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Critical Care Explorations Jun 2024To develop and validate a prediction model for 1-year mortality in patients with a hematologic malignancy acutely admitted to the ICU.
OBJECTIVES
To develop and validate a prediction model for 1-year mortality in patients with a hematologic malignancy acutely admitted to the ICU.
DESIGN
A retrospective cohort study.
SETTING
Five university hospitals in the Netherlands between 2002 and 2015.
PATIENTS
A total of 1097 consecutive patients with a hematologic malignancy were acutely admitted to the ICU for at least 24 h.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
We created a 13-variable model from 22 potential predictors. Key predictors included active disease, age, previous hematopoietic stem cell transplantation, mechanical ventilation, lowest platelet count, acute kidney injury, maximum heart rate, and type of malignancy. A bootstrap procedure reduced overfitting and improved the model's generalizability. This involved estimating the optimism in the initial model and shrinking the regression coefficients accordingly in the final model. We assessed performance using internal-external cross-validation by center and compared it with the Acute Physiology and Chronic Health Evaluation II model. Additionally, we evaluated clinical usefulness through decision curve analysis. The overall 1-year mortality rate observed in the study was 62% (95% CI, 59-65). Our 13-variable prediction model demonstrated acceptable calibration and discrimination at internal-external validation across centers (-statistic 0.70; 95% CI, 0.63-0.77), outperforming the Acute Physiology and Chronic Health Evaluation II model (-statistic 0.61; 95% CI, 0.57-0.65). Decision curve analysis indicated overall net benefit within a clinically relevant threshold probability range of 60-100% predicted 1-year mortality.
CONCLUSIONS
Our newly developed 13-variable prediction model predicts 1-year mortality in hematologic malignancy patients admitted to the ICU more accurately than the Acute Physiology and Chronic Health Evaluation II model. This model may aid in shared decision-making regarding the continuation of ICU care and end-of-life considerations.
Topics: Humans; Hematologic Neoplasms; Intensive Care Units; Male; Retrospective Studies; Middle Aged; Female; Aged; Netherlands; Adult; APACHE; Cohort Studies
PubMed: 38813435
DOI: 10.1097/CCE.0000000000001093 -
Journal of Nanobiotechnology May 2024Chemotherapy, as a conventional strategy for tumor therapy, often leads to unsatisfied therapeutic effect due to the multi-drug resistance and the serious side effects....
Chemotherapy, as a conventional strategy for tumor therapy, often leads to unsatisfied therapeutic effect due to the multi-drug resistance and the serious side effects. Herein, we genetically engineered a thermal-responsive murine Ferritin (mHFn) to specifically deliver mitoxantrone (MTO, a chemotherapeutic and photothermal agent) to tumor tissue for the chemotherapy and photothermal combined therapy of colorectal cancer, thanks to the high affinity of mHFn to transferrin receptor that highly expressed on tumor cells. The thermal-sensitive channels on mHFn allowed the effective encapsulation of MTO in vitro and the laser-controlled release of MTO in vivo. Upon irradiation with a 660 nm laser, the raised temperature triggered the opening of the thermal-sensitive channel in mHFn nanocage, resulting in the controlled and rapid release of MTO. Consequently, a significant amount of reactive oxygen species was generated, causing mitochondrial collapse and tumor cell death. The photothermal-sensitive controlled release, low systemic cytotoxicity, and excellent synergistic tumor eradication ability in vivo made mHFn@MTO a promising candidate for chemo-photothermal combination therapy against colorectal cancer.
Topics: Animals; Colorectal Neoplasms; Mice; Ferritins; Photothermal Therapy; Humans; Mitoxantrone; Lasers; Cell Line, Tumor; Reactive Oxygen Species; Mice, Inbred BALB C; Antineoplastic Agents; Mice, Nude; Female
PubMed: 38812019
DOI: 10.1186/s12951-024-02566-6 -
Journal of Medical Case Reports May 2024Although 5-aminolevulinic acid is useful for the photodynamic diagnosis of bladder tumors, it often causes severe intraoperative hypotension. We report a case of...
BACKGROUND
Although 5-aminolevulinic acid is useful for the photodynamic diagnosis of bladder tumors, it often causes severe intraoperative hypotension. We report a case of postoperative cardiac arrest in addition to severe intraoperative hypotension, probably owing to the use of 5-aminolevulinic acid.
