Case Basis Research Articles

Current Potential for Outpatient Care in Urology: What the IGES Report Means if Applied to Real Data

The hospital reform initiated through an expert opinion of the German research institute IGES places great emphasis on the aspect of outpatient care. In this context, the current IGES guidelines extend further than has previously been the case. There are only very isolated instances where this theoretical potential has been translated into practical application in urology. This study aims to reflect the theoretical potential calculated using real data from urology with a view to practical application. Using the algorithm of the "Hospital Structure Navigator" of DKTIG (Deutsche Krankenhaus TrustCenter und Informationsverarbeitung GmbH), focused on the extension of the AOP (Ambulatory Operations and Procedures) catalogue, section-21 data of the year 2022 from the Clinic for Urology at the University Hospital Schleswig-Holstein was analysed. The inclusion and exclusion criteria provided by IGES were applied, along with a limitation of the length of stay to two days and a minimum case number of 30 cases per year. Since this resulted in a very low potential for target DRGs (Diagnosis-Related Groups), the criteria were further modified. With this approach, a plausibility check for the outpatient treatment capability of identified cases was conducted. After applying the inclusion and exclusion criteria, only one applicable DRG (L18B) emerged, but with the expanded criteria, eight DRGs were identified. From the case flat rates determined, three appropriate OPS codes were identified:1.) Ureterorenoscopic removal of stones from the kidney with lithotripsy (5-550.31)2.) Transurethral resection of a bladder tumour, not fluorescence-supported (5-573.40)3.) Bougienage of a ureter, transurethral (5-560.2) CONCLUSION: With the current set of criteria defined by IGES for urology, no significant outpatient potential can be achieved. However, the expansion of criteria has uncovered areas that could be well implemented with a broader set of criteria and are currently seen more systematically in the realm of measures replacing inpatient procedures or hybrid DRGs. In addition to the need to clarify the fundamental outpatient feasibility of the methods on an individual case basis, there are limitations here, especially for multimorbid populations. Therefore, in expanding the catalogue, the legislator must take into account the higher risk and monitoring effort required for these patients.

Research on criminal asset sharing system in overseas recovery of stolen goods

It is not only necessary for China to establish the system of sharing criminal assets in the recovery of overseas assets, but also has sufficient theoretical basis and clear legal basis. From the perspective of extraterritorial rule of law, the modes of criminal asset sharing include fixed agreement mode and individual agreement mode. The confiscated criminal assets shall be returned to the victim or the legal owner first, and reasonable fees shall be deducted before the assets are shared; The proportion of sharing is mainly determined based on the contribution of the assisting country, and factors such as the nature of the crime and the damage suffered by the requesting country are comprehensively considered. The sharing of criminal assets has become a common practice for overseas recovery of stolen goods, showing obvious characteristics of international cooperation and incentive. Based on the practice of foreign-related rule of law, China can gradually fix the experience of asset sharing into bilateral agreements on the basis of successful cases of individual cooperation. According to the different nature of the case, different sharing strategies should be adopted to determine the reasonable standard of asset sharing. External liaison agencies and competent authorities that specify the sharing of assets; Establish a sound procedure mechanism for the proposal, review, decision and implementation of criminal asset sharing.

Venovenous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome in metastatic choriocarcinoma during systemic chemotherapy: Case report

