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During the last 30 years, our understanding of the development and diversification of postganglionic sympathetic neurons has dramatically increased. In parallel, the list of target structures has been critically extended from the cardiovascular system and selected glandular structures to metabolically relevant tissues such as white and brown adipose tissue, lymphoid tissues, bone, and bone marrow. A critical question now emerges for the integration of the diverse sympathetic neuron classes into neural circuits specific for these different target tissues to achieve the homeostatic regulation of the physiological ends affected.

BackgroundAsthma is a heterogeneous disease that can be divided into four inflammatory phenotypes: eosinophilic asthma (EA), neutrophilic asthma (NA), mixed granulocytic asthma (MGA), and paucigranulocytic asthma (PGA). While research has mainly focused on EA and NA, the understanding of PGA is limited. In this study, we aimed to identify underlying mechanisms and hub genes of PGA.MethodsBased on the dataset from Gene Expression Omnibus(GEO), weighted gene coexpression network analysis (WGCNA), differentially expressed genes (DEGs) analysis and protein–protein interaction (PPI) network analysis were conducted to construct a gene network and to identify key gene modules and hub genes. Functional enrichment analyses were performed to investigate the biological process, pathways and immune status of PGA. The hub genes were validated in a separate dataset.ResultsCompared to non-PGA, PGA had a different gene expression pattern, in which 449 genes were differentially expressed. One gene module significantly associated with PGA was identified. Intersection between the differentially expressed genes (DEGs) and the genes from the module that were most relevant to PGA were mainly enriched in inflammation and immune response regulation. The single sample Gene Set Enrichment Analysis (ssGSEA) suggested a decreased immune infiltration and function in PGA. Finally six hub genes of PGA were identified, includingADCY2,CXCL1,FPRL1,GPR109B, GPR109AandADCY3,which were validated in a separate dataset of GSE137268.ConclusionsOur study characterized distinct gene expression patterns, biological processes and immune status of PGA and identified hub genes, which may improve the understanding of underlying mechanism and provide potential therapeutic targets for PGA.

Torque Teno virus (TTV) is a group of chronically persisting viruses with a short circular DNA genome. TTV demonstrates a wide sequence diversity and a large majority of humans are chronically infected by one or more types of TTV. Since TTV is ubiquitous, and viral replication correlates with immune status, TTV has been studied as a marker to assess global functional immune competence in transplant recipients. Most studies of the prevalence, amounts, and variation in TTV have been performed using PCR assays. We here present a comparison of the most frequently used quantitative PCR (qPCR) assay for TTV with shotgun metagenomic sequencing for detection and characterization of TTV in a cohort of pediatric cancer patients. The results show that TTV is more common than the qPCR assays indicated, and analysis of the TTV genome sequences indicate that a qPCR with primers and probe designed on a conserved region of the TTV genome may fail to detect some of the TTV strains found in this study. This article is protected by copyright. All rights reserved.

The gut microbiome (GM) has been implicated in a vast number of human pathologies and has become a focus of oncology research over the past 5 years. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation and protection against pathogens. Strong evidence is emerging to support the effects of the GM on the development of some malignancies but also on responses to cancer therapies, most notably, immune checkpoint inhibition. Tools for manipulating the GM including dietary modification, probiotics and faecal microbiota transfer (FMT) are in development. Current understandings of the many complex interrelationships between the GM, cancer, the immune system, nutrition and medication are ultimately based on a combination of short‐term clinical trials and observational studies, paired with an ever-evolving understanding of cancer biology. The next generation of personalised cancer therapies focusses on molecular and phenotypic heterogeneity, tumour evolution and immune status; it is distinctly possible that the GM will become an increasingly central focus amongst them. The aim of this review is to provide clinicians with an overview of microbiome science and our current understanding of the role the GM plays in cancer.

Graphical abstract, Even given recent advances in nanomedicine development of breast cancer treatment in recent years and promising results in pre-clinical models, cancer nanomedicines often fail at the clinical trial stage. Limitations of conventional in vitro models include the lack of representation of the stromal population, the absence of a three-dimensional (3D) structure, and a poor representation of inter-tumor and intra-tumor heterogeneity. Herein, we review those cell culture strategies that aim to overcome these limitations, including cell co-cultures, advanced 3D cell cultures, patient-derived cells, bioprinting, and microfluidics systems. The in vivo evaluation of nanomedicines must consider critical parameters that include the enhanced permeability and retention effect, the host's immune status, and the site of tumor implantation. Here, we critically discuss the advantages and limitations of current in vivo models and report how the improved selection and application of breast cancer models can improve the clinical translation of nanomedicines.

In this paper, we developed an age-structured epidemic model that takes into account boosting and waning of immune status of host individuals. For many infectious diseases, the immunity of recovered individuals may be waning as time evolves, so reinfection could occur, but also their immune status could be boosted if they have contact with infective agent. According to the idea of the Aron's malaria model, we incorporate a boosting mechanism expressed by reset of recovery-age (immunity clock) into the SIRS epidemic model. We established the mathematical well-posedness of our formulation and showed that the initial invasion condition and the endemicity can be characterized by the basic reproduction number $ R_0 $. Our focus is to investigate the condition to determine the direction of bifurcation of endemic steady states bifurcated from the disease-free steady state, because it is a crucial point for disease prevention strategy whether there exist subcritical endemic steady states. Based on a recent result by Martcheva and Inaba [1], we have determined the direction of bifurcation that endemic steady states bifurcate from the disease-free steady state when the basic reproduction number passes through the unity. Finally, we have given a necessary and sufficient condition for backward bifurcation to occur.

This study aimed to examine changes in levels of cytokine and T cell surface molecules in chronic hepatitis B (CHB) patients receiving sequential interferon therapy following 1-year nucleos(t)ide analogs (NAs) treatment. Cytokine levels were measured in 30 patients, and T cell surface molecule expression was measured in 48 patients receiving sequential interferon therapy and 24 patients only receiving NA mono-therapy. An HBsAg titer of0.05 IU/ml was defined as a "functional cure." In the cured group (HBsAg 0.05 IU/ml), a decreasing probability was observed in IFN-γ (after Week 0), and IL-22 and IP-10 (after Week 12). In the non-cured group (HBsAg ≥ 0.05 IU/ml), a probability of slightly decreasing was observed for IFN-γ (after Week 12), and a probability of increasing IP-10 concentration (after Week 0) was observed. Generalized estimating equation (GEE) analyses showed significant differences in the levels of IL-10, IL-23, CCL-3, IL-1β, IL-2, and IL-12P70 between the two groups. In GEE analysis, there were significant differences in expressions of CD45RO

