Recent Submissions

  • Patient-reported outcomes after monitoring, surgery, or radiotherapy for prostate cancer

    Kynaston, H (2016-10-13)
    Background: Robust data on patient-reported outcome measures comparing treatments for clinically localized prostate cancer are lacking. We investigated the effects of active monitoring, radical prostatectomy, and radical radiotherapy with hormones on patient-reported outcomes. Methods: We compared patient-reported outcomes among 1643 men in the Prostate Testing for Cancer and Treatment (ProtecT) trial who completed questionnaires before diagnosis, at 6 and 12 months after randomization, and annually thereafter. Patients completed validated measures that assessed urinary, bowel, and sexual function and specific effects on quality of life, anxiety and depression, and general health. Cancer-related quality of life was assessed at 5 years. Complete 6-year data were analyzed according to the intention-to-treat principle. Results: The rate of questionnaire completion during follow-up was higher than 85% for most measures. Of the three treatments, prostatectomy had the greatest negative effect on sexual function and urinary continence, and although there was some recovery, these outcomes remained worse in the prostatectomy group than in the other groups throughout the trial. The negative effect of radiotherapy on sexual function was greatest at 6 months, but sexual function then recovered somewhat and was stable thereafter; radiotherapy had little effect on urinary continence. Sexual and urinary function declined gradually in the active-monitoring group. Bowel function was worse in the radiotherapy group at 6 months than in the other groups but then recovered somewhat, except for the increasing frequency of bloody stools; bowel function was unchanged in the other groups. Urinary voiding and nocturia were worse in the radiotherapy group at 6 months but then mostly recovered and were similar to the other groups after 12 months. Effects on quality of life mirrored the reported changes in function. No significant differences were observed among the groups in measures of anxiety, depression, or general health-related or cancer-related quality of life. Conclusions: In this analysis of patient-reported outcomes after treatment for localized prostate cancer, patterns of severity, recovery, and decline in urinary, bowel, and sexual function and associated quality of life differed among the three groups. (Funded by the U.K. National Institute for Health Research Health Technology Assessment Program; ProtecT Current Controlled Trials number, ISRCTN20141297 ; ClinicalTrials.gov number, NCT02044172 .).
  • Resveratrol for the management of human health: how far have we come? A systematic review of resveratrol clinical trials to highlight gaps and opportunities

    Brown, Karen; Pepper, Coral (2024-01-06)
    Resveratrol has long been proposed as being beneficial to human health across multiple morbidities, yet there is currently no conclusive clinical evidence to advocate its recommendation in any healthcare setting. A large cohort with high-quality clinical data and clearly defined biomarkers or endpoints are required to draw meaningful conclusions. This systematic review compiles every clinical trial conducted using a defined dose of resveratrol in a purified form across multiple morbidities to highlight the current 'state-of-play' and knowledge gaps, informing future trial designs to facilitate the realisation of resveratrol's potential benefits to human health. Over the last 20 years, there have been almost 200 studies evaluating resveratrol across at least 24 indications, including cancer, menopause symptoms, diabetes, metabolic syndrome, and cardiovascular disease. There are currently no consensus treatment regimens for any given condition or endpoint, beyond the fact that resveratrol is generally well-tolerated at a dose of up to 1 g/day. Additionally, resveratrol consistently reduces inflammatory markers and improves aspects of a dysregulated metabolism. In conclusion, over the last 20 years, the increasing weight of clinical evidence suggests resveratrol can benefit human health, but more large, high-quality clinical trials are required to transition this intriguing compound from health food shops to the clinic.
  • Myocardial calcium handling in type 2 diabetes: a novel therapeutic target

