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OBJECTIVE: Due to the aging population, the incidence of stroke is steadily increasing. In patients with stroke outcomes, sensory, motor and cognitive problems limit the performance of activities of daily living. The development of new technologies in rehabilitation is improving the quality and efficiency of functional recovery. Hunova robotic platform (Movendo Technology, srl, Genoa, Italy) is a robotic device for functional assessment and rehabilitation of balance. The purpose of this study is to evaluate the effects of rehabilitation with Hunova on cognitive function and balance in older adults with stroke. PATIENTS AND METHODS: This is a randomized, controlled, single-blind study. Twenty-four older adults with stroke outcomes were randomized into the Hunova group (HuG), which performed a specific rehabilitation program for balance using Hunova for 12 sessions in addition to conventional rehabilitation, and the control group (CoG), which performed only conventional rehabilitation. All patients underwent a clinical cognitive, balance, quality of life and fatigue assessment, and an instrumental balance assessment with Hunova at the beginning and end of treatment. RESULTS: Statistical analysis showed significant improvements in most clinical scales in both groups. Comparing the groups, HuG showed greater improvements in executive functions, speed of information processing, attention and discrimination of multiple stimuli, static and dynamic balance and autonomy in daily activities, standing postural sway, and trunk control in static and dynamic conditions. CONCLUSIONS: Data analysis showed that elderly with stroke who underwent balance technology treatment with Hunova in combination with conventional treatment had a greater improvement in cognitive functions, balance and reduced risk of falling. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Frailty is a common condition in older adults, characterized by multimorbidity, physical weakness and nutritional deficit. Frailty can be detected early and a prehabilitation treatment could reduce the incidence of disability. PATIENTS AND METHODS: Two-hundred-fifteen elderly patients were admitted to the Rehabilitation and Physical Medicine Unit of Policlinico Gemelli for one year. Patients were clinically assessed by Charlson Comorbidity Index (CCI) and blood sample values. Numerical Pain Rating Scale (NRS) and Hand Grip Test were assessed before (T0) and after (T1) hospitalization. Number of drugs and number of infections were recorded. RESULTS: Patients were originally hospitalized in orthopaedic, neurology and medical ward. Most patients (68%) after discharge return home. Negative correlations between albumin and CCI and between total protein and CCI were recorded. Positive correlation between CCI cognitive subscore and number of drugs and a negative correlation between that subscore and Vitamin D were detected. An improvement in NRS and in the handgrip strength was recorded. At discharge an increase in the number of drugs and the number of infections was noted. CONCLUSIONS: The handgrip strength improvement increases quality of life. Pain management and NRS indicate a better recovery of activities of daily living. Malnutrition is a real problem; albumin is the principal negative acutephase reactant and is related to a worse clinical condition and low vitamin D levels are associated with worse cognitive function. The goal of a Rehabilitation Unit is to create an effective multidisciplinary transitional care plan, involving the patient and caregivers, creating a continuity of care after discharge and a sustainable project. [ABSTRACT FROM AUTHOR]

The surface epithelial cells of Necturus gastric fundus mucosa contribute 7% and 13% to the total transepithelial conductance under control condition, and after Na+ conductance activation. These are poorly permeable cells and most of the conductance takes place through the oxyntopeptic cells in the glands. Histamine activates the oxyntopeptic cells, increases the transepithelial voltage, and decreases resistance. Consequently, the contribution of the surface epithelial cells falls.

Background and purpose Charcot−Marie−Tooth ( CMT) disease is the most common inherited neuropathy, but therapeutic options have been limited to symptom management. Past pharmacological trials have failed, possibly due to insensitive outcome measures ( OMs). The aim of the current study was to evaluate the validity and reliability of the 6-min walk test (6 MWT) and StepWatch™ Activity Monitoring ( SAM) with other previously validated OMs in CMT disease. Methods A prospective multicenter study was performed, consecutively enrolling 168 CMT patients (104 with CMT1A, 27 with CMT1B, 37 with X-linked CMT) from Italian centers specializing in CMT care. Results Statistical analysis showed that the 6 MWT was highly related with all previously used OMs. Some, but not all, SAM parameters were related to commonly used OMs but may provide more information about quality of life. Conclusions The current study demonstrated the validity and reliability of the 6 MWT and SAM as OMs for CMT. Moreover, SAM provides data that correlate better with quality of life measures, making it useful in future rehabilitation trials. [ABSTRACT FROM AUTHOR]

