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Background and aims: Inflammatory bowel diseases (IBD) are multifactorial chronic inflammatory disorders affecting the gastrointestinal tract. However, a broad spectrum of extraintestinal manifestations (EIMs) is associated with IBD, affecting several organs and systems, such as the skin, musculoskeletal and hepatobiliary systems, and, not least, the eye. Approximately 10% of IBD patients can develop ocular EIMs (O-EIMs) with a higher prevalence in Crohn's disease (CD). Eye-redness, photophobia, pain, and blurred vision are the common symptoms, with a wide rate of severity and clinical impact on the quality of life. This narrative review aims to summarize the prevalence, pathogenesis, and current evidence-based management of O-EIMs, underlying the importance of a holistic approach and specialties collaboration for a prompt diagnosis and treatment. Methods: PubMed was searched up to December 2023 to identify relevant studies investigating the pathogenesis, epidemiology, and treatment of O-EIMs in IBD patients. Results: The mechanisms underlying O-EIMs are partially unknown, encompassing immune dysregulation, shared antigens between the eye and the gut, genetic predisposition, and systemic inflammation driven by high levels of interleukins and cytokines in IBD patients. The complexity of O-EIMs' pathogenesis reflects in the management of these conditions, varying from topical and systemic steroids to immunomodulatory molecules and biologic therapy, such as anti-tumor necrosis factor (TNF)-alpha. A multidisciplinary approach is the backbone of the management of O-EIMs. [ABSTRACT FROM AUTHOR]

A total of 25 marketed quinoa seed samples different for origin, farming system and packaging were analyzed for the presence of mycotoxigenic fungi (by isolation both on Potato Dextrose Agar and with the deep-freezing blotter method) and relative contamination by mycotoxins (by LC-MS/MS analysis). Fungal microorganisms, but not mycotoxins, were detected in all the samples, and 25 isolates representative of the mycobiota were obtained. Morphological and molecular characterization and, for some isolates, the in vitro mycotoxigenic profile, allowed the identification of 19 fungal species within five different genera: Alternaria, Aspergillus, Penicillium, Cladosporium and Fusarium. Among the identified species, Alternaria abundans, A. chartarum, A. arborescens, Cladosporium allicinum, C. parasubtilissimum, C. pseudocladosporioides, C. uwebraunianum, Aspergillus jensenii, A. tubingensis, Penicillium dipodomyis, P. verrucosum and P. citreosulfuratum were first reported on quinoa, and Alternaria infectoria and Fusarium oxysporum were first reported on quinoa seeds. The geographical origin, farming system and packaging were showed to affect the amount and type of the isolated fungal species, highlighting that the level of fungal presence and their related secondary metabolites is conditioned by different steps of the quinoa supply chain. However, despite the presence of mycotoxigenic fungi, the marketed quinoa seeds analyzed resulted in being free from mycotoxins. [ABSTRACT FROM AUTHOR]

Purpose To assess the relationship of demographics, clinical characteristics and structural optical coherence tomography (OCT) findings to disease recurrence in a cohort of patients with newly diagnosed myopic choroidal neovascularisation (CNV) Methods In this retrospective, longitudinal study, a total of 64 participants (64 eyes) with successfully treated myopic CNV had obtained resolution of exudation after treatment (study baseline) and with 3 years of regular follow-ups. Several baseline OCT qualitative features and quantitative measurements were assessed at baseline and included in the analysis. Main outcome measures included incidence of disease recurrence and HR for demographics, clinical characteristics and OCT risk factors. Results At month 36, 40 eyes (62.5%) developed disease recurrence (active CNV). Multivariate linear regression analysis revealed that final visual acuity (dependent variable) was associated with visual acuity at the first visit after complete resolution of exudation (p<0.0001), baseline size of patchy atrophy (p=0.010), baseline subfoveal choroidal thickness (p=0.008), baseline maximum CNV height and width (p=0.011 and p=0.003) and recurrence of CNV exudation (p=0.007). The following factors were associated with an increased risk of disease recurrence: size of patchy atrophy had an HR of 1.14 (95% CI 1.01 to 1.29; p=0.036); maximum CNV width had an HR of 1.02 (95% CI 1.01 to 1.04; p<0.0001). Conclusion We identified OCT risk factors for the disease recurrence in eyes with successfully treated myopic CNV. Assuming that disease recurrence is a sight-threatening event, our findings may help in the identification of high-risk patients and eventually ameliorate their outcome. [ABSTRACT FROM AUTHOR]

