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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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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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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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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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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Approach to Lymphedema Management

alexandrossfakianakis shared this article with you from Inoreader Approach to Lymphedema Management via Seminars in Plastic Surgery 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. [...] 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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Black and White Patients with Staphylococcus aureus Bacteremia have Similar Outcomes but Different Risk Factors

alexandrossfakianakis shared this article with you from Inoreader Black and White Patients with Staphylococcus aureus Bacteremia have Similar Outcomes but Different Risk Factors via Clinical Infectious Diseases Advance Access Abstract BACKGROUND Staphylococcus aureus bacteremia (SAB) disproportionately affects Black patients. The reasons for this disparity are unclear. METHODS We evaluated a prospectively ascertained cohort of patients with SAB from 1995 to 2020. Clinical characteristics, bacterial genotypes, and outcome were compared among Black and White patients with SAB. Multivariable logistic regression models were used to determine factor s independently associated with the outcomes. RESULTS Among 3068 patients with SAB, 1107 (36%) were Black. Black patients were younger (Median: 56 years vs. 63 years; p < 0.001), had higher rates of diabetes (47.5% vs. 34.5%; p < 0.001), hemodialysis dependence (40.0% vs. 7.3%; p < 0.001), and HIV (6.4% vs. 0.6%; p < 0.001). Black patients had higher rates of methicillin-resistant S. aureus (49.3% vs 44.9%; p = 0.020), including the USA300 hypervirulent clone (11.5% vs. 8.4%; p = 0.007). White patients had higher rates of corticosteroid use (22.4% vs. 15.8%; p < 0.0001), and surgery in the preceding 30 days (28.1% vs. 18.7%; p < 0.001). Although median Acute Physiology Score (APS) at the time of initial SAB diagnosis was significantly higher in Black patients (Median APS 9, Interquartile Range [IQR] 5-14; vs. Median APS 7, IQR: 4-12; p < 0.001), race was not associated with 90-d ay mortality (risk ratio (RR): 1.02; 95% CI: 0.93–1.12, and rates of metastatic infection were lower among Black patients (37.2% vs. 41.3% White; p = 0.029). CONCLUSIONS Despite differences in Black patients' higher APS on presentation and more risk factors, including a 5 times higher risk of hemodialysis dependence, 90-day mortality among Black and White patients with SAB was similar. View on Web

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