Lymphocyte Count In Patients Research Articles

Efficacy and safety evaluation of mixed nutrition for postoperative esophageal cancer patients in China: a meta-analysis.

The purpose of this study was to evaluate the clinical effect of mixed nutrition and parenteral nutrition support on postoperative patients with esophageal cancer. By searching PubMed, Web of Science, Cochrane, CNKI, Wanfang and other databases, all the literatures until March 2024 about the comparison of randomized controlled Trial (RCT) of mixed nutrition and parenteral nutrition support in postoperative patients with esophageal cancer were screened. The inclusion criteria were that the patients were from randomized controlled trials or clinical trials in China, and the patients were all diagnosed with esophageal cancer by pathological biopsy. The exclusion criteria were the literature other than the above, including repeated published literature, non-Chinese and English literature, incomplete or missing analysis data, etc. After two researchers independently screened the literature, extracted the data and evaluated the risk of bias according to the criteria, Meta-analysis was carried out with RevMan 5.4 software. A total of 11 studies were included, including 1216 patients. Meta-analysis showed that, compared with parenteral nutrition, mixed nutrition can improve the levels of transferrin, serum albumin, prealbumin and lymphocyte counts in patients with esophageal cancer after surgery, shorten the time of anal recovery of exhaust, defecation and hospital stay after surgery, and reduce the incidence of pulmonary infection, abdominal distension, incision infection and anastomotic fistula, with statistical significance between the two groups (P < 0.05). The heterogeneity of individual results in this study is relatively high, the analysis comes from clinical heterogeneity, and the publication bias is analyzed through Funnel plot. Taking the incidence of lung infection as an example, the results are evenly distributed on both sides of the Funnel plot, and the publication bias has little impact on the results of the study. Compared with parenteral nutrition, mixed nutrition can improve the prognosis of postoperative patients with esophageal cancer and reduce the incidence of related adverse events.

Exploring the prognostic impact of absolute lymphocyte count in patients treated with immune-checkpoint inhibitors

BackgroundThe role of immune checkpoint inhibitors (ICI) expands but affordable and reproducible prognostic biomarkers are needed. We investigated the association between baseline and 3-month absolute lymphocyte count (ALC) and survival for patients on ICI.MethodsA retrospective study investigated patients who received ICI July 2014—August 2019. Survival probabilities were calculated for lymphocyte subsets. Univariate and multivariate analyses were performed to investigate risk factors for lymphopenia.ResultsAmong 179 patients, median age was 62 and 41% were female. The most common diagnoses were melanoma (41%) and lung cancer (40%). Median PFS was 6.5 months. 27% had baseline lymphopenia (ALC < 1 × 109cells/L) and no significant difference in PFS or OS to those with normal ALC. However, 31% had lymphopenia at 3 months and significantly shorter OS than those without (9.8 vs 18.3 months, p < 0.001). Those with baseline lymphopenia who recovered counts at 3 months had no difference in PFS (median NR vs 13.0 months, p = 0.48) or OS (22 vs 18.3 months, p = 0.548) to those never lymphopenic. The strongest risk factor for lymphopenia on multivariable analysis was previous radiation therapy (RT).Conclusions3-month lymphopenia is a negative prognostic marker in cancer patients on ICI. Previous RT is significantly associated with lymphopenia.

213P Prognostic significance of absolute lymphocyte count in patients with metastatic renal cell carcinoma treated with first-line combination immunotherapies: Results from the International metastatic renal cell carcinoma database consortium (IMDC)

213P Prognostic significance of absolute lymphocyte count in patients with metastatic renal cell carcinoma treated with first-line combination immunotherapies: Results from the International metastatic renal cell carcinoma database consortium (IMDC)

Diagnostic and Prognostic Value of Neutrophil-Lymphocyte Ratio in Adrenocortical Carcinoma