Purpose: To compare macular atrophy (MA) secondary to age-related macular degeneration (AMD) and Stargardt disease (STGD) using the choroidal vascularity index (CVI). Methods: In this multicentric retrospective study, two distinct cohorts were collected: patients with MA secondary to AMD and MA secondary to STGD. All patients were investigated using a multimodal imaging approach, including CVI in the subfoveal 1000 μm area. Of note, the CVI is not influenced by aging, which allows comparisons between different cohorts. Results: Seventy eyes were included: 35 eyes of 35 patients (mean age 78 ± 7 years) in the AMD group and 35 eyes of 35 patients (mean age 41 ± 16 years, p < 0.001) in the STGD group. Choroidal thickness was significantly lower in the AMD group in comparison to the STGD group (151 ± 80 μm vs 353 ± 105 μm, p < 0.001). The total choroidal area (TCA) was significantly greater in the STGD group in comparison to the AMD group (1.734 ± 0.958 mm2 vs 0.538 ± 0.391 mm2, respectively, p < 0.001). Interestingly, the CVI was significantly lower in AMD patients in comparison to STGD patients (27.322 ± 15.320% vs 49.880 ± 7.217%, respectively, p < 0.001), and this difference was confirmed in the subgroup of patients over 50 years old. Conclusion: Our results corroborate the hypothesis that large choroidal vessels were impaired to a greater extent in AMD than in STGD. CVI may help in differentiating AMD from STGD in the presence of MA, better understanding of the pathogenesis, and monitoring of therapeutic response. [ABSTRACT FROM AUTHOR]

Chronic obstructive lung disease (COPD) and lung cancer are both caused by smoking and often occur as comorbidity. The programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) axis is an important canonic immunoregulatory pathway, and antibodies that specifically block PD-1 or PD-L1 have demonstrated efficacy as therapeutic agents for non-small cell lung cancer. The role of the PD-1/PD-L1 axis in the pathogenesis of COPD is unknown. Here, we analyzed the function of the PD-1/PD-L1 axis in preclinical COPD models and evaluated the concentrations of PD-1 and PD-L1 in human serum and bronchoalveolar lavage (BAL) fluids as biomarkers for COPD. Anti-PD-1 treatment decreased lung damage and neutrophilic inflammation in mice chronically exposed to cigarette smoke (CS) or nontypeable Haemophilus influenzae (NTHi). Ex vivo stimulated macrophages obtained from anti-PD-1-treated mice released reduced amounts of inflammatory cytokines. PD-L1 concentrations correlated positively with PD-1 concentrations in human serum and BAL fluids. Lung sections obtained from patients with COPD stained positive for PD-L1. Our data indicate that the PD-1/PD-L1 axis is involved in developing inflammation and tissue destruction in COPD. Inflammation-induced activation of the PD-1 pathway may contribute to disease progression. [ABSTRACT FROM AUTHOR]

