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The impact of the COVID-19 pandemic influences of COPD patients. The worsening of their health status may contribute to a higher pain prevalence.The aim of this study was to analyze the pain-related variables before and during the COVID-19 pandemic in patients with chronic obstructive pulmonary disease.In this cross-sectional case-control study, stable patients with chronic obstructive pulmonary disease without a COVID-19 diagnosis were evaluated before and during the pandemic. The main outcomes were the pronociceptive pain profile (general pain sensitivity, pain intensity, pain interference, and pressure pain sensitivity) and the psychological vulnerability (perceived health status, anxiety, and depression).Our results showed that patients with chronic obstructive pulmonary disease during COVID-19 pandemic experienced higher general pain sensitivity and intensity with statistical differences in pain interference (p.001), being the overall perceived health status lower than before the pandemic (p.05).We concluded that patients with chronic obstructive pulmonary disease during the COVID-19 pandemic showed a rise the pronociceptive pain profile accompanied by increased psychological vulnerability.

Several antibody-drug conjugates (ADCs) have been recently approved to treat solid tumours. Since ADCs seem to have activity in multiple malignancies sharing the expression of a specific antigen, they may be mirroring the experience of histology-agnostic-targeted treatments. So, the possibility to interpret the activity of some ADCs across different cancer types in a biomarker-driven perspective arises. However, relevant biological, methodological, and regulatory challenges should be highlighted and addressed, in order to grant ADCs biomarker-driven regulatory approvals in the next future. In this review, we discuss challenges and opportunities posed by the pan-histological expansion of ADCs in solid tumours. In particular, we provide an overview about technological and manufacturing advancements; we offer up-to-date highlights of the current evidence from clinical trials investigating ADCs in solid tumours; we discuss the need for the identification of optimal predictive biomarkers, as well as major methodological, statistical, and regulatory considerations for a biomarker-driven histology-agnostic approach.

The treatment landscape of early triple-negative breast cancer (TNBC) has recently expanded after the Food and Drug Administration (FDA) approval of pembrolizumab in combination with neoadjuvant chemotherapy. The addition of this immune checkpoint inhibitor (ICI) has shown significantly increased pathological complete response (pCR) rate and event-free survival (EFS) in the KEYNOTE-522 phase III trial. Several additional studies are ongoing with the goal of further improving the outcomes and achieving an optimal integration of ICIs in the treatment of TNBC.The article examines pCR and survival rates in TNBC. It appraises clinical trials investigating neoadjuvant ICIs for TNBC and the improvement of pCR rates (biomarker-driven escalation of treatment, optimization of chemotherapy backbone, and addition of locoregional treatments or innovative agents). Insights into the role of pCR as a surrogate endpoint and the possibility of enhancing pCR rates for women affected by early TNBC are offered.The pharmacopoeia of early TNBC is growing and becoming more heterogeneous with the advent of ICIs; to enhance the clinical benefit of patients, it is necessary to develop response endpoints that consider the mechanism of action of experimental drugs, to optimize patient selection through validated biomarkers, and to compare the most promising treatment strategies in randomized clinical trials.

Patients with HER2-positive breast cancer account for approximately 15% to 20% of all breast cancers and represent one of the most aggressive breast cancer subtypes. Survival rates of patients with metastatic disease have improved dramatically and progressively. Many new agents have been developed, and long-term follow-up from trials of anti-HER2 agents has shown long-term responses. The availability of novel, highly active anti-HER2 treatments, together with the ongoing development of promising diagnostic tools, will offer the unprecedented opportunity to raise cure rates. Our ultimate goal is to tailor treatment intensity to disease and patient characteristics, hopefully increasing the fraction of cured patients while minimizing the risk for overtreatment. If conducted rationally and carefully, this plan has the potential to break a decades-long paradigm, leading to a new, precise era of treatment of HER2-positive breast cancer.

To evaluate the short- and medium-term effects of an 8-week individualized comprehensive rehabilitation program in women with chronic knee osteoarthritis as regards functionality, physical performance, and perceived health status.Women with chronic knee osteoarthritis were randomly assigned to the aquatic training group or to the individualized comprehensive rehabilitation (ICR) group. The main outcomes were functionality assessed with the Western Ontario and McMaster Universities Osteoarthritis Index, physical performance assessed with the Timed Up and Go test and the Stair Climbing Test, and perceived health status evaluated with the European Quality of Life- 5 Dimensions questionnaire. Participants were assessed after the treatment and at 3-month follow-up.Forty participants were included in the study. After the treatment, there were no significant between- group differences. At 3-month follow-up, there were significant between-group differences in functionality (stiffness P = 0.049, function P = 0.005, and total subscores P = 0.048) and physical performance (Timed Up and Go P = 0.031 and Stair Climbing Test P = 0.046) in favor of the ICR group.An 8-week ICR program improved functionality, physical performance, and perceived health status compared with an aquatic training program in women with chronic knee osteoarthritis.

Dreams may be recalled after awakening from sleep following a defined electroencephalographic pattern that involves local decreases in low-frequency activity in the posterior cortical regions. Although a dreaming experience implies bodily changes at many organ, system, and timescale levels, the entity and causal role of such peripheral changes in a conscious dream experience are unknown. We performed a comprehensive, causal, multivariate analysis of physiological signals acquired during rapid eye movement (REM) sleep at night, including high-density electroencephalography and peripheral dynamics including electrocardiography and blood pressure. In this preliminary study, we investigated multiple recalls and nonrecalls of dream experiences using data from nine healthy volunteers. The aim was not only to investigate the changes in central and autonomic dynamics associated with dream recalls and nonrecalls, but also to characterize the central-peripheral dynamical and (causal) directional interactions, and the temporal relations of the related arousals upon awakening. We uncovered a brain-body network that drives a conscious dreaming experience that acts with specific interaction and time delays. Such a network is sustained by the blood pressure dynamics and the increasing functional information transfer from the neural heartbeat regulation to the brain. We conclude that bodily changes play a crucial and causative role in a conscious dream experience during REM sleep.

The study was conducted to explore the degree to which caregiver burden is associated with sleep quality in parents of children with autism spectrum disorder, and to determine a statistically valid cutoff score for the Caregiver Burden Inventory (CBI) in order to identify parents of risk of poor sleep quality.We conducted a cross-sectional analysis. We assessed caregiver burden with the CBI, sleep quality with the Pittsburgh Sleep Quality Index, emotional status with the Hospital Anxiety and Depression Scale, and impact on family with the Impact on Family Scale. Caregiver burden was evaluated with a logistic regression analysis. The best fit model was used in a receiver operating characteristic analysis. Likelihood ratios and post-test probabilities were calculated.A total of 116 parents were included in this study. Higher caregiver burden was associated with a reduction in sleep quality in the logistic regression analysis (p0.001). The area under the curve for the univariate burden test model (best fit) was 76.70 (p0.001). The cutoff score for poor sleep quality was caregiver burden ≥26.50. The post-test probability of poor sleep quality increased to 82.02% from a pre-test probability of 76.72%.Our findings suggest that caregiver burden is associated with sleep quality among parents of children with autism spectrum disorder. The findings suggest that a CBI cutoff score of 26.50 may help to detect risk of poor sleep quality in parents of children with autism spectrum disorder.

