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BACKGROUND: The antidiabetic drugs sodium glucose cotransporter 2 inhibitors (SGLT2is) and thiazolidinediones have beneficial effects on the liver dysfunction of patients with nonalcoholic fatty liver disease and type 2 diabetes mellitus (T2DM). We aimed to determine the efficacy of these drugs for the treatment of liver disease in patients with metabolic dysfunction-associated fatty liver disease (MAFLD) and T2DM. METHODS: We undertook a retrospective study of 568 patients with MAFLD and T2DM. Of these, 210 were treating their T2DM with SGLT2is (n = 95), 86 with pioglitazone (PIO), and 29 with both. The primary outcome was the change in Fibrosis-4 (FIB-4) index between baseline and 96 weeks. RESULTS: At 96 weeks, the mean FIB-4 index had significantly decreased (from 1.79 ± 1.10-1.56 ± 0.75) in the SGLT2i group, but not in the PIO group. The aspartate aminotransferase to platelet ratio index, serum aspartate and alanine aminotransferase (ALT), hemoglobin A1c, and fasting blood sugar significantly decreased in both groups (ALT: SGLT2i group, -17 ± 3 IU/L; PIO group, -14 ± 3 IU/L). The bodyweight of the SGLT2i group decreased, but that of the PIO group increased (-3.2 kg and +1.7 kg, respectively). When the participants were allocated to two groups according to their baseline ALT (>30 IU/L), FIB-4 index significantly decreased in both groups. In patients taking pioglitazone, the addition of SGLT2i improved liver enzymes but not FIB-4 index for 96 weeks. CONCLUSIONS: Treatment with SGLT2i causes a larger improvement in FIB-4 index than PIO in patients with MAFLD over 96 weeks.
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BACKGROUND: Pathological angiogenesis is involved in the development of hepatocellular carcinoma. In patients with chronic hepatitis C (CHC), the level of angiogenic factor angiopoietin (ANGP)-2 is reported to be increased in the blood, correlating with fibrosis. In this study, we aimed to clarify whether blood ANGP-2 is useful as a biomarker for liver angiogenesis and fibrosis in CHC patients and to further reveal the relationship between such pathology in a carbon tetrachloride (CCl4)-treated liver fibrosis mouse model. METHODS: Plasma levels of ANGP-2, expression of a liver sinusoidal endothelial cell (LSEC) marker (CD31), collagen deposition (Sirius Red staining) in the liver, clinical fibrosis markers (Mac-2 binding protein glycosylation isomer, virtual touch quantification, and liver stiffness measurement), and liver function (albumin bilirubin score) were examined in CHC patients. To determine the effects of an anti-angiogenic agent on liver fibrosis in vivo, sorafenib was administered to the CCl4-treated mice (BALB/c male). RESULTS: The plasma levels of ANGP-2 were increased in CHC patients compared to healthy volunteers and decreased by the eradication of hepatitis C with direct-acting antivirals. In addition, plasma ANGP-2 levels were correlated with CD31 expression, collagen deposition, clinical fibrosis markers, and liver function. Sorafenib inhibited liver angiogenesis and fibrosis in the CCl4-treated mice and was accompanied by decreased ANGP-2 expression in LSECs. CONCLUSIONS: ANGP-2 may serve as a useful biomarker for liver angiogenesis and fibrosis in CHC patients. In addition, angiogenesis and fibrosis may be closely related.