Purpose To assess the associations among different optical coherence tomography (OCT) structural and angiography quantitative metrics used to characterise the choroid in healthy subjects. Methods In this cross-sectional study, macular structural OCT and OCT angiography (OCTA) images were acquired from healthy subjects. The main outcome measures were: (i) choriocapillaris (CC) flow deficits percentage (FD%), (ii) choroidal luminal (LA) and stromal (SA) areas and (iii) choroidal vascularity index (CVI), which was calculated as the LA divided by the total choroidal area. These measurements were generated using previously published algorithms and were separately computed in the foveal and extrafoveal regions. Results Eighty-five eyes from 85 subjects (44 males, 41 females) were included in the analysis. Mean±SD?age was 47.9±22.4 years (range: 19.0 to 85.0 years). Linear regression analysis displayed no significant associations between CC FD% and other parameters (LA, SA and CVI). Importantly, non-linear regression analysis showed that the relations of LA and SA to CC FD% were all best fitted by a quadratic function. Compared with the linear models, the use of the quadratic function allowed a relative increase in the R2 coefficients. No significant non-linear associations were found between CC FD% and CVI. Conclusion Based on our models, changes in the luminal and stromal areas in the choroid lead to an initial increase in CC perfusion. Subsequently, further increases in LA and SA amounts are accompanied by a progressive increment in CC FD%. [ABSTRACT FROM AUTHOR]

Neutrophilic inflammation results in loss of lung function in chronic obstructive pulmonary disease (COPD). Gram-negative bacteria, such as nontypeable Haemophilus influenzae (NTHi), trigger acute exacerbations of COPD (AECOPD) and contribute to chronic lung inflammation. The pro-inflammatory cytokine interleukin-17C (IL-17C) is expressed by airway epithelial cells and regulates neutrophilic chemotaxis. Here, we explored the function of IL-17C in NTHi- and cigarette smoke (CS)-induced models of COPD. Neutrophilic inflammation and tissue destruction were decreased in lungs of IL-17C-deficient mice (Il-17c-/-) chronically exposed to NTHi. Numbers of pulmonary neutrophils were decreased in Il-17c-/- mice after acute exposure to the combination of NTHi and CS. However, Il-17c-/- mice were not protected from CS-induced lung inflammation. In a preliminary patient study, we show that IL-17C is present in sputum samples obtained during AECOPD and associates with disease severity. Concentrations of IL-17C were significantly increased during advanced COPD (GOLD III/IV) compared to moderate COPD (GOLD I/II). Concentrations of IL-17A and IL-17E did not associate with disease severity. Our data suggest that IL-17C promotes harmful pulmonary inflammation triggered by bacteria in COPD. [ABSTRACT FROM AUTHOR]

Purpose: To estimate the impact of delayed care during the coronavirus disease 2019 (COVID-19) pandemic on the outcomes of patients with neovascular age-related macular degeneration (AMD). Methods: Consecutive patients with diagnosis of neovascular AMD were consecutively enrolled between March 9, 2020, and June 12, 2020, (during and immediately after the Italian COVID-19 quarantine). During the inclusion (or pandemic) visit (V0), patients received a complete ophthalmologic evaluation, including optical coherence tomography (OCT). Best-corrected visual acuity (BCVA) and OCT findings from the two preceding visits (V−1 and V−2) were compared with data at V0. Results: One-hundred patients (112 eyes) were enrolled in this study. The time interval between following visits was 110.7 ± 37.5 days within V0 and V−1 and 80.8 ± 39.7 days within V−1 and V−2, respectively (P < 0.0001). BCVA was statistically worse at the V0 visit as compared with the immediately preceding (V−1) visit (0.50 ± 0.43 LogMAR and 0.45 ± 0.38 LogMAR at the V0 and V−1 visits, respectively; P = 0.046). On structural OCT, 91 out of 112 (81.2%) neovascular AMD eyes displayed the evidence of exudative disease activity at the V0 visit, while 77 (68.7%) eyes exhibited signs of exudation at the V−1 visit (P = 0.022). No differences in terms of BCVA and OCT findings were detected between the V−1 and V−2 visits. In multiple regression analysis, the difference in BCVA between V0 and V−1 visits was significantly associated with the interval time within these two visits (P = 0.026). Conclusion: The COVID-19 pandemic-related postponement in patient care proved to be significantly associated with worse short-term outcomes in these patients. [ABSTRACT FROM AUTHOR]

