NK Cell Mitochondrial Membrane Potential-Associated Model Predicts Outcomes in Critically Ill Patients with COVID-19.

Purpose: This study investigated potential predictive models associated with natural killer (NK) cell mitochondrial membrane potential (MMP or ΔΨm) in predicting death among critically ill patients with COVID-19. Patients and Methods: We included 97 patients with COVID-19 of different severities attending Peking Union Medical College Hospital from December 2022 to January 2023. Patients were divided into three groups according to oxygen and mechanical ventilation use during specimen collection and were followed for survival and death at 3 months. The lymphocyte subpopulation MMP was detected via flow cytometry. We constructed a joint diagnostic model by integrating identified key indicators and generating receiver operating curves (ROCs) and evaluated its predictive performance for mortality risk in critically ill patients. Results: The NK-cell MMP median fluorescence intensity (MFI) was significantly lower in critically ill patients who died from COVID-19 (p<0.0001) and significantly and positively correlated with D-dimer content in critically ill patients (r=0.56, p=0.0023). The random forest model suggested that fibrinogen levels and NK-cell MMP MFI were the most important indicators. Integrating the above predictive models for the ROC yielded an area under the curve of 0.94. Conclusion: This study revealed the potential of combining NK-cell MMP with key clinical indicators (D-dimer and fibrinogen levels) to predict death among critically ill patients with COVID-19, which may help in early risk stratification of critically ill patients and improve patient care and clinical outcomes.

Investigation of coagulation and proteomics profiles in symptomatic feline hypertrophic cardiomyopathy and healthy control cats.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a crucial heart disease in cats. The clinical manifestations of HCM comprise pulmonary edema, dyspnea, syncope, arterial thromboembolism (ATE), and sudden cardiac death. D-dimer and prothrombin time (PT) are powerful biomarkers used to assess coagulation function. Dysregulation in these two biomarkers may be associated with HCM in cats. This study aims to assess D-dimer levels, PT, and proteomic profiling in healthy cats in comparison to cats with symptomatic HCM. RESULTS: Twenty-nine client-owned cats with HCM were enrolled, including 15 healthy control and 14 symptomatic HCM cats. The D-dimer concentration and PT were examined. Proteomic analysis was conducted by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry and liquid chromatography-tandem mass spectrometry (LC-MS/MS). In symptomatic cats, D-dimer levels were statistically significantly higher (mean ± SEM: 372.19 ng/ml ± 58.28) than in healthy cats (mean ± SEM: 208.54 ng/ml ± 10.92) with P-value of less than 0.01, while PT was statistically significantly lower in symptomatic cats (mean ± SEM: 9.8 s ± 0.15) compared to healthy cats (mean ± SEM: 11.08 s ± 0.23) with P-value of less than 0.0001. The proteomics analysis revealed upregulation of integrin subunit alpha M (ITGAM), elongin B (ELOB), and fibrillin 2 (FBN2) and downregulation of zinc finger protein 316 (ZNF316) and ectonucleoside triphosphate diphosphohydrolase 8 (ENTPD8) in symptomatic HCM cats. In addition, protein-drug interaction analysis identified the Ras signaling pathway and PI3K-Akt signaling pathway. CONCLUSIONS: Cats with symptomatic HCM have higher D-dimer and lower PT than healthy cats. Proteomic profiles may be used as potential biomarkers for the detection and management of HCM in cats. The use of D-dimer as a biomarker for HCM detection and the use of proteomic profiling for a better understanding of disease mechanisms remain to be further studied in cats.

Unified calibration of D-dimer can improve the uniformity of different detection systems.

