Total Lymphocyte Research Articles

Immune Redox Modulation Effects of Non-Electrolyzed Hypochlorous Acid Water on Helicobacter pylori-Infected C57BL/6 Mouse Model

Recently, non-electrolyzed HOCl water has gained the attention of researchers as a new disinfecting agent owing to its high sterilization power, easy accessibility, and safety. Non-electrolyzed HOCl water was developed through mixing at a specific ratio based on hypochlorite and mineral supplements, which revealed a high oxidizing power. In this study, we investigated the effects of non-electrolyzed HOCl water on Helicobacter pylori (H. pylori) infection in C57BL/6 mice over 10 weeks. Mice were divided into three groups: normal control (NC) group supplied with purified water (PW) without infection, PW + H. pylori group supplied with PW after H. pylori infection, and HOCl + H. pylori group supplied with HOCl after H. pylori infection. Our findings demonstrated that the HOCl + H. pylori group greatly inhibited WBC and its differential counts, including total white blood cell (WBC), neutrophils, lymphocytes, monocytes, and eosinophils, when compared to the PW + H. pylori group. Accordingly, the amount of reactive oxygen species and calcium activity significantly decreased in the HOCl + H. pylori group compared to the PW + H. pylori group in both serum and stomach lysates. In contrast, HOCl water treatment enhanced GPx activity compared to PW treatment after H. pylori infection in both serum and stomach lysates. Accordingly, the levels of granulocyte-macrophage colony-stimulating factor, IL-1β, and TNF-α cytokine levels were significantly decreased in the HOCl + H. pylori group compared to those in the PW + H. pylori group in the stomach lysate; however, there was no significant difference in serum. In addition, the expression levels of Bax, MMP-3, MMP-9, and TLR-4 were found to decrease after HOCl water treatment, whereas the expression level of Bcl-2 was found to be enhanced after HOCl water treatment in the stomach lysate. Taken together, our results suggest that drinking non-electrolyzed HOCl water has positive anti-oxidative, anti-inflammatory, and anti-apoptotic effects in H. pylori-infected mice through redox and immune regulation.

Severe lymphopenia as a prognostic factor in rectal cancer patients receiving adjuvant chemoradiotherapy: a retrospective study

The relationship between total lymphocyte counts (TLCs) and survival is not well documented in rectal cancer. This study aimed to investigate the association between TLCs and disease-free survival (DFS) and identify factors associated with lymphopenia in locally advanced rectal cancer patients receiving chemoradiotherapy. Thirty-six patients with locally advanced rectal cancer were retrospectively analyzed. TLCs were evaluated before surgery (pre-S), before radiotherapy (pre-RT), and during concurrent chemoradiotherapy (CCRT). The relationship between TLCs and DFS was analyzed by univariate and multivariate analysis. Potential clinical factors associated with lymphopenia were also evaluated. Median TLC declined significantly during radiotherapy. Severe lymphopenia during CCRT was significantly associated with poorer DFS on Kaplan–Meier analysis (p = 0.01), univariate regression analysis (p = 0.036), and multivariate regression analysis (p = 0.038). Pre-S TLCs (p = 0.009) and pre-RT TLCs (p = 0.042) were significantly associated with severe lymphopenia on univariate regression analysis; however, only pre-S TLCs (p = 0.026) were significantly associated with severe lymphopenia on multivariate regression analysis. Severe lymphopenia was a predictor of poorer DFS in patients with locally advanced rectal cancer receiving adjuvant chemoradiotherapy. Pre-S TLCs were predictors of severe lymphopenia. Further study is warranted to reduce the rate of severe lymphopenia.

Lymphocyte-to-C-Reactive Protein Ratio as an Early Sepsis Biomarker for Neonates with Suspected Sepsis.

Neonatal sepsis is an extremely dangerous and fatal disease among neonates, and its timely diagnosis is critical to treatment. This research is aimed at evaluating the clinical significance of the lymphocyte-to-C-reactive protein ratio (LCR) as an early sepsis indicator in neonates with suspected sepsis. Between January 2016 and December 2021, 1269 neonates suspected of developing sepsis were included in this research. Among them, sepsis was diagnosed in 819 neonates, with 448 severe cases, as per the International Pediatric Sepsis Consensus. Data related to clinical and laboratory tests were obtained via electronic medical records. LCR was calculated as total lymphocyte (109 cells/L)/C-reactive protein (mg/L). Multivariate logistic regression analysis was employed to evaluate the effectiveness of LCR as an independent indicator for determining sepsis in susceptible sepsis neonates. Receiver operating characteristic (ROC) curve analysis was conducted for investigating the diagnostic significance of LCR in sepsis. When suitable, the statistical tool SPSS 24.0 was used for statistical analyses. LCR decreased significantly in the control, mild, and severe sepsis groups. Further analyses exhibited that there was a substantially greater incidence of sepsis in neonates in the low-LCR group (LCR ≤ 3.94) as opposed to the higher LCR group (LCR > 3.94) (77.6% vs. 51.4%, p < 0.001). Correlation analysis indicated a substantial negative association of LCR with procalcitonin (r = -0.519, p < 0.001) and hospital stay duration (r = -0.258, p < 0.001). Multiple logistic regression analysis depicted LCR as an independent indicator for identifying sepsis and severe cases of this disease. ROC curve analysis indicated the optimal cutoff value of LCR in identifying sepsis to be 2.10, with 88% sensitivity and 55% specificity. LCR has proven to be a potentially strong biomarker capable of identifying sepsis in a timely manner in neonates suspected to have the disease.

