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1.
Diabetes Obes Metab ; 26(5): 1757-1765, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38356110

RESUMO

AIMS: To assess the impact of 'Oishi Kenko', a nutrition management application (app), on glycaemic control in patients with diabetes. MATERIALS AND METHODS: A propensity-score-matched retrospective cohort study was performed using data from the KAMOGAWA-DM cohort study conducted between January and June 2022 in Japan. We analysed data from patients with type 1 and type 2 diabetes, comparing users who used the Oishi Kenko app (app group) with non-users (control group) over 3 months. RESULTS: Among the 50 participants who actively used it, 47 participants in both the app and control cohorts were selected from the KAMOGAWA-DM cohort according to propensity-score matching. Within the app group, the median glycated haemoglobin (HbA1c) level was 51 mmol/mol (6.9%) at baseline, which slightly decreased to 50 mmol/mol (6.8%) at the 3-month mark (median change 0.0%). Conversely, in the control group, the baseline HbA1c level of 51 mmol/mol (6.9%) exhibited a marginal increase of 52 mmol/mol (7.0%) after 3 months (median change 0.20%). The median HbA1c level change between the groups was statistically significant, with the app group showing a significant positive change compared with the control group (p = 0.012). CONCLUSION: The Oishi Kenko app effectively improved glycaemic control in patients with diabetes; hence, it may be a promising tool for patient-driven dietary management.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas , Estudos de Coortes , Estudos Retrospectivos , Pontuação de Propensão , Glicemia , Hipoglicemiantes
2.
J Surg Oncol ; 129(4): 765-774, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38105473

RESUMO

BACKGROUND: The usefulness of inflammation-based prognostic scores for early recurrence (ER) after hepatectomy for hepatocellular carcinoma has rarely been reported. This study aimed to evaluate the potential of inflammation-based prognostic scores as predictors of ER and their relationship with tumor markers. METHODS: We enrolled 338 patients who underwent hepatectomy for hepatocellular carcinoma between January 2007 and December 2021. Clinicopathological factors were compared between patients who developed ER (ER group) and those who did not develop ER (non-ER group). The association between inflammation-based prognostic scores and ER status was evaluated. These scores were compared with those of well-established tumor markers. RESULTS: The platelet-to-lymphocyte ratio (PLR) correlated with ER of hepatocellular carcinoma, with an area under the curve (AUC) value of 0.70, sensitivity of 68.1%, and specificity of 67.7%. In patients with low tumor marker levels, the PLR showed a strong correlation with ER of hepatocellular carcinoma, with an AUC value of 0.851, sensitivity of 100%, and specificity of 76.2%. Multivariate analysis revealed that the PLR was an independent prognostic factor for ER. CONCLUSIONS: The PLR is useful and complementary to tumor markers for predicting ER after hepatectomy for hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Prognóstico , Biomarcadores Tumorais , Linfócitos/patologia , Inflamação , Estudos Retrospectivos
3.
Diabetes Obes Metab ; 25(12): 3682-3689, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37667649

RESUMO

AIM: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are available for individuals with type 1 diabetes, but appropriate use is recommended to prevent ketosis or ketoacidosis. This study aimed to evaluate the risk of ketosis in people with type 1 diabetes, focusing on the relationship between nutritional assessment, glycaemic status, c-peptide immunoreactivity (CPR) index and body composition. MATERIALS AND METHODS: In total, 46 Japanese patients with type 1 diabetes were included, and dietary assessment from food photographs and ketone levels were evaluated before and after taking SGLT2is. The effect of diet on morning ketone levels was also investigated. RESULTS: All patients had an increase in mean ketone concentrations after taking SGLT2is (before 0.12 ± 0.06 mmol/L, after 0.23 ± 0.16 mmol/L). A significant negative correlation was found between average morning ketone levels and age (r = -0.514, p < .001) and the CPR index (r = -0.523, p = .038) after taking SGLT2is. Using a mixed-effects model based on the results before starting the inhibitors, it was noted that both patient-to-patient and age, or patient-to-patient and capacity of insulin secretion, influenced the ketone levels. Multiple regression analysis showed that factors associated with the risk of increasing ketone levels after taking SGLT2is were younger age (ß = -0.504, p = .003) and a low ratio of basal to bolus insulin (ß = -0.420, p = .005). CONCLUSIONS: When administering SGLT2is to patients with a low CPR index or younger patients with type 1 diabetes, adequate instructions to prevent ketosis should be given.


