Reduction In Lymphocyte Count Research Articles

Association of clinical and imaging characteristics with pulmonary function testing in patients with Long-COVID

PurposeThe purpose of this study is to identify clinical and imaging characteristics associated with post-COVID pulmonary function decline. MethodsThis study included 22 patients recovering from COVID-19 who underwent serial spirometry pulmonary function testing (PFT) before and after diagnosis. Patients were divided into two cohorts by difference between baseline and post-COVID follow-up PFT: Decline group (>10 % decrease in FEV1), and Stable group (≤10 % decrease or improvement in FEV1). Demographic, clinical, and laboratory data were collected, as well as PFT and chest computed tomography (CT) at the time of COVID diagnosis and follow-up. CTs were semi-quantitatively scored on a five-point severity scale for disease extent in each lobe by two radiologists. Mann-Whitney U-tests, T-tests, and Chi-Squared tests were used for comparison. P-values <0.05 were considered statistically significant. ResultsThe Decline group had a higher proportion of neutrophils (79.47 ± 4.83 % vs. 65.45 ± 10.22 %; p = 0.003), a higher absolute neutrophil count (5.73 ± 2.68 × 109/L vs. 3.43 ± 1.74 × 109/L; p = 0.031), and a lower proportion of lymphocytes (9.90 ± 4.20 % vs. 21.21 ± 10.97 %; p = 0.018) compared to the Stable group. The Decline group also had significantly higher involvement of ground-glass opacities (GGO) on follow-up chest CT [8.50 (4.50, 14.50) vs. 3.0 (1.50, 9.50); p = 0.032] and significantly higher extent of reticulations on chest CT at time of COVID diagnosis [6.50 (4.00, 9.00) vs. 2.00 (0.00, 6.00); p = 0.039] and follow-up [5.00 (3.00, 13.00) vs. 2.00 (0.00, 5.00); p = 0.041]. ICU admission was higher in the Decline group than in the Stable group (71.4 % vs. 13.3 %; p = 0.014). ConclusionsThis study provides novel insight into factors influencing post-COVID lung function, irrespective of pre-existing pulmonary conditions. Our findings underscore the significance of neutrophil counts, reduced lymphocyte counts, pulmonary reticulation on chest CT at diagnosis, and extent of GGOs on follow-up chest CT as potential indicators of decreased post-COVID lung function. This knowledge may guide prediction and further understanding of long-term sequelae of COVID-19 infection.

Clinical characteristics and risk factors for bacterial co-infections in COVID-19 patients: A retrospective study

ObjectiveThis study aimed to analyze the bacterial composition, distribution, drug sensitivity, and clinical characteristics of COVID-19 patients who develop bacterial co-infections. MethodsWe conducted a retrospective study of 184 COVID-19 patients admitted between December 2022 and January 2023. Data on gender, age, length of hospital stay, pneumonia classification, underlying diseases, invasive surgery, hormone therapy, inflammation indicators, and other relevant information were collected. Samples of sputum, bronchoscopy sputum, alveolar lavage fluid, middle urine, puncture fluid, wound secretions, and blood were collected for pathogen isolation, identification, and drug sensitivity testing. ResultsThe majority of COVID-19 patients with bacterial co-infection were elderly and had underlying diseases. Invasive surgery and hormone therapy were identified as risk factors for co-infections. Laboratory analysis showed reduced lymphocyte count and elevated levels of CRP and PCT. The most common pathogens in co-infections were S. aureus, E. coli, K. pneumoniae, A. baumannii, and P. aeruginosa. The detection rate of drug-resistant strains, including MRSA, CRKP, CRAB, CRPA, and CRECO, increased with the severity of pneumonia. ConclusionRespiratory tract infections were the most common site of bacterial co-infection in COVID-19 patients. Severe cases were more susceptible to multidrug-resistant pathogens, leading to a higher mortality rate. Timely control and prevention of co-infection are crucial for improving the prognosis of COVID-19 patients.

Narrative Review on the Use of Cladribine Tablets as Exit Therapy for Stable Elderly Patients with Multiple Sclerosis.

