Construct validity, responsiveness and minimal important difference of the cumulated ambulation score in older adults with hip fracture in sub-acute rehabilitation facility.

OBJECTIVE: To assess the construct validity, responsiveness and minimal important difference of the cumulated ambulation score in patients with hip fracture in sub-acute rehabilitation facility. DESIGN: Observational, prospective, monocenter, cohort study. SETTING: Rehabilitation Institute. PARTICIPANTS: 456 older adults with hip fracture (≥65 years) admitted for inpatient rehabilitation. MAIN OUTCOME MEASURES: Cumulated ambulation score, functional independence measure and functional ambulation category were collected at admission and discharge. Construct validity and responsiveness were assessed through hypothesis testing and minimal important difference was determined using the anchor-based method; floor and ceiling effects were also assessed. RESULTS: The cumulated ambulation score showed strong correlations with the functional independence measure and functional ambulation category scores at both admission and discharge, satisfying all the hypotheses for construct validity. The effect size of cumulated ambulation score was 1.63. Changes in cumulated ambulation score had a moderate-to-strong correlation with changes of other instruments and were able to discriminate patients improved from those not-improved, and patients classified as independent ambulators from those dependent. A ceiling effect was found only at discharge. The estimated minimal important difference was 2 points. CONCLUSIONS: The cumulated ambulation score showed high levels of construct validity and responsiveness according to the hypothesis testing. A two points improvement at the end of rehabilitation was found to be clinically important in people with hip fracture in the sub-acute phase. The ceiling effect found at discharge suggested the limitation of the scale in assessing people with a partially recovered autonomy in performing postural changes and gait.

Effects of soft tissue mobilisation on subacute adherent linear scars: a single-group intervention study.

OBJECTIVE: Scar adherence due to a pathological healing process can cause physical and psychological disturbance. Soft tissue mobilisation (STM) techniques are widely used to treat and prevent scar adherence, but little is known on their effects. We aimed to analyse the effect of STM in patients with subacute post-surgical scar adhesions affecting the extremities. METHOD: A single-group quasi-experimental study was conducted on consecutive patients undergoing post-surgery limb rehabilitation. Patients with a baseline Adhesion Severity (AS) index of <0.5 at the worst scar point, as measured by the Adheremeter, were eligible. All patients who completed a minimum of five manual treatment sessions were included. The primary outcome was the AS index and the secondary outcome was the Italian version of the Patient and Observer Scar Assessment Scales (POSAS-I). RESULTS: A cohort of 19 patients underwent an average of eight STM sessions over a period of one month. The AS index value increased from a median of 0.12 at baseline (interquartile range (IQR): 0.05-0.25) to 0.41 post-treatment (IQR: 0.26-0.63; median change: 0.24; IQR: 0.16-0.40; p<0.001). A large effect size was observed for both AS and Observer Scar Assessment Scale (OSAS-I) (Cohen r=0.6), with a large probability of superiority (PS) (87% and 86%, respectively). A moderate effect was observed for the Patient Scar Assessment Scale (PSAS-I) (Cohen=0.4; PS=71%). Pre-post treatment changes exceeded the minimal detectable changes for the AS and OSAS-I in 68% of subjects, and for PSAS-I in 21% of subjects. CONCLUSION: STM manual techniques may produce a large effect on the mobility of adherent subacute post-surgical scars.

Minimal clinically important difference of the functional independence measure in older adults with hip fracture.

PURPOSE: To investigate the responsiveness and minimal clinically important difference (MCID) of the Functional Independence Measure (FIM) from a clinician's perspective in hip-fractured elderly undergoing inpatient rehabilitation. MATERIALS AND METHODS: Data of 701 hip-fractured elderly admitted to our rehabilitation institute were retrospectively collected. Ten a priori hypotheses were formulated. RESULTS: The effect size of the FIM scores after treatment were large (total = 1.38, motor = 1.78). Moderate correlations were found between the change total score of FIM and Barthel Index (BI, rs = 0.51), Functional Ambulation Categories (FAC, rs = 0.52) and a checklist regarding participants' independence in transfers (rs = 0.59). The area under the receiving operating characteristics were 0.82, 0.81, and 0.85 when BI, FAC and checklist were used as anchors, respectively. Based on these findings, the FIM showed high responsiveness (9/10 hypotheses met). Triangulation of findings showed that MCIDs of 22 and 21 points were the most appropriate for the FIM total and motor score, respectively. CONCLUSIONS: The FIM scale is appropriate for assessing independence and functional recovery in hip-fractured elderly. Improvements of 22 and 21 points at the total and motor FIM were identified as indicators of minimal clinical change in those admitted to a rehabilitation facility with an FIM total score between 40 and 80.

