Peripheral Blood Lymphocyte Count Research Articles

Predictive value of neutrophil-to-lymphocyte-ratio in neoadjuvant-treated patients with breast cancer

PurposeBreast cancer (BC) is the most common malignancy among women and prognosis is strongly influenced by tumor subtype. Neoadjuvant chemotherapy (NAC) is the standard treatment for both locally advanced- and early-stage triple-negative and Her2-positive BC. Pathologic complete response (pCR) to NAC is an important predictor of patient outcomes. Neutrophil-to-lymphocyte-ratio (NLR) in peripheral blood is associated with prognosis in various malignancies. Here, we investigated the value of the pretreatment NLR as a response predictor in neoadjuvant-treated patients with BC.MethodsA retrospective chart analysis of 862 patients with invasive BC treated with NAC at the Heidelberg University Hospital during 2003–2015 was conducted. NLR was calculated as the ratio of the absolute neutrophil and lymphocyte counts in peripheral blood, and pCR was defined as absence of invasive or in situ carcinoma in breast and axillary lymph nodes.ResultsA total of 151 patients with invasive BC who underwent NAC were included in this study. NLR tended to be higher in the pCR group than the non-pCR group (p < 0.1). Analyses of BC subtypes demonstrated that NLR was significantly higher in the pCR- compared with the non-pCR group (3.304 vs. 2.379, respectively; p = 0.048) in patients with luminal B/Her2-negative tumors. Further, we found a significant difference in NLR according to remission status in postmenopausal patients (2.861 vs. 2.313, respectively; p = 0.043).ConclusionNLR was significantly higher only for patients achieving pCR in the Luminal B/Her2-negative and postmenopausal subgroups. Hence, NLR is a candidate additional predictive factor in patients with Luminal B/Her2-negative BC.

Apheresis for chimeric antigen receptor T-cell production in adult lymphoma patients.

To date, in-depth analysis of leukapheresis products as starting material for CAR T-cell manufacturing, specifically Tisagenlecleucel production, are scarce. In this study, we report on lymphapheresis data for production of Tisagenlecleucel for elderly and pretreated lymphoma patients. Spectra Optia from Terumo BCT, Lakewood, CO, was employed for apheresis using the cMNC program. Apheresis success was defined as meeting a target total nucleated cell (TNC) count of ≥2 × 109 , a CD3-positive lymphocyte count of ≥1 × 109 and an overall viability of ≥70% in the lymphapheresis product. Twenty-three patients (age 37-77 years) and 24 apheresis runs were evaluated. The median CD3-positive lymphocyte count in peripheral blood at the beginning of apheresis was 565 cells/μl (range: 70-1345 cells/μl). Circulating lymphoma cells were detected in one patient prior to apheresis. Target criteria were met in 21 of 23 patients. The median TNC count in the apheresate was 11.2 × 109 (range: 2.9 × 109 -47.4 × 109 ). The median CD3-positive lymphocyte count in the apheresate was 2.55 × 109 (range: 0.370 × 109 -6.915 × 109 ), which resulted in a median collection efficiency for CD3-positive lymphocytes of 63.7% (range: 9.56%-93.6%). No adverse events associated with the apheresis process were observed. Lymphapheresis with the Spectra Optia cMNC program provided a sufficient quantity of CD3-positive lymphocytes for CAR T-cell manufacturing for the majority of patients despite their heavy pretreatment and advanced age. Moreover, we are the first to advocate early pre-emptive lymphocyte collection in DLBCL-NOS patients intended to undergo treatment with Tisagenlecleucel.

