Challenging Group Of Patients Research Articles

Outcomes of atrial fibrillation ablation in patients with or without silent pulmonary veins from prior ablation procedure

Pulmonary venous (PV) electrical recovery underlies most arrhythmia recurrences after atrial fibrillation (AF) ablation. Little is known about procedural profiles and outcomes of patients with electrically silent PVs upon redo ablation for AF. In a prospectively maintained registry, we enrolled 838 consecutive patients (2013-2016) undergoing redo ablation procedures. Ablation procedures targeted the PVs, the PV antra, and non-PV sites at operators' discretion. Procedural profiles and clinical outcomes were assessed. The primary outcome was freedom from AF after a 3-monthblanking period. The secondary outcome was improvement in quality of life. Most patients undergoing redo AF ablation (n = 684, 82%) had PV reconnection while the remaining 154 (18%) had electrically silent PVs. Patients with recurrent AF and electrically silent PVs were older (66 vs. 64 years, p = .02), had more prior ablation procedures (median 2 IQR 1-3 vs 1 IQR 1-2 p = .001), were more likely to have non-paroxysmal AF (62% vs. 49%, p = .004) and atrial flutter (48%vs. 29%, p = .001) and had significantly larger left atrial volumes (89 vs. 81 ml, p = .003). Patients with silent PVs underwent a more extensive non-PV ablation strategies with antral extension of prior ablation sets in addition to ablation of the roof, appendage, inferior to the right PVs, peri-mitral flutter lines, cavotricuspid isthmus lines and ablation in the coronary sinus. Upon one year of follow-up, patients with electrically silent PVs were less likely to remain free from recurrent atrial arrhythmias (64% vs. 76%, p = .008). Regardless of PV reconnection status, redo ablation resulted in improvement in quality of life. Rhythm control with extensive ablation allowed maintenance of sinus rhythm in about two thirds of patients with silent PVs during redo AF ablation procedures. Regardless of PV reconnection status, redo ablation resulted in improvement in quality of life. This remains a challenging group of patients, highlighting the need to better understand non-PV mediated AF.

Cementless Total Knee Arthroplasty Using a Highly Porous Tibial Baseplate in Morbidly Obese Patients: Minimum 5-Year Follow-Up.

Morbidly obese patients undergoing cemented primary total knee arthroplasty (TKA) can pose a challenging problem with implant survivorship due to greater stress at the cement-bone interface. With the advent of additive manufacturing (three-dimensional printing), highly porous implants are now readily available. The purpose of this study was to review the results of primary TKA in the morbidly obese (body mass index [BMI] ≥ 40) patient using a highly porous cementless tibial baseplate. This is a retrospective study of 167 TKAs in patients with morbid obesity undergoing primary cementless TKA with a minimum 5-year follow-up. A total of 6 patients died and 14 were lost to follow-up, leaving 147 TKAs in 136 patients with a mean follow-up of 66 months (range 60-79 months). The average age was 59 years (range 36-84 years) and average BMI was 45 kg/m2 (range 39.5-63.9). Clinical results, patient-reported outcome measures, radiographs, and complications were reviewed. There were 9 failures requiring revision, including 3 for aseptic tibial loosening (2.0%), 2 for deep infection (1.4%), 2 for patellar resurfacing (1.4%), 1 for patella instability (0.7%), and 1 for extensor mechanism rupture (0.7%). Knee Society Score (KSS) improved from 48 to 90 at 2- and 5-year follow-up. KSS function score improved from 49 to 68 and 79 at 2- and 5-year follow-up, respectively. Survivorship with aseptic loosening as the endpoint was 98.0% at 5 years. Cementless TKA using a highly porous tibial baseplate in morbidly obese patients demonstrated excellent clinical results with 98% survivorship at 5 years and appears to offer durable long-term biologic fixation as an alternative to mechanical cement fixation in this challenging group of patients.

