Impact of sleep-related hypoventilation in patients with pleuroparenchymal fibroelastosis.

BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) is a rare fibrosing lung disease with a predilection for the upper lobe and its progression causes hypoventilation, resulting in hypercapnia. Even though the association between sleep-related hypoventilation (SRH) and chronic obstructive pulmonary disease was well documented, its impact in patients with PPFE was not evaluated. The aim of this study is to clarify the impact of SRH on prognosis in PPFE. METHODS: A retrospective review of the medical records of 52 patients with PPFE who underwent transcutaneous carbon dioxide monitoring during sleep was done. Patients were stratified into SRH (n = 28) and non-SRH (n = 24) groups based on American Academy of Sleep Medicine criteria. The impact of SRH on the prognosis of PPFE, as well as the clinical factors and comorbidities of PPFE associated with SRH, were evaluated. RESULTS: Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), and carbon monoxide diffusing capacity (DLco) in the SRH group were significantly lower than the non-SRH group (P < .01). Chronic pulmonary aspergillosis (CPA) was found at a higher rate in the SRH group (P = .02). The median survival time for SRH patients was 330 days, whereas roughly 80% of non-SRH patients were alive during the 3-year observation period (P < .01). Body mass index was a significant prognostic factor in PPFE patients with SRH (HR .78; 95% CI; .64-.94; P < .01). Home oxygen therapy (HOT) during the day and noninvasive positive pressure ventilation (NPPV) at night while sleeping tended to improve prognosis in the SRH group, as indicated by HR of .25 (P = .07). CONCLUSIONS: SRH may be a poor prognostic factor for PPFE. Additionally, SRH may modify susceptibility to Aspergillosis in patients with PPFE. HOT plus NPPV may improve the disease outcomes in patients with SRH.

Management of Cutaneous Manifestations of Genetic Epidermolysis Bullosa: A Multiple Case Series.

BACKGROUND: Epidermolysis bullosa (EB) is a rare disease characterized by blistering and erosion of the skin and mucus membranes in response to minor external forces. Research focusing on daily skin care in EB patients is sparse. Two international clinical practice guidelines (CPGs) have been published in English, but they have not yet been translated into other languages such as Japanese. Therefore, their recommendations have not been adapted to multiple geographic regions in the world. This multiple case series describes our approach to the skin care of 3 Japanese patients with EB. RESULTS: All 3 patients were diagnosed with genetic EB. A 13-year-old male patient had dominant dystrophic EB and suffered skin breakdown covering nearly 1% to 6% of his total body surface area (TBSA) during a 21-week data collection period. A 3-year-old male patient had EB simplex; he suffered skin breakdown covering 2% to 40% of his TBSA during a 36-week data collection period. The third case was a 5-year-old male patient with recessive dystrophic EB who experienced skin breakdown covering 2% to 40% of his TBSA during a 35-week data collection period. Blisters were punctured daily and treated with a soft silicone dressing. Daily application of moisturizers was undertaken to prevent the skin from drying out and itching. CONCLUSION: Our experience suggests that application of published CPGs promoted wound healing. Nevertheless, given the nature of the disease, a complete resolution to an individual's vulnerability to skin lesions even with relatively minor trauma remains elusive. Additional research is needed to explore interventions for skin and ulcer care, along with symptom management, including pain and pruritus.

Tooth Loss Predicts Long-Term Prognosis of Esophageal Cancer After Esophagectomy.

BACKGROUND: Oral health is associated with various diseases, including cancer. Tooth loss is a simple and objective index of oral health. OBJECTIVE: The purpose of this study was to investigate the association between preoperative tooth loss and esophageal cancer prognosis after esophagectomy. METHODS: This study included 191 patients who underwent esophagectomy for esophageal cancer after perioperative dental evaluation and oral care at Kobe University Hospital from April 2011 to March 2016. Patients were divided into two groups: Group A (tooth loss < 7) and Group B (tooth loss ≥ 7). Three-year overall survival (OS) and multivariate analysis were performed, along with subgroup analysis for elderly patients (age ≥ 65 years). RESULTS: The 3-year OS rate was 68.1% in Group A (104 patients) and 49.2% in Group B (87 patients). Group A had significantly higher OS than Group B (p = 0.002), and there were no significant differences in sex and clinical T or N stage between the two groups. However, the mean age of Group A was younger than that of Group B (64.2 vs. 68.5 years; p = 0.0002). Among elderly patients, the 3-year OS rate was 68.2% in Group A (55 patients) and 45.1% in Group B (65 patients) [p = 0.003]. Multivariate analysis that included age demonstrated that tooth loss is an independent prognostic factor (hazard ratio 1.87, 95% confidence interval 1.22-2.87), in addition to clinical T stage and preoperative serum albumin. CONCLUSION: Tooth loss is an independent prognostic factor for esophageal cancer after esophagectomy.

