Helios Klinik Hagen Ambrock

Recent studies show that nasal high flow (NHF) therapy can support ventilation in patients with acute or chronic respiratory disorders. Clearance of dead space has been suggested as being the key mechanism of respiratory support with NHF therapy. The hypothesis of this study was that NHF in a dose-dependent manner can clear dead space of the upper airways from expired air and decrease rebreathing. The randomized crossover study involved 10 volunteers using scintigraphy with 81m Krypton ( 81m Kr) gas during a breath-holding maneuver with closed mouth and in 3 nasally breathing tracheotomized patients by volumetric capnography and oximetry through sampling CO 2 and O 2 in the trachea and measuring the inspired volume with inductance plethysmography following NHF rates of 15, 30, and 45 l/min. The scintigraphy revealed a decrease in 81m Kr gas clearance half-time with an increase of NHF in the nasal cavities [Pearson’s correlation coefficient cc = −0.55, P < 0.01], the pharynx (cc = −0.41, P < 0.01), and the trachea (cc = −0.51, P < 0.01). Clearance rates in nasal cavities derived from time constants and MRI-measured volumes were 40.6 ± 12.3 (SD), 52.5 ± 17.7, and 72.9 ± 21.3 ml/s during NHF (15, 30, and 45 l/min, respectively). Measurement of inspired gases in the trachea showed an NHF-dependent decrease of inspired CO 2 that correlated with an increase of inspired O 2 (cc = −0.77, P < 0.05). NHF clears the upper airways of expired air, which reduces dead space by a decrease of rebreathing making ventilation more efficient. The dead space clearance is flow and time dependent, and it may extend below the soft palate. NEW & NOTEWORTHY Clearance of expired air in upper airways by nasal high flow (NHF) can be extended below the soft palate and de facto causes a reduction of dead space. Using scintigraphy, the authors found a relationship between NHF, time, and clearance. Direct measurement of CO 2 and O 2 in the trachea confirmed a reduction of rebreathing, providing the actual data on inspired gases, and this can be used for the assessment of other forms of respiratory support.

Treadmill-based gait analysis is widely used to investigate walking pathologies and quantify treatment effects on locomotion. Differential sensorimotor conditions during overground vs. treadmill walking necessitate initial familiarization to treadmill walking. Currently, there is no standardized treadmill acclimatization protocol and insufficient familiarization potentially confounds analyses. We monitored initial adaptations to treadmill walking in 40 healthy adults. Twenty-six walking parameters were assessed over 10 minutes with marker-based kinematic analysis and acclimatization profiles were generated. While 16 walking parameters demonstrated initial acclimatization followed by plateau performance, ten parameters remained stable. Distal lower limb control including ankle range of motion, toe trajectory and foot clearance underwent substantial adaptations. Moreover, intralimb coordination and gait variability also demonstrated acclimatization, while measures of symmetry and interlimb coordination did not. All parameters exhibiting a plateau after acclimatization did so within 6-7 minutes (425 strides). Older participants and those naïve to treadmill walking showed adaptations with higher amplitudes but over similar timescales. Our results suggest a minimum of 6 minutes treadmill acclimatization is required to reach a stable performance, and that this should suffice for both older and naïve healthy adults. The presented data aids in optimizing treadmill-based gait analysis and contributes to improving locomotor assessments in research and clinical settings.

Constant continuous positive airway pressure (CPAP) is the treatment of choice for the obstructive sleep apnea syndrome (OSAS). To enable the pressure to be matched more accurately to actual requirements, and thus increase patient acceptance, an autoadjusting device based on the measurement of upper airway impedance was developed (APAP(FOT)). We investigated the efficacy and compliance in continuous use at home. Fifty-two patients were treated (randomized crossover) with CPAP and APAP(FOT) for 6 wk each. Respiratory disturbances, sleep profile, and arousals improved significantly with both modes (AHI: baseline, 35.1 +/- 26/h; APAP(FOT), 5.0 +/- 5.2; CPAP, 4.3 +/- 6.3; p < 0.001 baseline versus each mode). The mean pressure with APAP(FOT) was significantly reduced as compared with CPAP (CPAP, 7.8 +/- 1.5 cm H2O; APAP(FOT), 5.7 +/- 1.8 cm H2O; p < 0.001). Under APAP(FOT) the pressure was lower than that under CPAP for 81.5 +/- 21% of the time. Although overall use did not differ, 75% of the patients preferred APAP(FOT) for home treatment. We conclude that APAP(FOT) is as efficacious as constant CPAP in the treatment of OSAS. The treatment pressure can be reduced significantly, and sleep microstructure improved with APAP(FOT). These might be the reasons for patient preference of automatic therapy.

