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This study evaluates the cognitive impairment impact on the caregiver's burden and quality of life.Patient-caregiver dyads admitted to dementia Diagnostic-Therapeutic Care Pathway underwent a psychological and neuropsychological assessment. Overall, 30 caregivers (age 58.97 ± 14.68) of patients with dementia and 28 caregivers (age 58.57 ± 12.22) of patients with MCI were recruited. Caregiver's burden is positively correlated to the number (r = .37, p = .003) and severity (r = .37, p = .003) of neuropsychiatric patient's symptoms and with the caregiver's distress (r = .36, p = .004). It is also negatively related to good quality of life perception (r = - .52, p =

We aimed to examine biomechanical and neuroautonomic adaptation to blood volume displacement induced by tilt test in patients with previous inferoapical/inferolateral (IA-IL) or basal/apical septal (BS-AS) myocardial infarction (MI). Twenty-four patients with heart failure (HF) and previous IA-IL MI and 30 patients with HF and previous BS-AS MI were enrolled. All patients underwent head-up tilt test, radionuclide ventricular function monitoring (VEST), sympathovagal balance evaluation, and chronotropic 25-dose isoproterenol infusion test (CD25). Physiopathological reactions to stress-tests were assessed in both groups. Follow-up lasted 36 mo. IA-IL patients showed lower stroke volume (SV), cardiac output (CO), and left ventricle ejection fraction (LVEF) compared with BS-AS. End-diastolic volume decreased in IA-IL group (F = 3.1, P = 0.043) more than in BS-AS group during tilt test. The time trend of end-systolic volume, SV, CO, LVEF, and peak filling rate were similar in the two groups. Norepinephrine (IA-IL supine→tilting 499.5 (SD:28.8)→719.3 (SD:41.5) pg/mL vs. BS-AS supine→tilting 533.9 (SD:33.3)→768.8 (SD:47.9) pg/mL; P < 0.001) and epinephrine plasma concentrations (IA-IL supine→ tilting 125.7 (SD:9.8)→193.7 (SD:9.6) pg/mL vs. BS-AS supine→ tilting 118.8 (SD:8.9)→191.7 (SD:10.2) pg/mL; P < 0.001) increased in both groups. Low-to-high frequencies ratio significantly increased in IA-IL and decreased in BS-AS patients. CD25 was similar in IA-IL and BS-AS patients (IA-IL = 4.6 (SD:0.94), BS-AS = 5.0 (SD:1.06) mg; P = 0.79). CD25 predicted all-cause mortality (hazard ratio 1.48, 95% confidence interval 1.32–1.67; P < 0.0001) after adjusting for age/heart rate. In conclusion, patients with ischemic HF show abnormal biomechanical adaptation to volume displacement and compensatory sympathetic overdrive. The association of reduced b-adrenergic sensitivity and sympathetic denervation in such patients warrants for careful therapeutic choices. NEW & NOTEWORTHY The adaptation to volume displacement induced by tilt test was assessed in patients with heart failure and previous inferoapical/inferolateral or basal/apical septal myocardial infarction. The responsiveness of cardiac muscle to sympathetic nervous system stimulation predicts the mortality in patients with ischemic heart failure and may represent a useful tool for clinicians in the general assessment of this kind of patients.

Background Pisa syndrome (PS) is a clinical condition frequently associated with Parkinson's disease (PD). It is characterized by a trunk lateral flexion higher than 10 degrees and reversible when lying. One pathophysiological hypothesis is the altered verticality perception, due to a somatosensory impairment. Osteopathic Manipulative Treatment (OMT) manages fascial-system alterations, linked to somatic dysfunctions. Fascial system showed to be implicated in proprioceptive sensibility. Objective The aim of the study was to assess OMT efficacy on postural control in PD-PS patients by stabilometry. Methods In this single-blinded trial we studied 24 PD-PS patients, 12 of whom were randomly assigned to receive a multidisciplinary physical therapy protocol (MIRT) and sham OMT, while the other 12 received four OMT plus MIRT, for one month. The primary endpoint was the eye closed sway area assessment after the intervention. Evaluation of trunk lateral flexion (TLF) with DIERS formetrics was also performed. Results At one month, the sway area of the OMT group significantly decreased compared to placebo (mean delta OMT - 326.00±491.24 mm2, p = 0.01). In the experimental group TLF showed a mean inclination reduction of 3.33 degrees after treatment (p = 0.044, mean d = 0.54). Moreover, a significant positive association between delta ECSA and delta TLF was observed (p = 0.04, r = 0.46). Discussion Among PD-PS patients, MIRT plus OMT showed preliminary evidence of postural control and TLF improvement, compared to the control group.

BackgroundPersistent systemic inflammation leads to multidistrectual body dysfunctions. Attenuation of inflammation may improve patients’ functional and life prognoses. We hypothesized that essential amino acids (EAAs) given to elderly patients in rehabilitation after acute diseases may be associated with a reduced inflammatory state. Therefore, this retrospective study investigated whether the supplementation of EAAs – modulators of immune competence – was associated with a reduced inflammation rate in elderly patients.MethodsThe medical records of 282 patients admitted to the rehabilitation (rehab) institute after acute index events (surgery or medical diseases) (age: 81.18 ± 8.58 years; females: 67.9%) were analyzed.Results46 patients (16.3% of the entire population) had received EAA supplements (S), whereas the remaining 236 patients had not (N-S). Systemic inflammation (I) (serum C-reactive protein (CRP) > 0.5 mg/dL) was present in 67.4% of the I-S group and 57.2% of the I-N-S group. During rehab, the I-S group (but not the I-N-S group) showed a reduction in CRP levels ( p = 0.03) and an increase in circulating lymphocytes ( p = 0.035), immune cells of the adaptive immune system. C-reactive protein levels remained virtually unchanged in non-inflamed patients who received supplements but increased in non-inflamed patients who did not receive supplements ( p = 0.05). Stratified for developed infections, CRP levels reduced in S patients ( p = 0.008) but did not in N-S patients.ConclusionEAA supplementation was associated with reduced inflammation in both inflamed and infected patients. In addition, EAA supplementation was associated with increased circulating lymphocytes in inflamed patients.

Pancreatic Carcinoma (PC) cells have the ability to induce patient immunosuppression and to escape immunosurveillance. Low circulating lymphocytes are associated with an advanced stage of PC and reduced survival. Blood lymphocytes expressed as a percentage of Total White Blood Cells (L% TWBC) could predict chemotolerance (n° of tolerated cycles), survival time and Body Weight (BW) more effectively than lymphocytes expressed as an absolute value (LAB &gt, 1500 n°/mm3) or lymphocytes &gt, 22%, which is the lowest limit of normal values in our laboratory. Forty-one patients with advanced PC, treated with chemotherapy, were selected for this observational retrospective study. Patients were evaluated at baseline (pre-chemotherapy), and at 6, 12 and 18 months, respectively, after diagnosis of PC. The study found L ≥ 29.7% to be a better predictor of survival (COX model, using age, sex, BW, serum creatinine, bilirubin and lymphocytes as covariates), chemotolerance (r = +0.50, p = 0.001) and BW (r = +0.35, p = 0.027) than LAB &gt, 1500 or L &gt, 22%. BW did not significantly correlate with chemotolerance or survival. The preliminary results of this study suggest that L ≥ 29.7% is more effective than LAB &gt, 22% at predicting chemotolerance, survival time and nutritional status. A possible impact of nutritional status on chemotherapy and survival seems to be lymphocyte-mediated given the association between BW and L%. This study may serve as the basis for future research to explore whether nutritional interventions can improve lymphopenia, and if so, how this may be possible.

Background. Hand functionality and finger dexterity are impaired in patients with Parkinson’s disease (PD). These disturbances lead to a dependency in activities of daily living (ADL) and poor quality of life (QoL). Objective. We aimed to evaluate whether a specific occupational therapy (OT) program is effective in improving finger and hand dexterity and its impact on ADL in PD patients. Methods. We retrospectively studied PD patients, hospitalized for a 4-week multidisciplinary intensive rehabilitation treatment (MIRT) between January 2015 and June 2018. All patients underwent 1 h/day OT treatment, 5 days a week. The primary outcome measure was the O’Connor finger dexterity test; secondary outcome measures were the Minnesota dexterity test, UPDRS II, and Self-Assessment Parkinson’s Disease Disability Scale (SPDDS). These measures were assessed at admission (T0) and discharge (T1). Results. Based on the Hoehn and Yahr scale (H&Y), patients were divided into two groups: 262 subjects in H&Y stage Conclusions. We showed that PD patients who underwent a rehabilitation protocol including OT experienced improvements in finger dexterity and hand functionality. Our results underline the relevance of OT in improving autonomy and QoL in PD patients.

