Current treatment status of IgA nephropathy in Japan: a questionnaire survey.

BACKGROUND: In 2020, the Committee of Clinical Practical Guideline for IgA Nephropathy (IgAN) revised the clinical practice guidelines. Herein, we conducted a questionnaire survey to assess the potential discrepancies between clinical practice guidelines and real-world practice in Japan. METHODS: A web-based survey of members of the Japanese Society of Nephrology was conducted between November 15 and December 28, 2021. RESULTS: A total of 217 members (internal physicians: 203, pediatricians: 14) responded to the questionnaire. Of these respondents, 94.0% answered that the clinical practice guidelines were referred to "always" or "often." Approximately 66.4% respondents answered that histological grade (H-Grade) derived from the "Clinical Guidelines for IgA nephropathy in Japan, 3rd version" and the "Oxford classification" were used for pathological classification. Moreover, 73.7% respondents answered that the risk grade (R-grade) derived from the "Clinical Guidelines for IgA nephropathy in Japan, 3rd version" was referred to for risk stratification. The prescription rate of renin-angiotensin system blockers increased based on urinary protein levels (> 1.0 g/day: 88.6%, 0.5-1.0 g/day: 71.0%, < 0.5 g/day: 25.0%). Similarly, the prescription rate of corticosteroids increased according to proteinuria levels (> 1.0 g/day: 77.8%, 0.5-1.0 g/day: 52.8%, < 0.5 g/day: 11.9%). The respondents emphasized on hematuria when using corticosteroids. In cases of hematuria, the indication rate for corticosteroids was higher than in those without hematuria, even if the urinary protein level was 1 g/gCr or less. Few severe infectious diseases or serious deterioration in glycemic control were reported during corticosteroid use. CONCLUSION: Our questionnaire survey revealed real-world aspects of IgAN treatment in Japan.

Development and validation of a model to predict the need for emergency front-of-neck airway procedures in trauma patients.

The present study aimed to develop and validate a model for predicting the need for emergency front-of neck airway (eFONA) procedures among trauma patients. This was a multicentre retrospective cohort study using data from the Japan Trauma Data Bank between January 2004 and December 2017. Only adult trauma patients were included. The cohort was divided into development and validation cohorts. A simple scoring system was developed to predict the necessity for emergency front-of neck airway procedures in the development cohort using a logistic regression model. The external validity and diagnostic ability of the scoring system was assessed in the validation cohort. In total, 198,182 out of 294,274 patients were included; emergency front-of-neck airway occurred in 467 patients (0.24%) they were divided into development (n = 100,120 with 0.22% undergoing emergency front-of neck airway) and validation (n = 98,062 with 0.25% undergoing emergency front-of neck airway) cohorts. The 'eFONA' prediction scoring system was developed in the development cohort, with a score of +1 for each of the following: Eye opening (no eye opening in response to any stimuli); Fall from height or motor bike; Oral-maxillofacial injury; Neck tracheal injury; and Airway management by paramedics. In the validation cohort, the C-statistic of the scoring system was 0.820. Setting the cut-off value at one for rule-out, the sensitivity and negative likelihood ratios were 0.86 and 0.22, respectively. Setting the cut-off value at two for rule-in, the specificity and positive likelihood ratios were 0.91 and 6.6, respectively. The present scoring system may assist in predicting the need for emergency front-of neck airway procedures among the general trauma population.

Improved two-dimensional electrophoretic mapping of Japanese human hair proteins; application to curved and straight Japanese human hairs; and protein identification by MALDI MS and MS/MS quadrupole time-of-flight mass spectrometry.

