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1.
PLoS One ; 15(10): e0241343, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33112920

RESUMO

This study aims to investigate the changes in metamorphopsia after administering the treat-and-extend regimen of anti-vascular endothelial growth factor therapy for branch retinal vein occlusion-associated macular edema. We retrospectively examined 27 patients (27 eyes) with macula edema due to branch retinal vein occlusion who received intravitreal injections of anti-vascular endothelial growth factor agents using the treat-and-extend regimen for ≥18 months. We evaluated best-corrected visual acuity, central macular thickness, macular edema recurrence, and amount of metamorphopsia quantified by M-CHARTS. The best-corrected visual acuity (logarithm of minimum angle of resolution) and central macular thickness significantly improved at 18 months compared to baseline, the median value (interquartile range [IQR]), 0.30 (0.15-0.52) and 459 (373-542) µm at baseline, and 0 (-0.08-0.16) and 267 (232-306) µm at 18 months. The M-CHARTS score (the mean of vertical and horizontal scores) significantly decreased at 1, 6, and 12 months compared to baseline, but worsened at 18 month, the median value (IQR), 0.45 (0.250-0.925), 0.4 (0.15-0.70), 0.4 (0.150-0.625), 0.4 (0.225-0.550) and 0.45 (0.225-0.750) at baseline, 1 month, 6 months, 12 months and 18 months, respectively. The median cumulative number of macular edema recurrences was 2 (IQR, 0.5-3.0) at 18 months. Simple linear regression and multivariate analyses revealed that the change in the mean M-CHARTS score at 18 months was significantly correlated with the baseline score and the cumulative number of macular edema recurrences. Anti-vascular endothelial growth factor therapy using the treat-and-extend regimen improved metamorphopsia in branch retinal vein occlusion-related macular edema in the short to mid-term follow-up period, but not in the long term. Macular edema recurrence may be associated with persistent metamorphopsia.

2.
Materials (Basel) ; 13(21)2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33114102

RESUMO

One thin 5000 series aluminium alloy sheet and two thin 980 MPa grade cold rolled ultra-high strength steel sheets were joined by self-pierce riveting and mechanical clinching processes. The joinabilities for a combination of the aluminium and steel sheets in both processes were investigated for different die shapes in the experiment and finite element simulation. In self-pierce riveting, the three sheets were successfully joined for both combinations of the upper and lower aluminium alloy sheets by optimizing the shapes of a die and rivet. In mechanical clinching, the three sheets were successfully joined by an optimum die for the configuration of the upper aluminium alloy sheet. On the other hand, the three sheets for the configuration of the lower aluminium alloy sheet were not joined even by optimizing the die shape in the both finite element simulation and experiment, because the material flow of the steel sheets was insufficient to form the two interlocks. The tension-shear loads for the clinched and riveted sheets with the adhesive were almost the same, because the load for the adhesive was the highest. In the cross-tension test, however, the load by the adhesive was comparatively small.

3.
Sci Rep ; 10(1): 9299, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32518264

RESUMO

Ischemic proliferative retinopathy (IPR), such as proliferative diabetic retinopathy (PDR), retinal vein occlusion and retinopathy of prematurity is a major cause of vision loss. Our previous studies demonstrated that periostin (PN) and tenascin-C (TNC) are involved in the pathogenesis of IPR. However, the interactive role of PN and TNC in angiogenesis associated with IPR remain unknown. We found significant correlation between concentrations of PN and TNC in PDR vitreous humor. mRNA and protein expression of PN and TNC were found in pre-retinal fibrovascular membranes excised from PDR patients. Interleukin-13 (IL-13) promoted mRNA and protein expression of PN and TNC, and co-immunoprecipitation assay revealed binding between PN and TNC in human microvascular endothelial cells (HRECs). IL-13 promoted angiogenic functions of HRECs. Single inhibition of PN or TNC and their dual inhibition by siRNA suppressed the up-regulated angiogenic functions. Pathological pre-retinal neovessels of oxygen-induced retinopathy (OIR) mice were attenuated in PN knock-out, TNC knock-out and dual knock-out mice compared to wild-type mice. Both in vitro and in vivo, PN inhibition had a stronger inhibitory effect on angiogenesis compared to TNC inhibition, and had a similar effect to dual inhibition of PN and TNC. Furthermore, PN knock-out mice showed scant TNC expression in pre-retinal neovessels of OIR retinas. Our findings suggest that interaction of PN and TNC facilitates pre-retinal angiogenesis, and PN is an effective therapeutic target for IPR such as PDR.