Consensus on communication curriculum content in Danish undergraduate medical education: A Delphi study

Background The acquisition of skills in patient-centered communication is a critical aspect of medical education which demands both resource-intensive instruction and longitudinal opportunities for learning. Significant variation currently exists in the content and timing of communication education. The aim of this study was to establish consensus regarding communication curriculum content for undergraduate medical education (UME) within the country of Denmark. Methods This study employed a Delphi process which is a widely accepted method for establishing consensus among experts and can be utilized to guide planning and decision-making in education. For this study, consensus was based on greater than 60% agreement between participants. Diverse stakeholders, representing all four universities with medical schools in Denmark, participated in an iterative three-round Delphi process which involved: (1) identifying key curricular elements for medical student education, (2) rating the importance of each item, and (3) prioritizing items relative to one another and rating each item based on the level of mastery that was expected for each skill (i.e. knowledge, performance with supervision, or performance independently). Results A national sample of 149 stakeholders participated with a 70% response rate for round 1, 81% for round 2, and 86% for round 3. The completed Delphi process yielded 56 content items which were prioritized in rank order lists within five categories: (1) establishing rapport, engaging patient perspectives and responding to needs; (2) basic communication skills and techniques; (3) phases and structure of the encounter; (4) personal characteristics and skills of the student; (5) specific challenging patient groups and context-dependent situations. Discussion Using a Delphi process, it was possible to achieve consensus regarding communication curriculum content for UME. These findings provide an important foundation for ensuring greater uniformity in UME, as well as supporting the important longitudinal goals of communication skill development across medical training.

Primary intraocular lens implantation in infants with unilateral congenital cataract operated before 12 weeks of age

The aim of this study was to report visual outcome and safety after cataract surgery with primary intraocular lens implantation before 12 weeks of age. Infants with visually significant unilateral congenital cataract having primary IOL implantation in the capsular bag before 12 weeks of age in 2007-2016 were enrolled for a prospective study examination in 2017. The medical records were also reviewed. In total, 23 patients with a median age at cataract surgery of 32 days (range, 12-75 days) were included. Seventeen (74%) eyes had persistent foetal vasculature (PFV). After a median follow-up of 6.3 years (range, 1.4-10.9 years), the corrected distance visual acuity was 0.8 logMAR (range, 3.0-0.1 logMAR). All, except one eye, required surgery for visual axis opacification (VAO), with a median of two (range 0-5) additional surgical procedures. Four (17%) eyes developed secondary glaucoma. Cataract surgery with primary IOL implantation before 12 weeks of age resulted in a high number of VAO operations, and the visual outcome varied considerably, showing the range in outcome for this challenging patient group. Co-existent PFV in these young patients was common. The incidence of secondary glaucoma was similar to other studies, despite the young age at surgery, high percentage of PFV and number of surgical procedures for VAO.

How I treat triple‐class refractory multiple myeloma

Immunomodulatory imide drugs (IMiDs), proteasome inhibitors (PIs) and anti-CD38 monoclonal antibodies (MoAbs) are the pillars of modern multiple myeloma (MM) therapy. The prognosis of patients with MM that became refractory to these three classes (triple-class refractory [TCR]) is historically poor. Observational studies indicate an overall response rate of ~30% and overall survival inferior to 1 year with existing therapies. While no randomised trial has been completed in this setting, several agents exploring new mechanisms of action showed activity in TCR MM in single-arm trials, including anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T cells, anti-BCMA antibody-drug conjugates and exportin 1 (XPO1) inhibitors. Among agents in development, anti-BCMA bispecific T-cell engagers (TCE), and non-BCMA TCEs demonstrated activity in most patients. Additionally, specific agents may exhibit unique activity in biologically defined patient subsets, as exemplified by venetoclax in t(11;14) MM. The main open questions in TCR MM are preferred sequence of existing therapies, the utility of sequential use of agents with similar mechanism of action, but different immunotherapy target and the relative efficacy of the different anti-BCMA platforms. Here, we summarise the existing literature and provide general guidance on selecting therapy for this challenging and heterogenous group of patients.

Pain in Persons with Disorders of Consciousness.