Rationale: Gestational trophoblastic neoplasms are rare and include multiple different types of tumors such as hydatidiform moles, placental site trophoblastic tumors, and choriocarcinoma. Metastatic choriocarcinoma is well described with an excellent prognosis when treated appropriately with chemotherapy. The most common location for metastatic disease is the lungs which can unfortunately lead to severe acute respiratory distress syndrome (ARDS) in the most severe cases. Patient concerns: Metastatic cancer has historically been a contraindication for the use of extracorporeal life support (including extracorporeal membrane oxygenation or extracorporeal membrane oxygenation [ECMO]). With advancing technology and medicine, this contraindication has been called into question. Prior case reports describe the use of ECMO in complicated cases of metastatic cancer and even choriocarcinoma with lung metastasis and refractory ARDS. Diagnoses: We describe a case in which a patient with choriocarcinoma in viable pregnancy developed lung metastasis and ARDS. Interventions: The patient was managed with venovenous ECMO successfully. Outcomes: The patient was cannulated for VV-ECMO for 14 days with subsequent full pulmonary recovery. Lessons: The purpose of this work is to help providers understand the broad utility of ECMO and the need to assess candidacy for this therapy on a case by case basis, even in the setting of metastatic cancer.

Morphological and Dimensional Evolution of Nanosized Amorphous Silicon Nitride in α-Fe: Diffusional and Elastic Effects

We present a detailed analysis based on both experimental and 3D modelling approaches of the unique silicon nitride precipitation sequence observed in ferritic Fe-Si alloys upon nitriding. At 570 °C, Si3N4 silicon nitride was shown to form as an amorphous phase into α-Fe ferrite matrix, which is morphologically unstable over time. Precipitates nucleated with a spheroidal shape, then developed a cuboidal shape for intermediate sizes and octapod-like morphology for a longer time. Using transmission electron microscopy, we show that the transition between spheroid and cuboid morphology depended on particle size and resulted from competition between interfacial energy and elastic strain energy. The resulting morphology was then shown to be a cuboid shape whose faces were always parallel to the {100} planes of the α-Fe; the <100> directions of the matrix corresponded to the elastically soft directions. There was a critical size of around 45 nm for which the transition between the cuboid shape and the octapod-like morphology took place. This was characterised by a transformation of quasi-flat facets into concave ones and the development of lobes in the <111> directions of the bcc crystal. To better assess the kinetic effects of diffusion fields and internal stresses on the morphological instability observed, an original 3D model that explicitly coupled phase transformations and mechanical fields was developed and applied. The latter, validated on the basis of model cases, was shown to be able to describe the time-evolution of both chemical and mechanical fields and their interactions in diffusive mass transport. Using a model system, it was shown that the concentration field around the precipitates and the internal stresses played opposing roles in the cuboid to octapod-like morphological instability. This work gives some clarification regarding the morphological evolution of amorphous Si3N4 precipitates, an important point for controlling the mechanical properties of nitrogen steels.

MEDUSA: A Dynamic Codec Switching Approach in HTTP Adaptive Streaming

HTTP Adaptive Streaming (HAS) solutions utilize various Adaptive BitRate (ABR) algorithms to dynamically select appropriate video representations, aiming to adapt to fluctuations in network bandwidth. However, current ABR implementations have a limitation in that they are designed to function with one set of video representations, i.e. , the bitrate ladder, which differ in bitrate and resolution, but are encoded with the same video codec. When multiple codecs are available, current ABR algorithms select one of them prior to the streaming session and stick to it throughout the entire streaming session. Although newer codecs are generally preferred over older ones, their compression efficiencies differ depending on the content’s complexity, which varies over time. Therefore, it is necessary to select the appropriate codec for each video segment to reduce the requested data while delivering the highest possible quality. In this paper, we first provide a practical example where we compare compression efficiencies of different codecs on a set of video sequences. Based on this analysis, we formulate the optimization problem of selecting the appropriate codec for each user and video segment (on a per-segment basis in the outmost case), refining the selection of the ABR algorithms by exploiting key metrics, such as the perceived segment quality and size. Subsequently, to address the scalability issues of this centralized model, we introduce a novel distributed plug-in ABR algorithm for Video on Demand (VoD) applications called MEDUSA to be deployed on top of existing ABR algorithms. MEDUSA enhances the user’s Quality of Experience (QoE) by utilizing a multi-objective function that considers the quality and size of video segments when selecting the next representation. Using quality information and segment size from the modified Media Presentation Description (MPD) , MEDUSA utilizes buffer occupancy to prioritize quality or size by assigning specific weights in the objective function. To show the impact of MEDUSA, we compare the proposed plug-in approach on top of state-of-the-art techniques with their original implementations and analyze the results for different network traces, video content, and buffer capacities. According to the experimental findings, MEDUSA shows the ability to improve QoE for various test videos and scenarios. The results reveal an impressive improvement in the QoE score of up to 42% according to the ITU-T P.1203 model (mode 0). Additionally, MEDUSA can reduce the transmitted data volume by up to more than 40% achieving a QoE similar to the techniques compared, reducing the burden on streaming service providers for delivery costs.