Purpose: To quantify the shrinking in outpatient and intravitreal injections' volumes in a tertiary referral retina unit secondary to virus causing coronavirus disease 2019 (COVID-19). Methods: In this retrospective cross-sectional study, we reviewed the charts of all patients who had a visit at a medical retina referral center during the Italian quarantine (from 9th of March 2020 to 3rd of May 2020). Number and characteristics of these data were compared with data from the same period in 2019 (from 9th of March 2019 to 3rd of May 2019). Results: In the 2019 study period, there were 303 patients attending clinic (150 males, 153 females). In the 2020 study period, patients decreased to 75 (48 males, 27 females; P = 0.022 comparing gender prevalence between the two periods) with an overall reduction of 75.2%. Mean ± SD age was 71.4 ± 14.3 years (range 25–93 years) in the 2019 study period and 66.7 ± 13.1 years (range 32–91 years) in the 2020 study period (P = 0.005). The largest drop in outpatient volume was recorded in AMD patients (− 79.9%). Regarding the intravitreal treatments, there were 1252 injections in the 2019 period and 583 injections in the 2020 period (− 53.6% in injections). The drop in intravitreal treatments was larger in patients with posterior uveitis, retinal vein occlusion, and diabetes (− 85.7%, − 61.9%, and − 59.6%, respectively). Conclusion: The volume of outpatient visits and intravitreal injections declined during the COVID-19 quarantine. The short- and long-term impacts are that routine in-person visits and intravitreal injections are expected to increase after the quarantine and, even more, after the pandemic. [ABSTRACT FROM AUTHOR]

Optical coherence tomography angiography (OCTA) has significantly expanded our knowledge of the ocular vasculature. In this review, we provide a discussion of the fundamental principles of OCTA and the application of this imaging modality to study the retinal and choroidal vessels. These guidelines are focused on 2020, and include updates since the 2019 publication. Importantly, we will comment on recent findings on OCTA technology with a special focus on the three-dimensional (3D) OCTA visualization. [ABSTRACT FROM AUTHOR]

Placenta-specific 8 (PLAC8) is closely associated with the proliferation, apoptosis and autophagy of several tumor cells. However, the expression and function of PLAC8 in oral squamous cell carcinoma (OSCC) remain unknown. Therefore, the present study investigated the function and mechanism of PLAC8 in OSCC. Reverse transcription-quantitative PCR and western blot analyses were performed to quantify the expression of PLAC8 in OSCC cell lines. The function of PLAC8 in OSCC was investigated via transfection, the Transwell and Cell Counting Kit-8 assays, immunofluorescence staining and western blotting. The results demonstrated that PLAC8 exspression was downregulated in OSCC cell lines. PLAC8 inhibited the cell proliferation in OSCC. In addition, PLAC8 restrained invasion and epithelialmesenchymal transition of OSCC cells. Furthermore, β-catenin helped to repress PLAC8 expression by regulating the Wnt/β- catenin and PI3K/Akt/GSK3β signaling pathways in OSCC cells. Collectively, the results of the present study suggest that PLAC8 acts as a tumor suppressor in OSCC by downregulating β-catenin. [ABSTRACT FROM AUTHOR]

