Regression Of Mass Research Articles

Cardiac MRI measurements of pericardial adipose tissue volumes in patients on in-centre nocturnal hemodialysis.

Conversion from conventional hemodialysis (CHD) to in-centre nocturnal hemodialysis (INHD) is associated with left ventricular (LV) mass regression, but the underlying mechanisms are not fully understood. Using cardiac MRI (CMR), we examined the effects of INHD on epicardial adipose tissue (EAT) and paracardial adipose tissue (PAT), and the relationships between EAT, PAT and LV remodeling, biomarkers of nutrition, myocardial injury, fibrosis and volume. We conducted a prospective multicenter cohort study of 37 patients transitioned from CHD to INHD and 30 patients on CHD (control). Biochemical markers and CMR were performed at baseline and 52weeks. CMR images were analyzed by independent readers, blinded to order and treatment group. Among 64 participants with complete CMR studies at baseline (mean age 54; 43% women), there were no significant differences in EAT index(60.6 ± 4.3mL/m2 vs 64.2 ± 5.1mL/m2, p = 0.99) or PATindex (60.0 ± 5.4mL/m2 vs 53.2 ± 5.9mL/m2, p = 0.42) between INHD and CHD groups. Over 52weeks, EATindex and PAT indexdid not change significantly in INHD and CHD groups (p = 0.21 and 0.14, respectively), and the changes in EATindex and PATindex did not differ significantly between INHD and CHD groups (p = 0.30 and 0.16, respectively). Overall, changes in EAT indexinversely correlated with changes in LV end-systolic volume index (LVESVI) but not LV end-diastolic volume index (LVEDVI), LV mass index (LVMI), and LV ejection fraction (LVEF). Changes in PATindex inversely correlated with changes in LVESVI, LVMI and positively correlated with changes in LVEF. There were no correlations between changes in EAT indexor PAT indexwith changes in albumin, LDL, triglycerides, troponin-I, FGF-23, or NT-proBNP levels over 52weeks (all p > 0.30). INHD was not associated with any changes in EATindex and PATindex over 12months. Changes in EATindex were not significantly associated with changes in markers of LV remodeling, nutrition, myocardial injury, fibrosis, volume status. In contrast, changes in PATindex, which paradoxically is expected to exert less paracrine effect on the myocardium, were correlated with changes in LVESVI, LVMI and LVEF. Larger and longer-term studies may clarify the role of PAT in cardiac remodeling with intensified hemodialysis. CLINICALTRIALS. NCT00718848.

Effect of T-photocycle and wavelength on photoperiodic induction in Indian weaver bird (Ploceus philippinus)

ABSTRACT Photoperiodic responses of a photosensitive species depend on the species-specific critical day length (CD), determined by the entrainment of the endogenous circadian rhythm of photoinducibility. We examined the entrainment pathway of the circadian photoperiodic system of photosensitive weaver birds. Birds were subjected to T = 22,24 and 26 h photocycles, with 11- and 12-h photophase to study the photoperiodic induction and synchronization of bird’s circadian system with reference of different light wavelengths. Two experiments were performed on adult male weaver birds. In experiment 1, birds were exposed to T = 22 and 26 h LD-cycles, having 11-h photophase with red and blue light wavelength, while in experiment 2, birds were exposed to T = 22, 24 and 26 h LD-cycles, having 12-h photophase with red and blue light wavelength. Observations on change in body mass and testis size were recorded at monthly intervals. There was a significant effect of red light wavelength on photoperiodic induction of testicular growth in the birds exposed to T = 22 h (11L:11D and 12L:10D) and T = 26 h (11L:15D and 12L:14D; both wavelength), but not when exposed to T = 24 h (12L:12D) photophase. Further, body mass regression was faster in birds of T = 26 h photophase (12L:14D) under blue wavelength. Thus, the above results are indicative of the influence of light wavelength on the endogenous programming that times seasonal responses in body fattening and testicular growth-regression of Indian weaver bird.