Evaluation of models to estimate the bioaccumulation of organic chemicals in earthworms

Modelling approaches to estimate the bioaccumulation of organic chemicals by earthworms are important for improving the realism in risk assessment of chemicals. However, the applicability of existing models is uncertain, partly due to the lack of independent datasets to test them. This study therefore conducted a comprehensive literature review on existing empirical and kinetic models that estimate the bioaccumulation of organic chemicals in earthworms and gathered two independent datasets from published literature to evaluate the predictive performance of these models. The Belfroid et al. (1995a) model is the best-performing empirical model, with 91.2% of earthworm body residue simulations within an order of magnitude of observation. However, this model is limited to the more hydrophobic pesticides and to the earthworm species Eisenia fetida or Eisenia andrei. The kinetic model proposed by Jager et al. (2003b) which out-performs that of Armitage and Gobas (2007), predicted uptake of PCB 153 in the earthworm E. andrei to within a factor of 10. However, the applicability of Jager et al.’s model to other organic compounds and other earthworm species is unknown due to the limited evaluation dataset. The model needs to be parameterised for different chemical, soil, and species types prior to use, which restricts its applicability to risk assessment on a broad scale. Both the empirical and kinetic models leave room for improvement in their ability to reliably predict bioaccumulation in earthworms. Whether they are fit for purpose in environmental risk assessment needs careful consideration on a case by case basis.

Machine-Learning-Based Prediction Modeling for Debris Flow Occurrence: A Meta-Analysis

Machine learning (ML) has become increasingly popular in the prediction of debris flow occurrence, but the various ML models utilized as baseline predictors reported in previous studies are typically limited to individual case bases. A comprehensive and systematic evaluation of existing empirical evidence on the utilization of ML as baseline predictors for debris flow occurrence is lacking. To address this gap, we conducted a meta-analysis of ML-based prediction modeling of debris flow occurrence by retrieving papers that were published between 2000 and 2023 from the Scopus and Web of Science databases. The general findings were as follows: (1) A total of 84 papers, distributed across 37 different journals in this time period, reflecting an overall upward trend. (2) Debris flow disasters occur throughout the world, and a total of 13 countries carried out research on the prediction of debris flow occurrence based on ML; China made significant contributions, but more research efforts in African countries should be considered. (3) A total of 36 categories of ML models were utilized as baseline predictors for debris flow occurrence, with logistic regression (LR) and random forest (RF) emerging as the most popular choices. (4) Feature engineering and model comparison were the most commonly utilized strategies in predicting debris flow occurrence based on ML (53 and 46 papers, respectively). (5) Interpretation methods were rarely utilized in predicting debris flow occurrence based on ML, with only 16 papers reporting their utilization. (6) In the prediction of debris flow occurrence based on ML, interpretation methods were rarely utilized, searching by data materials was the most important sample data source, the topographic factors were the most commonly utilized category of candidate variables, and the area under the ROC curve (AUROC) was the most frequently reported evaluation metric. (7) LR’s prediction performance for debris flow occurrence was inferior to that of RF, BPNN, and SVM; SVM was comparable to RF, and all superior to BPNN. (8) The application process for the prediction of debris flow occurrence based on ML consisted of three main steps: data preparation, model construction and evaluation, and prediction outcomes. The research gaps in predicting debris flow occurrence based on ML include utilizing new ML techniques and enhancing the interpretability of ML. Consequently, this study contributes both to academic ML research and to practical applications in the prediction of debris flow occurrence.

