Analysis of the detection results of pulmonary nodules before and after the novel coronavirus epidemic——A multicenter retrospective analysis (preprint)

Objective: To analyse the screening results of pulmonary nodules before and after the COVID-19 epidemic to understand the influence of the COVID-19 epidemic on the detection rate of pulmonary nodules and the detection rate of malignant pulmonary nodules. Methods: A total of 18,906 cases of chest CT were completed from March to November 2022 and March to November 2023. In March-December 2022 was divided into pre-epidemic group, and subjects from March-December 2023 were divided into post-epidemic group. the detection rate of pulmonary nodules, suspected lung cancer and lung cancer nodules, different age group, sex group were analyzed. Results: A total of 11513 pulmonary nodules were detected in this screening. A total of 841 suspected lung cancer nodules were detected, The detection rate of solid nodules in the post-epidemic group was significantly higher than that in the pre-epidemic group . The detection rate of fibrosis changes in the post-epidemic group was significantly higher than that in the pre-epidemic group . The detection rate of pulmonary nodules after prevalence was significantly higher in 51 to 60 years and older than 61 years than in the pre-epidemic group, and the difference was statistically significant. Conclusion: The detection rate of pulmonary nodules increased after the prevalence of COVID-19, mainly dominated by the increase of solid pulmonary nodules.The increased detection rate of pulmonary nodules is concentrated in the medical subjects aged over 51 years, and the COVID-19 epidemic does not increase the detection rate of suspected lung cancer nodules.

The Interleukin 6 (IL-6) blockade for coronavirus disease 2019 (COVID-19) In Lung (preprint)

COVID-19 has caused global pandemics since the emergent outbreak and resulted in a large number of deaths. IL-6, as an important autoimmune cytokine, had been suggested for the treatment of acute respiratory distress syndrome (ARDS) patients in COVID-19. A review of the relevant literature revealed more than one role for IL-6 in the lung infection because of its diverse biological effects. It may have a variety of different physiological functions in the development of lung infection. We have summarized its role in different progress of COVID-19, including lung infection, pneumonia, ALI, pulmonary fibrosis, and lung translation and even lung cancer. This will facilitate a deeper understanding of the role of IL-6 in the treatment of COVID-19.

Early radical lung cancer outcome after prompt recovery from COVID-19 infection: A real-world study (preprint)

Background: There has been an increase in the number of patients with lung cancer who had previously contracted SARS-CoV-2 and currently require surgery. This study was to share the early postoperative outcomes in patients who underwent radical lung cancer surgery after early recovery of COVID-19 infection. Methods We retrospectively collected data for 99 patients who had undergone lung cancer surgery in our hospital during January 2022 and January 2023 (including the peak of the COVID-19 crisis）. The patients were divided into two groups according to the inclusion criteria and exclusion criteria. One of these included individuals with a history of SARS-CoV-2 infection. Perioperative and follow-up data at 30-day and 90-day were recorded. Results There were no statistical differences between groups (p > 0.05) in terms of their postoperative complications or 30-day and 90-day postoperative readmission rates. However, there were significant differences between groups (p < 0.05) in terms of their tumor sizes, pathological stages, total drainage volumes, drainage diversion times, and hospital stays. Conclusions The results of the present trial suggested that it is safe to implement radical curative lung cancer surgery in patients without pulmonary impairment and in the early stages (2–4 weeks) of recovery from SARS-CoV-2 infection.

Detection of Lung Cancer Cases in Chest CT Scans Utilizing Artificial Intelligence: A Retrospective Analysis of Data During the COVID-19 Pandemic (preprint)

