Types Of Terminals Research Articles

Medical Assistance in Dying in Oncology Patients: A Canadian Academic Hospital Experience

<h3>Purpose/Objective(s)</h3> Medical assistance in dying (MAID) was legislatively enacted in Canada in June 2016. MAID is performed most frequently for oncology patients. The aim of this study is to describe the patient, disease and process characteristics in this population. <h3>Materials/Methods</h3> We performed a single-institution review of all oncology patients who requested MAID at a tertiary care hospital between June 2016 and June 2020. A prospective database including patient demographics, terminal illness type, dates of assessment, cause of death, and date of death was used. Additional data such as demographic, oncologic, treatment-related, and symptom-related details were retrospectively collected. Descriptive statistics were reported. Our primary hypothesis is that performance status is one of the important factors associated with MAID provision. <h3>Results</h3> Between June 2016 and June 2020, 346 oncology patients requested and 103 received MAID. Identifiers were available and data were retrospectively collected for 92/103 patients. Median age was 72 (range 25-97) and 54% were female. The most common primary malignancies were lung (15/92, 16%), pancreaticobiliary (14/92, 16%), colorectal (13/92, 14%), and hematologic malignancy (11/92, 12%). Performance status was documented for 60 patients within 1 week of MAID provision; 90% of patients (54/60) had ECOG performance status of 3 or 4, and 42% patients (25/60) had ECOG performance status of 4. At the time of initial MAID request, 65% of patients (60/92) had metastatic disease, among which 52% of patients (31/60) received palliative-intent systemic therapy. Sixteen percent of patients with metastases (10/60) received at least 3 lines of palliative-intent systemic therapy. Median number of days from first MAID assessment to MAID provision was 7 days (range 0 to 349 days). Sixty-seven percent of patients (60/89) received MAID within 10 days of first MAID assessment and 87% (77/89) within 30 days. The most common debilitating symptoms were uncontrolled pain (53%, 49/92), fatigue (37%, 34/92), and dyspnea (27%, 25/92). <h3>Conclusion</h3> Ninety percent of oncology patients who received MAID had ECOG performance status of 3 or 4, which is reflective of patients' poor prognosis and limited ability to perform daily activity. The median time interval between first MAID assessment to MAID received was 7 days and most patients received MAID within 30 days.

DEVS-based modular modelling method of dry bulk terminals

ABSTRACT Considering the diversification of dry bulk terminal types and the complexity of terminal loading and unloading operations, a modular modelling method based on discrete event system specification (DEVS) modelling theory is proposed in this paper. First, we introduced the DEVS into the dry bulk terminal and explained the ideas and main steps of the DEVS-based modular modelling method. Second, a module library and model framework library for dry bulk terminals were developed, and the DEVS expression of the modules and model framework was given. Studies have shown that the production performance of a coal export terminal is generally positively correlated with ship loading and ship arrival density. Terminal operators can improve their ability to respond to future scenarios in two ways: upgrading berth levels and improving ship berthing strategies. The case verifies that the model framework and module library are effective, and the modelling method based on DEVS is feasible.

Analysis on key influence factors of air source heat pumps with field monitored data in Beijing

Air source heat pumps (ASHPs) are in wide use around the world, and their practical applications and continual improvement have attracted great attention. To more fully understand their actual-operational performance, field monitoring was carried out on 103 ASHP systems in Beijing during the 2018–2019 heating season, accompanied by a decoupling analysis of the key influencing factors on performance. The observed seasonal coefficient of system performance (SCOP) ranged from 1.54 to 2.95, with an average of 2.21. Based on this large sample, three key influencing factors were identified, namely: terminal type, operating load rate and capacity regulation characteristics. In terms of terminal type, floor heating systems obtained a relatively high SCOP of 2.37 on average, due to the lower water temperature, compared with a radiator system average of 2.10. As for load rate, oversized capacity is a common problem: the recorded average annual operating load rate was only around 0.48, which resulted in high energy consumption from frequent on–off losses, and also increased power consumption by the circulating pump. This analysis provides engineering reference and support for the design and technological improvement of ASHP systems.

