Lifestyle factors and hand eczema: A systematic review and meta‐analysis of observational studies

Evidence regarding the association between lifestyle factors and hand eczema is limited.To extensively investigate the association between lifestyle factors (smoking, alcohol consumption, stress, physical activity, body mass index, diet, and sleep) and the prevalence, incidence, subtype, severity, and prognosis of hand eczema, a systematic review and meta‐analysis were conducted in accordance with the Meta‐analysis Of Observational Studies in Epidemiology consensus statement. MEDLINE, Embase, and Web of Science were searched up to October 2021. The (modified) Newcastle‐Ottawa Scale was used to judge risk of bias. Quality of the evidence was rated using the Grades of Recommendation, Assessment, Development and Evaluation approach. Eligibility and quality were blindly assessed by two independent investigators; disagreements were resolved by a third investigator. Data were pooled using a random‐effects model, and when insufficient for a meta‐analysis, evidence was narratively summarized. Fifty‐five studies were included. The meta‐analysis (17 studies) found very low quality evidence that smoking is associated with a higher prevalence of hand eczema (odds ratio 1.18, 95% confidence interval 1.09‐1.26). No convincing evidence of associations for the other lifestyle factors with hand eczema were found, mostly due to heterogeneity, conflicting results, and/or the limited number of studies per outcome

The effect of insect meal as a feed ingredient on survival, growth, and metabolic and antioxidant response of juvenile prawn Palaemon adspersus (Rathke, 1837)

For successful prawn aquaculture, feeds should be based on readily consumed ingredients that promote survival and optimal growth performance. This pilot study investigates the rearing of juvenile Baltic prawn Palaemon adspersus. Two feeding trials were carried out for 60 days; both incorporated insect meals, the first one in fishmeal-based diets, whereas the second one in plant meal ones. Insect meals derived from larvae of Tenebrio molitor (TM), Hermetia illucens (HI) and Musca domestica (MD) were tested as feed ingredients. This study indicated that the inclusion of HI in fishmeal diets resulted in significantly higher growth performance and survival of the prawns, whereas the MD diet led to similarly high growth performance reducing significantly their survival. Growth performance was not affected by the insect inclusion in the plant-based diets, but survival was higher in the TM and HI inclusion diets. The inclusion of TM and HI resulted in higher protein and energy content of the prawns’ muscle when incorporated in fishmeal and plant meal diets respectively. No significant differences were observed in the activities of hepatopancreas’ amino acid-catabolizing enzymes. Concluding, the combinations fishmeal–HI and plant meal–TM can be used for the successful rearing of Baltic prawn. © 2020 John Wiley & Sons Lt

Study of patients with ocular hypertension with scanning laser polarimetry and short-wavelength automatic perimetry

Aims: To compare and correlate retinal nerve fiber layer (RNFL) measurements obtained by scanning laser polarimetry (SLP) with defects detected by short-wavelength automatic perimetry (SWAP) in eyes with ocular hypertension (OHT). Methods: SLP and SWAP were performed in 96 eyes of 48 consecutive patients with OHT. Results: Twenty-five eyes (26%) had SWAP visual field defects. Twenty-seven eyes (28.1%) had abnormal RNFL evaluation defined by the GDx neural network ('number'>29). Fourteen eyes of 10 patients (14.5%) had abnormal RNFL evaluation and SWAP visual field defects. RNFL thickness measurements were significantly reduced in eyes with abnormal SWAP. A weak but statistically significant correlation between the 'number' and pattern standard deviation (r = 0.3, p = 0.006) and the corrected pattern standard deviation (r = 0.3, p = 0.007) in SWAP was found. Areas of abnormal RNFL thickness corresponded to the localization of the SWAP visual field defects in corrected pattern deviation plots in 10 of the 14 eyes with defects in both tests. Conclusions: SWAP visual field defects frequently coexist and correspond with abnormalities of RNFL detected by SLP in eyes with OHT. In certain eyes, however, the two methods detect different glaucoma properties. Copyright © 2006 S. Karger AG

Clinical activity of an htert-specific cancer vaccine (Vx-001) in “immune desert” NSCLC