BackgroundThe aim was to explore the value of neutrophil-lymphocyte ratio (NLR) as a biomarker for predicting the prognosis or diagnosis in adrenocortical carcinoma (ACC). MethodsWe identified 262 patients with adrenal gland disease who underwent operation at our institution between 2013 and 2018. According to postoperative pathology, patients were divided into 2 groups: ACC and non-ACC groups. The neutrophil and lymphocyte count of patients were recorded. Within the intergroup comparison, data obtained from ACC and non-ACC groups were evaluated using ANOVA test. The cut-off values of NLR for the prognosis in ACC were determined according to 3 methods. ResultsThe NLR values of ACC and non-ACC groups were 5.36 ± 5.30 and (1.73 ± 0.26) ∼ (2.56 ± 1.35), respectively (P < .001). NLR carry a differential property was evaluated with ROC curve to distinguish the above 2 groups. The cut-off value of NLR was estimated as 2.65 according to the Youden index. With this value, sensitivity was found as 67.5%, specificity was 83.8% and AUC was 0.749 (P < .001, confidence interval = 0.638-0.860). In ACC, the higher NLR group was not shown significantly poorer overall survival than the lower NLR group (NLR ≥2.65 vs. NLR < 2.65, NLR ≥5 vs. NLR <5, NLR ≥5.36 vs. NLR <5.36) (P > .05). ConclusionAccording to the data in this study, it can be said that adrenocortical tumors are likely to be malignant by 67.5% if the NLR value is greater than 2.65. When we use the NLR to predict the prognosis of ACC, there is not statistically significant.

Association between pretreatment lymphocyte count and efficacy of immune-enhancing therapy in acute necrotising pancreatitis: a post-hoc analysis of the multicentre, randomised, placebo-controlled TRACE trial

Immune-enhancing thymosin alpha 1 (Tα1) therapy may reduce infected pancreatic necrosis (IPN) in acute necrotising pancreatitis (ANP). However, the efficacy might be impacted by lymphocyte count due to the pharmacological action of Tα1. In this post-hoc analysis, we tested the hypothesis that pre-treatment absolute lymphocyte count (ALC) determines whether patients with ANP benefit from Tα1 therapy. A post-hoc analysis of data from a multicentre, double-blind, randomised, placebo-controlled trial testing the efficacy of Tα1 therapy in patients with predicted severe ANP was performed. Patients from 16 hospitals of China were randomised to receive a subcutaneous injection of Tα1 1.6mg every 12h for the frst 7 days and 1.6mg once a day for the following 7 days or a matching placebo during the same period. Patients who discontinued the Tα1 regimen prematurely were excluded. Three subgroup analyses were conducted using the baseline ALC (at randomisation), and the group allocation was maintained as intention-to-treat. The primary outcome was the incidence of IPN 90 days after randomisation. The fitted logistic regression model was applied to identify the range of baseline ALC where Tα1 therapy could exert a maximum effect. The original trial is registered with ClinicalTrials.gov, NCT02473406. Between March 18, 2017, and December 10, 2020, a total of 508 patients were randomised in the original trial, and 502 were involved in this analysis, with 248 in the Tα1 group and 254 in the placebo group. Across the three subgroups, there was a uniform trend toward more significant treatment effects in patients with higher baseline ALC. Within the subgroup of patients with baseline ALC≥0.8×10ˆ9/L (n=290), the Tα1 therapy significantly reduced the risk of IPN (covariate adjusted risk difference,-0.12; 95% CI,-0.21,-0.02; p=0.015). Patients with baseline ALC between 0.79 and 2.00×10ˆ9/L benefited most from the Tα1 therapy in reducing IPN (n=263). This post-hoc analysis found that the efficacy of immune-enhancing Tα1 therapy on the incidence of IPN may be associated with pretreatment lymphocyte count in patients with acute necrotising pancreatitis. National Natural Science Foundation of China.

Prognostic Value of Absolute Lymphocyte Count in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab Plus Ipilimumab

Nivolumab and ipilimumab (NIVO + IPI) is standard therapy for patients with advanced renal cell carcinoma (RCC). Absolute lymphocyte count (ALC) is a valuable prognostic factor in patients with various cancers treated with immune checkpoint inhibitors. Herein, we determined the prognostic value of pretreatment ALC in advanced RCC patients treated with NIVO + IPI as first-line therapy. Data from 46 advanced RCC patients treated with NIVO + IPI between September 2018 and August 2022 were retrospectively reviewed and analyzed. Median progression-free survival (PFS) and overall survival (OS) were significantly shorter in patients with low than high ALC (PFS: p = 0.0095; OS: p = 0.0182). Multivariate analysis suggested that prior nephrectomy [hazard ratio (HR) = 3.854, 95% confidence interval (CI) = 1.433-10.359, p = 0.0075] and pretreatment ALC (HR = 2.513, 95% CI = 1.119-5.648, p = 0.0257) were independent factors for PFS. Our new prognostic ALNx model based on ALC and prior nephrectomy suggested that the poor-risk group was a predictor of significantly worse PFS (p < 0.0001) and OS (p = 0.0016). Collectively, the developed ALNx model may be a novel predictor of response in advanced RCC patients treated with NIVO + IPI.