Assuntos
Diabetes Mellitus Tipo 1 , Cetose , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Peptídeo C , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , População do Leste Asiático , Jejum , Cetonas , Cetose/induzido quimicamente , Cetose/prevenção & controle , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos
4.
J Clin Biochem Nutr ; 71(2): 136-142, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36213794

RESUMO

This cross-sectional study investigated the association of metabolic syndrome (MetS) with sarcopenia defined by absolute low muscle mass (aLMM) and absolute low muscle strength (aLMS), or sarcopenia defined by relative low muscle mass (rLMM) and relative low muscle strength (rLMS). The cut-off values for men and women were as follows: aLMM, appendicular muscle mass in kg/height|2 was <7.0 kg/m|2 and <5.7 kg/m|2; rLMM, appendicular muscle mass/body weight ×100 was <28.64% and <24.12%; aLMS, handgrip strength was <28 kg and <18 kg; and rLMS, handgrip strength/body weight ×100 was 51.26% and 35.38%. Among 207 men and 164 women, 41.5% men and 57.3% women had MetS, 14.0% men and 6.1% women had sarcopenia as defined by aLMM and aLMS, and 14.0% men and 22.0% women had sarcopenia defined by rLMM and rLMS. Compared with non-sarcopenia, adjusted OR of sarcopenia defined by aLMM and aLMS for the prevalence of MetS was 0.79 (95% CI 0.38-1.67), whereas that of sarcopenia defined by rLMM and rLMS for the prevalence of MetS was 20.6 (95% CI 7.81-54.3). Sarcopenia defined by rLMM and rLMS was associated with the risk of prevalence of MetS, whereas sarcopenia defined by aLMM and aLMS was not.

5.
J Clin Biochem Nutr ; 71(2): 158-164, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36213793

RESUMO

To clarify the frequency of hypoglycemia in patients with type 1 diabetes mellitus receiving dapagliflozin combination therapy to reduce their basal insulin dose. Sixty subjects were assigned to two groups according to their basal insulin-to-total daily dose (TDD) ratio: group A (basal insulin/TDD <40%) and group B (≥40%). Reduction of the basal insulin dose was instituted in group B, but not in group A. The number of hypoglycemic events per day and ketosis frequency were the primary and secondary endpoints, respectively. The hypoglycemia frequency before and after the intervention was 0.23 and 0.26 times/day in group A and 0.19 and 0.23 times/day in group B, respectively, with no significant difference between the groups. The total insulin dose reduction was approximately 10% in both groups. Ketosis frequency increased significantly after the intervention (from 0.013 to 0.086 times/day in group A and 0.013 to 0.059 times/day in group B). Time-in-range, mean amplitude of glycemic excursion, and glycated hemoglobin A1c improved in both groups. No significant difference in hypoglycemia frequency was observed between patients with and without reduction of the basal insulin dose. The combination therapy improved glycemic control and patient satisfaction regarding hyperglycemia. Nevertheless, adequate attention to ketosis is crucial.

6.
Medicina (Kaunas) ; 58(4)2022 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-35454320

RESUMO

The BMDs of the lumbar spine, whole femur, and femoral neck and TBS were measured. Change in BMD or TBS was defined as the BMD or TBS at follow-up, performed 1 year after baseline, minus baseline BMD or TBS. Results: This retrospective cohort study included 93 patients, of whom 52 received no medication, 26 received bisphosphonates, and 15 received weekly teriparatide. BMD of the lumbar spine increased in all three groups. There was no change in BMD of the whole femur and femoral neck in the no medication and bisphosphonates groups, whereas the BMD of the whole femur (from 0.73 (0.15) to 0.74 (0.15) g/cm2, p = 0.011) and femoral neck (from 0.59 (0.16) to 0.60 (0.16) g/cm2, p = 0.011) in the teriparatide group increased. The change in BMD of the femoral neck (no medication; -0.002 (0.034) g/cm2, bisphosphonates; -0.0001 (0.024) g/cm2, and teriparatide; 0.017 (0.022) g/cm2, p = 0.091) or TBS (no medication; -0.007 (0.051), bisphosphonates; -0.058 (0.258), and teriparatide; 0.021 (0.044), p = 0.191) in the teriparatide group tended to be higher than that in the other groups, although there was no statistically significant difference. Conclusions: Teriparatide increased the BMD of the femoral neck and TBS in osteoporosis patients with type 2 diabetes mellitus, compared to bisphosphonates and no medication.


