PIH Health Hospital

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the comparative effectiveness and safety of immunotherapy (anti PD‐1, anti PD‐L1, or anti CTLA‐4) plus chemotherapy compared to chemotherapy alone for the first‐line systemic treatment of extensive‐stage small cell lung cancer with a network meta‐analysis, and to identify relevant biomarkers or clinical factors.

Abstract Background: In early-stage triple-negative breast cancer (TNBC), there is accumulating evidence of a correlation between tumor-infiltrating lymphocytes in tumor tissue and favorable clinical outcomes, with a high CD8+/regulatory T-cell (Treg) ratio after neoadjuvant chemotherapy being predictive of overall survival and associated with pathologic complete response (Ladoire S, et al. Br J Cancer. 2011; Park YH, et al. Nat Commun. 2020). Trilaciclib is a transient inhibitor of cyclin-dependent kinase 4/6 that is administered intravenously prior to chemotherapy. In preclinical studies, trilaciclib has been shown to have immune-enhancing effects by differentially arresting CD8+ T-cell and Treg subsets, which is followed by the faster recovery of CD8+ T cells than Tregs in the tumor microenvironment. Methods: This phase 2, single-arm, open-label study aims to evaluate neoadjuvant, single-dose trilaciclib followed by trilaciclib plus dose-dense anthracycline/cyclophosphamide and taxane in patients with early-stage TNBC (NCT05112536). Patients with previously untreated, non-metastatic, confirmed TNBC and a primary tumor ≥ 1.5 cm of any nodal status receive a single dose of trilaciclib 240 mg/m2 during the lead-in phase, followed by 4 cycles of doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2, and 12 weekly cycles of paclitaxel 80 mg/m2. Trilaciclib 240 mg/m2 is administered prior to the first chemotherapy dose of each cycle. Pembrolizumab 400 mg every 6 weeks starting on day 1, cycle 1, and/or carboplatin AUC 1.5 every week starting on day 1, cycle 5, is allowed per investigator discretion. Tumor biopsies and peripheral blood samples are collected prior to any treatment, 7 days ± 1 day post administration of trilaciclib, and during surgery, with an additional blood sample collection on day 1, cycle 2. The primary objective is to evaluate the immune-based mechanism of action of trilaciclib after a single dose of trilaciclib, as measured by changes in the CD8+/Treg ratio in tumor tissue. Pathologic complete response, safety and tolerability, and additional exploratory immune biomarker endpoints will also be assessed. Results: As of June 3, 2022, 9 patients with early-stage TNBC had been enrolled and 8 patients had received the trilaciclib lead-in dose and initiated doxorubicin/cyclophosphamide. Patients had a median age of 53.0 years, and all had stage II tumors at diagnosis, with 7 having ductal carcinoma. The median number of chemotherapy cycles received was 3 (range 1–6), and all 8 patients received pembrolizumab. Seven patients continue study treatment; 1 patient discontinued due to disease progression. Five patients had an adverse event (AE) related to any study treatment, including 4 patients with ≥ 1 trilaciclib-related AE. There were no grade ≥ 3 treatment-related AEs or serious AEs. On-treatment, post-trilaciclib monotherapy biopsies were available for 4 patients. Following neoadjuvant trilaciclib treatment, the median density of stromal CD8+ T cells increased from 103.1/mm2 at baseline to 229.8/mm2 at day 7. The median CD8+/Treg ratio increased in 2 patients from 1.85 at baseline to 1.90 at day 7. Conclusions: Preliminary analysis of on-treatment tumor biopsies from 4 patients suggests that a single dose of trilaciclib may modulate the immune cell composition in the tumor microenvironment to support antitumor immune responses. The increase in CD8+ T cells following 7-day neoadjuvant treatment with trilaciclib supports previous data suggesting a role in T-cell infiltration. The complete dataset from all patients (estimated enrollment: N ≈ 24) and additional biomarker analyses will be presented. Citation Format: Michael Danso, Joyce O’Shaughnessy, Lisa S. Wang, Kailash Mosalpuria, Sara Hurvitz, Shom Goel, Sarah Ahn, Subing Cao, John S. Yi, Taofik Oyekunle, Amanda Jacobson, Andrew Beelen, Jeremy Force. Trilaciclib induces immune changes within the tumor microenvironment in early-stage triple-negative 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 P3-06-03.

Los Angeles, California became a warzone of COVID-19 infections with up to one death every 10 minutes at the end of 2020. As resources thinned, and ICU beds and ventilators became scarce, physicians began agonizing over potentially rationing medical care. In this study, we conducted a retrospective cohort analysis of 7,429 confirmed COVID-19 positive patients from two community hospitals in Los Angeles, California between March 16, 2020 and June 9, 2021. We applied the Cox proportional hazards regression model to determine the risk factors most strongly associated with in-hospital mortality. Using the multivariable Cox proportional hazards model, there was a higher hazard ratio (HR) for mortality in patients who were older (age ≥60 years) [HR 2.189, 95% CI 1.991–2.407, p<0.001], had low triage oxygenation < 90% [HR 1.439, 95% CI 1.339–1.546, p<0.001], had chronic kidney disease (CKD) [HR 1.348, 95% CI 1.234–1.496, p = 0.001)], and who were obese (BMI ≥ 30 kg/m^2) [HR 1.221, 95% CI 1.155–1.340, p = 0.003)]. Overall, our study concluded that age ≥ 60 years, low triage oxygenation less than 90%, chronic kidney disease, and obesity were the top patient characteristics associated with increased mortality for both the univariate and multivariate Cox proportional hazards model analyses. Furthermore, by separating our data set into a development and validation set, we created a novel prediction tool to forecast in-hospital mortality and achieved 86% accuracy.