The Effect of Motivation and Compensation on The Performance of Honorer Employees in Type a Simbuang Terminal Service Units Ministry of Transportation of The Republic of Indonesia in Mamuju District

Every agency certainly wants good employee or employee performance. In government agencies such as the Simbuang Type A Terminal of the Ministry of Transportation of the Republic of Indonesia in Mamuju Regency, there are temporary employees who are employed as terminal managers. Due to his status as an honorary employee, his salary scheme is certainly different from that of his colleague who is a civil servant. This study seeks to examine the effect of motivation and compensation obtained by honorary employees at the bus terminal on their performance. This study is a quantitative study that tested two variables and analyzed using multiple linear regression. Sources of data are respondents who are temporary employees at Terminal Type A Simbuang the Ministry of Transportation of the Republic of Indonesia in Mamuju Regency. Data collection techniques used are questionnaires, observation, and documentation studies. The results showed that the motivation variable and the compensation variable had a significant effect either partially or simultaneously on the performance given by the honorary employees.

Preventing Civil War Recurrence: Do Military Victories Really Perform Better than Peace Agreements? Causal Claim and Underpinning Assumptions Revisited

ABSTRACT Existing research suggests that peace is more stable after military victories than it is after peace agreements. This article challenges this conventional wisdom. By applying survival analysis, we demonstrate that peace agreements exhibit just as strong of a relationship to enduring peace as military victories do. Moreover, we investigate the assumptions that underpin the aforementioned claim. These assumptions link peace survival to the type of civil war termination and refer to intervening variables. Using time-series data for 48 civil wars that ended between 1990 and 2009, the empirical analysis finds support for only two underpinning assumptions in favour of victories.

Upper limb prosthesis users: A longitudinal cohort study.

No previous studies have followed prosthesis users with upper limb loss or limb deficiency using their own prostheses to assess change over time. (1) To describe prostheses and terminal device types used at baseline and 1-year follow-up; (2) to examine changes in functional outcomes and device satisfaction over time; and (3) to examine whether changes in outcomes varied across level of amputation and type of prosthesis used. Multisite, observational time series design with in-person functional performance and self-report data collected at baseline and 1-year follow-up. Baseline and follow-up outcome scores were compared using Wilcoxon signed-rank tests. Analyses were stratified by amputation level, time since amputation, prosthesis type, and change in device type. Published minimal detectable change (MDC) values were used to determine whether detectable change in outcome measures occurred. The longitudinal cohort consisted of 64 participants (mean age 64 years, 56% body-powered users). The only significant differences in outcome measures between baseline and follow-up (after adjustment for false discovery) were hours/day of prosthesis use, which increased from 6.0 (4.4) to 7.3 (5.3) hours (P = 0.0022). Differences in prosthesis use intensity remained significant in analyses stratified by amputation level, time since amputation, prosthesis type, and change in device type. Between 14 and 20% of the sample had change in one or more outcome measures that was greater than the known MDC. Most participants had stable outcomes over a year's time, whereas 14-20% experienced either improvement or decline in one or more tests indicating the importance of annual follow-up visits.

Changes in profibrotic activity in cardiovascular diseases

The myocardium consists of several types of cells: cardiomyocytes, cardiac fibroblasts, endothelial cells and smooth muscle cells. Fibroblasts are cells of mesenchymal origin and are present in all tissues in the body. Cardiac damage can activate available CFBs, provoke transformation of endothelial or epithelial cells into fibroblasts, or induce the production of CFBs from hematopoietic cells and bone marrow. The change in ECM is a key point in the remodeling of the heart in response to the disease process. Disruption of the reticular structure of the ECM alters the connection between myocardial cells and blood vessels, thereby disrupting the structure and function of the heart muscle. Type I and III collagen fibrils are the predominant part of the ECM of the heart. They are synthesized as procollagen, which is converted to a mature collagen molecule. Procollagen type I propeptide (PICP), amino-terminal propeptide type I procollagen (PINP) and N terminal type III collagen peptide (PIIINP) are released in proportional amounts in the synthesis of collagen types I and III and can be used as serum markers for these processes. On the other hand the differentiation from CFBs to myoFB is supported by the transforming growth factor beta (TGF-β), connective tissue growth factor (CTGF), a number of cytokines in the ECM and others. The scientific community is faced with the question of which biomarkers to use to identify the early stages of development of cardiac fibrosis, as well as how to assess the degree of progression of this pathological process.

