Single center outcomes after temporary mechanical circulatory assist device prior to Heartmate 3 implantation - a retrospective cohort study.

Objectives. Temporary mechanical circulatory support (TMCS) has become a component in the therapeutic strategy for treatment of cardiogenic shock as a bridge-to-decision. TMCS can facilitate recovery of cardiopulmonary function, end-organ function, and potentially reduce the surgical risk of left ventricular assist device (LVAD) implantation. Despite the improvements of hemodynamics and end-organ function, post-LVAD operative morbidity might be increased in these high-risk patients. The aim of the study was to compare outcomes after Heartmate 3 (HM3) implantation in patients with and without TMCS prior to HM3 implant. Methods. In this retrospective cohort study of all HM3 patients in the period between November 2015 and October 2021, patients with and without prior TMCS were compared. Patients' demographics, baseline clinical characteristics, laboratory tests, intraoperative variables, postoperative outcomes, and adverse events were collected from patient records. Results. The TMCS group showed an improvement in hemodynamics prior to LVAD implantation. Median TMCS duration was 19.5 (14-26) days. However, the TMCS group were more coagulopathic, had more wound infections, neurological complications, and more patients were on dialysis compared with patient without TMCS prior to HM3 implantation. Survival four years after HM3 implantation was 80 and 82% in the TMCS (N = 22) and non-TMCS group (N = 41), respectively. Conclusion. Patients on TMCS had an acceptable short and long-term survival and comparable to patients receiving HM3 without prior TMCS. However, they had a more complicated postoperative course.

Electrical stimulation enhances sciatic nerve regeneration using a silk-based conductive scaffold beyond traditional nerve guide conduits.

Despite recent advancements in peripheral nerve regeneration, the creation of nerve conduits with chemical and physical cues to enhance glial cell function and support axonal growth remains challenging. This study aimed to assess the impact of electrical stimulation (ES) using a conductive nerve conduit on sciatic nerve regeneration in a rat model with transection injury. The study involved the fabrication of conductive nerve conduits using silk fibroin and Au nanoparticles (AuNPs). Collagen hydrogel loaded with green fluorescent protein (GFP)-positive adipose-derived mesenchymal stem cells (ADSCs) served as the filling for the conduit. Both conductive and non-conductive conduits were applied with and without ES in rat models. Locomotor recovery was assessed using walking track analysis. Histological evaluations were performed using H&E, luxol fast blue staining and immunohistochemistry. Moreover, TEM analysis was conducted to distinguish various ultrastructural aspects of sciatic tissue. In the ES + conductive conduit group, higher S100 (p < 0.0001) and neurofilament (p < 0.001) expression was seen after 6 weeks. Ultrastructural evaluations showed that conductive scaffolds with ES minimized Wallerian degeneration. Furthermore, the conductive conduit with ES group demonstrated significantly increased myelin sheet thickness and decreased G. ratio compared to the autograft. Immunofluorescent images confirmed the presence of GFP-positive ADSCs by the 6th week. Locomotor recovery assessments revealed improved function in the conductive conduit with ES group compared to the control group and groups without ES. These results show that a Silk/AuNPs conduit filled with ADSC-seeded collagen hydrogel can function as a nerve conduit, aiding in the restoration of substantial gaps in the sciatic nerve with ES. Histological and locomotor evaluations indicated that ES had a greater impact on functional recovery compared to using a conductive conduit alone, although the use of conductive conduits did enhance the effects of ES.

Assessing Functional Recovery of Eupneic Diaphragm Activity Following Unilateral Cervical Spinal Cord Injury in Rats.