Background: D-dimer at a low level is important evidence for excluding the onset and progression of thrombosis. It is readily detectable and yields rapid results, although significant variability exists among different detection systems. Our study aims to enhance the consistency across various detection systems. Methods: Twelve detection systems were included in our study. We sought to address this inconsistency by using various calibrators (two supplied by manufacturers and two comprising pooled human plasma diluted with different diluents) to standardize D-dimer measurements. We categorized the data into three groups according to D-dimer concentration levels: low (≤0.5 mg/L), medium (>0.5 mg/L - <3 mg/L), and high (≥3 mg/L). We then analyzed the data focusing on range, consistency, comparability, negative coincidence rate, and false negative rate. Results: Calibrating with pooled human plasma led to narrower result ranges in the low and medium groups (P < 0.05). In the low group, consistency improved from weak to strong (ICC 0.4-0.7, P﹤0.05), while it remained excellent in the other groups and overall (ICCï¹¥0.75, P﹤0.05). The percentage of pairwise comparability increased in both the low and high groups. Additionally, there was an increase in the negative coincidence rate. Conclusion: These findings demonstrate that uniform calibration of D-dimer can significantly enhance the consistency of results across different detection systems.

Infective Endocarditis in Pregnancy Diagnosed Early Based on Elevated D-Dimer Levels: A Case Report.

We discuss a case where the blood cultures of a patient with clinical chorioamnionitis and elevated D-dimer levels enabled early diagnosis of infective endocarditis. A 31-year-old female with a 39-week pregnancy presented to the obstetrics department with a fever. Cardiotocography revealed fetal tachycardia and severe late deceleration. Preoperative examinations revealed a leukocyte count of 15,900/µL and D-dimer levels of 86.2 µg/mL. She was diagnosed with a non-reassuring fetal status due to clinical chorioamnionitis; accordingly, an emergency cesarean section was performed. Imaging studies ruled out the possibility of a thromboembolism. Subsequent maternal blood cultures were positive for Staphylococcus aureus. Echocardiography revealed vegetation on the aortic valve, leading to a diagnosis of infective endocarditis. Blood cultures can be useful in evaluating for sepsis in cases of clinical chorioamnionitis with elevated D-dimer levels as they may facilitate early diagnosis of infective endocarditis during pregnancy.

Systemic inflammation biomarkers during angioedema attacks in hereditary angioedema.

Background: Hereditary angioedema (HAE) is a rare disease characterized by localized and self-limited angioedema (AE) attacks. A local increase of bradykinin (BK) mediates AE attacks in HAE, however the role of inflammation in HAE has been poorly explored We aim to analyze the role of inflammatory mediators in HAE patients during AE attacks. Methods: Patients with a confirmed HAE diagnosis due to C1 inhibitor deficiency (HAE-C1INH) or patients F12 gene mutations (HAE-FXII) attending to our outpatient clinic between November-2019 and May-2022 were included. Demographic and clinical characteristics were analyzed. Blood samples were collected both during symptom-free periods (baseline) and during HAE attacks, and acute phase reactants (APR), such as serum amyloid A (SAA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D-Dimer and white blood cells were measured. Results: Seventy-eight patients were enrolled in the study, with a predominant representation of women (76%, n=59), and a mean age of 47.8 years (range 6-88). Among them, 67% (n=52) of patients had HAE-C1INH (46 classified as type 1 and 6 as type 2) while 33% (n=26) had HAE-FXII. During attack-free periods, the majority of patients exhibited normal levels of SAA, ESR, D-dimer, ACE and WCC. However, in a subset of patients (16% for SAA, 18% for ESR, and 14.5% for D-dimer), elevations were noted at baseline. Importantly, during HAE attacks, significant increases were observed in SAA in 88% of patients (p< 0.0001 vs. baseline), in ESR in 65% (p= 0.003 vs. baseline) and D-dimer in 71% (p=0.001 vs. baseline) of the patients. A comparison between baseline and acute attack levels in 17 patients revealed significant differences in SAA AA (p<0. 0001), ESR (p<0.0001) and D-dimer (p= 0.004). No significant differences were observed in CRP (p=0.7), ACE (p=0.67) and WCC (p=0.54). These findings remained consistent regardless of HAE type, disease activity or location of angioedema. Conclusion: The systemic increase in APR observed during HAE attacks suggests that inflammation extends beyond the localized edematous area. This finding underscores the potential involvement of inflammatory pathways in HAE and highlights the need for further investigation into their role in the pathophysiology of HAE.

Pulmonary embolism in patients with chronic coronary syndrome masquerading as acute coronary syndrome: a case report and literature review.