Background: Tumors can be separated into immunogenic/hot and non-immunogenic/cold on the basis of the presence of tumor-infiltrating lymphocytes (TILs), the expression of PD-L1 and the tumor mutation burden (TMB). In immunogenic tumors, TILs become unable to control tumor growth because their activity is suppressed by different inhibitory pathways, including PD-1/PD-L1. We hypothesized that tumor vaccines may not be active in the immunosuppressive microenvironment of immunogenic/hot tumors while they could be efficient in the immune naïve microenvironment of non-immunogenic/cold tumors. Methods: The randomized phase II Vx-001-201 study investigated the effect of the Vx-001 vaccine as maintenance treatment in metastatic non-small cell lung cancer (NSCLC) patients. Biopsies from 131 (68 placebo and 63 Vx-001) patients were retrospectively analyzed for PD-L1 expression and TIL infiltration. TILs were measured as tumor-associated immune cells (TAICs), CD3-TILs, CD8-TILs and granzyme B-producing TILs (GZMB-TILs). Patients were distinguished into PD-L1(+) and PD-L1(-) and into TIL high and TIL low. Findings: There was no correlation between PD-L1 expression and Vx-001 clinical activity. In contrast, Vx-001 showed a significant improvement of overall survival (OS) vs. placebo in TAIC low (21 vs. 8.1 months, p = 0.003, HR = 0.404, 95% CI 0.219–0.745), CD3-TIL low (21.6 vs. 6.6 months, p < 0.001, HR = 0.279, 95% CI 0.131–0.595), CD8-TIL low (21 vs. 6.6 months, p < 0.001; HR = 0.240, 95% CI 0.11–0.522) and GZMB-TIL low (20.7 vs. 11.1 months, p = 0.011, HR = 0.490, 95% CI 0.278–0.863). Vx-001 did not offer any clinical benefit in patients with TAIC high, CD3-TIL high, CD8-TIL high or GZMB-TIL high tumors. CD3-TIL, CD8-TIL and GZMB-TIL were independent predictive factors of Vx-001 efficacy. Conclusions: These results support the hypothesis that Vx-001 may be efficient in patients with non-immunogenic/cold but not with immunogenic/hot tumors. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Endoscopic transgastric procedures in anesthetized pigs: technical challenges, complications, and survival

Background and study alms: An incisionless endoscopic peroral transgastric approach to the peritoneal cavity has shown promise in animals as a potentially less invasive form of surgery. We present our experience with various endoscopic peroral transgastric procedures, reporting on the technical aspects and challenges that arose. Materials and methods: The following procedures were performed in 10 anesthetized pigs using a double-channel endoscope: peritoneoscopy (10 pigs), liver biopsy (one pig), cholecystectomy (six pigs), fallopian tube excision (one pig), and hysterectomy (one pig). Results: All the procedures were accomplished successfully. There were six minor intraoperative complications. Complete gastric cleansing and elimination of all bacteria was found to be impossible to achieve in the porcine model. Overinflation was a common problem. The lack of adequate endoscope support was a major limitation. Safe closure of the gastrotomy incision was difficult using the available clipping devices. Six pigs made an uncomplicated recovery after a follow-up period of 4-6 weeks. Subsequent pathological examination revealed deep gastric ulceration in one animal and a gastric wall abscess in another. Conclusions: Peroral transgastric surgery is technically feasible and safe in a porcine model. Although all the procedures were performed successfully, the study highlights some technical difficulties and illustrates the need for major technical innovations and extensive animal studies in order to evaluate the merits of incisionless surgery

Generation of non‐small cell lung cancer patient‐derived xenografts to study intratumor heterogeneity

Recent advances in sequencing technologies have allowed the in‐depth molecular study of tumors, even at the single cell level. Sequencing efforts have uncovered a previously unappreci-ated heterogeneity among tumor cells, which has been postulated to be the driving force of tumor evolution and to facilitate recurrence, metastasis, and drug resistance. In the current study, focused on early‐stage operable non‐small cell lung cancer, we used tumor growth in patient‐derived xeno-graft (PDX) models in mice as a fast‐forward tumor evolution process to investigate the molecular characteristics of tumor cells that grow in mice, as well as the parameters that affect the grafting efficiency. We found that squamous cell carcinomas grafted significantly more efficiently compared with adenocarcinomas. Advanced stage, patient age and primary tumor size were positively correlated with grafting. Additionally, we isolated and characterized circulating tumor cells (CTC) from patients’ peripheral blood and found that the presence of CTCs expressing epithelial‐to‐mesenchy-mal (EMT) markers correlated with the grafting potential. Interestingly, exome sequencing of the PDX tumor identified genetic alterations in DNA repair and genome integrity genes that were un-der‐represented in the human primary counterpart. In conclusion, through the generation of a PDX biobank of NSCLC, we identified the clinical and molecular properties of tumors that affected growth in mice. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Unique spatial immune profiling in pancreatic ductal adenocarcinoma with enrichment of exhausted and senescent t cells and diffused CD47-SIRPα expression