New findings What is the central question of this study? Ageing impairs the skin's thermal and tactile sensitivity: does ageing also induce loss of skin wetness sensitivity? What is the main finding and its importance? Older adults show an average 15% loss of skin wetness sensitivity, with this sensory deficit being mediated by a combination of reductions in skin's tactile sensing and hydration status. These findings increase knowledge of wetness sensing mechanisms across the lifespan. Abstract Humans use sensory integration mechanisms to sense skin wetness based on thermal and mechanical cues. Ageing impairs the skin's thermal and tactile sensitivity, yet we lack evidence on whether wetness sensing also changes with ageing. We mapped local skin wetness and temperature sensitivity in response to cold-, neutral- and warm-wet stimuli applied to the forehead, neck, lower back, dorsal foot, index finger and thumb, in 10 Younger (22.4 ± 1.1 years) and 10 Older (58.2 ± 5.1 years) males. We measured local skin temperature and conductance (i.e., a marker of hydration status) at the tested sites, to establish the role of skin's thermal and mechanical parameters in ageing-induced changes in wetness sensing. Irrespective of body site, Older reported overall lower wetness perceptions than Younger across all wet-stimulus temperatures (mean difference: -14.6 mm; 95% CI: -4.3, -24.9; P = 0.008; ∼15% difference). When considering regional wetness sensitivity, the effect of ageing was more pronounced in response to the cold-wet stimulus over the lover back (mean difference Older vs. Younger: -36.8 mm; 95% CI: -68.4, -5.2; P = 0.014; ∼37% difference) and dorsal foot (mean difference: -37.1 mm; 95% CI: -68.7, -5.5; P = 0.013; ∼37% difference). We found no differences between age groups on overall thermal sensations (P = 0.744) nor local skin temperature (P = 0.372); however, we found that Older presented overall lower skin conductance than Younger (mean difference: -1.56 μS; 95% CI: -0.49, -2.62; P = 0.005), which corresponded to an ∼78% reduction in skin hydration. We conclude that skin wetness sensing decreases with ageing primarily due to age-induced changes in skin mechanics and tactile sensitivity.

The possibility of predicting the specific features of forthcoming environmental events is fundamental for our survival since it allows us to proactively regulate our behaviour, enhancing our chance of survival. This is particularly crucial for stimuli providing socially relevant information for communication and interaction, such as faces. While it has been consistently demonstrated that the human brain shows preferential and ontogenetically early face-evoked activity, it is unknown whether specialized neural routes are engaged by face-predictive activity early in life. In this study, we recorded high-density electrophysiological (ERP) activity in adults and 9- and 4-month-old infants undergoing an audio-visual paradigm purposely designed to predict the appearance of faces or objects starting from congruent auditory cues (i.e., human voice vs nonhuman sounds). Contingent negative variation or CNV was measured to investigate anticipatory activity as a reliable marker of stimulus expectancy even in the absence of explicit motor demand. The results suggest that CNV can also be reliably elicited in the youngest group of 4-month-old infants, providing further evidence that expectation-related anticipatory activity is an intrinsic, early property of the human cortex. Crucially, the findings also indicate that the predictive information provided by the cue (i.e., human voice vs nonhuman sounds) turns into the recruitment of different anticipatory neural dynamics for faces and objects.

Mild cognitive impairment is frequent among people with Parkinson’s disease. Cognitive training seems effective for cognitive status and for mitigating anxiety and depression. With the COVID-19 outbreak, such therapeutic interventions were delivered online. This longitudinal mixed-method study was aimed at evaluating the effectiveness of an online cognitive treatment, carried out during COVID times and based on Parkinson’s-Adapted Cognitive Stimulation Therapy, on cognitive domains and mood of 18 older people with Parkinson’s disease. After screening, the cognitive status and mood were assessed three times by Addenbrooke’s Cognitive Examination-Revised scale and the Geriatric Depression Scale-Short Form. At the follow-up, patients were also interviewed for understanding their experience with the technology. Such treatment was effective on the participants’ cognitive functions, but not on their mood. Despite some initial problems with the technology, the online intervention was experienced as a way of not being ‘left behind’, staying in contact with others, and being safe during the lockdown. This suggests that online cognitive treatment can be adopted to integrate face-to-face interventions by increasing their efficacy, accessibility, and long-term outcomes. Suggestions for future research are given.

Metronomic chemotherapy (mCHT) refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen, with no prolonged drug-free breaks, that leads to antitumor activity. Aim of the present study is to describe the use of mCHT in a retrospective cohort of metastatic breast cancer (MBC) patients in order to collect data regarding the different types and regimens of drugs employed, their efficacy and safety. Between January 2011 and December 2016, data of 584 metastatic breast cancer patients treated with mCHT were collected. The use of VRL-based regimens increased during the time of observation (2011: 16.8% - 2016: 29.8%), as well as CTX-based ones (2011: 17.1% - 2016: 25.6%), whereas CAPE-based and MTX-based regimens remained stable. In the 1st-line setting, the highest ORR and DCR were observed for VRL-based regimens (single agent: 44% and 88%; combination: 36.7% and 82.4%, respectively). Assuming VRL-single agent as the referee treatment (median PFS: 7.2 months, 95% CI: 5.3–10.3), the longest median PFS were observed in VRL-combination regimens (9.5, 95%CI 88.8–11.3, HR = 0.72) and in CAPE-single agent (10.7, 95%CI 8.3–15.8, HR = 0.70). The VICTOR-6 study provides new data coming from the real-life setting, by adding new information regarding the use of mCHT as an option of treatment for MBC patients.

Background: Venous Access Devices (VADs) are the most used devices in COVID-19 patients. Objective: Identify VADs implanted, catheter related thrombosis (CRT), catheter-related bloodstream infection (CRBSI), and accidental remove of VADs in both COVID-19 positive and COVID-19 free patients. Successive analysis was conducted comparing COVID-19 positive patients with COVID-19 free with inverse probability propensity score weights using simple regression to account for these two confounders (peripheral tip as central/peripheral and hospitalization as no/yes). Methods: This multicenter, retrospective cohort study collected data from seven hospitals in Lombardy during the pandemic period from February 21st to May 31st 2020. Results: A total of 2206 VADs were evaluated, 1107 (50.2%) of which were inserted in COVID-19 patients. In COVID-19 cohort the first choice was Long Peripheral Cannula in 388 patients (35.1%) followed by Midline Catheter in 385 (34.8%). The number of “central tip” VADs inserted in COVID-free inpatients and COVID-19 positive were similar (307 vs 334). We recorded 42 (1.9%) CRT; 32 (79.2%) were observed in COVID-19 patients. A total of 19 CRBSI were diagnosed; 15 (78.95%) were observed in COVID-19. Accidental removals were the more represented complication with 123 cases, 85 (69.1%) of them were in COVID-19. COVID-19 significantly predicted occurrence of CRT (OR = 2.00(1.85–5.03); p Conclusions: CRT, CRBSI, and accidental removal are significantly more frequent in COVID-19 patients. Accidental removals are the principal complication, for this reason, the use of subcutaneously anchored securement is recommended for a shorter period than usual.