BACKGROUND: Pulmonary embolisms (PEs) exhibit clinical features similar to those of acute coronary syndrome (ACS), including electrocardiographic abnormalities and elevated troponin levels, which frequently lead to misdiagnoses in emergency situations. CASE PRESENTATION: Here, we report a case of PE coinciding with chronic coronary syndrome in which the patient's condition was obscured by symptoms mimicking ACS. A 68-year-old female with syncope presented to the hospital. Upon admission, she was found to have elevated troponin levels and an electrocardiogram showing ST-segment changes across multiple leads, which initially led to a diagnosis of ACS. Emergency coronary arteriography revealed occlusion of the posterior branches of the left ventricle of the right coronary artery, but based on the complexity of the intervention, the occlusion was considered chronic rather than acute. On the 3rd day after admission, the patient experienced recurrent chest tightness and shortness of breath, which was confirmed as acute PE by emergency computed tomography pulmonary angiography. Following standardized anticoagulation treatment, the patient improved and was subsequently discharged. CONCLUSIONS: This case report highlights the importance of recognizing the nonspecific features of PE. Clinicians should be vigilant when identifying other clinical features that are difficult to explain accompanying the expected disease, and it is necessary to carefully identify the causes to prevent missed diagnoses or misdiagnoses.

Nonspecific stress biomarkers for mortality prediction in older emergency department patients presenting with falls: a prospective multicenter observational study.

BACKGROUND: Older patients presenting to the emergency department (ED) after falling are increasingly prevalent. Falls are associated with functional decline and death. Biomarkers predicting short-term mortality might facilitate decisions regarding resource allocation and disposition. D-dimer levels are used to rule out thromboembolic disease, while copeptin and adrenomedullin (MR-proADM) may be used as measures of the patient`s stress level. These nonspecific biomarkers were selected as potential predictors for mortality. METHODS: Prospective, international, multicenter, cross-sectional observation was performed in two tertiary and two regional hospitals in Germany and Switzerland. Patients aged 65 years or older presenting to the ED after a fall were enrolled. Demographic data, Activities of Daily Living (ADL), and D-dimers were collected upon presentation. Copeptin and MR-proADM levels were determined from frozen samples. Primary outcome was 30-day mortality; and secondary outcomes were mortality at 90, 180, and 365 days. RESULTS: Five hundred and seventy-two patients were included. Median age was 83 [IQR 78, 89] years, 236 (67.7%) were female. Mortality overall was 3.1% (30 d), 5.4% (90 d), 7.5% (180 d), and 13.8% (365 d), respectively. Non-survivors were older, had a lower ADL index and higher levels of all three biomarkers. Elevated levels of MR-proADM and D-dimer were associated with higher risk of mortality. MR-proADM and D-dimer showed high sensitivity and low negative likelihood ratio regarding short-term mortality, whereas copeptin did not. CONCLUSION: D-dimer and MR-proADM levels might be useful as prognostic markers in older patients presenting to the ED after a fall, by identifying patients at low risk of short-term mortality. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02244983.

Diagnosis of acute aortic syndromes with ultrasound and d-dimer: the PROFUNDUS study.

BACKGROUND: In patients complaining common symptoms such as chest/abdominal/back pain or syncope, acute aortic syndromes (AAS) are rare underlying causes. AAS diagnosis requires urgent advanced aortic imaging (AAI), mostly computed tomography angiography. However, patient selection for AAI poses conflicting risks of misdiagnosis and overtesting. OBJECTIVES: We assessed the safety and efficiency of a diagnostic protocol integrating clinical data with point-of-care ultrasound (POCUS) and d-dimer (single/age-adjusted cutoff), to select patients for AAI. METHODS: This prospective study involved 12 Emergency Departments from 5 countries. POCUS findings were integrated with a guideline-compliant clinical score, to define the integrated pre-test probability (iPTP) of AAS. If iPTP was high, urgent AAI was requested. If iPTP was low and d-dimer was negative, AAS was ruled out. Patients were followed for 30 days, to adjudicate outcomes. RESULTS: Within 1979 enrolled patients, 176 (9 %) had an AAS. POCUS led to net reclassification improvement of 20 % (24 %/-4 % for events/non-events, P < 0.001) over clinical score alone. Median time to AAS diagnosis was 60 min if POCUS was positive vs 118 if negative (P = 0.042). Within 941 patients satisfying rule-out criteria, the 30-day incidence of AAS was 0 % (95 % CI, 0-0.41 %); without POCUS, 2 AAS were potentially missed. Protocol rule-out efficiency was 48 % (95 % CI, 46-50 %) and AAI was averted in 41 % of patients. Using age-adjusted d-dimer, rule-out efficiency was 54 % (difference 6 %, 95 % CI, 4-9 %, vs standard cutoff). CONCLUSIONS: The integrated algorithm allowed rapid triage of high-probability patients, while providing safe and efficient rule-out of AAS. Age-adjusted d-dimer maximized efficiency. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT04430400.

