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Idiopathic pulmonary fibrosis (IPF) is a fatal disorder without an effective therapy to date. In a double-blind, randomized, placebo-controlled trial, 107 patients were prospectively evaluated for efficacy of a novel compound, pirfenidone. The difference in the change in the lowest oxygen saturation by pulse oximetry (SpO[2]) during a 6-minute exercise test, the primary endpoint, from baseline to 6 months was not significant between the two groups (p = 0.0722). In a prespecified subset of patients who maintained a SpO[2] greater than 80% during a 6-minute exercise test at baseline, the lowest SpO[2] improved during a 6-minute exercise test in the pirfenidone group at 6 and 9 months (p = 0.0069 and 0.0305, respectively). Positive treatment effect was demonstrated in secondary endpoints: (1) change in VC measurements at 9 months (p = 0.0366) and (2) episodes of acute exacerbation of IPF occurring exclusively in the placebo group during the 9 months (p = 0.0031). Significant adverse events were associated with pirfenidone; however, adherence to treatment regimen was similar between pirfenidone and placebo groups. In conclusion, treatment with pirfenidone improved VC and prevented acute exacerbation of IPF during the 9 months of follow-up. Future long-term studies are needed to clarify the overall safety and efficacy of pirfenidone in IPF. [ABSTRACT FROM AUTHOR]

The effects of sodium thiosulfate (STS) were studied in patients who received a combination therapy of cis-dichlorodiammineplatinum (CDDP) and vindesine. In this study, 61 patients with non-small-cell lung carcinoma were randomized to receive either CDDP and vindesine (both given i.v.) with i.v. STS [30 patients, STS(+) group] or CDDP and vindesine without STS [31 patients, STS(-) group]. In the STS(+) group, 16 patients who showed an improvement (reduction in tumor size or relief of symptoms) after the first course received the second STS(+) treatment, and 15 patients in the STS(-) group who showed an improvement after the first course received the second STS(-) treatment. Urinary levels of beta 2-microglobulin (BMG) and N-acetyl-beta-D-glucosaminidase (NAG) were measured as an index of proximal tubular function. Analysis of both levels indicated that STS suppressed CDDP nephrotoxicity to a minimal level. Serum BMG, blood urea nitrogen (BUN), and total as well as 24-h creatinine clearance levels were measured as an index of glomerular function. There were no significant differences in these levels between the STS(+) and STS(-) groups. The urinary recoveries of total platinum 24 h after CDDP administration were 29% and 21% in the STS(+) and STS(-) groups, respectively. The mean plasma concentrations of total platinum at 24 h after CDDP administration were 2.24 and 2.70 micrograms/ml in the STS(+) and STS(-) groups, respectively. There were no significant differences in the response rates of the STS(+) and STS(-) groups at a fixed dose of 100 mg/m2 CDDP. Therefore, the present study clearly demonstrates that systemic administration of STS reduces the side effects of CDDP to a minimal level without impairing its antitumor activity and that STS treatment is applicable in a repeated chemotherapy using CDDP alone or in combination with other antitumor agents. [ABSTRACT FROM AUTHOR]

Objectives: We examined the relationship between plasma eicosapentaenoic acid (EPA) level and long-term all-cause death (ACD) and cardiovascular or limb events in patients with peripheral arterial disease (PAD). Method: We performed a prospective cohort study on 637 PAD patients. The endpoints were ACD, major adverse cardiovascular events (MACEs), and lower extremity arterial events (LEAEs). Results: The incidences of ACD, MACEs, and LEAEs had correlation with EPA levels (p <0.05). Plasma EPA level had significant positive correlations with high-density lipoprotein cholesterol, triglyceride, and estimated glomerular filtration rate (eGFR), and negative correlation with C-reactive protein (CRP). In Cox stepwise multivariate analysis, lower EPA (hazard ratio [HR]: 0.996, 95% confidence interval [CI]: 0.993-1.000, p = 0.034), ankle brachial pressure index (ABI), body mass index, serum albumin, eGFR, age, CRP, D-dimer, critical limb ischemia, diabetes, cerebrovascular disease (CVD), and statin were related to ACD (p <0.05); lower EPA (HR: 0.997, 95% CI: 0.994-1.000, p = 0.038), ABI, serum albumin, eGFR, age, diabetes, coronary heart disease, CVD, and statin were related to MACEs (p <0.05); and lower EPA (HR: 0.988, 95% CI: 0.982-0.993, p <0.001), ABI, and low-density lipoprotein cholesterol were related to LEAEs (p <0.05). Conclusions: Low plasma EPA level was a significant risk factor for ACD, MACEs, and LEAEs in patients with PAD., (@ 2024 The Editorial Committee of Annals of Vascular Diseases.)

