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Adult soft tissue myoepithelial carcinoma: treatment outcomes and efficacy of chemotherapy.
No full textSoft tissue myoepithelial carcinomas are a rare, malignant subgroup of myoepithelial tumours mostly arising in the extremities with equal predilection for women and men. The mainstay of management of localised disease is complete surgical resection. Despite optimal treatment, 40-45% of tumours recur. Data regarding the efficacy of systemic therapy for advanced and metastatic disease are lacking. The primary aim of this study was to evaluate the outcome of all patients with soft tissue myoepithelial carcinoma treated at a single referral centre. The secondary aim was to establish the efficacy of systemic therapies in patients with advanced disease. A retrospective review of the prospectively maintained Royal Marsden Sarcoma Unit database was performed to identify soft tissue myoepithelial carcinoma patients treated between 1996 and 2019. Patient baseline characteristics and treatment history were recorded. Response to systemic therapy was evaluated using RECIST 1.1. We identified 24 patients treated at our institution between 1996 and 2019,12 males and 12 females. Median age at presentation was 49.6 years [interquartile range (IQR) 40.5-63.3 years]. Twenty-two out of 24 patients (91.7%) underwent primary surgical resection. Nine patients (37.5%) received systemic treatment. A partial response was documented in one patient treated with doxorubicin. The median progression-free survival for first-line chemotherapy was 9.3 months. Myoepithelial carcinoma frequently recurs after complete surgical resection. Conventional chemotherapy demonstrated some activity in myoepithelial carcinoma, however, more effective systemic therapies are required and enrolment in clinical trial should be encouraged
The UK-DCD-Risk-Score - practical and new guidance for allocation of a specific organ to a recipient?
No full text: Multiple factors contribute to the overall outcome in donation after circulatory death liver transplantation. The majority is however inconsistently reported with various acceptance criteria and thresholds, when to decline a specific graft. Recent improvement in outcome was based on an increased awareness of the cumulative risk, combining donor and recipient parameters, which encouraged the community to accept livers with an overall higher risk. : This review pictures the large number of risk factors in this field with a special focus on parameters, which contribute to available prediction models. Next, features of the recently developed UK-DCD-Risk-Score, which led to a significantly impaired graft survival, above a suggested threshold of >10 score points, are discussed. The clinical impact of this new model on the background of other prediction tools with their subsequent limitations is highlighted in a next chapter. Finally, we provide suggestions, how to further improve outcomes in this challenging field of transplantation. : Despite the recent development of new prediction models, including the UK-DCD-Risk-Score, which provides a sufficient prediction of graft loss after DCD liver transplantation, the consideration of other confounders is essential to better understand the overall risk and metabolic liver status to improve the comparability of clinical studies. More uniform definitions and thresholds of individual risk factors are required
The NeST (neoadjuvant systemic therapy in breast cancer) study - Protocol for a prospective multi-centre cohort study to assess the current utilization and short-term outcomes of neoadjuvant systemic therapies in breast cancer.
No full textIntroduction
Neoadjuvant systemic therapy (NST) has several potential advantages in the treatment of breast cancer. However, there is currently considerable variation in NST use across the UK. The NeST study is a national, prospective, multicentre cohort study that will investigate current patterns of care with respect to NST in the UK.
Methods and analysis
Phase 1 - a national practice questionnaire (NPQ) to survey current practice.Phase 2 - a multi-centre prospective cohort study of breast cancer patients, undergoing NST.Women undergoing NST as their MDT recommended primary breast cancer treatment between December 2017 and May 2018 will be included. The breast surgery and oncological professional associations and the trainee research collaborative networks will encourage participation by all breast cancer centres.Patient demographics, radiological, oncological, surgical and pathological data will be collected, including complications and the need for further intervention/treatment. Data will be collated to establish current practice in the UK, regarding NST usage and variability of access and provision of these therapies. Prospective data on 600 patients from ~50 centres are anticipated.Trial registration: ISRCTN11160072.
Ethics and dissemination
Research ethics approval is not required for this study, as per the online Health Research Authority decision tool. The information obtained will provide valuable insights to help patients make informed decisions about their treatment. These data should establish current practice in the UK concerning NST, inform future service delivery as well as identifying further research questions.This protocol will be disseminated through the Mammary Fold Academic Research Collaborative (MFAC), the Reconstructive Surgery Trials Network and the Association of Breast Surgery. Participating units will have access to their own data and collective results will be presented at relevant conferences and published in appropriate peer-reviewed journals, as well as being made accessible to relevant patient groups
The Effects of Escalation of Respiratory Support and Prolonged Invasive Ventilation on Outcomes of Cardiac Surgical Patients: A Retrospective Cohort Study.