Background and objective: Patient selection criteria and experimental interventions of randomized controlled trials may not reflect how things work in practice. The aim of this study was to describe the characteristics of chronic obstructive pulmonary disease (COPD) patients undergoing an inpatient pulmonary rehabilitation program (PRP) and the correlates of success. Methods: Retrospective database review of 975 consecutive patients transferred from acute care hospitals after an acute exacerbation (group A: 14.6%) or admitted from home (group B: 75.4%), from 2010 to 2017. Patients were also divided according to the associated registered main diagnosis: COPD (group 1: 30.6%); COPD and respiratory failure (group 2: 51.7%); COPD and obstructive sleep apnea (group 3: 17.6%). Baseline correlates of post-PRP changes in six minute walking test (6MWT) were also evaluated. Results: Global Initiative for Chronic Obstructive Lung Disease stages 3 and 4 were the most commonly represented in group 2 (p = 0.0001). Comorbidity Index of all patients was 3.9 ± 1.8. The overall in-hospital mortality rate was 1.3% (5.6% vs 0.6%, in groups A and B, respectively; p = 0.0001). Hypertension, cardiac diseases and obesity were observed in 65.2, 52.2 and 29.6% of patients, respectively. Post-PRP 6MWT increased in all groups. Age, male gender, airway obstruction and baseline 6MWT were correlated with a post-PRP 30 meter increase in 6MWT. Conclusion: Confirming data of literature, this real-life study shows the characteristics of COPD patients undergoing an inpatient PRP with significant improvement in exercise capacity, independent of whether in stable state or after a recent exacerbation or of the associated main diagnosis. Keywords: Exercise training, COPD, Comorbidities, Exercise capacity, Respiratory failure, OSAS

Background Obstructive sleep apnea (OSA) is often associated with clinical, psychological and neuropsychological comorbidities such as Mild Cognitive Impairment (MCI). This study evaluated changes in clinical, psychosocial, Health Related Quality of Life (HRQoL) and neuropsychological profile in OSA subjects after ventilatory therapy, making comparison with normative data. The aim of the study was to verify the suitability of the HRQoL and neuropsychological screening tests in detecting variations in OSA subjects. Methods At baseline, 32 OSA subjects underwent the following assessment: EuroQol (EQ-5D-3L) and EQ VAS, Hospital Anxiety and Depression Scale (HADS), Montreal Cognitive Assessment (MoCA) and Frontal Assessment Battery (FAB). After the ventilatory titration, 31 OSA subjects repeated the EQ VAS, MoCA and FAB assessment. Results The analyzed subjects (77% male, 58.97±10.06 years old and 47.34±26.67 AHI [ev*hr-1]) showed low emotive distress, a lower perception of HRQoL than normative data and 35.48% of them exhibited executive deficits, too. MCI was detected in 3.2% and 48.4% of subjects after normative Italian and international correction, respectively. Subsequently the ventilatory therapy and the rehabilitative interdisciplinary treatment, subjects improved in EQ VAS (68.23±18.73 vs. 87.13±10.80, P=0.0001), FAB scores (15,30±2.03 vs. 16,65±1,40, P=0.007) and MoCA memory subtest scores (2.16±1.34 vs. 3.06±1.63, P=0.008). Conclusions Ventilatory therapy provided during a rehabilitative and interdisciplinary program increased subjects' HRQoL, executive functions and verbal memory.

Temporal asymmetry is a peculiar aspect of heart period (HP) variability (HPV). HPV asymmetry (HPVA) is reduced with aging and pathology, but its origin is not fully elucidated. Given the impact of respiration on HPV resulting in the respiratory sinus arrhythmia (RSA) and the asymmetric shape of the respiratory pattern, a possible link between HPVA and RSA might be expected. In this study we tested the hypothesis that HPVA is significantly associated with RSA and asymmetry of the respiratory rhythm. We studied 42 middle-aged healthy (H) subjects, and 56 chronic heart failure (CHF) patients of whom 26 assigned to the New York Heart Association (NYHA) class II (CHF-II) and 30 to NYHA class III (CHF-III). Electrocardiogram and lung volume were monitored for 8 minutes during spontaneous breathing (SB) and controlled breathing (CB) at 15 breaths/minute. The ratio of inspiratory (INSP) to expiratory (EXP) phases, namely the I/E ratio, and RSA were calculated. HPVA was estimated as the percentage of negative HP variations, traditionally measured via the Porta’s index (PI). Departures of PI from 50% indicated HPVA and its significance was tested via surrogate data. We found that RSA increased during CB and I/E ratio was smaller than 1 in all groups and experimental conditions. In H subjects the PI was about 50% during SB and it increased significantly during CB. In both CHF-II and CHF-III groups the PI was about 50% during SB and remained unmodified during CB. The PI was uncorrelated with RSA and I/E ratio regardless of the experimental condition and group. Pooling together data of different experimental conditions did not affect conclusions. Therefore, we conclude that the HPVA cannot be explained by RSA and/or I/E ratio, thus representing a peculiar feature of the cardiac control that can be aroused in middle-aged H individuals via CB.

It is still not known whether the oscillation in heart rate (HR) induced by sleep-disordered breathing (SDB) in patients with heart failure entails significant chronotropic effects. We hypothesised that since cyclical changes in ventilation and arterial blood gases during SDB affect HR through multiple and complexly interacting mechanisms characterised by large inter-subject variability, chronotropic effects may change from patient to patient. A total of 42 patients with moderate-to-severe chronic heart failure with systolic dysfunction underwent an in-hospital sleep study. Chronotropic effects of SDB were quantified by comparing the distribution of instantaneous HR during SDB with that during periods without SDB (noSDB) within the same night in each patient. Based on distribution changes from noSDB to SDB, 12, nine, 11, and 10 patients showed a significant tachycardic, bradycardic, tachycardic and bradycardic, and neither significant tachycardic nor significant bradycardic effect, respectively. Tachycardic and bradycardic effects were primarily due to an increase in the rate rather than in the magnitude of cyclical HR elevations and reductions, and were more prevalent and severe in patients with dominant obstructive and central events, respectively. The apnea-hypopnea index did not differ between groups. Conversely, the time spent with an oxygen saturation of

Conflicting results about alterations of plasma amino acid (AA) levels are reported in subjects with Alzheimer&rsquo, s disease (AD). The current study aimed to provide more homogeneous AA profiles and correlations between AAs and cognitive tests. Venous plasma AAs were measured in 54 fasting patients with AD (37 males, 17 females, 74.63 &plusmn, 8.03 yrs, 3.2 &plusmn, 1.9 yrs from symptom onset). Seventeen matched subjects without neurodegenerative symptoms (NNDS) served as a control group (C-NNDS). Patients were tested for short-term verbal memory and attention capacity and stratified for nutritional state (Mini Nutritional Assessment, MNA). Compared to C-NNDS, patients exhibited lower plasma levels of aspartic acid and taurine (p &lt, 0.0001) and higher 3-methylhistidine (p &lt, 0.0001), which were independent of patients&rsquo, MNA. In comparison to normonourished AD, the patients at risk of and with malnutrition showed a tendency towards lower ratios of Essential AAs/Total AAs, Branched-chain AAs/Total AAs, and Branched-chain AAs/Essential AAs. Serine and histidine were positively correlated with verbal memory and attention capacity deficits, respectively. Total AAs negatively correlated with attention capacity deficits. Stratifying patients with AD for MNA may identify a dual pattern of altered AAs, one due to AD per se and the other linked to nutritional state. Significant correlations were observed between several AAs and cognitive tests.

Sacubitril/valsartan improved the prognosis of patients with heart failure with reduced ejection fraction in the PARADIGM-HF study. Recently, the TRANSITION and PIONEER-HF studies demonstrated the safety and efficacy of sacubitril/valsartan in patients hospitalized for acute decompensated heart failure, with treatment initiated after hemodynamic and clinical stabilization. In this case series study, we assessed the short-term effects of sacubitril/valsartan on exercise capacity, inflammation, and biomarkers in patients with acute decompensated heart failure. Patients admitted for acute decompensated heart failure to the Department of Internal Medicine of Telese Terme Hospital and Cardiovascular Department, University of Bari, from 9 March, 2017 to 9 June, 2018 were enrolled. Following hemodynamic stabilization, patients initiated sacubitril/valsartan 24/26 mg twice a day for 4 weeks, with up-titration to 49/51 mg twice a day based on tolerability after 1 week. Efficacy outcomes included the 6-min walking test, N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and lymphocyte count. Safety outcomes included renal function, hyperkalemia, and symptomatic hypotension. In total, 40 patients completed the study and 27 (67.5%) patients were up-titrated. Compared with baseline, exercise capacity and relative lymphocyte count increased significantly after 4 weeks of treatment, while N-terminal pro-B-type natriuretic peptide and high-sensitivity C-reactive protein decreased significantly. N-terminal pro-B-type natriuretic peptide and relative lymphocyte count independently predicted the 6-min walking test distance (p = 0.021). No patients experienced any relevant side effects. Early initiation of sacubitril/valsartan in patients with heart failure with reduced ejection fraction after acute decompensated heart failure may be safe and effective in terms of functional capacity and biomarkers.

