In situ proteomic analysis by MALDI imaging identifies ubiquitin and thymosin-β4 as markers of malignant intraductal pancreatic mucinous neoplasms

PurposeIntraductal pancreatic mucinous neoplasms (IPMN) are precancerous cystic lesions. The aim was to investigate the in situ IPMN proteome using MALDI (Matrix-Assisted Laser Desorption/Ionisation) imaging and to characterize biomarkers associated with the grade of dysplasia.Experimental designFrozen human Branch duct -IPMN sections were selected according to dysplasia and proteomic analyses were performed by MALDI imaging to obtain mass spectra distribution. The most discriminating peaks were identified using tissue extraction and nanoLC-ESI-MS/MS. Identified peaks were validated in independent series of IPMN by immunochemistry on surgical specimens (tissue-microarrays (TMA), n = 45) and endoscopic ultrasound fine-needle aspiration (EUS FNA) samples (n = 25).ResultsBD-IPMN samples with low (n = 10) and high (n = 10) grades of dysplasia were analyzed. Differential spectra of proteins were found in the two groups with significantly different intensities (n = 15). The two peaks (intense in high grade IPMN) (m/z 8565 and 4747) were characterized as the monomeric ubiquitin (Mascot score = 319.22) and an acetylated fragment of thymosin-β4 (2–42) (Omssa score = 1.37 E−9). Validation on TMA and EUS FNA samples confirmed that ubiquitin was overexpressed in high grade dysplasia (p = 0.04 and p = 0.0004). Thymosin-β4 expression was confirmed on TMA by immunohistochemistry on high grade IPMN (p = 0.011).ConclusionUbiquitin and thymosin-β4 are overexpressed in IPMN with high grade dysplasia. Positive immunochemical staining on EUS-FNA material is a major argument in support of preventive resection.     

MACVIA-LR,Reference site of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) in Languedoc Roussillon

The Région Languedoc-Roussillon is the umbrella organisation for an interconnected and integrated project on AHA covering the 3 pillars of the European Innovation Partnership on Active and Healthy Ageing. All sub-activities (A1: electronic pharmaceutical file, A2: falls prevention initiative, A3: frailty, B3: chronic respiratory diseases, chronic diseases with comorbidities, oral health and hepatitis virus C chronic infection, C2 and D4 active and independent living and handicap) are included in MACVIA-LR that has a strong political commitment and includes all stakeholders (public, private, patients, policy makers). It is one of the Reference Sites of the European Innovation Partnership on Active and Healthy Ageing built around chronic diseases, ageing and handicap. The framework of MACVIA-LR has the vision that the prevention and management of CDs is essential for AHA promotion and for the reduction of handicap. The main objective of MACVIA-LR is to develop innovative solutions for a network of Living Labs in order to improve the care of patients affected by CDs in the Languedoc-Roussillon area and to disseminate the innovation.     

Optimization of the Esperanza window trap for the collection of the African onchocerciasis vector Simulium damnosum sensu lato

A simple inexpensive trap (Esperanza window trap) was shown recently to collect significant numbers of Simulium ochraceum sensu lato, a major vector of Onchocerca volvulus in Mesoamerica. Here, we report studies optimizing this trap for the collection of Simulium damnosum s.l., the major vector of O. volvulus in Africa. A shortened, blue and black striped version of the Esperanza window trap, when baited with a combination of CO₂ and worn trousers, rivalled human landing collections in the number of S. damnosum s.l. females collected. Traps baited with a commercially available human skin lure and CO₂ resulted in collections that were not significantly different than those obtained from traps baited with worn trousers and CO₂. This suggests that the Esperanza window trap may offer a replacement for human landing collections for monitoring onchocerciasis transmission in Africa.     

The lowest VE/VCO2 ratio best identifies chronic thromboembolic pulmonary hypertension

Introduction

The natural history of acute pulmonary embolism (PE) under treatment is about a gradual resolution of the thrombi, and uncommonly, the development of chronic thromboembolic pulmonary hypertension (CTEPH). We hypothesized that ventilatory efficiency parameters during cardiopulmonary exercise testing (CPET) may be able to monitor the process and predict CTEPH.

Methods

15 patients rehabilitated from acute PE (total resolution of thrombi), 44 patients with chronic PE (with residual thrombi), 66 patients with CTEPH, and 36 sedentary healthy controls performed incremental CPET.

Results

The lowest VE/VCO₂ was higher in CTEPH patients than that in chronic PE and rehabilitated patients (43.4 L/min vs 29.9 L/min vs 27.1 L/min, p < 0.005). The VE/VCO₂ slope (48.4 L/min/L/min vs 29.9 L/min/L/min vs 28.0 L/min/L/min, p < 0.005) and oxygen uptake efficiency plateau (OUEP) (37.1 L/min vs 27.0 L/min vs 25.2 L/min, p < 0.005) had the similar changes. In logistic regression analysis, the lowest VE/VCO₂ ≥ 34.35 L/min was the best predictor of CTEPH (OR 159.0, 95% CI 36.0-702.3, p < 0.001). The lowest VE/VCO₂ was higher in chronic PE patients compared with the controls (29.9 L/min vs 26.5 L/min, p < 0.05), but there was no difference between the rehabilitated patients and the controls. In multiple linear regression analysis, the percentage of vascular obstruction by ventilation-perfusion lung scanning (PVO) was the most significant independent predictor for indices of ventilatory efficiency in chronic PE and rehabilitated patients.