INTRODUCTION Asthma is characterized by recurrent episodes of wheezing, dyspnoea, chest tightness and cough. In addition to respiratory symptoms, previous studies have reported the presence of pain. OBJECTIVE To analyse the nociceptive processing of young adults with well-controlled asthma. METHODS A cross-sectional case-control study was performed. Patients diagnosed with persistent well-controlled asthma were recruited from the 'Complejo Hospitalario Universitario' (Granada). Main outcomes included pain processing, measured by the pressure-pain thresholds (PPTs) and temporal summation and latency of pain; symptoms, including cough (Leicester Cough Questionnaire) and dyspnoea (Borg scale); and catastrophic cognitions about breathlessness, assessed by the Breathlessness Catastrophizing Scale (BCS). RESULTS Seven-two participants were finally recruited in our study. Patients with asthma presented lower pressure thresholds (p

We present a case of a woman with epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma who received gefitinib for 2 years and obtained a partial response. The patient then developed liver metastasis and a breast lesion, displaying high estrogen receptor (ER) expression and harboring the same EGFR mutation. From the radiological studies, it was not possible to make a differential diagnosis between primary breast cancer and breast metastasis from lung cancer. After the removal of the breast nodule, thanks to the clinical history, radiology, and above all, molecular and immunohistochemical investigations, a diagnosis of breast metastasis from lung adenocarcinoma was made. This case emphasizes the importance of a comprehensive clinical, pathological, and molecular analysis in the differential diagnosis between primary breast cancer and metastases from extramammary tumor to guide adequate treatment decision making.

Longitudinal evaluation of circulating tumour DNA (ctDNA) represents a promising tool for monitoring tumour evolution. In patients with breast cancer, ctDNA dynamics for the assessment of molecular residual disease (MRD) and resistances may, respectively, help clinicians in treatment modulation of adjuvant treatments, and in anticipating resistance to ongoing treatments and switch treatments before clinical progression, to improve disease control. Anyway, the introduction of this dynamic biomarker into clinical practice requires the demonstration of analytical validity, clinical validity and clinical utility.In early breast cancer setting, several observational studies demonstrated the clinical validity of MRD monitoring through ctDNA in identifying patients at a higher risk of relapse, but many clinical trials evaluating the clinical utility are still ongoing, and few data resulted in inconclusive results.Instead, ctDNA dynamics for intercepting resistance have not been fully evaluated in terms of clinical validity, because monitoring schedules of most observational studies are not intensive. The only trial assessing their clinical utility (PADA-1) demonstrated a benefit in terms of progression-free survival, portraying a new landscape for clinical trials in this space.Rigorous clinical trials with adequate assays and patient-relevant endpoints are paramount to demonstrate the clinical utility of ctDNA dynamics and eventually increase clinical outcomes.

This pilot project was aimed at supporting those families caring at home for loved ones suffering from Alzheimer dementia. Fourteen dyads of "caregivers-loved ones with dementia" were recruited and assigned either to the experimental group (n = 7) or to the control group (n = 7). The experimental group attended a training course, an Alzheimer Café, a self-help group for caregivers, and the support from a volunteer and professional nurse in-home visits, while the control group's dyads attended a standard intervention. To investigate the effects of this integrated and interprofessional model of care, caregivers completed the Caregiver Burden Inventory and 2 ad hoc structured questions to evaluate whether quality of life of the dyads was changed. Moreover, the caregivers of the experimental group completed the Self-Assessment Single Questionnaire, version 6 (Q-UAV6). Only caregivers of the experimental group reported a significant reduction in burden and an improved quality of life of the dyad. They also showed a greater acceptance of the disease, became experts in the care of their loved ones, and improved their relationship. The creation of a service integration network of professionals, volunteers, and families has been shown to be useful in supporting those families caring at home for loved ones suffering from Alzheimer dementia.

Increasing attention has recently been devoted to the multidisciplinary investigation of functional brain-heart interplay (BHI), which has provided meaningful insights in neuroscience and clinical domains including cardiology, neurology, clinical psychology, and psychiatry. While neural (brain) and heartbeat series show high nonlinear and complex dynamics, a complexity analysis on BHI series has not been performed yet. To this end, in this preliminary study, we investigate BHI complexity modulation in 17 healthy subjects undergoing a 3-minute resting state and emotional elicitation through standardized image slideshow. Electroencephalographic and heart rate variability series were the inputs of an adhoc BHI model, which provides directional (from-heart-to-brain and from-brain-to-heart) estimates at different frequency bands. A Fuzzy entropy analysis was performed channel-wise on the model output for the two experimental conditions. Results suggest that BHI complexity increases in the emotional elicitation phase with respect to a resting state, especially in the functional direction from the heart to the brain. We conclude that BHI complexity may be a viable computational tool to characterize neurophysiological and pathological states under different experimental conditions.

The study of functional brain-heart interplay (BHI) aims to describe the dynamical interactions between central and peripheral autonomic nervous systems. Here, we introduce the Sympathovagal Synthetic Data Generation Model, which constitutes a new computational framework for the assessment of functional BHI. The model estimates the bidirectional interplay with novel quantifiers of cardiac sympathovagal activity gathered from Laguerre expansions of RR series (from the ECG), as an alternative to the classical spectral analysis. The main features of the model are time-varying coupling coefficients linking Electroencephalography (EEG) oscillations and cardiac sympathetic or parasympathetic activity, for either ascending or descending direction of the information flow. In this proof-of-concept study, functional BHI is quantified in the direction from-heart-to-brain, on data from 16 human volunteers undergoing a cold-pressor test. Results show that thermal stress induces heart-to-brain functional interplay originating from sympathetic and parasympathetic activities and sustaining EEG oscillations mainly in theδandγbands. The proposed computational framework could provide a viable tool for the functional assessment of the causal interplay between cortical and cardiac sympathovagal dynamics.

The aim of this study was to examine balance ability and occupational performance in patients with Parkinson's disease (PD) and on-medication-state freezing of gait (FOG).A cohort study with three groups was conducted.Seven patients with PD and on-medication-state FOG with optimized pharmacological therapy; seven patients with PD matched by age, gender, length of time since diagnosis, and Hoehn and Yahr stage; and seven controls were included. Outcomes included balance and occupational performance. Nonparametric analyses were used.Significant differences were found between the two subgroups of patients with PD in the Timed UpGo Test when adding a cognitive task, dual-task interference, and self-confidence in balance.Patients with PD and on-medication-state FOG had lower scores on dual-task interference and self-confidence than matched PD patients.The assessment and rehabilitation approach for patients with PD and on-medication-state FOG should include balance confidence and dual-task interference.

