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The American Journal of Emergency... Jun 2024Out-of-hospital cardiac arrest (OHCA) increases lactate levels and reduces albumin levels on admission and tends to lead to a poor neurological prognosis. In our...
BACKGROUND
Out-of-hospital cardiac arrest (OHCA) increases lactate levels and reduces albumin levels on admission and tends to lead to a poor neurological prognosis. In our experience, reduced cholesterol levels predict poor neurological prognosis. However, the relationship between cholesterol levels and neurological prognosis in OHCA survivors remains unclear.
METHODS
This retrospective observational study included data from January 2015 to June 2023 on 219 OHCA survivors at our intensive care unit. Patients were categorized into two groups based on cerebral functional classification (CPC) scores: Group A (CPC score of 1 or 2), including patients with a favorable neurological outcome, and Group B (CPC scores of 3 to 5), comprising those with a poor neurological outcome. We analyzed their lactate, albumin levels, and lipid profiles measured at 6 h after resuscitation. A model to predict the neurological prognosis of admission of OHCA survivors was developed.
RESULTS
Approximately 40% of the patients had favorable neurological outcomes at the 30-day follow-up. The lactate-to-albumin ratio (LAR) was significantly lower in Group A than in Group B (3.1 vs. 5.0 mmol/dag, p < 0.001). However, the albumin, total cholesterol, and high-density lipoprotein (HDL) cholesterol levels were significantly higher in Group A than in Group B (3.6 vs. 2.9 g/dL, 166.1 vs. 131.4 mg/dL, and 38.8 vs. 29.7 mg/dL, respectively, p < 0.001). Favorable neurological outcome was indicated at the following thresholds: LAR < 3.7 mmol/dag, albumin level > 3.1 g/dL, total cholesterol level > 146.4 mg/dL, and HDL-cholesterol level > 31.9 mg/dL. These findings underscore the high sensitivity and negative predictive value of the biomarkers. Furthermore, the area under the curve values for LAR, albumin, total cholesterol, and HDL-cholesterol levels were 0.70, 0.75, 0.71, and 0.71, respectively. The corresponding odds ratios were 3.37, 7.08, 3.67, and 3.94, respectively.
CONCLUSIONS
The LAR, albumin, total cholesterol, and HDL-cholesterol levels measured on admission may predict neurological prognosis in OHCA survivors. Thus, routine practice should include the measurement of these biomarkers at 6 h after resuscitation, especially in patients with a lactate level of > 5 mmol/L.
TRIAL REGISTRATION
ClinicalTrials.gov ID: NCT02633358.
PubMed: 38943710
DOI: 10.1016/j.ajem.2024.06.029 -
Iranian Journal of Immunology : IJI Jun 2024Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for β-thalassemia major in children. However, it often induces graft-versus-host-disease...
Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for β-thalassemia major in children. However, it often induces graft-versus-host-disease (GVHD), which is associated with complications. In the present study, we used cyclophosphamide (Cy) to treat a thalassemia patient post-HSCT to reduce the adverse effects of GVHD. We monitored the numbers and phenotype of granulocytes. In this case study, an 11-year-old female patient, diagnosed with β-thalassemia major (Pesaro class II), was treated with Cy before and after HSCT with mobilized CD34+ cells. Both the relative and absolute granulocyte counts, as well as CD33+CD11b+ cell counts, increased significantly after HSCT until day 56. However, they suddenly began to decrease after day 56, accompanied by severe diarrhea, skin rash, and a decrease in bilirubin levels compared to day -12. Furthermore, compared to day -12, IL-22 levels increased until day 56, and then decreased, while IDO levels continued to rise after day 56. Our data suggest the potential use of IL-22 and IDO as biomarkers for GVHD assessment. It also indicates that Cy promotes HSCT reconstitution by increasing CD33+CD11b+ cells, which may play a crucial role in reducing GVHD risks. However, further studies are needed to elucidate the mechanism behind GVHD recurrence.
PubMed: 38943529
DOI: 10.22034/iji.2024.101584.2752 -
Endocrinology, Diabetes & Metabolism Jul 2024Data suggest malfunctioning mitochondria reduce oxidation and adenosine triphosphate (ATP) production, disrupting insulin signalling. Cytochrome c (CC), acylcarnitine... (Observational Study)
Observational Study Comparative Study
INTRODUCTION
Data suggest malfunctioning mitochondria reduce oxidation and adenosine triphosphate (ATP) production, disrupting insulin signalling. Cytochrome c (CC), acylcarnitine (AC) and citrate synthase (CS) are essential components of the mitochondria machinery and can be used as reliable biomarkers of mitochondrial dysfunction. This study aimed to determine whether mitochondrial biomarkers (AC, CS and CC) are altered in individuals with type 2 diabetes mellitus (T2DM) and to examine the association between these biomarkers and insulin resistance.