Temporal evolution and differential patterns of cellular reconstitution after therapy for childhood cancers

The cellular reconstitution after childhood cancer therapy is associated with the risk of infection and efficacy of revaccination. Many studies have described the reconstitution after stem cell transplantation (SCT). The recovery after cancer treatment in children who have not undergone SCT has mainly been investigated in acute lymphoblastic leukemia (ALL), less for solid tumors. Here, we have examined the temporal evolution of total leukocyte, neutrophil and lymphocyte counts as surrogate parameters for the post-therapeutic immune recovery in a cohort of n = 52 patients with ALL in comparison to n = 58 patients with Hodgkin’s disease (HD) and n = 22 patients with Ewing sarcoma (ES). Patients with ALL showed an efficient increase in blood counts reaching the age-adjusted lower limits of normal between 4 and 5 months after the end of maintenance therapy. The two groups of patients with HD and ES exhibited a comparably delayed recovery of total leukocytes due to a protracted post-therapeutic lymphopenia which was most pronounced in patients with HD after irradiation. Overall, we observed a clearly more efficient resurgence of total lymphocyte counts in patients aged below 12 years compared to patients aged 12 to 18 years. Our results underline that the kinetics of cellular reconstitution after therapy for HD and ES differ significantly from ALL and depend on treatment regimens and modalities as well as on patient age. This suggests a need for disease, treatment, and age specific recommendations concerning the duration of infection prophylaxis and the timing of revaccination.

Nitric Oxide, Neutrophil/Lymphocyte, and Platelet/Lymphocyte Ratios as Promising Inflammatory Biomarkers in Complicated Crohn’s Disease: Outcomes of Corticosteroids and Anti-TNF-α Therapies

Crohn's disease (CD) is a relapsing-remitting inflammatory bowel disease with a progressive course. The aim of our study was to evaluate the relationship between nitric oxide (NO), pro-inflammatory cytokines, and blood count-based ratios in patients with complicated Crohn's disease as well as the outcome of corticosteroid or anti-TNF-α therapy. In this context, we evaluated the NLR as the ratio of neutrophils count to lymphocytes count, PLR as the ratio of platelets count to lymphocytes count, and MLR as the ratio of monocytes count to lymphocytes count in patients and controls. Furthermore, we assessed NO production by the Griess method in plasma along with iNOS and NF-κB expression by immunofluorescence method in intestinal tissues of patients and controls. In the same way, we evaluated plasma TNF-α, IL-17A, and IL-10 levels using ELISA. Our results indicate that blood count-based ratios NLR, PLR, and MLR were significantly higher in patients compared to controls. In addition, increased systemic levels of NO, TNF-α, and IL-17A and colonic expression of iNOS and NF-κB were observed in the same patients. Interestingly, the high ratio of NLR and MLR as well as NO production were significantly decreased in treated patients. Collectively, our findings suggest that nitric oxide as well as the blood count-based ratios (NLR, PLR, MLR) could constitute useful biomarkers in complicated Crohn's disease, predicting the response to treatments.

PEGylated Recombinant Adenosine Deaminase Maintains Detoxification and Lymphocyte Counts in Patients with ADA-SCID

PurposeMetabolic detoxification with enzyme replacement therapy (ERT) promotes immune recovery in patients with adenosine deaminase (ADA)–deficient severe combined immunodeficiency (ADA-SCID). Elapegademase is a PEGylated recombinant bovine ADA ERT developed to replace the now-discontinued bovine-derived pegademase. This study was a 1-way crossover from pegademase to elapegademase in 7 patients with ADA-SCID to assess efficacy and safety outcomes for elapegademase.MethodsAfter once-weekly pegademase dosage was adjusted to achieve therapeutic metabolic detoxification and trough ADA activity, patients transitioned to a bioequivalent dose of elapegademase. Maintenance of metabolic detoxification and adequate ADA activity were evaluated periodically.ResultsOne patient withdrew after 2 doses of an early elapegademase formulation due to injection-site pain caused by EDTA. The 6 remaining patients completed 71−216 weeks of elapegademase therapy with a formulation that did not contain EDTA. In these patients, elapegademase improved ADA activity compared with pegademase and maintained metabolic detoxification. Total lymphocyte counts increased for all completer patients from between 1.2- and 2.1-fold at the end of study compared with baseline. Elapegademase had a comparable safety profile to pegademase; no patient developed a severe infectious complication. Three patients had transient, non-neutralizing antibodies to pegademase, elapegademase, and/or polyethylene glycol ≤ 47 weeks of treatment without effect on trough plasma ADA activity or trough erythrocyte deoxyadenosine nucleotide levels.ConclusionElapegademase was safe, well tolerated, achieved stable trough plasma ADA activity with weekly dosing, was effective in maintaining metabolic detoxification, and was associated with maintenance or improvements in lymphocyte counts compared with pegademase therapy in patients with ADA-SCID.