Purpose Triple-negative breast cancer (TNBC) represents a subtype of breast cancer which lacks the expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2): TNBC accounts for approximately 20% of newly diagnosed breast cancers and is associated with younger age at diagnosis, greater recurrence risk and shorter survival time. Therapeutic options are very scarce. Aim of the present analysis is to provide further insights into the clinical activity of metronomic chemotherapy (mCHT), in a real-life setting. Methods We used data included in the VICTOR-6 study for the present analysis. VICTOR-6 is an Italian multicentre retrospective cohort study, which collected data of metastatic breast cancer (MBC) patients who have received mCHT between 2011 and 2016. Amongst the 584 patients included in the study, 97 were triple negative. In 40.2% of the TNBC patients, mCHT was the first chemotherapy treatment, whereas 32.9% had received 2 or more lines of treatment for the metastatic disease. 45.4% out of 97 TNBC patients received a vinorelbine (VRL)-based regimen, which resulted in the most used type of mCHT, followed by cyclophosphamide (CTX)-based regimens (30.9%) and capecitabine (CAPE)-based combinations (22.7%). Results Overall response rate (ORR) and disease control rate (DCR) were 17.5% and 64.9%, respectively. Median progression free survival (PFS) and overall survival (OS) were 6.0 months (95% CI: 4.9–7.2) and 12.1 months (95% CI: 9.6–16.7). Median PFS was 6.9 months for CAPE-based regimens (95% CI: 5.0–18.4), 6.1 months (95% CI: 4.0–8.9) for CTX-based and 5.3 months (95% CI: 4.1–9.5) for VRL-based ones. Median OS was 18.2 months (95% CI: 9.1-NE) for CAPE-based regimens and 11.8 months for VRL- (95% CI: 9.3–16.7 and CTX-based ones (95%CI: 8.7–52.8). Tumour response, PFS and OS decreased proportionally in later lines. Conclusion This analysis represents the largest series of TNBC patients treated with mCHT in a real-life setting and provides further insights into the advantages of using this strategy even in this poor prognosis subpopulation.

Objectives: We aimed to analyze the effects of a tailored rehabilitation nursing care program on functional ability and quality of life in patients with conservative treatment for rib fractures. Design: Randomized controlled trial. Setting: Inpatient rehabilitation hospital. Subjects: Rib fracture patients treated conservatively were randomized into two groups (experimental and control group). Interventions: Patients in control group received Treatment as Usual (TAU) and patients included in experimental group received TAU and an added tailored rehabilitation nursing care program (RNT). Main measures: At baseline, and end of hospitalization treatment, the functional ability was assessed with the Barthel Index, and the quality of life was evaluated with the EuroQol-5D. Additionally, the outcomes were assessed at six-month follow-up. Results: A total of 80 patients were included in the study, whose mean age was 77.19 SD 7.71 in the RNT group and 75.55 SD 9.46 in the TAU group. Our data showed a significant difference in the post-treatment gains in overall quality of life (74.25 SD 20.62 vs 60.28 SD 20.54), and functional ability (71.79 SD 23.85 vs 69.41 SD 24.30) between the RNT group and the TAU group ( P Conclusions: A tailored rehabilitation nursing care program added to the conservative treatment during hospitalization can improve the functional ability and quality of life of patients after rib fractures at discharge and at six-month follow-up. Trial registration: ClinicalTrial.gov Identifier: NCT04168996

Subclinical depression (dysphoria) is a common condition that may increase the risk of major depression and leads to impaired quality of life and severe comorbid somatic diseases. Despite its prevalence, specific biological markers are unknown; consequently, the identification of dysphoria currently relies exclusively on subjective clinical scores and structured interviews. Based on recent neurocardiology studies that link brain and cardiovascular disorders, it was hypothesized that multi-system biomarkers of brain–body interplay may effectively characterize dysphoria. Thus, an ad hoc computational technique was developed to quantify the functional bidirectional brain–heart interplay. Accordingly, 32-channel electroencephalographic and heart rate variability series were obtained from 24 young dysphoric adults and 36 healthy controls. All participants were females of a similar age, and results were obtained during a 5-min resting state. The experimental results suggest that a specific feature of dysphoria is linked to an augmented functional central-autonomic control to the heart, which originates from central, frontopolar, and occipital oscillations and acts through cardiovascular sympathovagal activity. These results enable further development of a large set of novel biomarkers for mood disorders based on comprehensive brain–body measurements.

A 75-year-old woman had an occasional finding of a left tonsil mass for dysphagia, which resulted a high-grade squamous carcinoma. Therefore, the patient was sent to have a left pharyngectomy. After the pharyngectomy, the patient reported persistent swallowing disorders and nasal reflux. Consequently, she had an oropharyngoesophageal scintigraphy, demonstrating irregular oral and pharyngeal swallowing phases and confirming reflux episodes into the rhinopharynx and into the oropharynx. In line with these findings, the patient was send to rehabilitation; the abnormal functional mechanisms, previously identified by the scintigraphy, allowed to guide the speech therapy, with a progressive clinical improvement.

Background The understanding of neurophysiological correlates underlying the risk of developing depression may have a significant impact on its early and objective identification. Research has identified abnormal resting-state electroencephalography (EEG) power and functional connectivity patterns in major depression. However, the entity of dysfunctional EEG dynamics in dysphoria is yet unknown. Methods 32-channel EEG was recorded in 26 female individuals with dysphoria and in 38 age-matched, female healthy controls. EEG power spectra and alpha asymmetry in frontal and posterior channels were calculated in a 4-minute resting condition. An EEG functional connectivity analysis was conducted through phase locking values, particularly mean phase coherence. Results While individuals with dysphoria did not differ from controls in EEG spectra and asymmetry, they exhibited dysfunctional brain connectivity. Particularly, in the theta band (4-8 Hz), participants with dysphoria showed increased connectivity between right frontal and central areas and right temporal and left occipital areas. Moreover, in the alpha band (8-12 Hz), dysphoria was associated with increased connectivity between right and left prefrontal cortex and between frontal and central-occipital areas bilaterally. Limitations All participants belonged to the female gender and were relatively young. Mean phase coherence did not allow to compute the causal and directional relation between brain areas. Conclusions An increased EEG functional connectivity in the theta and alpha bands characterizes dysphoria. These patterns may be associated with the excessive self-focus and ruminative thinking that typifies depressive symptoms. EEG connectivity patterns may represent a promising measure to identify individuals with a higher risk of developing depression.&nbsp

Introduction The COVID-19 outbreak highly impacted the acute ischemic stroke care management. The primary end point of the study was to evaluate the impact of the COVID-19 outbreak and the following lockdown measures on our hub-and-spoke network; the secondary end point was to evaluate if the impact of the COVID-19 outbreak was different in hub-and-spoke centers. Methods This was a retrospective multicenter observational study conducted at the Stroke Units of Policlinico Gemelli, Ospedale San Filippo Neri, Ospedale di Belcolle, and Ospedale San Camillo de Lellis. We collected clinical reports of all consecutive patients admitted with diagnosis of acute ischemic stroke or transient ischemic attack (TIA) during the phase 1 of the lockdown period (11 March 2020–4 May 2020). As controls, we used all consecutive patients admitted for acute ischemic stroke or TIA in the same period of the previous year. Results A total of 156 and 142 clinical reports were collected in 2019 and 2020, respectively. During the COVID-19 outbreak, we observed a reduction of number of thrombolysis, a reduction of the length of hospitalization, and an increase of pneumonia. Regarding performance indicators, we observed an increase in onset-to-door time and in door-to-groin time. We did not observe any statistically significant interaction between year (2019 vs 2020) and facility of admission (hub vs spoke) on all variables analyzed. Discussion Our observational study, involving hub-and-spoke stroke network of a wide regional area, indicates that the COVID-19 outbreak impacted on the acute stroke management. This impact was equally observed in hub as well as in spoke centers.