METHODOLOGY
A cross-sectional observational study that recruited 170 participants (88 with T2DM and 82 without DM) was conducted. Blood samples were collected from the recruits and analysed for levels of fasting glucose (FBG), AC, CS, CC, insulin, total cholesterol, triglycerides (TG), glycated haemoglobin (HbA1c) and magnesium. Blood pressure (BP) and anthropometric characteristics of participants were also taken. Appropriate formulas were used to determine %body fat, body mass index (BMI), waist-to-hip ratio (WHR), the homeostatic model assessment for insulin resistance (HOMA-IR) and insulin sensitivity (HOMA-β).
RESULTS
Patients with T2DM had higher levels of CC, %body fat, FBG, TG, HbA1c, BMI and HOMA-IR than controls (p < 0.05, respectively). Results showed a significant relationship between circulating CC levels versus HOMA-β (r = -0.40, p = 0.001), CS (r = -0.70, p = 0.001) and AC (r = -0.72, p = 0.001) levels in patients with T2DM. The adjusted odds increased in the T2DM patients for VLDL (OR = 6.66, p = 0.002), HbA1c (OR = 6.50, p = 0.001), FPG (OR = 3.17, p = 0.001), TG (OR = 2.36, p = 0.010), being female (OR = 2.09, p = 0.020) and CC (OR = 1.14, p = 0.016).
CONCLUSION
Overall, alterations in mitochondrial biomarkers, measured by AC, CC and CS, were observed in people with T2DM and showed a direct relationship with insulin resistance. These findings are potentially significant in Africa, although additional confirmation from a larger cohort is necessary.
Topics: Humans; Diabetes Mellitus, Type 2; Insulin Resistance; Cross-Sectional Studies; Male; Female; Biomarkers; Middle Aged; Mitochondria; Adult; Carnitine; Cytochromes c; Citrate (si)-Synthase; Glycated Hemoglobin; Blood Glucose; Aged; Body Mass Index
PubMed: 38943337
DOI: 10.1002/edm2.507 -
Nigerian Journal of Clinical Practice Jun 2024The burden of perinatal asphyxia remains high in our environment and when asphyxia is severe, vital organs are affected, with resultant multiorgan hypoxic-iscahemic...
BACKGROUND
The burden of perinatal asphyxia remains high in our environment and when asphyxia is severe, vital organs are affected, with resultant multiorgan hypoxic-iscahemic injury to the heart, the brain, adrenals and other organs.
STUDY AIM
To evaluate for myocardial injury in asphyxiated term neonates with hypoxic ischaemic encephalopathy using serum cardiac troponin-I (cTnI).
METHODS
The study was a hospital-based descriptive cross-sectional study involving sixty term asphyxiated neonates and sixty gestational age-and sex-matched controls. The subjects were term neonates with five-minute Apgar score ≤ 6 and HIE while the controls were healthy term neonates with five-minute Apgar score > 6. Five-minute Apgar score was utilized to classify asphyxia into mild, moderate and severe asphyxia. The degree of encephalopathy was determined by modified Sarnat and Sarnat criteria. The serum cTnI was measured in subjects and controls at 12-24 hours of life using Enzyme-linked immunosorbent assay technique. The serum bilirubin levels were also measured in participants to exclude hyperbilirubinemia.
RESULTS
The median serum cTnI levels was significantly higher in the subjects (0.56ng/mL; 0.25-0.94ng/mL) than in the controls (0.50ng/mL; 0.00-0.67ng/mL), respectively; p=0.001. Similarly, the median serum cTnI level in HIE stage II (0.56ng/mL; 0.38-0.72ng/mL) or III (0.56ng/ml; 0.50-0.94ng/mL) was also significantly higher than the median value in HIE stage I (0.38ng/mL;0.25-0.72ng/mL) or in controls (0.50ng/mL; 0.00-0.67ng/mL); p<0.001. There was significant positive correlation between serum cTnI levels and severity of HIE in asphyxiated neonates (rs = 0.505, p < 0.001).
CONCLUSION
serum cTnI levels were elevated in severely asphyxiated neonates with HIE. The concentration of serum cTnI demonstrated significant positive correlation with HIE severity. Hence, the presence of HIE in asphyxiated neonates should prompt an evaluation for myocardial injury using serum cTnI. Any derangement noted should warrant instituting cardiovascular support in order to improve outcome and reduce asphyxia-related mortality.