Background. Progressive increase of an aging population in Western countries will result in a growth of stroke prevalence. As many stroke survivors chronically show severe disability, increase in economic, social, and medical burden could be expected in the future. Objective and subjective measures of poststroke recovery are necessary to obtain predictive information, to improve the treatments, and to better allocate resources. Aim. To explore a measure of the temporal dimension of poststroke recovery, to search for predictive association with multiple clinical variables, and to improve tailoring of poststroke treatments. Method. In this observational monocentric cohort study, 176 poststroke inpatients at their first cerebrovascular event were consecutively enrolled. A novel measure based on the time needed to reach the main milestones of motor recovery was proposed. Moreover, two commonly used outcome measures, a measure of global functioning (Functional Independence Measure (FIM™)) and a measure of neurological poststroke deficit (Fugl-Meyer scale), were collected for the investigations of possible predictors. Results. The patients showed a substantial increase in Fugl-Meyer and FIM scores during the rehabilitative treatment. The acquisition of three milestones was significantly associated with female sex (autonomous standing), length of stay and Fugl-Meyer initial score (autonomous walking), and Fugl-Meyer initial score (functional arm). These findings provided quantitative data on motor milestone reacquisition in a sample of poststroke patients. It also demonstrated the value of the Fugl-Meyer score in predicting the acquisition of two motor milestones, relevant for daily life activities. Conclusion. Systematic recording of the timescale of poststroke recovery showed that motor milestone reacquisition happens, on average and when attainable, in less than 30 days in our sample of patients. The present study underscores the importance of the Fugl-Meyer score as a possible predictor for better improvement in reacquisition times of milestone functional recovery.

The field related to mood disorders in Parkinson’s disease (PD) is fragmented. The aim of this cohort observational study was to evaluate whether the episodes of mood alteration could appear in different disease stages and to verify how nonmotor symptoms were led off into different stages. We enrolled 93 PD outpatients (three groups: drug naive—DN; not exhibiting motor fluctuations—n-MF; and exhibiting motor fluctuations—MF) and 50 healthy controls. Mood state was assessed through the Internal State Scale (ISS) while depressive symptoms were evaluated through the Beck Depression Inventory-II (BDI-II), nonmotor symptoms by means of the Non-Motor Symptoms Scale (NMSS), and the presence of impulse control disorders (ICDs) with the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease (QUIP). Clinical and pharmacological data have also been recorded. No significant differences in mood state distribution between groups were observed. Nevertheless, as regards the mood state distribution within groups, in n-MF (47.6%) and MF patients (50%), (hypo)mania presence was significantly higher than other symptoms. In DN patients, hypomania showed a prevalence of 38.1% although it was not significant. At least one ICD was reported in 29.3% of n-MF and 50% of MF patients. In the MF group, a moderate positive correlation between ISS ACTivation subscale scores and the presence of ICDs and compulsive medication use emerged. Finally, MF patients reported higher BDI-II total scores than DN. Our results show that mood alterations in PD, considering both depressive symptoms and mood elevation, are related to the advanced stages of the disease as well as the presence of ICDs, and dopaminergic therapy would not always be able to restore a normal mood condition.

Objective Freezing of gait (FoG) is a debilitating problem in patients with PD. The multifactorial pathogenesis of FoG remains poorly understood. We aimed to find which factors are most strongly associated with the occurrence of FoG. Methods Three hundred five PD patients were enrolled and subdivided according to the presence (FoG +, n = 128) or absence (FoG-, n = 177) of FoG. Several clinical, functional, and neuropsychological data were collected and compared between groups. The association between the probability of presence of FoG and possible explanatory variables was assessed by logistic regression analysis. Results FoG + patients were younger at the diagnosis (p = 0.04), and their mean daily dose of dopaminergic drugs (p < 0.0001) was higher in comparison with FoG- patients. FoG + patients get worse in Frontal Assessment Battery (p = 0.005), had higher scores in Apathy Evaluation Scale (p = 0.03), and were much more impaired on Wisconsin Card Sorting Test (WCST) (p = 0.018), Trail Making Test A (p = 0.0013), and Ray Auditory Verbal Learning Test (p = 0.012). Levodopa equivalent dose, age (direct), age at disease onset (inverse), and WCST were significant predictors of FoG (p = 0.01, p = 0.0025, p = 0.0016, and p = 0.029, respectively). Conclusion FoG + patients show more deficits in executive functions and in motivation. The main explanatory variables of FoG occurrence are levodopa equivalent dose, age, age at disease onset, and WCST. These data suggest that a specific involvement of frontal cortical circuits in PD is responsible for certain cognitive–behavioral alterations related to the occurrence of FoG.

Background It has been hypothesized that pre-capillary pulmonary hypertension (PH) may trigger sleep disordered breathing (SDB). In patients with chronic thromboembolic PH (CTEPH), pulmonary endarterectomy (PEA) is potentially effective to improve PH. We assessed the pre- and post-operative prevalence of SDB in CTEPH patients submitted to PEA and the relationship between SDB and clinical, pulmonary and hemodynamic factors. Methods Unattended cardiorespiratory recording was performed the night before and one month after elective PEA in 50 patients. Results Before the intervention SDB prevalence (obstructive or central AHI ≥ 5/h) was 64%: 18 patients (66% female) had No-SDB, 22 (68% female) had dominant obstructive (dOSA), and 10 (20% female) had dominant central sleep apnea (dCSA). There were no differences in risk factors and the need for supplemental oxygen. Mean right atrial (mRAP) and pulmonary artery pressures (mPAP) showed a more compromised profile from No-SDB to dOSA and dCSA (mRAP: 5.5 ± 3.9 vs 7.0 ± 4.5 vs 9.7 ± 4.3 mm Hg (p = 0.054), mPAP: 39 ± 12 vs 48 ± 11 vs 51 ± 16 mm Hg (p = 0.0.47)). By contrast, cardiac index did not differ. At post-intervention, the prevalence of SDB was 68%: 16 patients had No-SDB, while 30 had dOSA and 4 dCSA, with no relationship with the relief from PH. Interestingly, 5 patients with previous CSA moved to the OSA group and 2 normalized. Conclusions Prevalence of SDB is high in patients with CTEPH even after resolution of PH. Our data support the hypothesis that pre-capillary PH may trigger CSA but not OSA, and suggest that OSA may play a role in the development of CTEPH.

BACKGROUND Parkinsonian patients in advanced stages of disease suffer from many motor and non-motor symptoms, whose responsiveness to dopamine replacement therapy and deep brain stimulation is poor. It is necessary to find complementary strategies in order to improve the clinical conditions of patients in advanced Parkinson's disease (PD) stages. OBJECTIVE We aimed to understand whether an inpatient, motor-cognitive, multidisciplinary, aerobic, intensive and goal-based rehabilitation treatment (MIRT), specifically designed for PD, is effective for patients in advanced stages of disease. METHODS 638 Parkinsonian patients, hospitalized to undergo a 4-week MIRT, were retrospectively identified. According to the Hoehn & Yahr (H&Y) scale, 496 were in H&Y stage 3 and 142 in H&Y stage 4-5. Outcome measures included: Unified Parkinson's Disease Rating Scale (UPDRS), Berg Balance Scale (BBS), Timed Up and Go Test (TUG), Six Minute Walk Test (6MWT), and Parkinson's Disease Disability Scale (PDDS). RESULTS At baseline all measures, except UPDRS IV, significantly worsened passing from H&Y stage 3 to H&Y stage 4-5 (p≤0.002 all). After rehabilitation all outcome measures significantly improved in both groups of patients (p