PB2137: INFLUENCE OF PREVIOUS RADIOTHERAPY ON THE EFFECT OF CART CELL THERAPY IN AGGRESSIVE B-CELL LYMPHOMA

Background: In previous studies, radiotherapy has an effect on the number and function of lymphocytes. In recent years, with the advent of CART cell therapy, the PFS and OS of relapsed and refractory highly aggressive B-cell lymphoma have been significantly improved. Whether previous radiotherapy is effective for CART cell therapy The impact is inconclusive. Aims: To investigate the influence of the radiotherapy history before CART cell therapy on the culture, expansion and treatment effect of CART cells in patients with aggressive B-cell lymphoma. Methods: A retrospective study from December 2018 to September 2021 in adult patients with aggressive B-cell lymphoma treated with CART cells at our center who underwent radiotherapy before lymphocyte collection. The patient’s previous radiotherapy dose, radiotherapy distance from lymphocyte collection time, peripheral blood lymphocyte count before lymphocyte collection, CART cell culture dose, reinfusion dose, and curative effect statistics of 3 months after CART cell reinfusion were counted. Statistical methods such as logistic regression and spearman correlation analysis were used for analysis. Results: 16 males and 18 females were eligible, with a median age of 45.5 years (18-86 years). These included 2 Burkitt lymphoma, 26 unspecified diffuse large B-cell lymphoma, 5 primary mediastinal B-cell lymphoma, and 1 primary central lymphoma. The median time from lymphocyte collection to previous radiotherapy was 151 (5-4772) days, and the median radiation dose was 46 (4-66) Gy. The absolute value of lymphocytes before the collection of lymphocytes was 0.79 (0.14-2.58)×10^9/L, which was lower than the normal reference value. The median culture dose of CART cells was 0.837(0.1-7.03)×10^6/kg, and the median infusion dose was 0.837(0.1-4.2)×10^6/kg. After CART cell infusion, the peak CART cell expansion was 18.6(0-919)×10^6/kg, 3-month CR: 20.59%, 3-month ORR: 44.12%. The time interval between previous radiotherapy and lymphocyte collection had a significant effect on 3-month CR, P=0.0417. The effect on 3-month ORR was not statistically significant, P=0.1388. There was no significant effect of previous radiotherapy dose on CR/ORR at 3 months, with P values ​​of 0.9188/0.5078, respectively. The effect of previous radiotherapy dose on the CART cell culture dose and the maximum value of CART cell expansion was not found to be statistically significant. CR and ORR at 3 months after reinfusion were significantly correlated with the reinfusion dose, with P values ​​of 0.0102 & 0.0121, respectively. There was no significant relationship between the absolute value of lymphocytes and the proportion of lymphocytes, the culture dose and the CR/ORR of the curative effect. Summary/Conclusion: Radiotherapy affects the number and cell quality of lymphocytes, the median culture dose is significantly lower than the 2×10^6/kg reported in the literature. In patients with aggressive B-cell lymphoma who had a history of radiotherapy, the CR/ORR at 3 months after CART cell therapy was significantly lower than that reported. This adverse effect was independent of radiation dose. The CR rate is affected by the time interval between radiotherapy and lymphocyte collection. The longer the interval, the greater the adverse effect.

Role of the Systemic Immune-Inflammation Index in Patients with Metastatic Renal Cell Carcinoma Treated with First-Line Ipilimumab plus Nivolumab.

Simple SummaryThe aim of this study was to evaluate the predictive and prognostic value of the systemic immune-inflammation index (SII), which is based on peripheral blood platelet, neutrophil, and lymphocyte counts, in patients with metastatic renal cell carcinoma (mRCC) treated with ipilimumab plus nivolumab in the first-line setting. High SII score was an independent prognostic factor for worse progression-free survival and overall survival. The clinical benefit rate was higher for patients with a low SII index if compared to a high SII index. An increase in SII of >20% from baseline after 12 weeks of therapy was significantly associated with tumor progression at first imaging. The SII index is both prognostic and predictive and could refine decision making in patients treated with ipilimumab plus nivolumab.Background: The aim of this study was to evaluate the predictive and prognostic value of the systemic immune-inflammation index (SII) in patients with metastatic renal cell carcinoma (mRCC) treated with first-line ipilimumab plus nivolumab. Methods: This retrospective study included forty-nine mRCC patients treated with first-line ipilimumab plus nivolumab at the Department of Urology of the University of Tuebingen, Germany. SII was assessed before starting ipilimumab plus nivolumab therapy at the time of first imaging and at tumor progression. Optimal SII cut-off was stratified by ROC-analysis. Univariable and multivariable Cox regression analyses were used to evaluate the predictive and prognostic value of SII. Results: Optimal SII cut-off was 788. Twenty-nine/forty-nine patients had high SII (≥788) before initiation of ipilimumab plus nivolumab. High SII was an independent prognostic factor for worse progression-free (HR 2.70, p = 0.014) and overall survival (HR 10.53, p = 0.025). The clinical benefit rate was higher for patients with low SII if compared to high SII (80% vs. 32.1%). An increase in SII > 20% from baseline after twelve weeks of therapy was associated with progression at first imaging (p = 0.003). Conclusions: SII is both prognostic and predictive and could refine decision making in patients with unclear imaging on therapy with ipilimumab plus nivolumab.

T-Cell Defects Associated to Lack of Spike-Specific Antibodies after BNT162b2 Full Immunization Followed by a Booster Dose in Patients with Common Variable Immune Deficiencies.