Topics: Humans; Infant, Newborn; Asphyxia Neonatorum; Troponin I; Female; Nigeria; Male; Cross-Sectional Studies; Case-Control Studies; Hospitals, Teaching; Apgar Score; Biomarkers; Hypoxia-Ischemia, Brain
PubMed: 38943306
DOI: 10.4103/njcp.njcp_169_24 -
Nigerian Journal of Clinical Practice Jun 2024Rhinoplasty is a common surgical procedure used in nose esthetics and pathologies. Shaping the nasal bones is a crucial step in achieving successful rhinoplasty surgery....
BACKGROUND
Rhinoplasty is a common surgical procedure used in nose esthetics and pathologies. Shaping the nasal bones is a crucial step in achieving successful rhinoplasty surgery. However, complications such as excessive bleeding, edema, mucosal damage, and periosteal damage may occur during osteotomy for nose shaping.
AIM
To investigate the damage to soft tissue and the effects on oxidative stress and proinflammatory cytokines in the blood caused by osteotomy performed on rabbits, using different osteotomy methods. Methods: Thirty-two albino New Zealand rabbits were divided into four groups. Group A was the sham group (n = 8), Group B the piezoelectric device group (n = 8), Group C the manual saw group (n = 8), and Group D the classical osteotomy group (n = 8). About 3 ml of blood was drawn to compare preoperative and postoperative interleukin-1ß (IL-1ß), thiobarbituric acid-reactive substances (TBARS), tumor necrosis factor-alpha (TNF-alpha), nitric oxide (NO), interleukin-10 (IL-10), and glutathione (GSH) levels. A 1 mm3 piece of soft tissue from the nasal bone of each animal in the study groups was sent for histopathological examination. The Chi-square test was used to analyze the incidence of postoperative necrosis, inflammation, and edema in the groups.
RESULTS
Histopathologically, edema was significantly higher in Group C and Group D compared to Group B. Inflammation was increased in all groups. The necrosis was significantly higher in Group B compared to Group C and Group D. Except for two parameters, no significant changes were found in the biochemical markers for all groups.
CONCLUSIONS
The piezoelectric device was found to be a better option for reducing edema and inflammation, while manual saws and classical osteotomy may lead to more tissue damage.
Topics: Animals; Oxidative Stress; Rabbits; Osteotomy; Rhinoplasty; Biomarkers; Nitric Oxide; Cytokines; Inflammation; Interleukin-1beta; Tumor Necrosis Factor-alpha; Thiobarbituric Acid Reactive Substances; Glutathione; Edema; Interleukin-10; Piezosurgery; Nose
PubMed: 38943295
DOI: 10.4103/njcp.njcp_686_23 -
ESC Heart Failure Jun 2024Inflammation has emerged as a potential key pathophysiological mechanism in heart failure (HF) in general and acute HF (AHF) specifically, with inflammatory biomarkers...
AIMS
Inflammation has emerged as a potential key pathophysiological mechanism in heart failure (HF) in general and acute HF (AHF) specifically, with inflammatory biomarkers shown to be highly predictive of adverse outcomes in these patients. The CORTAHF study builds on both these data and the fact that steroid burst therapy has been shown to be effective in the treatment of respiratory diseases and COVID-19. Our hypothesis is that in patients with AHF and elevated C-reactive protein (CRP) levels without symptoms or signs of infection, a 7-day course of steroid therapy will lead to reduced inflammation and short-term improvement in quality of life and a reduced risk of worsening HF (WHF) events.
METHODS AND RESULTS
The study, which is currently ongoing, will include 100 patients with AHF ages 18-85, regardless of ejection fraction, screened within 12 h of presentation. Patients will be included who have NT-proBNP > 1500 pg/mL and CRP > 20 mg/L at screening. Exclusion criteria include haemodynamic instability and symptoms and signs of infection. After signed consent, eligible patients will be randomized according to a central randomization scheme stratified by centre 1:1 to either treatment once daily for 7 days with 40 mg prednisone orally or to standard care. Patients will be assessed at study day 2, day 4 or at discharge if earlier, and at days 7 and 31 at the hospital; and at day 91 through a telephone follow-up. The primary endpoint is the change in CRP level from baseline to day 7, estimated from a mixed model for repeated measures (MMRM) including all measured timepoints, in patients without a major protocol violation. Secondary endpoints include the time to the first event of WHF adverse event, readmission for HF, or death through day 91; and changes to day 7 in EQ-5D visual analogue scale score and utility index. Additional clinical and laboratory measures will be assessed.