To face the COVID-19 pandemic, the need for fast and reliable diagnostic assays for the detection of SARS-CoV-2 is immense. We describe our laboratory experiences evaluating nine commercially available real-time RT-PCR assays. We found that assays differed considerably in performance and validation before routine use is mandatory.

Objective: The quantification of functional brain–heart interplay through the dynamics of the central and autonomic nervous systems may provide effective biomarkers for cognitive, emotional, and autonomic state changes. Despite several computational models were proposed to this end, none provides a directional estimation of such interplay in a time-resolved and probabilistic fashion. Methods: In this study, a multivariate inhomogeneous point-process model for heartbeat dynamics is employed to derive subject-specific, time-resolved, functional estimates of the directional interplay occurring from the brain to the heart, whose activity is represented by electroencephalography and R-peaks intervals series. An inverse-Gaussian probability density function is used to predict heartbeat events as a function of neural dynamics, which is modeled as an exogenous input to the autoregressive cardiac dynamics. Results: The performance is evaluated using heart rate variability and electroencephalography series gathered from 24 healthy volunteers undergoing a cold-pressor test, and the modeling goodness-of-fit is assessed through the time-rescaling theorem. The results suggest that cortical dynamics drives heartbeat series with specific time delays in the range of 30s to 60s and 90s to 120s from the peripheral thermal stress onset. Conclusion: The proposed framework provides novel insights in human neurophysiology, exploiting a fully probabilistic definition of the continuous functional brain–heart interplay.

Recent studies have established that cardiac and respiratory phases can modulate perception and related neural dynamics. While heart rate and respiratory sinus arrhythmia possibly affect interoception biomarkers, such as heartbeat-evoked potentials, the relative changes in heart rate and cardiorespiratory dynamics in interoceptive processes have not yet been investigated. In this study, we investigated the variation in heart and breathing rates, as well as higher functional dynamics including cardiorespiratory correlation and frontal hemodynamics measured with fNIRS, during a heartbeat counting task. To further investigate the functional physiology linked to changes in vagal activity caused by specific breathing rates, we performed the heartbeat counting task together with a controlled breathing rate task. The results demonstrate that focusing on heartbeats decreases breathing and heart rates in comparison, which may be part of the physiological mechanisms related to “listening” to the heart, the focus of attention, and self-awareness. Focusing on heartbeats was also observed to increase frontal connectivity, supporting the role of frontal structures in the neural monitoring of visceral inputs. However, cardiorespiratory correlation is affected by both heartbeats counting and controlled breathing tasks. Based on these results, we concluded that variations in heart and breathing rates are confounding factors in the assessment of interoceptive abilities and relative fluctuations in breathing and heart rates should be considered to be a mode of covariate measurement of interoceptive processes.

Non-muscle invasive bladder cancer (NMIBC) accounts for 70-75% of all bladder cancers and is a heterogeneous disease characterized by a wide spectrum of recurrences and progression. Adjuvant treatment for intermediate- and high-risk NMIBC is mainly represented by Bacillus Calmette Guerin (BCG). However, 20%-40% of patients develop disease recurrences or persistence following BCG treatment and are classified as "BCG unresponsive' (BCGu), thus representing a therapeutic challenge due to their worse prognosis and unavailability of effective intravesical treatments.We provide an overview of completed and ongoing clinical trials assessing the role of innovative immunological and target agents in patients with BCGu and BCG naive (BCGn) NMIBCs. New treatment options are emerging, demonstrating promising clinical activity, namely, pembrolizumab, atezolizumab, oportuzumab monatox, nadofaragene firadenovec, and N-803.The increasing number of newer therapeutic agents for patients with NMIBC poses challenges regarding the choice of the most suited treatment option for each patient and the best treatment sequence, given their diverse mechanisms of action and varying degrees of activity. Tailored treatment approaches are advocated, based on a deeper comprehension of disease features, available therapies, patient's characteristics, and consequently, on the identification and validation of prognostic and predictive biomarkers.

People with chronic pain conditions such as fibromyalgia may experience occupational limitations and imbalances in their basic and instrumental occupations of daily living, leisure, work, and social participation.To describe occupational balance in persons with fibromyalgia and to analyze whether it is associated with self-reported disability and self-efficacy to manage symptoms.A cross-sectional study was carried out. Individuals with fibromyalgia were invited to participate. Occupational balance was assessed with the Occupational Balance Questionnaire; self-reported disability was assessed with the World Health Organization Disability Assessment Schedule, WHODAS 2.0-12; and self-efficacy was evaluated with the 8-item version of the Arthritis Self-Efficacy Scale. Data were analyzed using multiple linear regression with a forward stepwise procedure.One hundred women with fibromyalgia were included. Occupational balance was 26.96 ± 12.09; however, scores differed between the mild disability group and the moderate disability group (33.11 ± 9.99 vs. 20.29 ± 10.61,Women with fibromyalgia showed low occupational balance. Self-reported disability and self-reported pain management were associated with occupational balance.Occupational therapy practitioners can design intervention programs focussing on occupational balance and self-efficacy to manage symptoms.

Objective: To assess the effect of speech and language therapy (SLT) on Hypokinetic dysarthria (HD) in Parkinson’s disease. Design: Systematic review and meta-analysis of randomized controlled trials. Methods: We performed a literature search of randomized controlled trials using PubMed, Web of Science, Science Direct and Cochrane database (last search October 2020). Quality assessment and risk of bias were assessed using the Downs and Black scale and the Cochrane tool. The data were pooled and a meta-analysis was completed for sound pressure levels, perceptual intelligibility and inflection of voice fundamental frequency. Results: We selected 15 high to moderate quality studies, which included 619 patients with Parkinson’s disease. After pooling the data, 7 studies, which compared different speech language therapies to no treatment, control groups and 3 of their variables, (sound pressure level, semitone standard deviation and perceptual intelligibility) were included in the analysis. Results showed significant differences in favor of SLT for sound pressure level sustained phonation tasks (standard mean difference = 1.79; 95% confidence interval = 0.86, 2.72; p ⩽ 0.0001). Significant results were also observed for sound pressure level and semitone standard deviation in reading tasks (standard mean difference = 1.32; 95% confidence interval = 1.03, 1.61; p ⩽ 0.0001). Additionally, sound pressure levels in monologue tasks showed similar results when SLT was compared to other treatments (standard mean difference = 0.87; 95% confidence interval = 0.46, 1.28; p ⩽ 0.0001). Conclusion: This meta-analysis suggests a beneficial effect of SLT for reducing Hypokinetic Dysarthria in Parkinson’s disease, improving perceptual intelligibility, sound pressure level and semitone standard deviation.

While neck pain can be severely disabling and costly, treatment options have shown moderate evidence of effectiveness.The objective of this study was to explore the effects of a 4-week active program based on myofascial release and neurodynamics on trigger point (TrP) examination, pain, and functionality in patients with chronic neck pain.Randomized controlled trial. A total of 40 patients with chronic neck pain were randomly allocated to an experimental or a control group (n = 20). The primary outcome measure was TrP examination. Secondary outcomes were pain, assessed with the Brief Pain Inventory and a visual analogue scale, and functionality, evaluated with the Neck Outcome Score.A between-group analysis showed significant differences (A 4-week self-administered program for patients with chronic neck pain was effective in reducing the presence of active TrPs. Pain severity, average pain, and some aspects of functionality also improved significantly after the intervention.