Background: The interleukin 17 receptor E (IL-17RE) is specific for the epithelial cytokine interleukin-17C (IL-17C). Asthma exacerbations are frequently caused by viral infections. Polyinosinic:polycytidylic acid (pIC) mimics viral infections through binding to pattern recognition receptors (e.g. TLR-3). We and others have shown that pIC induces the expression of IL-17C in airway epithelial cells. Using different mouse models, we aimed to investigate the function of IL-17RE in the development of experimental allergic asthma and acute exacerbation thereof.Methods: Wild-type (WT) and IL-17RE deficient (Il-17re-/-) mice were sensitized and challenged with OVA to induce allergic airway inflammation. pIC or PBS were applied intranasally when allergic airway inflammation had been established. Pulmonary expression of inflammatory mediators, numbers of inflammatory cells, and airway hyperresponsiveness (AHR) were analyzed.Results: Ablation of IL-17RE did not affect the development of OVA-induced allergic airway inflammation and AHR. pIC induced inflammation independent of IL-17RE in the absence of allergic airway inflammation. Treatment of mice with pIC exacerbated pulmonary inflammation in sensitized and OVA-challenged mice in an IL-17RE-dependent manner. The pIC-induced expression of cytokines (e.g. keratinocyte-derived chemokine (KC), granulocyte-colony stimulating factor (G-CSF)) and recruitment of neutrophils were decreased in Il-17re-/- mice. pIC-exacerbated AHR was partially decreased in Il-17re-/- mice.Conclusions: Our results indicate that IL-17RE mediates virus-triggered exacerbations but does not have a function in the development of allergic lung disease. [ABSTRACT FROM AUTHOR]

Introduction: To describe the ocular inflammatory and iatrogenic complications in a cohort of uveitic patients treated in an Italian referral centre. Material and methods: Retrospective non-comparative case series. Medical history and clinical findings of all consecutive patients referred to the uveitis center of Pisa University from January 2015 to January 2017 were reviewed. Only patients with at least three follow-up visits in our center were included in our series. Results: Three hundred and eighty-nine patients were visited in our center during study period; only 142 patients (90 men and 52 female) satisfied the inclusion criteria. Mean age at presentation was 41 ± 14 years. The most common ocular feature was anterior uveitis (46%) and was mainly unilateral. A specific etiological diagnosis was established in 61% of patients. At presentation, 71.43% of patients were on medical therapy for rheumatic disease; 42.86% of patients used systemic steroids Cataract and ocular hypertension were the most common ocular complications during the study period but were not statistically related to systemic steroid treatment. Conclusions: Systemic steroids treatment in uveitis patients does not seem to increase the risk of iatrogenic complications such as cataract and glaucoma. In our series, increasing age appears to be the main risk factor for cataract and glaucoma development. Key points • Cataract, ocular hypertension, and glaucoma are the most common iatrogenic complications. • Systemic steroids can be safely used in uveitis patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: Beta-blockers (BB) are under prescribed in elderly heart failure (HF) patients. We analysed predictors of BB treatment in relation to age in community patients seen at an HF clinic with nurse specialist support. Methods: BB prescription was assessed in 357 subjects, in relation to age tertiles:<67 (n =120), 67–73 (n =105) and ≥74 years (n =119). Results: 305 patients (85%) took BB at a median carvedilol-equivalent daily dose of 12.5 [12.5–25] mg. Patients ≥74 years received significantly less BB (78% vs 93% and 85%, p =0.002) and at lower doses than subjects aged <67 and 67–73 years (12.5 [6.25–20] mg vs 25 [12.5–32] and 12.5 [12.5–25], p =0.002). Older age, chronic obstructive airways disease, amiodarone, digoxin and baseline heart rate were independently associated with non-prescription of BB. Conclusion: Although older age is associated with non-prescription of BB, BB can be implemented in an outpatient HF clinic with nurse specialist support even in elderly patients. although lower doses are achieved than in younger subjects. [Copyright &y& Elsevier]