Method for evaluating the dynamic thermal performance of heating terminals based on an analysis of heat quantity and grade

Behavior energy conservation in buildings greatly impacts energy conservation and carbon reductions at the national level, and part-time space heating has become an important part of building operation. Under these conditions, heating terminals with different properties differ significantly in their heat consumption and heat grade demands. However, a comprehensive evaluation of the transference of quantities and grades of heat during the part-time heating of different terminals remains lacking. In this study, we developed a entransy-based analytical method and used it to compare the experimental and field-measured performances of three typical heating terminals (a radiator, radiant flooring, and a fan coil) from start-up to stabilization. The entire energy flow networks — from the heat source to the outdoor environment — were analyzed. Transient and cumulative entransy dissipation was analyzed to determine the energy utilization trends of the terminals. The dissipations between thermal nodes were also explored to intuitively reflect the key process(es) limiting heat transfer in a terminal. Further, we compared variations in heating performance under different operating durations to determine the applicability of each terminal type. Our results suggest that the radiant floor had the greatest entransy dissipation during start-up owing to its high thermal storage capacity and transfer resistance. However, because of the high thermal resistance of the terminal-to-chamber process, the entransy dissipation of the radiator was the greatest following stabilization (accounting for 57.0%), and the difference in the dissipation between radiators and the other terminal would increase with longer operating times.

Trifunctionalization of Aryl Iodides with Two Distinct Nitrogen and Carbon Electrophiles by Palladium/Norbornene Catalysis

Main observation and conclusionHerein, we report a highly chemo‐ and regioselective vicinal trifunctionalization of aryl iodides by palladium/norbornene (Pd/NBE) catalysis. The key feature of this new method is the introduction of two distinct nitrogen and carbon electrophiles, with a large gap in reactivity, for ortho‐unsubstituted aryl iodides via an intermolecular and intramolecular C―H functionalization, respectively. Eight types of ipso terminations can be coupled with both ortho‐amination and ortho‐alkylation, affording a variety of polysubstituted benzoheterocyclic scaffolds. Silicon‐tethered substrates can lead to polyfucntional arenes via a single‐step operation. Noteworthy, these products exhibit full‐color‐tunable strong fluorescence emissions with large Stokes shifts, and product 7r can serve as a fluorescent probe to specifically target lysosome in living cells.

Optimal Sizing of Electric Vehicle Charging Stations Considering Urban Traffic Flow for Smart Cities

Achieving high penetration of electric vehicles (EVs) is one of the objectives proposed by the scientific community to mitigate the negative environmental impact caused by conventional mobility. The limited autonomy and the excessive time to recharge the battery discourage the final consumer from opting for new environmentally friendly mobility alternatives. Consequently, it is essential to provide the urban road network with charging infrastructure (CI) to ensure that the demand generated by EV users is met. The types of terminals to be considered in charging stations (CS) are fast and ultra-fast. The high energy requirements in these types of terminals could stress the electrical systems, reducing the quality of service. To size and forecast the resources needed in CI, it is of great interest to model and predict the maximum number of EVs, in each hour, that each CS will have to serve according to the geographic area in which they are located. Our proposal is not based on an assumed number of vehicles to be served by each CS, but rather it is based on the analysis of vehicular traffic in geo-referenced areas, so that the load managers can design the topology of the CS. The maximum vehicular concentration is determined by some considerations such as the road system, direction of the route, length of the road segment, the intersections, and the economic zone to which it belongs. The topology of the road map is freely extracted from OpenStreetMap to know the latitude and longitude coordinates. Vehicular traffic will be modeled through the topology obtained from OpenStreetMap and other microscopic variables to understand the traffic engineering constraints. In addition, the Hungarian algorithm is used as a minimum cost decision tool to allocate demand to the CS by observing vehicular traffic as a cost variable. The multi commodity flow problem (MCFP) algorithm aims to make commodities flow through the road network with the minimum cost without exceeding the capacities of the road sections. Therefore, it is proposed to solve the transportation problem by directing the vehicular flow to the CS while minimizing the travel time. This situation will contribute significantly to the design of the topology of each CS, which will be studied in future research.

