European Consensus Recommendations Research Articles

Diagnosis of sarcopenia on thoracic computed tomography and its association with postoperative survival after anatomic lung cancer resection

Computer tomography-derived skeletal muscle index normalized for height in conjunction with muscle density enables single modality-based sarcopenia assessment that accounts for all diagnostic criteria and cutoff recommendations as per the widely accepted European consensus. Yet, the standard approach to quantify skeletal musculature at the third lumbar vertebra is limited for certain patient groups, such as lung cancer patients who receive chest CT for tumor staging that does not encompass this lumbar level. As an alternative, this retrospective study assessed sarcopenia in lung cancer patients treated with curative intent at the tenth thoracic vertebral level using appropriate cutoffs. We showed that skeletal muscle index and radiation attenuation at level T10 correlate well with those at level L3 (Pearson’s R = 0.82 and 0.66, p < 0.001). During a median follow-up period of 55.7 months, sarcopenia was independently associated with worse overall (hazard ratio (HR) = 2.11, 95%-confidence interval (95%-CI) = 1.38–3.23, p < 0.001) and cancer-specific survival (HR = 2.00, 95%-CI = 1.19–3.36, p = 0.009) of lung cancer patients following anatomic resection. This study highlights feasibility to diagnose sarcopenia solely by thoracic CT in accordance with the European consensus recommendations. The straightforward methodology offers easy translation into routine clinical care and potential to improve preoperative risk stratification of lung cancer patients scheduled for surgery.

Appropriate referral and selection of patients with chronic pain for spinal cord stimulation: European consensus recommendations and e-health tool.

BackgroundSpinal cord stimulation (SCS) is an established treatment for chronic neuropathic, neuropathic‐like and ischaemic pain. However, the heterogeneity of patients in daily clinical practice makes it often challenging to determine which patients are eligible for this treatment, resulting in undesirable practice variations. This study aimed to establish patient‐specific recommendations for referral and selection of SCS in chronic pain.MethodsA multidisciplinary European panel used the RAND/UCLA Appropriateness Method (RUAM) to assess the appropriateness of (referral for) SCS for 386 clinical scenarios in four pain areas: chronic low back pain and/or leg pain, complex regional pain syndrome, neuropathic pain syndromes and ischaemic pain syndromes. In addition, the panel identified a set of psychosocial factors that are relevant to the decision for SCS treatment.ResultsAppropriateness of SCS was strongly determined by the neuropathic or neuropathic‐like pain component, location and spread of pain, anatomic abnormalities and previous response to therapies targeting pain processing (e.g. nerve block). Psychosocial factors considered relevant for SCS selection were as follows: lack of engagement, dysfunctional coping, unrealistic expectations, inadequate daily activity level, problematic social support, secondary gain, psychological distress and unwillingness to reduce high‐dose opioids. An educational e‐health tool was developed that combines clinical and psychosocial factors into an advice on referral/selection for SCS.ConclusionsThe RUAM was useful to establish a consensus on patient‐specific criteria for referral/selection for SCS in chronic pain. The e‐health tool may help physicians learn to apply an integrated approach of clinical and psychosocial factors.SignificanceDetermining the eligibility of SCS in patients with chronic pain requires careful consideration of a variety of clinical and psychosocial factors. Using a systematic approach to combine evidence from clinical studies and expert opinion, a multidisciplinary European expert panel developed detailed recommendations to support appropriate referral and selection for SCS in chronic pain. These recommendations are available as an educational e‐health tool (https://www.scstool.org/).

CME-Laboratory 61: New European Consensus Recommendations on Dyslipidemia

CME-Laboratory 61: New European Consensus Recommendations on Dyslipidemia Abstract. The lipid status primarily serves to estimate the risk of atherosclerotic cardiovascular diseases (ASCVD). LDL cholesterol (LDL-C) is the primary target of lipid-lowering therapies. NonHDL cholesterol and apolipoprotein B are secondary targets. The European Cardiology and Atherosclerosis Societies have lowered their treatment targets for all risk groups. Triglycerides and HDL cholesterol are also recommended for risk assessment, but are not therapeutic goals. Lipoprotein (a) is a strongly genetically determined ASCVD risk factor and contains a statin-resistant part of LDL-C. The quality of laboratory diagnostics for all lipid risk factors is in need of improvement due to the fact that it is too dependent on methods and in view of the indication of new and expensive lipid-modifying therapies.

