Goal Of Therapy Research Articles

Functional capacity by cardiopulmonary exercise testing is not related to health status in obstructive hypertrophic cardiomyopathy

Abstract Background In obstructive hypertrophic cardiomyopathy (HCM), the primary goal of therapy is to improve patient quality of life by decreasing symptom burden. Increasingly, cardiopulmonary exercise testing (CPET), with peak oxygen consumption (pVO2) and ventilator efficacy (VE/VCO2), is used to assess efficacy of novel therapies in clinical studies and selectively in clinical practice to determine treatments. However, the relationship of CPET variables to symptom burden in HCM is not well established. Therefore, we examined the relationship between CPET variables and health status measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) and NYHA functional classification in a cohort of obstructive HCM patients. Methods Consecutive patients with HCM and resting left ventricular outflow tract (LVOT) obstruction (≥50 mmHg) underwent CPET between October 2022 to January 2024. Patients with a peak RER <1.0 were excluded (n=4). To investigate distribution of patient reported health status (KCCQ) and NYHA functional classification, patients were stratified into groups for pVO2 (<14, 14-20, and >20 mL/kg/min) to reflect moderate to severe, mild to moderate, and little to no functional limitation, respectively. Results Of 58 patients, clinical evaluation was at 59 ± 13 years of age, 55% male, with LVOT gradient of 83 ± 28 mmHg at rest with 84% NYHA class II or III and 76% with KCCQ overall summary (OS) <75. Both pVO2 and VE/VCO2 had significant but weak correlation with NYHA class and KCCQ scores (Table 1), with the strongest correlation observed with pVO2 and KCCQ-OS (R2= 0.13, p=0.004). In contrast, % predicted pVO2 was not significantly correlated with NYHA or KCCQ. Notably, despite 14 patients being classified as having little to no limitations by pVO2, 29% of these patients had mild to moderate disability and 29% had moderate to severe disability by KCCQ-OS (Figure 1). Conclusion In patients with symptomatic obstructive HCM, objective measures of exercise performance, including pVO2 and VE/VCO2, correlate poorly with measurements of health status. These data suggest that CPET results should not be considered a surrogate marker of heart failure symptom burden in obstructive HCM.

Gender differences in the treatment with PCSK9 monoclonal antibodies real world experience from a dedicated prevention clinic

Abstract Background Proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9 mAb) lower low-density lipoprotein cholesterol (LDL-C) levels and reduce atherosclerotic cardiovascular disease (ASCVD). There are gender differences in PCSK9 biological characteristics, which are not properly addressed in current data. Purpose Examining gender differences in treatment with PCSK9 mAb. Methods A retrospective study based on data from the Prevention Cardiology Clinic in Rabin Medical Center. Included were patients prescribed with PCSK9 mAb (evolocumab or alirocumab), for primary or secondary prevention. Data included medical background and treatment variables. Response to treatment was evaluated by changes in LDL-C at 3 and 12 months. Data was analyzed by gender. Results Study included 246 patients (mean age 67y, ASCVD 78.8%, mean baseline LDL-C 128.2 mg/dL). Women (42% of cohort) prescribed with PCSK9 mAb were older than men (69 vs. 65 years, respectively; p<0.001). The dominant indication for PCSK9 mAb for both genders was secondary prevention, while primary prevention indication was more prevalent in women vs. men (39.4% vs. 16.3%, respectively; p<0.001). Statin intolerance was observed in 82.4% and 58.6% were treated with combination therapy with PCSK9 mAb, without significant gender differences. Baseline mean LDL-C was higher among women vs. men (138.9 vs. 117.3 mg/dL; p<0.001). Overall, high adherence was observed (91.8% and 79.7% at 3 and 12 months, respectively). After 1-year, adherent men had lower LDL-C levels than women (46.8 mg/d and 61.9 mg/dL, respectively; P=0.001), and were more likely to reach their LDL-C therapy goals; below 70 mg/dL (76.1% vs. 62.2%, respectively; P=0.032) and below 55 mg/dL (60.1% vs. 39.8% respectively; P=0.003). Conclusions In patients treated with PCSK9 mAb, gender differences exist in prescription age, indications, baseline LDL-C and achieved LDL-C goals. In this study adherence to PCSK9 mAb was higher than reported before, possibly due to surveillance in a dedicated prevention clinic.LDL-C & Non-HDL-C levels under PCSK9 mABSex Differences in acheived LDL-C goals