4.
Clin J Gastroenterol ; 13(5): 891-895, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32468502

RESUMO

We treated a 66-year-old Japanese male with unresectable hepatocellular carcinoma (u-HCC) for multiple (>5) liver tumors (maximum 2.6 cm in size, Child-Pugh B score 7) in September 2018. The patient had a history of psoriasis vulgaris and sorafenib (SOR) was introduced (800 mg/day) because of transcatheter arterial chemoembolization (TACE) refractoriness. However, psoriasis vulgaris exacerbation and a high fever were observed 2 weeks later, and the patient was admitted, after which improvement of psoriasis vulgaris was obtained with external medicine administration and SOR intake discontinuation. Few reports have noted exacerbation of psoriasis vulgaris caused by SOR treatment.

5.
Graefes Arch Clin Exp Ophthalmol ; 258(4): 735-741, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31960130

RESUMO

PURPOSE: We evaluated changes in the numbers of microaneurysms (MAs) on fluorescein angiography (FA) and indocyanine green angiography (IA) in eyes with diabetic macular edema (DME) following intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents. METHODS: Twenty-one eyes of 16 patients with DME were included in this retrospective study. All patients received an initial loading dose of three monthly injections of anti-VEGF agents; thereafter, they received a pro re nata regimen for at least 12 months of follow-up. FA and IA images were obtained before and at 6 months after the initial injection. RESULTS: The median numbers of MAs significantly decreased from six (interquartile range [IQR] 3-7) MAs in early-phase FA, three (IQR 3-5) leaky MAs in late-phase FA, and two (IQR 1-4) MAs in late-phase IA at baseline to two (IQR 1-3) MAs in early-phase FA, one (IQR 0-2) leaky MA in late-phase FA, and one (IQR 0-2) MA in late-phase IA at 6 months (P < 0.0001 for all). Only the median numbers of MAs in late-phase IA at baseline and at 6 months were significantly higher in the recurrent DME group (13 eyes) than in the non-recurrent DME group (five eyes) (three [IQR 2-4] vs one [IQR 1-2], one [IQR 0.5-2] vs zero [P = 0.0185 and P = 0.009]). CONCLUSION: Intravitreal injection of anti-VEGF agents reduced the numbers of MAs in patients with DME. The numbers of MAs detected by late-phase IA might be useful predictors of DME recurrence.

6.
Hepatol Res ; 50(1): 92-100, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31729124

RESUMO

AIM: Although a reduced serum zinc level is often observed in patients with chronic liver disease due to hepatitis virus, its prognostic importance has not been adequately investigated. This study aimed to elucidate the association of zinc deficiency with prognosis, especially in early hepatocellular carcinoma (HCC) patients. METHODS: From 2005 to 2018, 466 patients with naïve HCC due to hepatitis virus were enrolled (327 men, 139 women; median age 70 years; hepatitis C virus [HCV] n = 389, hepatitis B virus [HBV] n = 69, hepatitis C virus and hepatitis B virus n = 8; Child-Pugh A n = 367, Child-Pugh B n = 82; Child-Pugh C n = 17; TNM-LCSGJ stage I n = 150, stage II n = 181, stage III n = 91, stage IVa n = 26, state IVb n = 18). Of the 466 patients, 287 were within the Milan criteria (early HCC) and treated curatively. Zinc deficiency was defined as <60 µg/dL. Clinical records and prognostic factors were retrospectively evaluated. RESULTS: The levels of serum zinc became lower with chronic liver disease progression (Child-Pugh A, B, C: 64.3 ± 14.3, 52.3 ± 15.7, 48.4 ± 13.5 µg/dL, respectively; P < 0.001). In early HCC patients treated curatively, overall survival and recurrence rates were better in patients treated curatively and without zinc deficiency as compared with patients with zinc deficiency (3-year overall survival 86.5% vs. 77.2%, 5-year overall survival 73.5% vs. 43.8%, P < 0.001; 3-year recurrence 44.8% vs. 58.3%, 5-year recurrence 56.8% vs. 77.5%, P = 0.002). Not only infection control of hepatitis virus (sustained virological response in HCV or nucleos(t)ide analogs in HBV; HR 0.078, P < 0.001), but also zinc deficiency (HR 1.773, P = 0.041) were significant prognostic factors for death. CONCLUSION: Serum levels of zinc were reduced in association with chronic liver disease grade progression. In addition to infection control of hepatitis virus, zinc deficiency might be a significant prognostic factor for survival in patients with early HCC due to viral hepatitis treated curatively.

