Frailty in chronic heart failure: a multidimensional assessment of older patients undergoing cardiac rehabilitation.

BACKGROUND: Chronic heart failure (CHF) is often associated with cognitive, psychological, and functional disorders. In addition, since patients suffering from this condition are often older adults, the presence of frailty could worsen the clinical situation. METHODS: The present multicentric observational study aimed to investigate, through a multidimensional evaluation, the associations between clinical, functional, cognitive, psychological, and frailty variables of older (age ≥65) CHF inpatients undergoing cardiac rehabilitation and to identify the eventual independent predictors of the frailty status. RESULTS: The study included 85 patients (mean age 73.88±5.84). The disease severity of the sample was moderate (left ventricular ejection fraction = 41.79±15.40). Among the patients, 32.94% had cognitive impairment, 12.94% and 14.11% reported moderate to severe anxious or depressive symptoms, respectively, and 34.12% were classified as frail (Clinical Frailty Scale [CFS] score ≥5). The CFS score showed a negative correlation with cognitive status (Addenbrooke's Cognitive Examination III [ACE III] [r=-0.48, P≤0.0001] and Frontal Assessment Battery [FAB] [r=-0.33, P=0.0001]) and functional status (Short Physical Performance Battery [SPPB] [r=-0.55, P≤0.0001] and Barthel Index [r=-0.52, P≤0.0001]), while showing a positive correlation with comorbidities (Cumulative Illness Rating Scale [CIRS] [r=0.40, P≤0.0001]). The stepwise regression analysis revealed that ACE III, SPPB, and CIRS were independent predictors of frailty status (CFS). CONCLUSIONS: Frailty is an important variable that should be considered since it is linked with most of the variables that play a role in the management and outcomes of older CHF patients and, thus, its evaluation should be integrated into the usual assessment in cardiac rehabilitation.

Nocturnal hypoxemic burden in patients with heart failure: Emerging prognostic role of its nonspecific component.

BACKGROUND: Nocturnal hypoxemic burden has been shown to be a robust, independent predictor of all-cause mortality in patients with heart failure and reduced ejection fraction (HFrEF) and to occur in a severe form even in patients with low or negligible frequency of respiratory events (apneas/hypopneas). This suggests the existence of two components of hypoxemic burden: one unrelated to respiratory events and the other related. The aim of this study was to characterize these two components and to evaluate their prognostic value. METHODS: Nocturnal hypoxemic burden was assessed in a cohort of 280 patients with HFrEF by measuring the percentage of sleep with an oxygen saturation (SpO2) <90% (T90), and the area of the SpO2 curve below 90% (Area90). Both indices were also recalculated within the sleep segments associated with respiratory events (event-related component: T90Eve, Area90Eve) and outside these segments (nonspecific component: T90Nspec, Area90Nspec). The outcome of the survival analysis (Cox regression) was all-cause mortality. RESULTS: During a median follow-up of 60 months, 87 patients died. T90, Area90, and their components were significant in univariate analysis (P < .05 all). However, when these indices were adjusted for known risk factors, T90, T90Nspec, Area90, and Area90Nspec remained statistically significant (P = .018, hazard ratio (HR)=1.12, 95%CI=(1.02, 1.23); P = .007, HR=1.20, 95% CI = [1.05, 1.37]; P = .020, HR = 1.05, 95% CI = [1.01, 1.10]; P = .0006, HR = 1.15, 95% CI = [1.06, 1.25]), whereas T90Eve and Area90Eve did not (P = .27, P = .28). These results were internally validated using bootstrap resampling. CONCLUSIONS: By demonstrating a significant independent association of nonspecific hypoxemic burden with all-cause mortality, this study suggests that this component of total nocturnal hypoxemic burden may play an important prognostic role in patients with HFrEF.

Multidimensional screening and intervention program for neurocognitive disorder in vascular and multimorbid outpatients: Study protocol for a randomized clinical trial.