Assuntos
Conservadores da Densidade Óssea , Diabetes Mellitus Tipo 2 , Osteoporose , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Osso Esponjoso , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Difosfonatos/uso terapêutico , Humanos , Vértebras Lombares , Osteoporose/tratamento farmacológico , Estudos Retrospectivos , Teriparatida/farmacologia , Teriparatida/uso terapêutico
7.
Diabetes Obes Metab ; 23(9): 2155-2160, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34085376

RESUMO

AIM: We aimed to develop an application to calculate mean amplitude of glycaemic excursions (MAGE) automatically and to evaluate its accuracy. MATERIALS AND METHODS: We named the application intermittently scanned continuous glucose monitoring (isCGM) calculator KAMOGAWA (Kyoto Auto MAGE Of Glucose cAlcutator With isCGM Application). The isCGM data from 20 patients, 10 with and 10 without diabetes, were used to compare manually calculated MAGE values with those calculated using KAMOGAWA. The rate of agreement for the MAGE values was calculated. RESULTS: Comparing the MAGE values calculated manually with those calculated using KAMOGAWA, the total mean rate of agreement was 81.6%. Nonmatching values were checked and it was found that the inconsistencies were all attributable to errors in manual calculations. After correcting errors in the manual calculation, the MAGE values matched to one decimal place for all data in the manual and KAMOGAWA calculations. CONCLUSIONS: KAMOGAWA can help diabetologists use MAGE in clinical practice, which could contribute to improving glycaemic control in patients who use isCGM.


Assuntos
Glicemia , Diabetes Mellitus , Automonitorização da Glicemia , Humanos
8.
Endocr J ; 67(7): 733-740, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32213726

RESUMO

We have previously reported that the creatinine (Cre) to cystatin C (CysC) ratio is associated with height-adjusted skeletal muscle mass index (SMI). However, weight-adjusted SMI is reported to be a more useful marker of insulin sensitivity than height-adjusted SMI. Thus, we hypothesized that the creatinine to (cystatin C × body weight [BW]) relationship (Cre/[CysC × BW]) might be associated with weight-adjusted SMI. In this cross-sectional study of 169 males and 132 females, a body composition analyzer was used and the weight-adjusted SMI was calculated as (absolute muscle mass [kg]/BW [kg]) × 100. The cut-off of low muscle mass was defined as weight-adjusted SMI <37.0% for males and <28.0% for females. The Cre/(CysC × BW) was correlated with weight-adjusted SMI in both males (r = 0.484, p < 0.001) and females (r = 0.538, p < 0.001). In addition, Cre/(CysC × BW) was associated with weight-adjusted SMI in both males (standardized ß = 0.493, p < 0.001) and females (standardized ß = 0.570, p < 0.001) after adjusting for covariates. According to the receiver operator characteristic (ROC) curve analysis, the optimal cut-off point of Cre/(CysC × BW) for low muscle mass was 0.0145 (area under the ROC curve [AUC] 0.756 [95% confidence interval {95% CI} 0.644-0.842], sensitivity = 0.96, specificity = 0.47, p < 0.001) in males and 0.0090 (AUC 0.976 [95% CI 0.894-0.995], sensitivity = 1.00, specificity = 0.93, p < 0.001) in females. There is a correlation between Cre/(CysC × BW) and weight-adjusted SMI. The Cre/(CysC × BW) could be a practical screening marker for low muscle mass.


Assuntos
Peso Corporal/fisiologia , Creatinina/sangue , Cistatina C/sangue , Músculo Esquelético/anatomia & histologia , Sarcopenia/diagnóstico , Idoso , Composição Corporal/fisiologia , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Tamanho do Órgão , Valor Preditivo dos Testes , Estudos Retrospectivos , Sarcopenia/sangue , Sarcopenia/patologia
9.
Surg Endosc ; 33(8): 2602-2611, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30357524