Background: In real-world studies, the rate of discontinuation of nintedanib (NT) varies from 4% to 53%. Switching anti-fibrotic treatment in patients with idiopathic pulmonary fibrosis (IPF) has not been adequately investigated, and data on the tolerability and efficacy of changes in anti-fibrotic treatment is limited in clinical practice., Objective: To identify factors associated with poor continuation of NT, efficacy and predictors of deterioration after switching from NT to pirfenidone (PFD) in patients with IPF., Subjects and Methods: One hundred and seventy patients with IPF in whom NT was introduced between April 2017 and March 2022 were included to investigate NT continuation status and the effect of switching to PFD., Results: A total of 123 patients (72.4%) continued NT for 1 year and had a significantly higher %forced vital capacity (FVC) at NT introduction than those who discontinued within 1 year (80.9% ± 16.3% vs. 71.9% ± 22.1%, P = 0.004). The determinant of poor NT continuation was the high GAP stage. On the other hand, 28 of 36 patients who discontinued NT because of disease progression switched to PFD. Consequently, FVC decline was suppressed before and after the change. The predictor of deterioration after the switch was a lower body mass index., Conclusions: In patients with IPF, early NT introduction increased continuation rates, and switching to PFD was effective when patients deteriorated despite initial NT treatment., Competing Interests: All authors contributed substantially to this work and are responsible for the consent of the manuscript. KS have received lecture fees from Nippon Boehringer Ingelheim Co., Ltd and Shionogi & Co., Ltd. The other authors have no financial relationships relevant to this article. All authors have no competing non-financial interests., (Copyright: © 2024 Sugino et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Osteoblast-derived semaphorin3A (Sema3A) has been reported to be involved in bone protection, and Sema3A knockout mice have been reported to exhibit chondrodysplasia. From these reports, Sema3A is considered to be involved in chondrogenic differentiation and skeletal formation, but there are many unclear points about its function and mechanism in chondrogenic differentiation. This study investigated the pharmacological effects of Sema3A in chondrogenic differentiation. The amount of Sema3A secreted into the culture supernatant was measured using an enzyme-linked immunosorbent assay. The expression of chondrogenic differentiation-related factors, such as Type II collagen (COL2A1), Aggrecan (ACAN), hyaluronan synthase 2 (HAS2), SRY-box transcription factor 9 (Sox9), Runt-related transcription factor 2 (Runx2), and Type X collagen (COL10A1) in ATDC5 cells treated with Sema3A (1,10 and 100 ng/mL) was examined using real-time reverse transcription polymerase chain reaction. Further, to assess the deposition of total glycosaminoglycans during chondrogenic differentiation, ATDC5 cells were stained with Alcian Blue. Moreover, the amount of hyaluronan in the culture supernatant was measured by enzyme-linked immunosorbent assay. The addition of Sema3A to cultured ATDC5 cells increased the expression of Sox9, Runx2, COL2A1, ACAN, HAS2, and COL10A1 during chondrogenic differentiation. Moreover, it enhanced total proteoglycan and hyaluronan synthesis. Further, Sema3A was upregulated in the early stages of chondrogenic differentiation, and its secretion decreased later. Sema3A increases extracellular matrix production and promotes chondrogenic differentiation. To the best of our knowledge, this is the first study to demonstrate the role of Sema3A on chondrogenic differentiation., (© 2024. The Author(s).)