A case of Marfan syndrome with massive haemoptysis from collaterals of the lateral thoracic artery.

BACKGROUND: Marfan Syndrome (MFS) is a heritable connective tissue disorder with a high degree of clinical variability including respiratory diseases; a rare case of MFS with massive intrathoracic bleeding has been reported recently. CASE PRESENTATION: A 32-year-old man who had been diagnosed with MFS underwent a Bentall operation with artificial valve replacement for aortic dissection and regurgitation of an aortic valve in 2012. Warfarin was started postoperatively, and the dosage was gradually increased until 2017, when the patient was transported to our hospital due to sudden massive haemoptysis. Computed tomography (CT) with a maximum intensity projection (MIP) revealed several giant pulmonary cysts with fluid levels in the apex of the right lung with an abnormal vessel from the right subclavian artery. Transcatheter arterial embolization was performed with angiography and haemostasis was achieved, which suggested that the bleeding vessel was the lateral thoracic artery (LTA) branch. CT taken before the incident indicated thickening of the cystic wall adjacent to the thorax; therefore, it was postulated that the bleeding originated from fragile anastomoses between the LTA and pulmonary or bronchial arteries. It appears that the vessels exhibited inflammation that began postoperatively, which extended to the cysts. CONCLUSION: We experienced a case of MFS with massive haemoptysis from the right LTA. We have to be aware of the possibility that massive haemoptysis could be induced in MFS with inflamed pulmonary cysts.

Long-Term Outcomes of Thoracoscopic Esophagectomy in the Prone versus Lateral Position: A Propensity Score-Matched Analysis.

BACKGROUND: Several studies have suggested that thoracoscopic esophagectomy (TE) in the prone position (TEP) may be more feasible than TE in the lateral position (TEL); however, few studies have compared long-term survival between the two procedures. We evaluated whether TEP is oncologically equivalent to TEL. METHODS: Surgical outcomes of TEs performed from January 2006 to December 2013 at our hospital were retrospectively analyzed. Propensity score matching was used to control for confounding factors. RESULTS: TE was performed in 200 patients diagnosed with esophageal squamous cell carcinoma; 78 patients were matched in two procedures. The mean thoracic operative time in TEL was shorter than in TEP (228.9 min vs. 299.1 min; p < 0.001); however, the mean thoracic blood loss in TEL was higher than in TEP (186.9 ml vs. 76.5 ml; p < 0.001). The mean number of thoracic lymph nodes harvested in TEL was lower than in TEP (23.5 vs. 26.9; p < 0.05), and the pulmonary complication rate in TEL was higher than in TEP (30.8% vs. 15.4%; p < 0.05). The 5-year overall survival rates in pathological stage I (81.2% vs. 81.6%; p = 0.82), stage II (65.3% vs. 80.9%; p = 0.21), stage III (26.7% vs. 24.2%; p = 0.86) and all stages (63.6% vs. 62.3%; p = 0.88), and the 5-year progression-free survival rates in pathological stage I (78.0% vs. 81.8%; p = 0.54), stage II (53.5% vs. 77.6%; p = 0.13), stage III (10.5% vs. 12.8%; p = 0.81) and all stages (53.6% vs. 57.9%; p = 0.50) were not significantly different between the two procedures. CONCLUSION: TEP and TEL provide equal oncological efficiency.

Borderline pulmonary hypertension is associated with exercise intolerance and increased risk for acute exacerbation in patients with interstitial lung disease.