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Angiopoyetina 2 , Hepatitis C Crónica , Angiopoyetina 2/uso terapéutico , Animales , Antivirales/uso terapéutico , Tetracloruro de Carbono , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/patología , Humanos , Hígado/patología , Cirrosis Hepática/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Neovascularización PatológicaRESUMEN
PURPOSE: We previously reported three cases of portal hypertension in patients with prolonged anorexia nervosa (AN) with laxative abuse and self-induced vomiting; we now report a fourth, similar case. METHODS: A 34-year-old woman with anorexia nervosa, binge-eating/purging type (AN-BP), presented to the Kohnodai Hospital National Center for Global Health and Medicine Psychosomatic Medicine Department for treatment of low body weight. We conducted hepatic and renal biopsies and cardiac magnetic resonance imaging (CMR) to evaluate her complicated liver disease, renal failure, and cardiac insufficiency, respectively. RESULTS: Enhanced computed tomography revealed ascites, splenomegaly, and gastroesophageal varices, indicating portal hypertension. The liver and kidney biopsies demonstrated chronic hepatitis without evidence of hepatic cirrhosis and tubulointerstitial nephritis, respectively. CMR demonstrated decreased myocardial mass. CONCLUSION: We found tubulointerstitial nephritis and decreased myocardial mass in a patient with non-cirrhotic portal hypertension and prolonged AN with laxative abuse and habitual self-induced vomiting. We propose that reciprocal interactions between multiple factors related to AN, including laxative toxicity, dehydration, renal disorder, and cardiac insufficiency, result in portal hypertension. Level of Evidence Level V.
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Anorexia Nerviosa , Hipertensión Portal , Adulto , Anorexia Nerviosa/complicaciones , Biopsia , Femenino , Humanos , Hipertensión Portal/complicaciones , Riñón , Laxativos/efectos adversosRESUMEN
AIMS: Rifaximin (RFX), a non-systemic antibiotic, improves liver/neuropsychological functions in patients with hepatic encephalopathy (HE). We aimed to investigate the clinical profiles associated with gut bacterial loads using exploratory data analysis and the effects of RFX on the gut microbiota of patients with HE. METHODS: We analyzed the data from 17 patients with HE who underwent fecal microbiota examination in phase II/III trials in Japan. Profiles associated with genera Streptococcus, Veillonella, and Lactobacillus loads were analyzed using classification and regression trees (CART). Changes in gut microbial consortia of seven patients with HE were then assessed 2 weeks after RFX treatment by principal component analysis. RESULTS: In the CART, the first and second divergence variables for each higher bacterial load were as follows: (i) in Streptococcus, the number connection test-A ≥39.55 s and presence of portal-systemic shunt; (ii) in Veillonella, serum potassium levels <4.75 mEq/L and total cholesterol level <129.5 mg/dL; and (iii) in Lactobacillus, white blood cell counts ≥3.4 × 103 /µL and aspartate aminotransferase level ≥44.5 U/L. There was no significant change in total bacterial load before and after RFX treatment; however, there was a decrease in Streptococcus, Veillonella, and Lactobacillus counts after RFX treatment. CONCLUSION: We report clinical profiles associated with gut bacterial loads in patients with HE, and showed that RFX altered gut microbiota components associated with liver/neuropsychological functions. Thus, RFX could improve liver/neuropsychological functions through the regulation of the gut microbial consortia in patients with HE.
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OBJECTIVE: There has been no report on portal hypertension related to anorexia nervosa (AN). METHOD: We describe three cases of portal hypertension manifesting with collateral circulation represented by gastroesophageal varices in prolonged AN with laxative abuse and self-vomiting. These women, in their 20s to 50s, were diagnosed as having AN binging and purging type (AN-BP) that included self-induced vomiting and abuse of irritating laxatives (more than 100 tablets daily). RESULTS: Case 1 showed prominent ascites and a gastro-renal shunt on computed tomography scanning. Case 2 showed gastroesophageal varices on endoscopic examination. Case 3 showed gastroesophageal varices on computed tomography scanning and endoscopic examination. We performed liver biopsies in all patients and found only slight pericellular fibrosis. Our patients showed typical symptoms of portal hypertension, although liver cirrhosis was not present. DISCUSSION: We speculated that abnormal eating and purging behaviors were involved in the development of portal hypertension. We hypothesized that long-term laxative abuse, dehydration, and abnormal eating behavior are involved in the development of portal hypertension, considering these were common features in our patients. Portal hypertension and gastroesophageal varices should be considered as one of the potentially existing complications in prolonged AN-BP with self-induced vomiting and abuse of irritating laxatives.
