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Infection and Drug Resistance 2024spp. infections have recently increased, and they are difficult to treat because of intrinsic antimicrobial resistance. This study aimed to investigate the clinical...
PURPOSE
spp. infections have recently increased, and they are difficult to treat because of intrinsic antimicrobial resistance. This study aimed to investigate the clinical characteristics of patients with pulmonary infection with spp. and reveal the risk factors for infection and death.
PATIENTS AND METHODS
In this retrospective case-control study, patients were divided into infection and control groups based on the bacterial identification results. Patients in the infection group were further divided into survival and death groups according to their hospital outcomes. Clinical characteristics between different groups were compared. We further analyzed antimicrobial susceptibility testing results of the isolated strains.
RESULTS
A total of the 316 patients were divided into infection (n = 79), 23 of whom died, and control (n = 237) groups. Multivariate logistic regression analysis showed that glucocorticoid consumption (OR: 2.35; 95% CI: 1.14-4.81; P = 0.02), endotracheal intubation (OR: 3.74; 95% CI: 1.62-8.64; P = 0.002), and colistin exposure (OR: 2.50; 95% CI: 1.01-6.29; P = 0.046) were significantly associated with pulmonary infection with spp. Advanced age (OR: 1.07, 95% CI: 1.00-1.15; P = 0.046), high acute physiology and chronic health evaluation (APACHE) II score (OR: 1.21; 95% CI: 1.01-1.45; P = 0.037), and low albumin level (OR: 0.73, 95% CI: 0.56-0.96; P = 0.025) were significantly associated with in-hospital mortality of infected patients. spp. was highly resistant to cephalosporins, carbapenems, macrolides, and aminoglycoside, and was sensitive to fluoroquinolones, minocycline, and co-trimoxazole in vitro.
CONCLUSION
Glucocorticoid consumption, tracheal intubation, and colistin exposure were associated with pulmonary infection with spp. for critically ill patients. Patients with advanced age, high APACHE II score, and low albumin level had higher risk of death from infection.
PubMed: 38953097
DOI: 10.2147/IDR.S460640 -
Transplantation Direct Jul 2024Solid organ transplant recipients have a high risk of severe outcomes from SARS-CoV-2 infection. A comprehensive understanding of the impact of the COVID-19 pandemic...
BACKGROUND
Solid organ transplant recipients have a high risk of severe outcomes from SARS-CoV-2 infection. A comprehensive understanding of the impact of the COVID-19 pandemic across multiple waves in the solid organ transplant population and how this compares to the general population is limited. We conducted a population-based cohort study using linked administrative healthcare databases from Ontario, Canada to answer this question.
METHODS
We included 15 306 solid organ transplant recipients and 12 160 904 individuals from the general population. Our primary outcome was the rate (per 100 person-years) of severe COVID-19 (ie, hospitalization or death with a positive SARS-CoV-2 test) occurring between January 25, 2020, and November 30, 2022.
RESULTS
Compared with the general population, solid organ transplant recipients had almost a 6 times higher rate of severe COVID-19 (20.39 versus 3.44 per 100 person-years), with almost 5.5 times as high a rate of death alone (4.19 versus 0.77 per 100 person-years). Transplant recipients with severe COVID-19 were substantially younger (60.1 versus 66.5 y) and had more comorbidities. The rate of severe COVID-19 declined over time in the solid organ transplant population, with an incidence rate of 41.25 per 100 person-years in the first wave (January 25, 2020, to August 31, 2020) and 18.41 in the seventh wave (June 19, 2022, to November 30, 2022, Omicron era).
CONCLUSIONS
Solid organ transplant recipients remain at high risk of severe outcomes when they are infected with SARS-CoV-2. Resources and strategies to mitigate the impact of SARS-CoV-2 exposure are needed in this vulnerable patient population.
PubMed: 38953040
DOI: 10.1097/TXD.0000000000001670 -
Transplantation Direct Jul 2024A prior single-center, retrospective cohort study identified baseline lung allograft dysfunction (BLAD) as a risk factor for death in bilateral lung transplant...
