Safety and efficacy of brain biopsy: Results from a single institution retrospective cohort study.

Introduction: Brain biopsy provides important histopathological diagnostic information for patients with new intracranial lesions. Although a minimally invasive technique, previous studies report an associated morbidity and mortality between 0.6% and 6.8%. We sought to characterise the risk linked to this procedure, and to establish the feasibility of instigating a day-case brain biopsy pathway at our institution. Materials and methods: This single-centre retrospective case series study included neuronavigation guided mini craniotomy and frameless stereotactic brain biopsies carried out between April 2019 and December 2021. Exclusion criteria were interventions performed for non-neoplastic lesions. Demographic data, clinical and radiological presentation, type of biopsy, histology and complications in the post-operative period were recorded. Results: Data from 196 patients with a mean age of 58.7 years (SD+/-14.4 years) was analysed. 79% (n=155) were frameless stereotactic biopsies and 21% (n=41) neuronavigation guided mini craniotomy biopsies. Complications resulting in acute intracerebral haemorrhage and death, or new persistent neurological deficits were observed in 2% of patients (n=4; 2 frameless stereotactic; 2 open). Less severe complications or transient symptoms were noted in 2.5% of cases (n=5). 8 patients had minor haemorrhages in the biopsy tract with no clinical ramifications. Biopsy was non-diagnostic in 2.5% (n=5) of cases. Two cases were subsequently identified as lymphoma. Other reasons included insufficient sampling, necrotic tissue, and target error. Discussion and conclusion: This study demonstrates that brain biopsy is a procedure with an acceptably low rate of severe complications and mortality, in line with previously published literature. This supports the development of day-case pathway allowing improved patient flow, reducing the risk of iatrogenic complications associated with hospital stay, such as infection and thrombosis.

Integration of a personalised mobile health (mHealth) application into the care of patients with brain tumours: proof-of-concept study (IDEAL stage 1).

Objectives: Brain tumours lead to significant morbidity including a neurocognitive, physical and psychological burden of disease. The extent to which they impact the multiple domains of health is difficult to capture leading to a significant degree of unmet needs. Mobile health tools such as Vinehealth have the potential to identify and address these needs through real-world data generation and delivery of personalised educational material and therapies. We aimed to establish the feasibility of Vinehealth integration into brain tumour care, its ability to collect real-world and (electronic) patient-recorded outcome (ePRO) data, and subjective improvement in care. Design: A mixed-methodology IDEAL stage 1 study. Setting: A single tertiary care centre. Participants: Six patients consented and four downloaded and engaged with the mHealth application throughout the 12 weeks of the study. Main outcome measures: Over a 12-week period, we collected real-world and ePRO data via Vinehealth. We assessed qualitative feedback from mixed-methodology surveys and semistructured interviews at recruitment and after 2 weeks. Results: 565 data points were captured including, but not limited to: symptoms, activity, well-being and medication. EORTC QLQ-BN20 and EQ-5D-5L completion rates (54% and 46%) were impacted by technical issues; 100% completion rates were seen when ePROs were received. More brain cancer tumour-specific content was requested. All participants recommended the application and felt it improved care. Conclusions: Our findings indicate value in an application to holistically support patients living with brain cancer tumours and established the feasibility and safety of further studies to more rigorously assess this.

The Use of Machine Learning to Reduce Overtreatment of the Axilla in Breast Cancer: Retrospective Cohort Study.

BACKGROUND: Patients with early breast cancer undergoing primary surgery, who have low axillary nodal burden, can safely forego axillary node clearance (ANC). However, routine use of axillary ultrasound (AUS) leads to 43% of patients in this group having ANC unnecessarily, following a positive AUS. The intersection of machine learning with medicine can provide innovative ways to understand specific risks within large patient data sets, but this has not yet been trialed in the arena of axillary node management in breast cancer. OBJECTIVE: The objective of this study was to assess if machine learning techniques could be used to improve preoperative identification of patients with low and high axillary metastatic burden. METHODS: A single-center retrospective analysis was performed on patients with breast cancer who had a preoperative AUS, and the specificity and sensitivity of AUS were calculated. Standard statistical methods and machine learning methods, including artificial neural network, naive Bayes, support vector machine, and random forest, were applied to the data to see if they could improve the accuracy of preoperative AUS to better discern high and low axillary burden. RESULTS: The study included 459 patients; 142 (31%) had a positive AUS; among this group, 88 (62%) had 2 or fewer macrometastatic nodes at ANC. Logistic regression outperformed AUS (specificity 0.950 vs 0.809). Of all the methods, the artificial neural network had the highest accuracy (0.919). Interestingly, AUS had the highest sensitivity of all methods (0.777), underlining its utility in this setting. CONCLUSIONS: We demonstrated that machine learning improves identification of the important subgroup of patients with no palpable axillary disease, positive ultrasound, and more than 2 metastatically involved nodes. A negative ultrasound in patients with no palpable lymphadenopathy is highly indicative of low axillary burden, and it is unclear whether sentinel node biopsy adds value in this situation. Further studies with larger patient numbers focusing on specific breast cancer subgroups are required to refine these techniques in this setting.