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Anorexia Nerviosa/complicaciones , Hipertensión Portal/etiología , Laxativos/efectos adversos , Adulto , Anorexia Nerviosa/patología , Femenino , Humanos , Hipertensión Portal/patología , Persona de Mediana EdadRESUMEN
In this report, we present the case of a female infant with peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease (PCWH) associated with a novel frameshift mutation (c.842dupT) in exon 5, the last exon of SOX10. She had severe hypoganglionosis in the small intestine and entire colon, and suffered from frequent enterocolitis. The persistence of ganglion cells made both the diagnosis and treatment difficult in the neonatal period. She also showed hypopigmentation of the irises, hair and skin, bilateral sensorineural deafness with hypoplastic inner year, severe demyelinating neuropathy with hypotonia, and diffuse brain hypomyelination. The p.Ser282GlnfsTer12 mutation presumably escapes from nonsense-mediated decay and may generate a dominant-negative effect. We suggest that hypoganglionosis can be a variant intestinal manifestation associated with PCWH and that hypoganglionosis and aganglionosis may share the same pathoetiological mechanism mediated by SOX10 mutations.
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Enfermedades Desmielinizantes/genética , Estudios de Asociación Genética , Enfermedad de Hirschsprung/genética , Mutación , Factores de Transcripción SOXE/genética , Síndrome de Waardenburg/genética , Biopsia , Encéfalo/anomalías , Encéfalo/diagnóstico por imagen , Análisis Mutacional de ADN , Enfermedades Desmielinizantes/diagnóstico , Exones , Facies , Femenino , Mutación del Sistema de Lectura , Enfermedad de Hirschsprung/diagnóstico , Humanos , Inmunohistoquímica , Lactante , Intestinos/patología , Imagen por Resonancia Magnética , Fenotipo , Cráneo/anomalías , Cráneo/diagnóstico por imagen , Síndrome de Waardenburg/diagnósticoRESUMEN
BACKGROUND: The expected MRI-based dimensions of the intracranial optic nerve and optic tract in neonates are unknown. OBJECTIVE: To evaluate the sizes of the intracranial optic nerve and optic tract in neonates at term-equivalent age using MRI. MATERIALS AND METHODS: We retrospectively analyzed brain MRI examinations in 62 infants (28 boys) without intracranial abnormalities. The images were obtained in infants at term-equivalent age with a 1.5-tesla MRI scanner. We measured the widths and heights of the intracranial optic nerve and optic tract and calculated the cross-sectional areas using the formula for an ellipse. RESULTS: The means ± standard deviation of the width, height and cross-sectional area of the intracranial optic nerve were 2.7 ± 0.2 mm, 1.7 ± 0.2 mm and 3.5 ± 0.5 mm(2), respectively. The width, height and cross-sectional area of the optic tract were 1.5 ± 0.1 mm, 1.6 ± 0.1 mm and 2.0 ± 0.2 mm(2), respectively. Using univariate and multivariate analyses, we found that postmenstrual age showed independent intermediate positive correlations with the width (r = 0.48, P < 0.01) and cross-sectional area (r = 0.40, P < 0.01) of the intracranial optic nerve. The lower bounds of the 95% prediction intervals for the width and cross-sectional area of the intracranial optic nerve were 0.07 × (postmenstrual age in weeks) - 0.46 mm, and 0.17 × (postmenstrual age in weeks) - 4.0 mm(2), respectively. CONCLUSION: We identified the sizes of the intracranial optic nerve and optic tract in neonates at term-equivalent age. The postmenstrual age at MRI independently positively correlated with the sizes.
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Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/normas , Nervio Óptico/anatomía & histología , Nervio Óptico/diagnóstico por imagen , Tracto Óptico/anatomía & histología , Tracto Óptico/diagnóstico por imagen , Algoritmos , Puntos Anatómicos de Referencia/anatomía & histología , Puntos Anatómicos de Referencia/diagnóstico por imagen , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Recién Nacido , Masculino , Tamaño de los Órganos , Valores de Referencia , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
This review discussed analyzing information dissemination and activities related to mental health conducted by the Centers of Disease Control and Prevention (CDC), considering their application in Japan, and disseminating them to the public is necessary for the Japanese New Center for Health Control. The Japanese government also explores the Japanese New Center For Health Control in addressing children's mental health issues potentially under the Japan health crisis. The findings underscore the urgency of prioritizing children's mental health and implementing effective strategies to mitigate the long-term effects of the COVID-19 pandemic.
