[Experiences of (care) professionals during a COVID-19 outbreak and results of serological tests in the staff of a heavily affected nursing home.] / Ervaringen van (zorg)medewerkers tijdens een COVID-19 uitbraak en resultaten van serologische testen bij personeel in een zwaar getroffen verpleeghuis.

Despite compliance with national (RIVM) guidelines, nursing home Mariënburght (the Netherlands) was severely affected during the first COVID-19 wave: 68 (68%) of the residents were infected. This resulted in a large emotional impact on the (nursing) staff. This study aims to describe the experiences of (nursing) staff, as well as the results of serological tests on COVID-19 that have been administered to professionals. All professionals (n=281) were invited for group interviews to share their experiences concerning the COVID-19 outbreak and for a serological test for COVID-19. The 29 professionals participating in the group interviews mentioned negative and positive experiences about their fear and anxiety, the changed care for residents, the team spirit, the use of personal protective equipment and the testing policy. Out of 240 professionals who underwent the serological test and completed a questionnaire, 94 professionals (39%) had COVID-19 antibodies. In this group, 18 professionals (19%) indicated not having experienced any (physical) complaints related to COVID. Insight into the experiences of professionals resulted in essential learning points, in particular the importance of clear communication with and emotional support for staff. This study also reveals that many professionals of nursing home Mariënburght were affected by COVID-19. An important finding is the high percentage of asymptomatic employees (19% of 94 infected). Our results contributed to changed national testing policies and adapted recommendations in the use of personal protective equipment in nursing homes.

Annexin-A1 and caldesmon are associated with resistance to tamoxifen in estrogen receptor positive recurrent breast cancer.

Tamoxifen therapy resistance constitutes a major cause of death in patients with recurrent estrogen receptor (ER) positive breast cancer. Through high resolution mass spectrometry (MS), we previously generated a 4-protein predictive signature for tamoxifen therapy outcome in recurrent breast cancer. ANXA1 and CALD1, which were not included in the classifier, were however the most differentially expressed proteins. We first evaluated the clinical relevance of these markers in our MS cohort, followed by immunohistochemical (IHC) staining on an independent set of tumors incorporated in a tissue microarray (TMA) and regression analysis in relation to time to progression (TTP), clinical benefit and objective response. In order to assess which mechanisms ANXA1 and CALD1 might been involved in, we performed Ingenuity pathway analysis (IPA) on ANXA1 and CALD1 correlated proteins in our MS cohort. ANXA1 (Hazard ratio [HR] = 1.83; 95% confidence interval [CI]: 1.22-2.75; P = 0.003) and CALD1 (HR = 1.57; 95% CI: 1.04-2.36; P = 0.039) based patient stratification showed significant association to TTP, while IHC staining on TMA showed that both ANXA1 (HR = 1.82; 95% CI: 1.12-3.00; P = 0.016) and CALD1 (HR = 2.29; 95% CI: 1.40-3.75; P = 0.001) expression was associated with shorter TTP independently of traditional predictive factors. Pearson correlation analysis showed that the majority of proteins correlated to ANXA1 also correlated with CALD1. IPA indicated that ANXA1 and CALD1 were associated with ER-downregulation and NFκB signaling. We hereby report that ANXA1 and CALD1 proteins are independent markers for tamoxifen therapy outcome and are associated to fast tumor progression.

Tumor-associated inflammation as a potential prognostic tool in BRCA1/2-associated breast cancer.

The prognosis of BRCA1/2-associated breast cancer partly depends on histologic characteristics. Most of these breast cancers, however, are poorly differentiated. BRCA1-associated cancers are mainly negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Consequently, the use of these histologic features for risk stratification in BRCA1/2 breast cancer is limited. We assessed the prognostic value of additional histologic features, including tumor-associated inflammation and tumor-associated stroma in BRCA1/2 breast cancer patients. From the Rotterdam Family Cancer Clinic database, we collected demographics, tumor characteristics, and follow-up data from female BRCA1/2 breast cancer patients. Tumor samples were centrally reviewed including histologic subtype, differentiation grade, tumor-associated inflammation density, amount of tumor-associated stroma, and intratumor necrosis. The impact of these factors on recurrence-free survival (RFS) was evaluated using univariate and multivariate Cox regression, adjusted for established prognostic features and year of diagnosis. We included 138 BRCA1 and 37 BRCA2 breast cancer patients. Median follow-up after diagnosis was 9.7 years. Independent prognostic factors for RFS were tumor size (hazard ratio [HR], 2.47 for >2 versus ≤2 cm; 95% confidence interval [95% CI], 1.10-5.57), tumor-associated inflammation (HR, 0.18 for moderate/marked versus absent/mild; 95% CI, 0.05-0.61), and intratumor necrosis (HR, 2.60 for presence versus absence; 95% CI, 1.12-6.05). Established prognostic factors as nodal status and differentiation grade were not significantly related to RFS. Subgroup analyses of 138 BRCA1 and 118 triple-negative breast cancer cases showed similar results. Tumor-associated inflammation density was the strongest predictor for RFS in this series of BRCA1/2 breast cancer patients. This provides a potential risk stratification tool that can easily be implemented in routine histologic examination.