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Study design:Multicenter, prospective study.Objectives:To assess the occurrence and predictors of return to work after traumatic spinal cord injury (SCI).Setting:Italian rehabilitation centers.Methods:We evaluated patients previously included in the Italian Group for the Epidemiological Study of Spinal Cord Injuries study. A standardised telephone interview was used to collect data after a mean follow-up of 3.8 years. The main outcome measure was employment at the end of follow-up.Results:A total of 403 patients, 336 men and 67 women, with a mean age of 41.8±16.3 years, were included in the follow-up. In all, 42.1% of patients were employed at the moment of the interview, though 62% reported a worsening in their employment level. Predictors of employment were education (P<0.0001), bowel continence (P=0.02), independence in mobility (P=0.0004), ability to drive (P<0.0001), participating in the community (P=0.0001) and ability to live alone (P<0.0001) while age (P<0.0001), being married (P<0.0001), tetraplegia (P=0.03), occurrence of recent medical problems (P=0.002), re-hospitalization (P=0.02), presence of architectonic barriers (P=0.009) and having a public welfare subsidy (P<0.0001), predicted unemployment. On the basis of multivariate analysis, younger age, education, absence of tetraplegia, ability to drive, ability to live alone, previous employment were independent predictors of employment after SCI. Employment at follow-up was related to several indicators of quality of life.Conclusion:Employment after SCI was rather frequent and was related to several patient characteristics and social factors. Specific interventions on the patient and on the social environment may favor employment after SCI and improve quality of life. [ABSTRACT FROM AUTHOR]

Gabapentinoids are first choice drugs for central neuropathic pain (CNP) despite limited evidence of efficacy and side effects affecting therapy outcomes. Nutraceuticals could improve their efficacy and tolerability. Our aim is to investigate the effect of NACVAN ® , in addition to gabapentinoids, on pain symptomatology in CNP patients. The effect of 6 weeks of treatment of NACVAN ® was preliminary observed among 29 adult inpatients with spinal cord injury (SCI) or stroke-related CNP recruited to the experimental group. Pain intensity, neuropathic pain, and quality-of-life were measured at baseline (T0) and after 3 (T1) and 6 weeks (T2). Change in each outcome over time was assessed through a repeated measures analysis of variance or Wilcoxon matched-pairs test. Preliminary results show a significant reduction in pain intensity (T0 → T1, p = 0.021; T0 → T2, p = 0.011; T1 → T2, p = 0.46), neuropathic symptoms (T0 → T1, p = 0.024; T0 → T2, p = 0.003), and evoked pain (T0 → T2, p = 0.048). There were no significant reductions in other neuropathic pain dimensions and in quality-of-life components. No side-effects were detected. NACVAN ® could have a beneficial adjuvant effect when used as an add-on to gabapentinoids in patients suffering from CNP due to SCI or stroke, with no adverse effect. Future analysis on a larger sample, compared with a placebo condition, could confirm these preliminary results.

Background: The efficacy of upper limb (UL) robot-assisted therapy (RAT) on functional improvement after stroke remains unclear. However, recently published randomized controlled trials have supported its potential benefits in enhancing the activities of daily living, arm and hand function, and muscle strength. Task-specific and high-intensity exercises are key points in facilitating motor re-learning in neurorehabilitation since RAT can provide an assisted-as-needed approach. This study aims to investigate the clinical effects of an exoskeleton robotic system for UL rehabilitation compared with conventional therapy (CT) in people with subacute stroke. As a secondary aim, we seek to identify patients' characteristics, which can predict better recovery after UL-RAT and detects whether it could elicit greater brain stimulation., Methods: A total of 84 subacute stroke patients will be recruited from 7 Italian rehabilitation centers over 3 years. The patients will be randomly allocated to either CT (control group, CG) or CT plus UL-RT through an Armeo ® Power (Hocoma AG, CH, Volketswil, Switzerland) exoskeleton (experimental group, EG). A sample stratification based on distance since onset, DSO (DSO ≤ 30; DSO > 30), and Fugl-Meyer Assessment (FM)-UL (FM-UL ≤ 22; 22 < FM-UL ≤ 44) will be considered for the randomization. The outcomes will be recorded at baseline (T0), after 25 + 3 sessions of intervention (T1), and at 6 months post-stroke (T2). The motor functioning assessed by the FM-UL (0-66) will be considered the primary outcome. The clinical assessments will be set based on the International Classification of Function, Disability and Health (ICF). A patient satisfaction questionnaire will be evaluated in the EG at T1. A subgroup of patients will be evaluated at T0 and T1 via electroencephalography. Their brain electrical activity will be recorded during rest conditions with their eyes closed and open (5 min each)., Conclusion: The results of this trial will provide an in-depth understanding of the efficacy of early UL-RAT through a whole arm exoskeleton and how it may relate to the neural plasticity process. The trial was registered at ClinicalTrial.gov with the registration identifier NCT04697368.