The number of ageing people with relapsing multiple sclerosis (RMS) is increasing. The efficacy of disease-modifying therapies (DMTs) for RMS declines with age. Also, older persons with MS may be more susceptible to infections, hospitalisations and malignancy. Aging people with MS have higher rates of comorbidities versus aged-matched controls, increasing the individual risk of disability. We review the therapeutic properties of cladribine tablets (CladT) in ageing people with RMS, with regard to their utility for allowing these individuals to cease continuous administration of a DMT (i.e. to act as an "exit therapy"). CladT is thought to be an immune reconstitution therapy, in that two short courses of oral treatment 1year apart provide suppression of MS disease activity in responders that far outlasts the duration of treatment and post-treatment reductions in lymphocyte counts. Post hoc analyses, long-term follow-up of populations with RMS in randomised trials, and real-world evidence suggest that the efficacy of CladT is probably independent of age, although more data in the elderly are still needed. No clear adverse signals for lymphopenia or other adverse safety signals have emerged with increasing age, although immunosenescence in the setting of age-related "inflammaging" may predispose elderly patients to a higher risk of infections. Updating vaccination status is recommended, especially against pneumococci and herpes zoster for older patients, to minimise the risk of these infections. CladT may be a useful alternative treatment for ageing people with MS who often bear a burden of multiple comorbidities and polypharmacy and who are more exposed to the adverse effects of continuous immunosuppressive therapy.

Factors Associated with Mortality Among Severe Omicron Patients for COVID-19.

The purpose of the study was to explore the potential risk factors of mortality in patients with severe pneumonia during the omicron pandemic in South China in 2022. Clinical data was collected from patients hospitalized with omicron COVID-19. Then, patients were categorized into the non-survival and survival groups. A comprehensive analysis was conducted to analyze the factors associated with negative outcome in individuals suffering from severe omicron COVID-19. In this study, 155 severe COVID-19 patients were included, comprising 55 non-survivors and 100 survivors. Non-survivors, in comparison to survivors, exhibited elevated levels of various biomarkers including neutrophil count, hypersensitive troponin T, urea, creatinine, C-reactive protein, procalcitonin, interleukin-6, plasma D-dimer, and derived neutrophil-to-lymphocyte ratio (dNLR) (P < 0.05). They also displayed reduced lymphocyte count, platelet count, and albumin levels (P < 0.05) and were more prone to developing comorbidities, including shock, acute cardiac and renal injury, acute respiratory distress syndrome, coagulation disorders, and secondary infections. Platelet count (PLT) <100 × 10^/L, interleukin-6 (IL-6) >100 pg/mL, and dNLR >5.0 independently contributed to the risk of death in patients suffering from severe COVID-19. PLT, IL-6, and dNRL independently contributed to the risk of mortality in patients with severe pneumonia during the 2022 omicron pandemic in South China.

The characteristic and prognostic role of blood inflammatory markers in patients with Huntington's disease from China.

This study aims to elucidate the role of peripheral inflammation in Huntington's disease (HD) by examining the correlation of peripheral inflammatory markers with clinical manifestations and disease prognosis. This investigation involved 92 HD patients and 92 matched healthy controls (HCs). We quantified various peripheral inflammatory markers and calculated their derived metrics including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII). Clinical assessments spanning cognitive, motor, and disease severity were administered. Comparative analysis of inflammatory markers and clinical correlations between HD and controls was performed. Kaplan-Meier survival analysis and Cox regression model were used to assess the effect of inflammatory markers on survival. The study revealed that HD patients had significantly reduced lymphocyte counts, and LMR. Conversely, NLR, PLR, and SII were elevated compared to HCs. Lymphocyte levels inversely correlated with the age of onset and monocyte levels inversely correlated with the UHDRS-total functional capacity (TFC) scores. After adjusting for age, sex, and CAG repeat length, lymphocyte count, NLR, PLR, and SII were significantly correlated with the progression rate of TFC scores. Elevated levels of white blood cells and monocytes were associated with an increased risk of disability and mortality in the HD cohort. Our findings indicate that HD patients display a distinct peripheral inflammatory profile with increased NLR, PLR, and SII levels compared to HCs. The peripheral inflammation appears to be linked with accelerated disease progression and decreased survival in HD.

Reliability of Droplet Digital PCR Alone and in Combination with Interleukin-6 and Procalcitonin for Prognosis of Bloodstream Infection.

