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Retrieval Augmented Therapy Suggestion for Molecular Tumor Boards: Algorithmic Development and Validation Study

JOURNAL OF medICAL INTERNET RESEARCH 2025年 27卷 e64364页

作者： Berman, Eliza Malek, Holly Sundberg Bitzer, Michael Malek, Nisar Eickhoff, Carsten Univ Hosp Tuebingen Ctr Digital Hlth Schaffhausenstr 77 D-72072 Tubingen Germany Univ Hosp Tuebingen Ctr Personalized Med Tubingen Germany Univ Hosp Tuebingen Dept Internal Med 1 Tubingen Germany

Background: Molecular tumor boards (MTBs) require intensive manual investigation to generate optimal treatment recommendations for patients. Large language models (LLMs) can catalyze MTB recommendations, decrease human error, improve accessibility to care, and enhance the efficiency of precision oncology. Objective: In this study, we aimed to investigate the efficacy of LLM-generated treatments for MTB patients. We specifically investigate the LLMs' ability to generate evidence-based treatment recommendations using Pubmed references. Methods: We built a retrieval augmented generation pipeline using Pubmed data. We prompted the resulting LLM to generate treatment recommendations with Pubmed references using a test set of patients from an MTB conference at a large comprehensive cancer center at a tertiary care institution. Members of the MTB manually assessed the relevancy and correctness of the generated responses. Results: A total of 75% of the referenced articles were properly cited from Pubmed, while 17% of the referenced articles were hallucinations, and the remaining were not properly cited from Pubmed. Clinician-generated LLM queries achieved higher accuracy through clinician evaluation than automated queries, with clinicians labeling 25% of LLM responses as equal to their recommendations and 37.5% as alternative plausible treatments. Conclusions:This study demonstrates how retrieval augmented generation-enhanced LLMscan bea powerful tool in accelerating MTB conferences, as LLMs are sometimes capable of achieving clinician-equal treatment recommendations. However, further investigation is required to achieve stable results with zero hallucinations. LLMs signify a scalable solution to the time-intensive process of MTB investigations. However, LLM performance demonstrates that they must be used with heavy clinician supervision, and cannot yet fully automate the MTB pipeline.

关键词： large language models retrieval augmented generation LLaMA precision oncology molecular tumor board molecular tumor LLMs augmented therapy MTB oncology tumor clinical trials patient care treatment evidence-based accessibility to care

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Cortisol stress response after musculoskeletal surgery: a narrative review

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EFORT OPEN REVIEWS 2025年第4期10卷 186-192页

作者： Mengere, Maximilian M. Histing, Tina Laschke, Matthias W. Ehnert, Sabrina Viergutz, Tim Fontana, Johann Eberhard Karls Univ Tuebingen BG Trauma Ctr Tuebingen Dept Trauma & Reconstruct Surg Tubingen Germany Saarland Univ Inst Clin & Expt Surg Homburg Germany Eberhard Karls Univ Tuebingen Siegfried Weller Inst Trauma Res BG Trauma Ctr Tuebingen Dept Trauma & Reconstruct Surg Tubingen Germany BG Trauma Ctr Tubingen Dept Anesthesiol & Intens Care Med Tubingen Germany Heidelberg Univ Med Fac Mannheim Mannheim Germany

center dot Trauma induced by surgery stimulates a neuroendocrine stress response, substantially increasing cortisol levels in the post-surgical setting. This has substantial effects on metabolism, water and electrolyte balance as well as on the cardiovascular, nervous and immune systems. center dot While there are valid data on cortisol level courses in a variety of specific pathologies, such as septic shock, acute respiratory distress syndrome, bacterial meningitis, cardiac arrest, community-acquired pneumonia and influenza, there is a persisting lack of data on the cortisol stress response after musculoskeletal surgery. center dot The present review provides an overview of the current state of research regarding trauma-induced cortisol response after musculoskeletal interventions, including both elective orthopedic surgery and trauma surgery. center dot Trauma induced by musculoskeletal surgery triggers a cortisol response, which varies significantly depending on the type of surgery and its invasiveness. Notably, elective orthopedic procedures demonstrate a smaller range of cortisol levels compared to musculoskeletal trauma and surgery. center dot In the future, high-quality prospective trials need to analyze the factors that may modulate the adequate adrenal response to stress, such as preoperative long-term treatments with glucocorticoids, as well as the potential impact of low cortisol levels and perioperative cortisol substitution therapy on pain management, blood requirements, catecholamine dependency, delirium and mortality after musculoskeletal surgery.