Background Dopamine Replacement Therapy (DRT) represents the most effective treatment for Parkinson’s disease (PD). Nevertheless, several symptoms are unresponsive to treatment and its long-term use leads to serious side effects. To optimize the pharmacological management of PD, dopamine-agonists are often prescribed to “de-novo” patients. Moreover, several studies have shown the effectiveness and the synergic effect of rehabilitation in treating PD. Objective To evaluate the synergism between DRT and rehabilitation in treating PD, by investigating the short and the long-term effectiveness of a multidisciplinary, intensive and goal-based rehabilitation treatment (MIRT) in a group of patients treated with Rotigotine. Materials and methods In this multicenter, single blinded, parallel-group, 1:1 allocation ratio, randomized, non-inferiority trial, 36 “de-novo” PD patients were evaluated along 18 months: 17 were treated with Rotigotine plus MIRT; 19 were treated with Rotigotine alone (R). The primary outcome measure was the total score of Unified Parkinson’s Disease Rating Scale (UPDRS). The secondary outcomes included the UPDRS sub-sections II and III (UPDRS II-III), the 6-Minute Walk Test (6MWT), the Timed Up and Go Test (TUG) and the amount of Rotigotine. Patients were evaluated at baseline (T0), 6 months (T1), 1 year (T2), and at 18 months (T3). Results No differences in UPDRS scores in the two groups (total score, III part and II part, p = 0.48, p = 0.90 and p = 0.40, respectively) were found in the time course. Conversely, a greater improvement in Rotigotine + MIRT group was observed for 6MWT (p

ObjectiveTo evaluate whether a 4-week multidisciplinary, aerobic, motor-cognitive and intensive rehabilitation treatment (MIRT) improves the quality of life (QoL) of patients with Parkinson’s disease (PD), in the short-term and long-term period.MethodsThis is a prospective, parallel-group, single-centre, single-blind, randomised clinical trial (ClinicalTrials.gov NCT02756676). 186 patients with PD, assigned to experimental group, underwent MIRT; conversely, 48 patients, assigned to control group, did not receive rehabilitation. Parkinson’s Disease Questionnaire-39 was assessed 2 (T0), 10 (T1) and 18 (T2, only experimental group) weeks after the enrolment. We compared T1 versus T0 scores within subjects and delta scores (T1–T0) between subjects. To investigate the long-term effects, we compared T2 and T0 scores in the experimental group.ResultsAt T0, no between-group differences in the Global Index Score (GBI) were observed (experimental group: 43.6±21.4, controls: 41.6±22.9, P=0.50). At T1, we did not find significant changes in controls (delta score: 1.2±9.9, P=0.23), and we found an improvement in GBI in the experimental group (delta score: −8.3±18.0, PConclusionsA rehabilitation treatment such as MIRT could improve QoL in patients with PD in the short-term and long-term period. Even though the single-blind design and the possible role of the placebo effect on the conclusive results must be considered as limitations of this study, the improvement in outcome measure, also maintained after a 3-month follow-up period, suggests the effectiveness of MIRT on the QoL.Clinical trial registrationNCT02756676: Pre-results.

Objective: To compare the effects on gait and balance of aquatic physiotherapy versus on-land training, in the context of an inpatient rehabilitation treatment tailored for peripheral neuropathies. Design: Parallel-group, single-center, single-blind randomized controlled trial. Subjects and setting: Consecutive patients affected by peripheral neuropathy admitted in our Neuro-Rehabilitation Unit. Interventions: Patients received a four-week rehabilitation program composed by daily sessions of conventional physiotherapy and three sessions/week of specific treatment (aquatic vs. on-land). Main measures: Primary outcome measures were Berg Balance Scale and Dynamic Gait Index. Secondary outcome measures were Neuropathic Pain Scale, Overall Neuropathy Limitations Scale, Functional Independence Measure, Functional Ambulation Classification, Conley Scale and Medical Research Council Scale score for the strength of hip and ankle flexor and extensor muscles. For each scale, we calculated the difference between the scores at discharge and admission and compared it between the two groups. Results: Forty patients were enrolled: 21 in the water-based rehabilitation group and 19 in the land-based one. Patients were similar between groups. When comparing the groups, we found that “in-water” patients had a significant better improvement in the Dynamic Gait Index score (6.00 (4.00, 7.25) vs. 4.00 (1.25, 6.00), P = 0.0433). On the opposite, the “on-land” group showed a better improvement of the Functional Ambulation Classification score (1.0 (0.75, 1.0) vs. 1.0 (1.0, 2.0), P = 0.0386). Conclusion: Aquatic physiotherapy showed an effect comparable to the land-based rehabilitation on gait and balance dysfunctions of neuropathic patients.

OBJECTIVE Several methods have been developed so far to estimate cardiac baroreflex sensitivity (BRS) through the analysis of spontaneous fluctuations of systolic arterial pressure (SAP) and R-R interval. Their relative performance in predicting cardiac mortality in heart failure patients is not known. The aim of this study was to compare the prognostic value of a set of representative indexes of spontaneous BRS in these patients. METHODS We studied 228 stable, moderate-to-severe heart failure patients with reduced ejection fraction, in sinus rhythm, who underwent an 8-min supine recording of ECG, arterial blood pressure and respiration during paced breathing (15 breaths/min). BRS was estimated according to the following methods: sequence (BRSSeq); nonparametric transfer function in the low-frequency band (BRSTF_NP-LF); parametric spectral computed in the low-frequency and high-frequency bands (BRSPS-LF and BRSPS-HF); parametric transfer function computed in the low-frequency and high-frequency bands (BRSTF_P-LF and BRSTF_P-HF); model-based closed loop (BRSCL); and bivariate phase-rectified signal averaging (BRSPRSA). RESULTS During a median follow-up of 36 months, 45 patients experienced a cardiac event. Only BRSTF_NP-LF, BRSPS-LF, BRSTF_P-LF and BRSPRSA were significantly associated with the outcome (P

Objectives To assess whether a specific land-based physical intervention with the inclusion of aquatic therapy is more effective than land-based rehabilitation alone for the treatment of balance dysfunction in patients with Parkinson disease (PD), immediately after therapy and at 6 months' follow-up. Design Randomized controlled study with 6-month follow-up. Setting A PD and brain injury rehabilitation department in a general hospital. Participants Patients (N=34) with moderate-stage PD. Intervention Seventeen patients underwent a land-based rehabilitation protocol called multidisciplinary intensive rehabilitation treatment (MIRT), and 17 underwent MIRT plus aquatic therapy (MIRT-AT). Main Outcome Measures The primary outcome measure was the Berg Balance Scale (BBS); secondary outcome measures were the Unified Parkinson Disease Rating Scale parts II and III (UPDRS II/III) and the Timed Up and Go (TUG) test. These measures were assessed in both groups at admission, at discharge, and after 6 months. Results BBS improved after treatment in both groups. Even though no statistically significant difference between groups was observed at each observation time, BBS scores at follow-up were significantly higher than at baseline in MIRT-AT patients. Both groups also showed an improvement in UPDRS II/III and TUG at the end of treatment compared with baseline, but these findings were lost at the 6-month follow-up. Conclusions Aquatic therapy added to land-based rehabilitation could provide a contribution to the treatment of balance dysfunction in patients with moderate-stage PD.

The purposes of this retrospective study were to document the prevalence of serum C-reactive protein (CRP), a biomarker of inflammation, and its potential predictive value for Rehabilitation outcomes in post-acute elderly inpatients. The medical records of 304 elderly subjects admitted to our Rehabilitation Institute for any disease following an acute event were examined. High levels of CRP (> 0.5 mg/dl) were present in 100% of the subjects, and the value > 1.5 mg/dl (n = 86) predicted unfavourable outcomes (n = 28; 32.5% of the patients: death or transfer to other institutions). Among the patients with favourable outcomes (discharge home n = 255), 62.7% still exhibited severe disabilities. Pressure ulcers and low functional status also predicted unfavourable outcomes. The study highlights the need for future investigations into the possible reduction of CRP levels, after an intensive nutritional approach and combined physical interventions.

Background: Attention is crucial to voluntary perform actions in Parkinson’s disease (PD), allowing patients to bypass the impaired habitual motor control. The asymmetrical degeneration of the dopaminergic system could affect the attentional functions. Objective: To investigate the relationship between the asymmetric dopaminergic degeneration and the attentional resources in Parkinsonian patients with right-side (RPD) and left-side (LPD) motor symptoms predominance. Methods: 50 RPD, 50 LPD, and 34 healthy controls underwent visual (V), auditory (A), and multiple choices (MC) reaction time (RTs) tasks. For PD patients, these tasks were performed before and after a 4-week intensive, motor-cognitive rehabilitation treatment (MIRT). The effectiveness of treatment was evaluated assessing Unified Parkinson’s disease Rating Scale (UPDRS) III and Timed-up and Go Test (TUG). Results: RTs did not differ between PD patients and healthy controls. Before MIRT, no differences between LPD and RPD patients were observed in RTs (p = 0.20), UPDRS III (p = 0.60), and TUG (p = 0.38). No differences in dopaminergic medication were found between groups (p = 0.44 and p = 0.66 before and after MIRT, respectively). After MIRT, LPD patients showed a significant reduction in MC RTs (p = 0.05), V RTs (p = 0.02), and MC-V RTs. A significant association between changes in RTs and improvements in UPDRS III and TUG was observed in LPD patients. Conclusion: attention does not differ among RPD patients, LPD patients and healthy controls. Only LPD patients improved their performances on attentional tasks after MIRT. We argue that the increased early susceptibility of the left nigrostriatal system to degeneration affects differently the cognitive modifiability and the neuroplastic potential. Our results could provide insight into new therapeutic approaches, highlighting the importance to design different treatments for RPD patients and LPD patients.

