Background
Carboplatin plus etoposide (CE) is a standard treatment for elderly patients with extensive‐disease small cell lung cancer (ED‐SCLC). However, amrubicin monotherapy (AMR) may be a feasible ...alternative. We compared the efficacies and safety profiles of CE and AMR for ED‐SCLC in elderly patients and chemotherapy‐naive patients with poor performance status (PS).
Methods
The records of SCLC patients who received CE or AMR as first‐line chemotherapy were retrospectively reviewed and their treatment outcomes evaluated.
Results
Eighty‐four patients (median age 72 years; 42 each received CR and AMR) were analyzed; 34 patients had a PS score of 2. There were no significant differences in patient characteristics between the treatment groups. The median progression‐free survival rates of patients in the CE and AMR groups were 5.8 and 4.8 months, respectively (P = 0.04); overall survival was 14.0 and 8.5 months, respectively (P = 0.089). Twenty‐three CE group patients received AMR as second‐line chemotherapy; their median overall survival from first‐line chemotherapy was 18.5 months. Grade 3 or higher neutropenia occurred more frequently in patients treated with AMR (64% vs. 40%; P = 0.02), as did febrile neutropenia (14% vs. 7%).
Conclusions
CE remains a suitable first‐line treatment for ED‐SCLC in elderly patients or those with poor PS in comparison with AMR.
Pegfilgrastim is a long-acting granulocyte colony-stimulating factor formulation that has been approved for the prevention of febrile neutropenia. We herein report a case of interstitial pneumonia ...following administration of pegfilgrastim. A 65-year-old man with stage IV small-cell lung cancer was treated with carboplatin and etoposide as third-line chemotherapy. Pegfilgrastim was administered during the second cycle of chemotherapy. On the day after the administration of pegfilgrastim, interstitial pneumonia developed. The respiratory condition improved with pulse steroid therapy; however, the patient eventually succumbed to cancer progression. In conclusion, interstitial pneumonia due to pegfilgrastim is rare; however, physicians should be aware of the possibility of this adverse effect.
Abstract Mantle cell lymphoma (MCL) is a subtype of B-cell non-Hodgkin's lymphoma. Most cases of MCL have extranodal involvement at the time of the initial diagnosis; however, endobronchial ...involvement is rare. An 87-year-old man was referred to our hospital because of dyspnea on exertion. A chest CT revealed diffuse irregular wall thickening of the trachea and bilateral bronchi. A bronchoscopy revealed a diffuse irregular surface of the tracheal and bilateral bronchial mucosa and polyposis-like lesions. He was diagnosed as having MCL based on an endobronchial biopsy, and the diagnosis was confirmed using immunohistochemical staining.
Background:
The infiltration of fat tissue into skeletal muscle, a condition referred to as muscle fatty infiltration or fatty degeneration, is regarded as an irreversible event that significantly ...compromises the motor function of skeletal muscle.
Purpose:
To investigate the effect of retinoic acid receptor (RAR) agonists in suppressing the adipogenic differentiation of fibroadipogenic progenitors (FAPs) in vitro and fatty infiltration after rotator cuff tear in mice.
Study Design:
Controlled laboratory study.
Methods:
FAPs isolated from mouse skeletal muscle were cultured in adipogenic differentiation medium in the presence or absence of an RAR agonist. At the end of cell culture, adipogenic differentiation was evaluated by gene expression analysis and oil red O staining. A mouse model of fatty infiltration—which includes the resection of the rotator cuff, removal of the humeral head, and denervation the supraspinatus muscle—was used to induce fatty infiltration in the supraspinatus muscle. The mice were orally or intramuscularly administered with an RAR agonist after the surgery. Muscle fatty infiltration was evaluated by histology and gene expression analysis.
Results:
RAR agonists effectively inhibited the adipogenic differentiation of FAPs in vitro. Oral and intramuscular administration of RAR agonists suppressed the development of muscle fatty infiltration in the mice after rotator cuff tear. In accordance, we found a significant decrease in the number of intramuscular fat cells and suppressed expression in adipogenic markers. RAR agonists also increased the expression of the transcripts for collagens; however, an accumulation of collagenous tissues was not histologically evident in the present model.
Conclusion:
Muscle fatty infiltration can be alleviated by RAR agonists through suppressing the adipogenic differentiation of FAPs. The results also suggest that RAR agonists are potential therapeutic agents for treating patients who are at risk of developing muscle fatty infiltration. The consequence of the increased expression of collagen transcripts by RAR agonists needs to be clarified.
Clinical Relevance:
RAR agonists can be used to prevent the development of muscle fatty infiltration after rotator cuff tear. Nevertheless, further studies are mandatory in a large animal model to examine the safety and efficacy of intramuscular injection of RAR agonists.
Introduction
The significance of the relationship between the spine and hip joints has been frequently discussed. However, the relationship between acetabular coverage and spinal sagittal alignment ...has not been fully elucidated as previous studies did not adequately control for factors that might affect the spinopelvic alignment. The aim of this study was to elucidate the impact of acetabular coverage on spinal sagittal alignment by comparing patient groups matched on sex, age, and the presence of hip and anterior impingement pain.
