Early Treatment with Methylprednisolone Pulse Therapy Combined with Tonsillectomy for Heavy Proteinuric Henoch-Schönlein Purpura Nephritis in Children

Background: There is no clear consensus as to which patients with Henoch-Schönlein purpura nephritis (HSPN) at risk of a poor outcome should be treated and what therapeutic regimen should be used. Methods: Nine children with heavy proteinuric HSPN received prompt initiation of methylprednisolone pulse therapy (MPT) combined with tonsillectomy in a prospective study. Results: At presentation, the mean values for the patients’ urine protein excretion (early-morning urinary protein/creatinine ratio), serum IgA, activity index (AI), and chronicity index (CI) were 5.0 ± 5.6 g/g Cr, 135.6 ± 56.5 mg/dl, 4.0 ± 0.7, and 1.7 ± 1.3, respectively. At the second biopsy, conducted approximately 24 months after initiation of therapy, the patients’ serum albumin had significantly increased (4.4 ± 0.2, p Conclusions: Early treatment with MPT combined with tonsillectomy is effective in ameliorating the histopathological progression and improving the clinical course of children with heavy proteinuric HSPN

Systemic Corticosteroids and Early Administration of Antiviral Agents for Pneumonia with Acute Wheezing due to Influenza A(H1N1)pdm09 in Japan

BACKGROUND: Pneumonia patients with wheezing due to influenza A(H1N1)pdm09 were frequently treated with systemic corticosteroids in Japan although systemic corticosteroid for critically ill patients with pneumonia caused by influenza A(H1N1)pdm09 has been controversial. Applicability of systemic corticosteroid treatment needs to be evaluated. METHODS/PRINCIPAL FINDINGS: We retrospectively reviewed 89 subjects who were diagnosed with influenza A(H1N1)pdm09 and admitted to a national hospital, Tokyo during the pandemic period. The median age of subjects (45 males) was 8 years (range, 0-71). All subjects were treated with antiviral agents and the median time from symptom onset to initiation of antiviral agents was 2 days (range, 0-7). Subjects were classified into four groups: upper respiratory tract infection, wheezing illness, pneumonia with wheezing, and pneumonia without wheezing. The characteristics of each group was evaluated. A history of asthma was found more frequently in the wheezing illness (55.6%) and pneumonia with wheezing (43.3%) groups than in the other two groups (p = 0.017). Corticosteroid treatment was assessed among subjects with pneumonia. Oxygen saturation was lower in subjects receiving corticosteroids (steroid group) than in subjects not receiving corticosteroids (no-steroid group) (p<0.001). The steroid group required greater oxygen supply than the no-steroid group (p<0.001). No significant difference was found by the Kaplan-Meier method between the steroid and the no-steroid groups in hours to fever alleviation from the initiation of antiviral agents and hospitalization days. In logistic regression analysis, wheezing, pneumonia and oxygen saturation were independent factors associated with using systemic corticosteroids. CONCLUSION: Patients with wheezing and a history of asthma were frequently found in the study subjects. Systemic corticosteroids together with early administration of antiviral agents to pneumonia with wheezing and possibly without wheezing did not result in negative clinical outcomes and may prevent progression to severe pneumonia in this study population

Comprehensive autoantibody profiling in systemic autoimmunity by a highly-sensitive multiplex protein array

Comprehensive autoantibody evaluation is essential for the management of autoimmune disorders. However, conventional methods suffer from poor sensitivity, low throughput, or limited availability. Here, using a proteome-wide human cDNA library, we developed a novel multiplex protein assay (autoantibody array assay; A-Cube) covering 65 antigens of 43 autoantibodies that are associated with systemic sclerosis (SSc) and polymyositis/dermatomyositis (PM/DM). The performance of A-Cube was validated against immunoprecipitation and established enzyme-linked immunosorbent assay. Further, through an evaluation of serum samples from 357 SSc and 172 PM/DM patients, A-Cube meticulously illustrated a diverse autoantibody landscape in these diseases. The wide coverage and high sensitivity of A-Cube also allowed the overlap and correlation analysis between multiple autoantibodies. Lastly, reviewing the cases with distinct autoantibody profiles by A-Cube underscored the importance of thorough autoantibody detection. Together, these data highlighted the utility of A-Cube as well as the clinical relevance of autoantibody profiles in SSc and PM/DM

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Can Rare Cancer Drugs Expect Sales in Japan?: A Prescription Pattern Analysis of Drugs for Chronic Myelogenous Leukemia and Neuroendocrine Tumor

Despite high unmet medical needs, investment in rare cancer drug development has stagnated, likely because the potential market for such drugs is small. In this context, we hypothesized that rare cancer drugs could achieve a higher sales margin. A dataset was created from publicly available information obtained from the IQVIA Solutions Japan K.K. Pharmaceutical Market database on the website of the Pharmaceuticals and Medical Devices Agency/Ministry of Health, Labour and Welfare of Japan. The total amount of sales and prescription volumes between 2010 and 2016 for drugs whose indications include chronic myelogenous leukemia (CML) and neuroendocrine tumor (NET) were investigated. Regarding drugs for CML, the sales and prescription volumes of imatinib have been decreasing every year, whereas those of dasatinib and nilotinib have been increasing. Regarding drugs for NET, the sales and prescription volumes of sunitinib, everolimus, and streptozocin have been increasing every year. The present study revealed two sales models for the development of rare cancer drugs. First, sales amounts can be assured if clinical positioning with other existing drugs is sufficiently clear. Second, obtaining a label for rare cancers can stimulate drug development for more common cancers. These findings suggest that rare cancer drugs can offer high market value and profit potential; thus, to meet high unmet medical needs, clinical development programs for the development of rare cancer drugs should be promoted. https://doi.org/10.21423/jrs-v07shibat

Primary sarcoidosis of the breast, a case study in connection with Propionibacterium acnes infection

A 77-year-old female underwent screening mammography with abnormal results. Core needle biopsy revealed a granulomatous lesion without necrosis, and sarcoidosis was considered although tuberculosis and granulomatous mastitis could not be ruled out. Three months later, the patient detected breast and axillary masses. Malignancy was suspected and both lesions were excised. The specimens contained epithelioid cell granulomas with no necrosis. Her angiotensin-converting enzyme level was normal, and radiographic examination revealed no evidence of involvement of other organs, including the lungs and mediastinal lymph nodes. Although sarcoidosis was highly suspected, it was not definitive. Immunohistochemistry with the PAB antibody, which specifically reacts with Propionibacterium acnes, the most commonly implicated causative agent of sarcoidosis, showed positive signals in granulomatous inflammation of the breast and within granulomas of the sentinel lymph node. This is the first case report of primary sarcoidosis of the breast involving the draining lymph node with confirmed P. acnes infection. Keywords: Immunohistochemistry, Mammary sarcoidosis, Isolated sarcoidosis, PAB antibody, Granulomatous mastitis, Tuberculosis mastiti