This study provides evidence of the high responsiveness of the Functional Independence Measure (FIM) total score and of its motor subscore, while the cognitive subscore is not responsive to change among older adults with hip fractures hospitalized for rehabilitation.After a rehabilitative program, a change of at least 22 points in the FIM total score is clinically important in older adults with hip fractures.This change scores will be useful for researchers and clinicians in order to determine a possible clinically meaningful improvement in independence as a response to rehabilitation after a hip fracture.

Vertical Ground Reaction Forces in Parkinson's Disease: A Speed-Matched Comparative Analysis with Healthy Subjects.

This study aimed to investigate and compare the vertical Ground Reaction Forces (vGRFs) of patients with Parkinson's Disease (PwPD) and healthy subjects (HS) when the confounding effect of walking speed was absent. Therefore, eighteen PwPD and eighteen age- and linear walking speed-matched HS were recruited. Using plantar pressure insoles, participants walked along linear and curvilinear paths at self-selected speeds. Interestingly, PwPD exhibited similar walking speed to HS during curvilinear trajectories (p = 0.48) and similar vGRF during both linear and curvilinear paths. In both groups, vGRF at initial contact and terminal stance was higher during linear walking, while vGRF at mid-stance was higher in curvilinear trajectories. Similarly, the time to peak vGRF at each phase showed no significant group differences. The vGRF timing variability was different between the two groups, particularly at terminal stance (p < 0.001). In conclusion, PwPD and HS showed similar modifications in vGRF and a similar reduction in gait speed during curvilinear paths when matched for linear walking speed. This emphasized the importance of considering walking speed when assessing gait dynamics in PwPD. This study also suggests the possibility of the variability of specific temporal measures in differentiating the gait patterns of PwPD versus those of HS, even in the early stages of the disease.

Effects of Aerobic Training in Patients with Subacute COVID-19: A Randomized Controlled Feasibility Trial.

Many clinical practice recommendations indicate rehabilitation as essential for patients with sequelae of severe or critical COVID-19 and suggest the prompt initiation of a multicomponent rehabilitation program focused on aerobic and endurance training. However, randomized controlled trials (RCTs) regarding aerobic exercise are lacking. Therefore, we aimed to assess the feasibility and effectiveness of the addition of aerobic training to standard rehabilitation in subjects with subacute COVID-19. Participants were 32/214 patients with the sequelae of severe or critical COVID-19 in the acute phase who were eligible and agreed to participate in the study (eligibility = 15%, recruitment = 100%). After randomization and assessment with functional and strength tests, all the participants underwent an inpatient-tailored rehabilitation program (50 min/day, 5 days/week, 10 sessions); in addition, the experimental group performed a low- to moderate-intensity aerobic exercise (30 min/day, 10 sessions). No dropouts or severe adverse events were reported, with an attendance rate of 95.6%. Most of the secondary outcomes significantly improved in both groups, but the improvement in the Functional Independence Measure and Cumulated Ambulation Score-Italian version was significantly greater in the experimental group (at least, p < 0.05). This RCT showed that aerobic exercise is feasible and safe in subacute COVID-19. Moreover, it appears to be beneficial and useful in improving patients' independence and mobility.

The Coronavirus Footprint on Dual-Task Performance in Post-Acute Patients after Severe COVID-19: A Future Challenge for Rehabilitation.

