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

alexandrossfakianakis shared this article with you from Inoreader VG161 activates systemic anti‐tumor immunity in pancreatic cancer models as a novel oncolytic herpesvirus expressing multiple immunomodulatory transgenes via Journal of Medical Virology 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. This article is protected by copyright. All rights reserved. View on Web

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Long‐Term Binaural Hearing Improvements for Cochlear Implant Users with Asymmetric Hearing Loss

alexandrossfakianakis shared this article with you from Inoreader Long‐Term Binaural Hearing Improvements for Cochlear Implant Users with Asymmetric Hearing Loss via The Laryngoscope Cochlear implant (CI) recipients with unilateral hearing loss reached early asymptote for binaural hearing abilities, and CI recipients with asymmetric hearing loss continued to improve out to 5-years post-activation for spatial release from masking when the masker was presented toward the better hearing ear. There was a significant correlation with improvement and age at implantation and contralateral hearing thresholds which may influence these differences. Objective To assess long-term binaural hearing abilities for cochlear implant (CI) users with unilateral hearing loss (UHL) or asymmetric hearing loss (AHL). Methods A prospective, longitudinal, repeated measures study was completed at a tertiary referral center evaluating adults with UHL or AHL undergoing cochlear implantation. Binaural hearing abilities were assessed with masked speech recognition tasks using AzBio sentences in a 10-talker masker. Performance was evaluated as the ability to benefit from spatial release from masking (SRM). SRM was calculated as the difference in scores when the masker was presented toward the CI-ear (SRMci) or the contralateral ear (SRMcontra) relative to the co-located condition (0°). Assessments were completed pre-operatively and at annual intervals out to 5 years post-activation. Results Twenty UHL and 19 AHL participants were included in the study. Linear Mixed Models showed significant main effects of interval and group for SRMcontra. There was a significant interaction between interval and group, with UHL participants reaching asymptotic performance early and AHL participants demonstrating continued growth in binaural abilities to 5 years post-activation. The improvement in SRM showed a significant positive correlation with contralateral unaided hearing thresholds (p = 0.050) as well as age at implantation (p = 0.031). Conclusions CI recipients with UHL and AHL showed improved SRM with long-term device use. The time course of improvement varied by cohort, with the UHL cohort reaching asymptotic performance early and the AHL cohort continuing to improve beyond 1 year. Differences between cohorts could be driven by differences in age at implantation as well as contralateral unaided hearing thresholds. Level of Evidence Level III Laryngoscope, 2022 View on Web

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

alexandrossfakianakis shared this article with you from Inoreader Virome analysis provides new insights into the association between viruses and Parkinson's disease via Journal of Medical Virology 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. This article is protected by copyright. All rights reserved. View on Web

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Mini‐hyper CVD + CRIB (condensed rituximab, inotuzumab ozogamicin, and blinatumomab) for refractory pediatric B‐acute lymphoblastic leukemia

alexandrossfakianakis shared this article with you from Inoreader Mini‐hyper CVD + CRIB (condensed rituximab, inotuzumab ozogamicin, and blinatumomab) for refractory pediatric B‐acute lymphoblastic leukemia via Pediatric Blood & Cancer Abstract Relapsed or refractory pediatric patients with B-acute lymphoblastic leukemia (B-ALL) have high rates of toxicities and relapse, and novel therapy is needed. We present a case of a 5-year-old male child with high-risk B-ALL that was refractory to several re-induction regimens. He was put into minimal residual disease-negative remission after re-induction with chemotherapy plus overlapping rituximab, inotuzumab ozogamicin, and blinatumomab, termed mini-hyper-CVD (cyclophosphamide, vincristine, and dexamethasone) plus CRIB (condensed rituximab, inotuzumab ozogamicin, and blinatumomab). This regimen was well tolerated, and he received his transplant and engrafted with no significant infections, toxicities, or sinusoidal obstruction syndrome. This is the first reported use of a condensed sequential immunotherapy/chemotherapy regimen in a pediatric leukemia patient. View on Web

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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 Analysis of oral microbiota alterations induced by Helicobacter pylori infection and vonoprazan‐amoxicillin dual therapy for Helicobacter pylori eradication via Helicobacter 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. View on Web

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Effect of Helicobacter pylori on immunotherapy is gaining more attention

alexandrossfakianakis shared this article with you from Inoreader Effect of Helicobacter pylori on immunotherapy is gaining more attention via Helicobacter 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. View on Web

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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 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 via Journal of Medical Virology 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. This article is protected by copyright. All rights reserved. View on Web

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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 Asystole Induced by Trigeminocardiac Reflex during Zygomatic Fracture Repositioning: A Rare Case Report via ScienceDirect Publication: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 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 View on Web

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

alexandrossfakianakis shared this article with you from Inoreader Survival Outcomes of Patients with Mycosis Fungoides Involving the External Ear and Ear Canal via The Laryngoscope 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 View on Web

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Resuscitative endovascular balloon occlusion of the aorta for life-threatening postpartum hemorrhage: A nationwide observational study in Japan

alexandrossfakianakis shared this article with you from Inoreader Resuscitative endovascular balloon occlusion of the aorta for life-threatening postpartum hemorrhage: A nationwide observational study in Japan via Journal of Trauma and Acute Care Surgery - Current Issue BACKGROUND Resuscitative endovascular balloon occlusion of the aorta (REBOA) is used for postpartum hemorrhage (PPH), which is one of the leading causes of maternal mortality worldwide; however, its utility in the obstetrics setting remains unclear. Thus, this study aimed to describe the characteristics, demographics, and mortality of patients with PPH who underwent REBOA. METHODS We used the Japanese Diagnosis Procedure Combination inpatient database to identify patients with PPH who underwent REBOA from April 2012 to March 2020. We examined the patients' characteristics, interventions administered, and in-hospital mortality. RESULTS We identified 143 patients with PPH who underwent REBOA. The most common cause of PPH was atonic postpartum hemorrhage (52.4%), followed by disseminated intravascular coagulation (29.4%) and amniotic fluid embolism documented (11.2%). Among patients who delivered at hospitals in which REBOA was performed (n = 55), 38.2% of patients experienced preterm births, and 70.9% delivered via cesarean delivery. The proportion of patients who underwent transcatheter arterial embolization and hysterectomy was 53.8% and 16.1%, respectively. In-hospital mortality was 7.0%. CONCLUSION The results of the present study could be helpful in clinical decision making and providing patients and families with additional treatment options for PPH. LEVEL OF EVIDENCE Therapeutic/Care Management; Level IV. View on Web

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