The effect of post-discharge oral nutritional supplements on outcomes after gastrointestinal surgery: A systematic review and meta-analysis

Malnutrition is a risk-factor for adverse postoperative outcomes. This systematic review and meta-analysis evaluated the impact of post-discharge oral nutritional supplements (ONS) on outcomes in patients undergoing gastrointestinal surgery. The Medline and Embase databases were searched for randomised clinical trials in patients undergoing gastrointestinal surgery who had received ONS for at least two weeks after discharge from hospital. The primary endpoint was weight change. Secondary endpoints included quality of life, total lymphocyte count, total serum protein and serum albumin. Analysis was performed using RevMan5.4 software. Fourteen studies with 2480 participants (1249 ONS/1231 controls) were included. Pooling of results revealed that a reduction in postoperative weight loss in patients taking ONS, when compared with control: overall weighted mean difference (WMD)-1.69kg, 95% CI -2.98 to-0.41, P=0.01. Serum albumin concentration was increased in the ONS group: WMD=1.06g/L, 95% CI 0.04 to 2.07, P=0.04. Haemoglobin was also increased: WMD= 2.91 g/L, 95% CI 0.58 to 5.25, P = 0.01. Total serum protein, total lymphocyte count, total cholesterol and quality of life did not differ between the groups. Patient compliance was relatively poor across the studies and there was variability in the composition of ONS, volume consumed and surgical procedures performed. There was a reduction in postoperative weight loss and an improvement in some biochemical parameters in patients receiving ONS after gastrointestinal surgery. Future RCTs with more consistent methodologies are needed to investigate the efficacy of ONS after discharge from hospital following gastrointestinal surgery.

16 Supplement Type Influenced the Immune Response of Nursing Ewes to the Natural Challenge of Gastrointestinal Parasites While Grazing in Woodlands

Abstract Nutritional status influences the immune response of grazing animals to naturally occurring diseases and parasites. Provision of supplementary nutrients may enhance the resiliency of grazing animals to gastrointestinal parasites, which are posing a major health problem in small ruminants raised in Southeastern pastures. Information is limited on the role of supplement type in influencing the immune response of grazing animals to natural health challenges. This study tested the hypothesis that the immune response of nursing ewes to gastrointestinal (GI) parasites would be the same irrespective of the supplement type. The objective of the study was to evaluate the cellular and humoral immune response of nursing ewes naturally infected with GI parasites when supplemented with energy- or protein-rich feeds. Katahdin-St. Croix cross-nursing ewes (n = 18) were divided into two groups. Each group was assigned to separate sets of woodland plots (3 plots/group) and rotated in the respective plots throughout the study period with ad libitum hay from May to August 2022. Group-1 ewes were supplemented with whole corn and Group-2 ewes with whole soybean (0.5% of body weight). Fecal samples and blood samples were collected on days 1, 45, and 70. Fecal samples were analyzed for the type and quantity of GI parasites using the McMaster technique. Blood samples were analyzed for WBC (Total WBC, lymphocytes, neutrophils, monocytes, eosinophils, and basophils) using the Procyte-Dx Analyzer. Enzyme-linked immunosorbent assays were performed on serum samples to quantify immunoglobulins (Ig): IgA, IgG, and IgE. Data were analyzed using GLM Procedure in SAS 9.4. Haemonchus contortus was the major GI parasite affecting ewes. No difference was found between groups for GI parasites, WBC, and IgE. However, IgA and IgG concentrations were less in Group-1 than in Group-2 ewes (P &amp;lt; 0.0001). Overall, the supplement type did not affect the GI-parasite load and the immune response in terms of cellular and IgE. However, the immune response in terms of IgA and IgG was amplified with protein-rich supplements.

Neutrophil Lymphocyte Ratio as Screening Tool for Neonatal Sepsis in Developing Countries

Objective: to recognize an alternate method for screening neonatal sepsis in patients while considering the sensitivity and accuracy of the diagnosis.&#x0D; Study Design: Cross sectional study.&#x0D; Place and Duration of Study: Combined Military Hospital, Rawalpindi Pakistan, from Jun to Dec 2021.&#x0D; Methodology: Patients admitted to the Neonatal Intensive Care Unit of the Combined Military Hospital were included in the study. Demographic data, including age, weight, gender, and gestational age, were recorded. In addition, a statistical comparison of total leucocyte count, absolute neutrophil and lymphocyte counts, neutrophil-lymphocyte ratio, and C-reactive protein test was carried out for the cases and controls.&#x0D; Results: It was evident from the results that a significant correlation between the neutrophil-lymphocyte ratio and neonatal sepsis exists. The mean NLR in non-septic individuals was (1.8±1.3) and in septic individuals, it was (2.9±1.9). The p-value was 0.001. Furthermore, ROC showed that at an NLR value of 1.6, sensitivity was 0.594 and 1-specificity 0.295.&#x0D; Conclusion: Neutrophil lymphocyte ratio was an efficient screening tool for determining sepsis in neonates, with comparable results to the C-reactive protein test.