    Dattani, Abhishek; Singh, Anvesha; McCann, Gerry P; Gulsin, Guarav S (2023-12-23)
    Type 2 diabetes (T2D) is a multisystem disease with rapidly increasing global prevalence. Heart failure has emerged as a major complication of T2D. Dysregulated myocardial calcium handling is evident in the failing heart and this may be a key driver of cardiomyopathy in T2D, but until recently this has only been demonstrated in animal models. In this review, we describe the physiological concepts behind calcium handling within the cardiomyocyte and the application of novel imaging techniques for the quantification of myocardial calcium uptake. We take an in-depth look at the evidence for the impairment of calcium handling in T2D using pre-clinical models as well as in vivo studies, following which we discuss potential novel therapeutic approaches targeting dysregulated myocardial calcium handling in T2D.
  • Guidelines for the diagnosis and management of adult aplastic anaemia: A British Society for Haematology Guideline

    Garg, Mamta (2024-01-21)
    Pancytopenia with hypocellular bone marrow is the hallmark of aplastic anaemia (AA) and the diagnosis is confirmed after careful evaluation, following exclusion of alternate diagnosis including hypoplastic myelodysplastic syndromes. Emerging use of molecular cyto-genomics is helpful in delineating immune mediated AA from inherited bone marrow failures (IBMF). Camitta criteria is used to assess disease severity, which along with age and availability of human leucocyte antigen compatible donor are determinants for therapeutic decisions. Supportive care with blood and platelet transfusion support, along with anti-microbial prophylaxis and prompt management of opportunistic infections remain key throughout the disease course. The standard first-line treatment for newly diagnosed acquired severe/very severe AA patients is horse anti-thymocyte globulin and ciclosporin-based immunosuppressive therapy (IST) with eltrombopag or allogeneic haemopoietic stem cell transplant (HSCT) from a matched sibling donor. Unrelated donor HSCT in adults should be considered after lack of response to IST, and up front for young adults with severe infections and a readily available matched unrelated donor. Management of IBMF, AA in pregnancy and in elderly require special attention. In view of the rarity of AA and complexity of management, appropriate discussion in multidisciplinary meetings and involvement of expert centres is strongly recommended to improve patient outcomes.
  • Role of the exercise professional in metabolic and bariatric surgery

    Herring, Louisa (2024-01)
    Background: Physical activity (PA) is important for the long-term health and weight management of patients who undergo metabolic and bariatric surgery (MBS). However, the roles of exercise professionals in MBS settings have not been systematically determined. Objectives: To investigate: (1) who are the professionals implementing PA programming in MBS clinical settings; and (2) what patient-centric tasks do they perform? Setting: Clinical and academic exercise settings worldwide. Methods: This multimethod study included a scoping review of PA programs in MBS described in the research literature. Data about job tasks were extracted and provided to 10 experts to sort into categories. Cluster analysis was utilized to find the hierarchical structure of tasks. A Delphi process was used to agree on a final model. Results: The majority of PA professionals were exercise physiologists in the USA and physiotherapists or other types of exercise professionals elsewhere. Forty-three tasks were identified, the most reported being supervision of exercise, fitness testing, and exercise prescription. Seven higher-order categories were determined: (1) Exercise-related health assessment, (2) Body composition and physical fitness assessment, (3) Lifestyle physical activity and sedentary behavior assessment, (4) Education, instruction, and prescription, (5) Exercise monitoring, (6) Behavioral counseling and psychosocial support, and (7) Dietary support. The following statements were rated an average of 9.0, classifying them as "imperative": 1) "Pre- and postoperative PA/exercise guidelines for MBS patients are needed", 2) "MBS programs need to include PA/exercise as part of multidisciplinary care". Conclusions: The expert group reached a consensus on 7 major classifications of job tasks for the exercise professional. It is important for governing medical associations across the world to formally recognize experienced exercise professionals as playing pivotal roles in continuing, multidisciplinary care for MBS patients. These findings also provide evidence-based information in the effort to solidify these positions within the greater context of healthcare.
  • Advance care planning for patients with end-stage kidney disease on dialysis: narrative review of the current evidence, and future considerations

