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Article ; Online: Streamlined Adeno-Associated Virus Production Using Suspension HEK293T Cells.

Kulkarni, Aditi A / Seal, Austin G / Sonnet, Corinne / Oka, Kazuhiro

2024 Volume 14, Issue 3, Page(s) e4931

Abstract: Recombinant adeno-associated viruses (rAAVs) are valuable viral vectors for in vivo gene transfer, also having significant ex vivo therapeutic potential. Continued efforts have focused on various gene therapy applications, capsid engineering, and ... ...

Abstract	Recombinant adeno-associated viruses (rAAVs) are valuable viral vectors for in vivo gene transfer, also having significant ex vivo therapeutic potential. Continued efforts have focused on various gene therapy applications, capsid engineering, and scalable manufacturing processes. Adherent cells are commonly used for virus production in most basic science laboratories because of their efficiency and cost. Although suspension cells are easier to handle and scale up compared to adherent cells, their use in virus production is hampered by poor transfection efficiency. In this protocol, we developed a simple scalable AAV production protocol using serum-free-media-adapted HEK293T suspension cells and VirusGEN transfection reagent. The established protocol allows AAV production from transfection to quality analysis of purified AAV within two weeks. Typical vector yields for the described suspension system followed by iodixanol purification range from a total of 1 × 10
Language	English
Publishing date	2024-02-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2833269-6
ISSN	2331-8325 ; 2331-8325
ISSN (online)	2331-8325
ISSN	2331-8325
DOI	10.21769/BioProtoc.4931
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Article ; Online: Adeno-Associated Virus as Gene Delivery Vehicle into the Retina.

Deng, Shuyun / Oka, Kazuhiro

Methods in molecular biology (Clifton, N.J.)

2019 Volume 2092, Page(s) 77–90

Abstract: Initially discovered as a contaminant of adenovirus preparations, adeno-associated virus (AAV) has proved one of the most promising viral vectors for human gene therapy. The safety profile of AAV has been well-characterized in vivo studies, and the first ...

Abstract	Initially discovered as a contaminant of adenovirus preparations, adeno-associated virus (AAV) has proved one of the most promising viral vectors for human gene therapy. The safety profile of AAV has been well-characterized in vivo studies, and the first gene therapy for patients with vision loss caused by Leber congenital amaurosis or retinitis pigmentosa was approved by the US Food and Drug Administration in 2017. This is an exciting era for investigators working on retina biology and treatments for blindness. In this chapter, we provide detailed methods for laboratory-scale production, purification, and characterization of AAV.
MeSH term(s)	Adenoviridae/genetics ; Cell Line ; Eye Proteins/genetics ; Gene Transfer Techniques ; Genetic Therapy/methods ; Genetic Vectors/genetics ; HEK293 Cells ; Humans ; Leber Congenital Amaurosis/genetics ; Retina/physiology ; Retinitis Pigmentosa/genetics
Chemical Substances	Eye Proteins
Language	English
Publishing date	2019-11-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-0175-4_7
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Article ; Online: Characterization and quantification of adeno-associated virus capsid-loading states by multi-wavelength analytical ultracentrifugation with UltraScan.

Henrickson, Amy / Ding, Xiaozhe / Seal, Austin G / Qu, Zhe / Tomlinson, Lauren / Forsey, John / Gradinaru, Viviana / Oka, Kazuhiro / Demeler, Borries

Nanomedicine (London, England)

2023 Volume 18, Issue 22, Page(s) 1519–1534

Abstract: Aim: ...

Abstract	Aim:
MeSH term(s)	Capsid ; Dependovirus/genetics ; Ultracentrifugation/methods ; Genetic Vectors ; Microscopy, Electron, Transmission
Language	English
Publishing date	2023-10-25
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2277839-1
ISSN	1748-6963 ; 1743-5889
ISSN (online)	1748-6963
ISSN	1743-5889
DOI	10.2217/nnm-2023-0156
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Article ; Online: Gene therapy for neuropathic pain using dorsal root ganglion-targeted helper-dependent adenoviral vectors with GAD67 expression.

Ogawa, Nobuhiro / Terashima, Tomoya / Oka, Kazuhiro / Chan, Lawrence / Kojima, Hideto

Pain reports

2018 Volume 3, Issue 6, Page(s) e695

Abstract: Introduction: Currently available medications for neuropathic pain are of limited efficacy. Moreover, they are administered systemically and are associated with significant side effects. Ideally, one can circumvent systemic side effects if such ... ...