RESUMO

BACKGROUND: How increasing age affects the characteristics of groin hernia remains uncertain. This study evaluated the association between age and the type of groin hernia, especially with respect to its multiplicity, observed during laparoscopic transabdominal preperitoneal (TAPP) hernia repair. METHODS: We retrospectively evaluated 634 consecutive patients with primary groin hernia who underwent laparoscopic TAPP repair between October 2000 and June 2017. Patients were stratified into 4 age groups: < 60 years, 60-69 years, 70-79 years, and 80 years or older. RESULTS: The incidence of occult contralateral hernia and multiple ipsilateral hernias increased significantly with each increasing age group: 7.3%, 10.4%, 12.7%, and 20.8% for occult contralateral hernia (p = 0.005), and 5.6%, 9.2%, 16.8%, and 21.7% for multiple ipsilateral hernias (p < 0.001), respectively. Univariate analyses showed that an older age (age ≥ 70 years) was the only factor significantly associated with the presence of multiple groin hernias (odds ratio, 2.69; 95% confidence interval, 1.89-3.81; p < 0.001). In patients with multiple ipsilateral hernias, the prevalent form in men was a pantaloons hernia, with an incidence of about 70% across all age groups, whereas in women it was groin hernias, with one component being a femoral hernia, an obturator hernia, or both. CONCLUSIONS: The multiple occurrence of groin hernias, either unilaterally or bilaterally, was a clinical feature in the elderly.


Assuntos
Hérnia Inguinal/complicações , Herniorrafia , Laparoscopia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Feminino , Virilha/cirurgia , Hérnia/classificação , Hérnia Femoral/complicações , Hérnia Inguinal/epidemiologia , Hérnia Inguinal/cirurgia , Hérnia do Obturador/complicações , Herniorrafia/métodos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos
10.
Endocr J ; 66(4): 369-377, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31019148

RESUMO

Association between heart failure and sarcopenia has been reported, however, the association between sarcopenia and brain natriuretic peptide (BNP) is unclear. Thus, we investigated the association between sarcopenia and BNP in type 2 diabetic patients without heart failure. In this cross-sectional study, skeletal muscle mass index (SMI, kg/m2) was calculated as appendicular muscle mass, measured by bioimpedance analyzer, by the square of the height. Sarcopenia was defined as having both handgrip strength of <26 kg for men and <18 kg for women, and SMI of <7.0 kg/m2 for men and <5.7 kg/m2 for women. To investigate the impact of BNP levels on the presence of sarcopenia, propensity-score matching analysis was used to remove the bias of confounding variables, including age, sex, duration of diabetes, body mass index, exercise, systolic blood pressure, smoking status, hemoglobin A1c, creatinine, energy and protein intake. The area under the curve (AUC) of BNP levels for the presence of sarcopenia was calculated by the receiver operating characteristic curve (ROC). Among 433 patients (236 men and 65.4 (11.1) years), 32 patients (7.4%) were diagnosed as sarcopenia. In the propensity-matched 58 patients, BNP levels (Δ10 pg/mL incremental) were associated with the presence of sarcopenia by logistic regression analysis, (odds ratio: 1.56, 95% confidence interval: 1.14-2.13, p = 0.002). The optimal cut-off point of BNP levels for sarcopenia is 27.3 pg/mL (AUC 0.777, 95%CI, 0.691-0.863, sensitivity = 0.813, specificity = 0.736, p < 0.001). In conclusion, BNP levels were associated with sarcopenia in type 2 diabetic patients without heart failure.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Insuficiência Cardíaca/sangue , Peptídeo Natriurético Encefálico/sangue , Sarcopenia/sangue , Idoso , Pressão Sanguínea/fisiologia , Índice de Massa Corporal , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Feminino , Força da Mão/fisiologia , Inquéritos Epidemiológicos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Estudos Prospectivos , Sarcopenia/complicações
11.
J Clin Biochem Nutr ; 63(2): 106-112, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30279621

RESUMO

Dipeptidyl peptidase-4 (DPP-4) is a critical molecule for the metabolism of incretins. In addition, DPP-4 is known as CD26, the receptor of T cells, and plays important role in activation of T cells. Recently, DPP-4 inhibitors (DPP4i) are reported to have several immunologic effects beyond glycemic control. DPP4i seem to have anti-inflammatory effects in patients with type 2 diabetes. This might be direct effects on T cells. However, the close mechanism is not clear. To evaluate the possibility, we performed ex vivo assays by using primarily human CD4+ T cells (CD4) and CD8+ T cells (CD8). We purified primary naïve CD4 and CD8 from human peripheral blood. Then, we evaluated the effect of DPP4i on the proliferation of naïve T cells and the cytokine production in ex vivo experiments. The proliferation of CD4 and CD8 were suppressed by adding DPP4i in a dose dependent manner. However, DPP4i did not inhibit cytokine production from CD4. It was revealed by phospho-flow that the T cell receptor (TCR) signaling was attenuated in the presence of DPP4i. Taken together, DPP4i modulated TCR signaling, which contributed to attenuate the proliferation of CD4 and CD8. DPP4i have adverse effects for the proliferation of human T cells.