Objectives: Post-stroke fatigue (PSF) is an experience characterized by an early feeling of exhaustion with fatigue, a lack of energy, and difficulty in exertion, both motor and cognitive. To counteract fatigue and limit its effects on activities of daily living, the use of vitamins and minerals is known in addition to the pharmacological approach. However, few studies have evaluated the effect of vitamin and mineral supplementation on fatigue management. SiderAL® Med is a food for special medical purposes with a complete formulation containing vitamins, sucrosomal minerals, copper and algal calcium. The aim of the study is to evaluate whether nutritional supplementation with SiderAL® Med improves the symptom of fatigue and motor and cognitive function in stroke patients., Design: This is a pilot, randomized study with a control group., Setting: Post-Acute Rehabilitation Unit of the Fondazione Policlinico "A. Gemelli" IRCCS., Participants: Twenty-four patients with stroke outcomes, admitted to rehabilitation, were recruited and randomized into the experimental group (Sid-G) and the control group (CG)., Intervention: The Sid-G patients, in association with the pharmacological and rehabilitation therapy foreseen during hospitalization, took SiderAL® Med, one sachet per day for 8 weeks, while the CG patients underwent only the pharmacological and rehabilitation therapy foreseen in the daily routine., Measurements: All patients were assessed at baseline (T0), after 4 weeks (T1), after 8 weeks (T2) and after 12 weeks (T3) for motor and cognitive fatigue, balance, walking, functional capacity, cognitive performance, autonomy, quality of life and body composition., Results: Both Sid-G and CG patients showed significant improvement on most rating scales between T0-T1-T2-T3 (p = 0.0001). When comparing the two groups, a statistically significant difference emerged in favor of Sid-G with regard to motor fatigue (p = 0.007), cognitive fatigue (p = 0.009) and total fatigue (p = 0.034); balance (p < 0.001), functional capacity (p < 0.001); cognitive performance (p = 0.004); bone mineral content (p = 0.005), lean mass (p = 0.005), total mass (p < 0.001) and percentage of fat mass (p = 0.039)., Conclusion: Nutritional supplementation with SiderAL® Med, in concert with intensive rehabilitation treatment, appears to be effective in managing fatigue and improving motor and cognitive performance and body composition, representing a valuable tool to associate with rehabilitation treatment in stroke patients., (Copyright © 2024. Published by Elsevier Masson SAS.)

Image-guided core needle biopsies (IG-CNB) represent a minimally invasive approach for obtaining tissue in patients with lymphadenopathy and suspected lymphoma. Despite their utility, diagnostic challenges persist, with lower efficacy compared with excisional biopsies. Our study aimed to evaluate the potential utility of incorporation of flow cytometry (FC) alongside immunohistochemistry (IHC) when performing IG-CNB for suspected lymphoproliferative diseases. Analyzing 170 consecutive cases, guided by ultrasound (n = 94) or computer tomography (n = 76), we employed a diagnostic algorithm, already established in our laboratory practice, utilizing three antibody cocktail-equipped tubes tailored for defining lymphomas, particularly those of B-cell origin. FC expedited the diagnostic process, yielding presumptive results in 87.6% of cases within 48 h, with a positive predictive value of 98%. Addition of FC to routine IHC enhanced the diagnostic rate from 91.2% to 95.3%, reducing IG-CNB failure rate by 45%, from 8.8% to 4.7%. This enhancement was particularly notable for deep-seated sites and in the setting of suspected disease recurrences. Consequently, FC emerges as a valuable adjunctive tool, allowing for the improvement of diagnostic performance, with a particular focus on the ability to quantify the expression of surface markers for targeted therapies, and holding the potential to diminish the necessity for repeat excisional biopsies subsequent to IG-CNB procedures., (© 2024 International Clinical Cytometry Society.)