Genomic Characterization Provides Diagnostic Clarity in Cases with Overlapping Bone Marrow Fibrosis and Monocytosis

Introduction: Chronic myelomonocytic leukemia (CMML) and primary myelofibrosis (MF) are distinct myeloid malignancies with clinical and pathologic features that often overlap. The presence of significant bone marrow fibrosis with concomitant monocytosis can be diagnostically challenging. Distinguishing between these two clinical entities has important prognostic and therapeutic implications. In this study, we aimed to genomically characterize cases with overlapping features of both fibrosis and monocytosis and describe their clinical outcomes. Then, using well-established CMML and MF databases, we aimed to identify disease-specific genomic abnormalities to allow for improved diagnostic characterization.Methods: Including molecularly annotated patients (pts) from our CMML and MF databases, we created 3 cohorts. Cohort 1 was comprised of MF pts without significant monocytosis. Cohort 2 included CMML pts with absent/minimal bone marrow fibrosis. Cohort 3 included CMML pts with fibrosis and MF pts with monocytosis. Significant fibrosis defined as grade 2-3 by European consensus recommendations. Monocytosis defined as an absolute (>800/µL, the upper limit of normal in our laboratory) and relative (>10%) peripheral monocyte count. Cohorts 1 and 2 were compared to establish disease-specific somatic gene mutation patterns. Enriched variables were those that occurred significantly more often with p < 0.05. Specificity threshold of > 95% was used. Blinded pathological review of overlap bone marrow cases revealed concordance with original diagnosis in > 95% of cases.Results: Cohorts 1, 2 and 3 were comprised of 181, 168 and 61 pts, respectively. Among 61 pts in cohort 3, 26 had a prior CMML diagnosis and 35 had prior MF diagnosis. Median OS (mOS) in cohort 1 was 161 months (mo) compared to 35 mo in cohort 2 (p < 0.001) and 42 mo in cohort 3 (p < 0.001). mLFS for cohorts 1, 2, and 3 were not reached, 61 mo and 42 mo, respectively (p < 0.001).We compared molecular and cytogenetic abnormalities between cohort 1 and 2, assessing individual and commonly co-occurring abnormalities. Genomic abnormalities more common in CMML were mutations in TET2 (p < 0.001), RAS (p < 0.001), RUNX1 (p < 0.001), SRSF2 (p < 0.001), CBL (p = 0.05), ASXL1 (p = 0.04), TET2/SRSF2 (p < 0.001), TET2/ASXL1 (p < 0.001), TET2/RUNX1 (p = 0.03), SRSF2/ASXL1 (p = 0.004), and normal karyotype (p = 0.002). Genomic abnormalities more common in MF included driver mutations (i.e. JAK2, MPL, or CALR) (p < 0.001), del 20q (p = 0.03), del 13q (p < 0.001), and trisomy 9 (p = 0.004). Disease-specific abnormalities were those that were enriched in either CMML or MF with a specificity of >95%. CMML-specific abnormalities included RAS mutations and co-mutations in TET2/RUNX1, TET2/SRSF2, and SRSF2/ASXL1. MF-specific genomic abnormalities included del20q, del13q, and trisomy 9.We applied these disease-specific genomic abnormalities to cohort 3 to see if these findings could stratify pts toward a CMML-like genotype or MF-like genotype. Of 61 patients, 29 displayed only CMML-like genomic features (genomic CMML), 7 only MF-like features (genomic MF), 4 had both CMML and MF-specific features (genomic overlap) and 21 genomically undefined. Among those in cohort 3 with clinical MF diagnosis, 16 (46%) were reclassified as genomic CMML, 6 (17%) as genomic MF, 3 (9%) as genomic overlap, and 10 (31%) as genomically undefined. Among those with an original clinical diagnosis of CMML, 1 was redefined as genomic MF. OS for genomic CMML did not differ from genomic MF (p = 0.70). There was a trend for inferior LFS in genomic CMML compared to genomic MF (40 mo vs 59 mo, p = 0.19). Multivariate analysis identified the strongest prognostic features in cohort 3 as age > 70 (OR 9.4, p = 0.05), platelet count < 100,000/µL (OR 4.6, p = 0.02) and degree of bone marrow fibrosis (OR 5.1, p = 0.009).Conclusions: Specific genomic features distinguish CMML from MF. Application of these findings to pts with overlapping clinicopathologic features provides clarity in >50% of cases, primarily reclassifying patients as CMML. Clinically, outcomes in this overlap group with bone marrow fibrosis and monocytosis mirror those of CMML, regardless of genomic assignment; however, the presence of thrombocytopenia and magnitude of bone marrow fibrosis provide further prognostic discrimination. Future studies testing CMML-like therapeutic strategies should be considered in MF with monocytosis. [Display omitted] DisclosuresKuykendall:Celgene: Honoraria; Janssen: Consultancy. Sweet:BMS: Honoraria; Celgene: Honoraria, Speakers Bureau; Jazz: Speakers Bureau; Astellas: Consultancy; Phizer: Consultancy; Novartis: Consultancy, Honoraria, Speakers Bureau; Agios: Consultancy; Jazz: Speakers Bureau; Agios: Consultancy; Phizer: Consultancy; Astellas: Consultancy; Novartis: Consultancy, Honoraria, Speakers Bureau; BMS: Honoraria; Celgene: Honoraria, Speakers Bureau. Sallman:Celgene: Research Funding, Speakers Bureau. List:Celgene: Research Funding. Komrokji:Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau.