Emergency Medical Services (EMS) systems have developed protocols for prehospital activation of the cardiac catheterization laboratory for patients with suspected ST-elevation myocardial infarction (STEMI) to decrease first-medical-contact-to-balloon time (FMC2B). The rate of "false positive" prehospital activations is high. In order to decrease this rate and expedite care for patients with true STEMI, the American Heart Association (AHA; Dallas, Texas USA) developed the Mission Lifeline PreAct STEMI algorithm, which was implemented in Los Angeles County (LAC; California USA) in 2015. The hypothesis of this study was that implementation of the PreAct algorithm would increase the positive predictive value (PPV) of prehospital activation. This is an observational pre-/post-study of the effect of the implementation of the PreAct algorithm for patients with suspected STEMI transported to one of five STEMI Receiving Centers (SRCs) within the LAC Regional System. The primary outcome was the PPV of cardiac catheterization laboratory activation for percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). The secondary outcome was FMC2B. A total of 1,877 patients were analyzed for the primary outcome in the pre-intervention period and 405 patients in the post-intervention period. There was an overall decrease in cardiac catheterization laboratory activations, from 67% in the pre-intervention period to 49% in the post-intervention period (95% CI for the difference, -14% to -22%). The overall rate of cardiac catheterization declined in post-intervention period as compared the pre-intervention period, from 34% to 30% (95% CI, for the difference -7.6% to 0.4%), but actually increased for subjects who had activation (48% versus 58%; 95% CI, 4.6%-15.0%). Implementation of the PreAct algorithm was associated with an increase in the PPV of activation for PCI or CABG from 37.9% to 48.6%. The overall odds ratio (OR) associated with the intervention was 1.4 (95% CI, 1.1-1.8). The effect of the intervention was to decrease variability between medical centers. There was no associated change in average FMC2B. The implementation of the PreAct algorithm in the LAC EMS system was associated with an overall increase in the PPV of cardiac catheterization laboratory activation.

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Legalization efforts in many states have heightened awareness of the medicinal uses of cannabis, and oncology nurses are more frequently caring for patients who have used or are using cannabis. Significant epidemiologic data on the prevalence of cannabis use in patients with cancer are not yet available, and not much is known about the effects of cannabis on cancer treatment. This article describes the effects cannabis may have on the lungs, reviews indications for cannabis use in patients with cancer, and explores an atypical case of progressive pulmonary toxicity in a young patient with a history of Hodgkin lymphoma and cannabis use. A review of the literature on cannabis-associated lung injury was conducted, with 32 articles selected for full review. As cannabis use in cancer care continues to gain support, further research evaluating cannabis use in patients treated with bleomycin is warranted. In addition, the pros and cons of cannabis use must be fully evaluated and discussed with the patient with cancer prior to recommending its use.

Case report publication has seen a resurgence in recent years as awareness of the value of case reports in clinical medicine has grown. Not all areas of medical research are amenable to large clinical trials. Many topics are better addressed by more detailed descriptions of multi-factorial components that contribute to outcomes, and these are areas where case reports shine. Determining the suitability of a case for publication requires background research and discussion. Writing a case or series reinforces many aspects of the medical training process, and house staff are encouraged to research, write, and submit reports. The medical community benefits in many ways from case reports, from improving individual patient care to guiding future research directions.

BackgroundAdolescents with type 1 diabetes face demanding challenges due to conflicting priorities between psychosocial needs and diabetes management. This conflict often results in poor glycaemic control and discord between adolescents and parents. Adolescent-parent conflicts are thus a barrier for health care providers (HCPs) to overcome in their attempts to involve both adolescents and parents in improvement of glycaemic control. Evidence-based interventions that involve all three parties (i.e., adolescents, parents and HCPs) and are integrated into routine outpatient clinic visits are lacking. The Guided Self-Determination method is proven effective in adult care and has been adapted to adolescents and parents (Guided Self-Determination-Young (GSD-Y)) for use in paediatric diabetes outpatient clinics. Our objective is to test whether GSD-Y used in routine paediatric outpatient clinic visits will reduce haemoglobin A1c (HbA1c) concentrations and improve adolescents' life skills compared with a control group.Methods/DesignUsing a mixed methods design comprising a randomised controlled trial and a nested qualitative evaluation, we will recruit 68 adolescents age 13 - 18 years with type 1 diabetes (HbA1c > 8.0%) and their parents from 2 Danish hospitals and randomise into GSD-Y or control groups. During an 8-12 month period, the GSD-Y group will complete 8 outpatient GSD-Y visits, and the control group will completes an equal number of standard visits. The primary outcome is HbA1c. Secondary outcomes include the following: number of self-monitored blood glucose values and levels of autonomous motivation, involvement and autonomy support from parents, autonomy support from HCPs, perceived competence in managing diabetes, well-being, and diabetes-related problems. Primary and secondary outcomes will be evaluated within and between groups by comparing data from baseline, after completion of the visits, and again after a 6-month follow-up. To illustrate how GSD-Y influences glycaemic control and the development of life skills, 10-12 GSD-Y visits will be recorded during the intervention and analysed qualitatively together with individual interviews carried out after follow-up.DiscussionThis study will provide evidence of the effectiveness of using a GSD-Y intervention with three parties on HbA1c and life skills and the feasibility of integrating the intervention into routine outpatient clinic visits.Danish Data Association ref nr. 2008-41-2322Trial registrationISRCTN54243636

No abstract available for this article.