The goal of this retrospective study was to document any alterations in plasma amino acids (AAs) in subjects with cardiorenal syndrome type 2 (CRS 2). We analyzed data from sixteen patients with CRS 2 and eight healthy subjects (control group, C), whose plasma arterial (A) and venous (V) AA concentrations had been measured. Compared to C, the group of CRS 2 patients showed significant reductions by more than 90% in A (p &lt, 0.01) and V (p &lt, 0.01) individual AAs, whereas negative A-V differences that indicated a net muscle AA release (muscle hypercatabolism) were found in 59% of CRS 2 patients (p &lt, 0.03). No significant differences in plasma A and V AA concentrations nor in A-V differences were found between patients with mild kidney damage (N = 5, estimated glomerular filtration rate, eGFR ≥ 60 mL/min/1.73 m2) and patients with moderate-severe kidney damage (N = 11, eGFR &lt, 60 mL/min/1.73 m2). Several plasma arterial AAs correlated with hemodynamic variables, but not with GFR. The study showed that patients with CRS 2 had very low concentrations of circulating AAs, independent of the degree of GFR damage.

INTRODUCTION AND OBJECTIVES Cardiologists' work distress has been seldom studied. The ItAliaN cardiologists' Undetected distress Study survey was designed to assess prevalence of work distress and satisfaction, and to gain insight into associations among these constructs and socio-demographics and job description. METHODS We invited members of our national cardiological society (Associazione Nazionale Medici Cardiologi Ospedalieri) to participate in an anonymous, self-report, exclusively web-based survey, posted on the Associazione Nazionale Medici Cardiologi Ospedalieri website. ItAliaN cardiologists' Undetected distress Study included socio-demographics, job description and a 15-item questionnaire on job-related distress and work satisfaction. RESULTS Of 7393 invited cardiologists, 1064 completed the survey. Organizational problems and worries about medico-legal controversies were reported by 71% and 49% of participants, respectively; over one-third reported loss of enthusiasm, helplessness, work-life imbalance and lack of control over work. Conversely, 86% felt competent at work, 67% rewarded by the moral/human meaning of their work and 52% satisfied with their professional fulfilment. Factor analysis revealed a meaningful underlying structure including four factors: job strain, positive meaning, emotional fatigue and relational difficulties. Relational difficulties were more frequent in cardiologists working in primary-level than in secondary and tertiary care hospitals (P = 0.017 and P = 0.013, respectively). Interventional cardiologists reported higher positive meaning than those in the clinical inpatients area and outpatient diagnostic settings (P = 0.007 and P = 0.025, respectively) and lower emotional fatigue than subjects in the clinical inpatients area (P = 0.0005). CONCLUSION Cardiologists' work distress should be interpreted integrating job-related negative aspects with a reappraisal of protective personal and relational resources, which should be fostered to promote physicians' wellbeing at the individual, collective and organizational levels.

Background The association among psychological, neuropsychological dysfunctions and functional/clinical variables in Chronic Heart Failure (CHF) has been extensively addressed in literature. However, only a few studies investigated those associations in the older population. Purpose To evaluate the psychological/neuropsychological profile of older CHF patients, to explore the interrelation with clinical/functional variables and to identify potential independent predictors of patients’ functional status. Methods This study was conducted with a multi-center observational design. The following assessments were performed: anxiety (Hospital Anxiety and Depression Scale, HADS), depression (Geriatric Depression Scale, GDS), cognitive impairment (Addenbrooke’s Cognitive Examination Revised, ACE-R), executive functions (Frontal Assessment Battery, FAB), constructive abilities (Clock Drawing Test, CDT), psychomotor speed and alternated attention (Trail Making Test, TMT-A/B), functional status (6-minute walking test, 6MWT) and clinical variables (New York Heart Association, NYHA; Brain Natriuretic Peptide, BNP; left ventricular ejection fraction, LVEF; left ventricular end diastolic diameter, LVEDD; left ventricular end diastolic volume, LVEDV; tricuspid annular plane systolic excursion, TAPSE). Results 100 CHF patients (mean age: 74.9±7.1 years; mean LVEF: 36.1±13.4) were included in the study. Anxious and depressive symptoms were observed in 16% and 24,5% of patients, respectively. Age was related to TMT-A and CDT (r = 0.49, p

Background: Parkinson's disease (PD) is a neurodegenerative disorder causing progressive gait disability. Although robot-assisted gait training (RAGT) using the Lokomat device has been demonstrated to improve gait in PD, it is not clear what the best training settings are, in particular if a self-selected treadmill speed can give better results. Aim: The aims of this study were: 1) to evaluate if self-selected speed training using Lokomat plus virtual reality (VR) can give better results compared to self-selected speed overground training; 2) to assess the possible influence of VR on patients' gait speed in the Lokomat group. Design: Retrospective analysis. Population: Patients with idiopathic PD (N.=20), aged 18-90 years, Hoehn & Yahr 2-3, Mini Mental State Examination (MMSE) ≥24, unchanged therapy, and without freezing episodes, dyskinesia, and neurological, orthopedic, cardiac, respiratory or severe visual impairments, who underwent four weeks of gait training (five 30-minute sessions/week): ten with Lokomat (Group 1) and ten without (Group 2). Setting: Rehabilitation hospital; inpatients. Methods: Group 1: Lokomat parameters: body weight support fixed at 30%, guidance force set at 80% bilaterally. Treadmill speed was self-selected by each patient, and subsequently modified on patient request. VR scenery was applied. Group 2: self-selected speed gait training on the ground. Both groups were assessed pre- and post-training with the Unified Parkinson's Disease Rating Scale (UPDRS), Functional Independence Measure (FIM) scale, and the 10-metre walking test (10-MWT). For group 1, a VR score was evaluated. Results: All patients showed significant post-training improvement in UPDRS and FIM scores, with a significantly better improvement in Group 1 for total UPDRS (P=0.037). Velocity at 10-MWT significantly improved after rehabilitation in Group 2 (P=0.002). Lokomat treadmill speed and VR score both improved significantly after rehabilitation, but without any association (P=0.48), while a significant inverse relationship (P=0.014) was observed between the changes in 10-MWT and in treadmill speed. Conclusions: Self-selected speed Lokomat training in PD patients can provide clinical enhancements but is not superior to self-selected speed overground gait training; the influence of VR on motor performance seems to be related to non-motor aspects. Clinical rehabilitation impact: Regarding self-selected speed gait training, there seems to be no difference between RAGT and conventional overground gait training. Other parameter settings for RAGT need to be carefully investigated for a tailored use of RAGT in PD.

Synergy and redundancy are concepts that suggest, respectively, adaptability and fault tolerance of systems with complex behavior. This study computes redundancy/synergy in bivariate systems formed by a target X and a driver Y according to the predictive information decomposition approach and partial information decomposition framework based on the minimal mutual information principle. The two approaches assess the redundancy/synergy of past of X and Y in reducing the uncertainty of the current state of X. The methods were applied to evaluate the interactions between heart and respiration in healthy young subjects (n = 19) during controlled breathing at 10, 15 and 20 breaths/minute and in two groups of chronic heart failure patients during paced respiration at 6 (n = 9) and 15 (n = 20) breaths/minutes from spontaneous beat-to-beat fluctuations of heart period and respiratory signal. Both methods suggested that slowing respiratory rate below the spontaneous frequency increases redundancy of cardiorespiratory control in both healthy and pathological groups, thus possibly improving fault tolerance of the cardiorespiratory control. The two methods provide markers complementary to respiratory sinus arrhythmia and the strength of the linear coupling between heart period variability and respiration in describing the physiology of the cardiorespiratory reflex suitable to be exploited in various pathophysiological settings.

