Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) in which dysregulation of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathways is the major pathogenic mechanism. Most patients with PMF carry a driver mutation in the JAK2, MPL (myeloproliferative leukemia), or CALR (calreticulin) genes. Mutations in epigenetic regulators and RNA splicing genes may also occur, and play critical roles in PMF disease progression. Based on revised World Health Organization diagnostic criteria for MPNs, both screening for driver mutations and bone marrow biopsy are required for a specific diagnosis. Clinical trials of JAK2 inhibitors for PMF have revealed significant efficacy for improving splenomegaly and constitutional symptoms. However, the currently available drug therapies for PMF do not improve survival. Although allogeneic stem cell transplantation is potentially curative, it is associated with substantial treatment-related morbidity and mortality. PMF is a heterogeneous disorder and decisions regarding treatments are often complicated, necessitating the use of prognostic models to determine the management of treatments for individual patients. This review focuses on the clinical aspects and outcomes of a cohort of Japanese patients with PMF, including discussion of recent advances in the management of PMF.
Asian Continental Ancestry Group ; Biopsy ; Bone Marrow ; Cohort Studies ; Diagnosis* ; Disease Progression ; Drug Therapy ; Epigenomics ; Humans ; Mass Screening ; Mortality ; Primary Myelofibrosis* ; RNA Splicing ; Splenomegaly ; Stem Cell Transplantation ; Transducers ; World Health Organization

It is common knowledge that exposure to asbestos causes asbestos-related diseases, such as asbestosis, lung cancer and malignant mesothelioma, not only in people who have had long-term contact with asbestos in their work environment but also in residents living near factories that handle asbestos. Since the summer of 2005, these revelations turned into a large medical problem and caused and social unrest. We have focused on the immunological effects of both asbestos and silica on the human immune system. In this brief review, we introduce immunological alterations found in patients with malignant mesothelioma and describe the experimental background in which these were found. Analyzing the immunological effects of asbestos may improve our understanding of the biological effects of asbestos.

BACKGROUND/AIMS: The ability of endoscopic submucosal dissection (ESD) to resect large early gastric cancers (EGCs) results in the need to treat large artificial gastric ulcers. This study assessed whether the combination therapy of rebamipide plus a proton pump inhibitor (PPI) offered benefits over PPI monotherapy. METHODS: In this prospective, randomized, multicenter, open-label, and comparative study, patients who had undergone ESD for EGC or gastric adenoma were randomized into groups receiving either rabeprazole monotherapy (10 mg/day, n=64) or a combination of rabeprazole plus rebamipide (300 mg/day, n=66). The Scar stage (S stage) ratio after treatment was compared, and factors independently associated with ulcer healing were identified by using multivariate analyses. RESULTS: The S stage rates at 4 and 8 weeks were similar in the two groups, even in the subgroups of patients with large amounts of tissue resected and regardless of CYP2C19 genotype. Independent factors for ulcer healing were circumferential location of the tumor and resected tissue size; the type of treatment did not affect ulcer healing. CONCLUSIONS: Combination therapy with rebamipide and PPI had limited benefits compared with PPI monotherapy in the treatment of post-ESD gastric ulcer (UMIN Clinical Trials Registry, UMIN000007435).
Adenoma ; Cicatrix ; Cytochrome P-450 CYP2C19 ; Endoscopy ; Genotype ; Humans ; Multivariate Analysis ; Prospective Studies ; Proton Pump Inhibitors ; Proton Pumps* ; Protons* ; Rabeprazole ; Stomach Neoplasms ; Stomach Ulcer* ; Ulcer

