[A case of myasthenia gravis with coexistence of anti-acetylcholine receptor antibodies and anti-P/Q-type VGCC antibodies].

A 79-year-old woman who presented ptosis and dysphagia were admitted to our hospital. Anti-acetylcholine receptor antibodies and anti-P/Q-type VGCC antibodies were both positive. Electrophysiological examination showed postsynaptic pattern which supported myasthenia gravis. She did not meet the diagnostic criteria for Lambert-Eaton myasthenic syndrome (LEMS). In cases which these antibodies coexist, careful electrophysiological evaluation is required for the diagnosis. In addition, although anti-P/Q-type VGCC antibodies have been specific to LEMS, patients with these antibodies represent various symptoms other than LEMS. Low and middle titer of the antibodies may be not specific to LEMS.

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase 2b Trial of P2X3 Receptor Antagonist Sivopixant for Refractory or Unexplained Chronic Cough.

INTRODUCTION: To determine the optimal dose of sivopixant, a highly selective P2X3 receptor antagonist, for refractory or unexplained chronic cough (RCC/UCC). METHODS: In this phase 2b, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial, patients received sivopixant 50, 150, or 300 mg or placebo once daily for 4 weeks. The primary endpoint was a change from baseline in 24-h cough frequency (coughs/h) with sivopixant vs placebo. RESULTS: Overall, 390/406 randomized patients completed the study. Placebo-adjusted changes in hourly cough count over 24 h were 13.17% (P = 0.3532), - 1.77% (P = 0.8935), and - 12.47% (P = 0.3241) and in cough severity (visual analog scale) were 1.75 mm (P = 0.5854), - 1.21 mm (P = 0.7056), and - 6.55 mm (P = 0.0433) with sivopixant 50, 150, and 300 mg, respectively. Placebo-adjusted changes from baseline in Leicester Cough Questionnaire total scores were - 0.37 (P = 0.4207), - 0.07 (P = 0.8806), and 0.69 (P = 0.1473) with sivopixant 50, 150, and 300 mg, respectively. Additionally, 61.3%, 78.3%, 86.8%, and 71.4% of patients receiving sivopixant 50, 150, and 300 mg and placebo, respectively, reported any improvements in Patient Global Impression of Change. The incidence of treatment-emergent adverse events (TEAEs) was 25.7%, 32.0%, 49.0%, and 20.6% in sivopixant 50, 150, and 300 mg and placebo groups, respectively; all TEAEs in the sivopixant group were mild-to-moderate. CONCLUSION: Sivopixant did not demonstrate a statistically significant difference vs placebo in change from baseline in 24-h cough frequency. The dose of 300 mg has potential for RCC/UCC, showing the greatest improvements in cough frequency and patient-reported outcomes and dose-related mild to moderate reversible taste disturbance, although further trials are needed. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04110054; registered September 26, 2019.

Anti-MDA5 antibody-positive clinically amyopathic dermatomyositis with diffuse alveolar damage diagnosed by transbronchial lung cryobiopsy: A case report.

Diffuse alveolar damage (DAD) is known to be a pathological hallmark of acute respiratory distress syndrome or acute interstitial pneumonia, and to have a poor prognosis. We report a case of anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive clinically amyopathic dermatomyositis (CADM) with rapidly progressive interstitial lung disease (RP-ILD), in which DAD was confirmed by transbronchial lung cryobiopsy at an early stage without respiratory failure. Although this patient initially did not show respiratory failure, his respiratory condition gradually worsened despite intensive immunosuppression therapy and he died 3 months later. Therefore, the early pathological findings of DAD did not match the clinical picture, which showed no respiratory failure. However, these findings were consistent with the subsequent course and poor outcome. Histological DAD, even in the absence of respiratory failure, may indicate a subsequent poor prognosis and explain the refractory course of RP-ILD with anti-MDA5 antibody-positive CADM.

Long-term Outcomes of Single-Site Laparoscopic Colectomy With Complete Mesocolic Excision for Colon Cancer: Comparison With Conventional Multiport Laparoscopic Colectomy Using Propensity Score Matching.