Abstract Gait dysfunction is a common and relevant symptom in multiple sclerosis (MS). This study aimed to profile gait pathology in gait-impaired patients with MS using comprehensive 3D gait analysis and clinical walking tests. Thirty-seven patients with MS walked on the treadmill at their individual, sustainable speed while 20 healthy control subjects walked at all the different patient’s paces, allowing for comparisons independent of walking velocity. Kinematic analysis revealed pronounced restrictions in knee and ankle joint excursion, increased gait variability and asymmetry along with impaired dynamic stability in patients. The most discriminative single gait parameter, differentiating patients from controls with an accuracy of 83.3% (χ 2 test; p = 0.0001), was reduced knee range of motion. Based on hierarchical cluster and principal component analysis, three principal pathological gait patterns were identified: a spastic-paretic, an ataxia-like, and an unstable gait. Follow-up assessments after 1 year indicated deterioration of walking function, particularly in patients with spastic-paretic gait patterns. Our findings suggest that impaired knee/ankle control is common in patients with MS. Personalised gait profiles and clustering algorithms may be promising tools for stratifying patients and to inform patient-tailored exercise programs. Responsive, objective outcome measures are important for monitoring disease progression and treatment effects in MS trials.

STUDY OBJECTIVES: To investigate the efficacy of tongue-muscle training by electrical neurostimulation of the upper-airway muscles as an alternative therapy option for obstructive sleep apnea syndrome. DESIGN: A randomized, placebo-controlled, double-blind study. SETTING: Department of pneumology and sleep laboratory, University of Witten/Herdecke, Germany. PATIENTS: 67 patients with an apnea-hypopnea index of 10 to 40 per hour were randomly assigned to 2 groups: a treatment group of 33 patients (mean age, 50.8 +/- 12.1 years; mean body mass index, 29.1 +/- 4.4 kg/m2) and a placebo group of 34 patients (mean age, 53.3 +/- 11.3 years; mean body mass index, 28.9 +/- 4.9 kg/m2). Fifty-seven patients completed the study. INTERVENTIONS: Tongue-muscle training during the daytime for 20 minutes twice a day for 8 weeks. MEASUREMENTS AND RESULTS: Treatment efficacy was examined by polysomnography. Snoring, but not apnea-hypopnea index, improved with stimulation (snoring baseline, 63.9 +/- 23.1 epochs per hour; stimulation training, 47.5 +/- 31.2; P < .05) but not with placebo training (snoring baseline, 62.4 +/- 26.1 epochs per hour; placebo, 62.1 +/- 23.8; NS.). CONCLUSIONS: Although tongue-muscle training cannot generally be recommended for the treatment of sleep apnea, the method has proven to be effective in the treatment of snoring.