EFFECTIVE APPROACHES TO ENHANCING CONNECTED SPEECH IN PREOPERATIVE CHILDREN WITH OPEN ORGANIC RHINOLALIA

Children with open organic rhinolalia, a condition often resulting from structural anomalies such as cleft palate, face unique challenges in speech development, particularly in the preoperative period. This article examines the methods, techniques, and strategies used to improve connected speech in these children before undergoing surgical intervention. Focusing on evidence-based practices, the article explores various speech therapy approaches, including breathing exercises, articulation drills, and resonance training, all tailored to address the specific needs of children with hypernasal speech. The goal of preoperative speech therapy is not only to prepare children for surgery but also to enhance their overall communication skills by developing more transparent and fluent speech. By reviewing current research and case studies, this article provides insights into effective treatment methods that can be applied in clinical settings to support children with open organic rhinolalia.

Investigation of Acoustic Voice Characteristics of Individuals Diagnosed with Muscle Tension Dysphonia.

Muscle tension dysphonia (MTD) is a functional voice condition that causes irregular and imbalanced laryngeal and paralaryngeal muscle activation. Our study aimed to examine the acoustic characteristics of patients with MTD and reveal the differences between genders. The study retrospectively reviewed the acoustic examination findings from the files of patients diagnosed with MTD during evaluations in the laryngology outpatient clinic at a tertiary reference hospital between 2015 and 2022. The parameters assessed in prolonged vowel phonation analysis were fundamental frequency (F0), jitter, shimmer, noise-to-harmonic-to-ratio, and soft phonation index; in the counting task analysis, they were intensity, frequency, and semitone. Gender differences in acoustic measurements obtained during prolonged vowel phonation and counting tasks were also examined. The study included 80 individuals diagnosed with MTD. Although all parameters in the acoustic analysis of/a/ phonation were increased, differences were statistically significant only in the F0 and jitter parameters between females and males (p≤0.05). In the analysis of the counting task, the mean and minimum F0 parameters were significantly higher in females than in males (p=0.000). The mean dB level was decreased, particularly in the counting task, but the results for the intensity parameter did not differ significantly between genders (p>0.05). The values in the acoustic voice analysis parameters of patients with MTD were determined. These acoustic parameters are thought to guide the clinician in evaluating voice and determining voice therapy goals for MTD patients.

Combination Dornase and Alteplase for Intra-abdominal Drain, Abscess, and Hematoma Clearance: A Retrospective Case Series

Background: Since the advent of the MIST2 trial, the combined instillation of dornase and alteplase has become an effective nonsurgical treatment option for empyema and pleural fluid collection. Percutaneous drainage of abdominal abscesses and fluid collections, rather than open surgical treatment, also has become commonplace. The are several case reports and studies on the use of fibrinolytics to drain abdominal fluid collections but no literature reporting use of both alteplase and dornase for abdominal administration. Objective: We present a case series from an academic medical center where dornase therapy was added to fibrinolytic therapy to treat intra-abdominal fluid collections, hematoma, and abdominal drainage catheters with low output. Methods: This is an institutional review board-approved retrospective case series of 13 patients who underwent combination use of alteplase and dornase via intra-abdominal route. The primary objective was to assess for increased drain output, reduction in size of the fluid collection, and adverse events. Results: Many patients had improved drain output after dornase-alteplase therapy. One patient had significant bleeding complications. Conclusions: All patients were discharged alive from the hospital. Clinical success was difficult to define due to variable goals of therapy. Further data are needed to establish the safety and efficacy of this practice, especially compared with intra-abdominal alteplase alone. Patients in our series generally received larger doses of alteplase than in prior studies due to use of dosing modeled on the MIST2 trial. Based on the limited experience of our study, we recommend holding therapeutic anticoagulation during the administration of intra-abdominal dornase-alteplase.