Magnetic resonance conditionality of abandoned leads from active implantable medical devices at 1.5 T.

During MR scans, abandoned leads from active implantable medical devices (AIMDs) can experience excessive heating at the lead tip, depending on the type of termination applied to the proximal contacts (proximal end treatment). The influence of different proximal end treatments (ie, [1] freely exposed in the tissue, [2] terminated with metal in contact with the tissue, or [3] capped with plastic, and thereby fully insulated, on the RF-induced lead-tip heating) are studied. A technique to ensure that MR Conditional AIMD leads remain MR Conditional even when abandoned is recommended. Abandoned leads from three MR Conditional AIMDs ([1] a sacral neuromodulation system, [2] a cardiac rhythm management pacemaker system, and [3] a deep brain stimulator system) were investigated in this study. The computational lead models (ie, the transfer functions) for different proximal end treatments were measured and used to assess the in vivo lead-tip heating for four virtual human models (FATS, Duke, Ella, and Billie) and compared with the lead-tip heating of the complete MR Conditional AIMD system. The average and maximum lead-tip heating for abandoned leads proximally capped with metal is always lower than that from the complete AIMD system. Abandoned leads proximally insulated could lead to an average in vivo temperature rise up to 3.5 times higher than that from the complete AIMD system. For the three investigated AIMDs under 1.5T MR scanning, our results indicate that RF-induced lead-tip heating of abandoned leads strongly depends on the proximal lead termination. A metallic cap applied to the proximal termination of the tested leads could significantly reduce the RF-induced lead-tip heating.

Fault tolerant control based on backstepping nonsingular terminal integral sliding mode and impedance control for a lower limb exoskeleton

In this paper, an active fault-tolerant control scheme is proposed for a lower limb exoskeleton, based on hybrid backstepping nonsingular fast terminal integral type sliding mode control and impedance control. To increase the robustness of the sliding mode controller and to eliminate the chattering, a nonsingular fast terminal integral type sliding surface is used, which ensures finite time convergence and high tracking accuracy. The backstepping term of this controller guarantees global stability based on Lyapunov stability criterion, and the impedance control reduces the interaction forces between the user and the robot. This controller employs a third order super twisting sliding mode observer for detecting, isolating ad estimating sensor and actuator faults. Motion stability based on zero moment point criterion is achieved by trajectory planning of waist joint. Furthermore, the highest level of stability, minimum error in tracking the desired joint trajectories, minimum interaction force between the user and the robot, and maximum system capability to handle the effect of faults are realized by optimizing the parameters of the desired trajectories, the controller and the observer, using harmony search algorithm. Simulation results for the proposed controller are compared with the results obtained from adaptive nonsingular fast terminal integral type sliding mode control, as well as conventional sliding mode control, which confirm the outperformance of the proposed control scheme.

МАСЪУЛИЯТИ ЧЕКЛАНГАН ЖАМИЯТНИНГ ҲУҚУҚИЙ МАҚОМИ (ХОРИЖИЙ МАМЛАКАТЛАР ТАЖРИБАСИ)

This article analyzes the legal status of limited liability companies. The research proposed in the article is aimed at giving a holistic view of the concept and types of business companies, the creation and termination of limited liability companies. Also, the scientific views of scientists, the legal practice of foreign countries, the application of civil legislation are considered. In conclusion, the author makes certain scientific conclusions and suggestions.