BACKGROUND: The heightened risk of dementia resulting from multiple comorbid conditions calls for innovative strategies. Engaging in physical and cognitive activities emerges as a protective measure against cognitive decline. This protocol aims to discuss a multidomain intervention targeting individuals with dementias secondary to cerebrovascular or other medical diseases, emphasizing an often underrepresented demographic. METHODS: This study primary objectives are: a) to identify patients affected by Neurocognitive disorder due to vascular disease or multiple etiologies (screening and diagnostic phase) and b) to evaluate the effectiveness of distinct rehabilitation protocols (intervention phase): motor training alone, paper-based cognitive rehabilitation combined with motor training, digital-based cognitive rehabilitation coupled with motor training. DISCUSSION: Identifying cognitive impairment beyond rigid neurological contexts can facilitate timely and targeted interventions. This protocol strives to address the complex interplay of cognitive decline and comorbidities through a multidimensional approach, providing insights that can shape future interventions and enhancing overall well-being in this vulnerable population. TRIAL REGISTRATION: The study has been registered on July 13, 2023 with the ClinicalTrials.gov NCT05954741 registration number (https://classic.clinicaltrials.gov/ct2/show/NCT05954741).

Impact of optimized transcutaneous auricular vagus nerve stimulation on cardiac autonomic profile in healthy subjects and heart failure patients.

Objective.To determine the optimal frequency and site of stimulation for transcutaneous vagus nerve stimulation (tVNS) to induce acute changes in the autonomic profile (heart rate (HR), heart rate variability (HRV)) in healthy subjects (HS) and patients with heart failure (HF).Approach.We designed three single-blind, randomized, cross-over studies: (1) to compare the acute effect of left tVNS at 25 Hz and 10 Hz (n= 29, age 60 ± 7 years), (2) to compare the acute effect of left and right tVNS at the best frequency identified in study 1 (n= 28 age 61 ± 7 years), and (3) to compare the acute effect of the identified optimal stimulation protocol with sham stimulation in HS and HF patients (n= 30, age 59 ± 5 years, andn= 32, age 63 ± 7 years, respectively).Main results.In study 1, left tragus stimulation at 25 Hz was more effective than stimulation at 10 Hz in decreasing HR (-1.0 ± 1.2 bpm,p< 0.001 and -0.5 ± 1.6 bpm, respectively) and inducing vagal effects (significant increase in RMSSD, and HF power). In study 2, the HR reduction was greater with left than right tragus stimulation (-0.9 ± 1.5 bpm,p< 0.01 and -0.3 ± 1.4 bpm, respectively). In study 3 in HS, left tVNS at 25 Hz significantly reduced HR, whereas sham stimulation did not (-1.1 ± 1.2 bpm,p< 0.01 and -0.2 ± 2.9 bpm, respectively). In HF patients, both active and sham stimulation produced negligible effects.Significance.Left tVNS at 25 Hz is effective in acute modulation of cardiovascular autonomic control (HR, HRV) in HS but not in HF patients (NCT05789147).

Sodium nitroprusside infusion in patients with advanced heart failure.

AIMS: Advanced heart failure (AdvHF) poses significant treatment challenges, particularly when mechanical circulatory support or transplant options are unavailable, highlighting a gap in evidence-based medical management. The aim of this study was to evaluate the safety and effectiveness of sodium nitroprusside infusion (SNP) for enhancing systemic and renal perfusion in patients with AdvHF, with or without concomitant inotropic support. METHODS AND RESULTS: We retrospectively analyzed the medical records of 406 patients with AdvHF admitted between October 2014 and September 2018 who received nocturnal SNP infusions for at least one week. In 55 patients with symptomatic hypotension or signs of peripheral hypoperfusion (differential systemic BP < 15 mmHg), continuous dobutamine infusion was added. In a subset of 155 patients who required multiple hospitalizations (median 3), data from the last hospitalization were used. No symptomatic hypotension leading to discontinuation of SNP (mean dose: 0.5 ± 0.1 µg/kg/min) was reported. Patients showed a significant increase in differential systemic blood pressure after infusion (29.2 ± 8.1 to 36.8 ± 11.6 mmHg, p < 0.001) independent of dobutamine use. Administration of SNP and dobutamine resulted in greater weight loss compared to SNP alone (-5.33 ± 7.02 vs -3.32 ± 4.0 kg, p < 0.003), but it was also associated with a significant increase in creatinine levels compared to SNP alone (+0.24 ± 0.87 vs +0.02 ± 0.43, p = 0.005). CONCLUSIONS: The results show that SNP is a safe therapeutic choice in AdvHF patients with or without concomitant inotropic support and highlight the potential efficacy of nitroprusside in improving systemic and renal perfusion in these advanced patients.

