Feasibility of Bioengineered Tracheal and Bronchial Reconstruction Using Stented Aortic Matrices.

Importance: Airway transplantation could be an option for patients with proximal lung tumor or with end-stage tracheobronchial disease. New methods for airway transplantation remain highly controversial. Objective: To establish the feasibility of airway bioengineering using a technique based on the implantation of stented aortic matrices. Design, Setting, and Participants: Uncontrolled single-center cohort study including 20 patients with end-stage tracheal lesions or with proximal lung tumors requiring a pneumonectomy. The study was conducted in Paris, France, from October 2009 through February 2017; final follow-up for all patients occurred on November 2, 2017. Exposures: Radical resection of the lesions was performed using standard surgical techniques. After resection, airway reconstruction was performed using a human cryopreserved (-80°C) aortic allograft, which was not matched by the ABO and leukocyte antigen systems. To prevent airway collapse, a custom-made stent was inserted into the allograft. In patients with proximal lung tumors, the lung-sparing intervention of bronchial transplantation was used. Main Outcomes and Measures: The primary outcome was 90-day mortality. The secondary outcome was 90-day morbidity. Results: Twenty patients were included in the study (mean age, 54.9 years; age range, 24-79 years; 13 men [65%]). Thirteen patients underwent tracheal (n = 5), bronchial (n = 7), or carinal (n = 1) transplantation. Airway transplantation was not performed in 7 patients for the following reasons: medical contraindication (n = 1), unavoidable pneumonectomy (n = 1), exploratory thoracotomy only (n = 2), and a lobectomy or bilobectomy was possible (n = 3). Among the 20 patients initially included, the overall 90-day mortality rate was 5% (1 patient underwent a carinal transplantation and died). No mortality at 90 days was observed among patients who underwent tracheal or bronchial reconstruction. Among the 13 patients who underwent airway transplantation, major 90-day morbidity events occurred in 4 (30.8%) and included laryngeal edema, acute lung edema, acute respiratory distress syndrome, and atrial fibrillation. There was no adverse event directly related to the surgical technique. Stent removal was performed at a postoperative mean of 18.2 months. At a median follow-up of 3 years 11 months, 10 of the 13 patients (76.9%) were alive. Of these 10 patients, 8 (80%) breathed normally through newly formed airways after stent removal. Regeneration of epithelium and de novo generation of cartilage were observed within aortic matrices from recipient cells. Conclusions and Relevance: In this uncontrolled study, airway bioengineering using stented aortic matrices demonstrated feasibility for complex tracheal and bronchial reconstruction. Further research is needed to assess efficacy and safety. Trial Registration: clinicaltrials.gov Identifier: NCT01331863.

[Design an educational intervention to prevent falls of older people in social housing: description of a research method]. / Concevoir une intervention éducative pour prévenir la chute des personnes âgées en logement social?: description d?une méthode de recherche.

INTRODUCTION: In a social environment in which prevention of falls in older people has become a public health issue, adaptation of housing for older people is particularly important. Based on the home-identity concept, the objective of this research was to design an educational model specifically adapted to the context of a Social Housing Company (SHC), focussing on elderly tenants who have experienced a fall in order to allow them to adapt their lodgings and avoid subsequent falls. METHOD: This article describes design-based research (DBR), which enabled the research committee (composed of professionals, tenants, and researchers) to construct the educational intervention based on analysis of the SHC context. RESULTS: The creation of a common approach within the research committee and the production of design-linked intentions enabled the creation of a formal intervention composed of four educational sessions, involving a private occupational therapist, an SHC social worker and a caretaker. DISCUSSION: The use of DBR can be justified by the research goal, i.e. validation of an educational model (based on the theoretical home-identity model) that can be transposed to a SHC. As this research is still underway, its quality criteria will only be partially described and will be completed by field experimentation. CONCLUSION: This exploratory study could eventually result in interventional research designed to assess this model in a multifactorial therapeutic patient education programme for older people at high risk of falls (e.g.: Personnes Âgées En Risque de Perte d'Autonomie device).

[Assessment of walking problems in the elderly person]. / Évaluation des troubles de la marche chez la personne âgée.

Walking problems represent a major public health issue in the geriatric population due to their frequency and the dramatic consequences they cause. They also mark a starting point of the physical frailty of elderly people. Their early detection should result in adapted functional rehabilitation in order to reduce the associated complications. Overview of walking problems in the elderly and the clinical means for assessing them.

[Training and action research in a short-stay geriatric oncology unit]. / Recherche-action et formation dans une unité de court séjour oncogériatrique.

A participative action research project was undertaken in a geriatric oncology hospital unit. It resulted in the training of paramedical staff regarding the specific care to be provided to elderly people with cancer.