Effect of lymphoid volume irradiation on radiation-induced lymphopenia in head and neck cancers

PurposeRadiotherapy induces significant and prolonged lymphopenia in head and neck cancer patients with poorer outcomes and reduced survival. Irradiated volumes may be correlated with lymphopenia with a potential impact on immunotherapy efficacy. We assessed associations between volumes treated with radiotherapy and the nadir of the lymphocyte count in patients with head and neck cancer. Materials and methodsWe conducted a monocentric retrospective study in patients with head and neck cancer treated with radiation. Univariate analysis used regression analysis to model nadir lymphocyte count and radiotherapy volumes; multivariate analysis then modelled factors associated with nadir lymphocyte count. ResultsOf the 77 included patients, 97% presented lymphopenia during radiotherapy with an average nadir of 431 cells/mm3 at a median of 40 days after the beginning of treatment. The volume of high-risk radiotherapy and gross tumour volume were correlated with nadir lymphocyte count with a Spearman coefficient of −0.267 (P=0.019) and −0.387 (P=0.001), respectively. After multivariate linear regression, high-risk radiotherapy was significantly associated with nadir lymphocyte count with a regression coefficient of −0.32 (per cubic centimetre) [95% CI=−0.60; −0.03] (P=0.028). ConclusionHigh-risk radiotherapy was significantly associated with nadir lymphocyte count in patients with head and neck cancer treated with radiation. Sparing lymphoid volumes from irradiation by elective nodal irradiation or proton therapy may limit lymphopenia and needs to be investigated in combination with immunotherapy.

Prevalence of Anti-Human Herpes Virus Type 7 IgG Positivity Rate among Children with Fever and Skin Rash in Diyala Province, Iraq.

Human herpesvirus 7 (HHV-7) is a T-lymphotropic virus isolated from peripheral blood mononuclear cells as beta herpes viruses. It is a highly prevalent virus since over 90% of adults are seropositive. The majority of primary infection occurs in early childhood, and its prevalence peaks at 60 % in 11-13-year-old. This study was designed to investigate the seroprevalence of HHV- 7 infections among apparently healthy children as well as child patients with fever and skin rash in the Diyala community and its association with certain socio-demographic variables. The current study is a cross-sectional study conducted in Diyala province-Iraq, extending from July 2020 to March 2021. A total of 180 child patients with fever and skin rash were included. Their age range was 1-14years. Additionally, 60 healthy age-matched children were enrolled as a control group. A special questionnaire was prepared for this study, including socio-demographic information, clinical notes and the results of a complete blood count. Human privacy was esteemed by obtaining parents' verbal approval. Blood specimen was aspirated from all study groups. Sera were separated and kept at -20 °C until tested. Enzyme-linked immunosorbent assay (ELISA) kits for the detection of anti-HHV-7 IgG were used (Mybiosource-China). Statistical analysis was done using Statistical Package of Social Science (SPSS) version 27, and the P value was considered significant wherever it was less than 0.05. The anti-HHV-7 IgG positivity rate in patients was 19.4%, and that in healthy individuals was 31.7%, with an insignificant difference (P=0.051). The highest HHV-7 IgG positivity rate was found among patients 1-4 years old, matching that in the healthy group with a statistically insignificant difference (P=0.675). The gender, residence and number of children/ family insignificantly affect the distribution of HHV-7 IgG in the control group. The mean±SD of hemoglobulin (Hb) concentration among participants with negative anti-HHV-7 IgG was insignificant compared to their positive counterparts (P=0.987). The mean±SD of total WBC count among those positive for anti-HHV-7 IgG was insignificantly higher than their negative counterpart (P=0.945). The mean±SD lymphocyte count in patients and healthy control positive for anti-HHV-7 IgG were insignificantly higher (P=0.241) and (P=0.344), respectively. Lastly, healthy control positive for anti-HHV-7 IgG had insignificantly higher lymphocyte count (P=0.710). About one-third of healthy children in our community were seropositive for anti-HHV 7 IgG antibodies that are most prevalent at 1-4 years old and are insignificantly associated with gender, residence, and the number of children per family. Furthermore, the HHV-7 infection is insignificantly associated with alterations of complete blood count parameters.