BACKGROUND
A prior single-center, retrospective cohort study identified baseline lung allograft dysfunction (BLAD) as a risk factor for death in bilateral lung transplant recipients. In this multicenter prospective cohort study, we test the association of BLAD with death in bilateral lung transplant recipients, identify clinical risk factors for BLAD, and assess its association with allograft injury on the molecular level.
METHODS
This multicenter, prospective cohort study included 173 bilateral lung transplant recipients that underwent serial pulmonary function testing and plasma collection for donor-derived cell-free DNA at prespecified time points. BLAD was defined as failure to achieve ≥80% predicted for both forced expiratory volume in 1 s and forced vital capacity after lung transplant, on 2 consecutive measurements at least 3 mo apart.
RESULTS
BLAD was associated with increased risk of death (hazard ratio, 1.97; 95% confidence interval [CI], 1.05-3.69; = 0.03) but not chronic lung allograft dysfunction alone (hazard ratio, 1.60; 95% CI, 0.87-2.95; = 0.13). Recipient obesity (odds ratio, 1.69; 95% CI, 1.15-2.80; = 0.04) and donor age (odds ratio, 1.03; 95% CI, 1.02-1.05; = 0.004) increased the risk of developing BLAD. Patients with BLAD did not demonstrate higher log(donor-derived cell-free DNA) levels compared with no BLAD (slope [SE]: -0.0095 [0.0007] versus -0.0109 [0.0007]; = 0.15).
CONCLUSIONS
BLAD is associated with an increased risk of death following lung transplantation, representing an important posttransplant outcome with valuable prognostic significance; however, early allograft specific injury on the molecular level does not increase the risk of BLAD, supporting further mechanistic insight into disease pathophysiology.
PubMed: 38953039
DOI: 10.1097/TXD.0000000000001669 -
Frontiers in Immunology 2024Unbalanced inflammatory response is a critical feature of sepsis, a life-threatening condition with significant global health burdens. Immune dysfunction, particularly... (Observational Study)
Observational Study
BACKGROUND
Unbalanced inflammatory response is a critical feature of sepsis, a life-threatening condition with significant global health burdens. Immune dysfunction, particularly that involving different immune cells in peripheral blood, plays a crucial pathophysiological role and shows early warning signs in sepsis. The objective is to explore the relationship between sepsis and immune subpopulations in peripheral blood, and to identify patients with a higher risk of 28-day mortality based on immunological subtypes with machine-learning (ML) model.
METHODS
Patients were enrolled according to the sepsis-3 criteria in this retrospective observational study, along with age- and sex-matched healthy controls (HCs). Data on clinical characteristics, laboratory tests, and lymphocyte immunophenotyping were collected. XGBoost and k-means clustering as ML approaches, were employed to analyze the immune profiles and stratify septic patients based on their immunological subtypes. Cox regression survival analysis was used to identify potential biomarkers and to assess their association with 28-day mortality. The accuracy of biomarkers for mortality was determined by the area under the receiver operating characteristic (ROC) curve (AUC) analysis.
RESULTS
The study enrolled 100 septic patients and 89 HCs, revealing distinct lymphocyte profiles between the two groups. The XGBoost model discriminated sepsis from HCs with an area under the receiver operating characteristic curve of 1.0 and 0.99 in the training and testing set, respectively. Within the model, the top three highest important contributions were the percentage of CD38CD8T cells, PD-1NK cells, HLA-DRCD8T cells. Two clusters of peripheral immunophenotyping of septic patients by k-means clustering were conducted. Cluster 1 featured higher proportions of PD1 NK cells, while cluster 2 featured higher proportions of naïve CD4T cells. Furthermore, the level of PD-1NK cells was significantly higher in the non-survivors than the survivors (15.1% vs 8.6%, <0.01). Moreover, the levels of PD1 NK cells combined with SOFA score showed good performance in predicting the 28-day mortality in sepsis (AUC=0.91,95%CI 0.82-0.99), which is superior to PD1 NK cells only(AUC=0.69, sensitivity 0.74, specificity 0.64, cut-off value of 11.25%). In the multivariate Cox regression, high expression of PD1 NK cells proportion was related to 28-day mortality (aHR=1.34, 95%CI 1.19 to 1.50; <0.001).
