was set at p-value less than 0.05. Results The study involved a total of 594 children, 297 of whom were HIV-positive and 297 negative. HBsAg was found in 8.7% of HIV-positive patients and 0.7% for HCV antibodies. On the other hand, among the HIV-negative patients, the proportion of HBsAg was 0.7% but no cases with anti-HCV antibodies were detected. HIV status increases by 14 times the risk of co-occurring with HBV [OR 14.1 (95% CI: 3.33–60.2); p
Læs mere Tjek på PubMedBMC Infectious Diseases, 15.08.2023
Tilføjet 15.08.2023
Abstract Background The geographical distribution of hepatitis B virus (HBV) and hepatitis D virus (HDV) genotypes is uneven and has its own clinical and organizational implications for health systems. Despite the introduction of vaccination and successful antiviral therapy the prevalence of chronic hepatitis B (with or without delta agent) increased over the past 5 years. This study aimed for the first time to investigate the molecular epidemiology of HBV and HDV in Kazakhstan. Methods Total 834 chronic hepatitis B (with or without delta agent) patients were included to the study from November 2017 to June 2019. The material was collected from the regional hepatological сenters from 13 cities of Kazakhstan. Genotyping of HBV/HDV isolates was carried out using phylogenetic analysis of null-binary sequences of Kazakhstani isolates, in comparison with the reference sequences. Nucleotide sequence alignment was performed using the ClustalW algorithm, the “neighbor-joining” method was used for the construction of phylogenetic trees and subsequent analysis. Results Overall 341 samples were PCR-positive and genotyped for HBV. Comparison and phylogenetic analysis of nucleotide sequences of HBV isolates showed that they were represented by genotypes HBV-D (95.9%), HBV-A (3.5%) and HBV-C (0.6%). At the same time, the identity of the nucleotide sequences of Kazakhstani isolates were: HBV-D (95–100%); HBV-A (97.2–100%) and HBV-C (99%). 256 samples were PCR positive and genotyped for HDV, all of them belonged to genotype 1. Conclusion This study describes for the first time the molecular epidemiology of HBV and HDV in Kazakhstan. The data obtained expand the knowledge of the global epidemiology of viruses; have potential implications for public health policy and for further clinical research on chronic hepatitis in Kazakhstan. Trial registration ClinicalTrials.gov NCT05095181 (registered on 27/10/2021).
Læs mere Tjek på PubMedBMC Infectious Diseases, 15.08.2023
Tilføjet 15.08.2023
Abstract Background Invasive candidiasis is the most common hospital-acquired fungal infection in intensive care units (ICU). The Geriatric Nutritional Risk Index (GNRI) score was developed to evaluate the nutritional status of elderly adults. We aimed to assess the association between the GNRI score and the risk of invasive candidiasis in elderly patients admitted to ICU. Methods Hospitalization information of elderly patients with invasive candidiasis was collected retrospectively from Medical Information Mart for Intensive Care (MIMIC) IV and MIMIC-III Clinical Database CareVue subset from 2001 to 2019. The main outcome of this study was the diagnosis of invasive candidiasis in patients. We employed a multivariable Cox regression and propensity score matching to balance the influence of confounding factors on the outcome. Furthermore, we conducted sensitivity analyses by categorizing the GNRI into classes based on thresholds of 98, 92, and 81. Results A total of 6739 patients were included in the study, among whom 134 individuals (2%) were diagnosed with invasive candidiasis. The GNRI scores of patients with invasive candidiasis upon admission to the ICU were significantly lower, measuring 88.67 [79.26–98.27], compared to the control group with a score of 99.36 [87.98-110.45] (P
Læs mere Tjek på PubMedBMC Infectious Diseases, 15.08.2023
Tilføjet 15.08.2023
Abstract Background Brucellosis is a zoonotic disease whose causative agent, Brucella spp., is endemic in many countries of the Mediterranean basin, including Greece. Although the occurrence of brucellosis must be reported to the authorities, it is believed that the disease is under-reported in Greece, and knowledge about the genomic diversity of brucellae is lacking. Methods Thus, 44 Brucella isolates, primarily B. melitensis, collected between 1999 and 2009 from humans and small ruminants in Greece were subjected to whole genome sequencing using short-read technology. The raw reads and assembled genomes were used for in silico genotyping based on single nucleotide substitutions and alleles. Further, specific genomic regions encoding putative virulence genes were screened for characteristic nucleotide changes, which arose in different genotype lineages. Results In silico genotyping revealed that the isolates belonged to three of the known sublineages of the East Mediterranean genotype. In addition, a novel subgenotype was identified that was basal to the other East Mediterranean sublineages, comprising two Greek strains. The majority of the isolates can be assumed to be of endemic origin, as they were clustered with strains from the Western Balkans or Turkey, whereas one strain of human origin could be associated with travel to another endemic region, e.g. Portugal. Further, nucleotide substitutions in the housekeeping gene rpoB and virulence-associated genes were detected, which were characteristic of the different subgenotypes. One of the isolates originating from an aborted bovine foetus was identified as B. abortus vaccine strain RB51. Conclusion The results demonstrate the existence of several distinct persistent Brucella sp. foci in Greece. To detect these and for tracing infection chains, extensive sampling initiatives are required.