Following the third booster dose of the mRNA vaccine, Common Variable Immune Deficiencies (CVID) patients may not produce specific antibodies against the virus spike protein. The T-cell abnormalities associated with the absence of antibodies are still a matter of investigation. Spike-specific IgG and IgA, peripheral T cell subsets, CD40L and cytokine expression, and Spike-specific specific T-cells responses were evaluated in 47 CVID and 26 healthy donors after three doses of BNT162b2 vaccine. Testing was performed two weeks after the third vaccine dose. Thirty-six percent of the patients did not produce anti-SARS-CoV-2 IgG or IgA antibodies. Non responder patients had lower peripheral blood lymphocyte counts, circulating naïve and central memory T-cells, low CD40L expression on the CD4+CD45+RO+ and CD8+CD45+RO+ T-cells, high frequencies of TNFα and IFNγ expressing CD8+ T-cells, and defective release of IFNγ and TNFα following stimulation with Spike peptides. Non responders had a more complex disease phenotype, with higher frequencies of structural lung damage and autoimmunity, especially autoimmune cytopenia. Thirty-five percent of them developed a SARS-CoV-2 infection after immunization in comparison to twenty percent of CVID who responded to immunization with antibodies production. CVID-associated T cell abnormalities contributed to the absence of SARS-CoV-2 specific antibodies after full immunization.

Nutrient Deficiency Correction in Ovarian Cancer Patients Following Surgical Treatment: a Clinical Case

Background. According to some studies, nutrient deficiencies reach an over-70% prevalence in ovarian cancer, among other gynaecological malignancies, thus constituting an important risk factor for postoperative mortality, surgical complications and longer hospital stays. Therefore, effective nutrient deficiency correction methods are warranted to improve the ovarian cancer outcomes, especially in patients following radical surgical interventions. New systematic evidence emerges in literature on the impact of such novel methods on the critical status of variant-category patients. Meanwhile, such evidence bears a recommendatory value only, with no current standard or protocol assumed for nutrient deficiency management. This issue presently remains open and requires careful research and analysis.Materials and methods. The clinical case demonstrates the efficacy of nutrient deficiency correction in an ovarian cancer patient following an individualised radical surgery.Results and discussion. The energy supplied on day 1 was &gt;42%, &gt;83% on day 3, and the target values had been achieved by day 7 of intensive therapy. The nutrient deficiency marker dynamics revealed the growth of transferrin, triglycerides and peripheral blood lymphocyte counts as early as by day 3 post-surgery. Albumin was the latest to respond, increasing only on day 7.Conclusion. The introduction of novel nutrition strategies and knowledge of their impact depend on further high-quality research, especially prospective studies, incorporating a greater homogeneity of intervention types and clinical outcomes, as well as wider sampling of female ovarian cancer.

The Effects of Treatment on Peripheral Blood Immune Cell Profile in Pancreatic Ductal Adenocarcinoma (PDAC).

This study evaluated whether circulating lymphocytes, assessed by flow cytometry, is a prognostic biomarker in pancreatic ductal adenocarcinoma (PDAC). We studied T cell subsets in blood samples from a cohort of 41 patients diagnosed with PDAC. Patients underwent surgery of the primary site and adjuvant chemotherapy or were treated with 1st line chemotherapy (mFOLFIRINOX regimen or gemcitabine alone). The changes in T cell subpopulations during treatment were evaluated at the initial diagnosis before surgery, and after 2 and 4 months. Friedman test was used for statistical analysis. A decline in CD19+ B lymphocytes, natural killer (NK) cells CD3-CD56+CD16+, and T regulatory cells CD4+FOXP3+ during treatment was observed. NKT-like cells CD3+CD56+ and cytotoxic T cells CD3+CD8+ tended to increase after two months and decrease after that. Statistically significant changes in lymphocyte counts in peripheral blood were detected in patients with PDAC during treatment.

MO1022: Torque Teno Virus Load in Kidney Transplantation: Association with Donor and Recipient Characteristics and Clinical Follow-Up Data

