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INTRODUCTION: In the 330-patient ADVOCATE trial of avacopan for the treatment of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, in which 81% of patients had renal involvement, estimated glomerular filtration rate (eGFR) increased on average 7.3 ml/min per 1.73 m(2) in the avacopan group and 4.1 ml/min per 1.73 m(2) in the prednisone group (P = 0.029) at week 52. This new analysis examines the results in the patient subgroup with severe renal insufficiency at enrollment into the trial, i.e., eGFR ≤20 ml/min per 1.73 m(2). METHODS: eGFR was determined at baseline and over the course of the trial. Changes in eGFR were compared between the 2 treatment groups. RESULTS: In ADVOCATE, 27 of 166 patients (16%) in the avacopan group and 23 of 164 patients (14%) in the prednisone group had a baseline eGFR ≤20 ml/min per 1.73 m(2). At week 52, eGFR increased on average 16.1 and 7.7 ml/min per 1.73 m(2) in the avacopan and prednisone groups, respectively (P = 0.003). The last eGFR value measured during the 52-week treatment period was ≥2-fold higher than baseline in 41% of patients in the avacopan group compared to 13% in the prednisone group (P = 0.030). More patients in the avacopan group versus prednisone group had increases in eGFR above 20, 30, and 45 ml/min per 1.73 m(2), respectively. Serious adverse events occurred in 13 of 27 patients (48%) in the avacopan group and 16 of 23 patients (70%) in the prednisone group. CONCLUSION: Among patients with baseline eGFR ≤20 ml/min per 1.73 m(2) in the ADVOCATE trial, eGFR improved more in the avacopan group than in the prednisone group.

The impact of body mass index (BMI) on postoperative survival in Japanese patients with pancreatic cancer is unclear. We examined the relationship between preoperative BMI and the prognosis of Japanese patients who underwent surgery for pancreatic cancer to determine whether BMI affects these patients’ prognosis. Of the patients who underwent pancreatectomy between January 2004 and August 2015 at our institution, 246 were pathologically diagnosed with pancreatic tubular adenocarcinoma; the cancer was located in the pancreatic head (n=161) and in the body and tail (n=85). We classified the patients by BMI: underweight (n=22), normal weight (n=190), and overweight/obese (n=34) groups. We retrospectively analyzed medical records for patient characteristics, lesion location, disease stage, postoperative complications, chemotherapy, and prognosis. Lesion location, disease stage, postoperative complications, and chemotherapy were not significantly different among the BMI groups. The median survival times were as follows (days): all patients, 686; underweight, 485; normal weight, 694; and overweight/obese, 839. In a multivariate analysis, after adjusting for competing risk factors, low BMI was associated with an increased risk of death (normal weight: HR 0.58, p=0.038; overweight/obese: HR 0.54, p=0.059). High BMI was not found to be a postoperative factor for poor prognosis in Japanese pancreatic cancer patients.

A variety of plants in diverse taxa can reproduce asexually via vegetative propagation, in which clonal propagules with a new meristem(s) are generated directly from vegetative organs. A basal land plant, Marchantia polymorpha, develops clonal propagules, gemmae, on the gametophyte thallus from the basal epidermis of a specialized receptacle, the gemma cup. Here we report an R2R3-MYB transcription factor, designated GEMMA CUP-ASSOCIATED MYB1 (GCAM1), which is an essential regulator of gemma cup development in M. polymorpha. Targeted disruption of GCAM1 conferred a complete loss of gemma cup formation and gemma generation. Ectopic overexpression of GCAM1 resulted in formation of cell clumps, suggesting a function of GCAM1 in suppression of cell differentiation. Although gemma cups are a characteristic gametophyte organ for vegetative reproduction in a taxonomically restricted group of liverwort species, phylogenetic and interspecific complementation analyses support the orthologous relationship of GCAM1 to regulatory factors of axillary meristem formation, e.g., Arabidopsis REGULATOR OF AXILLARY MERISTEMS and tomato Blind, in angiosperm sporophytes. The present findings in M. polymorpha suggest an ancient acquisition of a transcriptional regulator for production of asexual propagules in the gametophyte and the use of the regulatory factor for diverse developmental programs, including axillary meristem formation, during land plant evolution., 植物が芽を増やすための太古から受け継がれた仕組みを解明. 京都大学プレスリリース. 2019-11-12.