Introduction: The emergence of drug-resistant Mycobacterium tuberculosis (Mtb) strains has underscored the urgent need for novel therapeutic approaches. Carbon-based nanomaterials, such as graphene oxide (GO), have shown potential in anti-TB activities but suffer from significant toxicity issues., Methods: This study explores the anti-TB potential of differently functionalized graphene quantum dots (GQDs) - non-functionalized, L-GQDs, aminated (NH 2 -GQDs), and carboxylated (COOH-GQDs) - alone and in combination with standard TB drugs (isoniazid, amikacin, and linezolid). Their effects were assessed in both axenic cultures and in vitro infection models., Results: GQDs alone did not demonstrate direct mycobactericidal effects nor trapping activity. However, the combination of NH 2 -GQDs with amikacin significantly reduced CFUs in in vitro models. NH 2 -GQDs and COOH-GQDs also enhanced the antimicrobial activity of amikacin in infected macrophages, although L-GQDs and COOH-GQDs alone showed no significant activity., Discussion: The results suggest that specific types of GQDs, particularly NH 2 -GQDs, can enhance the efficacy of existing anti-TB drugs. These nanoparticles might serve as effective adjuvants in anti-TB therapy by boosting drug performance and reducing bacterial counts in host cells, highlighting their potential as part of advanced drug delivery systems in tuberculosis treatment. Further investigations are needed to better understand their mechanisms and optimize their use in clinical settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Santarelli, Perini, Salustri, Palucci, Rosato, Palmieri, Iacovelli, Bellesi, Sali, Sanguinetti, De Spirito, Papi, Delogu and De Maio.)

Flow cytometry (FCM) and quantitative PCR (qPCR) are conventional methods for assessing CAR-T expansion, while digital droplet PCR (ddPCR) is emerging as a promising alternative. We monitored CAR-T transcript expansion in 40 B-NHL patients post-infusion of CAR-T products (axi-cel; tisa-cel; and brexu-cel) with both His-Tag FCM and ddPCR techniques. Sensitivity and predictive capacity for efficacy and safety outcomes of ddPCR were analyzed and compared with FCM. A significant correlation between CAR-T counts determined by FCM and CAR transcripts assessed by ddPCR ( p < 0.001) was observed. FCM revealed median CD3+CAR+ cell counts at 7, 14, and 30 days post-infusion with no significant differences. In contrast, ddPCR-measured median copies of CAR-T transcripts demonstrated significant lower copy numbers in tisa-cel recipients compared to the other products at day 7 and day 14. Patients with a peak of CAR transcripts at day 7 exceeding 5000 copies/microg gDNA, termed "good CAR-T expanders", were more likely to achieve a favorable response at 3 months (HR 10.79, 95% CI 1.16-100.42, p = 0.036). Good CAR-T expanders showed superior progression-free survival at 3, 6, and 12 months compared to poor CAR-T expanders ( p = 0.088). Those reaching a peak higher than 5000 copies/microg gDNA were more likely to experience severe CRS and ICANS. DdPCR proves to be a practical method for monitoring CAR-T expansion, providing quantitative information that better predicts both treatment outcomes and toxicity.