Pain and suffering in persons with disorders of consciousness (DoC) remain poorly understood, frequently unaddressed or inadequately addressed, and controversial on numerous levels. This narrative literature review will address a number of critical issues germane to pain and suffering in this challenging group of patients, providing an introductory overview of the topic, perspectives on current knowledge regarding pain pathoanatomy and pathophysiology, and a review of common pain generators and factors that can lead to the chronifcation of pain. Caveats on bedside pain assessment challenges, as well as electrophysiologic and neuroimaging findings in these patients, will also be explored. Pain management techniques, including non-pharmacological and pharmacological, will be reviewed. Ethical considerations in the context of pain and suffering in persons with disorders of consciousness will round out the review prior to our concluding comments.

Transplant in acute alcoholic hepatitis: a relative contraindication.

The aim of this review is to provide a critical analysis of liver transplantation for alcoholic hepatitis, with an emphasis on barriers to long-term success in current implementation strategies across the United States. Alcohol-associated liver disease is the most rapidly increasing indication for liver transplantation in the USA. Its most severe form, acute alcoholic hepatitis, has a rising incidence particularly in the young, and is associated with a high mortality risk. Although excellent outcomes following liver transplantation for alcoholic hepatitis can be achieved, several barriers limit its routine use. These constraints include risk of allograft dysfunction, the recognition of alcohol use disorder as a multisystem disease and ethical considerations. Although liver transplantation is an important option in a carefully selected group of candidates, it should not be considered the standard of care in this condition. Consistency, transparency and consensus are necessary to formulate and implement policy changes at the national level. Following liver transplantation, wraparound services are important for relapse prevention, and to ensure long-term success and survival in this challenging group of patients.

Сучасні можливості ортезування в комплексному лікуванні еквінополоварусної деформації стоп у дітей

В матеріалах статті наведено сучасні варіанти використання ортезів (брейсів) різних конструкцій, що застосовуються у теперішній час для запобігання розвинення рецидивів у комплексному лікуванні еквінополоварусної деформації стоп у дітей різного віку. Авторами запропоновані до застосування власні патентовані конструкції брейсів та ортезів. Аналіз наявних ортезів показує, що їх використання у дітей з деформаціями стоп відповідає вимогам сьогодення та забезпечує: іммобілізацію сегмента; сприятливі умови для відновних процесів; опорну функцію сегмента; є профілактикою рецидивів деформацій, а при необхідності дозволяє провести поступове, поетапне усунення деформації при збереженні задовільної функції суглобів стопи, що значно покращує результати лікування цієї складної групи хворих і дає підставу рекомендувати ортези до широкого клінічного застосування.

Critical Care Management of the Parturient with Cardiac Disease

Parturient with heart disease forms a challenging group of patients and requires specialized critical care support in the peripartum period. Maternal heart disease may remain undiagnosed till the second trimester of pregnancy, presenting frequently after 20 weeks of gestation, due to increased demands imposed on the cardiovascular system and pose a serious risk to the life of mother and fetus. Management of critically ill parturient with heart disease must be tailored according to individual assessment of the patient and requires a strategic, multidisciplinary, and protocol-based approach. A dedicated obstetric intensive care unit (ICU) and team effort are the need of the hour.How to cite this articleGarg R, Hariharan UR, Malik I. Critical Care Management of the Parturient with Cardiac Disease. Indian J Crit Care Med 2021;25(Suppl 3):S230–S240.

Haematopoietic Stem Cell Transplantation in Adolescents and Young Adults With Acute Lymphoblastic Leukaemia: Special Considerations and Challenges.

Adolescents and young adults (AYAs) represent a challenging group of acute lymphoblastic leukaemia (ALL) patients with specific needs. While there is growing evidence from comparative studies that this age group profits from intensified paediatric-based chemotherapy, the impact and optimal implementation of haematopoietic stem cell transplantation (HSCT) in the overall treatment strategy is less clear. Over recent years, improved survival rates after myeloablative allogeneic HSCT for ALL have been reported similarly for AYAs and children despite differences in transplantation practise. Still, AYAs appear to have inferior outcomes and an increased risk of treatment-related morbidity and mortality in comparison with children. To further improve HSCT outcomes and reduce toxicities in AYAs, accurate stratification and evaluation of additional or alternative targeted treatment options are crucial, based on specific molecular and immunological characterisation of ALL and minimal residual disease (MRD) assessment during therapy. Age-specific factors such as increased acute toxicities and poorer adherence to treatment as well as late sequelae might influence treatment decisions. In addition, educational, social, work, emotional, and sexual aspects during this very crucial period of life need to be considered. In this review, we summarise the key findings of recent studies on treatment approach and outcomes in this vulnerable patient group after HSCT, turning our attention to the different approaches applied in paediatric and adult centres. We focus on the specific needs of AYAs with ALL regarding social aspects and supportive care to handle complications as well as fertility issues. Finally, we comment on potential areas of future research and concisely debate the capacity of currently available immunotherapies to reduce toxicity and further improve survival in this challenging patient group.