CONCLUSIONS
The results of the study will add to the knowledge of the role of inflammation in AHF and potentially inform the design of larger studies with possibly longer duration of anti-inflammatory therapies in AHF.
PubMed: 38943232
DOI: 10.1002/ehf2.14930 -
Cancer & Metabolism Jun 2024Even with systemic chemotherapy, cytoreductive surgery (CRS), and hyperthermic intraperitoneal chemotherapy (HIPEC), peritoneal metastases (PM) remain a common site of...
Even with systemic chemotherapy, cytoreductive surgery (CRS), and hyperthermic intraperitoneal chemotherapy (HIPEC), peritoneal metastases (PM) remain a common site of disease progression for colorectal cancer (CRC) and are frequently associated with a poor prognosis. The mass spectrometry (MS) method known as Matrix-Assisted Laser Desorption/Ionization - Time of Flight (MALDI-TOF) is frequently used in medicine to identify structural compounds and biomarkers. It has been demonstrated that lipids are crucial in mediating the aggressive growth of tumors. In order to investigate the lipid profiles, particularly with regard to histological distribution, we used MALDI-TOF MS (MALDI-MS) and MALDI-TOF imaging MS (MALDI-IMS) on patient-derived tumor organoids (PDOs) and PM clinical samples. According to the MALDI-IMS research shown here, the predominant lipid signature of PDOs in PM tissues, glycosphingolipid (GSL) sulfates or sulfatides, or STs, is unique to the areas containing tumor cells and absent from the surrounding stromal compartments. Bioactive lipids are derived from arachidonic acid (AA), and AA-containing phosphatidylinositol (PI), or PI (18:0-20:4), is shown to be highly expressed in the stromal components. On the other hand, the tumor components contained a higher abundance of PI species with shorter and more saturated acyl chains (C34 and C36 carbons). The cellular subversion of PI and ST species may alter in ways that promote the growth, aggressiveness, and metastasis of tumor cells. Together, these findings suggest that the GSL/ST metabolic programming of PM may contain novel therapeutic targets to impede or halt PM progression.
PubMed: 38943216
DOI: 10.1186/s40170-024-00345-3 -
Journal of Extracellular Vesicles Jul 2024Extracellular vesicles have gained wide momentum as potential therapeutics for osteoarthritis, a highly prevalent chronic disease that still lacks an approved treatment.... (Review)
Review
Extracellular vesicles have gained wide momentum as potential therapeutics for osteoarthritis, a highly prevalent chronic disease that still lacks an approved treatment. The membrane-bound vesicles are secreted by all cells carrying different cargos that can serve as both disease biomarkers and disease modifiers. Nonetheless, despite a significant peak in research regarding EVs as OA therapeutics, clinical implementation seems distant. In addition to scalability and standardization challenges, researchers often omit to focus on and consider the proper tropism of the vesicles, the practicality and relevance of their source, their low native therapeutic efficacy, and whether they address the disease as a whole. These considerations are necessary to better understand EVs in a clinical light and have been comprehensively discussed and ultimately summarized in this review into a conceptualized framework termed the nanodiamond concept. Future perspectives are also discussed, and alternatives are presented to address some of the challenges and concerns.
Topics: Humans; Extracellular Vesicles; Osteoarthritis; Biomarkers; Animals
PubMed: 38943211
DOI: 10.1002/jev2.12435 -
Trials Jun 2024Acute leukaemias (AL) are life-threatening blood cancers that can be potentially cured with treatment involving myelosuppressive, multiagent, intensive chemotherapy...
Biomarker Driven Antifungal Stewardship (BioDriveAFS) in acute leukaemia-a multi-centre randomised controlled trial to assess clinical and cost effectiveness: a study protocol for a randomised controlled trial.
BACKGROUND
Acute leukaemias (AL) are life-threatening blood cancers that can be potentially cured with treatment involving myelosuppressive, multiagent, intensive chemotherapy (IC). However, such treatment is associated with a risk of serious infection, in particular invasive fungal infection (IFI) associated with prolonged neutropenia. Current practice guidelines recommend primary antifungal (AF) prophylaxis to be administered to high-risk patients to reduce IFI incidence. AFs are also used empirically to manage prolonged neutropenic fever. Current strategies lead to substantial overuse of AFs. Galactomannan (GM) and β-D-glucan (BG) biomarkers are also used to diagnose IFI. Combining both biomarkers may enhance the predictability of IFI compared to administering each test alone. Currently, no large-scale randomised controlled trial (RCT) has directly compared a biomarker-based diagnostic screening strategy without AF prophylaxis to AF prophylaxis (without systematic biomarker testing).