Læs mere Tjek på PubMedAgustina Taglialegna
Nat Rev Microbiol, 14.08.2023
Tilføjet 14.08.2023
Ran Zhuo, Stephen B. Freedman, Jianling Xie, Carmen Charlton, Sabrina Plitt, Mathew A. Croxen, Vincent Li, Gillian A. M. Tarr, Bonita Lee, Samina Ali, Linda Chui, Jasper Luong, Xiaoli Pang
Journal of Medical Virology, 14.08.2023
Tilføjet 14.08.2023
Catherine Godfrey, John Nkengasong
New England Journal of Medicine, 13.08.2023
Tilføjet 13.08.2023
Infectious Disease Modelling, 13.08.2023
Tilføjet 13.08.2023
Publication date: Available online 12 August 2023 Source: Infectious Disease Modelling Author(s): Siwaphorn Kanchanarat, Kadkanok Nudee, Settapat Chinviriyasit, Wirawan Chinviriyasit
Læs mere Tjek på PubMedReid Gohmann, David Mackey
Trends in Parasitology, 13.08.2023
Tilføjet 13.08.2023
Pathogen-encoded virulence factors perturb host physiology and immune function to promote infection. Reinforcing the concept that protein phosphatase 2A (PP2A) is convergently targeted by virulence factors from diverse pathogens, Li et al. demonstrate that PP2A is coopted by members of a modular family of effector proteins from a plant-pathogenic oomycete.
Læs mere Tjek på PubMedBruno Douradinha
Trends in Parasitology, 13.08.2023
Tilføjet 13.08.2023
Attenuated plasmodial sporozoite-induced immune response includes intrahepatic nitric oxide (NO) production, which promotes apoptosis of infected hepatocytes and consequent parasite clearance. NO in excess reacts with superoxide, forming peroxynitrite, a powerful cytotoxic agent. Here, I suggest that peroxynitrite proapoptotic action may contribute to the attenuated malarial sporozoite-mediated protection.