Metastatic Lesions of the Clivus: A Systematic Review.

BACKGROUND: Metastatic lesions of the clivus are extremely rare, having previously been estimated as representing 0.02% of all intracranial tumors. Owing to its close intracranial relationship with the clivus before entering the cavernous sinus, clinical palsies of the sixth cranial nerve have been classically associated with destructive lesions of this structure. METHODS: A comprehensive search of PubMed was conducted for studies of patients with metastasis to the clivus from primary cancer at any site. Studies reported in English in the past 20 years from our last search on April 12, 2021 were included. The data collected included patient age, sex, symptoms at presentation, histopathology and treatment timeline of the primary tumor, treatment, follow-up, and mortality. RESULTS: After the literature review, 46 studies reporting on 58 patients with clivus metastasis were included in the final analysis. The mean age of the patients was 57.5 years, and 39 were male (67.2%). The most common sites of the primary tumor were the prostate (22%), gastrointestinal tract (15%), lung (13%), and kidney (11%). In 43% of patients, symptoms of clivus metastasis had presented before the diagnosis of primary cancer was known, and 71% of the patients had presented with sixth nerve palsy. Of the 58 patients, 53% had undergone surgery, and 37% had received adjuvant radiotherapy. Of the 58 patients, 25% had received radiotherapy alone. The endoscopic transsphenoidal approach to the clivus was almost uniquely used for surgical management. Survival data were available for 31 patients. Death had occurred at a mean of 9.4 months after the presentation of clivus metastasis. A strong correlation was found between the interval from primary cancer to the presentation of clivus metastasis and mortality. CONCLUSIONS: Although an extremely rare occurrence, clivus metastasis should be considered in patients with a history of malignancy, in particular, prostate malignancy, presenting with new-onset isolated sixth nerve palsy.

A systematic review of neo-adjuvant radiotherapy in the treatment of breast cancer.

INTRODUCTION: The use of neo-adjuvant radiotherapy (NRT) has been proven effective at improving cancer related outcome measures, including overall-survival (OS) in the management of solid cancers. However, its utilisation in breast cancer has not been explored to the extent of neo-adjuvant chemotherapy (NAC). The evidence for the application of NRT in breast cancer is evaluated. METHODS: PubMed, Embase and the Cochrane Library databases were searched systematically in August 2020 for studies that addressed the role of NRT in the treatment of breast cancer. Studies were deemed eligible if they reported on objective outcome measurements of OS, disease free-survival (DFS) or pathological complete response (pCR) and attained a satisfactory quality assessment. FINDINGS: A total of 23 studies reported upon 3,766 patients who had received NRT of which 3,233 also received NAC concurrently (neo-adjuvant chemo-radiotherapy (NCRT)). The pCR values ranged from 14% to 42%, 5-year DFS 61.4% to 81% and 5-year OS 71.6% to 84.2%. Complications were confined to radiation dermatitis with no cases of implant loss reported during breast reconstruction. The application of NRCT alone showed no significant difference in OS or DFS compared to NCRT followed by surgery. INTERPRETATION: Numbers of patients receiving exclusively NRT is small. However, NCRT is oncologically safe with a low side-effect profile including preceding breast reconstruction. Potential benefits include precise cancer volume targeting, chemosensitisation, elimination of delays in adjuvant therapies and alternatives to chemotherapy in oestrogen receptor positive patients. These factors warrant further exploration within randomised controlled-trials.

Conserving the axilla in breast cancer.

It is recognised that surgical conservatism is the most effective way of managing the axilla in breast cancer patients undergoing primary breast conserving surgery. The extended clinical scenarios in which a less aggressive approach can be safely adopted warrant consideration-including a group of patients who potentially could bypass surgical staging of the axilla altogether. The application of omission of further surgical management and axillary radiotherapy in the primary surgical and neoadjuvant chemotherapy settings are considered.

