Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Background The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions.Methods This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting.Findings Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey.Conclusions The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown.Subject terms: Breast cancer, Surgical oncology, Health care economics, Quality of life, Health policy     

Nurse-led dexmedetomidine sedation for magnetic resonance imaging in children: a 6-year quality improvement project

We aimed to safely introduce dexmedetomidine into a nurse-led sedation service for magnetic resonance imaging in children. Secondary aims were to increase the number of children eligible for sedation and to increase the actual number of children having sedation performed by our nurse sedation team. We analysed 1768 consecutive intravenous and 219 intranasal dexmedetomidine sedation episodes in infants, children and adolescents having magnetic resonance imaging scans between March 2016 and March 2022. The overall sedation success rate was 98.4%, with a 98.9% success rate for intravenous dexmedetomidine and a 95.0% success rate for intranasal dexmedetomidine. The incidence of scan interruption during intravenous and intranasal dexmedetomidine sedation was 8.8% and 21.9%, respectively. We conclude that paediatric sedation with dexmedetomidine for magnetic resonance scanning is safe and successful.     

General anaesthesia for ophthalmic surgery

The majority of ophthalmic surgeries are performed as day cases under topical or regional anaesthesia with or without intravenous sedation. However, general anaesthesia is necessary in certain circumstances e.g. local anaesthetic allergy or patients who are unable to cooperate or to lie flat or still. Patients for ophthalmic surgery are frequently elderly with multiple comorbidities, such as diabetes and hypertension. Patients with rare genetic syndromes may present for eye surgery. Therefore adequate preoperative evaluation and preparation will minimize perioperative complications. The goals of general anaesthesia are smooth induction and emergence, with stable intra-ocular pressure (IOP) and akinesia of the globe. These can be achieved with a combination of intravenous and inhalational agents with or without muscle relaxants and opiates. Use of the laryngeal mask airway has the advantage of causing a smaller rise in IOP on insertion and less coughing on emergence. Total intravenous anaesthesia with propofol and remifentanil has the advantages of causing less postoperative nausea and vomiting (PONV), reduced stress response to airway intervention, rapid recovery and smooth emergence. Some eye procedures require special consideration, for example, strabismus and vitreoretinal surgery involves traction of the rectus muscles producing a higher incidence of oculocardiac reflex and PONV. Most ophthalmic surgery produces mild to moderate pain amenable to non-opioid analgesics. Intraoperative topical and regional anaesthesia reduce postoperative pain and opiate requirement. Open globe injury and a full stomach present unique challenges to prevent increase in IOP as well as protecting the airway.     

The impact of canister geometry on chemical biological radiological and nuclear filter performance: A computational fluid dynamics analysis

Steady-state axisymmetric simulations using the Reynolds-Averaged Navier-Stokes equations have been carried out in order to optimize the performance of a Chemical, Biological, Radiological, and Nuclear (CBRN) canister filter for its use in a powered air-purifying respirator (PAPR). Alterations have been made to the shape of the canister, the spacing of the rear wall of the canister with regard to the carbon filter, and the bracketing between (i) the particulate filter and the carbon bed and (ii) the carbon bed and the canister wall. The pressure drops across the canister and the residence time distribution at the rear of the carbon bed have been analyzed in detail based on an extensive parametric analysis involving the aforementioned variations. It has been demonstrated that the non-uniform porosity profile of the carbon bed resulted in alternating regions of high and low velocity close to the canister wall, providing a possible route for breakthrough. Designs, which included a bracket at the rear of the carbon bed, blocked this route and consequently had a longer minimum mean residence time than those, which did not. It has also been shown that the spacing between the carbon bed and the canister rear wall had a large impact on both residence time and pressure drop. In cases where the carbon backed directly onto the canister rear wall flow in the axial direction from the outside wall toward the canister axis resulted in far greater pressure drop and a reduction in minimum mean residence time within the carbon bed.     

