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

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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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Oral Premalignant and Malignant Lesions in Fanconi Anemia Patients

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

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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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Effect of Helicobacter pylori on immunotherapy is gaining more attention

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

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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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Τρίτη 30 Αυγούστου 2022

Management of the open abdomen: A systematic review with meta-analysis and practice management guideline from the Eastern Association for the Surgery of Trauma

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imageBACKGROUND Multiple techniques describe the management of the open abdomen (OA) and restoration of abdominal wall integrity after damage-control laparotomy (DCL). It is unclear which operative technique provides the best method of achieving primary myofascial closure at the index hospitalization. METHODS A writing group from the Eastern Association for the Surgery of Trauma performed a systematic review and meta-analysis of the current literature regarding OA management strategies in the adult population after DCL. The group sought to understand if fascial traction techniques or techniques to reduce visceral edema improved the outcomes in these patients. The Grading of Recommendations Assessment, Development and Evaluation methodology was utilized, meta-analyses were performed, and an evidence profile was generated. RESULTS Nineteen studies met inclusion criteria. Overall, the use of fascial traction techniques was associated with improved primary myofascial closure during the index admission (relative risk, 0.32) and fewer hernias (relative risk, 0.11.) The use of fascial traction techniques did not increase the risk of enterocutaneous fistula formation nor mortality. Techniques to reduce visceral edema may improve the rate of closure; however, these studies were very limited and suffered significant heterogeneity. CONCLUSION We conditionally recommend the use of a fascial traction system over routine care when treating a patient with an OA after DCL. This recommendation is based on the benefit of improved primary myofascial closure without worsening mortality or enterocutaneous fistula formation. We are unable to make any recommendations regarding techniques to reduce visceral edema. LEVEL OF EVIDENCE Systematic Review and Meta-Analysis; Level IV.
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Hyperglycemia in nondiabetic adult trauma patients is associated with worse outcomes than diabetic patients: An analysis of 95,764 patients

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imageBACKGROUND The adverse impact of acute hyperglycemia is well documented but its specific effects on nondiabetic trauma patients are unclear. The purpose of this study was to analyze the differential impact of hyperglycemia on outcomes between diabetic and nondiabetic trauma inpatients. METHODS Adults admitted 2018 to 2019 to 46 Level I/II trauma centers with two or more blood glucose tests were analyzed. Diabetes status was determined from International Classification of Diseases—10th Rev.—Clinical Modification, trauma registry, and/or hemoglobin A1c greater than 6.5. Patients with and without one or more hyperglycemic result >180 mg/dL were compared. Logistic regression examined the effects of hyperglycemia and diabetes on outcomes, adjusting for age, sex, Injury Severity Score, and body mass index. RESULTS There were 95,764 patients: 54% male; mean age, 61 years; mean Injury Severity Score, 10; diabetic, 21%. Patients with hyperglycemia had higher mortality and worse outcomes compared with those without hyperglycemia. Nondiabetic hyperglycemic patients had the highest odds of mortality (diabetic: adjusted odds ratio, 3.11; 95% confidence interval, 2.8–3.5; nondiabetics: adjusted odds ratio, 7.5; 95% confidence interval, 6.8–8.4). Hyperglycemic nondiabetics experienced worse outcomes on every measure when compared with nonhyperglycemic nondiabetics, with higher rates of sepsis (1.1 vs. 0.1%, p
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