Læs mere Tjek på PubMedMalaria Journal, 13.08.2023
Tilføjet 13.08.2023
Abstract Background Anopheles funestus, which is considered as secondary vector of malaria in Ethiopia, is known to have several morphologically indistinguishable (sibling) species. Accurate identification of sibling species is crucial to understand their biology, behaviour and vector competence. In this study, molecular identification was conducted on the Ethiopian An. funestus populations. Moreover, insecticide resistance mechanism markers were detected, including ace N485I, kdr L1014F, L1014S, and CYP6P9a TaqMan qPCR was used to detect the infective stage of the parasite from field collected adult female An. funestus populations. Methods Adult female mosquito collection was conducted from Lare, Gambella Regional State of Ethiopia between June 2018 to July 2020 using CDC light traps and HLC. Sub-samples of the morphologically identified An. funestus mosquitoes were molecularly identified using species-specific PCR, and the possible presence of insecticide resistance alleles was investigated using TaqMan qPCR (N485I-Ace-1), PCR-Sanger sequencing (L1014F-kdr), and PCR–RFLP (CYP6P9a resistance allele). Following head/thorax dissection, the TaqMan qPCR assay was used to investigate the presence of the infective stage Plasmodium parasite species. Results A total of 1086 adult female An. funestus mosquitoes were collected during the study period. All sub-samples (N = 20) that were morphologically identified as An. funestus sensu lato (s.l.) were identified as An. funestus sensu stricto (s.s.) using species- specific PCR assay. The PCR–RFLP assay that detects the CYP6P9a resistance allele that confers pyrethroid resistance in An. funestus was applied in N = 30 randomly selected An. funestus s.l. specimens. None of the specimens showed a digestion pattern consistent with the presence of the CYP6P9a resistance allele in contrast to what was observed in the positive control. Consequently, all samples were characterized as wild type. The qPCR TaqMan assay that detects the N485I acetylcholinesterase-1 mutation conferring resistance to organophosphates/carbamates in An. funestus was used in (N = 144) samples. All samples were characterized as wild type. The kdr L1014F and L1014S mutations in the VGSC gene that confer resistance to pyrethroids and DDT were analysed with direct Sanger sequencing after PCR and clean-up of the PCR products were also characterized as wild type. None of the samples (N = 169) were found positive for Plasmodium (P. falciparum/ovale/malariae/vivax) detection. Conclusion All An. funestus s.l. samples from Lare were molecularly identified as An. funestus s.s. No CYP6P9, N485I acetylcholinesterase 1, kdr L1014F or L1014S mutations were detected in the An. funestus samples. None of the An. funestus samples were positive for Plasmodium. Although the current study did not detect any insecticide resistant mechanism, it provides a reference for future vector monitoring programmes. Regular monitoring of resistance mechanisms covering wider geographical areas of Ethiopia where this vector is distributed is important for improving the efficacy of vector control programs.
Læs mere Tjek på PubMedDominik Dietler, Fredrik Kahn, Malin Inghammar, Jonas Björk
Clinical Microbiology and Infection, 13.08.2023
Tilføjet 13.08.2023
Evidence on waning patterns in protection from vaccine-induced, infection-induced, and hybrid immunity against death is scarce. The aim of this study is to assess the temporal trends in protection against mortality.
Læs mere Tjek på PubMedClinical Infectious Diseases, 12.08.2023
Tilføjet 12.08.2023
AbstractBackgroundTuberculosis (TB) disease has been associated with pregnancy complications. However, the potential impact of TB infection (TBI) on pregnancy outcome is unknown. To investigate this, we conducted a register-based study in immigrant women screened with QuantiFERON assays for TBI in antenatal care in Sweden.MethodsWomen with history of immigration from TB-endemic countries were eligible for inclusion if national identification numbers and available QuantiFERON results obtained during pregnancy 2014-2018 were available. QuantiFERON results were linked to data on maternal characteristics and pregnancy outcomes from the national Pregnancy and Patient Registers. TBI was defined as nil-corrected QuantiFERON result ≥0.35 IU/ml, in the absence of TB disease. Pregnancies in women with TB disease or HIV infection were excluded, as well as multiplex pregnancies, pregnancies resulting in miscarriage, and pregnancies occurring >10 years after immigration. Odds of defined adverse pregnancy outcomes were compared by maternal TBI status using mixed effects logistic regression with adjustment for maternal age and region of origin.ResultsIn total, 7,408 women with 12,443 pregnancies were included. In multivariable analysis, stillbirth (adjusted Odds ratio [AOR] 1.90, 95% confidence interval [CI] 1.13-3.21, p=0.016), severe preeclampsia (AOR 1.62, 95% CI 1.03-2.56, p=0.036), low birthweight (
Læs mere Tjek på PubMedJournal of Infectious Diseases, 12.08.2023
Tilføjet 12.08.2023