7.
Graefes Arch Clin Exp Ophthalmol ; 258(3): 621-628, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31863397

RESUMO

PURPOSE: To investigate periostin (PN) and tenascin-C (TNC) expression in the aqueous humor and trabeculectomy specimens of patients with neovascular glaucoma (NVG) secondary to proliferative diabetic retinopathy (PDR). METHODS: This study enrolled 37 eyes of 37 patients who were grouped into (1) NVG secondary to PDR (NVG; n = 8); (2) PDR without NVG (PDR; n = 9); (3) primary open-angle glaucoma (POAG; n = 11); and (4) cataract surgery patients as a control group (CG; n = 9). Aqueous humor samples were collected from the anterior chamber at the start of surgery or intravitreal injection of anti-VEGF drug. The concentrations of PN, TNC, VEGF, and TGF-ß2 (transforming growth factor-beta 2) were measured by ELISA. Sclerostomy tissues containing trabecular meshwork were obtained from two NVG patients and a POAG patient who underwent trabeculectomy surgery. Immunohistochemical analyses were performed to determine the localization of PN and TNC expression in the sclerostomy tissues. RESULTS: PN and TNC-C levels were below detection threshold in the POAG and CG groups. The NVG group had significantly higher levels of PN and TNC compared with the PDR group (84.7 ng/ml vs 2.2 ng/ml and 18.5 ng/ml vs 4.6 ng/ml, respectively; p < 0.05). There was a significant correlation between the levels of PN and TNC-C in the NVG group (r = 0.86, p < 0.05). We found significant expression of PN in the trabecular meshwork and Schlemm's canal of sclerostomy tissues excised from patients with NVG. CONCLUSIONS: Increased PN and TNC expression suggests their possible involvement in the pathogenesis of NVG secondary to PDR.

8.
Hepatol Res ; 50(4): 502-511, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31830344

RESUMO

AIM: An easily performed method for examination of muscle abnormalities is anticipated. We aimed to elucidate the clinical usefulness of simple assessments for muscle abnormality including a simple five-item questionnaire (SARC-F) in chronic liver disease patients. METHODS: From February to July 2019, 383 outpatients (median age 71 years, 259 men; chronic hepatitis (CH) : liver cirrhosis Child-Pugh A : liver cirrhosis Child-Pugh B : liver cirrhosis Child-Pugh C = 157:176:39:11) who underwent a computed tomography examination were enrolled. SARC-F, previously reported cut-off values for muscle strength decline (MSD; handgrip), pre-muscle volume loss (pre-MVL), calf circumference and finger-circle test results were used, and these results were analyzed retrospectively. RESULTS: A high SARC-F score (≥4) was observed in 25 patients, and a low score (<4) in 358 patients. The frequency of high SARC-F increased significantly with progression of chronic liver disease (chronic hepatitis : liver cirrhosis Child-Pugh A : liver cirrhosis Child-Pugh B/C = 2.5%:8.0%:14.0%, P=0.010). MSD frequency was 22.4% in men and 41.1% in women. Muscle volume loss and pre-MVL were noted in 22% and 30.5%, respectively, of the male patients, and 9.7% and 32.3%, respectively, of the female patients. In cases with high SARC-F and MSD, calf circumference and finger-circle abnormalities were found in 56% and 40.0% of patients, respectively, whereas those values for patients with low SARC-F and MSD were 14.5% and 10.6%, respectively (P < 0.001, for each; positive/negative predictive values: 0.560/0.855 and 0.400/0.894, respectively). Each SARC-F item showed a good area under the curve for MSD, but not pre-MVL. CONCLUSION: SARC-F score in combination with MSD and calf circumference or finger-circle test results may be an easy and simple method for surveillance of chronic liver disease patients with a high risk of sarcopenia and decline of quality of life.

9.
Mol Clin Oncol ; 11(3): 325-330, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31384461

RESUMO

To examine the effectiveness of ultrasonography (US) for hepatocellular carcinoma (HCC) surveillance, the prognosis of HCC patients who underwent such screening at an expert medical institution or at general clinics were analyzed, as well as those without US surveillance. From October 2006 to December 2014, 872 patients with naïve HCC were enrolled and divided into the surveillance (S)-group (n=398), who underwent follow-up examinations with US, and the non-S group (n=474). The S-group was further subdivided into patients who underwent follow-up surveillance at Ehime Prefectural Central Hospital, an expert medical institution (SE-group, n=189), and those who received surveillance at general clinics (SG-group, n=209). Prognosis and clinical characteristics were analyzed. In the non-S group, the frequency of patients without viral hepatitis (NBNC-HCC) and Tumor, Node, Metastasis stage was greater. As a result, the median survival time (MST) of the non-S group was reduced, compared with the S group (non-S group, 34.1 vs. S group, 68.2 months; P<0.001). Tumor size was significantly different between the SE- and SG-groups (SE-group, 2.0±1.0 vs. SG-group, 2.5±1.3 cm; P<0.001), whereas tumor number (SE-group: 1.5±1.1 vs. SG-group, 1.7±1.2; P=0.164) and MST (SE-group, 72.1 vs. SG-group, 67.1 months; P=0.931) were not significantly different. Surveillance performed at either an expert medical institution or general clinic improved the prognosis of HCC patients. Dissemination of findings demonstrating the importance of surveillance for HCC to all clinicians as well as patients with chronic liver disease is important, and establishment of an effective surveillance strategy for NBNC-HCC is required.