Background: There are limited reports on the relationship between plasma homocysteine (Hcy) levels and long-term all-cause death (ACD), cardiovascular events, or limb events in patients with peripheral arterial disease (PAD). We examined the relationship between plasma Hcy levels and 15-year these events in PAD patients., Methods: We performed a prospective cohort study in 955 PAD patients. The patients were divided into four groups based on plasma Hcy levels with median (interquartile range). The endpoints were cumulative incidences of ACD, major adverse cardiovascular events (MACE), and MACE plus limb events (MACLE)., Results: The incidences of ACD, MACE, and MACLE were correlated with plasma Hcy levels (P < 0.05). In multiple regression analysis, plasma Hcy had positive correlations with C-reactive protein (CRP), men, and critical limb ischemia (CLI) and negative correlations with estimated glomerular filtration rate (eGFR) and high-density lipoprotein cholesterol (p < 0.05). In Cox multivariate analysis, higher Hcy (HR 1.614, 95 % CI 1.229-2.119, p = 0.001), age, CRP, brain natriuretic peptide (BNP), D-dimer, lower body mass index, ankle brachial pressure index (ABI), serum albumin, eGFR, CLI, coronary heart disease (CHD), cerebrovascular disease, and diabetes were related to ACD; higher Hcy (HR 1.242, 95 % CI 1.004-1.535, p = 0.045), age, BNP, lower ABI, serum albumin, diabetes, and CHD were related to MACE; and higher Hcy (HR 1.290, 95 % CI 1.057-1.574, p = 0.012), BNP, lower ABI, serum albumin, CHD, and diabetes were related to MACLE (P < 0.05). Statins improved ACD, MACE, and MACLE (p < 0.01)., Conclusions: Plasma Hcy was a risk factor for 15-year ACD, MACE, and MACLE in patients with PAD., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: Several studies have found associations between periodontitis and various types of cancer. Since the site of head and neck cancer (HNC) has contiguity or proximity to the oral cavity, it may be particularly influenced by oral inflammation. This study aimed to determine whether HNC patients have poor oral health as compared to those with other types of cancer., Methods: This study retrospectively examined oral environmental factors including periodontal inflamed surface area (PISA), a new periodontal inflammatory parameter. A total of 1030 cancer patients were divided into the HNC (n = 142) and other cancer (n = 888) groups. Furthermore, the HNC group was divided into high (n = 71) and low (n = 71) PISA subgroups, and independent risk factors affecting a high PISA value were investigated., Results: Multivariate logistic regression analysis showed that number of missing teeth (odds ratio 1.72, 95% CI 1.15-2.56, P < 0.01), PISA (odds ratio 1.06, 95% CI 1.03-1.06, P < 0.05), and oral bacterial count (odds ratio 1.02, 95% CI 1.01-1.03, P < 0.01) were independent factors related to HNC. In addition, multivariate logistic regression analysis indicated that current smoker (odds ratio 7.51, 95% CI 1.63-34.71, P < 0.01) and presence of untreated dental caries (odds ratio 3.33, 95% CI 1.23-9.00, P < 0.05) were independent risk factors affecting high PISA values in HNC patients., Conclusion: HNC patients have higher levels of gingival inflammation and poor oral health as compared to patients with other types of cancer, indicating that prompt oral assessment and an effective oral hygiene management plan are needed at the time of HNC diagnosis., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Estrogen is a steroid hormone that induces skeletal growth and affects endochondral ossification of the long tubular bone growth plate during the growth period. However, the effects of estrogen on endochondral ossification of the mandibular condylar cartilage are unclear. In this study, ovariectomized Wistar/ST rats were used to investigate the longitudinal effects of estrogen on mandibular growth. The rats were administered different doses of estrogen. Longitudinal micro-computed tomographic scanning, histological staining and ELISA on plasma growth hormone were performed to examine the effects of estrogen on mandibular growth. The results showed that mandibular growth was suppressed throughout the growth period by estrogen in a dose-dependent manner. In addition, long-term administration of a high dose of estrogen to the rats resulted in significant increase in growth hormone throughout the growth period, significant circularization of cell nuclei in the proliferative layer, intensely staining cartilage matrix in the subchondral bone, and significant suppression of estrogen receptor (ER) alpha and beta expression in the mandibular cartilage. However, regardless of estrogen concentration, in the posterior part of the mandibular cartilage, ER expression extended to both the hypertrophic and proliferative layers. These results indicate that estrogen suppresses mandibular growth throughout the growth period. Additionally, it influences endochondral ossification via its effect on ERs., Competing Interests: Declarations of competing interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We report a rare case of acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) after coronavirus disease 2019 (COVID-19) vaccination. Clinicians should be aware of this COVID-19 vaccination-induced AE in IPF., Competing Interests: None declared., (© 2022 The Authors. Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.)