Design, Synthesis, Physicochemical Properties, and Biological Activity of Thymidine Compounds Attached to 5,8-Quinolinedione Derivatives as Potent DT-Diaphorase Substrates.

After heart disease, cancer is the second-leading cause of death worldwide. The most effective method of cancer treatment is target therapy. One of the potential goals of therapy could be DT-diaphorase, which reduces quinone moiety to hydroquinone, and reactive oxygen species are create as a byproduct. The obtaining of hybrid compounds containing the quinone moiety and other bioactive compounds leads to new derivatives which can activate DT-diaphorase. The aim of this research was the synthesis and characterization of new hybrids of 5,8-quinolinedione with thymidine derivatives. The analysis of the physicochemical properties shows a strong relationship between the structure and properties of the tested compounds. The enzymatic assay shows that hybrids are good substrates of NQO1 protein. The analysis of the structure-activity relationship shows that the localization of nitrogen atoms influences the enzymatic conversion rate. The analysis was supplemented by a molecular docking study. Comparing the results of the enzymatic assay and the molecular docking presents a strong correlation between the enzymatic conversion rate and the scoring value.

Oral rehydration in diarrhea: from history to current guidelines. A review

Acute gastroenteritis (AGE) is usually defined as a change in stool consistency (liquid or unformed) and/or an increase in the frequency of bowel movements, which can also be accompanied by vomiting and fever. Fever increases the metabolic rate by more than 1.5 times; for every 1°C increase in body temperature, fluid loss increases by 10%. AGE is a common cause of morbidity and mortality among infants and children. The prognosis is favorable if the condition is recognized promptly and appropriate treatment is started. The main goal of AGE therapy is to restore water balance and prevent dehydration, which can be achieved with an oral rehydration solution. The composition and proportion of the components of rehydration agents are described in the guidelines of the European Society for Paediatric Gastroenterology Hepatology and Nutrition, of which the Russian Society of Pediatric Gastroenterologists is a collective member, and such agents are fully consistent with the balanced formulations of RehydroStandard and Rehydron Bio rehydration agents. The latter includes the probiotic strain Lactobacillus rhamnosus GG, well studied and recommended by the European Society for Paediatric Gastroenterology Hepatology and Nutrition for acute intestinal infections since this strain reduces the duration and severity of diarrhea according to the results of studies. Rehydron Bio and RehydroStandard can be recommended for use in clinical pediatric practice.

AML-VAC-XS15-01: protocol of a first-in-human clinical trial to evaluate the safety, tolerability and preliminary efficacy of a multi-peptide vaccine based on leukemia stem cell antigens in acute myeloid leukemia patients.

Acute myeloid leukemia (AML) has a dismal prognosis, mostly due to minimal residual disease-driven relapse, making an elimination of persisting therapy-resistant leukemia progenitor/stem cells (LPCs) the main goal for novel therapies. Peptide-based immunotherapy offers a low-side-effect approach aiming to induce T cell responses directed against human leukocyte antigen (HLA) presented tumor antigens on malignant cells by therapeutic vaccination. Mass spectrometry-based analysis of the naturally presented immunopeptidome of primary enriched LPC and AML samples enabled the selection of antigens exclusively expressed on LPC/AML cells, which showed de novo induction and spontaneous memory T cell responses in AML patients, and whose presentation and memory T cell recognition was associated with improved disease outcome. Based on these data the therapeutic vaccine AML-VAC-XS15 was designed, comprising two mutated HLA class I-restricted peptides from the common AML-specific mutation in NPM1 and seven HLA class II-restricted peptides (six non-mutated high-frequent AML/LPC-associated antigens and one mutated peptide from the AML-specific mutation R140Q in IDH2), adjuvanted with the toll like receptor 1/2 ligand XS15 and emulsified in Montanide ISA 51 VG. A phase I open label clinical trial investigating AML-VAC-XS15 was designed, recruiting AML patients in complete cytological remission (CR) or CR with incomplete blood count recovery. Patients are vaccinated twice with a six-week interval, with an optional booster vaccination four months after 2nd vaccination, and are then followed up for two years. The trial's primary objectives are the assessment of the vaccine's immunogenicity, safety and toxicity, secondary objectives include characterization of vaccine-induced T cell responses and assessment of preliminary clinical efficacy. The AML-VAC-XS15-01 study was approved by the Ethics Committee of the Bavarian State medical association and the Paul-Ehrlich Institut (P01392). Clinical trial results will be published in peer-reviewed journals.

