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  • 1
    Online Resource
    Online Resource
    Tu1696 The Diagnostic Utility of Me-NBI in Differentiating Malignant Gastric Mucosal Lesions Comparing With Wle and ME-WLI—a Prospective Multicentre Study
    Elsevier BV ; 2015
    In:  Gastrointestinal Endoscopy Vol. 81, No. 5 ( 2015-05), p. AB563-
    Details
    In: Gastrointestinal Endoscopy, Elsevier BV, Vol. 81, No. 5 ( 2015-05), p. AB563-
    Type of Medium: Online Resource
    ISSN: 0016-5107
    URL: Article
    DOI: 10.1016/j.gie.2015.03.1836
    RVK:
    XA 44545
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2015
    detail.hit.zdb_id: 2006253-9
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  • 2
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    Combined Infusion of Anti-CD19 and Anti-Bcma CART Cells after Early or Later Transplantation in the Front Line Was Superior to Salvage Therapy for High Risk MM
    American Society of Hematology ; 2019
    In:  Blood Vol. 134, No. Supplement_1 ( 2019-11-13), p. 1949-1949
    Details
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 1949-1949
    Abstract: Background: Multiple myeloma (MM) is an incurable plasma cell malignancies despite the advent of numerously new drugs especially for high risk patients. Our previous study showed good response for the de novo high risk patients who received CD19 and BCMA-specific CART cell therapy after ASCT in the front line with mild CRS and other side effects (reported on the 2018 ASH meeting). To determine the best time to do ASCT and CART cell treatment for those patients, we retrospectively analyzed the patients' outcome according to their time to do autologous transplantation (NCT 03455972). Methods:The high risk MM patients defined in this study were in R-ISS stage III, IgD/IgE type, or with measurable EMD,or who only achieved PR or less after 4 cycles of triplet induction or relapsed. Lymphocytes were collected from PBSCs and cultured with an anti-CD3 monoclonal antibody to activate T-cell proliferation after stem cell collection. The cells were transduced with recombinant lentiviral verctors which respectively contained the anti-BCMA or anti-CD19 single chain variable fragment (scFv), the cytoplasmic portion of the OX40 and CD28 costimulatory moiety, and the CD3z T-cell activation domain. This is the new third generation CAR technique applied in clinic. BuCy or Melphalan were used as conditioning, followed by infusion of autologous stem cells. CART-19 (1×107/kg on d0) and CART-BCMA cells as split-dose (40% on d1 and 60% on d2) were infused directly on d14 to d20 after transplantation. The cytokine release syndrome (CRS) was graded according to the UPen cytokine release syndrome grading system. Neurotoxic side effects and other toxicities were assessed according to the CARTOX and CTCAE v 4.03. Plasma levels of IL-2, IL-4, IL-6, IL-10, TNF-alpha, IFN-gamma, and IL-17A proteins were determined with a cytokine kit. IMiDs alone were given as maintenance therapy. Responses were assessed by IMWG criteria. 10-color flow cytometry was used to monitor MRD regularly after CART treatment. The median of follow-up was 13 (1~23) months. Results: To date, 32 patients have completed the CART cells infusion (Table 1). The median age was 53 years with 24 male and 8 female. CRS occurred in 31 patients (97%) with grade 1 or 2 and just 1 patient (3%) with grade 3. Tocilizumab was used to treating only one patient with grade 3 CRS. Six patients needed to use low-dose vascular active drugs. Other acute and chronic toxicities were slight and reversible. The ORR was 100% (32/32) in this study, with 72% of patients achieved CR or above. There was no TRM or neurologic complications or administration of corticosteroid. All patients were divided into three groups according to their time to transplant. Group 1 underwent ASCT and CART cell treatment as first line therapy; Group 2 underwent ASCT and CART cell treatment at second line because of induction failure or re-induction after PD or relapse; Group 3 underwent salvage ASCT and CART treatment at third line or more after disease progress or relapse.With a median follow-up of 13 months, the latest response of CR and above were 78% in group 1, 100% in group 2 and 44% in group 3. Except the group 3 patients, MRD negativity in BM of the other two groups increased continuously after CART therapy, and some patients achieved MRD negativity at the level 10-6 (shown in Table 1). Patients in group 1 and 2 were in continuous response but 5/9 (56%) patients relapsed in group 3 and 2 patients died of disease. The median PFS and OS of the patients in three groups were all not reached but 1-year PFS was 100%, 100%, 68% for group1, 2, 3 respectively (p 〈 0.05); 2-year OS was 100%, 100%, 64% for each group (p 〈 0.05) (Figure 1). Conclusions: Combined infusion of anti-CD19 and anti-BCMA CART cells after ASCT for high risk MM was safe and effective, especially as conjunction therapy to early or later transplant at front line even with primary resistant disease or early disease progress. For those RRMM patients, CART cell therapy followed by ASCT seems to be better to prolong patients' PFS than CART treatment alone with FC chemotherapy reported in our another study (NCT 03196414). Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2019-131546