BACKGROUND: Pulmonary hypertension (PH) is traditionally defined as a resting mean pulmonary artery pressure (mPAP) of ≥25 mmHg, while mPAP in the range of 21 to 24 mmHg is recognized as "borderline PH." Interstitial lung disease (ILD) is complicated by the development of PH, which is known to be linked with exercise intolerance and a poor prognosis. Even though it has recently been recommended that PH is redefined as a mPAP of > 20 mmHg, little is known about the clinical significance of borderline PH in ILD. We evaluated whether borderline PH has an impact on the exercise capacity, risk of acute exacerbation (AE), and mortality in patients with ILD. METHODS: A total of 80 patients with ILD who underwent right heart catheterization (RHC) between November 2013 and October 2016 were included. The patients were divided into 3 groups according to the mPAP values: mPAP ≤20 mmHg (No-PH group; n = 56), 20 < mPAP < 25 mmHg (Bo-PH group; n = 18), and mPAP ≥25 mmHg (PH group; n = 6). The demographic, hemodynamic, spirometric, and 6-min walk test (6MWT) data of the patients were collected. In addition, the 1-year incidence of AEs and 1-year survival of the patients after the initial RHC were also evaluated. RESULTS: There were no significant differences among the 3 groups in the mean age, pulmonary function parameters or the PaO2, however, 6-min walk distance was significantly lower in both the Bo-PH and PH groups (p < 0.001 for both) as compared to the No-PH group. The results of the Kaplan-Meier analysis revealed that while there was no significant difference in the 1-year survival rate among the three groups, the 1-year incidence of AEs was significantly higher in both the Bo-PH and PH groups (p < 0.001, p = 0.023, respectively) as compared to the No-PH group. CONCLUSIONS: The current study suggested that borderline PH may be associated with poorer exercise tolerance and an increased risk of AEs in patients with ILD. Therefore, the physicians should pay close attention to the presence of even mild elevation of the mPAP at the initial evaluation in patients with ILD.

Activated Fibroblast Program Orchestrates Tumor Initiation and Progression; Molecular Mechanisms and the Associated Therapeutic Strategies.

: Neoplastic epithelial cells coexist in carcinomas with various non-neoplastic stromal cells, together creating the tumor microenvironment. There is a growing interest in the cross-talk between tumor cells and stromal fibroblasts referred to as carcinoma-associated fibroblasts (CAFs), which are frequently present in human carcinomas. CAF populations extracted from different human carcinomas have been shown to possess the ability to influence the hallmarks of cancer. Indeed, several mechanisms underlying CAF-promoted tumorigenesis are elucidated. Activated fibroblasts in CAFs are characterized as alpha-smooth muscle actin-positive myofibroblasts and actin-negative fibroblasts, both of which are competent to support tumor growth and progression. There are, however, heterogeneous CAF populations presumably due to the diverse sources of their progenitors in the tumor-associated stroma. Thus, molecular markers allowing identification of bona fide CAF populations with tumor-promoting traits remain under investigation. CAFs and myofibroblasts in wound healing and fibrosis share biological properties and support epithelial cell growth, not only by remodeling the extracellular matrix, but also by producing numerous growth factors and inflammatory cytokines. Notably, accumulating evidence strongly suggests that anti-fibrosis agents suppress tumor development and progression. In this review, we highlight important tumor-promoting roles of CAFs based on their analogies with wound-derived myofibroblasts and discuss the potential therapeutic strategy targeting CAFs.

Practical Surgical Techniques for Lymphadenectomy Along the Right Recurrent Laryngeal Nerve During Thoracoscopic Esophagectomy in the Prone Position.

BACKGROUND: In esophageal squamous cell cancer (SCC), lymphadenectomy along the right recurrent laryngeal nerve (RLN) is important for disease control. The metastatic rate was 33% and the 5-year overall survival rate of these patients was 33.3%,1 but the risk of RLN palsy increases.2 We reported a reliable new method ('Pincers Maneuver')3 for lymphadenectomy along the right RLN during thoracoscopic esophagectomy in the prone position (TEP), and hereby present our video, aimed at providing a complete and safe dissection. METHOD: The 'Pincers Maneuver' is performed for all resectable clinical stage IA-III lower, middle, or upper thoracic esophageal SCCs. Patients above clinical stage IB were treated with neoadjuvant chemotherapy. The concept of this procedure is to first exfoliate the two-dimensional membrane (lateral pedicle), which includes the right RLN, lymph nodes, and the primary esophageal artery, from the right side of the trachea toward the neck. Improved mobility of the lateral pedicle, gained by closing in from its inner and outer sides, enables easy lymphadenectomy along the right RLN toward the right inferior thyroid artery. RESULTS: Using this method, we performed 31 TEPs in 2016 at Kobe University Hospital. Median body mass index was 23 kg/m2 (range 18-31). No right RLN palsy greater than Clavien-Dindo classification grade I was observed. On average, 5.2 ± 2.7 nodes were harvested along the right RLN, with a 23% metastatic rate. CONCLUSIONS: Our method for lymphadenectomy along the right RLN during TEP is safe and practical. It provides sufficient lymph node dissection, and no right RLN palsy has been observed.

