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Objective: To investigate the diagnostic value of D-dimer, platelet-lymphocyte rate (PLR) and CT signs for intestinal ischemia in patients with bowel obstruction. Methods: We retrospectively analyzed the clinical and imaging data of 105 patients diagnosed with bowel obstruction, and performed univariate and multivariate analyses to determine the independent risk factors for intestinal ischemia in patients with bowel obstruction. Moreover, the receiver operating characteristic curve (ROC) was plotted to examine the diagnostic value of D-dimer, PLR and CT signs in patients with bowel obstruction. Besides, Kappa tests were used to assess inter-observer agreement. Results: We included 56 men (53%) and 49 women (47%) with mean age of 66.05 ± 16 years. Univariate and multivariate analyses showed that D-dimer, PLR and two significant CT signs (i.e., increased unenhanced bowel-wall attenuation and mesenteric haziness) were independent risk factors for intestinal ischemia in patients with bowel obstruction. ROC analysis showed that the combined use of D-dimer, PLR and the said two CT signs had better performance than single indicators in predicting intestinal ischemia in patients with bowel obstruction. The area under the curve (AUC) of the joint model III was 0.925 [95%CI: 0.876–0.975], with a sensitivity of 79.2% [95CI%: 67.2–91.1] and a specificity of 91.2% [95%CI: 83.7–98.9]. Conclusion: The combined use of D-dimer, PLR and CT signs has high diagnostic value for intestinal ischemia in patients with bowel obstruction and will prompt surgical exploration to evaluate intestinal blood flow. [ABSTRACT FROM AUTHOR]

Purpose: The relationship between the levels of Systemic Immune-inflammation Index (SII) and chronic obstructive pulmonary disease (COPD), lung function, and COPD severity were not fully understood. We conducted this cross-sectional, population-based study to investigate the complex association between SII and COPD, lung function, and COPD severity among the US adults. Methods: Overall, 18,349 participants were included in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018. The exposure variable was SII, calculated from platelet counts, neutrophil counts, and lymphocyte counts. Weighted univariable and multivariable logistic regression, subgroup analysis, and restricted cubic spline (RCS) regression were performed to assess the relationship between COPD, lung function, COPD severity and SII. Last, we used a propensity score matching (PSM) analysis to reduce selective bias and validate these relationships. Results: Approximately 1,094 (5.96%) of the participants were diagnosed as COPD. The multivariable-adjusted odds ratio (OR) (95% confidence interval, CI) for the Q2 group (Log-SII > 2.740) was 1.39 (1.16 to 1.68). Before and after matching, multivariable logistic regression models revealed that increased Log-SII levels (SII Logarithmic transformation) associated positively with the risk of COPD. The subgroup analysis showed no interaction between Log-SII and a variety of variables (P for interaction > 0.05). RCS showed a reversed L-shaped relationship between Log-SII with COPD (P for nonlinear = 0.001) in individuals. In addition, we observed negative significant correlations between forced expiratory volume in one second (FEV1) / forced vital capacity (FVC) %, FEV1/FVC% predicted and SII, and reversed U-shaped curve relationships between FEV1, FEV1% predicted and SII. High SII level is associated with severity of COPD, especially at Global Initiative on Obstructive Lung Disease (GOLD) 1 and GOLD 3. Conclusions: In summary, the Log-SII level is associated with COPD risk, lung function, and COPD severity. [ABSTRACT FROM AUTHOR]

Background and aims: Pericardial effusion (PE) is a prevalent form of pericardial involvement in chronic kidney disease (CKD). This study aims to investigate the clinical and laboratory features associated with PE severity in patients with CKD. Methods: In this cross-sectional study, we examined the medical records of patients admitted to tertiary hospitals with International Classification of Diseases 10th Revision (ICD-10) codes associated with CKD and PE. We included 112 CKD patients in stage 4 and 5 non-dialysis (ND) with PE for assessing the clinical and laboratory features of severity. Results: Patients were divided into two categories based on the severity of PE. Seventy-two patients had mild and 40 had moderate and severe PE. Univariate analysis of demographic and laboratory features on the date of admission demonstrated that chest pain, dyspnea, serum albumin, and neutrophil-to-lymphocyte ratio (NLR) are associated with the severity of PE. The univariate analysis on the date of echocardiography showed significantly higher white blood cell count (WBC), neutrophil count (percentage and absolute count), and NLR, along with significantly lower lymphocyte percentage and serum albumin among patients with moderate and severe PE. In the multivariable analysis of laboratory features, on admission hypoalbuminemia (p-value = 0.014, OR = 4.03, CI: 1.32–12.25) and NLR greater than 5.5 (p-value = 0.015, OR = 4.22, CI: 1.32–13.50) were significantly associated with moderate and severe PE. In a parallel matter, at the time of echocardiography hypoalbuminemia (p-value = 0.004, OR = 5.38, CI: 1.74–16.65) and neutrophilia (p-value = 0.005, OR = 7.94, CI: 1.89–33.44) were significantly associated with moderate and severe PE. Conclusion: Despite advancements in the diagnosis and treatment of CKD, PE is still a concerning issue in these patients. This study revealed that hypoalbuminemia, neutrophilia, and NLR greater than 5.5 could be predictive factors of moderate and severe PE in CKD patients with PE. Further prospective study with larger sample size is needed to confirm these results. [ABSTRACT FROM AUTHOR]

Background: Absolute lymphocyte count (ALC) is a crucial indicator of immunity in critical illness, but studies focusing on long-term outcomes in critically ill patients, particularly surgical patients, are still lacking. We sought to explore the association between week-one ALC and long-term mortality in critically ill surgical patients. Methods: We used the 2015–2020 critical care database of Taichung Veterans General Hospital (TCVGH), a referral hospital in central Taiwan, and the primary outcome was one-year all-cause mortality. We assessed the association between ALC and long-term mortality by measuring hazard ratios (HRs) with 95% confidence intervals (CIs). Furthermore, we used propensity score-matching and -weighting analyses, consisting of propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and covariate balancing propensity score (CBPS), to validate the association. Results: A total of 8052 patients were enrolled, with their one-year mortality being 24.2%. Cox regression showed that low ALC was independently associated with mortality (adjHR 1.140, 95% CI 1.091–1.192). Moreover, this association tended to be stronger among younger patients, patients with fewer comorbidities and lower severity. The association between low ALC and mortality in original, PSM, IPTW, and CBPS populations were 1.497 (95% CI 1.320–1.697), 1.391 (95% CI 1.169–1.654), 1.512 (95% CI 1.310–1.744), and 1.511 (95% CI 1.310–1.744), respectively. Additionally, the association appears to be consistent, using distinct cutoff levels to define the low ALC. Conclusions: We identified that early low ALC was associated with increased one-year mortality in critically ill surgical patients, and prospective studies are warranted to confirm the finding. [ABSTRACT FROM AUTHOR]

Background: IgG subclass levels in hemochromatosis are incompletely characterized. Methods: We characterized IgG subclass levels of referred hemochromatosis probands with HFE p.C282Y/p.C282Y (rs1800562) and human leukocyte antigen (HLA)-A and -B typing/haplotyping and compared them with IgG subclass levels of eight published cohorts of adults unselected for hemochromatosis. Results: There were 157 probands (82 men, 75 women; mean age 49±13 y). Median serum ferritin, mean body mass index (BMI), median IgG4, and median phlebotomy units to achieve iron depletion were significantly higher in men. Diabetes, cirrhosis, and HLA-A*03,-B*44, -A*03,B*07, and -A*01,B*08 prevalences and median absolute lymphocyte counts in men and women did not differ significantly. Mean IgG subclass levels [95% confidence interval] were: IgG1 5.31 g/L [3.04, 9.89]; IgG2 3.56 g/L [1.29, 5.75]; IgG3 0.61 g/L [0.17, 1.40]; and IgG4 0.26 g/L [<0.01, 1.25]. Relative IgG subclasses were 54.5%, 36.6%, 6.3%, and 2.7%, respectively. Median IgG4 was higher in men than women (0.34 g/L [0.01, 1.33] vs. 0.19 g/L [<0.01, 0.75], respectively; p = 0.0006). A correlation matrix with Bonferroni correction revealed the following positive correlations: IgG1 vs. IgG3 (p<0.01); IgG2 vs. IgG3 (p<0.05); and IgG2 vs. IgG4 (p<0.05). There was also a positive correlation of IgG4 vs. male sex (p<0.01). Mean IgG1 was lower and mean IgG2 was higher in probands than seven of eight published adult cohorts unselected for hemochromatosis diagnoses. Conclusions: Mean IgG subclass levels of hemochromatosis probands were 5.31, 3.56, 0.61, and 0.26 g/L, respectively. Median IgG4 was higher in men than women. There were positive associations of IgG subclass levels. Mean IgG1 may be lower and mean IgG2 may be higher in hemochromatosis probands than adults unselected for hemochromatosis. [ABSTRACT FROM AUTHOR]

Background: Assessing Crohn's disease (CD) activity is critical for monitoring disease progression. In CD, monocytes could release TNF-α. Thus, it is extremely important to study its role in the disease activity and loss of response to anti-TNF-α biologics. Methods: In this study, we collected CD patients treated with biologics from January 2017 to May 2022. Indicators associated with disease activity were evaluated by Spearman correlation analysis and Mann-Whitney U test. Specifically, logistic analyses were used to explore the predictors of primary nonresponse (PNR) and secondary loss of response (SLOR) within 1 year of anti-TNF-α agents. In addition, a nomogram was developed for therapeutic effect prediction. Results: 283 patients with CD were identified. Disease activity group, defined as CDAI equal to or greater than 150, had significant elevated absolute monocyte counts than disease remission group based on CDAI score (p = 0.019, Z = -2.354). Logistic analyses showed that absolute monocyte counts could be an independent predictor of 1-year SLOR of anti-TNF-α agents in CD patients (p = 0.013). A nomogram established based on gender, absolute monocyte counts, and hemoglobin could predict SLOR within 1 year of anti-TNF-α agents reliably. Conclusion: The results of this study support the utility of absolute monocyte counts detecting disease activity and anti-TNF-α therapy effect in patients with CD. [ABSTRACT FROM AUTHOR]