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 3
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    Sequential CD19- and Bcma-Specific Chimeric Antigen Receptor T Cell Treatment for RRMM: Report from a Single Center Study
    American Society of Hematology ; 2019
    In:  Blood Vol. 134, No. Supplement_1 ( 2019-11-13), p. 578-578
    Details
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 578-578
    Abstract: Background: Relapsed and/or refractory multiple myeloma (RRMM) has a very poor prognosis, especially for chinese patients with limited therapeutic options. Chimeric antigen receptor transduced T cells (CARTs) had been approved to be one of the rescue strategies for malignant B cell hematological tumors. CARTs targeting B-Cell Maturation Antigen (BCMA) were effective against RRMM in recent published clinical studies. CD19 is expressed by B cells before terminal differentiation into plasma cells and is associated with the enhancement of tumor-propagating and drug-resistance properties of myeloma. Thus, CD19 is also a potential therapeutic target. To our knowledge, we firstly designed the clinical study to evaluate the safety and efficacy of sequential infusion of CD19 and BCMA-Specific CARTs for RRMM patients (pts) (NCT 03196414). Our initial results showed this stragety had substantial anti-myeloma activity and well tolerated toxicities, which had been released at the 59th ASH meeting. Here, we will report the latest clinical data of a total of 28 RRMM patients receiving combined autologous CARTs infusion. Methods: Human T cells were collected from autologous peripheral blood mononuclear cells (PBSC). CART production was performed by the Unicar-Therapy Bio-medicine Technology Company (Shanghai, China). In this trial, RRMM pts firstly receive FC regimen as lymphodepleting conditioning , then were infused into CART-19 (1×107/kg on day 0) and CART-BCMA (total dose range: 2-6.8×107/kg) cells as split-dose infusions (40% on day 1 and 60% on day 2). After one month from CARTs infusion, some pts were adminstrated IMiDs for maintence therapy after hematopoietic recovery, including oral thalidomide 50mg/d or lenalidomide 10mg/d. This trial design and observation was seen in Blood,2017,130(Suppl.):506.The median follow-up time was 16 (3-28) months. Results: By January 2019, 28 pts were enrolled in this clinical trial. Among them, 23 (82.1%) pts were males and 5 (17.9%) pts were females. The median age was 57.5 (range: 42-69) years old. All pts were resistant to proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), or both. These pts had received an average of 3 (2-8) lines of therapy prior to enrollment. The most common adverse event of CART therapy was acute cytokine release syndrome (CRS), which occurred in 28 pts (100%). 19 pts (67.9%) were evaluated grade 1-2 CRS. 7 pts (25.0%) were evaluated grade 3 CRS, and 2 pts (7.1%) were grade 4. High-grade CRS was associated with elevated levels of IL-6, IFNγ, IL-10 and CRP, especially IL-6 upgradation to thousands of times the baseline. Other toxicities within two weeks of CARTs infusion included fatigue (n=28; 100%), cytopenia (n=28; 100%), anemia (n=28; 100%), prolonged APTT (n=23; 82.1%), elevated creatinine (n=13; 46.4%), gastrointestinal reaction(n=9; 32.1%), elevated transaminase (n=9; 32.1%). Notably, one patient (CRS grade 4) developed grade 4 CRES who exhibited generalized seizure. But this life-threatening complication was quickly relieved after corticosteroids and sodium valproate administration. Two pts (7.1%) had HLH/MAS. No fatal or severe adverse events emerged after two weeks following the infusion. Chronic side effects included chronic diarrhea, hematocytopenia, mild infection, grade ≤2 bilirubin and/or transaminase elevation, hypogammaglobulinemia, etc. No treatment related mortality occurred in this group of pts. Among the 28 pts who completed the CARTs infusion, 27 pts were monitored at predetermined time points and one patient lost follow-up. The overall response rate was 92.6%, and 88.9% of the pts were above PR. 11 pts (40.7%) were CR or sCR, 8 pts (29.6%) were VGPR, 5 pts (18.5%) were PR and one (3.7%) was MR. The remaining 2 pts, one (3.7%) was evaluated as SD and another (3.7%) was PD. 4 pts died from myeloma progression during the follow-up. Of those pts, the median PFS was 8 months. The median OS was 16 months. Conclusions: Combined sequential administration of CART-19 and CART-BCMA cells can be manufactured from heavily-treated MM pts, and could elicit sustained remission for RRMM pts. Toxicities can be well tolerated. CARTs early expansion and persistence in vivo post infusion may be predictive of clinical outcome. How to prolong the survival time of CARTs in vivo is one of the subjects worth studying in the future. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2019-129740