Roles of spectral dual-layer CT, D-dimer concentration, and COVID-19 pneumonia in diagnosis of pulmonary embolism.

Purpose: To demonstrate advantages of spectral dual-layer computed tomography (CT) in diagnosing pulmonary embolism (PE). To compare D-dimer values in patients with PE and concomitant COVID-19 pneumonia to those in patients without PE and COVID-19 pneumonia. To compare D-dimer values in cases of minor versus extensive PE. Methods: A monocentric retrospective study of 1500 CT pulmonary angiographies (CTPAs). Three groups of 500 consecutive examinations: 1) using conventional multidetector CT (CTC), 2) using spectral dual-layer CT (CTS), and 3) of COVID-19 pneumonia patients using spectral dual-layer CT (COV). Only patients with known D-dimer levels were enrolled in the study. Results: Prevalence of inconclusive PE findings differed significantly between CTS and CTC (0.8 % vs. 5.4 %, p < 0.001). In all groups, D-dimer levels were significantly higher in PE positive patients than in patients without PE (CTC, 8.04 vs. 3.05 mg/L; CTS, 6.92 vs. 2.57 mg/L; COV, 10.26 vs. 2.72 mg/L, p < 0.001). There were also statistically significant differences in D-dimer values between minor and extensive PE in the groups negative for COVID-19 (CTC, 5.16 vs. 8.98 mg/L; CTS 3.52 vs. 9.27 mg/L, p < 0.001). The lowest recorded D-dimer value for proven PE in patients with COVID-19 pneumonia was 1.19 mg/L. Conclusion: CTPAs using spectral dual-layer CT reduce the number of inconclusive PE findings. Plasma D-dimer concentration increases with extent of PE. Cut-off value of D-dimer with 100 % sensitivity for patients with COVID-19 pneumonia could be doubled to 1.0 mg/L. This threshold would have saved 110 (22 %) examinations in our cohort.

D-dimer levels predict the treatment efficacy and prognosis of esophageal squamous cell carcinoma treated with PD-1/PD-L1 inhibitors.

OBJECTIVES: This study aimed to explore the value of D-dimer levels in predicting the treatment efficacy and prognosis of advanced esophageal squamous cell carcinoma (ESCC) treated with programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors. METHODS: The study retrospectively analyzed 233 ESCC patients who received PD-1/PD-L1 inhibitors. The optimal cut-off values for platelets, fibrinogen, and D-dimer were calculated based on maximally selected rank statistics for patients' overall survival. Univariate and multivariate analyses of progression-free survival and overall survival were conducted by Cox proportional hazards regression model. Subgroup analyses of D-dimer levels in different fibrinogen levels were performed by log-rank test. RESULTS: The multivariate Cox regression analyses demonstrated that ESCC patients with D-dimer levels > 236 ng/mL exhibited both poorer progression-free survival (P = 0.004) and overall survival (P < 0.0001) compared to those with low D-dimer levels. The subgroup analyses further indicated that in the group of low fibrinogen levels, the higher D-dimer levels of ESCC patients exhibited significantly shorter progression-free survival (P = 0.0021) and overall survival (P < 0.0001). CONCLUSIONS: The study revealed that the D-dimer levels possess predictive value for the treatment efficacy and prognosis of ESCC patients treated with PD-1/PD-L1 inhibitors.

