Long-term patterns of subjective wellbeing in schizophrenia: cluster, predictors of cluster affiliation, and their relation to recovery criteria in 2842 patients followed over 3 years

To study the longitudinal patterns of subjective wellbeing in schizophrenia using cluster analysis and their relation to recovery criteria, further to examine predictors for cluster affiliation, and to evaluate the sensitivity and specificity of baseline subjective wellbeing cut-offs for cluster affiliation.

Grey matter volumetric changes related to recovery from hand paresis after cortical sensorimotor stroke

Preclinical studies using animal models have shown that grey matter plasticity in both perilesional and distant neural networks contributes to behavioural recovery of sensorimotor functions after ischaemic cortical stroke. Whether such morphological changes can be detected after human cortical stroke is not yet known, but this would be essential to better understand post-stroke brain architecture and its impact on recovery. Using serial behavioural and high-resolution magnetic resonance imaging (MRI) measurements, we tracked recovery of dexterous hand function in 28 patients with ischaemic stroke involving the primary sensorimotor cortices. We were able to classify three recovery subgroups (fast, slow, and poor) using response feature analysis of individual recovery curves. To detect areas with significant longitudinal grey matter volume (GMV) change, we performed tensor-based morphometry of MRI data acquired in the subacute phase, i.e. after the stage compromised by acute oedema and inflammation. We found significant GMV expansion in the perilesional premotor cortex, ipsilesional mediodorsal thalamus, and caudate nucleus, and GMV contraction in the contralesional cerebellum. According to an interaction model, patients with fast recovery had more perilesional than subcortical expansion, whereas the contrary was true for patients with impaired recovery. Also, there were significant voxel-wise correlations between motor performance and ipsilesional GMV contraction in the posterior parietal lobes and expansion in dorsolateral prefrontal cortex. In sum, perilesional GMV expansion is associated with successful recovery after cortical stroke, possibly reflecting the restructuring of local cortical networks. Distant changes within the prefrontal-striato-thalamic network are related to impaired recovery, probably indicating higher demands on cognitive control of motor behaviour.

Acclimatization improves submaximal exercise economy at 5533m

We tested whether the better subjective exercise tolerance perceived by mountaineers after altitude acclimatization relates to enhanced exercise economy. Thirty-two mountaineers performed progressive bicycle exercise to exhaustion at 490 m and twice at 5533 m (days 6–7 and day 11), respectively, during an expedition to Mt. Muztagh Ata. Maximal work rate (Wmax) decreased from mean ± SD 356 ± 73 watts at 490 m to 191 ± 49 watts and 193 ± 45 watts at 5533 m, days 6–7 and day 11, respectively; corresponding maximal oxygen uptakes (VO2max) were 50.7 ± 9.5, 26.3 ± 5.6, 24.7 ± 7.0 mL/min/kg (P = 0.0001 5533 m vs 490 m). On days 6–7 (5533 m), VO2 at 75% Wmax (152 ± 37 watts) was 1.75 ± 0.45 L/min, oxygen saturation 68 ± 8%. On day 11 (5533 m), at the same submaximal work rate, VO2 was lower (1.61 ± 0.47 L/min, P < 0.027) indicating improved net efficiency; oxygen saturation was higher (74 ± 7%, P < 0.0004) but ratios of VO2 to work rate increments remained unchanged. On day 11, mountaineers climbed faster from 4497 m to 5533 m than on days 5–6 but perceived less effort (visual analog scale 50 ± 15 vs 57 ± 20, P = 0.006) and reduced symptoms of acute mountain sickness. We conclude that the better performance and subjective exercise tolerance after acclimatization were related to regression of acute mountain sickness and improved submaximal exercise economy because of lower metabolic demands for non-external work-performing functions.

Effect of acute hypoxia on maximal oxygen uptake and maximal performance during leg and upper-body exercise in Nordic combined skiers