There remains a general misconception that the immune status of the fetus and neonate is immature or insufficient. However, emerging research in immune ontogeny prompts reconsideration of this orthodoxy, reframing this period instead as one of unique opportunity. Vaccine responses (qualitative and quantitative) vary between individuals, and across demographic cohorts. Elements of baseline immune status and function predict vaccine response – some of these factors are well described, others remain a subject of ongoing research, especially with the rapidly expanding field of ‘omics’ research, enabled by development of highly granular immune profiling techniques and increasing computational capacity. Age is one of the strongest predictive factors associated with variability in the response to vaccination; and predictable variation in response to vaccination is a key to identify the crucial underlying mechanisms. Specifically, circulating maternal antibody in the young infant can modulate immune response to vaccination, acting as an ‘undercover adjuvant’ that, counter to current dogma, may offer a pathway to longer lasting, higher quality immune response to vaccination. Exciting avenues for novel research in this area have the potential to dramatically alter how we protect the world's most vulnerable population – the very young., SCOPUS: ar.j, info:eu-repo/semantics/published

e21509 Background: Immunosuppression (IS) is not currently considered in staging for Merkel cell carcinoma (MCC). We performed an analysis of the National Cancer Database (NCDB) to investigate immune status as an independent predictor of overall survival (OS) for patients with MCC and describe the relationship between immune status and other prognostic factors. Methods: The NCDB was queried for patients diagnosed with MCC from 2010 to 2016 with known immune status. Multivariable Cox proportional hazards models were used to define factors associated with OS. Adjuvant radiation and chemotherapy were treated as time-dependent predictors to limit immortal time bias. Secondary models were constructed to assess the association between IS etiology and OS. Multivariable logistic regression models were used to characterize relationships between immune status and other factors. Multiple imputation was used to minimize missing data bias. Results: The overall cohort included 3,882 patients (3,470 patients with known immunocompetence and 412 patients with known immunosuppression). Etiologies for profound IS included chronic lymphocytic leukemia (CLL, n = 118), Other including HIV/AIDS (n = 116), solid-organ transplant (n = 106), and Non-Hodgkin Lymphoma (NHL, n = 72). 2,864 patients (73.8%) underwent surgical nodal examination. The median follow-up time was 33 months (Interquartile Range: 18 to 55 months). The 3-year OS was lower for patients with IS (44.6%, CI 39.8-49.9%) compared to immunocompetent (IC) patients (68.7%, CI 67.1-70.4%, p < .0001). IS was associated with increased adjusted mortality hazard (HR 2.36, 95% CI 2.03-2.75). Etiology of IS was associated with OS ( p = .0015) with lowest 3-year OS (32.7%, CI 24.6%-43.5%) for patients with solid-organ transplantation. IS was associated with increased odds of greater nodal burden (OR 1.70, CI 1.37-2.11) and lymphovascular invasion (OR 1.58, CI 1.23-2.03). Conclusions: Immune status was independently prognostic for OS for patients with localized MCC. Etiology of IS may be associated with differential survival outcomes. Multiple adverse prognostic factors were associated with increased likelihood of IS. Immune status and potentially etiology of IS may be useful prognostic factors to consider for future MCC staging systems.

Background Acute Cerebral Nervous System Infections (ACNS) may cause death or severe complications even to promptly treated children. The role of the immune system in influencing the course and the outcome of meningitis has been studied but it is not yet completely understood. The aim of the research is to ascertain whether children who experienced ACNS infection had a normal immune system. Methods Patients under 18 years of age admitted at Bambino Gesù Children from January 2006 till June 2016 for meningitis were asked to participate to the follow-up study. The immune status was evaluated both clinically and by laboratory investigations. Results Most of the patients over 3 years at follow up had at least one immunological alteration at follow-up evaluation (74%). Considering ACNS infection etiology, certain pathogens were almost exclusive of patients affected by some immunological alteration, regardless of their age. Discussion Our preliminary results indicate that sub-clinical immunological defects may be associated to ACNS pediatric infections. Moreover, to the best of our knowledges, this is the first study correlating pathogens to immune evaluation in ACNS infections. It is, however, important to underline the high frequency of persistent immunological alterations in the analyzed patients. Further studies are needed to confirm our conclusions. Conclusions We recommend an immunological assessment at follow up evaluation in children who experienced an ACNS infection.

The objective of this research was to evaluate consequences to the immune system of long-term exposure to waste anesthetic gases (WAG) by medical theater personnel. Two groups were recruited: (i) 60 healthy male controls; (ii) 120 medical professionals exposed to WAG, subdivided according to theater role, i.e. surgeons, surgical assistants (SA), anesthetists, anesthetic assistants (AA), nurses, and workers. Serum levels of fluoride, hexafluoroisopropanol (HFIP), total lymphocyte counts, as well as of CD3, CD4, and CD8 cells, CD4/CD8 ratios, and immunoglobulins IgA, IgG, IgM, and IgE were assayed. The results showed that fluoride and HFIP titers were significantly increased in anesthetists and AA compared with the other exposed groups. All exposed groups demonstrated significant elevation in lymphocyte count, CD4+ cell levels, CD4/CD8 ratios, as well as levels of IgE, IgM and IgG compared with the controls. With regard to the latter outcomes, a significant increase in IgE was seen in the surgeon, nurse, and worker groups compared with the other professions. Surgeons, anesthetists and AA exhibited higher IgM titers compared with their colleagues. Significantly higher IgG levels were identified in the SA, anesthetists, AA, and workers than in their nurses and surgeon coworkers. Of the six sub-groups, only the anesthetists and their assistants (AA) displayed a significant increase in CD4+ cells and CD4/CD8 ratios and a decrease of CD8+ cells compared with the controls. This spectrum of results suggests that variation exists in immunomodulatory responses to WAG exposure amongst hospital personnel.

Background: Multidrug-resistant organisms (MDROs) are an important health care issue. Patients in Western societies often present an increased morbidity of chronic conditions accompanied by poor immune status and the use of devices. In particular, patients in palliative care (PC) are at greater risk of MDRO colonization, due to accompanying special devices and being hospitalized. Objective: To gain an overview of the literature regarding MDROs in PC. Design: Systematic review Data sources: On the 19th of October 2019 the databases " PubMed" and " CINAHL" were used to identify studies reporting on MDROs in PC; the search was updated on 16th of May 2020. Results: Seventeen out of 486 articles were included. Six represent qualitative data, 10 quantitative data, and one a mixed methods approach. Prevalence data range from 4.0% to 18%. MDRO colonization has a negative impact on patients and families. It leads to uncertainties and higher workload by staff members. Strategies for the management of MDROs in the field of PC are predominantly available for methicillin-resistant Staphylococcus aureus. Not even half of institutions utilize existing protocols. Recommendations for dealing with MDROs indicate required staff and time resources as well as information, communication, and specific knowledge. Conclusion: There is a great need for studies examining the prevalence of all MDROs in the PC setting. Additionally, not only patients but also a public enlightenment on MDROs should be provided to decrease knowledge gaps and therefore reduce transmission on MDROs.