OBJECTIVES: To evaluate improved protein extraction and two-dimensional electrophoresis (2DE) separation methods with Japanese reference human hair (JRH); to determine whether fibre curvature is related to protein composition in curly and straight Japanese women's human hair (JHH) samples; and to identify proteins from JRH 2DE maps and expression differences between curly and straight JHH. METHODS: Hair keratin and keratin-associated proteins (KAPs) were extracted intact with dithiothreitol or tris(2-carboxyethyl) phosphine from JRH or from curved or straight JHH. Extracted proteins were isoelectric-focused on first-dimensional pH gradient gel strips, then separated by molecular weight on laboratory-made, second-dimension, large format gels. The software compared protein abundance between duplicate 2DE gels of curved and straight JHH. Thirty-eight proteins from a JRH 2DE gel were enzyme-cleaved for MALDI-TOF-MS analysis to determine peptide composition, and where possible, de novo sequencing gave peptide sequence data. An in-house human hair protein database incorporating ninety-eight annotated protein sequences assisted MS analysis. RESULTS: 2DE gels of tris(2-carboxyethyl) phosphine-extracted JRH improved keratin and KAP resolution and number compared to those of dithiothreitol-extracted JRH and published commercially made second-dimensional gels. Silver-stained 2DE gels of the straight or curved JHH sets were remarkably similar. Over-staining to reveal basic proteins caused poor resolution of the major acidic protein classes. Software comparisons of fifty-nine resolved proteins revealed two were significantly different in abundance between curved and straight hairs but in insufficient amounts for MS analysis. MS identified twelve proteins from a JRH CBBG-stained 2DE gel: six type II keratins, three type I keratins and three high sulphur proteins. A further eight were potential conformational isoforms and isoelectric variants of the identified proteins bringing the total to twenty identified or partially identified proteins. CONCLUSION: Root-end human hair extraction with tris(2-carboxyethyl) phosphine improves protein resolution and visualizes more proteins on large format 2DE gels. The two minor protein differences between duplicate straight or curved JHH 2DE gels were unlikely to change fibre structure from straight to curved hair. MS results confirmed that multiple isoforms exist of various hair proteins. Low sequence coverage prevented distinction between members in rows of homologous protein spots of similar molecular weight.

OBJECTIFS: évaluer l'amélioration de l'extraction de protéines et les méthodes de séparation bidimensionnelle par électrophorèse (2DE) avec des cheveux humains de référence Japonais (JRH), déterminer si la courbure de la fibre est liée à la composition protéique dans les échantillons de cheveux humains des Japonaises (JHH) bouclés et raides et identifier les protéines issues des cartes JRH 2DE et les différences d'expression entre les JHH bouclés et raides. MÉTHODES: la kératine des cheveux et les protéines associées à la kératine (KAP) ont été extraites intactes avec du dithiothréitol ou du tris (2-carboxyéthyl) phosphine des JRH ou des JHH bouclés ou raides. Les protéines extraites ont subi une focalisation isoélectrique sur des bandes de gel à gradient de pH unidimensionnelles, puis ont été séparées par poids moléculaire sur des gels bidimensionnels de grand format, fabriqués en laboratoire. Le logiciel a comparé l'abondance des protéines entre les deux duplicatas de gels 2DE des JHH bouclés et raides. Trente-huit protéines provenant d'un gel 2DE JRH ont été clivés par enzyme pour l'analyse MALDI-TOF-MS afin de déterminer la composition des peptides, et dans la mesure du possible, un séquençage de novo a donné des données de séquence des peptides. Une base de données interne des protéines capillaires humaines incorporant 98 séquences de protéines annotées a aidé l'analyse MS. RÉSULTATS: les gels 2DE de JRH extraits par le tris (2-carboxyéthyl) ont amélioré la résolution et le nombre de la kératine et du KAP par rapport à ceux du JRH extrait par le dithiothréitol et des gels bidimensionnels fabriqués commercialement. Les gels 2DE à coloration argentée des ensembles de JHH raides ou bouclés étaient remarquablement similaires. La sur-coloration pour révéler les protéines de base a provoqué une mauvaise résolution des principales classes de protéines acides. Les comparaisons logicielles des 59 protéines résolues ont révélé que deux présentaient une différence significative d'abondance entre les cheveux bouclés et raides, mais en quantités insuffisantes pour une analyse MS. La MS a identifié douze protéines provenant d'un gel 2DE coloré CBBG JRH : six kératines de type II, trois kératines de type I et trois protéines à forte teneur en soufre. Huit autres étaient des isoformes conformationnels potentiels et des variantes isoélectriques des protéines identifiées, ramenant le total à 20 protéines identifiées ou partiellement identifiées. CONCLUSION: l'extraction des cheveux humains à la racine avec du tris (2-carboxyéthyl) phosphine améliore la résolution des protéines et permet de visualiser plus de protéines sur les gels 2DE grand format. Les deux différences de protéines mineures entre les duplicatas des gels 2DE JHH raides ou bouclés étaient peu susceptibles de changer la structure des fibres de cheveux raides à bouclés. Les résultats de la MS ont confirmé qu'il existe plusieurs isoformes de diverses protéines capillaires. Une faible couverture de séquence a empêché la distinction entre les protéines homologues de poids moléculaire similaire.