关键词： cortisol stress response surgery inflammation trauma

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Increased humeral retrotorsion is not a risk factor for overuse injury of the throwing shoulder in elite youth handball athletes

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JOURNAL OF SHOULDER AND ELBOW SURGERY 2025年第1期34卷 2-9页

作者： Achenbach, Leonard Limmer, Jonas Zeman, Florian Rudert, Maximilian Walter, Sven S. Julius Maximilians Univ Wurzburg Dept Orthoped Konig Ludwig Haus Wurzburg Germany Univ Med Ctr Regensburg Ctr Clin Studies Regensburg Germany Eberhard Karls Univ Tuebingen Univ Hosp Tuebingen Dept Diagnost & Intervent Radiol Tubingen Germany

Background: To identify the potential role of humeral retrotorsion (HRT) and range of motion (ROM) as a risk factor for shoulder overuse injury in elite youth handball players. The hypothesis was that increased HRT is associated with an increased risk of shoulder overuse injury. Methods: Over 2 seasons, 258 elite youth handball players (52% boys;age:14 +/- 0.8 years) were included. Preseason assessment included HRT and glenohumeral internal and external (ER) rotational ROM using ultrasound and a manual goniometer. Sportsspecific adaptations between male and female athletes and the dominant and nondominant shoulder were calculated. In addition, players completed standardized questionnaires over the 2018-2019 or 2019-20 season and reported any shoulder overuse symptoms using the Western Ontario Shoulder Index questionnaire. Results: Comparing male and female players showed significantly decreased HRT and decreased internal ROM in the dominant side of male athletes (P < .027). No other difference was found. Significant side-to-side differences between the dominant and nondominant shoulder were found for HRT, internal rotation, and ER, regardless of sex (P < .001). For total range of motion, only female athletes showed a significant increase in the dominant arm (P = .032). The dominant side showed a significantly higher glenohumeral internal rotation deficit in male athletes than in female athletes (10 degrees +/- 17 degrees vs 5 degrees +/- 10 degrees, P = .011). Adaptations in HRT, ER gain, and total range of motion gain were not significant. Over the course of the 2 seasons, 20 athletes reported shoulder overuse injuries. Although glenohumeral internal rotation deficit was borderline nonsignificant (P = .056), none of the parameters tested were significantly associated with shoulder overuse injuries. Conclusion: Despite significant side-to-side differences and sport-specific adaptations, individual preseason screening of humeral retrotorsion and soft tissue adaptatio

关键词： Shoulder adolescent overuse injury range of motion

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Randomised In Vitro Study Investigating PEEP-Stability During Application of CPAP With Binasal Prongs and Face Masks

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ACTA PAEDIATRICA 2025年第0期 2025 Jan 24页

作者： Sterzik, Hanna Molnar, Kriszta Stauch, Anette Wald, Martin Poets, Christian F. Haase, Bianca Univ Childrens Hosp Tuebingen Dept Neonatol Tubingen Germany Univ Childrens Hosp Tuebingen Ctr Peadiatr Clin Studies CPCS Tubingen Germany Paracelsus Med Univ Salzburg Dept Neonatol Div Pediat & Adolescent Med Salzburg Austria Univ Hosp Tuebingen Dept Diagnost & Intervent Radiol Tubingen Germany

