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Reviewing the effect of needle size on outcomes of Vacuum-Assisted excision of Breast lesionsWe are writing to highlight methodological concerns regarding the study Effect of Needle Size on Outcomes of Vacuum-Assisted Excision of Breast Lesions, published in the European Journal of Radiology [1]. While the study provides valuable insights into the comparative effectiveness of 7G and 10G needles, certain methodological issues may impact the validity of its conclusions.
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The Role of Combined Renin Angiotensin Aldosterone System Inhibitors RAASi) Plus Beta Blocker Therapy For Cardiotoxicity Prevention In Patients Under Chemotherapy For Breast Cancer: A MetaAnalysis of Randomized Controlled Trials.Introduction: Anti-neoplastic agents, including anthracyclines and trastuzumab, frequently employed in breast cancer treatment carry on considerable cardiotoxic effects impairing both cardiac chamber and cardiac fiber parameters leading to incident heart failure. In response to this challenging side effect, numerous randomized controlled trials (RCTs) have investigated the cardioprotective efficacy of RAASi and beta-blockers (BBs) in patients undergoing anthracycline and trastuzumab chemotherapy. We aim to perform an updated meta-analysis to elucidate the potential cardioprotective properties of these medications in patients undergoing chemotherapy for breast cancer.Methods: A comprehensive search of the literature was performed through April 2024 on PubMed, EMBASE and Clinicaltrials.gov. In total, data from 4 randomized studies were extracted and analyzed. The primary analysis was the effect of RAASi and BBs on LVEF as well as global longitudinal strain (GLS). Data were analyzed using a random-effects model to derive weighted mean differences (WMDs) and 95% confidence intervals for both LVEF and GLS. Data was analyzed using Review Manager 5.3 (RevMan 5.3) software.Results: In total, data from 248 patients (N = 124 on cardioprotection; N = 124 without cardioprotection) undergoing treatment with anti-neoplastic agents for breast cancer were included. At the end of treatment, patients undergoing cardioprotective therapy demonstrated improved LVEF preservation compared to the control group, (mean difference 2.14 [0.03, 4.25]; P=0.05; I2 = 79%). In addition, patients undergoing dual RAASi + BB therapy showed better GLS preservation compared to control group (mean difference –1.37 [-2.01, -0.72]; P < 0.0001; I2 = 0%).Conclusion: In breast cancer patients undergoing anti-neoplastic regimens comprising anthracycline and trastuzumab, the concomitant administration of RAASi and BBs demonstrated better LVEF as well as GLS preservation upon completion of treatment over those without cardioprotective therapy. These findings shed light on the potential benefit derived from the synergistic effects of RAASi and BBs therapy in safeguarding both cardiac chamber and fiber functions amidst aggressive anti-cancer regimens, although further investigations still need to be conducted.
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Flowrna in the Diagnosis of EBV-Related Lymphoproliferative DiseaseEpstein-Barr (EBV) viraemia is frequently encountered in the context of haemophagocytic lymphohistiocytosis (HLH), systemic inflammation and lymphoproliferative disease (LPD). Although EBV typically infects B lymphocytes triggering both polyclonal proliferation and lymphoma, EBV can also infect T and NK cells. Understanding the phenotype of EBV-infected cells can help identify the underlying diagnosis and guide the use of appropriate targeted therapy. We have developed an EBV FlowRNA assay combining the detection of EBV-encoded small RNA (EBER) with multicolour flow cytometry (Collins, Blood, 2020). Here we present a larger case series illustrating how this assay can be used in diagnostic workup.