CASE PRESENTATION
An 81-year-old Japanese man was scheduled to undergo transurethral resection of bladder tumor. The patient took 5-aminolevulinic acid orally 2 hours before entering the operating room. After the induction of anesthesia, his blood pressure decreased to 47/33 mmHg. The patient's hypotension did not improve even after noradrenaline was administered. After awakening from anesthesia, the patient's systolic blood pressure increased to approximately 100 mmHg, but approximately 5 hours after returning to the ward, cardiac arrest occurred for approximately 12 seconds.
CONCLUSION
We experienced a case of postoperative cardiac arrest in a patient, probably owing to the use of 5-aminolevulinic acid. Although the cause of cardiac arrest is unknown, perioperative hemodynamic management must be carefully performed in patients taking 5-aminolevulinic acid.
Topics: Humans; Male; Aminolevulinic Acid; Hypotension; Aged, 80 and over; Heart Arrest; Urinary Bladder Neoplasms; Postoperative Complications; Photosensitizing Agents; Intraoperative Complications
PubMed: 38811941
DOI: 10.1186/s13256-024-04589-x -
Revista Paulista de Pediatria : Orgao... 2024Pediatric cardiac tumors are rare and, among them, 90% are benign. Cardiac fibroma is the second most frequent tumor, after rhabdomyoma. The objective of this study is...
OBJECTIVE
Pediatric cardiac tumors are rare and, among them, 90% are benign. Cardiac fibroma is the second most frequent tumor, after rhabdomyoma. The objective of this study is to report a case of cardiac fibroma diagnosed incidentally in a patient admitted with acute viral bronchiolitis.
CASE DESCRIPTION
A 5-month-old male infant was admitted to the pediatric emergency department with acute viral bronchiolitis requiring hospitalization. He presented a detectable respiratory syncytial virus in oropharyngeal swab, blood test with lymphocytosis and a chest radiography revealed cardiomegaly. Further cardiologic testing was performed detecting elevation of cardiac biomarkers, an electrocardiogram with alteration of left ventricular repolarization and echocardiogram with a heterogeneous mass in the left ventricular, with areas of calcification. A chest angiotomography suggested rhabdomyosarcoma or cardiac fibroma and a magnetic resonance showed a mass, with characteristics suggesting fibroma. The final diagnosis was made after two cardiac catheterizations for biopsy of the lesion, confirming cardiac fibroma by anatomopathological examination. Because the patient had moderate to severe systolic dysfunction, he was submitted to heart transplant.
COMMENTS
One third of cardiac fibromas are asymptomatic, generally diagnosed late through tests ordered for other reasons. The gold-standard test for definitive diagnosis is biopsy. Cardiac fibroma usually does not present spontaneous regression and, in most cases, partial or total surgical resection is necessary. When tumors are unresectable, heart transplantation should be indicated. It is essential to have detailed characterization of the cardiac mass to establish the most appropriate therapeutic approach for each patient.
Topics: Humans; Male; Heart Neoplasms; Fibroma; Infant; Incidental Findings; Bronchiolitis, Viral; Acute Disease
PubMed: 38808864
DOI: 10.1590/1984-0462/2024/42/2022157 -
JAMA Network Open May 2024The ratio of red blood cell distribution width (RDW) to albumin concentration (RAR) has emerged as a reliable prognostic marker for mortality in patients with various...
IMPORTANCE
The ratio of red blood cell distribution width (RDW) to albumin concentration (RAR) has emerged as a reliable prognostic marker for mortality in patients with various diseases. However, whether RAR is associated with mortality in the general population remains unknown.
OBJECTIVES
To explore whether RAR is associated with all-cause and cause-specific mortality and to elucidate their dose-response association.
DESIGN, SETTING, AND PARTICIPANTS
This population-based prospective cohort study used data from participants in the 1998-2018 US National Health and Nutrition Examination Survey (NHANES) and from the UK Biobank with baseline information provided from 2006 to 2010. Included participants had complete data on serum albumin concentration, RDW, and cause of death. The NHANES data were linked to the National Death Index records through December 31, 2019. For the UK Biobank, dates and causes of death were obtained from the National Health Service Information Centre (England and Wales) and the National Health Service Central Register Scotland (Scotland) to November 30, 2022.