Museum Moving to Inpatients: Le Louvre à l'Hôpital.

Anxiety and depressive symptoms are common in hospitalized patients. Arts and cultural programs were reported to enhance their quality of life. The Le Louvre à l'hôpital study presents a new approach in which the museum moves to the hospital by displaying and discussing artworks with patients interactively. Over one year, four large statues were disposed in the hospital gardens, 30 reprints of large painting were exhibited in the hospital hall, dining rooms, and circulations areas. A total of 83 small-group guided art discussions (90 min) were organized, which 451 patients attended. The 200 small-size reproductions of paintings placed in the patients' rooms were chosen based on their individual preferences. Decreased anxiety after the art sessions was reported by 160 of 201 patients (79.6%). Out of 451 patients, 406 (90%) said the art program had met their expectations, and 372 (82.4%) wished to continue the experience with caregivers (162 paramedics trained for art activity during 66 workshops). In conclusion, moving the museum to the hospital constitutes a valuable way to provide art activities for inpatients in large numbers, which may reduce hospital-related anxiety in many instances.

Obesity survival paradox in cancer patients: Results from the Physical Frailty in older adult cancer patients (PF-EC) study.

BACKGROUND & AIMS: the obesity survival paradox is an emergent issue in oncology, but its existence remains unclear particularly in older cancer patients. We aimed to assess the obesity survival paradox in older cancer patients. METHODS: all consecutive cancer outpatients 65 years and older referred for geriatric assessment (GA) before a decision on cancer treatment between November 2013 and September 2016 were enrolled in the PF-EC cohort study. The main outcome was 6-month mortality. A Cox univariate and multivariate proportional hazard regression models were performed with baseline GA, oncological variables (cancer site, extension and treatment modalities) and C-reactive protein (CRP). We assessed the prognostic value of body mass index categories (i.e. malnutrition <21, 21 ≤ normal weight ≤24.9, 25 ≤ overweight ≤29.9 and obesity ≥30 kg/m2) in the whole study population and according to the metastatic status. RESULTS: 433 patients with a mean age of 81.2 ± 6.0 years were included, 51% were women, 44.3% had digestive cancers, 18% breast cancer and 14.5% lung cancer and 45% metastatic cancers. Eighty-eight of these patients (20.3%) were obese at baseline. Mortality rate was 17% during the 6-month follow-up period. After adjustment for sex, gait speed, Mini-Mental State Examination, cancer site and exclusive supportive care, obesity (compared to normal weight) was independently and negatively associated with 6-month mortality only in metastatic patients (aHR 0.17, 95% CI [0.03-0.92], P = 0.04). CONCLUSION: our study confirms the obesity survival paradox in older cancer patients only in the metastatic group.

Diagnostic performance of gait speed, G8 and G8 modified indices to screen for vulnerability in older cancer patients: the prospective PF-EC cohort study.

BACKGROUND: The diagnostic performance of tools used to screen vulnerability in older cancer patients varies widely. We assessed the diagnostic performance of gait speed (GS) for assessing vulnerability in such patients. METHODS: All consecutive outpatients 65 years and older were referred for geriatric oncology assessment (GA) before a therapeutic decision between November 2013 and April 2016 in a bicentric observational and prospective cohort study. Vulnerability was defined as impaired score on at least one of the 6 domains of the GA. GS and the G8 index and G8 modified index were assessed at the first geriatric oncology visit during the GA. Sensitivity, specificity, positive and negative predictive value and positive and negative likelihood ratio were estimated. The accuracy of the three tools was analysed by the area under the receiver operating characteristic curve (AUC). RESULTS: Among 269 included patients (mean [SD] age, 81.3 years [5.9]; 55% women, 94.4% solid tumors; 39.4% with metastasis), 252 (93.7%) had impaired GA. With the GS threshold of 1 m/s, sensitivity was 79.4% (95% CI, 73.8-84.2), specificity 64.7% (38.3-85.8), and AUC 82.0 (74.0-90.0). The corresponding values for the G8 index were 90.1% (85.7-93.5), 35.3% (14.2-61.7), and 79.0 (70.0-88.0) and G8 modified index were 89.3% (84.8-92.8), 64.7% (38.3-85.8), and 84.0 (74.0-92.0). CONCLUSIONS: GS < 1 m/s with a single measure could be used as a new screening tool for detecting vulnerability in older cancer outpatients. This first external validation of the G8 modified index was very good.

Impaired mobility, depressed mood, cognitive impairment and polypharmacy are independently associated with disability in older cancer outpatients: The prospective Physical Frailty in Elderly Cancer patients (PF-EC) cohort study.