Abstract BACKGROUND AND AIMS The apathogenic and torque teno virus (TTV) is associated with the state of immunosuppression in solid organ transplant recipients. After kidney transplantation, quantification of TTV viral load may serve as a risk stratification tool for allograft rejection and infectious events. Besides a robust and independent association between recipient age, sex and TTV load, respectively, limited data exists on other potential determinants of TTV load. This trial was designed to analyse the association between TTV and detailed recipient and donor baseline characteristics and clinical follow-up parameters. METHOD This retrospective analysis included all 386 consecutive adult recipients of a kidney allograft transplanted between 1 January 2016 and 30 June 2018 at the Medical University Vienna from the prospective observational TTV-POET trial (institutional review board approval number: 1785/2016; German Clinical Trials Registry number: DRKS00012335). For the present analysis, we included TTV measures before transplantation (d0), at month 1 (m1), at month 3 (m3) and at month 12 (m12) after transplantation. TTV DNA was extracted from patient plasma and assessed by real-time PCR with laboratory-developed primers. TTV load was associated with recipient and donor baseline characteristics and follow-up data. RESULTS The median recipient and donor age at transplantation was 55 years. A total of 135 (35%) kidney allograft recipients were female; 74 patients (19%) had a history of prior kidney transplantation; and 318 patients (82%) received a deceased donor kidney transplant. A total of 34 patients (9%) had pre-formed donor-specific antibodies (DSA); 19 patients (5%) received an AB0-incompatible transplant. For the whole cohort, 1-year patient survival was 95.6% and 1-year death censored graft survival was 94.8%. Baseline TTV load (d0) was lower in female recipients (P = 0.003) and higher in older recipients {β 0.033, [95% confidence interval (95% CI) 0.002–0.066]; P = 0.039}. Baseline TTV load was not associated with recipient body mass index and a history of immunological causes of end-stage renal disease and diabetes mellitus, respectively. TTV load within the first year after kidney transplantation did not show an association with the prevalence of preformed DSA, induction treatment, AB0-incompatibility and HLA-mismatch, respectively. Our trial detected an association between donor age and TTV load. Recipients from older donors showed higher TTV loads (m1, β 0.037, 95% CI 0.008–0.065, P = .01; m3, β 0.04, 95% CI 0.012–0.068, P = .005; m12, β 0.065, 95% CI 0.028–0.01, P = .001). There was no association between TTV load during the first year after transplantation and donor sex. When investigating the association between TTV load and clinical follow-up data, TTV levels showed a negative correlation with peripheral blood leukocyte and lymphocyte counts during the first year after transplantation [lymphocytes: m1, β –0.867, 95% CI –1.367–0.364, P = .01; m3, β –0.985, 95% CI –1.709–0.260, P = .008; m12, β –1.304, 95% CI –2.156–0.452, P = .003; data on leukocytes not shown). These findings might reflect the role of lymphocytes for TTV control. Additionally, TTV viral load negatively correlated with the estimated glomerular filtration rate (MDRD) within the first year after kidney transplantation (m1, β –0.043, 95% CI –0.066–0.02, P &amp;lt; .001; m3, β –0.024, 95% CI –0.049–0.001, P = .06; m12, β –0.078, 95% CI –0.111–0.045, P &amp;lt; .001). One might speculate that a higher eGFR might be a proxy for a healthier donor being more capable of controlling TTV infection. TTV viral load was associated with tacrolimus trough levels in month 12 after transplantation (β 1.262, 95% CI 0.0221–0.250; P = .019), but not with the amount of mycophenolic acid dosage. CONCLUSION This study revealed an association between TTV viral load and distinct baseline donor and recipient characteristics and clinical follow-up data, including kidney function. Further analysis, especially longitudinal assessment of TTV levels, may help to further dissect the interplay between TTV viral load and the state of immunosuppression in patients undergoing kidney transplantation.

The Fluctuation Trend of Serum Anti-SARS-CoV-2 IgM/IgG Antibodies Seroprevalence in the Non-COVID-19 Infected Population and Correlation with Peripheral Blood Leukocyte Parameters in Beijing, China, 2021: A Real-World Study.

Since 2019, the coronavirus disease 2019 (COVID-19) global pandemic has caused more than 300 million cases of disease and 5 million deaths. Vaccination has been widely accepted as the most effective measure for the prevention and control of this disease. However, there is little understanding about serum anti-SARS-CoV-2 IgM/IgG levels after inactivated vaccination as well as the relationship with peripheral blood leukocytes in the non-COVID-19 infected population. A total of 16,335 male and 22,302 female participants were recruited in this study, which was conducted in the Peking University Third Hospital located in Beijing (China). The level and seroprevalence of serum anti-SARS-CoV-2 receptor-binding domain (RBD) IgM/IgG and the association with peripheral blood leukocytes classification were investigated. With an increase in the number and percentage of full immunization of COVID-19 vaccinations in Beijing, serum anti-SARS-CoV-2 IgG antibodies levels and seroprevalence were significantly elevated (p < 0.01). The serum anti-SARS-CoV-2 IgG antibodies of 60 years and older persons were significantly lower than that of individuals that are 18~60 years old (p < 0.01), and there was a positive relationship between serum anti-SARS-CoV-2 IgG antibodies levels and peripheral blood lymphocyte count. The investigation of serum anti-SARS-CoV-2 IgM/IgG antibodies and the peripheral hematological index may prompt and help understand the adaptive immune response of vaccination.

Metagenomic Analyses Reveal Distinct Gut Microbiota Signature for Predicting the Neoadjuvant Chemotherapy Responsiveness in Breast Cancer Patients.