12.
World J Surg ; 41(11): 2817-2829, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28717913

RESUMO

BACKGROUND: Whether surgical resection for recurrent biliary tract carcinoma (BTC) prolongs survival and the patients who are most likely to benefit from such treatment remain unclear. METHODS: Among 251 patients with recurrences after the initial resection of BTC, a total of 21 patients (8.4%) underwent surgical resection for the recurrence, with a zero mortality rate. The clinicopathological features of these patients were compared with those of patients who did not undergo surgery. RESULTS: The median survival time (MST) after the first recurrence and the 5-year post-recurrent survival (PRS) rate were 19.8 months and 32.8%, respectively, for patients who underwent re-resection. Fourteen patients (66.7%) experienced second recurrences; however, none of these patients underwent further surgical resection. Surgical resection for recurrence was identified as an independent prognostic factor for survival after recurrence (hazard ratio of 0.33, 95% CI of 0.17-0.58, p < 0.001). Patients with less than three liver metastases had a significantly better PRS after surgical resection than after chemotherapy (p = 0.015). Among the patients with an isolated solitary liver metastasis, patients who underwent resection had a significantly longer MST after the first recurrence than patients receiving chemotherapy (22.8 vs. 10.9 months, p = 0.025), whereas the PRS was similar between the two groups among patients with two liver lesions. CONCLUSIONS: Surgical resection for recurrent BTC may prolong survival in highly selected patients. A hepatectomy might offer a survival benefit for patients with a solitary liver metastasis.


Assuntos
Neoplasias do Sistema Biliar/cirurgia , Carcinoma/cirurgia , Neoplasias Hepáticas/secundário , Recidiva Local de Neoplasia/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Neoplasias do Sistema Biliar/patologia , Carcinoma/secundário , Quimioterapia Adjuvante , Feminino , Hepatectomia , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Carga Tumoral
13.
Pancreatology ; 16(3): 397-402, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26850565

RESUMO

BACKGROUND/OBJECTIVE: No previous study has quantitatively investigated the degree of enhancement of pancreatic neuroendocrine tumors (pNETs) using a routine preoperative modality. The aim of this study was to evaluate the contrast-enhancement ratio (CER) of pNETs using multiphase enhanced CT and to assess the impact of the CER on disease recurrence after surgery. METHODS: A retrospective study was performed using data from 47 consecutive patients with pNETs who had undergone curative surgery. The CER of the tumor was calculated by dividing the CT attenuation value obtained during the maximum-enhanced phase by that obtained during the pre-enhanced phase. A region of interest was placed in the largest tumor dimension plane so as to cover as much surface of the tumor as possible while avoiding adjacent normal structures, calcification, and necrotic areas of the tumor. RESULTS: During a median follow-up period of 51 months (range, 1-132 months), a total of 4 patients (8.5%) developed disease recurrence. The median CER value was significantly lower for the patients with recurrence than for the patients without recurrence (2.9 vs. 4.3, P = 0.013). Univariate analyses showed that a CER ≤3.2 was significantly associated with disease recurrence (P < 0.001). All the patients with disease recurrence had tumors that were both large (>20 mm) and weakly enhanced (CER ≤ 3.2), whereas no recurrences were observed even in patients with tumors >20 mm when the CER was greater than 3.2. CONCLUSIONS: CER might be a useful predictor of disease recurrence in patients with pNETs.