Bloodstream infection(BSI) is linked with high mortality, underscoring the significance of prompt etiological diagnosis for timely and precise treatment. This study aims to investigate the diagnostic value of droplet digital polymerase chain reaction(ddPCR) in combination with conventional inflammatory markers [interleukin-6(IL-6) and procalcitonin(PCT)] concerning disease progression and treatment prognosis in BSI patients. Furthermore, the study aims to explore a more efficient clinical application strategy. This prospective case seried study centers on 176 patients suspected of or confirmed with BSI. Blood samples were collected to extract nucleic acids for identifying pathogens (bacteria, fungi, and viruses) and determining copy loads via ddPCR. The sensitivity of ddPCR was markedly higher compared to the culture method (74.71% vs 31.03%). A positive correlation existed between bacterial load and levels of inflammatory markers [IL-6 (P=0.0182), PCT (P=0.0029), and CRP (P=0.0005)]. In suspected BSI cases, the combination of ddPCR and inflammatory markers could predict sepsis risk [ROC: Area under the curve(AUC)=0.6071, P=0.0383]. Within confirmed BSI patients, the ddPCR bacterial load of those with SOFA<7 was lower than that of the SOFA≥7 (P=0.0334). ddPCR (OR: 1.789, P=0.035) monitoring combined with PCT (OR: 1.787, P=0.035) holded predictive value for SOFA progression (AUC=0.7913, P=0.0003). Similarly, BSI survivors displayed a lower burden than non-survivors (P=0.0170). Additionally, ddPCR combinated with IL-6 provided a more accurate and expedited insight into clinical outcomes prediction for BSI confirmed patients (AUC=0.7352, P=0.0030). Serial monitoring of bacterial load by ddPCR effectively mirrored the clinical course of BSI in patients. Notably, patients with positive ddPCR virus infection exhibited significantly reduced lymphocyte counts (P=0.0003). In a clinical context, qualitative ddPCR results and quantitative continuous monitoring can more precisely assess sepsis progression and treatment prognosis in BSI patients. Furthermore, ddPCR results offer quicker and more accurate reference points for clinical antibacterial and antiviral interventions.

Infection of domestic pigs with a genotype II potent strain of ASFV causes cytokine storm and lymphocyte mass reduction.

The whole-genome sequence of an African swine fever virus (ASFV) strain (HuB/HH/2019) isolated from Hubei, China, was highly similar to that of the Georgia 2007/1 strain ASFV. After infection with strong strains, domestic pigs show typical symptoms of infection, including fever, depression, reddening of the skin, hemorrhagic swelling of various tissues, and dysfunction. The earliest detoxification occurred in pharyngeal swabs at 4 days post-infection. The viral load in the blood was extremely high, and ASFV was detected in multiple tissues, with the highest viral loads in the spleen and lungs. An imbalance between pro- and anti-inflammatory factors in the serum leads to an excessive inflammatory response in the body. Immune factor expression is suppressed without effectively eliciting an immune defense. Antibodies against p30 were not detected in acutely dead domestic pigs. Sequencing of the peripheral blood mononuclear cell transcriptome revealed elevated transcription of genes associated with immunity, defense, and stress. The massive reduction in lymphocyte counts in the blood collapses the body's immune system. An excessive inflammatory response with a massive reduction in the lymphocyte count may be an important cause of mortality in domestic pigs. These two reasons have inspired researchers to reduce excessive inflammatory responses and stimulate effective immune responses for future vaccine development.

Expression of proBDNF/p75NTR in peripheral blood lymphocytes of patients with sepsis and its impact on lymphocyte differentiation.