Epigenetics is defined as the investigation of stably heritable changes of gene expressionthat occur without alteration ofthe DNA sequence itself.Epigenetic gene regulation usually involves DNA methylation and/or modification of histones. In mammalian cells, DNA methylation mainly occurs at the fifth carbon of the cytosine residuein a 5’-CG-3’ (CpG) dinucleotide and its occurrence is inversely correlated with the GCcontentand Cp Gdensity. Epigenetic regulation has a role in many biological processes, including gene transcription, imprinting, and transposon activity in embryonic stem cells, germ cells, somatic cells, and tumor cells.Histone modification represents an additional epigenetic mechanism that regulates gene expression, genomic imprinting, and X chromatin remodeling synergeticallyalong with DNA methylation.

It is important and difficult problem to manage patients with thyroid nodules which are indeterminate as papillary thyroid carcinoma (PTC) before surgery and identified as PTC after surgery. This paper highlighted whether immediate reoperation for such patients should be undergone or not. The prognosis of 196 patients with PTC who underwent lobectomy or subtotal thyroidectomy without neck dissection were studied (non-dissection group). The controls consisted of 783 patients with non-advanced PTC who underwent radical surgery during the same period (dissection group). There was no death due to PTC in both groups. Distant metastasis was observed 1.5% in non-dissection group and 2.2% in the dissection group. Local recurrence was observed 9.7% in the non-dissection group and 11.2% in the dissection group. The results suggested that immediate reoperation for the patient's who did not undergo neck dissection, is not necessary. It is thought that all of lymph node metastasis detected only by histology does not always behave in same.

In order to determine surgical strategy for locally advanced thyroid carcinoma, a multivariate analysis of prognostic factors was carried out with 70 patients of locally advanced thyroid carcinoma who underwent palliative surgery. Multivariate analysis was conducted by Cox's proportional hazard model. The patients have been followed up from 5 to 26 years. We have demonstrated the influence of age, sex, distant metastasis, pathological findings, numbers of adjacent organs, infiltrated, extent of resection, external irradiation and 131I therapy on survival. The result of this study showed that age had an impact on survival. The survival rate of the patients under 40 years was much better than that of the patients 40 years and over. The result implies that aggressive surgery and postoperative adjuvant therapy should be considered in the old patients, but not always be indication in the young patients.

One hundred thirty-six patients with suspected thyroid malignancy were studied prospectively with Ga-67 imaging of the thyroid and whole body. All patients subsequently had diagnoses proven by biopsy or surgical resection. Patients with malignant tumors (anaplastic carcinoma, malignant lymphoma, adenocarcinoma, medullary carcinoma, adenocarcinoma with squamous cell transformation, and metastases to the thyroid from other tumors) were examined serially after appropriate therapy. The authors draw on their own experience and a literature review to propose the following indications for Ga-67 imaging in patients with thyroid disease: 1) suspected anaplastic carcinoma or malignant lymphoma of the thyroid gland, 2) detection of distant metastases of anaplastic thyroid carcinoma and malignant lymphoma, 3) evaluation of efficacy of therapy, 4) suspected metastases to the thyroid gland from other malignancies, and 5) differentiation of malignant lymphoma from chronic thyroiditis. The strengths, limitations, and potential pit-falls of the technique are discussed.

The relationship between changes in glucose tolerance with treatment of hyperthyroidism and various factors that might be relevant to carbohydrate metabolism were investigated in 64 hyperthyroid patients with abnormal glucose tolerance, including 35 cases with fasting plasma glucose (FPG) levels of 140 mg/dl or more. All patients had diffuse toxic goiter. After correction of the hyperthyroidism, glucose intolerance improved in almost all cases, even in cases with fasting hyperglycemia, but diabetes mellitus in patients with FPG above 140 mg/dl and/or delta IRI/delta PG X 30' during a 50-g oral glucose tolerance test below 0.10, persisted. Patients who showed diabetic glucose tolerance even after remission from thyroid dysfunction had significantly lower delta IRI/delta PG X 30' values and a higher incidence of family histories of diabetes mellitus than those not showing diabetic glucose tolerance. There were no significant differences in serum T3 and T4 levels between these two groups of patients. The findings suggest that predisposition to diabetes may be an important factor in persistent glucose intolerance in the hyperthyroidism of Graves' disease. The FPG and delta IRI/delta PG X 30' values may be useful in predicting which patients with hyperthyroidism will have permanent diabetes.