Background Freezing of gait (FOG) is one of the most disabling symptoms of Parkinson disease (PD). Different land-based rehabilitation approaches based on motor and cognitive strategies can be effective in treating FOG. Although there are data about the efficacy of aquatic therapy in ameliorating this phenomenon, no study has explored the combined effect of land-based therapies plus aquatic therapy in patients with PD who have FOG. Objective The objective was to investigate the effectiveness of a multidisciplinary, intensive, motor-cognitive rehabilitation treatment (MIRT) in improving FOG and whether implementation with aquatic therapy (MIRT-AT) adds further benefits. Design The design consisted of a single-blind, parallel-group, 1:1 allocation ratio, randomized trial. Setting The Department of Parkinson Disease, Movement Disorders and Brain Injury Rehabilitation at “Moriggia-Pelascini” Hospital (Gravedona ed Uniti, Como, Italy) was used as the setting. Participants Sixty hospitalized patients with PD who had FOG in Hoehn and Yahr stage 2 or 5-3 were included. Intervention Sixty patients with PD + FOG were randomly assigned to 2 groups: 30 underwent a 4-week MIRT and 30 underwent a 4-week MIRT-AT. Measurements The primary outcome measure was the Freezing of Gait Questionnaire; secondary outcome measures were total Unified Parkinson Disease Rating Scale (UPDRS), UPDRS II, UPDRS III, Berg Balance Scale, Timed Up and Go Test, and 6-Minute Walk Test. These measures were assessed both at admission and discharge. Results Participants in the 2 groups had similar age, sex distribution, Hoehn and Yahr stage, and most-affected side. At baseline, no difference in outcome measures was observed between the 2 groups. After treatment, a significant time effect was observed for all variables in both groups. No significant time × group interaction was observed. A between-group analysis showed nonsignificant differences between values at T1 and values at T0 for all variables. Limitations The limitations were the lack of a control group and follow-up. Conclusions We showed that a multidisciplinary, intensive, and goal-based rehabilitation treatment, such as MIRT, improves FOG in patients with PD. Although aquatic therapy could be considered a useful approach for treating FOG, it does not add further benefits to this kind of motor-cognitive rehabilitation.

Background Prognostic stratification of elderly patients with chronic obstructive pulmonary disease (COPD) is difficult due to the wide inter-individual variability in the course of the disease. No marker can exactly stratify the evolution and natural history of COPD patients. Studies have shown that leukocyte count is associated with increased risk of mortality in COPD patients. The aim of this study was to evaluate the possible role of relative lymphocyte count as a risk marker for mortality in elderly patients with COPD. Methods and results This is a3-year prospective study. A total of 218patients, mean age 75.2±7 years, with moderate to severe COPD and free from conditions affecting lymphocyte count were enrolled. The population was divided into two groups according to the relative lymphocyte count, with a cut-off of 20%. Eighty-five patients (39%) had a relative lymphocyte count ≤20%. Three-year mortality rates from any cause in patients with relative lymphocyte count ≤ or > 20% were 68 and 51%, respectively (p = 0.0012). Survival curve analysis showed higher mortality in patients with relative lymphocyte count ≤20% (p = 0.0005). After adjustment for age and sex, the hazard ratio for mortality risk according to lymphocyte count was 1.79 (95% confidence interval [CI]: 1.26–2.57, p = 0.0013), even in the analysis limited to the 171 patients without congestive heart failure (1.63; 95% CI: 1.03–2.58, p = 0.038). Conclusions Low relative lymphocyte count was associated with higher mortality in elderly patients with severe COPD. Electronic supplementary material The online version of this article (10.1186/s12890-018-0685-6) contains supplementary material, which is available to authorized users.

Purpose: Early decannulation is considered a main rehabilitative goal in tracheostomized patients. Our aim is to evaluate whether a very early rehabilitation protocol helps to reduce the tracheostomy duration in patients affected by an Acquired Brain Injury (ABI).Methods: Data about consecutive tracheostomized patients admitted in our Neuro-Rehabilitation Unit (NRU) were retrospectively collected. We defined two groups: Early Rehabilitation Group patients came from our ICU, where they started the rehabilitative treatment; Delayed Rehabilitation Group patients arrived from external ICUs and started rehabilitation in our NRU. Primary outcome was the time from tracheostomy to decannulation. Secondary outcomes were: ICU length of stay, time from NRU admission to decannulation, Glasgow Coma Scale, Coma Recovery Scale revised and Levels of Cognitive Functioning scores at NRU discharge and the re-cannulation rate.Results: We enrolled 66 patients, 40 in the Early Rehabilitation Group and 26 in the Delayed Rehabilitation Group. 70% of patients for each group could be decannulated (p = 0.73) and were analyzed. Only one patient was re-cannulated. Early Rehabilitation Group showed a shorter tracheostomy duration (61.0 vs. 94.5 days, p = 0.013), a higher probability of occurrence of decannulation (p = 0.008) and a lower ICU length of stay (30.0 vs. 52.0 days, p = 0.001). The time to decannulation in NRU was similar between groups (30.0 vs. 45.50 days, p = 0.14). All the scale scores had a significant improvement in both groups (p < 0.0001 all).Conclusions: The present study shows that an early neuro-rehabilitation protocol helps to reduce the time to decannulation in tracheostomized patients affected by ABI.

BACKGROUND Extracorporeal Shock Wave Therapy (ESWT) is effective in the treatment of calcific tendinopathy of the rotator cuff, eliciting an analgesic/anti-inflammatory action and promoting tissue regeneration. Kinesio taping (KT), another recently-introduced rehabilitative tool, exerts an analgesic and biomechanical action on joints and muscles. ESWT and KT may have a synergic effect when used in combination, but the effectiveness of the association has not been established. AIM The aim of this study was to test if the association of KT with ESWT is superior to ESWT alone in the treatment of rotator cuff calcific tendinopathy. DESIGN Randomized controlled trial. SETTING Rehabilitation Institute outpatients. POPULATION Forty-two patients with rotator cuff calcific tendinopathy were randomly assigned to the experimental group (ESWT+KT, N.=21) or control (ESWT, N.=21). METHODS In the experimental group, patients underwent three sessions (once a week for 3 weeks) of ESWT with KT applied at the end of each session. Controls underwent three sessions of ESWT only. All patients were assessed before treatment (T0) and at 1 (T1), 4 (T2) and 12 weeks (T3) after the end of treatment with the following outcome measures: a visual analogue scale (VAS), the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, Subjective Shoulder Rating Questionnaire (SSRQ), and Oxford Shoulder Score (OSS). RESULTS Both groups showed significant improvement in all outcome measures, but the time course differed between the two groups. At T1 vs. T0, the improvement was significantly better in ESWT+KT than ESWT on VAS (P=0.007), DASH (P

BACKGROUND Systemic inflammation and its impact on rehabilitation for patients with non-traumatic haemorrhagic injury (HBI) sequelae has not yet been adequately documented. OBJECTIVE AND METHODS We therefore considered 31 patients with HBI, to determine the serum levels of inflammatory markers (C-Reactive Protein, CRP and or interleukine-6, IL-6) to establish their impact on functional status (Functional Independence Measure, FIM: 18 indicating the worst performance and 126, a normal score). RESULTS The results showed an inflammation prevalence (CRP >0.5 mg/dl and/or IL 6 >7 pg/ml) of 74.2% at admission to Rehab. FIM reduction was more pronounced in inflamed compared to non-inflamed subjects (p < 0.05) and significantly correlated with blood variables sensitive to inflammation, such as alpha 1 globulin (r = - 0.565) and neutrophil/ lymphocyte ratio (r = - 0.52), CRP (r = - 0.365). At discharge from Rehab, the inflammation rate diminished. Inflamed patients showed similar gains in FIM score as their controls. In the entire population, the FIM gain was significantly associated with a gain in serum albumin, only (r = +0.56). CONCLUSIONS We conclude that systemic inflammation is prevalent in HBI patients and contributes to reduce patient functional status. However, during the Rehab stage, inflammation does not hinder the improvement rate of functional capacity.

Objective The interplay between arousals and respiratory events during Cheyne-Stokes respiration (CSR) with central sleep apnea (CSA) in heart failure (HF) patients is still not fully understood. We investigated the temporal relationship between arousals and CSR-CSA. Methods Episodes of CSR-CSA during sleep stages N1-N2 were analyzed in 22 HF patients with an apnea-hypopnea index ≥15/h, dominant CSA and central apnea index ≥5/h. For each CSR-CSA cycle (apnea + hyperpnea), we determined the onset (ARonset, relative to hyperpnea onset) and duration of detected arousals. Results Arousals (N = 2348) mostly occurred within the first half of the hyperpneic phase (42.6%, ARonset = 10.6 ± 2.1 s; duration = 10.6 ± 5.2 s) or close to hyperpnea onset (21.5%, ARonset = −0.1 ± 0.6 s; duration = 13.9 ± 5.4 s). Within-apnea arousals were less frequent (12.4%, ARonset = −16.0 ± 4.7 s; duration = 3.8 ± 1.4 s). The proportion of CSR-CSA cycles without any hyperpnea-related arousal was 27.5 ± 18.2%. Hyperpnea-related arousability (total number of hyperpneic arousals/total duration of hyperpneas) and apnea-related arousability were 63.4 ± 21.0/h and 23.8 ± 16.9/h, respectively (p Conclusion During CSR-CSA, a significant proportion of arousals occur at hyperpnea onset, indicating a low arousal threshold. Hyperpneic arousals are not essential for CSR-CSA. Arousability markedly increases during hyperpneas, likely due to the concurrent increase in chemoreceptor stimulation. Significance This study extends current knowledge on the interplay between sleep instability and respiratory events during CSR-CSA.