BackgroundGrowing evidence supports the modulatory role of human gut microbiome on neoadjuvant chemotherapy (NAC) efficacy. However, the relationships among the gut microbiome, tumor-infiltrating lymphocytes (TILs), and NAC response for breast cancer (BC) patients remain unclear. We thus proposed this preliminary study to investigate the relationship between gut microbiome and BC patients’ responses to NAC treatment as well as underlying mechanisms.MethodsPrior to receiving NAC, the fecal metagenome collected from 23 patients with invasive BC was analyzed. Patients were subsequently assigned to the NAC non-effectual group and the NAC effectual group based on their response to NAC. The peripheral T lymphocyte subset counts were examined by flow cytometry methods. CellMinor analysis was employed to explore the relationship between CD4 mRNA expression and the reaction of tumor cells to NAC drugs.ResultsThe gut microbiomes of the NAC non-effectual group showed characteristics of low diversity with low abundances, distinct metagenomic composition with decreased butyrate-producing and indolepropionic acid-producing bacteria, and increased potential pathobionts compared with the NAC effectual group. The combination of Coprococcus, Dorea, and uncultured Ruminococcus sp. serves as signature bacteria for distinguishing NAC non-effectual group patients from the NAC effectual group. The absolute numbers of CD4+ and CD8+ TIL infiltration in tumors in the NAC non-effectual group were significantly lower than those in the effectual group. Similar findings were reported for the CD4+ T lymphocytes in the peripheral blood (p’s < 0.05). NAC effectual-related signature bacteria were proportional to these patients’ CD4+ T lymphocyte counts in peripheral blood and tumors (p’s < 0.05). CellMinor analysis showed that the CD4 mRNA expression level dramatically climbed with increased sensitivity of tumor cells to NAC drugs such as cyclophosphamide, cisplatin, and carboplatin (p’s < 0.05).ConclusionsThe composition of the gut microbial community differs between BC patients for whom NAC is effective to those that are treatment resistant. The modulation of the gut microbiota on host CD4+ T lymphocytes may be one critical mechanism underlying chemosensitivity and NAC pathologic response. Taken together, gut microbiota may serve as a potential biomarker for NAC response, which sheds light on novel intervention targets in the treatment of NAC non-effectual BC patients.

Predictive value of prognostic nutritional index on infection after radical gastrectomy: a retrospective study.

The prognostic nutritional index (PNI) is a useful tool to evaluate nutritional status, which is associated with postoperative complications and prognosis of patients with cancer. Recent studies have shown that PNI has important predictive value for postoperative infection in cancer patients. However, the role and clinical value of PNI in infection after radical gastrectomy remains unclear. This study investigated the relationship between PNI and infection after radical surgery for gastric cancer (GC), focusing on the predictive value of PNI. A total of 1,111 patients with primary gastric cancer who underwent radical surgery in our hospital from December 2010 to December 2020 were included in this retrospective study. The demographic and clinicopathological data of all patients were acquired through hospital information system (HIS). Preoperative serum albumin (ALB) level and peripheral blood lymphocyte count were obtained for PNI calculation. We selected 812 patients by propensity score matching to reduce biases due to the different distributions of co-variables among the comparable groups. The factors influencing postoperative infection in the matched patients were explored using univariate and multivariate analyses. Baseline characteristics significantly differed among patients with different PNI scores. After one-to-one matching, the clinicopathological data of the 2 groups were comparable, and 812 patients were included for further analysis. Among these patients, 101 developed infections, with an infection rate of 12.4%, which were mainly caused by gram-negative bacteria. The incidence of infection was significantly higher in the low PNI group than in the high PNI group. Univariate and multivariate analyses identified body mass index (BMI) ≥25 kg/m2 [odds ratio (OR) =2.314, P=0.004], diabetes mellitus (OR =1.827, P=0.042), PNI score <45 (OR =2.138, P=0.037), combined multi-organ resection (OR =2.946, P<0.001), operation time ≥240 minutes (OR =2.744, P=0.023), and perioperative blood transfusion (OR =2.595, P=0.025) as risk factors for infection after radical surgery for GC. Infection is the most common complication after radical gastrectomy for GC, and a low preoperative PNI score is a risk factor for postoperative infection.

The Prognostic Value of Prognostic Nutritional Index in Patients with Lymphoma--Review

The morbidity and mortality of hematological tumors have shown a rising tendency in recent years and become one of the major diseases which affect public health. The nutritional and inflammation status of the body has been proved to play an important role in the occurrence, development and prognosis of the blood system disease. The prognostic nutritional index (PNI) is an important index to reflect the nutritional and inflammation status of the body, and it can be calculated by serum albumin level and peripheral blood lymphocyte count. A large number of studies have reported that PNI can effectively predict the prognosis of several hematological tumors, including lymphoma. In this review, the prognostic value of PNI in patients with lymphoma was summarized briefly.

