Multimodale Therapie bei lokal fortgeschrittenem kutanem Plattenepithelkarzinom

alexandrossfakianakis shared this article with you from Inoreader Multimodale Therapie bei lokal fortgeschrittenem kutanem Plattenepithelkarzinom via Laryngo-Rhino-Otologie Laryngorhinootologie DOI: 10.1055/a-1949-2936 Die Therapieoptionen für lokal fortgeschrittene oder metastasierte Plattenepithelkarzinome waren bisher stark begrenzt und nicht standardisiert. Durch die Zulassung des monoklonalen Antikörpers Cemiplimab, der gegen den programmed death-1-Rezeptor (PD-1) gerichtet ist, hat sich die Prognose der betroffenen Patienten deutlich gebessert, wobei z.T. anhaltende Komplettremissionen erzielt werden können.In der vorgestellten Kasuistik wurde ein multimorbider, 81-jähriger Patient aufgrund eines ausgedehnten Plattenepithelkarzinoms frontoparietal mit Schädelkalotteninfiltration und Einbruch nach intrakraniell zunächst mit Cemiplimab behandelt. Immunvermittelte Nebenwirkungen sind nicht aufgetreten. Bei klinischer und radiologischer Remission wurde der Restbefund interdisziplinär operativ versorgt, wobei die defekte Schädelkalotte rekonstruiert wurde. Histologisch wurde eine pathologische Komplettremissio n des Plattenepithelkarzinoms nachgewiesen. 6 Monate postoperativ ergab sich kein Anhalt für ein Lokalrezidiv oder Metastasen.Dieser Fall zeigt exemplarisch einen Patienten, der trotz seines hohen Alters und Ko-Morbidität von der Therapie mit Cemiplimab profitiert hat. Darüber hinaus demonstriert dieser Fall die Relevanz eines interdisziplinären/multimodalen Therapieregimes im Management dieser in der Inzidenz deutlich ansteigenden Tumorentität. [...] Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany Article in Thieme eJournals: Table of contents  |  Abstract  |  Full text View on Web

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Staphylococcus aureus Carrier Types are not Evidence of Population Heterogeneity

alexandrossfakianakis shared this article with you from Inoreader Staphylococcus aureus Carrier Types are not Evidence of Population Heterogeneity via American Journal of Epidemiology - Advance Access Abstract Asymptomatic colonization by Staphylococcus aureus is a precursor for infection, so identifying the mode and source of transmission which leads to colonization could help target interventions. Longitudinal studies have shown that some people are persistently colonized for years, while others seem to carry S. aureus for weeks or less, and conventional wisdom attributes this disparity to an underlying risk factor in the persistently colonized. We analyze published data with mathematical models of acquisition and carriage to compare this hypothesis with alternatives. The null model assumes a homogeneous population and still produces highly variable colonization durations (mean of 1.94 years, 5th percentile 0.1 years, 95th percentile 5.8 years). Simulations show that this inherent variability, combined with censoring in longitudinal cohort studies, i s sufficient to produce the appearance of "persistent carriers," "intermittent carriers," and "noncarriers" in data. Our estimates for colonization duration exhibit sensitivity to the assumption that false positives can occur despite being rare, but our model-based approach simultaneously estimates specificity and sensitivity along with epidemiological parameters. Our results show it is plausible that S. aureus colonizes people indiscriminately, and improved understanding of the types of exposures which result in colonization is essential. View on Web

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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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Utility of microbiologic testing in surveillance bronchoscopy following lung transplantation: A retrospective cohort study

alexandrossfakianakis shared this article with you from Inoreader Utility of microbiologic testing in surveillance bronchoscopy following lung transplantation: A retrospective cohort study via Transplant Infectious Disease 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 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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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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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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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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