Abstract	Introduction: Currently available medications for neuropathic pain are of limited efficacy. Moreover, they are administered systemically and are associated with significant side effects. Ideally, one can circumvent systemic side effects if such treatment can be administered by delivery of the therapeutic agent directly to the diseased neurons. Towards this end, we previously reported the production of a recombinant helper-dependent adenovirus (HDAd) armed with a tissue-specific homing peptide to deliver transgenes targeting sensory neurons with high efficacy. Objectives: To develop an effective gene therapy for neuropathic pain by producing a dorsal root ganglion (DRG)-targeted HDAd vector that specifically expresses glutamic acid decarboxylase (GAD) 67 (HDAd-DRG-GAD67). Methods: We produced spinal nerve transection (SNT) mice as a neuropathic pain model and delivered HDAd-DRG-GAD67 by injection into spinal nerve or intrathecally to these animals. We evaluated the therapeutic efficacy by measuring ion channel gene expression and quantifying mechanical allodynia, a representative symptom of neuropathic pain, in treated animals. Results: Glutamic acid decarboxylase expression by HDAd-DRG-GAD67 reduced allodynia significantly in SNT mice. In addition, HDAd-DRG-GAD67 had a much greater transduction efficacy and expressed the therapeutic gene for a much longer time and at a lower dose of viral particles than wild-type HDAd. We found that SNT induced the upregulation of Cav3.2 mRNA in the DRG and GAD67 overexpression suppressed the elevation. Furthermore, the HDAd-DRG-GAD67-induced allodynia amelioration occurred even when we delayed intrathecal delivery of the therapeutic vector to day 7 after SNT. Conclusion: HDAd-mediated DRG-targeted gene therapy delivering GAD67 is an efficacious treatment for neuropathic pain in SNT mice.
Language	English
Publishing date	2018-10-15
Publishing country	United States
Document type	Journal Article
ISSN	2471-2531
ISSN (online)	2471-2531
DOI	10.1097/PR9.0000000000000695
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Article ; Online: Impact of Multidomain Frailty on the Mode of Death in Older Patients With Heart Failure: A Cohort Study.

Ohashi, Koichi / Matsue, Yuya / Maeda, Daichi / Fujimoto, Yudai / Kagiyama, Nobuyuki / Sunayama, Tsutomu / Dotare, Taishi / Jujo, Kentaro / Saito, Kazuya / Kamiya, Kentaro / Saito, Hiroshi / Ogasahara, Yuki / Maekawa, Emi / Konishi, Masaaki / Kitai, Takeshi / Iwata, Kentaro / Wada, Hiroshi / Hiki, Masaru / Kasai, Takatoshi /

Nagamatsu, Hirofumi / Ozawa, Tetsuya / Izawa, Katsuya / Yamamoto, Shuhei / Aizawa, Naoki / Wakaume, Kazuki / Oka, Kazuhiro / Momomura, Shin-Ichi / Minamino, Tohru

Circulation. Cardiovascular quality and outcomes

2024 , Page(s) e010416

Abstract: Background: Although frailty is strongly associated with mortality in patients with heart failure (HF), the risk of which specific cause of death is associated with being complicated with frailty is unclear. We aimed to clarify the association between ... ...

Abstract	Background: Although frailty is strongly associated with mortality in patients with heart failure (HF), the risk of which specific cause of death is associated with being complicated with frailty is unclear. We aimed to clarify the association between multidomain frailty and the causes of death in elderly patients hospitalized with HF. Methods: We analyzed data from the FRAGILE-HF cohort, where patients aged 65 years and older, hospitalized with HF, were prospectively registered between 2016 and 2018 in 15 Japanese hospitals before discharge and followed up for 2 years. All patients were assessed for physical, social, and cognitive dysfunction, and categorized into 3 groups based on their number of frailty domains (FDs, 0-1, 2, and 3). Kaplan-Meier survival analysis was used to evaluate the association between the number of FDs and all-cause mortality, whereas Fine-Gray competing risk regression analysis was used for assessing the impact on cause-specific mortality. Results: We analyzed 1181 patients with HF (81 years old in median, 57.4% were male), 530 (44.9%), 437 (37.0%), and 214 (18.1%) of whom were categorized into the FD 0 to 1, FD 2, and FD 3 groups, respectively. During the 2-year follow-up, 240 deaths were observed (99 HF deaths, 34 cardiovascular deaths, and 107 noncardiovascular deaths), and an increase in the number of FD was significantly associated with mortality (Log-rank: Conclusions: Although multidomain frailty is strongly associated with mortality in older patients with HF, it is mostly attributable to noncardiovascular death and not cardiovascular death, including HF death. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: UMIN000023929.
Language	English
Publishing date	2024-03-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	2483197-9
ISSN	1941-7705 ; 1941-7713
ISSN (online)	1941-7705
ISSN	1941-7713
DOI	10.1161/CIRCOUTCOMES.123.010416
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Article ; Online: Prognostic impact of MitraScore in elderly Asian patients with heart failure: sub-analysis of FRAGILE-HF.