CD4 + and CD8 + chimeric antigen receptor T cells (CAR-T) play different roles in the in vivo anti-tumour response, but the role of the CD4 + /CD8 + ratio among infused CAR-T has not been clearly defined yet. We analysed leftovers from infused anti-CD19 CAR-T bags of 31 patients with aggressive B-cell lymphomas. The median ratio was 1.44, lower for brexu-cel compared to tisa-cel and axi-cel. The CAR+CD4 + /CD8 + ratio was influenced by lactate dehydrogenase levels at apheresis, not by age, previous treatments or the CD4 + /CD8 + ratio in peripheral blood. Patients with a response at 3 months after CAR-T (M3) had a lower CAR+CD4 + /CD8 + ratio in the infused products compared to non-responders (ratio 0.74 vs. 2.47, p = 0.011). A CAR+CD4 + /CD8 + ratio higher than the cut point of 1.12 was associated with an increased risk of treatment failure at M3 (OR 23.3, p = 0.012) and M6 (OR 10, p = 0.028). The median 6-month PFS was 76% for patients with a ratio lower than 1.12% vs. 31% for the others. The prognostic role of the CAR+CD4 + /CD8 + ratio was independent of the costimulatory domain (CD28 vs. 4-1BB) of the product (OR 16.41, p = 0.041). Our data indicate a crucial role for CD8 + CAR-T and the CAR+CD4 + /CD8 + ratio in predicting CAR-T efficacy., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Intensive-Care-Unit-Acquired Weakness (ICU-AW) is the most common neuromuscular impairment in critically ill patients and can have a significant impact on long-term disability. Early rehabilitation has been suggested to facilitate the natural recovery process. This is a pilot, randomized, single-blind study that aimed to evaluate the effectiveness of intensive combined technological rehabilitation treatment including focal muscle vibration and non-immersive virtual reality for patients with severe acquired brain injury (sABI) and ICU-AW. Twenty-four patients were randomized into the conventional group, which performed only conventional rehabilitation, and the experimental group, which also performed technological treatment. At baseline and after 3 weeks of treatment, assessments of motor function, autonomy, disability and quality of life were conducted. At the end of the intervention, both groups showed significant improvements. However, patients in the experimental group achieved greater improvements in disability ( p = 0.001) and quality of life ( p = 0.001). The results show that intensive structured rehabilitation is effective in improving the motor function, disability and quality of life of patients with severe acquired brain injury and acquired weakness. The combination of non-immersive virtual reality training and focal muscle vibration can result in a significant improvement in overall disability and quality of life compared with conventional treatment alone.

Actigraphy is a tool used to describe limb motor activity. Some actigraphic parameters, namely Motor Activity (MA) and Asymmetry Index (AR), correlate with stroke severity. However, a long-lasting actigraphic monitoring was never performed previously. We hypothesized that MA and AR can describe different clinical conditions during the evolution of the acute phase of stroke. We conducted a multicenter study and enrolled 69 stroke patients. NIHSS was assessed every hour and upper limbs' motor activity was continuously recorded. We calculated MA and AR in the first hour after admission, after a significant clinical change (NIHSS ± 4) or at discharge. In a control group of 17 subjects, we calculated MA and AR normative values. We defined the best model to predict clinical status with multiple linear regression and identified actigraphic cut-off values to discriminate minor from major stroke (NIHSS ≥ 5) and NIHSS 5-9 from NIHSS ≥ 10. The AR cut-off value to discriminate between minor and major stroke (namely NIHSS ≥ 5) is 27% (sensitivity = 83%, specificity = 76% (AUC 0.86 p < 0.001), PPV = 89%, NPV = 42%). However, the combination of AR and MA of the non-paretic arm is the best model to predict NIHSS score (R 2 : 0.482, F: 54.13), discriminating minor from major stroke (sensitivity = 89%, specificity = 82%, PPV = 92%, NPV = 75%). The AR cut-off value of 53% identifies very severe stroke patients (NIHSS ≥ 10) (sensitivity = 82%, specificity = 74% (AUC 0.86 p < 0.001), PPV = 73%, NPV = 82%). Actigraphic parameters can reliably describe the overall severity of stroke patients with motor symptoms, supporting the addition of a wearable actigraphic system to the multi-parametric monitoring in stroke units.