B cell subsets in thymus from infants with Down syndrome

B lymphocytes are still poorly characterized in the human thymus, and due to the immunological peculiarities of Down syndrome, a detailed investigation of thymic B lymphocytes and their subsets was performed in <2-year-old infants. This is a period of intense thymic activity, and here we compared thymuses from infants with Down syndrome (DG) and age-matched control group (CG) with heart disease as the only described malformation, no clinical signs of immunodeficiency and normal blood lymphocyte numbers. MethodsThis study, approved by the institutional ethics committee, included 10 thymic samples from DG infants, and 20 from CG infants. Depending on thymus size and the type of surgical approach, babies were submitted to total thymectomy or only the removal of a small thymic fragment (mainly in the DG), always during cardiac surgery in order to correct congenital defects. Flow cytometry was used for immunophenotyping of cell suspension obtained from thymic tissue; and the B lymphocyte topographic localization was investigated by immunohistochemistry, and a quantitative evaluation of B-cells in each region was carried out using methods of digitized images analysis. ResultsFlow cytometry revealed that CD20+ cells represent around 1% of total lymphocytes in both groups, with higher naive and lower unswitched memory B lymphocyte frequencies in DG when compared to the CG, while B1 cells were present in much higher frequency in DG than in CG. All the other B-cell subpopulations (transitional, switched memory, plasmablasts and plasmocytes) were statistically equivalent between groups. Immunohistochemistry showed higher frequencies of CD20+ cells in medullary region compared to cortex, without differences between the groups (DG = 16.8% and CG = 17.1% of total cell number), while the cortex region had few B cells in both groups, with significantly lower frequency in DG group, reaching 0.25%, compared with the CG, which showed 0.6%. Conclusion: Flow cytometry revealed a different distribution of B-cell subtypes in DG thymus compared to CG and, thus, data obtained from such rare material could be relevant in the characterization and further analysis and understanding of the immunological mechanisms that involve the participation of B lymphocyte subpopulations in the thymus. FAPESP (grant 2014/50489-9).

Evaluation and Treatment of a Severe Case of Pediatric Idiopathic Hypereosinophilic Syndrome

BackgroundHypereosinophilic syndromes (HES) are a group of rare disorders characterized by marked peripheral eosinophilia resulting in end organ damage. When evaluating a patient with persistent hypereosinophilia, it is important to screen for the more common secondary causes of eosinophilia and assess for primary, myeloid HES. When no clear etiology is determined, a diagnosis of idiopathic HES is made. While this evaluation can be clinically challenging, making an accurate diagnosis can help guide effective treatment. CaseA 3-year-old Caucasian female with profound peripheral eosinophilia (70,100 cells/mL) and lymphocytosis (24,900 cells/mL) presented for immunologic evaluation following a two year history of persistent eosinophilia (1,450–27,700 cells/mL), presumably secondary to recurrent toxocariasis. The patient had been treated with albendazole three times for Toxocara after having positive serology and imaging consistent with visceral larva migrans in the context of an otherwise negative extensive infectious evaluation. Intermittent oral steroids and daily medium-dose inhaled steroids had also been started for wheezing. A bone marrow biopsy (BMbx) demonstrated increased numbers of eosinophils with cytoplasmic vacuoles, areas of hypogranulation, and subtle segmentation abnormalities, but genetic rearrangements for PDGFRA, PDGFRB, FIP1L1, and JAK2 were negative. An abnormal population of lymphocytes (CD3-CD4+) making up 1.7% of total lymphocytes was noted; however, this was not reproducible on repeat BMbx. Positron emission tomography redemonstrated bilateral pulmonary nodules and mild hilar lymphadenopathy, and bronchoalveolar lavage was normal other than an eosinophilia. The remainder of her immunologic evaluation was normal other than a pan-hypergammaglobulinemia without evidence ofT or B cell clonality. A 429 gene primary immunodeficiency panel was not felt to be clinically significant.Given the patient's persistent eosinophilia, oral steroids at 2 mg/kg were started with only a partial response (2,600 eosinophils/mL). Ultimately, mepolizumab 100 mg injected subcutaneously every 4 weeks was started as steroid sparing therapy with an excellent clinical response (780 eosinophils/mL) even after weaning off of oral steroids. ConclusionThis unique case illustrates the importance of a thorough evaluation of patients with persistent eosinophilia and the efficacy of mepolizumab in a child with marked idiopathic HES.

Prognostic Serum Biomarkers of Inflammaging in Patients Undergoing Emergency Laparotomy.