A new method (the "Pincers maneuver") for lymphadenectomy along the right recurrent laryngeal nerve during thoracoscopic esophagectomy in the prone position for esophageal cancer.

BACKGROUND: In esophageal squamous cell carcinoma, the number of dissected lymph nodes (LNs), including those along the recurrent laryngeal nerves (RLNs), influences prognosis and nodal staging accuracy. However, dissection of LNs along the RLN increases the risk of complications, especially RLN palsy. Therefore, complete dissection of these LNs with prevention of RLN palsy is recommended. We present herein a new method for lymphadenectomy along the right RLN, named the Pincers maneuver, during thoracoscopic esophagectomy in the prone position (TEP). METHODS: The fundamental concept in this new method is to first exfoliate the two-dimensional membrane (lateral pedicle), which includes the right RLN, LNs along the right RLN, and the primary esophageal artery, from the right side of the trachea toward the neck. Using a Pincers strategy, closing in from the inner and outer sides of the two-dimensional membrane (lateral pedicle), lymphadenectomy along the right RLN toward the right inferior thyroid artery should be easy. This technique was evaluated in 30 consecutive cases of TEP for squamous cell cancer. RESULTS: There were 15 patients who underwent the new method (Pincers maneuver; Pm) and 15 patients who underwent the conventional method (Cm). There were no significant differences between the two groups in the duration of the thoracic procedure and dissection along the right RLN. No intraoperative and postoperative morbidity related to the right RLN was observed in either group. The Pm group had a higher number of dissected LNs along the right RLN than the Cm group (6.3 vs 3.1, p = 0.044). CONCLUSIONS: The Pincers maneuver for lymphadenectomy along the right RLN during TEP is technically safe and feasible. It increases the number of dissected LNs along the right RLN.

Interstitial lung disease associated with amrubicin chemotherapy in patients with lung cancer: a single institutional study.

OBJECTIVE: Amrubicin, which is used as a chemotherapeutic agent for lung cancer, can induce interstitial lung disease. There is insufficient evidence on the incidence of amrubicin-associated interstitial lung disease under practical use settings. We therefore investigated the occurrence of interstitial lung disease in the patients with lung cancer who received amrubicin in our institution. METHODS: We reviewed the data of all patients with lung cancer who received amrubicin at the Nippon Medical School Hospital from March 2002 to April 2015. Interstitial lung disease was diagnosed based on clinical symptoms, radiographic findings and the exclusion of other diseases. RESULTS: We reviewed 92 consecutive patients with lung cancer. Amrubicin-associated interstitial lung disease occurred in 3 of the 92 patients (3.3%): 2 were definite interstitial lung disease and 1 was possible interstitial lung disease. The severity of interstitial lung disease was mild to moderate, and interstitial lung disease improved with or without corticosteroid therapy in all cases. The findings in a computed tomography image analysis showed preexisting pulmonary fibrosis (n = 13), including interstitial pneumonitis (n = 10) and radiation fibrosis (n = 3). No patients showed the presence of honeycomb lung. Among the 13 patients, 1 (7.7%) developed interstitial lung disease after amrubicin chemotherapy. CONCLUSION: Interstitial lung disease occurred in 3.3% of the patients in our study; this appeared to be less frequent than the rates in previous reports. Preexisting pulmonary fibrosis may be a risk factor for interstitial lung disease; however, no fatal cases were found among the patients with asymptomatic pulmonary fibrosis without honeycomb lung. It is thus considered to be necessary to carefully assess the possibility of preexisting pulmonary fibrosis and clarify the presence or absence of honeycomb lung before starting amrubicin chemotherapy.

[CLINICAL UTILITY OF T-SPOT.TB ASSAY WITH T-Cell Xtend REAGENT FOR ACTIVE TUBERCULOSIS DIAGNOSIS IN THE FIELD TEST AT OUR HOSPITAL].

