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Introduction: Cancer-related fatigue (CRF) is a common symptom in patients with metastatic breast cancer (MBC), who receive taxane-based chemotherapy, and is associated with poor outcomes. Current guidelines recommend regular screening for fatigue from the time of cancer diagnosis, during treatment, and after treatment is completed to identify CRF early, lessen its negative impact on quality of life, and prevent potential treatment interruptions. Fatigue is a subjective symptom and is assessed through patient questionnaires such as the FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) survey. However, there is currently no gold standard or recommended survey to assess CRF. Methods: A prospective, non-interventional, multicenter trial is ongoing to validate the FACIT-Fatigue scale in patients with locally advanced or metastatic breast cancer who are eligible to receive taxane-based chemotherapy. Adult patients who have documented locally advanced or metastatic breast cancer (not amenable to surgical resection), and mild-to-moderate CRF indicated by a score of 1 to 6 on a scale from 0 to 10 (10 being most severe), who are candidates to receive cycle one of taxane chemotherapy will be included. Patients who are unable to take oral medications, have other cancer-related causes of fatigue, are using oral morphine ≥60 mg/day, or are participating in another clinical trial will be excluded. The primary objective is to evaluate the change in FACIT-Fatigue scores at baseline and at the end of the study (16 weeks). Secondary endpoints include evaluation of quality-of-life outcomes. A subgroup of patients will participate in a phone-based cognitive interview at the end of study visit or within 2 weeks of this visit to explore fatigue factors deemed important to patients. Results: The total planned sample size is estimated to be 60 patients to allow for a minimum clinically important difference (MCID) with a minimum precision of 1.9 points, and standard deviation of 3 points. The qualitative assessment will be conducted as part of a substudy inclusive of data from 30 patients. Conclusions: This study is currently ongoing to determine the MCID in FACIT-Fatigue scores in patients with locally advanced or MBC receiving treatment with taxane-based chemotherapy. Contact usmedinfo@dompe.com for information related to clinical trial sites and this study. Citation Format: Alessandra Fabi, Steven Hager, Laura Lourdes, Rebecca Pedersini, Paola Malaguti, Elizabeth M. Gavioli, Renuka Wakade, Pier Adelchi Ruffini, Francesco Sergio, Manuela Leone, Flavio Mantelli, Marcello Allegretti, Anne Blaes. Trial In Progress: An Evaluation of FACIT-Fatigue in Patients with Locally Advanced or Metastatic Breast Cancer receiving Treatment with Taxane-based Chemotherapy [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 OT1-16-01.

Introduction: Fatigue is a debilitating and persistent condition of exhaustion that interferes with usual functioning. It is the most reported symptom across all cancer patients, and when related to the malignancy itself or to the neoplastic treatment, is referred to as cancer-related fatigue (CRF). Fatigue occurs in nearly all patients with metastatic breast cancer and is associated with poor clinical outcomes and worse quality-of-life. It is subjective and can be assessed from patient self-reports, such as the FACIT-Fatigue scale or Brief Fatigue Inventory, with no current gold-standard, which may lead to under reporting and lack of treatment intervention. Only since 2016, fatigue has been considered as a syndrome and included in the International Statistical Classification of Diseases, 10th edition, Clinical Modification (ICD-10-CM) according to specific criteria. The aim of this real-world data analysis was to describe the prevalence of fatigue, as reported by physicians using ICD-10-CM codes, in patients with locally advanced (Adv) or metastatic (Mtx) breast cancer (BC) undergoing single-agent taxane-based chemotherapy (CT), and to assess whether relapsed subjects had a higher prevalence versus those diagnosed de novo at an advanced stage. Methods: Electronic health records (EHR) were analyzed from TriNetX, a global research network containing real-world data from approximately 150 million patients in 115 Health Care Organizations (72 in the United States and 42 in the European Union). Using ICD-10-CM codes and structured data only (no medical notes), subjects were identified with a diagnosis of Adv-Mtx BC who underwent CT with single-agent taxane in 2020, 2021 and 2022 (first quarter). After splitting the cohort based on “relapsed” (second- or further line treatment) vs “de novo” (first-line treatment), we assessed the prevalence of fatigue (any type, R53.x) and CRF (R53.0) within the first 3 months after initiation of taxanes. Results: Among 379,880 BC patients under follow-up in 2021 across the 115 sites, 50,490 (13%) had Adv-Mtx BC, of whom 16,170 (32%) were diagnosed de novo and 34,330 (68%) experienced relapse. The proportion of patients undergoing single-agent taxane-based CT was 7.5% (1,220) and 13.4% (4,590), respectively. Almost one third (28%) of relapsed patients had previously received taxanes. The prevalence of fatigue (any type) and CRF was similar between the “de novo” and “relapsed” groups (24.6% vs 25.7% and 6.6% vs 5.4%, respectively). Overall, 27% and 21% of all fatigue was coded as CRF in the “de novo” and “relapsed” groups, respectively. No relevant differences were observed between 2020, 2021 and 2022 results. Conclusions: This real-world analysis reveals that at least one in four patients with Adv-Mtx BC undergoing taxane based CT suffer from fatigue, independent of disease history and other factors. Fatigue is an unmet medical need in patients with BC, particularly in patients receiving taxanes. Table. Fatigue prevalence (as per ICD-10-CM codes) within the first 3 months of single-agent taxane-based CT in patients with locally advanced or metastatic BC diagnosed “de novo” or relapsed in 2021 Citation Format: Anne Blaes, Elizabeth M. Gavioli, Renuka Wakade, Santiago Miracle, Giovanna DiTuri, Maria DePizzol, Pier Adelchi Ruffini, Francesco Sergio, Manuela Leone, Flavio Mantelli, Marcello Allegretti, Alessandra Fabi. Fatigue in patients with locally advanced or metastatic breast cancer undergoing single-agent taxane-based chemotherapy: de novo versus relapsed [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 P5-07-09.