Enoxaparin Effect on Interleukin-10 Levels in Iraqi Patients with COVID-19: A Case-Control Study.

BACKGROUND: Coronavirus disease 19 (COVID-19), an infectious disease resulting from a virus known as severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), was discovered in China in 2019 and causes several mild to moderate respiratory conditions. This study aimed to reveal the changes in serum interleukin-10 (IL-10) and other parameters in Iraqi COVID-19 patients compared with healthy controls by studying the effects of enoxaparin and evaluating the potential of IL-10 as a disease activity marker. METHODS: This was a case-control study that included 180 samples: 90 patients hospitalized with COVID-19 from November 2022 to 20 April 2023 (40 patients had never used enoxaparin, whereas 50 patients had taken enoxaparin) and 90 healthy, age- and sex-matched control. There were 44 female patients and 46 male patients. The mean age of the patients and controls was 53.8 years vs. 50.8 years, respectively. The sandwich enzyme-linked immunosorbent assay (ELISA) method was used to measure IL-10 levels, while other parameters were assessed using the colorimetric method. RESULTS: The results of the study indicated highly significant changes between the patients and healthy controls in IL-10, D-dimer, and C-reactive protein (CRP) levels, as well as liver and renal functions. These findings elucidated a significant change between enoxaparin patients and non-enoxaparin patients in IL-10, D-dimer, and CRP levels. However, the liver and renal functions were not significantly altered. The Spearman's rank correlation test investigated the relationship between serum IL-10 and CRP. CONCLUSIONS: The results displayed a strong positive relationship between IL-10 and CRP. There were no significant differences between the other analyzed parameters; consequently, the patients had higher concentrations of IL-10, D-dimer, and some other parameters than the healthy controls. Additionally, IL-10 may be used as a marker of disease activity. Enoxaparin will likely help control IL-10 and D-dimer concentrations in patients since IL-10 levels decreased in patients treated with enoxaparin.

Daytime plasma cortisol and cortisol response to dexamethasone suppression are associated with a prothrombotic state in hypertension.

Background and aims: A prothrombotic state was demonstrated in patients with Cushing's syndrome and is involved in the development and progression of cardiovascular and renal damage in hypertensive patients. This study was designed to examine the relationships between cortisol secretion and the hemostatic and fibrinolytic systems in hypertension. Methods: In 149 middle-aged, nondiabetic, essential hypertensive patients free of cardiovascular and renal complications, we measured hemostatic markers that express the spontaneous activation of the coagulation and fibrinolytic systems and assessed daily cortisol levels (8 AM, 3 PM, 12 AM; area under the curve, AUC-cortisol) together with the cortisol response to dexamethasone overnight suppression (DST-cortisol). Results: Plasma levels of D-dimer (D-dim), prothrombin fragment 1 + 2 (F1 + 2), and von Willebrand factor (vWF) were progressively and significantly higher across tertiles of AUC-cortisol and DST-cortisol, whereas no differences were observed in fibrinogen, tissue plasminogen activator, plasminogen activator inhibitor-1, antithrombin III, protein C, and protein S. D-dim, F1 + 2, and vWF were significantly and directly correlated with age and both AUC-cortisol and DST-cortisol. Multivariate regression analysis showed that both AUC-cortisol and DST-cortisol were related to plasma D-dim, F1 + 2, and vWF independently of age, body mass index, blood pressure, and renal function. Conclusion: Greater daily cortisol profile and cortisol response to overnight suppression are independently associated with a prothrombotic state in hypertensive patients and might contribute to the development of organ damage and higher risk of cardiovascular complications.

D-dimer as a Marker of Severity and Prognosis in Acute Pancreatitis.