In the last decade robotic devices have been applied in rehabilitation to overcome walking disability in neurologic diseases with promising results. Robot assisted gait training (RAGT) using the Lokomat seems not only to improve gait parameters but also the perception of well-being. Data on the psychosocial patient-robot impact are limited, in particular in the real-world of RAGT, in the rehabilitation setting. During rehabilitation training, the Lokomat can be considered an "assistive device for movement". This allowed the use of the Psychosocial Impact of Assistive Device Scale- PIADS to describe patient interaction with the Lokomat. The primary aim of this pilot study was to evaluate the psychosocial impact of the Lokomat in an in-patient rehabilitation setting using the PIADS; secondary aims were to assess whether the psychosocial impact of RAGT is different between pathological sub-groups and if the Lokomat influenced functional variables (Functional Independence Measure scale-FIM and parameters provided by the Lokomat itself). Thirty-nine consecutive patients (69% males, 54.0±18.0 years) eligible for Lokomat training, with etiologically heterogeneous walking disabilities (Parkinson's Disease, n = 10; Spinal Cord Injury, n = 21; Ictus Event, n = 8) were enrolled. Patients were assessed with the FIM before and after rehabilitation with Lokomat, and the PIADS was administered after the rehabilitative period with Lokomat. Overall the PIADS score was positive (35.8±21.6), as well as the three sub-scales, pertaining to "ability", "adaptability" and "self-esteem" (17.2±10.4, 8.9±5.5 and 10.1±6.6 respectively) with no between-group differences. All patients significantly improved in gait measure and motor FIM scale (difference after-before treatment values: 11.7±9.8 and 11.2±10.3 respectively), increased treadmill speed (0.4 ± 0.2m/s), reduced body weight support (-14.0±9.5%) and guidance force (-13.1 ± 10.7%). This pilot study indicates that Lokomat, in a real-world in-patient setting, may have a generalised approval, independent of disease, underlining the importance of the psycho-social framework for patients training with assistive robotic-devices.

Aims Obstructive (OSA) and central sleep apnoea (CSA) are a common comorbidity in patients with heart failure. The purpose of this study was to assess and compare the impact of body position on the severity of sleep apnoea in these two groups of patients. Methods and results Standard polysomnography was performed in consecutive, clinically stable, optimally treated patients with moderate-to-severe heart failure and systolic dysfunction. Patients with an apnoea–hypopnoea index (AHI) ≥15/h (n = 120) were included in the study. The severity of sleep-disordered breathing was quantified by the AHI, the mean value of oxygen desaturations (O2desat) and the apnoea ratio. Data from the right and left positions were combined into a single lateral position. Positional sleep apnoea was defined as a >50% reduction in the AHI between the supine and the lateral position. Twenty-nine and 91 subjects had dominant OSA and CSA, respectively. The AHI markedly decreased from the supine to the lateral position in both groups [OSA: (median [q1,q3]) 50.3 [36.9, 67.6]/h vs. 10.4 [7.0, 18.5]/h, P

Background Inspiratory resistive breathing (IRB) challenges affect respiratory muscle endurance in healthy individuals, which is considered to be an interleukin 6 (IL-6)–dependent mechanism. Whether nonpharmacological thermal therapies promote the endurance of loaded inspiratory muscles in chronic obstructive pulmonary disease (COPD) is unclear. The objectives of this study were to compare the effects of two thermal interventions on endurance time (ET) and plasma IL-6 concentration following an IRB challenge. Methods This study was a randomized, parallel-group, unblinded clinical trial in a single-center setting. Forty-two patients (aged 42–76 years) suffering from mild to severe COPD participated in this study. Both groups completed 12 sessions of the mud bath therapy (MBT) (n=22) or leisure thermal activity (LTA) (n=19) in a thermal spa center in Italy. Pre- and postintervention spirometry, maximum inspiratory pressure, and plasma mediators were obtained and ET and endurance oxygen expenditure (VO2Endur) were measured following IRB challenge at 40% of maximum inspiratory pressure. Results There was no difference in ΔIL-6 between the intervention groups. But, IRB challenge increased cytokine IL-6 plasma levels systematically. The effect size was small. A statistically significant treatment by IRB challenge effect existed in ET, which significantly increased in the MBT group (P=0.003). In analysis of covariance treatment by IRB challenge analysis with LnVO2Endur as the dependent variable, ΔIL-6 after intervention predicted LnVO2Endur in the MBT group, but not in the LTA group. Adverse events occurred in two individuals in the MBT group, but they were mainly transient. One patient in the LTA group dropped out. Conclusion MBT model improves ET upon a moderate IRB challenge, indicating the occurrence of a training effect. The LnVO2Endur/ΔIL-6 suggests a physiologic adaptive mechanism in respiratory muscles of COPD patients allocated to treatment. Both thermal interventions are safe., Video abstract

Background Gait disturbances in Parkinson's disease (PD) are highly disabling and poorly responsive to drugs, especially in advanced stages. While the efficacy of a treadmill training based on external feedback and cues (treadmill-plus) on gait disturbances in early PD stages is demonstrated, no definitive evidence exists about advanced stages. Objective We aimed to evaluate the feasibility and the effects of a treadmill-plus training on gait disturbances in advanced PD. Methods Two hundred and six PD patients from medium to more advanced Hoehn & Yahr stage (stage 2, n = 79, stage 3 n = 74, and stage 4 = 53) who underwent a 4-week treadmill-plus training, were retrospectively identified. All patients were able to walk on a treadmill for one minute at 1.5 km/h, without support. Feasibility was evaluated by measuring safety, adverse events, and attrition rate. The effects of treatment were evaluated by assessing, both at enrolment and at the end of treatment, the on-land, self-paced 6-minute Walking Test (6MWT) and the gait parameters obtained from the treadmill during a 1.5 km/h trial. Results All patients completed the treadmill-plus training and no adverse events were recorded, even among more disabled patients. After training, we observed a significant improvement in the 6MWT, an increase in step length and a reduction of cadence and step variability in the whole sample. After stratifying patients according to disease stage, we found that patients in more advanced stages experienced the same improvements in all gait parameters as patients in less advanced stages. Conclusions Treadmill-plus training is well tolerated and may have a positive impact on many aspects of gait in more advanced PD stages.

Objectives: A novel technique to assess spontaneous baroreflex sensitivity (BRS) by bivariate phase-rectified signal averaging (PRSA-BRS) has been recently proposed and its independent prognostic power demonstrated. This method, however, has never been compared with the phenyleprine test (Phe-BRS), commonly regarded as the reference method in clinical and research applications. Approach: In 192 heart failure (HF) and 41 post-myocardial infarction (post-MI) patients we compared PRSA-BRS with Phe-BRS, assessing both association and agreement. Main results: Phe-BRS and PRSA-BRS were (mean?????SD) 4.8?????5.0 (range:???3.8,25.0) and 1.2?????1.5 (?2.1,6.9) ms mmHg?1 in HF (p???0.0001), and 5.0?????3.8 (?1.2,12.5) and 0.8?????1.7 (?2.0,6.9) ms mmHg?1 in post-MI patients (p??=??0.001). Moderate association was observed (r??=??0.53, p??

In patients with chronic thromboembolic PH (CTEPH), pulmonary endoarterectomy (PEA) provides effective relief from PH. We assess the pre- and post-operative prevalence of SDB in patients with CTEPH who had been submitted to PEA and the relationship between SDB and clinical and physiological factors. Cardiorespiratory recording was performed on the night before intervention and 3-months later in 50 patients (mean age 62.5±11.1 yrs) undergoing PEA. Patients were classified as central sleep apnea (CSA) if >70% of the events were central or as obstructive sleep apnea (OSA) if > 70% were obstructive. At pre-intervention, 14 patients (57% female) had No SDB, 26 (73% female) had OSA, and 10 (20% female) CSA. There were no differences in the history of venous thrombosis, atrial fibrillation, hypertension, diabetes, COPD and in the presence of oxygen therapy. Mean right atrial pressure (RAP) and mean pulmonary artery pressure (PAP) and TAPSE showed a trend toward a more compromised profile from NoSDB to OSA and CSA. RAP: 5.6±4.2 vs 6.7±4.3 vs 9.7±4.3 mmHg (p=0.07), PAP: 40±13 vs 47±12 vs 51±16 mmHg (p=0.11), TAPSE: 19±4 vs 16±3 vs 17±3 (p=0.06). Cardiac Index, PaO2 and PaCO2 were similar among the 3 groups. At post-intervention, the prevalence of SDB did not change: 12 patients had NoSDB, while 34 had OSA and 4 CSA. However, no trend was found in the relief from PH. PAP was 27±9 vs 25±7 vs 23±6 mmHg (p=0.73). Interestingly, 7 patients with previous CSA moved to the OSA group. Prevalence of SDB is high in patients with CTEPH even after resolution of PH. These data do not support the hypothesis that precapillary PH may trigger SBD, but rather suggest that SDB may be a causative factor leading to PH.