5175 A Rare Case of Type B Insulin Resistance Syndrome

Abstract Disclosure: S. Fatima: None. A. Champion: None. S. Ward: None. Q. Aziz: None. K.E. Izuora: None. Introduction: Severe insulin resistance may be defined as a severely diminished response to insulin’s biological effects and is characterized by substantial hyperinsulinemia and impaired glucose response to endogenous and exogenous insulin. We hereby present a rare case of Type B Insulin Resistance Syndrome (TBIRS). Case:40-years old female with history of systemic lupus erythematosus (SLE), diabetes mellitus was admitted with multiple rheumatologic complaints, including arthralgias, oral ulcers, skin rash, and hair loss secondary to SLE flare. Endocrinology was consulted for diabetes management. Her HbA1c had increased from 7.3% to 11.6% in 3 months despite taking Glargine 45 units daily, Lispro 15 units pre-meals and metformin. She noticed 80 lbs weight loss for past 6 months. Her BMI was 26 and exam showed acanthosis of neck, armpits, groin, hair loss on scalp, multiple genital ulcers, and facial rash. She was noted to have refractory hyperglycemia despite high insulin doses. By 14th day of hospitalization, she was on 287 units of insulin (3.4units/kg) daily. We suspected TBIRS in the setting of SLE. Metformin and pioglitazone were started. Further testing showed insulin level 152mIU/ml (2.6-14.9mIU/ml), C-peptide 1.7 ng/ml (1.1-4.4 ng/ml), islet-cell antibody negative, GAD-65 antibody <5 u/ml, insulin antibody 6.5 uU/ml, IGF-1 14 (79-259 ng/ml), adiponectin 13.3 (2.4-17.9 ug/ml), testosterone 7 (8-60 ng/dl), free testosterone <0.2 (0-4.2 pg/ml), total cholesterol 200 mg/dl (<200 mg/dl), triglycerides 85 mg/dl (<150 mg/dl), LDL 154 mg/dl (<100 mg/dl), HDL 29 mg/dl (>60 mg/dl). She was transferred to National Institute of Health for further care. She was confirmed to have TBIRS by insulin receptor antibody testing, started on regular insulin U500 initially, and then switched to IV insulin drip requiring up to 1700 units of insulin per hour. She received methylprednisolone, cyclophosphamide (2 doses), rituximab (2 doses), hydroxychloroquine and IV immunoglobulin. Her stay was complicated by hemophagocytic lymphohistiocytosis. She was discharged on U-500 Regular insulin, 1000 units with breakfast and 500 units with lunch, Prednisone 60 mg daily and Hydroxychloroquine. Two months later she was found unresponsive at home secondary to hypoglycemic seizures. She required dextrose drip and was discharged on Glargine 16 units and Lispro 6 units with meals. Conclusion: TBIRS is caused by a highly specific polyclonal autoantibody against the cell surface insulin receptor that decreases the cellular insulin response and causes refractory hyperglycemia. About 100 cases have been reported in literature. 60% of the cases are associated with SLE. The goal of therapy is to reverse the hypercatabolic state with high doses of insulin and to eliminate the autoantibodies with immunosuppressive therapy. The most common cause of mortality is hypoglycemia. Presentation: 6/3/2024