Kaneko, Tomohiro / Kagiyama, Nobuyuki / Kasai, Takatoshi / Kamiya, Kentaro / Saito, Hiroshi / Saito, Kazuya / Ogasahara, Yuki / Maekawa, Emi / Konishi, Masaaki / Kitai, Takeshi / Iwata, Kentaro / Jujo, Kentaro / Wada, Hiroshi / Maeda, Daichi / Hiki, Masaru / Sunayama, Tsutomu / Dotare, Taishi / Nagamatsu, Hirofumi / Ozawa, Tetsuya /

Izawa, Katsuya / Yamamoto, Shuhei / Aizawa, Naoki / Makino, Akihiro / Oka, Kazuhiro / Momomura, Shin-Ichi / Matsue, Yuya / Minamino, Tohru

ESC heart failure

2024 Volume 11, Issue 2, Page(s) 1039–1050

Abstract: Aims: MitraScore is a novel, simple, and manually calculatable risk score developed as a prognostic model for patients undergoing transcatheter edge-to-edge repair (TEER) for mitral regurgitation. As its components are considered prognostic in heart ... ...

Abstract	Aims: MitraScore is a novel, simple, and manually calculatable risk score developed as a prognostic model for patients undergoing transcatheter edge-to-edge repair (TEER) for mitral regurgitation. As its components are considered prognostic in heart failure (HF), we aimed to investigate the usefulness of the MitraScore in HF patients. Methods and results: We calculated MitraScore for 1100 elderly patients (>65 years old) hospitalized for HF in the prospective multicentre FRAGILE-HF study and compared its prognostic ability with other simple risk scores. The primary endpoint was all-cause deaths, and the secondary endpoints were the composite of all-cause deaths and HF rehospitalization and cardiovascular deaths. Overall, the mean age of 1100 patients was 80 ± 8 years, and 58% were men. The mean MitraScore was 3.2 ± 1.4, with a median of 3 (interquartile range: 2-4). A total of 326 (29.6%), 571 (51.9%), and 203 (18.5%) patients were classified into low-, moderate-, and high-risk groups based on the MitraScore, respectively. During a follow-up of 2 years, 226 all-cause deaths, 478 composite endpoints, and 183 cardiovascular deaths were observed. MitraScore successfully stratified patients for all endpoints in the Kaplan-Meier analysis (P < 0.001 for all). In multivariate analyses, MitraScore was significantly associated with all endpoints after covariate adjustments [adjusted hazard ratio (HR) (95% confidence interval): 1.22 (1.10-1.36), P < 0.001 for all-cause deaths; adjusted HR 1.17 (1.09-1.26), P < 0.001 for combined endpoints; and adjusted HR 1.24 (1.10-1.39), P < 0.001 for cardiovascular deaths]. The Hosmer-Lemeshow plot showed good calibration for all endpoints. The net reclassification improvement (NRI) analyses revealed that the MitraScore performed significantly better than other manually calculatable risk scores of HF: the GWTG-HF risk score, the BIOSTAT compact model, the AHEAD score, the AHEAD-U score, and the HANBAH score for all-cause and cardiovascular deaths, with respective continuous NRIs of 0.20, 0.22, 0.39, 0.39, and 0.29 for all-cause mortality (all P-values < 0.01) and 0.20, 0.22, 0.42, 0.40, and 0.29 for cardiovascular mortality (all P-values < 0.02). Conclusions: MitraScore developed for patients undergoing TEER also showed strong discriminative power in HF patients. MitraScore was superior to other manually calculable simple risk scores and might be a good choice for risk assessment in clinical practice for patients receiving TEER and those with HF.
MeSH term(s)	Male ; Humans ; Aged ; Female ; Prognosis ; Prospective Studies ; Heart Failure/complications ; Risk Factors ; Risk Assessment/methods
Language	English
Publishing date	2024-01-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2814355-3
ISSN	2055-5822 ; 2055-5822
ISSN (online)	2055-5822
ISSN	2055-5822
DOI	10.1002/ehf2.14658
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Article ; Online: Functional Differences of Very-Low-Density Lipoprotein Receptor Splice Variants in Regulating Wnt Signaling.