PurposeTo evaluate the potential of using artificial intelligence (AI) focused pulmonary nodule search on chest CT data obtained during the COVID-19 pandemic to identify lung cancer (LC) patients. MethodsA multicenter, retrospective study in the Krasnoyarsk region, Russia analyzed CTs of COVID-19 patients using the automated algorithm, Chest-IRA by IRA Labs. Pulmonary nodules larger than 100 mm3 were identified by the AI and assessed by four radiologists, who categorized them into three groups: "high probability of LC", "insufficiently convincing evidence of LC", "without evidence of LC". Patients with findings were analyzed by radiologists, checked with the state cancer registry and electronic medical records. Patients with confirmed findings that were not available in the cancer registry were invited for chest CT and verification was performed according to the decision of the medical consilium. The study also estimated the economic impact of the AI by considering labor costs and savings on treatment for patients in the early stages compared to late stages, taking into account the saved life years and their potential contribution to the gross regional product. ResultsAn AI identified lung nodules in 484 out of 10,500 chest CTs. Of the 484, 355 could be evaluated, the remaining 129 had de-anonymization problems and were excluded. Of the 355, 252 cases having high and intermediate probabilities of LC, 103 were found to be false positives. From 252 was 100 histologically verified LC cases, 35 were in stages I-II and 65 were in stages III-IV. 2 lung cancers were diagnosed for the first time. Using AI instead of CT review by radiologists will save 2.43 million rubles (23,786 EUR/ 26690 USD/ 196,536 CNY) in direct salary, with expected savings to the regional budget of 8.22 million rubles (80,463 EUR/ 90,466 USD/ 666,162 CNY). The financial equivalent of the life years saved was 173.25 million rubles (1,695,892 EUR/ 1905750 USD/ 14,033,250 CNY). The total effect over five years is estimated at 183.9 million rubles (1,800,142 EUR/ 2,022,907 USD/ 14,895,949 CNY). ConclusionUsing AI to evaluate large volumes of chest CTs done for reasons unrelated to lung cancer screening may facilitate early and cost-effective detection of incidental pulmonary nodules that might otherwise be missed.

Random Measures, ANOVA Models and Quantifying Uncertainty in Randomized Controlled Trials (preprint)

This short paper introduces a novel approach to global sensitivity analysis, grounded in the variance-covariance structure of random variables derived from random measures. The proposed methodology facilitates the application of information-theoretic rules for uncertainty quantification, offering several advantages. Specifically, the approach provides valuable insights into the decomposition of variance within discrete subspaces, similar to the standard ANOVA analysis. To illustrate this point, the method is applied to datasets obtained from the analysis of randomized controlled trials on evaluating the efficacy of the COVID-19 vaccine and assessing clinical endpoints in a lung cancer study.

The Impact of the UK COVID-19 Lockdown on the Screening, Diagnostics and Incidence of Breast, Colorectal, Lung and Prostate Cancer in the UK: a Population-Based Cohort Study (preprint)

Objectives: This study aimed to assess the impact of the COVID-19 lockdown on the screening and diagnosis of breast, colorectal, lung, and prostate cancer. The study also investigated whether the rates returned to pre-pandemic levels by December 2021. Design: Cohort study. Setting: Electronic health records from UK primary care Clinical Practice Research Datalink (CPRD) GOLD database. Participants: The study included individuals registered with CPRD GOLD between January 2017 and December 2021, with at least 365 days of prior observation. Main outcome measures: The study focused on screening, diagnostic tests, referrals and diagnoses of first-ever breast, colorectal, lung, and prostate cancer. Incidence rates (IR) were stratified by age, sex and region, and incidence rate ratios (IRR) were calculated to compare rates during and after lockdown with the reference period before lockdown. Forecasted rates were estimated using negative binomial regression models. Results: Among 5,191,650 eligible participants, the initial lockdown resulted in reduced screening and diagnostic tests for all cancers, which remained dramatically reduced across the whole observation period for almost all tests investigated. For cancer incidence rates, there were significant IRR reductions in breast (0.69), colorectal (0.74), and prostate (0.71) cancers. However, the reduction in lung cancer incidence (0.92) was non-significant. Extrapolating to the entire UK population, an estimated 18,000 breast, 13,000 colorectal, 10,000 lung, and 21,000 prostate cancer diagnoses were missed from March 2020 to December 2021. Conclusion: The national COVID-19 lockdown in the UK had a substantial impact on cancer screening, diagnostic tests, referrals and diagnoses. Although incidence rates started to recover after the lockdown, they remained significantly lower than pre-pandemic levels for breast and prostate cancers and associated tests. Delays in diagnosis are likely to have adverse consequences on cancer stage, treatment initiation, mortality rates, and years of life lost. Urgent strategies are needed to identify undiagnosed cases and address the long-term implications of delayed diagnoses.