Electron microscopy and tomography reveal that sodium 2-naphthalene sulfonate incorporated into perming solutions swells and tilts trichocyte intermediate filaments causing straightening of curly Japanese human hair.

OBJECTIVE: A new hair-care process has been specifically developed for the straightening of curved Japanese woman's hair . The process included sodium 2-naphthalene sulfonate (SNS) in the reduction and oxidation steps of a conventional perming process. Our objective was to develop an understanding of how this process caused hair straightening by measuring the changes to morphology and ultrastructure between untreated, conventionally permed and SNS permed hair. Untreated and SNS permed Merino wool fibres were used to confirm structural changes. METHODS: Japanese hair samples were measured for single-fibre curvature before and after perming treatments. A silver staining method was developed to stain hair fibres without changing fibre curvature so that transmission electron microscopy could be used to measure changes in the lateral dimensions of all structural components from the cellular to protein filament level. Electron tomography determined intermediate filament slopes and slope changes after SNS perming relative to the central longitudinal axis of the fibre. RESULTS: SNS perming was found to cause greater lateral swelling than conventional perming of: the paracortical cells of wool; the cuticle, the cuticular cell membrane complex and the macrofibrillar centre-to-centre distance of hair; and of the intermediate filaments in wool and hair. In curved hair, SNS perming caused the intermediate filaments of the helical macrofibrils to simultaneously swell and to tilt further, resulting in the slight longitudinal contraction of the macrofibrils. The overall swelling and tilting was greatest in the helical macrofibrils of Type B cortical cells predominately located in the convex fibre half. The presence of a higher percentage of helical macrofibrils in the convex fibre half than in the concave fibre half caused a contraction differential between the two halves leading to straighten of the curved fibre. A mechanical model was proposed to explain how SNS perming straightened curly hair. CONCLUSION: The effects of conventional and SNS perming on the morphological and ultrastructural components of curved Japanese hair and high-curl Merino wool fibres have given clear insights into understanding the mechanism of fibre curvature change.

OBJECTIF: Un nouveau procédé de soin des cheveux a été spécialement conçu pour lisser les cheveux ondulés des Japonaises[1]. Le procédé utilise le sulfonate de naphthalène-2 sodium (SNS) dans les étapes de réduction et d'oxydation du procédé conventionnel de permanente. Notre objectif était de comprendre la façon dont ce procédé induisait le lissage des cheveux en mesurant les différences de changement morphologique et ultrastructural entre les cheveux non traités et ceux soumis à une permanente conventionnelle et une permanente à base de SNS. Des fibres de laine de mérinos non traitées et soumises à une permanente à base de SNS ont été utilisées pour confirmer les changements structurels. MÉTHODES: Des échantillons de cheveux japonais ont été utilisés pour mesurer la courbure d'une fibre isolée avant et après le traitement de permanente. Une méthode de coloration argent a été mise au point pour colorer les fibres de cheveux sans changer la courbure des fibres afin de pouvoir utiliser la microscopie électronique en transmission pour mesurer les modifications des dimensions en largeur de tous les composants structurels du filament, de la cellule aux protéines. Une tomographie électronique a déterminé les pentes intermédiaires et les changements de pente des filaments après permanente à base de SNS par rapport à l'axe longitudinal central de la fibre. RÉSULTATS: On a constaté que la permanente à base de SNS induisait un gonflement en largeur plus important que la permanente classique des cellules paracorticales de la laine; de la cuticule, du complexe de la membrane cellulaire cuticulaire et de la distance centre à centre des macrofibrilles du cheveu; et des filaments intermédiaires dans la laine et les cheveux. Dans les cheveux ondulés, la permanente à base de SNS a provoqué à la fois un gonflement et une inclinaison des filaments intermédiaires des macrofibrilles hélicoïdales, entraînant une légère contraction longitudinale des macrofibrilles. Au total, le gonflement et l'inclinaison étaient plus importants dans les macrofibrilles hélicoïdales des cellules corticales de type B situées principalement dans la moitié convexe de la fibre. La présence d'un pourcentage plus élevé de macrofibrilles hélicoïdales dans la moitié convexe par rapport à la moitié concave de la fibre a entraîné une contraction différentielle entre les deux moitiés qui a entraîné le redressement de la fibre courbée. Un modèle mécanique a été proposé pour expliquer comment la permanente à base de SNS lissait les cheveux bouclés. CONCLUSION: Les effets de la permanente conventionnelle et à base de SNS sur les composants morphologiques et ultrastructuraux des cheveux japonais ondulés et des fibres de laine très frisés de mérinos ont permis de mieux comprendre le mécanisme du changement de courbure des fibres.