Unvaccinated Children Are an Important Link in the Transmission of SARS-CoV-2 Delta Variant (B1.617.2): Comparative Clinical Evidence From a Recent Community Surge.

ObjectiveTo evaluate the necessity of Covid-19 vaccination in children aged < 12 y by comparing the clinical characteristics between unvaccinated children aged < 12 y and vaccinated patients aged ≥ 12y during the Delta surge (B.1.617.2) in Putian, Fujian, China.MethodsA total of 226 patients with SARS-Cov-2 Delta variant (B.1.167.2; confirmed by Real-time PCR positivity and sequencing) were enrolled from Sep 10th to Oct 20th, 2021, including 77 unvaccinated children (aged < 12y) and 149 people aged ≥ 12y, mostly vaccinated. The transmission route was explored and the clinical data of two groups were compared; The effect factors for the time of the nucleic acid negativization (NAN) were examined by R statistical analysis.ResultsThe Delta surge in Putian spread from children in schools to factories, mostly through family contact. Compared with those aged ≥ 12y, patients aged < 12y accounted for 34.07% of the total and showed milder fever, less cough and fatigue; they reported higher peripheral blood lymphocyte counts [1.84 (1.32, 2.71)×10^9/L vs. 1.31 (0.94, 1.85)×10^9/L; p<0.05), higher normal CRP rate (92.21% vs. 57.72%), lower IL-6 levels [5.28 (3.31, 8.13) vs. 9.10 (4.37, 15.14); p<0.05]. Upon admission, their COVID19 antibodies (IgM and IgG) and IgG in convalescence were lower [0.13 (0.00, 0.09) vs. 0.12 (0.03, 0.41), p<0.05; 0.02 (0.00, 0.14) vs. 1.94 (0.54, 6.40), p<0.05; 5.46 (2.41, 9.26) vs. 73.63 (54.63, 86.55), p<0.05, respectively], but longer NAN time (18 days vs. 16 days, p=0.13).ConclusionUnvaccinated children may be an important link in the transmission of SARS-CoV-2 delta variant (B1.617.2), which indicated an urgent need of vaccination for this particular population.

SARS-CoV-2 Dysregulates Neutrophil Degranulation and Reduces Lymphocyte Counts.

SARS-CoV-2, the virus that causes COVID-19, has given rise to one of the largest pandemics, affecting millions worldwide. High neutrophil-to-lymphocyte ratios have been identified as an important correlate to poor recovery rates in severe COVID-19 patients. However, the mechanisms underlying this clinical outcome and the reasons for its correlation to poor prognosis are unclear. Furthermore, the mechanisms involved in healthy neutrophils acquiring a SARS-CoV-2-mediated detrimental role are yet to be fully understood. In this study, we isolated circulating neutrophils from healthy donors for treatment with supernates from infected epithelial cells and direct infection with SARS-CoV-2 in vitro. Infected epithelial cells induced a dysregulated degranulation of primary granules with a decrease in myeloperoxidase (MPO), but slight increase in neutrophil elastase release. Infection of neutrophils resulted in an impairment of both MPO and elastase release, even though CD16 receptor shedding was upregulated. Importantly, SARS-CoV-2-infected neutrophils had a direct effect on peripheral blood lymphocyte counts, with decreasing numbers of CD19+ B cells, CD8+ T cells, and CD4+ T cells. Together, this study highlights the independent role of neutrophils in contributing to the aberrant immune responses observed during SARS-CoV-2 infection that may be further dysregulated in the presence of other immune cells.

The clinical effects of Vinorelbine for advanced and recurrent breast cancer patients

Background: Vinorelbine (VNB) is one of the key drugs for advanced and recurrent breast cancer, but it was often used in the later line because of the advent of eribulin and bevacizumab. We examined the effect of VNB by subtypes and the peripheral blood lymphocyte count (LY) and the ratio of peripheral blood neutrophil and lymphocyte count (NLR).

Serotherapy as Graft-Versus-Host Disease Prophylaxis in Haematopoietic Stem Cell Transplantation for Acute Lymphoblastic Leukaemia.