    Adenwalla, Sherna; Faull, Christina; Graham-Brown, MPM (2024-01-18)
    Patients with end-stage kidney disease (ESKD) have a high symptom-burden and high rates of morbidity and mortality. Despite this, evidence has shown that this patient group does not have timely discussions to plan for deterioration and death, and at the end of life there are unmet palliative care needs. Advance care planning is a process that can help patients share their personal values and preferences for their future care and prepare for declining health. Earlier, more integrated and holistic advance care planning has the potential to improve access to care services, communication, and preparedness for future decision-making and changing circumstances. However, there are many barriers to successful implementation of advance care planning in this population. In this narrative review we discuss the current evidence for advance care planning in patients on dialysis, the data around the barriers to advance care planning implementation, and interventions that have been trialled. The review explores whether the concepts and approaches to advance care planning in this population need to be updated to encompass current and future care. It suggests that a shift from a problem-orientated approach to a goal-orientated approach may lead to better engagement, with more patient-centred and satisfying outcomes.
  • Polatuzumab vedotin plus rituximab and lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study

    Miall, Fiona (2024-01-05)
    Background: Diffuse large B-cell lymphoma comprises nearly 30% of non-Hodgkin lymphoma cases and patients with relapsed or refractory diffuse large B-cell lymphoma who are ineligible for stem-cell transplantation have few treatment options and poor prognoses. We aimed to determine whether the novel combination of polatuzumab vedotin in combination with rituximab and lenalidomide (Pola+R+Len) would provide a tolerable treatment option with enhanced antitumour response in patients with relapsed or refractory diffuse large B-cell lymphoma. Methods: This completed phase 1b/2, open-label, multicentre, single-arm study (GO29834) evaluated the safety and efficacy of Pola+R+Len in patients with relapsed or refractory diffuse large B-cell lymphoma at 19 sites in three countries (USA, Spain, and UK). Patients (≥18 years old) were eligible for inclusion if they had histologically documented CD20-positive relapsed or refractory diffuse large B-cell lymphoma and Eastern Cooperative Oncology Group performance status of 2 or lower, had received at least one previous line of chemoimmunotherapy, including an anti-CD20 agent, and were ineligible for stem-cell transplantation. The dose-escalation phase (1b) used escalating doses of lenalidomide to find the recommended phase 2 dose. Patients received six 28-day cycles of induction treatment with intravenous rituximab 375 mg/m2 and intravenous polatuzumab vedotin 1·8 mg/kg (all cohorts) plus oral lenalidomide at the following doses: 10 mg (cohort A); 15 mg (cohort B); and 20 mg (cohort C). Rituximab and polatuzumab vedotin were administered on day 1 and lenalidomide on days 1-21 of each 28-day cycle. During the dose-expansion phase (2), patients received six 28-day cycles of Pola+R+Len at the recommended phase 2 dose established during dose escalation. In both phases, patients with a complete response or partial response at the end of induction were eligible for post-induction therapy with rituximab 375 mg/m2 on day 1 and lenalidomide 10 mg/day on days 1-21 of each 28-day cycle for a maximum of 6 cycles. The primary safety objective of the dose-escalation phase was identification of the maximum tolerated dose through incidence of dose-limiting toxic effects. The primary efficacy outcome of the dose-expansion phase was Independent Review Committee-assessed complete response rate at end of induction, based on PET-CT. Analyses were conducted in the safety population, which included all patients who received at least one dose of any study drug, and the efficacy population, which included all patients who received at least one dose of any study drug at the recommended phase 2 dose. This study is registered with ClinicalTrials.gov, number NCT02600897. Findings: Between July 11, 2017 and Feb 3, 2020, 57 patients were enrolled (median age 71 years [IQR 60-75]; 38 [67%] were male and 19 (33%) were female; 47 [82%] were not Hispanic or Latino; and the median previous lines of therapy was 2 [IQR 1-3]). 18 participants were included in phase 1b and 39 were included in phase 2. Phase 1b confirmed a 20 mg recommended phase 2 dose for lenalidomide. After a median follow-up of 11·8 months (IQR 4·7-25·8), the complete response rate, as assessed by the Independent Review Committee, was 31% (90% CI 20-43). The most common grade 3-4 adverse events were neutropenia (35 [61%] of 57) and thrombocytopenia (eight [14%] of 57). Serious adverse events were reported in 23 (40%) of 57 patients and one patient died due to a treatment-related adverse event (neutropenic sepsis). Interpretation: Although the combination of Pola+R+Len did not meet the prespecified activity threshold, some patients derived clinical benefit and the regimen had a tolerable safety profile in patients with relapsed or refractory diffuse large B-cell lymphoma. Funding: Genentech/F Hoffmann-La Roche.
  • The global landscape on the access to cancer medicines for breast cancer: the ONCOLLEGE experience