CONCLUSION
The study provides novel insights into the association between PD1NK cell profiles and prognosis of sepsis. Peripheral immunophenotyping could potentially stratify the septic patients and identify those with a high risk of 28-day mortality.
Topics: Humans; Sepsis; Male; Female; Programmed Cell Death 1 Receptor; Middle Aged; Aged; Killer Cells, Natural; Retrospective Studies; Biomarkers; Prognosis; Immunophenotyping; ROC Curve; Machine Learning
PubMed: 38953031
DOI: 10.3389/fimmu.2024.1426064 -
Frontiers in Immunology 2024Anoikis is a form of programmed cell death essential for preventing cancer metastasis. In some solid cancer, anoikis resistance can facilitate tumor progression....
BACKGROUND
Anoikis is a form of programmed cell death essential for preventing cancer metastasis. In some solid cancer, anoikis resistance can facilitate tumor progression. However, this phenomenon is underexplored in clear-cell renal cell carcinoma (ccRCC).
METHODS
Using SVM machine learning, we identified core anoikis-related genes (ARGs) from ccRCC patient transcriptomic data. A LASSO Cox regression model stratified patients into risk groups, informing a prognostic model. GSVA and ssGSEA assessed immune infiltration, and single-cell analysis examined ARG expression across immune cells. Quantitative PCR and immunohistochemistry validated ARG expression differences between immune therapy responders and non-responders in ccRCC.
RESULTS
ARGs such as CCND1, CDKN3, PLK1, and BID were key in predicting ccRCC outcomes, linking higher risk with increased Treg infiltration and reduced M1 macrophage presence, indicating an immunosuppressive environment facilitated by anoikis resistance. Single-cell insights showed ARG enrichment in Tregs and dendritic cells, affecting immune checkpoints. Immunohistochemical analysis reveals that ARGs protein expression is markedly elevated in ccRCC tissues responsive to immunotherapy.
CONCLUSION
This study establishes a novel anoikis resistance gene signature that predicts survival and immunotherapy response in ccRCC, suggesting that manipulating the immune environment through these ARGs could improve therapeutic strategies and prognostication in ccRCC.
Topics: Humans; Carcinoma, Renal Cell; Anoikis; Kidney Neoplasms; Single-Cell Analysis; Prognosis; Gene Expression Regulation, Neoplastic; Drug Resistance, Neoplasm; Tumor Microenvironment; Lymphocytes, Tumor-Infiltrating; Transcriptome; Cell Line, Tumor; Biomarkers, Tumor; T-Lymphocytes, Regulatory; Gene Expression Profiling; Male; Multiomics
PubMed: 38953023
DOI: 10.3389/fimmu.2024.1427475 -
Pathology Oncology Research : POR 2024Lung cancer is a leading cause of cancer-related death worldwide in both men and women, however mortality in the US and EU are recently declining in parallel with the... (Review)
Review
Lung cancer is a leading cause of cancer-related death worldwide in both men and women, however mortality in the US and EU are recently declining in parallel with the gradual cut of smoking prevalence. Consequently, the relative frequency of adenocarcinoma increased while that of squamous and small cell carcinomas declined. During the last two decades a plethora of targeted drug therapies have appeared for the treatment of metastasizing non-small cell lung carcinomas (NSCLC). Personalized oncology aims to precisely match patients to treatments with the highest potential of success. Extensive research is done to introduce biomarkers which can predict the effectiveness of a specific targeted therapeutic approach. The EGFR signaling pathway includes several sufficient targets for the treatment of human cancers including NSCLC. Lung adenocarcinoma may harbor both activating and resistance mutations of the EGFR gene, and further, mutations of KRAS and BRAF oncogenes. Less frequent but targetable genetic alterations include ALK, ROS1, RET gene rearrangements, and various alterations of MET proto-oncogene. In addition, the importance of anti-tumor immunity and of tumor microenvironment has become evident recently. Accumulation of mutations generally trigger tumor specific immune defense, but immune protection may be upregulated as an aggressive feature. The blockade of immune checkpoints results in potential reactivation of tumor cell killing and induces significant tumor regression in various tumor types, such as lung carcinoma. Therapeutic responses to anti PD1-PD-L1 treatment may correlate with the expression of PD-L1 by tumor cells. Due to the wide range of diagnostic and predictive features in lung cancer a plenty of tests are required from a single small biopsy or cytology specimen, which is challenged by major issues of sample quantity and quality. Thus, the efficacy of biomarker testing should be warranted by standardized policy and optimal material usage. In this review we aim to discuss major targeted therapy-related biomarkers in NSCLC and testing possibilities comprehensively.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Biomarkers, Tumor; Proto-Oncogene Mas
PubMed: 38953007
DOI: 10.3389/pore.2024.1611733 -
Western Pacific Surveillance and... 2024While the COVID-19 pandemic threatened the entire world, the extremely remote Pitcairn Islands faced unique vulnerabilities. With only a physician and a nurse to care...