Assessing of case-cohort design: a case study for breast cancer patients in Xinjiang, China.

To assess the effectiveness and clinical value of case-cohort design and determine prognostic factors of breast cancer patients in Xinjiang on the basis of case-cohort design. The survival data with different sample characteristics were simulated by using Cox proportional risk models. To evaluate the effectiveness for the case-cohort, entire cohort, and simple random sampling design by comparing the mean, coefficient of variation, etc., of covariate parameters. Furthermore, the prognostic factors of breast cancer patients in Xinjiang were determined based on case-cohort sampling designs. The models were comprehensively evaluated by likelihood ratio test, the area under the receiver operating characteristic curve (AUC), and Akaike Information Criterion (AIC). In a simulations study, the case-cohort design shows better stability and improves the estimation efficiency when the censored rate is high. In the breast cancer data, molecular subtypes, T-stage, N-stage, M-stage, types of surgery, and postoperative chemotherapy were identified as the prognostic factors of patients in Xinjiang. These models based on the different sampling designs both passed the likelihood ratio test (p<0.05). Moreover, the model constructed under the case-cohort design had better fitting effect (AIC=3,999.96) and better discrimination (AUC=0.807). Simulations study confirmed the effectiveness of case-cohort design and further determined the prognostic factors of breast cancer patients in Xinjiang based on this design, which presented the practicality of case-cohort design in actual data.

Target Vessel-Related Outcomes in Patients Managed With Branch Thoracic Aortic Endovascular Repair.

Data on target vessel (TV)-related outcomes in patients managed with branched thoracic endovascular aortic repair (BTEVAR) are limited. This study aimed to present the TV-related outcomes of BTEVAR in patients managed for aortic arch pathologies at 30 days and during follow-up. A retrospective analysis of consecutive patients, managed between September 1, 2011, and June 30, 2022, with custom-made aortic arch endografts (Cook Medical, Bloomington, IN, USA), presenting at least one branch configuration, were eligible. Primary outcomes were technical success, TV-related patency, and reinterventions at 30 days. In total, 255 TVs were revascularized using branches: 107 innominate arteries (IAs), 108 left common carotid arteries (LCCAs), and 40 left subclavian arteries (LSAs). Covered stents were used as bridging stents of which 10.2% were balloon expandable. Relining, using bare-metal stents (BMS), was performed in 14.0% of IAs, 35.2% of LCCAs, and 22.5% of LSAs. Technical success on case basis was 99.2%; no failure was related to unsuccessful TV bridging. At 30 day follow-up, no TV occlusion was detected. In 5.6% of cases, a type Ic or III endoleak, attributed to TVs, was recorded. Two patients needed early branch-related reintervention. The mean follow-up was 18.3±9.2 months. Freedom from TV instability was 94.6% (standard error [SE] 2.5%] at 12 months. No TV stenosis or occlusion was detected up to 48 months of follow-up. Freedom from TV-related reinterventions was 95.4% [SE 2.4%] at 12 months. TV stenosis or occlusion in BTEVAR cases is rare and TV-related reinterventions and instability events are mainly attributed to type Ic and III endoleak formation. Previous studies focusing on target vessel (TV) outcomes after endovascular aortic arch repair are limited. In this study, including 255 TVs revascularized using branched arch devices, bridging was performed with covered stents, of which 90% were self-expanding. Relining was at the discretion of the operator and was 14% for the innominate, 35.2% for the left common carotid and 22.5% for the left subclavian artery branches. No 30-day occlusion was detected. The freedom from TV instability was almost 95% at 12 months. TV instability and reintervention were mainly attributed to endoleaks type Ic and IIIc.

