APOE4 Increases Energy Metabolism in APOE-Isogenic iPSC-Derived Neurons.

The apolipoprotein E4 (APOE4) allele represents the major genetic risk factor for Alzheimer's disease (AD). In contrast, APOE2 is known to lower the AD risk, while APOE3 is defined as risk neutral. APOE plays a prominent role in the bioenergetic homeostasis of the brain, and early-stage metabolic changes have been detected in the brains of AD patients. Although APOE is primarily expressed by astrocytes in the brain, neurons have also been shown as source for APOE. However, the distinct roles of the three APOE isoforms in neuronal energy homeostasis remain poorly understood. In this study, we generated pure human neurons (iN cells) from APOE-isogenic induced pluripotent stem cells (iPSCs), expressing either APOE2, APOE3, APOE4, or carrying an APOE knockout (KO) to investigate APOE isoform-specific effects on neuronal energy metabolism. We showed that endogenously produced APOE4 enhanced mitochondrial ATP production in APOE-isogenic iN cells but not in the corresponding iPS cell line. This effect neither correlated with the expression levels of mitochondrial fission or fusion proteins nor with the intracellular or secreted levels of APOE, which were similar for APOE2, APOE3, and APOE4 iN cells. ATP production and basal respiration in APOE-KO iN cells strongly differed from APOE4 and more closely resembled APOE2 and APOE3 iN cells, indicating a gain-of-function mechanism of APOE4 rather than a loss-of-function. Taken together, our findings in APOE isogenic iN cells reveal an APOE genotype-dependent and neuron-specific regulation of oxidative energy metabolism.

PENDAH program for parents with children with attention deficit hyperactivity disorder. French adaptation of a behavioral parent training group: pilot study.

Behavioral parent training (BPT) is recognized as an effective part of the care offered to children with attention deficit hyperactivity disorder (ADHD). The aim of this pilot study was to objectively examine the effect that this intervention may have on motor activity, in addition to the measures classically found in this type of study. Parents of 24 school-aged children (6-12 year) with ADHD who met eligibility criteria were enrolled in the study. Before, after and five months after the intervention, we used three-dimensional accelerometers over one-week periods to measure the children's motor activity, and questionnaires for parental stress, quality of life, ADHD symptoms, anxiety and sensory disorders. To measure motor activity, a control group of normotypic children matched for age, sex and socio-professional category was set up. The experimental group showed slight decreases in motor activity compared with the control group, particularly in the classroom. The intervention showed improvements for parents in average stress and quality of life, and for children in average intensity global ADHD symptom, inattention, opposition and aggression, in line with previous studies on the effectiveness of BPT. The trial is the first clinical study to assess the effects of BPT on motor activity in children with ADHD.

Tracheoplasty With Use of an Intercostal Muscle Flap for Caustic Necrosis.

We report a case of intercostal muscle flap used in tracheobronchial reconstruction for extensive necrosis after burn lesions of the posterior wall. A 32-year-old man attempted suicide by ingestion of caustic material. He underwent emergency total esogastrectomy, tracheostomy, and feeding jejunostomy. Ten days later, endoscopy showed complete destruction of the membranous trachea, extending from the tracheostomy to the carina. Reconstruction was conducted with the patient under venovenous extracorporeal membrane oxygenation by use of a pedicled intercostal muscle flap. The patient was weaned from respiratory support on the 14th postoperative day. Examination of a biopsy specimen from the flap 7 months after tracheoplasty showed ciliated neoepithelium.

Prophylactic tracheotomy and lung cancer resection in patient with low predictive pulmonary function: a randomized clinical trials.