EFFECTIVENESS OF CONTINUOUS GLUCOSE MONITORING IN UNCONTROLLED TYPE-2 DIABETICS IN TERTIARY HEALTHCARE CENTRE

Long term diabetic complications can be prevented or reduced by achieving good metabolic control, reflected by HbA1c <6.5–7.0%.1-3 Glucose excursions might also contribute to the development of diabetic complications.4,5 Fear of hypoglycemia limits the ability to reach strict glycemic control, because it is usually accompanied by reluctance of the patient to intensify insulin therapy. Indeed, the goal of intensive therapy is to normalize HbA1c and control fasting and postprandial glycemia, while concurrently limiting the number and severity of hypoglycemic events. To reach tight glycemic control, frequent self- monitoring of blood glucose (SMBG) must be performed.6 SMBG devices provide the patient with accurate but discreet blood glucose levels. They do not provide trend information nor do they reflect glycemic fluctuations, which is possible by using continuous glucose monitoring (CGM) systems. Thus, implementation of strict glycemic control may be facilitated by a CGM device. This manuscript critically reviews the proposed benefits and indications of CGM and the current evidence of CGM on health outcomes in diabetic patients.

Do Occupational Therapy Goals for Children with Autism Spectrum Disorder Reflect Participation? A Mapping to the ICF - CY and ICF Core Sets Study.

Autism Spectrum Disorder (ASD) is on the rise worldwide with an increasing acknowledgement that its continuum of care to enhance participation should be multidisciplinary. The International Classification of Functioning, Disability, and Health (ICF) and its derivatives ICF - Children and Youth (ICF - CY) and ICF Core Sets have been increasingly used among health professionals to enhance communication and documentation of outcomes. This study aimed at investigating the comprehensiveness of the ICF - CY and ICF Core Sets with regard to occupational therapy goals and the extent of participation representation in these goals. Forty occupational therapists working with children with ASD stated their most common three long-term goals. The goals were then mapped to the ICF - CY two level classification. The percentage of goals reflecting "Participation" was calculated. The overlap between ICF - CY and the ICF ASD Core Sets was assessed. A total of 155 goals were extracted, of which only seven (4.5%) related to sensory processing were not linked to the ICF - CY categories. 35.1% of the total linked goals were regarded as reflecting "Participation". 84.5% of ICF - CY categories overlapped with the ICF ASD Core Sets. Categories related to hand function, and taking care of body parts were found to be lacking in the ICF ASD Core Sets. The ICF - CY and the ICF ASD Core Sets may be feasible clinical tools for children with ASD, however, they may not be sufficient to cover occupational therapy goals. Goals also need to be modified to better reflect participation.

Management of follicular thyroid carcinoma.

Follicular thyroid carcinoma (FTC) is the second most common histological type of thyroid carcinoma. This review aims to summarize the available evidence and guidelines and provide an updated consensus regarding the management of FTC. The cytoarchitectural features of FTC are similar to those of follicular adenoma (FA), and it is difficult to preoperatively distinguish between FA and FTC. For nodules with Bethesda class III-V cytology, molecular test results (if available) should be considered before the operation. However, it should be noted that molecular tests are not available in all countries. The goals of initial surgical therapy for patients with FTC are to improve overall and disease-specific survival, reduce the risk of persistent/recurrent disease and associated morbidity, and permit accurate disease staging and risk stratification while minimizing treatment-related morbidity and unnecessary therapy. Previous studies have reported some prognostic factors such as distant metastasis, age, tumor size, vascular invasion, TERT promoter mutation, and histological subtype. In particular, the degree of vascular invasion is becoming increasingly important. Evaluating these prognostic factors is essential for prognostic prediction and precise management of patients with FTC. Recurrence and distant metastasis of FTC are treated with radioactive iodine (RAI). However, some FTCs become refractory to RAI. Multi-tyrosine kinase inhibitors such as sorafenib and lenvatinib are utilized for treating RAI-refractory FTCs. In addition, given that renin-angiotensin system (RAS) is the most common driver gene for FTC, it is also important to develop RAS inhibitors.

Updates on Clinical Language Sampling Practices: A Survey of Speech-Language Pathologists Practicing in the United States.