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Cost-effectiveness of a novel, non-active implantable device as a treatment for refractory gastro-esophageal reflux disease.Aims: Gastro-esophageal reflux disease (GERD) is a common, chronic gastrointestinal condition characterized by heartburn, chest pain, regurgitation, and bloating. The current standard of care includes chronic treatment with proton pump inhibitors (PPIs) or, in selected patients, laparoscopic anti-reflux surgery. RefluxStop is a novel implantable device indicated for GERD patients eligible for laparoscopic surgical treatment. The aim of this analysis was to assess the cost-effectiveness of RefluxStop against available treatment options for GERD. Material and methods: A Markov model was developed to assess the cost-effectiveness of RefluxStop compared with PPI-based medical management (MM) and two surgical management options, LNF and magnetic sphincter augmentation (MSA, LINX system), in people with GERD. Clinical outcomes and costs were estimated over a lifetime horizon from the UK National Health Service perspective and an annual discount rate of 3.5% was applied. Results: RefluxStop showed favorable surgical outcomes compared with both LNF and MSA. The base case incremental cost-effectiveness ratios compared with MM, LNF, and MSA were £4,156, £6,517, and £249 per QALY gained, respectively. At the UK cost-effectiveness threshold of £20,000 per QALY gained, the probability that RefluxStop was cost-effective against MM, LNF, and MSA was 100%, 93%, and 100%, respectively. Limitations: The model presented the results of a comparison, with evidence for RefluxStop derived from its single-arm CE mark trial and that for comparators from the literature. The varied clinical care pathway of individual GERD patients was necessarily simplified for modeling purposes, and necessary assumptions were made; however, the model results proved robust to sensitivity analyses. Conclusions: Introduction of RefluxStop was estimated to extend life expectancy and improve quality-of-life of GERD patients when compared with MM, LNF, and MSA. The results of the cost-effectiveness analysis demonstrated that RefluxStop is highly likely to be a cost-effective treatment option within NHS England.
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Attitudes to radiation safety and cholangiogram interpretation in endoscopic retrograde cholangiopancreatography (ERCP): A UK surveyBackground Fluoroscopy during endoscopic retrograde cholangiopancreatography (ERCP) exposes staff and patients to potentially harmful ionizing radiation. We performed a UK survey to explore trainee and trainer attitudes to radiation protection and cholangiogram interpretation in ERCP. Methods An electronic 10-point survey was prospectively distributed to endoscopy unit leads, training programme directors between October and November 2019. Only UK-based ERCP trainees and trainers with hands-on procedural exposure were eligible for the survey. Results The survey was completed by 107 respondents (58 trainees and 49 trainers), with an estimated overall response rate of 46%. Overall, 49% of respondents were up to date with their radiation protection course, 38% were aware of European Basic safety standards directive (BSSD), 38% wore radiation protection goggles, and 40% were aware of the average radiation screening dose per ERCP procedure. Compared with trainers, trainees were less likely to routinely wear thyroid protection shields (76% vs 92%; p=0.028), have awareness of the BSSD (20% vs 49%; p=0.037) or know their average procedural radiation dosages (21% vs 63%; p<0.001). With regard to cholangiogram interpretation, only 26% had received formal training, with 97% of trainees expressing a desire for further training. Conclusion This survey highlights a relative complacency in safety attitudes to radiation protection during ERCP. These data provide impetus to improve training and quality assurance in radiation protection, which should be regarded as a mandatory safety aspect prior to commencing hands-on ERCP training.
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Pathophysiologic mechanisms of angiogenesisThe growth of new blood vessels may be either beneficial or harmful. The angiogenic process may be measured by a variety of techniques, although it may often be the quality rather than quantity of resulting blood vessels that determines function. Endothelial cells play a key role in the initiation of angiogenesis, and vascular endothelial growth factor (VEGF) may be viewed as a prototypical direct‐acting angiogenic factor. VEGF acts through multiple cell surface receptors and signaling pathways to stimulate endothelial cell proliferation, survival, and migration. By inducing other growth factor expression, VEGF stimulates a cascade of angiogenic activity. Different tissues may utilize various angiogenic pathways that are modulated by diverse host tissue responses. Furthermore, a single tissue may progress through a sequence of angiogenic pathways, for example, as acute injury progresses to chronic inflammation. The phenotype of the resulting neovasculature is critically dependent on the context in which it is formed. Biomarkers of angiogenesis are being developed as an aid to assessing human disease. Histological assessment of vascular density and angiogenic factor expression, in vivo imaging, Doppler ultrasound, and biofluid assays each may have clinical utility. Therapeutic targeting of angiogenesis will depend both on the generation of acceptable pharmacological agents and on the identification of patients who may and do gain benefit from such treatments.