BACKGROUND: Whether prophylactic tracheotomy can shorten the duration of mechanical ventilation (MV) in high risk patients eligible for lung cancer resection. The objective was to compare duration of MV and outcome in 39 patients randomly assigned to prophylactic tracheotomy or control. METHODS: Prospective randomized controlled, single-center trial (ClinicalTrials.gov Identifier: NCT01053624). The primary outcome measure was the cumulative number of MV days after operation until discharge. The secondary outcome measures were the 60 days mortality rate, the ICU and the hospital length of stay, the incidence of postoperative respiratory, cardiac and general complications, the reventilation rate, the need of noninvasive ventilation (NIV), the need of a tracheotomy in control group and the tracheal complications. RESULTS: The duration of MV was not significantly different between the tracheotomy group (3.5±6 days) and the control group (4.7±9.3 days) (P=0.54). Among patients needing prolonged MV >4 days, tracheotomy patients had a shortened duration of MV than control patients (respectively 11.4±7.1 and 20.4±9.6 days, P=0.04). The rate of respiratory complications were significantly lower in the tracheotomy group than in the control group (28% vs. 51%, P=0.03). Six patients (15%) needed a postoperative tracheotomy in the control group because of a prolonged MV >7 days. Tracheotomy was associated with a reduced need of NIV (P=0.04). There was no difference in 60-day mortality rate, cardiac complications, intensive care unit and hospital length of stay. No death was related with the tracheotomy. CONCLUSIONS: Prophylactic tracheotomy in patients with ppo FEV1 <50% who underwent thoracotomy for lung cancer resection provided benefits in terms of duration of prolonged MV and respiratory complications but was not associated with a decreased mortality rate, ICU and hospital length of stay and non-respiratory complications.

Extended resection of non-small cell lung cancer invading the left atrium, is it worth the risk?

Only few reports of surgical approach to T4 lung carcinoma invading the heart have been reported in the medical literature. It is also controversial if such cancer should be treated by surgery. The aim of this review is to assess the current risk/benefit ratio of the surgical management of non-small cell lung cancer (NSCLC) invading the left atrium, especially in the light of a multidisciplinary approach. We also expose our surgical experience and the procedure we have developed in order to increase our rate of complete resection as this criterion appears to be mandatory as well as patients' nodal status in order to increase life expectancy.

Lymphovenous anastomosis for recurrent swelling syndrome and chylous effusion due to cervical thoracic duct cyst.

Thoracic duct (TD) cyst is an uncommon abnormality that can be manifested as a cervical swelling. Pathogenesis includes congenital or degenerative weakness of the wall of the TD and obstruction of the lymphoid flow. Diagnosis is crucial to eliminate malignant disease or vein thrombosis and can be established by imaging and needle aspiration. We report a case of recurrent cervical swelling with spontaneous chylothorax and chyloperitoneum. A TD cyst with a terminal obstruction of the TD was diagnosed on lymphangiography. Treatment by microsurgical lymphovenous anastomosis was successful, and the patient was free of symptom 3 years later.

Left atrial resection for T4 lung cancer without cardiopulmonary bypass: technical aspects and outcomes.

BACKGROUND: Extended resection for lung cancer may improve survival of selected patients. Left-atrial resection is infrequently performed and surgical techniques are rarely reported; thus, oncologic results and survival rates remain uncertain. Our study describes surgical techniques, postoperative outcomes, and oncologic results of patients who received a combined multimodality treatment. METHODS: Between October 2004 and March 2012 in our institution, 19 patients underwent extended lung resection involving the left atrium without cardiopulmonary bypass. We reviewed perioperative treatments, surgical procedures, and postoperative morbidity, mortality, and long-term survival rates. RESULTS: Sixteen patients (68.4%) underwent neoadjuvant treatment including chemotherapy or radiotherapy. Eighteen pneumonectomies (94.7%) were performed, of which 12 (63.1%) were right sided. Dissection of the interatrial septum was complete in 4 patients (33.3%). Complete resection was achieved in 17 patients (89.4%) and 2 other patients (10.5%) were considered R1. The T-status was pT4 in all patients. Overall postoperative morbidity was 52.6%. The 30-day mortality rate was 10.5% and the 90-day mortality rate was 15.7%. Fifteen patients (93.7%) underwent adjuvant treatment. The mean follow-up time was 32.5 months. The 5-year probability of survival was 43.7%. Three patients (15.7%) were alive at greater than 6 years postsurgery. CONCLUSIONS: Extended lung surgery with partial resection of the left atrium is a feasible procedure with acceptable morbidity. An interatrial septum dissection, by increasing the length of the atrial cuff, allows complete resection. Long-term survival can be achieved in highly selected patients who have undergone multimodal therapy.