Disappearance of perihepatic lymph node enlargement after hepatitis C viral eradication with direct-acting antivirals.

Perihepatic lymph node enlargement (PLNE) which has been shown to be negatively associated with hepatocellular carcinoma (HCC) occurrence is frequently observed in chronic liver disease; however, changes in the state of perihepatic lymph nodes after eradication of hepatitis C virus (HCV) have not been investigated yet. We aimed to evaluate this issue. We enrolled 472 patients with chronic HCV infection who achieved viral eradication with direct-acting antivirals (DAA). We investigated whether the status of perihepatic lymph nodes changed before and after HCV eradication (primary endpoint). We also evaluated the association between PLNE and clinical findings such as liver fibrosis or hepatocellular injury before HCV eradication (secondary endpoint). Perihepatic lymph node enlargement was detected in 164 of 472 (34.7%) patients before DAA treatment. Surprisingly, disappearance of PLNE was observed in 23.8% (39 patients) of all PLNE-positive patients after eradication of HCV. Disappearance of PLNE was not associated with baseline clinical parameters or changing rates of clinical findings before and after DAA treatment. At baseline, presence of PLNE was significantly associated with a lower serum HCV-RNA level (P = .03), a higher serum AST level (P = .004) and a higher ALT level (P < .001) after adjustment for sex and age. In conclusion, PLNEs became undetectable after DAA treatment in 23.8% of PLNE-positive patients. Further study with a longer follow-up period is needed to clarify the clinical importance of this phenomenon especially in relationship with the risk of HCC development.

Viral load and ganciclovir (GCV) concentration in cerebrospinal fluid of patients successfully treated with GCV or valGCV for human herpesvirus 6 encephalitis/myelitis following umbilical cord blood transplantation.

We describe successful treatment of 3 cases of human herpesvirus 6 (HHV-6) encephalitis/myelitis following cord blood transplantation (CBT). Ganciclovir (GCV) (10 mg/kg/day) reduced HHV-6 load to undetectable levels in cerebrospinal fluid (CSF). Early dose reduction in the presence of HHV-6 detectable in CSF resulted in an increased HHV-6 load. GCV was capably shifted to valganciclovir (VGCV) with an almost equivalent concentration. GCV/VGCV may be effective for HHV-6 encephalitis/myelitis after CBT, although HHV-6 load in CSF should be monitored.

Effects of HLA-DPB1 genotypes on chronic hepatitis B infection in Japanese individuals.

