Citations

ObjectiveTo describe people with gout who were diagnosed with coronavirus disease 2019 (COVID‐19) and hospitalized and to characterize their outcomes.MethodsData on patients with gout hospitalized for COVID‐19 between March 12, 2020, and October 25, 2021, were extracted from the COVID‐19 Global Rheumatology Alliance registry. Descriptive statistics were used to describe the demographics, comorbidities, medication exposures, and COVID‐19 outcomes including oxygenation or ventilation support and death.ResultsOne hundred sixty‐three patients with gout who developed COVID‐19 and were hospitalized were included. The mean age was 63 years, and 85% were male. The majority of the group lived in the Western Pacific Region (35%) and North America (18%). Nearly half (46%) had two or more comorbidities, with hypertension (56%), cardiovascular disease (28%), diabetes mellitus (26%), chronic kidney disease (25%), and obesity (23%) being the most common. Glucocorticoids and colchicine were used pre‐COVID‐19 in 11% and 12% of the cohort, respectively. Over two thirds (68%) of the cohort required supplemental oxygen or ventilatory support during hospitalization. COVID‐19‐related death was reported in 16% of the overall cohort, with 73% of deaths documented in people with two or more comorbidities.ConclusionThis cohort of people with gout and COVID‐19 who were hospitalized had high frequencies of ventilatory support and death. This suggests that patients with gout who were hospitalized for COVID‐19 may be at risk of poor outcomes, perhaps related to known risk factors for poor outcomes, such as age and presence of comorbidity.

Tumor-infiltrating lymphocytes (TILs) are prognostic in invasive breast cancer. However, their prognostic significance in ductal carcinoma in situ (DCIS) has been controversial. To investigate the prognostic role of TILs in DCIS outcome, we used different scoring methods for TILs in multi-national cohorts from Asian and European women. Self-described race was genetically confirmed using QC Infinium array combined with radmixture software. Stromal TILs, touching TILs, circumferential TILs, and hotspots were quantified on H&E-stained slides and correlated with the development of second breast cancer events (BCE) and other clinico-pathological variables. In univariate survival analysis, age older than 50 years, hormone receptor positivity and the presence of circumferential TILs were weakly associated with the absence of BCE at the 5-year follow-up in all cohorts (p < 0.03; p < 0.02; and p < 0.02, respectively, adjusted p = 0.11). In the multivariable analysis, circumferential TILs were an independent predictor of a better outcome (Wald test p = 0.01), whereas younger age was associated with BCE. Asian patients were younger with larger, higher grade, HR negative DCIS lesions, and higher TIL variables. The spatial arrangement of TILs may serve as a better prognostic indicator in DCIS cases than stromal TILs alone and may be added in guidelines for TILs evaluation in DCIS.

The study’s objective was to assess facilitators and barriers of Tele-Critical Care (TCC) perceived by SCCM members. By utilizing a survey distributed to SCCM members, a cross-sectional study was developed to analyze survey results from December 2019 and July 2020. SCCM members responded to the survey (n = 15,502) with a 1.9% response rate for the first distribution and a 2.54% response rate for the second survey (n = 9985). Participants (n = 286 and n = 254) were almost equally distributed between non-users, providers, users, and potential users of TCC services. The care delivery models for TCC were similar across most participants. Some consumers of TCC services preferred algorithmic coverage and scheduled rounds, while reactive and on-demand models were less utilized. The surveys revealed that outcome-driven measures were the principal form of TCC performance evaluation. A 1:100 (provider: patients) ratio was reported to be optimal. Factors related to costs, perceived lack of need for services, and workflow challenges were described by those who terminated TCC services. Barriers to implementation revolved around lack of reimbursement and adequate training. Interpersonal communication was identified as an essential TCC provider skill. The second survey introduced after the onset pandemic demonstrated more frequent use of advanced practice providers and focus on performance measures. Priorities for effective TCC deployment include communication, knowledge, optimal operationalization, and outcomes measurement at the organizational level. The potential effect of COVID-19 during the early stages of the pandemic on survey responses was limited and focused on the need to demonstrate TCC value.