Block-Supersymmetric Polynomials on Spaces of Absolutely Convergent Series

In this paper, we consider a supersymmetric version of block-symmetric polynomials on a Banach space of two-sided absolutely summing series of vectors in Cs for some positive integer s&gt;1. We describe some sequences of generators of the algebra of block-supersymmetric polynomials and algebraic relations between the generators for the finite-dimensional case and construct algebraic bases of block-supersymmetric polynomials in the infinite-dimensional case. Furthermore, we propose some consequences for algebras of block-supersymmetric analytic functions of bounded type and their spectra. Finally, we consider some special derivatives in algebras of block-symmetric and block-supersymmetric analytic functions and find related Appell-type sequences of polynomials.

On the structure of Lotka-Volterra coalgebras

We address the structure of real Lotka-Volterra coalgebras endowed with genetic realization, deepening on the role natural bases have when dealing with this problem. We also tackle the problem of determining all possible natural bases in the two-dimensional case, and solve this problem in terms of a parametrization provided by the natural bases.

Numerical study of motorbike aerodynamic wing kit

Abstract This study aims to design the configuration of an aerodynamic wing kit (AWK) on a racing motorbike to achieve the highest downforce-to-drag ratio. The numerical study involves a motorbike traveling in a straight line, where the AWK improves performance and safety by generating downforce to prevent lift. The geometry of the AWK uses a NACA 4412 airfoil with a span of 0.6 m. The computational mesh is generated using SnappyHexMesh and installed on a simplified motorbike to minimize the mesh skewness. The Navier–Stokes equations are solved with OpenFOAM computational fluid dynamics using the Reynolds-averaged Navier–Stokes k-ω SST and large eddy simulation (LES) turbulence models. Case 1 compares a motorbike with and without a dummy, both equipped with the AWK, varying the angle of attack (AoA) from 0 to −41°. Case 2 studies the single wing at different wind speeds (i.e. 20, 60 and 100 m/s) to determine the highest downforce-to-drag ratio at an AoA of −37°. These results serve as the basis for Case 3, which investigates non-parallel wing configurations with a fixed upper wing and a rotating lower wing. In Case 4, where both upper and lower wings rotate simultaneously as parallel wings, the peak downforce-to-drag ratio occurs at an AoA of −41°. Finally, Case 5 modifies the AoA of −41° of the parallel wing of Case 4 to a closed-wing version to comply with Fédération Internationale de Motocyclisme safety regulations. With the LES turbulence model, unsteady and complex turbulence structures can be visualized using the Q-criterion. A comparison of the time-averaged lift coefficient between the wingless and closed-wing configurations shows an increase in downforce of approximately 360%. Subsequently, the popularity of AWK will contribute to the safety of racing motorbike driving.

Separability and the Law Applicable to the Substantive Validity of Arbitration Agreements

This article discusses the related topics of the doctrine of separability and the law applicable to arbitration agreements, showing the continuous interaction between them. It fosters an approach according to which, while the law of the seat will continue to play a significant role in the evaluation of the validity of arbitration agreements, such validity may also be ascertained on the basis of other systems of law – relevant on a case by case basis – as dictated by the principle of favor arbitrati, which today provides a mandatory approach for domestic law judges. separability, arbitration agreement, applicable law, validation principle, favor arbitrati, New York Convent

Therapeutic Choices in Patients with Ph-Positive Chronic Myelogenous Leukemia In Mexico in the Era of Tyrosine Kinase Inhibitors: Stem Cell Transplantation or Tyrosine Kinase Inhibitors? Fifteen Years Later.