Clinical characteristics of children infected with SARS-CoV-2 Omicron variant combined with allergic disease

Objective: To investigate the clinical characteristics of children with allergic diseases suffering from SARS-CoV-2 Omicron variant strains. Methods: This was a cross-sectional study. A total of 43 pediatric patients with allergic diseases infected by SARS-CoV-2 from April 25, 2022 to June 8, 2022 in Shanghai Jiao Tong University School of Medicine were selected as the allergic disease group, while 114 cases without underlying diseases and 16 cases with other underlying diseases were selected as control groups diagnosed at the same period. Clinical data including clinical features, laboratory tests, duration of hospitalization, and the time to negative turn of novel coronavirus nucleic acid were collected and analysed. Kruskal-Wallis H test, chi-square test or Fisher exact test were used for comparison among three groups. Results: Among the 43 patients with allergic diseases, 28 were males and 15 were females, with an age of 4.4 (2.1, 8.2) years on admission, including 32 mild cases and 11 common cases. The allergic disease group included 20 cases (46.5%) of atopic dermatitis and eczema, followed by 14 cases (32.6%) of rhinitis, 8 cases (18.6%) of food allergies, 7 cases (16.3%) of asthma, 4 cases (9.3%) of allergic conjunctivitis and 2 cases (4.7%) of drug allergy. Among the 114 cases without underlying diseases, 57 were males and 57 were females, with an age of 2.8 (1.2, 5.6) years on admission, including 93 mild cases and 21 common cases. Among the 16 cases with other underlying diseases, 9 were males and 7 were females, with an age of 3.0 (2.6, 10.8) years on admission, including 13 cases mild and 3 cases common cases. Children with allergic diseases had higher frequency of sore throat and vomiting than those without underlying diseases (10 cases (23.3%) vs.9 cases (7.9%), 14 cases (32.6%) vs. 11 cases (9.6%), χ²=6.93, 12.24, both P<0.05). The lymphocyte count of patients with allergic disease was lower than those without underlying disease (1.1 (0.7,1.7)×109 vs. 1.6 (1.1,2.7)×109/L, H=-28.00,P=0.005). There were no significant differences in age, gender, typing of SARS-CoV-2, the duration of hospitalization, cycle threshold values of SARS-CoV-2 and the time to negative turn of novel coronavirus nucleic acid among the three groups (all P>0.05). Conclusions: Children with allergic diseases may suffer from sore throat and vomiting more frequently when infected with SARS-CoV-2 Omicron variant. The combination of allergic diseases hardly influenced the disease course of SARS-CoV-2 in children.

Relation between Cytokine Levels and Pulmonary Dysfunction in COVID-19 Patients: A Case-Control Study.

Aim: The study aimed to assess the relationships between serum cytokine levels and pulmonary dysfunctions in individuals with COVID-19. These correlations may help to suggest strategies for prevention and therapies of coronavirus disease. Patients and methods: Fifty healthy participants and one hundred COVID-19 patients participated in this study. COVID-19 participants were subdivided into moderate and severe groups based on the severity of their symptoms. In both patients and healthy controls, white blood cells (WBCs) and lymphocytes counts and serum C-reactive protein (CRP), interleukin (IL)-1, IL-4, IL-6, IL-18, and IL-35 levels were estimated. All the patients were examined by chest computed tomography (CT) and the COVID-19 Reporting and Data System (CO-RADS) score was assessed. Results: All COVID-19 patients had increased WBCs count and CRP, IL-1β, IL-4, IL-6, IL-18, and IL-35 serum levels than healthy controls. Whereas WBCs, CRP, and cytokines like IL-6 showed significantly higher levels in the severe group as compared to moderate patients, IL-4, IL-35, and IL-18 showed comparable levels in both disease groups. Lymphocytes count in all patient groups exhibited a significant decrease as compared to the heathy controls and it was significantly lower in severe COVID-19 than moderate. Furthermore, CO-RADS score was positively connected with WBCs count as well as CRP and cytokine (IL-35, IL-18, IL-6, IL-4 and IL-1β) levels in both groups. CO-RADS score, also demonstrated a positive correlation with lymphocytes count in the moderate COVID-19 patients, whereas it demonstrated a negative correlation in the severe patients. The receiver operator characteristic (ROC) curve analysis indicated that IL-1β, IL-4, IL-18, and IL-35 were fair (acceptable) predictors for COVID-19 in moderate cases. Whereas IL-6 was good predictor of COVID-19 in severe cases (AUC > 0.800), IL-18 and IL-35 were fair. Conclusion: Severe COVID-19 patients, compared to individuals with moderate illness and healthy controls, had lower lymphocyte counts and increased CRP with greater WBCs counts. In contrast to moderate COVID-19 patients, severe COVID-19 patients had higher levels of IL-6, but IL-4, IL-18, and IL-35 between both illness categories were at close levels. IL-6 level was the most potent predictor of COVID-19 progress and severity. CO-RADS 5 was the most frequent category in both moderate and severe cases. Patients with a typical CO-RADS involvement had a higher CRP and cytokine (IL-1β, IL-6, IL-4, IL-18, and IL-35) levels and WBCs count with a lower lymphocyte number than the others. Cytokine and CRP levels as well as WBCs and lymphocyte counts were considered surrogate markers of severe lung affection and pneumonia in COVID 19 patients.

