Wednesday, November 16, 2022

Cardiovascular outcomes after tixagevimab and cilgavimab use for pre-exposure prophylaxis against COVID-19: a population-based propensity-matched cohort study

alexandrossfakianakis shared this article with you from Inoreader

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Abstract
Tixagevimab and cilgavimab treatment was associated with higher rates of cardiovascular events in a post-hoc analysis of a phase 3 trial. In this large population-based propensity-matched study, we found no increased risk of cardiovascular events up to 90 days after tixagevimab and cilgavimab administration, including in patients with pre-existing cardiovascular disease.
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Utility of microbiologic testing in surveillance bronchoscopy following lung transplantation: A retrospective cohort study

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

The utility of surveillance bronchoscopy for the clinical management of lung transplant recipients is undefined. This study evaluates the role of surveillance bronchoscopy in the monitoring and care of lung transplant recipients.

Methods

We retrospectively analyzed all lung transplant recipients who had surveillance bronchoscopy at Henry Ford Hospital in Detroit, Michigan between August 2014 and August 2019. Bronchoscopies performed for clinical symptoms, new radiographic abnormalities, and to assess stents or acute rejection were excluded. A total of 107 lung transplant recipients and 449 bronchoscopies were analyzed. The primary outcome was rate of change in clinical care based on microbiologic and pathologic test results. Secondary outcomes were rates of microbiologic and pathologic test positivity and rates of adverse effects.

Results

The most common microbiologic tests performed on bronchoalveolar lavage were bacterial (96.9%), fungal (95.3%), and acid-fast bacillus (95.1%) stains and cultures. Of 2,560 microbiologic tests, 22.0% were positive and resulted in therapy changes for 2.9%. Positive galactomannan, acid-fast bacillus tests, and Pneumocystis jirovecii antigen/PCR did not result in therapy changes. Of the 370 transbronchial biopsies performed, 82.2% were negative for acute rejection and 13% were positive for A1/A2 rejection. Immunosuppressive therapy changes occurred after 15.8% with reduction in immunosuppression due to positive microbiologic tests in 16.9%. Adverse events occurred in 8.0% of patients.

Conclusion

Diagnostic stewardship is warranted when performing surveillance bronchoscopy in lung transplant recipients.

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DNA virus oncoprotein HPV18 E7 selectively antagonizes cGAS‐STING‐triggered innate immune activation

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Cellular infections by DNA viruses trigger innate immune responses mediated by DNA sensors. The cyclic GMP–AMP synthase (cGAS)-stimulator of interferon gene (STING) signaling pathway has been identified as a DNA-sensing pathway that activates interferons in response to viral infection and, thus, mediates host defense against viruses. Previous studies have identified oncogenes E7 and E1A of the DNA tumor viruses, human papillomavirus 18 (HPV18) and adenovirus, respectively, as inhibitors of the cGAS-STING pathway. However, the function of STING in infected cells and the mechanism by which HPV18 E7 antagonizes STING-induced IFNβ production remain unknown. We report that HPV18 E7 selectively antagonizes STING-triggered NF-κB activation but not IRF3 activation. HPV18 E7 binds to STING in a region critical for NF-κB activation and blocks the nuclear accumulation of p65. Moreover, E7 inhibition of STING-triggered NF-κB activation is related to HPV pathogenic ity but not E7–Rb binding. HPV18 E7, SARS-CoV-2 ORF3a, HIV-2 Vpx, and KSHV vIRF1 selectively inhibited STING-triggered NF-κB or IRF3 activation, suggesting a convergent evolution among these viruses toward antagonizing host innate immunity. Collectively, selective suppression of the cGAS-STING pathway by viral proteins is likely to be a key pathogenic determinant, making it a promising target for treating oncogenic virus-induced tumor diseases.

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Reply to Letter to the Editor on disease severity and efficacy of homologous vaccination among patients infected with SARS‐CoV‐2 Delta or Omicron VOCs, compared to unvaccinated using main biomarkers

alexandrossfakianakis shared this article with you from Inoreader

Abstract

We appreciate the commenters' interest in our article detailing the "Disease severity and efficacy of homologous vaccination among patients infected with SARS-CoV-2 Delta or Omicron VOCs, compared to unvaccinated using main biomarkers

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Chickenpox and multiple sclerosis: A Mendelian randomization study

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Observational studies have suggested a suspected association between varicella-zoster virus (VZV) infection and multiple sclerosis (MS), but the connection has remained unclear. The aim of the present study is to evaluate the causal relationship between chickenpox which is caused by VZV infection and MS.

Methods

We performed a two‑sample Mendelian randomization analysis to investigate the association of chickenpox with MS using summary statistics from genome‑wide association studies (GWAS). The GWAS summary statistics data for chickenpox was from the 23andMe cohort including 107,769 cases and 15,982 controls. A large summary of statistical data from the International Multiple Sclerosis Genetics Consortium (IMSGC) was used as the outcome GWAS data set, including 14,802 MS cases and 26,703 controls.

Results

We found evidence of a significant association between genetically predicted chickenpox and risk of MS (odds ratio [OR] = 35.27 , 95% confidence interval [CI] = 22.97–54.17, P = 1.46E-59).