Aim Face masks and binasal prongs are commonly used interfaces for applying continuous positive airway pressure (CPAP) in neonatology. We aimed to assess CPAP stability in a randomised controlled in vitro study. Methods In a simulated resuscitation scenario of a 1000-g preterm infant with respiratory distress, 20 operators (10 with/without neonatology experience) aimed to maintain a CPAP of 5 cmH(2)O as precisely as possible using face masks or binasal prongs in random order. The primary outcome was the minimum-achieved CPAP at the Y-piece (PYmin). Secondary outcomes included time to target CPAP, CPAP stability and the impact of operator experience. Results Binasal prongs enabled more consistent maintenance of the target CPAP of 5 cmH(2)O than face masks (median [IQR]: PYmin: binasal prongs, 3.74 cmH(2)O [3.54-3.88]) vs. 3.20 cmH(2)O (2.72-3.73), with no significant deviation from the target CPAP. Target CPAP was achieved significantly faster with face masks (2.89 s [1.67-5.64] vs. 6.49 s [4.76-13.62] [p < 0.05]). No significant differences were observed on the basis of operator experience (p > 0.05). Conclusion Binasal prongs allow more accurate CPAP maintenance than face masks regardless of the operator's experience, although current clinical studies offer limited evidence on the superiority of nasal interfaces compared with that of face masks.

关键词： CPAP in vitro interface neonate prongs resuscitation

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Platelet potential to switch to procoagulant phenotype compensates bleeding tendency in patients with hemophilia A

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BLOOD ADVANCES 2025年第5期9卷 1181-1184页

作者： Althaus, Karina Kieninger, Sophie Baeuerle, Anna Hammer, Stefanie Wolska, Nina Uzun, Guenalp Weich, Karoline Alberio, Lorenzo Aliotta, Alessandro Faul, Christoph Moyses, Margarete Holzer, Ursula Icheva, Vanya Gorodezki, David Hoerber, Sebastian Halimeh, Susan Zlamal, Jan Bakchoul, Tamam Univ Hosp Tuebingen Inst Clin & Expt Transfus Med Med Fac Tuebingen Otfried-Mueller-Str 4-1 D-72076 Tubingen Germany Univ Hosp Tuebingen Ctr Clin Transfus Med Tubingen Germany Univ Hosp Tuebingen Hemophilia Treatment Ctr Tuebingen Tubingen Germany Univ Lausanne Lausanne Univ Hosp Div Hematol & Cent Hematol Lab Lausanne Switzerland Univ Hosp Tuebingen Dept Internal Med Hematol Oncol Clin Immunol & Rhe Tubingen Germany Univ Tubingen Univ Childrens Hosp Dept Hematol & Oncol Tubingen Germany Univ Tubingen Univ Childrens Hosp Dept Pediat Cardiol Pulmonol & Intens Care Med Tubingen Germany Univ Hosp Tuebingen Inst Clin Chem & Pathobiochem Dept Diag Lab Med Tubingen Germany Gerinnungszentrum Rhein Ruhr Duisburg Germany

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Göttingen minipigs present with significant regeneration kinetics after sphincter injury compared to German landrace gilts;a feasibility study

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BMC VETERINARY RESEARCH 2025年第1期21卷 1-13页

作者： Knoll, Jasmin Harland, Niklas Amend, Bastian Stenzl, Arnulf Aicher, Wilhelm K. Eberhard Karls Univ Tubingen Univ Tuebingen Hosp Ctr Med Res Dept Urol D-72072 Tubingen Germany Eberhard Karls Univ Tubingen Univ Tuebingen Hosp Dept Urol D-72076 Tubingen Germany Zentrun Med Forsch Urol Univ Klin Waldhoernlestr 22 D-72072 Tubingen Germany