Die Insomnie, d. h. eine Ein- und/oder Durchschlafstörung, die sich negativ auf die Leistungsfähigkeit und Tagesbefindlichkeit auswirkt, ist eine der häufigsten Erkrankungen in der Allgemeinbevölkerung. Sie wird derzeit meistens pharmakologisch und/oder psychotherapeutisch behandelt, wobei die pharmakologische Behandlung mit Benzodiazepin-Rezeptor-Agonisten zu Abhängigkeit führen kann und die Verfügbarkeit von für die Insomnie-Therapie ausgebildeten Psychotherapeuten momentan nicht in ausreichendem Maße gegeben ist. Durch innovative Behandlungsmethoden könnte hier eine Versorgungslücke effektiv geschlossen werden. Hierzu zählt die auditorische Stimulation, welche vorhandene Sinneskanäle nutzt, um den Schlaf zu beeinflussen. Bisher wurde die auditorische Stimulation vor allem zur Untersuchung von Prozessen der Gedächtniskonsolidierung bei gesunden Probanden angewendet, wobei erfolgreich eine Erhöhung langsamer Oszillationen erreicht wurde, welche vor allem während des Tiefschlafs auftreten. Erste Befunde und sekundäre Outcome-Parameter liefern Hinweise, dass die Potenzierung langsamer Oszillationen durch auditorische Stimulation den Schlaf vertiefen kann, jedoch wurde hierzu bislang keine Studie mit Insomniepatienten durchgeführt. Weitere Forschung bezüglich des Einflusses der Potenzierung langsamer Oszillationen auf die Linderung von Ein- und Durchschlafproblemen bei vorliegender nichtorganischer Insomnie erscheint daher geboten zu sein, um der hohen Beschwerdelast dieser Patientengruppe entgegenzuwirken.

The COPD Patient Management European Trial (COMET) investigated the efficacy and safety of a home-based COPD disease management intervention for severe COPD patients. The study was an international open-design clinical trial in COPD patients (forced expiratory volume in 1 s &lt;50% of predicted value) randomised 1:1 to the disease management intervention or to the usual management practices at the study centre. The disease management intervention included a self-management programme, home telemonitoring, care coordination and medical management. The primary end-point was the number of unplanned all-cause hospitalisation days in the intention-to-treat (ITT) population. Secondary end-points included acute care hospitalisation days, BODE (body mass index, airflow obstruction, dyspnoea and exercise) index and exacerbations. Safety end-points included adverse events and deaths. For the 157 (disease management) and 162 (usual management) patients eligible for ITT analyses, all-cause hospitalisation days per year (mean± sd ) were 17.4±35.4 and 22.6±41.8, respectively (mean difference −5.3, 95% CI −13.7 to −3.1; p=0.16). The disease management group had fewer per-protocol acute care hospitalisation days per year (p=0.047), a lower BODE index (p=0.01) and a lower mortality rate (1.9% versus 14.2%; p&lt;0.001), with no difference in exacerbation frequency. Patient profiles and hospitalisation practices varied substantially across countries. The COMET disease management intervention did not significantly reduce unplanned all-cause hospitalisation days, but reduced acute care hospitalisation days and mortality in severe COPD patients.

Catumaxomab is a trifunctional monoclonal antibody consisting of a mouse immunoglobulin G2a part and a rat immunoglobulin G2b part with 2 different antigen binding sites binding the epithelial cell adhesion molecule antigen on tumor cells and CD3 on T lymphocytes. The intact Fc region provides a third functional binding site, binding and activating selectively Fcgamma receptor I, IIa, and III-positive accessory cells. These binding properties lead to specific tumor cell killing. As catumaxomab demonstrated efficacy in patients with malignant ascites, we performed this phase 1/2 trial in patients with malignant pleural effusion (MPE). We investigated a series of 3 escalating doses of 5 to 200 microg catumaxomab administered intrapleurally to patients with MPE containing epithelial cell adhesion molecule -positive cells. Primary objectives were determination of dose-limiting toxicity, safety, and tolerability. Secondary objectives were efficacy and pharmacodynamics. Twenty-four patients were treated with catumaxomab. Most frequent adverse events were pyrexia, elevated liver enzymes, nausea, and decreased lymphocytes. Dose-limiting toxicities were observed in 2 patients: One had pleural empyema and fatal sepsis and 1 had grade 3 erythema and hepatobiliary disorder. Five patients with breast cancer out of 7 evaluable patients had a response to treatment. Intrapleural administration of catumaxomab is feasible although the substantial number of drop-outs and deaths in short proximity to study treatment raise questions whether MPE is the right indication for catumaxomab or whether the patient population should be defined different. Safety profile was as expected reflecting catumaxomab's mode of action. Preliminary efficacy showed a suggestion of improvement in some patients.