Prognostic significance of neutrophil to lymphocyte ratio in patients with metastatic breast cancer on the background of eribulin therapy

Background. The neutrophil to lymphocyte ratio (NLR) is a prognostic marker in various carcinomas, including breast cancer. The NLR reflects the balance of systemic immunity and is associated with survival in patients with solid tumors.Aim. This study retrospectively evaluated the significance of the NLR and the absolute lymphocyte count in patients with breast cancer who received eribulin therapy.Materials and methods. The prognostic significance of the NLR and the absolute lymphocyte count in 33 patients with metastatic breast cancer treated with eribulin in 2020–2021 was analyzed.Results. The median follow-up time for patients was 9 [6; 15] months. Twenty-six of 33 (78.8 %) patients progressed. Seven of 33 (21.2 %) patients were censored due to therapy discontinuation, complete discontinuation after 1 course was required in 3 (9.1 %) patients and was associated with the development of hematological toxicity: 1 (3 %) case of a combination of grade 3 leucopenia and grade 3 thrombocytopenia, 2 (6 %) cases of grade 3 neutropenia. According to the analysis results, the NLR was a statistically significant risk factor for progression in patients on eribulin therapy, both without taking into account the influence of other factors (univariate model) and with the underlying influence of the absolute neutrophil count and the absolute lymphocyte count: hazard ratio (95 % confidence interval) was 1.21 [1.04; 1.41], p = 0.015 and 1.30 [1.07; 1.57], p = 0.008, respectively. There was no statistically significant effect of the absolute neutrophil count and the absolute lymphocyte count in both univariate and multivariate models. To illustrate the impact of SNL on the onset of progression, patients were divided into two subgroups based on median SNL: SNL˂ 2.46 and SNL ≥2.46. The median survival in patients with SNL ≥2.46 was 9 months, and in patients with SNL˂ 2.46 it was 15 months.Conclusion. The results of the pilot study state the NLR is a potential prognostic marker of long-term treatment with eribulin for patients with metastatic breast cancer, and can be used in clinical practice.

Prognostic value of absolute lymphocyte count in patients with advanced esophageal cancer treated with immunotherapy: a retrospective analysis.

BackgroundImmunotherapy has become the standard of treatment for recurrent metastatic esophageal cancer (EC), and the value of efficacy predictive markers represented by programmed death-ligand 1 (PD-L1) is limited. The purpose of this study is to analyze the prognostic value of peripheral blood absolute lymphocyte count (ALC) at baseline in patients with recurrent metastatic EC treated with immunotherapy, and to further investigate the relationship between the minimal ALC value (Min ALC) and radiotherapy (RT) parameters.MethodsThe main inclusion criteria were: histologically or imaging confirmed recurrent or metastatic EC; complete routine blood test data. A total of 105 patients were included in a single-center institution, 65 of whom had previously received RT. The optimal cut-off value for baseline lymphopenia was determined by the receiver operating characteristic (ROC) curve. The prognostic value of baseline phase lymphopenia for immunotherapy were determined by cox regression analysis and the associated factors affecting lymphopenia were explored by logistic regression analysis.ResultsThe cut-off value for baseline ALC predicting 1-year overall survival (OS) was 625 cells/µL. The OS was significantly lower in the lymphopenia group (ALC ≤625 cells/µL) than in the non-lymphopenia group (ALC >625 cells/µL) (median OS: 6 vs. 12 months, P=0.002). Multivariate analysis showed that pre-immunotherapy lymphopenia was an important factor influencing patient prognosis [hazard ratio (HR): 1.771, 95% confidence interval (CI): 1.051–2.985; P=0.032)] (adjusted for clinical factors including sex, age, tumor location, histology, degree of differentiation, distant metastasis, use of RT). Patients with a previous grade 4 (G4) Min ALC during RT were more likely to develop pre-immunotherapy lymphopenia following diagnosis of recurrent metastasis [odds ratio (OR): 10.809, 95% CI: 2.185–53.471; P=0.004]. Planning target volume (PTV) volume greater than 521.2 cm3 (OR: 19.981, 95% CI: 1.372–290.985; P=0.028) was an independent risk factor affecting the G4 Min ALC during RT.ConclusionsLymphopenia is associated with a poorer immunotherapy prognosis in patients with recurrent metastatic EC and those with previous G4 Min ALC after RT. RT-related parameters, especially irradiation volume, can significantly affect lymphocyte counts.