Perspectives and Expertise in Establishing a Therapeutic Drug Monitoring Programme for Challenging Childhood Cancer Patient Populations.

The utility of Therapeutic Drug Monitoring (TDM) in the setting of childhood cancer is a largely underused tool, despite the common use of cytotoxic chemotherapeutics. While it is encouraging that modern advances in chemotherapy have transformed outcomes for children diagnosed with cancer, this has come at the cost of an elevated risk of life-changing long-term morbidity and late effects. This concern can limit the intensity at which these drugs are used. Widely used chemotherapeutics exhibit marked inter-patient variability in drug exposures following standard dosing, with fine margins between exposures resulting in toxicity and those resulting in potentially suboptimal efficacy, thereby fulfilling criteria widely accepted as fundamental for TDM approaches. Over the past decade in the UK, the paediatric oncology community has increasingly embraced the potential benefits of utilising TDM for particularly challenging patient groups, including infants, anephric patients and those receiving high dose chemotherapy. This has been driven by a desire from paediatric oncologists to have access to clinical pharmacology information to support dosing decisions being made. This provides the potential to modify doses between treatment cycles based on a comprehensive set of clinical information, with individual patient drug exposures being used alongside clinical response and tolerability data to inform dosing for subsequent cycles. The current article provides an overview of recent experiences of conducting TDM in a childhood cancer setting, from the perspectives of the clinicians, scientists and pharmacists implementing TDM-based dosing recommendations. The ongoing programme of work has facilitated investigations into the validity of current approaches to dosing for some of the most challenging childhood cancer patient groups, with TDM approaches now being expanded from well-established cytotoxic drugs through to newer targeted treatments.

Comment on: Safety of phakic intraocular collamer lens implantation in 95 highly myopic special-needs children

We discussed the study by Reynolds et al. during the ESCRS journal club on July 7, 2021.1 In this retrospective case series, the investigators presented perioperative and longer-term adverse event data from 95 special-needs children or adults with myopia who could not comply with spectacles and/or contact lenses and underwent implantation of an intraocular collamer lens (ICL). Although this study addressed an important clinical question in a challenging patient group, we would like to highlight some points of discussion that are of relevance to the interpretation of the study. The definition of adverse events as minor or major seemed somewhat controversial. For example, in this study, wound leak requiring repair was designated as major since it necessitated a return to the theater, whereas endothelial cell loss was classed as minor. Although this nomenclature may be understandable in the context of a short-term clinical study after intervention, these definitions may not lend appropriate weight to possible serious longer-term safety concerns. The endothelial cell count was only measured in 31 of 160 eyes (ie, less than 19% of the cohort). Consequently, firm conclusions about the long-term safety of ICL implantation in this patient group cannot be made. Furthermore, these eyes are likely to be unrepresentative of the cohort since they are presumably from the most cooperative individuals. A greater yield may have been possible through specular microscopy in the lateral decubitus position undertaken under general anesthesia, although we appreciate that repeated anesthesia may have an overall detrimental effect on special-needs children. In this highly heterogeneous patient group, a more detailed presentation of the data might have allowed the reader to appreciate the relationships between clinical parameters (ie age and refraction) and adverse events. For example, the mean preoperative spherical equivalent refractive error was −11 D (range: −4 to −22) and mean age was 9.3 years (range: 1.8 to 25) with some nonpediatric patients. Illustration of distribution of refractive error and age as individual datapoints would have allowed the reader to determine, for example, whether there is a relationship between preoperative refractive error or age and postoperative endothelial cell loss? Moreover, could these parameters predict the development of postoperative pupil block? Furthermore, the details of adverse events by group (age, refraction, and underlying disorder) would have been helpful. Although the authors reported that there were 95 children and 160 implanted eyes, the article states that 35 unilateral and 60 bilateral surgeries were performed, which adds up to only 155 eyes. Previous studies on the subject have shown that ICL implantation is safe in children with a low rate of adverse events.2 Many of these studies were conducted by the same study group.3,4 Nevertheless, randomized controlled studies are needed in a larger number of pediatric patients to argue that the benefits outweigh the risks as stated by the researchers in their conclusion. Specifically, the measurement of postoperative endothelial cell counts in most individuals in such cohorts are required to make meaningful statements about long-term safety.

