[Geriatric Trauma Center DGU®: Evaluation of clinical and economic parameters : A pilot study in a german university hospital]. / AltersTraumaZentrum DGU®: Evaluation klinischer und ökonomischer Parameter : Eine Pilotstudie an einer deutschen Universitätsklinik.

BACKGROUND: Previous studies on orthogeriatric models of care suggest that there is substantial variability in how geriatric care is integrated in the patient management and the necessary intensity of geriatric involvement is questionable. OBJECTIVE: The aim of the current prospective cohort study was the clinical and economic evaluation of fragility fracture treatment pathways before and after the implementation of a geriatric trauma center in conformity with the guidelines of the German Trauma Society (DGU). METHODS: A comparison of three different treatment models (6 months each) was performed: A: Standard treatment in Orthopaedic Trauma; B: Special care pathways with improvement of the quality management system and implementation of standard operating procedures; C: Interdisciplinary treatment with care pathways and collaboration with geriatricians (ward round model). RESULTS: In the 151 examined patients (m/w 47/104; 83.5 (70-100) years; A: n = 64, B: n = 44, C: n = 43) pathways with orthogeriatric comanagement (C) improved frequency of postoperative mobilization (p = 0.021), frequency of osteoporosis prophylaxis (p = 0.001) and the discharge procedure (p = 0.024). In comparison to standard treatment (A), orthogeriatric comanagement (C) was associated with lower rates of mortality (9% vs. 2%; p = 0.147) and cardio-respiratory complications (39% vs. 28%; p = 0.235) by trend. In this context, there were low rates of myocardial infarction (6% vs. 0%), dehydration (6% vs. 0%), cardiac dysrhythmia (8% vs. 0%), pulmonary decompensation (28% vs. 16%), electrolyt dysbalance (34% vs. 19%) and pulmonary edema (11% vs. 2%). Duration of stay in an intensive care unit was 29 h (A) and 18 h (C) respectively (p = 0.205), with consecutive reduction in costs. A sole establishment of a special care pathway for older hip fracture patients (B) showed a lower rate of myocardial infarction (A: 11%, B: 0%, C: 0%; p = 0.035). CONCLUSION: There was a clear tendency to a better overall result in patients receiving multidisciplinary orthogeriatric treatment using a ward visit model of orthogeriatric comanagement, with lower rates of cardiorespiratory complications and mortality. While special care pathways could reduce the rate of myocardial infarction in hip fracture patients, costs and revenues showed no difference between all care models evaluated. However, patients with hip fracture or periprosthetic fracture represent cohorts at clinical and economic risk as well.

Bioavailability of suppository acetaminophen in healthy and hospitalized ill dogs.

To determine the plasma pharmacokinetics of suppository acetaminophen (APAP) in healthy dogs and clinically ill dogs. This prospective study used six healthy client-owned and 20 clinically ill hospitalized dogs. The healthy dogs were randomized by coin flip to receive APAP orally or as a suppository in crossover study design. Blood samples were collected up to 10 hr after APAP dosing. The hospitalized dogs were administered APAP as a suppository, and blood collected at 2 and 6 hr after dosing. Plasma samples were analyzed by ultra-performance liquid chromatography with triple quadrupole mass spectrometry. In healthy dogs, oral APAP maximal concentration (CMAX =2.69 µg/ml) was reached quickly (TMAX =1.04 hr) and eliminated rapidly (T1/2 = 1.81 hr). Suppository APAP was rapidly, but variably absorbed (CMAX =0.52 µg/ml TMAX =0.67 hr) and eliminated (T1/2  = 3.21 hr). The relative (to oral) fraction of the suppository dose absorbed was 30% (range <1%-67%). In hospitalized ill dogs, the suppository APAP mean plasma concentration at 2 hr and 6 hr was 1.317 µg/ml and 0.283 µg/ml. Nonlinear mixed-effects modeling did not identify significant covariates affecting variability and was similar to noncompartmental results. Results supported that oral and suppository acetaminophen in healthy and clinical dogs did not reach or sustain concentrations associated with efficacy. Further studies performed on different doses are needed.

Early weaning is beneficial to prevent atopic dermatitis occurrence in young children.