Background Chemotherapy is effective in metastatic pancreatic adenocarcinoma (mPA), but new approaches are still needed to improve patients' survival and quality of life. We have previously published good efficacy and tolerability results on a sequential treatment strategy of gemcitabine followed by an intensified FOLFIRI (5FU+irinotecan) regimen. In the present study, we evaluated the same sequence but replaced gemcitabine by the new gemcitabine + nab-paclitaxel standard first-line combination. Patients and methods We randomised chemotherapy-naive patients with proven mPA, bilirubin levels ≤1.5 upper limit of normal values and performance status 0–2 to alternately receive gemcitabine + nab-paclitaxel for 2 months then FOLFIRI.3 for 2 months in arm A, or gemcitabine + nab-paclitaxel alone until progression in arm B. The primary objective was to increase the 6-month progression-free survival (PFS) rate from 40% (H0) to 60% (H1); using the binomial exact method, 124 patients were required. Analyses were carried out in preplanned modified intention-to-treat (mITT) and per-protocol (PP) populations. Results Between November 2015 and November 2016, 127 patients were enrolled. Main grade III–IV toxicities (% in arm A/B) were: diarrhoea (12.5/1.7), neutropenia (46.9/31, including febrile neutropenia: 1.6/0), skin toxicity (6.3/13.8), and peripheral neuropathy (6.3/8.6). No toxic deaths occurred. The objective response rate was 40.3% (95% confidence interval [CI]: 28.1–53.6) in arm A and 26.7% (95% CI: 16.1–39.7) in arm B. The primary end-point (6-month PFS rate) was 45.2% [one-sided 95% CI: 34.3–56.4] in arm A and 23.3% in arm B [one-sided 95% CI: 14.3–32.3] in the mITT population. In the PP population, median PFS and OS were 7.6 months and 6 months and 14.5 months and 12.2 months in arm A and B, respectively. Conclusions The FIRGEMAX strategy with gemcitabine + nab-paclitaxel alternating with FOLFIRI.3 every 2 months, appears feasible and effective, with manageable toxicities, in patients able to reach >2mo of treatment. Trial registration information EudraCT: 2014-004449-28: NCT: 0282701.

Knowledge of the deficits underlying handgrip performance is fundamental for the development of targeted interventions.The purpose of this study was to evaluate maximal handgrip strength, fatigue resistance, grip work, and muscle fatigue in mildly affected stroke persons.We conducted a prospective observational study. A total of 20 individuals after a first unilateral ischemic/hemorrhagic chronic stroke (months poststroke: mean 33.64 ± 19.60), mildly affected according to functional score (FIM: 112.71 ± 16.14) and with arm motor impairment (upper-extremity Fugl-Meyer score: mean 57.07 ± 7.82 on the contralesional side); and 20 sex and age-matched controls were included. The outcomes assessed were maximal handgrip strength evaluated through maximal voluntary contraction, fatigue resistance defined as the seconds during which grip strength dropped to 50% of its maximum and gripwork, which was calculated using the equation grip work = maximal grip strength * 0.75 * fatigue resistance. Muscle fatigue was assessed using surface electromyography during a sustained contraction over 50% of maximal voluntary contraction.Persons with stroke demonstrated significantly reduced handgrip performance regarding maximal handgrip strength, resistance to fatigue, grip work, and muscle fatigue for the contralesional hand. In addition, a reduced grip resistance and muscle fatigue was shown for the ipsilesional hand compared with controls. We found no effect of the hemispheric side of the lesion on the grip performance measures assessed.Our findings provide evidence that handgrip performance remain impaired after 6 months after stroke, and may serve as a target for interventions to improve these abilities after stroke.

To assess the effectiveness of an individualized comprehensive rehabilitation program (ICPR) on impaired postural control, pain, self-perceived health status, and functionality in women with chronic pelvic pain.Randomized controlled trial.Women with chronic pelvic pain were recruited from the Gynecology Department of the University Hospital San Cecilio in Granada, Spain.Participants (N=38) who were randomly divided into 2 groups.The intervention group received an 8-week ICRP, and the control group received a leaflet with ergonomic information.The main outcomes included were postural control (Mini Balance Evaluation Systems [Mini BESTest] and timed Up and Go [TUG]), pain (Brief Pain Inventory), self-perceived health status (EuroQol 5 dimensions [EQ-5D]), and functionality (Oswestry Disability Index [ODI]).Significant differences were found between groups in the Mini BESTest and TUG scores with large effect sizes. The Brief Pain Inventory, EQ-5D, and ODI also presented significant differences in the between-groups analysis, with better scores in the intervention group after treatment. In the follow-up analysis, significant differences were found between groups in the Mini BESTest (P.001), the cognitive TUG subscale (P=.032), interference of pain (P.001), anxiety and depression (P=.001), and visual analog scale EQ-5D (P=.026) subscales, as well as the ODI (P.001).Our results show significant improvements on postural control, pain, self-perceived health status, and functionality in women with chronic pelvic pain who received an 8-week ICRP.

Background Improving the quality of information and communication is a priority in organised breast cancer screening and an ethical duty. Programmes must offer the information each woman is looking for, promoting informed decision-making. This study aimed to develop and evaluate a web-based dynamic decision aid (DA). Methods A pragmatic randomised trial carried out in six regional organised screening programmes recruited women at the first invitation receiving DA or a web-based standard brochure (SB). The primary outcome was informed choice measured on knowledge, attitudes, and intentions. Follow-up period: 7–10 days. Secondary outcomes included participation rate, satisfaction, decisional conflict, and acceptability of DA. Results Two thousand one hundred and nineteen women were randomised and 1001 completed the study. Respectively, 43.9% and 36.9% in the DA and SB reached the informed choice. The DA gave a 13-point higher proportion of women aware about overdiagnosis compared to SB (38.3% versus 25.2%, p Conclusion DA increases informed choice. Complete information including the pros, cons, controversies, and overdiagnosis–overtreatment issues boost a woman’s knowledge without reducing the rate of actual screening participation. Clinical trial registration ClinicalTrials.gov number NCT 03097653.

Italy was the first Western country to face the COVID-19 pandemic. Here we report the results of a national survey on kidney transplantation activity in February and March 2020, and the results of a three-round Delphi consensus promoted by four scientific societies: the Italian Society of Organ Transplantation, the Italian Society of Nephrology, the Italian Society of Anesthesia and Intensive Care, and the Italian Group on Antimicrobial Stewardship. All 41 Italian transplant centers were invited to express their opinion in the Delphi rounds along with a group of seven experts. The survey revealed that, starting from March 2020, there was a decline in kidney transplantation activity in Italy, especially for living-related transplants. Overall, 60 recipients tested positive for SARS-CoV2 infection, 57 required hospitalization, 17 were admitted to the ICU, and 11 died. The online consensus had high response rates at each round (95.8%, 95.8%, and 89.5%, respectively). Eventually, 27 of 31 proposed statements were approved (87.1%), 12 at the first or second round (38.7%), and 3 at the third (9.7%). Based on the Italian experience, we discuss the reasons for the changes in kidney transplantation activity during the COVID-19 pandemic in Western countries. We also provide working recommendations for the organization and management of kidney transplantation under these conditions. Electronic supplementary material The online version of this article (10.1007/s40620-020-00755-8) contains supplementary material, which is available to authorized users.