P128 BOTULINUM TOXIN A IN CONJUNCTION WITH NEGATIVE PRESSURE WOUND THERAPY AND MESH-MEDIATED FASCIAL TRACTION PROVIDES HIGH RATE OF FASCIAL CLOSURE IN PATIENTS WITH OPEN ABDOMEN

Abstract Aim Presentation of our data on Vacuum-Assisted Wound Closure and Permanent Onlay Mesh-Mediated Fascial Traction (VAWCPOM) in combination with Botulinum Toxin A (BTX-A) injection in the lateral abdominal wall as a treatment of the open abdomen (OA). Material and Methods This is a retrospective case series including patients treated for OA from January 2017 till March 2021 with VAWCPOM and BTX-A. Patient records were collected from medical charts, incl. age, sex, body mass index (BMI), comorbidity, initial fascial defect size, time until fascial closure, complications and, when available, outpatient follow-up. Results A total of 33 patients with OA were included. The mean age was 62,5 years, male/female ratio was 15:18, with a mean BMI of 35,4 kg/m2. The mean width of the fascial defect was 13,5 cm (5 - 25cm). The rate of fascial closure was 96,9%, achieved within a mean of 22,7 days. Fascial closure was not attainable in one patient who developed enterocutaneous fistula under treatment. 22 patients experienced in-hospital complications. Short-term follow-up was conducted in 22 patients, with hernia recurrences in three. Conclusions Treatment of OA remains a surgical challenge. This case series shows promising results with a high rate of fascial closure using a combination of VAWCPOM and BTX-A and an acceptable rate of postoperative complications in this severely challenging patient group. The rate of primary closure indicates that this may be the future management of open abdomen.

Persistent challenges in endovascular treatment decision-making for acute ischaemic stroke.

Although endovascular treatment (EVT) is the gold standard for treating acute stroke patients with large vessel occlusion (LVO), multiple challenges in decision-making for specific conditions persist. Recent evidence on a selection of patient subgroups will be discussed in this narrative review. Two randomized controlled trials (RCTs) have been published in EVT of basilar artery occlusion (BAO). Large single arm studies showed promising results in Patients with low Alberta stroke program early CT score (ASPECTS) and more distal vessel occlusions. Recent data confirm patients with low National Institutes of Health Stroke Scale (NIHSS) despite LVO to represent a heterogeneous and challenging patient group. The current evidence does not justify withholding EVT from BAO patients as none of the RCTs showed any signal of superiority of BMT alone vs. EVT. Patients with low ASPECTS, more distal vessel occlusions and patients with low NIHSS scores should be included into RCTs if possible. Without participation in a RCT, patients should be selected for EVT based on age, severity and type of neurological impairment, time since symptom onset, location of the ischaemic lesion and perhaps also results of advanced imaging.

