RationaleLung transplantation is the ultimate treatment option for patients with end-stage respiratory diseases but bears the highest mortality rate among all solid organ transplantations due to chronic lung allograft dysfunction (CLAD). The mechanisms leading to CLAD remain elusive due to insufficient understanding of the complex post-transplant adaptation processes.ObjectivesTo better understand these lung adaptation processes after transplantation, and to investigate their association with future changes in allograft function.MethodsWe performed an exploratory cohort study in 78 patients on bronchoalveolar lavage samples from lung donors and recipients. We analysed the alveolar microbiome using 16S rRNA sequencing, the cellular composition using flow-cytometry, as well as metabolome and lipidome profiling.Measurements and Main ResultsWe established distinct temporal dynamics for each of the analysed data sets. Comparing matched donor and recipient samples, we revealed that recipient-specific as well as environmental factors, rather than the donor microbiome, shape the long-term lung microbiome. We further discovered that the abundance of certain bacterial strains correlated with underlying lung diseases even after transplantation. A decline in forced expiratory volume during the first second (FEV1) is a major characteristic of lung allograft dysfunction in transplant recipients. By using a machine learning approach, we could accurately predict future changes in FEV1 from our multi-omics data, whereby microbial profiles showed a particularly high predictive power.ConclusionBronchoalveolar microbiome, cellular composition, metabolome and lipidome show specific temporal dynamics after lung transplantation. The lung microbiome can predict future changes in lung function with high precision.

BACKGROUND:Patients with human papillomavirus (HPV)-positive oropharyngeal carcinoma (OC) have better prognosis than patients with HPV-negative OC. The objective of the current study was to assess how different practices across the United States treat patients with OC with respect to screening for HPV DNA or p16. METHODS: Five hundred forty-two randomly selected radiation oncologists were sent an 11-question survey by email regarding the use of HPV/p16 screening in OC. The questionnaire addressed demographics of the practice, intensity-modulated radiotherapy (IMRT) use, screening practices for HPV DNA or p16, which year this began, the use of HPV or p16 data to direct patient care, and future plans for its use if it had not already been instituted. RESULTS: One hundred ninety-two responses (39.6%) were received. Thirty-five percent of respondents (67 of 188) reported screening for HPV DNA routinely, whereas 4.8% of respondents (9 of 188) reported screening for p16. Of the physicians who did not use screening techniques, 37.2% (44 of 118 respondents) reported future plans to institute these screening techniques, 20% (9 of 45 respondents) stated plans to institute these techniques in the next 6 months, 55.5% (25 of 45 respondents) stated plans to institute these techniques within 6 months to 1 year, and 22.2% (10 of 45 respondents) stated plans to institute these techniques within 1 to 2 years. Academic physicians were more likely to use screening techniques (62.7%; P < .001) compared with private practitioners (31.4%). Only 12.4% of respondents reported using HPV or p16 data to direct care. CONCLUSIONS: Approximately 40.4% of radiation oncology practices that responded to a survey in the United States screened for HPV DNA or p16 in OC, whereas only 12.4% used it to further direct care. This number appears to be growing rapidly. Clinical trials to further elucidate how HPV or p16 status should direct care in OC are warranted. Cancer 2010;116:514-9.

Background The virome of lung transplant recipients (LTRs) under immunosuppressive therapy is dominated by non-pathogenic Anelloviridae and further includes several pathogenic viruses such as Herpesviruses or respiratory viruses. It is unclear whether the donor-derived virome in the transplanted lung influences recipient virome dynamics in other body compartments and if so, to which degree. Likewise, it is unknown whether dependencies exist among virus populations that mutually shape viral loads and kinetics. Results To address these questions, we characterized viral communities in airways and plasma of 49 LTRs and analyzed their abundance patterns in a data modeling approach. We found distinct viral clusters that were specific for body compartments and displayed independent dynamics. These clusters robustly gathered specific viral species across the patient cohort. In the lung, viral cluster abundance associated with time after transplantation and we detected mutual exclusion of viral species within the same human host. In plasma, viral cluster dynamics were associated with the indication for transplantation lacking significant short-time changes. Interestingly, pathogenic viruses in the plasma co-occurred specifically with Alpha torque virus genogroup 4 and Gamma torque virus strains suggesting shared functional or ecological requirements. Conclusions In summary, the detailed analysis of virome dynamics after lung transplantation revealed host, body compartment, and time-specific dependency patterns among viruses. Furthermore, our results suggested genetic adaptation to the host microenvironment at the level of the virome and support the hypothesis of functional complementarity between Anellovirus groups and other persistent viruses.

A detailed understanding of the physics of space-charge dominated beams is vital for many advanced accelerators that desire to achieve high beam intensity. In that regard, low-energy, high-intensity electron beams provide an excellent model system. The University of Maryland Electron ring (UMER), currently under construction, has been designed to study the physics of space-charge dominated beams with extreme intensity in a strong focusing lattice with dispersion. The tune shift in UMER will be more than an order of magnitude greater than exiting synchrotrons and rings. The 10-keV, 100 mA, UMER beam has a generalized perveance in the range of 0.0015, and a tune shift of 0.9. Though compact (11-m in circumference), UMER is a very complex device, with over 140 focusing and bending magnets. We report on the unique design features of this research facility, the beam physics to be investigated, and early experimental results.

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Acquired haemophilia A (AHA) is an autoimmune bleeding disorder caused by autoantibodies blocking coagulation factor VIII (FVIII). Haemostatic management of AHA and concomitant thrombotic risk is difficult. We cover the management of a 75‐year‐old male with severe Covid‐19, a prothrombotic disease, and de novo AHA with severe muscle bleeding, a disease requiring highly thrombogenic haemostatic therapy and immunosuppression—a challenging combination. FVIII activity was measured using human and bovine reagents to differentiate between endo‐ and exogenous FVIII activity. For haemostatic control, recombinant human activated FVII was given, followed by emicizumab, as a less thrombogenic long‐term haemostatic agent. Steroids were used as initial immunosuppressive therapy. Later, rituximab was used for inhibitor eradication. No thromboembolic events occurred, and bleeding was effectively controlled. Emicizumab achieved haemostatic balance in a patient under haemorrhagic and thrombogenic conditions. Individual risk assessment is needed to guide treatment decisions in patients threatened by simultaneous bleeding and thrombosis.

Laryngotracheal resections have become a clinical routine in experienced airway centers and even extended glotto-subglottic resections and reconstructions can be performed with low complication rates and excellent long-term airway patency. However, reports on the functional outcome after laryngotracheal resections are sparse and there is no general agreement among airway surgeons, which functional evaluations should be performed before and after surgery. The following review provides an overview on basic assessment tools, which can be used to objectively report functional outcome after laryngotracheal surgery.

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