Assuntos
Recidiva Local de Neoplasia/diagnóstico por imagem , Tumores Neuroendócrinos/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Cuidados Pré-Operatórios , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Estudos Retrospectivos , Resultado do Tratamento
14.
Hepatology ; 58(3): 1153-65, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23532995

RESUMO

UNLABELLED: MicroRNAs (miRNAs) are evolutionary conserved small RNAs that post-transcriptionally regulate the expression of target genes. To date, the role of miRNAs in liver development is not fully understood. By using an experimental model that allows the induced and controlled differentiation of mouse fetal hepatoblasts (MFHs) into mature hepatocytes, we identified miR-148a as a hepatospecific miRNA highly expressed in adult liver. The main finding of this study revealed that miR-148a was critical for hepatic differentiation through the direct targeting of DNA methyltransferase (DNMT) 1, a major enzyme responsible for epigenetic silencing, thereby allowing the promotion of the "adult liver" phenotype. It was also confirmed that the reduction of DNMT1 by RNA interference significantly promoted the expression of the major hepatic biomarkers. In addition to the essential role of miR-148a in hepatocyte maturation, we identified its beneficial effect through the repression of hepatocellular carcinoma (HCC) cell malignancy. miR-148a expression was frequently down-regulated in biopsies of HCC patients as well as in mouse and human HCC cell lines. Overexpressing miR-148a led to an enhancement of albumin production and a drastic inhibition of the invasive properties of HCC cells, whereas miR-148a silencing had the opposite consequences. Finally, we showed that miR-148a exerted its tumor-suppressive effect by regulating the c-Met oncogene, regardless of the DNMT1 expression level. CONCLUSION: miR-148a is essential for the physiology of the liver because it promotes the hepatospecific phenotype and acts as a tumor suppressor. Most important, this report is the first to demonstrate a functional role for a specific miRNA in liver development through regulation of the DNMT1 enzyme.


Assuntos
Carcinoma Hepatocelular/patologia , Transformação Celular Neoplásica/patologia , Hepatócitos/patologia , Neoplasias Hepáticas/patologia , MicroRNAs/fisiologia , Fenótipo , Albuminas/metabolismo , Animais , Carcinoma Hepatocelular/metabolismo , Diferenciação Celular , Linhagem Celular Tumoral , DNA (Citosina-5-)-Metiltransferase 1 , DNA (Citosina-5-)-Metiltransferases/metabolismo , Modelos Animais de Doenças , Regulação para Baixo/fisiologia , Humanos , Neoplasias Hepáticas/metabolismo , Camundongos , Invasividade Neoplásica/patologia
15.
Langenbecks Arch Surg ; 399(8): 1047-55, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25335877

RESUMO

PURPOSE: The aim of this study was to construct a prediction model for posthepatectomy liver failure (PHLF), as defined by the International Study Group of Liver Surgery, and evaluate its accuracy in hepatocellular carcinoma (HCC) patients with cirrhosis or chronic hepatitis. METHODS: A total of 277 consecutive hepatectomies for HCC between 2005 and 2013 were analyzed retrospectively. Multivariate logistic regression analysis was used to develop a predictive model for PHLF. The sensitivity, specificity, and area under the receiver operating characteristic (AUROC) curve were evaluated. The Hosmer-Lemeshow goodness-of-fit test was used to assess the model calibration. The constructed model was internally validated by k-fold cross-validation (k=5). RESULTS: PHLF developed in 12.6% of hepatectomies. Multivariate analysis identified the following variables as predictors of PHLF: elevated preoperative serum bilirubin level, elevated preoperative international normalized ratio, and intraoperative packed red blood cell transfusion. The predictive model allowed discrimination between patients who developed PHLF and those who did not, with a sensitivity of 82.9%, specificity of 72.3%, and AUROC curve of 0.81 (95% CI, 0.74 to 0.89). The Hosmer-Lemeshow test indicated a good fit (P=0.545). The AUROC curve of the developed model was significantly greater than that of the model for end-stage liver disease (MELD) score (P=0.014), suggesting that the former model is better at predicting the PHLF than the latter one. CONCLUSIONS: The developed model could be useful for predicting the occurrence of PHLF in HCC patients with underlying liver disease.


Assuntos
Carcinoma Hepatocelular/cirurgia , Falência Hepática/epidemiologia , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Idoso , Bilirrubina/análise , Transfusão de Sangue/estatística & dados numéricos , Feminino , Hepatectomia/métodos , Humanos , Coeficiente Internacional Normatizado , Masculino , Estudos Retrospectivos , Sensibilidade e Especificidade
16.
Int J Clin Oncol ; 19(5): 871-9, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24218280