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BACKGROUND: The branched-chain amino acids (BCAAs) to tyrosine (Tyr) ratio (BTR) test is used to evaluate the progression of chronic liver disease (CLD). However, the differences across sex, age, body mass index (BMI) and etiologies are still unclear. METHODS: We retrospectively reviewed data from 2,529 CLD cases with free amino acids (FAAs) in peripheral blood from four hospitals and 16,421 general adults with FAAs data from a biobank database. In total, 1,326 patients with CLD (covering seven etiologies) and 8,086 healthy controls (HCs) were analyzed after exclusion criteria. We investigated the change of BTR in HCs by sex, age and BMI and then compared these to patients divided by modified ALBI (mALBI) grade after propensity score matching. RESULTS: BTR is significantly higher in males than females regardless of age or BMI and decreases with aging in HCs. In 20 types of FAAs, 7 FAAs including BCAAs were significantly decreased, and 11 FAAs including Tyr were significantly increased by mALBI grade in total CLD. The decreasing timings of BTR were at mALBI grade 2b in all CLD etiologies compared to HCs, however in chronic hepatitis C (CHC), chronic hepatitis B (CHB) and alcoholic liver disease (ALD), BTR started to decrease at 2a. There was a positive correlation between BCAAs and albumin among parameters in BTR and mALBI. The correlation coefficients in PBC, ALD and MASLD were higher than those of other etiologies. CONCLUSIONS: BTR varies by sex and age even among healthy adults, and decreasing process and timing of BTR during disease progression is different among CLD etiologies.
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Aminoácidos de Cadena Ramificada , Progresión de la Enfermedad , Hepatopatías , Tirosina , Humanos , Masculino , Femenino , Aminoácidos de Cadena Ramificada/sangre , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Anciano , Tirosina/sangre , Hepatopatías/etiología , Hepatopatías/sangre , Factores Sexuales , Índice de Masa Corporal , Enfermedad Crónica , Factores de Edad , Adulto Joven , Estudios de Casos y Controles , Hepatopatías Alcohólicas/complicaciones , Hepatopatías Alcohólicas/sangre , Biomarcadores/sangreRESUMEN
UNLABELLED: Assessment of liver fibrosis in patients with chronic hepatitis C (CHC) is critical for predicting disease progression and determining future antiviral therapy. LecT-Hepa, a new glyco-marker derived from fibrosis-related glyco-alteration of serum alpha 1-acid glycoprotein, was used to differentiate cirrhosis from chronic hepatitis in a single-center study. Herein, we aimed to validate this new glyco-marker for estimating liver fibrosis in a multicenter study. Overall, 183 CHC patients were recruited from 5 liver centers. The parameters Aspergillus oryzae lectin (AOL) / Dature stramonium lectin (DSA) and Maackia amurensis lectin (MAL)/DSA were measured using a bedside clinical chemistry analyzer in order to calculate LecT-Hepa levels. The data were compared with those of seven other noninvasive biochemical markers and tests (hyaluronic acid, tissue inhibitor of metalloproteases-1, platelet count, aspartate aminotransferase-to-platelet ratio index [APRI], Forns index, Fib-4 index, and Zeng's score) for assessing liver fibrosis using the receiver-operating characteristic curve. LecT-Hepa correlated well with the fibrosis stage as determined by liver biopsy. The area under the curve (AUC), sensitivity, and specificity of LecT-Hepa were 0.802, 59.6%, and 89.9%, respectively, for significant fibrosis; 0.882, 83.3%, and 80.0%, respectively, for severe fibrosis; and 0.929, 84.6%, and 88.5%, respectively, for cirrhosis. AUC scores of LecT-Hepa at each fibrosis stage were greater than those of the seven aforementioned noninvasive tests and markers. CONCLUSION: The efficacy of LecT-Hepa, a glyco-marker developed using glycoproteomics, for estimating liver fibrosis was demonstrated in a multicenter study. LecT-Hepa given by a combination of the two glyco-parameters is a reliable method for determining the fibrosis stage and is a potential substitute for liver biopsy.