PROBLEM
While the COVID-19 pandemic threatened the entire world, the extremely remote Pitcairn Islands faced unique vulnerabilities. With only a physician and a nurse to care for an ageing population of fewer than 40 residents, and with very limited referral pathways, Pitcairn encountered distinct challenges in preparing for and responding to the COVID-19 pandemic.
CONTEXT
The Pitcairn Islands is an overseas territory of United Kingdom of Great Britain and Northern Ireland consisting of four islands in the South Pacific: Pitcairn, Henderson, Ducie and Oeno. Pitcairn is the only inhabited island with a local resident population of approximately 31 people, around half of whom were over 60 years old in 2023. The islands are only accessible by sea and are located more than 2000 km from the nearest referral hospital in French Polynesia.
ACTIONS
Pitcairn's Island Council took aggressive action to delay the importation of SARS-CoV-2, vaccinate its small population and prepare for the potential arrival of the virus.
OUTCOMES
As of May 2024, Pitcairn was one of the only jurisdictions in the world not to have had a single COVID-19 hospitalization or death. Nevertheless, the pandemic presented the islands' population with many economic, social and health challenges.
DISCUSSION
Pitcairn's population avoided COVID-19-related hospitalizations and deaths despite its elderly population's vulnerability to COVID-19, a significant level of comorbidities, and limited clinical management capabilities and options for emergency referrals. The pandemic highlighted some of the population's health vulnerabilities while also underscoring some of their innate strengths.
Topics: Humans; COVID-19; SARS-CoV-2; Pandemics; United Kingdom; Pandemic Preparedness
PubMed: 38953003
DOI: 10.5365/wpsar.2024.15.2.1068 -
PeerJ 2024Andrographolide (Andro), an extract of (Burm.f.) Wall. ex Nees (Acanthaceae), possesses diverse biologically active properties. However, the precise mechanisms and...
BACKGROUND
Andrographolide (Andro), an extract of (Burm.f.) Wall. ex Nees (Acanthaceae), possesses diverse biologically active properties. However, the precise mechanisms and effects of Andro on pancreatic cancer (PC) remain unclear.
METHODS
The cytotoxic potential of Andro and underlying mechanism towards PC cells was investigated through experiments and a xenograft mouse model. PC cells were first subjected to varying concentrations of Andro. The reactive oxygen species (ROS) was assessed using flow cytometry and DCFH-DA staining. The apoptosis rate was detected by flow cytometry. Additionally, western blot was applied to evaluate the expression levels of cleaved-caspase-3, DJ-1, LC3-I, LC3-II, and p62. To further elucidate the involvement of ROS accumulation and autophagy, we employed N-acetylcysteine as a scavenger of ROS and 3-Methyladenine as an inhibitor of autophagy.
RESULTS
Andro demonstrated potent anti-proliferative effects on PC cells and induced apoptosis, both and . The cytotoxicity of Andro on PC cells was counteracted by DJ-1 overexpression. The reduction in DJ-1 expression caused by Andro led to ROS accumulation, subsequently inhibiting the growth of PC cells. Furthermore, Andro stimulated cytoprotective autophagy, thus weakening the antitumor effect. Pharmacological blockade of autophagy further enhanced the antitumor efficacy of Andro.
CONCLUSION
Our study indicated that ROS accumulation induced by the DJ-1 reduction played a key role in Andro-mediated PC cell inhibition. Furthermore, the protective autophagy induced by the Andro in PC cells is a mechanism that needs to be addressed in future studies.