We report a very rare case of combined small cell lung carcinoma (C-SCLC) which presented as persistent cough and was due to endotracheal metastases. Clinicians should be aware of this unusual site of metastases from a C-SCLC., Competing Interests: None declared., (© 2022 The Authors. Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.)

Competing Interests: Competing interests: None declared.

A 53-year-old non-smoking Japanese woman was admitted to our hospital with a 20-year history of wet cough and dyspnoea on exertion. Bronchial asthma (BA) had been diagnosed 20 years earlier. Although she has been treated with high-dose inhaled corticosteroid, she had experienced frequent exacerbation of BA, and short-term oral corticosteroid bursts were occasionally administered. High-resolution CT of the chest revealed diffuse centrilobular nodules with bronchial wall thickening and patchy ground-glass opacities in both lungs. Lung biopsy specimens showed widespread cellular bronchiolitis with follicle formations in the membranous and respiratory bronchioles, accompanied by marked infiltration of plasma cells and eosinophils. In addition, immunohistochemical immunoglobulin G4 (IgG4) staining revealed many IgG4-positive plasma cells, and the ratio of IgG4-positive cells to IgG-positive cells exceeded 40%. The final diagnosis was eosinophilic bronchiolitis with marked IgG4-positive plasma cell infiltration in association with BA. With benralizumab therapy, her clinical condition dramatically improved., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Although antifibrotic drugs, including nintedanib and pirfenidone, slow the progression of idiopathic pulmonary fibrosis (IPF), there is little data about the timing of start of antifibrotic treatment in real-world clinical practice. The present study aimed to clarify the efficacy of nintedanib and pirfenidone in patients with early-stage IPF., Methods: We compared survival and disease progression between patients with IPF with Japanese Respiratory Society (JRS) disease severity system stage I with and without oxygen desaturation on the 6-min walk test (6MWT) and increased the gender-age-physiology (GAP) staging. We examined the efficacy of antifibrotic drugs in patients with early-stage IPF., Results: The severity of stage I IPF (n = 179) according to the JRS criteria consisted of the following GAP staging criteria: stage I, 111 cases; stage II, 58 cases; stage III, 10 cases. The duration from the initial visit to disease progression and survival time was significantly shorter in JRS stage I patients with oxygen desaturation on the 6MWT or with increased GAP staging (unfavorable group) compared with patients without those factors. In the unfavorable group, the relative decline in percentage predicted forced vital capacity (%FVC) over 6 months was significantly lower in patients undergoing antifibrotic treatment compared with non-treated patients., Conclusion: Antifibrotic drugs have a beneficial effect on the decline in %FVC in Japanese patients with early-stage IPF who have oxygen desaturation on the 6MWT or increased GAP staging., (© 2021. The Author(s).)