10.
Oncology ; 96(5): 242-251, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30893698

RESUMO

AIM/BACKGROUND: In HCC patients with multiple tumors in separate segments, monotherapy with surgical resection is often difficult when the estimated residual liver volume after surgery is thought to be inadequate. We evaluated the usefulness of resection combined with low invasive radiofrequency ablation (RFA) for treatment of such cases. MATERIALS/METHODS: We analyzed 115 HCC patients with countable multiple tumors (≤5) without vascular invasion and/or extrahepatic metastasis, and treated solely with resection (SR group: n = 82), or with both resection and RFA (Comb group: n = 33) from January 2000 to December 2017. Clinical characteristics, overall survival rate (OSR), and disease-free survival rate (DFSR) were analyzed in a retrospective manner. RESULTS: There were 88 males (76.5%) and the average age of all patients was 67.8 ± 8.9 years. The average number of tumors and average maximum tumor size were 2.4 ± 0.7 and 4.1 ± 2.1 cm, respectively. Forty-two (36.5%) patients were classified as beyond up-to-7 criteria. The 3- and 5-year OSRs in the SR group were 82.0 and 67.0%, respectively, and in the Comb group were 75.2 and 65.6%, respectively (p = 0.244), while the 3- and 5-year DFSRs in the SR group were 45.2 and 28.0%, respectively, and those in the Comb group were 37.3 and 23.3%, respectively (p = 0.257). CONCLUSION: The combination of surgical resection and complementary RFA may be an effective strategy for treating HCC patients with countable multiple tumors, who are otherwise difficult to treat with surgical resection or RFA alone.


Assuntos
Carcinoma Hepatocelular/terapia , Hepatectomia/métodos , Neoplasias Hepáticas/terapia , Ablação por Radiofrequência/métodos , Idoso , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Carga Tumoral
11.
J Cachexia Sarcopenia Muscle ; 10(2): 347-354, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30793533

RESUMO

BACKGROUND: Muscle atrophy (MA) and muscle strength decline are important clinical features in chronic liver disease (CLD) patients. An easy to perform MA screening method without need for special equipment would be helpful. We evaluated the usefulness of the previously reported finger-circle test as screening for MA in CLD patients. METHODS: We retrospectively enrolled 358 Japanese CLD outpatients (70.8 ± 10.2 years, male/female = 234/124) who had undergone a computed tomography examination from December 2017 to March 2018, of whom 137 had chronic hepatitis, 169 had liver cirrhosis Child-Pugh A, and 52 had liver cirrhosis Child-Pugh B/C. Bilateral psoas muscle area at the middle of the third lumber vertebra (L3) was evaluated with computed tomography findings, which was performed as a screening of hepatocellular carcinoma, using a previously reported parameter for MA [psoas index (PI): total psoas muscle area (cm2 )/height (m)2 ] [mean PI ± standard deviation (SD) of male patients: 6.50 ± 1.13 cm2 /m2 and those of female patients: 4.30 ± 0.90 cm2 /m2 ]. We then evaluated the correlation between MA and finger-circle test results in these patients. RESULTS: The mean PI values for finger-circle test results Bigger, Just-fits, and Smaller were 5.64 ± 1.34, 5.00 ± 1.25, and 4.83 ± 1.46 cm2 /m2 , respectively, in male patients (P < 0.001) and 4.31 ± 1.06, 3.93 ± 0.97, and 3.42 ± 0.94 cm2 /m2 , respectively, in female patients (P = 0.001). We found that a finger-circle test result in male patients other than Bigger (Just-fits and Smaller) predicted a decline in psoas muscle area of L3 to PI 5.25 cm2 /m2 (sensitivity/specificity 0.619/0.667, area under the curve 0.654, 95% confidence interval 0.583-0.724), which was approximately mean minus 1 SD (5.37 cm2 /m2 ). On the other hand, a Smaller test result in female patients predicted a decline in psoas muscle area of L3 to PI 3.33 cm2 /m2 (sensitivity/specificity 0.740/0.583, area under the curve 0.698, 95% confidence interval 0.583-0.813), approximately mean minus 1 SD (3.40 cm2 /m2 ). CONCLUSIONS: The finger-circle test is an easy to perform and effective screening method for predicting earlier stage of MA in CLD patients without the need for special equipment.