Significant associations of HLA-DP alleles with chronic hepatitis B (CHB) infection are evident in Asian and Arabian populations, including Japanese, Han Chinese, Korean, and Saudi Arabian populations. Here, significant associations between CHB infection and five DPB1 alleles (two susceptibility alleles, DPB1(*) 05:01 and (*) 09:01, and three protective alleles, DPB1(*) 02:01, (*) 04:01, and (*) 04:02) were confirmed in a population comprising of 2582 Japanese individuals. Furthermore, odds ratios for CHB were higher for those with both DPB1 susceptibility alleles than for those with only one susceptibility allele; therefore, effects of susceptibility alleles were additive for risk of CHB infection. Similarly, protective alleles showed an additive effect on protection from CHB infection. Moreover, heterozygotes of any protective allele showed stronger association with CHB than did homozygotes, suggesting that heterozygotes may bind a greater variety of hepatitis B-derived peptides, and thus present these peptides more efficiently to T-cell receptors than homozygotes. Notably, compound heterozygote of the protective allele (any one of DPB1*02:01, *04:01, and *04:02) and the susceptible allele DPB1*05:01 was significantly associated with protection against CHB infection, which indicates that one protective HLA-DPB1 molecule can provide dominant protection. Identification of the HLA-DPB1 genotypes associated with susceptibility to and protection from CHB infection is essential for future analysis of the mechanisms responsible for immune recognition of hepatitis B virus antigens by HLA-DPB1 molecules.

Multidrug resistance protein 4 (MRP4) polymorphisms impact the 6-mercaptopurine dose tolerance during maintenance therapy in Japanese childhood acute lymphoblastic leukemia.

Multidrug resistance protein 4 (MRP4) is involved in the efflux of nucleoside derivatives and has a role in the determination of drug sensitivity. We investigated the relationship between MRP4 genetic polymorphisms and doses of the 6-mercaptopurine (6-MP) and methotrexate. Further, we evaluated the frequency of therapeutic interruption during maintenance therapy in Japanese children with acute lymphoblastic leukemia (ALL). Ninety-four patients received an initial 6-MP dose in the range of 30-50 mg m(-2) in this analysis. Patients with homozygous variant allele in any of MRP4 G2269A, C912A and G559T required high frequency of 6-MP dose reduction compared with non-homozygous individuals. Average 6-MP dose for patients with homozygous variant allele on either MRP4 or inosine triphosphate pyrophosphatase was significantly lower than that for patients with non-homozygous variant allele during maintenance therapy (30.5 versus 40.0 mg m(-2), P=0.024). Therefore, MRP4 genotyping may be useful for personalizing the therapeutic dose of 6-MP during the ALL maintenance therapy in Japanese.

Subcutaneous abscess due to the basidiomycete Phellinus mori in a patient with chronic granulomatous disease.

Chronic granulomatous disease (CGD), a primary immunodeficiency caused by impaired phagocyte killing of intracellular pathogens, is characterized by recurrent, life-threatening, bacterial and fungal infections. As a result of improvements in microbiologic culture and identification techniques, a number of unique filamentous fungi have been reported as significant pathogens in patients with CGD. We report a case of subcutaneous basidiomycete Phellinus mori infection in a patient with CGD. To the best of our knowledge, this is the first reported case of human infection by this fungus. The causative fungus was identified on the basis of its morphological characteristics and nucleotide sequence on the internal transcribed spacer region of the ribosomal RNA gene. This is the fifth case report of filamentous basidiomycetes infecting a patient with CGD; all of these cases have been caused by Phellinus species. We highlight the importance of recognizing filamentous basidiomycetes Phellinus species as possible agents of non-Aspergillus fungal infections in patients with CGD.

Prognostic nomogram for nonresectable pancreatic cancer treated with gemcitabine-based chemotherapy.

BACKGROUND: A nomogram is progressively being used as a useful predictive tool for cancer prognosis. A nomogram to predict survival in nonresectable pancreatic cancer treated with chemotherapy has not been reported. METHODS: Using prospectively collected data on patients with nonresectable pancreatic cancer receiving gemcitabine-based chemotherapy at five Japanese hospitals, we derived a predictive nomogram and internally validated it using a concordance index and calibration plots. RESULTS: In total, 531 patients were included between June 2001 and February 2013. The American Joint Committee on Cancer (AJCC) TNM stages were III and IV in 204 and 327 patients, respectively. The median survival time of the total cohort was 11.3 months. A nomogram was generated to predict survival probabilities at 6, 12, and 18 months and median survival time, based on the following six variables: age; sex; performance status; tumour size; regional lymph node metastasis; and distant metastasis. The concordance index of the present nomogram was higher than that of the AJCC TNM staging system at 12 months (0.686 vs 0.612). The calibration plots demonstrated good fitness of the nomogram for survival prediction. CONCLUSIONS: The present nomogram can provide valuable information for tailored decision-making early after the diagnosis of nonresectable pancreatic cancer.