Background Animals serve as important models for exploring the pathology, diagnosis, and therapy of different diseases and injuries. While smaller animals are preferred for bulk cohort studies, larger animals offer opportunities to investigate surgical procedures at proportions close to the human situation. Therefore, in a feasibility study, we investigated urethral sphincter deficiency in German landrace gilts and G & ouml;ttingen minipigs to develop a model of urinary incontinence as a basis for future preclinical studies of incontinence therapies. Urethral sphincter deficiency was induced surgically by transurethral electrocautery and balloon dilatation, and the deficiency was determined by urodynamics after injury and during follow-up. In cryosections, sphincter injury was visualized by histochemistry. Results Sphincter deficiency was induced in two cohorts and groups of four female G & ouml;ttingen minipigs each (total n = 20) by two different treatments. One cohort of minipigs showed an initially significant urethral sphincter deficiency (treatment 1;n = 16, p < 0.001). However, spontaneous sphincter regeneration was observed within one to two weeks. The other cohort of minipigs (treatment 2;n = 4) displayed a non-significant reduction of urethral sphincter pressure and an increase in muscle strength over time as well. In contrast, German landrace gilts presented immediately after treatment with significant sphincter deficiency (treatment 1;n = 6, 21%, p < 0.001) and suffered from significant loss of sphincter function for at least five weeks (67%, p < 0.01). Conclusion G & ouml;ttingen minipigs inherit significantly superior sphincter regeneration capacities compared to landrace pigs. This difference may bias preclinical studies in urology and other fields and explain in part seemingly contradictory results from different animal studies.

关键词： Wound healing animal model Urinary incontinence Sphincter deficiency G & ouml ttingen minipigs Landrace pigs

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One-day dual-tracer examination in neuroendocrine neoplasms: a real advantage of low activity LAFOV PET imaging

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EUROPEAN JOURNAL OF NUCLEAR medICINE AND MOLECULAR IMAGING 2025年 1-14页

作者： Calderon, Eduardo Kiefer, Lena S. Schmidt, Fabian P. Lan, Wenhong Brendlin, Andreas S. Reinert, Christian P. Singer, Stephan Reischl, Gerald Hinterleitner, Martina Dittmann, Helmut la Fougere, Christian Trautwein, Nils F. Univ Hosp Tuebingen Nucl Med & Clin Mol Imaging Otfried Mueller Str 14 D-72076 Tubingen Germany Eberhard Karls Univ Tubingen Werner Siemens Imaging Ctr Preclin Imaging & Radiopharm Roentgenweg 13 D-72076 Tubingen Germany Univ Hosp Tuebingen Diagnost & Intervent Radiol Hoppe Seyler Str 3 D-72076 Tubingen Germany Univ Hosp Tuebingen Dept Pathol Liebermeisterstr 8 D-72076 Tubingen Germany Univ Hosp Tuebingen Med Oncol & Pneumol Internal Med 8 Otfried Mueller Str 14 D-72076 Tubingen Germany Univ Hosp Tuebingen ENETS Ctr Excellence Otfried Mueller Str 14 D-72076 Tubingen Germany Univ Tubingen DFG Cluster Excellence 2180 Image Guided & Funct I Roentgenweg 11 D-72076 Tubingen Germany German Canc Consortium DKTK German Canc Res Ctr DKFZ Partner Site Tuebingen Morgenstelle 15 D-72076 Tubingen Germany

Purpose: Somatostatin receptor (SSTR)-PET is crucial for effective treatment stratification of neuroendocrine neoplasms (NENs). In highly proliferating or poorly differentiated NENs, dual-tracer approaches using additional [F-18]FDG PET can effectively identify SSTR-negative disease, usually requiring separate imaging sessions. We evaluated the feasibility of a one-day dual-tracer imaging protocol with a low activity [F-18]FDG PET followed by an SSTR-PET using the recently introduced [F-18]SiFAlin-TATE tracer in a long axial field-of-view (LAFOV) PET/CT scanner and its implications in patient management. Methods: Twenty NEN patients were included in this study. Initially, a low activity [F-18]FDG PET was performed (0.5 +/- 0.01 MBq/kg;PET scan 60 min p.i.). After 4.2 +/- 0.09 h after completion of the [F-18]FDG PET, a standard activity of [F-18]SiFAlin-TATE was administered (3.0 MBq/kg;PET scan 90 min p.i.). To ensure the quantification accuracy of the second scan, we evaluated the potential impact of residual [F-18]FDG activity by segmenting organs with minimal physiological SSTR-tracer uptake, such as the brain and myocardium, and assessing the activity concentrations (ACTs) of tumor lesions. Residual tumor lesion ACTs of [F-18]FDG were calculated by factoring fluorine-18 decay, identifying a maximum residual ACT of 15% (R15%). To account for increased [F-18]FDG trapping over time, higher residual ACTs of 20% (R20%) were considered. These simulated [F-18]FDG ACTs were compared with those measured in the second PET scan with [F-18]SiFAlin-TATE. The influence of the dual-tracer PET/CT results on therapeutic strategies was evaluated. Results: [F-18]FDG cerebral uptake significantly decreased in the subsequent SSTR-PET (mean uptake [F-18]FDG: SUVmean 6.0 +/- 0.4;mean uptake in [F-18]SiFAlin-TATE PET: SUVmean 0.2 +/- 0.01;p < 0.0001);with similar results recorded for the myocardium. Simulated residual [F-18]FDG ACTs represented only a minimal percentage of ACTs measure

