Highlights • The aim of this study is to determine the molecular mechanisms behind stereotactic body radiation therapy (SBRT) stimulating mesenchymal stem cell (MSC) migration and differentiation. • ...Bone-marrow derived MSCs migrate to the tumor parenchyma and differentiate into pericytes, inducing tumor vasculogenesis after SBRT, and promoting tumor recurrence. • MSC migration and maturation may be abrogated with AMD3100 and imatinib. • This novel treatment strategy warrants clinical investigation.
Abstract Background and aims The body composition of patients with ulcerative colitis (UC) remains unclear. This study evaluated body composition in adult patients with UC and the associations of ...body composition with disease activity and surgical intervention. Methods This study included 99 patients with UC, 105 with Crohn’s disease (CD) and 60 controls. Skeletal muscle area (SMA), visceral fat area (VFA) and subcutaneous fat area (SFA) of the third lumbar vertebrae were evaluated by abdominal computed tomography. The effects of medical therapy and surgery on body composition in UC patients were determined. Results Sarcopenia was more frequent in UC patients (27.3%) than in controls (8.3%), but less frequent than in CD patients (59.0%). The prevalence of sarcopenia was significantly higher (33.8% vs. 4.5%, p <0.001), and SMA (144.26 vs. 182.32 cm2 , p <0.001), skeletal muscle index (SMI) (52.22 vs. 65.52 cm2 /m2 , p <0.001)significantly lower, in UC patients with high (≥6) than low (<6) Mayo score, but SFA and VFA were similar. The prevalence of sarcopenia and alterations in body composition were reversed, along with UC disease activity, following medical treatment or surgery. SMA and SMI correlated significantly with disease activity in UC patients. Multivariate analysis showed that sarcopenia (odds ratio, 8.49; 95% confidence interval, 1.80-40.10; p =0.007) was a negative predictor of high Mayo score in UC patients. Sarcopenic patients with UC had high probability of need for colectomy in Kaplan-Meier survival curves. Conclusions Sarcopenia is associated with high disease activity and poor clinical outcome in UC patients. Medical treatment and colectomy have positive effects on sarcopenia and skeletal muscle depletion.
Real-world data on the range and impact of comorbid health conditions that affect pediatric asthma are scant, especially from developing countries. Lack of data hinders effective diagnosis, ...treatment, and overall management of these complex cases. We, hereby, describe the common pediatric asthma comorbid conditions in terms of evidence for association, potential mechanisms of impact on asthma control, and treatment benefit. Obesity, upper airway allergies, dysfunctional breathing, multiple sensitizations, depressive disorders, food allergy, and gastro-esophageal reflux are common associations with difficult-to-treat asthma. On the other hand, asthma symptoms and/or management may negatively impact the well-being of children through drug adverse effects, worsening of anaphylaxis symptoms, and disturbing mental health.
Awareness of these ailments may be crucial for designing the optimum care for each asthmatic child individually and may ultimately improve the quality of life of patients and their families. A multidisciplinary team of physicians is required to identify and manage such comorbidities aiming to mitigate the over-use of asthma pharmacotherapy. Asthma research should target relevant real-world difficulties encountered at clinical practice and focus on interventions that would mitigate the impact of such comorbidities. Finally, policymakers and global healthcare organizations are urged to recognize pediatric asthma control as a healthcare priority and allocate resources for research and clinical interventions. In other words, global asthma control needs support by compassionate scientific partnership.
Abstract Objective Due to the limitations of the small single incision, an ideal preoperative localization technique is essential for surgical resection of small pulmonary nodules by uniportal ...video-assisted thoracoscopic surgery (VATS). The aim of this study is to evaluate the usefulness and safety of preoperative computed tomography (CT)-guided patent blue vital (PBV) dye localization in patients with small indeterminate pulmonary nodules who have undergone uniportal VATS for lung resection. Methods In this retrospective study, 177 consecutive patients (196 pulmonary nodules) who underwent preoperative CT-guided PBV dye localization and uniportal VATS from January 2013 to September 2015 were enrolled. Results The CT-dye localization procedure was performed successfully and correctly for 99.5% (195/196) of the nodules within a mean procedure time of 30 minutes. The mean size of the nodules was 7.8 mm, and their mean depth from the pleural surface was 18.3 mm. Most of the nodules (78.6%, 154/196) were pure ground-glass nodules (GGNs) and part-solid GGN with ground-glass opacity (GGO) of 50% or more. Asymptomatic pneumothorax occurred in 29.4% (52/177) of patients after the localization procedure, but none required invasive treatment. All nodules were successfully resected using uniportal VATS without any conversion to thoracotomy. The postoperative course was smooth, with a short mean hospital stay (3.3 ± 1.2 days) and a low morbidity rate (0.6%, 1/177). Conclusions Preoperative CT-guided PBV dye localization is a feasible, safe, and accurate procedure. It makes uniportal VATS easy for small, poorly located pulmonary nodules with GGO predominance and synchronous multiple nodules.