No full textOBJECTIVES
The aim of this study was to determine the effects of escalation of respiratory support and prolonged postoperative invasive ventilation on patient-centered outcomes, and identify perioperative factors associated with these 2 respiratory complications.
DESIGN
A retrospective cohort analysis of cardiac surgical patients admitted to the cardiothoracic intensive care unit (ICU) between August 2015 and January 2018. Escalation of respiratory support was defined as "unplanned continuous positive airway pressure," "non-invasive ventilation," or "reintubation" after surgery; prolonged invasive ventilation was defined as "invasive ventilation beyond the first 12 hours following surgery." The primary endpoint was the composite of escalation of respiratory support and prolonged ventilation.
SETTING
Tertiary cardiothoracic ICU.
PARTICIPANTS
A total of 2,098 patients were included and analyzed.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
The composite of escalation of support or prolonged ventilation occurred in 509 patients (24.3%). Patients who met the composite had higher mortality (2.9% v 0.1%; p < 0.001) and longer median [interquartile range] length of ICU (2.1 [1.0-4.9] v 0.9 [0.8-1.0] days; p < 0.0001) and hospital (10.6 [8.0-16.0] v 7.2 [6.2-10.0] days; p < 0.0001) stay. Hypoxemia and anemia on admission to ICU were the only 2 factors independently associated with the need for escalation of respiratory support or prolonged invasive ventilation.
CONCLUSIONS
Escalation of respiratory support or prolonged invasive ventilation is frequently seen in cardiac surgery patients and is highly associated with increased mortality and morbidity. Hypoxemia and anemia on admission to the ICU are potentially modifiable factors associated with escalation of respiratory support or prolonged invasive ventilation
Response-adapted intensification with cyclophosphamide, bortezomib, and dexamethasone versus no intensification in patients with newly diagnosed multiple myeloma (Myeloma XI): a multicentre, open-label, randomised, phase 3 trial.
No full textBACKGROUND
Multiple myeloma has been shown to have substantial clonal heterogeneity, suggesting that agents with different mechanisms of action might be required to induce deep responses and improve outcomes. Such agents could be given in combination or in sequence on the basis of previous response. We aimed to assess the clinical value of maximising responses by using therapeutic agents with different modes of action, the use of which is directed by the response to the initial combination therapy. We aimed to assess response-adapted intensification treatment with cyclophosphamide, bortezomib, and dexamethasone (CVD) versus no intensification treatment in patients with newly diagnosed multiple myeloma who had a suboptimal response to initial immunomodulatory triplet treatment which was standard of care in the UK at the time of trial design.
METHODS
The Myeloma XI trial was an open-label, randomised, phase 3, adaptive design trial done at 110 National Health Service hospitals in the UK. There were three potential randomisations in the study: induction treatment, intensification treatment, and maintenance treatment. Here, we report the results of the randomisation to intensification treatment. Eligible patients were aged 18 years or older and had symptomatic or non-secretory, newly diagnosed multiple myeloma, had completed their assigned induction therapy as per protocol (cyclophosphamide, thalidomide, and dexamethasone or cyclophosphamide, lenalidomide, and dexamethasone) and achieved a partial or minimal response. For the intensification treatment, patients were randomly assigned (1:1) to cyclophosphamide (500 mg daily orally on days 1, 8, and 15), bortezomib (1·3 mg/m subcutaneously or intravenously on days 1, 4, 8, and 11), and dexamethasone (20 mg daily orally on days 1, 2, 4, 5, 8, 9, 11, and 12) up to a maximum of eight cycles of 21 days or no treatment. Patients were stratified by allocated induction treatment, response to induction treatment, and centre. The co-primary endpoints were progression-free survival and overall survival, assessed from intensification randomisation to data cutoff, analysed by intention to treat. Safety analysis was per protocol. This study is registered with the ISRCTN registry, number ISRCTN49407852, and clinicaltrialsregister.eu, number 2009-010956-93, and has completed recruitment.
FINDINGS
Between Nov 15, 2010, and July 28, 2016, 583 patients were enrolled to the intensification randomisation, representing 48% of the 1217 patients who achieved partial or minimal response after initial induction therapy. 289 patients were assigned to CVD treatment and 294 patients to no treatment. After a median follow-up of 29·7 months (IQR 17·0-43·5), median progression-free survival was 30 months (95% CI 25-36) with CVD and 20 months (15-28) with no CVD (hazard ratio [HR] 0·60, 95% CI 0·48-0·75, p<0·0001), and 3-year overall survival was 77·3% (95% Cl 71·0-83·5) in the CVD group and 78·5% (72·3-84·6) in the no CVD group (HR 0·98, 95% CI 0·67-1·43, p=0·93). The most common grade 3 or 4 adverse events for patients taking CVD were haematological, including neutropenia (18 [7%] patients), thrombocytopenia (19 [7%] patients), and anaemia (8 [3%] patients). No deaths in the CVD group were deemed treatment related.