关键词： Dual-tracer PET LAFOV PET/CT Low activity [F-18]FDG PET Neuroendocrine neoplasms

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Pathologien der Peroneussehnen und deren charakteristische Bildgebung

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ROFO-FORTSCHRITTE AUF DEM GEBIET DER RONTGENSTRAHLEN UND DER BILDGEBENDEN VERFAHREN 2025年第5期197卷 486-492页

作者： Horger, Marius Fritz, Jan Gohla, Georg Hagen, Florian Heckl, Stefan Univ Hosp Tuebingen Dept Diagnost & Intervent Radiol Tubingen Germany New York Univ Radiol Med Ctr New York NY USA Univ Hosp Tuebingen Dept Diagnost & Intervent Neuroradiol D-72076 Tubingen Germany Hirslanden Pk Hosp Radiol Zurich Switzerland

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Low-activity [¹⁸F]-somatostatin receptor (SSTR) imaging using [¹⁸F]SiTATE on a long axial field-of-view PET/CT scanner

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EJNMMI PHYSICS 2025年第1期12卷 1-15页

作者： Trautwein, Nils F. Calderon, Eduardo Linder, Pia M. Reischl, Gerald Driessen, Philippe Lan, Wenhong Brendlin, Andreas S. Gross, Thorben Dittmann, Helmut Hinterleitner, Martina la Fougere, Christian Schmidt, Fabian P. Kiefer, Lena S. Univ Hosp Tuebingen Dept Nucl Med & Clin Mol Imaging Otfried Mueller Str 14 D-72076 Tubingen Germany Univ Hosp Tuebingen ENETS Ctr Excellence Otfried Mueller Str 14 D-72076 Tubingen Germany Eberhard Karls Univ Tuebingen Werner Siemens Imaging Ctr Dept Preclin Imaging & Radiopharm Roentgenweg 13 D-72076 Tubingen Germany Univ Hosp Tuebingen Dept Diagnost & Intervent Radiol Hoppe Seyler Str 3 D-72076 Tubingen Germany Univ Hosp Tuebingen Dept Med Oncol & Pneumol Internal Med 8 Otfried Mueller Str 14 D-72076 Tubingen Germany Univ Tubingen DFG Cluster Excellence Image Guided & Funct Instru Roentgenweg 11 D-72076 Tubingen Germany German Canc Consortium DKTK German Canc Res Ctr DKFZ Partner Site Tuebingen Auf Morgenstelle 15 D-72076 Tubingen Germany