BACKGROUND: Complete mesocolic excision has been suggested to improve oncological outcomes for patients with colon cancer. However, the long-term outcomes of single-site laparoscopic colectomy with complete mesocolic excision remain unclear. OBJECTIVE: We evaluated the long-term outcomes of single-site laparoscopic colectomy with complete mesocolic excision compared with conventional multiport laparoscopic colectomy for colon cancer, as well as the short-term outcomes. DESIGN: This is a single-center, retrospective study. SETTINGS: The study was conducted at Osaka University Hospital in Japan. PATIENTS: A total of 971 consecutive patients who underwent laparoscopic surgery for colon cancer between 2008 and 2014 were included. Of these patients, 517 were analyzed using propensity score matching (231 with single-site laparoscopic colectomy and 286 with conventional multiport laparoscopic colectomy). MAIN OUTCOME MEASURES: Recurrence, survival, intraoperative morbidity, and postoperative complications were analyzed. RESULTS: Before propensity score matching, the single-site laparoscopic colectomy group had greater proportions of women and of patients with right-sided and early stage tumors compared with the conventional multiport laparoscopic colectomy group. After matching, the 2 groups each included 200 patients and did not significantly differ in any patient characteristics. The median follow-up period was 41.4 months. The 2 groups showed similar rates of intraoperative morbidity (p = 0.22) and postoperative complications (p = 0.87). Rates of 3-year disease-free and overall survival in single-site laparoscopic colectomy and conventional, multiport, laparoscopic colectomy groups were 95.5% and 91.3% (p = 0.44) and 100.0% and 98.7% (p = 0.24). The 3-year disease-free and overall survival rates in each stage did not significantly differ between the 2 groups. LIMITATIONS: This study was limited by its retrospective nature. CONCLUSIONS: Single-site laparoscopic colectomy with complete mesocolic excision for colon cancer provided acceptable perioperative outcomes and oncological outcomes, similar to those achieved with conventional multiport laparoscopic colectomy. Evidence accumulation from randomized controlled trials will be necessary to promote the wide acceptance of single-site laparoscopic colectomy. See Video Abstract at http://links.lww.com/DCR/A326.

Epidemiological analysis of childhood cancer in Japan based on population-based cancer registries, 1993-2009.

BACKGROUND: There are few recent data on trends in childhood cancer incidence using population-based cancer registries in Japan. METHODS: This study comprised 6110 reported cases of patients aged 0-14 years who were diagnosed as having primary cancer between 1993 and 2009. We chose cancer registries of seven prefectures, according to the international cancer registry standard of fewer than 10% death certificate only cases among cancer registries in Japan. We analyzed population-based cancer registration data in the seven prefectures between 1993 and 2009. We calculated childhood cancer incidence, age-specific incidence, crude incidence rate, age-adjusted incidence rate, confidence intervals and annual change for each prefecture and classified the data into 12 diagnostic groups, according to the International Classification of Childhood Cancer (ICCC). RESULTS: According to sex-specific incidence, males accounted for slightly more cases than females. Children 0-3 years old accounted for 41.1% of patients. Leukemia accounted for 36.0% of cancers, followed by central nervous system tumors with 15.0%, according to the ICCC. The crude incidence rate did not change substantially, remaining at an average 8-11 per 100 000 population. In addition, the age-adjusted incidence rate remained constant with an average 2 per 100 000 population. CONCLUSIONS: Using population-based cancer registry data, age-specific incidence and 12 diagnostic groups according to the ICCC showed characteristics of childhood cancers. The incidence rate of childhood cancers has been nearly stable in Japan over the past 15 years.

[A case of neurologic muscle weakness, ataxia, and retinitis pigmentosa (NARP) syndrome with a novel mitochondrial mutation m.8729 G>A].