MAIN OUTCOMES AND MEASURES
Potential associations between RAR and the risk of all-cause and cause-specific mortality were evaluated using Cox proportional hazards regression models. Restricted cubic spline regressions were applied to estimate possible nonlinear associations.
RESULTS
In NHANES, 50 622 participants 18 years of age or older years were included (mean [SD] age, 48.6 [18.7] years; 26 136 [51.6%] female), and their mean (SD) RAR was 3.15 (0.51). In the UK Biobank, 418 950 participants 37 years of age or older (mean [SD], 56.6 [8.1] years; 225 038 [53.7%] female) were included, and their mean RAR (SD) was 2.99 (0.31). The NHANES documented 7590 deaths over a median (IQR) follow-up of 9.4 (5.1-14.2) years, and the UK Biobank documented 36 793 deaths over a median (IQR) follow-up of 13.8 (13.0-14.5) years. According to the multivariate analysis, elevated RAR was significantly associated with greater risk of all-cause mortality (NHANES: hazard ratio [HR], 1.83 [95% CI, 1.76-1.90]; UK Biobank: HR, 2.08 [95% CI, 2.03-2.13]), as well as mortality due to malignant neoplasm (NHANES: HR, 1.89 [95% CI, 1.73-2.07]; UK Biobank: HR, 1.93 [95% CI, 1.86-2.00]), heart disease (NHANES: HR, 1.88 [95% CI, 1.74-2.03]; UK Biobank: HR, 2.42 [95% CI, 2.29-2.57]), cerebrovascular disease (NHANES: HR, 1.35 [95% CI, 1.07-1.69]; UK Biobank: HR, 2.15 [95% CI, 1.91-2.42]), respiratory disease (NHANES: HR, 1.99 [95% CI, 1.68-2.35]; UK Biobank: HR, 2.96 [95% CI, 2.78-3.15]), diabetes (NHANES: HR, 1.55 [95% CI, 1.27-1.90]; UK Biobank: HR, 2.83 [95% CI, 2.35-3.40]), and other causes of mortality (NHANES: HR, 1.97 [95% CI, 1.86-2.08]; UK Biobank: HR, 2.40 [95% CI, 2.30-2.50]) in both cohorts. Additionally, a nonlinear association was observed between RAR levels and all-cause mortality in both cohorts.
CONCLUSIONS AND RELEVANCE
In this cohort study, a higher baseline RAR was associated with an increased risk of all-cause and cause-specific mortality in the general population. These findings suggest that RAR may be a simple, reliable, and inexpensive indicator for identifying individuals at high risk of mortality in clinical practice.
Topics: Humans; Female; Male; Erythrocyte Indices; Middle Aged; Prospective Studies; Nutrition Surveys; Adult; Aged; Cause of Death; United States; Serum Albumin; Proportional Hazards Models; Mortality; Risk Factors; Biomarkers; United Kingdom
PubMed: 38805227
DOI: 10.1001/jamanetworkopen.2024.13213 -
Technology in Cancer Research &... 2024Colorectal cancer is a highly aggressive malignant tumor that primarily affects the digestive system. It is frequently diagnosed at an advanced stage. Cuproptosis is a...
Colorectal cancer is a highly aggressive malignant tumor that primarily affects the digestive system. It is frequently diagnosed at an advanced stage. Cuproptosis is a copper-dependent form cell death mechanism, distinct from all other known pathways underlying cell death, tumor progression, prognosis, and immune response. Although the role of cuproptosis in colorectal cancer has been investigated over time, there is still an urgent need to explore new methods and insights to understand its potential function. The Gene Expression Omnibus and The Cancer Genome Atlas gene expression data were systematically explored to investigate the role of cuproptosis in colon adenocarcinoma. The weighted gene coexpression network analysis was used to construct a gene coexpression network and identify the critical module and cuproptosis-related genes correlated with colon adenocarcinoma prognosis. A cuproptosis-related genes prognostic signature for colon adenocarcinoma was identified and validated. To validate the identified gene signature, quantitative reverse transcription-polymerase chain reaction was performed. Cell proliferation assays were analyzed by CCK8 and cell cycle detection. In addition, reactive oxygen species assay was also analyzed. Five hub cuproptosis-related genes (Dihydrolipoamide S-acetyltransferase, Cyclin-dependent kinase inhibitor 2A, ATOX1, VEGFA, and ULK1) were screened and a prognostic risk model for predicting overall survival was established based on these genes. The model was successfully tested in the validation cohort and the GEPIA database. Colon adenocarcinoma patients were categorized into high-risk and low-risk groups based on risk scores. The study revealed that patients with higher risk scores were more likely to have a poor prognosis. Moreover, Dihydrolipoamide S-acetyltransferase was a tumor suppressor gene that can induce cell death and affected the redox reactions in the colon cancer cell line. These findings suggest that the newly identified 5-gene signature may serve as a more reliable prognostic factor than clinical factors such as age and stage of disease. These findings offer a theoretical foundation for further investigation into potential cuproptosis-related biomarkers for predicting colon adenocarcinoma prognosis in the future.