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Hepatitis C Crónica/sangre , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Cirrosis Hepática/sangre , Cirrosis Hepática/virología , Proteínas de la Membrana/metabolismo , Orosomucoide , Factores de Edad , Anciano , Análisis de Varianza , Aspartato Aminotransferasas/sangre , Biomarcadores/sangre , Estudios de Cohortes , Intervalos de Confianza , Progresión de la Enfermedad , Femenino , Glicoproteínas/sangre , Humanos , Lectinas/sangre , Pruebas de Función Hepática , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Curva ROC , Medición de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Estadísticas no ParamétricasRESUMEN
A 69-year-old female was referred to our hospital with hematochezia. Dynamic computed tomography demonstrated a large tumor with rim enhancement and central necrosis that invaded into the transverse colon. The tumor was resected, and histopathological examination revealed mixed adenocarcinoma and squamous cell carcinoma with partial abscess formation. On the basis of a literature review and the findings from the present case, rim enhancement with central necrosis on imaging appears to be characteristic of this disease.
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Carcinoma Adenoescamoso/patología , Enfermedades del Colon/etiología , Hemorragia Gastrointestinal/etiología , Neoplasias Hepáticas/patología , Anciano , Carcinoma Adenoescamoso/complicaciones , Carcinoma Adenoescamoso/diagnóstico , Femenino , Humanos , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/diagnóstico , Invasividad NeoplásicaRESUMEN
BACKGROUND: Ethanol injection is the best-known image-guided percutaneous ablation for hepatocellular carcinoma (HCC) and a well-tolerated, inexpensive procedure with few adverse effects. However, there have been few reports on its long-term results. AIMS: We report a 20-year consecutive case series at a tertiary referral centre. METHODS: We performed 2147 ethanol injection treatments on 685 primary HCC patients and analysed a collected database. RESULTS: Final computed tomography demonstrated complete ablation of treated tumours in 2108 (98.2%) of the 2147 treatments. With a median follow-up of 51.6 months, 5-, 10- and 20-year survival rates were 49.0% [95% confidence interval (CI) = 45.3-53.0%], 17.9% (95% CI = 15.0-21.2%) and 7.2% (95% CI = 4..5-11.5%) respectively. Multivariate analysis demonstrated that age, Child-Pugh class, tumour size, tumour number and serum alpha-fetoprotein level were significant prognostic factors for survival. Five-, 10- and 20-year local tumour progression rates were 18.2% (95% CI = 15.0-21.4%), 18.4% (95% CI = 15.2-21.6%) and 18.4% (95% CI = 15.2-21.6%) respectively. Five-, 10- and 20-year distant recurrence rates were 53.5% (95% CI = 49.4-57.7%), 60.4 (95% CI = 56.3-64.5%) and 60.8% (95% CI = 56.7-64.9%) respectively. There were 45 complications (2.1%) and two deaths (0.09%). CONCLUSIONS: Ethanol injection was potentially curative for HCC, resulting in survival for more than 20 years. This study suggests that new ablation therapies will achieve similar or even better long-term results in HCC.