Recent studies suggest that also the non-critical form of COVID-19 infection may be associated with executive function impairments. However, it is not clear if they result from cognitive impairments or by COVID-19 infection per se. We aimed to investigate if patients in the post-acute stage of severe COVID-19 (PwCOVID), without manifest cognitive deficits, reveal impairments in performing dual-task (DT) activities compared to healthy controls (HS). We assessed balance in 31 PwCOVID vs. 30 age-matched HS by stabilometry and the Timed Up and Go (TUG) test with/without a cognitive DT. The DT cost (DTC), TUG test time and sway oscillations were recorded; correct cognitive responses (CCR) were calculated to evaluate cognitive performance. Results show a significant difference in overall DT performance between PwCOVID and HS in both stabilometry (p < 0.01) and the TUG test (p < 0.0005), although with similar DTCs. The main difference in the DTs between groups emerged in the CCR (effect size > 0.8). Substantially, PwCOVID gave priority to the motor task, leaving out the cognitive one, while HS performed both tasks simultaneously. Our findings suggest that PwCOVID, even without a manifest cognitive impairment, may present a deficit in executive function during DTs. These results encourage the use of DTs and CCR in PwCOVID.

Rasch Validation of the Mini-BESTest in People With Parkinson Disease.

BACKGROUND AND PURPOSE: The Mini-BESTest is a balance measure with robust psychometric properties widely used in people with Parkinson disease. The aim of this study was to examine-with advanced psychometric techniques-some key properties of the Mini-BESTest (including unidimensionality, functioning of rating categories, internal construct validity, reliability indexes) in a consecutive sample of individuals with Parkinson disease admitted for balance rehabilitation. METHODS: Confirmatory factor analysis and Rasch analysis (partial credit model) were performed on 193 individual raw scores of the Mini-BESTest items. RESULTS: Confirmatory factor analysis fit indices and principal component analysis of the residuals confirmed the scale's unidimensionality. At Rasch analysis, the 3-level rating scale demonstrated appropriate functioning. All items fitted the Rasch model. Item response dependence was negligible. No differential item functioning was found across gender and age groups. DISCUSSION AND CONCLUSIONS: We confirmed and extended the evidence (demonstrated in different populations) on the general psychometric soundness of the Mini-BESTest, even when tested with rigorous statistical methods. In addition, 2 forms were created: (i) to transform raw scores into linear estimates of dynamic balance; and (ii) to compare the individual's item responses with those expected by the Rasch model (thus providing an aid for tailored interventions) and manage missing responses. Further independent studies using advanced psychometric techniques are warranted, also in people with balance disturbances of different etiology. Our study further increases the confidence in using the Mini-BESTest to assess dynamic balance in people with Parkinson disease and provides some useful additional clinical aids for interpreting the results and calculating more precise change scores.See the Supplementary Video, available at: http://links.lww.com/JNPT/A384.

Correlation between fall risk increasing drugs (FRIDs) and fall events at a rehabilitation hospital.

Background and aim Falls and fall-related injuries are a major public health issue which needs global attention due to its clinical and socioeconomic impact. Important risk factors for falls are polypharmacy and the assumption of so-called Fall Risk Increasing Drugs (FRIDs). Aims of our study were to investigate the associations between falls and the use of medications among inpatients by conducting a retrospective case-control study in a rehabilitation hospital in Northern Italy in 2018. Methods A Conditional Logistic Regression was performed to analyze the impact that 13 types of FRIDs individually and the number of administrated FRIDs had on the risk of falling. A second regression model was obtained adjusting the case-control matching for CIRS, Morse and Barthel scores. Results We identified 148 cases and 444 controls. 3 types of FRIDs were significantly correlated (p < 0,05) with an increased risk of falling: Antipsychotics, Antidepressants, Diuretics. Antidepressants were the only type of FRID significantly correlated (p=0,008) even in the model adjusted for CIRS, Morse and Barthel scores. The unadjusted model showed that the addition of one type of FRID to therapy was significantly associated with the fall event (p<0.05). Conclusion Assumption of drugs, in particular antidepressant and polypharmacy, can play a role in hospital falling. The fall risk assessment tools available, suffer from low specificity and sensitivity and do not assess these risk factors. A holistic approach with a multidimensional evaluation of the patient through screening tools, functional assessment tools and a full medical evaluation should be pursued to improve prediction.

Balance performance in patients with post-acute COVID-19 compared to patients with an acute exacerbation of chronic obstructive pulmonary disease and healthy subjects.