Anterior T-Wave Inversion in Young White Athletes and Nonathletes: Prevalence and Significance

BackgroundAnterior T-wave inversion (ATWI) on electrocardiography (ECG) in young white adults raises the possibility of cardiomyopathy, specifically arrhythmogenic right ventricular cardiomyopathy (ARVC). Whereas the 2010 European consensus recommendations for ECG interpretation in young athletes state that ATWI beyond lead V1 warrants further investigation, the prevalence and significance of ATWI have never been reported in a large population of asymptomatic whites. ObjectivesThis study investigated the prevalence and significance of ATWI in a large cohort of young, white adults including athletes. MethodsIndividuals 16 to 35 years of age (n = 14,646), including 4,720 females (32%) and 2,958 athletes (20%), were evaluated by using a health questionnaire, physical examination, and 12-lead ECG. ATWI was defined as T-wave inversion in ≥2 contiguous anterior leads (V1 to V4). ResultsATWI was detected in 338 individuals (2.3%) and was more common in women than in men (4.3% vs. 1.4%, respectively; p < 0.0001) and more common among athletes than in nonathletes (3.5% vs. 2.0%, respectively; p < 0.0001). T-wave inversion was predominantly confined to leads V1 to V2 (77%). Only 1.2% of women and 0.2% of men exhibited ATWI beyond V2. No one with ATWI fulfilled diagnostic criteria for ARVC after further evaluation. During a mean follow-up of 23.1 ± 12.2 months none of the individuals with ATWI experienced an adverse event. ConclusionsATWI confined to leads V1 to V2 is a normal variant or physiological phenomenon in asymptomatic white individuals without a relevant family history. ATWI beyond V2 is rare, particularly in men, and may warrant investigation.

Recommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry disease: the European Fabry Working Group consensus document.