Surgeons are increasingly faced with an ageing and frail patient population. There is a significant absence of biomarkers capable of risk stratifying patients undergoing emergency laparotomy. Inflammaging describes a state of chronic inflammation associated with ageing and frailty that may predict worse outcomes after surgery. This retrospective observational study evaluated pre-morbid inflammatory markers in the prognostication of older adult patients undergoing emergency laparotomy. Patients aged ≥65 years undergoing surgery between 1 April 2017 and 1 April 2022 were identified. Pre-admission and acute C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), total white cell count (WCC), neutrophil count (NC) and lymphocyte count (LC) datapoints were captured. Pre-operative risk stratification scores and post-operative outcomes were recorded using the National Emergency Laparotomy Audit (NELA) database. A cohort of 196 patients was included: 57.7% were female, median age 74.5 years. High risk (NELA risk of mortality ≥ 5%) and frail (clinical frailty scale ≥ 4) patients experienced a significantly longer hospital and critical care stay (p < 0.05). Pre-admission ESR ≥ 16 and LC ≥ 4.1 were significantly associated with a longer critical care stay (p < 0.05); no statistical significance was observed with CRP, WCC and NC in predicting adverse outcomes. We found that an elevated pre-morbid ESR and LC identifies a potential inflammaging cohort that demonstrates worse outcomes following emergency laparotomy. The prognostication of older adult surgical patients remains a challenge and represents an area of research deserving of future attention.

Age-Dependent Normalization Functions for T Lymphocytes in Healthy Individuals.

Lymphocyte numbers naturally change through age. Normalization functions to account for this are sparse and mostly disregard measurements from children in which these changes are most prominent. In this study, we analyze cross-sectional numbers of mainly T lymphocytes (CD3+, CD3+CD4+, and CD3+CD8+) and their subpopulations (naive and memory) from 673 healthy Dutch individuals ranging from infancy to adulthood (0-62 y). We fitted the data by a delayed exponential function and estimated parameters for each lymphocyte subset. Our modeling approach follows general laboratory measurement procedures in which absolute cell counts of T lymphocyte subsets are calculated from observed percentages within a reference population that is truly counted (typically the total lymphocyte count). Consequently, we obtain one set of parameter estimates per T cell subset representing both the trajectories of their counts and percentages. We allow for an initial time delay of half a year before the total lymphocyte counts per microliter of blood start to change exponentially, and we find that T lymphocyte trajectories tend to increase during the first half a year of life. Thus, our study provides functions describing the general trajectories of T lymphocyte counts and percentages of the Dutch population. These functions provide important references to study T lymphocyte dynamics in disease, and they allow one to quantify losses and gains in longitudinal data, such as the CD4+ T cell decline in HIV-infected children and/or the rate of T cell recovery after the onset of treatment.

Using preoperative control nutritional status scores as prognostic factors for endometrial cancer.

Previous investigations have reported that controlling nutritional (CONUT) status scores, incorporating total cholesterol (TC) and serum albumin (SA) values, and total lymphocyte (LY) counts, are reliable malignant tumor predictors. However, CONUT scores for predicting endometrial cancer (EC) remain unexplored. To evaluate preoperative CONUT scores as prognostic factors for postoperative EC. We retrospectively evaluated preoperative CONUT scores in 785 surgically resected EC patients at our hospital between June 2012 and May 2016. Using time-dependent receiver operating characteristic (ROC) analyses, patients were split into: 1) CONUT-high (CH) (≥1) and 2) CONUT-low (CL) (<1) groups. Relationships between CONUT scores and different clinicopathological, pathological differentiation, muscle layer infiltration depth, and prognosis factors were examined, and Cox regression analyses performed to assess prognostic values on overall survival (OS) rates. We assigned 404 (51.5%) and 381 (58.5%) patients to CH and CL groups, respectively. In the CH group, body mass index (BMI), prognostic nutrition index (PNI), and LY/monocyte ratios (LMR) were decreased, however, neutrophil/LY (NLR) and platelet/LY ratios (PLR) were increased. Pathological differentiation analyses showed that G1 proportions were higher in the CL group, while G2 and G3 proportions were more prevalent in the CH group. Muscle layer infiltration depth in CL patients was < 50%, while that it was ≥50% in the CH group. No significant differences in OS rates were recorded between CH and CL groups over 60 months. However long-term survival (LTS) rates after 60 months in the CH group were significantly lower when compared with the CL group, and was more obvious in type II EC patients. Also, periuterine infiltration and preoperative CONUT scores were independent prognostic factors for OS rates as indicated by multi-factor analyses. CONUT scores not only facilitated the estimation of nutritional status, but were highly beneficial for predicting OS rates in patients with EC after curative resection. CONUT scores provided high predictive values for LTS rates over 60 months in these patients.