Development of a Fully Automated Method to Obtain Reproducible Lymphocyte Counts in Patients With Colorectal Cancer.

Colorectal cancer (CRC) is the third most common cancer worldwide. Although clinical outcome varies among patients diagnosed within the same TNM stage it is the cornerstone in treatment decisions as well as follow-up programmes. Tumor-infiltrating lymphocytes have added value when evaluating survival outcomes. The aim of this study was to develop a fully automated method for quantification of subsets of T lymphocytes in the invasive margin and central tumor in patients with CRC based on Deep Learning powered artificial intelligence. The study cohort consisted of 163 consecutive patients with a primary diagnosis of CRC followed by a surgical resection. Double-labeling immunohistochemical staining with cytokeratin in combination with CD3 or CD8, respectively, was performed on 1 representative slide from each patient. Visiopharm Quantitative Digital Pathology software was used to develop Application Protocol Packages for visualization of architectural details (background, normal epithelium, cancer epithelium, surrounding tissue), identification of central tumor and invasive margin as well as subsequent quantitative analysis of immune cells. Fully automated counts for CD3 and CD8 positive T cells were obtained in 93% and 92% of the cases, respectively. In the remaining cases, manual editing was required. In conclusion, the development of a fully automated method for counting CD3 + and CD8 + lymphocytes in a cohort of patients with CRC provided excellent results eliminating not only observer variability in lymphocyte counts but also in identifying the regions of interest for the quantitative analysis. Validation of the performance of the Application Protocol Packages including clinical correlation is needed.

Coinfections in hospitalized COVID-19 patients are associated with high mortality: need for improved diagnostic tools

Background: Hospitalized patients with COVID-19 often receive antimicrobial therapies due to concerns for bacterial and fungal coinfections. We analyzed patients admitted with COVID-19 to our VA facility to understand antimicrobial use, frequency of coinfections, and outcomes in our population. Methods: This retrospective study included veterans who were 18 years or older and hospitalized with COVID-19 from March 10, 2020, to March 9, 2021 at the Louis Stokes VA Medical Center in Cleveland, Ohio. We identified antimicrobials administered and coinfections with bacterial or fungal pathogens. Patients were deemed to have coinfection if there was supporting microbiological data and a consistent clinical course upon review of clinical records. Urinary tract infections were excluded because of difficulty determining infection. Odds ratios (ORs) and 95% confidence intervals (CIs) for 30-day mortality were derived using multivariate logistic regression models that included age, Charlson comorbidity index (CCI), corticosteroid use, and time of infection. Results: In our cohort of 312 patients, the median age was 70 years and 97% of the patients were male. The mean CCI was 3.7 (SD, 3.0), and 111 patients (35.6%) had a score ≥5. Oxygen was administered to 250 patients (80.1%), and 20 (6.4%) required mechanical ventilation. Antimicrobials were administered to 164 patients (52.6%) (Fig. 1). Of 20 patients (6.4%) with coinfection, 11 (3.5%) had a bloodstream infection (BSI) and 9 (2.9%) had bacterial pneumonia (Fig. 2). The overall 30-day mortality rate was 12.5% (39 of 312). Among patients with coinfection, the 30-day mortality rate was 45% (9 of 20). Diagnoses of BSI (OR, 6.35; 95% CI, 1.41–26.30) and bacterial pneumonia (OR, 9.34; 95% CI, 2.01–46.34) were associated with increased mortality. Of the data available, 12 (63%) of 19 patients with coinfection had elevated procalcitonin levels (ie, &gt;0.50). At the time of COVID-19 diagnosis, the median absolute lymphocyte count in patients who died was 0.7 K/mm3 (95% CI, 0.6–1.12) in comparison to 1 K/mm3 (95% CI, 0.7–1.4) in patients who survived at 30 days. Conclusions: Our analysis of hospitalized COVID-19 patients with advanced age and underlying comorbid conditions demonstrated that coinfections were infrequent but that they were independently associated with increased mortality. This finding highlights the need for better tools to diagnose the presence or absence of bacterial and fungal coinfection in COVID-19 patients. Our findings also emphasize the need for judicious use of antimicrobials while discerning which patients are at risk of critical illness and mortality.Funding: NoneDisclosures: None