Antonia Pierobon,1 Elisa Sini Bottelli,1 Laura Ranzini,1 Claudio Bruschi,2 Roberto Maestri,3 Giorgio Bertolotti,4 Marinella Sommaruga,5 Valeria Torlaschi,1 Simona Callegari,1 Anna Giardini1 1Psychology Unit, 2Department of Pulmonary Rehabilitation, 3Department of Biomedical Engineering, Istituti Clinici Scientifici Maugeri, IRCCS, Montescano, 4Psychology Unit, Istituti Clinici Scientifici Maugeri, IRCCS, Tratate, 5Clinical Psychology and Social Support Unit, Istituti Clinici Scientifici Maugeri, IRCCS, Camaldoli, Italy Abstract: In addition to clinical comorbidities, psychological and neuropsychological problems are frequent in COPD and may affect pulmonary rehabilitation delivery and outcome. The aims of the study were to describe a COPD population in a rehabilitative setting as regards the patients depressive symptoms, anxiety, mild cognitive impairment (MCI) and self-reported adherence and to analyze their relationships; to compare the COPD sample MCI scores with normative data; and to investigate which factors might predict adherence to prescribed physical exercise. This was a multicenter observational cross-sectional study. Of the 117 eligible stable COPD inpatients, 84 were enrolled according to Global initiative for chronic Obstructive Lung Disease (GOLD) criteria (mainly in Stage III–IV). The assessment included Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), anxiety, depression and self-reported pharmacological and nonpharmacological adherence. From the MMSE, 3.6% of patients were found to be impaired, whereas from the MoCA 9.5% had a likely MCI. Patients referred had mild-severe depression (46.7%), anxiety (40.5%), good pharmacological adherence (80.3%) and difficulties in following prescribed diet (24.1%) and exercise (51.8%); they struggled with disease acceptance (30.9%) and disease limitations acceptance (28.6%). Most of them received good family (89%) or social (53%) support. Nonpharmacological adherence, depression, anxiety and MCI showed significant relations with 6-minute walking test, body mass index (BMI) and GOLD. Depression was related to autonomous long-term oxygen therapy modifications, disease perception, family support and MCI. In the multivariate logistic regression analysis, higher BMI, higher depression and lower anxiety predicted lower adherence to exercise prescriptions (P=0.0004, odds ratio=0.796, 95% CI=0.701, 0.903; P=0.009, odds ratio=0.356, 95% CI=0.165, 0.770; and P=0.05, odds ratio=2.361, 95% CI=0.995, 5.627 respectively). In COPD patients, focusing on pharmacological and nonpharmacological adherence enhance the possibility of tailored pulmonary rehabilitation programs. Keywords: depression, anxiety, mild cognitive impairment, adherence, COPD, pulmonary rehabilitation

Quality of life (QoL) is the sense of well-being perceived by people. The improvement of parkinsonian patient’s QoL is a crucial goal for clinicians involved in rehabilitative care. In order to provide an appropriate endpoint for the assessment of the effectiveness of rehabilitation treatments on QoL of patients with Parkinson’s Disease (PD), in this study we have first translated and then validated the Belastungsfragebogen Parkinson kurzversion (BELA-P-k). This tool allows evaluating separately two crucial aspects: i) the loss of personal autonomy in activities of daily life and ii) the psychological and psychosocial impact of the disease. The BELA-P-k was translated from Dutch into Italian. Subsequently 202 PD patients filled out the questionnaire. Patients were also evaluated by using the Parkinson Disease Questionnaire −39 (PDQ39), the Unified Parkinson’s Disease Rating Scale (UPDRS), the Mini Mental State Examination (MMSE) and the Frontal Assessment Battery (FAB). The internal consistency for total of two different scores Bothered by (Bb) and Need for Help (NfH) was excellent (p = 0.91) for both categories. The correlation between Bb and NfH categories was significant and strong, very-strong, ranging from 0.78 to 0.88 (all p

Background The pattern of oxygen saturation (SaO2) measured by pulse oximetry at the finger after apnea-induced hypoxemia has been shown to be a delayed and distorted version of the same measurement at the ear (i.e. in close proximity to carotid chemoreceptors). The impact of these different sites of recording on measures of hypoxemia during Cheyne-Stokes respiration (CSR) in heart failure (HF) patients is not known. Aims and objectives The aim of this study was to investigate the difference in SaO2 measured at the ear and at the finger during CSR in HF patients. Methods We studied 8 HF patients who developed CSR during a 40min laboratory recording of SaO2 by two identical pulse oximeters with finger and ear probe. The average SaO2, the mean value of oxygen desaturations and of minima and maxima and the delay between ear and finger signals were computed and compared by bias and 95% limits of agreement (LoA). Results Data are reported in Table as mean±SD. The delay between finger and ear signals was 20.6±7.2s. Conclusions This pilot study shows that, despite little, non-significant bias, the LoA were rather wide, indicating poor agreement between SaO2 measurements at the ear and finger, with clinically relevant differences in some patients. This may potentially lead to wrong assessment of the hypoxemic burden in some HF patients during CSR.

Background Arousals from sleep are thought to play an important role in sustaining Cheyne-Stokes respiration (CSR) in heart failure (HF) patients. Whether they represent a regular or occasional component of CSR and when they occur, however, have not yet been thoroughly investigated. Aims and objectives To determine the incidence and time of occurrence of arousals during CSR. Methods We studied 20 stable HF patients with reduced ejection fraction, an apnea-hypopnea index ≥15/h and dominant central sleep apnea. Arousal onset (ARon) was objectively determined using dedicated software. The analysis focused on all arousals at least partly concurrent with the hyperpneic phase of CS. Arousals were classified as “Early” (EA), if ARonoccurred before 3 s from hyperpnea onset; “Almost synchronous” (AS), if ARonoccurred between 3 s before hyperpnea onset and the end of the first post-apneic breath; “Late” (LA), if ARonoccurred after the first post-apneic breath. Results Incidence data (number of arousals /number of CSR cycles x 100) from the studied patients are given below (from 2048 CSR cycles): Conclusions Although, on average, the great majority of CSR cycles are associated with an arousal, there are large differences between patients both in the total incidence and in the time of occurrence of arousals. These findings suggest that attempts at stabilizing breathing by pharmacological manipulation of the arousal threshold should be patient specific.

Background to date, there are no medical or surgical treatments for progressive supranuclear palsy (PSP). It is possible to speculate that patients with PSP could benefit from rehabilitative treatments designed for Parkinson's disease, including the use of robot-assisted walking training. Objective to evaluate whether the use of the robotic device Lokomat® is superior in PSP patients to the use of treadmill with visual cues and auditory feedbacks (treadmill-plus) in the context of an aerobic, multidisciplinary, intensive, motor-cognitive and goal-based rehabilitation treatment (MIRT) conceived for Parkinsonian patients. Methods we enrolled twenty-four PSP patients. Twelve subjects underwent a 4-week MIRT exploiting the use of the treadmill-plus (MIRT group). Twelve subjects underwent the same treatment, but replacing the treadmill-plus with Lokomat® (MIRT-Lokomat group). Subjects were evaluated with clinical and functional scales at admission and discharge. The primary outcomes were the total PSP Rating Scale (PSPRS) score and its "limb" and "gait" sub-scores. Secondary outcomes were Berg Balance Scale (BBS), Six Minutes Walking test (6MWT) and the number of falls. Results total PSPRS, PSPRS-gait sub-score, BBS, 6MWT and number of falls improved significantly in both groups (p ≤ 0.003 all, except 6MWT, p = 0.032 and p = 0.018 in MIRT-Lokomat and MIRT group respectively). The PSPRS-limb sub-score improved significantly only in the MIRT group (p = 0.002). A significant difference between groups was observed only for total PSPRS, indicating a slightly better improvement for patients in the MIRT group (p = 0.047). No differences between groups were revealed for the other outcomes, indicating that the effect of rehabilitation was similar in both groups. Conclusions Lokomat® training, in comparison with treadmill-plus training, does not provide further benefits in PSP patients undergoing MIRT. Our findings suggest the usefulness of an aerobic, multidisciplinary, intensive, motor-cognitive and goal-based approach for the rehabilitation of patients suffering from such a complex disease as PSP. Trial registration This trial was registered on ClinicalTrials.gov, NCT02109393.