BACKGROUND: T-SPOT.TB (T-SPOT), an interferon-gamma release assay, has shown promise as a diagnostic tool for active tuberculosis (TB), and its use is expanding. Addition of the T-Cell Xtend (TCX) reagent may allow delayed processing, and this characteristic is important for using this test in the field. However, limited data is available on the usefulness of T-SPOT with TCX as a field test for diagnosing active TB. PURPOSE: To investigate the clinical utility of T-SPOT with TCX and the risk factors for a false-negative result in patients with active TB. METHODS: A total of 57 patients with active TB who underwent the T-SPOT test with TCX prior to treatment were enrolled between May 2013 and May 2015. One patient with an indeterminate result for T-SPOT was excluded; therefore, the data of 56 patients were eventually included in the final analysis. The basic characteristics and clinical findings were compared between the true-positive and false-negative T-SPOT groups. RESULTS: Of the 56 patients, 40 (71.4%), 13 (23.2%), 3 (5.4%) had true-positive, false-negative, and borderline T-SPOT results, respectively. This study did not reveal any significant risk factors for a false-negative T-SPOT result. CONCLUSION: In this clinical study, the proportion of patients with a false-negative result for T-SPOT with TCX for active TB was higher than that reported previously. Therefore, careful interpretation of a negative result for T-SPOT with TCX is necessary, regardless of the patient's background.

[Anesthetic Management Using Transesophageal Echocardiography and EV1000 in a Patient with Ebstein's Anomary Undergoing Scoliosis Surgery].

An 18-year-old female patinet with Ebstein anomaly underwent surgical repair of scoliosis under total intravenous anesthesia. In addtition to normal monitors, we used transesophageal echocardiography (TEE) and EV1000 (Edwards Lifesciences, Irvine, USA), which show stroke volume variation and stroke volume index simultaneously in a rectangular coordinates. TEE detected reversal of intracardiac shunt which caused SpO2 decrease during fixing screws at thoracic vertebrae, then manual ventilation with oxygen unproved SpO2. Because of a high venous pressure due to Ebstein anomaly, surgical bleeding seemed to be larger than usual. By using EV1000, volume status and cardiac contractility were estimated and adequate volume loading and inoptrope injection were performed to stabilize circulatory condition. The operation was completed without any cardiac and respiratory complications.

Pirfenidone inhibits fibrocyte accumulation in the lungs in bleomycin-induced murine pulmonary fibrosis.

BACKGROUND: Bone marrow-derived fibrocytes reportedly play important roles in the pathogenesis of idiopathic pulmonary fibrosis. Pirfenidone is an anti-fibrotic agent; however, its effects on fibrocytes have not been investigated. The aim of this study was to investigate whether pirfenidone inhibits fibrocyte pool size in the lungs of bleomycin-treated mice. METHODS: Bleomycin (100 mg/kg) was infused with osmotic pumps into C57BL/6 mice, and pirfenidone (300 mg/kg/day) was orally administered daily for 2 wk. The lungs were removed, and single-cell suspensions were subjected to fluorescence-activated cell sorter (FACS) analysis to detect fibrocytes, which were defined as CD45 and collagen-I double-positive cells. Immunohistochemistry was performed on the lung specimens to quantify fibrocytes. Chemokines in the lung digests were measured with enzyme-linked immunosorbent assay. The effect of pirfenidone on alveolar macrophages was evaluated with bronchoalveolar lavage (BAL). In a therapeutic setting, pirfenidone administration was initiated 10 days after bleomycin treatment. For chemotaxis assay, lung fibrocytes were isolated with immunomagnetic selection (CD45-positive mesenchymal cells) after culture and allowed to migrate toward chemokines in the presence or absence of pirfenidone. Moreover, the effect of pirfenidone on the expression of chemokine receptors on fibrocytes was evaluated. RESULTS: Pirfenidone significantly ameliorated bleomycin-induced pulmonary fibrosis as assessed with quantitative histology and collagen measurement. Fibrocyte pool size in bleomycin-treated mice lungs was attenuated from 26.5% to 13.7% by pirfenidone on FACS analysis. This outcome was also observed in a therapeutic setting. Immunohistochemistry revealed that fibrocytes were significantly decreased by pirfenidone administration compared with those in bleomycin-treated mice (P = 0.0097). Increased chemokine (CC motif) ligand-2 (CCL2) and CCL12 production in bleomycin-treated mouse lungs was significantly attenuated by pirfenidone (P = 0.0003 and P < 0.0001, respectively). Pirfenidone also attenuated macrophage counts stimulated by bleomycin in BAL fluid. Fibrocyte migration toward CCL2 and chemokine (CC motif) receptor-2 expression on fibrocytes was significantly inhibited by pirfenidone in vitro. CONCLUSIONS: Pirfenidone attenuated the fibrocyte pool size in bleomycin-treated mouse lungs via attenuation of CCL2 and CCL12 production in vivo, and fibrocyte migration was inhibited by pirfenidone in vitro. Fibrocyte inhibition is considered a mechanism of anti-fibrotic action of pirfenidone.