The Relationship between Severity of Lung Involvement Based on High-Resolution Computed Tomography (HRCT) Findings and Lymphopenia in Patients with COVID-19

Background: Lymphopenia may reflect the degree of lung injury in patients with coronavirus disease 2019 (COVID-19). Given that few studies have been conducted in this regard, this study aimed to evaluate the association between severity of lung involvement based on high-resolution computed tomography (HRCT) findings and lymphocyte count in patients with COVID-19. Materials and Methods: This descriptive-analytical study was conducted on 123 patients with COVID-19 from March 2020 to April 2020 in Shahid Sadoughi hospital, Yazd, Iran. Data including age, gender, hospitalization ward, lymphocyte count, and computed tomography (CT) scan findings were extracted from medical records. Results: The mean lung involvement score was 36.8±22.34. The mean lymphocyte count in these patients was 1229.25±536.80 µL. Lymphopenia was observed in 79 patients (64%). No relationship was seen between HRCT findings and lymphopenia in patients with COVID-19 (P=0.31). Although a significant relationship was seen between HRCT findings and lymphopenia in females (P&lt;0.05), there was no relationship between HRCT findings and lymphopenia, regarding age, male gender, and hospitalization wards (P&gt;0.05). Conclusion: There was no significant relationship between HRCT and lymphopenia findings, and parameters such as age and inpatient ward in patients with Covid-19. However, there was an interesting relationship between lymphopenia and lung involvement in women; therefore, more studies are needed to prove this hypothesis.

Utility of Follow-up With Absolute Lymphocyte Count in Patients Undergoing Eribulin Treatment for Early Detection of Progressive Advanced or Metastatic Breast Cancer.

Eribulin, a non-taxane microtubule inhibitor, improves the tumor immune microenvironment via vascular remodeling. Systemic peripheral immune markers such as absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) have been reported as prognostic factors of patients treated with eribulin. However, the usefulness of the longitudinal changes of these blood parameters during eribulin treatment remains unknown. A total of 97 patients with locally advanced or metastatic breast cancer treated with eribulin were recruited. ALC and NLR values were collected at each cycle of treatment. The correlation between ALC and NLR and prognosis and antitumor effects was retrospectively evaluated. Progression-free and overall survival for patients with a base line ALC ≥1,500/μl was significantly better than that for those with a lower ALC (p=0.049 and p=0.004, respectively). The mean ALC in the non-progressive disease (PD) group increased, while that in the PD group slightly decreased over time. A low ALC at the last cycle was significantly correlated with PD (p=0.030). Of the 64 patients with PD, 47 were classified as having progression due to a pre-existing lesion (PPL), and 17 patients were classified as having progression due to new metastasis (PNM). The mean ALC for the PPL group slightly increased during eribulin treatment, while that for the PNM group decreased. Eribulin treatment may have improved the immune status in eribulin responders. Monitoring ALC values may be useful for early assessment of response to therapy.

Lymphopenia as a Predictor for Adverse Clinical Outcomes in Hospitalized Patients with COVID-19: A Single Center Retrospective Study of 4485 Cases.

Lymphopenia is commonly present in patients with COVID-19. We sought to determine if lymphopenia on admission predicts COVID-19 clinical outcomes. A retrospective chart review was performed on 4485 patients with laboratory-confirmed COVID-19, who were admitted to the hospital. Of those, 2409 (57.3%) patients presented with lymphopenia (absolute lymphocyte count < 1.1 × 109/L) on admission, and had higher incidences of ICU admission (17.9% versus 9.5%, p < 0.001), invasive mechanical ventilation (14.4% versus 6.5%, p < 0.001), dialysis (3.4% versus 1.8%, p < 0.001) and in-hospital mortality (16.6% versus 6.6%, p < 0.001), with multivariable-adjusted odds ratios of 1.86 (95% confidence interval [CI], 1.55–2.25), 2.09 (95% CI, 1.69–2.59), 1.77 (95% CI, 1.19–2.68), and 2.19 (95% CI 1.76–2.72) for the corresponding outcomes, respectively, compared to those without lymphopenia. The restricted cubic spline models showed a non-linear relationship between lymphocyte count and adverse outcomes, with an increase in the risk of adverse outcomes for lower lymphocyte counts in patients with lymphopenia. The predictive powers of lymphopenia, expressed as areas under the receiver operating characteristic curves, were 0.68, 0.69, 0.78, and 0.79 for the corresponding adverse outcomes, respectively, after incorporating age, gender, race, and comorbidities. In conclusion, lymphopenia is a useful metric in prognosticating outcomes in hospitalized COVID-19 patients.