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Τετάρτη 31 Αυγούστου 2022

VG161 activates systemic anti‐tumor immunity in pancreatic cancer models as a novel oncolytic herpesvirus expressing multiple immunomodulatory transgenes

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Abstract

The VG161 represents the first recombinant oncolytic herpes simplex virus type 1 carrying multiple synergistic anti-tumor immuno-modulating factors. Here, we report its anti-tumor mechanisms and thus provide firm theoretical foundation for the upcoming clinical application in pancreatic cancer. Generally, the VG161-mediated anti-tumor outcomes were analyzed by a collaboration of techniques, namely the single cell sequencing, airflow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADSI-MSI) and Nanostring techniques. In vitro, the efficacy of VG161 together with immune checkpoint inhibitors (ICIs) has been successfully shown to grant a long-term anti-tumor effect by altering tumor immunity and remodeling tumor microenvironment (TME) metabolisms. Cellular functional pathways and cell subtypes detected from patient samples before and after the treatment had undergone distinctive changes including upregulated CD8+ T and NK cells. More importantly, significant antitumor signals have emerged since the administration of VG161 injection. In conclusion, VG161 can systematically activate acquired and innate immunity in pancreatic models, as well as improve the tumor immune microenvironment, indicative of strong anti-tumor potential. The more robusting anti-tumor outcome for VG161 monotherapy or in combination with other therapies on pancreatic cancer is worth of being explored in further clinical trials.

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Virome analysis provides new insights into the association between viruses and Parkinson's disease

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Abstract

Parkinson's disease (PD) is a kind of neurodegenerative disease that causes a huge burden to society. Previous studies have suggested the association between PD and multiple viruses. However, there is still a lack of a virome study about PD. This study systematically identified viruses from the public RNA-Seq data of more than 700 samples from both PD patients and the control group (most were healthy people). Only nine viruses such as Human betaherpesvirus 5 and Merkel cell polyomavirus have been detected in several human brain tissues of the central nervous system, the appendix, and blood of PD patients, and all of these viruses were also detected in the control group. Most viruses were observed to have low abundance in no more than three tissues. No statistically significant differences were observed between the virus abundance in the PD patients and the control group for all viruses. The positive rates of most viruses in PD patients were higher or similar to that in the control group, although those were less than 5% for most viruses. Overall, this is the first study to systematically investigate the virome in PD patients, and provides new insights into the association between viruses and PD.

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Longitudinal Analysis of Swallowing Displacement Kinematics After Oropharyngeal Cancer Treatment

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Longitudinal Analysis of Swallowing Displacement Kinematics After Oropharyngeal Cancer Treatment

We aimed to longitudinally assess quantitative swallowing displacement kinematic measurements and correlate them with functional swallowing outcomes. Quantitative swallowing kinematic measures can effectively track changes in swallowing physiology. Increased posterior pharyngeal wall thickness and restricted hyolaryngeal movement were seen in patients with oropharyngeal squamous cell carcinoma after treatment and correlated with change in swallowing outcome, emphasizing the need for serial videofluoroscopic swallow studies monitoring and targeted intervention.


Background/Objective

Quantitative swallowing displacement kinematics evolve in patients treated for oropharyngeal squamous cell carcinoma (OPSCC). We aimed to longitudinally assess these measurements and correlate them with functional swallowing outcomes.

Method

A retrospective review was conducted on patients with OPSCC treated with definitive (chemo)radiation ([C]RT) or surgery with adjuvant (chemo)radiation (S-[C]RT) who completed at least two videofluoroscopic swallow studies (VFSS). Longitudinal analysis was accomplished via mixed-effects logistic regression for the Functional Oral Intake Scale (FOIS), and Penetration Aspiration Scale (PAS), and mixed-effects linear regression for kinematic measures. Spearman's correlation was conducted between changes in FOIS/PAS and kinematic measures.

Results

Ninety-seven patients (76 males; mean age 61) completed 245 VFSS studies. A total of 94% had human papillomavirus (HPV)/p16 positive OPSCC and 74% were T0–T2. Sixty-four patients underwent [C]RT while 33 patients underwent S-[C]RT. After treatment, posterior pharyngeal wall at hold (PPWhold) increased 3.2 standard deviation (SD) between 0 and 6 months (p < 0.001), then decreased 2.2 SD between 6 and 12 months (p < 0.001) and did not return to baseline. Hyoid-to-larynx (HL) (p = 0.046) and maximal hyoid displacement (Hmax) + HL (p = 0.042) increased between 6 and 12 months. Hmax (p = 0.020) and Hmax + HL (p < 0.001) decreased between 12–24 months beyond baseline values. The decrease in HL and increase in PPWhold (p < 0.05) correlated with an increase in PAS. From baseline, increased pharyngeal constriction ratio correlated with decreased FOIS and PPWhold (< i>p < 0.05).