Serotherapy comprising agents such as anti-thymocyte globulin, anti-T-lymphocyte globulin, and the anti-CD52 monoclonal antibody alemtuzumab is used widely to reduce the incidence of graft-versus-host disease (GvHD) after paediatric haematopoietic stem cell transplantation (HSCT). The outcome of transplants using matched unrelated donors now approaches that of matched sibling donors. This is likely due to better disease control in recipients, the use of donors more closely human-leukocyte antigen (HLA)-matched to recipients, and more effective graft-versus-host disease (GvHD) prophylaxis. The price paid for reduced GvHD is slower immune reconstitution of T cells and thus more infections. This has led to studies looking to optimise the amount of serotherapy used. The balance between prevention of GvHD on one side and prevention of infections and relapse on the other side is quite delicate. Serotherapy is given with chemotherapy-/radiotherapy-based conditioning prior to HSCT. Due to their long half-lives, agents used for serotherapy may be detectable in patients well after graft infusion. This exposes the graft-infused T cells to a lympholytic effect, impacting T-cell recovery. As such, excessive serotherapy dosing may lead to no GvHD but a higher incidence of infections and relapse of leukaemia, while under-dosing may result in a higher chance of serious GvHD as immunity recovers more quickly. Individualised dosing is being developed through studies including retrospective analyses of serotherapy exposure, population pharmacokinetic modelling, therapeutic drug monitoring in certain centres, and the development of dosing models reliant on factors including the patient's peripheral blood lymphocyte count. Early results of “optimal” dosing strategies for serotherapy and conditioning chemotherapy show promise of improved overall survival.

Radiomitigation by Melatonin in C57BL/6 Mice: Possible Implications as Adjuvant in Radiotherapy and Chemotherapy.

Melatonin (N-acetyl-5-methoxytryptamine), a chief secretory molecule of the pineal gland, has multiple properties, and numerous clinical investigations regarding its actions are in progress. This study investigated the radiomitigative role of melatonin in C57BL/6 mice. Melatonin (100 mg/kg) was orally administered once daily starting at 1 h on day 1 and subsequently every 24 h until day 7 after whole-body irradiation (WBI) and survival was monitored for 30 days. The bone marrow, spleen, and intestine were studied to evaluate the mitigative potential of melatonin after radiation-induced damage. Melatonin significantly improved the survival upto 60% and 90% after 9 Gy (lethal) and 7.5 Gy (sub-lethal) WBI, respectively. Melatonin alleviated WBI-induced myelosuppression and pancytopenia, and increased white blood cell, red blood cell, platelet, and lymphocyte (CD4+ and CD8+) counts in peripheral blood. Bone marrow and spleen cellularity were restored through enhanced haematopoiesis. Melatonin ameliorated the damage in the small intestine, and promoted recovery of villi length, crypts number, and goblet cell count. Melatonin mitigates the radiation-induced injury in the gastrointestinal and haematopoietic systems. The observed radiomitigative properties of melatonin can also be useful in the context of adjuvant therapy for cancer and radiotherapy.

Coronavirus Disease 2019: Hysteresis Effect of Chest CT and the Correlation with its Severity.

The purpose of this study was to investigate the influencing factors for chest CT hysteresis and severity of coronavirus disease 2019 (COVID-19). The chest CT data of patients with confirmed COVID-19 in 4 hospitals were retrospectively analyzed. An independent assessment was performed by one clinician using the DEXIN FACT Workstation Analysis System, and the assessment results were reviewed by another clinician. Furthermore, the mean hysteresis time was calculated according to the median time from progression to the most serious situation to improve chest CT in patients after fever relief. The optimal scaling regression analysis was performed by including variables with statistical significance in univariate analysis. In addition, a multivariate regression model was established to investigate the relationship of the percentage of lesion/total lung volume with lymphocyte and other variables. In the included 166 patients with COVID-19, the average value of the most serious percentage of lesion/total lung volume was 6.62, of which 90 patients with fever had an average hysteresis time of 4.5 days after symptom relief, with a similar trend observed in those without fever. Multivariate analysis revealed that lymphocyte count in peripheral blood and transcutaneous oxygen saturation decreased with the increase of the percentage of lesion/total lung volume. There is a hysteresis effect in the improvement of chest CT image relative to fever relief in patients with COVID-19. The pulmonary lesions may be related to the severity as well as decreased lymphocyte count or percutaneous oxygen saturation.