COVID-19 leaves important sequelae in patients, not only in those who had the experience of a critical illness but also in patients with severe form. Understanding the impairments allows us to target rehabilitation to patients' real needs; balance impairments are an assumed sequela of COVID-19, but no study has specifically evaluated balance performance in these patients. Their performance was compared to that of patients with a pulmonary disease that leads to systemic diseases, such as patients with an acute exacerbation of chronic obstructive pulmonary disease (PwAECOPD), and of healthy subjects. A total of 75 subjects were assessed: 25 patients with COVID-19 (PwCOVID) with a severe form in the acute phase, 25 PwAECOPD and 25 healthy subjects sex- and age-matched. A stabilometric platform was used to evaluate static balance, both with eyes open and closed, while the dynamic balance was assessed with the Mini-BESTest and the Timed Up and Go test. When compared to healthy subjects, results showed that PwCOVID had worse performance in both static (P < 0.005) and dynamic (P < 0.0001) balance, with a large effect size in all measures (>0.8). Moreover, PwCOVID showed similar results to those of PwAECOPD. In conclusion, PwCOVID showed a balance deficit in both dynamic and static conditions. Therefore, as for PwAECOPD, they should require not only respiratory rehabilitation but also balance and mobility physiotherapy to prevent today's PwCOVID from becoming tomorrow's fallers.

Which model best assesses gait in healthy elderly? A confirmatory factor analysis of existing conceptual gait models.

BACKGROUND: Various conceptual gait models have been created with exploratory factor analysis to assess gait performance in healthy individuals or patients with orthopaedic or neurological diseases. However, a direct comparison between these models, to determine which is best for assessing gait in healthy elderly subjects, has never been performed. Confirmatory factor analysis is a statistical technique which allows to compare the structure of these models and to evaluate their validity and reliability. RESEARCH QUESTION: Which of the current models for evaluating gait shows the best construct, convergent and discriminant validity and reliability when replicated in a sample of healthy elderly subjects? METHODS: 92 healthy elderly subjects (aged 73.3 ± 6.8 years) were enrolled. Participants were instructed to walk on a baropodometric walkway; gait variables were then extracted and analyzed according to 8 different gait models (published between 2007 and 2019). Correlation between variables of each model were investigated. The number of factors to include for each model was assessed with different criteria of principal component analysis. The construct validity of the gait models was assessed in terms of goodness of fit indexes through confirmatory factor analysis. Convergent and discriminant validity and reliability of the models were also assessed. RESULTS: Of the models considered, only our model previously created for patients with Parkinson's Disease reached convergence, with an excellent fit in all indexes (χ2 = 18.34, df = 13, p = 0.15, RMSEA = 0.06 (95%CI = 0.00-0.13), CFI = 0.98, TLI = 0.96, SRMR = 0.05). The model showed an acceptable convergent validity. The three factors resulted to be mutually independent (correlations among factors <0.85) and reliable. Most of the other seven considered models presented a high number (12.5-65%) of highly inter-related variables and more factors than necessary. SIGNIFICANCE: Future studies can use our gait model as a framework for clinical practice or research.

A pathophysiological model of gait captures the details of the impairment of pace/rhythm, variability and asymmetry in Parkinsonian patients at distinct stages of the disease.

Locomotion in people with Parkinson' disease (pwPD) worsens with the progression of disease, affecting independence and quality of life. At present, clinical practice guidelines recommend a basic evaluation of gait, even though the variables (gait speed, cadence, step length) may not be satisfactory for assessing the evolution of locomotion over the course of the disease. Collecting variables into factors of a conceptual model enhances the clinical assessment of disease severity. Our aim is to evaluate if factors highlight gait differences between pwPD and healthy subjects (HS) and do it at earlier stages of disease compared to single variables. Gait characteristics of 298 pwPD and 84 HS able to walk without assistance were assessed using a baropodometric walkway (GAITRite®). According to the structure of a model previously validated in pwPD, eight spatiotemporal variables were grouped in three factors: pace/rhythm, variability and asymmetry. The model, created from the combination of three factor scores, proved to outperform the single variables or the factors in discriminating pwPD from HS. When considering the pwPD split into the different Hoehn and Yahr (H&Y) stages, the spatiotemporal variables, factor scores and the model showed that multiple impairments of gait appear at H&Y stage 2.5, with the greatest difference from HS at stage 4. A contrasting behavior was found for the asymmetry variables and factor, which showed differences from the HS already in the early stages of PD. Our findings support the use of factor scores and of the model with respect to the single variables in gait staging in PD.