Abstract Objective To demonstrate the clinical efficacy of autologous mitochondrial transplantation in preparation for translation to human application using an in vivo swine model. Methods A left ...mini-thoracotomy was performed on Yorkshire pigs. The pectoralis major was dissected, and skeletal muscle tissue was removed and used for the isolation of autologous mitochondria. The heart was subjected to regional ischemia (RI) by temporarily snaring the circumflex artery. After 24 minutes of RI, hearts received 8 × 0.1 mL injections of vehicle (vehicle-only group; n = 6) or vehicle containing mitochondria (mitochondria group; n = 6) into the area at risk (AAR), and the snare was released. The thoracotomy was closed, and the pigs were allowed to recover for 4 weeks. Results Levels of creatine kinase-MB isoenzyme and cardiac troponin I were significantly increased ( P = .006) in the vehicle-only group compared with the mitochondria group. Immune, inflammatory, and cytokine activation markers showed no significant difference between groups. There was no significant between-group difference in the AAR ( P = .48), but infarct size was significantly greater in the vehicle group ( P = .004). Echocardiography showed no significant differences in global function. Histochemistry and transmission electron microscopy revealed damaged heart tissue in the vehicle group that was not apparent in the mitochondria group. T2-weighted magnetic resonance imaging and histology demonstrated that the injected mitochondria were present for 4 weeks. Conclusions Autologous mitochondrial transplantation provides a novel technique to significantly enhance myocardial cell viability following ischemia and reperfusion in the clinically relevant swine model.
Background A circular muscle myotomy preserving the longitudinal outer esophageal muscular layer is often recommended during peroral endoscopic myotomy (POEM) for achalasia. However, because the ...longitudinal muscle fibers of the esophagus are extremely thin and fragile, and completeness of myotomy is the basis for the excellent results of conventional surgical myotomy, this modification needs to be further debated. Here, we retrospectively analyzed our prospectively maintained POEM database to compare the outcomes of endoscopic full-thickness and circular muscle myotomy. Study Design According to the myotomy depth, 103 patients with full-thickness myotomy were assigned to group A, while 131 patients with circular muscle myotomy were assigned to group B. Symptom relief, procedure-related parameters and adverse events, manometry outcomes, and reflux complications were compared between groups. Results The mean operation times were significantly shorter in group A compared with group B (p = 0.02). There was no increase in any procedure-related adverse event after full-thickness myotomy (all p < 0.05). During follow-up, treatment success (Eckardt score ≤ 3) persisted for 96.0% (95 of 99) of patients in group A and for 95.0% (115 of 121) of patients in group B (p = 0.75). There were no statistically significant differences in pre- and post-treatment D-value of symptom scores and lower esophageal sphincter pressures between groups (both p > 0.05). The overall clinical reflux complication rates were also similar (21.2% vs 16.5%, p = 0.38). Conclusions Short-term symptom relief and manometry outcomes of each method were comparable. Full-thickness myotomy significantly reduced the procedure time but did not increase the procedure-related adverse events or clinical reflux complications.
Objective Primary neuroendocrine tumors of the thymus (TNET) are exceedingly rare. We studied a large series of TNET identified through the International Thymic Malignancy Interest Group and the ...European Society of Thoracic Surgeons databases. Methods This was a retrospective multicenter study of patients undergoing operation for TNET between 1984 and 2012. Outcome measures were: overall survival (OS) and cumulative incidence of recurrences (CIR). OS was analyzed using the Kaplan-Meier method and CIR was analyzed using competing risk analysis. Associations with clinical and prognostic factors for OS and CIR were evaluated using the log rank test and Gray test. Results Two hundred five patients with TNET were treated: 25 patients received induction therapy (19 chemotherapy CT and 6 radiotherapy RT). Data about resection status were available in 47% of cases: complete resection was performed in 52 patients (54%). Masaoka-Koga stages I, II, III, and IV were observed in 12, 33, 56, and 47 patients, respectively. Atypical carcinoid was the commonest histologic subtype (71 cases; 40%). One hundred one patients with TNET received adjuvant treatment; 52 patients died and 36 experienced a recurrence. The median OS was 7.5 years; 5-year OS was 68%, and 5-year CIR was 39%. OS was significantly influenced by Masaoka-Koga stage ( P = .02) and completeness of resection ( P = .03). CIR significantly increased in high Masaoka-Koga stages ( P = .04). Histologic subtype was not associated with either OS or CIR. Conclusions Our results confirm the high biologic aggressiveness of these rare neoplasms; pathologic stage and completeness of resection were demonstrated to be strong prognostic factors, whereas histology did not influence patients outcome.