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Angiogenesis and nerve growth factor at the osteochondral junction in rheumatoid arthritis and osteoarthritisObjectives. The osteochondral junction can be a source of pain in both RA and OA. Growth of blood vessels and nerves from the subchondral bone into articular cartilage may mediate the association between joint pathology and symptoms. We have investigated associations between angiogenesis, inflammation and neurovascular growth factor expression at the osteochondral junction in human arthritis. Methods. Osteochondral junctions from medial tibial plateaux of patients undergoing arthroplasty for RA (n = 10) or OA (n = 11), or from non-arthritic post-mortem controls (n = 11) were characterized by immunohistochemistry for CD34 and smooth muscle α-actin (blood vessels), CD68 (macrophages), CD3 (lymphocytes), proliferating cell nuclear antigen, vascular endothelial, platelet-derived and nerve growth factor (NGF). Results. Osteochondral angiogenesis was demonstrated as increased endothelial cell proliferation and vascular density in non-calcified articular cartilage, both in RA and OA. Osteochondral angiogenesis was associated with subchondral bone marrow replacement by fibrovascular tissue expressing VEGF, and with increased NGF expression within vascular channels. RA was characterized by greater lymphocyte infiltration and PDGF expression than OA, whereas chondrocyte expression of VEGF was a particular feature of OA. NGF was observed in vascular channels that contained calcitonin gene-related peptide-immunoreactive sensory nerve fibres. Conclusions. Osteochondral angiogenesis in RA and OA is associated with growth factor expression by cells within subchondral spaces, vascular channels and by chondrocytes. NGF expression and sensory nerve growth may link osteochondral angiogenesis to pain in arthritis.
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Predicting responses in patients with rheumatoid arthritis to disease-modifying agents using baseline clinical dataObjectives: The optimal treatment for active rheumatoid arthritis (RA) is unresolved, particularly in early RA. We used data from an observational cohort to develop the simple predictor algorithm and evaluated its application in two completed clinical trials in early and established RA. We assessed whether using a simple algorithm can identify patients who have persisting active disease despite treatment with disease-modifying drugs (DMARDs). We also examined if patients who have lower likelihoods of persisting active RA are likely to benefit from intensive treatment. Methods: We developed a simple predictive score for persisting disease activity using conventional clinical assessments in an observational cohort of patients with early RA (ERAN). It was tested in two trials in early (CARDERA) and established (TACIT) RA. Persistent disease activity was defined as disease activity score for 28 joints (DAS28) >3.2 at both 6 and 12 months. Results: Regression modelling identified three main predictors of persisting active disease in ERAN; tender joint counts, health assessment questionnaire (HAQ) scores and ESR. We dichotomised these predictors (≥6 tender joint counts, ≥1.0 HAQ ≥20 mm/h ESR) in a four-point prediction score. This simple prediction score predicted persisting active disease in the ERAN cohort and both CARDERA and TACIT trials. Patients with high scores were more likely to have persistently active disease at 6 and 12 months. The relationship was weaker in TACIT because no patients were without any predictive factors. Conclusions: Combining tender joint counts, ESR and HAQ in a simple predictive score prospectively identifies patients with higher risks of persistent disease activity over the next 12 months. More patients with all three risk factors had persistent active disease than those with none or one risk factor.
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Refining surgical models of osteoarthritis in mice and rats alters pain phenotype but not joint pathologyThe relationship between osteoarthritis (OA) structural change and pain is complex. Surgical models of OA in rodents are often rapid in onset, limiting mechanistic utility and translational validity. We aimed to investigate the effect of refining surgical small rodent models of OA on both joint pathology and pain behaviour. Adult male C57BL/6 mice (n = 76, 10-11 weeks of age at time of surgery) underwent either traditional (transection of the medial meniscotibial ligament [MMTL]) or modified (MMTL left intact, transection of the coronary ligaments) DMM surgery, or sham surgery. Adult male Sprague Dawley rats (n = 76, weight 175-199g) underwent either modified meniscal transection (MMNX) surgery (transection of the medial meniscus whilst the medial collateral ligament is left intact) or sham surgery. Pain behaviours (weight bearing asymmetry [in mice and rats] and paw withdrawal thresholds [in rats]) were measured pre-surgery and weekly up to 16 weeks post-surgery. Post-mortem knee joints were scored for cartilage damage, synovitis, and osteophyte size. There was a significant increase in weight bearing asymmetry from 13 weeks following traditional, but not modified, DMM surgery when compared to sham operated mice. Both traditional and modified DMM surgery led to similar joint pathology. There was significant pain behaviour from 6 weeks following MMNX model compared to sham operated control rats. Synovitis was significant 4 weeks after MMNX surgery, whereas significant chondropathy was first evident 8 weeks post-surgery, compared to sham controls. Pain behaviour is not always present despite significant changes in medial tibial plateau cartilage damage and synovitis, reflecting the heterogeneity seen in human OA. The development of a slowly progressing surgical model of OA pain in the rat suggests that synovitis precedes pain behaviour and that chondropathy is evident later, providing the foundations for future mechanistic studies into the disease.