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 4
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    Sequential CD19 and BCMA‐specific CAR T‐cell treatment elicits sustained remission of relapsed and/or refractory myeloma
    Wiley ; 2021
    In:  Cancer Medicine Vol. 10, No. 2 ( 2021-01), p. 563-574
    Details
    In: Cancer Medicine, Wiley, Vol. 10, No. 2 ( 2021-01), p. 563-574
    Abstract: The low rate of durable response against relapsed and/or refractory multiple myeloma (RRMM) in recent studies indicates that chimeric antigen receptor T‐cell (CART) treatment is yet to be optimized. This study aims to investigate the safety and efficacy of sequential infusion of CD19‐CART and B‐cell maturation antigen (BCMA)‐CARTs for RRMM with a similar 3 + 3 dose escalation combined with a toxicity sentinel design. We enrolled 10 patients, among whom 7 received autologous infusion and 3 received allogeneic infusion. The median follow‐up time was 20 months. The most common grade 3/4 treatment‐emergent toxicities were hematological toxicities. Cytokine‐release syndrome (CRS) adverse reactions were grade 1/2 in 9 out of 10 subjects. No dose‐limited toxicity (DLT) was observed for BCMA‐CAR‐positive T cells ≤5 × 10 7 /kg), while two patients with dose‐levels of 5–6.5 × 10 7 /kg experienced DLTs. The overall response rate was 90% (five partial responses and four stringent complete responses). Three out of four patients with stringent complete responses to autologous CART had progression‐free survival for over 2 years. The three patients with allogeneic CART experienced disease progression within 2 months. These results evidence the sequential infusion's preliminarily tolerability and efficacy in RRMM, and present a simple and safe design applicable for the establishment of multiple CART therapy.
    Type of Medium: Online Resource
    ISSN: 2045-7634 , 2045-7634
    URL: Issue
    URL: Article
    DOI: 10.1002/cam4.v10.2
    DOI: 10.1002/cam4.3624
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2659751-2
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  • 5
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    Landscape of Adverse Events Related to Peroral Endoscopic Myotomy in 3135 Patients and a Risk-Scoring System to Predict Major Adverse Events
    Elsevier BV ; 2021
    In:  Clinical Gastroenterology and Hepatology Vol. 19, No. 9 ( 2021-09), p. 1959-1966.e3
    Details
    In: Clinical Gastroenterology and Hepatology, Elsevier BV, Vol. 19, No. 9 ( 2021-09), p. 1959-1966.e3
    Type of Medium: Online Resource
    ISSN: 1542-3565
    URL: Article
    DOI: 10.1016/j.cgh.2021.04.033
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
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  • 6
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    Prevalence and risk factors of stroke-related sarcopenia at the subacute stage: A case control study
    Frontiers Media SA ; 2022
    In:  Frontiers in Neurology Vol. 13 ( 2022-8-8)
    Details
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 13 ( 2022-8-8)
    Abstract: To investigate the prevalence and risk factors of stroke-related sarcopenia (SRS) in hospitalized patients receiving rehabilitation treatment. Methods Approximately, 259 patients with stroke that satisfied the inclusion and exclusion criteria were consecutively recruited between June 2020 and July 2022. The epidemiologic data, history, clinical data, and measured data of the skeletal muscle index were collected. The patients were divided into the sarcopenia and non-sarcopenia group for comparison and analysis with the univariate and multivariate analysis. Results SRS was presented in 121 (46.7%) patients with a mean age of 59.6 ± 9.7 years, including 42 women and 79 men. Multivariate logistic regression analysis revealed the following parameters to be significant ( p & lt; 0.05) risk factors for SRS: college degree or above (OR, 2.1, 95% CI, 1.1–4.1), ICU stay (OR, 1.7, 95% CI, 1.06–2.8), pneumonia (OR, 1.9, 9% CI, 1.1–3.6), walking ability (OR, 2.6, 95% CI, 1.5–4.6), cognitive impairment (OR, 1.8, 95%, 1.1–2.9), aphasia (OR, 2.1, 95% CI, 1.2–3.5), nasogastric feeding (OR, 3.7, 95%, 1.9–7.3), age (OR, 1.04, 95% CI, 1–1.1), and creatine kinase (OR, 1.1, 95% CI,0.9–1.2). Conclusions Older age, light weight, severer clinical conditions, cognitive impairment, and significantly decreased levels of albumin, RAG, creatinine, uric acid, red blood cell count, hemoglobin, prealbumin, iron, and creatine kinase are more significantly present in patients with SRS compared with those without SRS.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    URL: Article
    DOI: 10.3389/fneur.2022.899658
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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  • 7
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    Tandom Autologous Transplantation and Combined Infusion of CD19 and Bcma-Specific Chimeric Antigen Receptor T Cells for High Risk MM: Initial Safety and Efficacy Report from a Clinical Pilot Study