Pathological complete response after afatinib treatment of stage IV oligometastatic adenocarcinoma of the lung: the role of pulmonary surgery

BackgroundSome oligometastatic lung cancer patients, after induction systemic chemotherapy or tyrosine kinases inhibitor treatment, followed by aggressive radical consolidative treatment, have improved overall survival. Unfortunately, clinical criteria cannot assess such patients.Case presentationWe hereby reported the case of a 55-year-old female with lower back pain and bilateral lower leg numbness for months and who had an osteolytic bone lesion over the third lumbar vertebra. In February 2017, a third lumbar vertebra biopsy showed metastatic adenocarcinoma, compatible with lung origin (thyroid transcription factor-1 positive [TTF-1], L858R mutation positive). Complete imaging of the right lower lobe (RLL) showed a spiculated mass of about 3.4 × 2.2 cm, and a trans-bronchoscopic lung biopsy revealed non-small cell carcinoma of lung origin (positive for TTF-1 and negative for p40). Tentative diagnosis was RLL adenocarcinoma, cT2aN0M1b, with bone metastasis at L3. The epidermal growth factor receptor-tyrosine kinase inhibitor afatinib was prescribed beginning April 2017. A November 2018 follow-up CT scan showed regression in the RLL lung mass. A whole-body positron emission tomography-computed tomography showed RLL lung nodule with faint uptake and mildly increased uptake in the L3 vertebra. After providing informed consent, the patient received uniportal video-assisted thoracoscopic RLL lobectomy and radical mediastinal lymph node dissection on December 25, 2018. The final pathology report was fibrotic scar with no residual tumor cells, compatible with post-treatment status, ypT0N0. Curative intent radiotherapy was also applied to the L3 vertebra after the operation. The patient is still alive for more than 32 months after initially diagnosed with metastatic lung adenocarcinoma.ConclusionsOur case provides additional data to support that tissue assessment through primary lung tumor resection after systemic treatment of oligometastic lung cancer by minimally invasive surgery can reveal the treatment effect and potentially provide a surrogate endpoint in further clinical trials.

PD-L1/PD-1 Axis in Glioblastoma Multiforme.

Glioblastoma (GBM) is the most popular primary central nervous system cancer and has an extremely expansive course. Aggressive tumor growth correlates with short median overall survival (OS) oscillating between 14 and 17 months. The survival rate of patients in a three-year follow up oscillates around 10%. The interaction of the proteins programmed death-1 (PD-1) and programmed cell death ligand (PD-L1) creates an immunoregulatory axis promoting invasion of glioblastoma multiforme cells in the brain tissue. The PD-1 pathway maintains immunological homeostasis and protects against autoimmunity. PD-L1 expression on glioblastoma surface promotes PD-1 receptor activation in microglia, resulting in the negative regulation of T cell responses. Glioblastoma multiforme cells induce PD-L1 secretion by activation of various receptors such as toll like receptor (TLR), epidermal growth factor receptor (EGFR), interferon alpha receptor (IFNAR), interferon-gamma receptor (IFNGR). Binding of the PD-1 ligand to the PD-1 receptor activates the protein tyrosine phosphatase SHP-2, which dephosphorylates Zap 70, and this inhibits T cell proliferation and downregulates lymphocyte cytotoxic activity. Relevant studies demonstrated that the expression of PD-L1 in glioma correlates with WHO grading and could be considered as a tumor biomarker. Studies in preclinical GBM mouse models confirmed the safety and efficiency of monoclonal antibodies targeting the PD-1/PD-L1 axis. Satisfactory results such as significant regression of tumor mass and longer animal survival time were observed. Monoclonal antibodies inhibiting PD-1 and PD-L1 are being tested in clinical trials concerning patients with recurrent glioblastoma multiforme.

P912Outcomes of aortic valve surgery in non-stenotic valves: mechanical replacement versus repair