Background: Chronic myelogenous leukemia is a neoplastic proliferation of the granulocytic series. In Mexico, chronic myelogenous leukemia accounts for approximately 10% of all leukemias. Tyrosine-kinase inhibitors are considered front-line therapy in high-income countries, whereas allogeneic hematopoietic stem cell transplantation is a recognized therapeutic approach, mainly in low- and middle-income countries. Objective: To analyze the overall survival of persons with chronic myelogenous leukemia who have received tyrosine-kinase inhibitors or allogeneic hematopoietic stem cell transplantation in a medical center, since 1994, and briefly discuss the current indications of these treatments in the tyrosine-kinase inhibitors era. Methods: We retrospectively analyzed all patients with a diagnosis of chronic myelogenous leukemia treated in a medical center between 1994 and 2023; subsets of individuals who received an allogeneic hematopoietic stem cell transplantation or tyrosine-kinase inhibitors therapy as first-line treatment were analyzed. Results: 60 persons with chronic myelogenous leukemia were treated with allogeneic hematopoietic stem cell transplantation or tyrosine-kinase inhibitors: 35 received an allogeneic hematopoietic stem cell transplantation, whereas 25 were given tyrosine-kinase inhibitors. All patients who underwent an allogeneic hematopoietic stem cell transplantation engrafted successfully, and the procedure was completed on an outpatient basis in most cases (29/35). The median survival in allogeneic hematopoietic stem cell transplantation was 78.3 months (CI 95%: 0-205.6) and in persons given tyrosine-kinase inhibitors the median was not reached. Conclusion: Tyrosine-kinase inhibitors were significantly superior to allogeneic hematopoietic stem cell transplantation in prolonging the overall survival of persons with chronic myelogenous leukemia in our single institution experience. (Rev Invest Clin. 2024;76(2):91-6).

Кейс-метод в обучении специалистов органов опеки и попечительства и специалистов аппарата уполномоченного по правам ребенка

&lt;p style="text-align: justify;"&gt;&lt;span lang="EN-US"&gt;The article describes the experience of using the case method in training specialists from guardianship and guardianship authorities and specialists from the Office of the Commissioner for Children's Rights in the Russian Federation as part of the implementation of the supervision webinar cycle. Supervisory support of specialists in the field is organized in the format of online meetings, during which case studies from the practice of students were analyzed. The article offers an overview of the topics highlighted in the analysis of cases received from students, describes the key points in the discussion of the proposed cases from the standpoint of competence-based and practice-oriented approaches to adult learning. Supervision, built on the basis of real cases, contributed to the improvement and acquisition of new professional competencies within the framework of the qualifications of specialists in the field of child protection. The analysis of the received cases made it possible to identify the main deficits and educational needs of specialists, which can be used in further training of specialists.&lt;/span&gt;&lt;/p&gt;

Topology Optimization Using Neural Networks With Conditioning Field Initialization for Improved Efficiency

Abstract We propose conditioning field initialization for neural network-based topology optimization. In this work, we focus on (1) improving upon existing neural network-based topology optimization and (2) demonstrating that using a prior initial field on the unoptimized domain, the efficiency of neural network-based topology optimization can be further improved. Our approach consists of a topology neural network that is trained on a case by case basis to represent the geometry for a single topology optimization problem. It takes in domain coordinates as input to represent the density at each coordinate where the topology is represented by a continuous density field. The displacement is solved through a finite element solver. We employ the strain energy field calculated on the initial design domain as an additional conditioning field input to the neural network throughout the optimization. Running the same number of iterations, our method converges to a lower compliance. To reach the same compliance, our method takes fewer iterations. The addition of the strain energy field input improves the convergence speed compared to standalone neural network-based topology optimization.

TO STUDY PALLIATION OF SYMPTOMS BY A HYPOFRACTIONATED RADIOTHERAPY SCHEDULE IN ADVANCED INOPERABLE SQUAMOUS CELL CARCINOMAS OF THE ORAL CAVITY