Seaports during the COVID-19 Pandemic: The Terminal Operators’ Tactical Responses to Disruptions in Maritime Supply Chains

The world-wide crisis caused by the Coronavirus disease 2019 (COVID-19) pandemic had a significant impact on the global economy functioning and the sustainable development of supply chains. The changes also affected seaports being the key links of maritime supply chains. The purpose of the research study described in this article was to identify the sources and kinds of disruptions observed in various maritime supply chains as a result of the COVID-19 pandemic and their impact on the operations of various types of seaport terminals, namely those serving bulk (universal, specialised) and general cargoes (universal, specialised). An additional purpose was to identify the dependencies between the type of terminal and its main function, and the tactical decisions adopted by the particular terminals. The research was carried out using the multiple-case study method. The study covered some selected port terminals functioning in Polish seaports (Gdańsk, Szczecin, Świnoujście), applying direct, semi-structured in-depth interviews. The analysis of the results was carried out using the inductive reasoning method. The research study has shown that as a result of the COVID-19 pandemic some maritime supply chains ceased to exist, some of them were operating with decreased cargo volumes, while in other cases the transshipment volumes actually rose during the pandemic. Among terminal operators’ tactical responses to disruptions in maritime supply chains, there were pro-active and adaptive measures. Pro-active (offensive) measures included actions taken by an enterprise in order to engage in new maritime supply chains, and even participating in establishing new maritime chains in response to limitations caused by the pandemic. Adaptive (defensive) measures covered actions taken by the port terminals as a consequence of changes in the existing maritime supply chains, caused by the pandemic in the port’s foreland or hinterland. The research study results revealed that the terminals extent of engagement and tactical decisions related to the pandemic were depended on the type of terminal (universal or specialised) and its main function played within a supply chain.

Edge effects on the intrinsic magnetism in ferromagnetic triangular phosphorene quantum dots using fully spin-polarized calculations

This project involves discovering the electronic and magnetic properties of nanometer-sized phosphorene structures with triangular shapes in both zigzag and armchair termination types. The goal is to discuss the relationship between the electronic states belonging to the different conditions of these phosphorene quantum dots and their intrinsic magnetic properties. For this purpose, we consider electronic interactions utilizing the spin-polarized density functional theory calculations, and then the results compare with the data generated from tight-binding calculations. Both descriptions yield mid-gap states in the spectrum of ferromagnetic structures. Our results in non-spin computations without any geometry optimization were matched by tight-binding calculations which shows that the tight-binding method is an inefficient approximation in analyzing the optimized spin samples. Unlike graphene, in our spin-polarized calculations, we have obtained empty mid-gap states in the spectrum of ferromagnetic triangular phosphorene quantum dots. The edge atoms of these structures are known as the magnetic atoms with an unequal contribution of spin up and spin down. To prevent deforming the initial structures, the dangling bonds at the edge atoms were passivated in two types, fully hydrogenated and partial passivation with oxygen atoms. Oxygen doping was required for introducing magnetism to the non-spin edges of the fully hydrogenated case.

GABAergic Inhibition of Presynaptic Ca2+ Transients in Respiratory PreBötzinger Neurons in Organotypic Slice Cultures.