We report a patient having classical clinical feature of neurologic muscle weakness, ataxia, and retinitis pigmentosa (NARP) and a novel mutation, m.8729 G>A in mitochondria DNA. The patient was referred to our hospital because of progressive ataxia in her limbs and trunk. She had a history of incapability of running long distances from childhood. Neurological examination revealed cerebellar ataxia, distal dominant muscle weakness in the limbs, hyporeflexia, hypoesthesia, myoclonus, sensorineural deafness, and retinitis pigmentosa. Magnetic resonance imaging (MRI) showed atrophy of brain stem and cerebellum as well as calcification of basal ganglia. In both serum and cerebrospinal fluid, lactate and pyruvate levels were elevated. Histological examination of biopsied muscle revealed chronic neurogenic changes without ragged red fibers. Genetic analysis of mitochondrial DNA (mtDNA) of the muscle revealed a heteroplasmic mutation, m.8729 G>A. Chemical analysis of the respiratory chain complexes in her muscle specimen demonstrated lower activities of complexes I and V. In our case, novel mutation of m.8729 G>A in mtDNA was indicated as the cause of NARP syndrome.

[Adult onset Langerhans cell histiocytosis with progressive cerebellar ataxia and spastic paraparesis].

A 44-year-old woman with progressive cerebellar ataxia and spastic paraparesis was referred to our hospital. Brain MRI showed bilateral high signals in superior, middle, and inferior cerebellar peduncles on the T2 weighted images. After 3 years, her symptoms progressively worsened in spite of various therapies including whole brain irradiation and high dose oral prednisone. No evidence of diabetes insipidus was noted. In MRI, brainstem lesions expanded to both hemispheres of the cerebellum without enhancement by contrast medium. We confirmed diagnosis of LCH by skin biopsy of intractable truncal rash which emerged after neurological symptoms.

HLA typing in focal myositis.

It is still controversial if idiopathic focal myositis is a part of systemic polymyositis. We present here four patients, including identical twins, with focal myositis accompanied by the same HLA typings. Gradually developing unilateral calf muscle pain was an initial symptom in all patients. Neither muscular weakness nor creatine kinase (CK) elevation was observed, while minimal inflammatory findings such as erythrocyte sedimentation rate (ESR) increase appeared in serum. Magnetic resonance imaging (MRI) revealed localized abnormalities of calf muscles. Biopsy specimen was characterized by perimysial and endomysial inflammatory infiltration consisted of T cells and macrophages and rare necrotic fibers. Corticosteroid administrations ameliorated their symptoms and signs, though recurrence occurred along with decreasing doses. HLA typings common to all patients were A2, B62, Cw3, and DQ3, whereas HLA-D DNA typings were DQB1 *0303 for two patients, and DQB1*0302 for three patients. These findings suggest that at least some focal myositis may be a new disease unit, with a common genetic background but not a part of systemic polymyositis.

Focal myositis in monozygotic twins.

Focal myositis is a rare disease with unknown etiology and a broad spectrum. Here, we present two cases in monozygotic twins who complained of recurrent pain of their calves and showed histological signs of inflammation and MRI image compatible with the diagnosis of focal myositis. The occurrence of twin cases not living in the same household suggests a genetic susceptibility to the disease.

Direct effects of tumor necrosis factor alpha (TNF-alpha) on L6 myotubes.

Tumor necrosis factor (TNF)-alpha is a pleiotropic cytokine responsible for a diverse range of signaling events within cells. We studied direct effects of TNF-alpha on skeletal muscle protein content. Incubation of the L6 myotubes with 1 to 10 U/ml of TNF-alpha resulted in a significant increase of total and myofibrillar protein contents as compared with the control. However, incubation with lower (0.001-0.1 U/ ml) or higher (100-300 U/ml) doses of TNF-alpha resulted in a decrease of protein content. These findings suggest that TNF-alpha may elicit both anabolic and catabolic effects on L6 myotubes in a dose dependent manner. The anabolic effect of TNF-alpha was mediated at least in part by mitogen activated protein kinase (MAPK), especially by an extracellular-regulated kinases (ERK). This divergent effect of TNF-alpha may be crucial to elucidate the complexity of TNF-alpha action on the skeletal muscle.