Conclusions

Our findings provided evidence indicating a causal effect of chickenpox on MS. Further elucidations of this association and underlying mechanisms are needed for identifying feasible interventions to promote MS prevention.

This article is protected by copyright. All rights reserved.

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Cervical Dorsal Root Ganglion Stimulation for Complex Regional Pain Syndrome: Technical Description and Results of Seven Cases

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Introduction

Complex regional pain syndrome (CRPS) is characterized by nociplastic pain with alterations in sympathetic function. Neuromodulation could be a useful alternative therapy option. Dorsal root ganglion (DRG) stimulation has demonstrated better results than conventional spinal cord stimulation (SCS) for patients with CRPS in lower limbs.

Methods

We report a case series of seven patients treated with cervical DRG stimulation for CRPS of the hand that required neuromodulation for pain relief, after no response with other analgesic techniques (medication and interventional). We report retrospective data collection of seven consecutive patients with a one year follow up.

Results

Seven patients were trialed, and six were implanted with a permanent pulse generator after achieving more than 50% pain relief during two to seven days of trial phase. The average pain relief (rated on a standard 100 mm visual analog scale) after one year of treatment was 64.3% ± 16.6. No major complications were observed during a one year follow up.

Discussion

The results for cervical DRG stimulation are similar to other DRG stimulation studies for the treatment of refractory CRPS at lower levels. The cervical DRG implant technique guided with C-arm fluoroscopy and under conscious sedation could be a safe and effective option for relieving pain of the upper limbs CRPS. Monitoring neural status is required for cervical DRG stimulation either with a responder awake patient or with intraoperative neural monitoring in non-responder patients.

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Innovative Fudan rT staging in endoscopic surgery for recurrent nasopharyngeal carcinoma

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) rT staging have great clinical impracticality. The aim of the present study was to establish a new rT staging to guide endoscopic surgery for the treatment of recurrent nasopharyngeal carcinoma (rNPC).

Methods

This surgical rT staging (named Fudan rT staging) was constructed using two significant risk factors: the distance from the tumor margin to the internal carotid artery, and dural invasion. Log-rank and receiver operating characteristic (ROC) curve analyses were used to evaluate its effectiveness.

Results

Fudan rT staging can effectively separate the overall survival (OS) and progression-free survival (PFS) of patients with rNPC according to the different rT stages (p < 0.05). In addition, ROC analysis showed that the Fudan rT staging exhibited enhanced prognostic value for OS and PFS compared with the AJCC/UICC rT staging.

Conclusions

The innovative Fudan rT staging has a better predictive value for the survival of patients with rNPC than AJCC/UICC rT staging.

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Correlation between asparaginase enzyme activity levels and coagulation parameters during childhood acute lymphoblastic leukemia treatment

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Thromboembolism is a serious toxicity in the treatment of acute lymphoblastic leukemia (ALL), but little is known about the correlation between asparaginase enzyme activity (ASA) levels and coagulation parameters. We included 65 non-high risk ALL patients, aged 1–17 years. Coagulation parameters and corresponding ASA levels were measured during asparaginase treatment. We found ASA to be negatively correlated with antithrombin and fibrinogen up to ASA levels of 250 IU/L, after which these parameters reached a plateau and did not decrease further with further increase of ASA. Patients with silent inactivation of asparaginase had normal coagulation parameters.

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Approach to Complex Lower Extremity Reconstruction

alexandrossfakianakis shared this article with you from Inoreader

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Semin Plast Surg
DOI: 10.1055/s-0042-1758205

Composite injuries to the lower extremity from etiologies including trauma and infection present a complex dilemma for the reconstructive surgeon, and require multidisciplinary collaboration amongst plastic, vascular, and orthopaedic surgical specialties. Here we present our algorithm for lower-extremity reconstructive management, refined over the last decades to provide an optimized outcome for our patients. Reconstruction is pred icated on the establishment of a clean and living wound, where quality of the wound-bed is prioritized over timing to soft-tissue coverage. Once established, soft-tissues and fractures are provisionally stabilized; our preference for definitive coverage is for microvascular free-tissue, due to the paucity of healthy soft-tissue available at the injury, and ability to avoid the zone of injury for microvascular anastomosis. Finally, definitive bony reconstruction is dictated by the length and location of long-bone defect, with a preference to utilize bone transport for defects longer than 5 cm.
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Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Approach to Lymphedema Management

alexandrossfakianakis shared this article with you from Inoreader

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Semin Plast Surg
DOI: 10.1055/s-0042-1758691

Millions of people worldwide suffer from lymphedema. In developed nations, lymphedema most commonly stems secondarily from oncologic treatment, but may also result from trauma. More recently, lymphedema has been identified in patients after gender-affirmation phalloplasty reconstruction. Regardless of the etiology, the underlying pathophysiology involves blockage of lymphatic flow, resulting in lymph stasis, thus triggering a casca de of inflammation culminating in fibrosis and adipose deposition. Recent technical advances led to the refinement of physiologic and reductive surgeries—including lymphovenous anastomosis and free functional lymphatic transfer, which collectively encompass a variety of flap procedures including lymph node transfer, lymph channel transfer, and lymphatic system transfer. This article provides a summary of our approach in the assessment and management of the lymphedema patient, including detailed intraoperative photography and imaging, in addition to advanced technical considerations in physiologic reconstruction.
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Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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