652. Comparison of QuantiFERON-TB Gold Plus and T-SPOT.TB in the Diagnosis of Active Tuberculosis

Background Objective: To compare the accuracy of Quantiferon ®- TB Gold Plus (QFT-Plus) and T-SPOT.TB in the diagnosis of active tuberculosis (ATB).MethodsFrom April 2020 to May 2021, patients with pathologically confirmed or clinically diagnosed ATB in Peking Union Medical College Hospital and Beijing Chest Hospital were enrolled as case group, while patients excluded from ATB in the same period were enrolled as control group, The clinical and laboratory information were collected. QFT-Plus and T-SPOT. TB were tested simultaneously to evaluate the consistency of the results and compare the sensitivity, specificity, predictive values and likelihood ratios for diagnosing ATB.ResultsFifty-seven ATB patients and 159 non-ATB patients were included. 33 (57.9%) ATB patients were pathologically confirmed. The proportions of indeterminate results in QFT-Plus and T-SPOT.TB were 3.7% vs 0%, respectively. The agreement between the results of the QFT-Plus and T-SPOT.TB was substantial (kappa=0.644, p＜0.001). The area under the ROC curve of the QFT-Plus and T-SPOT.TB for diagnosing ATB was 0.759 (95%CI 0.689-0.829) vs 0.810 (95%CI 0.742-0.877), respectively, and there was no significant difference (p=0.303). the sensitivity of the QFT-Plus and T-SPOT.TB was 85.2% vs 89.5%, while the specificity was 61.7% vs 52.2%, respectively. In 33 Patients with pathologically confirmed ATB, the sensitivity of QFT-Plus and T-SPOT.TB was 87.9% vs 93.9% (p=0.669), respectively. In 78 patients (36.1%) who received glucocorticoid / immunosuppressive / biological agents, the positive rate of QFT-Plus was 35.9% (28/78), which was significantly lower than that of those who did not receive these agents (77 / 138pm,55.8%) (p=0.005), but there was no significant difference in the positive rate of T-SPOT.TB between the two groups (52.6% vs. 62.3%, p=0.162). The positive rate for both tests was independent of the peripheral blood lymphocyte count (p=0.675 for QFT-Plus vs. P=0.138 for T-SPOT.TB). ConclusionThere was no significant difference between the QFT-Plus and T-SPOT.TB in the diagnosis of ATB. QFT-plus might be prone to indeterminate results and influenced by the immunosuppressive status. The results need to be verified by a prospective cohort study with large sample. Disclosures All Authors: No reported disclosures

Analysis of clinical characteristics of patients with chronic critical illness after sepsis

To investigate the clinical characteristics of patients who develop chronic critical illness (CCI) after sepsis. The survival patients with sepsis admitted to the department of critical medicine of Baoan Central Hospital of Shenzhen for the first time from April 2019 to October 2020 were enrolled. According to clinical outcomes, patients were divided into CCI group [intensive care unit (ICU) stay ≥ 14 days, with persistent organ dysfunction] and rapid recovery (RAP) group. The baseline characteristic on admission and clinical outcomes of patients in the two groups were collected and compared. Blood samples were collected to measure serum interleukins (IL-6, IL-10) levels and peripheral blood lymphocyte count (LYM) count were obtained from all patients after admission. The differences of above indexes on the 1st, 7th and 14th day in ICU between the two groups were compared, the 180 day cumulative survival rate of the two groups was observed. (1) Twenty-two septic patients developed CCI and 28 patients with RAP were included. There were no significant differences in gender and infection site between the two groups. The age, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), proportion of septic shock, mechanical ventilation time, length of ICU stay, total length of hospital stay and proportion of secondary infection of CCI patients were higher than those in RAP group [age (years old): 61.0±13.8 vs. 50.3±13.9, proportion of patients aged ≥ 65 years old: 54.5% (12/22) vs. 25.0% (7/28), APACHE II score: 20.5±4.4 vs. 14.4±4.3, SOFA score: 10 (7, 12) vs. 5 (3, 8), septic shock ratio: 40.9% (9/22) vs. 17.9% (5/28), time of mechanical ventilation (days): 18.5 (12.0, 28.0) vs. 5.0 (3.0, 7.0), length of ICU stay (days): 26 (18, 46) vs. 8 (6, 12), total length of hospital stay (days): 31 (26, 51) vs. 14 (12, 17), secondary infection ratio: 72.7% (16/22) vs. 7.1% (2/28), all P < 0.05]. (2) The IL-6 levels of CCI group were higher than that of RAP group at all time points (ng/L: 176.86±103.54 vs. 113.32±71.34 on the 1st day, 84.72±46.06 vs. 54.98±26.61 on the 7th day, 44.28±20.20 vs. 17.76±4.70 on the 14th day, all P < 0.05). On the 1st and 7th day of admission, there were no significant differences in IL-10 and LYM levels between the two groups. On the 14th day of admission, IL-10 levels in CCI group were higher than that in RAP group (ng/L: 15.09±3.61 vs. 8.92±1.98, P < 0.05), while LYM was relatively lower [×109/L: 0.62 (0.43, 1.02) vs. 1.17 (0.93, 1.71), P < 0.05]. (3) The Log-Rank test results of Kaplan-Meier survival curve showed that the 180-day cumulative survival rate of CCI group was significantly lower than that of RAP group (63.6% vs. 96.4%, Log-Rank: χ2 = 9.024, P = 0.007). Septic patients with advanced age, high APAHCE II score and high SOFA score are prone to secondary CCI, resulting in long hospital stay, high secondary infection rate and poor prognosis. The occurrence of CCI may be related to the continuous expression of proinflammatory mediators and subsequent immunosuppression.