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Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Etanol/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidad , Estudios de Cohortes , Progresión de la Enfermedad , Etanol/administración & dosificación , Femenino , Humanos , Inyecciones Intralesiones , Japón/epidemiología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Pronóstico , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
We report clinical and molecular findings in three Japanese patients with N-acetylneuraminic acid synthetase-congenital disorder of glycosylation (NANS-CDG). Patient 1 exhibited a unique constellation of clinical features including marked hydrocephalus, spondyloepimetaphyseal dysplasia (SEMD), and thrombocytopenia which is comparable to that of an infant reported by Faye-Peterson et al., whereas patients 2 and 3 showed Camera-Genevieve type SMED with intellectual/developmental disability which is currently known as the sole disease name for NANS-CDG. Molecular studies revealed a maternally inherited likely pathogenic c.207del:p.(Arg69Serfs*57) variant and a paternally derived likely pathogenic c.979_981dup:p.(Ile327dup) variant in patient 1, a homozygous likely pathogenic c.979_981dup:p.(Ile327dup) variant caused by maternal segmental isodisomy involving NANS in patient 2, and a paternally inherited pathogenic c.133-12T>A variant leading to aberrant splicing and a maternally inherited likely pathogenic c.607T>C:p.(Tyr203His) variant in patient 3 (reference mRNA: NM_018946.4). The results, together with previously reported data, imply that (1) NANS plays an important role in postnatal growth and fetal brain development; (2) SMED is recognizable at birth and shows remarkable postnatal evolution; (3) NANS-CDG is associated with low-normal serum sialic acid, obviously elevated urine N-acetylmannosamine, and normal N- and O-glycosylation of serum proteins; and (4) NANS-CDG is divided into Camera-Genevieve type and more severe Faye-Peterson type.
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Trastornos Congénitos de Glicosilación , Ácido N-Acetilneuramínico , Trastornos Congénitos de Glicosilación/genética , Glicosilación , Humanos , Lactante , Recién Nacido , Japón , Ligasas , ARN MensajeroRESUMEN
It is well-known that sustained virological response (SVR) by interferon (IFN)-based therapy against hepatitis C virus (HCV) infection reduced the incidence of hepatocellular carcinoma (HCC). However, whether IFN-free direct-acting antivirals reduce the risk of HCC is controversial. Therefore, this study aims to compare the incidence of HCC after the achievement of SVR between sofosbuvir combined with ledipasvir (SOF/LDV) and simeprevir with pegylated interferon plus ribavirin (Sim+IFN). Japanese patients with HCV infection (genotype 1) who achieved SVR between January 2013 and December 2014 by SOF/LDV (NCT01975675, n = 320) or Sim+IFN (000015933, n = 289) therapy in two nationwide, multicenter, phase III studies were prospectively monitored for the development of HCC by ultrasonography for 5 years after the end of treatment (EOT). No HCC was detected before the treatment. HCC was detected in 9 and 7 patients in the SOF/LDV and the Sim+IFN group in 5 years, respectively. The cumulative incidences of HCC rates 1, 3, and 5 years after EOT were similar between the two groups (1.5%, 2.7%, and 3.2% for the SOF/LDV and 1.8%, 2.8%, and 3.0% for the Sim+IFN group, respectively). No HCC was developed 3.5 years after EOT. Interestingly, a retrospective careful review of imaging taken before therapy revealed hepatic nodules in 50% of HCC patients, suggesting HCC was pre-existed before therapy. In conclusion, we could not find any differences in the incidence of HCC after the HCV eradication between the two therapeutic regimens, suggesting no enhancement of HCC development by DAA.
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We focused on determining the most accurate and convenient genotyping methods and most appropriate single nucleotide polymorphism (SNP) among four such polymorphisms associated with interleukin-28B (IL-28B) in order to design tailor-made therapy for patients with chronic hepatitis C virus (HCV) patients. First, five different methods (direct sequencing, high-resolution melting analysis [HRM], hybridization probe [HP], the InvaderPlus assay [Invader], and the TaqMan SNP genotyping assay [TaqMan]) were developed for genotyping four SNPs (rs11881222, rs8103142, rs8099917, and rs12979860) associated with IL-28B, and their accuracies were compared for 292 Japanese patients. Next, the four SNPs associated with IL-28B were genotyped by Invader for 416 additional Japanese patients, and the response to pegylated interferon/ribavirin (PEG-IFN/RBV) treatment was evaluated when the four SNPs were not in linkage disequilibrium (LD). HRM failed to genotype one of the four SNPs in five patients. In 2 of 287 patients, the results of genotyping rs8099917 by direct sequencing differed from the results of the other three methods. The HP, TaqMan, and Invader methods were accurate for determination of the SNPs associated with IL-28B. In 10 of the 708 (1.4%) patients, the four SNPs were not in LD. Eight of nine (88.9%) patients whose rs8099917 was homozygous for the major allele were virological responders, even though one or more of the other SNPs were heterozygous. The HP, TaqMan, and Invader methods were suitable to determine the SNPs associated with IL-28B. The rs8099917 polymorphism should be the best predictor for the response to the PEG-IFN/RBV treatment among Japanese chronic hepatitis C patients.
