Citations

Spinal cord stimulation (SCS) has demonstrated effectiveness for neuropathic pain. Unfortunately, some patients report inadequate long-term pain relief. Patient selection is emphasized for this therapy; however, the prognostic capabilities and deployment strategies of existing selection techniques, including an SCS trial, have been questioned. After approval by the Board of Directors of the American Society of Regional Anesthesia and Pain Medicine, a steering committee was formed to develop evidence-based guidelines for patient selection and the role of an SCS trial. Representatives of professional organizations with clinical expertize were invited to participate as committee members. A comprehensive literature review was carried out by the steering committee, and the results organized into narrative reports, which were circulated to all the committee members. Individual statements and recommendations within each of seven sections were formulated by the steering committee and circulated to members for voting. We used a modified Delphi method wherein drafts were circulated to each member in a blinded fashion for voting. Comments were incorporated in the subsequent revisions, which were recirculated for voting to achieve consensus. Seven sections with a total of 39 recommendations were approved with 100% consensus from all the members. Sections included definitions and terminology of SCS trial; benefits of SCS trial; screening for psychosocial characteristics; patient perceptions on SCS therapy and the use of trial; other patient predictors of SCS therapy; conduct of SCS trials; and evaluation of SCS trials including minimum criteria for success. Recommendations included that SCS trial should be performed before a definitive SCS implant except in anginal pain (grade B). All patients must be screened with an objective validated instrument for psychosocial factors, and this must include depression (grade B). Despite some limitations, a trial helps patient selection and provides patients with an opportunity to experience the therapy. These recommendations are expected to guide practicing physicians and other stakeholders and should not be mistaken as practice standards. Physicians should continue to make their best judgment based on individual patient considerations and preferences.

Antistaphylococcal penicillins (ASP) and cefazolin are first-line treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Borderline oxacillin resistance (i.e., oxacillin MICs 1-8 μg/mL) is observed in strains hyperproducing beta-lactamases.

Abstract Background Stereotactic radiosurgical rhizolysis of the trigeminal nerve is an established modality increasingly employed to alleviate the symptoms of refractory trigeminal neuralgia. This study analyzes the academic impact of the top 100 cited articles on the radiosurgical management of trigeminal neuralgia. Methods The Scopus database was searched for articles containing “radiosurgery” and one or more of “trigeminal neuralgia,” “trigeminus neuralgia,” and “tic douloureux.” The top 100 articles written in English were arranged in descending order by citation count. Documents were evaluated for authors, publication year, journal and impact factor, total citations, nationality, study type, radiosurgical modality, and the affiliated institution. Quantitative and qualitative analyses were performed on the data. Results The most cited articles were published between 1971 and 2019. The average citation per year was 4.3. The most targeted anatomic area was the “root entry zone” or proximal portion of the cisternal segment of the trigeminal nerve. The most utilized modality was Gamma Knife radiosurgery. The country with the highest number of publications was the United States. Thirty-six percent of the articles were published in the Journal of Neurosurgery. Lunsford, Kondziolka, Flickinger, and Régis, respectively, were the most frequently listed co-authors. The most prolific institute was the University of Pittsburgh Medical Center. Conclusion Stereotactic radiosurgery is an important modality in the management of medically or surgically refractory trigeminal neuralgia. This analysis assesses its contributions over the past five decades to identify trends in treatment practices for neurosurgeons and to highlight areas where further study is needed.

Multiplex immunofluorescence (MxIF) images provide detailed information of cell composition and spatial context for biomedical research. However, compromised data quality could lead to research biases. Comprehensive image quality checking (QC) is essential for reliable downstream analysis. As a reliable and specific staining of cell nuclei, 4′,6-diamidino-2-phenylindole (DAPI) signals were used as references for tissue localization and auto-focusing across MxIF staining–scanning–bleaching iterations and could potentially be reused for QC. To confirm the feasibility of using DAPI as QC reference, pixel-level DAPI values were extracted to calculate signal fluctuations and tissue content similarities in staining–scanning–bleaching iterations for identifying quality issues. Concordance between automatic quantification and human experts’ annotations were evaluated on a data set consisting of 348 fields of view (FOVs) with 45 immune and tumor cell markers. Cell distribution differences between subsets of QC-pass vs QC-failed FOVs were compared to investigate the downstream effects. Results showed that 87.3% FOVs with tissue damage and 73.4% of artifacts were identified. QC-failed FOVs showed elevated regional gathering in cellular feature space compared with the QC-pass FOVs. Our results supported that DAPI signals could be used as references for MxIF image QC, and low-quality FOVs identified by our method must be cautiously considered for downstream analyses.