Conclusions

CTEPH is associated with weakened ventilatory efficiency. The lowest VE/VCO2 ratio has the best capability to predict CTEPH. Ventilatory inefficiency improves along with recovery of acute PE.     

Clinical significance of the WHO grades of follicular lymphoma in a population-based cohort of 505 patients with long follow-up times

The prognostic value of grading follicular lymphoma has been debated since the 1980s. There is consensus that World Health Organization (WHO) grades 1 and 2 are indolent, but not whether grades 3A or 3B are aggressive. We retrospectively reviewed the follicular lymphoma diagnoses according to the 2008 WHO classification in all diagnostic specimens from a population-based cohort of 505 patients with a median follow-up time of 10·0years (range, 4·6-16·0). After excluding 43 patients with concomitant diffuse large B-cell lymphoma, 345 remained with grade 1-2, 94 with grade 3A, and 23 with grade 3B follicular lymphoma. Grades 1-2 and 3A seemed equally indolent, with indistinguishable clinical courses, even in patients receiving anthracyclines. Compared with grades 1-3A and independently of clinical factors, grade 3B correlated with higher mortality (P=0·008), but outcome was improved after upfront anthracycline-containing therapy (P=0·015). In contrast to grade 1-3A patients, grade 3B patients experienced no relapses or deaths beyond 5years of follow-up. Furthermore, patients with grade 3B were predominantly male and seldom presented with bone-marrow involvement. We conclude that follicular lymphoma grade 1-3A is indolent and incurable with conventional therapy. Grade 3B appears to be an aggressive but curable disease.     

Surgical safety checklist and operating room efficiency: results from a large multispecialty tertiary care hospital

Background

The Surgical Safety Checklist (SSC) improves patient safety and outcomes; however, barriers to effective use include the perceived negative impact on operating room (OR) efficiency. The purpose of this study was to determine the effect of SSC implementation on OR efficiency.

Methods

All operations at our large multispecialty tertiary care hospital were reviewed for 1-year pre- and 1-year post-SSC implementation. OR efficiency included operating room time, operation time, first starts on time, same-day cancellations, and OR disposable cost.

Results

A total of 35,570 operations were reviewed: 17,204 pre-SSC and 18,366 post-SSC. There was no difference between groups for operating room time (P = .93), operation time (P = .66), first starts on time (P = .15), and same-day cancellations (P = .57). The mean OR disposable cost was significantly lower ($70/operation) for the post-SSC group (P < .01).

Conclusions

The implementation of an SSC does not negatively impact OR efficiency and should not be considered a barrier to effective use. Our data suggest that SSC use can reduce overall cost per surgical procedure.     

胃大部切除术后3年胃癌患者生活质量的EORTC QLQ-C30与QLQ-STO22联合评价

目的:采用欧洲癌症研究与治疗组织(EORTC)生活质量核心30问卷调查(QLQ-C30)和QLQ-STO22评价胃癌术后3年患者的生活质量(QOL).方法:对96名胃大部切除术后3年的胃癌患者和90名年龄和性别相匹配的门诊体检健康者进行研究.胃癌患者和健康者平均年龄分别为53.2岁±8.1岁和54.8岁±7.9岁.88.5%患者为I期胃癌术后.患者自行完成QLQ-C30量表和QLQ-STO22量表,对各评分进行统计分析.结果:胃癌患者和健康者EORTC QLQ-C30整体健康状况和QOL评分无显著差异.胃癌患者的认知功能、情绪功能和疲劳要优于对照健康者.但胃癌患者恶心和呕吐评分、经济困难、反流、进食受限和体型评分较健康者差.其他评分未见显著差异.结论:胃癌术后3年,患者的QOL整体评分基本恢复至正常水平,但在某些方面,特别是与上消化道相关的症状(如恶心呕吐、反流、进食受限等)与健康者存在差距.有必要基于这些差异采取针对性的措施进行治疗和护理.     

A case of an anaplastic meningioma metastasizing to the mediastinal lymph nodes

Context: Grade II and III (World Health Organization classification) meningiomas rarely develop in the spinal cord. However, we experienced a case with an anaplastic meningioma that developed in the spinal cord at the cervicothoracic junction and metastasized to the mediastinal lymph nodes. No such cases have previously been reported.

Findings: The patient was a 68-year-old man who developed back pain that did not affect his daily living. He developed left lower limb paralysis, and was admitted after magnetic resonance imaging (MRI) revealed an intramedullary tumor at the level of cervical vertebra 7 and thoracic vertebra 1. Positron emission tomography revealed tracer uptake in the intramedullary tumor and the mediastinal lymph nodes, suggesting a metastatic spinal cord tumor or malignant lymphoma. A lymph node biopsy was then performed. Although the tumor was highly malignant, its primary site was not identified. Detailed examinations by several other departments revealed no abnormalities. On hospital day 30, his left lower limb paralysis deteriorated, and MRI revealed that the tumor had grown. Thus, laminaplasty, laminectomy, and tumor resection were performed. The tumor was an anaplastic meningioma that resembled mediastinal lymph node tissue, and other tumor lesions were not found. These findings suggested that an anaplastic meningioma had metastasized to the mediastinal lymph nodes. The patient did not respond to radiotherapy, and he was transferred to another hospital.

Conclusion: In cases of intramedullary spinal tumors with metastasis without other potential primary tumor lesions, early diagnosis and treatment should be performed while considering anaplastic meningioma.