Sepsis is a life-threatening organ dysfunction caused by the host's imbalanced response to infection. Due to lack of effective treatments, it has always been the difficulty and focus of clinical treatment of sepsis. Studies have shown that pro-brain-derived neurotrophic factor (proBDNF) binds to the high-affinity total neurotrophic factor p75 neurotrophin receptor (p75NTR), which activates downstream signaling cascades and disrupts immunological inflammation and plays an important role in the progression of sepsis. This study aims to explore the expression changes of lymphocyte-derived proBDNF/p75NTR in patients with sepsis and its effect on lymphocyte differentiation. From the healthy donors (control group, n=40) and sepsis patients (sepsis group, n=40) admitted to the hospital for the first time, peripheral blood samples and blood routine clinical detection indicators were obtained. By using flow cytometry, the proportion of lymphocyte subsets and their expression of proBDNF/p75NTR were examined. The peripheral blood lymphocytes were isolated from the control group and incubated with lipopolysaccharide (LPS). Flow cytometry analysis technology was used to detect the expression of proBDNF/p75NTR on LPS-treated lymphocyte subsets. On this basis, we investigated the effects on lymphocyte differentiation by inhibiting p75NTR. White blood cell count, neutrophil count, and neutrophil percentage of the patients in the sepsis group at admission were significantly higher than those in the control group; on the contrary, lymphocyte count and lymphocyte percentage in the sepsis group were lower than those in the control group (all P<0.001). The patients in the sepsis group had considerably greater neutrophil/lymphocyte and monocyte/lymphocyte ratios than those in the control group (both P<0.05). In the peripheral blood of sepsis patients, proBDNF expression was upregulated on CD19+ B cells, whereas p75NTR expression was elevated on B cells, CD4+ T cells, and CD8+ T cells (all P<0.05). ProBDNF/p75NTR expression was upregulated by LPS stimulation in vitro in peripheral blood cells of the control group (P<0.05), and this tendency was similar to the expression alterations in peripheral lymphocytes of the sepsis group. Inhibition of p75NTR increased CD4+ T cell and CD19+ B cell percentages, cytokine expression of IL-4 and IL-10, and reduced IL-1β and IL-6 production (all P<0.05). The immunosuppressive state of sepsis patients is indicated by a reduction in lymphocyte count and an increase in the proportion of inactive neutrophils. ProBDNF/p75NTR expression is upregulated in the peripheral blood lymphocytes of sepsis patients, and p75NTR inhibition may control lymphocyte differentiation involved in sepsis progression.

Epidemiological, Clinical, and Laboratory Findings of 235 Hospitalized COVID-19 Adult Patients (Survivors and Non-Survivors) at Sohar Hospital in Oman.

The aim of this study was to describe the epidemiological and clinical characteristics and laboratory findings of coronavirus disease 2019 (COVID-19) patients at the Sohar Hospital, Sohar, Oman. This retrospective study of admitted COVID-19 patients at Sohar Hospital in Oman was carried out from March to October 2020. Demographics and laboratory data of 19 tests for 235 COVID-19 patients, of which 202 were survivors and 33 were non-survivors, were collected from the hospital information system after ethics approval. Thirteen factors were significantly correlated with in-hospital mortality, including older age, having chronic disease, high neutrophil count, high troponin T, high creatinine, low albumin (p < 0.0001), high white blood cell (WBC) count, low hemoglobin, high D-dimer (p < 0.001), high C-reactive protein (CRP) (p < 0.002), low lymphocyte count (p < 0.003), high alkaline phosphatase (ALP) enzyme (p < 0.007) and high ferritin (p < 0.045). The most common laboratory blood test abnormalities that were highly correlated with mortality were increased values of CRP (100% of non-survivors), D-dimer (94.1% of non-survivors), ferritin (88.2% of non-survivors), and troponin T (85% of non-survivors) and reduced lymphocyte count (73.9% of non-survivors). These findings could help in categorizing COVID-19 patients for risk-based assessment and early identification of patients with poor prognosis.

Camrelizumab (a PD-1 inhibitor) plus apatinib (an VEGFR-2 inhibitor) and hepatic artery infusion chemotherapy for hepatocellular carcinoma in Barcelona Clinic Liver Cancer stage C (TRIPLET): a phase II study

Hepatic arterial infusion chemotherapy (HAIC) using a combination of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) has shown promise for hepatocellular carcinoma (HCC) patients classified under Barcelona Clinic Liver Cancer (BCLC) stage C. In China, the combined therapy of camrelizumab and apatinib is now an approved first-line approach for inoperable HCC. This study (NCT04191889) evaluated the benefit of combining camrelizumab and apatinib with HAIC-FOLFOX for HCC patients in BCLC stage C. Eligible patients were given a maximum of six cycles of HAIC-FOLFOX, along with camrelizumab and apatinib, until either disease progression or intolerable toxicities emerged. The primary outcome measured was the objective response rate (ORR) based on the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Thirty-five patients were enrolled. Based on RECIST v1.1 criteria, the confirmed ORR stood at 77.1% (95% CI: 59.9% to 89.6%), with a disease control rate of 97.1% (95% CI: 85.1% to 99.9%). The median progression-free survival was 10.38 months (95% CI: 7.79 to 12.45). Patient quality of life had a transient deterioration within four cycles of treatment, and generally recovered thereafter. The most frequent grade ≥3 or above treatment-related adverse events included reduced lymphocyte count (37.1%) and diminished neutrophil count (34.3%). The combination of camrelizumab, apatinib, and HAIC demonstrated encouraging results and manageable safety concerns for HCC at BCLC stage C.