BACKGROUND: Epidemiological data on infant feeding practices and allergic diseases are controversial. The purpose of this study was to explore the association of early weaning with the occurrence of atopic dermatitis (AD). METHODS: We conducted a matched case-control study on incident physician-diagnosed AD in early childhood including 451 cases and 451 controls. Data on several factors, including feeding practices, were collected through an interviewer-administered questionnaire. Odds ratios (OR) and the corresponding 95% confidence intervals (CIs) were estimated through logistic regression models, conditioned on study center, age, sex, and period of interview, and adjusted for potential confounders. RESULTS: Early weaning, defined as the introduction of solid foods at 4 or 5 months of age, was inversely related to the risk of AD, with children weaned at 4 months having lower AD risk (OR = 0.41, 95% CI, 0.20-0.87) compared to those exclusively breastfed. Similar results were observed for weaning started at 5 months of age (OR = 0.39, 95% CI, 0.18-0.83). This association persisted when children with and without family history of allergy were considered separately. Prolonged partial breastfeeding (breastmilk plus milk formulas) was not associated with AD. Consistently, the introduction of a high number of different solid foods reduced the risk of AD (P trend = 0.02 at 4 months of age and P trend = 0.04 at 5 months). CONCLUSION: Our data provide evidence against the preventing role of prolonged exclusive (but not partial) breastfeeding in AD occurrence and confirm recent results indicating a beneficial role of early weaning in AD.

Next-generation DNA sequencing of a Swedish malignant hyperthermia cohort.

Malignant hyperthermia (MH)-related mutations have been identified in the ryanodine receptor type 1 gene (RYR1) and in the dihydropyridine gene (CACNA1S), but about half of the patients do not have causative mutations in these genes. We wanted to study the contribution of other muscle genes to the RYR1 phenotypes. We designed a gene panel for sequence enrichment targeting 64 genes of proteins involved in the homeostasis of the striated muscle cell. Next-generation sequencing (NGS) resulted in >50,000 sequence variants which were further analyzed by software filtering criteria to identify causative variants. In four of five patients we identified previously reported RYR1 mutations while the fifth patient did not show any candidate variant in any of the genes investigated. In two patients pathogenic variants were found in other genes known to cause a muscle disorders. All but one patient carried likely benign rare polymorphisms. The NGS technique proved convenient in identifying variants in the RYR1. However, with a clinically variable phenotype-like MH, the pre-selection of genes poses problems in variant interpretation.

Characterization of spatial coherence of synchrotron radiation with non-redundant arrays of apertures.

A method to characterize the spatial coherence of soft X-ray radiation from a single diffraction pattern is presented. The technique is based on scattering from non-redundant arrays (NRAs) of slits and records the degree of spatial coherence at several relative separations from 1 to 15 µm, simultaneously. Using NRAs the spatial coherence of the X-ray beam at the XUV X-ray beamline P04 of the PETRA III synchrotron storage ring was measured as a function of different beam parameters. To verify the results obtained with the NRAs, additional Young's double-pinhole experiments were conducted and showed good agreement.

Quantification of circulating house dust mite-specific IL-4- and IL-13-secreting T cells correlates with rhinitis severity in asthmatic children and varies with the seasons.

BACKGROUND: Defining suitable markers to diagnose and monitor allergy and its severity is essential to correctly assign patients for specific immunotherapy. Circulating levels of specific IgE are good markers of sensitization, but not of clinically symptomatic allergy. OBJECTIVE: To quantify circulating interleukin (IL)-4- and IL-13-secreting T cells specific for house dust mite (HDM) in children presenting HDM-allergic asthma associated or not with rhinitis and correlate results with clinical symptoms. METHODS: We analysed 26 children with HDM respiratory disease (allergic rhinitis and asthma) together with six children with non-allergic asthma. Peripheral blood mononuclear cells were stimulated with HDM extract in a 24-h ELISpot assay to quantify the number of HDM-specific IL-4- and IL-13-secreting T cells. Asthma severity and control, and rhinitis severity were scored according to the Global Initiative for Asthma (GINA) and the Allergic Rhinitis and its Impact on Asthma (ARIA) Guidelines. RESULTS: The number of HDM-specific IL-4- and IL-13-secreting T cells was higher in patients with allergic asthma as compared to patients with non-allergic asthma. It varied with the season of blood sampling with two peaks in the fall and early spring. Independently of the season, the number of HDM-specific IL-4-secreting T cells correlated with rhinitis severity (OR = 2; 95% IC:1.1-3.8; P = 0.04). CONCLUSIONS AND CLINICAL RELEVANCE: Allergen-specific IL-4- and IL-13-producing T cells were only detected in HDM-allergic asthmatic children (not in patients with non-allergic asthma). Their numbers correlated with clinical severity of allergic rhinitis.