Chemotherapy-Induced Changes in Plasma Amino Acids and Lipid Oxidation of Resected Patients with Colorectal Cancer: A Background for Future Studies.

Previous studies have documented that FOLFOX and XELOX therapies negatively impact the metabolism of skeletal muscle and extra-muscle districts. This pilot study tested whether three-month FOLFOX or XELOX therapy produced changes in plasma amino acid levels (PAAL) (an estimation of whole-body amino acid metabolism) and in plasma levels of malondialdehyde (MDA), a marker of lipid hyper oxidation. Fourteen ambulatory, resected patients with colorectal cancer scheduled to receive FOLFOX (n = 9) or XELOX (n = 5) therapy, after overnight fasting, underwent peripheral venous blood sampling, to determine PAAL and MDA before, during, and at the end of three-month therapy. Fifteen healthy matched subjects (controls) only underwent measures of PAAL at baseline. The results showed changes in 87.5% of plasma essential amino acids (EAAs) and 38.4% of non-EAAs in patients treated with FOLFOX or XELOX. These changes in EAAs occurred in two opposite directions: EAAs decreased with FOLFOX and increased or did not decrease with XELOX (interactions: from p = 0.034 to p = 0.003). Baseline plasma MDA levels in both FOLFOX and XELOX patients were above the normal range of values, and increased, albeit not significantly, during therapy. In conclusion, three-month FOLFOX or XELOX therapy affected plasma EAAs differently but not the baseline MDA levels, which were already high.

Estimating maximum work rate during cardiopulmonary exercise testing from the six-minute walk distance in patients with heart failure.

Background: Exercise is recommended for patients with chronic heart failure (CHF) and its intensity is usually set as a percentage of the maximal work rate (MWR) during cardiopulmonary exercise testing (CPX) or a symptom-limited incremental test (SLIT). As these tests are not always available in cardiac rehabilitation due to logistic/cost constraints, we aimed to develop a predictive model to estimate MWR at CPX (estMWR@CPX) in CHF patients using anthropometric and clinical measures and the 6-min walk test (6 MWT), the most widely used exercise field test. Methods: This is a multicentre cross-sectional retrospective study in a cardiac rehabilitation setting. Six hundred patients with HF in New York Heart Association (NYHA) functional class I-III underwent both CPX and 6 MWT and, through multivariable linear regression analysis, we defined several predictive models to define estMWR@CPX. Results: The best model included 6 MWT, sex, age, weight, NYHA class, left ventricular ejection fraction (LVEF), smoking status and chronic obstructive pulmonary disease COPD (adjusted R2 = 0.55; 95% LoA -39 to 33 W). When LVEF was excluded as a predictor, the resulting model performed only slightly worse (adjusted R2 = 0.54; 95% LoA -42 to 34 W). Only in 34% of cases was the percentage difference between estMWR@CPX and real MWR@CPX <10% in absolute value. EstMWR@CPX tended to overestimate low values and underestimate high values of true MWR@CPX. Conclusions: Our results showed a lack of accuracy in the predictive model evaluated; therefore, for an accurate prescription of cycle-ergometer exercise training, it is necessary to assess MWR by CPX or SLIT.

Effect of lateral position on rostral fluid shift and relationship to severity of Cheyne-Stokes respiration in heart failure patients.

PURPOSE: Lateral sleep position has a significant beneficial effect on the severity of Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) in patients with heart failure (HF). We hypothesized that a reduction in rostral fluid shift from the legs in this position compared with the supine position may contribute to this effect. METHODS: In patients with CSR-CSA and an apnea-hypopnea index (AHI) ≥ 15/h (by standard polysomnography), uncalibrated leg fluid volume was measured in the supine, left lateral decubitus, and right lateral decubitus positions (in-laboratory assessment). The correlation between postural changes in fluid volume and corresponding changes in AHI was evaluated. Since there was no difference in both leg fluid volume and AHI between the right and left positions, measurements in these two conditions were combined into a single lateral position. RESULTS: In 18 patients with CSR-CSA, leg fluid volume increased by 2.7 ± 3.1% (p = 0.002) in the lateral position compared to the supine position, while AHI decreased by 46 ± 20% (p < 0.0001) with the same postural change. The correlation between postural changes in AHI and leg fluid volume was 0.22 (p = 0.42). Changes in leg fluid volume were a slow phenomenon, whereas changes in CSR-CSA severity were almost synchronous with changes in posture. CONCLUSION: Lateral position causes a reduction in rostral fluid shift compared to the supine position, but this change does not correlate with the corresponding change in CSR-CSA severity. The two changes occur on different time scales. These findings question the role of postural changes in rostral fluid shift as a determinant of corresponding changes in CSR-CSA severity.