Trends and Predictors of Peripheral CD19+ B-cell Repopulation in Patients Treated with Ocrelizumab during COVID-19 Pandemic (P7-3.014)

<h3>Objective:</h3> To assess the predictors of B-cell repopulation in patients treated with ocrelizumab during COVID-19 pandemic. <h3>Background:</h3> Ocrelizumab (OCR) is used for multiple sclerosis (MS) administered every 6 months (SID). Peripheral CD19+ lymphocyte (CD19L) count is a surrogate marker of efficacy of OCR. B-cell repopulation (≥1% CD19L of total lymphocytes) is a potential biomarker to guide OCR extended interval dosing (EID) beyond 6 months. During COVID-19 pandemic, adjusted OCR treatment-cycle based on CD19L repopulation has been a strategy to minimize the risk of prolonged B-cell depletion associated higher potential complications of COVID. We studied the predictors of B-cell repopulation in patients treated with OCR. <h3>Design/Methods:</h3> Retrospective study of patients receiving OCR between 2020–2022 in whom CD19L counts were available &lt;30 days prior to next infusion. Data collected included age, gender, race, body mass index (BMI), MS subtype, prior immunosuppressive therapy, time-to-repopulation. Multiple linear regression was used to look for predictors of B-cell repopulation. <h3>Results:</h3> Total 248 patients (mean age 48±12.8 years; 172 female, 76 male) studied. Forty-five percent (111 patients) had CD19L repopulation, fifty-five percent (137 patients) had persistently low (&lt;1%) counts. Mean number of infusion cycles prior to CD19L repopulation was significantly longer in extended interval group (4.36±2.16 days vs. 2.33±2.04; p&lt;0.05). BMI and inter-infusion interval were predictors of repopulation (p&lt;0.001); age, race, gender, disease type, prior immunosuppressive therapy did not predict repopulation. All patients remained clinically stable. <h3>Conclusions:</h3> In this observational study of MS patients treated with OCR with standard or extended interval dosing, BMI and inter-infusion dosing interval were the only predictors of B-cell repopulation. The number of infusions prior to repopulation was higher in the extended dosing group. In the future, these data can be used to provide guidance on extending OCR dosing interval. <b>Disclosure:</b> Dr. Padron has nothing to disclose. Ms. Jimsheleishvili has nothing to disclose. Dr. Tornes has nothing to disclose. Dr. Delgado has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Delgado has received research support from Novartis. The institution of Dr. Delgado has received research support from EMD Serono. The institution of Dr. Delgado has received research support from NIH/NINDS. Dr. Garg has nothing to disclose.

Activation of telomerase by TA-65 enhances immunity and reduces inflammation post myocardial infarction

Myocardial infarction (MI) accelerates immune ageing characterised by lymphopenia, expansion of terminally differentiated CD8+ T-lymphocytes (CD8+ TEMRA) and inflammation. Pre-clinical data showed that TA-65, an oral telomerase activator, reduced immune ageing and inflammation after MI. We conducted a double blinded randomised controlled pilot trial evaluating the use of TA-65 to reduce immune cell ageing in patients following MI. Ninety MI patients aged over 65 years were randomised to either TA-65 (16 mg daily) or placebo for 12 months. Peripheral blood leucocytes were analysed by flow cytometry. The pre-defined primary endpoint was the proportion of CD8+ T-lymphocytes which were CD8+ TEMRA after 12 months. Secondary outcomes included high-sensitivity C-reactive protein (hsCRP) levels. Median age of participants was 71 years. Proportions of CD8+ TEMRA did not differ after 12 months between treatment groups. There was a significant increase in mean total lymphocyte count in the TA-65 group after 12 months (estimated treatment effect: + 285 cells/μl (95% CI: 117–452 cells/ μ l, p < 0.004), driven by significant increases from baseline in CD3+, CD4+, and CD8+ T-lymphocytes, B-lymphocytes and natural killer cells. No increase in lymphocyte populations was seen in the placebo group. At 12 months, hsCRP was 62% lower in the TA-65 group compared to placebo (1.1 vs. 2.9 mg/L). Patients in the TA-65 arm experienced significantly fewer adverse events (130 vs. 185, p = 0.002). TA-65 did not alter CD8+ TEMRA but increased all major lymphocyte subsets and reduced hsCRP in elderly patients with MI after 12 months.

Effect of rituximab on immune status in children with mature B-cell non-Hodgkin lymphoma: a prespecified secondary analysis of the Inter-B-NHL Ritux 2010 trial