IntroductionFabry disease (FD) is a lysosomal storage disorder resulting in progressive nervous system, kidney and heart disease. Enzyme replacement therapy (ERT) may halt or attenuate disease progression. Since administration is burdensome and expensive, appropriate use is mandatory. We aimed to define European consensus recommendations for the initiation and cessation of ERT in patients with FD.MethodsA Delphi procedure was conducted with an online survey (n = 28) and a meeting (n = 15). Patient organization representatives were present at the meeting to give their views. Recommendations were accepted with ≥75% agreement and no disagreement.ResultsFor classically affected males, consensus was achieved that ERT is recommended as soon as there are early clinical signs of kidney, heart or brain involvement, but may be considered in patients of ≥16 years in the absence of clinical signs or symptoms of organ involvement. Classically affected females and males with non-classical FD should be treated as soon as there are early clinical signs of kidney, heart or brain involvement, while treatment may be considered in females with non-classical FD with early clinical signs that are considered to be due to FD. Consensus was achieved that treatment should not be withheld from patients with severe renal insufficiency (GFR < 45 ml/min/1.73 m2) and from those on dialysis or with cognitive decline, but carefully considered on an individual basis. Stopping ERT may be considered in patients with end stage FD or other co-morbidities, leading to a life expectancy of <1 year. In those with cognitive decline of any cause, or lack of response for 1 year when the sole indication for ERT is neuropathic pain, stopping ERT may be considered. Also, in patients with end stage renal disease, without an option for renal transplantation, in combination with advanced heart failure (NYHA class IV), cessation of ERT should be considered. ERT in patients who are non-compliant or fail to attend regularly at visits should be stopped.ConclusionThe recommendations can be used as a benchmark for initiation and cessation of ERT, although final decisions should be made on an individual basis. Future collaborative efforts are needed for optimization of these recommendations.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-015-0253-6) contains supplementary material, which is available to authorized users.

WITHDRAWAL OF MAINTAINENCE INFLIXIMAB THERAPY

Aims/BackgroundInfliximab (IFX) is a chimeric monoclonal antibody effective for inducing and maintaining remission in Crohn's disease (CD) and ulcerative colitis (UC). Long term therapy is efficacious for maintaining clinical remission;...

Concordance of HIV Type 1 Tropism Phenotype to Predictions Using Web-Based Analysis of V3 Sequences: Composite Algorithms May Be Needed to Properly Assess Viral Tropism

Genotypic prediction of HIV-1 tropism has been considered a practical surrogate for phenotypic tests and recently an European Consensus has set up recommendations for its use in clinical practice. Twenty-five antiretroviral-experienced patients, all heavily treated cases with a median of 16 years of antiretroviral therapy, had viral tropism determined by the Trofile assay and predicted by HIV-1 sequencing of partial env, followed by interpretation using web-based tools. Trofile determined 17/24 (71%) as X4 tropic or dual/mixed viruses, with one nonreportable result. The use of European consensus recommendations for single sequences (geno2pheno false-positive rates 20% cutoff) would lead to 4/24 (16.7%) misclassifications, whereas a composite algorithm misclassified 1/24 (4%). The use of the geno2pheno clinical option using CD4 T cell counts at collection was useful in resolving some discrepancies. Applying the European recommendations followed by additional web-based tools for cases around the recommended cutoff would resolve most misclassifications.

Hepatitis B vaccine -- do we need boosters?

This review analyses the cumulated data from a number of long-term follow-up studies among infants, children and adults vaccinated against hepatitis B in industrialised and developing countries. Despite low or undetectable antibody responses years after vaccination, the development of HBsAg was a rarity and, if present, only transient. Some vaccinees developed anti-HBc responses but none developed an HB carrier state or clinical manifestations of disease. Studies demonstrating anamnestic responses among those with low or undetectable anti-HBs levels following challenge with HB vaccine, together with the production of anti-HBs in circulating B-cells by spot ELISA, confirmed the presence of immune memory among vaccinees. Anamnestic anti-HBs responses all correlate close in kinetics and magnitude with proliferative T-cell responses. The accumulated data from studies assessed in this Review indicate that protection is dependent on immune memory, rather than declining anti-HBs responses and add additional weight to the European Consensus recommendations (12) that following a complete course of vaccination, booster doses are unnecessary in immunocompetent persons. If implemented, this recommendation will have considerable cost benefits world-wide.