Abstract Improving the chances of curing patients with cancer who have had surgery to remove metastatic sites of disease is a priority area for cancer research. Pexa-Vec (Pexastimogene Devacirepvec; JX-594, TG6006) is a principally immunotherapeutic oncolytic virus that has reached late-phase clinical trials. We report the results of a single-center, nonrandomized biological end point study (trial registration: EudraCT number 2012-000704-15), which builds on the success of the presurgical intravenous delivery of oncolytic viruses to tumors. Nine patients with either colorectal cancer liver metastases or metastatic melanoma were treated with a single intravenous infusion of Pexa-Vec ahead of planned surgical resection of the metastases. Grade 3 and 4 Pexa-Vec–associated side effects were lymphopaenia and neutropaenia. Pexa-Vec was peripherally carried in plasma and was not associated with peripheral blood mononuclear cells. Upon surgical resection, Pexa-Vec was found in the majority of analyzed tumors. Pexa-Vec therapy associated with IFNα secretion, chemokine induction, and resulted in transient innate and long-lived adaptive anticancer immunity. In the 2 patients with significant and complete tumor necrosis, a reduction in the peripheral T-cell receptor diversity was observed at the time of surgery. These results support the development of presurgical oncolytic vaccinia virus-based therapies to stimulate anticancer immunity and increase the chances to cure patients with cancer.

ObjectiveThe aim of this study was to determine whether selection of treatment for children with infantile spasms (IS) varies by race/ethnicity.MethodsThe prospective US National Infantile Spasms Consortium database includes children with IS treated from 2012 to 2018. We examined the relationship between race/ethnicity and receipt of standard IS therapy (prednisolone, adrenocorticotropic hormone, vigabatrin), adjusting for demographic and clinical variables using logistic regression. Our primary outcome was treatment course, which considered therapy prescribed for the first and, when needed, the second IS treatment together.ResultsOf 555 children, 324 (58%) were non‐Hispanic white, 55 (10%) non‐Hispanic Black, 24 (4%) non‐Hispanic Asian, 80 (14%) Hispanic, and 72 (13%) other/unknown. Most (398, 72%) received a standard treatment course. Insurance type, geographic location, history of prematurity, prior seizures, developmental delay or regression, abnormal head circumference, hypsarrhythmia, and IS etiologies were associated with standard therapy. In adjusted models, non‐Hispanic Black children had lower odds of receiving a standard treatment course compared with non‐Hispanic white children (odds ratio [OR], 0.42; 95% confidence interval [CI], 0.20–0.89; p = 0.02). Adjusted models also showed that children with public (vs. private) insurance had lower odds of receiving standard therapy for treatment 1 (OR, 0.42; CI, 0.21–0.84; p = 0.01).InterpretationNon‐Hispanic Black children were more often treated with non‐standard IS therapies than non‐Hispanic white children. Likewise, children with public (vs. private) insurance were less likely to receive standard therapies. Investigating drivers of inequities, and understanding the impact of racism on treatment decisions, are critical next steps to improve care for patients with IS. ANN NEUROL 2022;92:32–44