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Improving collateral history taking in the geriatric population.Introduction The geriatric population has a high incidence of dementia, delirium and frailty meaning often these patients cannot give comprehensive histories themselves. We are left with missing pieces of the puzzle; we might not know their ‘normal’ and frequently ask: ‘Are they always like this?’ A collateral history becomes a valuable tool, contributing to a Comprehensive Geriatric Assessment and assisting the whole MDT to make informed decisions for patient-centred care. The primary aim of this project was to improve the quality of collateral histories taken for patients admitted to the geriatric wards, with content measured against 8 domains. A secondary aim was to encourage timely collateral histories within 48 hours of admission to the ward. Method Using PDSA methodology, collateral histories were analysed before and after implementation of a poster and teaching session. Results At baseline each domain was covered a mean of 40.5% of the time (range 9%—81%). Following intervention this increased by 22% to 62.5% (range 18%—89%), demonstrating a significant improvement (paired t-test, P < 0.05). It was already common practice to take collateral histories within 48 hours of admission to the ward (91%) which was sustained post-intervention (88%). Conclusion Use of a poster as a prompt, and delivering teaching, led to more thorough collateral histories. This suggests two barriers are knowing what to ask and perceived importance, elements which could be integrated into early postgraduate education. The impact on patient care has the potential to be significant and multidimensional but further work would be needed to understand this.
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EFFECTIVENESS AND SAFETY OF BIOSIMILAR ETANERCEPT GP2015 IN PATIENTS WITH RHEUMATOID ARTHRITIS IN THE UK: RESULTS FROM THE COMPACT STUDYAbstract Background/Aims COMPACT is a non-interventional, multinational cohort study to evaluate effectiveness, safety and quality of life (QoL) outcomes in patients with rheumatic diseases treated with GP2015, an approved etanercept (ETN) biosimilar, under real-world conditions. Here, we present data from patients in the UK with rheumatoid arthritis (RA) enrolled in the COMPACT study, focusing on those who switched to GP2015 from reference ETN or another biosimilar ETN. Methods The COMPACT study included patients (≥18 years of age) with rheumatic diseases treated with GP2015. This analysis includes patients from the UK diagnosed with RA who were in treatment Group A (patients in clinical remission or low disease activity under treatment with reference ETN or other biosimilar ETN, who switched to GP2015 prior to study enrolment). Effectiveness and QoL outcomes were assessed using Disease Activity Score 28-joint count (DAS28) and health assessment questionnaire-disability index (HAQ-DI), respectively, and are presented up to Week 24. Safety outcomes were assessed, including rates of adverse events (AEs) and serious AEs (SAEs). Results A total of 112 patients with RA who switched to GP2015 from reference ETN or another biosimilar ETN (Group A) were enrolled in the UK. The mean ± standard deviation (SD) age was 62.9 ± 11.3 years and 74.1% of patients were female. The mean ± SD DAS28 score remained unchanged from baseline (2.6 ± 1.3) to Week 24 (2.5 ± 1.6). The mean ± SD HAQ-DI score displayed no major difference between baseline (1.2 ± 0.8) and Week 24 (0.9 ± 0.8). Overall, 67.9% (n = 76) of patients experienced ≥1 AE and 9.8% (n = 11) of patients experienced ≥1 SAE (Table). Conclusion Over 24 weeks of treatment with GP2015, disease activity remained low and stable in patients with RA previously switched from reference ETN or from another biosimilar ETN, with no new safety concerns observed. These results from a cohort of patients with RA treated in the UK are consistent with effectiveness, QoL and safety data reported previously for the total population in the COMPACT study.
