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Simple Summary: Treatment with cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), has demonstrated significantly improved progression-free survival in patients with hormone receptor-positive, HER2-negative, advanced breast cancer, when used in combination with endocrine therapies. However, limited data exists on its cutaneous adverse events (AE). The aim of our retrospective study was to investigate the prevalence, types and management of cutaneous AE during CDK4/6i. 79 adult advanced breast cancer patients affected by 125 skin adverse events during treatment with CDK4/6i were recruited at eleven centers. The most frequent cutaneous reactions were pruritus (49/79 patients), alopecia (25/79), and ec-zematous lesions (24/79). We showed that skin reactions are usually mild in severity, and prompt management may limit the negative impact on patients, facilitating beneficial continuation of oncologic treatment. Background: The introduction of cyclin-dependent kinase inhibitors (CDK4/6i) was a great advance in therapeutics for patients with estrogen receptor+/human epidermal growth factor receptor (HER2) locally advanced and metastatic breast cancer. Despite the increasing use of these agents, their adverse drug-related events have not yet been fully characterized. We describe the spectrum of cutaneous adverse reactions occurring in advanced breast cancer patients treated with cyclin-dependent kinase inhibitors, analyzing types, severity, time to onset, and possible treatment outcomes. Methods: We performed a multicentric retrospective study including patients with advanced breast cancer who developed cutaneous lesions during treatment with CDK4/6i in the period from June 2020 to June 2021. Patients > 18 years were recruited at eleven onco-dermatology units located in Albania (1), Argentina (1), France (1), Greece (3), Italy (3), and Spain (2). We evaluated patients' epidemiological and clinical characteristics, types of cutaneous adverse events, their time to onset, and treatment outcomes. The severity of the skin reactions was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 score. Results: Seventy-nine patients (median age: 62.3 years; range 39–83 years) were included in the study, and, collectively, we recorded a total of 165 cutaneous adverse events during follow-up visits. The most frequent cutaneous reactions were pruritus (49/79 patients), alopecia (25/79), and eczematous lesions (24/79). Cutaneous toxicities were usually mild in severity (>65%) and occurred after a median of 6.5 months. Only four patients (5%) required treatment discontinuation due to the severity of the skin lesions. The majority of the skin reactions were managed with topical treatments. Conclusions: To the best of our knowledge, we present the largest case series of cutaneous adverse events developing in advanced breast cancer patients treated with CDK4/6i. We showed that cutaneous toxicities are usually mild in severity, and manageable with standard supportive care; however, in selected cases, they can lead to treatment discontinuation with possible implications for patients' clinical outcomes. [ABSTRACT FROM AUTHOR]

Diagnosis of type I hypersensitivity reactions (IgE-mediated reactions) to penicillins is based on clinical history, skin tests (STs), and drug provocation tests (DPTs). Among in vitro complementary tests, the fluoro-enzyme immunoassay (FEIA) ImmunoCAP® (Thermo-Fisher, Waltham, MA, USA) is the most widely used commercial method for detecting drug-specific IgE (sIgE). In this study, we aimed to analyze the utility of ImmunoCAP® for detecting sIgE to penicillin G (PG) and amoxicillin (AX) in patients with confirmed penicillin allergy. The study includes 139 and 250 patients evaluated in Spain and Italy, respectively. All had experienced type I hypersensitivity reactions to penicillins confirmed by positive STs. Additionally, selective or cross-reactive reactions were confirmed by DPTs in a subgroup of patients for further analysis. Positive ImmunoCAP® results were 39.6% for PG and/or AX in Spanish subjects and 52.4% in Italian subjects. When only PG or AX sIgE where analyzed, the percentages were 15.1% and 30.4%, respectively, in Spanish patients; and 38.9% and 46% in Italian ones. The analysis of positive STs showed a statistically significant higher percentage of positive STs to PG determinants in Italian patients. False-positive results to PG (16%) were detected in selective AX patients with confirmed PG tolerance. Low and variable sensitivity values observed in a well-defined population with confirmed allergy diagnosis, as well as false-positive results to PG, suggest that ImmunoCAP® is a diagnostic tool with relevant limitations in the evaluation of subjects with type I hypersensitivity reactions to penicillins. [ABSTRACT FROM AUTHOR]

Conflicts of Interest The authors declare no conflict of interest. Reference 1 Torra J., Royo-Esnal A., Romano Y., Osuna M.D., León R.G., Recasens J. Amaranthus palmeri a New Invasive Weed in Spain with Herbicide Resistant Biotypes. The authors would like to make the following correction to the published paper [[1]]: Revise the content in Section 2.4 from "All mutations conferring ALS resistance in I A. palmeri i in positions Ser653, Trp574, Pro197, Pro197, Ala122 and Ala122 of CAD and BE domains" to "All mutations conferring ALS resistance in I A. palmeri i in positions Gly654, Ser653, Trp574, Ala205, Pro197 and Ala122 of CAD and BE domains". [Extracted from the article]

Amaranthus palmeri is the most prominent invasive weed in agricultural land from North America, partly due to its propensity to evolve resistance to multiple herbicide sites of action. In the last two decades, reports of this species have increased throughout the American continent and occasionally in other continents. In 2007, A. palmeri populations were found in three localities in northeastern Spain, and they are still present today. To determine whether these three populations resulted from a common or independent introduction events—and when and from where they could have occurred—research was carried out aiming to characterize the resistance profile and mechanisms to 5-enolpyruvylshikimate-3-phosphate synthase-and acetolactate synthase (ALS)-inhibiting herbicides and to analyze the relationship between these three populations using inter simple sequence repeat DNA fingerprinting. Dose–response trials confirmed that the three populations were susceptible to glyphosate but resistant to nicosulfuron-methyl. Resistance to ALS inhibitors was due to several amino acid substitutions in positions Pro197, Trp574 and Ser653. Moreover, the substitutions Ser653Ile and Pro197Thr are described for the first time in this species. At field-labeled rates, all populations were fully controlled with alternative herbicides with other sites of action. Amaranthus palmeri individuals were clustered in three groups based on unweighted pair group method with arithmetic mean analysis, which corresponded to the three sampled populations, with a 67% of genetic relationship among them. Considering this high genetic variability and the different positions and amino acid substations found between populations, it was hypothesized that different colonization events occurred from the American continent probably prior to the introduction of glyphosate resistant crops. Prevention from new introductions is warranted because new herbicide resistance traits could arrive, complicating the management of this invasive weed species, while managing or eradicating the already established populations. [ABSTRACT FROM AUTHOR]