Abstract Background Considering selected patients and the expertise of the surgical team, aortic valve repair (REPAIR) has been recognized as an alternative to aortic valve replacement. Aim To compare mid-term survival, need of reoperation and hemodynamic results after mechanical replacement (MECH) or REPAIR in non-stenotic aortic valve disease. Methods Retrospective single-center cohort study including consecutive patients younger than 70 years-old, with non-stenotic aortic valve disease, who underwent 1st aortic valve surgery with MECH or REPAIR (2 experienced surgeons), during a 6-year period. Concomitant procedures were not excluded. First follow-up echocardiogram was performed within 3 months after surgery (median). Mean follow-up time was 4 years, maximum 7. According to the data distribution appropriate statistical tests to compare independent samples were used. Mid-term survival and need of reoperation were studied through Kaplan-Meier curves and Cox regression. Results MECH was performed in 94 (56.6%) and REPAIR in 72 patients. Individuals in MECH group were older and presented higher NYHA functional class than REPAIR group (51±11 vs 47±13 years, p=0.048; 30 vs 4%, p<0.001). MECH group presented higher prevalence of rheumatic etiology (17 vs 3%, p<0.001). Although aortic root intervention was more frequent in MECH group (41 vs 17%, p<0.001), there were no differences in cardiopulmonary bypass and cross clamping aortic times (166 vs 148 minutes, p=0.16; and 121 vs 108 minutes, p=0.15 in MECH and REPAIR group, respectively). Left ventricle mass regression was similar (18 vs 21%, p=0.450, in MECH and REPAIR group, respectively). Mid-term survival (REPAIR cumulative survival 97% and MECH 93%, Log-Rank test p=0.752) and reoperation rates were similar between the two groups. REPAIR procedure failed in 3 patients: 2 months (new aortic regurgitation, AR), 7 months (infective endocarditis, IE) and 4 years (AR). MECH failed in 2 patients: 6 months (IE) and 2 months after surgery (prosthesis thrombosis) (Figure 1). Conclusion Aortic valve repair seems to be safe and effective in this single-center study showing similar results comparing with mechanical aortic valve replacement. We should reinforce the need of judiciously select patients for this complex surgical technique and the specialized training of the surgical team. Further studies are needed to provide reliable recommendations on this theme.

TCT-140 Impact of Left Ventricular Mass Regression on Long-Term Clinical Outcomes After Transcatheter Aortic Valve Replacement: An Analysis of the PARTNER 1 and 2 Trials and Registries

TCT-140 Impact of Left Ventricular Mass Regression on Long-Term Clinical Outcomes After Transcatheter Aortic Valve Replacement: An Analysis of the PARTNER 1 and 2 Trials and Registries

TCT-135 The Impact of Baseline Aortic Regurgitation on the Degree of Left Ventricular Remodeling After Transcatheter Aortic Valve Implantation

The effect of baseline aortic regurgitation (AI) on left ventricular (LV) geometry regression following transcatheter aortic valve replacement (TAVR) is not well defined. We aimed to assess the effect of native valve AI on LV mass regression and changes in LV dimensions at 1-year post-TAVR. We

Regression of Left Ventricular Mass in Athletes Undergoing Complete Detraining Is Mediated by Decrease in Intracellular but Not Extracellular Compartments.

Background:Athletic cardiac remodeling can occasionally be difficult to differentiate from pathological hypertrophy. Detraining is a commonly used diagnostic test to identify physiological hypertrophy, which can be diagnosed if hypertrophy regresses. We aimed to establish whether athletic cardiac remodeling assessed by cardiovascular magnetic resonance is mediated by changes in intracellular or extracellular compartments and whether this occurs by 1 or 3 months of detraining.Methods:Twenty-eight athletes about to embark on a period of forced detraining due to incidental limb bone fracture underwent clinical assessment, ECG, and contrast-enhanced cardiovascular magnetic resonance within a week of their injury and then 1 month and 3 months later.Results:After 1 month of detraining, there was reduction in left ventricular (LV) mass (130±28 to 121±25 g; P<0.0001), increase in native T1 (1225±30 to 1239±30 ms; P=0.02), and extracellular volume fraction (24.5±2.3% to 26.0±2.6%; P=0.0007) with no further changes by 3 months. The decrease in LV mass was mediated by a decrease in intracellular compartment volume (94±22 to 85±19 mL; P<0.0001) with no significant change in the extracellular compartment volume. High LV mass index, low native T1, and low extracellular volume fraction at baseline were all predictive of regression in LV mass in the first month.Conclusions:Regression of athletic LV hypertrophy can be detected after just 1 month of complete detraining and is mediated by a decrease in the intracellular myocardial compartment with no change in the extracellular compartment. Further studies are needed in athletes with overt and pathological hypertrophy to establish whether native T1 and extracellular volume fraction may complement electrocardiography, echocardiography, cardiopulmonary exercise testing, and genetic testing in predicting the outcome of detraining.

Left ventricular mass regression in patients without patient-prosthesis mismatch after aortic valve replacement for aortic stenosis.