Study Design: Multicentre cross-sectional study., Objective: The objective of this study is to evaluate prevalence, location and characteristics of pain in hospital inpatients people with spinal cord injury (SCI)., Setting: Ten Italian rehabilitation centres specialized in spinal injury care, where inpatients are admitted both after the acute lesion and for late complications (time since injury, median [IQR]: 0.8 [0.2-8.2] years)., Methods: All the persons were submitted to AIS scale assessment [1] and modified Ashworth scale [2]; personal data and anamnesis were recorded; any pain within 1 week was investigated and the International Spinal Cord Injury Pain Basic Data Set (ISCIPBDS) Italian version [3] was administered by physicians expert in type of pain definition., Results: Of 385 included persons, 275 (72%) suffered pain, with the score value median [IQR]: 6 [4-8]. The worst pain of the person was nociceptive in 52% and neuropathic in 48% of the cases; 46% of nociceptive pain was located in the neck-shoulder region, whereas 67% of neuropathic pain was located in the sublesional part of the body. In 48% of the whole population, spasticity was observed but only 74% of them had pain. Being old and female are associated with high pain development, OR (95% CI): 1.24 (1.01-1.04) and 1.83 (1.05-3.20), respectively., Conclusions: A high prevalence of pain is confirmed in persons with SCI, with both nociceptive and neuropathic pain characteristics. Only old age and female sex resulted as variables highly associated with pain., (© 2021. The Author(s), under exclusive licence to International Spinal Cord Society.)

Depression is the most prevalent psychological issue after a spinal cord injury (SCI) and is associated with noticeable disability, mortality and health expenditure. As SCI mainly occurs in sexually active men at a young age, and can lead to them suffering from an organic neurogenic erectile dysfunction (ED), we supposed that ED could be a major correlate of depressive status in men with SCI. As documented by a Beck Depression Inventory-II (BDI-II) score ≥14, depression was reported in 17 out of 57 men with a chronic SCI (29.8%). They exhibited a significantly higher prevalence of ED and a more severe bowel and bladder dysfunction when compared to the group without depression. At the multiple logistic regression analysis, depression showed a significant independent association with ED (OR = 19.0, 95% CI: 3.1, 203.3; p = 0.004) and, to a lesser extent, with a severe impairment of bowel and bladder function (OR = 0.84; 95% CI: 0.72, 0.94; p = 0.01). Depression was observed in 43.7% of men with ED and only in 12.0% of those without ED ( p = 0.002). In conclusion, healthcare providers should give the right level of importance to the management of ED in men with SCI, as this represents a major independent correlate of depression, which, in turn, might hinder physical rehabilitation and exacerbate physical health issues related to SCI.

Study Design: Observational case-control study., Objective: Individuals with spinal cord injury (SCI) develop systemic physiological changes that could increase the risk of severe evolution of coronavirus disease 2019 (COVID-19) and result in atypical clinical features of COVID-19 with possible delay in both diagnosis and treatment. We evaluated differences in clinical features and evolution of COVID-19 between people with SCI and able-bodied individuals., Setting: The study was conducted in an Italian inpatient rehabilitation referral center for individuals with SCI during the lockdown for the COVID-19 pandemic., Methods: We compared clinical information between patients with SCI and able-bodied healthcare workers of the same center who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the nasopharyngeal swab polymerase chain reaction., Results: Overall, 15 out of the 25 SCI patients admitted to the center and 17 out of the 69 healthcare workers tested positive for SARS-CoV-2. Patients with SCI exhibited a significantly more advanced age and a higher prevalence of comorbidities. Nevertheless, no significant differences in clinical expression of COVID-19 and treatment strategies were observed between the two groups. All hospitalized subjects were treated in nonintensive care units and no deaths occurred in either group., Conclusions: This study does not support the supposed notion that COVID-19 could exhibit atypical clinical features or a worse evolution in the frail population of people with SCI.