Topics: Humans; Prognosis; Colonic Neoplasms; Adenocarcinoma; Biomarkers, Tumor; Gene Regulatory Networks; Gene Expression Regulation, Neoplastic; Gene Expression Profiling; Transcriptome; Computational Biology; Cell Proliferation; Cell Line, Tumor; Databases, Genetic; Kaplan-Meier Estimate; Male
PubMed: 38802999
DOI: 10.1177/15330338241250285 -
BMC Public Health May 2024No study has concentrated on the association of LE8 with cancer risk and death. We aim to examine the association of LE8 with death and cancer.
BACKGROUND
No study has concentrated on the association of LE8 with cancer risk and death. We aim to examine the association of LE8 with death and cancer.
METHODS
A total of 94733 adults aged 51.42 ± 12.46 years and 77551 participants aged 54.09±12.06 years were enrolled in longitudinal and trajectory analysis respectively. Baseline LE8 was divided into three groups based on the American Heart Association criteria and three trajectory patterns by latent mixture models. We reviewed medical records and clinical examinations to confirm incident cancer during the period from 2006 to 2020. Death information was collected from provincial vital statistics offices. Cox models were used.
RESULTS
12807 all-cause deaths and 5060 cancers were documented during a 14-year follow-up. Relative to participants with high LE8 at baseline, participants with lower levels of LE8 have a significantly increased risk of mortality and incident cancer. All these risks have an increasing trend with LE8 level decreasing. Meanwhile, the trajectory analysis recorded 7483 all-cause deaths and 3037 incident cancers after approximately 10 years. The associations of LE8 with death and cancer were identical to the longitudinal study. In the subtype cancer analysis, LE8 has a strong effect on colorectal cancer risk. Moreover, the cut point is 56.67 in the association between LE8 and death, while the cut point altered to 64.79 in the association between LE8 and incident cancers. These associations were enhanced among younger adults.
CONCLUSIONS
There was a significant association of LE8 with death and cancer risk, especially for the young population.
Topics: Humans; Male; Middle Aged; Neoplasms; Female; Prospective Studies; Adult; Cause of Death; Aged; Risk Factors; Longitudinal Studies; China; Risk Assessment
PubMed: 38802806
DOI: 10.1186/s12889-024-18879-y -
Turkish Journal of Haematology :... May 2024It has been shown that clonal mutations occur in hematopoietic stem cells with advancing age and increase the risk of death due to atherosclerotic vascular diseases,...
OBJECTIVE
It has been shown that clonal mutations occur in hematopoietic stem cells with advancing age and increase the risk of death due to atherosclerotic vascular diseases, just like in myeloproliferative neoplasms. It is known that endothelial cells (EC) and hematopoietic stem cells develop from a common stem cell called hemangioblast in early embryonic period. However, the presence of hemangioblast in the postnatal period is controversial. In this study, JAK2 gene variants was examined in patients with atherosclerotic carotid disease and without any hematological malignancy.
MATERIALS AND METHODS
Ten consecutive patients (8 men and 2 women) with symptomatic atherosclerotic carotid stenosis were included in this study. EC (CD31+CD45-) were separated from tissue samples taken by carotid endarterectomy. JAK2 variants was examined in EC, peripheral blood mononuclear cells and oral epithelial cells of the patients with next generation sequencing.