We examined the effect of normobaric hypoxia (3200 m) on maximal oxygen uptake (VO2max) and maximal power output (Pmax) during leg and upper-body exercise to identify functional and structural correlates of the variability in the decrement of VO2max (DeltaVO2max) and of maximal power output (DeltaPmax). Seven well trained male Nordic combined skiers performed incremental exercise tests to exhaustion on a cycle ergometer (leg exercise) and on a custom built doublepoling ergometer for cross-country skiing (upper-body exercise). Tests were carried out in normoxia (560 m) and normobaric hypoxia (3200 m); biopsies were taken from m. deltoideus. DeltaVO2max was not significantly different between leg (-9.1+/-4.9%) and upper-body exercise (-7.9+/-5.8%). By contrast, Pmax was significantly more reduced during leg exercise (-17.3+/-3.3%) than during upper-body exercise (-9.6+/-6.4%, p<0.05). Correlation analysis did not reveal any significant relationship between leg and upper-body exercise neither for DeltaVO2max nor for DeltaPmax. Furthermore, no relationship was observed between individual DeltaVO2max and DeltaPmax. Analysis of structural data of m. deltoideus revealed a significant correlation between capillary density and DeltaPmax (R=-0.80, p=0.03), as well as between volume density of mitochondria and DeltaPmax (R=-0.75, p=0.05). In conclusion, it seems that VO2max and Pmax are differently affected by hypoxia. The ability to tolerate hypoxia is a characteristic of the individual depending in part on the exercise mode. We present evidence that athletes with a high capillarity and a high muscular oxidative capacity are more sensitive to hypoxia.

Different response to eccentric and concentric training in older men and women

Sarcopenia is the age-related loss of muscle mass and strength and has been associated with an increased risk of falling and the development of metabolic diseases. Various training protocols, nutritional and hormonal interventions have been proposed to prevent sarcopenia. This study explores the potential of continuous eccentric exercise to retard age-related loss of muscle mass and function. Elderly men and women (80.6 +/- 3.5 years) were randomized to one of three training interventions demanding a training effort of two sessions weekly for 12 weeks: cognitive training (CT; n = 16), conventional resistance training (RET; n = 23) and eccentric ergometer training (EET; n = 23). Subjects were tested for functional parameters and body composition. Biopsies were collected from M. vastus lateralis before and after the intervention for the assessment of fiber size and composition. Maximal isometric leg extension strength (MEL: +8.4 +/- 1.7%) and eccentric muscle coordination (COORD: -43 +/- 4%) were significantly improved with EET but not with RET (MEL: +2.3 +/- 2.0%; COORD: -13 +/- 3%) and CT (MEL: -2.3 +/- 2.5%; COORD: -12 +/- 5%), respectively. We observed a loss of body fat (-5.0 +/- 1.1%) and thigh fat (-6.9 +/- 1.5%) in EET subjects only. Relative thigh lean mass increased with EET (+2.5 +/- 0.6%) and RET (+2.0 +/- 0.3%) and correlated negatively with type IIX/type II muscle fiber ratios. It was concluded that both RET and EET are beneficial for the elderly with regard to muscle functional and structural improvements but differ in their spectrum of effects. A training frequency of only two sessions per week seems to be the lower limit for a training stimulus to reveal measurable benefits.

MR Spectroscopy and Spectroscopic Imaging for Evaluation of Skeletal Muscle Metabolism: Basics and Applications in Metabolic Diseases

Magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) provide metabolic information on the musculoskeletal system, thus helping to understand the biochemical and pathophysiological nature of numerous diseases. In particular, MRS has been used to study the energy metabolism of muscular tissue since the very beginning of magnetic resonance examinations in humans when small-bore magnets for studies of the limbs became available. Even more than in other organs, the observation of non-proton-nuclei was important in muscle tissue. Spatial localization was less demanding in these studies, however, high temporal resolution was necessary to follow metabolism during exercise and recovery. The observation of high-energy phosphates during and after the application of workload gives insight into oxidative phosphorylation, a process that takes place in the mitochondria and characterizes impaired mitochondrial function. New applications in insulin-resistant patients followed the development of volume-selective 1H-MRS in whole-body magnets. Nowadays, multinuclear MRS and MRSI of the musculoskeletal system provide several windows to vital biochemical pathways noninvasively. It is shown how MRS and MRSI have been used in numerous diseases to characterize an involvement of the muscular metabolism.

Exercise-associated glucose metabolism in individuals with type 1 diabetes mellitus.

PURPOSE OF REVIEW The primary focus of this review is threefold: first, to summarize available knowledge on exercise-associated glucose metabolism in individuals with type 1 diabetes mellitus (T1DM); second, to elucidate physiological mechanisms predisposing to glycemic variations in patients in T1DM; and third, to describe novel approaches derived from physiological perceptions applicable to stabilize exercise-related glycemia in individuals with T1DM. RECENT FINDINGS Recent studies corroborate the concept that despite partial differences in counter-regulatory mechanisms individuals with T1DM do not fundamentally differ in their glucose response to exercise when compared with healthy individuals if studies are performed under standardized conditions with insulin and glucose levels held close to physiological ranges. Novel approaches derived from a better understanding of exercise-associated glucose metabolism (e.g., the concept of intermittent high-intensity exercise) may provide alternative ways to master the challenges imposed by exercise to individuals with T1DM. SUMMARY Exercise still imposes high demands on patients with T1DM and increases risks for hypoglycemia and hyperglycemia. Deeper insight into the associated metabolic pathways has revealed novel options to stabilize exercise-associated glucose levels in these patients.