Casein-specific IL-4- and IL-13-secreting T cells: a tool to implement diagnosis of cow's milk allergy.

BACKGROUND: Cow's milk allergy (CMA) is a frequent food allergy in young children. The oral food challenge is the gold standard for diagnosis, and there is currently no reliable biological test. Our aim was to evaluate the diagnostic potential of a functional assay quantifying allergen-specific Th2 cells in CMA children. METHODS: A total of 29 children aged 2.8-10.5 years underwent a double-blind, placebo-controlled food challenge (DBPCFC) to cow's milk. Blood was collected before performing the DBPCFC, and peripheral mononuclear cells were cultured in an 18-h ELISpot assay with casein, α-lactalbumin, or ß-lactoglobulin. Numbers of antigen-specific IL-4- and IL-13-secreting lymphocytes and serum-specific IgE, IgG4, and total IgE levels were assessed. Receiver operating characteristic (ROC) curves were generated. RESULTS: A total of 17 (59%) children reacted to cow's milk and were therefore considered as allergic to cow's milk (CMA). The mean number of casein-specific IL-4- and IL-13-secreting T cells was higher in CMA than in non-CMA children (P = 0.009, 0.004, respectively). Moreover, it was inversely correlated with the cumulative dose of cow's milk tolerated (P = 0.003, 0.0009, respectively). ROC curve of combined IL-4 and IL-13 analysis showed an area under the curve of 0.98 (95% CI 0.90-1.06). For a cutoff of 10 IL-4- and 12 IL-13-secreting T cells, sensitivity and negative predictive value were 100%. CONCLUSIONS: Enumeration of casein-specific IL-4- and IL-13-secreting T cells appears a promising tool to improve diagnosis and, if confirmed in larger studies, could permit less frequent use of the oral food challenge.

Visceral smooth muscle α-actin deficiency associated with chronic intestinal pseudo-obstruction in a Bengal cat (Felis catus x Prionailurus bengalensis).

An adult Bengal cat (Felis catus × Prionailurus bengalensis) with a prolonged history of partial anorexia, regurgitation, and weight loss and a clinical, radiographic, and ultrasonographic diagnosis of persistent megaesophagus and gastrointestinal ileus was submitted for necropsy. The intestinal tract was diffusely distended by gas and fluid with appreciable loss of muscle tone and an absence of luminal obstruction, consistent with the clinical history of chronic intestinal pseudo-obstruction. Histologically, the autonomic nervous system was intact, but the smooth muscle within the gastrointestinal wall exhibited a marked basophilia that was most pronounced in the jejunum. Immunohistochemistry for neurofilament, synaptophysin, CD117, and desmin demonstrated that the number of myenteric ganglia, number of interstitial cells, and leiomyocyte desmin content were similar when compared with the unaffected age- and species-matched control. Immunohistochemistry for smooth muscle α-actin demonstrated a striking loss of immunoreactivity, predominantly in the circular layer of the jejunum, that corresponded with the tinctorial change in leiomyocytes. Transmission electron microscopy revealed loss of myofibrils, loss of organelle polarity, and significantly larger central mitochondria (megamitochondria) in affected leiomyocytes, as well as nonspecific degenerative changes. Although the presence of a primary leiomyopathy and a causal relationship could not be confirmed in this case, leiomyopathies are considered a cause of chronic intestinal pseudo-obstruction in human medicine, and loss of smooth muscle α-actin immunoreactivity is one recognized marker for intestinal dysmotility.

Accuracy of iodine quantification in dual energy CT: A phantom study across 3 different CT systems.

INTRODUCTION: No study has rigorously compared the performances of iodine quantification on recent CT systems employing different emission-based technologies, depending on the manufacturers and models. METHODS: A specific bespoke phantom was used for this study, with 12 known concentrations of iodinated contrast agent: 0.4, 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 10.0, 15.0, 20.0, 30.0 and 50.0 mg/mL. Three different dual-energy scanners were tested: one system using dual-source acquisition (CT#1) and two systems using Fast kilovolt-peak switching technology ± artificial intelligence (AI) reconstruction methods (CT#2 and #3) from two different manufacturers. For each system, helical scans were performed following recommended clinical protocols. Four acquisitions were performed per iodine concentration (mg/mL), and measurements were made on iodine-maps using ROIs. Mean measured values were compared to the known concentrations, and the absolute quantification error (AQE) and the relative percentage error (RPE) were used to compare the performances of each CT. RESULTS: The accuracy of the obtained measurements varied depending on the studied model but not on the acquisition mode (dual-source vs kVp switch ± AI). The quantification was more precise at high concentrations. RPE values were below 10 % with CT#2 (kVp switch) and below 25 % with CT#1 (dual-source), but were significantly higher with CT#3 (kVp switch + AI), exceeding 50 % at low concentrations (<3 mg/mL). CONCLUSIONS: With the help of a phantom, we identified variability in the results accuracy depending on the CT model, with sometimes significant deviation. Considering the performances of the different DECT technologies in iodine mapping, dual-source (CT#1) and kVp switch (CT#2) technologies appear more accurate than kVp switch technology combined with deep-learning-based reconstruction (CT#3) especially at low concentrations (<3 mg/mL). IMPLICATIONS FOR PRACTICE: As the primary and daily user of medical imaging devices, the radiographer role is to be attentive to the performance of imaging systems, particularly when performing quantitative acquisitions like iodine-quantification. In CT quantitative imaging (iodine map), it's essential for radiographers to consider their CT systems as measuring tools, and to be aware of their accuracies and limits.

