Τετάρτη 16 Νοεμβρίου 2022

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

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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

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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.

This article is protected by copyright. All rights reserved

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

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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

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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

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

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

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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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Anti‐glycoprotein autoantibodies are related to bleeding severity in children with newly diagnosed ITP and very low platelet counts

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Abstract

Background and objective

Immune thrombocytopenia (ITP) is an autoimmune-mediated hemorrhagic disease. Anti-glycoprotein autoantibodies play a key role in the pathophysiology of ITP, but the relationship between platelet-specific antibodies and bleeding severity is unclear. This study aimed to analyze the relationship between anti-glycoprotein autoantibodies and bleeding severity in children with newly diagnosed ITP and platelet count less than 10 × 109/L.

Method

This was a single-center prospective observational study that analyzed children with newly diagnosed ITP and platelet count less than 10 × 109/L between June 2018 and September 2021 at our hospital. The children were classified into the mild and severe groups based on the bleeding scores. The type and titer of anti-glycoprotein autoantibodies were detected using an enzyme-linked immunosorbent assay (ELISA) kit (PAKAUTO). We analyzed the relationship between bleeding severity and anti-glycoprotein autoantibodies.

Results

A total of 86 cases were enrolled, including 42 in the mild group and 44 in the severe group. Patients with anti-GPIIb/IIIa or anti-GPIb/IX antibodies suffered more severe bleeding than patients without them (χ 2 = 7.303, p = .007; χ 2 = 3.875, p = .049), but there was no significant difference between patients with or without anti-GPIa/IIa antibodies (χ 2 = 0.745, p = .388). When antibodies were analyzed together, patients with three antibodies suffered more severe bleeding than those without three antibodies (χ 2 = 5.053, p = .025). Patients with higher antibody titer in the eluent, but not in the plasma, suffered more severe bleeding in all three antibodies (Z = −2.389, p = .017; Z = −2.108, p = .035; Z = −2.557, p = .011).

Conclusion

Anti-glycoprotein autoantibodies led to more severe bleeding in children under 18 years of age without drug treatment with newly diagnosed ITP and platelet count less than 10 × 109/L.

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Approach to Complex Lower Extremity Reconstruction

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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:
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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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