The virtual fracture clinic improves quality of care for patients with hand and wrist injuries: an assessment of 3709 patients.

Fracture clinic services are under significant pressures to meet patients' expectations of a high-quality service. The virtual fracture clinic has shown early promise in helping to reduce such pressures. We used the virtual fracture clinic for hand and wrist injuries treated in the orthopaedic fracture clinic and used key quality indicators to measure improvement. Over the first 21 months, key patient outcome measures and satisfaction scores for patients discharged from the virtual fracture clinic with education to self-care were excellent. Our results show that a virtual fracture clinic model can be applied to provide high-quality care for hand and wrist injuries. The main advantage of the virtual fracture clinic is its ability to direct patients to the right person for timely treatment. We conclude from our 21-month experience that this model of care allows safe, effective, patient-centred, efficient and equitable care to the patients with hand and wrist fractures.Level of evidence: IV.

Multi-input Synapses, but Not LTP-Strengthened Synapses, Correlate with Hippocampal Memory Storage in Aged Mice.

Long-lasting changes at synapses enable memory storage in the brain. Although aging is associated with impaired memory formation, it is not known whether the synaptic underpinnings of memory storage differ with age. Using a training schedule that results in the same behavioral memory formation in young and aged mice, we examined synapse ultrastructure and molecular signaling in the hippocampus after contextual fear conditioning. Only in young, but not old mice, contextual fear memory formation was associated with synaptic changes that characterize well-known, long-term potentiation, a strengthening of existing synapses with one input. Instead, old-age memory was correlated with generation of multi-innervated dendritic spines (MISs), which are predominantly two-input synapses formed by the attraction of an additional excitatory, presynaptic terminal onto an existing synapse. Accordingly, a blocker used to inhibit MIS generation impaired contextual fear memory only in old mice. Our results reveal how the synaptic basis of hippocampal memory storage changes with age and suggest that these distinct memory-storing mechanisms may explain impaired updating in old age.

Is sentinel node biopsy necessary in the radiologically negative axilla in breast cancer?

PURPOSE: The steady move towards axillary conservatism in breast cancer is based on studies demonstrating that axillary node clearance affords no survival benefit in a subset of patients with a positive pre-operative axillary ultrasound (AUS). However, less attention has been paid to AUS-negative patients who receive sentinel node biopsy as standard. METHODS: Previously assembled systematic review data was reassessed to evaluate nodal burden amongst patients with breast cancer and a clinically and radiologically negative axilla. RESULTS: Pooled data from four cohort studies reporting pre-operative axillary ultrasound in 5139 patients with breast cancer show it has a negative predictive rate of 0.951 (95% confidence interval 0.941-0.960). CONCLUSIONS: Reconsidering the use of ultrasound in patients with early breast cancer and non-palpable axillae reveals that sentinel node biopsy itself may represent surgical over-treatment in patients with a negative axillary ultrasound. The implications of this on the future of surgical management of the axilla are discussed.

Nonmotor Symptoms in Amyotrophic Lateral Sclerosis: A Systematic Review.

BACKGROUND: ALS is a progressive neurodegenerative disease with no curative treatment. Nonmotor symptoms presenting in ALS may cause significant distress, worsen prognosis, and affect survival. OBJECTIVE: To systematically review evidence for the prevalence of nonmotor ALS symptoms, and treatment options. METHODS: Multiple medical literature databases were searched and studies screened using predefined inclusion criteria. Of 4580 studies, 44 were eligible for inclusion with 25 relating to treatment and 19 to the prevalence of nonmotor symptoms in ALS. RESULTS: Nonmotor symptoms involve neuropsychiatric, autonomic, gastrointestinal, and vascular systems, and affect between 5% and 80% of people with ALS. Screening tools for individual nonmotor symptoms are useful in classifying symptom severity and to compare between treatment options. Several methods to relieve nonmotor symptoms have been trialed with varying success rates. CONCLUSIONS: Many of the current studies of nonmotor symptoms in ALS have small sample sizes, requiring more evidence to increase precision in prevalence estimates. Further research is needed to assess the efficacy of current treatments and to find new therapies. Symptom relief or treatment of these nonmotor symptoms should therefore be considered during the clinical management of ALS.