Oral glucose tolerance tests (OGTT) were performed on108patients with hyperthyroidism who were suspected, from their clinical records, of having abnormalities in carbohydrate metabolism. Of these, intravenous glucose tolerance tests (IVGTT) were performed on24patients and intravenous tolbutamide tests (IVTT) on34. Five control subjects were included in the study. In OGTT, an oxyhyperglycemic pattern (OH) was observed in31patients, a borderline pattern in13, and a diabetic pattern with FBS

It is well known that a certain percentage of patients with polymyositis and dermatomyositis (PM/DM) is corticosteroid resistant. Established and novel approaches to steroid-resistant PM/DM are discussed in this review. Methotrexate (MTX) is a first-line treatment in the case that steroid therapy fails. Azathioprine and cyclophosphamide also fall into this category. Cyclosporine, a specific inhibitor of calcineurin, has been reported almost as effective as MTX. Tacrolimus, also a calcineurin inhibitor, and mycophenolate mofetil could be additional alternatives for the treatment. Several clinical trials have demonstrated that high-dose intravenous immunoglobulin is promising. Recently favorable data have been published using intravenous high-dose pulse cyclophosphamide or cyclosporine for the poorly prognostic interstitial pneumonitis or pulmonary fibrosis accompanied with PM/DM.

Familial occurrence of nonmedullary thyroid carcinoma is rare but this has been increasingly recognized over the recent years. Epidemiological studies showed that relatives of thyroid cancer cases were at increased risk of the same site. Surveying published familial cases, there were two groups of familial thyroid carcinoma; groups related to other familial diseases(familial adenomatous polyposis FAP, Gardner's syndrome, Cowden's disease) and another independent of accompanying disease. Familial thyroid carcinomas independent of accompanying disease were reported aggressive features and several authors recommended aggressive treatments. Genetic bases has not been clearly elucidated identification of genetic defects should undoubtedly aid an understanding of pathogenesis of sporadic cases.

Two hundreds and sixteen patients with Graves' disease who underwent subtotal thyroidectomy at Ito Hospital during 1983 and 1984 were studied in order to known about the relationship between the prognosis and preoperative values of TRAb. There were 65 euthyroid patients (30.1%), 112 hypothyroid (51.8%), and 39 hyperthyroid (18.1%). No relationship between postoperative thyroid function and preoperative values of TRAb was observed. Postoperative values of TRAb were significantly higher in hyperthyroid group than in euthyroid group and hypothyroid group at any period. Postoperative values of TRAb were negative in about 90% of the patients of euthyroid group. On the other hand, negative postoperative values of TRAb were also observed in about 40% patients of hyperthyroid group. It is concluded that postoperative thyroid function could not be estimated from preoperative values of TRAb and much care is thought to be necessary to estimate the prognosis from postoperative values of TRAb.

Objectives To investigate whether maternal history and ultrasound findings can be predictors for massive hemorrhage during Cesarean section in patients with placenta previa and adherence of the placenta. Methods We reviewed 127 singleton pregnancies with placenta previa. Maternal history, antenatal ultrasound findings of the placenta, including location, presence of placental lacunae, lack of a clear zone, presence of sponge-like findings of the cervix and presence of a marginal sinus in cases of placenta previa were reviewed retrospectively, and their association with amount of bleeding during Cesarean section was analyzed. Results Logistic regression analysis revealed that advan-ced maternal age (odds ratio (OR), 5.4; 95% CI, 1.8–16.4), previous Cesarean section (OR, 20.4; 95% CI, 4.0–105.2) and sponge-like findings in the cervix (OR, 5.6; 95% CI, 1.8–17.0) were associated with massive bleeding (> 2500 mL). Placental adherence occurred in five cases and was more frequent in cases where the placenta was located at the site of the scar of a previous Cesarean section (OR, 123.1; 95% CI, 4.5–3395.2) and where there was lack of a clear zone (OR, 48.0; 95% CI, 3.8–604.7). Conclusions Advanced maternal age, previous Cesarean section and presence of sponge-like findings in the cervix are risk factors for massive bleeding during Cesarean section in cases of placenta previa, regardless of whether placental adherence is present. Placental location on the scar of a previous Cesarean section and lack of a clear zone are risk factors for placental adherence. When these findings are identified preoperatively, management should be tailored accordingly. Copyright © 2009 ISUOG. Published by John Wiley & Sons, Ltd.