Unleashing the Power of Artificial Intelligence: Unraveling the Intricate Dynamics between Viral and Bacterial Infections, Immune Factors, COVID-19, and Cancer in Women's Health (preprint)

The intricate interplay between viral and bacterial infections, immune factors, COVID-19, and cancer in women's health has garnered significant attention in recent research. This comprehensive study aimed to unravel the complex dynamics between these factors and provide valuable insights into their implications for women's health. Through meticulous analysis of available data, this study elucidated the prevalence of viral and bacterial infections in women, encompassing influential pathogens such as influenza, human papillomavirus, Staphylococcus aureus, Escherichia coli, and Streptococcus pneumoniae. Additionally, it explored the relationship between specific cytokine types, including Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), Interferon-gamma (IFN-γ), and Interleukin-10 (IL-10), and viral infections. The prevalence of various cancer types, such as breast cancer, lung cancer, colorectal cancer, ovarian cancer, and cervical cancer, was also assessed. Furthermore, this study examined the correlations between immune factors and viral infections, uncovering significant associations that shed light on the intricate interplay between immune responses and viral infections. Immune markers such as IL-6, TNF-α, IFN-γ, Interleukin-1beta (IL-1β), and Interleukin-12 (IL-12) exhibited diverse levels of correlation with specific viral infections. These findings hold promise for disease prognosis and treatment optimization. Additionally, the association between bacterial infections and women's health conditions was explored, revealing the impact of pathogens like Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Enterococcus faecalis on gynecological infections, reproductive disorders, and other relevant conditions. This highlights the need for effective strategies to prevent and manage bacterial infections, aiming to mitigate their adverse effects on women's health. In the context of COVID-19, this study investigated immune factors as predictors of disease outcomes in women. Various cytokines, including IL-6, TNF-α, IL-1β, IFN-γ, IL-10, IL-8, IL-4, IL-2, IL-12, and IL-17, demonstrated associations with disease severity, offering potential prognostic markers for identifying individuals at higher risk of severe illness. Furthermore, the relationship between viral and bacterial infections and cancer incidence in women was explored. Viral infections, such as human papillomavirus and influenza, showed associations with specific cancer types, including breast cancer, cervical cancer, lung cancer, skin cancer, and stomach cancer. Bacterial infections, such as Staphylococcus aureus and Escherichia coli, were linked to ovarian cancer, colorectal cancer, pancreatic cancer, bladder cancer, kidney cancer, and esophageal cancer. These findings provide valuable insights into the potential role of infectious etiologies in cancer development among women. In conclusion, this comprehensive study unveils the intricate dynamics between viral and bacterial infections, immune factors, COVID-19, and cancer in women's health. The findings emphasize the importance of considering the interconnectedness of these factors to enhance disease prevention, diagnosis, and treatment strategies in women. Further research is warranted to unravel the underlying mechanisms and translate these findings into clinical applications.

Association of ACE and ACE2 genes elevate the risk of lung cancer (preprint)

Background: ACE and ACE2 are biologically potential biomarkers responsible for the production and progression of lung cancer. Multiple factors and bioprocesses are associated with in tumorigenesis and metastasis of lung cancer, including cellular senescence and immune evasion. We aimed to analyzed the expression and association of ACE and ACE2 genes in lung cancer & Covid-19. We also aimed to identify prognostic and immune-meditating effects of ACE and ACE2 in lung cancer.Subjects and methods: Web-based bioinformatics tools were used to assess the association of ACE and ACE2 with lung cancer risks. The prognostic significance of mRNA expression of ACE and ACE2 in lung cancer were evaluated using the Kaplan–Meier plotter. Correlation analyses were performed to reveal the association among key factor, immune infiltration, T cell biomarkers and immune checkpoints. Univariate and multivariate Cox proportional hazards regression analysis were performed to determine whether ACE and ACE2 are an independent risk factor for overall survival (OS) and fast progression (FP) of lung cancer patients. Additionally, STRING database was used to analyze protein-protein interactions.Result: Our data confirmed that ACE is significantly expressed and associated with higher lung cancer risks where ACE2 role in developing lung cancer is controversial but in Covid-19. Moreover, high expression of ACE and ACE2 might predict poor OS and FP in lung cancer patients. Besides, disease stage and expression level of ACE and ACE2 were correlated with fast progression and overall survival in lung cancer. Both ACE and ACE2 were found highly co-expressed with different immune checkpoints. Analysis of protein-protein interaction based on STRING database gained top 10 genes which could interact with ACE (including, AGT, KNG1, REN, RHOA, RHOC, ATTR1, AGTR2, BDKRB2, MME and NR3C2) and ACE2 (including, SLC6A19, AGT, DPP4, REN, MME, PRCP, MEPIA, SLC1A7, TMPRSS2 and CLEC4M)Conclusion: Our results indicate that, aberrant expression of ACE in lung cancer is greater than ACE2 and might be involved in the pathogenesis of lung cancer risk whereas ACE2 in Covid-19.

Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC.

BACKGROUND: Among patients with resected, epidermal growth factor receptor (EGFR)-mutated, stage IB to IIIA non-small-cell lung cancer (NSCLC), adjuvant osimertinib therapy, with or without previous adjuvant chemotherapy, resulted in significantly longer disease-free survival than placebo in the ADAURA trial. We report the results of the planned final analysis of overall survival. METHODS: In this phase 3, double-blind trial, we randomly assigned eligible patients in a 1:1 ratio to receive osimertinib (80 mg once daily) or placebo until disease recurrence was observed, the trial regimen was completed (3 years), or a discontinuation criterion was met. The primary end point was investigator-assessed disease-free survival among patients with stage II to IIIA disease. Secondary end points included disease-free survival among patients with stage IB to IIIA disease, overall survival, and safety. RESULTS: Of 682 patients who underwent randomization, 339 received osimertinib and 343 received placebo. Among patients with stage II to IIIA disease, the 5-year overall survival was 85% in the osimertinib group and 73% in the placebo group (overall hazard ratio for death, 0.49; 95.03% confidence interval [CI], 0.33 to 0.73; P<0.001). In the overall population (patients with stage IB to IIIA disease), the 5-year overall survival was 88% in the osimertinib group and 78% in the placebo group (overall hazard ratio for death, 0.49; 95.03% CI, 0.34 to 0.70; P<0.001). One new serious adverse event, pneumonia related to coronavirus disease 2019, was reported after the previously published data-cutoff date (the event was not considered by the investigator to be related to the trial regimen, and the patient fully recovered). Adjuvant osimertinib had a safety profile consistent with that in the primary analysis. CONCLUSIONS: Adjuvant osimertinib provided a significant overall survival benefit among patients with completely resected, EGFR-mutated, stage IB to IIIA NSCLC. (Funded by AstraZeneca; ADAURA ClinicalTrials.gov number, NCT02511106.).

Impact of COVID-19-related health care disruptions on pathologic cancer staging during the first pandemic year: a retrospective cohort study from March 2018 to March 2021.

BACKGROUND: The COVID-19 pandemic has created major disruptions in cancer care, with reductions in diagnostic tests and treatments. We evaluated the impact of these health care-related changes on cancer staging by comparing cancers staged before and during the pandemic. METHODS: We performed a retrospective cohort study at London Health Sciences Centre and St. Joseph's Health Care London, London, Ontario, Canada. We evaluated all pathologically staged breast, colorectal, prostate, endometrial and lung cancers (the 5 most common cancers by site, excluding nonmelanoma skin cancer) over a 3-year period (Mar. 15, 2018-Mar. 14, 2021). The pre-COVID-19 group included procedures performed between Mar. 15, 2018, and Mar. 14, 2020, and the COVID-19 group included procedures performed between Mar. 15, 2020, and Mar. 14, 2021. The primary outcome was cancer stage group, based on the pathologic tumour, lymph node, metastasis system. We performed univariate analyses to compare demographic characteristics, pathologic features and cancer stage between the 2 groups. We performed multivariable ordinal regression analyses using the proportional odds model to evaluate the association between stage and timing of staging (before v. during the pandemic). RESULTS: There were 4055 cases across the 5 cancer sites. The average number of breast cancer staging procedures per 30 days increased during the pandemic compared to the yearly average in the pre-COVID-19 period (41.3 v. 39.6), whereas decreases were observed for endometrial cancer (15.9 v. 16.4), colorectal cancer (21.8 v. 24.3), prostate cancer (13.6 v. 18.5) and lung cancer (11.5 v. 15.9). For all cancer sites, there were no statistically significant differences in demographic characteristics, pathologic features or cancer stage between the 2 groups (p > 0.05). In multivariable regression analysis, for all cancer sites, cases staged during the pandemic were not associated with higher stage (breast: odds ratio [OR] 1.071, 95% confidence interval [CI] 0.826-1.388; colorectal: OR 1.201, 95% CI 0.869-1.661; endometrium: OR 0.792, 95% CI 0.495-1.252; prostate: OR 1.171, 95% CI 0.765-1.794; and lung: OR 0.826, 95% CI 0.535-1.262). INTERPRETATION: Cancer cases staged during the first year of the COVID-19 pandemic were not associated with higher stage; this likely reflects the prioritization of cancer procedures during times of reduced capacity. The impact of the pandemic period on staging procedures varied between cancer sites, which may reflect differences in clinical presentation, detection and treatment.