Truncating mutations in CCM1, encoding KRIT1, cause hereditary cavernous angiomas.

Cavernous angiomas are vascular malformations mostly located in the central nervous system and characterized by enlarged capillary cavities without intervening brain parenchyma. Clinical symptoms include seizures, haemorrhage and focal neurological deficits. Cavernous angiomas prevalence is close to 0.5% in the general population. They may be inherited as an autosomal dominant condition in as much as 50% of cases. Cerebral cavernous malformations (CCM) loci were previously identified on 7q, 7p and 3q (refs 4,5). A strong founder effect was observed in the Hispano-American population, all families being linked to CCM1 on 7q (refs 4,7). CCM1 locus assignment was refined to a 4-cM interval bracketed by D7S2410 and D7S689 (ref. 8). Here we report a physical and transcriptional map of this interval and that CCM1, a gene whose protein product, KRIT1, interacts with RAP1A (also known as KREV1; ref. 9), a member of the RAS family of GTPases, is mutated in CCM1 families. Our data suggest the involvement of the RAP1A signal transduction pathway in vasculogenesis or angiogenesis.

Effects of improved early-life conditions on health, welfare, and performance of pigs raised on a conventional farm.

Nowadays, most pigs are raised indoors, on intensive farms providing a poor environment. In these conditions, the risk of the occurrence of damaging behaviours is high, with dramatic consequences for animal health and welfare as well as economic losses for farmers. Early-life conditions may predispose individuals to develop damaging behaviours later in life. In contrast, reinforcing affiliative behaviours between piglets before weaning might help to prevent tail-biting episodes. In this field study, we aimed at improving early-life conditions of piglets on a commercial farm by completely suppressing painful procedures and staggering their exposure to weaning stress factors. The alternative early-life management strategy combined housing in free-farrowing pens with temporary crating of the sow, socialisation during the lactation period with whole-life maintenance of the hierarchical groups, and delayed transfer to the postweaning room after sow removal. Control conditions included birth in farrowing crates, tail docking, absence of socialisation during the lactation period, abrupt weaning with immediate transfer to the postweaning room and mixing with non-littermates. We evaluated the health, welfare, and performance of alternatively raised pigs (n = 80) as compared to controls (n = 75). Visits were made throughout the lifespan of individuals to evaluate their growth and health status. Body and tail lesions were scored as proxy measures of aggressiveness and impaired welfare. Blood and bristle samples were periodically collected to evaluate stress, inflammation and immune competence. While the whole-life performance of pigs was similar among groups, the alternative early-life conditions prevented the growth slowdown usually observed after weaning. In addition, alternatively raised pigs displayed more neutrophils, eosinophils and monocytes the day after weaning, as well as higher C-Reactive Protein levels. One week later, their monocytes displayed greater phagocytic capacity. Altogether, these data suggest an enhanced innate immune competence for alternatively raised pigs around weaning. Piglets reared under alternative conditions also exhibited fewer and less severe body lesions than standard pigs, one week after weaning. In contrast, they showed more tail lesions on days 36 and 66 associated with greater levels of acute phase proteins (C-Reactive Protein and haptoglobin). To conclude, alternative early-life management better prepared piglets for weaning. However, the whole-life maintenance of early-established social groups was not sufficient to prevent the occurrence of damaging behaviours in undocked pigs.

Induction of allograft tolerance by monoclonal CD3 antibodies: a matter of timing.