A lower risk of prostate cancer has been reported in men with spinal cord injury (SCI) as compared to that observed in able-bodied subjects. As injury-related consequences can have opposite effects on prostate pathophysiology, this meta-analysis aimed to (1) establish the existence/quantify the extent of decreased prostate cancer risk following SCI and (2) find out if there is any statistically significant difference in prostate-specific antigen (PSA) levels between SCI and able-bodied subjects. MEDLINE, Cochrane Library, Scopus, CINAHL, and ScienceDirect databases were used. Only studies reporting a prostate cancer diagnosis and/or PSA levels following SCI and in able-bodied controls were included. Five studies provided information about prostate cancer on 35 293 subjects with SCI and 158 140 controls. Six studies were included in PSA analysis which reported information on 391 men with SCI and 1921 controls. Pooled estimates indicated that SCI reduced the prostate cancer risk by approximately 50% as compared to controls, whereas differences in PSA levels were not statistically significant. Funnel plots suggested the presence of publication bias only in PSA analysis. Between-study heterogeneity was established and when, according to meta-regression models, analysis was restricted to studies including men with mean age over 55 years, prostate cancer risk in SCI decreased up to 65.0% than that in controls with no heterogeneity (P = 0.33, I 2 = 9%). In conclusion, in men over 55 years old, SCI decreases the prostate cancer risk up to 65.0% than that in controls. The large between-study heterogeneity on PSA confirms its poor reliability as a screening tool for prostate cancer in SCI., Competing Interests: None

Study Design: Longitudinal cohort study., Objective: To explore the longitudinal association of baseline vitamin D levels with 1-year change in physical function outcomes in people with chronic spinal cord injury (SCI)., Setting: Rehabilitation institute., Methods: Sixty-seven patients (44 men and 23 women) with chronic SCI admitted to a rehabilitation program were included. Functional independence in daily living activities (as evaluated by the Spinal Cord Independence Measure version III, SCIM III) and leisure time physical activity (LTPA) were assessed as measures of physical function at the admission and re-assessed 1-year later. Comorbidity was scored by Charlson comorbidity index (CCI)., Results: A 1-year worsening in SCIM and LTPA were registered in 44 and 40 patients (66% and 60% of the study population), respectively. They exhibited significantly lower baseline 25(OH)D levels, higher CCI, and shorter distance from the injury. At the multiple linear regression analyses, lower baseline 25(OH)D levels exhibited a significant independent association with higher percentages of 1-year worsening in both SCIM and LTPA. At ROC analysis, baseline 25(OH)D levels <18.6 and <18.2 ng/mL discriminated individuals with 1-year worsening in SCIM and LTPA, respectively. According to these cut-off points, at the multiple logistic regression analysis, patients with low baseline 25(OH)D levels exhibited an OR of worsening in SCIM and LTPA engagement 2.8- and 2.6-fold higher, after adjustment for CCI, distance from injury, and post-follow-up 25(OH)D levels., Conclusions: In people with chronic SCI, a low 25(OH)D level may represent an independent predictor of worsening in physical function outcomes over time.