Several dementia subtypes and mild cognitive impairment share brain reduction of neurotransmitter precursor amino acids, impaired energy metabolism, and lipid hyperoxidation.

Objective: Dementias and mild cognitive impairment (MCI) are associated with variously combined changes in the neurotransmitter system and signaling, from neurotransmitter synthesis to synaptic binding. The study tested the hypothesis that different dementia subtypes and MCI may share similar reductions of brain availability in amino acid precursors (AAPs) of neurotransmitter synthesis and concomitant similar impairment in energy production and increase of oxidative stress, i.e., two important metabolic alterations that impact neurotransmission. Materials and methods: Sixty-five demented patients (Alzheimer's disease, AD, n = 44; frontotemporal disease, FTD, n = 13; vascular disease, VaD, n = 8), 10 subjects with MCI and 15 control subjects (CTRL) were recruited for this study. Cerebrospinal fluid (CSF) and plasma levels of AAPs, energy substrates (lactate, pyruvate), and an oxidative stress marker (malondialdehyde, MDA) were measured in all participants. Results: Demented patients and subjects with MCI were similar for age, anthropometric parameters, biohumoral variables, insulin resistance (HOMA index model), and CSF neuropathology markers. Compared to age-matched CTRL, both demented patients and MCI subjects showed low CSF AAP tyrosine (precursor of dopamine and catecholamines), tryptophan (precursor of serotonin), methionine (precursor of acetylcholine) limited to AD and FTD, and phenylalanine (an essential amino acid largely used for protein synthesis) (p = 0.03 to <0.0001). No significant differences were found among dementia subtypes or between each dementia subtype and MCI subjects. In addition, demented patients and MCI subjects, compared to CTRL, had similar increases in CSF and plasma levels of pyruvate (CSF: p = 0.023 to <0.0001; plasma: p < 0.002 to <0.0001) and MDA (CSF: p < 0.035 to 0.002; plasma: p < 0.0001). Only in AD patients was the CSF level of lactate higher than in CTRL (p = 0.003). Lactate/pyruvate ratios were lower in all experimental groups than in CTRL. Conclusion: AD, FTD, and VaD dementia patients and MCI subjects may share similar deficits in AAPs, partly in energy substrates, and similar increases in oxidative stress. These metabolic alterations may be due to AAP overconsumption following high brain protein turnover (leading to phenylalanine reductions), altered mitochondrial structure and function, and an excess of free radical production. All these metabolic alterations may have a negative impact on synaptic plasticity and activity.

Patients' Clinical and Psychological Status in Different COVID-19 Waves in Italy: A Quanti-Qualitative Study.

BACKGROUND: COVID-19 waves have been characterized by different clinical manifestations, a decrease of functional abilities, and the presence of psychological symptoms. The aims of this study were to investigate differences in physical and psychological symptoms during the three Italian waves of the coronavirus pandemic. METHODS: Patients undergoing a functional, cardiological and pneumological check-up follow-up at ICS Maugeri Institutes, 2-3 months after recovery from COVID-19 were consecutively recruited to participate in the study, completing a quanti-qualitative questionnaire about anxiety, depression, PTSD symptoms, and personal resources. RESULTS: 104 patients were recruited: 44 and 60 during the first and second/third pandemic waves, respectively. Physical comorbidities were more present in the second/third waves compared to the first one, while no significant differences were found in anxious and depressive symptoms, which were significantly higher than normal during the three waves; PTSD symptoms were reported by 56.3% of patients. Family, social support, and a positive mindset were described as resources to cope with the COVID-19 burden. Negative affects arose during outbreaks (panic) and the disease (fear), while positive affect (joy) characterized only the follow-up period. CONCLUSION: This study shows how psychophysical symptoms might change during the pandemic waves and highlights the importance of protective factors to balance the subjective distress.