Background: Multiple Sclerosis (MS) is a disease that often results in motor and/or cognitive disability. Despite the increasing availability of effective drug therapies, rehabilitation is very important means of counteracting the progression of disability and improving physical function, impacting social participation and improving quality of life. Several rehabilitation approaches can be used in the context of neuro-motor rehabilitation, but there is insufficient evidence for them in the literature., Objectives: This study has the twofold purpose of: (i) investigate whether rehabilitation according to Bobath Concept can improve balance and some aspects of cognitive function in MS patients; (ii) explore whether the ability to improve postural control, an indirect index of adaptive neuroplasticity, is preserved in MS patients and whether it can be improved with rehabilitation., Method: This is an independent wait-listed study. Forty people with MS (pwMS) were enrolled: patients in the Bobath group underwent 8 weeks of rehabilitation according to the Bobath Concept. For aim 1, pwMS were assessed at baseline (T0), at the end of the 8 weeks of treatment (T1) and after 8 weeks of observation (T2) with motor and cognitive scales. For aim 2, the same 40 pwMS were matched with healthy controls and were subjected to a postural learning task using the force platform at T0, T1 and T2., Results: Patients in Bobath group scored better on balance and cognitive function at T1, but this improvement was not maintained at T2. All patients were less accurate than controls in the postural learning task at each assessment; however, patients also demonstrated an increase in accuracy after training, similar to that of healthy controls. The learning curve was better for patients randomized to the active group than the waitlist at T1 time, but this advantage was not maintained at the T2 assessment., Conclusion: In light of the results, this study supports the use of rehabilitation according to Bobath Concept to improve balance control and some executive functions in MS. Despite worse baseline performance, pwMS were able to learn a postural control task on par with healthy controls. Also, supports the hypothesis that adaptive plasticity is preserved despite MS and can be promoted by rehabilitation., Competing Interests: Declaration of competing interest LC: consulting fees from Almirall. CP: scientific advisory boards for Actelion, Biogen, Genzyme, Hoffmann-La Roche Ltd, Merck Serono, Novartis, Sanofi, Teva; consulting and/or speaking fees, research support and travel grants from Allergan, Almirall, Biogen, Genzyme, Hoffmann-La Roche Ltd, Merck Serono, Novartis, Sanofi and Teva.STAI: State-Trait Anxiety Inventory Form Y 1-2; BDI-II: Beck Depression Inventory Scale-II; SDMT: Symbol Digit Modalities Test; CVLT-II: California Verbal Learning Test-II; BVMT-R: revised Brief Visuospatial Memory Test; SCWT: Stroop Colour Word Test; BBS: Berg Balance Scale; CoP path ST: Center Of Pressure Single Task: CoP path DT: Center Of Pressure Dual Task; G-BR: Group Bobath Rehabilitation; G-WL: Group Waiting List., (Copyright © 2022. Published by Elsevier B.V.)

The use of quantitative methods to analyze the loss in gait smoothness, an increase in movement intermittency which is a distinguishing hallmark of motor deficits in stroke patients, has gained considerable attention in recent years. In the literature, the spectral arc length (SPARC), as well as metrics based on the measurement of the jerk, such as the log dimensionless jerk (LDLJ), are currently employed to assess smoothness. However, the optimal measure for evaluating the smoothness of walking in stroke patients remains unknown. Here, we investigated the smoothness of the body's center of mass (BCoM) trajectory during gait, using an optoelectronic system, in twenty-two subacute and eight chronic patients before and after a two-month rehabilitation program. The two measures were evaluated for their discriminant validity (ability to differentiate the smoothness of the BCoM trajectory calculated on the cycle of the affected and unaffected limb, and between subacute and chronic patients), validity (correlation with clinical scales), and responsiveness to the intervention. According to our findings, the LDLJ outperformed the SPARC in terms of the examined qualities. Based on data gathered using an optoelectronic system, we recommend using the LDLJ rather than the SPARC to investigate the gait smoothness of stroke patients.