Introduction: Decisions regarding optimal integration of surgery, radiation, and chemotherapy should be made on a case to case basis in a multidisciplinary tumor board setting. Treatment planning of advanced oral cavity cancers is derived from trials that included a heterogeneous group of patients which included all head and neck sites and observational data from the oral cavity cancer patient series. Aim: The aim of the study was to study palliation of symptoms and improvements in quality of life (QoL) in inoperable squamous cell cancers of the oral cavity with a hypofractionated radiotherapy schedule. Methods: It is a prospective and observational study in patients with locally advanced squamous cell cancers of the oral cavity attending the outpatient clinic who have been deemed inoperable after discussion in a multidisciplinary team were considered. The data was tested using Friedman’s test for the significance in QoL. Results: All of the functional scales were found significant in this study with physical functioning, emotional functioning and cognitive functioning (CF) being significant at 1% alpha level while role functioning (RF) and social functioning (SF) are significant at 5% alpha level. RF was assessed based on the capabilities of the patient to finish daily activities. The median score remained at 33 but the interquartile range (IQR) was showing an increasing trend. Both pain and head-and-neck specific pain had significantly reduced over time. Fatigue had shown a constant reduction during radiation and during the first follow-up as well. The increase in nausea, vomiting, and constipation during radiation can be attributed to the use of morphine during radiation for pain control and as an effect of radiation itself. There was weight loss during radiation which improved during subsequent follow-up visits. Conclusions: In patients diagnosed with inoperable oral cavity cancer, hypofractionated radiotherapy delivering 50 Gy in 20 fractions over 4 weeks is a well-tolerated and safe regimen. In our study, statistically significant QoL improvement in global health score, SF, and CF lasting for a minimum of 6 weeks was attained after completion of treatment with this regimen.

Indikátor přívalových povodní – zkušenosti z provozu

Flash floods are one of the most risky natural phenomena. It is very difficult to predict exactly where they will occur and they usually come very quickly. When there is a threat of flash floods, early warning is exactly what decides on the protection of the lives and property of inhabitants. For these reasons, a Flash Flood Indicator (FFI) has being developed in the Czech Hydrometeorological Institute (CHMI) for a long time, aiming to draw attention to the possibility of a flash flood or local flooding. The main purpose of this contribution is not to describe details of FFI algorithms, but to evaluate the functioning of the FFI on the basis of more than ten years of operation experience. On a basis of specific cases of significant rainfall episodes, especially from recent years, the potential benefits of FFI are shown, not only for the operational forecasting service of the CHMI, but also for wider public. At the end of the contribution, the possibilities of further development of FFI are outlined.

Cultural expertise in Sami land rights litigation: Epistemic strategies in the Girjas and Fosen cases

How do parties mobilise cultural expertise in Indigenous rights litigation in Scandinavia? Recently, Sami groups have litigated to claim Indigenous rights to land and natural resources, winning some remarkable victories in the Supreme Courts of Norway and Sweden. In this paper, we draw on socio-legal mobilisation theory to analyse the epistemic strategies of Sami litigants and their adversaries in two recent landmark Supreme Court cases on Indigenous rights to usage of land: the 2020 Girjas case in Sweden and the 2021 Fosen case in Norway. Conceptualising cultural expertise as a strategic framing contest, we analyse how the parties struggled over the epistemic basis of the respective case by legitimating their claims to cultural knowledge, drawing on academic research, and discrediting their opponents’ epistemic claims. Our findings suggest that in both cases, Sami claimants successfully established an epistemic basis where their traditional, experiential knowledge combined with independent academic expertise effectively challenged the knowledge claims of their adversaries. Yet, both cases also demonstrate how the linkage between Sami Indigeneity and reindeer husbandry in the national law of both countries excludes non-reindeer herding Sami persons from the Indigenous rights affirmed by the courts.