AbstractTo examine the potential for respiratory transmission of rotavirus, we systematically assessed if rotavirus RNA is detectable by qRT-PCR from nasal and oropharyngeal swab specimens of Bangladeshi children with acute rotavirus gastroenteritis. Forehead swabs were collected to assess skin contamination. Among 399 children aged
Læs mere Tjek på PubMedJournal of Infectious Diseases, 12.08.2023
Tilføjet 12.08.2023
Journal of Infectious Diseases, 12.08.2023
Tilføjet 12.08.2023
AbstractObjectivesWe sought to identify potential antigens for discerning between humoral responses elicited after vaccination with CoronaVac (a SARS-CoV-2 inactivated vaccine), natural infection, or breakthrough cases.MethodsSerum samples obtained from volunteers immunized with CoronaVac (two and three doses), breakthrough cases, and from convalescent individuals were analyzed to determine the IgG responses against three structural, and eight non-structural SARS-CoV-2 antigens.ResultsImmunization with CoronaVac induced higher levels of antibodies against the viral membrane (M) protein compared to convalescent subjects both, after primary vaccination and a booster dose. Individuals receiving a booster dose displayed equivalent levels of IgG antibodies against the nucleoprotein (N), similar to convalescents subjects. Breakthrough cases produced the highest antibody levels against the N and M proteins. Antibodies against non-structural viral proteins were present in more than 50% of the convalescent subjects.ConclusionsVaccinated individuals elicited a different humoral response compared to convalescent subjects. The analysis of particular SARS-CoV-2 antigens could be used as biomarkers for determining infection in subjects previously vaccinated with CoronaVac.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 12.08.2023
Tilføjet 12.08.2023
AbstractThis was a household-based prospective cohort study conducted in Rio de Janeiro, in which people with laboratory-confirmed Covid-19 and their household contacts were followed from April 2020 through June 2022. Ninety-eight reinfections were identified, with 71 (72.5%) confirmed by genomic analyses and lineage definition in both infections. During the pre-Omicron period, one dose of any Covid-19 vaccine was associated with a reduced risk of reinfection, but during the Omicron period not even booster vaccines had this effect. Most reinfections were asymptomatic or milder in comparison with primary infections, a justification for continuing active surveillance to detect infections in vaccinated individuals. Our findings demonstrated that vaccination may not prevent infection or reinfection with SARS CoV-2, then we highlight the need to continuously update the antigenic target of SARS CoV-2 vaccines and administer booster doses to the population regularly, a strategy well established in the development of vaccines for influenza immunization programs.
Læs mere Tjek på PubMedImmunity, 12.08.2023
Tilføjet 12.08.2023
Publication date: Available online 11 August 2023 Source: Immunity Author(s): Erin E. West, Nicolas S. Merle, Marcin M. Kamiński, Gustavo Palacios, Dhaneshwar Kumar, Luopin Wang, Jack A. Bibby, Kirsten Overdahl, Alan K. Jarmusch, Simon Freeley, Duck-Yeon Lee, J. Will Thompson, Zu-Xi Yu, Naomi Taylor, Marc Sitbon, Douglas R. Green, Andrea Bohrer, Katrin D. Mayer-Barber, Behdad Afzali, Majid Kazemian
Læs mere Tjek på PubMedInfection, 12.08.2023
Tilføjet 12.08.2023
Abstract Purpose Panel PCR tests provide rapid pathogen identification. However, their diagnostic performance is unclear. We assessed the performance of the Biofire© FilmArray pneumonia (PN)-panel against standard culture in broncho-alveolar lavage (BAL) samples. Methods Setting: University Hospital Basel (February 2019 to July 2020), including hospitalized patients with a BAL (± pneumonia). We determined sensitivity and specificity of the PN-panel against standard culture. Using univariate logistic regression, we calculated odds ratios (OR) for pneumonia according to PN-panel and culture status, stratifying by chronic pulmonary disease. We calculated ORs for pneumonia for different pathogens to estimate the clinical relevance. Results We included 840 adult patients, 60% were males, median age was 68 years, 35% had chronic pulmonary disease, 21% had pneumonia, and 36% had recent antibiotic use. In 1078 BAL samples, bacterial pathogens were detected in 36% and 16% with PN-panel and culture, respectively. The overall sensitivity and specificity of the PN-panel was high, whereas the positive predictive value was low. The OR of pneumonia was 1.1 (95% CI 0.7–1.6) for PN-panel-positive only; 2.6 (95% CI 1.3–5.3) for culture-positive only, and 1.6 (95% CI 1.0–2.4) for PN-panel and culture-positive. The detection rate of Haemophilus influenzae, Staphylococcus aureus, and Moraxella catarrhalis in the PN-panel was high but not associated with pneumonia. Conclusion While sensitivity and specificity of PN-panel are high compared to culture, pathogen detection did not correlate well with a pneumonia diagnosis. Patients with culture-positive BAL had the highest OR for pneumonia—thus the impact of the PN-panel on clinical management needs further evaluation in randomized controlled trials.