Background The response rate and survival benefit of immunotherapy vary among patients, implying specific immune status of an individual could be associated with the effect of immunotherapy. However, in-depth studies of immune subtypes (ISs), immune landscape and tumour microenvironment of oesophageal cancer (ESCA) and their clinical implications are less reported. Methods We first accessed data from publicly available databases and preprocessed it based on a standard protocol. Then, ISs were identified by unsupervised learning. Thereafter, the association of these ISs and tumour mutation burden (TMB), biomarkers of chemotherapy-induced immune response, tumour markers were also assessed. In addition, the immune characteristics, immune landscape, co-expression network of immune genes, and clinical implications were visualized and analysed. Results We identified three immunoclusters based on immune-associated genes with intra-class heterogeneity and prognostic value. Cluster-specific associations with TMB, markers of chemotherapy-induced immune response, and tumour markers were revealed. A 4-gene signature (risk score= −0.16514291×BHLHE22−0.03964046×MXRA8−0.15242778×SLIT2−0.05553572×SPON1) based on co-expressed genes in the immunoclusters was developed and externally validated. Conclusions In summary, we identified clinically relevant immunoclusters in both adenocarcinoma and squamous cell carcinoma of oesophagus, revealing the necessity of assessing the complexity and diversity of immune microenvironment for cancer immunotherapy.

The development of immunotherapy has led to a paradigm shift in the treatment of both solid and hematologic malignancies. As immunomodulatory therapies are employed with increasing frequency, a greater number of immune-related adverse reactions are being reported, and the majority of these involve the skin. As a result, dermatologists are increasingly becoming involved in the management of these cutaneous adverse reactions-often providing critical recommendations regarding ongoing cancer treatment. Cutaneous immune-related adverse reactions can vary significantly from patient to patient, making early recognition and timely intervention imperative to mitigate associated morbidity and potential treatment interruption. Although there is considerable overlap in the cutaneous adverse events caused by these immune checkpoint inhibitors, specific eruptions are characteristically associated with particular checkpoint inhibitors. In addition, a patient's comorbidities or immune status can play a significant role in the presentation and management of such adverse reactions. This review characterizes and provides management guidelines for the various cutaneous toxicities associated with checkpoint inhibitor therapy, including CTLA-4 inhibitors, PD-1 inhibitors, and PD-L1 inhibitors. © 2020 Elsevier Inc. All rights reserved.

Background Aim of the pilot study was the histologic classification of the inflamed peri-implant soft tissue around ceramic implants (CI) in comparison with titanium implants (TI). Methods Peri-implant tissue were retrieved from 15 patients (aged 34 to 88 years, seven males/eight females) with severe peri-implantitis (eight CI, seven TI). The peri-implant soft tissue samples were retrieved from the sites during scheduled removal of the implant and prepared for immunohistochemical analysis. Monoclonal antibodies (targeting CD3, CD20, CD138, and CD68) were used to identify T- and B-cells, plasma cells and macrophages. Quantitative assessment was performed by one histologically trained investigator. Linear mixed regression models were used. Results A similar numerical distribution of the cell population was found in peri-implantitis around CI compared with TI. CD3 (TI, 17% to 85% versus CI, 20% to 70% of total cell number) and CD138 (TI, 1% to 73% versus CI, 12% to 69% of total cell number) were predominantly expressed. Notably, patient-individual differences of numerical cell distribution were detected. Co-localization of B- and T-lymphocytes was observed. Conclusions Peri-implantitis around CI in comparison with TI seems to have a similar histological appearance. Differences in cellular composition of peri-implantitis lesions might also depend on the patient's specific immune status and not only on the material used.

Burkitt lymphoma is a rare and aggressive non-Hodgkin lymphoma with three classifications: endemic, sporadic, and immunodeficiency-related. High-intensity chemotherapeutic regimens have considerably improved overall survival for patients with Burkitt lymphoma. In this Review of HIV-associated Burkitt lymphoma, we summarise expert opinion and provide general recommendations for the treatment of Burkitt lymphoma in patients with HIV on the basis of retrospective and prospective studies, taking into consideration immune status, CD4 cell counts, the presence of systemic disease, and the risk of CNS involvement or relapse. We also discuss the role of rituximab and antiretroviral therapy. We highlight the reasons behind the possible different mechanisms of lymphomagenesis in HIV-associated Burkitt lymphoma and endemic Burkitt lymphoma, which indicate that HIV might have either a direct or indirect oncogenic role in Burkitt lymphoma. We discuss the possible mechanisms by which HIV and HIV proteins could directly contribute to lymphomagenesis. Identifying these mechanisms might lead to the development of therapies that have fewer toxic effects than high-intensity chemotherapeutic regimens.

Background: Papillary renal cell carcinoma (pRCC) was the 2nd most common subtype, accounting for approximately 15% incidence of renal cell carcinoma (RCC). Immune related long non-coding RNAs (IR-lncRs) plentiful in immune cells and immune microenvironment (IME) are potential in evaluating prognosis and assessing the effects of immunotherapy. A completed and meaningful IR-lncRs analysis based on abundant pRCC gene samples from The Cancer Genome Atlas (TCGA) will provide insight in this field. Results: 17 IR-lncRs were selected by Pearson correlation analysis of immune score and the lncRNA expression level, and 5 sIRlncRs were significantly correlated with the OS of pRCC patients. 4 sIRlncRs ({"type":"entrez-nucleotide","attrs":{"text":"AP001267.3","term_id":"9857615","term_text":"AP001267.3"}}AP001267.3, {"type":"entrez-nucleotide","attrs":{"text":"AC026471.3","term_id":"15638671","term_text":"AC026471.3"}}AC026471.3, SNHG16 and ADAMTS9-AS1) with the most remarkable prognostic values were identified to establish the IRRS model and the OS of the low-risk group was longer than that in the high-risk group. The IRRS was certified as an independent prognosis factor and correlated with the OS. The high-risk group and low-risk group showed significantly different distributions and immune status through PCA and GSEA. In addition, we further found the expression levels of SNHG16 was remarkably enhanced in female patients with more advanced T-stages, but ADAMTS9-AS1 showed the opposite results. Conclusion: The IRRS model based on the identified 4 sIRlncRs showed the significant values on forecasting prognoses of pRCC patients, with the longer OS in the low-risk group. Methods: We integrated the expression profiles of LncRNA and overall survival (OS) in the 322 pRCC patients based on the TCGA dataset. The immune scores calculated on account of the expression level of immune-related genes were used to verify the most relevant IR-lncRs. Survival-related IR-lncRs (sIRlncRs) were estimated by COX regression analysis in pRCC patients. The high-risk group and low-risk group were identified by the median immune-related risk score (IRRS) model established by the screened sIRlncRs. Functional annotation was displayed by gene set enrichment analysis (GSEA) and principal component analysis (PCA), and the immune composition and purity of the tumor were evaluated through microenvironment cell count records. The expression levels of sIRlncRs of pRCC samples were verified by real-time quantitative PCR.