Safety, tolerability, and feasibility of antifungal prophylaxis with micafungin at 2 mg/kg daily in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: Micafungin (MCFG) is used for the prophylaxis of invasive fungal disease (IFD) after allogeneic hematopoietic stem cell transplantation (HSCT). However, the safety, efficacy, or optimal dosage/blood levels as prophylaxis is uncertain in pediatric HSCT-patients. METHODS: We prophylactically administered MCFG at 2 mg/kg once daily to 38 children and adolescents undergoing allogeneic HSCT. RESULTS: During MCFG prophylaxis, infusion reactions or adverse events (grades 2-5) related to MCFG use were not found in all the patients. Thus, MCFG prophylaxis was not discontinued and other antifungal agents were not added except for 2 patients in whom probable or possible IFDs developed (completion rate, 94.7 %). To elucidate the influence of HSCT-related complications/drugs on blood concentration of MCFG, we determined the plasma trough and peak levels in 13 and 10 among 38 patients, respectively. The mean trough and peak levels were 3.04 ± 1.21 µg/mL (569 samples) and 9.63 ± 3.62 µg/mL (44 samples), respectively. The peak levels were moderately correlated to the trough levels (R (2) = 0.466). In a patient, the trough level of MCFG transiently increased up to 10.21 µg/mL during hepatic dysfunction due to acute graft-versus-host disease. The MCFG trough levels strongly correlated with T-Bil value (R (2) = 0.894). There was no relationship between the trough levels of MCFG and the circulating concentrations of tacrolimus (R (2) = 0.040). Additionally, MCFG levels were not influenced by treatment with cyclophosphamide or corticosteroids. CONCLUSIONS: Prophylaxis with MCFG at 2 mg/kg once daily may be safe, tolerable, and feasible in pediatric HSCT-patients.

Efficacy of porcine placental extract on wrinkle widths below the eye in climacteric women.

OBJECTIVE: Injections of human placental extract, which is known to play a role in skin regulation, have long been used for the treatment of skin wrinkles and non-healing wounds. Porcine placental extract (PPE), an oral supplement, was recently developed for this purpose. The aim of this study was to assess whether PPE has a positive effect on the improvement of fine wrinkles below the eye in climacteric women. METHODS: We first non-invasively measured wrinkle widths with a skin analyzer in a cross-section of 185 healthy adult Japanese women. Next, 44 climacteric women with mild or few climacteric symptoms were enrolled into an open-label, randomized, controlled study of the effect of PPE on wrinkle widths. A retrospective comparison of wrinkle widths in 123 climacteric women with climacteric symptoms with or without PPE treatment was also performed. RESULTS: Wrinkle widths below the eye in women ≥ 30 years of age were significantly higher than in women 20-29 years of age. Treatment with three capsules of PPE per day was significantly (p < 0.05) effective in reducing wrinkle widths at 24 weeks compared with control subjects. Retrospective analysis showed that subjects treated with three (p < 0.05) and six (p < 0.01) capsules of PPE per day observed a significant reduction in wrinkle widths compared with untreated subjects. CONCLUSION: Oral PPE treatment is a possible option for improving the appearance of fine wrinkles below the eye in climacteric women.

Successful ganciclovir therapy in a patient with human herpesvirus-6 encephalitis after unrelated cord blood transplantation: usefulness of longitudinal measurements of viral load in cerebrospinal fluid.