Chen, Qian / Takahashi, Yusuke / Oka, Kazuhiro / Ma, Jian-Xing

Molecular and cellular biology

2016 Volume 36, Issue 20, Page(s) 2645–2654

Abstract: The very-low-density lipoprotein receptor (VLDLR) negatively regulates Wnt signaling. VLDLR has two major alternative splice variants, VLDLRI and VLDLRII, but their biological significance and distinction are unknown. Here we found that most tissues ... ...

Abstract	The very-low-density lipoprotein receptor (VLDLR) negatively regulates Wnt signaling. VLDLR has two major alternative splice variants, VLDLRI and VLDLRII, but their biological significance and distinction are unknown. Here we found that most tissues expressed both VLDLRI and VLDLRII, while the retina expressed only VLDLRII. The shed soluble VLDLR extracellular domain (sVLDLR-N) was detected in the conditioned medium of retinal pigment epithelial cells, interphotoreceptor matrix, and mouse plasma, indicating that ectodomain shedding of VLDLR occurs endogenously. VLDLRII displayed a higher ectodomain shedding rate and a more potent inhibitory effect on Wnt signaling than VLDLRI in vitro and in vivo O-glycosylation, which is present in VLDLRI but not VLDLRII, determined the differential ectodomain shedding rates. Moreover, the release of sVLDLR-N was inhibited by a metalloproteinase inhibitor, TAPI-1, while it was promoted by phorbol 12-myristate 13-acetate (PMA). In addition, sVLDLR-N shedding was suppressed under hypoxia. Further, plasma levels of sVLDLR-N were reduced in both type 1 and type 2 diabetic mouse models. We concluded that VLDLRI and VLDLRII had differential roles in regulating Wnt signaling and that decreased plasma levels of sVLDLR-N may contribute to Wnt signaling activation in diabetic complications. Our study reveals a novel mechanism for intercellular regulation of Wnt signaling through VLDLR ectodomain shedding.
MeSH term(s)	Animals ; Cells, Cultured ; Culture Media, Conditioned/chemistry ; Diabetes Mellitus, Type 1/metabolism ; Diabetes Mellitus, Type 2/metabolism ; Disease Models, Animal ; Down-Regulation ; Glycosylation ; Humans ; Mice ; Protein Isoforms/metabolism ; Receptors, LDL/blood ; Receptors, LDL/genetics ; Receptors, LDL/metabolism ; Retina/metabolism ; Retinal Pigment Epithelium/cytology ; Retinal Pigment Epithelium/metabolism ; Tissue Distribution ; Wnt Signaling Pathway
Chemical Substances	Culture Media, Conditioned ; Protein Isoforms ; Receptors, LDL ; VLDL receptor
Language	English
Publishing date	2016--15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	779397-2
ISSN	1098-5549 ; 0270-7306
ISSN (online)	1098-5549
ISSN	0270-7306
DOI	10.1128/MCB.00235-16
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Article ; Online: Prognostic impact of cachexia by multi-assessment in older adults with heart failure: FRAGILE-HF cohort study.

Maekawa, Emi / Noda, Takumi / Maeda, Daichi / Yamashita, Masashi / Uchida, Shota / Hamazaki, Nobuaki / Nozaki, Kohei / Saito, Hiroshi / Saito, Kazuya / Ogasahara, Yuki / Konishi, Masaaki / Kitai, Takeshi / Iwata, Kentaro / Jujo, Kentaro / Wada, Hiroshi / Kasai, Takatoshi / Nagamatsu, Hirofumi / Ozawa, Tetsuya / Izawa, Katsuya /

Yamamoto, Shuhei / Aizawa, Naoki / Yonezawa, Ryusuke / Oka, Kazuhiro / Ako, Junya / Momomura, Shin-Ichi / Kagiyama, Nobuyuki / Matsue, Yuya / Kamiya, Kentaro

Journal of cachexia, sarcopenia and muscle

2023 Volume 14, Issue 5, Page(s) 2143–2151

Abstract: Background: Cachexia substantially impacts the prognosis of patients with heart failure (HF); however, there is no standard method for cachexia diagnosis. This study aimed to investigate the association of Evans's criteria, consisting of multiple ... ...