Background: There are no established therapeutic options available for idiopathic pleuroparenchymal fibroelastosis (IPPFE) apart from supportive care and lung transplantation. Furthermore, it is known that IPPFE with a usual interstitial pneumonia (UIP) pattern and lower lobe predominance is a disease entity distinct from idiopathic pulmonary fibrosis (IPF). To our knowledge, few studies are available that report on the efficacy of antifibrotic agents for IPPFE with UIP., Aim: The aim of this study was to compare the efficacy of antifibrotic agents between IPPFE with UIP and typical IPF in real-world clinical practice., Patients and Methods: A retrospective analysis was performed on the medical records of all patients at two interstitial lung disease centres. Sixty-four patients were diagnosed as having IPPFE with UIP and 195 patients were diagnosed with typical IPF. We compared the efficacy of antifibrotic agents between these two groups., Results: Survival time was significantly shorter in the patients with IPPFE with UIP. Some 125 patients were administered antifibrotic agents for over 6 months (34 with IPPFE with UIP and 91 with typical IPF). Reduced forced vital capacity (FVC) 6 months after treatment with antifibrotic agents was significantly greater in the IPPFE with UIP group than in those in the typical IPF group. Moreover, the change in % predicted FVC was significantly greater during the follow-up in patients with IPPFE with UIP compared with those with typical IPF., Conclusions: The efficacy of antifibrotic agents was limited in patients with IPPFE with UIP. Thus, IPPFE with UIP remains a fatal and progressive disease., Competing Interests: Conflict of interest: K. Sugino reports a lecture fee from Nippon Boehringer Ingelheim Co., Ltd., outside the submitted work. Conflict of interest: H. Ono has nothing to disclose. Conflict of interest: H. Shimizu has nothing to disclose. Conflict of interest: T. Kurosawa has nothing to disclose. Conflict of interest: K. Matsumoto has nothing to disclose. Conflict of interest: M. Ando has nothing to disclose. Conflict of interest: K. Mori has nothing to disclose. Conflict of interest: E. Tsuboi has nothing to disclose. Conflict of interest: S. Homma reports a lecture fee from Nippon Boehringer Ingelheim Co., Ltd., outside the submitted work; and is a member of an endowed department sponsored by Teijin Pharma, Co., Ltd, Nippon Boehringer Ingelheim, Co., Ltd, Shionogi & Co., Ltd, Chugai Pharmaceutical Co., Ltd, and Asahi Kasei Pharma Co., Ltd. Conflict of interest: K. Kishi reports a lecture fee from Nippon Boehringer Ingelheim Co., Ltd., outside the submitted work., (Copyright ©ERS 2021.)

Objectives: Excessive mechanical stress is assumed to be a major cause of temporomandibular joint (TMJ) osteoarthritis (OA). +Focal adhesion kinase (FAK) is a cytoplasmic non-receptor tyrosine kinase involved in a variety of signaling pathways. Little has been reported on the function of FAK in TMJ-OA. In the present study, we investigated the effect of FAK inhibition on TMJ cartilage under excessive mechanical loading stress., Materials and Methods: Articular cartilage explants were harvested from the TMJ of rats and subjected to mechanical loading in the presence of an FAK inhibitor in organ culture. The gene expression of inflammatory cytokines was examined after the application of mechanical loading with or without FAK inhibitor. Paraffin-embedded sections of articular cartilage were stained with hematoxylin and eosin, safranin O and fast Green, toluidine blue, TUNEL staining, and immunohistochemical staining and was performed to investigate the protein expression of IL-1β and MMP-13., Results: Treatment with FAK inhibitor reduced the gene expression of inflammatory cytokines and inhibited the degradation of articular cartilage, as determined histologically. FAK inhibitor treatment also suppressed the protein expression of IL-1β and MMP-13 in the hypertrophic zone, as determined immunohistologically., Conclusion: Treatment with FAK inhibitor suppresses inflammation and protects condylar cartilage under excessive mechanical loading., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)

