Epidemiology of Mpox Cases, and Tecovirimat and JYNNEOS Utilization, Alameda County, California, June-October 2022.

CONTEXT: The 2022 United States mpox outbreak disproportionately affected racial and ethnic minority gay, bisexual, and other men who have sex with men. PROGRAM: We utilized surveillance data and vaccination registries to determine whether populations most impacted by mpox in Alameda County received JYNNEOS vaccines and tecovirimat (TPOXX) during June 1-October 31, 2022. IMPLEMENTATION: Alameda County Public Health Department responded to the mpox epidemic through partnerships with local health care providers who serve communities disproportionately affected by mpox. EVALUATION: During June 1-October 31, 2022, a total of 242 mpox cases were identified in Alameda County. Mpox incidence rates per 100 000 were highest among Black/African American (35.7; 95% confidence interval [CI], 26.8-46.5) and Hispanic/Latinx (25.1; CI, 20.1-30.9) residents, compared to Asian (3.8; CI, 2.3-5.9) and White (10.5; CI, 7.7-13.9) residents. Most confirmed cases were identified as gay, lesbian, or same-gender-loving (134, 67.3%) and bisexual (31, 15.6%); 226 (93.8%) cases were male. Sixty-nine (28.5%) mpox patients received TPOXX. There were no statistically significant differences in demographic and clinical characteristics of mpox cases when compared by TPOXX receipt status. JYNNEOS vaccine was received by 8277 Alameda County residents. The largest proportion of vaccinees were White residents (40.2%). Administration rates per 100 000 men who have sex with men were lowest among Asian and Hispanic/Latinx individuals, at 8779 (CI, 8283-9296) and 14 953 (CI, 14 156-15 784), respectively. Black/African American and Hispanic/Latinx males had the lowest vaccination-to-case ratios at 16.7 and 14.8, respectively. DISCUSSION: Mpox disproportionately affected Black/African American and Hispanic/Latinx men who have sex with men in Alameda County. Strong partnerships with local health care providers ensured that persons with mpox received TPOXX treatment when indicated. However, higher JYNNEOS vaccine uptake in Black and Latinx communities needs improvement through ongoing and meaningful engagement with Black/African American and Hispanic/Latinx gay, bisexual, and transgender communities.

Adenocarcinoma Harboring EGFR-RAD51 Fusion Treated With Osimertinib: A Case Report.

EGFR mutations are among the most common driver mutations in lung adenocarcinoma. Rare alterations, such as the EGFR-RAD51 fusion, respond to treatment with EGFR tyrosine kinase inhibitors but can be missed by limited genomic sequencing panels. Here, we report a case of metastatic lung adenocarcinoma in a never-smoker patient who initially did not have a targetable alteration identified on two different sequencing panels. The initial response to combination chemoimmunotherapy was short-lived. A rare EGFR-RAD51 fusion was then identified using a more in-depth sequencing panel. The patient experienced a dramatic and durable response to osimertinib. This case highlights the rarity of EGFR-RAD51 fusions, the efficacy of EGFR tyrosine kinase inhibitors, and the importance of a thorough search for targetable alterations in never-smokers with lung adenocarcinoma.

Humoral and cellular correlates of a novel immune-related adverse event and its treatment.

Immune-related adverse events (irAE) may affect almost any organ system and occur at any point during treatment with immune checkpoint inhibitors (ICI). We present a patient with advanced lung cancer receiving antiprogrammed death 1 checkpoint inhibitor who developed a delayed-onset visual irAE treated with corticosteroids. Through assessment of longitudinal biospecimens, we analyzed serial autoantibodies, cytokines, and cellular populations. Months after ICI initiation and preceding clinical toxicity, the patient developed broad increases in cytokines (most notably interleukin-6 (IL-6), interferon-γ (IFNγ), C-X-C motif chemokine ligand 2 (CXCL2), and C-C motif chemokine ligand 17 (CCL17)), autoantibodies (including anti-angiotensin receptor, α-actin, and amyloid), CD8 T cells, and plasmablasts. Such changes were not observed in healthy controls and ICI-treated patients without irAE. Administration of corticosteroids resulted in immediate and profound decreases in cytokines, autoantibodies, and inflammatory cells. This case highlights the potential for late-onset changes in humoral and cellular immunity in patients receiving ICI. It also demonstrates the biologic effects of corticosteroids on these parameters. Application of humoral and cellular immune biomarkers across ICI populations may inform toxicity monitoring and management.