Abstract	Background: Cachexia substantially impacts the prognosis of patients with heart failure (HF); however, there is no standard method for cachexia diagnosis. This study aimed to investigate the association of Evans's criteria, consisting of multiple assessments, with the prognosis of HF in older adults. Methods: This study is a secondary analysis of the data from the FRAGILE-HF study, a prospective multicentre cohort study that enrolled consecutive hospitalized patients aged ≥65 years with HF. Patients were divided into two groups: the cachexia and non-cachexia groups. Cachexia was defined according to Evans's criteria by assessing weight loss, muscle weakness, fatigue, anorexia, a decreased fat-free mass index and an abnormal biochemical profile. The primary outcome was all-cause mortality, as assessed in the survival analysis. Results: Cachexia was present in 35.5% of the 1306 enrolled patients (median age [inter-quartile range], 81 [74-86] years; 57.0% male); 59.6%, 73.2%, 15.6%, 71.0%, 44.9% and 64.6% had weight loss, decreased muscle strength, a low fat-free mass index, abnormal biochemistry, anorexia and fatigue, respectively. All-cause mortality occurred in 270 patients (21.0%) over 2 years. The cachexia group (hazard ratio [HR], 1.494; 95% confidence interval [CI], 1.173-1.903; P = 0.001) had a higher mortality risk than the non-cachexia group after adjusting for the severity of HF. Cardiovascular and non-cardiovascular deaths occurred in 148 (11.3%) and 122 patients (9.3%), respectively. The adjusted HRs for cachexia in cardiovascular mortality and non-cardiovascular mortality were 1.456 (95% CI, 1.048-2.023; P = 0.025) and 1.561 (95% CI, 1.086-2.243; P = 0.017), respectively. Among the cachexia diagnostic criteria, decreased muscle strength (HR, 1.514; 95% CI, 1.095-2.093; P = 0.012) and low fat-free mass index (HR, 1.424; 95% CI, 1.052-1.926; P = 0.022) were significantly associated with high all-cause mortality, but there was no significant association between weight loss alone (HR, 1.147; 95% CI, 0.895-1.471; P = 0.277) and all-cause mortality. Conclusions: Cachexia evaluated by multi-assessment was present in one third of older adults with HF and was associated with a worse prognosis. A multimodal assessment of cachexia may be helpful for risk stratification in older patients with HF.
Language	English
Publishing date	2023-07-11
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2586864-0
ISSN	2190-6009 ; 2190-5991
ISSN (online)	2190-6009
ISSN	2190-5991
DOI	10.1002/jcsm.13291
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Article ; Online: Prognostic implications of six-minute walking distance in patients with heart failure with preserved ejection fraction.

Fujimoto, Yudai / Maeda, Daichi / Kagiyama, Nobuyuki / Sunayama, Tsutomu / Dotare, Taishi / Jujo, Kentaro / Saito, Kazuya / Kamiya, Kentaro / Saito, Hiroshi / Ogasahara, Yuki / Maekawa, Emi / Konishi, Masaaki / Kitai, Takeshi / Iwata, Kentaro / Wada, Hiroshi / Hiki, Masaru / Kasai, Takatoshi / Nagamatsu, Hirofumi / Ozawa, Tetsuya /

Izawa, Katsuya / Yamamoto, Shuhei / Aizawa, Naoki / Wakaume, Kazuki / Oka, Kazuhiro / Momomura, Shin-Ichi / Matsue, Yuya

International journal of cardiology

2023 Volume 379, Page(s) 76–81

Abstract: Background: The incremental prognostic value of the six-minute walking test over conventional risk factors has not been evaluated in an adequate number of patients with heart failure with preserved ejection fraction (HFpEF). Therefore, we aimed to ... ...