The relationship between the degree of a postoperative effective orifice area and temporal regression of a left ventricular mass after aortic valve replacement for aortic stenosis is unclear in patients without patient-prosthesis mismatch. We therefore investigated the relationship and independent predictors of left ventricular mass regression. Among 307 consecutive patients who underwent aortic valve replacement for aortic stenosis between 2008 and 2013, 223 patients receiving a periodic inspection by echocardiography for at least 3 consecutive years after surgery without patient-prosthesis mismatch were enrolled in the present study. Temporal regression of left ventricular mass index was compared between two groups that were classified equally according to effective orifice area index obtained at a 1-week postoperative echocardiographic examination: < 1.20cm2/m2 (n = 112) and > 1.20cm2/m2 (n = 111). We also determined the predictors affecting left ventricular mass regression. No difference existed in the preoperative left ventricular mass index between the two groups (p = 0.431). Temporal regression of the left ventricular mass index was similar in the two groups. The independent predictors of left ventricular mass regression were male gender (p = 0.007) and preoperative left ventricular mass index (p = 0.003), but valve size was not (p = 0.641). There was no relationship between the degree of postoperative effective orifice area and temporal regression of the left ventricular mass in patients without patient-prosthesis mismatch. The independent predictors of left ventricular mass regression were male gender and preoperative left ventricular mass index.

Aortic valve replacement-induced changes in native T1 are related to prognosis in severe aortic stenosis: T1 mapping cardiac magnetic resonance imaging study.

Native T1 times from T1 mapping cardiac magnetic resonance (CMR) are associated with myocardial fibrosis in aortic stenosis (AS). We investigated whether changing patterns in native T1 predict clinical outcomes after aortic valve replacement (AVR) in severe AS patients. Forty-three patients with severe AS (65.9 ± 8.1 years; 24 men) who underwent T1 mapping CMR at baseline and 1 year after AVR were prospectively enrolled. Upper limit of native T1 from healthy volunteers was used to define normal myocardium and diffuse fibrosis (native T1 < 1208.4 and ≥1208.4 ms, respectively). Participants were categorized into Group 1 (pre- and post-AVR normal myocardium; n = 11), Group 2 (pre-AVR diffuse fibrosis and post-AVR normal myocardium; n = 18), and Group 3 (post-AVR diffuse fibrosis; n = 14). Native T1 significantly decreased 1 year after AVR (pre-AVR, 1233.8 ± 49.7 ms; post-AVR, 1189.1 ± 58.4 ms; P < 0.001), which was associated with left ventricular (LV) mass regression (△native T1 vs. △LV mass index, r = 0.454, P = 0.010) and systolic function improvement (△native T1 vs. △LV ejection fraction, r = -0.379, P = 0.012). Group 2 showed greater functional improvements, whereas these benefits were blunted in Group 3. Group 3 had significantly worse outcomes than Group 1 [hazard ratio (HR), 9.479, 95% confidence interval (CI) 1.176-76.409; P = 0.035] and Group 2 (HR 3.551, 95% CI 1.178-10.704; P = 0.024). AVR-induced changes in native T1 values are associated with LV systolic functional changes as well as prognosis in severe AS. Post-AVR T1 mapping CMR can be used as an imaging biomarker.

Hemodynamics and reverse remodeling associated with Mosaic, Perimount and Trifecta aortic bioprostheses.

ABSTRACTIntroduction: The implantation rate of aortic bioprostheses is increasing. Their durability has improved to some extent over the years and they allow for future transcatheter valve-in-valve deployment. In the lack of long term follow up, their hemodynamic profile, i.e. transvalvular mean pressure gradient and effective orifice area indexed, and the associated left ventricular reverse remodeling indexed are useful surrogates for clinical outcomes.Areas covered: A systematic review of the literature was conducted by searching Medline, Cochrane, Scielo, Embase databases, and grey literature until July 2018 for articles that perform comparisons among the three most popular aortic bioprostheses. Six randomized and 12 non-randomized studies were included with 565 patients receiving a Mosaic, 1334 a Perimount and 557 a Trifecta valve. These articles are heterogeneous but they allow the meta-analytic comparison of the abovementioned outcomes.Expert opinion: Compared to the Perimount valve, the Mosaic is hemodynamically inferior, while the Trifecta is superior. Despite these statistically significant differences, the left ventricular mass regression indexed, that is indicative of reverse remodeling, was comparable in all groups.All patients were similarly benefited. The predilection among these valves is fueled by their hemodynamic profile but not supported by the comparable reverse remodeling.