Observational pilot study: A comparison of amino acids and derangement of intestinal function between healthy ageing subjects and patients affected by chronic kidney disease stage CKD3b-4 in conservative management.

BACKGROUND AND AIMS: A comparison of the amino acid (AA) plasma profile and markers of intestinal absorption-inflammation between healthy subjects aged 65-70 years and age-matched patients affected by stage 3b-4 chronic kidney disease (CKD3b-4) was performed. METHODS: Eleven healthy volunteers were compared with 12 CKD3b-4 patients at their first outpatient control (T0) and after 12-months (T12). Adherence to a low protein diet (LPD, 0.6 ± 0.1 g/kg/day) was assessed by Urea Nitrogen Appearance. The following parameters were assessed: renal function, nutritional parameters, bioelectrical impedance analysis, plasma levels of 20 total amino acids (TAAs), both essential (EAAs) including branched-chain amino acids (BCAAs) and non-essential (NEAAs). Zonulin and faecal Calprotectin markers were used to evaluate intestinal permeability/inflammation. RESULTS: Four patients dropped out of the study; in the remaining 8 residual kidney function (RKF) remained stable, their LPD adherence had risen to 0.89  g/kg/day, anaemia had worsened and extracellular body fluid had increased. In comparison to healthy subjects, TAA levels of histidine, arginine, asparagine, threonine, glycine, and glutamine had all increased. No variation in BCAAs was observed. A significant increase was detected in faecal calprotectin and zonulin levels in CKD patients as the disease progressed. CONCLUSIONS: This study confirms the finding in aged patients of an alteration in plasmatic levels of several AAs secondary to uraemia. Intestinal markers provide confirmation of a relevant alteration to the intestinal function in CKD patients.

Subjective HRQoL in Patients with Sleep Apnea Syndrome Who Underwent PAP Therapy in a Rehabilitation Setting: A Longitudinal Study.

BACKGROUND: Obstructive sleep apnea (OSA) is often associated with decreased health-related quality of life (HRQoL). The aims of this study were to evaluate HRQoL, the clinical and psychological profile of suspected or verified OSA patients, and the impact of PAP therapy at 1-year follow-up. METHODS: At T0, OSA-suspected subjects underwent clinical, HRQoL, and psychological assessment. At T1, OSA patients underwent PAP therapy in a multidisciplinary rehabilitation setting. At 1 year follow-up, OSA patients were evaluated for the second time. RESULTS: At T0, OSA patients (n = 283) and suspected OSA subjects (n = 187) differed for AHI, BMI, and ESS. At T0, the PAP-treatment group (n = 101) showed moderate-severe anxious (18.7%) and depressive (11.9%) symptoms. At 1 year follow-up (n = 59), the sleep breathing pattern had normalized and there was a reduction of ESS scores and anxious symptoms. There was also an improvement in HRQoL (0.6 ± 0.4 vs. 0.7 ± 0.5, p = 0.032; 70.4 ± 19.0 vs. 79.2 ± 20.3, p = 0.001) and in satisfaction with sleep quantity (52.3 ± 31.7 vs. 71.4 ± 26.2, p = 0.001), sleep quality (48.1 ± 29.7 vs. 70.9 ± 27.1, p = 0.001), mood (58.5 ± 24.9 vs. 71.0 ± 25.6, p = 0.001), and physical resistance (61.6 ± 28.4 vs. 67.8 ± 27.4, p = 0.039). CONCLUSION: Considering the impact of PAP treatment on patients' psychological and HRQoL evaluations that we observed, our data are valuable for unveiling different profiles characterizing this clinical population.

Technology Assisted Rehabilitation Patient Perception Questionnaire (TARPP-Q): development and implementation of an instrument to evaluate patients' perception during training.

