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 Cardiovascular outcomes after tixagevimab and cilgavimab use for pre-exposure prophylaxis against COVID-19: a population-based propensity-matched cohort study via Clinical Infectious Diseases Advance Access 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. View on Web

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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 DNA virus oncoprotein HPV18 E7 selectively antagonizes cGAS‐STING‐triggered innate immune activation via Journal of Medical Virology 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. This article is protected by copyright. All rights reserved. View on Web

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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 DNA virus oncoprotein HPV18 E7 selectively antagonizes cGAS‐STING‐triggered innate immune activation via Journal of Medical Virology 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. This article is protected by copyright. All rights reserved. View on Web

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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 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 via Journal of Medical Virology 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. View on Web

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Chickenpox and multiple sclerosis: A Mendelian randomization study

alexandrossfakianakis shared this article with you from Inoreader Chickenpox and multiple sclerosis: A Mendelian randomization study via Journal of Medical Virology 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. View on Web

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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 Correlation between asparaginase enzyme activity levels and coagulation parameters during childhood acute lymphoblastic leukemia treatment via Pediatric Blood & Cancer 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. View on Web

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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 Cervical Dorsal Root Ganglion Stimulation for Complex Regional Pain Syndrome: Technical Description and Results of Seven Cases via Pain Practice 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. View on Web

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Innovative Fudan rT staging in endoscopic surgery for recurrent nasopharyngeal carcinoma

alexandrossfakianakis shared this article with you from Inoreader Innovative Fudan rT staging in endoscopic surgery for recurrent nasopharyngeal carcinoma via Head & Neck 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. View on Web

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

alexandrossfakianakis shared this article with you from Inoreader Anti‐glycoprotein autoantibodies are related to bleeding severity in children with newly diagnosed ITP and very low platelet counts via Pediatric Blood & Cancer 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. View on Web

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Differences in palliative opportunities across diagnosis groups in children with cancer

alexandrossfakianakis shared this article with you from Inoreader Differences in palliative opportunities across diagnosis groups in children with cancer via Pediatric Blood & Cancer Abstract Background Childhood cancer causes significant physical and emotional stress. Patients and families benefit from palliative care (PC) to reduce symptom burden, improve quality of life, and enhance family-centered care. We evaluated palliative opportunities across leukemia/lymphoma (LL), solid tumors (ST), and central nervous system (CNS) tumor groups. Procedure A priori, nine palliative opportunities were defined: disease progression/relapse, hematopoietic stem cell transplant, phase 1 trial enrollment, admission for severe symptoms, social concerns or end-of-life (EOL) care, intensive care admission, do-not-resuscitate (DNR) status, and hospice enrollment. A single-center retrospective review was completed on 0–18-year olds with cancer who died from January 1, 2012 to November 30, 2017. Demographic, disease, and treatment data were collected. Descriptive statistics were performed. Opportunities were evaluated from diagnosis to death and across disease groups. Results Included patients (n = 296) had LL (n = 87), ST (n = 114), or CNS tumors (n = 95). Palliative opportunities were more frequent in patients with ST (median 8) and CNS tumors (median 7) versus LL (median 5, p = .0005). While patients with ST had more progression/relapse opportunities (p < .0001), patients with CNS tumors had more EOL opportunities (p < .0001), earlier PC consultation, DNR status, and hospice enrollment. Palliative opportunities increased toward the EOL in all diseases (p < .0001). PC was consulted in 108 (36%) patients: LL (48%), ST (30%), and CNS (34%, p = .02). Conclusions All children with cancer incur many events warranting PC support. Patients with ST and CNS tumors had more palliative opportunities than LL, yet received less subspecialty PC. Understanding palliative opportunities within each disease group can guide PC utilization to ease patient and family stress. View on Web

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Approach to Complex Lower Extremity Reconstruction

alexandrossfakianakis shared this article with you from Inoreader Approach to Complex Lower Extremity Reconstruction via Seminars in Plastic Surgery 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. [...] Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA Article in Thieme eJournals: Table of contents  |  Abstract  |  Full text View on Web

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