Time Trends in Histopathological Findings in Mammaplasty Specimens in a Dutch Academic Pathology Laboratory

Background: Reduction mammaplasties are often performed at a relatively young age. Necessity of routine pathological investigation of the removed breast tissue to exclude breast cancer has been debated. Past studies have shown 0.05%-4.5% significant findings in reduction specimens, leading to an ongoing debate whether this is cost-effective. There is also no current Dutch guideline on pathological investigation of mammaplasty specimens. Because the incidence of breast cancer is rising, especially among young women, we re-evaluated the yield of routine pathological investigation of mammaplasty specimens over three decades in search of time trends. Methods: Reduction specimens from 3430 female patients examined from 1988 to 2021 in the UMC Utrecht were evaluated. Significant findings were defined as those that may lead to more intensive follow-up or surgical intervention. Results: Mean age of patients was 39 years. Of the specimens, 67.4% were normal; 28.9% displayed benign changes; 2.7%, benign tumors; 0.3%, premalignant changes; 0.8%, in situ; and 0.1%, invasive cancers. Most patients with significant findings were in their forties (P < 0.001), the youngest patient being 29 years. Significant findings increased from 2016 onward (P = 0.0001), 86.8% found after 2016. Conclusions: Over three decades, 1.2% of mammaplasty specimens displayed significant findings on routine pathology examination, with an incidence rising to 2.1% from 2016 onward. The main reason for this recent increase is probably attributable to super-specialization by the pathologists. While awaiting formal cost-effectiveness studies, the frequency of significant findings for now seems to justify routine pathological examination of mammaplasty reduction specimens

Heart failure and promotion of physical activity before and after cardiac rehabilitation (HF-aPProACH):a study protocol

Abstract Aims Lifestyle changes, such as increasing physical activity (PA), are a cornerstone of treatment of patients with chronic heart failure (HF). However, improving PA in HF patients is challenging, and low participation rates for cardiac rehabilitation (CR) as well as relapse to low PA levels after CR are major issues. We designed a randomized controlled trial to investigate if PA monitoring with motivational feedback before and after centre‐based CR in HF patients with reduced ejection fraction (HFrEF) will lead to a clinically meaningful increase in physical fitness. Methods and results A randomized controlled trial will be conducted in a sample of 180 HFrEF patients (New York Heart Association Class II/III) who are referred to 12‐week standard CR. Patients will be randomized (2:1) to (1) standard of care (SoC) plus wearing a PA monitoring device (Fitbit Charge 3) with personalized step goals, feedback and motivation or (2) SoC only. The intervention lasts ±7 months: 4–5 weeks before CR, 12 weeks during CR and 12 weeks after CR. Measurements will take place at three time points. The primary endpoint is the change in the distance in 6‐min walking test (6MWT) over the entire study period. Other endpoints include step count, grip strength, quality of life and all‐cause mortality or hospitalization. Conclusions HF‐aPProACH will provide novel information on the effectiveness of remote PA stimulation and feedback before, during and after standard CR using a commercially available device to improve physical fitness in HFrEF patients

Population-based impact of COVID-19 on incidence, treatment, and survival of patients with pancreatic cancer

Background: The COVID-19 pandemic has put substantial strain on the healthcare system of which the effects are only partly elucidated. This study aimed to investigate the impact on pancreatic cancer care. Methods: All patients diagnosed with pancreatic cancer between 2017 and 2020 were selected from the Netherlands Cancer Registry. Patients diagnosed and/or treated in 2020 were compared to 2017–2019. Monthly incidence was calculated. Patient, tumor and treatment characteristics were analyzed and compared using Chi-squared tests. Survival data was analyzed using Kaplan–Meier and Log-rank tests. Results: In total, 11019 patients were assessed. The incidence in quarter (Q)2 of 2020 was comparable with that in Q2 of 2017–2019 (p = 0.804). However, the incidence increased in Q4 of 2020 (p = 0.031), mainly due to a higher incidence of metastatic disease (p = 0.010). Baseline characteristics, surgical resection (15% vs 16%; p = 0.466) and palliative systemic therapy rates (23% vs 24%; p = 0.183) were comparable. In 2020, more surgically treated patients received (neo)adjuvant treatment compared to 2017–2019 (73% vs 67%; p = 0.041). Median overall survival was comparable (3.8 vs 3.8 months; p = 0.065). Conclusion: This nationwide study found a minor impact of the COVID-19 pandemic on pancreatic cancer care and outcome. The Dutch health care system was apparently able to maintain essential care for patients with pancreatic cancer