BACKGROUND: The introduction of technology-assisted rehabilitation (TAR) uncovers promising challenges for the treatment of motor disorders, particularly if combined with exergaming. Patients with neurological diseases have proved to benefit from TAR, improving their performance in several activities. However, the subjective perception of the device has never been fully addressed, being a conditioning factor for its use. The aims of the study were: (a) to develop a questionnaire on patients' personal experience with TAR and exergames in a real-world clinical setting; (b) to administer the questionnaire to a pilot group of neurologic patients to assess its feasibility and statistical properties. METHODS: A self-administrable and close-ended questionnaire, Technology Assisted Rehabilitation Patient Perception Questionnaire (TARPP-Q), designed by a multidisciplinary team, was developed in Italian through a Delphi procedure. An English translation has been developed with consensus, for understandability purposes. The ultimate version of the questionnaire was constituted of 10 questions (5 with multiple answers), totalling 29 items, exploring the patient's performance and personal experience with TAR with Augmented Performance Feedback. TARPP-Q was then administered pre-post training in an observational, feasible, multi-centric study. The study involved in-patients aged between 18 and 85 with neurological diseases, admitted for rehabilitation with TAR (upper limb or gait). FIM scale was run to control functional performance. RESULTS: Forty-four patients were included in the study. All patients answered the TARPP-Q autonomously. There were no unaccounted answers. Exploratory factor analyses identified 4 factors: Positive attitude, Usability, Hindrance perception, and Distress. Internal consistency was measured at T0. The values of Cronbach's alpha ranged from 0.72 (Distress) to 0.92 (Positive attitude). Functional Independence Measure (FIM®) scores and all TARPP-Q factors (Positive attitude, Usability, Hindrance perception, except for Distress (p = 0.11), significantly improved at the end of the treatment. A significant positive correlation between Positive attitude and Usability was also recorded. CONCLUSIONS: The TARPP-Q highlights the importance of patients' personal experience with TAR and exergaming. Large-scale applications of this questionnaire may clarify the role of patients' perception of training effectiveness, helping to customize devices and interventions.

Can we add whey protein supplementation in patients with Parkinson's disease without interfering with levodopa response?

OBJECTIVE: The main endpoint of the study was to evaluate if a daily intake of whey protein-based dietary supplement causes a worse response to levodopa in people with Parkinson's Disease (PWPD). BACKGROUND: In PWPD, the competition between large neutral aminoacids and levodopa at intestinal absorption level may interfere with dopaminergic therapy's (DRT) effect; therefore, protein redistribution dietary regimen has been suggested. Many dietary supplementations are available to help people in balancing the protein intake and overcoming muscle mass loss. However, most of the products contain protein and could potentially affect levodopa action in PWPD. METHODS: We performed a randomised single blind monocentric study on PWPD admitted in the rehabilitative unit for a 4-week multidisciplined intensive aerobic rehabilitation treatment. All patients received a standard protein redistribution dietary regimen plus a whey protein-based oral formula (N = 26) or Magnesium (N = 25) twice daily for 28 days. Neurological assessment and physical evaluation were conducted before (T0) and after (T1) rehabilitative treatment; DRT was recorded T0 and T1 as well. The delta of changes within groups in neurological (UPDRS III) and physical (TUG, 6 MW) evaluation scales was compared between groups. RESULTS: Groups were comparable at baseline in clinical and demographic data; at T1, both groups showed a decrease in UPDRS III, TUG and 6 MWT and no differences between deltas were found. DRT remained stable in both groups. CONCLUSIONS: Our results show that whey protein supplementation does not interfere with DRT's efficacy and can be used in PWPD who need a protein supplementation without restrictions in intake hours.

Postural changes in lung volumes in patients with heart failure and Cheyne-Stokes respiration: Relationship with sleep apnea severity.

BACKGROUND AND AIM: It has been proposed that the increased severity of sleep apnea frequently observed in heart failure (HF) patients with Cheyne-Stokes respiration (CSR) when sleeping in the supine compared to the lateral position, may be caused by the concomitant reduction in functional residual capacity (FRC). We assessed positional changes in FRC in patients with CSR and investigated the relationship between these changes in the laboratory and corresponding changes in CSR severity during sleep. METHODS: After a diagnostic polysomnography, 18 HF patients with dominant CSR and an apnea-hypopnea index (AHI)≥15 events/h underwent a standard pulmonary function test in the sitting position. Measurements were repeated in the supine, left lateral and right lateral. The latter two measurements were averaged to obtain a single lateral measurement. RESULTS: The FRC in the seated position was 3.0 ± 0.5 L (85 ± 13% of predicted), decreased to 2.3 ± 0.3 L (-21 ± 8%, p < 0.0001) in the supine position, and increased to 2.8 ± 0.4 L (+21 ± 12%, p < 0.0001) from the supine to the lateral position (-5±8% vs seated, p = 0.013). During sleep, the AHI and the apnea index (AI) decreased from 47 ± 15 events/h to 26 ± 12 events/h (-46 ± 20%, p < 0.0001) and from 29 ± 21 events/h to 12 ± 10 events/h (-61 ± 40%, p < 0.001) from the supine to the lateral position. Changes in the AI were significantly correlated with corresponding changes in FRC (ρ = -0.55, p = 0.032). CONCLUSION: In patients with HF and CSR, lying in the supine position causes a significant reduction in FRC in the context of a chronically reduced FRC. The negative correlation between postural changes in FRC and AI supports the hypothesis that the reduction in lung gas stores in the supine position may promote/exacerbate respiratory control instability.