Background: In spinocerebellar degeneration (SCD) patients, general and regional anesthesia may cause postoperative dysfunction of respiratory, nerve and muscle systems. We present the surgical case of thymoma developed in patient with SCD., Case Presentation: A 47-year-old woman with spinocerebellar degeneration was admitted because of a well-defined mass measuring 48 × 31 mm in anterior mediastinum. She showed limb, truncal, ocular, and speech ataxia; hypotonia; areflexia; sensory disturbances; and muscle weakness. Her eastern cooperative oncology group performance status was 4. Surgical resection was performed via video-assisted thoracic surgery and under general anesthesia only without epidural analgesia. The mass was diagnosed as type B1 thymoma without capsular invasion (Masaoka stage I). The patients got a good postoperative course by cooperation with anesthesiologists and neurologists in perioperative managements. She has been well over 3 years of follow-up., Conclusions: In conclusion, careful surgical and anesthesia management is essential for providing an uneventful postoperative course in patients with SCD. Especially, selection of minimal invasive approach and avoid diaphragmatic nerve damage are the most important points in surgical procedures.

Although bronchogenic cysts are the most common primary mediastinal cysts, intracardiac bronchogenic cysts are extremely rare. We report a case of a bronchogenic cyst of the interatrial septum in a 42-year-old woman who presented with recent onset of dyspnea on exertion. Cardiac investigations including transthoracic echocardiography and computed tomography revealed a cystic homogeneous mass in the interatrial septum. The patient underwent surgical resection, and the resultant atrial septal defect was repaired using an autologous pericardial patch. Histopathological examination of the resected specimen revealed findings consistent with a benign bronchogenic cyst. Although bronchogenic cysts are extremely rare, they should be considered in the differential diagnoses of intracardiac tumors. Complete resection of bronchogenic cysts is recommended primarily for diagnostic and potentially therapeutic purposes.

Pulmonary sarcoidosis should be considered in the differential diagnosis of miliary opacities in bilateral upper lobes predominance., (© 2020 The Authors. Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.)

An 81-year-old woman presented with progressive congestive heart failure. Seventeen years before, she had undergone mitral valve replacement with a mechanical prosthesis. Echocardiography revealed severe aortic stenosis with a depressed left ventricular ejection fraction of 32%.At first, rescue balloon aortic valvuloplasty (BAV) was performed. After transient improvement of symptoms, she was readmitted 2 months later with recurrence of severe congestive heart failure. Transcatheter aortic valve implantation (TAVI) with an Edwards Sapien valve was performed. During the procedure, BAV was performed to confirm that the balloon did not interfere the movement of the mechanical valve. Moreover, supported by a veno-arterial extracorporeal membrane oxygenation, we could prevent myocardial ischemia during rapid pacing and slowly deploy the valve in a precise position. TAVI can be safely and successfully performed in patients with a preexisting mechanical mitral prosthesis.

Background Statins reduce aneurysm growth in mouse models of Marfan syndrome, although the mechanism is unknown. In addition to reducing cholesterol, statins block farnesylation and geranylgeranylation, which participate in membrane-bound G-protein signaling, including Ras. We dissected the prenylation pathway to define the effect of statins on aneurysm reduction. Methods and Results Fbn1 C1039G/+ mice were treated with (1) pravastatin (HMG-CoA [3-hydroxy-3-methylglutaryl coenzyme A] reductase inhibitor), (2) manumycin A ( MA ; FPT inhibitor), (3) perillyl alcohol ( GGPT 1 and -2 inhibitor), or (4) vehicle control from age 4 to 8 weeks and euthanized at 12 weeks. Histological characterization was performed. Protein analysis was completed on aortic specimens to measure ERK (extracellular signal-regulated kinase) signaling. In vitro Fbn1 C1039G/+ aortic smooth muscle cells were utilized to measure Ras-dependent ERK signaling and MMP (matrix metalloproteinase) activity. Pravastatin and MA significantly reduced aneurysm growth compared with vehicle control (n=8 per group). In contrast, PA did not significantly decrease aneurysm size. Histology illustrated reduced elastin breakdown in MA -treated mice compared with vehicle control (n=5 per group). Although elevated in control Marfan mice, both phosphorylated c-Raf and phosphorylated ERK 1/2 were significantly reduced in MA -treated mice (4-5 per group). In vitro smooth muscle cell studies confirmed phosphorylated cR af and phosphorylated ERK 1/2 signaling was elevated in Fbn1 C1039G/+ smooth muscle cells (n=5 per group). Fbn1 C1039G/+ smooth muscle cell Ras-dependent ERK signaling and MMP activity were reduced following MA treatment (n=5 per group). Corroborating in vitro findings, MMP activity was also decreased in pravastatin-treated mice. Conclusions Aneurysm reduction in Fbn1 C1039G/+ mice following pravastatin and MA treatment was associated with a decrease in Ras-dependent ERK signaling. MMP activity can be reduced by diminishing Ras signaling.