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RELIABILITY OF QUANTITATIVE SENSORY TESTING, DISEASE ACTIVITY SCORE 28, ULTRASOUND AND CENTRAL ASPECTS OF PAIN QUESTIONNAIRE IN INDIVIDUALS WITH RHEUMATOID ARTHRITIS.Background/Aims Disease Activity Score 28 (DAS28), ultrasound, quantitative sensory testing (QST) and central aspect of pain (CAP) questionnaire measure disease activity and pain hypersensitivity. We investigated their inter-rater and test-retest reliability in Central Aspects of Pain in Rheumatoid Arthritis (CAP-RA) participants. Methods Participants who attended the CAP-RA study visit and agreed to one or more reliability assessments were included. The same two raters completed all assessments, including clinical examination for DAS28, using a single blood sample per participant. QST modalities in the sequence: Pressure Pain detection Threshold (PPT) at the medial joint line of the most painful knee, tibialis anterior and contralateral brachioradialis, Temporal Summation (TS) at rectus femoris of the most painful knee and Conditioned Pain Modulation (CPM), with ischaemic arm pain conditioning and PPT at tibialis anterior. Ultrasound followed the Backhaus 7 protocol, plus the knee. Two trained sonographers scored each joint scan for grey scale (GS), power Doppler and a combined score (PDUS) using EULAR-OMERACT methodology. Joint scores were summated to give an overall score for GS, Doppler and PDUS. Participants could complete questionnaires at invitation, prior to and at baseline, 1-week post-baseline, prior to and at follow-up visit. Any combination of questionnaires completed within 7 days of each other assessed repeatability. Data were assessed for normality, interclass correlation coefficients, and Bland and Altman plots in R studio. Results 196 people were recruited into CAP-RA (median (IQR)) age 66 (58-75) y, 139 (75%) female, 190 (98%) white. 97 (49%) undertook study visits. Characteristics of the 66 people undertaking reliability did not significantly differ from the total population. Measurements are shown in Table 1. Moderate to excellent reliability was found across all measures except CPM (Table 1). The swollen joint count was the least reliable of the DAS28 components. Conclusion Measures of inflammatory disease activity and pain sensitivity are at least moderately reliable within a research context. Only low reliability for CPM might indicate imprecision, or reflect fluctuations in symptoms or pain sensitivity. High reliability of DAS28 and US might reflect relative stability of clinical signs of inflammation. Suppressing day-to-day fluctuations could reduce the unpredictability of rheumatoid arthritis.
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A Review and Comparison of Immune-Checkpoint Inhibitors in the Treatment of Metastatic Uveal Melanoma.Introduction: Metastatic uveal melanoma (mUM) is a rare and aggressive malignancy characterised by poor responsiveness to conventional chemotherapies, posing significant treatment challenges. Immune checkpoint inhibitor (ICI) therapies, including monotherapies with Ipilimumab, pembrolizumab, and nivolumab, as well as dual ICI therapy, have emerged as potential treatments. Whilst current research favours dual therapy over single therapy, comprehensive individualised comparisons of the efficacy and safety profiles of these therapies remain limited. This meta-analysis aims to evaluate the clinical outcomes of single ICI therapies individually and compare against combination therapy to guide optimal treatment strategies for mUM. Methods: A systematic literature review was conducted to identify studies reporting objective response rates (ORR), disease control rates (DCR), median progression-free survival (MPFS), and adverse event rates (AER) for Ipilimumab, pembrolizumab, nivolumab, and dual ICI therapy. Data were aggregated using forest plots and analysed to compare the efficacy and safety of each regimen. Results: Dual ICI therapy demonstrated the highest ORR and DCR but showed no statistically significant advantage over monotherapies. Dual therapy also had a lower MPFS than both pembrolizumab and nivolumab monotherapies. Furthermore, dual therapy was associated with a much greater AER compared to any single therapy, including pembrolizumab and nivolumab. Conclusions: While dual ICI therapy offers improved ORR and DCR on aggregate analyses, monotherapies like pembrolizumab provide comparable outcomes in specific metrics, particularly MPFS, with significantly reduced toxicity. These findings underscore the need for personalised ICI regimens tailored to individual patient profiles rather than defaulting to dual therapy. Further research is essential to refine treatment guidelines and optimise outcomes for mUM patients.
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Symptomatic vitamin A deficiency in a patient on long-term colesevelam.Introduction Bile acid sequestrants including colesevelam are increasingly used by gastroenterologists. The risk of fat-soluble vitamin deficiency when sequestrants are used is recognised. Vitamin A deficiency is uncommon in the UK, but delayed diagnosis can cause irreversible blindness. There are no guidelines for the monitoring of fat-soluble vitamin levels. Case discussion We describe a 63-year-old man who had a neuroendocrine tumour, treated with ileal resection and lanreotide and complicated by the development of severe bile acid malabsorption, pancreatic exocrine insufficiency and intermittent episodes of small intestinal bacterial overgrowth. Three and a half years after starting colesevelam, he developed progressive visual symptoms due to severe vitamin A deficiency. After diagnosis and parenteral vitamin A replacement, his visual symptoms improved but have not resolved. Conclusions Clinicians prescribing bile acid sequestrants should be aware that vitamin A deficiency may arise and should consider regular monitoring of serum levels.