In organ transplantation, a reproducible and robust immune-monitoring assay has not been established to determine individually tailored immunosuppressants (IS). We applied humanized mice reconstituted with human (hu-) peripheral blood mononuclear cells (PBMCs) obtained from living donor liver transplant recipients to evaluate their immune status. Engraftment of 2.5 x 10(6) hu-PBMCs from healthy volunteers and recipients in the NSG mice was achieved successfully. The reconstituted lymphocytes consisted mainly of hu-CD3(+) lymphocytes with predominant CD45RA(-)CD62L(lo) T-EM and CCR6(-)CXCR3(+)CD4(+) Th1 cells in hu-PBMC-NSG mice. Interestingly, T cell allo-reactivity of hu-PBMC-NSG mice was amplified significantly compared with that of freshly isolated PBMCs (p < 0.05). Furthermore, magnified hu-T cell responses to donor antigens (Ag) were observed in 2/10 immunosuppressed recipients with multiple acute rejection (AR) experiences, suggesting that the immunological assay in hu-PBMC-NSG mice revealed hidden risks of allograft rejection by IS. Furthermore, donor Ag-specific hyporesponsiveness was maintained in recipients who had been completely weaned off IS (n = 4), despite homeostatic proliferation of hu-T cells in the hu-PBMC-NSG mice. The immunological assay in humanized mice provides a new tool to assess recipient immunity in the absence of IS and explore the underlying mechanisms to maintaining operational tolerance.

Hepatocellular carcinoma (HCC) is a highly heterogeneous disease, which makes the prognostic prediction challenging. Ferroptosis, an iron-dependent form of regulated cell death, can be induced by sorafenib. However, the prognostic value of ferroptosis-related genes in HCC remains to be further elucidated. In this study, the mRNA expression profiles and corresponding clinical data of HCC patients were downloaded from public databases. The least absolute shrinkage and selection operator (LASSO) Cox regression model was utilized to construct a multigene signature in the TCGA cohort. HCC patients from the ICGC cohort were used for validation. Our results showed that most of the ferroptosis-related genes (81.7%) were differentially expressed between HCC and adjacent normal tissues in the TCGA cohort. Twenty-six differentially expressed genes (DEGs) were correlated with overall survival (OS) in the univariate Cox regression analysis (all adjusted P< 0.05). A 10-gene signature was constructed to stratify patients into two risk groups. Patients in the high-risk group showed significantly reduced OS compared with patients in the low-risk group (P < 0.001 in the TCGA cohort and P = 0.001 in the ICGC cohort). The risk score was an independent predictor for OS in multivariate Cox regression analyses (HR> 1, P< 0.01). Receiver operating characteristic (ROC) curve analysis confirmed the signature's predictive capacity. Functional analysis revealed that immune-related pathways were enriched, and immune status were different between two risk groups. In conclusion, a novel ferroptosis-related gene signature can be used for prognostic prediction in HCC. Targeting ferroptosis may be a therapeutic alternative for HCC.

Immunosuppressed (IS) patients are at increased risk for developing Merkel cell carcinoma (MCC) with worsened outcomes compared to immunocompetent (IC) patients. We sought to determine the effects of immune status on the efficacy of adjuvant RT regarding OS for patients with stage I, II or III (localized) MCC of the head and neck. The National Cancer Database was queried for patients with resected, localized MCC of the head and neck with known immune status. Kaplan–Meier methods were used to describe OS. Log-rank tests, multivariable Cox regression models and interaction effect testing were used to compare OS by subgroup categorized by patient and treatment factors including immune status and adjuvant RT receipt. A total of 892 (89.6%) IC and 104 (10.4%) IS patients with MCC of the head and neck were included. Adjuvant RT was associated with improved 3-year OS rate for both IS patients (49.4% vs. 35.5%, p = 0.0467) and stage I/II IC patients (72.4% vs. 62.9%, p = 0.0092). Adjuvant RT was associated with decreased hazard of death (HR 0.77, 95% CI 0.62–0.95). Interaction effect testing did not demonstrate a difference in the efficacy of adjuvant RT on OS between IC and IS status (p = 0.157). In this NCDB analysis, adjuvant RT was associated with decreased hazard of death for patients with localized MCC of the head and neck regardless of immune status and should be considered for both IS and IC patients.

Purpose: To assess the immune status of acute retinal necrosis (ARN) patients and to investigate the immune cell types involved in the immunopathogenesis.Methods: Peripheral blood and intraocular f...

Children with haematologic malignancies and haematopoietic stem cell transplant recipients are at high risk for invasive fungal diseases (IFD). There has been an increased number of at-risk children over the past two decades due to improvements in cancer therapies resulting in improved survival of children with high-risk and refractory malignancies. The predominant organisms that cause IFD include Candida spp., Aspergillus spp. and the Mucorales molds. Clinical presentations of IFD vary based on host immune status and the causative organism. Though serum biomarkers such as the galactomannan assay and beta-D-glucan assay have been validated in adults, there are limited data regarding their diagnostic value in children. Thus, the gold standard for IFD diagnosis remains tissue biopsy with histopathological and microbiological evaluation. Treatment of IFD is multimodal and involves antifungal drugs, correction of immune dysfunction and surgical resection when feasible. Paediatric practice regarding IFD is largely extrapolated from data generated in adult patients; in this review, we evaluate both primary paediatric studies and guidelines intended for adult patients that are applied to paediatric patients. There remain significant knowledge gaps with respect to the prevention, diagnosis and treatment of IFD in immunocompromised children, and further research is needed to help guide management decisions.

Background Small cell lung cancer (SCLC) is an aggressive disease involving immunodeficiency for which chemotherapy is the standard treatment. Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) is widely used for primary or secondary prophylaxis of febrile neutropenia (FN) in chemotherapy. However, whether PEG-rhG-CSF influences immune cells, such as lymphocytes, remains unclear. Methods A total of 17 treatment-naive SCLC patients were prospectively enrolled and divided into the PEG-rhG-CSF and control groups according to their FN risk. Longitudinal sampling of peripheral blood was performed before, after and 4-6 days after the first cycle of chemotherapy. Flow cytometry was used to assess lymphocyte subsets, including CD3+ T, CD4+ T, CD8+ T, NK, and B cells. The diversity and clonality of the T-cell receptor (TCR) repertoire was analyzed by next-generation sequencing. Results In the PEG-rhG-CSF group, the proportions of CD3+ T and CD4+ T cells had increased significantly (P = 0.002, P = 0.020, respectively), whereas there was no increase in CD8+ T cells. Further, TCR diversity increased (P = 0.009) and clonality decreased (P = 0.004) significantly after PEG-rhG-CSF treatment. However, these factors showed opposite trends before and after chemotherapy. Vβ and Jβ gene fragment types, which determine TCR diversity, were significantly amplified in the PEG-rhG-CSF group. The change in TCR diversity was significantly correlated with changes in the CD3+ T or CD4+ T cell proportions, but not the CD8+ T cell proportion. Conclusions PEG-rhG-CSF regulates the immune status of SCLC patients; CD4+ T cells may be the main effector cells involved in this process. These findings may optimize the treatment of SCLC. Key points PEG-rhG-CSF regulates SCLC immunity. PEG-rhG-CSF increased CD3+ T and CD4+ T cell proportions. PEG-rhG-CSF increased TCR diversity and decreased clonality in peripheral blood. Change in TCR diversity were correlated with CD3+ T or CD4+ T changes.