Language sample analysis (LSA) provides many benefits for assessing, identifying therapy goals, and monitoring the progress of children with language disorders. Despite these widely recognized advantages, previous surveys suggest the declining use of LSA by speech-language pathologists (SLPs). This study aimed to provide updates on clinical LSA use following the recent introduction of two new LSA protocols, namely, the Sampling Utterances and Grammatical Analysis Revised (SUGAR) protocol and the Computerized Language Analysis KIDEVAL program. Survey data from SLPs practicing in the United States (N = 337) were used to examine rates of LSA use, methods, and protocols. Factors predicting LSA use and reported facilitators and barriers were also examined. Results indicated that 60% of SLPs used LSA in the past year. LSA skill level, training, and serving preschool or elementary school children predicted LSA use, whereas workplace, caseload, and years of experience were not significant predictors. Most SLPs reported using self-designed LSA protocols (62%), followed by Systematic Analysis of Language Transcripts (23%) and SUGAR (12%) protocols. SLPs who did not use LSA reported limited time (74%), limited resources (59%), and limited expertise (41%) as barriers and identified additional training on LSA computer programs (52%) and access to automatic speech recognition programs (49%) as facilitators to their adoption of LSA. Reported rates of LSA use and methods were consistent with previous survey findings. This study's findings highlight the ongoing needs for more extensive preprofessional training in LSA.

Osteoarthritis: An Update on Diagnosis & Management.

Osteoarthritis (OA) is the most prevalent joint condition. It is a progressively degenerating disease that involves the entire joint, including the articular cartilage, subchondral bone, ligaments, capsule, synovial fluid, and periarticular muscles. Physicians understand that osteoarthritis is diagnosed late during the illness, which may be too late for patients to receive significant benefits from medications that change their condition. The goals of OA therapy are to preserve function while minimizing pain and stiffness. This article focuses on the current and potential treatments for osteoarthritis and various diagnostic methodologies for this disease. In the coming years, despite having numerous treatments for symptomatic relief, the treatment plan should be more specialized because everyone might experience improved outcomes.

Thrombopoietin Receptor Agonists as Second-Line Treatment in Children With Ongoing Immune Thrombocytopenia

What Is the Issue? Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelets and an increase in bleeding risk; in the pediatric population, the reported incidence rate varies between 2 and 5 per 100,000 children per year. Spontaneous remission may be observed in up to 70% of patients, while 20% of patients may experience severe bleeding symptoms. In children whose ITP does not respond to first-line corticosteroids, IV immunoglobulin (IVIG), or anti-D immunoglobulin, guidelines recommend the use of thrombopoietin receptor agonists (TPO-RAs), i.e., eltrombopag or romiplostim (avatrombopag did not have a marketing authorization and Notice of Compliance at the time that the review was initiated). Rituximab is considered a subsequent-line of therapy. Splenectomy is not usually considered an appropriate treatment option in children. The goal of therapy in pediatric patients with ITP is to reduce bleeding and improve quality of life. Platelet response is considered a valid and appropriate surrogate end point in studies and routine assessment in clinical practice. Children whose ITP does not respond to available first-line drugs may require subsequent treatment with off-label drugs because they do not have access to TPO-RAs. What Did We Do? We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence. A systematic review of the literature identified 5 studies (4 randomized controlled trials [RCTs] and 1 observational study), which were synthesized narratively. The review addressed the following policy questions: In children with ongoing, active ITP, what is the overall body of evidence supporting the use of TPO-RAs and rituximab after failure of first-line therapies? Based on the level and quality of clinical evidence, should TPO-RAs be reimbursed for use earlier in the treatment sequencing for children with ongoing, active ITP, instead of being reimbursed only after a course of rituximab? What Did We Find? Evidence from 2 RCTs (n = 159) suggests that eltrombopag likely increases and maintains platelet response over time, in addition to decreasing the use of rescue medication and clinically significant bleeding compared to placebo, which were considered clinically meaningful outcomes for pediatric patients with ITP. There was a low risk of bias in the studies, but uncertainty was introduced due to the small sample sizes. Evidence from 1 RCT (n = 62) suggests that romiplostim may also increase and maintain platelet response, as well as reduce clinically significant bleeding compared to placebo. However, there was some concern due to a high risk of bias in the studies and uncertainty due to the small sample size, which suggests a need for caution in the interpretation of the findings. The effectiveness of rituximab was inconclusive due to the lack of evidence, as no comparative RCTs could be identified, while the observational study included presented only descriptive comparisons. No evidence was identified in support of trying rituximab before accessing TPO-RAs. What Does This Mean? Given that ITP is rare in children, there is a gap in available relevant evidence, and robust evidence from large RCTs in this patient population are unlikely to be conducted. Jurisdictions may consider requesting an implementation advice panel for use of eltrombopag and romiplostim after failure of first-line therapies in children with ongoing, active ITP.

