Postpartum Breast Cancer and Survival in Women With Germline BRCA Pathogenic Variants.

Importance: In young-onset breast cancer (YOBC), a diagnosis within 5 to 10 years of childbirth is associated with increased mortality. Women with germline BRCA1/2 pathogenic variants (PVs) are more likely to be diagnosed with BC at younger ages, but the impact of childbirth on mortality is unknown.

Objective: To determine whether time between most recent childbirth and BC diagnosis is associated with mortality among patients with YOBC and germline BRCA1/2 PVs.

Salivary Steroid Collection in Children Under Conditions Replicating Home Sampling.

Context: Measurement of salivary glucocorticoids is an accepted method for testing adrenal function but there are few data on stability during home collection. Current salivary collection techniques require active participation or present a choking hazard and are unsuitable for young children.

Objective: We sought to compare different salivary collection methods; assess the stability of salivary glucocorticoids under conditions replicating home collection; and assess patient tolerability and caregiver acceptability of a salivary collection device for young children, a swab encased in an infant pacifier (SaliPac).

Uptake of bilateral-risk-reducing-mastectomy: Prospective analysis of 7195 women at high-risk of breast cancer.

Background: Bilateral-Risk-Reducing-Mastectomy-(BRRM) is well described in BRCA1/2 pathogenic variant carriers. However, little is known about the relative uptake, time trends or factors influencing uptake in those at increased breast cancer risk not known to be carriers. The aim of this study is to assess these factors in both groups.

The impact of digitisation of a virtual fracture clinic on referral quality, outcomes and assessment times.

Background: Virtual fracture clinics (VFCs) have become widely adopted, aiming to improve efficiency, standardise patient care and reduce clinic appointments for injuries that can be managed conservatively. A variety of means exist to manage VFC referrals and assessment, including paper-based and digital methods. This study assesses VFC referral quality and outcomes before and after implementation of a digital VFC referral and management system.

The effect of COVID-19 on a Major Trauma Network. An analysis of mechanism of injury pattern, referral load and operative case-mix.

Purpose: The aim of this study was to evaluate changes in both mechanism and diagnoses of injuries presenting to the orthopaedic department during this lockdown period, as well as to observe any changes in operative case-mix during this time.

Methods: A study period of twelve weeks following the introduction of the nationwide "lockdown period", March 23 - June 14, 2020 was identified and compared to the same time period in 2019 as a "baseline period". A retrospective analysis of all emergency orthopaedic referrals and surgical procedures performed during these time frames was undertaken.

Long-Term Evaluation of Women Referred to a Breast Cancer Family History Clinic (Manchester UK 1987-2020).

Clinics for women concerned about their family history of breast cancer are widely established. A Family History Clinic was set-up in Manchester, UK, in 1987 in a Breast Unit serving a population of 1.8 million.

Postmarket Experience With HeartMate 3 Left Ventricular Assist Device: 30-Day Outcomes From the ELEVATE Registry.

Background: The HeartMate 3 left ventricular assist device (Abbott, Chicago, IL) is designed to provide circulatory support with enhanced hemocompatibility for patients with advanced heart failure. The purpose of this study was to compare the surgical outcomes between patients treated during the European Conformity Mark (CE Mark [CEM]) clinical trial and those treated in the postmarket era.

Methods: The prospective, observational, multinational ELEVATE (Evaluating the HeartMate 3 with Full MagLev Technology in a Post-Market Approval Setting) registry includes patients receiving the HeartMate 3 following CEM approval.

Thrombo-embolic events in left ventricular endocardial pacing: long-term outcomes from a multicentre UK registry.

Aims: Endocardial left ventricular (LV) pacing is a viable alternative in patients with failed coronary sinus (CS) lead implantation. However, long-term thrombo-embolic risk remains unknown. Much of the data have come from a small number of centres.

Primary Mutational Landscape Linked with Pre-Docetaxel Lactate Dehydrogenase Levels Predicts Docetaxel Response in Metastatic Castrate-Resistant Prostate Cancer.

Background: Docetaxel chemotherapy is a standard of care for metastatic castrate-resistant prostate cancer (mCRPC): 40-50% of patients achieve a biochemical response. However, there is a lack of response predictive biomarkers.

Objective: To assess lactate dehydrogenase (LDH) as a docetaxel response biomarker in mCRPC and to examine the association of LDH with genomic alterations in primary diagnostic biopsies.

Young age at first pregnancy does protect against early onset breast cancer in BRCA1 and BRCA2 mutation carriers.

Purpose: Previous research assessing the impact of pregnancy and age at first pregnancy on breast cancer risk in BRCA1 and BRCA2 mutation carriers has produced conflicting results, with some studies showing an increased risk following early first pregnancy in contrast to the reduced risk in the general population of women. The present study addresses these inconsistencies.

Methods: Female BRCA1 and BRCA2 carriers from North West England were assessed for breast cancer incidence prior to 50 years of age comparing those with an early first full-term pregnancy (< 21 years) to those without a full-term pregnancy.

Use of salivary cortisol and cortisone in the high- and low-dose synacthen test.

Context: Salivary cortisone reflects serum cortisol levels, is more sensitive than salivary cortisol at lower values of serum cortisol and is noninvasive.

Objective: To investigate the relationship between serum cortisol and salivary cortisol and cortisone following low- and high-dose synacthen.

Design And Setting: Prospective pharmacodynamic studies in clinical research facilities.