"It's a place that gives me hope": A qualitative evaluation of a buprenorphine-naloxone group visit program in an urban federally qualified health center.

Background: Medication for opioid use disorder (MOUD) with buprenorphine is effective in treating opioid use disorder yet remains underutilized. Scant research has examined the experience of patients, clinic staff, and providers in a "low-threshold" group-based MOUD program. This study evaluates a "low-threshold" MOUD program at a federally qualified health center (FQHC) in Philadelphia, Pennsylvania through the perspectives of its key stakeholders. Methods: This qualitative study involved focus groups of patients, providers, and clinic staff. Focus groups were conducted between October 2017 and June 2018. Grounded theory was used for analysis. Results: There were a total of 10 focus groups, including 20 patient participants and 26 staff members. Program participants noted that a strength of the program is its person-centered harm reduction approach, which is reflected in the program's policies and design. Program participants discussed the programmatic design choices that facilitated their participation and engagement in the program: ease of access, integration into primary care, and group-based visit model. Challenges in program implementation included varying acceptance and understanding of harm reduction among staff, the unpredictability of clinic volume and workflow, and the need to balance access to primary care and MOUD. Conclusion: This group-based MOUD program's philosophy of person-centered harm reduction, low-barrier approach, the structure of group-based visits, and integrated care contributes to increased patient access and retention. Understanding the strengths and challenges of the program may be useful for other safety-net clinics considering a MOUD program.

Type and case volume of health care facility influences survival and surgery selection in cases with early-stage non-small cell lung cancer.

BACKGROUND: With the expansion of non-small cell lung cancer (NSCLC) screening methods, the percentage of cases with early-stage NSCLC is anticipated to increase. Yet it remains unclear how the type and case volume of the health care facility at which treatment occurs may affect surgery selection and overall survival for cases with early-stage NSCLC. METHODS: A total of 332,175 cases with the American Joint Committee on Cancer (AJCC) TNM stage I and stage II NSCLC who were reported to the National Cancer Data Base (NCDB) by 1302 facilities were studied. Facility type was characterized in the NCDB as community cancer program (CCP), comprehensive community cancer program (CCCP), academic/research program (ARP), or integrated network cancer program (INCP). Each facility type was dichotomized further into high-volume or low-volume groups based on the case volume. Multivariate Cox proportional hazard models, the logistic regression model, and propensity score matching were used to evaluate differences in survival and surgery selection among facilities according to type and volume. RESULTS: Cases from ARPs were found to have the longest survival (median, 16.4 months) and highest surgery rate (74.8%), whereas those from CCPs had the shortest survival (median, 9.7 months) and the lowest surgery rate (60.8%). The difference persisted when adjusted by potential confounders. For cases treated at CCPs, CCCPs, and ARPs, high-volume facilities had better survival outcomes than low-volume facilities. In facilities with better survival outcomes, surgery was performed for a greater percentage of cases compared with facilities with worse outcomes. CONCLUSIONS: For cases with early-stage NSCLC, both facility type and case volume influence surgery selection and clinical outcome. Higher surgery rates are observed in facilities with better survival outcomes.

Development and Validation of a Nomogram Prognostic Model for Patients With Advanced Non-Small-Cell Lung Cancer.