RESUMO

PURPOSE: The aim of the present study was to evaluate whether serum alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) trends might be correlated with overall survival rates in patients with recurrent hepatocellular carcinoma (HCC) undergoing trans-catheter arterial chemo-embolization (TACE). METHODS: We performed a retrospective cohort study of 142 patients with recurrent HCC who were treated by TACE at our hospital from April 1990 to December 2011. Patients were divided into three groups, as follows, according to the trends of the two tumor markers AFP and DCP: the low group, comprising patients with tumor marker levels below the cutoff values (AFP 100 ng/mL and DCP 100 mAU/mL) both pre- and post-TACE; the decreased group, comprising patients with elevated tumor marker levels pre-TACE in whom the levels decreased post-TACE; and the elevated group, comprising patients with elevated tumor marker levels post-TACE. RESULT: Analysis using a Cox proportional hazards model identified the DCP trend (elevated group vs. low group, hazard ratio 8.47, 95 % confidence interval 4.53-15.84, p < 0.0001), but not the AFP trend, as an independent prognostic factor for survival. While the AFP trend was correlated only with the overall response rate assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST; p = 0.041), the DCP trend was strongly associated with both the overall response rate (p = 0.009) and the disease control rate (p = 0.004). CONCLUSION: The DCP trend might be useful for assessing treatment outcomes after TACE in patients with recurrent HCC.


Assuntos
Biomarcadores/sangue , Carcinoma Hepatocelular/sangue , Neoplasias Hepáticas/sangue , Recidiva Local de Neoplasia/sangue , Precursores de Proteínas/sangue , alfa-Fetoproteínas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Prognóstico , Modelos de Riscos Proporcionais , Protrombina , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
17.
PLoS One ; 19(1): e0295998, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38206908

RESUMO

BACKGROUND: This randomized, parallel-group study aims to investigate the effects of the probiotic Bifidobacterium bifidum G9-1 (BBG9-1) on the symptoms of diarrhea or constipation in patients with type 2 diabetes mellitus (T2DM). METHODS: This study will examine 100 patients with T2DM who suffering from symptoms of diarrhea or constipation. Eligible patients will be randomly assigned 1:1 to two groups (group A, BBG9-1 group; group B, control group), after the baseline examination. Patients assigned to group A will receive probiotic BBG9-1 oral administration along with their current treatment for 12 weeks, and patients assigned to group B will continue the current treatment for 12 weeks without probiotic BBG9-1 oral administration. Subsequently, examinations similar to the baseline examinations will be performed. The primary endpoint will be a change in the Gastrointestinal Symptom Rating Scale (GSRS) total score from baseline to week 12. Secondary endpoints will include the following: change and percent change in parameters such as GSRS subdomain scores, fecal properties/Bristol stool form scale, defecation frequency, biomarkers, gut microbiota, and macronutrients and factors that affect GSRS total score or constipation/diarrhea subdomain scores from baseline to week 12. DISCUSSION: The results of this study will clarify the utility of probiotic BBG9-1 in the treatment of diarrhea or constipation in patients with T2DM. TRIAL REGISTRATION: jRCTs051220127.


Assuntos
Bifidobacterium bifidum , Diabetes Mellitus Tipo 2 , Gastroenteropatias , Probióticos , Humanos , Bifidobacterium , Diabetes Mellitus Tipo 2/complicações , Gastroenteropatias/complicações , Diarreia/microbiologia , Constipação Intestinal/terapia , Resultado do Tratamento , Probióticos/uso terapêutico , Probióticos/farmacologia , Método Duplo-Cego , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
J Diabetes Investig ; 15(8): 1042-1046, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38655665

RESUMO

AIMS/INTRODUCTION: We aimed to investigate the association between glycemic variability and quality of life (QOL) in patients with diabetes, which has not been studied previously. MATERIALS AND METHODS: Patients who were undergoing treatment at the Kyoto Prefectural University of Medicine Hospital and Kameoka City Hospital participated in the KAMOGAWA-DM study, and completed the diabetes therapy-related (DTR)-QOL questionnaire from January 2016 to July 2020 were included in this study. We used linear regression analyses to compare the association between DTR-QOL scores and glycemic variability. RESULTS: We included a total of 635 patients in this analysis. The hemoglobin A1c (HbA1c) levels of these patients were measured at least four times during the 9-month period, before and after answering the questionnaire. Results showed that HbA1c variability, HbA1c mean and duration of diabetes were negatively associated with the total DTR-QOL score. Conversely, the body mass index and total DTR-QOL score were positively associated with HbA1c variability. CONCLUSIONS: A small variation in HbA1c level was associated with higher total DTR-QOL scores and the scores for each factor. Reducing blood glucose variability is significant when we treat diabetes.