Background and Objectives: Acute pancreatitis (AP) scores need a battery of tests that are not helpful at an early stage. Can a single test predict Complicated Acute Pancreatitis (CAP) which includes moderate and severe AP, local complications, and need for intensive care unit (ICU). Methodology: 30 patients of AP. D-dimer, C-reactive protein levels done within 3 days of AP onset. APACHE II, Ranson's score, CT severity index were done. Inhospital disease course for development of organ failure and need for ICU care was followed daily. Results: D-dimer in CAP was 2732 ng/L (MAP 567 ng/L), in abnormal computed tomography (CT) was 1916 ng/L (normal CT 363 ng/L), and in organ failure was 4776 ng/L (776.5 ng/L absent organ failure). D-dimer increases as the severity of organ failure increases (P = 0.04). D-dimer in ICU patients was significantly elevated (P = 0.021). D-dimer correlates with APACHE II score well, with an increase in predictive mortality rate (P = 0.01). On receiver operator characteristics, D-dimer >933.5 ng/L predicts CAP, >827.5 ng/L predicts positive CT findings (local complications), and >1060.5 ng/L predicts the development of organ failure. Conclusion: Coagulopathy and microthrombi play a significant role in early pathogenesis. D-dimer test acts at the level of this core pathogenesis, even before the complications set in. D-dimer within 72 h of AP correlates well with the CT findings after 72 h. This is the first study that correlates D-dimer levels with CT scores, ICU requirement. D-dimer can guide primary care physicians in selecting AP patients for referral to a higher center in a resource-limited setting.

Clinical value of measuring plasma D-dimer levels in patients with esophageal cancer.

BACKGROUND: Esophageal cancer represents a significant public health concern; however, reliable diagnostic and prognostic markers have not been established. This study aimed to investigate the clinical value of plasma D-dimer levels in patients with esophageal cancer. METHODS: Overall, 120 patients with esophageal cancer who underwent radical surgical resection at our department between January 2019 and 2020 were included (esophageal cancer group). Plasma D-dimer levels were measured preoperatively and on postoperative days 1 and 14. Additionally, 60 healthy participants (control group) with measured plasma D-dimer levels were included. The preoperative D-dimer levels and positive D-dimer test rates were compared between the groups. The 3-year survival rate in patients with esophageal cancer was calculated using the Kaplan-Meier method. RESULTS: Preoperative D-dimer concentration in the esophageal cancer group was (0.65 ± 0.859 µg/mL) significantly higher than that in the control group (0.32 ± 0.369 µg/mL). The positivity rate in the esophageal cancer group (35.0%, 42/120) was significantly higher than that in the control group (15%, 9/60). D-dimer concentrations were significantly higher 1 day postoperatively than preoperatively. Conversely, D-dimer concentrations were significantly lower 14 days postoperatively than preoperatively. Patients in the esophageal cancer group with plasma D-dimer concentrations ≤ 0.5 µg/mL had significantly higher 3-year survival rates than those with higher concentrations. In the logistic multivariate analysis, tumor pathological stage and preoperative plasma D-dimer levels were independent prognostic factors of 3-year survival rates in patients with esophageal cancer. CONCLUSION: Plasma D-dimer concentrations are clinically valuable in esophageal cancer diagnosis, postoperative recurrence monitoring, and prognosis prediction.

Effect of Enoxaparin on D-dimer levels in hospitalized Corona Virus patients with a comparison of its level in patients with comorbid conditions.

OBJECTIVE: Aim: The main goal is to assess the levels of comorbid diseases and examine the changes in D-dimer in hospitalized patients before and following SC enoxaparin medication. PATIENTS AND METHODS: Material and Methods: At the Al-Yarmouk Teaching Hospital in Baghdad, Iraq, from October 2022 to May 2023, 86 patients who were hospitalized and had severe to critical COVID-19 infections provided data for a retrospective analysis. RESULTS: Results: The medical records of all COVID-19 patients who were hospitalized and whose D-dimer level was greater than 0.5 mg/l and who were given enoxaparin (40 mg subcutaneously) were reviewed with the requisite authorization from the relevant authorities. The D-dimer level was assessed following therapy on the day of admission and day five after commencing enoxaparin. An examination of 86 case records revealed that persons with COVID-19 had significantly decreased D-dimer levels after taking subcutaneous enoxaparin (p-value<0.0001). The comorbidities (diabetes mellitus, hypertension) of patients who received the drug were compared. CONCLUSION: Conclusions: Enoxaparin and other anticoagulants were utilized to treat the coagulopathy brought on by COVID-19. Low molecular weight heparin enoxaparin has demonstrated positive outcomes in the management of VTE. A decrease in D-dimer level is anticipated when COVID-19 patients are treated with subcutaneous enoxaparin, partly because decreased coagulation results in lower fibrin formation.