The problem of pregnancy losses and infertility in autoimmune pathology is one of the most urgent problems of modern reproductive medicine. Antiphospholipid antibodies (aPL) are very often connected with reproductive failures such as miscarriage, antenatal fetal death, preeclampsia and even infertility and failure ofTo evaluate the difference in immune status of aPL-positive women with infertility compared to healthy women and explain the possible mechanism of pathological effects of aPL, a correlation analysis between the level of aPL and the lymphocytes subpopulation was performed.We observed 280 women of reproductive age. Of these, 191 who met the inclusion and exclusion criteria were included in the study. All 191 women were tested for lupus anticoagulant (LA), antibodies (isotypes IgG, IgM) to cardiolipin (aCL), ß2-glycoprotein-1 (b2-GpI). Of these, 128 women had high level of aPL. The subpopulation of lymphocyte in aPL-positive women was compared with healthy women without reproductive pathology.In women with aPL, the absolute number of CD3T-regulatory cells play an important role in inducing tolerance to fetal alloantigens and limiting the intensity of the immune response. NK cells play an important role in processes of trophoblast invasion and spiral artery remodeling. Significantly reduced level of T-cells found in women with aPL may be associated with insufficient decidualization of endometrium for embryo invasion, which is clinically manifested by IVF failure.

Purpose Contact lens wearers aged 15–25 years are at higher risk of corneal inflammation, yet little is known about corneal inflammatory state in this group. Previous investigations show density of corneal epithelial dendritic cells (CEDC) may increase with contact lens wear. However, it is not known how corneal distribution or morphology of CEDC alters with lens wear or whether these markers are affected by age. This study characterised CEDC in adolescent and young adult contact lens wearers to determine effects of contact lens wear and age on CEDC density, distribution and morphology. Method Forty participants (20 contact lens wearers, 20 healthy non-wearers; age 16–36 years; 16M:24F) completed this pilot study. Corneal images were captured using in vivo confocal microscopy (HRTII, Rostock). CEDC were manually counted in a 1 mm2 area of the central and mid-peripheral cornea, and ratio of central to midperipheral density was calculated. CEDC morphology and dendrite length were graded. Differences between groups and between regions, and associations with age were examined. Significance was determined at P Results A lower ratio of central to mid-peripheral CEDC density was found with younger age (ρ = 0.42, P = 0.01). CEDC morphology was not associated with age or contact lens wear. CEDC density in the mid-peripheral cornea was higher in soft lens wearers than non-wearers (P = 0.04), but central density did not differ. CEDC density and morphology were not significantly different between centre (median density 11 cells/mm2, range 0–120) and mid-periphery (10 cells/mm2, 0–58). Conclusion Density, distribution and morphology of CEDC do not differ in established contact lens wearers. A relatively lower density of CEDC in the central cornea of younger patients may allude to a more naive immune status in this group and warrants further study. Decreased central CEDC density identified in orthokeratology lens wear requires confirmation in a larger group.

Monitoring allograft function after kidney transplant has routinely relied on the use of nonspecific markers, such as serum creatinine, glomerular filtration rate, proteinuria, and donor-specific antibodies. These traditional markers have low sensitivity and fail to detect subclinical changes. Diagnosis of renal allograft dysfunction still requires an allograft biopsy, as it remains the criterion standard for assessment of graft status. However, renal biopsy is an invasive procedure, and sampling errors may result in misdiagnosis, perhaps causing graft failure. New biomarkers have been developed to monitor allograft function, although many are not yet routinely used. Other shortcomings, such as lack of standardization and high cost, should be solved before their widespread application in the clinic. A recipient's immune status could be monitored by use of urine or blood samples. These include functional cell-based assays and the evaluation of molecular expression at the messenger RNA or protein levels. Molecular technologies, including molecular microscope diagnostic systems, have been recently developed to improve the yield of histologic evaluation of the allograft biopsy. Prospective, interventional trials are required to demonstrate whether these new biomarkers improve patient or transplant outcomes. Implementation of these technologies into standard clinical practice remains challenging until their generalizability, cost, ease of interpretation, and the identification of patients who may benefit from more than standard-of-care surveillance can be determined. These biomarkers could allow immunosuppressive therapy to be individualized for patients.

Background Metabolic dysfunction-associated fatty liver disease (MAFLD) is a highly heterogeneous disease and its heterogeneity might be associated with ferroptosis because ferroptosis plays an important role in the development of MAFLD. We aimed to perform integrative analysis of ferroptosis related genes and MAFLD subtypes using bioinformatics. Methods A differential expression analysis was performed to identify key ferroptosis-related genes associated with the clinical characteristics of MAFLD. Furthermore, consensus k clustering was utilized to distinguish ferroptosis-related clinical subtypes of MAFLD and assess the association of ferroptosis-related gene expression and clinical features between patients with different subtypes of MAFLD. Moreover, the variation in the immune status and regulatory relationship of ferroptosis-related genes in individuals with MAFLD was also explored using single sample gene set enrichment analysis, weighted gene coexpression network analysis and enrichment analyses. Results Eight ferroptosis-related genes were identified as closely associated with both the hepatic steatosis grade and non-alcoholic fatty liver disease activity score. Two subtypes of MAFLD based on ferroptosis-related genes were identified by consensus clustering. They exhibited significantly different clinical features, immune statuses, biological processes and outcomes. The progression of the two subtypes was associated with immunity. Conclusions Two highly heterogeneous subtypes of MAFLD with significantly distinct clinical features, biological processes and immune statuses were identified based on ferroptosis-associated genes, which strongly supports the hypothesis that ferroptosis plays an important role in the development of MAFLD.

Besides the two main histologic types of papillary thyroid carcinoma (PTC), the classical PTC (CL-PTC) and the follicular variant PTC (FV-PTC), several other variants are described. The encapsulated FV-PTC variant was recently reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) due to its similarities to benign lesions. Specific molecular signatures, however, are still unavailable. It is well known that improper DNA repair of dysfunctional telomeres may cause telomere-related genome instability. The mechanisms involved in the damaged telomere repair processing may lead to detrimental outcomes, altering the three-dimensional (3D) nuclear telomere and genome organization in cancer cells. This pilot study aimed to evaluate whether a specific 3D nuclear telomere architecture might characterize NIFTP, potentially distinguishing it from other PTC histologic variants. Our findings demonstrate that 3D telomere profiles of CL-PTC and FV-PTC were different from NIFTP and that NIFTP more closely resembles follicular thyroid adenoma (FTA). NIFTP has longer telomeres than CL-PTC and FV-PTC samples, and the telomere length of NIFTP overlaps with that of the FTA histotype. In contrast, there was no association between BRAF expression and telomere length in all tested samples. These preliminary findings reinforce the view that NIFTP is closer to non-malignant thyroid nodules and confirm that PTC features short telomeres.