Despite remarkable progress in organ transplantation through the development of a wealth of immunosuppressive drugs highly effective at controlling acute rejection, two major problems still remain, the loss of transplants due to chronic rejection and the growing number of sensitized recipients due to previous transplants, transfusions or pregnancies. Induction of immune tolerance appears to be the only way to curb this complex situation. Here we describe that a therapy, already successfully used to restore immune tolerance to self-antigens in overt autoimmunity, is effective at promoting transplant tolerance. We demonstrate that a short low-dose course with CD3 antibodies started after transplantation, at the time of effector T cell priming to alloantigens, induces permanent acceptance of fully mismatched islet allografts. Mechanistic studies revealed that antigen-specific regulatory and effector T cells are differentially affected by the treatment. CD3 antibody treatment preferentially induces apoptosis of activated alloreactive T cells which is mandatory for tolerance induction. In contrast, regulatory T cells are relatively spared from CD3 antibody-induced depletion and can transfer antigen-specific tolerance thus arguing for their prominent role in sustaining long-term graft survival.

Comparison of different radiographic scores with associated echocardiographic measurements and prediction of heart enlargement in dogs with and without myxomatous mitral valve disease.

INTRODUCTION: Staging of myxomatous mitral valve disease (MMVD) requires an echocardiographic examination along with thoracic radiographs. The aims of this study were to calculate mean values for radiographic scores vertebral heart size (VHS), left atrial width (LAWidth), radiographic left atrial dimension (RLAD), and vertebral left atrial size (VLAS) in conventional and grayscale inverted images in healthy dogs and dogs with different stages of MMVD, and to find cutoff values for a stage assignment. ANIMALS: One hundred fifty dogs in different stages of MMVD and 50 unaffected dogs were evaluated. METHODS: Radiographic scores, echocardiographic left atrium-to-aorta ratio and normalized left ventricular internal dimension at end-diastole, and results of a clinical examination were obtained. Analyses were performed to evaluate the correlation between radiographic scores and echocardiographic values, to determine cutoff values for a radiographic stage assignment, and to compare measurements in conventional and inverted radiographs. RESULTS: After excluding breed-specific higher VHS, the means of VHS, LAWidth, RLAD, and VLAS were similar in the control group and stage B1. All radiographic scores increased in stages B2 and C. The cutoff values identifying heart enlargement, and therefore differentiating stages B1 and B2, were 11.0 for VHS, 1.8 for LAWidth, 2.0 for RLAD, and 2.3 for VLAS. Besides RLAD, scores were similar in conventional and inverted radiographs. CONCLUSION: Cutoff values for the different radiographic scores for stage assignment were calculated. Radiographic cardiac scores using either conventional or inverted grayscale could be a tool to differentiate between different stages of MMVD when echocardiography is unavailable.

Activation of natural killer T cells by alpha-galactosylceramide treatment prevents the onset and recurrence of autoimmune Type 1 diabetes.

Type 1 diabetes (T1D) in non-obese diabetic (NOD) mice may be favored by immune dysregulation leading to the hyporesponsiveness of regulatory T cells and activation of effector T-helper type 1 (Th1) cells. The immunoregulatory activity of natural killer T (NKT) cells is well documented, and both interleukin (IL)-4 and IL-10 secreted by NKT cells have important roles in mediating this activity. NKT cells are less frequent and display deficient IL-4 responses in both NOD mice and individuals at risk for T1D (ref. 8), and this deficiency may lead to T1D (refs. 1,6-9). Thus, given that NKT cells respond to the alpha-galactosylceramide (alpha-GalCer) glycolipid in a CD1d-restricted manner by secretion of Th2 cytokines, we reasoned that activation of NKT cells by alpha-GalCer might prevent the onset and/or recurrence of T1D. Here we show that alpha-GalCer treatment, even when initiated after the onset of insulitis, protects female NOD mice from T1D and prolongs the survival of pancreatic islets transplanted into newly diabetic NOD mice. In addition, when administered after the onset of insulitis, alpha-GalCer and IL-7 displayed synergistic effects, possibly via the ability of IL-7 to render NKT cells fully responsive to alpha-GalCer. Protection from T1D by alpha-GalCer was associated with the suppression of both T- and B-cell autoimmunity to islet beta cells and with a polarized Th2-like response in spleen and pancreas of these mice. These findings raise the possibility that alpha-GalCer treatment might be used therapeutically to prevent the onset and recurrence of human T1D.

Functional evaluation of platelet aspirin resistance after on-pump coronary bypass grafting using multiple aggregation tests.