    Hussain, Sadaqat (2023)
    There is a growing global debate over barriers affecting the timely access to innovative anticancer therapies. Access to medicines is often traced back to the issue of costs: however, more commonly, the distance between valuable innovative treatments and the actual treatment of patients is far beyond the mere problem of financial barriers. A comprehensive approach to understand, assess to medicines should be pursued, to dissect the determinants and formulate solutions for all patients. In this chapter, we discuss drivers of access to innovation for patients with breast cancer, based on a case study of access to HER2-diagnositcs and therapeutics yielding a global landscape analysis, based on the efforts and expertise of the global collaborative group "ONCOLLEGE".
  • Real-world efficacy of single-agent belantamab mafodotin in relapsed systemic AL amyloidosis

    Garg, Mamta (2024-01-03)
    Systemic light chain (AL) amyloidosis is a relapsing plasma cell disorder. Therapy is limited, particularly for triple-class refractory disease. We report the use of belantamab mafodotin, a BCMA-directed drug-antibody conjugate, for relapsed AL amyloidosis, including patients traditionally excluded from clinical trials. Thirty-one patients were reviewed, with a median of three prior lines of therapy. The median follow-up was 12 months (95% CI 4-19), and a median of five doses were delivered. The best haematological overall response rate was 71%, and the complete/very good partial response was 58%. Sixty-eight percent had keratopathy and improved in all. Belantamab mafodotin has high efficacy and good tolerability in patients with relapsed AL amyloidosis.
  • Identification and characterisation of a rare MTTP variant underlying hereditary non-alcoholic fatty liver disease

    Barwell, Julian; Gupta, Pankaj; Neal, Christopher P; Tobin, Martin D; Vemala, Vishwaray M (2023-04-23)
    Background & aims: Non-alcoholic fatty liver disease (NAFLD) is a complex trait with an estimated prevalence of 25% globally. We aimed to identify the genetic variant underlying a four-generation family with progressive NAFLD leading to cirrhosis, decompensation, and development of hepatocellular carcinoma in the absence of common risk factors such as obesity and type 2 diabetes. Methods: Exome sequencing and genome comparisons were used to identify the likely causal variant. We extensively characterised the clinical phenotype and post-prandial metabolic responses of family members with the identified novel variant in comparison with healthy non-carriers and wild-type patients with NAFLD. Variant-expressing hepatocyte-like cells (HLCs) were derived from human-induced pluripotent stem cells generated from homozygous donor skin fibroblasts and restored to wild-type using CRISPR-Cas9. The phenotype was assessed using imaging, targeted RNA analysis, and molecular expression arrays. Results: We identified a rare causal variant c.1691T>C p.I564T (rs745447480) in MTTP, encoding microsomal triglyceride transfer protein (MTP), associated with progressive NAFLD, unrelated to metabolic syndrome and without characteristic features of abetalipoproteinaemia. HLCs derived from a homozygote donor had significantly lower MTP activity and lower lipoprotein ApoB secretion than wild-type cells, while having similar levels of MTP mRNA and protein. Cytoplasmic triglyceride accumulation in HLCs triggered endoplasmic reticulum stress, secretion of pro-inflammatory mediators, and production of reactive oxygen species. Conclusions: We have identified and characterised a rare causal variant in MTTP, and homozygosity for MTTP p.I564T is associated with progressive NAFLD without any other manifestations of abetalipoproteinaemia. Our findings provide insights into mechanisms driving progressive NAFLD. Impact and implications: A rare genetic variant in the gene MTTP has been identified as responsible for the development of severe non-alcoholic fatty liver disease in a four-generation family with no typical disease risk factors. A cell line culture created harbouring this variant gene was characterised to understand how this genetic variation leads to a defect in liver cells, which results in accumulation of fat and processes that promote disease. This is now a useful model for studying the disease pathways and to discover new ways to treat common types of fatty liver disease.
  • Timing of elective surgery and risk assessment after SARS-CoV-2 infection: 2023 update: a multidisciplinary consensus statement on behalf of the Association of Anaesthetists, Federation of Surgical Specialty Associations, Royal College of Anaesthetists and Royal College of Surgeons of England