Interpretable Deep Learning Identified the Significance of 1 Gy Volume on Lymphopenia after Radiotherapy in Breast Cancer

Lymphopenia is common after radiotherapy (RT) and is known for its significance on poor survival outcomes in patients with breast cancer. Previous work has demonstrated the significance of point dosimetric factors like the volume receiving 5 Gy. Considering the full dosimetric data together, this study aimed to develop and validate predictive models for lymphopenia after RT in breast cancer. Patients with breast cancer treated with radiation therapy in adjuvant setting and with complete dosimetric data were eligible. Combining dose-volume histogram (DVH) dosimetric and clinical factors, dense neural network (DNN) models were developed to predict both the reduction in lymphocyte counts and the graded lymphopenia in breast cancer patients after adjuvant RT. A Shapley additive explanation was applied to explain each feature's directional contributions. The generalization of DNN models was validated in both internal and independent external validation cohorts. P<0.05 was considered to be significant. A total of 928 consecutive patients with invasive breast cancer were eligible for this study. Treatment volumes of nearly all irradiation dose levels of DVH were significant predictors for lymphopenia after RT, including volumes at very low-dose 1 Gy (V1) of all structures considered including the lung, heart and body. DNN models using full DVH dosimetric and clinical factors were built and a simplified model was further established and validated in both internal and external validation cohorts. This simplified DNN AI model, combining full DVH dosimetric parameters of all OARs and five key clinical factors including baseline lymphocyte counts, tumor stage, RT technique, RT fields and RT fractionation, showed a predictive accuracy of 77% and above. This study demonstrated and externally validated the significance of an AI model of combining clinical and full dosimetric data, especially the volume of low dose at as low as 1 Gy of all critical structures on lymphopenia after RT in patients with breast cancer. The significance of V1 deserves special attention, as modern arc RT technology often has relatively high value of this parameter. Further study warranted for breast cancer RT plan optimization.

4G mobile phone radiation alters some immunogenic and vascular gene expressions, and gross and microscopic and biochemical parameters in the chick embryo model.

The risks to human health have grown over the past 10 years due to the excessive use of mobile phones. The study was designed to determine the harmful effects of 4G mobile phone radiation on the expression of immunogenic and vascular genes and gross, microscopic and biochemical alterations in the development of chicken embryos. Sixty individuals in the exposure group were subjected to mobile phones with a specific absorption rate of 1.4W/kg and a frequency of 2100MHz positioned at a distance of 12cm in the incubator for 60min/night for 14 days. The histopathological examination involved hematoxylin and eosin staining, whereas cresyl violet staining was used to evaluate the condition and number of neurons in the brain. The biochemical parameters of amniotic fluid were analysed using the photometry method, and the expression of VEGF-A and immunity genes (AvBD9, IL6) was measured using the real-time PCR (qPCR) technique. Compared to the control, the exposure group's body weight and length significantly decreased (p<0.05). Subcutaneous bleeding was seen in the exposure group. Urea, creatinine, alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase levels were all significantly higher than in the control group (p<0.05). The exposed group showed pathological lesions in the liver and degenerated neurons with lightly stained nuclei in the cerebral cortex. Hyperchromatic neurons were significantly higher in the exposure group (58.8±2.28) compared to the control (6.6±0.44) (p<0.05). 4G exposure reduced lymphocyte count in the caecal tonsil (86.8±5.38) compared to the control (147.2±9.06) (p<0.05). Vascular gene mRNA expression was higher, but immune gene expression was lower in the exposed group. Exposure to mobile phone radiation may result in gross, microscopic and biochemical changes, as well as alterations in gene expression that could hinder embryonic development.

Application of clinical and CT imaging features in the evaluation of disease progression in patients with COVID-19