INTERPRETATION
Intensification treatment with CVD significantly improved progression-free survival in patients with newly diagnosed multiple myeloma and a suboptimal response to immunomodulatory induction therapy compared with no intensification treatment, but did not improve overall survival. The manageable safety profile of this combination and the encouraging results support further investigation of response-adapted approaches in this setting. The substantial number of patients not entering this trial randomisation following induction therapy, however, might support the use of combination therapies upfront to maximise response and improve outcomes as is now the standard of care in the UK.
FUNDING
Cancer Research UK, Celgene, Amgen, Merck, Myeloma UK
SOCIETY FOR ENDOCRINOLOGY EMERGENCY ENDOCRINE GUIDANCE: Emergency management of acute hypocalcaemia in adult patients
No full textIn this addendum to the above paper, the Society for Endocrinology Clinical Committee and the original authors provide additional advice on the dose equivalence of calcium gluconate and calcium chloride.
The ‘Severe hypocalcaemia’ section, which appeared in the September 2016 issue of Endocrine Connections (volume 5, page G8, https://doi.org/10.1530/EC-16-0056 reads as follows:
Severe hypocalcaemia
Severe hypocalcaemia: serum calcium <1.9 mmol/L and/or symptomatic at any level below reference range.
This is a medical emergency
Administer i.v. calcium gluconate
Initially, give 10–20 mL 10% calcium gluconate in 50–100 mL of 5% dextrose i.v. over 10 min with ECG monitoring. This can be repeated until the patient is asymptomatic. It should be followed up with a calcium gluconate infusion as follows:
Dilute 100 mL of 10% calcium gluconate (10 vials) in 1 L of Normal saline or 5% dextrose and infuse at 50–100 mL/h. (Calcium chloride can be used as an alternative to calcium gluconate, but it is more irritant to veins and should only be given via a central line)
Titrate the rate of infusion to achieve normocalcaemia and continue until treatment of the underlying cause has taken effect
The Society for Endocrinology Clinical Committee and the original authors now provide this additional advice on the dose equivalence of calcium gluconate and calcium chloride, as follows:
Each 10 mL vial of 10% calcium gluconate contains 2.2 mmol of calcium. Calcium chloride for i.v. administration is available in a number of preparations including, commonly, 10 mL of 7.35% calcium chloride (which contains 5 mmol of calcium) and 5 mL of 14.7% calcium chloride (which also contains 5 mmol of calcium). Great care should be taken since other preparations are also available. If using calcium chloride in place of calcium gluconate, 4.4 mL of 7.35% calcium chloride or 2.2 mL of 14.7% calcium chloride for i.v. administration should therefore be used as equivalent to 10 mL of 10% calcium gluconate. If other calcium chloride preparations are used, the required volume should be calculated, aiming to achieve 2.2–4.4 mmol i.v. loading bolus followed by a 1.1–2.2 mmol/h maintenance infusion
What is the cause of hypotension? A rare complication of percutaneous coronary intervention of a chronic total occlusion: a case report.
No full textBackground
In the last few years, complex techniques and advanced equipment became available to treat chronically occluded coronary arteries. Such procedures portend a series of possible complications that operators should be ready to quickly recognize and deal with.
Case summary
A 75-year-old lady with uncontrolled stable angina underwent percutaneous treatment of a chronically occluded right coronary artery. After balloon angioplasty and stenting, she developed a severe hypotension, refractory to fluid resuscitation and vasopressors. Computerized tomography scan demonstrated an intramural haematoma (IMH) of the right atrioventricular groove resulting in life-threatening pseudotamponade (or dry tamponade), as further confirmed by cardiac magnetic resonance imaging (MRI). The decision was for conservative management and haemodynamic support by intra-aortic balloon pump. Clinically, the patient improved and was discharged a few days later. Follow-up MRI confirmed resolution of the IMH.
Discussion
Severe hypotension during percutaneous treatment of chronically occluded coronary arteries may be related to various causes. Differential diagnosis is thus important in this setting and should include IMH, a rare but potentially fatal complication as it may cause compression of cardiac chambers and lead to pseudotamponade. A high index of suspicion is required to diagnose IMH but there are no clear guidelines for management of such cases
A simple ex vivo model of human renal allograft preservation using the gonadal vein.