Toxoplasma gondii is a widespread protozoan parasite infecting approximately one third of the world population. After proliferation of tachyzoites during the acute stage, the parasite forms tissue cysts in various anatomical sites and establishes chronic infection. Nowadays the nature of the interplay between the protozoan and its human host remains elusive. This is clearly evident in ocular toxoplasmosis, in which the parasite establishes an ambivalent relationship with the eye, manipulating the immune response and inducing variable initial lesions and further relapses. This review will focus on epidemiology and environmental, parasite and host related risk factors, clinical manifestations and laboratory findings, treatment and prophylaxis approaches in ocular toxoplasmosis. An image collection of patients referred to the Unit of Ophthalmology of Pisa's Hospital will be presented, too.

As of October 2021, coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global emergency, and novel therapeutics are urgently needed. Here we describe human single chain variable fragment (scFv) antibodies (76clAbs) that block an epitope of the SARS-CoV-2 spike protein essential for ACE2-mediated entry into cells. 76clAbs neutralize the delta variant and other variants being monitored (VBMs) and inhibit spike-mediated pulmonary cell-cell fusion, a critical feature of COVID-19 pathology. In two independent animal models, intranasal administration counteracted the infection. Due to high efficiency, remarkable stability, resilience to nebulization and low production cost, 76clAbs may become a relevant tool for rapid, self-administrable early intervention in SARS-CoV-2-infected subjects independently of their immune status.

Purpose: The role of different circulating lymphocyte subsets, as well as their correlation with clinical characteristics of small cell lung cancer patients have not yet been fully understood. This study aims to evaluate the influence of the fluctuating absolute numbers of lymphocyte subpopulations in peripheral blood of patients with small cell lung cancer. Methods: The absolute counts and percentages of lymphocyte subsets in peripheral blood of 329 patients with small cell lung cancer were retrospectively analyzed. The numbers of CD3+, CD3+CD4+, and CD3+CD8+ T lymphocytes, CD3−CD19+ B lymphocytes, and CD3−CD16+CD56+ NK cells were evaluated by flow cytometry. Their relationship with the patients’ clinical characteristics were statistically evaluated. Results: The CD4/CD8 values derived from the absolute number and percentage of CD3+CD4+ cells divided by CD3+CD8+ cells were identical (1.86 ± 0.99). There was no association between any of the lymphocyte subsets levels and age/sex of the 329 patients with small cell lung cancer. The patients with advanced stage had a reduction in CD3+ and CD3+CD4+ T cell counts and a decreased CD4/CD8 ratio. The levels of CD3+CD4+ T cells, CD3−CD19+ B cells, CD3−CD16+CD56+ NK cells, and CD4/CD8 ratio were associated with advanced tumor-node-metastasis stage. Patients who had undergone radiotherapy were characterized by lymphopenia with lower numbers of CD3+, CD3+CD4+, CD3+CD8+ T lymphocyte, B lymphocyte, NK cell, and CD4/CD8 ratio. The evaluation of individual CD4/CD8 ratio should be combined with other clinical parameters. Conclusions: Patients with small cell lung cancer have altered lymphocyte homeostasis. Lymphopenia was a long-lasting feature of the enrolled patients who were treated with radiotherapy. The available lymphocyte subsets levels might be used to manage the clinical treatment scheme.

Background Infiltrating immune and stromal cells are important components of the endometrial cancer (EC) microenvironment, which has a significant effect on the biological behavior of EC, suggesting that unique immune-related genes may be associated with the prognosis of EC. However, the association of immune-related genes with the prognosis of EC has not been elucidated. We attempted to identify immune-related genes with potentially prognostic value in EC using The Cancer Genome Atlas database and the relationship between immune microenvironment and EC. Methods We analyzed 578 EC samples from TCGA database and used weighted gene co-expression network analysis to screen out immune-related genes. We constructed a protein–protein interaction network and analyzed it using STRING and Cytoscape. Immune-related genes were analyzed through conjoint Cox regression and random forest algorithm analysis were to identify a multi-gene prediction model and stratify low-risk and high-risk groups of EC patients. Based on these data, we constructed a nomogram prediction model to improve prognosis assessment. Evaluation of Immunological, gene mutations and gene enrichment analysis were applied on these groups to quantify additional differences. Results Using conjoint Cox regression and random forest algorithm, we found that TRBC2, TRAC, LPXN, and ARHGAP30 were associated with the prognosis of EC and constructed four gene risk models for overall survival and a consistent nomogram. The time-dependent receiver operating characteristic curve analysis revealed that the area under the curve for 1-, 3-, and 5-y overall survival was 0.687, 0.699, and 0.76, respectively. These results were validated using a validation cohort. Immune-related pathways were mostly enriched in the low-risk group, which had higher levels of immune infiltration and immune status. Conclusion Our study provides new insights for novel biomarkers and immunotherapy targets in EC.

BackgroundMuch research shows that blood calcidiol (25(OH)D3) levels correlate strongly with SARS-CoV-2 infection severity. There is open discussion regarding whether low D3 is caused by the infection or if deficiency negatively affects immune defense. The aim of this study was to collect further evidence on this topic.MethodsSystematic literature search was performed to identify retrospective cohort as well as clinical studies on COVID-19 mortality rates versus D3 blood levels. Mortality rates from clinical studies were corrected for age, sex and diabetes. Data were analyzed using correlation and linear regression.ResultsOne population study and seven clinical studies were identified, which reported D3 blood levels pre-infection or on the day of hospital admission. They independently showed a negative Pearson correlation of D3 levels and mortality risk (r(17)=-.4154, p=.0770/r(13)=-.4886, p=.0646). For the combined data, median (IQR) D3 levels were 23.2 ng/ml (17.4 – 26.8), and a significant Pearson correlation was observed (r(32)=-.3989, p=.0194). Regression suggested a theoretical point of zero mortality at approximately 50 ng/ml D3.ConclusionsThe two datasets provide strong evidence that low D3 is a predictor rather than a side effect of the infection. Despite ongoing vaccinations, we recommend raising serum 25(OH)D levels to above 50 ng/ml to prevent or mitigate new outbreaks due to escape mutations or decreasing antibody activity.Trial registrationNot applicable.

Background We characterized the clinical features, radiographic characteristics, and response to treatment of immunocompetent and immunocompromised patients with pulmonary cryptococcosis (PC). Methods We retrospectively reviewed the medical records and radiological profiles of patients diagnosed with PC who received surgical resection between May 2015 and November 2020 in a tertiary referral center. Results A total of 21 males and 18 females were included in the study. 23 patients were immunocompetent and 20 out of the 39 were asymptomatic. Immunocompetent patients were diagnosed with PC at a younger age than immunocompromised patients (48.9 vs 57.1 years, P = 0.02). Single nodule pattern was the most frequent lesion pattern (33 out of 39, 84.6%) and right upper lobe was the most common site of location (15 out of 47, 31.9%). The majority of lesions were located peripherally (38 out of 47, 80.9%) and most lesions were 1–2 cm in diameter (30 out of 47, 63.8%). Cavitation was more likely to occur in immunocompromised patients (5 out of 11, 45.5%) than in immunocompetent patients (6 out of 36, 16.7%) (P = 0.04) and there was complete resolution of PC in all patients treated with anti-fungal therapy. Conclusions Immunocompetent patients were diagnosed with PC at a younger age than immunocompromised patients. Single nodule pattern was the most frequent lesion pattern in PC patients. Cavitation was more likely to occur in immunocompromised patients than in immunocompetent patients.