Background: ATL1102 is a 2'MOE gapmer antisense oligonucleotide to the CD49d alpha subunit of VLA-4, inhibiting expression of CD49d on lymphocytes, reducing survival, activation and migration to sites of inflammation. Children with DMD have dystrophin deficient muscles susceptible to contraction induced injury, which triggers the immune system, exacerbating muscle damage. CD49d is a biomarker of disease severity in DMD, with increased numbers of high CD49d expressing T cells correlating with more severe and progressive weakess, despite corticosteroid treatment. Methods: This Phase 2 open label study assessed the safety, efficacy and pharmacokinetic profile of ATL1102 administered as 25 mg weekly by subcutaneous injection for 24 weeks in 9 non-ambulatory boys with DMD aged 10–18 years. The main objective was to assess safety and tolerability of ATL1102. Secondary objectives included the effect of ATL1102 on lymphocyte numbers in the blood, functional changes in upper limb function as assessed by Performance of Upper Limb test (PUL 2.0) and upper limb strength using MyoGrip and MyoPinch compared to baseline. Results: Eight out of nine participants were on a stable dose of corticosteroids. ATL1102 was generally safe and well tolerated. No serious adverse events were reported. There were no participant withdrawals from the study. The most commonly reported adverse events were injection site erythema and skin discoloration. There was no statistically significant change in lymphocyte count from baseline to week 8, 12 or 24 of dosing however, the CD3+CD49d+ T lymphocytes were statistically significantly higher at week 28 compared to week 24, four weeks past the last dose (mean change 0.40x109/L 95%CI 0.05, 0.74; p = 0.030). Functional muscle strength, as measured by the PUL2.0, EK2 and Myoset grip and pinch measures, and MRI fat fraction of the forearm muscles were stable throughout the trial period. Conclusion: ATL1102, a novel antisense drug being developed for the treatment of inflammation that exacerbates muscle fibre damage in DMD, appears to be safe and well tolerated in non-ambulant boys with DMD. The apparent stabilisation observed on multiple muscle disease progression parameters assessed over the study duration support the continued development of ATL1102 for the treatment of DMD. Trial registration: Clinical Trial Registration. Australian New Zealand Clinical Trials Registry Number: ACTRN12618000970246. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to investigate the role of preoperative lymphocytes, albumin, neutrophils, and LANR in the prognosis of patients with stage IB-IIA cervical cancer (CC). Methods: We made a retrospective analysis of the clinical information and related materials of 202 patients with stage IB-IIA primary cervical cancer who had undergone a radical hysterectomy in the Department of Gynecology at the Affiliated Hospital of Jiangnan University between January 2017 and December 2018. The definition of LANR was as follows: LANR, lymphocyte × albumin / neutrophil. The receiver operating characteristic curve (ROC) was generated to determine the best cut-off values for these parameters, as well as the sensitivity and specificity of LANR in predicting recurrence and survival. The Kaplan–Meier method was employed to draw survival curves in our survival analysis. Univariate analysis, multifactorial analysis, and subgroup analysis were used to evaluate the prognostic significance of LANR in overall and progression-free survival. Results: The median follow-up time of the study was 55 months. In overall survival, the area under the curve for LANR was 0.704 (95% CI: 0.590–0.818, p<0.05). And in progression-free survival, the area under the curve for LANR was 0.745 (95% CI: 0.662–0.828, p<0.05). Univariate and multivariate analyses showed that the value of LANR was associated with both overall survival and progression-free survival (p< 0.05). Kaplan-Meier analysis demonstrated that OS (p< 0.001) and PFS (p< 0.001) in patients with high LANR levels were significantly higher than those with low LANR levels. Conclusions: Our findings suggested that LANR might serve as a clinically reliable and effective independent prognostic indicator in patients with stage IB-IIA cervical cancer. [ABSTRACT FROM AUTHOR]

Background: The occurrence of variations in routine hematological parameters is closely associated with disease progression, the development of severe illness, and the mortality rate among COVID-19 patients. This study aimed to investigate hematological parameters in COVID-19 hospitalized patients from the 1st to the 5th waves of the current pandemic. Methods: This cross-sectional study included a total of 1501 hospitalized patients with laboratory-confirmed COVID-19 based on WHO criteria, who were admitted to Shahid Sadoughi Hospital (SSH) in Yazd, Iran, from February 2020 to September 2021. Throughout, we encountered five COVID-19 surge waves. In each wave, we randomly selected approximately 300 patients and categorized them based on infection severity during their hospitalization, including partial recovery, full recovery, and death. Finally, hematological parameters were compared based on age, gender, pandemic waves, and outcomes using the Mann-Whitney U and Kruskal-Wallis tests. Results: The mean age of patients (n = 1501) was 61.1±21.88, with 816 (54.3%) of them being men. The highest mortality in this study was related to the third wave of COVID-19 with 21.3%. There was a significant difference in all of the hematological parameters, except PDW, PLT, and RDW-CV, among pandemic waves of COVID-19 in our population. The highest rise in the levels of MCV and RDW-CV occurred in the 1st wave, in the 2nd wave for lymphocyte count, MCHC, PLT count, and RDW-SD, in the 3rd wave for WBC, RBC, neutrophil count, MCH, and PDW, and in the 4th wave for Hb, Hct, and ESR (p < 0.01). The median level of Hct, Hb, RBC, and ESR parameters were significantly higher, while the mean level of lymphocyte and were lower in men than in women (p < 0.001). Also, the mean neutrophil in deceased patients significantly was higher than in those with full recovered or partial recovery (p < 0.001). Conclusion: The findings of our study unveiled notable variations in hematological parameters across different pandemic waves, gender, and clinical outcomes. These findings indicate that the behavior of different strains of the COVID-19 may differ across various stages of the pandemic. [ABSTRACT FROM AUTHOR]

Objective: Malnutrition, accompanied by an inflammatory profile, is a risk factor for poor prognosis in hemodialysis patients. The purpose of this study was to investigate the predictive value of NLR combined with GNRI for all-cause and cardiovascular mortality in hemodialysis patients. Methods: A total of 240 maintenance hemodialysis (MHD) patients in hemodialysis centers were enrolled in this retrospective study. The influencing factors of all-cause death in hemodialysis patients were analyzed by COX regression. The cut-off values of GNRI and NLR for predicting mortality in enrolled MHD patients were 89.01 and 4, respectively. Based on these cut-off values, the patients were divided into four groups: G1: high GNRI (≥ 89.01) + high NLR (≥ 4) group; G2: high GNRI (≥ 89.01) + low NLR (<4) group, G3: low GNRI (< 89.01) + high NLR (≥4) group; G4: low GNRI (< 89.01) + low NLR (<4). Results: During the follow-up period (average: 58 months), the all-cause mortality was 20.83%(50/240) and the cardiovascular mortality was 12.08%(29/240). Both NLR and GNRI were independent risk factors for the prognosis of MHD patients (P<0.05). Survival analysis showed that patients with low GNRI had a lower survival rate than those with high GNRI, whereas patients with high NLR had a lower survival rate than those with low NLR. Kaplan-Meier curve for all-cause mortality revealed that compared to G1, G2, and G4, G3 had the lowest survival rate, while G2 had the highest survival rate among all groups (P < 0.05). Kaplan-Meier curve for cardiovascular mortality showed that G3 had lower survival than G1, G2, and G4 (P < 0.001). Conclusions: Our study demonstrates that bothGNRI and NLR are associated with all-cause mortality and cardiovascular mortality in MHD patients. Combining these two factorsmay contribute to a prognostic evaluation for MHD patients. [ABSTRACT FROM AUTHOR]

Preoperative nutritional status is an important prognostic factor in gastric cancer patients. This study will evaluate whether preoperative oral dysfunction is associated with prognostic nutrition index (PNI). This case-control study analyzed 95 patients who underwent oral function management. We assessed the following parameters: body mass index, stage of gastric cancer, C-reactive protein, total lymphocyte count, albumin, and prognostic nutritional index. The patients were divided into groups with prognostic nutritional indexes <45 and >45. Logistic regression analysis was used to assess the association between the measurements of oral function and the prognostic nutritional index. Univariate analysis of factors associated with decreased oral function and prognostic nutritional index showed significant differences between the two groups in C-reactive protein, neutrophils, and tongue pressure (p<0.01). However, oral hygiene, oral dryness, occlusal force, tongue–lip motor function, masticatory function, and swallowing function were not significantly different. Multivariate analysis showed that C-reactive protein (odds ratio: 0.12, 95% confidence interval: 0.30–0.45, p<0.01) and tongue pressure (odds ratio: 3.62, 95% confidence interval: 1.04–12.60, p<0.05) were independent risk factors for oral hypofunction. Oral function decreased in perioperative patients with gastric cancer, and decreased tongue pressure is associated with a decreased prognostic nutritional index. [ABSTRACT FROM AUTHOR]

Introduction: Parkinson's disease (PD) is the most common movement disorder, and its prevalence is increasing rapidly worldwide with an ageing population. The UK Biobank is the world's largest and most comprehensive longitudinal study of ageing community volunteers. The cause of the common form of PD is multifactorial, but the degree of causal heterogeneity among patients or the relative importance of one risk factor over another is unclear. This is a major impediment to the discovery of disease-modifying therapies. Methods: We used an integrated machine learning algorithm (IDEARS) to explore the relative effects of 1,753 measured non-genetic variables in 334,062 eligible UK Biobank participants, including 2,719 who had developed PD since their recruitment into the study. Results: Male gender was the highest-ranked risk factor, followed by elevated serum insulin-like growth factor 1 (IGF-1), lymphocyte count, and neutrophil/lymphocyte ratio. A group of factors aligned with the symptoms of frailty also ranked highly. IGF-1 and neutrophil/lymphocyte ratio were also elevated in both sexes before PD diagnosis and at the point of diagnosis. Discussion: The use of machine learning with the UK Biobank provides the best opportunity to explore the multidimensional nature of PD. Our results suggest that novel risk biomarkers, including elevated IGF-1 and NLR, may play a role in, or are indicative of PD pathomechanisms. In particular, our results are consistent with PD being a central manifestation of a systemic inflammatory disease. These biomarkers may be used clinically to predict future PD risk, improve early diagnosis and provide new therapeutic avenues. [ABSTRACT FROM AUTHOR]