No full textINTRODUCTION
Hypothermic machine perfusion, an organ preservation modality, involves flow of chilled preservation fluid through an allograft's vasculature. This study describes a simple, reproducible, human model that allows for interrogation of flow effects during ex vivo organ perfusion.
MATERIALS AND METHODS
Gonadal veins from deceased human renal allografts were subjected to either static cold storage or hypothermic machine perfusion for up to 24 hours. Caspase-3, Krüppel-like factor 2 expression and electron microscopic analysis were compared between 'flow' and 'no-flow' conditions, with living donor gonadal vein sections serving as negative controls.
RESULTS
The increase in caspase-3 expression was less pronounced for hypothermic machine-perfused veins compared with static cold storage (median-fold increase 1.2 vs 2.3; < 0.05). Transmission electron microscopy provided ultrastructural corroboration of endothelial cell apoptosis in static cold storage conditions. For static cold storage preserved veins, Krüppel-like factor 2 expression diminished in a time-dependent manner between baseline and 12 hours ( < 0.05) but was abrogated and reversed by hypothermic machine perfusion ( < 0.05).
CONCLUSIONS
Our methodology is a simple, reproducible and successful model of ex vivo perfusion in the context of human organ preservation. To demonstrate the model's utility, we establish that two widely used markers of endothelial health (caspase-3 and Krüppel-like factor 2) differ between the flow and no-flow conditions of the two predominant kidney preservation modalities. These findings suggest that ex vivo perfusion may mediate the induction of a biochemically favourable endothelial niche which may contribute tohypothermic machine perfusion's association with improved renal transplantation outcomes
Patient journey following lumbar discectomy surgery: protocol for a single-centre qualitative analysis of the patient rehabilitation experience (DiscJourn).
No full textINTRODUCTION
Lumbar discectomy is a widely used surgical procedure internationally with the majority of patients experiencing significant benefit. However, approximately 20% of patients report suboptimal functional recovery and quality of life. The impact and meaning of the surgical experience from the patients' perspective are not fully understood. Furthermore, there is limited evidence guiding postoperative management with significant clinical practice variation and it is unclear if current postoperative support is valued, beneficial or meets patients' needs and expectations. This study aims to address the evidence gap by moving beyond current knowledge to gain insight into the lived experiences relating to patients' lumbar discectomy surgery journey. Results will inform more meaningful and specific care, thus, enhance rehabilitation and outcomes.
METHODS AND ANALYSIS
A qualitative investigation using interpretative phenomenology analysis (IPA) will provide a flexible inductive research approach. A purposive sample (n=20) of patients undergoing primary discectomy will be recruited from one UK NHS secondary care centre. Semi-structured interviews will be conducted postsurgery discharge. A topic guide, developed from the literature and our previous work with input from two patient co-investigators, will guide interviews with the flexibility to explore interesting or patient-specific points raised. Providing longitudinal data, patients will keep weekly diaries capturing experiences and change over time throughout 12 months following surgery. A second interview will be completed 1 year postsurgery with its topic guide informed by initial findings. This combination of patient interviews and diaries will capture patients' attitudes and beliefs regarding surgery and recovery, facilitators and barriers to progress, experiences regarding return to activities/function and interactions with healthcare professionals. The rich density of data will be thematically analysed in accordance with IPA, supported by NVivo software.
ETHICS AND DISSEMINATION
Ethical approval has been granted by the London-Bloomsbury Research Ethics Committee (18/LO/0459; IRAS 241345). Conclusions will be disseminated through conferences and peer-reviewed journals
Multicentre review of readmission rates within 30 days of discharge following lung cancer surgery.
No full textPostoperative complications following curative lung cancer surgery are well recognised, but there is limited data on 30-day readmission rates. The UK Thoracic Surgery Group conducted a multicentre review over a 3-month period to assess readmission rates. Overall readmission among the 268 patients who had undergone primary lung cancer surgery was 30 (11%); 14/30 of readmissions occurred within 7 days of discharge, with 13/30 patients readmitted to a hospital that had not performed the surgery. The causes of readmission were mainly pulmonary related (16/30). Readmission was associated with being discharged with a pleural drain 11/30 (<0.01), having two or more postoperative complications 11/30 (<0.01) and a patient's readiness for discharge 9/30 (=0.001). There was a trend toward an association with smoking 13/30 (=0.18). The authors suggest that a greater focus on patients presenting with characteristics associated with readmission, and incorporating a patient's readiness for discharge, may reduce readmission, although more studies are needed