BackgroundAlthough immune checkpoint inhibitors (ICIs), especially programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) axis blockers, exhibit prominent antitumor effects against numerous malignancies, their benefit for patients with prostate cancer (PCa) has been somewhat marginal. This study aimed to assess the feasibility of B7-H3 or HHLA2 as alternative immunotherapeutic targets in PCa.MethodsImmunohistochemistry was performed to evaluate the expression pattern of PD-L1, B7-H3 and HHLA2 and the infiltration of CD8+ and Foxp3+ lymphocytes in 239 PCa tissues from two independent cohorts. The correlations between B7-H3 and HHLA2 and clinicopathological features, including the presence of CD8+ and Foxp3+ tumor-infiltrating lymphocytes (TILs), were explored.ResultsHHLA2 expression was much higher than PD-L1 expression but lower than B7-H3 expression in PCa tissues. High expression of both B7-H3 and HHLA2 was significantly associated with higher Gleason score and tumor stage, lymph node metastasis and dismal overall survival (OS) and cancer-specific survival (CSS). Moreover, a high B7 score, defined as high B7-H3 expression and/or high HHLA2 expression, was an independent prognostic predictor for PCa. Of note, a high B7 score was negatively correlated with CD8+ TILs. Importantly, a new immune classification, based on the B7 score and CD8+ TILs, successfully stratified OS and CSS in PCa.ConclusionsBoth B7-H3 and HHLA2 have a critical impact on the immunosuppressive microenvironment, and the B7 score could be used as an independent prognostic factor for PCa. The B7 score combined with CD8+ TILs could be used as a new immune classification to stratify the risk of death, especially cancer-related death, for patients with PCa. These findings may provide insights that could improve response to immune-related comprehensive therapy for PCa in the future.

Immunoglobulins are the primary protective products in human milk and are responsible for transferring maternal pathogen memory to the infant, providing protection by binding to recognized pathogens and inhibiting virulence. To better understand potentially protective/anti-infective compounds in human milk, the establishment of human milk–tailored analytical approaches is crucial, as most contemporary analytical methods have been optimized for plasma or serum. One of the most prominent immunoglobulins in human milk is secretory immunoglobulin A (sIgA), which may be relevant for the protection of breastfed infants from harmful pathogens. Advanced sIgA detection methods can help monitor the immune status and development of the mother-infant dyad. We therefore developed an enzyme-linked immunosorbent assay (ELISA) sIgA method for the quantitative analysis of IgA plus secretory component (SC), validated with sIgA standards and substantiated by mass spectrometry (MS)–based proteomics. A very strong correlation was observed between the MS-detected IgA1 and the human milk–specific sIgA ELISA (r = 0.82). Overall, the MS data indicate that the developed human milk sIgA ELISA does not differentiate between sIgA1 and sIgA2 and is, therefore, a reflection of total sIgA. Furthermore, our MS data and the human milk–derived sIgA ELISA data are better correlated than data derived from a standard serum IgA ELISA kit (relative to MS IgA1 r = 0.82 and r = 0.42, respectively). We therefore propose our human milk–specific sIgA ELISA as an ideal quantitative indicator of total sIgA with advantages over current serum IgA ELISA kits. Supplementary Information The online version contains supplementary material available at 10.1007/s00216-021-03468-4.

COVID-19 implications are still a threat to global health. In the face of this pandemic, food and nutrition are key issues that can boost the immune system. The bioactivity of functional foods and nutrients (probiotics, prebiotics, water- and fat-soluble vitamins, minerals, flavonoids, glutamine, arginine, nucleotides, and PUFAs) contributes to immune system modulation, which establishes the status of nutrients as a factor of immune competence. These foods can contribute, especially during a pandemic, to the minimization of complications of SARS-CoV-2 infection. Therefore, it is important to support the nutritional strategies for strengthening the immune status, associated with good eating habits, as a way to confront COVID-19.

The treatment of chronic inflammatory and degenerative diseases by low dose radiation therapy (LDRT) is promising especially for patients who were refractory for classical therapies. LDRT aims to reduce pain of patients and to increase their mobility. Although LDRT has been applied since the late 19th century, the immunological mechanisms remain elusive. Within the prospective IMMO-LDRT01 trial (NCT02653079) the effects of LDRT on the peripheral blood immune status, as well as on pain and life quality of patients have been analyzed. Blood is taken before and after every serial irradiation with a single dose per fraction of 0.5Gy, as well as during follow-up appointments in order to determine a detailed longitudinal immune status by multicolor flow cytometry. Here, we report the results of an interim analysis of 125 patients, representing half the number of patients to be recruited. LDRT significantly improved patients’ pain levels and induced distinct systemic immune modulations. While the total number of leukocytes remained unchanged in the peripheral blood, LDRT induced a slight reduction of eosinophils, basophils and plasmacytoid dendritic cells and an increase of B cells. Furthermore, activated immune cells were decreased following LDRT. Especially cells of the monocytic lineage correlated to LDRT-induced improvements of clinical symptoms, qualifying these immune cells as predictive biomarkers for the therapeutic success. We conclude that LDRT improves pain of the patients by inducing systemic immune modulations and that immune biomarkers could be defined for prediction by improved patient stratification in the future.

Summary Diet modulates the gut microbiome, which in turn can impact the immune system. Here, we determined how two microbiota-targeted dietary interventions, plant-based fiber and fermented foods, influence the human microbiome and immune system in healthy adults. Using a 17-week randomized, prospective study (n = 18/arm) combined with -omics measurements of microbiome and host, including extensive immune profiling, we found diet-specific effects. The high-fiber diet increased microbiome-encoded glycan-degrading carbohydrate active enzymes (CAZymes) despite stable microbial community diversity. Although cytokine response score (primary outcome) was unchanged, three distinct immunological trajectories in high-fiber consumers corresponded to baseline microbiota diversity. Alternatively, the high-fermented-food diet steadily increased microbiota diversity and decreased inflammatory markers. The data highlight how coupling dietary interventions to deep and longitudinal immune and microbiome profiling can provide individualized and population-wide insight. Fermented foods may be valuable in countering the decreased microbiome diversity and increased inflammation pervasive in industrialized society.

We recently demonstrated how sepsis influences the subsequent development of experimental autoimmune encephalomyelitis (EAE) presented a conceptual advance in understanding the postsepsis chronic immunoparalysis state. However, the reverse scenario (autoimmunity prior to sepsis) defines a high-risk patient population whose susceptibility to sepsis remains poorly defined. In this study, we present a retrospective analysis of University of Iowa Hospital and Clinics patients demonstrating increased sepsis prevalence among multiple sclerosis (MS), relative to non-MS, patients. To interrogate how autoimmune disease influences host susceptibility to sepsis, well-established murine models of MS and sepsis and EAE and cecal ligation and puncture, respectively, were used. EAE, relative to non-EAE, mice were highly susceptible to sepsis-induced mortality with elevated cytokine storms. These results were further recapitulated in LPS and Streptococcus pneumoniae sepsis models. This work highlights both the relevance of identifying highly susceptible patient populations and expands the growing body of literature that host immune status at the time of septic insult is a potent mortality determinant.