A case of pneumocystis pneumonia associated with everolimus therapy for renal cell carcinoma.

A 76-year-old female with advanced renal cell carcinoma had been treated with everolimus for 3 months. She visited our hospital because of a cough and fever lasting a few days. Chest X-rays showed bilateral infiltrative shadows, and a chest computed tomography scan showed homogeneous ground-glass opacities with mosaic patterns, especially in the apical region. The laboratory results revealed a decreased white blood cell count with lymphocytopenia and high levels of lactate dehydrogenase, C-reactive protein and KL-6. Pneumonitis was suspected and, therefore, everolimus therapy was interrupted. At that time, the pneumonitis was thought to be drug-induced interstitial lung disease. However, it was not possible to rule out pneumocystis pneumonia, because the patient was immunocompromised and the computed tomography findings suggested the possibility of pneumocystis pneumonia. The pneumonitis progressed rapidly and the patient developed respiratory failure, so we performed bronchoalveolar lavage to make a definitive diagnosis, and simultaneously started treatment with prednisolone and trimethoprim-sulfamethoxazole to cover both interstitial lung disease and pneumocystis pneumonia. A polymerase chain reaction assay of the bronchoalveolar lavage fluid was positive for Pneumocystis carinii DNA, and the serum level of ß-d-glucan was significantly elevated. Thus, the patient was diagnosed with pneumocystis pneumonia, which was cured by the treatment. Interstitial lung disease is a major adverse drug reaction associated with everolimus, and interstitial lung disease is the first condition suspected when a patient presents with pneumonitis during everolimus therapy. Pneumocystis pneumonia associated with everolimus therapy is rare, but our experience suggests that pneumocystis pneumonia should be considered as a differential diagnosis when pneumonitis is encountered in patients receiving everolimus therapy.

A multicenter phase II study on the safety of rho-kinase inhibitor (ripasudil) with needling for the patients after trabeculectomy.

Background: There is no established method of maintaining or reducing intra ocular pressure after the needling procedure for failing blebs post trabeculectomy. Regarding newer antihypertensive medications, ripasudil, which is a rho-associated protein kinase inhibitor ophthalmic solution, was able to prevent excessive scarring in vitro. This study aims to evaluate the safety of glaucoma patients submitted to the needling procedure and administered ripasudil for preventing scarring after the procedure. We also investigate the efficacy of ripasudil after needling for bleb failure through suppression of fibrosis to the bleb. Methods: This study is a multicenter, open-label, single-arm, phase II trial to evaluate the safety and efficacy of ripasudil in glaucoma patients after the needling procedure. Forty patients who will undergo needling at least 3 months after trabeculectomy will be recruited in Hiroshima university hospital and Hiroshima eye clinic. All the patients will instill ripasudil two times per day for three months after the needling procedure. The primary endpoint is the safety of ripasudil. Conclusions: We plan to establish the safety of ripasudil and to collect information involving the efficacy of ripasudil widely in this study.

Safety and Efficacy of the Rho-Kinase Inhibitor (Ripasudil) in Bleb Needling after Trabeculectomy: A Prospective Multicenter Study.

Ripasudil, a rho-associated protein kinase inhibitor ophthalmic solution, shows a protective effect in preventing excessive scarring in vitro. This study aims to evaluate the safety and efficacy of ripasudil for glaucoma patients submitted to the needling procedure. In this prospective, multicenter, single-arm study, we included 20 eyes of 20 patients with glaucoma who underwent the needling procedure without antimetabolites. All patients administered ripasudil after needling for three months. The primary endpoint of this study was the safety of ripasudil in patients, and the secondary endpoint was the change in IOP at 12 weeks after the needling procedure. No serious complications were found in the patients. One eye experienced pruritus and conjunctival follicle, while another eye had conjunctival follicle. These complications were transient and resolved quickly after discontinuation of ripasudil. The mean preoperative IOP was 14.6 ± 4.6 mmHg, which decreased to 11.0 ± 4.7 mmHg (p = 0.0062) at 1 week postoperatively. The IOP reduction effect continued to 12 weeks (11.8 ± 3.1 mmHg; p = 0.0448). The administration of the ROCK inhibitor, ripasudil, after the needling procedure is safe and effective in maintaining IOP for 12 weeks.