An integrated cell atlas of the lung in health and disease.

Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1+ profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas.

Effects of a 12-Week Multimodal Exercise Intervention Among Older Patients with Advanced Cancer: Results from a Randomized Controlled Trial.

BACKGROUND: Older patients with cancer are at risk of physical decline and impaired quality of life during oncological treatment. Exercise training has the potential to reduce these challenges. The study aim was to investigate the feasibility and effect of a multimodal exercise intervention in older patients with advanced cancer (stages III/IV). PATIENTS AND METHODS: Eighty-four older adults (≥65 years) with advanced pancreatic, biliary tract, or non-small cell lung cancer who received systemic oncological treatment were randomized 1:1 to an intervention group or a control group. The intervention was a 12-week multimodal exercise-based program including supervised exercise twice weekly followed by a protein supplement, a home-based walking program, and nurse-led support and counseling. The primary endpoint was change in physical function (30-second chair stand test) at 13 weeks. RESULTS: Median age of the participants was 72 years (interquartile range [IQR] 68-75). Median adherence to the exercise sessions was 69% (IQR 21-88) and 75% (IQR 33-100) for the walking program. At 13 weeks, there was a significant difference in change scores of 2.4 repetitions in the chair stand test, favoring the intervention group (p < .0001). Furthermore, significant beneficial effects were seen for physical endurance (6-minute walk test), hand grip strength, physical activity, symptom burden, symptoms of depression and anxiety, global health status (quality of life), and lean body mass. No effects were seen for dose intensity, hospitalizations, or survival. CONCLUSION: A 12-week multimodal exercise intervention with targeted support proved effective in improving physical function in older patients with advanced cancer during oncological treatment.

COVID-19 Outcomes by Cancer Status, Site, Treatment, and Vaccination.

BACKGROUND: Studies have shown an increased risk of severe SARS-CoV-2-related (COVID-19) disease outcome and mortality for patients with cancer, but it is not well understood whether associations vary by cancer site, cancer treatment, and vaccination status. METHODS: Using electronic health record data from an academic medical center, we identified a retrospective cohort of 260,757 individuals tested for or diagnosed with COVID-19 from March 10, 2020, to August 1, 2022. Of these, 52,019 tested positive for COVID-19 of whom 13,752 had a cancer diagnosis. We conducted Firth-corrected logistic regression to assess the association between cancer status, site, treatment, vaccination, and four COVID-19 outcomes: hospitalization, intensive care unit admission, mortality, and a composite "severe COVID" outcome. RESULTS: Cancer diagnosis was significantly associated with higher rates of severe COVID, hospitalization, and mortality. These associations were driven by patients whose most recent initial cancer diagnosis was within the past 3 years. Chemotherapy receipt, colorectal cancer, hematologic malignancies, kidney cancer, and lung cancer were significantly associated with higher rates of worse COVID-19 outcomes. Vaccinations were significantly associated with lower rates of worse COVID-19 outcomes regardless of cancer status. CONCLUSIONS: Patients with colorectal cancer, hematologic malignancies, kidney cancer, or lung cancer or who receive chemotherapy for treatment should be cautious because of their increased risk of worse COVID-19 outcomes, even after vaccination. IMPACT: Additional COVID-19 precautions are warranted for people with certain cancer types and treatments. Significant benefit from vaccination is noted for both cancer and cancer-free patients.

Disparities in lung cancer.

Lung cancer is the second most common cancer and the leading cause of cancer death among men and women in the United States. Despite a substantial decline in lung cancer incidence and mortality across all races in the last few decades, medically underserved racial and ethnic minority populations continue to carry the greatest burden of disease throughout the lung cancer continuum. Black individuals experience a higher incidence of lung cancer due to lower rates of low-dose computed tomography screening, which translate into advanced disease stage at diagnosis and poorer survival outcomes compared with White individuals. With respect to treatment, Black patients are less likely to receive gold standard surgery, have access to biomarker testing or high-quality treatment compared with White patients. The reasons for those disparities are multifactorial and include socioeconomic (eg, poverty, lack of health insurance, and inadequate education), and geographic inequalities. The objective of this article is to review the sources of racial and ethnic disparities in lung cancer, and to propose recommendations to help address them.