RESULTS
The median age of the patients was 74 (58-80) and the median BMI was 24,44 (18,42-30,85) kg/m2. Smoking history was present in 50%, hypertension in 80%, diabetes in 70%, and ischemic heart disease in 70% of the patients. JAK2V617F mutation was detected in peripheral blood mononuclear cells in three out of 10 patients, two of them also had JAK2V617F mutation in their EC. JAK2V617F mutation was not found in oral epithelial cells in any of the patients.
CONCLUSION
In this study, for the first time in the literature, we showed that JAK2V617F mutation was found somatically in both peripheral blood cells and EC in patients with atherosclerosis. This finding may support that EC and hematopoietic cells originate from a common clone or that the somatic mutation can be transmitted to EC by other mechanisms. Examining the molecular and functional changes caused by JAK2V617F mutation in EC may help open a new avenue for treating atherosclerosis.
PubMed: 38801025
DOI: 10.4274/tjh.galenos.2024.2024.0161 -
Reumatologia 2024Fracture of the proximal femur is common in elderly patients, in fact threatening their lives. Age-related sarcopenia may be involved in the imbalance resulting in the...
INTRODUCTION
Fracture of the proximal femur is common in elderly patients, in fact threatening their lives. Age-related sarcopenia may be involved in the imbalance resulting in the injury. Handy and readily accessible biochemical tests would be useful to assess the musculoskeletal system condition in daily practice. The aim of the study was to determine whether there is any relation between muscle decay and fracture of the proximal femur and to assess bone quality in elderly patients.
MATERIAL AND METHODS
In the study 22 patients who represented the treatment group were hospitalized due to proximal femur fracture. Eighteen patients from the control group with no fracture in their history were admitted to the Internal Medicine Department. Anyone treated for osteoporosis, immune disease affecting protein balance, neoplasm, mental illness, heart failure, or myocardial infarction was excluded from the study. In every case a blood sample from an elbow vein was drawn, collected in EDTA-K2 tubes, and then centrifuged to separate plasma from the whole blood. Subsequently, the concentrations of C-terminal cross-linked telopeptide of type I collagen (CTX-I), sex hormone binding globulin (SHBG) and creatine kinase (CK) in plasma were determined using commercial enzyme-linked immunosorbent assays.
RESULTS
The CK plasma concentration differed between the patient groups ( = 0.011). The SHBG plasma concentration was significantly higher in the treatment group ( = 0.006), whereas a slight difference in CTX-I plasma concentration between the groups was found ( = 0.038). No significant correlations between plasma CK, SHBG or CTX-I were found ( > 0.05).
CONCLUSIONS
Creatine kinase is actually not an appropriate marker for the clinical assessment of muscle tissue quality in patients with or at risk of proximal femur fracture. Analyzing the quality of bone tissue, we can conclude it was poorer in patients with proximal femur fracture than in the control group.
PubMed: 38799774
DOI: 10.5114/reum/187096 -
Frontiers in Public Health 2024Pollution is a critical concern of modern society for its heterogeneous effects on human health, despite a widespread lack of awareness. Environmental pollutants promote... (Review)
Review
Pollution is a critical concern of modern society for its heterogeneous effects on human health, despite a widespread lack of awareness. Environmental pollutants promote several pathologies through different molecular mechanisms. Pollutants can affect the immune system and related pathways, perturbing its regulation and triggering pro-inflammatory responses. The exposure to several pollutants also leads to alterations in gut microbiota with a decreasing abundance of beneficial microbes, such as short-chain fatty acid-producing bacteria, and an overgrowth of pro-inflammatory species. The subsequent intestinal barrier dysfunction, together with oxidative stress and increased inflammatory responses, plays a role in the pathogenesis of gastrointestinal inflammatory diseases. Moreover, pollutants encourage the inflammation-dysplasia-carcinoma sequence through various mechanisms, such as oxidative stress, dysregulation of cellular signalling pathways, cell cycle impairment and genomic instability. In this narrative review, we will describe the interplay between pollutants, gut microbiota, and the immune system, focusing on their relationship with inflammatory bowel diseases and colorectal cancer. Understanding the biological mechanisms underlying the health-to-disease transition may allow the design of public health policies aimed at reducing the burden of disease related to pollutants.
Topics: Humans; Gastrointestinal Microbiome; Environmental Pollutants; Immune System; Inflammatory Bowel Diseases; Colorectal Neoplasms; Oxidative Stress
PubMed: 38799688
DOI: 10.3389/fpubh.2024.1285186