Organizing Pneumonia in a Case of cold Agglutinin Disease with Pulmonary Thrombosis.

Cold agglutinin disease is a subtype of autoimmune hemolytic anemia that occurs via the activation of specific anti-red blood cell antibodies (agglutinins) at low temperatures. Autoimmune hemolytic anemia has been reported to cause interstitial pneumonia; however, the underlying mechanism remains unclear. We herein report a 46-year-old man diagnosed with cold agglutinin disease complicated by pulmonary thrombosis and organizing pneumonia. Treatment with prednisolone improved the course of cold agglutinin disease and organizing pneumonia in a similar manner. To our knowledge, this is the first report of cold agglutinin associated with organizing pneumonia, suggesting a potential link between the two.

Clinicopathological features of malignant lymphoma in Japan: the Miyagi Study.

The Miyagi Study is an epidemiological study of malignant lymphoma, including immunological and genetic analyses, constructed by a population-based registration system covering Miyagi prefecture, Japan. A total of 1,552 newly diagnosed cases in Miyagi between 2002 and 2008 were enrolled in this study; 75% were B-cell lymphomas, 19% were T-cell and natural killer-cell (T/NK-cell) lymphomas, and 5% were Hodgkin's lymphomas. The most frequent subtype of B-cell lymphoma is diffuse large B-cell lymphoma, followed by follicular lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (51%, 24% and 8%, respectively). Thus, follicular lymphoma accounts for 18.2% of newly diagnosed cases in Miyagi; unexpectedly, its frequency is similar to that reported in Western countries. The common subtypes of T/NK-cell lymphoma are peripheral T-cell lymphoma, angioimmunoblastic T-cell lymphoma, and adult T-cell leukemia/lymphoma (30%, 15% and 14%, respectively). Most of the data are similar to those reported in Asian countries, except for follicular lymphoma. We also analyzed the CD20 expression in B-cell lymphomas by flow cytometry for the cell membrane expression and by immunohistochemistry for the cytoplasmic expression. The cell membrane expression of CD20 protein may determine the susceptibility of B-cell lymphomas to anti-CD20 antibody therapy. The lack of CD20 expression was confirmed by both methods in 4 cases of 585 newly diagnosed cases (0.7%) and in 5 of 67 recurrent cases (7.5%). Furthermore, 23 cases (6.5%) showed the discrepancy of CD20 expression between both methods. The Miyagi Study has revealed the latest epidemiological features of malignant lymphoma in Japan.

Primary Intramuscular Classic Hodgkin Lymphoma: A Rare Case Report.

Hodgkin lymphoma (HL) is a hematologic malignancy that typically presents with lymphadenopathy. We herein report a patient with HL who presented with an intramuscular mass that required differentiation from an inflammatory lesion. A 65-year-old Japanese woman was referred to our hospital with a chief complaint of chronic and expanding tumor in her left thigh. By surgical resection, she was diagnosed with primary intramuscular, Epstein-Barr virus-positive, mixed-cellularity classic HL. She received combined modality therapy, resulting in a complete response. Primary intramuscular classic HL is extremely rare. It should be listed as a differential diagnosis of intramuscular tumors.

Molecular machinery for non-vesicular trafficking of ceramide.

Synthesis and sorting of lipids are essential for membrane biogenesis; however, the mechanisms underlying the transport of membrane lipids remain little understood. Ceramide is synthesized at the endoplasmic reticulum and translocated to the Golgi compartment for conversion to sphingomyelin. The main pathway of ceramide transport to the Golgi is genetically impaired in a mammalian mutant cell line, LY-A. Here we identify CERT as the factor defective in LY-A cells. CERT, which is identical to a splicing variant of Goodpasture antigen-binding protein, is a cytoplasmic protein with a phosphatidylinositol-4-monophosphate-binding (PtdIns4P) domain and a putative domain for catalysing lipid transfer. In vitro assays show that this lipid-transfer-catalysing domain specifically extracts ceramide from phospholipid bilayers. CERT expressed in LY-A cells has an amino acid substitution that destroys its PtdIns4P-binding activity, thereby impairing its Golgi-targeting function. We conclude that CERT mediates the intracellular trafficking of ceramide in a non-vesicular manner.