Changes in Left Ventricular Global Longitudinal Strain after Transcatheter Aortic Valve Implantation according to Calcification Burden of the Thoracic Aorta

After transcatheter aortic valve replacement (TAVR), changes in left ventricular (LV) function are partly influenced by the vascular afterload. The burden of thoracic aorta calcification is a component of vascular afterload. To assess changes in LV systolic function measured with global longitudinal strain (GLS) in relation to the burden of thoracic aorta calcification in patients with severe aortic stenosis treated with TAVR. Calcification of the thoracic aorta was estimated on noncontrast computed tomography in 210 patients (50% male, 80±7years) undergoing TAVR. Conventional and speckle-tracking echocardiography were performed at baseline (prior to TAVR) and 3-6months and 12months after TAVR. Patients were divided according to tertiles of calcification burden of the thoracic aorta. At baseline, patients within the first tertile of thoracic aorta calcification (0-1,395 Hounsfield Units, HU) had better LV systolic function (LV ejection fraction [LVEF], 47%±9%; and LV GLS, -15%±5%) as compared with the second tertile (1,396-4,634 HU; LVEF, 46%±10%; and LV GLS, -14%±4%), and the third tertile (>4,634 HU; LVEF, 44%±10%; and LV GLS, -12%±4%). During follow-up, patients within tertile 1 of calcification of thoracic aorta achieved significantly better LV systolic function and larger regression of LV mass at 12months of follow-up than patients within the other tertiles. This pattern was more pronounced in patients with reduced LVEF at baseline. After TAVR, LVEF and GLS improves and LV mass index is reduced significantly at 3-6 and 12months of follow-up. Patients within the lowest burden of thoracic aorta calcification achieved the best values of LVEF and LV GLS at 1-year follow-up.

New therapeutic target for pediatric anaplastic ependymoma control: study of anti-tumor activity by a Kunitz-type molecule, Amblyomin-X

EPNs comprise a heterogeneous group of neuroepithelial tumors, accounting for about 10% of all intracranial tumors in children and up to 30% of brain tumors in those younger than 3 years. Actually, the pattern therapy for low-grade EPNs includes complete surgical resection followed by radiation therapy. Total surgical excision is often not possible due to tumor location. The aim of this study was to evaluate, for the first time, the anti-tumor activity of Amblyomin-X in 4 primary cultures derived from pediatric anaplastic posterior fossa EPN, Group A (anaplastic, WHO grade III) and one primary culture of a high grade neuroepithelial tumor with MN1 alteration, which was initially misdiagnosed as EPN: i) by in vitro assays: comparisons of temozolomide and cisplatin; ii) by intracranial xenograft model. Amblyomin-X was able to induce cell death in EPN cells in a more significant percentage compared to cisplatin. The cytotoxic effects of Amblyomin-X were not detected on hFSCs used as control, as opposed to cisplatin-treatment, which promoted a substantial effect in the hAFSCs viability. TEM analysis showed ultrastructural alterations related to the process of cell death: mitochondrial degeneration, autophagosomes and aggregate-like structures. MRI and histopathological analyzes demonstrated significant tumor mass regression. Our results suggest that Amblyomin-X has a selective effect on tumor cells by inducing apoptotic cell death and may be a therapeutic option for Group AEPNs.

Sex and regional differences in myocardial plasticity in aortic stenosis are revealed by 3D model machine learning.