Background: Stroke, the incidence of which increases with age, has a negative impact on motor and cognitive performance, quality of life, and the independence of the person and his or her family, leading to a number of direct and indirect costs. Motor recovery is essential, especially in elderly patients, to enable the patient to be independent in activities of daily living and to prevent falls. Several studies have shown how robotic training associated with physical therapy influenced functional and motor outcomes of walking after stroke by improving endurance and walking strategies. Considering data from previous studies and patients' needs in gait and balance control, we hypothesized that robot-assisted balance treatment associated with physical therapy may be more effective than usual therapy performed by a physical therapist in terms of improving static, dynamic balance and gait, on fatigue and cognitive performance., Methods: This is an interventional, single-blinded, preliminary randomized control trial. Twenty-four patients of both sexes will be recruited, evaluated, and treated at the UOC Rehabilitation and Physical Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome from January to December 2022. Patients will be randomized into two groups: the experimental group will perform specific rehabilitation for balance disorder using the Hunova® robotic platform (Movendo Technology srl, Genoa, IT) for 3 times a week, for 4 weeks (12 total sessions), and for 45 min of treatment, in addition to conventional treatment, while the conventional group (GC) will perform only conventional treatment as per daily routine. All patients will undergo clinical and instrumental evaluation at the beginning and end of the 4 weeks of treatment., Conclusions: The study aims to evaluate the improvement in balance, fatigue, quality of life, and motor and cognitive performance after combined conventional and robotic balance treatment with Hunova® (Movendo Technology srl, Genoa, IT) compared with conventional therapy alone. Robotic assessment to identify the most appropriate and individualized rehabilitation treatment may allow reducing disability and improving quality of life in the frail population. This would reduce direct and indirect social costs of care and treatment for the National Health Service and caregivers., Trial Registration: ClinicalTrials.gov NCT05280587. Registered on March 15, 2022., (© 2022. The Author(s).)

Background: Cognitive and behavioural symptoms due to involvement of the central nervous system (CNS) are among the main clinical manifestations of Myotonic Dystrophy type 1 (DM1). Such symptoms affect patients' quality of life and disease awareness, impacting on disease prognosis by reducing compliance to medical treatments. Therefore, CNS is a key therapeutic target in DM1. Deeper knowledge of DM1 pathogenesis is prompting development of potential disease-modifying therapies: as DM1 is a rare, multisystem and slowly progressive disease, there is need of sensitive, tissue-specific prognostic and monitoring biomarkers in view of forthcoming clinical trials. Circulating Neurofilament light chain (NfL) levels have been recognized as a sensitive prognostic and monitoring biomarker of neuroaxonal damage in various CNS disorders., Methods: We performed a cross-sectional study in a cohort of 40 adult DM1 patients, testing if serum NfL might be a potential biomarker of CNS involvement also in DM1. Moreover, we collected cognitive data, brain MRI, and other DM1-related diagnostic findings for correlation studies., Results: Mean serum NfL levels resulted significantly higher in DM1 (25.32 ± 28.12 pg/ml) vs 22 age-matched healthy controls (6.235 ± 0.4809 pg/ml). Their levels positively correlated with age, and with one cognitive test (Rey's Auditory Verbal learning task). No correlations were found either with other cognitive data, or diagnostic parameters in the DM1 cohort., Conclusions: Our findings support serum NfL as a potential biomarker of CNS damage in DM1, which deserves further evaluation on larger cross-sectional and longitudinal studies to test its ability in assessing brain disease severity and/or progression., (© 2022. The Author(s).)

Recently, the use of robotic technology in gait and balance rehabilitation of stroke patients has been introduced, with positive results. The purpose of this study was to evaluate the effectiveness of robotic gait and trunk rehabilitation compared to robotic gait training alone on balance, activities, and participation measures in patients with subacute stroke. The study was a randomized, controlled, single blind, parallel group clinical trial. Thirty-six patients with first ischemic or hemorrhagic stroke event were enrolled, and they were randomized in two groups: Gait Group (GG), where they received only robotic treatment for gait rehabilitation through an end-effector system, and Gait/Trunk Group (GTG) where they performed end-effector gait rehabilitation and balance with a robotic platform, 3 times/week for 12 sessions/month. At the end of the study, there was an improvement in balance ability in both groups. Instead, the lower limb muscle strength and muscle tone significantly improved only in the GTG group, where we found a significant reduction in the trunk oscillations and displacement during dynamic exercises more than the GG group. The robotic platform which was added to the gait robotic treatment offers more intense and controlled training of the trunk that positively influences the tone and strength of lower limb muscles., Competing Interests: The authors declare no conflict of interest.