    Summerton, D J (2023-09)
    Guidance for the timing of surgery following SARS-CoV-2 infection needed reassessment given widespread vaccination, less virulent variants, contemporary evidence and a need to increase access to safe surgery. We, therefore, updated previous recommendations to assist policymakers, administrative staff, clinicians and, most importantly, patients. Patients who develop symptoms of SARS-CoV-2 infection within 7 weeks of planned surgery, including on the day of surgery, should be screened for SARS-CoV-2. Elective surgery should not usually be undertaken within 2 weeks of diagnosis of SARS-CoV-2 infection. For patients who have recovered from SARS-CoV-2 infection and who are low risk or having low-risk surgery, most elective surgery can proceed 2 weeks following a SARS-CoV-2 positive test. For patients who are not low risk or having anything other than low-risk surgery between 2 and 7 weeks following infection, an individual risk assessment must be performed. This should consider: patient factors (age; comorbid and functional status); infection factors (severity; ongoing symptoms; vaccination); and surgical factors (clinical priority; risk of disease progression; grade of surgery). This assessment should include the use of an objective and validated risk prediction tool and shared decision-making, taking into account the patient's own attitude to risk. In most circumstances, surgery should proceed unless risk assessment indicates that the risk of proceeding exceeds the risk of delay. There is currently no evidence to support delaying surgery beyond 7 weeks for patients who have fully recovered from or have had mild SARS-CoV-2 infection.
  • Attitudes and barriers to participation in window-of-opportunity trials reported by White and Asian/Asian British ethnicity patients who have undergone treatment for endometrial cancer

    Amirthanayagam, Anumithra; Moss, Esther (2023-11-23)
    Purpose: Window-of-opportunity trials (WOT) are a study design that have been used to investigate drug activity in endometrial cancer (EC). Recruitment to cancer clinical trials by patients from ethnic minority groups is reported to be lower than for patients of White ethnicity. Methods: A verbal questionnaire was conducted with White and Asian/Asian British ethnicity patients who had undergone treatment for EC. Strategic purposeful sampling was used to recruit patients from diverse social/educational backgrounds. Questions explored: background knowledge of clinical research, WOT study design, and views on medications that might be investigated. Thematic analysis was used to explore motivations for WOT participation and perceived barriers. Results: In total, 21 patients were recruited to the study (15 White and 6 Asian/Asian British). Views on optimum time to receive trial information differed, preferences ranging from 'at the time of diagnosis' to 'a few days after diagnosis'. The choice of medication under investigation had a strong influence on potential willingness to participate, with greater interest reported in medications derived from vitamins or food supplements rather than hormone-based drugs. Potential barriers to participation included concern over potential side-effects and the emotional/physical burden of a cancer diagnosis prior to major surgery. Discussion: This study provides important insights into patients' views on WOT participation in EC and raises issues that need to be considered for future trial design and participant recruitment materials. The timing and format of study information and type of substance under investigation were factors influencing potential participation. Future studies should consider using multi-lingual visual information videos to address information needs, as this may encourage participation by ethnic minority patients.
  • Anticancer actions of carnosine in cellular models of prostate cancer