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Antivirales/administración & dosificación , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Interleucinas/genética , Polimorfismo de Nucleótido Simple , Ribavirina/administración & dosificación , Anciano , Pueblo Asiatico , Quimioterapia Combinada/métodos , Femenino , Pruebas Genéticas/métodos , Genotipo , Humanos , Interferones , Japón , Masculino , Persona de Mediana Edad , Pronóstico , Resultado del TratamientoRESUMEN
We designed a retrospective cohort study using the Diagnosis Procedure Combination database, a national inpatient database for acute-care inpatients in Japan, to examine whether recent global diagnostic criteria for preeclampsia, phenotypes of hypertensive disorders of pregnancy (HDP) and features of the disease are useful as predictors of placental abruption and whether other risk factors are associated with the onset of placental abruption. A total of 85,858 hospitalized patients with a diagnosis of HDP who gave birth during hospitalization between July 2010 and March 2018 were included in this study. We examined the associations between the occurrence of placental abruption after hospitalization and several factors, including gestational age (GA) at placental abruption onset, HDP subtypes, GA on admission, maternal age, body mass index, smoking, multiple pregnancy, prelabor rupture of membranes, diabetes mellitus, emergency admission by ambulance, and consciousness, using a multivariate logistic regression analysis. Placental abruption occurred in 541 patients (0.63%) after hospital admission, and the occurrence increased acutely after 32 weeks GA. A decrease in abruption was significantly associated with maternal BMI on admission (≥30 kg/m2; odds ratio [OR], 0.54; 95% confidence interval [CI], 0.41-0.70) and multiple pregnancy (OR, 0.29; 95% CI, 0.18-0.46). An increase in abruption was associated with earlier GA on admission (<34 weeks' GA; OR, 3.77; 95% CI, 3.13-4.53) and emergency admission by ambulance (OR, 1.34; 95% CI, 1.09-1.65). Individual features of severe PE showed no significant associations with the occurrence of abruption. In conclusion, HDP at an earlier GA was suggested to be a risk factor for placental abruption, and we recommend hospitalization and careful management of such patients to improve their prognosis.
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Hipertensión Inducida en el Embarazo , Desprendimiento Prematuro de la Placenta/epidemiología , Femenino , Humanos , Hipertensión Inducida en el Embarazo/epidemiología , Pacientes Internos , Japón/epidemiología , Fenotipo , Placenta , Preeclampsia/epidemiología , Embarazo , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Hyperglycemia in extremely low-birth weight infants (ELBWIs) is frequently observed during the acute perinatal phase, (i.e., first 1-2 weeks postnatal period); however it can occasionally persists for >2 weeks, extending to the post-acute phase. Since such prolonged hyperglycemia (PH) is not typical for ELBWIs, the aim of the present study was to further understand the clinical details of PH. Twenty-five hyperglycemic ELBWIs born before 28 weeks of gestation from 2015 to 2018 were included in the study. Based on the duration of hyperglycemia, we separated the subjects into two groups: non-prolonged hyperglycemia (NPH) who achieved remission within ≤2 weeks [n = 18, median 3.0 (range, 2.0-4.0) days], and PH, whose hyperglycemia persisted for >2 weeks [n = 7, median 50.0 (range, 33.5-66.0) days]. Compared to the NPH group, glucose metabolism of the PH group was more deteriorate. The peak blood glucose level was significantly higher in the PH group [PH: median 472 mg/dL, NPH: median 275 mg/dL, p < 0.001], and a higher proportion of subjects in the PH group required insulin therapy [PH: 100% (7/7) vs. NPH: 22% (4/22)]. Multivariate analysis revealed that among perinatal factors, prematurity was the only independent risk factor for PH (glucocorticoid therapy: p = 0.884, gestational age: p = 0.006), with a cutoff of 23W4D determined by receiver operating characteristic analysis. Our data revealed distinctive clinical features of PH, suggesting a type different from the previously reported hyperglycemia in ELBWIs. Specifically, extreme prematurity, less than 24 weeks of gestation, is a risk for PH, and aggressive interventions, such as insulin would be required.