Topics: Reactive Oxygen Species; Diterpenes; Pancreatic Neoplasms; Autophagy; Protein Deglycase DJ-1; Animals; Humans; Mice; Cell Line, Tumor; Apoptosis; Xenograft Model Antitumor Assays; Mice, Nude
PubMed: 38952980
DOI: 10.7717/peerj.17619 -
Metabolism Open Jun 2024Diabetic kidney disease (DKD) is an important complication of diabetes as it results in end-stage renal disease; hence, several drugs have been developed for its...
INTRODUCTION
Diabetic kidney disease (DKD) is an important complication of diabetes as it results in end-stage renal disease; hence, several drugs have been developed for its treatment. However, even with treatment with renin-angiotensin system inhibitors and sodium-glucose cotransporter-2 inhibitors, the residual risk of DKD remains. While this risk is an issue, the renoprotective effects of finerenone, a novel non-steroidal mineralocorticoid receptor antagonist, are becoming evident. High proteinuria increases the risk of cardiovascular death as well as renal failure. Hence, it is especially important to address cases of urine protein to nephrotic levels in DKD, however, no previous studies have assessed the safety and efficacy of finerenone in patients with DKD and nephrotic syndrome. Therefore, this study aimed to assess whether finerenone has a renoprotective effect in advanced DKD complicated by nephrotic syndrome.
METHODS
Nine patients with DKD and nephrotic syndrome who received 10-20 mg/day of finerenone were retrospectively analyzed. The average observation period was 9.7 ± 3.4 months. Patients with serum potassium levels greater than 5.0 mEq/L at the start of finelenone were excluded. Changes in urinary protein levels, estimated glomerular filtration rate (eGFR), and serum potassium levels were studied before and after finerenone administration.
RESULTS
The mean changes in the urinary protein creatinine ratio (UPCR) at baseline were 6.6 ± 2.0. After finerenone treatment, the mean UPCR decreased to -0.6 ± 3.9; however, this change was not statistically significant.The eGFR decline slope also tended to decrease with finerenone treatment (before vs. after: 3.1 ± 4.9 vs. -1.7 ± 3.2 mL/min/1.73 m. Furthermore, finerenone did not increase serum potassium levels.
CONCLUSIONS
Patients treated with finerenone showed decreased UPCR; hence, it is suggested that finerenone may be effective in treating nephrotic syndrome in patients with DKD. These findings may be applicable to real-world clinical settings. Nonetheless, it is important to note that this study was a retrospective analysis of a single-center cohort and had a limited sample size, highlighting the need for additional large-scale investigations.
PubMed: 38952893
DOI: 10.1016/j.metop.2024.100294 -
Nigerian Medical Journal : Journal of... 2023Neurological disorders constitute major causes of morbidity, and globally, they are the leading causes of death. There is a dearth of neurologists in most African...
BACKGROUND
Neurological disorders constitute major causes of morbidity, and globally, they are the leading causes of death. There is a dearth of neurologists in most African countries and the very few available ones are concentrated in urban areas. The cardiovascular and communicable risk factors responsible for most cases of acute and chronic neurological disorders are also prevalent in rural areas. Although patients from the neighbouring states attend the study centre, the majority are indigent. Therefore, there is a need to observe the pattern of these disorders in Ekiti, to appreciate the disease burden as it would help in the judicious allocation of human and other healthcare resources.
METHODOLOGY
We reviewed the case files of patients seen at the neurology clinic and admitted via the emergency department into the Federal Teaching Hospital, Ido-Ekiti, over a period of 6 years (2016 to 2021).
RESULTS
A total of 881patients were seen during the study period, and they were mostly elderly male patients with chronic disorders in which stroke was the most common neurological disorder (44.9%) followed by seizure disorder (13.1%), and neurodegenerative disorders (9.9%). Tumors and myopathies were the least seen disorders.
CONCLUSION
Health literacy on cardiovascular risk factors and even the distribution of manpower and material resources will help reduce the burden of neurological disorders among the attendees of the Ekiti tertiary health institution.
PubMed: 38952889
DOI: 10.60787/NMJ-64-4-218