Objective: To explore the effects of an eight-week core stability program on balance ability in persons with Parkinson’s disease. Design: Randomized controlled trial. Setting: A local Parkinson’s association. Subjects: A total of 44 participants with a clinical diagnosis of Parkinson’s disease were randomly assigned to an experimental ( n = 22) or control group ( n = 22). Intervention: The experimental group received 24 sessions of core training, while the control group received an intervention including active joint mobilization, muscle stretching, and motor coordination exercises. Main measures: The primary outcome measure was dynamic balance evaluated using the Mini-Balance Evaluation Systems Test. Secondary outcomes included the balance confidence assessed with the Activities-specific Balance Confidence Scale and standing balance assessed by the maximal excursion of center of pressure during the Modified Clinical Test of Sensory Interaction on Balance and the Limits of Stability test. Results: After treatment, a significant between-group improvement in dynamic balance was observed in the experimental group compared to the control group (change, 2.75 ± 1.80 vs 0.38 ± 2.15, P = 0.002). The experimental group also showed a significant improvement in confidence (change, 16.48 ± 16.21 vs 3.05 ± 13.53, P = 0.047) and maximal excursion of center of pressure in forward (change, 0.86 ± 1.89 cm vs 0.17 ± 0.26 cm, P = 0.048), left (change, 0.88 ± 2.63 cm vs 0.07 ± 0.48 cm, P = 0.010), and right (change, 1.63 ± 2.82 cm vs 0.05 ± 0.17 cm, P = 0.046) directions of limits of stability compared to the control group. Conclusion: A program based on core stability in comparison with non-specific exercise benefits dynamic balance and confidence and increases center of mass excursion in patients with Parkinson’s disease.

Outcomes after transplantation of lungs (LuTX) treated with ex-vivo lung perfusion (EVLP) are debated. In a single-center 8 years of retrospective analysis, we compared: donors' and recipients' characteristics, gas exchange and lung mechanics at ICU admission, 3, 6, and 12 months, and patients' survival of LuTX from standard donors compared with EVLP-treated grafts. A total of 193 LuTX were performed. Thirty-one LuTX, out of 50 EVLP procedures, were carried out: 7 from nonheart beating and 24 from extended criteria brain-dead donors. Recipients' characteristics were similar. At ICU admission, compared with standard donors, EVLP patients had worse PaO2 /FiO2 [276 (206; 374) vs. 204 (133; 245) mmHg, P < 0.05], more frequent extracorporeal support (18% vs. 32%, P = 0.053) and longer mechanical ventilation duration [28 days of ventilator-free days: 27 (24; 28) vs. 26 (19; 27), P < 0.05]. ICU length of stay [4 (2; 9) vs. 6 (3; 12) days, P = 0.208], 28-day survival (99% vs. 97%, P = 0.735), and 1-year respiratory function were similar between groups. Log-rank analysis (median follow-up 2.5 years) demonstrated similar patients' survival (P = 0.439) and time free of chronic lung allograft disease (P = 0.484). The EVLP program increased by 16% the number of LuTX. Compared to standard donors, EVLP patients had worse respiratory function immediately after LuTX but similar early and mid-term outcomes.

Mammographic screening contributes to a reduction in specific mortality, but it has disadvantages. Decision aids are tools designed to support people's decisions. Because these aids influence patient choice, their quality is crucial. The objective of the current study was to conduct a systematic review of decision aids developed for women eligible for mammographic screening who have an average breast cancer risk and to assess the quality of these aids. The systematic review included articles published between January 1, 1997, and August 1, 2019, in the PubMed, Embase, Cochrane, and PsycInfo databases. The studies were reviewed independently by 2 reviewers. Any study containing a decision aid for women eligible for mammographic screening with an average breast cancer risk was included. Two double-blind reviewers assessed the quality of the selected decision aids using the International Patient Decision Aid Standards instrument, version 3 (IPDASi). Twenty-three decision aids were extracted. Classification of decision aid quality using the IPDASi demonstrated large variations among the decision aids (maximum IPDASi score, 188; mean ± SD score, 132.6 ± 23.8; range, 85-172). Three decision aids had high overall scores. The 3 best-rated dimensions were disclosure (maximum score, 8; mean score, 6.8), focusing on transparency; information (maximum score, 32; mean score, 26.1), focusing on the provision of sufficient details; and probabilities (maximum score, 32; mean score 25), focusing on the presentation of probabilities. The 3 lowest-rated dimensions were decision support technology evaluation (maximum score, 8; mean score, 4.3), focusing on the effectiveness of the decision aid; development (maximum score, 24; mean score, 12.6), evaluating the development process; and plain language (maximum score, 4; mean score, 1.9), assessing appropriateness for patients with low literacy. The results of this review identified 3 high-quality decision aids for breast cancer screening.

OBJECTIVE Patients with stroke frequently present postural control impairment. This review aimed to assess the effectiveness of core exercising on postural control in patients with stroke. TYPE: Systematic review and meta-analysis. LITERATURE SURVEY Systematic review in the following databases: PubMed/MEDLINE, Web of Science, ScienceDirect, CINAHL, Scopus, and Physiotherapy Evidence Database (PEDro). Studies up to July 2019 were included. METHODOLOGY Studies were included if the sample was composed of adults with stroke, the intervention followed a core exercising approach (alone or combined with another intervention), and the study was a randomized controlled trial including at least one measurement related to posture control. Studies were independently screened for inclusion and data were extracted by two researchers, with a third researcher arbitrating any disputes. Study quality was assessed using the Downs and Black scale. SYNTHESIS After screening of 1540 records, a total of 14 studies met the specified inclusion criteria and involved 520 participants. Two studies exhibited "excellent" quality and five exhibited "poor" quality. The meta-analysis was performed with data from the Trunk Impairment Scale (mean difference 0.98; 95% confidence interval, 0.69 to 1.27; P

Tarsal coalitions may cause painful pes planovalgus and recurrent sprains, and can lead to arthrosis if improperly managed. In this review, we discuss the current topics related to talocalcaneal and calcaneonavicular coalitions.Tarsal coalitions are initially managed with conservative therapy, and when this approach fails, surgery is performed. Treatment of calcaneonavicular coalitions involves resection of the coalition and interposition of the extensor digitorum brevis muscle or fat, and in cases of marked valgus deformity, correction of the deformity. In talocalcaneal coalitions, recommendations include coalition resection for those affecting less than 50% of the area of the posterior facet and with a less than 16° valgus, coalition resection and valgus correction for those affecting less than 50% of the area and valgus greater than 16°, and isolated valgus correction for those affecting more than 50% of the area and with a more than or less than 16° valgus. Arthrodesis is reserved as a salvage procedure.Talocalcaneal and calcaneonavicular coalitions can cause painful pes planovalgus. Their diagnoses are confirmed by plain radiograph, computed tomography, and, in cases of fibrous or cartilaginous coalitions, MRI. Initial treatment is conservative, and when symptoms persist, resection of the coalition is recommended along with tissue graft interposition with or without associated valgus correction. Arthrodesis is indicated as a salvage procedure whenever treatment fails or with advanced arthrosis.