Continuity of care for patients with de novo metastatic cancer during the COVID-19 pandemic:A population-based observational study

During the COVID-19 pandemic recommendations were made to adapt cancer care. This population-based study aimed to investigate possible differences between the treatment of patients with metastatic cancer before and during the pandemic by comparing the initial treatments in five COVID-19 periods (weeks 1–12 2020: pre-COVID-19, weeks 12–20 2020: 1st peak, weeks 21–41 2020: recovery, weeks 42–53 2020: 2nd peak, weeks 1–20 2021: prolonged 2nd peak) with reference data from 2017 to 2019. The proportion of patients receiving different treatment modalities (chemotherapy, hormonal therapy, immunotherapy or targeted therapy, radiotherapy primary tumor, resection primary tumor, resection metastases) within 6 weeks of diagnosis and the time between diagnosis and first treatment were compared by period. In total, 74,208 patients were included. Overall, patients were more likely to receive treatments in the COVID-19 periods than in previous years. This mainly holds for hormone therapy, immunotherapy or targeted therapy and resection of metastases. Lower odds were observed for resection of the primary tumor during the recovery period (OR 0.87; 95% CI 0.77–0.99) and for radiotherapy on the primary tumor during the prolonged 2nd peak (OR 0.84; 95% CI 0.72–0.98). The time from diagnosis to the start of first treatment was shorter, mainly during the 1st peak (average 5 days, p &lt;.001). These findings show that during the first 1.5 years of the COVID-19 pandemic, there were only minor changes in the initial treatment of metastatic cancer. Remarkably, time from diagnosis to first treatment was shorter. Overall, the results suggest continuity of care for patients with metastatic cancer during the pandemic.</p

Hearing loss in Pompe disease revisited: results from a study of 24 children

Little information is available regarding the auditory function in Pompe patients. Hearing loss has been reported in classic infantile patients, but it is still unknown whether central nervous system involvement interferes with auditory function and whether enzyme replacement therapy can improve hearing. Audi

Effectiveness of Omicron XBB.1.5 vaccine against infection with SARS-CoV-2 Omicron XBB and JN.1 variants, prospective cohort study, the Netherlands, October 2023 to January 2024

We estimated vaccine effectiveness (VE) of SARS-CoV-2 Omicron XBB.1.5 vaccination against self-reported infection between 9 October 2023 and 9 January 2024 in 23,895 XBB.1.5 vaccine-eligible adults who had previously received at least one booster. VE was 41% (95% CI: 23-55) in 18-59-year-olds and 50% (95% CI: 44-56) in 60-85-year-olds. Sequencing data suggest lower protection against the BA.2.86 (including JN.1) variant from recent prior infection (OR = 2.8; 95% CI:1.2-6.5) and, not statistically significant, from XBB.1.5 vaccination (OR = 1.5; 95% CI:0.8-2.6)

A Multifactorial Approach for Surveillance of Shigella spp. and Entero-Invasive Escherichia coli Is Important for Detecting (Inter)national Clusters