Assuntos
Hepatopatias/complicações , Hepatopatias/epidemiologia , Músculo Esquelético/patologia , Atrofia Muscular/epidemiologia , Atrofia Muscular/etiologia , Idoso , Idoso de 80 Anos ou mais , Antropometria/métodos , Biomarcadores , Feminino , Humanos , Hepatopatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Atrofia Muscular/diagnóstico por imagem , Atrofia Muscular/patologia , Tamanho do Órgão , Vigilância em Saúde Pública , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
12.
Hepatol Res ; 49(7): 823-829, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30770617

RESUMO

AIM: Falling is known to be associated with cognitive function. We evaluated the relationship between muscle function and falls in patients with chronic liver disease (CLD). METHODS: We enrolled 100 sequential CLD patients without dementia who were admitted to our institution for scheduled treatment from July 2017 to May 2018 (age 71.0 ± 10.2 years; 76 men). All subjects were self-reliant in regard to activities of daily living. On admission, handgrip strength was determined and falls within 1 month of admission were noted. For determining handgrip strength decline (HSD), previously reported values were used (men, <26 kg; women, <18 kg). The relationship between HSD and falls in CLD patients was evaluated in a retrospective manner. RESULTS: Thirty-two patients had chronic hepatitis and 49 had liver cirrhosis (LC) Child-Pugh A, 17 had LC Child-Pugh B, and 2 had LC Child-Pugh C. Twelve (12.0%) had a history of falling, including 8 (26.7%) of 30 with and 4 (5.7%) of 70 without HSD (P = 0.006). The cut-off value for age in relationship to falling was 69.0 years old (area under the receiver operating characteristic curve, 0.668; 95% confidence interval, 0.514-0.821). A fall during hospitalization was noted more often in patients with a history of falling than in those without (16.7% [2/12] vs. 2.3% [2/88], P = 0.018). CONCLUSION: In CLD patients, the presence of HSD and older age might be independent risk factors for predicting a fall. Assessment of handgrip strength could be an effective clinical tool for easily assessing the risk of falling, especially in elderly CLD patients.

13.
J Gastroenterol Hepatol ; 34(2): 436-441, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29996177

RESUMO

BACKGROUND AND AIM: To develop a scoring method using with common clinical data for predicting hepatocellular carcinoma (HCC) development after sustained virological response at 24 weeks (SVR24) after treatment with direct acting antivirals (DAAs), we retrospectively evaluated clinical features of patients who obtained SVR24. METHODS: From October 2014 to December 2017, 1069 hepatitis C virus patients without a past history of HCC, who obtained SVR24 by DAAs at two different areas, were enrolled (the training [n = 484, ChuShikoku-group] and validation [n = 585, Chubu-group] sets). All were examined by ultrasonography as surveillance for HCC at the time of starting DAAs and twice a year after SVR24. We identified three parameters at SVR24, male gender, FIB-4 index > 3.25, and α-fetoprotein level > 5.0 ng/mL, as risk factors for HCC development and gave them point values, with the sum used as After DAAs Recommendation for Surveillance (ADRES) score. RESULTS: In the ChuShikoku-group, the respective 1-/2-year rates for HCC incidence rates ADRES score 0 were 0.0%/0.0%, for a score 1 were 1.1%/2.1%, score 2 were 8.8%/15.9%, and score 3 were 17.1%/28.1%. On the other hand, those respective scores for the Chubu-group were 0.0%/0.0%, 0.0%/0.7%, 7.9%/10.6%, and 19.5%/not available. The c-index of the predictive value for HCC development in the training set after SVR24 was 0.835 while 0.899 in the validation set. Finally, those of the entire cohort were 0.0%/0.0%, 0.5%/1.6%, 8.4%/13.4%, and 18.0%/32.8%. CONCLUSION: The present ADRES score was simple and easy to use and may be useful for predicting risk of HCC development in short term after reaching SVR24 by DAAs.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/diagnóstico por imagem , Técnicas de Apoio para a Decisão , Detecção Precoce de Câncer/métodos , Hepatite C/tratamento farmacológico , Neoplasias Hepáticas/diagnóstico por imagem , Idoso , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/virologia , Feminino , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Hepatite C/virologia , Humanos , Incidência , Japão/epidemiologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Resposta Viral Sustentada , Fatores de Tempo , Resultado do Tratamento
14.
Hepatol Res ; 48(7): 502-508, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29314571