BackgroundThe Corona Virus Disease 2019(COVID-19) pandemic has strained healthcare systems worldwide, necessitating the early prediction of patients requiring critical care. This study aimed to analyze the laboratory examination indicators, CT features, and prognostic risk factors in COVID-19 patients.MethodsA retrospective study was conducted on 90 COVID-19 patients at the First Affiliated Hospital of Gannan Medical University between December 17, 2022, and March 17, 2023. Clinical data, laboratory examination results, and computed tomography (CT) imaging data were collected. Logistic multivariate regression analysis was performed to identify independent risk factors, and the predictive ability of each risk factor was assessed using the area under the receiver operating characteristic (ROC) curve.ResultsMultivariate logistic regression analysis revealed that comorbid diabetes (odds ratio [OR] = 526.875, 95%CI = 1.384-1960.84, P = 0.053), lymphocyte count reduction (OR = 8.773, 95%CI = 1.432–53.584, P = 0.064), elevated D-dimer level (OR = 362.426, 95%CI = 1.228-984.995, P = 0.023), and involvement of five lung lobes (OR = 0.926, 95%CI = 0.026–0.686, P = 0.025) were risk factors for progression to severe COVID-19. ROC curve analysis showed the highest predictive value for 5 lung lobes (AUC = 0.782). Oxygen saturation was positively correlated with normally aerated lung volume and the proportion of normally aerated lung volume (P < 0.05).ConclusionsThe study demonstrated that comorbid diabetes, lymphocyte count reduction, elevated D-dimer levels, and involvement of the five lung lobes are significant risk factors for severe COVID-19. In CT lung volume quantification, normal aerated lung volume and the proportion of normal aerated lung volume correlated with blood oxygen saturation.

Effects of COVID-19 and vaccination on the human immune system: cases of lymphopenia and autoimmunity

Effects of COVID-19 and vaccination on the human immune system: cases of lymphopenia and autoimmunity

#3974 EFFECTIVE PREDICTION OF NEED FOR CHRONIC DIALYSIS IN CHILDREN, BASED ON RANDOM FORREST ALGORITHMS USING BLOOD CELL COUNT-DRIVEN PARAMETERS

Abstract Background and Aims Persistent, low-grade inflammation is a significant component of chronic kidney disease (CKD) that plays a pivotal role in its pathophysiology, progression, complications, and all-cause mortality. Previous studies have searched for simple, cost-effective, and universally available markers useful in the systemic inflammation assessment in CKD patients. In the adult population, an increase in neutrophil count, correlated with a reduction in lymphocyte count, indicates the rate of progression to dialysis and predicts mortality in hemodialysis and peritoneal dialysis patients. Due to modulating role of platelets within the inflammatory pathways, a mean platelet volume (MPV) and platelet-to-lymphocyte ratio have also been proposed as markers of inflammation. The systemic immune inflammation index (SII) is a newly defined ratio combining neutrophil, lymphocyte, and platelet counts. It is proposed as a prognostic indicator comprehensively reflecting patients' inflammatory and immune status. Recently, elevated SII has shown a predictive value for mortality risk among CKD adult patients. SII has not been evaluated in the pediatric CKD population so far. Thus, the study aimed to analyze complete blood cell count (CBC) driven parameters, including SII, in children with CKD and to assess their potential usefulness in the prediction of the need for chronic replacement therapy with the use of artificial intelligence tools. Method The study group consisted of 27 predialysis children with CKD stages 4-5 (stage 4 - 11 patients, stage 15 - 16 children) and 40 patients on chronic dialysis (HD - 21 children, APD - 19 patients). The patients’ age ranged from 5 to 18 years, children under 5 were excluded due to the different CBC profile regarding neutrophil – lymphocyte proportions. The evaluated CBC parameters were: hemoglobin, hematocrit, leukocyte, neutrophil, monocyte, lymphocyte, platelet counts and MPV. Kidney function, standard biochemical parameters, CRP and SII were also analyzed. This database was used for further analysis. The recursively selected subsets of input variables constituted the input of random forrest classifier (RFC). Each variant has been optimized, taking into account various features (accuracy, AUROC, precision, recall, MCC), then the best model was saved. The aim was to narrow the set of input parameters so that high predictive power is secured, whereas overfitting or overcomplicating could be avoided. Moreover, the GINI importance was measured in order to define the parameter with the largest share in the prediction. Results The best Random Forest Classifier contained neutrophil count, MPV, and SII as input variables, and achieved the following values: AUROC 0.9286, accuracy 93.75%, precision 0.9437, recall 0.9375 and MCC 0.87. The statistics for each class were as follows: precision 0.90, recall 1.00 and f1-score 0.95 for children with CKD 4-5 on conservative treatment; precision 1.0, recall 0.86, and f1-score 0.92 for patients on chronic dialysis. The values of mean GINI importance measured for 40 random splits of the base for MPV, neutrophil count and SII, were 0.28, 0.32 and 0.39, respectively. Conclusion RFC built up with the input variables of neutrophil count, MPV, and SII, was the best predictor of progression into pediatric end stage kidney disease requiring chronic dialysis. SII turned out the most important parameter in the created model, having the largest share in the prediction of need for renal replacement therapy.