GABAergic somatodendritic inhibition in the preBötzinger complex (preBötC), a medullary site for the generation of inspiratory rhythm, is involved in respiratory rhythmogenesis and patterning. Nevertheless, whether GABA acts distally on presynaptic terminals, evoking presynaptic inhibition is unknown. Here, we begin to address this problem by measuring presynaptic Ca2+ transients in preBötC neurons, under rhythmic and non-rhythmic conditions, with two variants of genetically encoded Ca2+ indicators (GECIs). Organotypic slice cultures from newborn mice, containing the preBötC, were drop-transduced with jGCaMP7s, or injected with jGCaMP7f-labeling commissural preBötC neurons. Then, Ca2+ imaging combined with whole-cell patch-clamp or field stimulation was obtained from inspiratory preBötC neurons. We found that rhythmically active neurons expressed synchronized Ca2+ transients in soma, proximal and distal dendritic regions, and punctate synapse-like structures. Expansion microscopy revealed morphologic characteristics of bona fide synaptic boutons of the en passant and terminal type. Under non-rhythmic conditions, we found that bath application of the GABAA receptor agonist muscimol, and local microiontophoresis of GABA, reduced action potential (AP)-evoked and field stimulus-evoked Ca2+ transients in presynaptic terminals in inspiratory neurons and commissural neurons projecting to the contralateral preBötC. In addition, under rhythmic conditions, network rhythmic activity was suppressed by muscimol, while the GABAA receptor antagonist bicuculline completely re-activated spontaneous activity. These observations demonstrate that the preBötC includes neurons that show GABAergic inhibition of presynaptic Ca2+ transients, and presynaptic inhibition may play a role in the network activity that underlies breathing.

EXTRA-HEPATIC PART OF PORTAL VEIN – A CADAVERIC STUDY IN ADULTS & FOETUSES

Background: Variations of the Hepatic Portal Vein are encountered during abdominal surgeries. Aim: The present study is an observational study of the extrahepatic part of Portal Vein &amp; its variations on cadavers. Materials &amp; Methods: A total of 50 upper abdomen dissections were carried out to delineate extra-hepatic Portal Vein anatomy. The Results: mean length of Portal Vein was 5.96cm. The mean diameter of Portal Vein was 1.35cm. The most common type of formation of Portal Vein was Type I, found in 64%. The Right Gastric Vein commonly emptied into the trunk of the Portal Vein. The Left Gastric Vein commonly emptied into the trunk of the Portal Vein in 87.18%. The most common type of Portal Vein termination was Extra-Hepatic, found in 76% of 50 dissections. The Bifurcation pattern was the most common pattern of Portal Vein termination, found in 94% of dissections. The ndings of the present Conclusion: study highlight the variations that may occur in the hepatic portal venous system in its extra-hepatic part. Sound knowledge of portal venous anatomy is needed for success in the surgeries of the liver &amp; adjacent viscera.

Cellular Diversity and Differential Subcellular Localization of the G-Protein Gαo Subunit in the Mouse Cerebellum.

Heterotrimeric guanine nucleotide-binding proteins (G proteins) transduce signals from G protein-coupled receptors (GPCRs) to effector ion channels and enzymes Gαo, a member of the pertussis toxin-sensitive Gi/o family, is widely expressed in the brain, although its role within a neuronal context remains largely unknown. Using immunohistochemical and quantitative immunoelectron microscopy techniques, we have investigated the expression, cellular and subcellular localization of Gαo in the cerebellar cortex. Histoblot revealed that Gαo is expressed in many brain regions, including the cerebellum. At the cellular level, Gαo protein was distributed in Purkinje cells, basket cells, stellate cells, granule cells and Golgi cells. At the subcellular level, pre-embedding immunoelectron microscopy revealed mainly a postsynaptic localization of Gαo along the extrasynaptic plasma membrane of Purkinje cell dendritic shafts and spines, and dendrites of basket, stellate and granule cells. To a lesser extent, immunolabeling for Gαo was localized in different types of axon terminals establishing excitatory synapses. Moreover, post-embedding immunoelectron microscopy revealed the synaptic localization of Gαo on PSDs of glutamatergic synapses between Purkinje cell spines and parallel fiber terminals and its co-localization with GABAB1 in the same spines. Quantitative analysis of Gαo immunoparticles revealed they preferentially localized on the cytoplasmic face of the plasma membrane. Furthermore, the analysis revealed a high concentration of Gαo around excitatory synapses on Purkinje cell dendritic spines, but a uniform distribution in granule cell dendrites. These molecular-anatomical findings suggest that Gαo is a major signal transducer of specific GPCRs in different neuronal populations in the cerebellum.