Positive events in psychotherapy: What do adolescents and young adults say is helpful?

Background The significant challenge in adolescent and young adult therapy lies in the fact that research in this field does not provide many clinical indications. This study addresses domains contributing to the establishment and sustenance of engagement, satisfaction, and progress among adolescents and young adults in their treatment by delving into the impact of events that, from the perspective of clients, have positively influenced their therapeutic process. Methods Employing a qualitative research approach, we conducted semi-structured interviews with 13 adolescents and young adults undergoing therapy, recounting positive and constructive events during their treatment. Results A structured thematic analysis revealed six primary domains of positive events: events linked to the management of the setting, events shaping the definition of therapy goals, occurrences tied to the therapist’s active role, collaborative events between therapists and clients, and events associated with both clients’ external and internal worlds. Conclusions The findings suggest that working with adolescents shares similarities with psychotherapy involving adult clients but demands specific attention to adolescents and young adults’ families, surrounding environment, and rapidly changing needs.

Disrupted self, therapy, and the limits of conversational AI

ABSTRACT Conversational agents (CA) are thought to be promising for psychotherapy because they give the impression of being able to engage in conversations with human users. However, given the high risk for therapy patients who are already in a vulnerable situation, there is a need to investigate the extent to which CA are able to contribute to therapy goals and to discuss CA’s limitations, especially in complex cases. In this paper, we understand psychotherapy as a way of dealing with existential situations and position CAs in the context of the therapeutic experience of patients. This experience is determined by the patient’s unique personal context and specific therapy goals. We suggest that psychotherapy is a fundamentally dialogical activity, because it crucially involves work on the self and one’s self-narrative. This brings us to our central question: is it possible for CAs to engage in a productive therapeutic dialogue, given their limitations as epistemic agents? We will discuss several of those limitations, show how these undermine the possibility of engaging in a therapeutic dialogue, and illustrate those limitations through discussions of the cases of grief and abuse.

Curculigoside Regulates Apoptosis and Oxidative Stress Against Spinal Cord Injury by Modulating the Nrf-2/NQO-1 Signaling Pathway In Vitro and In Vivo.

Spinal cord injury (SCI) is a severe neurological disorder that can lead to paralysis or death. Oxidative stress during SCI is a critical phase causing extensive nerve cell damage and apoptosis, thereby impairing spinal cord healing. Thus, a primary goal of SCI drug therapy is to mitigate oxidative stress. Curculigoside (CUR), a phenolic glucoside extracted from the dried root and rhizome of Curculigo orchioides Gaertn, possesses neuroprotective and antioxidant properties. This study aimed to investigate whether CUR effectively promotes the recovery of spinal cord tissue following SCI and elucidate its mechanism. We employed a hydrogen peroxide (H2O2)-induced PC12 cell model and an SCI rat model to observe the effects of CUR on oxidation and apoptosis. The results demonstrated that CUR significantly reduced the expression of apoptosis-related proteins (Bax and Caspase-3), Annexin V/propidium iodide (PI), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), while increasing the expression of the anti-apoptotic protein Bcl-2. Moreover, CUR effectively enhanced levels of antioxidants (glutathione [GSH)] and decreased reactive oxygen species (ROS) in vitro. Furthermore, CUR facilitated functional recovery through its anti-apoptotic and anti-oxidative stress effects on spinal cord tissues in SCI rats. These effects were mediated via the Nrf2/NQO1 signaling pathway. Therefore, our study showed that CUR acted as an anti-apoptotic and anti-oxidative stress agent, inhibiting astrocyte activation and promoting neuronal reconstruction and functional recovery. These findings may contribute significantly to the development of SCI treatments and advance the field of SCI drug therapy.