[The relationship between physical exercise and gut microbiota in the human being: a systematic review]. / Relazione tra esercizio fisico e microbiota intestinale nell'essere umano: revisione sistematica.

BACKGROUND: the relationship between physical exercise and gut microbiota has opened new therapeutic frontiers for many inflammatory diseases. However, there is still a lot of uncertainty about how to administer exercise. OBJECTIVES: to review the literature to bridge this gap and examine the relationship between cardiorespiratory fitness (CRF) and microbiota. DESIGN: systematic review. SETTING AND PARTICIPANTS: studies involving humans who undergoing exercise programmes of any lengths, intensities, and types were included. The research was carried out through PubMed, Scopus, and Web of Science. MAIN OUTCOME MEASURES: the primary outcome was change in gut microbiota composition (α and ß-diversity), while the secondary outcome was the CRF level. RESULTS: the 15 studies included (all with PEDro scale <=5) used aerobic training alone or combined with resistance exercises. In general, exercise has shown positive effects on the microbiota, influencing the faecal count of some bacterial phyla (in particular Bacteroidetes, Firmicutes, and Proteobacteria), with a weak tendency towards proportionality in relation to training duration and intensity. However, the evidence supporting the exercise effects on the gut microbiota and the relationship with CRF are of low quality. CONCLUSIONS: despite the weak evidence in favour of the effects of the practice of physical exercise on the intestinal microbiota, there are still many aspects that need to be explored. In particular, future studies shall have higher quality and methodological rigour, standardize the methods for outcome assessment, and determine type and thresholds of interventions intensity and duration.

Writing with the Eyes: The Effect of Age on Eye-Tracking Performance in Non-Disabled Adults and a Comparison with Bimanual Typing.

Eye-tracking technology is advancing rapidly, becoming cheaper and easier to use and more robust. This has fueled an increase in its implementation for Augmentative and Alternative Communication (AAC). Nowadays, Eye-Tracking Communication Devices (ETCDs) can be an effective aid for people with disabilities and communication problems. However, it is not clear what level of performance is attainable with these devices or how to optimize them for AAC use. The objective of this observational study was to provide data on non-disabled adults' performance with ETCD regarding (a) range of eye-typing ability in terms of speed and errors for different age groups and (b) relationship between ETCD performance and bimanual writing with a conventional PC keyboard and (c) to suggest a method for a correct implementation of ETCD for AAC. Sixty-seven healthy adult volunteers (aged 20-79 years) were asked to type a sample sentence using, first, a commercial ETCD and then a standard PC keyboard; we recorded the typing speed and error rate. We repeated the test 11 times in order to assess performance changes due to learning. Performances differed between young (20-39 years), middle-aged (40-59 years), and elderly (60-79 years) participants. Age had a negative impact on performance: as age increased, typing speed decreased and the error rate increased. There was a clear learning effect, i.e., repetition of the exercise produced an improvement of performance in all subjects. Bimanual and ETCD typing speed showed a linear relationship, with a Pearson's correlation coefficient of 0.73. The assessment of the effect of age on eye-typing performance can be useful to evaluate the effectiveness of man-machine interaction for use of ETCDs for AAC. Based on our findings, we outline a potential method (obviously requiring further verification) for the setup and tuning of ETCDs for AAC in people with disabilities and communication problems.

Insights Into the Mini-BESTest Scoring System: Comparison of 6 Different Structural Models.

