Resolution of vascular inflammation in patients with new-onset giant cell arteritis: data from the RIGA study.

OBJECTIVES: Efficacy evaluation of GCA treatment is primarily based on non-specific symptoms and laboratory markers. We aimed to assess the change in vascular inflammation in patients with large vessel (LV)-GCA under different treatments using [18F]FDG PET/CT. METHODS: Observational study on patients with new-onset, active LV-GCA starting treatment with either prednisolone monotherapy (PRED) or combination with MTX or tocilizumab (TOC). All patients underwent baseline and follow-up PET/CT. The aorta and its major branches were assessed using PET vascular activity score (PETVAS) by independent readers. Cumulative glucocorticoid doses and cessation of glucocorticoid treatment were documented in all patients. RESULTS: We included 88 LV-GCA patients, 27 were treated with PRED, 42 with MTX and 19 with TOC. PETVAS decreased from 18.9-8.0 units at follow-up in the overall population (P <0.001). PETVAS changes were numerically higher in patients receiving MTX (-12.3 units) or TOC (-11.7 units) compared with PRED (-8.7). Mean cumulative prednisolone dosages were 5637, 4418 and 2984 mg in patients treated with PRED, MTX and TOC (P =0.002). Risk ratios for glucocorticoid discontinuation at the time of follow-up PET/CT were 6.77 (95% CI: 1.01, 45.29; P =0.049) and 16.25 (95% CI: 2.60, 101.73; P =0.003) for MTX and TOC users compared with PRED users. CONCLUSION: Treatment of LV-GCA inhibits vascular inflammation in the aorta and its major branches. While similar control of vascular inflammation was achieved with PRED, MTX and TOC treatments, TOC showed a strong glucocorticoid sparing effect, supporting the concept of initial combination therapy.

Bidentate Nitrogen-Ligated I(V) Reagents, Bi(N)-HVIs: Preparation, Stability, Structure, and Reactivity.

Hypervalent iodine(V) reagents are a powerful class of organic oxidants. While the use of I(V) compounds Dess-Martin periodinane and IBX is widespread, this reagent class has long been plagued by issues of solubility and stability. Extensive effort has been made for derivatizing these scaffolds to modulate reactivity and physical properties but considerable room for innovation still exists. Herein, we describe the preparation, thermal stability, optimized geometries, and synthetic utility of an emerging class of I(V) reagents, Bi(N)-HVIs, possessing datively bound bidentate nitrogen ligands on the iodine center. Bi(N)-HVIs display favorable safety profiles, improved solubility, and comparable to superior oxidative reactivity relative to common I(V) reagents. The highly modular synthesis and in situ generation of Bi(N)-HVIs provides a novel and convenient screening platform for I(V) reagent and reaction development.

A dual-center evaluation of platelet culture vials to detect the presence of microorganisms in platelets.

BACKGROUND: Microorganism contamination of platelets results in a high risk of transfusion-related sepsis. Here, the ability of culture vials (BD BACTEC Platelet Aerobic/F and Platelet Anaerobic/F vials, Becton, Dickinson and Company) to detect microorganisms in leukoreduced apheresis platelets (LRAPs) and leukoreduced whole blood platelet concentrates (LRWBPCs) was assessed. METHODS: LRAPs or LRWBPCs were inoculated into Aerobic/F and Anaerobic/F vials and placed in a blood culturing system (BD BACTEC FX System, Becton, Dickinson and Company) for growth/monitoring over 7 days to detect preexisting contamination during false-positive testing. Subsequently, platelets were seeded with microorganisms at approximately 10 CFU/mL or approximately 1 CFU/mL to simulate contamination. Aerobic/F and Anaerobic/F vials were inoculated with platelets (sets of 12). Microorganism growth was detected in the BACTEC FX instrument over 7 days. Overall, 2925 vials were tested. RESULTS: Of the 1905 vials included in the microorganism detection phase, 63 (3.3%) Aerobic/F and 16 (0.8%) Anaerobic/F vials were both BACTEC FX and subculture negative. From the remaining 1827 vials, two (0.1%) Anaerobic/F vials were false positive; no false positives were observed in Aerobic/F vials, and no false negatives occurred in either vial type. Of the remaining 1825 vials (99.9%), 955 Aerobic/F and 870 Anaerobic/F vials were true positives. The mean-time-to-detection range was 8.5 to 77 hours. All true-positive Aerobic/F and Anaerobic/F vials showed 100% agreement with subculture for positive identification of seeded microorganisms. CONCLUSION: Aerobic/F and Anaerobic/F vials facilitate contamination detection in LRAPs and LRWBPCs down to approximately 1 CFU/mL. These results support the use of Aerobic/F and Anaerobic/F vials for quality control testing of platelets before transfusion.

Baclofen bridging, weaning protocol and pain management of a person with T6 paraplegia who required removal of intrathecal baclofen pump due to wound infection.

Intrathecal baclofen is recognised as an effective treatment option for severe symptoms of segmental spasticity after spinal cord injury. We present our experience of a case of a patient who was admitted to our centre for elective intrathecal baclofen pump revision surgery, but postsurgical complications of a blocked catheter and subsequent wound infections meant the pump had to be removed. In this case, treatment of severe spasticity and nociceptive pain was required while avoiding potentially lethal side effects of sudden baclofen withdrawal. We suggest an effective bridging and weaning protocol for oral drug titration to treat spasticity and pain as a blended syndrome in this challenging situation.