Hematological Changes in Patients with Severe COVID-19: Systematic Review and Meta-Analysis

Aims: To produce a systematic review with meta-analysis on the hematological manifestations of COVID-19, comparing the changes among the clinical severity groups.&#x0D; Study Design: We conducted a systematic review with meta-analyses.&#x0D; Methodology: A systematic review was carried out based on the PRISMA 2020 protocol in Medline/Pubmed, Embase, LILACS and SciElo databases. A standardized mean difference was calculated to assess the differences between the groups, with a confidence interval of 95%. Heterogeneity was calculated using the Chi-square test and the I2 test. Significant heterogeneity was defined as p&lt;0.10 or I2&gt;50%.&#x0D; Results: The systematic review search identified a total of 2682 articles, and at the end of the screening, 55 were selected for review and 16 for meta-analysis. The selected articles enrolled 13,289 participants, 10,312 with a mild to moderate clinical condition and 3977 with a severe to critical clinical condition. When comparing the severe disease group with the mild disease group, it was found that the mean values of leukocytes, neutrophils, C-reactive protein (CRP), ferritin, fibrinogen, and prothrombin time (PT) were significantly higher, and the lymphocyte count was significantly lower in the severe group.&#x0D; Conclusions: Individuals with severe COVID-19 had reduced lymphocyte count and elevated leukocytes, neutrophils, CRP, ferritin, fibrinogen, and PT.

Jatropha tanjorensis Euphorbiaceae Ethanolic Leaves Extract Reverses Phenylhydrazine Induced Haematological Alterations in Albino Wistar Rats

Introduction: Phenylhydrazine has been used in many studies to evaluate its modulatory effects in various biochemical parameters in whole blood and red blood cell lysate. Jatropha tanjorensis Euphorbiaceae have high antioxidants properties; its leaves phytochemical analysis shows the presence of flavonoids, tanins, terpenoids, saponis. This study investigated the ameliorative effects of Jatropha tanjorensis Euphorbiaceae on phenylhydrazine induced haematological alterations in albino Wistar rats. &#x0D; Materials and Methods: Wistar rats of both sexes (180-200g) were divided into 4 groups (n=5). Group 1 received rat chow; Group 2 received (200 mg/kg) of J. tanjorensis orally. Group 3 received phenylhydrazine only (10 mg/kg). Group 4 received phenylhydrazine (10 mg/kg) + J. tanjorensis (250 mg/kg). All animals were allowed free access to clean drinking water and normal rat chow ad libitum for 35 days. After which animals were sacrificed and blood samples collected for biochemical analysis.&#x0D; Results: Results obtained showed that phenylhydrazine induced normochromic anemia with significant increase in white blood cell count, and neutrophil counts, eosinophils (insignificant) count with a significant reduction in lymphocyte count. However, J. tanjorensis extract reversed the adverse haematological changes induced by phenylhydrazine.&#x0D; Conclusion: In conclusion, Jatropha tanjorensis Euphorbiaceae demonstrated antioxidant, anti-inflammatory, and anti-thrombotic effects and reversed the haematological alterations brought upon by phenylhydrazine administration.

Nomogram Based on Preoperative Absolute Lymphocyte Count to Predict Local Recurrence in Patients with Non-Small Cell Lung Cancer After Microwave Ablation.

This study aims to investigate the prognostic value of preoperative absolute lymphocyte count (preALC) for non-small cell lung cancer (NSCLC) after microwave ablation (MWA) and build a combined nomograph with clinical features to predict the local recurrence. A total of 118 NSCLC patients who underwent microwave ablation were enrolled in this study. The median local recurrence-free survival (LRFS) was 35.5 months. Independent prognostic factors obtained by multivariate analysis were included in the prediction model. The prognostic value of the model was assessed by the area under the time-dependent receiver operating characteristic curve (T-AUC). Histological subtype and preALC were independent risk factors for local relapse-free survival. According to the time-dependent receiver operating characteristic curve (T-ROC), the optimal cut-off value of preALC was 1.965×109/L, the sensitivity was 0.837, and the specificity was 0.594. The area under the T-ROC curve (AUC) of preALC was 0.703. To establish a nomogram to predict the local recurrence rate of NSCLC after MWA based on the prognostic factors revealed by Cox regression. Preoperative lymphocyte count reduction is associated with poor prognosis of NSCLC. The nomogram model combined with preALC can provide a good individualized prediction of local recurrence after microwave ablation.