Minimum toe clearance (MTC) occurs during a highly dynamic phase of the gait cycle and is associated with the highest risk of unintentional contact with obstacles or the ground. Age, cognitive function, attention and visual feedback affect foot clearance but how these factors interact to influence MTC control is not fully understood. We measured MTC in 121 healthy individuals aged 20-80 under four treadmill walking conditions; normal walking, lower visual field restriction and two Stroop colour/word naming tasks of two difficulty levels. Competition for cognitive and attentional resources from the Stroop task resulted in significantly lower mean MTC in older adults, with the difficult Stroop task associated with a higher frequency of extremely low MTC values and subsequently an increased modelled probability of tripping in this group. While older adults responded to visual restriction by markedly skewing MTC distributions towards higher values, this condition was also associated with frequent, extremely low MTC values. We reveal task-specific, age-dependent patterns of MTC control in healthy adults. Age-related differences are most pronounced during heavy, distracting cognitive load. Analysis of critically-low MTC values during dual-task walking may have utility in the evaluation of locomotor control and fall risk in older adults and patients with motor control deficits.

Schwellen sind in der Spiroergometrie für die Leistungsbemessung bei schwierig zu beurteilender Kooperation bzw. Motivation im Rahmen einer Belastungsuntersuchung, zur Trainingssteuerung, in der Transplantationsplanung, der Operabilitätsbeurteilung und der Begutachtung erforderlich. In der Literatur besteht eine kaum übersehbare Vielfalt von Schwellenterminologien, die einen Vergleich von Protokollen und Studien nur schwer möglich machen und auch im Alltag der Spiroergometrieinterpretation bzw. –auswertung zu terminologischen Unsicherheiten führen. Daraus ergibt sich die Notwendigkeit einer klaren Terminologie. Anhand der Literatur wurde eine Festlegung der Schwellendefinitionen vorgenommen. Danach ist zwischen einer konzeptionellen und operationalen (methodischen) Schwellenbetrachtung zu unterscheiden. Das konzeptionelle Schwellenkonzept bedeutet, dass es zwei ventilatorische (VT1 und VT2) und zwei metabolische Schwellen (Laktatschwelle [LT] 1 und 2) gibt. Diese Schwellen sind pathophysiologisch erklärbar. Beide Schwellenkonzepte kennzeichnen den Beginn und das Ende des aerob-anaeroben Übergangs. Während die Laktatschwellen 1 und 2 direkt die metabolischen Änderungen anzeigen, beschreiben die ventilatorischen Schwellen 1 und 2 die respiratorische Antwort auf diese metabolischen Änderungen. So kennzeichnet VT1 die infolge des Laktatanstiegs und der erforderlichen Laktatpufferung notwendige Steigerung der Ventilation und CO₂-Abgabe im Verhältnis zur Sauerstoffaufnahme. Der VT2 liegt ein Überschreiten des Laktat-Steady-State mit konsekutivem Laktatexzess, Auftreten einer metabolischen Azidose und daraus resultierender überproportionaler Steigerung der Ventilation zugrunde. Demgegenüber bezeichnet das operationale Schwellenkonzept die Methode, mit der die jeweilige Laktat- und ventilatorische Schwelle bestimmt werden. Dies kann in einem weiteren Schritt noch ergänzt werden durch die Angabe der Belastungsform, die zur Schwellenbestimmung herangezogen wurde.

INTRODUCTION: Narcolepsy is an orphan neurological disease and presents with sleep-wake, motoric, neuropsychiatric and metabolic symptoms. Narcolepsy with cataplexy is most commonly caused by an immune-mediated process including genetic and environmental factors, resulting in the selective loss of hypocretin-producing neurons. Narcolepsy has a major impact on workableness and quality of life. Areas covered: This review provides an overview of the temporal available treatment options for narcolepsy (type 1 and 2) in adults, including authorization status by regulatory agencies. First- and second-line options are discussed as well as combination therapies. In addition, treatment options for frequent coexisting co-morbidities and different phenotypes of narcolepsy are presented. Finally, this review considers potential future management strategies. Non-pharmacological approaches are important in the management of narcolepsy but will not be covered in this review. Expert opinion: Concise evaluation of symptoms and type of narcolepsy, coexisting co-morbidities and patients´ distinct needs is mandatory in order to identify a suitable, individual pharmacological treatment. First-line options include Modafinil/Armodafinil (for excessive daytime sleepiness, EDS), Sodium Oxybate (for EDS and/with cataplexy), Pitolisant (for EDS and cataplexy) and Venlafaxine (for cataplexy (off-label) and co-morbid depression). New symptomatic and causal treatment most probably will be completed by hypocretin-replacement and immune-modifying strategies.