Survival of children and adolescents with high-risk, mature B-cell non-Hodgkin lymphoma is improved by the addition of rituximab to chemotherapy. The effect of rituximab on immune reconstitution after therapy has not been well described. Herein, we evaluate the immune effects of the addition of rituximab to intensive chemotherapy, a prespecified secondary aim of the Inter-B-NHL Ritux 2010 trial. The Inter-B-NHL Ritux 2010 trial was an international, open-label, randomised, phase 3 trial in children (age 6 months to 18 years) with high-risk, mature B-cell non-Hodgkin lymphoma, comparing chemotherapy alone or chemotherapy with rituximab. Measures of immune status were completed at baseline, 1 month from the end of treatment, and 1 year from the start of therapy, and yearly thereafter until normalised. For this secondary analysis, we report on the proportions of patients with low lymphocyte counts and immunoglobulin concentrations at these timepoints with total lymphocyte count, B-cell count, and IgG concentration as the main endpoints. Other endpoints of interest included exposure to immunoglobulin replacement therapy and vaccine serologies. The population assessed for immune endpoints was the eligible per-protocol population with at least one immune parameter at one timepoint. Comparisons of immune status were made between the randomised treatment groups. Safety in the post-therapy period was assessed in the population eligible for the immunity study who were followed up at least 3 months after the end of treatment and without cancer-related events. The Inter-B-NHL Ritux 2010 study was registered with ClinicalTrials.gov, NCT01516580; status completed, with analyses of secondary aims ongoing. From Dec 19, 2011, to June 13, 2017, 421 patients (344 [82%] boys and 77 [18%] girls; mean age was 8·8 years [SD 4·1]) were enrolled and had immune data at baseline during follow-up, or both. The study population included randomly assigned patients (n=289) and a non-randomised cohort enrolled after the planned interim analysis (n=132). At baseline, 99 (34%) of 290 patients with available data (excluding patients with bone marrow disease with peripheral blast cells) had lymphopenia, and 178 (48%) of 368 had hypogammaglobulinemia. 1 month from the end of therapy, patients who received chemotherapy with rituximab were more likely than those who received chemotherapy alone to have lymphopenia (86 [81%] of 106 vs 53 (60%) of 89, odds ratio [OR] 2·92 [95% CI 1·53-5·57], p=0·0011), B-cell lymphopenia (72 [96%] of 75 vs 36 [64%] of 56, OR 13·33 [3·71-47·84], p<0·0001), and hypogammaglobulinemia (67 [71%] of 95 vs 37 [47%] of 79, OR 2·72 [1·45-5·07], p=0·0017). Differences remained at 1 year for hypogammaglobulinemia only (52 [55%] of 94 vs 16 [25%] of 63, OR 3·64 [1·81-7·31], p=0·0003). Patients in the chemotherapy with rituximab group were more likely than those in the chemotherapy group to receive immunoglobulin replacement (26 [16%] 164 vs nine [7%] of 158, hazard ratio [HR] 2·63 [95% CI 1·23-5·62], p=0·010), mainly due to low immunoglobulin concentration. In the combined treatment groups, including non-randomly assigned patients, the proportion of patients who had loss of protective serologies to a vaccine preventable infection varied from four (9%) of 47 for polio to 21 (42%) of 50 for Streptococcus pneumoniae (pneumococcus). One patient (chemotherapy with rituximab group) had a life-threatening infectious event of polymicrobial bacterial sepsis reported 2 months after the final chemotherapy administration. Children with high-risk mature B-cell non-Hodgkin lymphoma receiving chemotherapy with rituximab were at risk of prolonged hypogammaglobulinemia, although severe infections were rare. Strategies for immunoglobulin replacement and revaccination are needed. Clinical Research Hospital Program of the French Ministry of Health, Cancer Research UK, National Institute for Health Research Clinical Research Network in England, Children's Cancer Foundation Hong Kong, US National Cancer Institute, F Hoffmann-La Roche.

Hypoalbuminemia increases the risk of failure following one-stage septic revision for periprosthetic joint infection.

Malnutrition is a potentially modifiable risk factor of periprosthetic joint infection (PJI). The purpose of this study was to analyze the role of nutritional status as a risk factor for failure after one- stage revision hip or knee arthroplasty for PJI. Retrospective, single-center, case-control study. Patients with PJI according to the 2018 International Consensus Meeting criteria were evaluated. Minimum follow-up was 4years. Total lymphocyte count (TLC), albumin values, hemoglobin, C-reactive protein, white blood cell (WBC) count and glucose levels were analyzed. An analysis was also made of the index of malnutrition. Malnutrition was defined as serum albumin < 3.5g/dL and TLC < 1500/mm3. Septic failure was defined as the presence of local or systemic symptoms of infection and the need of further surgery as a result of persistent PJI. No significant differences were found between increased failure rates after a one-stage revision hip or knee arthroplasty for PJI and TLC, hemoglobin level, WBC count, glucose levels, or malnutrition. Albumin and C-reactive protein values were found to have a positive and significant relationship with failure (p < 0.05). Multivariate logistic regression identified only hypoalbuminemia (serum albumin < 3.5g/dL) (OR 5.64, 95% CI 1.26-25.18, p = 0.023) as a significant independent risk factor for failure. The receiver operating characteristic (ROC) curve for the model yielded an area under the curve of 0.67. TLC, hemoglobin; WBC count; glucose levels; and malnutrition, understood as the combination of albumin and TLC, were not found to be statically significant risk factors for failure after single-stage revision for PJI. However, albumin < 3.5g/dL, alone was a statically significant risk factor for failure after single-stage revision for PJI. As hypoalbuminemia seems to influence the failure rate, it is advisable to measure albumin levels in preoperative workups.