Purpose: To investigate whether the coronavirus disease 2019 (COVID-19) pandemic-associated postponement in care had effects on the baseline clinical presentation of patients with newly diagnosed treatment-naïve exudative neovascular age-related macular degeneration (AMD). Methods: We included the first 50 consecutive patients referred within the COVID-19 pandemic with a diagnosis of treatment-naïve exudative neovascular AMD. Two groups of fifty consecutive patients with newly diagnosed neovascular exudative AMD presenting in 2018 and 2019 (control periods) were also included for comparisons. Results: Baseline visual acuity was statistically worse in patients referred during the COVID-19 pandemic period (0.87 ± 0.51 logarithm of the minimum angle of resolution (LogMAR)) as compared with both the "2019" (0.67 ± 0.48 LogMAR, p = 0.001) and "2018" (0.69 ± 0.54 LogMAR, p = 0.012) control periods. Data on the visual function after a loading dose of anti-vascular endothelial growth factor (VEGF) was available in a subset of patients (43 subjects in 2020, 45 in 2019 and 46 in 2018, respectively). Mean ± SD best corrected visual acuity (BCVA) at the 1-month follow-up visit after the third anti-VEGF injection was still worse in patients referred during the COVID-19 pandemic (0.82 ± 0.66 LogMAR) as compared with both the "2019" (0.60 ± 0.45 LogMAR, p = 0.021) and "2018" (0.55 ± 0.53 LogMAR, p = 0.001) control periods. On structural optical coherence tomography (OCT), the maximum subretinal hyperreflective material (SHRM) height and width were significantly greater in the COVID-19 pandemic patients. Conclusions: We demonstrated that patients with newly diagnosed treatment-naïve exudative neovascular AMD referred during the COVID-19 pandemic had worse clinical characteristics at presentation and short-term visual outcomes. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the relative prevalence and clinical differences between age-related macular degeneration (AMD) and pachychoroid disease in patients older than 50 years with newly diagnosed exudative neovascular maculopathy, and also assess the rate of misdiagnosis between these two disorders. In this retrospective observational study, we reviewed data from patients 50 years of age and older with newly diagnosed treatment-naïve exudative macular neovascularization (MNV) secondary to AMD or pachychoroid disease. Of the 139 patients (139 eyes) who fulfilled the inclusion criteria, 35 patients were graded as being affected by pachychoroid disease complicated by exudative MNV and 104 subjects had neovascular AMD. Therefore, prevalence of pachychoroid disease complicated by exudative MNV was 25.2% (confidence interval—CI 18.2–33.2%). Mean ± SD age was 67.0 ± 8.8 years in the pachychoroid disease group and 80.6 ± 6.6 years in the neovascular AMD group (P < 0.0001). At baseline, BCVA was better in patients with pachychoroid disease complicated by exudative MNV (0.4 ± 0.3 LogMAR vs. 0.7 ± 0.5 LogMAR, P = 0.003). At the 1-year follow-up visit, BCVA was still better in patients with pachychoroid-associated MNV (0.34 ± 0.32 LogMAR vs. 0.59 ± 0.52 LogMAR; P = 0.005). In our study cohort, 19 patients were graded to be affected by pachychoroid disease complicated by exudative MNV even though a diagnosis of neovascular AMD was erroneously reported in their medical records at baseline. In conclusion, pachychoroid disease is a frequent cause of exudative MNV in aged patients with a high rate of misdiagnosis. A correct diagnosis may be important as these two disorders differ in terms of clinical characteristics and prognosis. [ABSTRACT FROM AUTHOR]

Central serous chorioretinopathy (CSC) is a complex and not entirely understood retinal disease. The aim of our research was to describe a novel optical coherence tomography (OCT) finding named "choroidal rift", which may be identified in the choroid of eyes with CSC. We collected data from 357 patients (488 eyes) with CSC who had structural OCT and OCT angiography (OCTA) scans obtained. Choroidal rifts were identified as polygonal (and not round-shaped) hyporeflective lesions without hyperreflective margins. Choroidal rifts had to be characterized by a size superior to that of the largest choroidal vessel. Finally, hyporeflective lesions were graded as choroidal rifts only if these lesions had a main development perpendicular to the retinal pigment epithelium. OCT analysis allowed the identification of choroidal rifts in ten eyes from nine patients, all with chronic CSC, with an estimated prevalence rate of 2.1%. In three out of ten cases with choroidal rifts, these lesions spanned all the choroidal layers. In the remaining cases, choroidal rifts only partially spanned the choroidal thickness. In OCTA, choroidal rifts were characterized by the absence of flow. Combining structural OCT and OCTA information, we hypothesized that choroidal rifts may represent interruptions of the choroidal stroma in correspondence of fragile regions (in between expanded larger-sized choroidal vessels). Choroidal rift represents a novel OCT feature, which may characterize eyes with chronic CSC and may have a role in the development of irreversible chorio-retinal changes. [ABSTRACT FROM AUTHOR]