Purpose: F-18-labelled somatostatin receptor tracers have recently gained popularity due to their better spatial resolution, longer half-life and lower costs compared to Ga-68-labeled tracers. The aim of this study was to evaluate the impact and limitations of reduced administered activities of [F-18]SiTATE on image quality, lesion detectability and quantitative PET parameters in a long axial field-of-view (LAFOV) PET/CT scanner. Methods: Twenty-four patients with histologically confirmed neuroendocrine tumor, who underwent clinically indicated [F-18]SiTATE PET/CT examination (3.0 MBq/kg, 5 min PET scan time) on a Siemens Biograph Vision Quadra LAFOV PET/CT, were included retrospectively in this study. PET list-mode data were rebinned for shorter frame durations to simulate 5 min scans with lower activities of injected radiotracer. A comparison of image reconstruction in high sensitivity (HS) and ultra-high sensitivity mode (UHS) mode was performed. Subjective image quality, noise and lesion detectability of n = 122 lesions were rated using a 5-point Likert scale. The molecular tumor volume (MTV), signal-to-noise ratio (SNR), tumor-to-liver activity concentration ratio (TLR) and standardized uptake values (SUV) were analyzed. Results: Subjective image quality decreased with simulated reduction of injected activity with generally superior ratings in the UHS mode compared to the HS mode. Despite a reduction to 1 MBq/kg of [F-18]SiTATE all lesions were still detected while at 0.25 MBq/kg lesion detectability decreased to 70% (HS) and 93% (UHS). Only minor changes in SUVmean and TLR were detected with reduced activity. However, reduced activities led to an increase in SUVSD, which in turn caused a decrease in SNR (at 1 MBq/kg: 7.3 in HS and 9.0 in UHS mode and an increase in deviation of the MTV. Conclusion: Reducing the administered activity of injected [F-18]SiTATE by 66% to 1 MBq/kg (HS & UHS) is feasible in a LAFOV PET/CT scanner, maintaining clinically diagnostic i

关键词： LAFOV PET/CT Total-Body-PET [F-18]SiTATE Low-activity [F-18]SiTATE PET [F-18]-SSTR imaging

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Psychotherapy in patients with long/post-COVID - A systematic review on the feasibility, acceptability, safety, and efficacy of available and emerging interventions

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JOURNAL OF PSYCHOSOMATIC RESEARCH 2025年 190卷 112048-112048页

作者： Schurr, Marisa Graf, Johanna Junne, Florian Giel, Katrin Elisabeth Med Univ Hosp Tuebingen Dept Psychosomat Med & Psychotherapy Osianderstr 5 D-72076 Tubingen Germany Klinikum Stuttgart Clin Psychosomat Med & Psychotherapy Priessnitzweg 24 D-70374 Stuttgart Germany Univ Hosp Magdeburg Dept Psychosomat Med & Psychotherapy Leipziger Str 44 D-39120 Magdeburg Germany Univ Tubingen Ctr Excellence Eating Disorders Tuebingen KOMET Tubingen Germany German Ctr Mental Hlth DZPG Berlin Germany

Backgrounds: There is an urgent need for effective treatments for patients with long/post-COVID. Current recommendations for management favor a multimodal approach including psychotherapy and emphasize that interventions should also consider the mental health impact of living with long/post-COVID. This systematic review synthesizes psychotherapeutic interventions that currently target long/post-COVID complaints and summarizes data on the feasibility, acceptability, safety, and efficacy of psychotherapy for patients with long/ post-COVID. Methods: This systematic review was conducted according to the PRISMA statement. Studies were retrieved from three databases (Pubmed, PsycInfo, Web of Science) and independently assessed by two raters. Studies investigating patients of any age suffering from long/post-COVID were included if the intervention involved psychotherapeutic treatment and changes in long/post-COVID symptoms were reported. The review has been preregistered on PROSPERO. Results: A total of 12 studies were included in the analysis. Of these, 10 were multimodal approaches with integrated psychotherapeutic interventions, and two were studies on stand-alone psychotherapy. The majority of studies were uncontrolled and demonstrate pre-post improvements in a range of long/post-COVID symptoms. Only one RCT could be identified, which supports the benefit of CBT for COVID-related fatigue. It was not possible to draw general conclusions regarding the efficacy of psychotherapy for long/post-COVID. However, data on feasibility, acceptability, and safety support the potential of psychotherapy as a treatment approach for long/post-COVID. Conclusion: Future studies investigating the potential of psychotherapy approach for long/post-COVID which go beyond the pilot stage are needed to systematically assess feasibility, acceptability, safety, and efficacy in largescale confirmatory trials.

关键词： Long-COVID Post-COVID Psychotherapy approach

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