Shigella spp. and entero-invasive Escherichia coli (EIEC) can cause mild diarrhea to dysentery. In Netherlands, although shigellosis is a notifiable disease, there is no laboratory surveillance for Shigella spp. and EIEC in place. Consequently, the population structure for circulating Shigella spp. and EIEC isolates is not known. This study describes the phenotypic and serological characteristics, the phenotypic and genetic antimicrobial resistance (AMR) profiles, the virulence gene profiles, the classic multi-locus sequence types (MLST) and core genome (cg)MLST types, and the epidemiology of 414 Shigella spp. and EIEC isolates collected during a cross-sectional study in Netherlands in 2016 and 2017. S. sonnei (56%), S. flexneri (25%), and EIEC (15%) were detected predominantly in Netherlands, of which the EIEC isolates were most diverse according to their phenotypical profile, O-types, MLST types, and cgMLST clades. Virulence gene profiling showed that none of the isolates harbored Shiga toxin genes. Most S. flexneri and EIEC isolates possessed nearly all virulence genes examined, while these genes were only detected in approximately half of the S. sonnei isolates, probably due to loss of the large invasion plasmid upon subculturing. Phenotypical resistance correlated well with the resistant genotype, except for the genes involved in resistance to aminoglycosides. A substantial part of the characterized isolates was resistant to antimicrobials advised for treatment, i.e., 73% was phenotypically resistant to co-trimoxazole and 19% to ciprofloxacin. AMR was particularly observed in isolates from male patients who had sex with men (MSM) or from patients that had traveled to Asia. Furthermore, isolates related to international clusters were also circulating in Netherlands. Travel-related isolates formed clusters with isolates from patients without travel history, indicating their emergence into the Dutch population. In conclusion, laboratory surveillance using whole genome sequencing as high-resolution typing technique and for genetic characterization of isolates complements the current epidemiological surveillance, as the latter is not sufficient to detect all (inter)national clusters, emphasizing the importance of multifactorial public health approaches

External validation and clinical utility assessment of PREDICT breast cancer prognostic model in young, systemic treatment-naïve women with node-negative breast cancer

Background: The validity of the PREDICT breast cancer prognostic model is unclear for young patients without adjuvant systemic treatment. This study aimed to validate PREDICT and assess its clinical utility in young women with node-negative breast cancer who did not receive systemic treatment. Methods: We selected all women from the Netherlands Cancer Registry who were diagnosed with node-negative breast cancer under age 40 between 1989 and 2000, a period when adjuvant systemic treatment was not standard practice for women with node-negative disease. We evaluated the calibration and discrimination of PREDICT using the observed/expected (O/E) mortality ratio, and the area under the receiver operating characteristic curve (AUC), respectively. Additionally, we compared the potential clinical utility of PREDICT for selectively administering chemotherapy to the chemotherapy-to-all strategy using decision curve analysis at predefined thresholds. Results: A total of 2264 women with a median age at diagnosis of 36 years were included. Of them, 71.2% had estrogen receptor (ER)-positive tumors and 44.0% had grade 3 tumors. Median tumor size was 16 mm. PREDICT v2.2 underestimated 10-year all-cause mortality by 33% in all women (O/E ratio:1.33, 95%CI:1.22–1.43). Model discrimination was moderate overall (AUC10-year:0.65, 95%CI:0.62–0.68), and poor for women with ER-negative tumors (AUC10-year:0.56, 95%CI:0.51–0.62). Compared to the chemotherapy-to-all strategy, PREDICT only showed a slightly higher net benefit in women with ER-positive tumors, but not in women with ER-negative tumors. Conclusions: PREDICT yields unreliable predictions for young women with node-negative breast cancer. Further model updates are needed before PREDICT can be routinely used in this patient subset.</p

Seroprevalence and Risk Factors of Lyme Borreliosis in The Netherlands: A Population-Based Cross-Sectional Study

Lyme borreliosis (LB) is not notifiable in many European countries, and accurate data on the incidence are often lacking. This study aimed to determine the seroprevalence of Borrelia burgdorferi sensu lato (s.l.)-specific antibodies in the general population of The Netherlands, and to determine risk factors associated with seropositivity. Sera and questionnaires were obtained from participants (n = 5592, aged 0-88 years) enrolled in a nationwide serosurveillance study. The sera were tested for B. burgdorferi s.l.-specific IgM and IgG antibodies using ELISA and immunoblot. Seroprevalence was estimated controlling for the survey design. Risk factors for seropositivity were analyzed using a generalized linear mixed-effect model. In 2016/2017, the seroprevalence in The Netherlands was 4.4% (95% CI 3.5-5.2). Estimates were higher in men (5.7% [95% CI 4.4-7.2]) than in women (3.1% [95% CI 2.0-4.0]), and increased with age from 2.6% (95% CI 1.4-4.4) in children to 7.7% (95% CI 5.9-7.9) in 60- to 88-year-olds. The seroprevalence for B. burgdorferi s.l. in the general population in The Netherlands was comparable to rates reported in European countries. The main risk factors for seropositivity were increasing age, being male and the tick bite frequency. The dynamics of LB infection are complex and involve variables from various disciplines. This could be further elucidated using infectious disease modelling