Paclobutrazol ameliorates cigarette smoke-induced chronic obstructive pulmonary disease (COPD) in experimental rats

BackgroundThe cigarette smoking epidemic is one of the desperate threats experienced all over the world. Cigarettes cause diseases such as chronic obstructive pulmonary disease (COPD), asthma, lung cancer, stroke, heart diseases, etc. Paclobutrazol is a growth regulator hormone that increases antioxidant enzymes, mineral absorption, carbohydrate synthesis, and flowering and fruit production in plants. ObjectiveIn the current study, we assessed the ameliorative effect of paclobutrazol against chronic cigarette smoke-induced COPD in rats. MethodologyA side-stream cigarette exposure rat model was used for the study, which is a well-accepted model to evaluate cigarette smoke-induced lung damage. The paclobutrazol treatment was given for 12 weeks, and since the reduction in body weight is the primary symptom of COPD, the food efficiency and the weight gain were measured. Muscular strength was analyzed with a grip strength test, and respiratory functions were assessed with a whole-body plethysmograph. Plasma leptin was measured to detect the fat mass index. C-reactive protein was quantified to assess the level of inflammation. Further bronchoaleveolar fluid was collected and analyzed for the total white blood cell count, neutrophils, lymphocytes, and monocytes to evaluate the inflammation. In order to confirm the anti-inflammatory property of paclobutrazol against cigarette smoke-induced lung inflammation, histopathological analysis of lung tissue was done. ResultsThe paclobutrazol treatment increased the body weight, improved respiratory functions, and decreased inflammation in the rats exposed to secondhand cigarette smoke. Our results of histopathological analysis confirm that paclobutrazol has effectively inhibited cigarette smoke-induced lung tissue damage in young Wistrar rats. ConclusionHence, it can be used as a supplementary drug to protect smokers from cigarette smoke-induced lung damage.

The impact of multidisciplinary team nutrition management on nutritional and toxicity status in patients with nasopharyngeal carcinoma

ObjectiveTo explore the impact of multidisciplinary team (MDT) nutrition management on the nutritional and toxicity status of patients with nasopharyngeal carcinoma undergoing chemoradiotherapy. MethodsA total of 104 patients undergoing chemoradiotherapy for nasopharyngeal carcinoma admitted to our hospital from July 2018 to February 2021 were retrospectively enrolled, including who received conventional nutrition management (the routine group, n ​= ​52) and who received MDT nutrition management (the experimental group, n ​= ​52). Nutritional indicators (dietary intake, body mass index, serum albumin, serum prealbumin, hemoglobin, total lymphocyte count, serum transferrin [TRF]), the Nutrition Risk Screening 2002 (NRS2002) score and acute toxicity level were recorded before, during, and after chemoradiotherapy. Multiple regression analysis was performed to identify nutritional risk indicators. ResultsDuring and after chemoradiotherapy, the body mass index, albumin, prealbumin, hemoglobin, total lymphocyte count, TRF, dietary intake, number of patients with an NRS2002 score < 3, and acute toxicity score in the experimental group improved compared to those in the routine group (P ​< ​0.05). Concurrent chemotherapy, the NRS2002 score and a half-diet strategy were independent factors affecting the nutritional status of nasopharyngeal carcinoma patients who underwent chemoradiotherapy. ConclusionsActive screening and evaluation of the nutritional status of patients with nasopharyngeal carcinoma during chemoradiotherapy as well as MDT nutrition management can be used to detect nutritional problems, thus improving quality of life and reducing related toxicity.

Platelet-to-lymphocyte ratio a potential prognosticator in acute myocardial infarction: A prospective longitudinal study.

The ratio of platelets to lymphocytes (PLR) can serve as a potential biomarker for predicting the prognosis of individuals with acute myocardial infarction (AMI). The purpose of the research was to evaluate the in-hospital outcomes of AMI patients and the predictive significance of PLR on major adverse cardiac events (MACE). A total of 799 AMI patients who had successful primary PCI within 12 h of the onset of chest pain were separated into low PLR (n = 511) and high PLR (n = 288) groups using a PLR cutoff value of 178. At admission, total white blood cell, neutrophil, lymphocyte, and platelet counts were assessed. In patients with a high PLR group with PLR > 178, the incidence of MACE: heart rupture, acute heart failure, total adverse events, and mortality due to all events was considerably greater. In an analysis of the receiver operating characteristic curve, a high PLR > 178 accurately predicted adverse outcomes (73% specificity and 65% sensitivity). Age, hypertension, and PLR were found as independent predictors of adverse outcomes by multiple logistic regression. AMI patients with high PLR had poor hospital outcomes. These findings recommend PLR as an independent risk factor for hospital-acquired complications, suggesting that inflammation and prothrombotic state may contribute to the poor prognosis of high PLR patients.