Materials and methods
We prospectively enrolled 30 women undergoing periacetabular osteotomy (PAO) for developmental dysplasia of the hip (DDH) and 30 women undergoing hip arthroscopic surgery (HAS) for labral tears. The lateral centre edge angle was measured on hip radiographs. In addition, the sagittal vertical axis, pelvic tilt, pelvic incidence, sacral slope (SS), and lumbar lordosis (LL) were measured on preoperative plain radiographs of the whole spine to assess the sagittal spinal alignment. Clinical and radiologic data were compared between the two groups (PAO vs. HAS).
Results
The patient groups did not differ in age and body mass index. The mean SS was significantly greater in the PAO group (41.6° ± 1.6°) than in the HAS group (35.3° ± 1.5°;
P
= 0.0039). Additionally, the mean LL was significantly greater in the PAO group (54.5° ± 2.0°) than in the HAS group (45.1° ± 1.9°;
P
= 0.0015).
Conclusions
The SS and LL were greater in patients with DDH than in patients with hip pain, but without DDH. Patients with DDH might show lumbar hyperlordosis to rotate the pelvis anteriorly, increasing the anterosuperior acetabular coverage.
Introduction: There are few reports on body composition, particularly muscle mass, in patients with adolescent idiopathic scoliosis (AIS). The purpose of this study was to measure body composition ...including muscle mass and estimated bone mass of patients with AIS using bioelectrical impedance analysis (BIA) and to clarify the relationship between the degree of scoliosis and body composition.Methods: The subjects were 210 girls (mean age 14.0 years, range 10-18 years) whose body composition was evaluated using BIA (Tanita MC-780). Body mass index (BMI), percent body fat (%BF), lean muscle mass index (LMI: muscle mass/height^2), and estimated bone mass index (eBoneMI: estimated bone mass/height^2) were determined by age and compared with those of previous reports. We divided 111 subjects whose bone maturation was complete into two groups for comparison of body composition metrics: those with Cobb angle <40° (moderate scoliosis group) and those with Cobb angle ≥40° (severe scoliosis group). The relationships between Cobb angle and each body composition parameter were evaluated.Results: Age-adjusted BMI, %BF, and LMI tended to be low at all ages compared with means for the healthy Japanese population as previously reported. BMI, LMI, and eBoneMI were significantly lower in the severe scoliosis group compared with those in the moderate scoliosis group (p<0.05). In addition, all BMI, LMI, and eBoneMI were weakly correlated with Cobb angle (r= −0.20, −0.26, and −0.24).Conclusions: On the basis of the results of this study, patients with AIS are thinner, with lower BMI, %BF, and LMI compared with healthy girls of the same age. Furthermore, factors such as lower BMI, lower muscle mass, and lower estimated bone mass were correlated with progressive scoliosis.
Fatty infiltration in muscle is often observed in patients with sizable rotator cuff tear (RCT) and is thought to be an irreversible event that significantly compromises muscle plasticity and ...contraction strength. These changes in the mechanical properties of the affected muscle render surgical repair of RCT highly formidable. Therefore, it is important to learn more about the pathology of fatty infiltration to prevent this undesired condition. In the present study, we aimed to generate a mouse model that can reliably recapitulate some of the important characteristics of muscular fatty infiltration after RCT in humans. We found that fatty infiltration can be efficiently induced by a combination of the following procedures: denervation of the suprascapular nerve, transection of the rotator cuff tendon, and resection of the humeral head. Using this model, we found that platelet-derived growth factor receptor-α (PDGFRα)-positive mesenchymal stem cells are induced after this intervention and that inhibition of PDGFR signaling by imatinib treatment can significantly suppress fatty infiltration. Taken together, the present study presents a reliable fatty infiltration mouse model and suggests a key role for PDGFRα-positive mesenchymal stem cells in the process of fatty infiltration after RCT in humans.
Neurotrophins such as NGF promote neuronal survival and differentiation via the cell surface TrkA neurotrophin receptor. Compounds with neurotrophic actions that are low in molecular weight and can ...permeate the blood–brain barrier are promising therapeutic agents against neurodegenerative diseases such as Alzheimer’s disease. Carnosic acid (CA), an electrophilic compound in rosemary, activates antioxidant responsive element (ARE)-mediated transcription via activation of Nrf2. In the present study, we discovered that CA strongly promotes neurite outgrowth of PC12h cells. NGF as well as CA activated Nrf2, whereas CA and NGF-mediated neuronal differentiation was suppressed by Nrf2 knockdown. On the other hand, CA activated TrkA-downstream kinase Erk1/2 independently of Nrf2. CA-induced p62/ZIP expression in an Nrf2-dependent manner, while the CA-induced neural differentiation was suppressed by p62/ZIP knockdown. Furthermore, CA-induced ARE activation was attenuated both by p62/ZIP knockdown and a Trk signal inhibitor. These results suggest that the CA induction of p62/ZIP by Nrf2 enhances TrkA signaling which subsequently potentiates Nrf2 pathway. This is the first demonstration that activation of the Nrf2-p62/ZIP pathway by a low-molecular natural electrophilic compound plays important roles in TrkA-mediated neural differentiation and may represent the common molecular mechanism for neurotrophic activities of electrophilic compounds.
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