BACKGROUND: Prolonged-release fampridine (PR-fampridine, 4-aminopyridine) increases walking speed in the timed 25-foot walk test (T25FW) in some patients (timed-walk responders) with multiple sclerosis (MS). OBJECTIVE: To explore the effects of PR-fampridine on different aspects of walking function and to identify associated gait modifications in subjects with MS. METHODS: In this prospective, randomized, placebo-controlled, double-blind, phase II study (FAMPKIN; clinicaltrials.gov, NCT01576354), subjects received a 6-week course of oral placebo or PR-fampridine treatment (10 mg, twice daily) before crossing over. Using 3D-motion-analysis, kinematic and kinetic parameters were assessed during treadmill walking (primary endpoint). Clinical outcome measures included T25FW, 6-minute walk test (6MWT), and balance scales. Physical activity in everyday life was measured with an accelerometer device. RESULTS: Data from 55 patients were suitable for analysis. Seventeen subjects were timed-walk responders under PR-fampridine. For the total study population and for responders, a significant increase in walking speed (T25FW) and distance (6MWT) was observed. Gait pattern changes were found at the single-subject level and correlated with improvements in the T25FW and 6MWT. Physical activity was increased in responders. CONCLUSION: PR-fampridine improves walking speed, endurance, and everyday physical activity in a subset of subjects with MS and leads to individual modifications of the gait pattern.

Walking impairment is a hallmark of multiple sclerosis (MS). It affects > 90% of individuals over time, reducing independence and negatively impacting health-related quality of life, productivity, and daily activities. Walking impairment is consistently reported as one of the most distressing impairments by individuals with MS. Prolonged-release (PR)-fampridine previously has been shown to improve objectively measured walking speed in walking-impaired adults with MS. The impact of PR-fampridine from the perspective of the individual with MS warrants full and detailed examination. The objective of this study was to evaluate whether PR-fampridine has a clinically meaningful effect on self-reported walking ability in walking-impaired participants with MS. ENHANCE was a phase III, randomized, double-blind, placebo-controlled study of PR-fampridine 10 mg twice daily in walking-impaired individuals age 18–70 years with either relapsing or progressive forms of MS and an Expanded Disability Status Scale (EDSS) score of 4.0–7.0 at screening. Participants were stratified by EDSS score (≤ 6.0 or 6.5–7.0) at randomization to ensure a balanced level of disability in the treatment groups. The primary endpoint was the proportion of participants with a mean improvement in the 12-item Multiple Sclerosis Walking Scale (MSWS-12) score exceeding the predefined threshold for clinically meaningful improvement (≥ 8 points) over 24 weeks. Secondary endpoints included the proportion with ≥ 15% improvement in Timed Up and Go (TUG) speed, and mean changes in Multiple Sclerosis Impact Scale physical impact subscale (MSIS-29 PHYS), Berg Balance Scale (BBS), and ABILHAND scores over 24 weeks. In total, 636 participants with MS were randomized (PR-fampridine, n = 317; placebo, n = 319; modified intention-to-treat sample: PR-fampridine, n = 315; placebo, n = 318). At baseline in the PR-fampridine and placebo groups, 46% and 51% had a progressive form of MS, median [range] EDSS scores were 6.0 [4.0–7.0] and 5.5 [4.0–7.0], mean [range] MSWS-12 scores were 63.6 [0–100] and 65.4 [0–100], and mean [range] TUG speed was 0.38 [0.0–1.0] and 0.38 [0.0–1.2] feet/s, respectively. A significantly higher percentage of PR-fampridine-treated participants (136/315 [43.2%]) had clinically meaningful improvement in MSWS-12 score over 24 weeks versus placebo (107/318 [33.6%]; odds ratio 1.61 [95% confidence interval 1.15–2.26]; p = 0.006). For PR-fampridine versus placebo, significantly more participants had a ≥ 15% improvement in TUG speed, and there was significantly greater mean improvement in MSIS-29 PHYS score (p < 0.05); numerical improvements that were not statistically significant were observed in BBS/ABILHAND. Adverse events that were more common in the PR-fampridine group than placebo group (difference ≥ 3%) by Medical Dictionary for Regulatory Activities (MedDRA®) Preferred Term were urinary tract infection and insomnia. There were no seizures reported. PR-fampridine treatment resulted in sustained, clinically meaningful improvements over 24 weeks in self-reported walking and functional ability in walking-disabled participants with MS. NCT02219932.