OBJECTIVE: To assess the prevalence of disability and the oncologic factors associated with disability in older outpatients with cancer. MATERIALS AND METHODS: The Physical Frailty in Elderly Cancer patients (PF-EC) study (France) is a prospective bicentric observational cohort study. Two hundred and ninety outpatients with cancer were included. A cross-sectional analysis of oncologic factors and geriatric variables associated with disability that were collected using a comprehensive geriatric assessment (CGA) was conducted. Disability was defined as impairment in activities of daily living (ADL) and/or instrumental activities of daily living (IADL), simplified to four items. Univariate and multivariate logistic models of disabled patients were performed. The three final multivariate models were compared using the area under the receiver operating characteristic curve (AUC/ROC) of the logistic model. RESULTS: The mean age was 80.6years, and 51% of the patients were women with various types of cancer. The prevalence of disability was 67.6%. No oncologic factors (cancer site, cancer extension) were associated with disability. Impaired mobility, poor functional status, depressive mood, cognitive impairment and polypharmacy were independently associated with disability (P<0.05). The AUC/ROC of the final models was similar. CONCLUSION: Disability was highly prevalent in older cancer outpatients before cancer treatment but was not associated with oncologic factors. Impaired mobility, depressed mood, cognitive impairment and polypharmacy were the geriatric variables significantly and independently associated with disability. Identifying these factors prior to cancer treatment could enable the implementation of corrective actions to improve patient autonomy before treatment and during follow-up.

Measurement of gait speed in older adults to identify complications associated with frailty: A systematic review.

Several frailty screening tests in older cancer patients were developed but their statistical performance is low. We aimed to assess whether measurement of usual gait speed (GS) alone could be used as a frailty screening test in older cancer patients. This systematic review was conducted on "pub med" between 1984 and 2014 and included reviews and original studies. Eligibility criteria were: GS over a short distance, alone or included in composite walking tests (Timed Get Up and Go test: TGUG, Short Physical Performance Battery: SPPB) in older people (aged 65 and over) living in a community setting and predictive value of GS on medical complications associated with frailty. 46 articles were finally selected. GS alone is consensual and recommended for screening sarcopenia in elderly. A slow GS is predictive of early death, disability, falls and hospitalization/institutionalization in older people living in a community setting. GS alone is comparable to composite walking tests that do not provide additional information on the medical complications associated with frailty. Despite few studies in geriatric oncology, GS seems to predict overall survival and disability. We suggest GS over 4m (at a threshold of 1m/s) as a new frailty screening test in older cancer patients (65 and over) to guide the implementation of a comprehensive geriatric assessment during the initial management phase or during follow-up. Prospective cohort studies are needed to validate this algorithm and compare it with other screening tool.

Comparison of the efficacy and safety of single-agent and doublet chemotherapy in advanced non-small cell lung cancer in the elderly: a meta-analysis.

BACKGROUND: In patients with advanced non-small cell lung cancer (NSCLC) aged more than 70 years, the benefit-to-risk ratio of doublet chemotherapy vs single-agent is not established. METHODS: We performed a meta-analysis (MA), with a PubMed query using keywords simultaneously (Randomized controlled trial, Aged, Anti-neoplastic combined chemotherapy protocols/therapeutic use, Carcinoma, Non-small cell lung/drug therapy). Abstracts from ASCO, WCLC, and ESMO proceedings were reviewed. Articles were also obtained by cross-checking references. Third-generation agents (gemcitabine, vinorelbine, paclitaxel, docetaxel) in combination with or without platinum were included. The efficacy outcomes were Overall Response Rate (ORR) and 1-Year Overall Survival (OS). We used EasyMA software and a random-effect model in case of heterogeneity. RESULTS: This MA comprised 10 studies including 2605 patients (mean age 74; 1866 men and 620 women; 654 stage IIIB and 1677 stage IV; 839 squamous cell cancers, 968 adenocarcinomas, 521 other pathological types). One-year OS (including the last trial by Abe) did not significantly improve for doublets compared with single-agents (HR 0.92; 95% Confidence Interval or CI: 0.82-1.03) whereas it improved significantly before inclusion of this last study, when the study by Quoix et al., the most favorable to doublets, was included. However, doublet chemotherapy significantly improved ORR after inclusion of Abe study (HR 1.51; 1.22-1.86; p<0.001). OS was not significantly improved, neither by doublets including platinum (HR 0.90, 0.70-1.16), nor by those without platinum (HR 0.94, 0.84-1.07). ORR, but not OS, was improved by doublets including a taxane (docetaxel and paclitaxel) (HR 1.72; 1.28-2.33) except for paclitaxel with a significant OS and ORR benefit. All-grade neutropenia thrombocytopenia and anemia were significantly more frequent with doublets than with single-agents (HR 1.26, 1.15-1.39; 1.75, 1.11-2.77 and 1.33, 1.17-1.52 respectively). Grade 3/4 thrombocytopenia and anemia but not neutropenia were significantly more frequent with doublets (HRs 2.13, 1.01-4.49 and 1.84, 1.29-2.63 respectively). CONCLUSION: Compared with single-agents, doublets significantly improved ORR but not OS. They induced significantly more frequent thrombocytopenia and anemia. The benefit-to-risk ratio of doublets in advanced NSCLC might be more favorable than that of single agents, based on ORR but not OS.