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Hiperglucemia , Recien Nacido con Peso al Nacer Extremadamente Bajo , Enfermedades del Prematuro , Peso al Nacer , Femenino , Edad Gestacional , Humanos , Hiperglucemia/epidemiología , Lactante , Recién Nacido , EmbarazoRESUMEN
There has been little information demonstrating the roles of dimethylarginine dimethylaminohydrolase (DDAH), which is the hydrolyzing enzyme of endogenous nitric oxide synthase (NOS) inhibitors and, in turn, modulates the intracellular concentrations of NOS inhibitors, in the myometrium during the course of pregnancy. Therefore, the present experiments were designed to investigate whether or not DDAH activity, protein and mRNA expression levels are altered during gestation of the rat and, if altered, those changes reflect on the levels of endogenous inhibitors and endothelin-1 (ET-1), and NO-dependent cyclic GMP generation in the myometrium. The up-regulated changes in DDAH activity, DDAH-2 protein and DDAH-2 mRNA expression at mid-gestation were accompanied by the reduced monomethylarginine and asymmetric dimethylarginine as NOS inhibitors, and ET-1 levels, and by the enhanced NO-dependent cyclic GMP production. At term gestation, on the other hand, down-regulated changes in DDAH activity, DDAH-2 protein and DDAH-2 mRNA expression were accompanied by the increased NOS inhibitors and ET-1 levels, and decreased NO-dependent cyclic GMP generation. These results suggest that alterations in DDAH/NOS inhibitors/NO-dependent cyclic GMP/ET-1 pathway are possibly involved in maintaining myometrial quiescence during gestation and controlling delivery at term.
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Amidohidrolasas/metabolismo , Miometrio/metabolismo , Contracción Uterina/metabolismo , Amidohidrolasas/genética , Animales , Arginina/análogos & derivados , Arginina/metabolismo , Western Blotting , GMP Cíclico/metabolismo , Endotelina-1/metabolismo , Femenino , Técnicas In Vitro , Embarazo , Ratas , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
A 45-year-old male active homosexual was given a diagnosis of HIV-1 and acute hepatitis B in August 2007. Since his liver function became rapidly impaired, anti-HBV therapy with oral administration of entecavir (ETV) was started, and resulted in a favorable outcome. However, serum concentration of HIV-RNA decreased by log 1.26 within 60 days, which strongly suggested the inhibition of HIV proliferation by ETV. To prevent the appearance of mutated HIV, novel therapeutic strategies should be established in HIV/HBV-coinfected patients.
Asunto(s)
Antivirales/uso terapéutico , Guanina/análogos & derivados , Infecciones por VIH/tratamiento farmacológico , Hepatitis B/tratamiento farmacológico , ARN Viral/análisis , Guanina/uso terapéutico , Infecciones por VIH/virología , Homosexualidad , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The present experiments were designed to investigate whether electrically polarized hydroxyapatite (HA electret) modifies reendothelialization and intimal hyperplasia occurring after endothelial removal of the rabbit carotid artery. Both HA electret and non-polarized HA, which served as a control, had been powdered and mixed with agarose gel. One of the two was applied around the external surface of the carotid artery. Histological analyses revealed that HA electret but not control HA significantly inhibited intimal hyperplasia. The number of Ki67-positive cells detectable in the intimal layer was significantly fewer in the HA electret group. In the HA electret group, abundant TUNEL-positive cells were detected in the media. The number of CD31-positive cells detected on the luminal surface was significantly higher in the HA electret group. Endothelium- and nitric oxide (NO)-dependent relaxation in response to carbachol was significantly improved only in the HA electret group. In conclusion, this is the first report demonstrating that HA electret significantly improved intimal hyperplasia by accelerating the regeneration of functioning endothelial cells and enhancing the apoptosis of medial smooth muscle cells.