Left ventricular hypertrophy (LVH) in aortic stenosis (AS) varies widely before and after aortic valve replacement (AVR), and deeper phenotyping beyond traditional global measures may improve risk stratification. We hypothesized that machine learning derived 3D LV models may provide a more sensitive assessment of remodelling and sex-related differences in AS than conventional measurements. One hundred and sixteen patients with severe, symptomatic AS (54% male, 70 ± 10 years) underwent cardiovascular magnetic resonance pre-AVR and 1 year post-AVR. Computational analysis produced co-registered 3D models of wall thickness, which were compared with 40 propensity-matched healthy controls. Preoperative regional wall thickness and post-operative percentage wall thickness regression were analysed, stratified by sex. AS hypertrophy and regression post-AVR was non-uniform-greatest in the septum with more pronounced changes in males than females (wall thickness regression: -13 ± 3.6 vs. -6 ± 1.9%, respectively, P < 0.05). Even patients without LVH (16% with normal indexed LV mass, 79% female) had greater septal and inferior wall thickness compared with controls (8.8 ± 1.6 vs. 6.6 ± 1.2 mm, P < 0.05), which regressed post-AVR. These differences were not detectable by global measures of remodelling. Changes to clinical parameters post-AVR were also greater in males: N-terminal pro-brain natriuretic peptide (NT-proBNP) [-37 (interquartile range -88 to -2) vs. -1 (-24 to 11) ng/L, P = 0.008], and systolic blood pressure (12.9 ± 23 vs. 2.1 ± 17 mmHg, P = 0.009), with changes in NT-proBNP correlating with percentage LV mass regression in males only (ß 0.32, P = 0.02). In patients with severe AS, including those without overt LVH, LV remodelling is most plastic in the septum, and greater in males, both pre-AVR and post-AVR. Three-dimensional machine learning is more sensitive than conventional analysis to these changes, potentially enhancing risk stratification. Regression of myocardial fibrosis after aortic valve replacement (RELIEF-AS); NCT02174471. https://clinicaltrials.gov/ct2/show/NCT02174471.

Allopurinol treatment adversely impacts left ventricular mass regression in patients with well-controlled hypertension.

Objectives:Previous studies have demonstrated that high-dose allopurinol is able to regress left ventricular (LV) mass in cohorts with established cardiovascular disease. The aim of this study was to assess whether treatment with high-dose allopurinol would regress LV mass in a cohort with essential hypertension, LV hypertrophy and well-controlled blood pressure but without established cardiovascular disease.Methods:We conducted a mechanistic proof-of-concept randomized, placebo-controlled, double-blind trial of allopurinol (600 mg/day) versus placebo on LV mass regression. Duration of treatment was 12 months. LV mass regression was assessed by Cardiac Magnetic Resonance. Secondary outcomes were changes in endothelial function (flow-mediated dilatation), arterial stiffness (pulse wave velocity) and biomarkers of oxidative stress.Results:Seventy-two patients were randomized into the trial. Mean baseline urate was 362.2 ± 96.7 μmol/l. Despite good blood pressure control, LV mass regression was significantly reduced in the allopurinol cohort compared with placebo (LV mass −0.37 ± 6.08 versus −3.75 ± 3.89 g; P = 0.012). Oxidative stress markers (thiobarbituric acid reactive substances) were significantly higher in the allopurinol group versus placebo (0.26 ± 0.85 versus −0.34 ± 0.83 μmol/l; P = 0.007). Other markers of vascular function were not significantly different between the two groups.Conclusion:Treatment with high-dose allopurinol in normouricemic controlled hypertensive patients and LV hypertrophy is detrimental. It results in reduced LV mass regression and increased oxidative stress over a 12-month period. This may be because of an adverse impact on redox balance. Cohort selection for future cardiovascular trials with allopurinol is crucial.

Global longitudinal strain in prosthesis-patient mismatch: relation to left ventricular mass regression and outcomes.

Aortic prosthesis-patient mismatch (PPM) increases left ventricular (LV) afterload and prevents LV mass regression (LVMR) after surgery. This study was designed to investigate the association between the baseline global longitudinal strain (GLS) and the postoperative LVMR, and its relation to adverse outcomes. A total of 316 patients with aortic stenosis undergoing isolated mechanical prosthesis implantation were screened, and data from 91 patients with aortic PPM and 165 non-PPM patients were retrospectively collected. All 256 patients underwent measurement of GLS by two-dimensional speckle-tracking echocardiography preoperatively, and were followed up for postoperative changes of LV mass index (LVMi) and other clinical outcomes. During the follow-up, LVMi in PPM patients decreased significantly from 139.6 ± 20.8 to 119.6 ± 26.5 g/m (P < 0.001). These patients were divided into two groups according to the median value of the reduction rate of LVMi at final follow-up, and preoperative GLS markedly decreased in PPM patients with insignificant reduction in LVMi. Multivariate analysis identified preoperative GLS (odds ratio 3.45, 95% confidence interval 1.27-11.05, P = 0.002) and preoperative LVMi (odds ratio 2.87, 95% confidence interval 1.21-8.13, P = 0.012) as independently associated with an insignificant LVMR. Moreover, PPM patients with limited reduction in LVMi were at an increased risk of cardiac death and major adverse valve-related events. In patients with aortic PPM early after surgery, reduced preoperative GLS could be a novel sensitive risk factor for a limited regression of LV hypertrophy, and this is associated with an increased risk of adverse events in PPM patients.