Sex-specific differences in the clinical profile among psychiatric patients with pulmonary Embolism: a hospital-based retrospective study.

BACKGROUND: Pulmonary embolism (PE) is a severe and life-threatening complication of venous thromboembolism. However, there is a lack of systematic studies on differences between female and male PE patients. This paper aimed to compare the sex-specific differences in clinical characteristics and laboratory indicators in psychotic patients with PE. METHODS: This retrospective study enrolled psychiatric patients with PE from June 2018 to June 2022 at Shenzhen Kangning Hospital (Shenzhen Mental Health Center). Demographic characteristics, factors associated with PE, and laboratory indices were collected to assess sex-specific differences. RESULTS: Of the 168 patients, 87 (51.8%) were female and 81 (48.2%) were male, with a mean age of 58 years for females and 46 years for male patients. The male group had higher ratio of hyperprolactinemia, more patients using antipsychotic medications, higher D-dimer levels at PE onset, greater D-dimer difference, and a higher rate of D-dimer elevation than the female group (p < 0.05). Female patients were significantly older, exhibited a higher prevalence of diabetes, and had a greater number of patients taking antidepressants and hypnotics/sedatives than male patients (p < 0.05). Schizophrenia spectrum disorders were more prevalent in male patients, while female patients had a higher incidence of mood disorders (p < 0.05). Among patients aged < 45 years, the male group had higher D-dimer levels at PE onset and greater D-dimer difference (p < 0.05). Among all 112 patients aged ≥ 45 years, male patients were more likely than female patients to have respiratory tract infections, higher D-dimer levels at PE onset, greater D-dimer difference, and a higher rate of D-dimer elevation (p < 0.05). The multiple linear regression analysis indicated that hyperprolactinemia and the use of first-generation antipsychotics (FGAs) were associated with D-dimer levels at PE onset in male patients, while the time of PE onset and protective restraints were associated with D-dimer levels at PE onset in female patients (p < 0.05). CONCLUSION: PE-associated clinical features differ between male and female patients. These differences may imply that the processes and mechanisms of PE onset are sex specific. Male patients are more likely to have respiratory tract infections and higher D-dimer levels at PE onset than female patients. The use of FGAs may be associated with increased D-dimer in male psychiatric patients, while protective restraints may be associated with increased D-dimer in female psychiatric patients.

The Impact of Cytokines on Coagulation Profile in COVID-19 Patients: Controlled for Socio-Demographic, Clinical, and Laboratory Parameters.

Background: Severe coagulation abnormalities are common in patients with COVID-19 infection. We aimed to investigate the relationship between pro-inflammatory cytokines and coagulation parameters concerning socio-demographic, clinical, and laboratory characteristics. Methods: Our study included patients hospitalized during the second wave of COVID-19 in the Republic of Serbia. We collected socio-demographic, clinical, and blood-sample data for all patients. Cytokine levels were measured using flow cytometry. Results: We analyzed data from 113 COVID-19 patients with an average age of 58.15 years, of whom 79 (69.9%) were male. Longer duration of COVID-19 symptoms before hospitalization (B = 69.672; p = 0.002) and use of meropenem (B = 1237.220; p = 0.014) were predictive of higher D-dimer values. Among cytokines, higher IL-5 values significantly predicted higher INR values (B = 0.152; p = 0.040) and longer prothrombin times (B = 0.412; p = 0.043), and higher IL-6 (B = 0.137; p = 0.003) predicted longer prothrombin times. Lower IL-17F concentrations at admission (B = 0.024; p = 0.050) were predictive of higher INR values, and lower IFN-γ values (B = -0.306; p = 0.017) were predictive of higher aPTT values. Conclusions: Our findings indicate a significant correlation between pro-inflammatory cytokines and coagulation-related parameters. Factors such as the patient's level of education, gender, oxygen-therapy use, symptom duration before hospitalization, meropenem use, and serum concentrations of IL-5, IL-6, IL-17F, and IFN-γ were associated with worse coagulation-related parameters.

A multi-trait epigenome-wide association study identified DNA methylation signature of inflammation among people with HIV.

Inflammation underlies many conditions causing excess morbidity and mortality among people with HIV (PWH). A handful of single-trait epigenome-wide association studies (EWAS) have suggested that inflammation is associated with DNA methylation (DNAm) among PWH. Multi-trait EWAS may further improve statistical power and reveal pathways in common between different inflammatory markers. We conducted single-trait EWAS of three inflammatory markers (soluble CD14, D-dimers, and interleukin 6) in the Veteran Aging Cohort Study (n = 920). The study population was all male PWH with an average age of 51 years, and 82.3% self-reported as Black. We then applied two multi-trait EWAS methods-CPASSOC and OmniTest-to combine single-trait EWAS results. CPASSOC and OmniTest identified 189 and 157 inflammation-associated DNAm sites respectively, of which 112 overlapped. Among the identified sites, 56% were not significant in any single-trait EWAS. Top sites were mapped to inflammation-related genes including IFITM1, PARP9 and STAT1. These genes were significantly enriched in pathways such as "type I interferon signaling" and "immune response to virus". We demonstrate that multi-trait EWAS can improve the discovery of inflammation-associated DNAm sites, genes, and pathways. These DNAm sites suggest molecular mechanisms in response to inflammation associated with HIV and might hold the key to addressing persistent inflammation in PWH.

Citrate and low-dose heparin combined anticoagulation in pediatric continuous renal replacement therapy.

There remains no optimal anticoagulation protocol for continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in pediatric patients with elevated D-dimer levels. We aimed to assess the effects of different anticoagulation strategies on the risk of CRRT filter clotting in these patients. Pediatric patients undergoing CRRT were retrospectively grouped based on pre-CRRT D-dimer levels and anticoagulant: D-RCA group (normal D-dimer, RCA only, n = 22), D+ RCA group (elevated D-dimer, RCA only, n = 50), and D+ RCA+ systemic heparin anticoagulation (SHA) group (elevated D-dimer, RCA combined with SHA, n = 55). The risk of filter clotting and incidence of bleeding were compared among the groups. Among the groups, the D+ RCA+ SHA group had the longest filter lifespan; further, the incidence of bleeding was not increased by concurrent use of low-dose heparin for anticoagulation. Moreover, concurrent heparin anticoagulation was associated with a decreased risk of filter clotting. Contrastingly, high pre-CRRT hemoglobin and D-dimer levels and post-filter ionized calcium level > 0.4 mmol/L were associated with an increased risk of filter clotting. RCA combined with low-dose heparin anticoagulation could reduce the risk of filter clotting and prolong filter lifespan without increasing the risk of bleeding in patients with elevated D-dimer levels undergoing CRRT.

Associations of RBC counts and incidence of DVT in patients with spinal cord injury: a five year observational retrospective study.

BACKGROUND: The role of red blood cell (RBC) counts as potential independent risk factors for deep vein thrombosis (DVT) in patients with spinal cord injury (SCI) remains uncertain. This study aims to clarify the associations between RBC counts and DVT incidence among this population. METHODS: A retrospective analysis was performed on 576 patients with SCI admitted to the rehabilitation medicine department from January 1, 2017 to December 31, 2021. After exclusions, 319 patients were analyzed, among which 94 cases of DVT were identified. RESULTS: Mode of injury, D-dimer and anticoagulant therapy were significant covariates (P < 0.05). Age, fibrinogen, D-dimer, anticoagulant therapy and American Spinal Cord Injury Association impairment scale (AIS) grades were associated with RBC counts and DVT incidence (P < 0.05). Adjusting for these factors, a 1.00 × 10^12/L increase in RBC counts correlated with a 45% decrease in DVT incidence (P = 0.042), revealing a "U" shaped relationship with a pivot at 4.56 × 10^12/L (P < 0.05). CONCLUSION: RBC counts below 4.56 × 10^12/L serve as a protective factor against DVT, while counts above this threshold pose a risk. These findings could inform the development of DVT prevention strategies for patients with SCI, emphasizing the need for targeted monitoring and management of RBC counts.