Working towards inclusive and equitable trauma treatment guidelines: a child-centered reflection.

Clinical practice guidelines, such as those focusing on traumatic stress treatment, can play an important role in promoting inclusion and equity. Based on a review of 14 international trauma treatment guidance documents that explicitly mentioned children, we reflect on two areas in which these guidelines can become more inclusive and equitable; a) representation of children's cultural background and b) children's opportunity to have their voice heard. While a few guidelines mentioned that treatment should be tailored to children's cultural needs, there was little guidance on how this could be done. Moreover, there still appears to be a strong white Western lens across all stages of producing and evaluating the international evidence base. The available documentation also suggested that no young people under the age of 18 had been consulted in the guideline development processes. To contribute to inclusion and equity, we suggest five elements for future national guideline development endeavours. Promoting research and guideline development with, by, and for currently under-represented communities should be a high priority for our field. Our national, regional and global professional associations are in an excellent position to (continue to) stimulate conversation and action in this domain.

Las guías de práctica clínica, como las que se centran en el tratamiento del estrés traumático, pueden desempeñar un papel importante en la promoción de la inclusión y la equidad. Basados en una revisión de 14 documentos internacionales de orientación sobre el tratamiento del trauma que mencionaban explícitamente a los niños, reflexionamos sobre dos áreas en las que estas guías pueden ser más inclusivas y equitativas; a) representación de los antecedentes culturales de los niños y b) oportunidad de los niños para que se escuche su voz. Si bien en algunas pautas se mencionó que el tratamiento debería adaptarse a las necesidades culturales de los niños, hubo poca orientación sobre cómo hacerlo. Más aún, todavía parece haber una fuerte perspectiva occidental blanca en todas las etapas de producción y evaluación de la base de evidencia internacional. Las directrices disponibles también sugirieron que no se había consultado a ningún joven menor de 18 años en sus procesos de elaboración. Para contribuir a la inclusión y la equidad, sugerimos cinco elementos para futuros esfuerzos de desarrollo de directrices nacionales. Promover la investigación y el desarrollo de directrices con, por y para las comunidades actualmente subrepresentadas debe ser una alta prioridad para nuestro campo. Nuestras asociaciones profesionales nacionales, regionales y mundiales se encuentran en una excelente posición para (continuar) estimulando la conversación y la acción en este ámbito.

The coming storm Medicare wage index overhaul signals changes for hospitals.

Recent recommendations by the Medicare Payment Advisory Commission (MedPAC) could, if implemented, substantially alter the wage index-and redistribute billions to hospitals in the process. The Centers for Medicare & Medicaid Services (CMS) is expected to publish its recommendations soon. Whether CMS will endorse or reject MedPAC's recommendations is unclear.

Flexible visual processing of spatial relationships.

Visual processing breaks the world into parts and objects, allowing us not only to examine the pieces individually, but also to perceive the relationships among them. There is work exploring how we perceive spatial relationships within structures with existing representations, such as faces, common objects, or prototypical scenes. But strikingly, there is little work on the perceptual mechanisms that allow us to flexibly represent arbitrary spatial relationships, e.g., between objects in a novel room, or the elements within a map, graph or diagram. We describe two classes of mechanism that might allow such judgments. In the simultaneous class, both objects are selected concurrently. In contrast, we propose a sequential class, where objects are selected individually over time. We argue that this latter mechanism is more plausible even though it violates our intuitions. We demonstrate that shifts of selection do occur during spatial relationship judgments that feel simultaneous, by tracking selection with an electrophysiological correlate. We speculate that static structure across space may be encoded as a dynamic sequence across time. Flexible visual spatial relationship processing may serve as a case study of more general visual relation processing beyond space, to other dimensions such as size or numerosity.

The karyopherin Msn5/Kap142 requires Nup82 for nuclear export and performs a function distinct from translocation in RPA protein import.

Protein transport between the nucleus and cytoplasm requires interactions between nuclear pore complex proteins (nucleoporins) and soluble nuclear transport factors (karyopherins, importins, and exportins). Exactly how these interactions contribute to the nucleocytoplasmic transport of substrates remains unclear. Using a synthetic lethal screen with the nucleoporin NUP1, we have identified a conditional allele of NUP82, encoding an essential nuclear pore complex protein in Saccharomyces cerevisiae. This nup82-3 allele also exhibits synthetic genetic interactions with mutants of the karyopherin MSN5. nup82-3 mutants accumulate the Msn5 export substrate Pho4 within the nucleus at non-permissive temperatures. The nuclear import of the RPA complex subunit Rfa2 is impaired in nup82-3 and in mutants of the karyopherin KAP95, but is not affected by the loss of MSN5. Interestingly, deletion of MSN5 results in retention of Rfa2-GFP within the nucleus under conditions in which it normally diffuses out. These data provide evidence that Nup82 is important for Msn5-mediated nuclear protein export and Kap95-mediated protein import. In addition, Msn5 may play a role independent of import in the localization of Rfa2.