Human transplantation of a biologic airway substitute in conservative lung cancer surgery.

BACKGROUND: Pneumonectomies for lung cancer are associated with a high postoperative mortality, especially when right-sided, after neoadjuvant radiochemotherapy, and in patients over 70 years of age. Preliminary studies in our laboratory have shown that aortic grafts could be valuable airway substitutes. We report the first human bronchial transplantation of a cryopreserved aortic allograft used as a biologic airway substitute to prevent a pneumonectomy for lung cancer. METHODS: The procedure was performed in a high-risk 78-year old patient with an extensive right bronchopulmonary malignant tumor pretreated with chemotherapy. After a complete resection of the lung cancer using an upper bilobectomy with lymph node removal, mobilization procedures did not allow for a primary end-to-end bronchial anastomosis. A stent-supported cryopreserved aortic allograft from a certified tissue bank was interposed to restore the bronchial continuity with sparing of the lower lobe. RESULTS: The postoperative course was eventful for a supraventricular arrhythmia leading to mild pulmonary edema that resolved using standard medical therapy, and a right lower lobe atelectasis with bacterial colonization that required fiberoptic bronchoscopies in addition to antibiotic treatment. A 1-year postoperative evaluation found a well-functioning reimplanted lower lobe with no complications related to the cryopreserved aortic allograft or the stent. The patient recovered to his baseline activity with a satisfying health-related quality of life. CONCLUSIONS: We demonstrate the feasibility of this surgical innovation to prevent the high-risk procedure of pneumonectomy in a single case. If confirmed in larger series of selected patients, it could bring new perspectives in conservative lung cancer surgery.

Impact of 6-year body weight change on cardiac geometry and function in ageing adults: the SUpplémentation en Vitamines et Minéraux AntioXydants -2 (SU.VI.MAX-2) cardiovascular ultrasound substudy.

BACKGROUND AND OBJECTIVE: Although the relationships between BMI and cardiac geometry and function have been established, information remains limited on the impact of BMI, waist circumference and body composition variations over time on echocardiographic changes in ageing adults. METHODS AND RESULTS: Multiple linear regressions were used to correlate cardiac echographic parameters and baseline anthropometric data and their changes over 6 years in 280 participants of the SU.VI.MAX 2 cohort study. During the follow-up, BMI increased by 0.6 (95% confidence interval: 0.3-0.8) kg/m, waist circumference by 2.3 (1.6-3.0) cm and percentage body fat mass (%BFM) by 4.0 (3.4-4.6) %. A 6-year change (2001-2007) by 1 kg/m in BMI or 1 cm in waist circumference was associated with an increase in indexed left ventricular mass by 2.3 g/m (1.3-3.3, P < 0.001) and 0.4 g/m (0.06-0.6, P < 0.017), respectively, and an increase in left atrial area by 0.3 cm (0.1-0.5, P < 0.001) and 0.05 cm (0.003-0.10, P < 0.037), respectively. Follow-up left ventricular mass and left atrial area were not impacted by changes in percentage body fat mass. A significant correlation was observed between E-wave transmitral flow deceleration time and baseline BMI and waist circumference, but not with their changes over time. CONCLUSION: Changes in anthropometric markers over time are associated with increased left ventricular mass and left atrial size. These findings reinforce the potential benefit of a healthy diet and lifestyle to maintain body weight and, in turn, cardiac geometry and function in ageing adults.

[Avoidable hospital drug prescription in the elderly. A review of the literature]. / Iatrogénie médicamenteuse hospitalière évitable et personnes âgées.

Elderly persons are particularly exposed to drug reactions, especially drug interactions subsequent to multiple prescriptions. It is also recognized that the drug risk is the leading hospital risk involving 1 to 10% of all hospitalized patients. An analysis of the avoidable nature of drug reactions leads to consideration of a sequence of 4 events leading to drug exposure: prescription, delivery, administration and compliance. Each event in this sequence corresponds to a distinct person: physician, pharmacist, nurse, patient. This suggests that the prevention of drug reactions in hospitalized elderly persons requires implementation of an "alert-causal attributability-avoidability-prevention" system by the healthcare teams where physicians, pharmacists, and nurses work in close coordination with the patient.