Significance Statement Changes in albuminuria and GFR slope are individually used as surrogate end points in clinical trials of CKD progression, and studies have demonstrated that each is associated with treatment effects on clinical end points. In this study, the authors sought to develop a conceptual framework that combines both surrogate end points to better predict treatment effects on clinical end points in Phase 2 trials. The results demonstrate that information from the combined treatment effects on albuminuria and GFR slope improves the prediction of treatment effects on the clinical end point for Phase 2 trials with sample sizes between 100 and 200 patients and duration of follow-up ranging from 1 to 2 years. These findings may help inform design of clinical trials for interventions aimed at slowing CKD progression. Background Changes in log urinary albumin-to-creatinine ratio (UACR) and GFR slope are individually used as surrogate end points in clinical trials of CKD progression. Whether combining these surrogate end points might strengthen inferences about clinical benefit is unknown. Methods Using Bayesian meta-regressions across 41 randomized trials of CKD progression, we characterized the combined relationship between the treatment effects on the clinical end point (sustained doubling of serum creatinine, GFR <15 ml/min per 1.73 m 2 , or kidney failure) and treatment effects on UACR change and chronic GFR slope after 3 months. We applied the results to the design of Phase 2 trials on the basis of UACR change and chronic GFR slope in combination. Results Treatment effects on the clinical end point were strongly associated with the combination of treatment effects on UACR change and chronic slope. The posterior median meta-regression coefficients for treatment effects were −0.41 (95% Bayesian Credible Interval, −0.64 to −0.17) per 1 ml/min per 1.73 m 2 per year for the treatment effect on GFR slope and −0.06 (95% Bayesian Credible Interval, −0.90 to 0.77) for the treatment effect on UACR change. The predicted probability of clinical benefit when considering both surrogates was determined primarily by estimated treatment effects on UACR when sample size was small (approximately 60 patients per treatment arm) and follow-up brief (approximately 1 year), with the importance of GFR slope increasing for larger sample sizes and longer follow-up. Conclusions In Phase 2 trials of CKD with sample sizes of 100–200 patients per arm and follow-up between 1 and 2 years, combining information from treatment effects on UACR change and GFR slope improved the prediction of treatment effects on clinical end points.

18 Background: TRITON3 (NCT02975934) is a randomized, multicenter, open-label, phase 3 study of rucaparib vs physician’s choice (docetaxel [DTX], abiraterone [ABI] or enzalutamide [ENZ]) in patients (pts) with chemotherapy-naïve mCRPC with BRCA1/2 (BRCA) or ATM alterations. It was previously reported that rucaparib significantly improved the primary endpoint of radiographic progression-free survival (rPFS) vs physician’s choice in pts with BRCA or ATM alterations. We report here the interim overall survival (OS) and also report on efficacy of rucaparib compared individually with either DTX or ABI/ENZ. Methods: Pts had disease progression after 1 prior second-generation androgen pathway inhibitor therapy in any setting and were randomized 2:1 to rucaparib 600 mg BID or physician’s choice of DTX, ABI or ENZ. An ordered step-down multiple comparisons procedure was used to control the overall error rate. OS was a key secondary endpoint with rPFS as the primary endpoint tested first in the BRCA subgroup, then the intent-to-treat (ITT) population. Subgroup analyses based on physician’s choice were exploratory. Results: As of August 25, 2022, 302 pts with BRCA and 103 pts with ATM alterations were randomized. OS maturity was 54% in the BRCA subgroup and 59% in the ITT population. rPFS and OS are shown. The most frequent treatment-emergent adverse event (TEAE) in the rucaparib, DTX and ABI/ENZ groups was asthenia/fatigue (61.1%, 67.6% and 57.6%, respectively). The most frequent grade ≥3 TEAE in the rucaparib, DTX and ABI/ENZ groups was anemia (23.7%), neutropenia (14.1%), and hypertension (10.2%), respectively. Conclusions: Rucaparib significantly improved rPFS vs either DTX or ABI/ENZ; safety was consistent with prior reports. Interim OS results suggest a trend towards improvement for rucaparib vs DTX or ABI/ENZ in pts with mCRPC and BRCA alterations. Clinical trial information: NCT02975934 . [Table: see text]