IMPORTANCE: The risk of developing adrenal insufficiency (AI) following adrenalectomy has been insufficiently studied in the context of multivisceral resection (MVR). OBJECTIVE: To evaluate the incidence of AI in patients undergoing MVR with en bloc adrenalectomy. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational longitudinal study in a single referral center including 56 consecutive adult patients undergoing retroperitoneal sarcoma surgery from June 2019 to August 2020. Those who were candidates for MVR with en bloc adrenalectomy and had no preexisting adrenal impairment were considered eligible. Of these, 4 individuals were excluded because they did not receive adrenalectomy at the time of surgery and 2 because they were not considered evaluable for the main end point. Follow-up was set at 4 months after surgery, and 49 patients completed follow-up. Data were analyzed from October 2020 to September 2021. EXPOSURES: Diagnosis of AI was determined by low-dose (1 μg) adrenocorticotropic hormone (ACTH) stimulation test with a threshold of 20 μg/dL in blood samples retrieved 30 and 60 minutes after stimulation. ACTH test was repeated on postoperative days 1 and 10 and at 4 months’ follow-up. MAIN OUTCOME AND MEASURES: The primary end point was incidence and relevance of AI after MVR. Secondary end points were associations with patient- and tumor-related factors, impact on perioperative hemodynamic management, and association with postoperative morbidity and mortality. RESULTS: Fifty patients (26 female; median [IQR] age, 59 [46-67] years) were evaluable. Incidence of AI was 64% (32 of 50 patients) in the early postoperative period and 38.5% (15 of 39 patients) at follow-up. Patients with AI showed lower postoperative cortisol values. Factors associated with risk of AI at univariate analysis were high American Society of Anesthesiologists score (odds ratio [OR], 0.31; 95% CI, 0.14-0.48) and high malignancy grade (OR, 0.35; 95% CI, 0.24-0.46). Clinical outcomes not associated with AI included morbidity, mortality, reoperation rate, admission to intensive care unit, length of intensive care unit stay, total hospital stay, and long-term quality of life. CONCLUSIONS AND RELEVANCE: In this study, AI after MVR with en bloc adrenalectomy was frequent, even in patients with adequate preoperative adrenal function. Despite this, adrenalectomy can be safely performed. Patients at risk should be monitored in the long term to exclude underrated impairment of adrenal function.

To adapt the Interaction with Disabled Persons Scale (IDP) into Spanish and examine its factor structure. A forward and back translation of the IPD was performed by professional translators of scholarly articles. Spanish-speaking professional translators provided modifications in order to develop the final version of the scale. Participants filled in the Spanish version of the IDP, Positive and Negative Affect Schedule (PANAS), Multidimensional Attitudes Scale toward persons with disabilities (MAS), and Semantic Differential Technique (SDT). A total of 523 persons (62.6% women), with a mean age of 29.22 (SD = 14.03) ranking from 18 to 81. The confirmatory factor analysis showed a reliable brief version of the IDP with adequate psychometric properties and two factors: (χ(19)2=28.98, p < 0.001, CFI = 0.94, TLI = 0.91, RMSEA (90% IC)=0.05 (0.01, 0.08), SRMR = 0.06). The first factor solution was Coping/Succumbing Framework and the second factor was Discomfort in Social Interaction. The internal consistency reliability for the first factor was 0.63 and for the second 0.66. Our findings provide evidence of the psychometric properties of the IDP as a brief measure of attitude toward individual with special needs in Spanish population.Implications for rehabilitationThe Interaction with Disabled Persons Scale (IDP) was successfully translated into Spanish language.The Spanish version of IDP Scale has a good acceptability, acceptable internal consistency, and high test–retest reliability.The Spanish version of IDP can been used to assist the clinicians, educators, and researchers in identifying the attitudes of the Spanish population toward persons with functional diversity in Spanish.Identifying the attitudes will permit to improve the inclusion polity and to design social programs toward greater inclusion. The Interaction with Disabled Persons Scale (IDP) was successfully translated into Spanish language. The Spanish version of IDP Scale has a good acceptability, acceptable internal consistency, and high test–retest reliability. The Spanish version of IDP can been used to assist the clinicians, educators, and researchers in identifying the attitudes of the Spanish population toward persons with functional diversity in Spanish. Identifying the attitudes will permit to improve the inclusion polity and to design social programs toward greater inclusion.

Several approaches for estimating complexity in physiological time series at various time scales have recently been developed, with a special focus on heart rate variability (HRV) series. While numerous multiscale complexity quantifiers have been investigated, a multiscale Kolmogorov-Sinai (K-S) entropy for the characterization of cardiovascular dynamics still has to be properly assessed. In this pilot study, we investigate the Algorithmic Information Content, which is calculated using an effective compression algorithm, to quantify multiscale partition- based K-S entropy on experimental HRV series. Data were gathered from publicly available datasets comprising long-term, unstructured recordings from 10 healthy subjects, as well as 10 patients with congestive heart failure (CHF) and 10 patients with atrial fibrillation. Results show that multiple time scales and domain partitions statistically discern healthy vs. pathological cardiovascular dynamics. We conclude that the proposed multiscale partition-based K-S entropy may constitute a viable tool for the complexity assessment of cardiovascular variability series.

Heartbeat regulation is achieved through different routes originating from central autonomic network sources, as well as peripheral control mechanisms. While previous studies successfully characterized cardiovascular regulatory mechanisms during a single stressor, to the best of our knowledge, a combination of multiple concurrent elicitations leading to the activation of different autonomic regulatory routes has not been investigated yet. Therefore, in this study, we propose a novel modeling framework for the quantification of heartbeat regulatory mechanisms driven by different neural routes. The framework is evaluated using two heartbeat datasets gathered from healthy subjects undergoing physical and mental stressors, as well as their concurrent administration. Experimental results indicate that more than 70% of the heartbeat regulatory dynamics is driven by the physical stressor when combining physical and cognitive/emotional stressors. The proposed framework provides quantitative insights and novel perspectives for neural activity on cardiac control dynamics, likely highlighting new biomarkers in the psychophysiology and physiopathology fields. A Matlab implementation of the proposed tool is available online. [Figure not available: see fulltext.]

Recent developments in computational physiology have successfully exploited advanced signal processing and artificial intelligence tools for predicting or uncovering characteristic features of physiological and pathological states in humans. While these advanced tools have demonstrated excellent diagnostic capabilities, the high complexity of these computational 'black boxes’ may severely limit scientific inference, especially in terms of biological insight about both physiology and pathological aberrations. This theme issue highlights current challenges and opportunities of advanced computational tools for processing dynamical data reflecting autonomic nervous system dynamics, with a specific focus on cardiovascular control physiology and pathology. This includes the development and adaptation of complex signal processing methods, multivariate cardiovascular models, multiscale and nonlinear models for central-peripheral dynamics, as well as deep and transfer learning algorithms applied to large datasets. The width of this perspective highlights the issues of specificity in heartbeat-related features and supports the need for an imminent transition from the black-box paradigm to explainable and personalized clinical models in cardiovascular research. This article is part of the theme issue 'Advanced computation in cardiovascular physiology: new challenges and opportunities'.