Detailed Profiling of the Tumor Microenvironment in Ethnic Breast Cancer, Using Tissue Microarrays and Multiplex Immunofluorescence.

Breast cancer poses a global health challenge, yet the influence of ethnicity on the tumor microenvironment (TME) remains understudied. In this investigation, we examined immune cell infiltration in 230 breast cancer samples, emphasizing diverse ethnic populations. Leveraging tissue microarrays (TMAs) and core samples, we applied multiplex immunofluorescence (mIF) to dissect immune cell subtypes across TME regions. Our analysis revealed distinct immune cell distribution patterns, particularly enriched in aggressive molecular subtypes triple-negative and HER2-positive tumors. We observed significant correlations between immune cell abundance and key clinicopathological parameters, including tumor size, lymph node involvement, and patient overall survival. Notably, immune cell location within different TME regions showed varying correlations with clinicopathologic parameters. Additionally, ethnicities exhibited diverse distributions of cells, with certain ethnicities showing higher abundance compared to others. In TMA samples, patients of Chinese and Caribbean origin displayed significantly lower numbers of B cells, TAMs, and FOXP3-positive cells. These findings highlight the intricate interplay between immune cells and breast cancer progression, with implications for personalized treatment strategies. Moving forward, integrating advanced imaging techniques, and exploring immune cell heterogeneity in diverse ethnic cohorts can uncover novel immune signatures and guide tailored immunotherapeutic interventions, ultimately improving breast cancer management.

Microscopic Heterotopic Extraovarian Sex Cord-Stromal Proliferations: Expanding the Histologic Spectrum.

Microscopic, heterotopic extraovarian sex cord-stromal proliferations have only recently been reported in the literature. We describe the largest series to date, of 30 cases of microscopic, incidentally detected, heterotopic extraovarian sex cord-stromal proliferation, in women aged 25-79 yr who had undergone surgery for a range of benign and malignant gynecologic conditions. In 14 patients the foci of proliferation comprised ovarian cortical stroma, in some cases with an ovarian fibroma-like appearance. Ten cases of adenofibroma and cystadenofibroma were also identified, including 1 Brenner adenofibroma; 2 cases comprised both ovarian cortical stroma and serous cystadenofibroma; 4 cases showed sex cord proliferation resembling microscopic adult granulosa cell tumors. Immunohistochemistry, where possible, confirmed the sex cord nature of the heterotopic proliferations. The foci of proliferation were <1-7 mm, and most were at the fimbrial end of the fallopian tube. These proliferations are likely to be encountered with increasing frequency as we sample the adnexa more extensively. Previous reports postulated that the proliferations probably represent embryonic rests caused by anomalous migration but we suggest that incorporation of exposed ovarian parenchymal tissue into the fimbrial stroma at the time of ovulation may be another possible cause.

The ageing population is neglected in research studies of traumatic brain injury.

INTRODUCTION: The UK population is ageing with increasing number of elderly patients suffering traumatic brain injury (TBI). The purpose of this study was to identify national TBI admission demographics, analyse the temporal evolution of TBI mortality in a single centre and conduct a systematic review of the literature to identify whether there is an age bias amongst researchers studying TBI. METHODS: National demographics for TBI were obtained from Health Episode Statistics. TBI patients admitted from 2000 to 2011 to Cambridge University Hospitals Neurocritical Care Unit (NCCU) were divided into age groups (<60, 60-74, ≥75 years). Temporal evolution of mortality was analysed using a logistic regression method. A systematic literature review was conducted to identify primary TBI research studies. Patient's ages were extracted and an average mean age was calculated and compared over time. RESULTS: From 1998, national TBI admissions have increased with the greatest rise in >60-year age group (p < 0.0001). In a tertiary referral critical care unit (n = 1145), the 60-74 year age group (compared to <60) had a significantly lower improvement in mortality over time (OR: 1.15, 95% CI: 1.02-1.31). A literature review revealed a mean age of 32.73 years (SD ± 12.85) for patients recruited to primary TBI studies. CONCLUSION: Despite increased admissions of elderly patients following TBI and static mortality (single centre, 60-74 year age group) there is little or no evidence of a corresponding increase in the age of patients recruited for TBI studies. In addition to the difficulties this presents in forming evidence-based decisions for the patient with TBI, it may also represent a wider problem for ICU research in an ever-ageing critical care population. More research needs to be conducted to establish the treatment end points for an ageing population.

Tracheostomy in special groups of critically ill patients: Who, when, and where?

Tracheostomy is one of the most common procedures undertaken in critically ill patients. It offers many theoretical advantages over translaryngeal intubation. Recent evidence in a heterogeneous group of critically ill patients, however, has not demonstrated a benefit for tracheostomy, in terms of mortality, length of stay in Intensive Care Unit (ICU), or incidence of ventilator-associated pneumonia. It may be a beneficial intervention in articular subsets of ICU patients. In this article, we will focus on the evidence for the timing of tracheostomy and its effect on various subgroups of patients in critical care.

Clinical, Histopathologic Features and Outcome of Breast Cancer in UK Women of Ethnic Origin.

OBJECTIVE: Breast cancer (BC) in non-Caucasian females is understudied and its management is based on Caucasian data. 30 % of the West Midlands females are non-Caucasian. We aimed to elucidate the pathologic features, molecular profile, and outcome of non-Caucasian breast cancer. METHODS: Breast cancers (BCs) of different ethnic origins diagnosed at a large Birmingham tertiary referral hospital between 2000 and 2016 were identified. Detailed clinical and histological data were collected and statistically analyzed. RESULTS: Out of 7554 BC cases, 749 were of ethnic ancestry and median age of 51 years. These comprised 47 in-situ and 702 invasive carcinomas of presenting symptomatically in 86.2% of patients. 53.4% of the invasive carcinomas measured >20 mm. Cancers were predominantly of grade 3 (45%), and grade 2 (42.4%). Median NPI was 4.35. 65.1% of the ethnic carcinomas were of luminal subtype, 18.6% were Her2 positive and 16.2% triple-negative. Median overall survival was 62 months. Five and ten-year survival was 81.7% & 68.4% respectively. Ethnicity correlated with higher NPI (p <0.001), larger tumour size (p= 0.001) and larger number of positive axillary nodes (p=0.007). Negative correlations were found between age at diagnosis and both invasive tumour size & grade (p< 0.001) and between tumour grade and overall survival (p= 0.006). CONCLUSION: Compared with Caucasian breast cancer, non-Caucasian tumours presented predominantly symptomatically at younger age, were of larger size, higher grade with more unfavorable phenotypes and shorter survival. This is important in counselling, planning management and follow up of non-Caucasian patients.

The functional outcome of the fractured clavicle.

BACKGROUND: The severity of symptoms, rate and completeness of recovery after closed treatment of the fractured clavicle has not been fully explored. METHODS: The severity and duration of pain, analgesic requirements, ability to perform daily activities, return to work, driving and sport along with appearance of the shoulder were recorded in 56 patients between 1 and 2 years after fracture. Radiographs were assessed by Robinson's classification [8]. RESULTS: Twenty-two out of 56 patients described functional restriction 1-2 years after injury. The majority of patients ceased to experience pain (34/56) and returned to work (19/46) within 3 months. Thirty-eight out of 56 patients noted cosmetic deformity, the severity of which was associated with worse functional outcome (p = 0.002). The degree of fracture displacement was associated with cosmetic deformity (p = 0.02) and functional outcome (p = 0.015). CONCLUSION: The majority of patients perceive a cosmetic deformity and 22/56 impaired function after clavicular fracture.