Background In the past few years, immunotherapy has changed the way we treat solid tumors. People pay more and more attention to the immune microenvironment of laryngeal squamous cell carcinoma (LSCC). In this study, our immunotherapy research took advantage of the clinical database and focused our in-depth analysis on the tumor microenvironment (TME). Methods This study evaluated the relationship between the clinical outcome and the local tissue and overall immune status in 412 patients with primary LSCC. We constructed and validated a risk model that could predict prognosis, assess immune status, identify high-risk patients, and develop personalized treatment plans through bioinformatics. In addition, through immunohistochemical analysis, we verified the differential expression of CTSL and KDM5D genes with the largest weight coefficients in the model in LSCC tissues and their influence on the prognosis and tumor-infiltrating lymphocytes (TILs). Results We found that interstitial tumor-infiltrating lymphocytes (iTILs), tumor parenchymal infiltrating lymphocyte volume (TILv), tumor infiltrates lymphocytes of frontier invasion (TILf), and the platelet-to lymphocyte ratio (PLR) were independent factors affecting the prognosis of patients with LSCC. A novel risk model can guide clinicians to accurately predict prognosis, identify high-risk patients, and formulate personalized treatment plans. The differential expression of genes such as CTSL and KDM5D can significantly affect the TILs of LSCC and the prognosis of patients. Conclusion Local and systemic inflammatory markers in patients with laryngeal squamous cell carcinoma are reliable prognostic factors. The risk model and CTSL, KDM5D gene have important potential research value.

Currently, 2 genotypes of Influenza B viruses (IFB) are cocirculating in humans: Victoria (VIC) and Yamagata (YAM). Infection and viral load (VL) were analyzed in 105 genotyped IFB (59 VIC and 46 YAM) out of 3452 respiratory samples from immunodepressed (ID), immunocompetent (IC) including outpatients (OP) and hospitalized patients (HP) attended during 2001‐2013 at São Paulo Hospital. VL (Log10 RNA copies/mL) calculation was possible in 78 samples (47 VIC, 31 YAM). The age group of 12 to 18 years presented the highest detection (14.13%). Rates of infection among groups were of 3.67% (IC), 1.68% (ID), 3.50% (OP), 0.6% (HP), and VLs varied from 2.8 to 10.13 with no difference regarding age, immune status, and disease severity. From 10 OP vaccinated against influenza, 8 (7 children, 1 ID) received a matching strain shot (VIC), and 2 a monovalent influenza A H1N1pdm09. Those patients presented a VL of 6.31 ± 1.62 (mean ± SD). IFB infection rates follow an age pattern, but VL seems not to be related to frequency or clinical outcome. IFB patients with previous immunization could point to some protection for VIC infections since there was no HP. Other immunological aspects, such as lineage infection immune priming, previous infections, and vaccinations, should be further investigated., Research Highlights The age group of 12–18 years old presented the highest IFB detection.IFB YAM infections occurred more frequently among those with

Background It was reported that tumor-expressed dickkopf-related (DKK) proteins affect micro-environment. However, the influence of DKK1 on colorectal cancer (CRC) liver oligometastases (CRCLOM) remains unclear. Methods CRC cases after resection of liver oligometastases were enrolled in Sun Yat-Sen University Cancer Center with intact clinical data. Serum DKK1 was detected by ELISA assay. Immunofluorescent staining examination for CD3 and CD8 in slices were also conducted. Results Among 65 patients included, the recurrence-free survival (RFS) and overall survival (OS) were significantly better in the low serum DKK1 group (RFS: P = 0.021; OS: P = 0.043). DKK1 was overexpressed in stage IV CRC patients in TCGA data. The number of CD8+ tumor-infiltrating lymphocytes (TILs) in invasive margin of CRC liver oligometastases was significantly higher in low serum DKK1 group (P = 0.042). Conclusion Elevated serum DKK1 level was associated with poorer RFS and OS, and less CD8+ TILs in invasive margin in CRC liver oligometastases. DKK1 might serve as a supplementalprognostic factor for clinical risk score and a potential target for immunotherapy.

The lack of stable housing can impair access and continuity of care for patients living with human immunodeficiency virus (HIV). This study investigated the relationship between housing status assessed at multiple time points and several core HIV-related outcomes within the same group of HIV patients experiencing homelessness. Patients with consistently stable housing (CSH) during the year were compared to patients who lacked CSH (non-CSH group). The study outcomes included HIV viral load (VL), CD4 counts, and health care utilization. Multivariable and propensity weighted analyses were used to assess outcomes adjusting for potential group differences. Of 208 patients, 88 (42%) had CSH and 120 (58%) were non-CSH. Patients with CSH had significantly higher proportion of VL suppression and higher mean CD4 counts. The frequency of nurse visits in the CSH group was less than a half of that in the non-CSH group. Patients with CSH were less likely to be admitted to the medical respite facility, and if admitted, their length of stay was about a half of that for the non-CSH group. Our study findings show that patients with CSH had significantly better HIV virologic control and immune status as well as improved health care utilization.

Background Pulmonary cryptococcosis (PC) is not considered an rare, opportunistic infection anymore. The immunocompetent population accounts for an increasing proportion of the morbidity. Objective This study investigated the clinical characteristics of PC patients spanning 20 years, in a referral centre of China. Patients/methods We retrospectively investigated the clinical data of 99 patients with PC who were diagnosed at Peking Union Medical College Hospital (PUMCH) from January 1998 to December 2017. Results Pulmonary cryptococcosis incidence in PUMCH has seen sharp increase in two decades. There were 40.4% (40/99), 17.2% (17/99) and 42.4% (42/99) immunocompetent, mildly immunocompromised and severe immunocompromised patients, respectively. Significantly higher (P = .035) male predominance in immunocompetent and mildly immunocompromised groups (68.4%, 39/57) compared with severe immunocompromised group (45.2%, 19/42) was found. Overall, 27.5% (11/40) immunocompetent patients reported a significant difference (P = .02) in history of more than weekly drinking, higher than mildly or severe immunocompromised. No significant difference occurred in symptoms and radiographic characteristics among the groups. In pulmonary computerised tomography findings, the non-air pathway feature was the dominant distribution characteristics in all patients with PC (P = .002). The gap in body dissemination frequency between immunocompetent combined with mildly immunocompromised (5.26%, 3/57) and severe immunocompromised (19.0%, 8/42) was marginally significant (P = .05). Conclusions Gender and alcohol drinking could be PC risk factors of concern in patients without severe immunodeficiency. No significant difference occurred in symptoms or radiographic characteristics between patients with different levels of immune status. The unique radiographic non-air pathway distribution in the lung may be the feature of Cryptococcus invasion that may enhance accurate diagnosis.