Treatment Rationale and Design of a Phase III Study of Afatinib or Chemotherapy in Patients with Non-small-cell Lung Cancer Harboring Sensitizing Uncommon Epidermal Growth Factor Receptor Mutations (ACHILLES/TORG1834).

We describe the treatment rationale and design of our randomized phase III study, the ACHILLES trial (Japan Registry of Clinical Trials: jRCTs031180175). The aim of this study is to investigate the superiority of afatinib over chemotherapy as first-line treatment in patients with advanced nonsquamous non-small-cell lung cancer with sensitizing uncommon or compound epidermal growth factor receptor (EGFR) mutations, with the exception of de novo T790M mutations and exon 20 insertions. Eligible patients will be randomized at a 1:2 ratio to receive either chemotherapy or afatinib until disease progression or unacceptable toxicity.

The impact of adjuvant surgical treatment of nontuberculous mycobacterial pulmonary disease on prognosis and outcome.

Background: Lung resection in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) has been reported to be associated with favorable outcomes. However, little is known regarding the risk and prognostic factors for refractory and recurrent cases. We aimed to evaluate the overall impact and benefit of adjuvant lung surgery by comparing NTM-PD patients who underwent adjuvant lung resection with those treated exclusively with antibiotics.

Efficacy of recombinant thrombomodulin for poor prognostic cases of acute exacerbation in idiopathic interstitial pneumonia: secondary analysis of the SETUP trial.

Background: Acute exacerbation (AE) in idiopathic pulmonary fibrosis and other idiopathic interstitial pneumonias (IIPs) are poor prognostic events although they are usually treated with conventional therapy with corticosteroids and immunosuppressants. Previously, we demonstrated the safety and efficacy of recombinant human soluble thrombomodulin (rhTM) for AE-IIP in the SETUP trial. Here, we aimed to clarify the efficacy of rhTM for poor-prognosis cases of AE-IIP.

Association Between Early Immune-related Adverse Events and Clinical Outcomes in Patients With Non-Small Cell Lung Cancer Treated With Immune Checkpoint Inhibitors.

Introduction: Previous studies have described an association between immune-related adverse events (irAEs) and better outcomes in patients administered nivolumab for advanced non-small-cell lung cancer. However, the patients in previous studies were not stratified by potential predictive factors, such as programmed cell death ligand 1 status and treatment lines. Additionally, little is known of whether the timing and type of irAEs can inform the prediction of outcomes.

A Japanese lung cancer registry study on demographics and treatment modalities in medically treated patients.

This study provides the benchmark statistics on medically treated patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) in Japan. Demographic background, treatment, and prognosis were obtained from patients with lung cancer pathologically diagnosed in 2012, who received nonsurgical treatment. Descriptive statistics and their associations with survival were analyzed.

Arc-welders' pneumoconiosis with atypical radiological and bronchoalveolar lavage fluid findings: A case report.

Arc-welders' pneumoconiosis (AWP) is an occupational lung disease and has nonspecific symptoms typically with the patterns of centrilobular and/or branching opacities on chest high-resolution computed tomography (HRCT) which are similar to those of hypersensitivity pneumonitis (HP) and/or respiratory tract infections. Therefore, the differential diagnosis is often difficult if they are not suspected. We report a case of AWP which was initially suspected to be pulmonary tuberculosis because of the chest HRCT findings: centrilobular opacities distributed predominantly on the right lobe.

Propensity score-weighted analysis of chemotherapy after PD-1 inhibitors versus chemotherapy alone in patients with non-small cell lung cancer (WJOG10217L).

Background: Studies have suggested that chemotherapy after immune checkpoint inhibitors may confer an improved response for non-small cell lung cancer (NSCLC). However, potential selection bias in such studies has not been addressed. We therefore applied propensity score analysis to investigate the efficacy of chemotherapy after PD-1 inhibitor treatment (CAP) compared with chemotherapy alone.

Acute lung injury after plasma exchange in a patient with anti-MDA5 antibody-positive, rapidly progressive, interstitial lung disease：A case report.

The presence of anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) is closely associated with rapidly progressive interstitial lung disease (RP-ILD) in patients with clinically amyopathic dermatomyositis. Despite intensive immunosuppressive therapies, some of these patients still have a poor prognosis with few treatment options. Although removal of pathogenic autoantibodies and cytokines by plasma exchange (PE) could be a treatment option, its safety and efficacy have never been determined.

Natural Autoantibodies in Chronic Pulmonary Diseases.

In autoantibody-mediated autoimmune diseases, pathogenic autoantibodies generated by a failure of central or peripheral tolerance, have different effects mediated by a variety of mechanisms. Interestingly, even non-autoimmune chronic diseases have a set of disease-specific natural autoantibodies that are maintained for a long time. Because most of these natural autoantibodies target intracellular proteins or long non-coding RNAs, they are speculated to be non-pathological and have some important as yet unrecognized physiological functions such as debris clearance.

Newborn Screening for Spinal Muscular Atrophy: DNA Preparation from Dried Blood Spot and DNA Polymerase Selection in PCR.

Background: Polymerase chain reaction (PCR) analysis using DNA from dried blood spot (DBS) samples on filter paper is a critical technique for spinal muscular atrophy (SMA) newborn screening. However, DNA extraction from DBS is time-consuming, and elimination of PCR inhibitors from DBS is almost impossible.

Methods: Exon 7 of the two homologous SMA-related genes, survival motor neuron (SMN) 1 and SMN2, of five SMA patients and five controls were amplified by PCR with a punched-out circle of the DBS paper.

S-1 plus cisplatin with concurrent radiotherapy for locally advanced thymic carcinoma: Study protocol of LOGIK1605/JART-1501.