Changes in dynamic left ventricular function, assessed by the strain-volume loop, relate to reverse remodeling after aortic valve replacement.

Aortic valve replacement (AVR) leads to remodeling of the left ventricle (LV). Adopting a novel technique to examine dynamic LV function, our study explored whether post-AVR changes in dynamic LV function and/or changes in aortic valve characteristics are associated with LV mass regression during follow-up. We retrospectively analyzed 30 participants with severe aortic stenosis who underwent standard transthoracic echocardiographic assessment before AVR [88 (IQR or interquartile range: 22-143) days], post-AVR [13 (6-22) days], and during follow-up [455 (226-907) days]. We assessed standard measures of LV structure, function, and aortic valve characteristics. Novel insight into dynamic LV function was provided through a four-chamber image by examination of the temporal relation between LV longitudinal strain (ε) and volume (ε-volume loops), representing the contribution of LV mechanics to volume change. AVR resulted in immediate changes in structural valve characteristics, alongside a reduced LV longitudinal peak ε and improved coherence between the diastolic and systolic part of the ε-volume loop (all P < 0.05). Follow-up revealed a decrease in LV mass (P < 0.05) and improvements in LV ejection fraction and LV longitudinal peak ε (P < 0.05). A significant relationship was present between decline in LV mass during follow-up and post-AVR improvement in coherence of the ε-volume loops (r = 0.439, P = 0.03), but not with post-AVR changes in aortic valve characteristics or LV function (all P > 0.05). We found that post-AVR improvements in dynamic LV function are related to long-term remodeling of the LV. This highlights the potential importance of assessing dynamic LV function for cardiac adaptations in vivo.NEW & NOTEWORTHY Combining temporal measures of left ventricular longitudinal strain and volume (strain-volume loop) provides novel insights in dynamic cardiac function. In patients with aortic stenosis who underwent aortic valve replacement, postsurgical changes in the strain-volume loop are associated with regression of left ventricular mass during follow-up. This provides novel insight into the relation between postsurgery changes in cardiac hemodynamics and long-term structural remodeling, but also supports the potential utility of the assessment of dynamic cardiac function.

PB2189 FREE LIGHT CHAINS IN MULTIPLE MYELOMA: IS IT TIME TO EXTEND THEIR APPLICATION?

Background:Free Light Chain (FLC) assay is used for multiple myeloma screening, prediction of risk progression and response assessment as indicated by IMWG guidelines, particularly to define stringent complete response (sCR). The assay is also recommended in cases of unmeasurable (non‐secretory, NS) or low values of M‐protein (oligo‐secretory, OS).Aims:Here we describe the value of FLC assay in predicting extramedullary relapse in four MM patients.MethodsDuring the course of therapy, FLC was monitored routinely on a monthly basis.Results:An OS MM IgG κ patient (first case) started in May 2017 4th line KRd therapy, due to new lytic lesions, with negative BM biopsy. During the course of therapy, sIFE remained negative, while sFLC continued to rise (May 2017–March 2018: sFLC κ 175 vs 340 mg/L, rFLC 4.2 vs 19.9). In March 2018 a right femur mass appeared and histology, confirmed EMD relapse. Patient underwent surgical removal and rFLC returned within normal range (1.3).Considering that it was the only site of disease, KRD regimen was restarted in June 2018 for four more cycles. Unfortunately, in November 2018 the knee mass reappeared, and, once again, sFLC was altered (FLC κ 124 mg/L, ratio 25), with negative sIFE. Biopsy of the mass confirmed EMD relapse, BM biopsy remained negative.A patient with IgG κ MM (second case) started in May 2017 2nd line KRd therapy for disease progression, confirmed by BM biopsy. A partial response was obtained quickly, but since March 2018 a progressive rise of rFLC was noticed (March–September 2018: rFLC 0.67 vs 1.67), and it anticipated of 5 months the increase of MP (August 2018). In June 2018 patient complained vague gastrointestinal symptoms and in September a CT scan revealed hepatic nodularities, confirmed by biopsy as hepatic EMD.A LC MM λ patient (third case) started in March 2017 KRd as 2nd line treatment for disease progression (MP 0.7 g/dL, sFLC λ 2000 mg/dL, rFLC 171), with positive BM biopsy. Patient obtained CR after the first cycle, but during the treatment in June 2018 sFLC started increasing and in July alteration of liver and bilirubin tests was noticed, without any clinical sign, always with negative sIFE. In October 2018 sIFE became positive and in November MP reappeared (0.37 g/dL) while both the sFLC (June–November 2018: sFLC λ 53 vs 207 mg/dL; rFLC 6 vs 68) and the liver tests continued to rise. A solid hepatic mass was revealed and biopsy confirmed an EMD relapse.A MM IgA λ patient (fourth case) diagnosed with biopsy of soft paravertebral tissues, was treated with 1st line VMP treatment in September 2018. During the treatment the patient complained sight loss and a CT scan showed the presence of a right ocular mass. The MP was reduced while sFLC increased (September–October 2018: MP 2.4 vs 0.2 g/dL; sFLC λ 158 vs 263 mg/dL; rFLC 5.7 vs 29.4). Biopsy confirmed an aggressive EMD relapse and the patient started 2nd line KRD treatment in October 2018. A complete remission was obtained with ocular mass regression, negative sIFE and improvement of FLC.Unfortunately, in January 2019 during the fourth cycle, a cutaneous lesion appeared on the right tibia, confirmed as EMD relapse. While both the sIFE and BM biopsy remained negative, a slight increase of sFLC was noticed, although always within range.Summary/Conclusion:In all four cases an increase of FLC always preceded the diagnosis of EMD relapse irrespective of MP measurement. We therefore recommend serial use of sFLC assay, particularly in heavily pretreated patients for early detection of aggressive and/or EMD relapse.