Conclusions

Quantitative swallowing kinematic measures can effectively track changes in swallowing physiology. Increased PPWhold and restricted hyolaryngeal movement were seen in patients with OPSCC after treatment and correlated with a change in swallowing outcome, emphasizing the need for serial VFSS monitoring and targeted intervention.

Level of Evidence

3 Laryngoscope, 2022

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Oral Premalignant and Malignant Lesions in Fanconi Anemia Patients

alexandrossfakianakis shared this article with you from Inoreader

Objective

There is a lack of data supporting cancer surveillance in pediatric Fanconi Anemia patients. We sought to describe the rates of upper aerodigestive lesions and malignancy in this population to augment current management guidelines.

Methods

A retrospective cohort study of patients with Fanconi Anemia from a quaternary referral center between 2007–2021 was completed for head and neck cancer risk.

Results

One hundred and five FA patients were reviewed. Average age at presentation was 11.3 years old and 90.5% of patients underwent hematopoietic stem cell transplant (HSCT). A total of 8.6% of patients had leukoplakia or erythroplakia and 3.8% developed malignancy. The standardized incidence ratio of head and neck malignancy was 483.8. Patients presented with leukoplakia and malignancy at an average age of 14.6 and 25.1 years old, respectively. Malignancies were aggressive and marked by recurrence. There were no premalignant or malignant lesions found on flexible laryngoscopy. This series represents the largest longitudinal series of pediatric FA head and neck lesions.

Conclusions

Fanconi Anemia patients should begin screening for head and neck cancer at age 10 or after HSCT.

Level of Evidence

Level 4 Laryngoscope, 2022

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Endoscopic pituitary surgery: A national database review

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Abstract

Background

Pituitary tumors surgery is increasingly performed via endoscopic transsphenoidal approach (TSP). This study describes outcomes of TSP surgery in the United States.

Methods

A retrospective cross-sectional analysis of adult patients with pituitary adenoma was performed using the Nationwide Readmissions Database, 2010–2015.

Results

A total of 5891 patients were identified. The average age was 51.29 ± 0.29 years. The risk of postoperative epistaxis, diabetes insipidus, cerebrospinal fluid (CSF) leak, and other general postoperative complications was 0.71%, 10.20%, 8.35%, and 2.37%, respectively. Independent risk factors of CSF leak included: age <65-year, male, body mass index ≥25, and multiple comorbidities (p < 0.001 each). The prevalence of CSF leak was not associated with hospital TSP volume and teaching status.

Conclusion

This study provides a national epidemiological perspective on TSP in the United States. The risk of postoperative CSF leak appears to be associated with intrinsic patient factors rather than resource and expertise availability.

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Effect of Helicobacter pylori on immunotherapy is gaining more attention

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Immunotherapy, especially immune checkpoint inhibitors, has been widely used in tumor therapy and have shown ideal clinical efficacy. However, some cancers still do not respond to PD-1/PD-L1 blockade therapy effectively. Helicobacter pylori infection might affect the curative effect of immunotherapy while it is rarely reported. We aimed to visualize the research hotspots and trends of H. pylori and immunotherapy using a bibliometric analysis to help understand the future development of basic and clinical research.

Methods

The relevant publications on H. pylori and immunotherapy were searched on April 20, 2022, in the Web of Science Core Collection Database (WOSCC). The document types were limited to articles and reviews. The VOSviewer 1.6.16 software was used to assess the co-authorship, co-occurrence, citation of countries, institutions, authors, journals, and hotspot keywords. The research status and trend change of H. pylori and immunotherapy were analyzed by bibliometric analysis.

Results

A total of 95 studies authored by 561 researchers were eventually included in this study. The majority of the retrieved studies were 55 (58%) original research articles. China conducted the greatest number of studies, followed by USA and Italy. The related topics included the following three aspects: the relationship between microorganisms and cancer, the relationship between gastric cancer and immunity, and the relationship between H. pylori and immunotherapy, including purified/cloned components of H. pylori acting as efficient adjuvant to boost tumor responses and H. pylori infection which modulate host immune responses and impact on the efficacy of antitumor immunity initiated by immune checkpoint inhibitors. The timing diagram revealed that the current research hotspots focused on effects of microorganisms on immunotherapy.

Conclusion

The effect of H. pylori on cancer immunotherapy is getting more and more attention in these years. It still remains uncertain, and more studies are needed in the future.

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Analysis of oral microbiota alterations induced by Helicobacter pylori infection and vonoprazan‐amoxicillin dual therapy for Helicobacter pylori eradication

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

The oral cavity is considered a potential reservoir of Helicobacter pylori (H. pylori), and the imbalance of oral microbiota directly reflects the health of the host. We aimed to explore the relationship among oral microbiota, H. pylori infection, and vonoprazan-amoxicillin (VA) dual therapy for H. pylori eradication.

Methods

Helicobacter pylori-positive patients were randomized into low- or high-dose VA dual therapy (i.e., amoxicillin 1 g b.i.d. or t.i.d. and vonoprazan 20 mg b.i.d) for 7 or 10 days. H. pylori-negative patients served as normal controls. Saliva samples were collected from 41 H. pylori-positive patients and 13 H. pylori-negative patients. The oral microbiota was analyzed by 16S rRNA gene sequencing, followed by bioinformatics analysis.