A 69-year-old man underwent carotid artery stenting through the right femoral artery with a percutaneous vascular closure device for hemostasis. Eleven days later, an infective femoral artery pseudoaneurysm was diagnosed by computed tomography. At surgery, a defect in the femoral artery was observed, corresponding to the remnants of the closure device. Removal of the foreign material, debridement, wound irrigation, and arterial patch plasty were performed, but the infection and leg ischemia did not improve. After several failed attempts to revascularize and control the infection, obturator foramen bypass was performed. The postoperative course was uneventful, indicating the usefulness of this procedure.

Background: Total arch replacement and ascending aorta and arch replacement are the gold standard treatments for aortic arch aneurysm and are possible treatment strategies for chronic type A dissection, with good reported outcomes. However, because total arch replacement is extremely invasive, it can be difficult to perform in some patients. We designed an endovascular total arch repair procedure with the use of in situ fenestration and commercially available devices, and we present our initial experience., Methods: Seven patients (chronic type A aortic dissection, n = 3; thoracic arch aneurysm, n = 4) who underwent endovascular total arch repair with the use of in situ fenestration thoracic endovascular aortic repair from a zone 0 landing were retrospectively analyzed. All the procedures were performed under general anesthesia and cardiopulmonary bypass. The triple branches were manually punctured in a retrograde manner with the use of an 18-gauge/30-cm needle or a 21-gauge aspiration needle, and all the branches were reconstructed with the use of stent grafts; balloon touch-up was performed if appropriate., Results: The procedure was successful in 6 of the 7 patients; the remaining 1 patient additionally underwent an axillary-axillary artery bypass during the operation because the left subclavian artery was difficult to puncture. All the patients had an acceptable postoperative course, with no 30-day and in-hospital deaths. None of the patients had endoleaks, and all the patients exhibited a reduction in aneurysm diameter or thrombosed false lumen during a mean follow-up period of 17.6 months., Conclusions: Endovascular total arch repair with the use of in situ fenestration can be performed with commercially available devices with acceptable interim results., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Fifteen consecutive prosthetic valve endocarditis (PVE) patients were operated from March 2009 to September 2014. The average age of patients was 68 years ( range 49 to 82) and 7 patients were male. The interval between initial surgery and reoperation was 62.4 months(range 2.6 to 340.9). Seven of these cases(47%) developed PVE within the 1st year after surgery were defined as early PVE. All microorganisms isolated from blood cultures in early PVE were Staphylococcus species. Generally, the infective prosthetic valve was removed 1st, then all infective tissues were excised from the periannular cavity. A new prosthetic valve was replaced in supra-annular fashion. One patient who had a severe discontinuity between the most part of left ventricle and aorta necessitated a root replacement. One patient in aortic PVE, needed an additional patch-plasty of anterior mitral leaflet. The mean cardiopulmonary bypass and aortic clamping times were 250 minutes( range 132 to 426) and 165 minutes( range 117 to 309), respectively. Four patients needed permanent pacemaker implanted for complete A-V block. Five patients had transient acute renal failure, and 1 required dialysis could be weaned at 40 post operative day. Average postoperative hospital stay was 39 days (range 21 to 108), and the operative mortality was 0%. The postoperative follow up was 3.1 years( range 0.6 to 6.0), all patients were doing well without re-infection and heart failure except 1 patient died by non-cardiac disease.