Abstract Background In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR‐Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR‐Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence‐based findings and recommendation from the full document. Methods ICAR‐Allergic Rhinitis 2023 employed established evidence‐based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work. Results ICAR‐Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost. Conclusion The ICAR‐Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment.

Abstract Purpose: To determine the rate of rib fracture in a cohort of patients with breast cancer treated with proton therapy and enrolled on a prospective registry. In series investigating photon therapy for breast cancer, the rib fracture rate ranges from 0.3-13% Methods: From a prospective database, we identified patients treated with proton therapy for breast cancer at our institution between January 1, 2012 and December 31, 2020. Clinical and dosimetric data was extracted from the electronic medical record. The cumulative incidence method assessed rib fracture rate; the Fine-Gray test statistic assessed prognostic significance select variables. Results: 225 patients were identified, 223 women and 2 men. Median age at the time of radiation was 57.8 years (range, 25 – 87). 26% of patients were black, 69% white and 5% were other races or race not disclosed. 5% were Hispanic. 74% of patients had left-sided breast cancer, 5% bilateral, and 21% right-sided. DEXA scan was normal in 20%, showed osteopenia in 34%, osteoporosis in 6%, and not performed in 40%. 57% of patients received antiendocrine therapy with an aromatase inhibitor. For 16% of patients, the breast +/- internal mammary nodes (IMN) were treated, while 32% underwent proton therapy to treat the breast and comprehensive regional lymphatics. 1% of patients had chest wall +/- IMN treated, while 51% underwent proton therapy to treat the chest wall and comprehensive regional lymphatics. 41% of patients were treated with passive scatter proton therapy (n=92); 52% of these had mastectomy. 58% of patients received treatment with pencil beam scanning (PBS) proton therapy (n=131); 53% of these had mastectomy. A combination of passive scatter and PBS was used for 2 patients (1%). 85% of patients received a boost. Median follow-up was 3.1 years (range, 0.2 – 9.1). 97% of patients had &gt; 12 months of follow-up. The 3 year cumulative incidence of in-field rib fracture was 3.7% (95%CI: 1.6%-7.1%). In total, 8 patients developed in-field rib fractures, one symptomatic and 7 identified incidentally on surveillance imaging, for a 0.4% rate of symptomatic rib fracture. Median time from completion of radiation to identification of rib fracture was 1.8 years (range, 0.4-7.4 years). Rib fractures occurred within 2.2 years from radiotherapy completion for seven of the eight patients who experienced this side effect. Three patients developed rib fractures outside of the radiation field, for a cumulative incidence of out-of-field rib fracture of 0.9% (95%CI: 0.2-3.0%). No variables were associated with rib fracture on univariate analysis. Of those with in-field rib fractures, 3 had low and 3 had normal bone density while 2 had not undergone testing; of those with out-of-field rib fractures, 2 had osteopenia and 1 did not have testing. Conclusions: Although a proton beam has higher biological dose deposition at end-of-range than the assumed constant RBE=1.1, the 3 year rate of any in-field rib fractures in our series remains low at 3.7%, with a 0.4% rate of symptomatic rib fracture. Contouring ribs as an OAR and establishing a dose constraint warrants further investigation as a means to maintaining a low rate of rib fracture with proton therapy. Citation Format: Julie Bradley, Xiaoying Liang, Raymond Mailhot Vega, Chunbo Liu, Eric Brooks, Teena Burchianti, Emma Viviers, Roi Dagan, Oluwadamilola Oladeru, Christopher Morris, Nancy Mendenhall. Incidence of rib fracture following treatment with proton therapy for breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-08.