OBJECTIVE: The Mini-Balance Evaluation Systems Test (Mini-BESTest) is a balance scale common to clinical practice, but different scoring has been proposed, that is, total score and/or subsections. This study aimed to investigate Mini-BESTest validity by comparing 6 structural models and to establish the best model for discriminating fallers from nonfallers, that is, those who did or did not report at least 2 falls in the 6 months before evaluation. METHODS: In this cross-sectional validation study, data from 709 individuals with idiopathic Parkinson disease (Hoehn and Yahr stages 1-3) were analyzed. Individuals were evaluated with the Mini-BESTest, and fall history was recorded. Construct, convergent, and discriminant validity and reliability of the 6 models were analyzed. The ability of the models to adequately identify individuals with or without a history of falls was tested with receiving operating characteristic curves. RESULTS: Confirmatory factor analysis showed that the unidimensional models and the 4-factor solutions showed the best fit indexes. Conversely, second-order models, which allowed reporting of both total and subsections, did not converge. Most models and factors showed a low convergent validity (average variance extracted values <0.5). Correlations among the anticipatory postural adjustments factor with both the sensory orientation and the dynamic gait factors of multidimensional models were high (r ≥ 0.85). Unidimensional model reliability was good, whereas low values were found in one-half of the subsections. Finally, both unidimensional models showed a large area under the receiving operating characteristic curve (0.81). CONCLUSION: The original unidimensional Mini-BESTest model-with a total score of 28-showed the highest validity and reliability and was best at discriminating fallers from nonfallers. Conversely, its 4 subsections should not be reported separately, because they were highly correlated and had low reliability; therefore, they are not actually capable of measuring different aspects of balance. IMPACT: This study shows that the Mini-BESTest should be used only with the original unidimensional scoring system in people with Parkinson disease.

Psychological functioning in survivors of COVID-19: Evidence from recognition of fearful facial expressions.

Evidence about the psychological functioning in individuals who survived the COVID-19 infectious is still rare in the literature. In this paper, we investigated fearful facial expressions recognition, as a behavioural means to assess psychological functioning. From May 15th, 2020 to January 30th, 2021, we enrolled sixty Italian individuals admitted in multiple Italian COVID-19 post-intensive care units. The detection and recognition of fearful facial expressions were assessed through an experimental task grounded on an attentional mechanism (i.e., the redundant target effect). According to the results, our participants showed an altered behaviour in detecting and recognizing fearful expressions. Specifically, their performance was in disagreement with the expected behavioural effect. Our study suggested altered processing of fearful expressions in individuals who survived the COVID-19 infectious. Such a difficulty might represent a crucial sign of psychological distress and it should be addressed in tailored psychological interventions in rehabilitative settings and after discharge.

Does the type of hip fracture affect functional recovery in elderly patients undergoing inpatient rehabilitation?

BACKGROUND: Hip fractures should not be considered as a single, homogeneous condition. Various determinants of functional recovery of patients with hip fracture have been proposed, such as age or type of fracture. The aim of this study was to determine if patients with an intertrochanteric fracture (ITF) had lower functional recovery characteristics with respect to those with a femoral neck fracture (FNF). METHODS: A retrospective study was carried out on 531 elderly patients with hip fracture, surgically treated, admitted to a rehabilitation institute between December 1, 2014, and December 31, 2017. Patients underwent an individualized rehabilitation program for improving their physical function. The outcome measures of this study were the length of stay (LOS) in the rehabilitation institute, the Functional Independence Measure (FIM) gain, i.e. the difference in FIM score between discharge and admission, and the FIM efficiency, which represents the daily gain. Patients were also stratified by age categories and by different levels of functional independence, as evaluated with the FIM total score at baseline. RESULTS: Age (p<0.05), LOS (p<0.005) and rehabilitation outcomes (FIM score and efficiency; p<0.05) differed significantly between patients with FNF and ITF. In particular, patients with ITF were older and more dependent at baseline. Moreover, they showed a lower FIM efficiency with respect to patients with FNF (p<0.05), which obtained a similar improvement in FIM total score of about 26 points but were discharged on average 3 days before. With aging, FIM efficiency decreased, while LOS increased. Patients highly dependent at baseline (FIM total score <40) had the lowest FIM gain and efficiency and the longest LOS respect to the more independent patients. Moreover, in older (85+ years) and in higher dependent patients the differences in the outcome measures between ITF and FNF were reduced. CONCLUSIONS: The type of hip fracture could affect the LOS and FIM efficiency of younger and more independent patients with hip fracture during inpatient rehabilitation. In particular, patients with ITF require a longer rehabilitation period to achieve a similar functional gain as those with FNF.

Characterization and Functional Analysis of CD44v6.CAR T Cells Endowed with a New Low-Affinity Nerve Growth Factor Receptor-Based Spacer.