Background: Allergic sensitization is a key step in the pathogenesis of asthma. However, little is known about the molecules that are critical regulators for establishing allergic sensitization of the airway. Thus, we conducted global gene expression profiling to identify candidate genes and signaling pathways involved in house dust mite (HDM)-induced allergic sensitization in the murine airway., Methods: We sensitized and challenged mice with HDM or saline as a control through the airway on days 1 and 8. We evaluated eosinophilia in bronchoalveolar lavage fluid (BALF), airway inflammation, and mucus production on days 7 and 14. We extracted total RNA from lung tissues of HDM- and saline-sensitized mice on days 7 and 14. Microarray analyses were performed to identify up-regulated genes in the lungs of HDM-sensitized mice compared to the control mice. Data analyses were performed using GeneSpring software and gene networks were generated using Ingenuity Pathways Analysis (IPA)., Results: We identified 50 HDM-mediated, stepwise up-regulated genes in response to allergic sensitization and amplification of allergic airway inflammation. The highest expressed gene was myeloid differentiation-2 (MD-2), a lipopolysaccharide (LPS)-binding component of Toll-like receptor (TLR) 4 signaling complex. MD-2 protein was expressed in lung vascular endothelial cells and was increased in the serum of HDM-sensitized mice, but not in the control mice., Conclusions: Our data suggest MD-2 is a critical regulator of the establishment of allergic airway sensitization to HDM in mice. Serum MD-2 may represent a potential biomarker for the amplification of allergic sensitization and allergic inflammation., (Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Inhaled corticosteroids enhance airway epithelial barrier integrity. However, the mechanism by which they accomplish this is unclear. Therefore, we investigated steroid-inducible genes and signaling pathways that were involved in enhancing airway epithelial barrier integrity., Methods: A human bronchial epithelial cell line (16HBE cells) was cultured with 10(-6) M dexamethasone (DEX) for 3 days to enhance epithelial barrier integrity. After measuring transepithelial electrical resistance (TER) and paracellular permeability, we extracted total RNA from 16HBE cells and performed microarray and pathway analysis. After we identified candidate genes and a canonical pathway, we measured TER and immunostained for tight junction (TJ) and adherent junction (AJ) proteins in cells that had been transfected with specific small interfering RNAs (siRNAs) for these genes., Results: We identified a nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated oxidative stress response pathway which was primarily involved in the steroid-induced enhancement of airway epithelial barrier integrity. Transfecting cells with Nrf2 specific siRNA reduced the steroid-induced enhancement of airway epithelial barrier integrity and the accumulation of TJ and AJ proteins at sites of cell-cell contact. Moreover, based on pathway analysis, aldehyde oxidase 1 (AOX1) was identified as a downstream enzyme of Nrf2. Transfecting cells with AOX1-specific siRNA also reduced the steroid-induced enhancement of airway epithelial barrier integrity., Conclusions: Our results indicated that the Nrf2/AOX1 pathway was important for enhancing airway epithelial barrier integrity. Because the airway epithelium of asthmatics is susceptible to reduced barrier integrity, this pathway might be a new therapeutic target for asthma., (Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

We report the case of a 74-year-old man who developed type IA endoleak after endovascular thoracic aortic repair. The patient was admitted with expansion of the aneurysm after TEVAR, for additional therapy. Fluoroscopy and cone-beam computed tomography-guided direct transthoracic sac puncture and complete embolization of the endoleak channels with metal coils and glue were performed, and resulted in complete exclusion of the endoleak. One month after the coil embolization, the type IA endoleak was completely excluded, and the thoracic aneurysm had decreased in size.