Risk algorithms that include pathology adjustment for HER2 amplification need to make further downward adjustments in likelihood scores.

To assess the need for adjustment in the likelihood of germline BRCA1/2 mutations in women with HER2+ breast cancers. We analysed primary mutation screens on women with breast cancer with unequivocal HER2 overexpression and assessed the likelihood of BRCA1/BRCA2 mutations by age, oestrogen receptor status and Manchester score. Of 1111 primary BRCA screens with confirmed HER2 status only 4/161 (2.

The Diagnosis and Management of Early Deep Vein Thrombosis.

The diagnosis and management of an acute DVT is difficult and mistakes are often made. The cost to the National Health Service (NHS) of litigation arising from failure to diagnose and treat DVT early is substantial. Clinical diagnosis alone is often unreliable and a large proportion of DVT occurring in hospital are asymptomatic.

The Prevention of Venous Thromboembolism in Surgical Patients.

Patients undergoing surgery are at an increased risk of VTE. Since the early 1990s the prevention of VTE has been dominated by the administration of low-molecular weight heparin during admission. New oral anticoagulants have been extensively researched and have increased in popularity.

Sensitivity of BRCA1/2 testing in high-risk breast/ovarian/male breast cancer families: little contribution of comprehensive RNA/NGS panel testing.

The sensitivity of testing BRCA1 and BRCA2 remains unresolved as the frequency of deep intronic splicing variants has not been defined in high-risk familial breast/ovarian cancer families. This variant category is reported at significant frequency in other tumour predisposition genes, including NF1 and MSH2. We carried out comprehensive whole gene RNA analysis on 45 high-risk breast/ovary and male breast cancer families with no identified pathogenic variant on exonic sequencing and copy number analysis of BRCA1/2.

Low prevalence of HER2 positivity amongst BRCA1 and BRCA2 mutation carriers and in primary BRCA screens.

The aim of this study is to delineate more clearly the prevalence of HER2+ breast cancer in women with germline BRCA1/2 mutations. For this purpose, we analysed primary mutation screens on women with breast cancer with unequivocal HER2 amplification and assessed the proportion of BRCA1 and BRCA2 breast cancers that were HER2+ comparing this with the existing literature. The results are that 1063 primary BRCA screens had confirmed tumour HER2 status.

Sacral nerve stimulation--hidden costs (uncovered).

Aim: The aim of this study is to determine the occurrence of surgical revision in a cohort of patients treated with sacral nerve stimulation (SNS) for faecal incontinence and constipation and to establish the types of procedures performed and indications for surgery.

Method: From the years 2002 to 2014, 125 patients were identified who had undergone permanent SNS therapy with 36 (28.8 %) patients requiring surgical intervention postimplantation.

Pericarditis and pericardial effusions in the military patient.

The pericardium is the thin double-walled sac encapsulating the heart which has a number of important physiological roles including fixing the heart in the mediastinum, protecting it from cross-organ infection (eg, lung) and lubricating cardiac contraction. The pericardium is associated with several disease syndromes that occasionally affect the military population. These include acute and recurrent pericarditis, pericardial effusion and tamponade, which may result from a large number of different aetiological agents.

Risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a 30-year semi-prospective analysis.

BRCA1 and BRCA2 mutation carriers have an increased risk of contralateral breast cancer after primary breast cancer. Risk reduction strategies are discussed after assessment of risk factors for developing contralateral breast cancer. We assessed potential risk factors that could be of use in clinical practice, including the novel use of single nucleotide polymorphisms (SNP) testing.

Can the breast screening appointment be used to provide risk assessment and prevention advice?

Breast cancer risk is continuing to increase across all societies with rates in countries with traditionally lower risks catching up with the higher rates in the Western world. Although cure rates from breast cancer have continued to improve such that absolute numbers of breast cancer deaths have dropped in many countries despite rising incidence, only some of this can be ascribed to screening with mammography, and debates over the true value of population-based screening continue. As such, enthusiasm for risk-stratified screening is gaining momentum.

The microbiome and emerging pathogens in cystic fibrosis and non-cystic fibrosis bronchiectasis.

Chronic pulmonary sepsis is the predominant cause of morbidity for patients with cystic fibrosis (CF) and non-CF bronchiectasis. Previously it was thought that respiratory infection in these patients was mostly limited to a very small number of typical pathogens; however, in recent years there have been increasing reports of infection with other emerging potential pathogens including Burkholderia, Stenotrophomonas, Achromobacter, Ralstonia, Pandoraea, nontuberculous mycobacteria, and fungal species. Furthermore, culture-independent methodologies have established that the lungs of patients with CF and non-CF bronchiectasis comprise mixed microbiological communities of aerobic and anaerobic bacteria, fungal and viral species, collectively referred to as the lung microbiome.

Long-term prospective clinical follow-up after BRCA1/2 presymptomatic testing: BRCA2 risks higher than in adjusted retrospective studies.

Background: The risks of breast cancer associated with BRCA1 and BRCA2 mutations vary considerably across studies but few have assessed prospective risks, which are likely to provide more reliable risk estimates for women undergoing presymptomatic testing.

Methods: Prospective breast cancer risks were assessed in 254 unaffected women with BRCA1 mutations and 238 with BRCA2 mutations. Rates of breast cancer were calculated allowing for lead time bias and censored at time of risk reducing mastectomy.