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The Impact of Baseline Comorbidities and Performance Status on HER2-Targeted Therapy Outcomes.We read with great interest the article by Kook et al.,1 comparing adjuvant trastuzumab plus pertuzumab (TP) versus trastuzumab alone (T) in patients with HER2-positive breast cancer who achieved a pathologic complete response (pCR) following neoadjuvant chemotherapy. While the authors concluded that there was no significant difference in recurrence-free survival (RFS) or distant recurrence-free survival (DRFS) between the 2 regimens, we believe the study may have overlooked an important confounding variable: baseline comorbidities and performance status.
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Ramadan intermittent fasting for patients with gastrointestinal and hepatobiliary diseases: practical guidance for health-care professionalsRamadan intermittent fasting can pose challenges and risks for some groups of patients. Based on a narrative literature review and our clinical expertise, we provide practical guidance for clinicians managing patients with gastrointestinal and hepatobiliary conditions who wish to fast during Ramadan. Following the established International Diabetes Federation and Diabetes and Ramadan International Alliance risk stratification framework, we categorised patients' risk as low or moderate, high, or very high. We advise all patients at very high risk and most patients at high risk to not observe fasting due to potential harm. For others, we offer nuanced recommendations on medication rescheduling, lifestyle changes, and tailored fasting advice to minimise adverse effects. Shared decision making that respects patients' religious motivations is essential, with risks and benefits carefully weighed on an individual basis.
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The Efficacy Of Catheter Ablation Compared To Medical Therapy In Heart Failure Patients With Concomitant Atrial Fibrillation: A Meta-analysis Of Randomized Controlled Trials.The management of atrial fibrillation in patients with heart failure continues to be a topic of ongoing debate. We conducted a meticulous comparison between two primary treatment modalities: catheter ablation versus medical therapy. Our aim is to assess the efficacy of these interventions in patients presenting with both atrial fibrillation and heart failure, drawing from the randomized controlled trials. A comprehensive literature search was conducted up to February 2024, utilizing databases including PubMed, EMBASE, and Clinicaltrials.gov. A total of 10 randomized studies were identified and their data were extracted and analyzed. The primary outcomes assessed included the impact of catheter ablation on all-cause mortality, cardiovascular death, left ventricular ejection fraction (LVEF %), and 6-minute walk test (6MWT) in meters. Data were analyzed utilizing a random-effects model to calculate weighted mean differences for LVEF and 6MWT, and risk ratios for all-cause mortality and cardiovascular death on Review Manager 5.3 (RevMan 5.3) software. In totality, data from 1944 heart failure patients (N = 966 on catheter ablation; N = 978 on medical therapy) with concomitant atrial fibrillation were included. Patients in the catheter ablation group exhibited a significant reduction in all-cause mortality (RR 0.63 [95% CI 0.48, 0.83]; P=0.001; I2 = 17%). Moreover, there was a notable decrease in cardiovascular death among patients undergoing catheter ablation (RR 0.53 [95% CI 0.34, 0.81]; P=0.004; I2 = 20%). Patients who underwent catheter ablation demonstrated a marked improvement in LVEF (MD 5.79 [95% CI 3.13, 8.44]; P <0.0001; I2 = 82%). The 6MWT revealed superior outcomes in the catheter ablation group (MD 22.69 [95% CI 9.87, 35.50]; P=0.0005; I2 = 38%). Heart failure patients with concomitant atrial fibrillation undergoing catheter ablation therapy exhibited notable improvements in LVEF and 6MWT, alongside a significantly reduced risk of all-cause mortality and cardiovascular death compared to those receiving solely medical therapy. These findings shed light on the potential advantages and superior outcomes associated with catheter ablation therapy in preserving cardiac chamber function and mitigating mortality in such a patient cohort. However, further investigations are warranted to understand the long-term benefits and optimal management strategies for such individuals. [ABSTRACT FROM AUTHOR]