    Khan, M A (2023-11-29)
    Treatments for organ-confined prostate cancer include external beam radiation therapy, radical prostatectomy, radiotherapy/brachytherapy, cryoablation and high-intensity focused ultrasound. None of these are cancer-specific and are commonly accompanied by side effects, including urinary incontinence and erectile dysfunction. Moreover, subsequent surgical treatments following biochemical recurrence after these interventions are either limited or affected by the scarring present in the surrounding tissue. Carnosine (β-alanyl-L-histidine) is a histidine-containing naturally occurring dipeptide which has been shown to have an anti-tumorigenic role without any detrimental effect on healthy cells; however, its effect on prostate cancer cells has never been investigated. In this study, we investigated the effect of carnosine on cell proliferation and metabolism in both a primary cultured androgen-resistant human prostate cancer cell line, PC346Flu1 and murine TRAMP-C1 cells. Our results show that carnosine has a significant dose-dependent inhibitory effect in vitro on the proliferation of both human (PC346Flu1) and murine (TRAMP-C1) prostate cancer cells, which was confirmed in 3D-models of the same cells. Carnosine was also shown to decrease adenosine triphosphate content and reactive species which might have been caused in part by the increase in SIRT3 also shown after carnosine treatment. These encouraging results support the need for further human in vivo work to determine the potential use of carnosine, either alone or, most likely, as an adjunct therapy to surgical or other conventional treatments.
  • Ibrutinib as first line therapy for mantle cell lymphoma: a multicentre, real-world UK study

    Allchin, Rebecca; Walter, Harriet Sarah; Miall, Fiona (2023-12-21)
    During the Covid-19 pandemic, ibrutinib +/- rituximab was approved in England for initial treatment of mantle cell lymphoma (MCL) instead of immunochemotherapy. As limited data are available in this setting, we conducted an observational cohort study evaluating safety and efficacy. Adults receiving ibrutinib +/- rituximab for untreated MCL were evaluated for treatment toxicity, response and survival, including outcomes in high-risk MCL (TP53 mutation/deletion/p53 overexpression, blastoid/pleomorphic, or Ki67 >/=30%). 149 patients from 43 participating centres were enrolled: 74.1% male, median age 75, 75.2% ECOG 0-1, 36.2% high-risk, 8.9% autologous transplant candidates. All patients received >/= 1 cycle ibrutinib (median 8 cycles), 39.0% with rituximab. Grade >/= 3 toxicity occurred in 20.3%, 33.8% required dose reductions/delays. At 15.6 months (mo) median follow-up, 41.6% discontinued ibrutinib; 8.1% due to toxicity. Of 104 response-assessed patients, overall (ORR) and complete response (CR) rates were 71.2% and 20.2% respectively. ORR was 77.3% (low-risk) vs. 59.0% (high-risk), p=0.05, and 78.7% (ibrutinib-rituximab) vs. 64.9% (ibrutinib), p=0.13. Median progression-free survival was 26.0mo (all patients); 13.7mo (high-risk) vs. not reached (NR) (low-risk), p=0.004. Median overall survival was NR (all); 14.8mo (high-risk) vs. NR (low-risk), p=0.005. Median post-ibrutinib survival was 1.4mo, longer in 41.9% patients receiving subsequent treatment (median 8.6 vs 0.6mo, p=0.002). Ibrutinib +/- rituximab was effective and well tolerated as first-line treatment of MCL, including older and transplant-ineligible patients. PFS and OS were significantly inferior in one-third of patients with high-risk disease and those unsuitable for post-ibrutinib treatment, highlighting the need for novel approaches in these groups.
  • Chronic lymphocytic leukemia therapy guided by measurable residual disease