Background: Optical coherence tomography (OCT) has recently been introduced in the operating theatre. The aim of this review is to present the actual role of microscope-integrated optical coherence tomography (MI-OCT) in ophthalmology. Method: A total of 314 studies were identified, following a literature search adhering to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. After full-text evaluation, 81 studies discussing MI-OCT applications in ophthalmology were included. Results: At present, three microscope-integrated optical coherence tomography systems are commercially available. MI-OCT can help anterior and posterior segment surgeons in the decision-making process, providing direct visualization of anatomic planes before and after surgical manoeuvres, assisting in complex cases, and detecting or confirming intraoperative complications. Applications range from corneal transplant to macular surgery, including cataract surgery, glaucoma surgery, paediatric examination, proliferative diabetic retinopathy surgery, and retinal detachment surgery. Conclusion: The use of MI-OCT in ophthalmic surgery is becoming increasingly prevalent and has been applied in almost all procedures. However, there are still limitations to be overcome and the technology involved remains difficult to access and use. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is associated with neutrophilic lung inflammation and CD8 T cell exhaustion and is an important risk factor for the development of non-small cell lung cancer (NSCLC). The clinical response to programmed cell death-1 (PD-1) blockade in NSCLC patients is variable and likely affected by a coexisting COPD. The pro-inflammatory cytokine interleukin-17C (IL-17C) promotes lung inflammation and is present in human lung tumors. Here, we used a Kras-driven lung cancer model to examine the function of IL-17C in inflammation-promoted tumor growth. Genetic ablation of Il-17c resulted in a decreased recruitment of inflammatory cells into the tumor microenvironment, a decreased expression of tumor-promoting cytokines (e.g. interleukin-6 (IL-6)), and a reduced tumor proliferation in the presence of Haemophilus influenzae- (NTHi) induced COPD-like lung inflammation. Chronic COPD-like inflammation was associated with the expression of PD-1 in CD8 lymphocytes and the membrane expression of the programmed death ligand (PD-L1) independent of IL-17C. Tumor growth was decreased in Il-17c deficient mice but not in wildtype mice after anti-PD-1 treatment. Our results suggest that strategies targeting innate immune mechanisms, such as blocking of IL-17C, may improve the response to anti-PD-1 treatment in lung cancer patients. [ABSTRACT FROM AUTHOR]

Background: Sarcoidosis is a systemic disease of unknown etiology. The disease mechanisms are largely speculative and may include the role microbial patterns that initiate and drive an underlying immune process. The aim of this study was to characterize the microbiota of the lung of patients with sarcoidosis and compare its composition and diversity with the results from patients with other interstitial lung disease (ILD) and historic healthy controls.Methods: Patients (sarcoidosis, n = 31; interstitial lung disease, n = 19) were recruited within the PULMOHOM study, a prospective cohort study to characterize inflammatory processes in pulmonary diseases. Bronchoscopy of the middle lobe or the lingula was performed and the recovered fluid was immediately sent for analysis of the pulmonary microbiota by 16sRNA gene sequencing. Subsequent bioinformatic analysis was performed to compare the groups.Results: There were no significant differences between patients with sarcoidosis or other ILDs with regard to microbiome composition and diversity. In addition, the abundance of the genera Atopobium, Fusobacterium, Mycobacterium or Propionibacterium were not different between the two groups. There were no gross differences to historical healthy controls.Conclusion: The analysis of the pulmonary microbiota based on 16sRNA gene sequencing did not show a significant dysbiosis in patients with sarcoidosis as compared to other ILD patients. These data do not exclude a microbiological component in the pathogenesis of sarcoidosis. [ABSTRACT FROM AUTHOR]