Comparison of microscopy to a semi-automated method (FlowCAM®) for characterization of individual-, population-, and community-level measurements of zooplankton

Fully or semi-automated methods are becoming viable, cost-effective alternatives to manual approaches for characterizing zooplankton. The goal of this study was to compare a semi-automated approach (FlowCAM®) and a traditional microscopy method for characterizing zooplankton body size, density, and community structure. We demonstrate that estimating mass from FlowCAM® profile area had similar accuracy to a commonly used length to mass regression model. FlowCAM® and microscopy produced related length measurements for Daphnia, Calanoida, and Cyclopoida. Length measurements of rotifers, nauplii, and Sididae were not significantly related between the two methods, likely because of high morphological variation within taxa. Density comparisons between methods indicated high correlation between the semi-automated approach and microscopy-derived densities with a subtle bias of lower densities with the semi-automated method. After applying a correction factor, independent samples showed similar density estimates between methods, with community composition also not differing between methods. Comparison of processing time between the two methods showed that the semi-automated approach was 11 min (33%) faster per sample. With corrections, semi-automated methods represent a viable and cost-effective alternative to traditional microscopy methods for the processing of zooplankton samples.

Validity of basal metabolic rate prediction equations in elderly women living in an urban tropical city of Brazil

To measure basal metabolic rate (BMR) and to compare it with the values obtained from predictive equations in a sample of elderly (≥60y) women. Cross-sectional study. Seventy-nine women living in Niterói, Rio de Janeiro, Brazil enrolled in physical activity programs open to the community. Anthropometric measures were obtained using standard procedures. Percent body fat (PBF) was assessed by DXA. BMR was measured (BMRm) by indirect calorimetry under standardized conditions and compared with BMR estimated by 14 predictive equations that included elderly individuals in their development. Mean (±SD) age, BMI and PBF were 69.7±6.5y, 27.2±4.6 kg/m2 and 42.1±5.9%. BMRm (4188.3±707.2kJ/day) was significantly lower than estimated BMR by all predictive equations, including the equation developed for the Niteroian adult population (4565.6±607.9kJ/day). This population-specific equation provided the largest number of results within ±10% of BMRm and the lowest overestimation (10.6±15.4%), much lower than the results from the internationally recommended Schofield equation (27.2±17.6%). Regression of calf circumference (CC), age and body mass on BMRm provided similar estimates in comparison to models with fat-free mass (FFM). All predictive equations provided biased, inaccurate estimates of BMR values in comparison to BMRm. Anthropometry and body composition explained only approximately 50% of the variability of BMRm. New equations should account for the variability of organ-metabolic rates and underlying undetected health conditions in older individuals living in tropical regions.