Background: Pancreatic ductal adenocarcinoma (PDAC) is resistant to single-agent immunotherapies. To understand the mechanisms leading to the poor response to this treatment, a better understanding of the PDAC immune landscape is required. The present work aims to study the immune profile in PDAC in relationship to spatial heterogeneity of the tissue microenvironment (TME) in intact tissues. Methods: Serial section and multiplex in situ analysis were performed in 42 PDAC samples to assess gene and protein expression at single-cell resolution in the: (a) tumor center (TC), (b) invasive front (IF), (c) normal parenchyma adjacent to the tumor, and (d) tumor positive and negative draining lymph nodes (LNs). Results: We observed: (a) enrichment of T cell subpopulations with exhausted and senescent phenotype in the TC, IF and tumor positive LNs; (b) a dominant type 2 immune response in the TME, which is more pronounced in the TC; (c) an emerging role of CD47-SIRPα axis; and (d) a similar immune cell topography independently of the neoadjuvant chemotherapy. Conclusion: This study reveals the existence of dysfunctional T lymphocytes with specific spatial distribution, thus opening a new dimension both conceptually and mechanistically in tumor-stroma interaction in PDAC with potential impact on the efficacy of immune-regulatory therapeutic modalities. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Associations of angiogenesis-related proteins with specific prognostic factors, breast cancer subtypes and survival outcome in early-stage breast cancer patients. A Hellenic Cooperative Oncology Group (HeCOG) trial

Several studies support an important role of angiogenesis in breast cancer growth and metastasis. The main objectives of the study were to investigate the immunohistochemical expression of vascular endothelial growth factor (VEGF) family ligands (VEGF-A and VEGF-C) and receptors (VEGFR1, VEGFR2 and VEGFR3) in breast cancer and their associations with clinicopathological parameters, cancer subtypes/subgroups and patient outcome. Formalin-fixed paraffin-embedded tumor tissue samples were collected from early-stage breast cancer patients treated with anthracycline-based chemotherapy within a randomized trial. Immunohistochemistry was performed on serial 2.5 μm thick tissue sections from tissue microarray blocks. High VEGF-A, VEGF-C, VEGFR1, VEGFR2 and VEGFR3 protein expression was observed in 11.8% (N = 87), 80.8% (N = 585), 28.1% (N = 202), 64.6% (N = 359) and 71.8% (N = 517) of the cases, respectively. Significant associations were observed among all proteins (all p-values <0.05), with the exception of the one between VEGF-C and VEGFR1 (chi-square test, p = 0.15). Tumors with high VEGF-A protein expression, as compared to tumors with low expression were more frequently ER/PgR-negative (33.3% vs. 20.8%, chi-square test, p = 0.009) and HER2-positive (44.8% vs. 20.6%, p<0.001). In addition, tumors with high VEGFR1 expression, were more frequently HER2-positive (32.8% vs. 19.6%, p<0.001), while tumors with high VEGFR3 expression were more frequently ER/PgR-negative (24.9% vs. 17.0%, p = 0.024) and HER2-positive (26.9% vs. 14.8%, p = 0.001). High VEGF-A and VEGF-C protein expression was associated with increased DFS in the entire cohort (HR = 0.57, 95% CI 0.36–0.92, Wald’s p = 0.020 and HR = 0.71, 95% CI 0.52–0.96, p = 0.025, respectively), as well as in specific subtypes/subgroups, such as HER2-positive (VEGF-A, HR = 0.32, 95% CI 0.14–0.74, p = 0.008) and triple-negative (VEGF-C, HR = 0.44, 95% CI 0.21–0.91, p = 0.027) patients. High vs. low VEGFR1 expression was an unfavorable factor for DFS in triple-negative patients (HR = 2.74, 95% CI 1.26–5.98, p = 0.011), whereas the opposite was observed among the ER/PgR-positive patients (HR = 0.69, 95% CI 0.48–0.98, p = 0.041). Regarding OS, high VEGF-C protein expression was associated with increased OS in the entire cohort (HR = 0.64, 95% CI 0.46–0.89, Wald’s p = 0.008), as well as in in specific subtypes/subgroups, such as ER/PgR-negative (HR = 0.37, 95% CI 0.20–0.71, p = 0.003) and triple-negative (HR = 0.42, 95% CI 0.19–0.90, p = 0.026) patients. In conclusion, high expression of angiogenesis-related proteins is associated with adverse clinicopathological parameters in early-stage breast cancer patients and may be surrogate markers of biologically distinct subgroups of ER/PgR-negative or triple-negative tumors with superior outcome. Further validation of our findings in independent cohorts is needed. © 2018 Goussia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited