Passive SOBP generation from a static proton pencil beam using 3D-printed range modulators for FLASH experiments

The University Proton Therapy facility in Dresden (UPTD), Germany, is equipped with an experimental room with a beamline providing a static pencil beam. High proton beam currents can be achieved at this beamline which makes it suitable for FLASH experiments. However, the established experimental setup uses only the entrance channel of the proton Bragg curve. In this work, a set of 3D-printed range modulators designed to generate spread out Bragg peaks (SOBPs) for radiobiological experiments at ultra-high dose rate at this beamline is described. A new method to optimize range modulators specifically for the case of a static pencil beam based on the central depth dose profile is introduced. Modulators for two different irradiation setups were produced and characterized experimentally by measurements of lateral and depth dose distributions using different detectors. In addition, Monte Carlo simulations were performed to assess profiles of the dose averaged linear energy transfer (LETD) in water. These newly produced range modulators will allow future proton FLASH experiments in the SOBP at UPTD with two different experimental setups

Management of peripheral facial nerve palsy

Peripheral facial nerve palsy (FNP) may (secondary FNP) or may not have a detectable cause (Bell’s palsy). Three quarters of peripheral FNP are primary and one quarter secondary. The most prevalent causes of secondary FNP are systemic viral infections, trauma, surgery, diabetes, local infections, tumor, immunological disorders, or drugs. The diagnosis of FNP relies upon the presence of typical symptoms and signs, blood chemical investigations, cerebro-spinal-fluid-investigations, X-ray of the scull and mastoid, cerebral MRI, or nerve conduction studies. Bell’s palsy may be diagnosed after exclusion of all secondary causes, but causes of secondary FNP and Bell’s palsy may coexist. Treatment of secondary FNP is based on the therapy of the underlying disorder. Treatment of Bell’s palsy is controversial due to the lack of large, randomized, controlled, prospective studies. There are indications that steroids or antiviral agents are beneficial but also studies, which show no beneficial effect. Additional measures include eye protection, physiotherapy, acupuncture, botulinum toxin, or possibly surgery. Prognosis of Bell’s palsy is fair with complete recovery in about 80% of the cases, 15% experience some kind of permanent nerve damage and 5% remain with severe sequelae

Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes

BACKGROUND The cardiovascular effects of ertugliflozin, an inhibitor of sodium–glucose cotransporter 2, have not been established. METHODS In a multicenter, double-blind trial, we randomly assigned patients with type 2 diabetes and atherosclerotic cardiovascular disease to receive 5 mg or 15 mg of ertugliflozin or placebo once daily. With the data from the two ertugliflozin dose groups pooled for analysis, the primary objective was to show the noninferiority of ertugliflozin to placebo with respect to the primary outcome, major adverse cardiovascular events (a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke). The noninferiority margin was 1.3 (upper boundary of a 95.6% confidence interval for the hazard ratio [ertugliflozin vs. placebo] for major adverse cardiovascular events). The first key secondary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure. RESULTS A total of 8246 patients underwent randomization and were followed for a mean of 3.5 years. Among 8238 patients who received at least one dose of ertugliflozin or placebo, a major adverse cardiovascular event occurred in 653 of 5493 patients (11.9%) in the ertugliflozin group and in 327 of 2745 patients (11.9%) in the placebo group (hazard ratio, 0.97; 95.6% confidence interval [CI], 0.85 to 1.11; P<0.001 for noninferiority). Death from cardiovascular causes or hospitalization for heart failure occurred in 444 of 5499 patients (8.1%) in the ertugliflozin group and in 250 of 2747 patients (9.1%) in the placebo group (hazard ratio, 0.88; 95.8% CI, 0.75 to 1.03; P=0.11 for superiority). The hazard ratio for death from cardiovascular causes was 0.92 (95.8% CI, 0.77 to 1.11), and the hazard ratio for death from renal causes, renal replacement therapy, or doubling of the serum creatinine level was 0.81 (95.8% CI, 0.63 to 1.04). Amputations were performed in 54 patients (2.0%) who received the 5-mg dose of ertugliflozin and in 57 patients (2.1%) who received the 15-mg dose, as compared with 45 patients (1.6%) who received placebo. CONCLUSIONS Among patients with type 2 diabetes and atherosclerotic cardiovascular disease, ertugliflozin was noninferior to placebo with respect to major adverse cardiovascular events. (Funded by Merck Sharp & Dohme and Pfizer; VERTIS CV ClinicalTrials.gov number, NCT01986881.)

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Quantitative sensory testing in physically active individuals and patients who underwent multidisciplinary pain therapy in the longitudinal course

Ulrike Dapunt, Simone Gantz, Anastasiya Zhuk, Katharina Gather, Haili Wang, Marcus Schiltenwolf Center for Orthopaedics, Trauma Surgery and Spinal Cord Injury, Heidelberg University Hospital, Schlierbacher Landstrasse, Heidelberg, Germany Objective: The aim of this study was to evaluate possible differences of quantitative sensory testing (QST) results in healthy individuals (group control, n=20), physically active individuals (group sport, n=30) and in patients suffering from chronic musculoskeletal pain (group pain, n=30). Methods: Thermal detection thresholds, thermal pain thresholds and blunt pressure pain thresholds were measured at various sites (T0). Additionally, group pain was treated in multidisciplinary pain therapy for 4 weeks. All groups were retested after 4 weeks to evaluate the reliability of QST measurements and to investigate possible early changes following treatment (T1).Results: Importantly, QST-measurements showed stable test results for group sport and group control at both time points. Athletes demonstrated the highest pain thresholds in general (cold pain threshold mean in degree Celsius for the hand: 5.76, lower back right: 7.25, lower back left: 7.53; heat pain threshold mean in degree Celsius for the hand: 46.08, lower back right: 45.77, lower back left: 45.70; and blunt pressure pain mean in kilograms for the hand: 3.54, lower back right: 5.26, lower back left: 5.46). Patients who underwent therapy demonstrated significant differences at T1 (cold pain threshold hand mean in degree Celsius for the hand: 11.12 [T0], 15.12 [T1]; and blunt pressure pain mean in kilograms for the lower back right: 2.87 [T0], 3.56 [T1]). They were capable of enduring higher blunt pressure, but on the other hand cold pain tolerance had decreased (P=0.045 and P=0.019, respectively).Conclusions: In conclusion, we were able to demonstrate significant differences of QST results among the three groups and we detected early changes following multidisciplinary pain therapy, which will be discussed. Keywords: quantitative sensory testing, chronic musculoskeletal pain, multidisciplinary pain therap

Are atrophic long-bone nonunions associated with low-grade infections?

Ulrike Dapunt,1 Ole Spranger,2 Simone Gantz,1 Irene Burckhardt,3 Stefan Zimmermann,3 Gerhard Schmidmaier,2 Arash Moghaddam2 1Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, 2HTRG&ndash;Heidelberg Trauma Research Group, Trauma and Reconstructive Surgery, Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Heidelberg University Hospital, 3Department for Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg, Germany Abstract: Impaired fracture healing, especially when associated with bacterial infection, is a severe complication following long-bone fractures and requires special treatment. Because standard diagnostic techniques might provide falsely negative results, we evaluated the sonication method for detection of bacteria on implants of patients with fracture nonunions. A total of 49 patients with a nonunion (group NU) and, for comparison, 45 patients who had undergone routine removal of osteosynthetic material (group OM), were included in the study. Five different diagnostic methods (culture of tissue samples, culture of intraoperative swabs, histopathology of tissue samples, culture of sonication fluid, and 16S ribosomal DNA polymerase chain reaction of sonication fluid) were compared and related to clinical data. Among the diagnostic tests, culture of sonication fluid demonstrated by far the highest detection rate of bacteria (57%) in group NU, and rather unexpectedly 40% in group OM. Culture of sonication samples also revealed a broad spectrum of bacteria, in particular Propionibacterium spp. In conclusion, our results indicate that more bacteria can be detected on implants of patients with atrophic nonunions of long-bone fractures by means of the sonication procedure, which provides a valuable additional diagnostic tool to decide on a surgical procedure (eg, two-step procedure) and to further specify antimicrobial therapy. Keywords: sonication, osteosynthetic material, osteomyelitis&nbsp