Læs mere Tjek på PubMedInfection, 12.08.2023
Tilføjet 12.08.2023
Abstract Background Few studies have reported on mortality beyond one year after sepsis. We aim to describe trends in short- and long-term mortality among patients admitted with sepsis, and to describe the association between clinical characteristics and mortality for improved monitoring, treatment and prognosis. Methods Patients ≥ 18 years admitted to all Norwegian hospitals (2008–2021) with a first sepsis episode were identified using Norwegian Patient Registry and International Classification of Diseases 10th Revision codes. Sepsis was classified as implicit (known infection site plus organ dysfunction), explicit (unknown infection site), or COVID-19-related sepsis. The outcome was all-cause mortality. We describe age-standardized 30-day, 90-day, 1-, 5- and 10-year mortality for each admission year and estimated the annual percentage change with 95% confidence interval (CI). The association between clinical characteristics and all-cause mortality is reported as hazard ratios (HRs) adjusted for age, sex and calendar year in Cox regression. Results The study included 222,832 patients, of whom 127,059 (57.1%) had implicit, 92,928 (41.7%) had explicit, and 2,845 (1.3%) had COVID-19-related sepsis (data from 2020 and 2021). Trends in overall age-standardized 30-day, 90-day, 1- and 5-year mortality decreased by 0.29 (95% CI − 0.39 to − 0.19), 0.43 (95% CI − 0.56 to − 0.29), 0.61 (95% CI − 0.73 to − 0.49) and 0.66 (95% CI − 0.84 to − 0.48) percent per year, respectively. The decrease was observed for all infections sites but was largest among patients with respiratory tract infections. Implicit, explicit and COVID-19-related sepsis had largely similar overall mortality, with explicit sepsis having an adjusted HR of 0.980 (95% CI 0.969 to 0.991) and COVID-19-related sepsis an adjusted HR of 0.916 (95% CI 0.836 to 1.003) compared to implicit sepsis. Patients with respiratory tract infections have somewhat higher mortality than those with other infection sites. Number of comorbidities was positively associated with mortality, but mortality varied considerably between different comorbidities. Similarly, number of acute organ dysfunctions was strongly associated with mortality, whereas the risk varied for each type of organ dysfunction. Conclusion Overall mortality has declined over the past 14 years among patients with a first sepsis admission. Comorbidity, site of infection, and acute organ dysfunction are patient characteristics that are associated with mortality. This could inform health care workers and raise the awareness toward subgroups of patients that needs particular attention to improve long-term mortality.
Læs mere Tjek på PubMedChahui Tan, Xingliang Qin, Yongyao Tan, Xinhuai Dong, Delin Chen, Linyue Liang, Jinling Li, Ruoxi Niu, Kaiyuan Cao, Zhenjian He, Guohong Wei, Mingxing Huang, Xun Zhu
Journal of Medical Virology, 12.08.2023
Tilføjet 12.08.2023
Yigen Li, Molly R. Patterson, Ethan L. Morgan, Christopher W. Wasson, Emma L. Ryder, Diego Barba‐Moreno, James A. Scarth, Miao Wang, Andrew Macdonald
Journal of Medical Virology, 12.08.2023
Tilføjet 12.08.2023
Mona L. Taouk, Eike Steinig, George Taiaroa, Ivana Savic, Thomas Tran, Nasra Higgins, Stephanie Tran, Alvin Lee, Maxwell Braddick, Michael A. Moso, Eric P. F. Chow, Christopher K. Fairley, Janet Towns, Marcus Y. Chen, Leon Caly, Chuan K. Lim, Deborah A. Williamson
Journal of Medical Virology, 12.08.2023
Tilføjet 12.08.2023