Safety and immunogenicity of a ChAdOx1 vaccine against Rift Valley fever in UK adults: an open-label, non-randomised, first-in-human phase 1 clinical trial

Rift Valley fever is a viral epidemic illness prevalent in Africa that can be fatal or result in debilitating sequelae in humans. No vaccines are available for human use. We aimed to evaluate the safety and immunogenicity of a non-replicating simian adenovirus-vectored Rift Valley fever (ChAdOx1 RVF) vaccine in humans. We conducted a phase 1, first-in-human, open-label, dose-escalation trial in healthy adults aged 18-50 years at the Centre for Clinical Vaccinology and Tropical Medicine, Oxford, UK. Participants were required to have no serious comorbidities or previous history of receiving an adenovirus-based vaccine before enrolment. Participants were non-randomly allocated to receive a single ChAdOx1 RVF dose of either 5 × 109 virus particles (vp), 2·5 × 1010 vp, or 5 × 1010 vp administered intramuscularly into the deltoid of their non-dominant arm; enrolment was sequential and administration was staggered to allow for safety to be assessed before progression to the next dose. Primary outcome measures were assessment of adverse events and secondary outcome measures were Rift Valley fever neutralising antibody titres, Rift Valley fever GnGc-binding antibody titres (ELISA), and cellular response (ELISpot), analysed in all participants who received a vaccine. This trial is registered with ClinicalTrials.gov (NCT04754776). Between June 11, 2021, and Jan 13, 2022, 15 volunteers received a single dose of either 5 × 109 vp (n=3), 2·5 × 1010 vp (n=6), or 5 × 1010 vp (n=6) ChAdOx1 RVF. Nine participants were female and six were male. 14 (93%) of 15 participants reported solicited local adverse reactions; injection-site pain was the most frequent (13 [87%] of 15). Ten (67%) of 15 participants (from the 2·5 × 1010 vp and 5 × 1010 vp groups only) reported systemic symptoms, which were mostly mild in intensity, the most common being headache (nine [60%] of 15) and fatigue (seven [47%]). All unsolicited adverse events reported within 28 days were either mild or moderate in severity; gastrointestinal symptoms were the most common reaction (at least possibly related to vaccination), occurring in four (27%) of 15 participants. Transient decreases in total white cell, lymphocyte, or neutrophil counts occurred at day 2 in some participants in the intermediate-dose and high-dose groups. Lymphopenia graded as severe occurred in two participants in the 5 × 1010 vp group at a single timepoint, but resolved at the subsequent follow-up visit. No serious adverse events occurred. Rift Valley fever neutralising antibodies were detectable across all dose groups, with all participants in the 5 × 1010 vp dose group having high neutralising antibody titres that peaked at day 28 after vaccination and persisted through the 3-month follow-up. High titres of binding IgG targeting Gc glycoprotein were detected whereas those targeting Gn were comparatively low. IFNγ cellular responses against Rift Valley fever Gn and Gc glycoproteins were observed in all participants except one in the 5 × 1010 vp dose group. These IFNγ responses peaked at 2 weeks after vaccination, were highest in the 5 × 1010 vp dose group, and tended to be more frequent against the Gn glycoprotein. ChAdOx1 RVF was safe, well tolerated, and immunogenic when administered as a single dose in this study population. The data support further clinical development of ChAdOx1 RVF for human use. UK Department of Health and Social Care through the UK Vaccines Network, Oak Foundation, and the Wellcome Trust. For the Swahili translation of the abstract see Supplementary Materials section.

Regulatory B Cells Profile in Kidney Transplant Recipients With Chronic-Active Antibody-Mediated Rejection

This study aims to reveal the relationship between regulatory B cell (Breg) subsets and chronic-active antibody-mediated rejection (c-aABMR) in renal transplant recipients. Our study involved 3 groups of participants: renal transplant recipients with biopsy-proven c-aABMR as the chronic rejection group (c-aABMR, n=23), recipients with stable graft functions as the patient control group (PC; n=11), and healthy volunteers (HV; n=11). Breg subsets, immature/transitional B cells, plasmablastic cells, B10 cells, and BR1 cells were isolated from venous blood samples by flow cytometry. The median values of Breg frequencies in the total lymphocyte population were analyzed. There were no significant differences between the study groups for immature and/or transitional B cell frequencies. Plasmablastic cell frequencies of the c-aABMR group (7.80 [2.10-27.40]) and the PC group (6.00 [1.80-55.50]) were similar, but both of these values were significantly higher than the HVs' (3.40 [1.20-8.50]), (respectively, P=.005 and P=.039). B10 cell frequencies were also similar, comparing the c-aABMR (4.20 [0.10-7.40]) and the PC groups (4.10 [0.10-5.90]), whereas the HVs (5.90 [2.90-8.50]) had the highest B10 cell frequency with an only statistical significance against the PC group (respectively, P=.09 and P=.028). The c-aABMR and the PC groups were similar regarding BR1 cell frequencies. However, the HV group significantly had the highest frequency of BR1 cells (5.50 [2.80-10.80]) than the other groups (P < .001 for both). We demonstrated that frequencies of B10 and BR1 cells were higher in HVs than in transplant recipients, regardless of rejection state. However, there was no significant relation between Breg frequencies and the c-aABMR state.