Abstract 11962: Applying a Deep-Learning Approach for Automated Quantification of Epicardial Adipose Tissue on Coronary Computed Tomography Angiography in Challenging Clinical Populations

Introduction: Epicardial adipose tissue (EAT) is a visceral fat deposit within the pericardial sac. The automated quantification of EAT volume is possible from routine CCTA scans via a deep-learning approach. Purpose: To apply a deep-learning approach for automated segmentation of EAT from CCTA scans in challenging clinical populations to assess the real-world viability of automated segmentation. Methods: A deep-learning automated EAT segmentation tool using a 3D Residual-U-Net neural network architecture for 3D volumetric segmentation of CCTA data was created and trained on over 2500 consecutive CCTA scans performed as part of clinical care in patients with stable chest pain from 2015 onwards within the European arm of the Oxford Risk Factors And Non Invasive Imaging (ORFAN) Study. External validation was performed in 817 scans from USA ORFAN sites (Figure 1A demonstrates human vs machine segmented EAT volume for a single case). The network was then applied to sets of unseen CCTAs from the AdipoRedOx Study (UK, n=253) and the SCOTHEART trial (UK, n=1558) to test its ability to perform EAT segmentations in challenging but common patient populations: 1) recent cardiac surgery (<6 weeks post operation), 2) BMI ≥ 40, 3) CAC ≥ 400, 4) significant metallic artefact within the pericardium, and 5) a combined group of recent open-heart surgery, BMI ≥ 30 & CAC ≥ 400. Results: There was excellent correlation between machine and human expert in the within-ORFAN validation cohort (Lin's concordance correlation coefficient (CCC) = 0.972, for both whole pericardial volume and EAT volume). CCC for machine vs human experts for all five challenging but common patient groups were also excellent (range 0.955-0.962) and are presented in Figure 1B-F. Conclusions: A new deep learning network achieves excellent automated segmentation of EAT and can be used to provide this information in a highly accurate and reproducible way, even in challenging common clinical populations.

Tissue Sodium Storage in Patients With Heart Failure: A New Therapeutic Target?

Preclinical data suggest sodium deposited (without water) in tissues may lead to aberrant remodeling and systemic inflammation, independently of fluid overload in patients with heart failure (HF). Tissue salt storage can be measured noninvasively and quantitatively with 23Na-magnetic resonance imaging. We aimed to investigate the possibility that patients with HF complicated by renal dysfunction are subject to higher tissue sodium concentration exposure than patients with chronic kidney disease alone. We conducted an exploratory study including 18 patients with HF, 34 hemodialysis patients (with no meaningful renal clearance of sodium), and 31 patients with chronic kidney disease, with glomerular filtration rate matched to the patients with HF. Every patient underwent 23Na-magnetic resonance imaging of the calf, to quantify tissue sodium and allow comparison among the 3 patient groups. There were no differences in age, sex, and body mass index between groups. Median (interquartile range) skin sodium content in HF (31 [23-37] mmol/L) was very high and indistinguishable from skin sodium content in hemodialysis patients (30 [22-35] mmol/L), P=0.6. Patients with HF exhibited significantly higher skin sodium content than matched estimated glomerular filtration rate chronic kidney disease patients (22 [19-26] mmol/L), P=0.005. Median muscle sodium content in patients with HF was significantly higher than in patients with chronic kidney disease, P=0.002. There was no relationship with estimated glomerular filtration rate in patients with HF. We report a significant correlation between skin sodium and urinary sodium (P=0.04) but no correlation with muscle sodium. Patients who were assessed as being volume depleted (sodium excretion fraction <1%) had lower skin sodium content than patients with sodium excretion fraction >1% (P=0.03). We have demonstrated that patients with HF characteristically have very high levels of skin sodium storage, comparable to well-characterized extreme levels seen in patients with end-stage kidney disease requiring hemodialysis. 23Na-magnetic resonance imaging may allow precision medicine in the management of this challenging group of patients with HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03004547.

The systemic right ventricle in adult congenital heart disease: why is it still such a challenge and is there any hope on the horizon?

Adult congenital heart disease patients with systemic right ventricle comprise a distinctly clinically challenging group of patients with increased morbidity and mortality. This article aims to review the different subgroups, most common complications and different treatment strategies. Most commons long-term complications include heart failure and arrhythmias. Heart failure medical therapy treatments include several new agents, which show promise in systemic right ventricle patients. In addition, interventional therapies to mitigate atrioventricular valve regurgitation, baffle/conduit stenosis are discussed. Furthermore, several electrophysiological approaches to manage tachyarrhythmias as well as bradycardias are discussed. There is ongoing excitement on the new medical as well as interventional therapies that could provide benefit in additional to standard goal-directed medical therapy. There is an array of medications as well as interventions aimed to treat patients with systemic right ventricle with limited benefits. A multidisciplinary approach with a prudent combination of such therapies to maximize benefit is imperative. This article reviews the data supporting such therapies.