    American Society of Hematology ; 2018
    In:  Blood Vol. 132, No. Supplement 1 ( 2018-11-29), p. 1009-1009
    Details
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 1009-1009
    Abstract: Background: Multiple myeloma (MM) is an incurable plasma cell malignancies despite the advent of numerously new drugs. Survival was poor particularly for high risk patients such as R-ISS stage III. The preliminary data from our center showed that the median PFS after auto-HSCT was 24 months for patients with R-ISS III stage, while 17 months for patients that achieved PR or less after induction. Chimeric antigen receptor (CAR)-transduced T cells is a promising strategy for cancer immunotherapy. Our previous study showed good response for RRMM patients after CD19 and BCMA-specific CART therapy without severe CRS and other deadly side effects. To improve the survival of high risk patients, this study was designed to observe the safety and efficacy of combined infusion of CD19 and BCMA-specific CART cells after autologous transplantation (SZ-MM-CART02 study, NCT 03455972). Methods:18-65y NDMM in R-ISS stage III, or who only achieved PR or less after 4 cycles of PAD triplet induction were enrolled with serum creatinine (Cr) 〈 2.0 mg/dL, and adequate hepatic, cardiac and pulmonary function. BCMA and CD19 expression on MM cells were analyzed by flow cytometry. Lymphocytes were collected from PBSCs and cultured with an anti-CD3 monoclonal antibody to activate T-cell proliferation. The cells were transduced with recombinant lentiviral verctors which respectively contained the anti-BCMA or anti-CD19 single chain variable fragment (scFv), the cytoplasmic portion of the OX40 and CD28 costimulatory moiety, and the CD3z T-cell activation domain. This is the new third generation CAR technique applied in clinic. BUCY were used as conditioning, followed by infusion of autologous stem cells. Median time to engraftment were 10 days for nutrophils. CART-19 (1×107/kg on d0) and CART-BCMA cells as split-dose (40% on d1 and 60% on d2) were infused derectly on d14 to d20 after autologous transplantation. Levels of CAR-transduced cells are measured by qPCR. The cytokine release syndrome (CRS) was graded according to the UPen cytokine release syndrome grading system. Neurotoxic side effects and other toxicities were assessed according to the CTCAE v 4.03. Plasma levels of IL-2, IL-4, IL-6, IL-10, TNF-alpha, IFN-gamma, and IL-17A proteins were determined with a cytokine kit. Imids alone were given as maintenance therapy. Responses were assessed by IMWG criteria. 10-color flow cytometry was used to monitor MRD regularly after CART treatment. The median of follow-up was 3 (2∼11) months. Results: To date, 9 patients have completed the CART cells infusion (cohort 1). All cases expressed BCMA 〉 50% without CD19 expression on MM cells. CRS occurred in 9 patients (100%) grade1 or 2 associated with fever(n=9), fatigue (n=9), elevated IL-6 and CRP (n=9), elevated ALT (n=1, grade 1). Two patients needed to use low-dose vascular active drugs (pts 04 and 07). Other toxicities to date included coagulopathy (n=6, grade 1 for 4 pts and grade 2 for 2 pts), elevated troponin T (n=4, grade 1), and atrial flutter (n=1). There was no serious CRS or neurologic complications occurred in this group of patients. The ORR was 100% with all patients were monitored for a period of more than 2 months, which may be eventually further improved. There were 2 CR, 1 VGPR, 4 PR, 2 SD after induction; 3 CR, 2 VGPR, 4 PR after APBSCT; 3 CR, 6 VGPR after CART therapy. MRD negativity in BM increased from 37.5% after transplantation to 66.7% after CART therapy latest. Four patients (pts 02, 03, 06 and 07) obtained partial PR after transplantation, and got VGPR after CART cells infusion. We found dramatic in vivo CART expansion that median of peak value of CART copies was 1059.54 folds (ranged from 536.90 to 10997.93 folds) which was 100 folds to that with RRMM patients in our previous study. Conclusions: Tandom autologous transplantation and combined infusion of CART-19 and CART-BCMA cells could be another choice of consolidation treatment for high risk MM patients. Toxicities to date including CRS and organ function impairment seemed to be mild and reversable. It is worthy of further study to compare DFS, OS between single autologous transplantation and tandom transplantation with CART therapy. Immune environment in high risk patients with multiple myelomaI remodelled by auto-HSCT may contribute to more rapid expansion of CART cells than that in RRMM patients, suggesting that the extent of CART expansion depends more than tumor burden. Table Table. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2018-99-117964
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
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  • 8
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    Transoesophageal endoscopic removal of a benign mediastinal tumour: a new field for endotherapy?