Co-ultramicronized palmitoylethanolamide/luteolin normalizes GABAB-ergic activity and cortical plasticity in long COVID-19 syndrome.

OBJECTIVE: Transcranial magnetic stimulation (TMS) studies showed that patients with cognitive dysfunction and fatigue after COVID-19 exhibit impaired cortical GABAB-ergic activity, as revealed by reduced long-interval intracortical inhibition (LICI). Aim of this study was to test the effects of co-ultramicronized palmitoylethanolamide/luteolin (PEA-LUT), an endocannabinoid-like mediator able to enhance GABA-ergic transmission and to reduce neuroinflammation, on LICI. METHODS: Thirty-nine patients (26 females, mean age 49.9 ± 11.4 years, mean time from infection 296.7 ± 112.3 days) suffering from persistent cognitive difficulties and fatigue after mild COVID-19 were randomly assigned to receive either PEA-LUT 700 mg + 70 mg or PLACEBO, administered orally bid for eight weeks. The day before (PRE) and at the end of the treatment (POST), they underwent TMS protocols to assess LICI. We further evaluate short-latency afferent inhibition (SAI) and long-term potentiation (LTP)-like cortical plasticity. RESULTS: Patients treated with PEA-LUT but not with PLACEBO showed a significant increase of LICI and LTP-like cortical plasticity. SAI remained unaffected. CONCLUSIONS: Eight weeks of treatment with PEA-LUT restore GABAB activity and cortical plasticity in long Covid patients. SIGNIFICANCE: This study confirms altered physiology of the motor cortex in long COVID-19 syndrome and indicates PEA-LUT as a candidate for the treatment of this post-viral condition.

Positive affect as a predictor of non-pharmacological adherence in older Chronic Heart Failure (CHF) patients undergoing cardiac rehabilitation.

In Chronic Heart Failure (CHF) patients, psychological and cognitive variables and their association with treatment adherence have been extensively reported in the literature, but few are the investigations in older people. The present study aimed to evaluate the psychological, cognitive, and adherence to treatment profile of older (>65 years) CHF patients, the interrelation between these variables, and identify possible independent predictors of self-reported treatment adherence. CHF inpatients undergoing cardiac rehabilitation were assessed for: anxiety, depression, cognitive impairment, positive and negative affect, and self-reported adherence (adherence antecedents, pharmacological adherence, and non-pharmacological adherence). 100 CHF inpatients (mean age: 74.9 ± 7.1 years) were recruited. 16% of patients showed anxiety and 24.5% depressive symptoms; 4% presented cognitive decline. Cognitive functioning negatively correlated to depression, anxiety, and negative affect (p < 0.01). The adherence antecedents (disease acceptance, adaptation, knowledge, and socio-familiar support) negatively correlated to anxiety (p < 0.05), depression (p < 0.001), and negative affect (p < 0.05), while they positively correlated to positive affect (p < 0.01). Pharmacological adherence negatively correlated to anxiety and negative affect (p < 0.05). Conversely, non-pharmacological adherence and positive affect positively correlated (p < 0.05). Furthermore, depression and anxiety negatively predicted adherence antecedents (ß = -0.162, p = 0.037) and pharmacological adherence (ß = -0.171, p = 0.036), respectively. Finally, positive affect was found as an independent predictor of non-pharmacological adherence (ß = 0.133, p = 0.004). In cardiac rehabilitation, a specific psychological assessment focused on anxiety, depression, and affect can provide useful information to manage CHF older patients' care related to treatment adherence. In particular, positive affect should be targeted in future interventions to foster patients' non-pharmacological adherence.