RESUMO

AIM: There are few reports regarding relative changes in muscle function of patients with chronic liver disease (CLD). We examined CLD patients to evaluate relative changes in handgrip strength and muscle volume. METHODS: We enrolled 413 CLD outpatients who underwent handgrip strength measurements in both 2015 and 2017 (age 67.9 ± 10.0 years; male / female = 242/171; hepatitis C virus [HCV] / hepatitis B virus [HBV] / HBV and HCV / alcohol / others = 239/92/4/22/56; Child-Pugh score [CPS] in 2015 [5/6/7/8/9/≥10 = 335/51/12/11/3/1]). Relative change in muscle volume (ΔPI) from 2015 to 2017 was evaluated using computed tomography findings in 230 of the patients, using a previously reported method. Clinical characteristics, as well as relative changes of handgrip strength (ΔHGS) and ΔPI were analyzed. RESULTS: For the patient cohort as a whole, CPS became significantly worse in 2017 (5/6/7/8/9/≥10 = 319/56/13/11/5/9; P = 0.002). In individual patients with CPS decline, serum albumin level was significantly decreased (3.78 ± 0.50 to 3.33 ± 0.61 g/dL; P < 0.001), whereas no decrease was seen in those without such a decline (4.16 ± 0.48 to 4.20 ± 0.44 g/dL; P = 0.028). Furthermore, ΔHGS (-1.4 ± 4.8 [n = 59] vs. 0.7 ± 4.8 kg [n = 354]; P = 0.002) and ΔPI (-0.44 ± 0.88 [n = 38] vs. 0.03 ± 0.64 cm2 /m2 [n = 192]; P = 0.003) were worse in patients with, compared to those without, a decline in CPS. Age was not significantly different between patients with and without handgrip strength decline (66.5 ± 10.3 vs. 65.3 ± 9.9 years; P = 0.256). There was a significant relationship between ΔHGS, ΔPI and relative change in serum albumin (r = 0.161, P = 0.001 and r = 0.225, P < 0.001, respectively). CONCLUSION: Decline in CPS, especially decreasing serum albumin level, showed a significant relationship with muscle function reduction and muscle volume loss.

15.
Hepatol Res ; 48(3): E354-E359, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28940597

RESUMO

AIM: We examined the prognosis of liver cirrhosis (LC) patients with and without portal hypertension (PHT) and muscle volume loss (MVL). METHODS: From 2006 to 2016, 346 LC outpatients (PHT/non-PHT = 173/173) were enrolled (median age, 69 years; men / women, 204/142; Child-Pugh A / B, 230/116; and presence of MVL 15.6% in each group) after propensity matching, following exclusion of those with hepatocellular carcinoma (HCC) beyond the Milan criteria and Child-Pugh C. Portal hypertension was defined as positive for significant esophagogastric varices; MVL was diagnosed based on a previously reported index using CT imaging. Overall survival rate (OSR) was evaluated from the viewpoints of PHT and MVL. RESULTS: There were no significant differences in clinical background (age, gender, etiology, presence of HCC [within Milan criteria], or Child-Pugh class) between the groups. Although there was no significant difference regarding OSR between patients with and without MVL in the non-PHT group (P = 0.076, Holm's method), the OSR of patients with MVL in the PHT group was lower compared to those without MVL in both groups (P = 0.017 and P = 0.012, respectively, Holm's method). As a result, the OSR of patients with MVL (n = 54) was lower than the other patients (n = 292) (3- and 5-year OSR, 69.0% vs. 86.4% and 35.8% vs. 74.1%, respectively; P < 0.001). Multivariate Cox hazard analysis showed that positive for HCC (hazard ratio [HR], 2.028; 95% confidence interval [CI], 1.189-3.460; P = 0.009) and positive for MVL (HR, 2.768; 95% CI, 1.575-4.863; P < 0.001) were significant independent prognostic factors for death. CONCLUSION: Muscle volume loss and HCC, but not PHT, were found to be independent prognostic factors for death in LC patients.

16.
J Gastroenterol Hepatol ; 33(6): 1271-1276, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29193248

RESUMO

BACKGROUND AND AIM: This study investigated the prognostic impact of muscle volume loss (MVL) and muscle function decline in patients undergoing resection for hepatocellular carcinoma (HCC). METHODS: This study enrolled 171 naïve HCC patients treated with resection from 2007 to 2015, after excluding those lacking spirometry or computed tomography findings, who had received non-curative treatments, or with restrictive or obstructive lung disorders. The median peak expiratory flow rate (%PEF) was set as the cut-off value for muscle function decline, and MVL was diagnosed using a previously reported value. Clinical backgrounds and prognosis were retrospectively evaluated. RESULTS: Overall survival rate was lower in the MVL (n = 35) as compared with the non-MVL (n = 136) group (1/3/5-year overall survival rate = 88.2%/81.6%/55.6% vs 91.0%/81.5%/74.8%, respectively; P = 0.0083), while there were no differences regarding hepatic function or tumor burden between the groups. Child-Pugh class B (hazard ratio [HR] 3.510, 95% confidence interval [CI]: 1.558-7.926, P = 0.0025), beyond Milan criteria (HR 1.866, 95%CI: 1.024-3.403, P = 0.042), and presence of MVL (HR 1.896, 95%CI: 1.052-3.416, P = 0.033) were significant prognostic factors. The decreased %PEF group (n = 84) showed a higher rate of postoperative delirium than the others (n = 87) (27.4% vs 11.5%, P = 0.0088). The cut-off values for %PEF and age for postoperative delirium were 63.3% (area under receiver operating characteristic [AUROC] 0.697) and 73 years old (AUROC 0.734), respectively. Delirium was observed in 50.0% (14/28) of patients with both factors, 23.8% (15/63) of those with 1 factor, and 5.0% (4/80) of those without either factor. CONCLUSION: Muscle volume loss is an independent prognostic factor in HCC patients treated with surgical resection, while advanced age and decreased muscle function might indicate high risk for postoperative delirium.


Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Tamanho do Órgão , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Delírio/epidemiologia , Delírio/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Risco
17.
Oncology ; 93 Suppl 1: 120-126, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29258105

RESUMO

BACKGROUND/AIM: Determination of failure of transarterial chemoembolization (TACE) for treatment of Barcelona Clinic Liver Cancer stage B (BCLC-B) hepatocellular carcinoma (HCC) has become important because of the development of tyrosine kinase inhibitor (TKI) treatment. We evaluated the usefulness and efficacy of the newly proposed time to TACE progression (TTTP). PATIENTS AND METHODS: From 2006 to 2016, 192 BCLC-B HCC patients [median age 72 years, male/female ratio = 149/43, Child-Pugh score 5/6/7 = 106/56/30, albumin-bilirubin (ALBI) grade 1/2 = 64/128, Kinki criteria B1/B2 = 64/128] were enrolled. TTTP was defined based on a previous report and first imaging performed 3 months after initial TACE had been used to obtain baseline images. The patients were divided into three groups according to TTTP (<5, 5-10, and ≥10 months; group I, II, and III, respectively). We evaluated the relationship between TTTP and overall survival (OS) as well as the prognostic factors for death. RESULTS: The median number of TACE procedures was 4 (interquartile range 3-7). There was a moderate correlation between TTTP and OS (r = 0.527, 95% CI 0.416-0.622, p < 0.001). The median survival for group I (n = 78), II (n = 49), and III (n = 65) was 24.6, 34.7, and 49.5 months, respectively (group I vs. group II, p = 0.023; group I vs. group III, p < 0.001; group II vs. group III, p = 0.037; Holm's method). ALBI grade 2 (HR 1.548, 95% CI 1.004-2.388, p = 0.048), alpha-fetoprotein (>100 ng/mL) (HR 1.540, 95% CI 1.035-2.291, p = 0.033), and TTTP (<5 months) (HR 2.157, 95% CI 1.447-3.215, p < 0.001) were significant prognostic factors for death in multivariate Cox hazard analysis. CONCLUSION: In patients with reduced TTTP, especially <5 months, it might be difficult to improve prognosis with a repeated TACE procedures. In such cases, reconsideration of the therapeutic strategy might be needed when possible.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Idoso , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Inibidores de Proteínas Quinases/administração & dosagem , Taxa de Sobrevida
18.
Eur J Gastroenterol Hepatol ; 29(12): 1416-1423, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29016470

RESUMO

BACKGROUND/AIM: Sarcopenia is recognized as a condition related to quality of life and prognosis in patients with chronic liver disease, although no useful strategy for improving muscle volume and strength has been established. Here, we evaluated the efficacy of supplementation with branched-chain amino acid (BCAA) administration and walking exercise. PATIENTS AND METHODS: From December 2015 to July 2016, 33 Japanese outpatients with liver cirrhosis were enrolled (median: 67 years, HCV : HBV : alcohol : others=26 : 2 : 2 : 3, male : female=13 : 20, Child-Pugh A : B=30 : 3). None had a history of BCAA supplementation. After calculating the average number of daily steps using a pedometer for a 2-3-week period, BCAA supplementation (protein 13.5 g, 210 kcal/day) as a late evening snack and walking exercise (additional 2000 steps/day prescribed) were started. Body composition including muscle volume was analyzed using a bioelectrical impedance analysis method, and serological data and muscle strength (leg, handgrip) were evaluated at enrollment, and then 1, 2, and 3 months after starting the protocol. RESULTS: The median average number of daily steps was 3791 (interquartile range: 2238-5484). The average period of BCAA supplementation was 2.7±0.7 months. During the period from enrollment to 3 months after starting the protocol, HbA1c and NH3 were not significantly changed, whereas the BCAA/tyrosine ratio improved (4.3±1.35 to 5.24±2.04, P=0.001). In addition, the ratios for average daily steps (1.595, P=0.02) as well as muscle volume, leg strength, and handgrip strength (1.013, 1.110, and 1.056, respectively; all P<0.01) were increased at 3 months. CONCLUSION: BCAA supplementation and walking exercise were found to be effective and easily implemented for improving muscle volume and strength in liver cirrhosis patients.