BACKGROUND: There have been no reports of human herpesvirus-6 (HHV-6) encephalitis treatment based on both HHV-6 DNA load and the antiviral agent's concentration in the cerebrospinal fluid (CSF). PATIENT: A 20-year-old male with a hematological malignancy developed HHV-6 encephalitis 15 days after unrelated cord blood transplantation (UCBT). He had fever, chest pain, memory impairment, and insomnia. His CSF showed no increased cell counts, but the amount of HHV-6 DNA was elevated to 2.0 × 10(6) copies/ìgDNA. Magnetic resonance imaging (MRI) of the head revealed abnormal high-intensity signals in the left limbic system on T2-weighted and diffusion-weighted images. Intravenous administration of ganciclovir (GCV) was initiated at 5 mg/kg every 12 h on day 18, and was continued until day 137. The amount of HHV-6 DNA in the plasma became undetectable on day 25. The HHV-6 load in the CSF decreased to 1.5 × 10(3) copies/ìgDNA on day 32, and reached undetectable levels on day 53. The mean concentration of GCV 1 h after an infusion of 5 mg/kg was 4.12 mg/mL in plasma and 0.7 mg/mL in CSF. The chest pain and insomnia disappeared on days 35 and 47, respectively. Memory defects recovered up to day 85. CONCLUSION: Serial quantification of HHV-6 DNA in CSF may be useful for successful treatment with GCV in post-transplant HHV-6 encephalitis.

Efficacy of porcine placental extract on shoulder stiffness in climacteric women.

OBJECTIVES: Some of the most common climacteric symptoms are somatic symptoms, such as muscle and joint pain, which cause limitations in performing daily tasks. This study aimed to assess whether oral porcine placental extract (PPE) affects patients with shoulder stiffness, one of the most common types of muscle-tendon stiffness, in climacteric women and postmenopausal women with hormone therapy (HT). METHODS: Sixty-six climacteric women (33 each in the control and study groups) with shoulder stiffness and 54 postmenopausal women (27 each in the control and study groups) with HT-resistant shoulder stiffness were enrolled into this open-label, randomized, controlled study. The control subjects received Toki-shakuyaku-san (TJ23; 7.5 g/day, daily per os), an oral herbal remedy used to alleviate climacteric symptoms, and study subjects received PPE orally for 24 weeks in climacteric women and for 12 weeks in postmenopausal women with HT. Changes in the degree of shoulder stiffness were evaluated by the Visual Analog Scale (VAS). RESULTS: Treatment with PPE was significantly effective in reducing the VAS score for shoulder stiffness during the study period compared with the control group in both climacteric and postmenopausal women with HT. The VAS score at the end of treatment was significantly reduced (p < 0.01 vs. baseline) by 76.4% for climacteric women and 64.8% for postmenopausal women with HT compared with baseline. CONCLUSIONS: PPE is useful as an oral supplement for shoulder stiffness in climacteric women without HT or in postmenopausal women with HT-resistant, long-term shoulder stiffness.

Efficacy of porcine placental extract on climacteric symptoms in peri- and postmenopausal women.

OBJECTIVES: Injections of human placental extract have long been used to treat menopausal symptoms. Recently, porcine placental extract (PPE), an oral supplement, has been developed for this purpose. The aim of this study was to assess whether PPE has an impact on climacteric symptoms in perimenopausal and postmenopausal women. METHODS: Seventy-six women with climacteric symptoms were enrolled into this open-label, randomized, controlled study. The control group (n = 38) underwent 24 weeks of open treatment with Toki-shakuyaku-san (TJ23), an oral herbal remedy used to alleviate climacteric symptoms. The PPE group (n = 38) received three capsules of PPE/day orally for the initial 12 weeks and six capsules/day for the next 12 weeks. Climacteric symptoms were evaluated in both groups using the Simplified Menopausal Index (SMI) score, Zung's Self-Rating Depression Scale (ZSDS) and the Spielberger State-Trait Anxiety Inventory (STAI) before commencing treatment, after 12 weeks of treatment and on completion of treatment. RESULTS: Treatment with PPE was significantly (p < 0.01) more effective in reducing the SMI, ZSDS and STAI measures at 12 and 24 weeks than TJ23 treatment alone. Treatment with PPE was also significantly effective (p < 0.01) in reducing the subscale scores of the SMI for items such as hot flushes, insomnia, irritability, depression, fatigue and joint pain. PPE treatment had no significant adverse effects. CONCLUSION: Oral PPE treatment is another possible option for treating perimenopausal and postmenopausal women with climacteric symptoms.