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The Role Of Combined Renin-Angiotensin-Aldosterone System Inhibitors (RAASi) Plus Beta Blocker Therapy For Cardiotoxicity Prevention In Patients Under Chemotherapy For Breast Cancer: A Meta-analysis Of Randomized Controlled Trials.Introduction: Anti-neoplastic agents, including anthracyclines and trastuzumab, frequently employed in breast cancer treatment carry on considerable cardiotoxic effects impairing both cardiac chamber and cardiac fiber parameters leading to incident heart failure. In response to this challenging side effect, numerous randomized controlled trials (RCTs) have investigated the cardioprotective efficacy of RAASi and beta-blockers (BBs) in patients undergoing anthracycline and trastuzumab chemotherapy. We aim to perform an updated meta-analysis to elucidate the potential cardioprotective properties of these medications in patients undergoing chemotherapy for breast cancer.Methods: A comprehensive search of the literature was performed through April 2024 on PubMed, EMBASE and Clinicaltrials.gov. In total, data from 4 randomized studies were extracted and analyzed. The primary analysis was the effect of RAASi and BBs on LVEF as well as global longitudinal strain (GLS). Data were analyzed using a random-effects model to derive weighted mean differences (WMDs) and 95% confidence intervals for both LVEF and GLS. Data was analyzed using Review Manager 5.3 (RevMan 5.3) software.Results: In total, data from 248 patients (N = 124 on cardioprotection; N = 124 without cardioprotection) undergoing treatment with anti-neoplastic agents for breast cancer were included. At the end of treatment, patients undergoing cardioprotective therapy demonstrated improved LVEF preservation compared to the control group, (mean difference 2.14 [0.03, 4.25]; P=0.05; I2 = 79%). In addition, patients undergoing dual RAASi + BB therapy showed better GLS preservation compared to control group (mean difference –1.37 [-2.01, -0.72]; P < 0.0001; I2 = 0%).Conclusion: In breast cancer patients undergoing anti-neoplastic regimens comprising anthracycline and trastuzumab, the concomitant administration of RAASi and BBs demonstrated better LVEF as well as GLS preservation upon completion of treatment over those without cardioprotective therapy. These findings shed light on the potential benefit derived from the synergistic effects of RAASi and BBs therapy in safeguarding both cardiac chamber and fiber functions amidst aggressive anti-cancer regimens, although further investigations still need to be conducted.
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The genomic and clinical consequences of replacing procarbazine with dacarbazine in escalated BEACOPP for Hodgkin lymphoma: a retrospective, observational studyBackground: Procarbazine-containing chemotherapy regimens are associated with cytopenias and infertility, suggesting stem-cell toxicity. When treating Hodgkin lymphoma, procarbazine in escalated-dose bleomycin-etoposide-doxorubicin-cyclophosphamide-vincristine-procarbazine-prednisolone (eBEACOPP) is increasingly replaced with dacarbazine (eBEACOPDac) to reduce toxicity. We aimed to investigate the impact of this drug substitution on the mutation burden in stem cells, patient survival, and toxicity. Methods: In this two-part retrospective, observational study, we first compared mutational landscapes in haematopoietic stem and progenitor cells (HSPCs) from patients with advanced-stage Hodgkin lymphoma in remission for at least 6 months who had been treated with eBEACOPDac (eBEACOPDac cohort), eBEACOPP (real-world eBEACOPP cohort), or doxorubicin-bleomycin-vinblastine-dacarbazine (ABVD); in buccal DNA from five children of a female patient with classical Hodgkin lymphoma treated with eBEACOPP before conceiving the third child; in sperm DNA from a patient with mild oligospermia treated with eBEACOPP; and in caecal adenocarcinoma and healthy colon tissue from a survivor of Hodgkin lymphoma treated with chlorambucil-vinblastine-procarbazine-prednisolone. For the second part, we analysed efficacy and toxicity data from adult patients (aged >16 years) treated with first-line eBEACOPDac (eBEACOPDac cohort) at 25 centres across UK, Ireland, and France; efficacy was compared with the German HD18 eBEACOPP trial data and toxicity with a UK real-world dataset. Participants in the German HD18 and UK real-world datasets were adults (aged >16 years) with previously untreated Hodgkin lymphoma, treated with first-line eBEACOPP. We had two co-primary objectives: to define the comparative stem-cell mutation burden and mutational signatures after treatment with or without procarbazine-containing chemotherapy (first study part); and to determine progression-free survival of patients with Hodgkin lymphoma treated with eBEACOPP or eBEACOPDac (second study part). Secondary objectives included overall survival and explored differences in specific toxicity outcomes, including transfusion requirements and measures of reproductive health (second study part). Findings: In the first part of the study (mutational analysis), patients treated with eBEACOPP (n=5) exhibited a higher burden of point mutations in HSPCs compared with those treated with eBEACOPDac (n=4) or ABVD (n=3; excess mutations 1150 [95% CI 934-1366] vs 290 [241-339] vs 186 [116-254]). Two novel mutational signatures, SBSA (SBS25-like) and SBSB, were identified in HSPCs and in a single neoplastic and healthy colon sample from patients who received procarbazine-containing chemotherapy. SBSB was also identified in germline DNA of three children conceived after eBEACOPP and in sperm of a male patient treated with eBEACOPP. SBSC was detected in patients treated with either ABVD or eBEACOPDac. In the second part of the study (efficacy and toxicity analysis), dacarbazine substitution did not appear to compromise efficacy or safety. 