Objective: Non-alcoholic fatty liver disease (NAFLD) has been claimed as a liver phenotype of metabolic syndrome, which in turn is associated with male hypogonadism. We assessed whether an independent association between NAFLD and androgen deficiency could be revealed in men with chronic spinal cord injury (SCI), who exhibit a high prevalence of biochemical androgen deficiency and a combination of risk factors for metabolic syndrome., Design: Fifty-five consecutive men with chronic SCI admitted to a rehabilitation program underwent clinical/biochemical evaluations and liver ultrasonography., Results: NAFLD was diagnosed in 27 patients (49.1%). Men with NAFLD were older and exhibited significantly higher body mass index, Homeostatic model assessment of insulin resistance, triglycerides and gamma-glutamyl transpeptidase values, lower total and free testosterone levels and they were engaged in a significantly poorer weekly leisure time physical activity (LTPA). At the multiple logistic regression analysis, only total and free testosterone levels exhibited a significant independent association with NAFLD. The risk of having NAFLD increased indeed of 1% for each decrement of 1 ng/dL of total testosterone and of 3% for each decrement of 1 pg/mL of free testosterone, after adjustment for confounders. In men with total testosterone < 300 ng/dL (36.4%) the prevalence of NAFLD reached 85%: they had a risk of having NAFLD significantly higher (∼12-fold) than those with total testosterone ≥ 300 ng/dL, after adjustment for confounders., Conclusion: The evidence of an independent association between NAFLD and low testosterone is strongly reinforced by its demonstration in men with chronic SCI, in spite of the many confounders peculiar to this population.

Objective: As an independent linear association between 25-hydroxyvitamin D (25(OH)D) and testosterone levels is controversial, this study aimed to explore this topic in men with chronic spinal cord injury (SCI), who exhibit a high prevalence of both androgen and vitamin D deficiency., Design: Forty-nine men with chronic SCI consecutively admitted to a rehabilitation program underwent clinical/biochemical evaluations., Results: Deficiency of 25(OH)D (<20 ng/mL) was found in 36 patients (73.5%). They exhibited significantly lower total testosterone and free testosterone levels, higher parathyroid hormone (PTH) and HOMA-IR, a poorer functional independence degree, and were engaged in poorer weekly leisure time physical activity (LTPA). Significant correlates of 25(OH)D levels were: total testosterone, free testosterone, PTH, functional independence degree and weekly LTPA. At the linear regression models, lower 25(OH)D levels were associated with both lower total and free testosterone after adjustment for age, smoking, alcohol consumption, comorbidities and HOMA-IR. However, after full adjustment, also including functional independence degree, BMI and LTPA, only the association of lower 25(OH)D with lower free testosterone was still significant., Conclusion: In men with SCI, 25(OH)D correlates with total and free testosterone and exhibits an independent linear association with free testosterone. Regardless of this independent link, hypovitaminosis D and androgen deficiency are markers of poor health, sharing common risk factors to take into account in the rehabilitative approach to patients with SCI.

Background and Purpose. Stroke incidence increases with age and is likely to increase in the aging populations. We investigated incidence, outcome, and resource use in very old subjects with stroke. Methods. We performed a systematic review of available data through electronic search of the literature databases and manual search of reference lists. Data were extracted for the age groups of over 80, 80 to 84 years old, and over 85. Overall incidence rates, expressed as the number of first strokes per 1000 person-years, were estimated using Poisson regression analysis. Odds ratios for the comparisons between subjects over and under 80 were calculated with the Mantel-Haenszel method. Results. We found a high incidence of stroke in the very old. The estimated incidence rates were 20.78 (95% CI 19.69 to 21.87) in subjects over 80, 17.23 (95% CI 15.97 to 18.49) for those 80 to 85 years old, and 20.78 (95% CI 16.74 to 23.78) for those over 85. Subjects over 80 contributed 29.95% of strokes; rates were similar among genders. Thirty-day case fatality rate and occurrence of dependency were higher in subjects over 80, although associated with less frequent hospital and stroke unit admission and less diagnostic resource use. Conclusions. The contribution of very old subjects to the global burden of stroke is relevant and may require efficient dedicated stroke services.