With the COVID-19 pandemic having caused unprecedented numbers of infections and deaths, large research efforts have been undertaken to increase our understanding of the disease and the factors which determine diverse clinical evolutions. Here we focused on a fully data-driven exploration regarding which factors (clinical or otherwise) were most informative for SARS-CoV-2 pneumonia severity prediction via machine learning (ML). In particular, feature selection techniques (FS), designed to reduce the dimensionality of data, allowed us to characterize which of our variables were the most useful for ML prognosis. We conducted a multi-centre clinical study, enrolling n = 1548 patients hospitalized due to SARS-CoV-2 pneumonia: where 792, 238, and 598 patients experienced low, medium and high-severity evolutions, respectively. Up to 106 patient-specific clinical variables were collected at admission, although 14 of them had to be discarded for containing ⩾60% missing values. Alongside 7 socioeconomic attributes and 32 exposures to air pollution (chronic and acute), these became d = 148 features after variable encoding. We addressed this ordinal classification problem both as a ML classification and regression task. Two imputation techniques for missing data were explored, along with a total of 166 unique FS algorithm configurations: 46 filters, 100 wrappers and 20 embeddeds. Of these, 21 setups achieved satisfactory bootstrap stability (⩾0.70) with reasonable computation times: 16 filters, 2 wrappers, and 3 embeddeds. The subsets of features selected by each technique showed modest Jaccard similarities across them. However, they consistently pointed out the importance of certain explanatory variables. Namely: patient's C-reactive protein (CRP), pneumonia severity index (PSI), respiratory rate (RR) and oxygen levels –saturation Sp O2, quotients Sp O2/RR and arterial Sat O2/Fi O2–, the neutrophil-to-lymphocyte ratio (NLR) –to certain extent, also neutrophil and lymphocyte counts separately–, lactate dehydrogenase (LDH), and procalcitonin (PCT) levels in blood. A remarkable agreement has been found a posteriori between our strategy and independent clinical research works investigating risk factors for COVID-19 severity. Hence, these findings stress the suitability of this type of fully data-driven approaches for knowledge extraction, as a complementary to clinical perspectives. [ABSTRACT FROM AUTHOR]

PurposeTo describe the trajectory of respiratory failure in COVID-19 and explore factors associated with risk of invasive mechanical ventilation (IMV).Materials and methodsA retrospective, observational cohort study of 112 inpatient adults diagnosed with COVID-19 between March 12 and April 16, 2020. Data were manually extracted from electronic medical records. Multivariable and Univariable regression were used to evaluate association between baseline characteristics, initial serum markers and the outcome of IMV.ResultsOur cohort had median age of 61 (IQR 45-74) and was 66% male. In-hospital mortality was 6% (7/112). ICU mortality was 12.8% (6/47), and 18% (5/28) for those requiring IMV. Obesity (OR 5.82, CI 1.74-19.48), former (OR 8.06, CI 1.51-43.06) and current smoking status (OR 10.33, CI 1.43-74.67) were associated with IMV after adjusting for age, sex, and high prevalence comorbidities by multivariable analysis. Initial absolute lymphocyte count (OR 0.33, CI 0.11-0.96), procalcitonin (OR 1.27, CI 1.02-1.57), IL-6 (OR 1.17, CI 1.03-1.33), ferritin (OR 1.05, CI 1.005-1.11), LDH (OR 1.57, 95% CI 1.13-2.17) and CRP (OR 1.13, CI 1.06-1.21), were associated with IMV by univariate analysis.ConclusionsObesity, smoking history, and elevated inflammatory markers were associated with increased need for IMV in patients with COVID-19.

Background: Hypertension (HTN) is associated with severe COVID-19 infection; however, it remains unknown if the level of blood pressure (BP) predicts mortality. We tested whether the initial BP in the emergency department of hospitalized patients portends mortality in COVID-19 positive(+) patients. Methods: Data from COVID-19(+) and negative (-) hospitalized patients at Stony Brook University Hospital from March to July 2020 were included. The initial mean arterial BPs (MABPs) were categorized into tertiles (T) of MABP (65–85 [T1], 86–97 [T2] and ≥98 [T3] mmHg). Differences were evaluated using univariable (t-tests, chi-squared) tests. Multivariable (MV) logistic regression analyses were computed to assess links between MABP and mortality in hypertensive COVID-19 patients. Results: 1549 adults were diagnosed with COVID-19 (+) and 2577 tested negative (-). Mortality of COVID-19(+) was 4.4-fold greater than COVID-19(-) patients. Though HTN prevalance did not differ between COVID-19 groups, the presenting systolic BP, diastolic BP, and MABP were lower in the COVID-19(+) vs (-) cohort. When subjects were categorized into tertiles of MABP, T2 tertile of MABP had the lowest mortality and the T1 tertile of MABP had greatest mortality compared to T2; however, no difference in mortality was noted across tertiles of MABP in COVID-19 (-). MV analysis of COVID-19 (+) subjects exposed death as a risk factor for T1 MABP. Next, the mortality of those with a historic diagnosis of hypertension or normotension were studied. On MV analysis, T1 MABP, gender, age, and first respiratory rate correlated with mortality while lymphocyte count inversely correlated with death in hypertensive COVID-19 (+) patients while neither T1 nor T3 categories of MABP predicted death in non-hypertensives. Conclusions: Low-normal admitting MABP in COVID-19 (+) subjects with a historical diagnosis of HTN is associated with mortality and may assist in identifying those at greatest mortality risk. [ABSTRACT FROM AUTHOR]

No biomarkers have been identified in bronchoalveolar lavage fluid (BALF) for predicting fibrosis progression or prognosis in progressive fibrosing interstitial lung disease (PF-ILD). We investigated BALF biomarkers for PF-ILD diagnosis and prognosis assessment. Overall, 120 patients with interstitial pneumonia who could be diagnosed with PF-ILD or non PF-ILD were enrolled in this retrospective study. PF-ILD was diagnosed according to Cottin's definition. All patients underwent bronchoscopy and BALF collection. We evaluated blood and BALF parameters, high-resolution computed tomography (HRCT) patterns, and spirometry data to identify factors influencing PF-ILD diagnosis and prognosis. On univariate logistic analysis, age, sex, the BALF white blood cell fraction (neutrophil, lymphocyte, eosinophil, and neutrophil-to-lymphocyte ratio), BALF flow cytometric analysis (CD8), and an idiopathic pulmonary fibrosis/usual interstitial pneumonia pattern on HRCT were correlated with PF-ILD diagnosis. Multivariate logistic regression analysis revealed that sex (male), age (cut-off 62 years, area under the curve [AUC] 0.67; sensitivity 0.80; specificity 0.47), white blood cell fraction in BALF (NLR, neutrophil, and lymphocyte), and CD8 in BALF (cut-off 34.2; AUC 0.66; sensitivity, 0.74; specificity, 0.62) were independent diagnostic predictors for PF-ILD. In BALF, the NLR (cut-off 8.70, AUC 0.62; sensitivity 0.62; specificity 0.70), neutrophil count (cut-off 3.0, AUC 0.59; sensitivity 0.57; specificity 0.63), and lymphocyte count (cut-off 42.0, AUC 0.63; sensitivity 0.77; specificity 0.53) were independent diagnostic predictors. In PF-ILD patients (n = 77), lactate dehydrogenase (cut-off 275, AUC 0.69; sensitivity 0.57; specificity 0.78), Krebs von den Lungen-6 (cut-off 1,140, AUC 0.74; sensitivity 0.71; specificity 0.76), baseline forced vital capacity (FVC) (cut-off 1.75 L, AUC 0.71; sensitivity, 0.93; specificity, 0.46), and BALF neutrophil ratio (cut-off 6.0, AUC 0.72; sensitivity 0.79; specificity 0.80) correlated with death within 3 years. The BALF cellular ratio, particularly the neutrophil ratio, correlated with the diagnosis and prognosis of PF-ILD. These findings may be useful in the management of patients with interstitial pneumonia. [ABSTRACT FROM AUTHOR]

Background: The increased procoagulant platelets and platelet activation are associated with thrombosis in COVID-19. In this study, we investigated platelet activation in COVID-19 patients and their association with other disease markers. Methods: COVID-19 patients were classified into three severity groups: no pneumonia, mild-to-moderate pneumonia, and severe pneumonia. The expression of P-selectin and activated glycoprotein (aGP) IIb/IIIa on the platelet surface and platelet-leukocyte aggregates were measured prospectively on admission days 1, 7, and 10 by flow cytometry. Results: P-selectin expression, platelet-neutrophil, platelet-lymphocyte, and platelet-monocyte aggregates were higher in COVID-19 patients than in uninfected control individuals. In contrast, aGPIIb/IIIa expression was not different between patients and controls. Severe pneumonia patients had lower platelet-monocyte aggregates than patients without pneumonia and patients with mild-to-moderate pneumonia. Platelet-neutrophil and platelet-lymphocyte aggregates were not different among groups. There was no change in platelet-leukocyte aggregates and P-selectin expression on days 1, 7, and 10. aGPIIb/IIIa expression was not different among patient groups. Still, adenosine diphosphate (ADP)-induced aGPIIb/IIIa expression was lower in severe pneumonia than in patients without and with mild-to-moderate pneumonia. Platelet-monocyte aggregates exhibited a weak positive correlation with lymphocyte count and weak negative correlations with interleukin-6, D-dimer, lactate dehydrogenase, and nitrite. Conclusion: COVID-19 patients have higher platelet-leukocyte aggregates and P-selectin expression than controls, indicating increased platelet activation. Compared within patient groups, platelet-monocyte aggregates were lower in severe pneumonia patients. [ABSTRACT FROM AUTHOR]

Lung cancer is a product of inflammation and a dysfunctional immune system, and depression has similar dysregulation. Depression disproportionately affects lung cancer patients, having the highest rates of all cancers. Systemic inflammation and depression are both predictive of non-small cell lung cancer (NSCLC) survival, but the existence and extent of any co-occurrence is unknown. Studied is the association between systemic inflammation ratio (SIR) biomarker levels and patients' depressive symptoms, with the hypothesis that depression severity would be significantly associated with prognostically poor inflammation. Newly diagnosed stage-IV non-small cell lung cancer (NSCLC; N = 186) patients were enrolled (ClinicalTrials.gov Identifier: NCT03199651) and blood draws and depression self-reports (Patient Health Questionnaire-9) were obtained. For SIRs, cell counts of neutrophils (N), lymphocytes (L), and platelets (P) were abstracted for ratio (R) calculations for NLR, PLR, and the Advanced Lung cancer Inflammation Index (ALI). Patients were followed and biomarkers were tested as predictors of 2-year overall survival (OS) to confirm their relevance. Next, multivariate linear regressions tested associations of depression with NLR, PLR, and ALI. Overall 2-year mortality was 61% (113/186). Cox model analyses confirmed higher NLR [hazard ratio (HR) = 1.91; p = 0.001] and PLR (HR = 2.08; p<0.001), along with lower ALI (HR = 0.53; p = 0.005), to be predictive of worse OS. Adjusting for covariates, depression was reliably associated with biomarker levels (p ≤ 0.02). Patients with moderate/severe depressive symptoms were 2 to 3 times more likely to have prognostically poor biomarker levels. Novel data show patients' depressive symptoms were reliably associated with lung-relevant systemic inflammation biomarkers, all assessed at diagnosis/pretreatment. The same SIRs were found prognostic for patients' 2-year OS. Intensive study of depression, combined with measures of cell biology and inflammation is needed to extend these findings to discover mechanisms of depression toxicity for NSCLC patients' treatment responses and survival. [ABSTRACT FROM AUTHOR]

Massive apoptosis of lymphocytes is a hallmark of sepsis. The resulting immunosuppression is associated with secondary infections, which are often lethal. Moreover, sepsis-survivors are burdened with increased morbidity and mortality for several years after the sepsis episode. The duration and clinical consequences of sepsis induced-immunosuppression are currently unknown. We have used the mouse model of peritoneal contamination and infection (PCI) to investigate the quantitative and qualitative recovery of T lymphocytes for 3.5 months after sepsis with or without IL-7 treatment. Thymic output and the numbers of naive and effector/memory CD4+ and CD8+ lymphocytes quickly recovered after sepsis. IL-7 treatment resulted in an accelerated recovery of CD8+ lymphocytes. Next generation sequencing revealed no significant narrowing of the T cell receptor repertoire 3.5 months after sepsis. In contrast, detailed functional analyses of T helper (Th)-cell responses towards a fungal antigen revealed a significant loss of Th cells. Whereas cytokine production was not impaired at the single cell level, the absolute number of Th cells specific for the fungal antigen was reduced. Our data indicate a clinically relevant loss of pathogen-specific T cell clones after sepsis. Given the small number of naive T lymphocytes specific for a given antigen, this decrement of T cell clones remains undetected even by sensitive methods such as deep sequencing. Taken together, our data are compatible with long lasting impairments in CD4+ T-cell responses after sepsis despite rapid recovery of T lymphocyte populations.