P748 Pharmacokinetics, relative bioavailability, and dose proportionality of a tablet formulation of the sphingosine 1-phosphate-1 receptor modulator VTX002 (formerly OPL-002)

Abstract Background VTX002 is an oral selective sphingosine 1-phosphate-1 receptor (S1P1R) modulator in clinical development for treatment of ulcerative colitis (UC). Single and multiple doses of a spray-dried dispersion (SDD) oral suspension of VTX002 were well-tolerated up to 45 mg in a phase 1 study in healthy participants and were accompanied by dose proportional reductions in lymphocyte counts, an expected pharmacodynamic outcome of treatment.1 A separate phase 1 study compared the pharmacokinetics (PK) and pharmacodynamics of the SDD oral suspension and a tablet formulation of VTX002. Methods Healthy adult participants (N=12) were randomised (4 per dose group) in an open-label 3-way crossover study to receive single oral doses of 5 mg or 20 mg VTX002 tablets, or 20 mg VTX002 SDD suspension followed by at least a 1-week washout between each dose as shown in Fig. 1. Study assessments included: VTX002 plasma concentrations, PK parameters, change from baseline in absolute lymphocyte count (ALC), and adverse events (AE). Results A total of 10 participants completed the study. Mean plasma VTX002 concentrations were greatest with a single oral dose of 20 mg VTX002 SDD suspension (Fig. 2). The geometric mean peak (Cmax) and total (AUCinf) exposure to VTX002 were lower with the 5 mg (dose normalized to 20 mg tablet) and 20 mg VTX002 tablets compared to the 20 mg VTX002 SDD suspension (Table 1). Geometric mean ratios for the tablet and SDD formulations of VTX002 are shown in Table 2. Maximum percent (SD) reduction in ALC from baseline was greatest for the 20 mg VTX002 SDD suspension and was observed at 6 hours post-dose both for the SDD suspension and the 20 mg VTX002 tablet (59.9% [11.0%] and 51.6% [9.4%], respectively). The maximum percent reduction in ALC from baseline for the 5 mg VTX002 tablet was 22.4% (9.2%) which occurred 2 hours post-dose. A total of 23 AEs were reported; of which 19 were considered mild, and 4 were moderate. Conclusion All doses and formulations of VTX002 were well-tolerated and associated with ALC reductions. Data from this relative bioavailability study was used to convert the results from the prior phase 1 multiple ascending dose study performed with VTX002 SDD suspension to AUC equivalent tablet doses and enable tablet dose selection for phase 2. A phase 2 study of VTX002 tablets for treatment of UC is underway (ClinicalTrials.gov Identifier:NCT05156125). 1Luo A, et al. 2020 Gastroenterology. 2020;158(6):S1188.

Phase I Study of Safety and Pharmacokinetics of RO7297089, an Anti-BCMA/CD16a Bispecific Antibody, in Patients with Relapsed, Refractory Multiple Myeloma

IntroductionThis phase 1 trial assessed the safety, pharmacokinetics, and preliminary antitumor activity of RO7297089, an anti-BCMA/CD16a bispecific antibody.MethodsRO7297089 was administered weekly by intravenous infusion to patients with relapsed/refractory multiple myeloma. The starting dose was 60 mg in this dose-escalation study utilizing a modified continual reassessment method with overdose control model.ResultsOverall, 27 patients were treated at doses between 60 and 1850 mg. The maximally administered dose was 1850 mg due to excipients in the formulation that did not allow for higher doses to be used. The maximum tolerated dose was not reached. The most common adverse events irrespective of grade and relationship to the drug were anemia, infusion-related reaction, and thrombocytopenia. Most common treatment-related grade ≥ 3 toxicities were ALT/AST increase and reduced lymphocyte count. Pharmacokinetic studies suggested non-linear pharmacokinetics and target-mediated drug disposition, with a trend of approaching linear pharmacokinetics at doses of 1080 mg and higher. Partial response was observed in two patients (7%), minimal response in two patients (7%), and stable disease in 14 patients (52%).ConclusionsRO7297089 was well tolerated at doses up to 1850 mg, and the efficacy data supported activity of RO7297089 in multiple myeloma. Combination with other agents may further enhance its potential as an innate immune cell engager in multiple myeloma.Trial RegistrationClinicalTrials.gov: NCT04434469; Registered June 16, 2020; https://www.clinicaltrials.gov/ct2/show/NCT04434469.