Introduction. Stroke in the young may have a dramatic impact on the quality of life in survivors. This study was aimed to evaluate incidence of first-ever stroke in the young by means of a systematic review. Materials and Methods. All papers on incidence of stroke in the young published after 1980, were identified by electronic search of Medline and manual search of reference lists. Only studies recruiting subjects under 44 years of age and with a lower age limit not higher than 20 years were included. Incidence rates were standardized to the 2000 European population according to the direct method. Poisson regression analysis was used to compare studies. Results. 29 studies including 3548 participants were identified. Incidence rates, after excluding a few outliers, ranged between 8.63 and 19.12 for crude rates and between 8.70 and 21.02 for standardized rates. Heterogeneity among studies was statistically significant but improved after excluding 4 studies. Few studies reported the proportions of stroke subtypes. Conclusions. Stroke in subjects under 45 years of age is not such a rare disease and requires specific preventive programs.

The occurrence of tyrosine phosphorylation (TP) in the sperm head during capacitation has been poorly investigated, and no data exist on the relationship of its dynamics with the acquisition of sperm fertilizing ability. This study localized TP of head proteins in human spermatozoa during capacitation and explored its relationship with acquisition of the ability to display progesterone (P)-stimulated acrosome reactions (ARs) and to penetrate zona-free hamster oocytes. By immunofluorescence, TP immunoreactivity was revealed in the acrosomal region of formaldehyde-fixed/unpermeabilized samples, whereas it was abolished in fixed/permeabilized samples, in which TP immunoreactivity was high in the principal piece. No TP immunoreactivity was detectable in unfixed spermatozoa. Head TP immunoreactivity was localized externally to the acrosome, close to the cytoplasmic membrane, as assessed by transmission electron microscopy. The increase in head TP was an early event during capacitation, occurring within 1 h in capacitating conditions. At this time, the P-stimulated ARs were also increased, whereas egg penetration was as poor as in uncapacitated spermatozoa. At 5 h of capacitation, the extent of neither head TP nor the P-induced ARs were greater than that at 1 h, whereas egg penetration had significantly increased. Seminal plasma inhibited head TP, P-induced ARs and egg penetration. None of these inhibitory effects, unlike those on tail TP, were prevented by the cAMP analogue dbcAMP (N,2-O-dibutyryladenosine 3',5'-cyclic monophosphate). In conclusion, head TP is a subsurface event occurring early during capacitation and is closely related to acquisition of the ability to display P-stimulated ARs, whereas the ability to fuse with oolemma and to decondense is a later capacitation-related event.

Mitochondria are dynamic organelles capable of significant changes of their ultrastructural features according to the tissue-specific energy demands. In human biopsies of vastus lateralis and anterior tibialis muscles from young (25.0 ± 4.4 years), middle-aged (50.4 ± 7.5 years) and old (75.5±3.9 years) healthy volunteers, we carried out a morphometric study on subsarcolemmal and intermyofibrillar mitochondria to assess whether age-related alterations of the morphology of these organelles contribute to the muscle performance decay in aging. By computer-assisted methods, we measured: the average area (MAA), the longer diameter (Dmax) and the ratio perimeter to area (pleomorphic index: Plei) of mitochondria. No significant age-related ultrastructural differences were found either in subsarcolemmal or intermyofibrillar organelles. However, in middle-aged as well as in the old group of patients vs. the young one, MAA and Dmax showed a clear trend to decrease, while Plei showed a marked, age-related tendency to increase. Higher percentages of less pleomorphic organelles were found in the youngest group of patients and this was particularly evident in the subsarcolemmal mitochondrial population. In addition to reporting on discrete aspects of mitochondrial ultrastructure, MAA, Dmax and Plei are closely related to each other and provide a reliable index of the muscle mitochondria adaptive response to age. Thus, we interpret our results as indicating a substantial preservation of muscle mitochondrial ultrastructure during aging.

The expression of two factors involved in the nuclear-mitochondrial crosstalk, namely the mitochondrial transcription factor A (TFAM) and the nuclear respiratory factor-1 (NRF-1), was studied in human skeletal muscle biopsies of young and aged subjects. Aged subjects presented a 2.6-fold and an 11-fold increase of the levels of TFAM protein and TFAM mRNA, respectively. The increased expression of TFAM was associated to the doubling of NRF-1 DNA-binding affinity and to a 6-fold increase of NRF-1 mRNA level. The upregulation of TFAM and NRF-1, in aged skeletal muscle, appears involved in the pathway leading to the age-related increase of mitochondrial DNA content.