HIV infection after prenatal screening: an open window leading to perinatal infection

Despite a dramatic decrease in vertical transmission of HIV in the developed world, maternal HIV infection acquired after negative prenatal screening still leaves a window of vulnerability. Through quality assurance programs in two Canadian Provinces, five cases where perinatal HIV transmission occurred despite negative prenatal screening were identified between 2005 and 2015. Maternal risk factors such as intravenous drug use, high–risk sexual behavior, hepatitis C virus co–infection, and belonging to high prevalence minority groups were common. Two mothers had their negative HIV test performed in the first trimester and three mothers had negative testing in the third trimester. All babies were clinically healthy at delivery with a normal weight. Three babies were tested following subsequent identification of maternal HIV infection and two babies presented with opportunistic infections leading to their diagnoses. The characteristics of these cases suggest that to achieve complete elimination of vertical HIV transmission, selective and innovative clinical management of mothers at high risk for HIV may be required.     

Co-targeting bromodomain and extra-terminal proteins and MCL1 induces synergistic cell death in melanoma

The treatment of melanoma has been markedly improved by the introduction of targeted therapies and checkpoint blockade immunotherapy. Unfortunately, resistance to these therapies remains a limitation. Novel anticancer therapeutics targeting the MCL1 anti-apoptotic protein have shown impressive responses in haematological cancers but are yet to be evaluated in melanoma. To assess the sensitivity of melanoma to new MCL1 inhibitors, we measured the response of 51 melanoma cell lines to the novel MCL1 inhibitor, S63845. Additionally, we assessed combination of this drug with inhibitors of the bromodomain and extra-terminal (BET) protein family of epigenetic readers, which we postulated would assist MCL1 inhibition by downregulating anti-apoptotic targets regulated by NF-kB such as BCLXL, BCL2A1 and XIAP, and by upregulating pro-apoptotic proteins including BIM and NOXA. Only 14% of melanoma cell lines showed sensitivity to S63845, however, combination of S63845 and I-BET151 induced highly synergistic apoptotic cell death in all melanoma lines tested and in an in vivo xenograft model. Cell death was dependent on caspases and BAX/BAK. Although the combination of drugs increased the BH3-only protein, BIM, and downregulated anti-apoptotic proteins such as BCL2A1, the importance of these proteins in inducing cell death varied between cell lines. ABT-199 or ABT-263 inhibitors against BCL2 or BCL2 and BCLXL, respectively, induced further cell death when combined with S63845 and I-BET151. The combination of MCL1 and BET inhibition appears to be a promising therapeutic approach for metastatic melanoma, and presents opportunities to add further BCL2 family inhibitors to overcome treatment resistance.     

Mechanical and morphological determinants of peak power output in elite cyclists

Mechanical peak power output (PPO) is a determinant of performance in sprint cycling. The purpose of this study was to examine the relationship between PPO and putative physiological determinants of PPO in elite cyclists, and to compare sprint performance between elite sprint and endurance cyclists. Thirty-five elite cyclists (18 endurance; 17 sprint) performed duplicate sprint cycling laboratory tests to establish PPO and its mechanical components. Quadriceps femoris (Q_VOL) and hamstring muscle volume (HAM_VOL) were assessed with MRI, vastus lateralis pennation angle (Pθ_VL) and fascicle length (FL_VL) were determined with ultrasound imaging, and neuromuscular activation of three muscles was assessed using EMG at PPO during sprint cycling. For the whole cohort, there was a wide variability in PPO (range 775-2025 W) with very large, positive, bivariate relationships between PPO and Q_VOL (r = .87), HAM_VOL (r = .71), and Pθ_VL (r = .81). Step-wise multiple regression analysis revealed that 87% of the variability in PPO between cyclists was explained by two variables Q_VOL (76%) and Pθ_VL (11%). The sprint cyclists had greater PPO (+61%; P < .001 vs endurance), larger Q_VOL (P < .001), and BF_VOL (P < .001) as well as more pennate vastus lateralis muscles (P < .001). These findings emphasize the importance of quadriceps muscle morphology for sprint cycling events.