BACKGROUND: Repetitive sensory stimulation (RSS) adapts the timing of stimulation protocols used in cellular studies to induce synaptic plasticity. In healthy subjects, RSS leads to widespread sensorimotor cortical reorganization paralleled by improved sensorimotor behavior. Here, we investigated whether RSS reduces sensorimotor upper limb impairment in patients with subacute stroke more effectively than conventional therapy. METHODS: A single-blinded sham-controlled clinical trial assessed the effectiveness of RSS in treating sensorimotor deficits of the upper limbs. Patients with subacute unilateral ischemic stroke were randomly assigned to receive standard therapy in combination with RSS or with sham RSS. Patients were masked to treatment allocation. RSS consisted of intermittent 20 Hz electrical stimulation applied on the affected hand for 45 min/day, 5 days per week, for 2 weeks, and was transmitted using custom-made stimulation-gloves with built-in electrodes contacting each fingertip separately. Before and after the intervention, we assessed light-touch and tactile discrimination, proprioception, dexterity, grip force, and subtasks of the Jebsen Taylor hand-function test for the non-affected and the affected hand. Data from these quantitative tests were combined into a total performance index serving as primary outcome measure. In addition, tolerability and side effects of RSS intervention were recorded. RESULTS: Seventy one eligible patients were enrolled and randomly assigned to receive RSS treatment (n = 35) or sham RSS (n = 36). Data of 25 patients were not completed because they were transferred to another hospital, resulting in n = 23 for each group. Before treatment, sensorimotor performance between groups was balanced (p = 0.237). After 2 weeks of the intervention, patients in the group receiving standard therapy with RSS showed significantly better restored sensorimotor function than the control group (standardized mean difference 0.57; 95% CI -0.013-1.16; p = 0.027) RSS treatment was superior in all domains tested. Repetitive sensory stimulation was well tolerated and accepted, and no adverse events were observed. CONCLUSIONS: Rehabilitation including RSS enhanced sensorimotor recovery more effectively than standard therapy alone. Rehabilitation outcome between the effects of RSS and standard therapy was largest for sensory and motor improvement; however, the results for proprioception and everyday tasks were encouraging warranting further studies in more severe patients. TRIAL REGISTRATION: The trial was retrospectively registered January 31, 2012 under DRKS00003515 ( https://www.drks.de/drks_web/navigate.do;jsessionid=AEE2585CCB82A22A2B285470B37C47C8?navigationId=results ).

Background: COPD patients who develop chronic hypercapnic respiratory failure have a poor prognosis. Treatment of choice, especially the best form of ventilation, is not well known. Objectives: This study compared the effects of pressure-controlled (spontaneous timed [ST]) non-invasive ventilation (NIV) and NIV with intelligent volume-assured pressure support (IVAPS) in chronic hypercapnic COPD patients regarding the effects on alveolar ventilation, adverse patient/ventilator interactions and sleep quality. Methods: This prospective, single-center, crossover study randomized patients to one night of NIV using ST then one night with the IVAPS function activated, or vice versa. Patients were monitored using polysomnography (PSG) and transcutaneous carbon dioxide pressure (PtcCO 2 ) measurement. Patients rated their subjective experience (total score, 0–45; lower scores indicate better acceptability). Results: Fourteen patients were included (4 females, age 59.4±8.9 years). The total number of respiratory events was low, and similar under pressure-controlled (5.4±6.7) and IVAPS (8.3±10.2) conditions ( P =0.064). There were also no clinically relevant differences in PtcCO 2 between pressure-controlled and IVAPS NIV (52.9±6.2 versus 49.1±6.4 mmHg). Respiratory rate was lower under IVAPS overall; between-group differences reached statistical significance during wakefulness and non-rapid eye movement sleep. Ventilation pressures were 2.6 cmH 2 O higher under IVAPS versus pressure-controlled ventilation, resulting in a 20.1 mL increase in breathing volume. Sleep efficiency was slightly higher under pressure-controlled ventilation versus IVAPS. Respiratory arousals were uncommon (24.4/h [pressure-controlled] versus 25.4/h [IVAPS]). Overall patient assessment scores were similar, although there was a trend toward less discomfort during IVAPS. Conclusion: Our results show that IVAPS NIV allows application of higher nocturnal ventilation pressures versus ST without affecting sleep quality or inducing ventilation-associated events. Keywords: NIV, IVAPS, COPD, hypercapnia

BACKGROUND: Cryoextraction is a procedure used for the recanalization of obstructed airways caused by visible exophytic endobronchial tumor. Biopsy samples obtained by this technique have been shown to be useful for histological assessment. OBJECTIVES: The aim of the present animal study was to systematically evaluate biopsy size, histological quality and bleeding risk after cryobiopsy with new, flexible cryoprobes in comparison with forceps biopsy, serving as the gold standard. METHODS: Biopsies were obtained from anesthetized pigs with the flexible bronchoscopy technique, and evaluated histologically with respect to their size and quality. Bleeding frequency, bleeding duration and histological changes in the biopsy bed were also recorded. RESULTS: Cryobiopsies were significantly larger than forceps biopsies. The size of cryobiopsies was dependent on the freezing time. The histological quality of the cryobiopsy specimenswas not impaired by the freezing process, whereas forceps biopsies showed typical crush artifacts. Despite the larger defects left in the tracheobronchial system after cryobiopsy, bleeding frequency and duration were not higher compared to forceps biopsy. CONCLUSIONS: Since cryobiopsy sampling is not associated with a higher bleeding risk compared with forceps biopsy, this new biopsy technique offers--in addition to a good specimen quality--a safe and valuable tool with the potential of improving the outcome of diagnostic endoscopy.

BACKGROUND: Patients with obstructive sleep apnea syndrome (OSAS) often complain of dryness of mouth and throat prior to and during nasal continuous positive airway pressure (nCPAP). It is believed that this is due to mouth breathing (MB). However, the association between mouth breathing and apneas/hypopneas and the effect of CPAP on MB has not been studied. OBJECTIVES: The purpose of the present study was, therefore, to assess the frequency and duration of episodes of MB prior to and during treatment with nCPAP. METHODS: MB was recorded prior to and during nCPAP with a closely fitting mouth mask connected to a pneumotachograph and nasal flow was measured via nasal prongs. MB episodes were expressed as the number of events divided by total sleep time x 60, to give the MB event index per hour of sleep. MB time divided by total sleep time x 60 was calculated in minutes to get the MB time index per hour of sleep. PATIENTS: Eleven male patients with OSAS (mean age 57.9 +/- 8.3 years, body mass index 30.2 +/- 3.8) were recruited to the study. RESULTS: Prior to nCPAP, the apnea/hypopnea index was 55.8 +/- 26 and decreased during nCPAP to 8.0 +/- 3.4. The lowest SaO2 measured was 82.9 +/- 4.7%, and increased to 87.5 +/- 2.7% under nCPAP. The mean nCPAP was 7.8 +/- 1.6 cm H2O. MB event index per hour of sleep decreased from 35.2 +/- 19.7 prior to treatment to 5.0 +/- 5.2 under nCPAP (p < 0.01). In 52.2 +/- 27.4% of obstructive respiratory events, MB started at the end of an apnea/hypopnea episode, decreasing to 8.5 +/- 12.5% with nCPAP treatment. MB time index per hour of sleep was reduced from 13.5 +/- 10.2 min prior to treatment to 4.6 +/- 5.5 min under nCPAP (p < 0.05). CONCLUSIONS: In OSAS patients, MB episodes often appear at the termination of an apnea/hypopnea episode. In many cases, MB episodes can be markedly reduced by nCPAP treatment. When patients on nCPAP complain of dry mouth, appropriate measurements should be performed to verify MB.

During nasal high flow (NHF) an increased breathing frequency, which is commonly observed in acute respiratory failure, can lead to decreased dead-space clearance. Higher NHF rates increase the clearance and reduce the rebreathing which may eventually lower the respiratory rate and the work of breathing. Monitoring of the respiratory rate could be an important indicator of not only the respiratory function but also the NHF rate selection and the therapy efficacy.

Cognitive impairment is as an important feature of Multiple Sclerosis (MS), and might be even more relevant to patients than mobility restrictions. Compared to the multitude of studies investigating memory deficits or basic cognitive slowing, executive dysfunction is a rarely studied cognitive domain in MS, and its neural correlates remain largely unexplored. Even rarer are topological studies on specific cognitive functions in MS. Here we used several structural MRI parameters - including cortical thinning and T2 lesion load - to investigate neural correlates of executive dysfunction, both on a global and a regional level by means of voxel- and vertex-wise analyses. Forty-eight patients with relapsing-remitting MS and 48 healthy controls participated in the study. Five executive functions were assessed, i.e. verbal and figural fluency, working memory, interference control and set shifting. Patients scored lower than controls in verbal and figural fluency only, and displayed widespread cortical thinning. On a global level, cortical thickness independently predicted verbal fluency performance, when controlling for lesion volume and central brain atrophy estimates. On a regional level, cortical thinning in the anterior cingulate region correlated with deficits in verbal and figural fluency and did so in a lateralised manner: Left-sided thinning was related to reduced verbal - but not figural - fluency, whereas the opposite pattern was observed for right-sided thinning. We conclude that executive dysfunction in MS patients can specifically affect verbal and figural fluency. The observed lateralised clinico-anatomical correlation has previously been described in brain-damaged patients with large focal lesions only, for example after stroke. Based on focal grey matter atrophy, we here show for the first time comparable lateralised findings in a white matter disease with widespread pathology.

BACKGROUND: Transbronchial cryobiopsy (TBCB) is a minimally invasive procedure to establish a diagnosis of interstitial lung disease though with the disadvantage that samples have to be extracted together with the bronchoscope. OBJECTIVES: The aim of the present study was to evaluate the feasibility of a new cryoprobe with which biopsy samples can be obtained through the working channel of the flexible bronchoscope. METHODS: The feasibility of obtaining transbronchial specimens with TBCB was tested and the technique was compared to transbronchial forceps biopsy (TBFB) in a prospectively randomized ex vivo animal study using a standard flexible bronchoscopy technique. The rate of successful biopsies and the duration of the sampling procedure were recorded for both methods. Size and quality of the biopsies were histologically evaluated and measured. RESULTS: Biopsy samples could be obtained in 93.3% of TBCB and in 79.0% of TBFB procedures (p = 0.182). Sampling procedure time did not differ in any clinically relevant manner between the two methods. The mean specimen area of TBCB samples was significantly higher compared to that of TBFB samples (8.08 ± 5.80 vs. 2.61 ± 2.14 mm2; p < 0.0001). TBCB specimens showed less artifacts and a significantly higher percentage of alveolar tissue (53.57 vs. 25.42%; p = 0.0285) than TBFB specimens. CONCLUSIONS: It is feasible to retrieve TBCB samples of good quality and size with the new mini cryoprobe through the working channel of the bronchoscope, while the bronchoscope remains within the central airways throughout the whole procedure. Further studies are necessary to evaluate the safety and efficacy in an in vivo setting.