OBJECT: The predominant mechanism of early graft failure after coronary artery bypass grafting (CABG) is associated with antiplatelet treatment using drugs such as acetylsalicylic acid (ASA). Impaired hemostasis of multiple etiologies is often present in patients undergoing on-pump cardiac surgery. We investigated the impact of intravenous ASA administration on platelet function in this setting. METHODS: Forty-two patients were enrolled in the study. Patients received 100 mg oral ASA once daily, beginning in the early postoperative period. Noncompliance was eliminated by the administration of 300 mg ASA intravenously at 6-8 days post-operation. Blood was drawn immediately before, 1 h and 24 h after ASA administration. RESULTS: A platelet function analyzer (PFA-100™) was used to evaluate closure time (CT), turbidimetric platelet aggregation (TPA) and impedance platelet aggregation (IPA) induced by arachidonic acid (AA), collagen and ADP and results were compared with the respective values from 120 healthy individuals. At 1 h and 24 h after administration, we found that intravenous ASA caused CEPI-CT to be significantly prolonged with a reduction of AA and collagen-induced IPA. Despite postoperative oral ASA administration for 6-8 days, PFA-100™ CEPI and CADP-CT were significantly shorter and ADP-TPA and IPA values induced by any agonist were significantly greater in patients than in controls. Intravenous ASA had no significant influence on CADP-CT or ADP-induced IPA (ADP-IPA). CONCLUSION: Platelet tests for diagnosing patients as aspirin responders (ASA-R) or aspirin non-responders (ASA-NR) were found to be not comparable. Patients after CABG show augmented platelet dysfunction. Intravenous ASA administration may indicate a promising approach to reduce laboratory resistance after CABG procedure. The reason for this is not clear and requires additional clinical studies.

[Special training therapy to reduce inflammation in Anti-Jo-1 syndrome]. / Spezielle Trainingstherapie zur Reduktion der Inflammation bei Anti-Jo-1-Syndrom.

A 46-year-old patient was frequently seen with a medically treated Anti-Jo-1 syndrome. The patient had already been treated with azathioprine and oral corticosteroids on account of decreasing lung function, dyspnoea, fatigue, and beginning signs of myositis. Although high doses of steroids and azathioprine were administered, the muscleskeletal syndromes increased steadily. The patient used to be an active long-distance runner (20 km), but now was unable to perform that kind of physical exercise. It was decided to start a treatment with the GalileoTM training device for active muscle training of the lower extremities. Before and after three months of training the following assessment was performed: measurement of health-related quality of life (St. Georges respiratory questionnaire, SGRQ), ultrasound measurement of the cross-sectional area of the quadriceps muscle, 6 minute walk test (6 MWT), lung function testing, and assessment of serum markers of inflammation (TNF-alpha, interleukin-8, CRP, CK, myoglobin). After only two months, training with the GalileoTM five times a week has improved the patient's conditions dramatically. The training will be continued.

Noninvasive ventilatory support in morbid obesity.

BACKGROUND: In the conventional management of the morbidly obese that normalizes the apnea-hypopnea index (AHI), CO2 levels often remain elevated. METHODS: A retrospective review of morbidly obese patients using volume preset settings up to 1800ml to positive inspiratory pressures (PIPs) of 25-55cm H2O, or pressure control at 25-50cm H2O pressure via noninvasive interfaces up to continuously (CNVS). RESULTS: Twenty-six patients, mean 55.6±14.8 years of age, weight 108-229kg, mean BMI 56.1 (35.5-77)kg/m2, mean AHI 69.0±24.9, depended on up to CNVS for 3 weeks to up to 66 years. There were eleven extubations and seven decannulations to CNVS despite failure to pass spontaneous breathing trials. Thirteen were CNVS dependent for 92.2 patient-years with little to no ventilator free breathing ability (VFBA). Six used NVS from 10 to 23h a day, and others only for sleep. Fifteen patients with cough peak flows (CPF) less than 270L/m had access to mechanical insufflation-exsufflation (MIE) in the peri-extubation/decannulation period and long-term. The daytime end-tidal (Et)CO2 of 14 who were placed on sleep NVS without extubation or decannulation to it decreased from mean EtCO2 61.0±9.3-38.5±3.6mm Hg and AHI normalized to 2.2. Blood gas levels were normal while using NVS/CNVS. Pre-intubation PaCO2 levels, when measured, were as high as 183mm Hg before extubation to CNVS. CONCLUSIONS: Ventilator unweanable morbidly obese patients can be safely extubated/decannulated and maintained indefinitely using up to CNVS rather than resort to tracheotomies.