Effects of lung recruitment maneuvers on splanchnic organ perfusion during endotoxin-induced pulmonary arterial hypertension

Lung recruitment maneuvers (RMs), used to reopen atelectatic lung units and to improve oxygenation during mechanical ventilation, may result in hemodynamic impairment. We hypothesize that pulmonary arterial hypertension aggravates the consequences of RMs in the splanchnic circulation. Twelve anesthetized pigs underwent laparotomy and prolonged postoperative ventilation. Systemic, regional, and organ blood flows were monitored. After 6 h (= baseline), a recruitment maneuver was performed with sustained inflation of the lungs. Thereafter, the pigs were randomly assigned to group C (control, n = 6) or group E with endotoxin-induced pulmonary arterial hypertension (n = 6). Endotoxemia resulted in a normotensive and hyperdynamic state and a deterioration of the oxygenation index by 33%. The RM was then repeated in both groups. Pulmonary artery pressure increased during lipopolysaccharide infusion from 17 ± 2 mmHg (mean ± SD) to 31 ± 10 mmHg and remained unchanged in controls (P < 0.05). During endotoxemia, RM decreased aortic pulse pressure from 37 ± 14 mmHg to 27 ± 13 mmHg (mean ± SD, P = 0.024). The blood flows of the renal artery, hepatic artery, celiac trunk, superior mesenteric artery, and portal vein decreased to 71% ± 21%, 69% ± 20%, 76% ± 16%, 79% ± 18%, and 81% ± 12%, respectively, of baseline flows before RM (P < 0.05 all). Organ perfusion of kidney cortex, kidney medulla, liver, and jejunal mucosa in group E decreased to 65% ± 19%, 77% ± 13%, 66% ± 26%, and 71% ± 12%, respectively, of baseline flows (P < 0.05 all). The corresponding recovery to at least 90% of baseline regional blood flow and organ perfusion lasted 1 to 5 min. Importantly, the decreases in regional blood flows and organ perfusion and the time to recovery of these flows did not differ from the controls. In conclusion, lipopolysaccharide-induced pulmonary arterial hypertension does not aggravate the RM-induced significant but short-lasting decreases in systemic, regional, and organ blood flows.

Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more: results of a multicenter phase 3 study

In older patients with acute myeloid leukemia (AML), the prevention of relapse has remained one of the major therapeutic challenges, with more than 75% relapses after complete remission. The anti-CD33 immunotoxin conjugate gemtuzumab ozogamicin (GO) has shown antileukemic remission induction activity in patients with relapsed AML. Patients with AML or refractory anemia with excess blasts in first complete remission attained after intensive induction chemotherapy were randomized between 3 cycles of GO (6 mg/m(2) every 4 weeks) or no postremission therapy (control) to assess whether GO would improve outcome. The 2 treatment groups (113 patients receiving GO vs 119 control patients) were comparable with regard to age (60-78 years, median 67 years), performance status, and cytogenetics. A total of 110 of 113 received at least 1 cycle of GO, and 65 of 113 patients completed the 3 cycles. Premature discontinuation was mainly attributable to incomplete hematologic recovery or intercurrent relapse. Median time to recovery of platelets 50 x 10(9)/L and neutrophils 0.5 x 10(9)/L after GO was 14 days and 20 days. Nonhematologic toxicities were mild overall, but there was 1 toxic death caused by liver failure. There were no significant differences between both treatment groups with regard to relapse probabilities, nonrelapse mortality, overall survival, or disease-free survival (17% vs 16% at 5 years). Postremission treatment with GO in older AML patients does not provide benefits regarding any clinical end points. The HOVON-43 study is registered at The Netherlands Trial Registry (number NTR212) and at http://www.controlled-trials.com as ISRCTN77039377.

Clinical use of temporary percutaneous left ventricular assist devices

Temporary percutaneous left ventricular assist devices (TPLVAD) can be inserted and removed in awake patients. They substitute left ventricular function for a period of up to a few weeks and provide an excellent backup and bridge to recovery or decision.