Assuntos
Aminoácidos de Cadeia Ramificada/uso terapêutico , Suplementos Nutricionais , Cirrose Hepática/complicações , Músculo Esquelético/patologia , Sarcopenia/prevenção & controle , Caminhada/fisiologia , Idoso , Aminoácidos de Cadeia Ramificada/sangue , Amônia/sangue , Composição Corporal , Teste de Esforço , Terapia por Exercício , Feminino , Hemoglobina A Glicada/metabolismo , Força da Mão , Humanos , Cirrose Hepática/sangue , Extremidade Inferior/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Sarcopenia/sangue , Sarcopenia/etiologia , Tirosina/sangue
19.
Dig Dis ; 35(6): 498-505, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29040981

RESUMO

AIM/BACKGROUND: Evaluations of abdominal ultrasonography (US) findings of primary and secondary tumor-forming hepatic malignant lymphoma (HML) have not been adequately reported. In this study, we elucidated US and contrast-enhanced US (CEUS) findings in patients with HML. MATERIALS/METHODS: From January 2006 to March 2017, 25 patients with HML were enrolled (primary 7, secondary 18), each of whom was diagnosed pathologically. They were divided into 2 groups based on tumor diameter (cutoff, 30 mm). US imaging findings were retrospectively analyzed. RESULTS: All tumors in patients with a small HML (<30 mm in diameter, small group, n = 14) were revealed as homogeneous hypo-echoic type (100%), with penetrating sign observed in only 1 patient. Tumors in 11 patients in the small group, examined with CEUS, showed homogeneous enhancement in the early vascular phase (91%) and a washout pattern in the portal phase (100%), and they were revealed as defective in the post-vascular phase (100%). In the large group (≥30 mm; n = 11), tumors were revealed as a heterogeneous hypo-echoic lesion in 10 (91%) and penetrating sign was observed in 8 (73%). Dilatation of the distal intrahepatic bile duct by the tumor was observed in 4 patients in the large group. In 7 large group patients examined with CEUS, imaging findings in the early vascular phase varied, with 5 (71%) showing a washout pattern in the portal phase and 5 (71%) revealed as defective in the post-vascular phase. CONCLUSION: We found that US imaging features of HML differ depending on the tumor diameter.


Assuntos
Abdome/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Linfoma/diagnóstico por imagem , Linfoma/patologia , Ultrassonografia , Abdome/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
J Innate Immun ; 9(2): 217-228, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28068663

RESUMO

Collectins are C-type lectins that are involved in innate immunity as pattern recognition molecules. Recently, collectin kidney 1 (CL-K1) has been discovered, and in vitro studies have shown that CL-K1 binds to microbes and activates the lectin complement pathway. However, in vivo functions of CL-K1 against microbes have not been elucidated. To investigate the biological functions of CL-K1, we generated CL-K1 knockout (CL-K1-/-) mice and then performed a Streptococcus pneumoniae infection analysis. First, we found that recombinant human CL-K1 bound to S. pneumoniae in a calcium-dependent manner, and induced complement activation. CL-K1-/- mice sera formed less C3 deposition on S. pneumoniae. Furthermore, immunofluorescence analysis in the wild-type (WT) mice demonstrated that CL-K1 and C3 were localized on S. pneumoniae in infected lungs. CL-K1-/- mice revealed decreased phagocytosis of S. pneumoniae. Consequently, less S. pneumoniae clearance was observed in their lungs. CL-K1-/- mice showed severe pulmonary inflammation and weight loss in comparison with WT mice. Finally, the decreased clearance and severe pulmonary inflammation caused by S. pneumoniae infection might cause higher CL-K1-/- mice lethality. Our results suggest that CL-K1 might play an important role in host protection against S. pneumoniae infection through the activation of the lectin complement pathway.


Assuntos
Colectinas/metabolismo , Complemento C3/metabolismo , Pulmão/imunologia , Infecções Pneumocócicas/imunologia , Pneumonia/imunologia , Receptores de Reconhecimento de Padrão/metabolismo , Streptococcus pneumoniae/fisiologia , Animais , Carga Bacteriana , Colectinas/genética , Lectina de Ligação a Manose da Via do Complemento/genética , Humanos , Imunidade Inata , Pulmão/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fagocitose , Receptores de Reconhecimento de Padrão/genética , Transgenes/genética
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