IMPORTANCE: Nomogram prognostic models can facilitate cancer patient treatment plans and patient enrollment in clinical trials. OBJECTIVE: The primary objective is to provide an updated and accurate prognostic model for predicting the survival of advanced non-small-cell lung cancer (NSCLC) patients, and the secondary objective is to validate a published nomogram prognostic model for NSCLC using an independent patient cohort. DESIGN: 1817 patients with advanced NSCLC from the control arms of 4 Phase III randomized clinical trials were included in this study. Data from 524 NSCLC patients from one of these trials were used to validate a previously published nomogram and then used to develop an updated nomogram. Patients from the other 3 trials were used as independent validation cohorts of the new nomogram. The prognostic performances were comprehensively evaluated using hazard ratios, integrated area under the curve (AUC), concordance index, and calibration plots. SETTING: General community. MAIN OUTCOME: A nomogram model was developed to predict overall survival in NSCLC patients. RESULTS: We demonstrated the prognostic power of the previously published model in an independent cohort. The updated prognostic model contains the following variables: sex, histology, performance status, liver metastasis, hemoglobin level, white blood cell counts, peritoneal metastasis, skin metastasis, and lymphocyte percentage. This model was validated using various evaluation criteria on the 3 independent cohorts with heterogeneous NSCLC populations. In the SUN1087 patient cohort, the continuous risk score output by the nomogram achieved an integrated area under the receiver operating characteristics (ROC) curve of 0.83, a log-rank P-value of 3.87e-11, and a concordance index of 0.717. In the SAVEONCO patient cohort, the integrated area under the ROC curve was 0.755, the log-rank P-value was 4.94e-6 and the concordance index was 0.678. In the VITAL patient cohort, the integrated area under the ROC curve was 0.723, the log-rank P-value was 1.36e-11, and the concordance index was 0.654. We implemented the proposed nomogram and several previously published prognostic models on an online Web server for easy user access. CONCLUSIONS: This nomogram model based on basic clinical features and routine lab testing predicts individual survival probabilities for advanced NSCLC and exhibits cross-study robustness.

Evaluation of the 7th and 8th editions of the AJCC/UICC TNM staging systems for lung cancer in a large North American cohort.

PURPOSE: The new 8th American Joint Committee on Cancer (AJCC)/International Union for Cancer Control (UICC) lung cancer staging system was developed and internally validated using the International Association for the Study of Lung Cancer (IASLC) database, but external validation is needed. The goal of this study is to validate the discriminatory ability and prognostic performance of this new staging system in a larger, independent non-small cell lung cancer (NSCLC) cohort with greater emphasis on North American patients. METHODS: A total of 858,909 NSCLC cases with one malignant primary tumor collected from 2004 to 2013 in the National Cancer Database (NCDB) were analyzed. The primary coding guidelines of the Collaborative Staging Manual and Coding Instructions for the new 8th edition AJCC/UICC lung cancer staging system was used to define the new T, M and TNM stages for all patients in the database. Kaplan-Meier curves, Cox regression models and time-dependent receiver operating characteristics were used to compare the discriminatory ability and prognostic performance of the 7th and the revised 8th T, M categories and overall stages. RESULTS: We demonstrated that the 8th staging system provides better discriminatory ability than the 7th staging system and predicts prognosis for NSCLC patients using the NCDB. There were significant survival differences between adjacent groups defined by both clinical staging and pathologic staging systems. These staging parameters were significantly associated with survival after adjusting for other factors. CONCLUSIONS: The updated T, M, and overall TNM stage of the 8th staging system show improvement compared to the 7th edition in discriminatory ability between adjacent subgroups and are independent predictors for prognosis.

Directed ortho metalation-boronation and Suzuki-Miyaura cross coupling of pyridine derivatives: a one-pot protocol to substituted azabiaryls.

A general method for the synthesis of azabiaryls 19a-t by a one-pot procedure involving a Directed ortho metalation (DoM)-boronation-Suzuki-Miyaura cross coupling sequence is described. Aside from the three isomeric pyridyl carboxamides 15a-c, chloro-, fluoro-, and O-carbamoyl pyridines are adapted to this method providing a range of azabiaryls (Table 2). The method has an advantage in that it avoids the recognized difficult isolation of pyridyl boronic acids and their instability toward deboronation. The efficient synthesis of hydroxypicolinamides 12-14 (Scheme 3) by a one-pot metalation-boronation-oxidation sequence with the LDA-B(OiPr)3 in situ procedure that avoids self-condensation of incipient ortho-metalated species (Scheme 2) is delineated. The conversion of azabiaryls 19b,e,h,l into azafluorenones 20b,e,h,l by a directed remote metalation protocol is demonstrated (Table 3). A comprehensive survey of pyridyl boronates, of considerable interest in contemporary heterocyclic synthetic chemistry, is given (Figure 1).