Continuous flow left ventricular assist devices: a valid option for heart failure patients

Recent outstanding clinical advances with new mechanical circulatory systems (MCS) have led to additional strategies in the treatment of end stage heart failure (HF). Heart transplantation (HTx) can be postponed and for certain patients even replaced by smaller implantable left ventricular assist devices (LVAD). Mechanical support of the failing left ventricle enables appropriate hemodynamic stabilisation and recovery of secondary organ failure, often seen in these severely ill patients. These new devices may be of great help to bridge patients until a suitable cardiac allograft is available but are also discussed as definitive treatment for patients who do not qualify for transplantation. Main indications for LVAD implantation are bridge to recovery, bridge to transplantation or destination therapy. LVAD may be an important tool for patients with an expected prolonged period on the waiting list, for instance those with blood group 0 or B, with a body weight over 90 kg and those with potentially reversible secondary organ failure and pulmonary artery hypertension. However, LVAD implantation means an additional heart operation with inherent peri-operative risks and complications during the waiting period. Finally, cardiac transplantation in patients with prior implantation of a LVAD represents a surgical challenge. This review summarises the current knowledge about LVAD and continuous flow devices especially since the latter have been increasingly used worldwide in the most recent years. The review is also based on the institutional experience at Berne University Hospital between 2000 and 2012. Apart from short-term devices (Impella, Cardiac Assist, Deltastream and ECMO) which were used in approximately 150 cases, 85 pulsatile long-term LVAD, RVAD or bi-VAD and 44 non-pulsatile LVAD (mainly HeartMateII and HeartWare) were implanted. After an initial learning curve, one-year mortality dropped to 10.4% in the last 58 patients.

The role of stress hormones in the relationship between resting blood pressure and coagulation activity

BACKGROUND: Systemic hypertension confers a hypercoagulable state. We hypothesized that resting mean blood pressure (MBP) interacts with stress hormones in predicting coagulation activity at rest and with acute mental stress. METHODS: We measured plasma clotting factor VII activity (FVII:C), FVIII:C, fibrinogen, D-dimer, epinephrine and norepinephrine, and saliva cortisol in 42 otherwise healthy normotensive and hypertensive medication-free men (mean age 43 +/- 14 years) at rest, immediately after stress, and twice during 60 min of recovery from stress. RESULTS: At rest, the MBP-by-epinephrine interaction predicted FVII:C (beta = -0.33, P < 0.04) and D-dimer (beta = 0.26, P < 0.05), and the MBP-by-cortisol interaction predicted D-dimer (beta = 0.43, P = 0.001), all independent of age and body mass index (BMI). Resting norepinephrine predicted fibrinogen (beta = 0.42, P < 0.01) and D-dimer (beta = 0.37, P < 0.03), both independent of MBP. MBP predicted FVIII:C change from rest to immediately post-stress independent of epinephrine (beta = -0.37, P < 0.03) and norepinephrine (beta = -0.38, P < 0.02). Cortisol change predicted FVIII:C change (beta = -0.30, P < 0.05) independent of age, BMI and MBP. Integrated norepinephrine change from rest to recovery (area under the curve, AUC) predicted D-dimer AUC (beta = 0.34, P = 0.04) independent of MBP. The MBP-by-epinephrine AUC interaction predicted FVII:C AUC (beta = 0.28) and fibrinogen AUC (beta = -0.30), and the MBP-by-norepinephrine AUC interaction predicted FVIII:C AUC (beta = -0.28), all with borderline significance (Ps < 0.09) and independent of age and BMI. CONCLUSIONS: MBP significantly altered the association between stress hormones and coagulation activity at rest and, with borderline significance, across the entire stress and recovery interval. Independent of MBP, catecholamines were associated with procoagulant effects and cortisol reactivity dampened the acute procoagulant stress response.

Percutaneous left ventricular assist devices for treatment of patients with cardiogenic shock

PURPOSE OF REVIEW: This review will discuss the rationale and clinical utility of percutaneous left ventricular assist devices in the management of patients with cardiogenic shock. RECENT FINDINGS: Left ventricular assist devices maintain partial or total circulatory support in case of severe left ventricular failure. Currently, two percutaneous left ventricular assist devices are available for clinical use: the TandemHeart and the Impella Recover LP system. Compared with the intraaortic balloon pump, the TandemHeart has been shown to significantly reduce preload and to augment cardiac output. In a randomized comparison between the TandemHeart and intraaortic balloon pump support in patients with cardiogenic shock, the improved cardiac index afforded by the left ventricular assist device resulted in a more rapid decrease in serum lactate and improved renal function. There were, however, no significant differences with respect to 30-day mortality, and complications including limb ischemia and severe bleeding were more frequent with left ventricular assist devices than intraaortic balloon pump support. SUMMARY: The advent of percutaneous left ventricular assist devices constitutes an important advance in the management of patients with severe cardiogenic shock and may serve as bridge to recovery or heart transplantation in carefully selected patients. While improvement of hemodynamic parameters appears promising, it remains to be determined whether this benefit translates into improved clinical outcome.