Results

Helicobacter pylori-positive patients had higher richness and diversity and better evenness of oral microbiota than normal controls. Beta diversity analysis estimated by Bray–Curtis or weighted UniFrac showed distinct clustering between H. pylori-positive patients and normal controls. The number of bacterial interactions was reduced in H. pylori-positive patients compared with that in negative patients. Forty-one patients evaluated before and after successful H. pylori eradication were divided into low (L-VA) and high dose (H-VA) amoxicillin dose groups. The alpha and beta diversity of the oral microbiota between L-VA and H-VA patients exhibited no differences at the three time points (before eradication, after eradication, and at confirmation of H. pylori infection cure).

Conclusion

Helicobacter pylori infection could alter the diversity, composition, and bacterial interactions of the oral microbiota. Both L-VA and H-VA dual therapy showed minimal influence on the oral microbiota.

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Association of viral load with TRAIL, IP‐10, CRP biomarker signature and disease severity in children with respiratory tract infection or fever without source: a prospective, multicentre cohort study

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

To investigate the association of viral load (VL) with (i) tumor necrosis factor-related apoptosis inducing ligand (TRAIL), interferon-gamma induced protein-10, C-reactive protein and a combinatorial score (BV score); and (ii) clinical severity.

Study Design

In this prospective, multicentre cohort sub-study, children with respiratory tract infection or fever without source were enrolled. VL for influenza virus, rhinovirus, respiratory syncytial virus, and adenovirus were measured from nasopharyngeal swabs. The reference standard diagnosis was established based on expert panel adjudication.

Results

Of 1140 recruited patients, 333 had a virus mono-detection. VL for the aggregated dataset correlated with TRAIL and IP-10 levels, with length of oxygen therapy, and inversely with the BV score. On single viral level, only influenza virus yielded a correlation with TRAIL, IP-10 levels, and the BV score. Children with a viral reference standar d diagnosis had significantly higher VL than those with bacterial infection (p = 0.0005). Low TRAIL (incidence rate ratio, IRR 0.6, 95% confidence interval, CI 0.39-0.91) and young age (IRR 0.62, 95%CI 0.49-0.79) were associated with longer hospital stay, while young age (IRR 0.33, 95%CI 0.18-0.61), low TRAIL (IRR 0.25, 95%CI 0.08-0.76), and high VL (IRR 1.16, 95%CI 1.00-1.33) were predictive of longer oxygen therapy.

Conclusion

These findings indicate that VL correlates with biomarkers and may serve as a complementary tool pertaining to disease severity.

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Asystole Induced by Trigeminocardiac Reflex during Zygomatic Fracture Repositioning: A Rare Case Report

alexandrossfakianakis shared this article with you from Inoreader

Publication date: Available online 31 August 2022

Source: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology

Author(s): Reon Morioka, Tatsuo Okui, Junichi Kanayama, Hiroto Tatsumi, Satoe Okuma, Akira Kato, Tomoko Ichiyama, Takahiro Kanno

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Survival Outcomes of Patients with Mycosis Fungoides Involving the External Ear and Ear Canal

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Survival Outcomes of Patients with Mycosis Fungoides Involving the External Ear and Ear Canal

This manuscript reports our retrospective review of 40 patients with mycosis fungoides, and it demonstrates a comparison in outcomes of patients with ear involvement with those without ear involvement. Overall survival was shorter when the ear canals were involved.


Objectives/Hypothesis

Mycosis Fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma. Disease involvement of specific locations may be more significant than simply the symptoms associated with that site; it is possible that involvement of certain sites could be associated with poor prognosis. We aimed to evaluate the outcomes of patients with MF with documented involvement of the EAC and external ear.

Study Design

Retrospective analysis.

Methods

We retrospectively reviewed 40 patients with MF that were treated by otologists between 2012 and 2021.

Results

We report the largest series of patients with MF involving the external ear and EAC. Of the 40 patients included in this study, 17 presented with Mycosis Fungoides in the otologic region (MFO). Of these 17 MFO patients, 2/17 had involvement of the external ear only, 3/17 of the EAC only, 11/17 of both the external ear and EAC, and 1/17 of the periauricular skin. Of note, 11/14 (79%) patients presenting with EAC disease died compared to11/26 (42%) of patients without involvement. In addition, eight of the 13 (62%) patients with external ear involvement died compared to 14/27 (52%) of patients without involvement. Ear canal involvement was associated with a statistically significant shorter overall survival duration in patients with MF (p = 0.03). Furthermore, disease in the EAC was found to have a hazard ratio value of 2.565 (CI 1.102–5.970).

Conclusions

Involvement of the EAC by MF portends a poor prognosis. This finding highlights the need for a more in-depth otologic evaluation of patients with MF.

Level of Evidence

Level 4 Laryngoscope, 2022

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