Fingolimod (FTY720) is a drug derived from the fungicidal compound myriocin. As it was unclear whether FTY720 has antifungal effects as well, we aimed to characterize its effect on Candida albicans in vitro and in a mouse candidiasis model. First, antifungal susceptibility testing was performed in vitro. Then, a randomized, six-arm, parallel, open-label trial was conducted on 48 mice receiving oral FTY720 (0.3 mg/kg/day), intraperitoneal C. albicans inoculation, or placebo with different combinations and chorological patterns. The outcome measures of the trial included serum concentrations of interleukin-10 and interferon-gamma, absolute lymphocyte counts, and fungal burden values in the mice's livers, kidneys, and vaginas. Broth microdilution assay revealed FTY720's minimum inhibitory concentration (MIC99) to be 0.25 mg/mL for C. albicans. The infected mice treated with FTY720 showed lower fungal burden values than the ones not treated with FTY720 (p<0.05). As expected, the mice treated with FTY720 showed a less-inflammatory immune profile compared to the ones not treated with FTY720. We hypothesize that FTY720 synergizes the host's innate immune functions by inducing the production of reactive oxygen species. Further studies are warranted to unveil the mechanistic explanations of our observations and clarify further aspects of repurposing FTY720 for clinical antifungal usage. [ABSTRACT FROM AUTHOR]

Objective: To relate preevacuation platelet count and leukogram findings, especially neutrophil/lymphocyte ratios (NLR) and platelet/lymphocyte ratios with the occurrence of gestational trophoblastic neoplasia (GTN) after complete hydatidiform mole (CHM) among Brazilian women. Methods: Retrospective cohort study of patients with CHM followed at Rio de Janeiro Federal University, from January/2015-December/2020. Before molar evacuation, all patients underwent a medical evaluation, complete blood count and hCG measurement, in addition to other routine preoperative tests. The primary outcome was the occurrence of postmolar GTN. Results: From 827 cases of CHM treated initially at the Reference Center, 696 (84.15%) had spontaneous remission and 131 (15.85%) developed postmolar GTN. Using optimal cut-offs from receiver operating characteristic curves and multivariable logistic regression adjusted for the possible confounding variables of age and preevacuation hCG level (already known to be associated with the development of GTN) we found that ≥2 medical complications at presentation (aOR: 1.96, CI 95%: 1.29–2.98, p<0.001) and preevacuation hCG ≥100,000 IU/L (aOR: 2.16, CI 95%: 1.32–3.52, p<0.001) were significantly associated with postmolar GTN after CHM. However, no blood count profile findings were able to predict progression from CHM to GTN. Conclusion: Although blood count is a widely available test, being a low-cost test and mandatory before molar evacuation, and prognostic for outcome in other neoplasms, its findings were not able to predict the occurrence of GTN after CHM. In contrast, the occurrence of medical complications at presentation and higher preevacuation hCG levels were significantly associated with postmolar GTN and may be useful to guide individualized clinical decisions in post-molar follow-up and treatment of these patients. [ABSTRACT FROM AUTHOR]

Background: Patients have difficult unmet needs when standard chemotherapy produces a median survival of less than 1 year or many patients will experience severe toxicities. Blood tests can predict their survival. Methods: Analyses evaluate predictive blood tests to identify patients who often survive 1 and 2 years. A four-test model includes: albumin, absolute neutrophil count, neutrophil-lymphocyte ratio, and lymphocyte-monocyte ratio. Individual tests include: alkaline phosphatase, lymphocytes, white blood count, platelet count, and hemoglobin. Eligible patients have advanced: resistant 3rd line colorectal, and both resistant and new pancreatic and intrahepatic bile duct cancers. Eligibility characteristics include: biopsy-proven, measurable metastatic disease, NCI grade 0–2 blood tests, Karnofsky Score 100–50, and any adult age. Drugs are given at 1/4–1/3 of their standard dosages biweekly: gemcitabine, irinotecan, fluorouracil, leucovorin, and day 2 oxaliplatin every 2 weeks. In case of progression, Docetaxel is added (except colon cancer), with or without Mitomycin C, and next cetuximab (except pancreatic and KRAS BRAF mutation cancers). Bevacizumab is substituted for cetuximab in case of another progression or ineligibility. Consent was written and conforms with Helsinki, IRB, and FDA criteria (FDA #119005). Results: Median survival is 14.5 months. Of 205 patients, 60% survive 12, and 37% survive 24 months (95% CI ± 8%). Survival is > 24, 13, and 3.8 months for patients with 0, 1–2, and 3–4 unfavorable tests, respectively. Individual "favorable and unfavorable" tests predict long and short survival. Neither age nor prior therapy discernibly affects survival. Net rates of clinically significant toxicities are less than 5%. Conclusion: Treatments reproduce predictable, greater than 12 and 24-month chances of survival for the aged and for patients with drug-resistant tumors. Evaluation of blood tests may change practice, expand eligibility, and personalize treatments. Findings support investigation of drug combinations and novel dosages to reverse resistance and improve safety. [ABSTRACT FROM AUTHOR]

Background: Although hyperinflammatory response influences the severity of coronavirus disease 2019 (COVID-19), little has been reported about the utility of tumor necrosis factor (TNF)-related biomarkers in reflecting the prognosis. We examined whether TNF receptors (TNFRs: TNFR1, TNFR2) and progranulin (PGRN) levels, in addition to interleukin 6 (IL-6) and C-reactive protein (CRP), are associated with mortality or disease severity in COVID-19 patients. Methods: This retrospective study was conducted at Juntendo University Hospital. Eighty hospitalized patients with various severities of COVID-19 were enrolled. Furthermore, serum levels of TNF-related biomarkers were measured using enzyme-linked immunosorbent assay. Results: Twenty-five patients died during hospitalization, and 55 were discharged. The median (25th and 75th percentiles) age of the study patients was 70 (61–76) years, 44 (55.0%) patients were males, and 26 (32.5%) patients had chronic kidney disease (CKD). When comparing with patients who received and did not receive treatment at the intensive care unit (ICU), the former had a higher tendency of being male and have diabetes, hypertension, and CKD; had higher levels of white blood cells, D-dimer, and lactate dehydrogenase; and had lower body mass index, estimated glomerular filtration rate, and lymphocyte counts. Significant differences were observed in TNFR, PGRN, IL-6, and CRP levels between each severity (mild–severe) group. Furthermore, the serum levels of TNFR, IL-6, and CRP, but not PGRN, in ICU patients were significantly higher than in the patients who were not admitted to the ICU. Multivariate logistic regression analysis demonstrated that high levels of TNFR2 were only associated with mortality in patients with COVID-19 even after adjustment for relevant clinical parameters. Conclusions: High TNFR2 level might be helpful for predicting mortality or disease severity in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Aim: To develop an accurate lab score based on in-hospital patients' potent clinical and biological parameters for predicting COVID-19 patient severity during hospital admission. Methods: To conduct this retrospective analysis, a derivation cohort was constructed by including all the available biological and clinical parameters of 355 COVID positive patients (recovered = 285, deceased = 70), collected in November 2020-September 2021. For identifying potent biomarkers and clinical parameters to determine hospital admitted patient severity or mortality, the receiver operating characteristics (ROC) curve and Fischer's test analysis was performed. Relative risk regression was estimated to develop laboratory scores for each clinical and routine biological parameter. Lab score was further validated by ROC curve analysis of the validation cohort which was built with 50 COVID positive hospital patients, admitted during October 2021-January 2022. Results: Sensitivity vs. 1-specificity ROC curve (>0.7 Area Under the Curve, 95% CI) and univariate analysis (p<0.0001) of the derivation cohort identified five routine biomarkers (neutrophil, lymphocytes, neutrophil: lymphocytes, WBC count, ferritin) and three clinical parameters (patient age, pre-existing comorbidities, admitted with pneumonia) for the novel lab score development. Depending on the relative risk (p values and 95% CI) these clinical parameters were scored and attributed to both the derivation cohort (n = 355) and the validation cohort (n = 50). ROC curve analysis estimated the Area Under the Curve (AUC) of the derivation and validation cohort which was 0.914 (0.883–0.945, 95% CI) and 0.873 (0.778–0.969, 95% CI) respectively. Conclusion: The development of proper lab scores, based on patients' clinical parameters and routine biomarkers, would help physicians to predict patient risk at the time of their hospital admission and may improve hospital-admitted COVID-19 patients' survivability. [ABSTRACT FROM AUTHOR]

Neonatal necrotizing enterocolitis (NEC) occurs worldwide and is a major source of neonatal morbidity and mortality. Researchers have developed many methods for predicting NEC diagnosis and prognosis. However, most people use statistical methods to select features, which may ignore the correlation between features. In addition, because they consider a small dimension of characteristics, they neglect some laboratory parameters such as white blood cell count, lymphocyte percentage, and mean platelet volume, which could be potentially influential factors affecting the diagnosis and prognosis of NEC. To address these issues, we include more perinatal, clinical, and laboratory information, including anemia—red blood cell transfusion and feeding strategies, and propose a ridge regression and Q-learning strategy based bee swarm optimization (RQBSO) metaheuristic algorithm for predicting NEC diagnosis and prognosis. Finally, a linear support vector machine (linear SVM), which specializes in classifying high-dimensional features, is used as a classifier. In the NEC diagnostic prediction experiment, the area under the receiver operating characteristic curve (AUROC) of dataset 1 (feeding intolerance + NEC) reaches 94.23%. In the NEC prognostic prediction experiment, the AUROC of dataset 2 (medical NEC + surgical NEC) reaches 91.88%. Additionally, the classification accuracy of the RQBSO algorithm on the NEC dataset is higher than the other feature selection algorithms. Thus, the proposed approach has the potential to identify predictors that contribute to the diagnosis of NEC and stratification of disease severity in a clinical setting. [ABSTRACT FROM AUTHOR]

Immunodeficient animals are valuable models for the engraftment of exogenous tissues; they are widely used in many fields, including the creation of humanized animal models, as well as regenerative medicine and oncology. Compared with mice, laboratory rats have a larger body size and can more easily undergo transplantation of various tissues and organs. Considering the absence of high-quality resources of immunodeficient rats, we used the CRISPR/Cas9 genome editing system to knock out the interleukin-2 receptor gamma chain gene (Il2rg) in F344/Jcl rats—alone or together with recombination activating gene 2 (Rag2)—to create a high-quality bioresource that researchers can freely use: severe combined immunodeficiency (SCID) rats. We selected one founder rat with frame-shift mutations in both Il2rg (5-bp del) and Rag2 ([1-bp del+2-bp ins]/[7-bp del+2-bp ins]), then conducted mating to establish a line of immunodeficient rats. The immunodeficiency phenotype was preliminarily confirmed by the presence of severe thymic hypoplasia in Il2rg-single knockout (sKO) and Il2rg/Rag2-double knockout (dKO) rats. Assessment of blood cell counts in peripheral blood showed that the white blood cell count was significantly decreased in sKO and dKO rats, while the red blood cell count was unaffected. The decrease in white blood cell count was mainly caused by a decrease in lymphocytes. Furthermore, analyses of lymphocyte populations via flow cytometry showed that the numbers of B cells (CD3- CD45+) and natural killer cells (CD3- CD161+) were markedly reduced in both knockout rats. In contrast, T cells were markedly reduced but showed slightly different results between sKO and dKO rats. Notably, our immunodeficient rats do not exhibit growth retardation or gametogenesis defects. This high-quality SCID rat resource is now managed by the National BioResource Project in Japan. Our SCID rat model has been used in various research fields, demonstrating its importance as a bioresource. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most frequent and fatal cancer type globally. The fatality rate of breast cancer is mostly due to disease complications like hematological alterations. Therefore, this study aimed to assess the hematological abnormalities before, during, and after the initiation of cancer treatment in breast cancer patients at the University of Gondar comprehensive specialized hospital. Methodology: Hematological profiles were collected from 267 breast cancer patients who attended the cancer treatment center from September 2017 to August 2021. A data extraction sheet was used to extract data from the patient's medical chart, including sociodemography, clinical, and hematological profiles. EPI info version 3.5.1 and SPSS Version 25 softwares were used for data entrance and analysis, respectively. Descriptive statistics were summarized using frequency and percentage. The Friedman test followed by a Wilcoxon signed rank test was used to compare the mean difference between the hematological profiles at zero and after the 4th and 8th cycles of treatment. Result: Of the total participants, 91% were females, and the median age of the study participants was 45 (IQR = 36, 55) years. Red blood cell, white blood cell, and lymphocyte counts, as well as hematocrit and hemoglobin values, were significantly reduced after the initiation of cancer treatment, while the platelet count and red cell distribution width were significantly increased. The prevalence of anemia was 21.7% (95% CI: 16.6, 26.8), 22.7% (95% CI: 17.6, 27.8), and 26.4% (95% CI: 21.3, 31.5) before, during, and after the initiation of cancer treatment, respectively. The prevalence of leukopenia before, during, and after treatment was 9.7%, 18.8%, and 15.1%, respectively. Finally the prevalence of thrombocytopenia was 6.3%, 3.4%, and 8% at before, during, and after treatment, respectively. Conclusion: This study concluded that many hematological parameters were significantly affected by the breast cancer treatment. Therefore, proper patient follow-up and provide appropriate interventions related to their hematological abnormalities is crucial. It is also important to conduct further prospective studies to confirm the findings of this study. [ABSTRACT FROM AUTHOR]

Purpose: Available but insufficient evidence shows that changes may occur in the immune system following coronavirus disease 2019 (COVID-19). The present study aimed at evaluating immunological changes in patients with severe acute respiratory syndrome coronavirus‐2 (SARS-CoV-2) pneumonia compared with the control group. Method: The present study was performed on 95 patients with COVID-19 (32 severe and 63 moderate cases) and 22 healthy controls. Relationship between immune cells, disease severity and lung involvement was assessed. Binary logistic regression and ROC curve tests were used for statistical analysis. Results: A significant decrease was observed in CD20+ cell counts of the patients. To differentiate patients from healthy individuals, the cutoff point for the CD4+ cell count was 688 /μL, sensitivity 0.96, and specificity 0.84. An increase in CD4+ cells reduces the odds of severe disease (odds ratio = 0.82, P = 0.047) and death (odds ratio = 0.74, P = 0.029). CD4+ cells play a pivotal role in the severity of lung involvement (P = 0.03). In addition to CD4+ cells, Fc gamma receptor III (FcγRIII) (CD16) also played a significant prognosis (odds ratio = 0.55, P = 0.047). In severe cases, C-reactive protein, Blood urea nitrogen, and Creatine phosphokinase levels, as well as neutrophil counts, were significantly higher than those of moderate ones whereas lymphocyte count in severe cases was lower than that of moderate ones. Conclusion: The number of total T-cells and B-cells in patients with COVID-19 was lower than that of controls; however, their NK cells increased. FcγRIII and CD4+ cells are of great importance due to their association with COVID-19 prognosis. [ABSTRACT FROM AUTHOR]

The objectives of this study were to evaluate the proper anticoagulants coated in blood-collecting tube for the peripheral blood mononuclear cells (PBMCs) isolation and to evaluate the proper culture temperature for the Varanus salvator's PBMCs, in addition, the hematological characteristics also reported. The heparin treated blood (n = 10) and EDTA treated blood (n = 10) from Varanus salvator were obtained for PBMCs evaluation. The PBMCs obtained from the heparin treated blood was significantly higher than that of EDTA treated blood during the culture period (P < 0.05) indicated heparin would be more appropriated anticoagulant for blood collection. The PBMCs cultured under 37°C and 27°C were not significantly difference on first three days but 37°C showed significantly higher effect in the following days (P < 0.05) indicated both temperatures can be used which 37°C should be an optimal for PBMCs preparation. The peripheral blood cells of Varanus salvator (n = 49) were analyzed for hematological profiles and characteristics which the number of erythrocytes 1.19 ± 0.04 x 1012/L (1.17–1.35 x 1012/L) and WBC 2.41 ± 0.13 x 109/L (2.29–2.81 x 109/L) with absolute differential count of heterophils 0.92 ± 0.02 x 109/L (0.87–0.95 x 109/L), lymphocytes 1.17 ± 0.01 x 109/L (1.15–1.23 x 109/L), azurophils 0.40 ± 0.01 x 109/L (0.37–0.42 x 109/L), basophils 0.000 ± 0.001 x 109/L (0.004–0.011 x 109/L) and monocytes 0.027 ± 0.002 x 109/L (0.028–0.039 x 109/L). These results would play an important role on the cell immunological studies of the Varanus salvator in the future. [ABSTRACT FROM AUTHOR]

Background: COVID-19 pandemic has led to a catastrophic shortage of ICU beds. This has resulted in the need to identify patients that can be discharged early before full clinical recovery. We designed this study to determine if in changes routine tests like CBCD and CRP can be a useful complement to clinical status when deciding to discharge patients from ICU. Methods: This retrospective study was conducted in Rafic Hariri University Hospital. Levels of biomarkers measured at admission (T1) and within 3 days of outcome (T2) were collected and ratios (T2/T1) were calculated. The Odds Ratios of association between the changes in these biomarkers and outcome were estimated. Multivariate analysis and AUC for the performance of these biomarkers were also conducted. Results: We found on multivariate analysis that reduction in counts of lymphocyte and platelets and elevation in counts of neutrophils and level of CRP (T2/T1 ratio > 1) are strongly associated with mortality with respective ORs estimated at 6.74, 3.26, 5.65 and 4.34 [p-values < 0.001]. AUCs were found to lie in a range of 0.68 to 0.81 indicating fair to good performance. Other factors found to impact survival were AKI, AF and ACS [p-values < 0.01]. In contrast to other studies, risk factors didn't show an association with survival when adjusted for effects of complications and changes in biomarker levels. Conclusions: Our results confirm that inexpensive tests like lymphocyte count and CRP can be reliably used to follow COVID-19 patients in ICU and to support the decision to discharge patients. [ABSTRACT FROM AUTHOR]

The acute effects of exercise on metabolic energy expenditure and inflammation are well studied, but the long-term effects of regular daily physical activity on metabolic and endocrine effects are less clear. Further, prior studies investigating the impact of daily physical activity in large cohorts have generally relied on self-reported activity. Here, we used the U.S. National Health and Nutrition Examination Survey (NHANES) to investigate the relationship between daily physical activity and both thyroid and immune activity. Daily physical activity was assessed through accelerometry or accelerometry-validated survey responses. Thyroid activity was assessed from circulating levels of thyroid stimulating hormone (TSH) and thyroxine (T4). Immune function was assessed from circulating cytokines (C-reactive protein [CRP], immunoglobulin E [IgE], fibrinogen) and blood cell counts. In general linear models including body mass index, age, gender, activity and TSH as factors, active adults had a lower levels of T4 and reduced slope of the TSH:T4 relationship. Similarly, greater physical activity was associated with lower CRP and fibrinogen levels (but not IgE) and lower white blood cell, basophil, monocyte, neutrophil, and eosinophil (but not lymphocyte) counts. Daily physical activity was also associated with lower prevalence of clinically elevated CRP, WBC, and lymphocytes in a dose-response manner. These results underscore the long-term impact of daily physical activity on both systemic metabolic activity (thyroid) and on specific physiological tasks (immune). The regulatory effects of physical activity on other bodily systems are clinically relevant and should be incorporated into public health strategies promoting exercise. [ABSTRACT FROM AUTHOR]