Persisting Cardiac Dysfunction and Quality of Response Predict Survival in Patients with AL Amyloidosis Who Respond to Upfront Therapy

Introduction. The presence and severity of heart involvement at diagnosis is by far the most important prognostic factor in AL amyloidosis, and our ability to prognosticate survival and assess response to therapy based on cardiac biomarkers has revolutionized the management of this disease. However, very little is known on the impact of persisting cardiac dysfunction after upfront chemotherapy in patients with AL amyloidosis. This is particularly relevant to identify subjects who can benefit most from the different therapies targeting amyloid deposits that are currently being tested in clinical trials in patients who still have cardiac dysfunction after successful upfront therapy.Methods. The prospectively maintained database of the Pavia Amyloidosis Research and Treatment Center was searched for patients who obtained at least a partial hematologic response (PR) after upfront therapy. Survival was measured from the time of best hematologic response to death or last follow-up. Cutoffs of N terminal pro natriuretic peptide type B (NT-proBNP) best predicting survival after response were identified by Receiver Operator Characteristic (ROC) analyses based on death at 2 years.Results. A total of 507 patients diagnosed between 2004 and 2015 were included in the study. Best hematologic response was achieved after a median of 3.6 months from upfront therapy initiation and was complete response (CR) in 22%, very good PR (VGPR) in 56%, and PR in 22%. At diagnosis the heart was involved in 77% of patients. After a median follow-up of living patients of 52 months, median overall survival (OS) from the time of best response was 76 months. Median OS by response category was not reached for CR, 78 months for VGPR (P=0.004 compared to CR), and 40 months for PR (P<0.001 compared to VGPR). The presence of heart involvement remained a predictor of poorer survival also after achievement of hematologic response (median 70 months vs. not reached, P<0.001). Baseline NT-proBNP was >650 ng/L (evaluable for cardiac response) in 347 patients (68%). Of them, 121 [35%, 95% confidence interval (CI) 29-42%] achieved a cardiac response by the time of best hematologic response. Cardiac response was associated with improved survival (median 86 vs. 46 months, P<0.001). The cutoff of NT-proBNP concentration best predicting survival after hematologic response was 3500 ng/L (median 16 vs. 93 months, P<0.001). Importantly, patients whose NT-proBNP was <3500 ng/L had a longer survival within each hematologic response category (CR median not reached vs. 74 months, P=0.012; VGPR median not reached vs. 21 months, P<0.001; PR median 50 vs. 4 months, P<0.001). At multivariate analysis achievement of CR/VGPR after upfront therapy [hazard ratio (HR) 0.54, 95%CI 0.39-0.75, P<0.001], a concentration of NT-proBNP above 3500 ng/L (HR 2.61, 95%CI 1.88-3.63, P<0.001), and NT-proBNP response (HR 0.68, 95%CI 0.48-0.98, P=0.036) were independent predictors of survival. The quality of response (achievement of CR/VGPR and/or cardiac response) and NT-proBNP concentration (cutoff 3500 ng/L) identified 3 groups with significantly different survivals after upfront therapy (Figure 1).Discussion. In AL amyloidosis heart dysfunction persisting after achievement of best hematologic response retains its ominous prognostic impact also in patients obtaining good quality hematologic response. A novel staging system incorporating NT-proBNP concentration and hematologic and cardiac response allows best prediction of survival of patients with heart involvement after response to upfront therapy, identifying those in greater need of further improving heart involvement and/or quality of hematologic response. [Display omitted] DisclosuresPalladini:Prothena: Honoraria, Other: Travel grant; Celgene: Other: Travel grants; Jannsen-Cilag: Membership on an entity's Board of Directors or advisory committees.