METHODS
BioDriveAFS is a multicentre, parallel, two-arm RCT of 404 participants from UK NHS Haematology departments. Participants will be allocated on a 1:1 basis to receive either a biomarker-based antifungal stewardship (AFS) strategy, or a prophylactic AF strategy, which includes existing standard of care (SoC). The co-primary outcomes will be AF exposure in the 12-month post randomisation and the patient-reported EQ-5D-5L measured at 12-month post randomisation. Secondary outcomes will include total AF exposure, probable/proven IFI, survival (all-cause mortality and IFI mortality), IFI treatment outcome, AF-associated adverse effects/events/complications, resource use, episodes of neutropenic fever requiring hospital admission or outpatient management, AF resistance in fungi (non-invasive and invasive) and a Desirability of Outcome Ranking. The trial will have an internal pilot phase during the first 9 months. A mixed methods process evaluation will be integrated in parallel to the internal pilot phase and full trial, aiming to robustly assess how the intervention is delivered. Cost-effectiveness analysis will also be performed.
DISCUSSION
The BioDriveAFS trial aims to further the knowledge of strategies that will safely optimise AF use through comparison of the clinical and cost-effectiveness of a biomarker-led diagnostic strategy versus prophylactic AF to prevent and manage IFI within acute leukaemia. The evidence generated from the study will help inform global clinical practice and approaches within antifungal stewardship.
TRIAL REGISTRATION
ISRCTN11633399. Registered 24/06/2022.
Topics: Humans; Antifungal Agents; Cost-Benefit Analysis; Randomized Controlled Trials as Topic; Invasive Fungal Infections; Multicenter Studies as Topic; Biomarkers; Galactose; Mannans; Treatment Outcome; beta-Glucans; Antimicrobial Stewardship; Leukemia; Time Factors; Cost-Effectiveness Analysis
PubMed: 38943201
DOI: 10.1186/s13063-024-08272-w -
Cancer Imaging : the Official... Jun 2024This study was based on MRI features and number of tumor-infiltrating CD8 + T cells in post-operative pathology, in predicting meningioma recurrence risk.
OBJECTIVE
This study was based on MRI features and number of tumor-infiltrating CD8 + T cells in post-operative pathology, in predicting meningioma recurrence risk.
METHODS
Clinical, pathological, and imaging data of 102 patients with surgically and pathologically confirmed meningiomas were retrospectively analyzed. Patients were divided into recurrence and non-recurrence groups based on follow-up. Tumor-infiltrating CD8 + T cells in tissue samples were quantitatively assessed with immunohistochemical staining. Apparent diffusion coefficient (ADC) histogram parameters from preoperative MRI were quantified in MaZda. Considering the high correlation between ADC histogram parameters, we only chose ADC histogram parameter that had the best predictive efficacy for COX regression analysis further. A visual nomogram was then constructed and the recurrence probability at 1- and 2-years was determined. Finally, subgroup analysis was performed with the nomogram.
RESULTS
The risk factors for meningioma recurrence were ADCp1 (hazard ratio [HR] = 0.961, 95% confidence interval [95% CI]: 0.937 ~ 0.986, p = 0.002) and CD8 + T cells (HR = 0.026, 95%CI: 0.001 ~ 0.609, p = 0.023). The resultant nomogram had AUC values of 0.779 and 0.784 for 1- and 2-years predicted recurrence rates, respectively. The survival analysis revealed that patients with low CD8 + T cells counts or ADCp1 had higher recurrence rates than those with high CD8 + T cells counts or ADCp1. Subgroup analysis revealed that the AUC of nomogram for predicting 1-year and 2-year recurrence of WHO grade 1 and WHO grade 2 meningiomas was 0.872 (0.652) and 0.828 (0.751), respectively.
CONCLUSIONS
Preoperative ADC histogram parameters and tumor-infiltrating CD8 + T cells may be potential biomarkers in predicting meningioma recurrence risk.
CLINICAL RELEVANCE STATEMENT
The findings will improve prognostic accuracy for patients with meningioma and potentially allow for targeted treatment of individuals who have the recurrent form.
Topics: Humans; Meningioma; Nomograms; Male; Female; Neoplasm Recurrence, Local; Middle Aged; CD8-Positive T-Lymphocytes; Retrospective Studies; Meningeal Neoplasms; Lymphocytes, Tumor-Infiltrating; Aged; Adult; Magnetic Resonance Imaging; Risk Factors; Prognosis
PubMed: 38943200
DOI: 10.1186/s40644-024-00731-6