Background and Aim: Ustekinumab, a new anti-interleukin-12/23 antibody, is an effective treatment for ulcerative colitis; however, data regarding predictive factors of its efficacy are limited. Predicting treatment efficacy in advance would be useful for selecting a therapeutic agent. This study aimed to identify biomarkers that can predict the long-term outcome of ustekinumab treatment., Materials and Methods: We retrospectively reviewed the records of patients with active ulcerative colitis treated with ustekinumab at Osaka Medical and Pharmaceutical University Hospital from June 2020 to January 2023. We divided patients into non-remission and remission groups, and examined whether baseline biomarkers, including C-reactive protein-to-lymphocyte ratio, and early treatment response could predict clinical remission at week 48 of ustekinumab treatment., Results: Of the 33 patients included in the study, 21 (63.6%) were in clinical remission at week 48 of ustekinumab treatment. Baseline C-reactive protein-to-lymphocyte ratio values were significantly higher in the non-remission than in the remission group. The baseline C-reactive protein-to-lymphocyte ratio value was identified as an independent prognostic factor for clinical remission at week 48 (odds ratio: 10, 95% confidence interval: 1.6-62.4, p = 0.014), with the cutoff value of 3.353 showing excellent prognostic performance (sensitivity: 71.4%, specificity: 83.3%). Furthermore, the clinical response at week 4 (odds ratio: 10, confidence interval: 1.78-56.1, p = 0.009) and that at week 8 (odds ratio: 12, confidence interval: 2.16-66.5, p = 0.005) were significantly associated with clinical remission at week 48., Conclusions: The baseline C-reactive protein-to-lymphocyte ratio value and early treatment response are useful biomarkers to predict the long-term efficacy of ustekinumab treatment., Competing Interests: Shiro Nakamura reports receiving speaking fees from AbbVie GK, EA Pharma Co., Ltd., Mitsubishi Tanabe Pharma Corporation., Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd, and Janssen Pharmaceutical K.K. Dr., (Copyright: © 2024 Koshiba et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To evaluate whether the neutrophil-to-lymphocyte ratio (NLR) can predict the need for ureteral catheterization in patients with renal colic. Materials and methods: We retrospectively studied 15,887 patients with renal colic between 2005 and 2019. Patients with prior antibiotics treatment (156), with hematological diseases (15), with negative computerized tomography scan (CTS) for stone disease (473) or with no available laboratory findings (1750) were excluded. A ureteral double J stent (DJS) was inserted in case of ongoing pain, fever, sepsis, single kidney and elevated blood creatinine levels concomitant with hydronephrosis. A cut-off value of 2.1 NLR was determined to stratify and to compare patients using multivariable logistic regression models. A locally weighted scatterplot smoothing (LOWESS) plot was also applied to show the relationship between NLR and predicted probability for DJS insertion. Results: Thirteen-thousand and 493 patients with a mean age of 42.7 years (30% females and 70% males) were included in the study. Five-hundred and 57 patients (4.1%) underwent early DJS insertion: 5.3% vs. 1.5% of patients with high vs. low NLR, respectively, (p<0.001). High NLR was significantly associated with longer hospitalization time, admission to the intensive care unit and overall mortality within a month from admission (p<0.05). LOWESS plot showed that NLR value >2.1 escalates progressively the probability for DJS insertion. Conclusions: A high NLR is associated with the need for early internal DJS insertion due to urolithiasis. The NLR is easily calculated from simple blood tests and based on our results can be used for clinical decision making in patients with renal colic needing renal decompression. [ABSTRACT FROM AUTHOR]

Introduction: Increased systemic oxidative stress is common in schizophrenia (SZ) patients. NADPH-oxidase 4 (NOX4) is the cell oxidoreductase, catalyzing the hydrogen peroxide formation. Presumably, NOX4 is the main oxidative stress factor in a number of diseases such as cardiovascular diseases and cancer. We hypothesized that NOX4 may be involved in the oxidative stress development caused by the disease in the schizophrenic patients' peripheral blood lymphocytes (PBL). Materials and methods: The SZ group included 100 patients (68 men and 32 women aged 28 ± 11 years). The control group included 60 volunteers (35 men and 25 women aged 25 ± 12 years). Flow cytometry analysis (FCA) was used for DNA damage markers (8-oxodG, ɣH2AX), pro- and antiapoptotic proteins (BAX1 and BCL2) and the master-regulator of anti-oxidant response NRF2 detection in the lymphocytes of the untreated SZ patients (N = 100) and the healthy control (HC, N = 60). FCA and RT-qPCR were used for NOX4 and RNANOX4 detection in the lymphocytes. RT-qPCR was used for mtDNA quantitation in peripheral blood mononuclear cells. Cell-free DNA concentration was determined in blood plasma fluorimetrically. Results: 8-oxodG, NOX4, and BCL2 levels in the PBL in the SZ group were higher than those in the HC group (p < 0.001). ɣH2AX protein level was increased in the subgroup with high 8-oxodG (p<0.02) levels and decreased in the subgroup with low 8-oxodG (p <0.0001) levels. A positive correlation was found between 8-oxodG, ɣH2AX and BAX1 levels in the SZ group (p <10−6). NOX4 level in lymphocytes did not depend on the DNA damage markers values and BAX1 and BCL2 proteins levels. In 15% of PBL of the HC group a small cellular subfraction was found (5–12% of the total lymphocyte pool) with high DNA damage level and elevated BAX1 protein level. The number of such cells was maximal in PBL samples with low NOX4 protein levels. Conclusion: Significant NOX4 gene expression was found a in SZ patients' lymphocytes, but the corresponding protein is probably not a cause of the DNA damage. [ABSTRACT FROM AUTHOR]

Background: Despite the guidelines provided by the World Health Organization for the treatment of malaria, treatment failure occurs in many hospitalized patients. Objective: Evaluate whether blood cell count parameters may serve as predictors for malaria treatment. Methodology: A cross-sectional study with a quantitative approach. Results: Of the 219 patients, 21.5% showed failure to antimalarial treatment, Patient with 21 and 40 years (72.6%), male (53.4%), from peri-urban area (47.5%), with high parasitemia (59.8%), treated with Arthemeter (90.9%) and the mortality were 5.9%. Significant associations were observed between occupation, level of parasitemia and outcome with resistance to antimalarial treatment (p<0.05). Patients with normal Hb [OR: 0.75 (95% CI: 0.39–1.44), p = 0.393], RBC [OR: 0.83 (95% CI: 0.40–1.72), p = 0.632], RDW [OR: 0.54 (95% CI: 0.27–1.09), p = 0.088], MCV [OR: 0.61 (95% CI: 0.28–1.31), p = 0.204] were less likely to have malaria treatment failures after artemisinin-based therapy failure. In contrast, those with normal values of segmented neutrophils [OR: 0.32 (95% CI: 0.11–0.96), p = 0.042] and lymphocyte counts [OR: 0.24 (95% CI: 0.05–1.04), p = 0.055]. We also found that patients with significant low levels of Hct [OR: 0.31 (95% CI: 0.15–0.64) p = 0.002], and high leukocytes [OR: 8.88 (95% CI: 2.02–37.2), p = 0.004] and normal platelet values [OR: 1.42 (95% CI: 0.73–2.95), p = 0.280] demonstrated high probability of treatment failure. Conclusion: The importance of blood cell count parameters in monitoring malaria therapy necessitates the urgent need to re-evaluate Artemether-based therapy. Future studies involving more participants in different settings are needed to provide further evidence. [ABSTRACT FROM AUTHOR]

Soluble B and T lymphocyte attenuator (sBTLA) has been shown to be associated with severity and outcome, in critically ill septic patients. We aimed to assess the dynamic expression of sBTLA, as a prognostic biomarker of long-term mortality in patients with bloodstream infection (BSI) and sepsis, and to evaluate its association with biomarkers indicative of inflammation and immune dysregulation. Secondarily, sBTLA was evaluated in association with severity and bacterial etiology. Patients with BSI (n = 108) were prospectively included, and serially sampled from admission to day 28. Blood and plasma donors (n = 31), sampled twice 28 days apart, served as controls. sBTLA concentration in plasma was determined with enzyme-linked immunosorbent assay. Associations between sBTLA on day 1–2 and 7, and mortality at 90 days and 1 year, were determined with unadjusted, and adjusted Cox regression. Differences related to severity was assessed with linear regression. Mixed model was used to assess sBTLA dynamics over time, and sBTLA associations with bacterial etiology and other biomarkers. sBTLA on day 1–2 and 7 was associated with mortality, in particular failure to normalize sBTLA by day 7 was associated with an increased risk of death before day 90, adjusted HR 17 (95% CI 1.8–160), and one year, adjusted HR 15 (95% CI 2.8–76). sBTLA was positively associated with CRP, and negatively with lymphocyte count. sBTLA on day 1–2 was not linearly associated with baseline SOFA score increase. High SOFA (≥4) was however associated with higher mean sBTLA than SOFA ≤3. sBTLA was not associated with bacterial etiology. We show that sustained elevation of sBTLA one week after hospital admission is associated with late mortality in patients with BSI and sepsis, and that sBTLA concentration is associated with CRP and decreased lymphocyte count. This suggests that sBTLA might be an indicator of sustained immune-dysregulation, and a prognostic tool in sepsis. [ABSTRACT FROM AUTHOR]

COVID-19 pandemic has posed a severe healthcare challenge calling for an integrated approach in determining the clues for early non-invasive diagnostics of the potentially severe cases and efficient patient stratification. Here we analyze the clinical, laboratory and CT scan characteristics associated with high risk of COVID-19-related death outcome in the cohort of severely-ill patients in Russia. The data obtained reveal that elevated dead lymphocyte counts, decreased early apoptotic lymphocytes, decreased CD14+/HLA-Dr+ monocytes, increased expression of JNK in PBMCs, elevated IL-17 and decreased PAI-1 serum levels are associated with a high risk of COVID-19-related mortality thus suggesting them to be new prognostic factors. This set of determinants could be used as early predictors of potentially severe course of COVID-19 for trials of prevention or timely treatment. [ABSTRACT FROM AUTHOR]

Background: The vast majority of COVID-19 cases both symptomatic and asymptomatic develop immunity after COVID-19 contagion. Whether lasting differences exist between infection and vaccination boosted immunity is yet to be known. The aim of this study was to determine how long total anti-SARS-CoV2 antibodies due to past infection persist in peripheral blood and whether sex, age or haematological features can influence their lasting. Material and methods: A series of 2421 donations either of SARS-CoV-2 convalescent plasma or whole blood from 1107 repeat donors from January 2020 to March 2021 was analysed. An automated chemiluminescence immunoassay for total antibodies recognizing the nucleocapsid protein of SARS-CoV-2 in human serum and plasma was performed. Sex, age, blood group, blood cell counts and percentages and immunoglobulin concentrations were extracted from electronic recordings. Blood donation is allowed after a minimum of one-month post symptom's relapse. Donors were 69.7% males and their average age was 46. The 250 donors who had later donations after a positive one underwent further analysis. Both qualitative (positivity) and quantitative (rise or decline of optical density regarding consecutive donations) outcomes were evaluated. Results and discussion: In 97.6% of donors with follow-up, anti-SARS-CoV-2 protein N total antibodies remained positive at the end of a follow-up period of 12.4 weeks median time (1–46, SD = 9.65) after the first positive determination. The blood group was not related to antibody waning. Lower lymphocyte counts and higher neutrophils would help predict future waning or decay of antibodies. Most recovered donors maintain their total anti-SARS-CoV-2 N protein antibodies for at least 16 weeks (at least one month must have been awaited from infection resolution to blood donation). The 10 individuals that could be followed up longer than 40 weeks (approximately 44 weeks after symptom's relapse) were all still positive. [ABSTRACT FROM AUTHOR]