Background Combination herpes simplex virus (HSV) oncolytic virotherapy and BRAF inhibitors (BRAFi) represent promising immunogenic treatments for BRAF mutant melanoma, but an improved understanding of the immunobiology of combinations is needed to improve on the benefit of immune checkpoint inhibitors (ICI). Methods Using a BRAFV600E-driven murine melanoma model, we tested the immunogenicity of HSV/BRAFi in immunocompetent C57BL mice. In addition to standard FACS analysis, we used the ‘Timer of Cell Kinetics and Activity’ system, which can analyze the temporal dynamics of different T cell subsets. This immune data was used to inform the selection of ICI for triple combination therapy, the effects of which were then further characterized using transcriptomics. Results Adding BRAFi treatment to HSV improved anti-tumor effects in vivo but not in vitro. Immune characterization showed HSV or dual therapy led to fewer intratumoral Treg, although with a more activated phenotype, together with more effector CD8 +T cells. Tocky analysis further showed that HSV/BRAFi dual treatment reduced the Tocky signal (reflecting engagement with cognate antigen), in both Treg and conventional subsets of CD4+, but not in CD8 +cells. However, a higher percentage of Treg than of conventional CD4 +maintained frequent engagement with antigens on treatment, reflecting a predominance of suppressive over effector function within the CD4 +compartment. The only T cell subset which correlated with a reduction in tumor growth was within Tocky signal positive conventional CD4+, supporting their therapeutic role. Targeting CD25 high, antigen-engaged Treg with a depleting anti-CD25 ICI, achieved complete cures in 100% of mice with triple therapy. Transcriptomic analysis confirmed reduction in Foxp3 on addition of anti-CD25 to HSV/BRAFi, as well as increases in expression of genes reflecting interferon signaling and cytotoxic activity. Conclusions Combination HSV/BRAFi is an immunogenic therapy for BRAF mutant melanoma, but cannot fully control tumors. Dual therapy results in changes in T cell dynamics within tumors, with relatively maintained antigen signaling in Treg compared with conv CD4+. Antigen-engaged CD4 +effectors correlate with tumor growth control, and depletion of Treg by addition of an anti-CD25 ICI, releasing suppression of conventional CD4 +effectors by Treg, enhances survival and activates immune signaling within tumors.

Background and objectives Documentation is important for quality improvement, education, and research. There is currently a lack of recommendations regarding key aspects of documentation in regional anesthesia. The aim of this study was to establish recommendations for documentation in regional anesthesia. Methods Following the formation of the executive committee and a directed literature review, a long list of potential documentation components was created. A modified Delphi process was then employed to achieve consensus amongst a group of international experts in regional anesthesia. This consisted of 2 rounds of anonymous electronic voting and a final virtual round table discussion with live polling on items not yet excluded or accepted from previous rounds. Progression or exclusion of potential components through the rounds was based on the achievement of strong consensus. Strong consensus was defined as ≥75% agreement and weak consensus as 50%–74% agreement. Results Seventy-seven collaborators participated in both rounds 1 and 2, while 50 collaborators took part in round 3. In total, experts voted on 83 items and achieved a strong consensus on 51 items, weak consensus on 3 and rejected 29. Conclusion By means of a modified Delphi process, we have established expert consensus on documentation in regional anesthesia.

Abstract Background: Somatic EGFR mutations define a subset of non–small cell lung cancers (NSCLC) that have clinical impact on NSCLC risk and outcome. However, EGFR-mutation-status is often missing in epidemiologic datasets. We developed and tested pragmatic approaches to account for EGFR-mutation-status based on variables commonly included in epidemiologic datasets and evaluated the clinical utility of these approaches. Methods: Through analysis of the International Lung Cancer Consortium (ILCCO) epidemiologic datasets, we developed a regression model for EGFR-status; we then applied a clinical-restriction approach using the optimal cut-point, and a second epidemiologic, multiple imputation approach to ILCCO survival analyses that did and did not account for EGFR-status. Results: Of 35,356 ILCCO patients with NSCLC, EGFR-mutation-status was available in 4,231 patients. A model regressing known EGFR-mutation-status on clinical and demographic variables achieved a concordance index of 0.75 (95% CI, 0.74–0.77) in the training and 0.77 (95% CI, 0.74–0.79) in the testing dataset. At an optimal cut-point of probability-score = 0.335, sensitivity = 69% and specificity = 72.5% for determining EGFR-wildtype status. In both restriction-based and imputation-based regression analyses of the individual roles of BMI on overall survival of patients with NSCLC, similar results were observed between overall and EGFR-mutation-negative cohort analyses of patients of all ancestries. However, our approach identified some differences: EGFR-mutated Asian patients did not incur a survival benefit from being obese, as observed in EGFR-wildtype Asian patients. Conclusions: We introduce a pragmatic method to evaluate the potential impact of EGFR-status on epidemiological analyses of NSCLC. Impact: The proposed method is generalizable in the common occurrence in which EGFR-status data are missing.