Thymic carcinoma is a rare epithelial tumor of the thymus with a poor prognosis, and multimodal approaches are important for its treatment. Recently, a number of studies have indicated that S-1 treatment is effective against thymic carcinoma. S-1 plus cisplatin with concurrent radiotherapy is a commonly used treatment for other malignancies, including non-small cell lung cancer (NSCLC).

Prediction of patients with a tumor proportion score > 50% who do not respond to first-line monotherapy with pembrolizumab.

Background: Pembrolizumab is effective as first-line therapy against advanced non-small cell lung cancer (NSCLC) in patients with programmed death ligand-1 (PD-L1) expression levels ≥50% [1]. However, it is not effective in all patients, and the factors predicting responses among this population remain unknown.

Methods: We retrospectively analyzed patients with NSCLC and a PD-L1 tumor proportion score (TPS) > 50%, who received first-line monotherapy with pembrolizumab from February 1, 2017 to April 30, 2018.

Early phase 2 trial of TAS-205 in patients with Duchenne muscular dystrophy.

Objective: Duchenne muscular dystrophy (DMD) is a progressive muscular disease characterized by chronic cycles of inflammatory and necrotic processes. Prostaglandin D (PGD ) is produced by hematopoietic PGD synthase (HPGDS), which is pathologically implicated in muscle necrosis. This randomized, double-blind, placebo-controlled early phase 2 study (NCT02752048) aimed to assess the efficacy and safety of the novel selective HPGDS inhibitor, TAS-205, with exploratory measures in male DMD patients aged ≥5 years.

[Study of care practices for patients with myotonic dystrophy in Japan-Nationwide patient survey].

We conducted a comprehensive anonymous questionnaire survey on medical care and treatment for patients with myotonic dystrophy, who registered in the Japanese national registry (Remudy) or were undergoing care in seven hospitals specializing neuromuscular diseases. The questionnaire consisted of 49 questions were distributed to 813 patients, and 342 valid responses were collected. Most prevalent symptoms or complaints were dysfunction of fingers and fatigue.

[Study of medical practices for patients with myotonic dystrophy in Japan-Nationwide specialist survey].

To reveal current status of medical practice, we made a nationwide self-questionnaire survey to Japanese certified Neurologists and Child Neurologists. Most specialists seeing patients with myotonic dystrophy (DM) were aware that genetic analysis is approved in health insurance. The ratio of pre-explanation about genetic analysis was also high however written informed consent was not always obtained.

Characteristic chest CT findings for progressive cavities in Mycobacterium avium complex pulmonary disease: a retrospective cohort study.

Background: Although cavities are an important finding in Mycobacterium avium complex pulmonary disease (MAC-PD), there is little information regarding the types of cavities that indicate disease progression. This study was performed to identify cavity characteristics that were associated with disease progression in patients with MAC-PD.

Methods: This retrospective cohort study included 97 patients presenting with MAC-PD with cavities between December 2006 and June 2016.

A clinicopathological study of ALS with L126S mutation in the SOD1 gene presenting with isolated inferior olivary hypertrophy.

We report an autopsy case of amyotrophic lateral sclerosis with L126S mutation in the superoxide dismutase 1 (SOD1) gene (SOD1). The patient was a 69-year-old Japanese man without relevant family history, who initially presented with slow progressive muscle weakness of the lower extremities without upper motor neuron signs, and died of respiratory failure 6 years after the onset. Neuropathological examination revealed a loss of lower motor neurons and degeneration of Clarke's column commensurate with that of the posterior spinocerebellar tract and the middle root zone of the posterior column.

[A case of systemic AL amyloidosis diagnosed on muscle biopsy].

A 69-year-old man was admitted to our hospital with a 1-year history of progressive easy fatigability while walking. He presented with proximal muscle weakness dominant in the lower extremities, hoarseness, and mild dysphagia. Muscle pseudo-hypertrophy was observed in the gastrocnemius.

Clinical Effects Of Acupuncture On The Pathophysiological Mechanism Of Chronic Obstructive Pulmonary Disease During Exercise.

Purpose: Pharmacological therapy and pulmonary rehabilitation are useful for exertional dyspnoea in patients with chronic obstructive pulmonary disease (COPD); however, several patients have no meaningful improvements. Although acupuncture significantly improves exercise intolerance and dyspnoea, the pathophysiological mechanism of these effects is unknown; therefore, we evaluated this mechanism using cardiopulmonary exercise testing in a single-arm, open experimental study.

Patients And Methods: Sixteen patients with COPD underwent acupuncture once a week for 12 weeks.

Population pharmacokinetics of afatinib and exposure-safety relationships in Japanese patients with EGFR mutation-positive non-small cell lung cancer.

To investigate the exposure-safety relationships of afatinib in Japanese population, we performed population pharmacokinetics (PK) analysis of afatinib in Japanese advanced non-small cell lung cancer patients harboring epidermal growth factor receptor mutation. Plasma samples were collected at 0.5-1, 2-3, 8-12, and 24 h after oral afatinib (40 mg) administration on day 1 and day 8.

Association between metastatic sites and first-line pembrolizumab treatment outcome for advanced non-small cell lung cancer with high PD-L1 expression: a retrospective multicenter cohort study.

Associations between treatment outcomes of immune checkpoint inhibitors and metastatic sites in advanced non-small cell lung cancer (NSCLC) are not well known. Therefore, this multicenter retrospective study aimed to investigate the predictive factors of metastatic sites after first-line pembrolizumab treatment for advanced NSCLC with a PD-L1 tumor proportion score (TPS) ≥50%. We retrospectively analyzed advanced NSCLC patients with a PD-L1 TPS ≥50% who underwent first-line pembrolizumab therapy at 11 institutions between February 2017 and April 2018.