Objective: Juvenile-onset systemic lupus erythematosus (JSLE) is a complex and heterogeneous immune-mediated disease. Cellular components have crucial roles in disease phenotypes and outcomes. We aimed to determine the associations of lymphocyte subsets with clinical manifestations and long-term outcomes in JSLE patients. Methods: A cohort of 60 JSLE patients provided blood samples during active disease, of whom 34 provided further samples during inactive disease. In a longitudinal study, blood samples were obtained from 49 of the JSLE patients at 0, 3, and 6 months. The healthy control (HC) group consisted of 42 age-matched children. Lymphocyte subsets were analyzed by flow cytometry. Results: The percentages of CD4+ T, γδ T, and NK cells were significantly decreased in JSLE patients compared with HC, while the percentages of CD8+ T, NKT, and CD19+ B cells were significantly increased. The percentage of regulatory T cells (Tregs) was significantly lower in JSLE patients with lupus nephritis (LN) than in non-LN JSLE patients and HC. The patients were stratified into high and low groups by the median frequency of each lymphocyte subset. The γδ T cells high group and NK cells high group were significantly related to mucosal ulcer. The CD4+ T cells high group was significantly associated with arthritis, and the NKT cells high group was substantially linked with autoimmune hemolytic anemia. The CD8+ T cells low group was mainly related to vasculitis, and the Tregs low group was significantly associated with LN. The percentage of Tregs was significantly increased at 6 months of follow-up, and the LN JSLE group had a lower Treg percentage than the non-LN JSLE group. Predictors of remission on therapy were high Tregs, high absolute lymphocyte count, direct Coombs test positivity, and LN absence at enrollment. Conclusion: JSLE patients exhibited altered lymphocyte subsets, which were strongly associated with clinical phenotypes and long-term outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Although patients with severe COVID-19 are known to be at high risk of developing thrombotic events, the effects of anticoagulation (AC) dose and duration on in-hospital mortality in critically ill patients remain poorly understood and controversial. The goal of this study was to investigate survival of critically ill COVID-19 patients who received prophylactic or therapeutic dose AC and analyze the mortality rate with respect to detailed demographic and clinical characteristics. Materials and methods: We conducted a retrospective, observational study of critically ill COVID-19 patients admitted to the ICU at Stony Brook University Hospital in New York who received either prophylactic (n = 158) or therapeutic dose AC (n = 153). Primary outcome was in-hospital death assessed by survival analysis and covariate-adjusted Cox proportional hazard model. Results: For the first 3 weeks of ICU stay, we observed similar survival curves for prophylactic and therapeutic AC groups. However, after 3 or more weeks of ICU stay, the therapeutic AC group, characterized by high incidence of acute kidney injury (AKI), had markedly higher death incidence rates with 8.6 deaths (95% CI = 6.2–11.9 deaths) per 1,000 person-days and about 5 times higher risk of death (adj. HR = 4.89, 95% CI = 1.71–14.0, p = 0.003) than the prophylactic group (2.4 deaths [95% CI = 0.9–6.3 deaths] per 1,000 person-days). Among therapeutic AC users with prolonged ICU admission, non-survivors were characterized by older males with depressed lymphocyte counts and cardiovascular disease. Conclusions: Our findings raise the possibility that prolonged use of high dose AC, independent of thrombotic events or clinical background, might be associated with higher risk of in-hospital mortality. Moreover, AKI, age, lymphocyte count, and cardiovascular disease may represent important risk factors that could help identify at-risk patients who require long-term hospitalization with therapeutic dose AC treatment. [ABSTRACT FROM AUTHOR]

Gene expression-based signatures help identify pathways relevant to diseases and treatments, but are challenging to construct when there is a diversity of disease mechanisms and treatments in patients with complex diseases. To overcome this challenge, we present a new application of an in silico gene expression deconvolution method, ISOpure-S1, and apply it to identify a common gene expression signature corresponding to response to treatment in 33 juvenile idiopathic arthritis (JIA) patients. Using pre- and post-treatment gene expression profiles only, we found a gene expression signature that significantly correlated with a reduction in the number of joints with active arthritis, a measure of clinical outcome (Spearman rho = 0.44, p = 0.040, Bonferroni correction). This signature may be associated with a decrease in T-cells, monocytes, neutrophils and platelets. The products of most differentially expressed genes include known biomarkers for JIA such as major histocompatibility complexes and interleukins, as well as novel biomarkers including α-defensins. This method is readily applicable to expression datasets of other complex diseases to uncover shared mechanistic patterns in heterogeneous samples.

The final step of triacylglycerol synthesis is catalyzed by acyl-CoA:diacylglycerol acyltransferases (DGATs). We have previously shown that ApoE-/-Dgat1-/- mice are protected from developing atherosclerosis in association with reduced foam cell formation. However, the role of DGAT1, specifically in myeloid and other hematopoietic cell types, in determining this protective phenotype is unknown. To address this question, we reconstituted the bone marrow of irradiated Ldlr-/-mice with that from wild-type (WT→ Ldlr-/-) and Dgat1-/-(Dgat1-/-→ Ldlr-/-) donor mice. We noted that DGAT1 in the hematopoietic compartment exerts a sex-specific effect on systemic cholesterol homeostasis. However, both male and female Dgat1-/-→ Ldlr-/-mice had higher circulating neutrophil and lower lymphocyte counts than control mice, suggestive of a classical inflammatory phenotype. Moreover, specifically examining the aortae of these mice revealed that Dgat1-/-→ Ldlr-/-mice have atherosclerotic plaques with increased macrophage content. This increase was coupled to a reduced plaque collagen content, leading to a reduced collagen-to-macrophage ratio. Together, these findings point to a difference in the inflammatory contribution to plaque composition between Dgat1-/-→ Ldlr-/-and control mice. By contrast, DGAT1 deficiency did not affect the transcriptional responses of cultured macrophages to lipoprotein treatment in vitro, suggesting that the alterations seen in the plaques of Dgat1-/-→ Ldlr-/-mice in vivo do not reflect a cell intrinsic effect of DGAT1 in macrophages. We conclude that although DGAT1 in the hematopoietic compartment does not impact the overall lipid content of atherosclerotic plaques, it exerts reciprocal effects on inflammation and fibrosis, two processes that control plaque vulnerability.

Background and objectives: At present, the focus of the fighting against COVID-19 in China is shifting to strictly prevent the entrance of cases from abroad and disease transmission. Therefore, it is extremely urgent to better understand the clinical features of imported cases from overseas countries, which is conductive to formulate the corresponding countermeasures. This study aimed to describe the clinical features of COVID-19 cases imported from Russia through the Suifenhe port, in order to identify baseline and clinical data associated with disease progression and present corresponding countermeasures. Methods: All COVID-19 cases imported from Russia through the Suifenhe port were included in this retrospective study. According to the "Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (seventh edition)", imported COVID-19 cases were divided into asymptomatic infection, mild, moderate, severe, and critical groups. Baseline and clinical data, including age, gender, comorbidities, disease severity, symptoms at onset, body temperature, white blood cell (WBC) count, lymphocyte (LYMPH) count, lymphocyte percentage (LYM%), C-reactive protein (CRP), oxygenation index (OI), and the use therapeutic modalities were obtained on admission, and then compared between groups. Results: A total of 375 COVID-19 cases imported from Russia through Suifenhe port were included, of whom the asymptomatic infection, mild, moderate, severe, and critical groups accounted for 4.0%, 13.9%, 75.5%, 5.3%, and 1.3%, respectively. The majority of the imported COVID-19 cases were men (61.9%) with a median age of 38.72 years who had no comorbidity (87.7%). Nearly one-third of them (33.1%) were asymptomatic at onset, and common initial symptoms included fever (36.5%), cough (36.0%), pharyngeal discomfort (12.3%), expectoration (8.0%), and chest tightness (5.3%). In total, 180 (48%) and 4 (1.1%) enrolled imported cases received nasal tube oxygen inhalation therapy and high-flow oxygen absorption, respectively; the remaining patients did not undergo oxygen therapy. The values of age, body temperature, WBC, LYMPH, LYM%, CRP, and OI were 38.72 ± 10.50, 35.10 ± 7.92, 5.59 ± 1.97, 1.67 ± 0.68, 31.05 ± 10.22, 8.00 ± 14.75, and 389.03 ± 74.07, respectively. Gender, age, LYMPH, LYM%, symptoms at onset, cough, fever, other rare symptoms, and oxygen therapy showed significant differences between groups (P = 0.036, < 0.001, < 0.001, < 0.001, < 0.001, < 0.001, < 0.001, = 0.045, < 0.001, respectively). Conclusions: Compared with domestic confirmed patients, COVID-19 patients who arrived at China from Russia through the Suifenhe port had significantly different clinical features, and the differences in gender, age, LYMPH, LYM%, symptoms at onset, cough, fever, other rare symptoms, and oxygen therapy between groups were statistically significant. Therefore, detailed and comprehensive countermeasures were developed to manage and prevent another outbreak based on these clinical features. [ABSTRACT FROM AUTHOR]