Liver Involvement and d FLC Level Affect Survival of Patients with Non-Cardiac Light Chain Amyloidosis: A European Study of 334 Patients

Introduction. The presence of heart involvement is the most important determinant of survival in amyloid light chain (AL) amyloidosis. However, in approximately 20% of patients the heart is not involved at diagnosis. These patients can be identified as stage I by the 2004 Mayo Clinic staging system, having normal (<332 ng/L) N terminal pro natriuretic peptide type B (NT-proBNP) and cardiac troponin (cTn) I <0.1 ng/mL or cTnT <0.035 ng/L. Stage I subjects generally have a good outcome, but have not been specifically studied yet, and little is known on variables possibly identifying patients who die earlier.Methods. The prospectively maintained databases of the Pavia and Heidelberg amyloid centers have been systematically searched for Stage I AL excluding symptomatic multiple myeloma patients. Age, sex, type and number of organs involved, markers of cardiac, renal and liver function, the difference between involved and uninvolved free light chains (dFLC), and bone marrow plasma cell infiltrate were tested for their impact on survival. Pavia patients were used as the testing set and Heidelberg patients as the validation set. Overall survival (OS) from diagnosis and rate of early deaths (defined as occurring in the first 12 months from diagnosis) were analyzed. Cutoffs of variables predicting survival were identified by ROC analyses based on death at 12 months in the Pavia cohort. Variables predicting early death were assessed by logistic regression analysis.Results. The Pavia cohort comprised 161 (15% of all patients) and the Heidelberg cohort included 173 patients (14%). Their clinical characteristics are listed and compared in Table 1. The majority of patients in both cohorts had renal involvement. More Heidelberg patients received ASCT or no chemotherapy compared to the Pavia cohort. Median OS was not reached (with 94% of patients surviving 1 year and 78% surviving 5 years) in the Pavia cohort, and 132 months (with 91% of patients surviving 1 year and 74% surviving 5 years) in Heidelberg patients (P=0.620), after a median follow-up of living patients of 50 and 52 months, respectively. The only variable consistently predicting OS in the 2 cohorts was dFLC (best cutoff 50 mg/L). A baseline dFLC of <50 mg/L was associated with better OS both in the Pavia (median not reached vs. 85 months, with 96% vs. 92% of patients surviving 1 year and 86% vs. 72% surviving 5 years, P=0.009) and in the German cohorts (median not reached vs. 97 months, with 98% vs. 86% of patients surviving 1 year and 79% vs. 74% surviving 5 years, P=0.014). Liver involvement and elevated alkaline phosphatase (ALP) concentration were the only variables associated with early deaths. The odds ratio (and 95% confidence interval) for early death for an increase by 1 time the upper reference limit for ALP was 2.42 (1.55-3.78) in Pavia patients (P<0.001), and 1.56 (1.20-2.03) in Heidelberg patients (P<0.001). For liver involvement, the odds ratio was 7.59 (2.00-28.94) in Pavia patients (P=0.003), and 3.09 (1.04-9.18) in Heidelberg patients (P=0.042). We compared the outcomes of patients treated with different regimens after stratifying for the presence of risk factors (i.e. dFLC >50 mg/L or liver involvement). The analysis was performed in the whole population due to relatively small numbers. There was no significant difference in survival according to treatment type in patients without risk factors, nor in patients with one or both risk factors who received melphalan / dexamethasone or bortezomib-based therapy (data not shown). However, we found a significant survival advantage for patients with dFLC >50 mg/L, liver involvement or both who underwent autologous stem cell transplant (ASCT) as first-line therapy (median 132 vs. 89 months, with 98% vs. 85% of patients surviving 1 year and 83% vs. 69% surviving 5 years, P=0.016).Discussion. Patients with AL amyloidosis without heart involvement have a very good outcome with median survival exceeding 10 years. However, dFLC concentration >50 mg/L is associated with poorer long term outcome, while liver involvement and elevated ALP identify patients at higher risk of death in the first year. Stage I patients with these newly defined adverse prognostic factors might be considered for upfront ASCT. [Display omitted] DisclosuresPalladini:Prothena: Honoraria, Other: Travel grant; Celgene: Other: Travel grants; Jannsen-Cilag: Membership on an entity's Board of Directors or advisory committees. Hegenbart:Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Prothena: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Speakers Bureau. Schönland:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding; Takeda: Speakers Bureau; prothena: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.