Abstract	Background: The incremental prognostic value of the six-minute walking test over conventional risk factors has not been evaluated in an adequate number of patients with heart failure with preserved ejection fraction (HFpEF). Therefore, we aimed to examine its prognostic significance using data from the FRAGILE-HF study. Methods and results: A total of 513 older patients who were hospitalized for worsening heart failure were examined. Patients were classified according to the tertiles of six-minute walking distance (6MWD): T1 (<166 m), T2 (166-285 m), and T3 (≥285 m). During the 2-year follow-up period after discharge, 90 all-cause deaths occurred. Kaplan-Meier curves showed that the T1 group had significantly higher event rates than the other groups (log-rank p = 0.007). Cox proportional hazard analysis revealed that the T1 group was independently associated with lower survival, even after adjusting for conventional risk factors (T3: hazard ratio 1.79, 95% confidence interval 1.02-3.14, p = 0.042). The addition of the 6MWD to the conventional prognostic model showed a statistically significant incremental prognostic value (net reclassification improvement 0.27, 95% confidence interval 0.04-0.49; p = 0.019). Conclusions: The 6MWD is associated with survival in patients with HFpEF and has an incremental prognostic value over conventional well-validated risk factors.
MeSH term(s)	Humans ; Prognosis ; Stroke Volume ; Ventricular Function, Left ; Heart Failure/diagnosis ; Risk Factors
Language	English
Publishing date	2023-03-11
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	779519-1
ISSN	1874-1754 ; 0167-5273
ISSN (online)	1874-1754
ISSN	0167-5273
DOI	10.1016/j.ijcard.2023.03.025
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Article ; Online: Prevalence and prognostic impact of the coexistence of cachexia and sarcopenia in older patients with heart failure.

Izawa, Katsuya / Yamamoto, Shuhei / Aizawa, Naoki / Wakaume, Kazuki / Oka, Kazuhiro / Momomura, Shin-Ichi / Matsue, Yuya

International journal of cardiology

2023 Volume 381, Page(s) 45–51

Abstract: Background: No study with an adequate patients' number has examined the relationship/overlap between sarcopenia and cachexia. We examined the prevalence of the overlap and prognostic implications of sarcopenia and cachexia in older patients with heart ... ...

Abstract	Background: No study with an adequate patients' number has examined the relationship/overlap between sarcopenia and cachexia. We examined the prevalence of the overlap and prognostic implications of sarcopenia and cachexia in older patients with heart failure using well-accepted definitions. Methods: This was a post-hoc sub-analysis of the FRAGILE-HF study, a prospective, multicenter, observational study conducted at 15 hospitals in Japan. In total, 905 hospitalized older patients were classified into four groups based on the presence or absence of cachexia and/or sarcopenia, which were defined according to the Evans and Asian Working Group for Sarcopenia criteria revised in 2019, respectively. The primary endpoint was 2-year all-cause mortality. Results: Cachexia and sarcopenia prevalence rates were 32.7% and 22.7%, respectively. Patients were classified into the non-cachexia/non-sarcopenia (55.7%), cachexia/non-sarcopenia (21.7%), non-cachexia/sarcopenia (11.6%), and cachexia/sarcopenia (11.0%) groups. During the 2-year follow-up period after discharge, 158 (17.5%) all-cause deaths (124 cardiovascular deaths [CVD] and 34 non-CVD) were observed. The cachexia/sarcopenia group had the lowest body fat mass and exhibited significantly higher mortality rates (log-rank P < 0.001). Cox proportional hazard analysis revealed that cachexia/sarcopenia was an independent prognostic factor after adjusting for known prognostic factors (versus non-cachexia/non-sarcopenia: hazard ratio, 2.78; 95% confidence interval, 1.80-4.29; P < 0.001). Neither cachexia/non-sarcopenia nor non-cachexia/sarcopenia were significantly associated with all-cause mortality compared with non-cachexia/non-sarcopenia. Conclusions: Cachexia and sarcopenia are prevalent among older hospitalized patients with heart failure; nonetheless, the overlap is not as prominent as previously expected. The presence of cachexia and sarcopenia is a risk factor for all-cause mortality.
MeSH term(s)	Humans ; Aged ; Prognosis ; Prospective Studies ; Prevalence ; Sarcopenia/diagnosis ; Sarcopenia/epidemiology ; Sarcopenia/etiology ; Cachexia/diagnosis ; Cachexia/epidemiology ; Cachexia/etiology ; Heart Failure/complications ; Heart Failure/diagnosis ; Heart Failure/epidemiology
Language	English
Publishing date	2023-03-17
Publishing country	Netherlands
Document type	Observational Study ; Multicenter Study ; Journal Article
ZDB-ID	779519-1
ISSN	1874-1754 ; 0167-5273
ISSN (online)	1874-1754
ISSN	0167-5273
DOI	10.1016/j.ijcard.2023.03.035
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