MicroRNAs and liver function.

MicroRNAs (miRNAs) are small, noncoding RNA molecules that regulate gene expression post-transcriptionally through complementary base pairing with thousands of messenger RNAs. Although the target genes and precise biological functions of individual miRNAs remain largely unknown, miRNAs are speculated to play important roles in diverse biological processes in both normal and pathological states. The liver is a vital organ that plays major roles in a number of physiological functions. Recent advances in the study of liver miRNAs using gene-modified mice or in vivo nucleic acid delivery to overexpress specific miRNAs or inhibit miRNA functions have revealed the crucial biological roles of individual miRNAs in physiologically essential liver functions in vivo. Because miRNA-based strategies are being applied to clinical therapeutics, the importance of precise knowledge of miRNA functions cannot be underestimated, not only from a scientific point of view, but also from a clinical perspective to make the most of such drugs and avoid unexpected harmful effects. The aims of this review are to describe current knowledge regarding both known and as-yet-undiscovered molecular aspects of the biological roles of miRNAs in the liver, with a special emphasis on lipid, glucose, drug, and iron metabolism as vital functions of the liver as well as important therapeutic targets.

Comparison of the prognostic value of inflammation-based prognostic scores in patients with hepatocellular carcinoma.

BACKGROUND: Inflammation-based prognostic scores including the Glasgow Prognostic Score (GPS), neutrophil to lymphocyte ratio (NLR), and Prognostic Nutritional Index (PNI) are associated with survival in patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate the prognostic value of these inflammation-based prognostic scores in patients with HCC. METHODS: In total, 150 patients with newly diagnosed HCC were prospectively evaluated. Patients were divided according to the GPS, modified GPS, NLR, platelet to lymphocyte ratio (PLR), Prognostic Index (PI), and PNI. The area under the receiver operating characteristics curve (AUC) was calculated to compare the predictive ability of each of the scoring systems. A univariate and multivariate analysis were performed to identify the clinicopathological variables associated with overall survival. RESULTS: The GPS consistently had a higher AUC value at 6 months (0.768), 12 months (0.787), and 24 months (0.758) in comparison with other inflammation-based prognostic scores. A multivariate analysis showed that the GPS was independently associated with overall survival. CONCLUSION: This study demonstrates that the GPS, an inflammation-based prognostic score, is an independent marker of poor prognosis in patients with HCC and is superior to the other inflammation-based prognostic scores in terms of prognostic ability.

A multicentre randomised phase II trial of gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer: GEMSAP study.

BACKGROUND: This randomised phase II trial compared gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer. METHODS: Patients were randomly assigned to 4-week treatment with gemcitabine alone (1000, mg m(-2) gemcitabine by 30-min infusion on days 1, 8, and 15) or gemcitabine and S-1 combination therapy (1000, mg m(-2) gemcitabine by 30-min infusion on days 1 and 15 and 40 mg m(-2) S-1 orally twice daily on days 1-15). The primary end point was progression-free survival (PFS). RESULTS: Between July 2006 and February 2009, 106 patients were enrolled. The PFS in gemcitabine and S-1 combination arm was significantly longer than in gemcitabine arm (5.4 vs 3.6 months), with a hazard ratio of 0.64 (P=0.036). Overall survival (OS) for gemcitabine and S-1 combination was longer than that for gemcitabine monotherapy (13.5 vs 8.8 months), with a hazard ratio of 0.72 (P=0.104). Overall, grade 3 or 4 adverse events were similar in both arms. CONCLUSION: Gemcitabine and S-1 combination therapy demonstrated longer PFS in advanced pancreatic cancer. Improved OS duration of 4.7 months was found for gemcitabine and S-1 combination therapy, though this was not statistically significant.