Effectiveness of adoptively transferred chimeric antigen receptor (CAR) T cells strongly depends on the quality of CAR-mediated interaction of the effector cells with the target antigen on tumor cells. A major role in this interaction is played by the affinity of the single-chain variable fragment (scFv) for the antigen, and by the CAR design. In particular, the spacer domain may impact on the CAR T cell function by affecting the length and flexibility of the resulting CAR. This study addresses the need to improve the manufacturing process and the antitumor activity of CD44v6-specific CAR T cells by defining the optimal structure of a spacer region derived from the extracellular domain of the human low-affinity nerve growth factor receptor (LNGFR). We tailored the LNGFR spacer to modulate CAR length to efficiently recognize distal or proximal epitopes and to allow selection of transduced CAR T cells by the use of clinical-grade validated manufacturing systems. The different LNGFR spacers investigated in this study are responsible for the generation of CAR T cells with a different memory phenotype, which is mainly related to the level of CAR expression and the extent of the associated tonic signaling. In particular, the CD44v6-NWN2.CAR T cells are enriched in central memory cells and show improved in vitro functions in terms of killing capability, and in vivo antitumor activity against hematological and solid tumors. Clinical Trial Registration numbers: clinicaltrial.gov NCT04097301; ClinicalTrials.gov, NCT00423124.

Addition of aerobic training to conventional rehabilitation after hip fracture: a randomized, controlled, pilot feasibility study.

OBJECTIVES: To determine the feasibility and safety of aerobic training with an arm crank ergometer and its effectiveness in improving functional capacity and gait in patients with recent hip fracture. DESIGN: Randomized, controlled, assessor-blinded pilot study, with intention-to-treat analysis. SETTING: Inpatients, rehabilitation department. SUBJECTS: 40 patients with hip fracture surgically treated. INTERVENTIONS: Training group performed aerobic exercise with an arm crank ergometer (15 sessions, 30 minutes/day) at an intensity of 64% to 76% of maximum heart rate, in addition to conventional inpatient rehabilitation. MAIN MEASURES: Primary outcome was the feasibility (including eligibility rate, recruitment rate, number of drop-outs and adverse events, adherence). Secondary measures were the Timed Up and Go test, ability to walk independently, muscle torque of knee extensors of fractured and non-fractured leg, Functional Independence Measure. RESULTS: Mostly due to pre-existing disability and fracture type, only 40/301 (13%) patients were eligible (age 84.6 ± 7.6 years, 75% female); all agreed to participate and 90% completed the trial, without adverse events. Adherence to aerobic exercise was good, with high attendance at sessions (93%), a strong compliance to exercise duration (95%) but lower compliance to the prescribed intensity (73%). After the program, more patients were able to walk independently in the training group (n = 18) compared to control (n = 13) (P < 0.05). Also the muscle torque of fractured leg knee extensors was higher in the training group (P < 0.05). CONCLUSION: Aerobic training in addition to conventional rehabilitation after a hip fracture is feasible and safe and it was effective in improving gait performance and strength of fractured leg. TRIAL REGISTRATION: NCT04025866.

Relationship between work fatigue and manual dexterity in dental professionals: observational study.

BACKGROUND: Neuro-muscular fatigue (ANM) in the upper limbs can cause impaired coordination and dexterity. The main purpose of the study was to investigate whether ANM induced by a working day produced a reduction in digital dexterity in a population of dental health workers (OSD). Secondary objective was to investigate whether there were relationships between any reductions in dexterity and independent socio-demographic variables (gender, age and profession). METHODS: A cohort of OSD was assessed before and at the end of a working day of at least 7 hours using the Functional Dexterity Test (FDT). The effects of ANM (time), of the tested limb (dominance), and of their interaction on dexterity were investigated using two-way ANOVA. A multiple linear regression model was applied to explore the relationship between dexterity performance and independent variables. RESULTS: A total of 50 OSDs were included. The net time of the FDT at the end of the day was always higher than in the morning. The ANOVA showed a significant difference for time (p <0.001) and side (p <0.001), but an effect from the interaction between the two factors was not identified (p = 0.428). The worsening of manual dexterity appears to be weakly correlated with age on both sides, and with the profession in the dominant limb. CONCLUSION: The ANM appears to have negatively affected the dexterity of both hands in the sample examined. The results of this study may be useful for planning the OSD's work agenda more carefully.