Permissive Cardiotoxicity As a Guiding Principle to CAR-T Therapy with Reduced Ejection Fraction Heart Failure

Introduction: Pivotal CAR-T registrational trials for the six CAR-T therapies currently FDA approved have excluded those with heart failure (HF), defined either by low ejection fraction (EF) or clinical symptoms of HF (NYHA functional classification). This has created a real-world dilemma for clinicians desiring to treat this patient population. There is concern that those with HF may not tolerate the physiologic and hemodynamic stressors associated with cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) and thus have increased risk of severe morbidity or death. The emerging concept of permissive cardiotoxicity seeks to allow for an acceptable level of cardiac toxicity to allow for treatment with highly efficacious but potentially cardiac toxic treatments like CAR-T therapy. To that end, in this study, we provide our real-world, single-institution experience with CAR-T therapy in patients with medically optimized HF with reduced EF (HFrEF) prior to date of apheresis. Methods: This was a retrospective review of 168 (100 B-cell lymphoma and 68 multiple myeloma) CAR-T therapy patients, with 20 (12%) identified with HFrEF of ≤50% prior to apheresis by two-dimensional transthoracic echocardiogram as part of the standard CAR-T screening process and without clinical symptoms of HF at time of apheresis. 19/20 patients received standard of care CAR-T products. This study was conducted following IRB approval. Statistical analysis was done using R version 4.2.3. Kaplan-Meier curves were used to calculate progression free survival(PFS) and overall survival(OS). Results: Twenty patients with HFrEF prior to CAR-T infusion were identified with median EF of 44.1% (range 25-50%) (see Table 1, Baseline Characteristics). The median age was 63.5 (37-82) years-old, predominately male gender (80%), Caucasian (70%), with ECOG of 1 (95%), and 10 patients (50%) received axicabtagene ciloleucel (axi-cel). Most patients received CAR-T for B-cell lymphoma (80%). Cardiac history included 5 (25%) with previous CAD, 1 (5%) with previous PAD, and 4 (20%) with history of atrial fibrillation/flutter. Cardio-Oncology was consulted prior to CAR-T therapy in 10 (50%) and 12 (60%) were optimized on goal-directed therapy (GDT). CKD was pre-existing in 4 (20%) patients. Where measured, all patients had a pre-CAR-T troponin within normal institutional limits (&amp;lt;0.05ng/mL). NT-BNP at baseline was only measured in 6 (30%) patients with a median value of 110pg/mL (49-3200, upper limit of normal 125pg/mL). Longitudinal strain prior to CAR-T was measured in 5 (25%) patients with median value of -16% (-19 to -10%, &amp;lt;-17% normal). There were no cases of grade ≥3 CRS with 3 (15%) grade 1 and 12 (60%) grade 2 CRS (see Table 1, Safety Outcomes). There were 4 (20%) with grade 3 ICANS, although most patients 12 (60%) did not experience ICANS. Compared to ZUMA-1, the 10 patients receiving axi-cel did not have significantly higher rates of CRS or ICANS. Tocilizumab was administered in 15 (75%) of patients and steroids given in 10 (50%) of patients. Following CAR-T infusion, 11 (55%) of patients required ICU admission, no patients required vasopressors, 6 (30%) experienced an AKI, 2 (10%) had LFT abnormalities, 4 (20%) had an arrhythmia, and 5 (25%) had further decline in EF with recovery occurring in most cases where measured. Only 2 (10%) of patients had an HF exacerbation within 30 days of CAR-T infusion. PFS and OS were 11.3 and 26 months, respectively. Conclusion: Given that all registrational CAR-T trials excluded HF, notable reservation exists among clinicians in the use of CAR-T therapy in patients with a history of HF and particularly HFrEF. In our institutional experience of 20 patients with good performance status and medically optimized on GDT, we demonstrate that CAR-T therapy can be given safely with rates of CRS and ICANS similar to that expected in the non-HF population. Additionally, while ICU utilization was high, the incidence of arrhythmias, renal or hepatic toxicity as indicators of end organ dysfunction, non-recovering EF decline, and heart failure exacerbation following CAR-T infusion were quite low. It is thus our practice to consider CAR-T therapy on a case by case basis in those with a history of HFrEF. The key to success being maximal cardiac optimization achieved through early engagement of our Cardio-Oncology colleagues based upon the concept of permissive cardiotoxicity.