BACKGROUND/AIMS: The ability of endoscopic submucosal dissection (ESD) to resect large early gastric cancers (EGCs) results in the need to treat large artificial gastric ulcers. This study assessed whether the combination therapy of rebamipide plus a proton pump inhibitor (PPI) offered benefits over PPI monotherapy. METHODS: In this prospective, randomized, multicenter, open-label, and comparative study, patients who had undergone ESD for EGC or gastric adenoma were randomized into groups receiving either rabeprazole monotherapy (10 mg/day, n=64) or a combination of rabeprazole plus rebamipide (300 mg/day, n=66). The Scar stage (S stage) ratio after treatment was compared, and factors independently associated with ulcer healing were identified by using multivariate analyses. RESULTS: The S stage rates at 4 and 8 weeks were similar in the two groups, even in the subgroups of patients with large amounts of tissue resected and regardless of CYP2C19 genotype. Independent factors for ulcer healing were circumferential location of the tumor and resected tissue size; the type of treatment did not affect ulcer healing. CONCLUSIONS: Combination therapy with rebamipide and PPI had limited benefits compared with PPI monotherapy in the treatment of post-ESD gastric ulcer (UMIN Clinical Trials Registry, UMIN000007435).
Adenoma ; Cicatrix ; Cytochrome P-450 CYP2C19 ; Endoscopy ; Genotype ; Humans ; Multivariate Analysis ; Prospective Studies ; Proton Pump Inhibitors ; Proton Pumps* ; Protons* ; Rabeprazole ; Stomach Neoplasms ; Stomach Ulcer* ; Ulcer

Previous study reported that baseball pitchers had a decreased shoulder internal rotation (IR) range of motion after pitching. However, whether the decreased range of motion associated with pitching is caused by tightness of the posterior shoulder has not been clarified yet. The joint stiffness in the passive torque can be compared with posterior shoulder tightness before and after pitching. Hence, this study aimed to compare shoulder IR stiffness based on passive torque before and after pitching in baseball pitcher. Eleven health male collage baseball pitchers were recruited. Passive torque during IR (max IR, peak torque and stiffness) of dominant and non-dominant arms was measured using an isokinetic dynamometer. Measurements were taken before, after, and post 24 hours after pitching (105 pitches). It was observed that after pitching, max IR and peak torque were significantly decreased compared to those before pitching. However, there was no difference in the stiffness of passive torque among three measurements. In conclusion, healthy college baseball pitchers have a decreased IR range of motion after pitching. However, this result is not due to posterior shoulder tissue tightness, but because of altered stretch tolerance.

BACKGROUND/AIMS: Antithrombotic/nonsteroidal antiinflammatory drug (NSAID) therapies increase the incidence of upper gastrointestinal bleeding. The features of hemorrhagic peptic ulcer disease in patients receiving antithrombotic/NSAID therapies were investigated. METHODS: We investigated the medical records of 485 consecutive patients who underwent esophagogastroduodenoscopy and were diagnosed with hemorrhagic gastroduodenal ulcers. The patients treated with antithrombotic agents/NSAIDs were categorized as the antithrombotic therapy (AT) group (n=213). The patients who were not treated with antithrombotics/NSAIDs were categorized as the control (C) group (n=263). The clinical characteristics were compared between the groups. RESULTS: The patients in the AT group were significantly older than those in the C group (p<0.0001). The hemoglobin levels before/without transfusion were significantly lower in the AT group (8.24+/-2.41 g/dL) than in the C group (9.44+/-2.95 g/dL) (p<0.0001). After adjusting for age, the difference in the hemoglobin levels between the two groups remained significant (p=0.0334). The transfusion rates were significantly higher in the AT group than in the C group (p=0.0002). However, the outcome of endoscopic hemostasis was similar in the AT and C groups. CONCLUSIONS: Patients with hemorrhagic peptic ulcers receiving antithrombotic/NSAID therapies were exposed to a greater risk of severe bleeding that required transfusion but were still treatable by endoscopy.
Anti-Inflammatory Agents, Non-Steroidal ; Endoscopy ; Endoscopy, Digestive System ; Hemoglobins ; Hemorrhage ; Hemostasis, Endoscopic ; Humans ; Incidence ; Medical Records ; Peptic Ulcer