Background Robotic hepatectomy has been suggested as a safe and effective management of liver disease. However, no large case series have documented the learning curve for robotic major hepatectomy. ...Method We conducted a retrospective study for robotic major hepatectomy performed by the same operative team between January 2012 and October 2015 and evaluated the learning curve for operation time using the cumulative sum method, presented as cumulative sumoperation time. Results Overall, there were 183 robotic hepatectomies, 92 of which were performed in patients who underwent robotic major hepatectomy: left hemihepatectomy was performed in 32 (34.8%) patients, right hemihepatectomy in 41 (44.6%), left trisectionectomy in 3 (3.3%), right trisectionectomy in 6 (6.5%), and 8-5-4 trisegmentectomy in 10 (10.8%). The median duration of surgery was 434 minutes (142–805 minutes) and the median blood loss was 195 mL (50–2,000 mL). Fifty-nine percent of patients had malignancies, and those with advanced stages of cancer had more blood loss during an operation. The cumulative sumoperation time model of robotic major hepatectomy suggested that the learning curve comprised 3 characteristic phases: initial (phase 1, 15 patients), intermediate (phase 2, 25 patients), and mature (phase 3, 52 patients). The learning effects were underlined by shorter operation time and hospital stay after phase 1 and less blood loss after phase 2. Conclusion This is the largest series regarding robotic major hepatectomy. Our findings suggest that a solid training program based on the learning curve should be considered for beginners of robotic hepatectomy. Participants should evaluate the evolution of our minimally invasive hepatectomy before considering our robotic experience.
Summary Background Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation, and has many components including mucus hypersecretion, oxidative stress, and airway ...inflammation. We aimed to assess whether carbocisteine, a mucolytic agent with anti-inflammatory and antioxidation activities, could reduce the yearly exacerbation rate in patients with COPD. Methods We did a randomised, double-blind, placebo-controlled study of 709 patients from 22 centres in China. Participants were eligible if they were diagnosed as having COPD with a postbronchodilator forced expiratory volume in 1 s (FEV1 ) to forced vital capacity (FVC) ratio (FEV1 /FVC) of less than 0·7 and an FEV1 between 25% and 79% of the predicted value, were aged between 40 and 80 years, had a history of at least two COPD exacerbations within the previous 2 years, and had remained clinically stable for over 4 weeks before the study. Patients were randomly assigned to receive 1500 mg carbocisteine or placebo per day for a year. The primary endpoint was exacerbation rate over 1 year, and analysis was by intention to treat. This trial is registered with the Japan Clinical Trials Registry ( http://umin.ac.jp/ctr/index/htm ) number UMIN-CRT C000000233. Findings 354 patients were assigned to the carbocisteine group and 355 to the placebo group. Numbers of exacerbations per patient per year declined significantly in the carbocisteine group compared with the placebo group (1·01 SE 0·06 vs 1·35 SE 0·06), risk ratio 0·75 (95% CI 0·62–0·92, p=0·004). Non-significant interactions were found between the preventive effects and COPD severity, smoking, as well as concomitant use of inhaled corticosteroids. Carbocisteine was well tolerated. Interpretation Mucolytics, such as carbocisteine, should be recognised as a worthwhile treatment for prevention of exacerbations in Chinese patients with COPD. Funding Kyorin Pharmaceuticals.
We propose a method for detecting many-body localization (MBL) in disordered spin systems. The method involves pulsed coherent spin manipulations that probe the dephasing of a given spin due to its ...entanglement with a set of distant spins. It allows one to distinguish the MBL phase from a noninteracting localized phase and a delocalized phase. In particular, we show that for a properly chosen pulse sequence the MBL phase exhibits a characteristic power-law decay reflecting its slow growth of entanglement. We find that this power-law decay is robust with respect to thermal and disorder averaging, provide numerical simulations supporting our results, and discuss possible experimental realizations in solid-state and cold-atom systems.
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