    BMJ ; 2020
    In:  Gut Vol. 69, No. 10 ( 2020-10), p. 1727-1729
    Details
    In: Gut, BMJ, Vol. 69, No. 10 ( 2020-10), p. 1727-1729
    Type of Medium: Online Resource
    ISSN: 0017-5749 , 1468-3288
    URL: Article
    DOI: 10.1136/gutjnl-2020-321128
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 1492637-4
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  • 9
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    Realization of thousand-second improved confinement plasma with Super I-mode in Tokamak EAST
    American Association for the Advancement of Science (AAAS) ; 2023
    In:  Science Advances Vol. 9, No. 1 ( 2023-01-06)
    Details
    In: Science Advances, American Association for the Advancement of Science (AAAS), Vol. 9, No. 1 ( 2023-01-06)
    Abstract: Steady state high-confinement Super I-mode plasma can be achieved andmaintained in EAST for over 1056 s.
    Type of Medium: Online Resource
    ISSN: 2375-2548
    URL: Article
    DOI: 10.1126/sciadv.abq5273
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2023
    detail.hit.zdb_id: 2810933-8
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  • 10
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    Accuracy of Calf Circumference Measurement, SARC-F Questionnaire, and Ishii's Score for Screening Stroke-Related Sarcopenia
    Frontiers Media SA ; 2022
    In:  Frontiers in Neurology Vol. 13 ( 2022-4-29)
    Details
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 13 ( 2022-4-29)
    Abstract: The purpose of this study was to investigate the accuracy of sarcopenia diagnosis in patients with stroke using calf circumference (CC), SARC-F questionnaire, and Ishii's score in comparison with the Asian Working Group for Sarcopenia 2019 (AWGS) sarcopenia diagnostic criteria. Materials and Methods In this cross-sectional study, a total of 364 consecutive patients with stroke were enrolled and evaluated with the CC measurement, SARC-F questionnaire, and Ishii's score. The diagnostic accuracy was analyzed. Results Based on the AWGS criteria, sarcopenia was present in 180 (49.5%) patients, with an age range of 49–74 (mean 63 ± 14.7) years. In all patients, the cutoff value of CC in the accuracy of diagnosing sarcopenia was 30.5 cm, with an AUC of 0.85, sensitivity of 81.8%, specificity of 90.1%, Kappa value of 0.72, and Youden index of 0.72. In the accuracy of diagnosing sarcopenia in all patients, Ishii's score had a cutoff value of 118, AUC of 0.78, sensitivity of 90.1%, specificity of 36.0%, Kappa value of 0.4, and Youden index of 0.55. For accuracy of diagnosing sarcopenia, the SARC-F questionnaire had a cutoff value of 5, AUC of 0.731, sensitivity of 94.7%, specificity of 40%, Kappa value of 0.34, and Youden index of 0.41. Conclusions Based on the AWGS criteria, calf circumference measurement has the optimal performance in screening stroke-related sarcopenia compared with the SARC-F questionnaire and Ishii's score. In patients with stroke, the cutoff value of calf circumference for sarcopenia is & lt; 31 cm in men and 30 cm in women, and with an AUC of 0.85.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    URL: Article
    DOI: 10.3389/fneur.2022.880907
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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