Assuntos
Glicemia , Hemoglobinas Glicadas , Qualidade de Vida , Humanos , Hemoglobinas Glicadas/análise , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Glicemia/análise , Inquéritos e Questionários , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/psicologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus/sangue , Diabetes Mellitus/psicologia , Controle Glicêmico , Hipoglicemiantes/uso terapêutico , Seguimentos , Biomarcadores/sangue , Prognóstico
19.
Asian J Surg ; 47(2): 893-898, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37923599

RESUMO

OBJECTIVE: Accurate assessment of renal function prior to surgery for hepatocellular carcinoma is important for patient outcome, but current methods such as the estimated glomerular filtration rate (eGFR) are inadequate. We developed a new prediction formula that incorporates preoperative computed tomography (CT) imaging data to determine renal function. METHODS: We retrospectively analyzed 400 patients who underwent hepatectomy for hepatocellular carcinoma between January 2010 and December 2021. Predictors associated with renal function were identified by multivariate analysis. RESULTS: Age, sex, body height, body weight, body surface area, body mass index, serum creatinine, and muscle areas including third lumbar vertebra total muscle area (L3 TMA) determined by preoperative CT were identified as independent predictors likely to be associated with renal function. These were used to construct a new prediction formula using multiple regression analysis performed with a stepwise method: 232.2 + (-1.17 × age) + (-89.0 × serum creatinine) + (0.28 × L3 TMA). The median difference between conventional eGFR and CCr was 47.6 ml/min (range, 1.7-137.9 ml/min), while that between the new eGFR and CCr was 14.3 ml/min (range, 0.02-64.7 ml/min). Spearman rank correlation analysis revealed that the new eGFR was more positively correlated with CCr than conventional eGFR (ρ = 0.623, P < 0.05; ρ = 0.700, P < 0.05, respectively), and hence more accurately reflected renal function. CONCLUSION: A new prediction formula based on L3 TMA determined by CT is more accurate than conventional eGFR for evaluating renal function.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Creatinina , Estudos Retrospectivos , Músculos , Rim
20.
Asian J Surg ; 47(9): 3870-3876, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38688761

RESUMO

BACKGROUND: Portal vein embolization (PVE) followed by major hepatectomy is a common treatment strategy for patients with perihilar cholangiocarcinoma (PHCC); however, the long-term dynamics of the liver remnant volume (LRV) remain unclear. Here, we report the dynamics of the LRV in patients who underwent hepatectomy following PVE. METHODS: A total of 39 patients with PHCC who underwent right hemihepatectomy or left trisectionectomy with extrahepatic bile duct resection between 2004 and 2021 were enrolled in this study [PVE (n = 27) and non-PVE (n = 12]). Long-term remnant liver dynamics were analyzed in propensity score-matched pairs (n = 10/group). RESULTS: The LRV/future liver remnant volume (FLRV) at 1 week to 1 month after hepatectomy were smaller in the PVE group than in the non-PVE group (1.53 vs. 1.69, p = .044 and 1.52 vs 1.99, p = .003, respectively). In the non-PVE group, the LRV/FLRV ratio plateaued 1-3 months postoperatively, whereas progressive hypertrophy occurred in the PVE group, and the LRV/FLRV ratio became equal in both groups at 1 year after hepatectomy (1.96 vs. 1.97; p = .799). Multivariate analysis revealed that FLRV/total liver volume (TLV) ≤ 0.43 was the only independent predictor of LRV/FLRV ≥1.9 at 1 year after hepatectomy (odds ratio:5.345, 95% confidence interval:1.210-23.615; p = .027). CONCLUSION: Although the long-term LRV was nearly equal in both groups, short-term LRV hypertrophy was lower in the PVE group than in the non-PVE group.


Assuntos
Neoplasias dos Ductos Biliares , Embolização Terapêutica , Hepatectomia , Tumor de Klatskin , Fígado , Veia Porta , Humanos , Hepatectomia/métodos , Masculino , Feminino , Embolização Terapêutica/métodos , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/terapia , Pessoa de Meia-Idade , Idoso , Tumor de Klatskin/cirurgia , Tumor de Klatskin/patologia , Tumor de Klatskin/terapia , Tamanho do Órgão , Fígado/irrigação sanguínea , Fígado/patologia , Fatores de Tempo , Resultado do Tratamento , Estudos Retrospectivos , Pontuação de Propensão
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