Background: Occupational welding fumes contain varieties of toxic metal particles and may affect cardiovascular system like the Particulate Matters (PM). Few studies have focused on the effects of toxic metals on the hemodynamic balance; however, the reporting results were not consistent. This study aimed to investigate the association between toxic metals exposure (Chromium (Cr), Manganese (Mn) and Lead (Pb)) and blood hemostatic parameters status after a 3-week exposure cessation among workers exposed to welding fumes. Methodology: Structured interviews and biological samplings were conducted for 86 male workers without a history of Anemia and Cardiovascular diseases (CVDs) and working in a confined space to construct crude oil tanks. Metal levels of Cr, Mn and Pb in urine were measured during the working days using Inductively Coupled Plasma Mass Spectrometer (ICP-MS) method. The concentrations of hemostatic proteins in blood (White blood cell counts (WBC), Lymphocytes, Monocyte, Eosinophil, Neutrophil, Hematocrit (Hct) were assessed after a 3 weeks exposure cessation. Workers were divided into groups based on occupation type (welder group and non-welder group), and based on metal levels (high and low exposure groups) for comparison. Linear regression models were used to explore the association between metal exposure and multiple blood hemostatic parameters adjusted for age, Body Mass Index (BMI), and smoking status. Results: Urine Mn and Cr level of the welder group was significantly higher than the non-welder group (Mn: 0.96 VS 0.22 ug/g creatinine, p < 0.001; Cr: 0.63 VS 0.22 ug/g creatinine, p < 0.01). The mean value of Hct in the welder group was 44.58 ± 2.84 vol%, significantly higher than the non-welder group (43.07 ± 3.31 vol%, p = 0.026). The median value of WBC in the high Mn-exposed group (6.93 ± 1.59 X 106 Cell/ml) was significantly lower than the low Mn-exposed group (7.90 ± 2.13 X 106 Cell/ml, p = 0.018). The linear regression analyses showed that there was a significantly negative association between log transformed WBC value and the Mn exposure groups (high and low) after adjusting for age, BMI, and smoking status (β = - 0.049, p = 0.045), but no significant result was found between WBC and occupation types (welder and non-welder) (p > 0.05). Multiple linear regression analysis also showed positive association between Hct and occupational types (welder and non-welders) (β = 0.014, p = 0.055). The other hemostatic parameters were not different from controls when divided by occupation type or metal level groups. Conclusions: Our results showed that welders were exposed to about 3 to 4 times higher Mn and Cr concentrations than non-welders. Moreover, one third of the non-welders were exposed to high-exposure groups of Mn and Cr metals. Regression models revealed a significant association of the WBC counts with the Mn exposure group. Therefore, we infer that Mn exposure may play a significant role on the blood hemostatic parameters of workers in the confined space. Hazard identification for non-welders should also be conducted in the confined space. [ABSTRACT FROM AUTHOR]

Several studies of patients with COVID-19 have evaluated biological markers for predicting outcomes, most of them retrospectively and with a wide scope of clinical severity. We followed a prospective cohort of patients admitted in hospital wards with moderate COVID-19 disease, including those with a history of kidney transplantation, and examined the ability of changes in routine hematologic laboratory parameters to predict and mirror the patients' clinical course regarding the severity of their condition (classified as critical vs. non-critical) and in-hospital mortality or hospital discharge. Among the 68 patients, 20 (29%) were kidney transplanted patients (KT), and they had much higher mortality than non-kidney transplanted patients in this cohort (40% X 8.3%). Lymphocytes, neutrophils and neutrophils/lymphocytes ratio (NLR) at admission and platelets as well as the red blood cells parameters hemoglobin, hematocrit, and RDW by the time of hospital discharge or death clearly differentiated patients progressing to critical disease and those with clinical recovery. Patients with deteriorating clinical courses presented elevated and similar NLRs during the first week of hospitalization. However, they were dramatically different at hospital discharge, with a decrease in the survivors (NLR around 5.5) and sustained elevation in non-survivors (NLR around 21). Platelets also could distinguish survivors from non-survivors among the critical patients. In conclusion, routine hematologic tests are useful to monitor the clinical course of COVID-19 patients admitted with moderate disease. Unexpectedly, changes in hematologic tests, including lymphopenia, were not predictive of complicated outcomes among KT recipients. [ABSTRACT FROM AUTHOR]

Background: Clinical observations have shown that there is a relationship between coronavirus disease 2019 (COVID-19) and atypical lymphocytes in the peripheral blood; however, knowledge about the time course of the changes in atypical lymphocytes and the association with the clinical course of COVID-19 is limited. Objective: Our purposes were to investigate the dynamics of atypical lymphocytes in COVID-19 patients and to estimate their clinical significance for diagnosis and monitoring disease course. Materials and methods: We retrospectively identified 98 inpatients in a general ward at Kashiwa Municipal Hospital from May 1st, 2020, to October 31st, 2020. We extracted data on patient demographics, symptoms, comorbidities, blood test results, radiographic findings, treatment after admission and clinical course. We compared clinical findings between patients with and without atypical lymphocytes, investigated the behavior of atypical lymphocytes throughout the clinical course of COVID-19, and determined the relationships among the development of pneumonia, the use of supplemental oxygen and the presence of atypical lymphocytes. Results: Patients with atypical lymphocytes had a significantly higher prevalence of pneumonia (80.4% vs. 42.6%, p < 0.0001) and the use of supplemental oxygen (25.5% vs. 4.3%, p = 0.0042). The median time to the appearance of atypical lymphocytes after disease onset was eight days, and atypical lymphocytes were observed in 16/98 (16.3%) patients at the first visit. Atypical lymphocytes appeared after the confirmation of lung infiltrates in 31/41 (75.6%) patients. Of the 13 oxygen-treated patients with atypical lymphocytes, approximately two-thirds had a stable or improved clinical course after the appearance of atypical lymphocytes. Conclusion: Atypical lymphocytes frequently appeared in the peripheral blood of COVID-19 patients one week after disease onset. Patients with atypical lymphocytes were more likely to have pneumonia and to need supplemental oxygen; however, two-thirds of them showed clinical improvement after the appearance of atypical lymphocytes. [ABSTRACT FROM AUTHOR]

Objective: Transcatheter aortic valve implantation (TAVI) provokes early injury response, represented in part by dynamic changes in the inflammatory markers. The association of self-expanding valves (SEVs) and balloon-expandable valves (BEVs) with the consequent inflammatory response remains uncertain. Materials and methods: Patients with severe symptomatic aortic stenosis who underwent transfemoral TAVI: SEVs or BEVs, from January 2010 to December 2019 were enrolled. Whole white blood cells (WBC) and subpopulation dynamics as well the neutrophil to lymphocyte ratio (NLR) were evaluated. Results: Three-hundred seventy consecutive patients (mean age 81.75 ± 6.8 years, 199 women's) were enrolled. In the entire population, significant kinetic changes in the WBC response (p <0.0001) between admission and first 24 hours post procedure, with a significant increase in total WBC (7.46 ± 2.26 to 10.08 ± 3.55) and absolute neutrophil count (4.97 ± 2.06 to 8.19 ± 3.43), NL ratio (3.72 ± 2.8 to 9.76 ± 7.29), and a meaningful decrease in absolute lymphocytes count (1.67 ± 1.1 to 1.1 ± 0.76). When compared between the types of valves, SEVs were associated with a more pronounced inflammatory response than BEVs, with total WBC (10.44 ± 3.86 vs. 9.45 ± 3.19) neutrophils (8.56 ± 3.75 vs. 7.55 ± 3.06) with p 0.016 and 0.012 respectively. Conclusion: This is the first description of a differential inflammatory response between the two leading delivery systems. SEV appears to trigger a more robust inflammatory response as compared to BEV. Clinical studies are warranted to assess the long term effect of our findings. [ABSTRACT FROM AUTHOR]

To determine whether preoperative white blood cell (WBC) counts reflect risk of anastomotic leak (AL) for patients with colorectal cancer (CRC), we retrospectively examined data from records of 208 consecutive patients who had undergone resections for left-sided CRC, including their clinicopathological parameters and preoperative laboratory data. The diagnostic value of WBC count for AL was evaluated and compared with those of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, lymphocyte-monocyte ratio and platelet count × C-reactive protein level multiplier (P-CRP) value; optimal cut-off values were derived from receiver operating characteristic curves. AL was observed in 11 of the 208 patients (5.3%). Compared with the no-AL group, the AL group had a significantly higher mean WBC count and smoking rate. In multivariate analysis, WBC count and smoking were independent risk factors for AL. Compared with the other tested inflammatory indicators, the cut-off value for WBC (6,200/μL) had the highest sensitivity (81.8%) and negative predictive value (98.4%), as well as the lowest likelihood ratio (0.289). Preoperative WBC count could therefore be a convenient predictor of AL in patients with left-sided CRC. [ABSTRACT FROM AUTHOR]

Dialysis patients are both the most likely to benefit from vaccine protection against SARS-CoV-2 and at the highest risk of not developing an immune response. Data from the medical field are thus mandatory. We report our experience with a BNT162b2-mRNA vaccine in a retrospective analysis of 241 dialysis patients including 193 who underwent anti-Spike-Protein-Receptor-Binding-Domain (RBD) IgG analysis. We show that a pro-active vaccine campaign is effective in convincing most patients to be vaccinated (95%) and frequently elicits a specific antibody response (94.3% after two doses and 98.4% after three doses). Only immunocompromised Status is associated with lack of seroconversion (OR 7.6 [1.5–38.2], p = 0.02). We also identify factors associated with low response (last quartile; IgG<500AU/mL): immunocompromised status, age, absence of RAAS inhibitors, low lymphocytes count, high C Reactive Protein; and with high response (high quartile; IgG>7000AU/mL): age; previous SARS-CoV-2 infection and active Cancer. From this experience, we propose a strategy integrating anti-spike IgG monitoring to guide revaccination and dialysis center management in pandemic times. [ABSTRACT FROM AUTHOR]

Background: The Neutrophil-to-Lymphocyte Ratio (NLR) is a clinical indicator of peripheral inflammation that is easily accessible. It is worth noting that the formation of amyloid-β (Aβ) plaques and neurofibrillary tangles has been linked to inflammation and immune dysregulation. The main objective of this systematic review and meta-analysis is to comprehensively evaluate the existing body of research concerning the NLR in the context of Alzheimer's disease (AD) and mild cognitive impairment (MCI)., Method: We conducted a comprehensive online search and included studies that evaluated the NLR in 1) patients with AD or MCI and 2) healthy control (HC) participants. We also pooled mean and standard deviation (SD) data for each group., Results: Ultimately, 12 studies encompassed 1,309 individuals diagnosed with AD with mean NLR levels of 2.68, 1,929 individuals with MCI with mean NLR levels of 2.42, and 2,064 HC with mean NLR levels of 2.06 were included in this systematic review and meta-analysis. The mean NLR was 0.59 higher in AD patients compared to HC participants (mean difference (MD) = 0.59 [0.38; 0.80]). Similarly, the mean NLR was higher in AD than MCI patients (MD = 0.23 [0.13; 0.33]). Additionally, the mean NLR was higher in individuals with MCI compared to HC participants (MD = 0.37 [0.22; 0.52]). In the subgroup meta-analysis based on the Mini-Mental State Examination (MMSE), AD patients with lower MMSE scores (using a cut-off of 20) exhibited significantly higher mean NLR (3.10 vs. 2.70, with a p-value for subgroup differences < 0.01)., Conclusion: The NLR, which serves as a marker of peripheral inflammation, shows increased levels in individuals with AD and MCI compared to HC participants. Furthermore, our study indicates that NLR levels are significantly higher in AD than MCI. Additionally, our novel finding suggests significantly higher NLR levels among AD patients with more severe cognitive decline compared to AD patients with less severe cognitive decline. So, it can be concluded that the higher cognitive decline in humans is accompanied by higher NLR levels. Further longitudinal researches are needed to explore more details about the relationship between inflammation and dementia., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mohammadi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)