312 patients treated with eBEACOPDac (eBEACOPDac cohort; treated 2017-22, 186 [60%] male, median follow-up 36·0 months [IQR 25·2-50·1]) had a 3-year progression-free survival of 93·3% (95% CI 90·3-96·4), which was similar to the 93·3% [95% CI 92·1-94·4]) progression-free survival seen in 1945 patients in the German HD18 eBEACOPP trial (treated 2008-14, 1183 [61%] male, median follow-up 57·0 months [35·4-64·7]). Patients treated with eBEACOPDac required fewer blood transfusions (mean 1·70 units [SD 2·77] vs 3·69 units [3·89]; p<0·0001), demonstrated higher post-chemotherapy sperm concentrations (median 23·4 million per mL [IQR 11·0-632·3] vs 0·0 million per mL [0·0-0·001]; p=0·0040), and had earlier resumption of menstrual periods (mean 5·04 months [SD 3·07] vs 8·77 months [5·57]; p=0·0036) compared with 73 patients treated with eBEACOPP in the UK real-world dataset. Interpretation: Procarbazine induces a higher mutation burden and novel mutational signatures in patients with Hodgkin lymphoma treated with eBEACOPP and their germline DNA, raising concerns for the genomic health of survivors of Hodgkin lymphoma and hereditary consequences for their offspring. However, replacing procarbazine with dacarbazine appears to mitigate gonadal and stem-cell toxicity while maintaining similar clinical efficacy. Funding: Addenbrooke's Charitable Trust and Wellcome Trust.
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A Case of Dual Secreting Adrenal Lesion With Multiple Complications Resulting From Hormonal Abnormalities.Introduction: Dual secreting adrenal tumours with catecholamine and ACTH secretion are rare. This dual secretion may alter the presentation of a Pheochromocytoma, which makes the diagnosis challenging [1]. Case report: A 47-year-old woman presented to the local emergency department with intermittent palpitations, abdominal pain and high blood pressure 220/96 mmHg.Investigation showed hypokalemia 3.0 mmol/L (3.5 - 5.3), and metabolic alkalosis (pH7.50, HCO3 32 mmol/L). A CT abdomen showed a 36 mm right adrenal lesion, which was initially reported as a myelolipoma by the local hospital. Plasma normetadrenaline 1.18 nmol/L (0 - 1.07), metadrenaline 0.88 nmol/L (0 - 0.33), and cortisol 2251 nmol/L were raised. She was started on spironolactone and phenoxybenzamine. Subsequent MRI showed a 3.4 cm right adrenal adenoma with cystic areas. ACTH was 156 ng/L (7.2-63.3) and 1mg overnight Dexamethasone suppression test failed to suppress serum cortisol. MRI pituitary was normal.Whilst awaiting outpatient review, the patient was re-admitted with DKA (new onset diabetes mellitus with high ketones and anion gap acidosis), and severe hypokalemia 1.4mmol/L, requiring critical care admission. She also required intubation and a broncho-alveolar lavage and was treated for pneumocystis jiroveci pneumonia (PJP). A discussion at the regional specialised endocrine MDT made a diagnosis of right pheochromocytoma with ectopic ACTH secretion with hyperplasia of the left adrenal gland, with no other clear source of ACTH on axial imaging, and high dose metyrapone initiated resulting in rapid control of the hypercortisolaemia. Autoantibodies for Type 1 diabetes mellitus were negative. On review at the regional endocrine centre, she was clearly Cushingoid, but with normal electrolytes, and maintained on medical therapy for 30 weeks to improve her clinical state prior to a right retroperitoneal adrenalectomy. Following this there was complete resolution of her clinical state and normalisation of plasma metanephrines, blood glucose, blood pressure, and plasma ACTH levels (30 ng/L) on no therapy. Histology showed a pheochromocytoma and adrenal cortical hyperplasia, although ACTH immunoreactivity was negative. Conclusion: This case highlights an unusual presentation of Cushing’s syndrome secondary to an ACTH-secreting pheochromocytoma (the challenges were absence of initial clinical signs of Cushing’s and borderline plasma metanephrine levels); complicated by new onset Diabetes Mellitus, DKA (in the absence of absolute insulin deficiency), and development of PJP [2]. Clinical resolution following surgery points towards the pheochromocytoma being the source of ACTH, as ACTH immunoreactivity may be negative. Normal pituitary morphology argues against ectopic CRH secretion.
