Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Wednesday, August 31, 2022

Meningoencephalitis following Le Fort I osteotomy: a case report

alexandrossfakianakis shared this article with you from Inoreader
Le Fort I osteotomies, although they are common procedures, carry a degree of risk of injury to the surrounding structures. Skull base fractures and cerebrospinal fluid rhinorrhoea are amongst the most serious on the list of complications. This is the first reported case of meningoencephalitis post Le Fort I osteotomy, shedding some light on its identification, causes, and management. (Source: International Journal of Oral and Maxillofacial Surgery)
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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

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.

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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

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.

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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

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

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Longitudinal Analysis of Swallowing Displacement Kinematics After Oropharyngeal Cancer Treatment

alexandrossfakianakis shared this article with you from Inoreader
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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Endoscopic pituitary surgery: A national database review

alexandrossfakianakis shared this article with you from Inoreader

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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Non‐neutropenic fever in children with cancer: Management, outcomes and clinical decision rule validation

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Introduction

Fever and infection are an important complication of childhood cancer therapy. Most research and guideline development has focussed on febrile neutropenia, with a paucity directed at non-neutropenic fever (NNF). We describe the clinical presentation, management and outcomes of NNF in children with cancer, and externally validate the Esbenshade Vanderbilt (EsVan) clinical decision rules (CDR) to predict bacteraemia.

Method

Using a prospective database, retrospective data were collected on consecutive NNF episodes (fever ≥38.0°C and absolute neutrophil count >1.0 cells/mm3). Sensitivity, specificity and area under the receiver operator characteristic curve (AUC-ROC) of the CDR were compared to derivation study.

Results

There were 203 NNF episodes occurring in 125 patients. Severe sepsis was uncommon (n = 2, 1%) and bacteraemia occurred in 10 (4.9%, 95% confidence interval [CI]: 2.7%–8.8%) episodes. A confirmed or presumed bacterial infection requiring antibiotics occurred in 31 (15%) patients. Total 202 (99%) episodes received at least one dose of intravenous broad-spectrum antibiotic and 141 (70%) episodes were admitted to hospital. Six (3%) episodes required intensive care unit (ICU)-level care and there were no infection-related deaths. The EsVan 1 rule had an AUC-ROC of 0.67, 80% were identified as low risk, and sensitivity and specificity were 50% and 81.5%, respectively, for a risk threshold of 10%.

Conclusions

Serious infection and adverse outcome are uncommon in children with NNF. Many children did not have a bacterial cause of infection identified, but were still treated with broad-spectrum antibiotics and admitted to hospital. National clinical practice guidelines should be developed for this important cohort to enable risk stratification and optimise antibiotic management. Further research is required to determine appropriateness of EsVan CDR in our cohort.

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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

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.

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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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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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