CD4+ T-cell immunity of SARS-CoV-2 patients determine pneumonia development (preprint)

Most humans infected with SARS-CoV-2 will recover without developing pneumonia. A few SARS-CoV-2 infected patients, however, develop pneumonia, and occasionally develop cytokine storms. In such cases, it is assumed that there is an inadequate immune response to eliminate viral infected cells and an excessive inappropriate immune response causing organ damage, but little is known about this mechanism. In this study, we used single cell RNA sequencing and mass cytometry to analyze peripheral blood T cells from patients hospitalized with proven COVID-19 infection in order to clarify the differences in host immune status among COVID-19 pneumonia cases, non-pneumonia cases, and healthy controls. The results showed that a specific CD4+ T cell cluster with chemokine receptor expression patterns, CXCR3+CCR4-CCR6+ (Th1/17), was less abundant in COVID-19 pneumonia patients. Interestingly, these CD4+ T-cell clusters were identical to those we have reported to correlate with antitumor immunity and predict programmed cell death (PD)-1 blockade treatment response in lung cancer. The Th1/17 cell percentages had biomarker performance in diagnosing pneumonia cases. In addition, CTLA-4 expression of type17 helper T cells (Th17) and regulatory T cells (Treg) was found to be significantly lower. This indicates that functional suppression of Th17 was less effective and Treg function was impaired in pneumonia cases. These results suggest that imbalance of CD4+ T-cell immunity generates excessive immunity that does not lead to viral eradication. This might be a potential therapeutic target mechanism to prevent severe viral infections.

The Effects of GCSF Primary Prophylaxis on Survival Outcomes and Toxicity in Patients with Advanced Non-Small Cell Lung Cancer on First-Line Chemoimmunotherapy: A Sub-Analysis of the Spinnaker Study.

GCSF prophylaxis is recommended in patients on chemotherapy with a >20% risk of febrile neutropenia and is to be considered if there is an intermediate risk of 10−20%. GCSF has been suggested as a possible adjunct to immunotherapy due to increased peripheral neutrophil recruitment and PD-L1 expression on neutrophils with GCSF use and greater tumour volume decrease with higher tumour GCSF expression. However, its potential to increase neutrophil counts and, thus, NLR values, could subsequently confer poorer prognoses on patients with advanced NSCLC. This analysis follows on from the retrospective multicentre observational cohort Spinnaker study on advanced NSCLC patients. The primary endpoints were OS and PFS. The secondary endpoints were the frequency and severity of AEs and irAEs. Patient information, including GCSF use and NLR values, was collected. A secondary comparison with matched follow-up duration was also undertaken. Three hundred and eight patients were included. Median OS was 13.4 months in patients given GCSF and 12.6 months in those not (p = 0.948). Median PFS was 7.3 months in patients given GCSF and 8.4 months in those not (p = 0.369). A total of 56% of patients receiving GCSF had Grade 1−2 AEs compared to 35% who did not receive GCSF (p = 0.004). Following an assessment with matched follow-up, 41% of patients given GCSF experienced Grade 1−2 irAEs compared to 23% of those not given GCSF (p = 0.023). GCSF prophylaxis use did not significantly affect overall or progression-free survival. Patients given GCSF prophylaxis were more likely to experience Grade 1−2 adverse effects and Grade 1−2 immunotherapy-related adverse effects.

The aggregate index of systemic inflammation may predict mortality in COVID-19 patients with chronic renal failure.