Acute respiratory distress syndrome (ARDS) is an acute inflammatory condition with a dramatic increase in incidence since the beginning of the coronavirus disease 19 (COVID-19) pandemic. Neutrophils play a vital role in the immunopathology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by triggering the formation of neutrophil extracellular traps (NETs), producing cytokines including interleukin-8 (CXCL8), and mediating the recruitment of other immune cells to regulate processes such as acute and chronic inflammation, which can lead to ARDS. CXCL8 is involved in the recruitment, activation, and degranulation of neutrophils, and therefore contributes to inflammation amplification and severity of disease. Furthermore, activation of neutrophils also supports a prothrombotic phenotype, which may explain the development of immunothrombosis observed in COVID-19 ARDS. This review aims to describe hyperinflammatory ARDS due to SARS-CoV-2 infection. In addition, we address the critical role of polymorphonuclear neutrophils, inflammatory cytokines, and the potential targeting of CXCL8 in treating the hyperinflammatory ARDS population.

Introduction: Acute lung injury and acute respiratory distress syndrome are common complications in patients with coronavirus disease 2019 (COVID-19). Poor outcomes in patients with COVID-19 are associated with cytokine release syndrome. Binding of interleukin-8 (CXCL8/IL-8) to its chemokine receptors, CXCR1/2, may mediate this inflammatory process. The aim of this clinical trial was to determine if CXCR1/2 blockade with reparixin can improve clinical outcomes in hospitalized patients with severe COVID-19 pneumonia. The dose and safety of reparixin have been investigated in clinical trials of patients with metastatic breast cancer. Methods: This was a phase 2,open-label, multicenter, randomized study in hospitalized adult patients with severe COVID-19 pneumonia from May5, 2020 until November27, 2020. Patients were randomized 2:1 to receive 1200mg reparixin orally three times daily or standard of care (SOC) for up to 21days. The primary endpoint was defined as a composite of clinical events: use of supplemental oxygen, need for mechanical ventilation, intensive care unit admission, and/or use of rescue medication. Results: Fifty-five patients were enrolled between reparixin (n = 36) and SOC (n = 19). The rate of clinical events was statistically significantly lower in the reparixin group compared with the SOC group (16.7% [95%CI 6.4-32.8%] vs. 42.1% [95%CI 20.3-66.5%], P = 0.02). The sensitivity analysis based on the Cox regression model provided an adjusted hazard ratio of 0.33 with statistical significance lower than 0.05 (95%CI 0.11-0.99; P = 0.047). Reparixin treatment appeared to be well tolerated. Conclusion: In patients with severe COVID-19, reparixin led to an improvement in clinical outcomes when compared with the SOC. A larger phase3 clinical study is needed to confirm these results. Trial registration: EudraCT identifier, 2020-001645-40; registered May6, 2020 (retrospectively registered), and clinicaltrials.gov (NCT04794803) on March 8, 2021.

Secondary bacterial infections and bacterial coinfections are an important complication of coronavirus disease 2019 (COVID-19), leading to antibiotic overuse and increased rates of antimicrobial resistance (AMR) during the COVID-19 pandemic. In this literature review, we summarize the reported rates of secondary bacterial infections and bacterial coinfections in patients with COVID-19, the impact on patient outcomes, the antibiotic treatment approaches employed, and the resistance patterns observed. The reported data suggest that although the incidence of secondary bacterial infections or bacterial coinfections is relatively low, they are associated with worse outcomes such as prolonged hospitalization, intensive care unit admission, mechanical ventilator use, and increased mortality. Interestingly, antibiotic prescription rates are typically higher than secondary bacterial and bacterial coinfection rates, and reports of AMR are common. These findings highlight the need for an improved understanding of secondary bacterial and bacterial coinfection in patients with COVID-19, as well as improved treatment options, to mitigate inappropriate antibiotic prescribing and AMR.

Pyoderma gangrenosum (PG) is a rare, ulcerating, inflammatory disease that is often misdiagnosed as a skin and soft tissue infection. If PG is identified, it is treated with topical or systemic immunosuppressants to reduce inflammation and induce remission. However, the use of immunosuppressants has been linked to a higher risk of superimposed infections. The authors report the case of a 24-year-old female patient with bilateral lower extremity PG with a superimposed infection of Pseudomonas aeruginosa and Bacteroides fragilis after intralesional corticosteroid therapy.