Relevance of therapist feedback in the context of group‑based exercise programs in medical rehabilitation – Results from a qualitative study with patients and exercise therapists

Background Although group-based exercise programs account for nearly half of exercise therapy services provided in German medical rehabilitation facilities, information regarding the application and effects of therapist feedback in this setting is sparse. Therefore, the aim of this qualitative study was to develop an understanding of the relevance of therapist feedback in the context of group-based exercise programs from the patients’ and therapists’ perspective. Methods Semi-structured interviews were conducted with five rehabilitation patients as well as five exercise therapists with work experience in group-based exercise therapy. Data were analysed using structuring content analysis. Results Three types of therapist feedback with respective modalities and characteristics were identified. Besides corrective feedback to support the patients’ exercise instruction, motivational feedback and performance feedback were used to aid the strengthening of psychological resources. Although therapist feedback constituted an important component of patient-therapist-interaction, evidence suggesting a facilitation of coping strategies, participation or long-term physical activity adherence was sparse. Conclusions While therapist feedback in group-based exercise programs likely aids the recovery of physical and psychological functions, its potential to promote the long-term goals of exercise therapy in medical rehabilitation appears to be underutilised.

547. DISEASE SPECIFIC MORTALITY OF EARLY-STAGE ESOPHAGEAL NEOPLASIA IN BARRETT’S ESOPHAGUS TREATED WITH ENDOSCOPIC THERAPY

Abstract Background High-grade dysplasia (HGD) and intramucosal (T1a) esophageal adenocarcinoma (EAC) are indication for endoscopic eradication therapy (EET) with endoscopic resection (ER) and/or radiofrequency ablation (RFA). The goal of the endoscopic therapy is to prevent progression to advanced EAC and cure the underlying Barrett’s esophagus (BE) when present. Previous studies have showed high rate of success of EET in short term, however little is known about long term results of EET. We aimed to evaluate long-term outcome of EET with particular reference to disease specific mortality and progression to major surgery. Methods We conducted a single center retrospective study including patients who underwent EET for HGD and T1a EAC January 2005-December 2022. We excluded patients with gastric disease and evidence of T1b EAC at baseline ER. Primary outcomes assessed disease specific mortality (DSM) of esophageal cancer in this longitudinal cohort, which is defined as death within 12 months of progression to advanced cancer. Secondary outcomes evaluate endoscopic recurrence, progression to esophagectomy, post-procedure complications and 5-year overall survival. Results 299 patients were included in this study. 252 were treated with a combination of ER and RFA, whereas 47 only received primary RFA. Median number of EET sessions in both patient groups is 4(p=0.48). Patients with HGD were more likely to be detected on surveillance compared to those with T1a EAC (p=0.004). We demonstrate a DSM rate of 2.7%(n=8), with a 5-year overall survival of 74.6%(n=223). 5.7%(n=17) of patients sustained severe post-procedure complications (Clavien-Dindo>3). Endoscopic recurrence occurred in 18.7%(n=56) and 6.7%(n=20) developed disease progression that required surgical intervention. Baseline T1a was associated with higher rates of esophagectomy compared to HGD (p=0.0135). Conclusion EET is a safe and effective treatment for patients with early-stage esophageal neoplasia. In comparison to esophago-gastric surgery, EET offers excellent results with a significantly lower morbidity and mortality risk. However, it is resource intensive as patients often require multiple treatments with long-term, routine surveillance. Patients also require strict compliance to maximize therapeutic outcomes and prevent recurrence or progression. Further studies are required to improve risk-stratification in this cohort and determine the optimal surveillance strategy post EET.