OBJECTIVE: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was first detected in December 2019 and then spread globally, resulting in a pandemic. Initially, it was unknown if chronic kidney disease (CKD) contributed to the mortality caused by COVID-19. The immunosuppression associated with this disease may minimize the COVID-19-described hyper-inflammatory state or immunological dysfunction, and a high prevalence of comorbidities may lead to a poorer clinical prognosis. Patients with COVID-19 have abnormal circulating blood cells associated with inflammation. Risk stratification, diagnosis, and prognosis primarily rely on hematological features, such as white blood cells and their subpopulations, red cell distribution width, mean platelet volume, and platelet count, in addition to their combined ratios. In non-small-cell lung cancer, the aggregate index of systemic inflammation (AISI), (neutrophils x monocytes x platelets/lymphocytes) is evaluated. In light of the relevance of inflammation in mortality, the objective of this study is to determine the impact of AISI on the hospital mortality of CKD patients. PATIENTS AND METHODS: This study is an observational retrospective study. Data and test outcomes of all CKD patients, stages 3-5, hospitalized for COVID-19 and followed between April and October 2021 were analyzed. RESULTS: Patients were divided into two groups according to death (Group 1-Alive, Group 2-Died). Neutrophil count, AISI and C-reactive protein (CRP) levels were increased in Group-2 [10.3±4.6 vs. 7.65±4.22; p=0.001, 2,084.1 (364.8-2,577.5) vs. 628.9 (53.1-2,275); p=0.00 and 141.9 (20.5-318) vs. 84.75 (0.92-195); p=0.00; respectively]. Receiver operating characteristic (ROC) analysis demonstrated 621.1 as a cut-off value for AISI to predict hospital mortality with 81% sensitivity and 69.1% specificity [area under ROC curve 0.820 (95% CI: 0.733-0.907), p<.005]. Cox regression analysis was used to analyze the effect of risk variables on survival. In survival analysis, AISI and CRP were identified as important survival predictors [hazard ratio (HR): 1.001, 95% CI: 1-1.001; p=0.00 and HR: 1.009, 95% CI: 1.004-1.013; p=0.00]. CONCLUSIONS: This study demonstrated the discriminative effectiveness of AISI in predicting disease mortality in COVID-19 patients with CKD. Quantification of AISI upon admission might assist in the early detection and treatment of individuals with a bad prognosis.

Antibody response to SARS-CoV-2 WT and Omicron BA.4/5 of inactivated COVID-19 vaccine in patients with lung cancer after second and booster immunization.

COVID-19 inactivated vaccine-induced humoral responses in patients with lung cancer (LCs) to SARS-CoV-2 wild-type (WT) strain and variants BA.4/5 after the primary 2-dose and booster vaccination remained unknown. We conducted a cross-sectional study in 260 LCs, 140 healthy controls (HC) and additional 40 LCs with serial samples by detecting total antibodies, IgG anti-RBD and neutralizing antibodies (NAb) toward WT and BA.4/5. SARS-CoV-2-specific antibody responses were augmented by the booster dose of inactivated vaccines in LCs, whereas they were lower than that in HCs. Enhanced humoral responses waned over time after triple injection, notably in NAb against WT and BA.4/5. The NAb against BA.4/5 was much lower than WT. Age ≥ 65 was risk factor for immunization of NAb to WT. Undergoing treatment resulted in a lower antibody response than those without and radiotherapy was a also risk factor for seroconversion of NAb to WT. Lower lymphocyte counts contributed to a lower titer of IgG anti-RBD and NAb against BA.4/5 in LCs than HCs. Specifically, total B cells, CD4+T cells and CD8+T counts were correlated with the humoral response. These results should be taken into consideration for the elderly patients under treatment.

Delivery of a novel membrane-anchored Fc chimera enhances NK cell-mediated killing of tumor cells and persistently virus-infected cells.

Antibody-dependent cellular cytotoxicity (ADCC) is one of the most powerful mechanisms for Natural Killer (NK) cells to kill cancer cells or virus-infected cells. A novel chimeric protein (NA-Fc) was created, which when expressed in cells, positions an IgG Fc domain on the plasma membrane, mimicking the orientation of IgG bound to the cell surface. This NA-Fc chimera was tested with PM21-NK cells, produced through a previously developed particle-based method which yields superior NK cells for immunotherapeutic applications. Real time viability assays revealed higher PM21-NK killing of both ovarian and lung cancer cells expressing NA-Fc, which correlated with increased release of TNF-α and IFN-γ cytokines from NK cells and was dependent on CD16-Fc interactions. Lentivirus delivery of NA-Fc to target cells increased the rate of PM21-NK cell killing of A549 and H1299 lung, SKOV3 ovarian and A375 melanoma cancer cells. This NA-Fc-directed killing was extended to virus infected cells, where delivery of NA-Fc to lung cells that were persistently infected with Parainfluenza virus resulted in increased killing by PM21-NK cells. In contrast to its effect on PM21-NK cells, the NA-Fc molecule did not enhance complement mediated lysis of lung cancer cells. Our study lays the foundation for application of the novel NA-Fc chimera that could be delivered specifically to tumors during oncolytic virotherapy to mark target cells for ADCC by co-treatment with adoptive NK cells. This strategy would potentially eliminate the need to search for unique cancer specific antigens for development of new antibody therapeutics.