    Kennedy, Ben (2023-11-10)
    Background: The combination of ibrutinib and venetoclax has been shown to improve outcomes in patients with chronic lymphocytic leukemia (CLL) as compared with chemoimmunotherapy. Whether ibrutinib-venetoclax and personalization of treatment duration according to measurable residual disease (MRD) is more effective than fludarabine-cyclophosphamide-rituximab (FCR) is unclear. Methods: In this phase 3, multicenter, randomized, controlled, open-label platform trial involving patients with untreated CLL, we compared ibrutinib-venetoclax and ibrutinib monotherapy with FCR. In the ibrutinib-venetoclax group, after 2 months of ibrutinib, venetoclax was added for up to 6 years of therapy. The duration of ibrutinib-venetoclax therapy was defined by MRD assessed in peripheral blood and bone marrow and was double the time taken to achieve undetectable MRD. The primary end point was progression-free survival in the ibrutinib-venetoclax group as compared with the FCR group, results that are reported here. Key secondary end points were overall survival, response, MRD, and safety. Results: A total of 523 patients were randomly assigned to the ibrutinib-venetoclax group or the FCR group. At a median of 43.7 months, disease progression or death had occurred in 12 patients in the ibrutinib-venetoclax group and 75 patients in the FCR group (hazard ratio, 0.13; 95% confidence interval [CI], 0.07 to 0.24; P<0.001). Death occurred in 9 patients in the ibrutinib-venetoclax group and 25 patients in the FCR group (hazard ratio, 0.31; 95% CI, 0.15 to 0.67). At 3 years, 58.0% of the patients in the ibrutinib-venetoclax group had stopped therapy owing to undetectable MRD. After 5 years of ibrutinib-venetoclax therapy, 65.9% of the patients had undetectable MRD in the bone marrow and 92.7% had undetectable MRD in the peripheral blood. The risk of infection was similar in the ibrutinib-venetoclax group and the FCR group. The percentage of patients with cardiac severe adverse events was higher in the ibrutinib-venetoclax group than in the FCR group (10.7% vs. 0.4%). Conclusions: MRD-directed ibrutinib-venetoclax improved progression-free survival as compared with FCR, and results for overall survival also favored ibrutinib-venetoclax. (Funded by Cancer Research UK and others; FLAIR ISRCTN Registry number, ISRCTN01844152; EudraCT number, 2013-001944-76.).
  • Artificial intelligence applications in diagnosing and managing non-syndromic craniosynostosis: a comprehensive review

    Bangi, Shifa F (2023-09-15)
    Craniosynostosis is characterised by the premature fusion of one or more cranial sutures, resulting in an abnormal head shape. The management of craniosynostosis requires early diagnosis, surgical intervention, and long-term monitoring. With the advancements in artificial intelligence (AI) technologies, there is great potential for AI to assist in various aspects of managing craniosynostosis. The main aim of this article is to review available literature describing the current uses of AI in craniosynostosis. The main applications highlighted include diagnosis, surgical planning, and outcome prediction. Many studies have demonstrated the accuracy of AI in differentiating subtypes of craniosynostosis using machine learning (ML) algorithms to classify craniosynostosis based on simple photographs. This demonstrates its potential to be used as a screening tool and may allow patients to monitor disease progression reducing the need for CT scanning. ML algorithms can also analyse CT scans to aid in the accurate and efficient diagnosis of craniosynostosis, particularly when training junior surgeons. However, the lack of sufficient data currently limits this clinical application. Virtual surgical planning for cranial vault remodelling using prefabricated cutting guides has been shown to allow more precise reconstruction by minimising the subjectivity of the clinicians' assessment. This was particularly beneficial in reducing operating length and preventing the need for blood transfusions. Despite the potential benefits, there are numerous challenges associated with implementing AI in craniosynostosis. The integration of AI in craniosynostosis holds significant promise for improving the management of craniosynostosis. Further collaboration between clinicians, researchers, and AI experts is necessary to harness its full potential.
  • Robotic-assisted surgery in high-risk surgical patients with endometrial cancer

    Moss, Esther (2023-11-04)
    Many patients diagnosed with an endometrial cancer are at high-risk for surgery due to factors such as advanced age, raised body mass index or frailty. Minimally-invasive surgery, in particular robotic-assisted, is increasingly used in the surgical management of endometrial cancer however, there are a lack of clinical trials investigating outcomes in high-risk patient populations. This article will review the current evidence and identify areas of uncertainty where future research is needed.

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