36 research outputs found
Comprehensive multiplexed immune profiling of the ductal carcinoma in situ immune microenvironment regarding subsequent ipsilateral invasive breast cancer risk
Background: Ductal carcinoma in situ (DCIS) is treated to prevent subsequent ipsilateral invasive breast cancer (iIBC). However, many DCIS lesions will never become invasive. To prevent overtreatment, we need to distinguish harmless from potentially hazardous DCIS. We investigated whether the immune microenvironment (IME) in DCIS correlates with transition to iIBC.Methods: Patients were derived from a Dutch population-based cohort of 10,090 women with pure DCIS with a median follow-up time of 12 years. Density, composition and proximity to the closest DCIS cell of CD20+ B-cells, CD3+CD8+ T-cells, CD3+CD8- T-cells, CD3+FOXP3+ regulatory T-cells, CD68+ cells, and CD8+Ki67+ T-cells was assessed with multiplex immunofluorescence (mIF) with digital whole-slide analysis and compared between primary DCIS lesions of 77 women with subsequent iIBC (cases) and 64 without (controls).Results: Higher stromal density of analysed immune cell subsets was significantly associated with higher grade, ER negativity, HER-2 positivity, Ki67 ≥ 14%, periductal fibrosis and comedonecrosis (P Conclusion: IME features analysed by mIF in 141 patients from a well-annotated cohort of pure DCIS with long-term follow-up are no predictors of subsequent iIBC, but do correlate with other factors (grade, ER, HER2 status, Ki-67) known to be associated with invasive recurrences.</p
Dutch Prospective Observational Study on Prehospital Treatment of Severe Traumatic Brain Injury: The BRAIN-PROTECT Study Protocol
Background: Severe traumatic brain injury (TBI) is associated with a high mortality rate and those that survive
commonly have permanent disability. While there is a
broad consensus that appropriate prehospital treatment is
crucial for a favorable neurological outcome, evidence to
support currently applied treatment strategies is scarce. In
particular, the relationship between prehospital treatments
and patient outcomes is unclear. The BRAIN-PROTECT
study therefore aims to identify prehospital treatment
strategies associated with beneficial or detrimental outcomes. Here, we present the study protocol. Study
Protocol: BRAIN-PROTECT is the acronym for BRAin
INjury: Prehospital Registry of Outcome, Treatments and
Epidemiology of Cerebral Trauma. It is a prospective
observational study on the prehospital treatment of
patients with suspected severe TBI in the Netherlands.
Prehospital epidemiology, interventions, medication strategies, and nonmedical factors that may affect outcome are
studied. Multivariable regression based modeling will be
used to identify confounder-adjusted relationships
between these factors and patient outcomes, including
mortality at 30 days (primary outcome) or mortality and
functional neurological outcome at 1 year (secondary outcomes). Patients in whom severe TBI is suspected during
prehospital treatment (Glasgow Coma Scale score 8 in
combination with a trauma mechanism or clinical findings
suggestive of head injury) are identified by all four helicopter emergency medical services (HEMS) in the
Netherlands. Patients are prospectively followed up in 9
participating trauma centers for up to one year. The
manuscript reports in detail the objectives, setting, study
design, patient inclusion, and data collection process.
Ethical and juridical aspects, statistical considerations, as
well as limitations of the study design are discussed.
Discussion: Current prehospital treatment of patients
with suspected severe TBI is based on marginal evidence,
and optimal treatment is basically unknown. The BRAINPROTECT study provides an opportunity to evaluate and
compare different treatment strategies with respect to
patient outcomes. To our knowledge, this study project is
the first large-scale prospective prehospital registry of
patients with severe TBI that also collects long-term follow-up data and ma
Increased Oocyte Degeneration and Follicular Atresia during the Estrous Cycle in Anti-Müllerian Hormone Null Mice
Anti-Müllerian hormone (AMH) plays an important role in folliculogenesis. AMH null mice display an increased recruitment of primordial follicles. Nevertheless, these mice do not have proportionally more preovulatory follicles. Therefore, AMH null mice provide an interesting genetic model to study the regulation of species-specific number of preovulatory follicles. We studied the follicle pool throughout the estrous cycle at 4 months of age. Analysis of the follicle pool revealed that AMH null mice have an increased and earlier cyclic recruitment of growing follicles despite a blunted FSH surge at estrus. However, FSH levels at estrus were apparently too low to support growth to the preovulatory stage because an increased level of atresia was observed, which neutralized the increased cyclic recruitment. When AMH null mice were subjected to a superovulation scheme, the rise in FSH levels resulted in the rescue of the recruited cohort of growing follicles. Analysis of the follicle pool also revealed that the increased recruitment of primordial follicles in AMH null mice was neutralized by an increased loss of follicles during the transition from small preantral to large preantral follicle. This major loss of follicles was not completely reflected by a corresponding augmentation of atresia but did correspond with an increased number of oocyte remnants observed in AMH null mice. We conclude that a combination of increased oocyte degeneration and increased follicular atresia neutralizes the increased initial and cyclic recruitment in AMH null mice to a normal number of preovulatory follicles.