Optimal echocardiographic assessment of myocardial dysfunction for arrhythmic risk stratification in phospholamban mutation carriers.

Aims Phospholamban (PLN) p.Arg14del mutation carriers are at risk of developing malignant ventricular arrhythmias (VAs) and/or heart failure. Currently, left ventricular ejection fraction (LVEF) plays an important role in risk assessment for VA in these individuals. We aimed to study the incremental prognostic value of left ventricular mechanical dispersion (LVMD) by echocardiographic deformation imaging for prediction of sustained VA in PLN p.Arg14del mutation carriers.Methods and resultsWe included 243 PLN p.Arg14del mutation carriers, which were classified into three groups according to the ‘45/45’ rule: (i) normal left ventricular (LV) function, defined as preserved LVEF ≥45% with normal LVMD ≤45 ms (n = 139), (ii) mechanical LV dysfunction, defined as preserved LVEF ≥45% with abnormal LVMD >45 ms (n = 63), and (iii) overt LV dysfunction, defined as reduced LVEF <45% (n = 41). During a median follow-up of 3.3 (interquartile range 1.8–6.0) years, sustained VA occurred in 35 individuals. The negative predictive value of having normal LV function at baseline was 99% [95% confidence interval (CI): 92–100%] for developing sustained VA. The positive predictive value of mechanical LV dysfunction was 20% (95% CI: 15–27%). Mechanical LV dysfunction was an independent predictor of sustained VA in multivariable analysis [hazard ratio adjusted for VA history: 20.48 (95% CI: 2.57–162.84)].Conclusion LVMD has incremental prognostic value on top of LVEF in PLN p.Arg14del mutation carriers, particularly in those with preserved LVEF. The ‘45/45’ rule is a practical approach to echocardiographic risk stratification in this challenging group of patients. This approach may also have added value in other diseases where LVEF deterioration is a relative late marker of myocardial dysfunction.

1232P Understanding the diagnostic and treatment landscape in EGFRm advanced non-small cell lung cancer (aNSCLC) patients with exon 20 insertion mutations (Ex20ins)

While most EGFR mutations are tyrosine kinase inhibitor (TKI) sensitive, Ex20ins are generally resistant to TKI treatment, making this a challenging patient group to treat. This study examined the treatment patterns and diagnostic landscape of aNSCLC patients with Ex20ins.

Defining the Role of Cellular Immune Signatures in Diagnostic Evaluation of Suspected Tuberculosis.

BackgroundDiagnosis of paucibacillary tuberculosis (TB) including extrapulmonary TB is a significant challenge, particularly in high-income, low-incidence settings. Measurement of Mycobacterium tuberculosis (Mtb)-specific cellular immune signatures by flow cytometry discriminates active TB from latent TB infection (LTBI) in case-control studies; however, their diagnostic accuracy and clinical utility in routine clinical practice is unknown.MethodsUsing a nested case-control study design within a prospective multicenter cohort of patients presenting with suspected TB in England, we assessed diagnostic accuracy of signatures in 134 patients who tested interferon-gamma release assay (IGRA)-positive and had final diagnoses of TB or non-TB diseases with coincident LTBI. Cellular signatures were measured using flow cytometry.ResultsAll signatures performed less well than previously reported. Only signatures incorporating measurement of phenotypic markers on functional Mtb-specific CD4 T cells discriminated active TB from non-TB diseases with LTBI. The signatures measuring HLA-DR+IFNγ + CD4 T cells and CD45RA−CCR7−CD127− IFNγ −IL-2−TNFα + CD4 T cells performed best with 95% positive predictive value (95% confidence interval, 90–97) in the clinically challenging subpopulation of IGRA-positive but acid-fast bacillus (AFB) smear-negative TB suspects.ConclusionsTwo cellular immune signatures could improve and accelerate diagnosis in the challenging group of patients who are IGRA-positive, AFB smear-negative, and have paucibacillary TB.