Following cSCI, activation of the DIAm can be impacted depending on the extent of the injury. The present manuscript describes a unilateral C2 hemisection (C2SH) model of cSCI that disrupts eupneic ipsilateral diaphragm (iDIAm) electromyographic (EMG) activity during breathing in rats. To evaluate recovery of DIAm motor control, the extent of deficit due to C2SH must first be clearly established. By verifying a complete initial loss of iDIAm EMG during breathing, subsequent recovery can be classified as either absent or present, and the extent of recovery can be estimated using the EMG amplitude. Additionally, by measuring the continued absence of iDIAm EMG activity during breathing after the acute spinal shock period following C2SH, the success of the initial C2SH may be validated. Measuring contralateral diaphragm (cDIAm) EMG activity can provide information about the compensatory effects of C2SH, which also reflects neuroplasticity. Moreover, DIAm EMG recordings from awake animals can provide vital physiological information about the motor control of the DIAm after C2SH. This article describes a method for a rigorous, reproducible, and reliable C2SH model of cSCI in rats, which is an excellent platform for studying respiratory neuroplasticity, compensatory cDIAm activity, and therapeutic strategies and pharmaceuticals.

Quantitative pupillometry as a biomarker for prediction of return to play in mild traumatic brain injury: a Military Traumatic Brain Injury Initiative study.

OBJECTIVE: This study aimed to determine the validity of quantitative pupillometry to predict the length of time for return to full activity/duty after a mild traumatic brain injury (mTBI) in a cohort of injured cadets at West Point. METHODS: Each subject received baseline (T0) quantitative pupillometry, in addition to evaluation with the Balance Error Scoring System (BESS), Standardized Assessment of Concussion (SAC), and Sport Concussion Assessment Tool 5th Edition Symptom Survey (SCAT5). Repeat assessments using the same parameters were conducted within 48 hours of injury (T1), at the beginning of progressive return to activity (T2), and at the completion of progressive return to activity protocols (T3). Pupillary metrics were compared on the basis of length of time to return to full play/duty and the clinical scores. RESULTS: The authors' statistical analyses found correlations between pupillometry measures at T1, including end-initial diameter and maximum constriction velocity, with larger change and faster constriction predicting earlier return to play. There was also an association with maximum constriction velocity at baseline (T0), predicting faster return to play. CONCLUSIONS: The authors conclude that that pupillometry may be a valuable tool for assessing time to return to duty from mTBI by providing a measure of baseline resiliency to mTBI and/or autonomic dysfunction in the acute phase after mTBI.

The influence of prior COVID-19 diagnosis on concussion recovery outcomes.

OBJECTIVE: While the clinical presentations of COVID-19 and concussion are not identical, there is a significant overlap in symptomology (e.g., fatigue, headache) and neurological deficits (e.g., cognitive, vestibular). However, limited research has examined the effect of prior COVID-19 diagnosis on concussion outcomes. Therefore, the purpose of this study was to determine if prior diagnosis of COVID-19 influences concussion outcomes, including concussion assessment scores and recovery time, in college-aged individuals. METHODS: A prospective study of college-aged individuals (COVID-19: n = 43, mean age 21.3 [SD 2.5] years; no COVID-19: n = 51, mean age 21.0 [SD 2.5] years) diagnosed with concussion was conducted. Demographics, injury details, the Sport Concussion Assessment Tool 5th Edition (SCAT5), and the Vestibular/Ocular Motor Screening (VOMS) were completed at the acute (within 5 days after concussion) and full medical clearance (FMC) (within 3 days after FMC) visits. Mann-Whitney U-tests determined differences in concussion outcomes between groups. Cox proportional hazards regression models were fitted to assess the relationship between factors associated with concussion symptom resolution and days to FMC, and covariates were selected based on previous literature indicating potential confounds (e.g., female sex, acute symptom severity, preexisting mental health conditions). Hazard ratios with 95% confidence intervals were reported for each predictor variable. RESULTS: No significant differences were found between groups for SCAT5 and VOMS composite and total scores. Significant differences were found between COVID-19 and no-COVID-19 groups in days to symptom resolution (11.5 days vs 8 days, p = 0.021), but not in days to FMC (14 days vs 12 days, p = 0.099). The association between COVID-19 groups and days to clearance was not significant when adjusting for sex, race, history of depression/anxiety, and total number of concussion symptoms at the acute visit [χ2(5) = 8.349, p = 0.138]. However, male sex (HR 2.036, 95% CI 1.033-4.014; p = 0.040) was associated with a quicker time to FMC. CONCLUSIONS: Prior COVID-19 diagnosis did not influence cognitive abilities and vestibular/ocular functioning as measured by the SCAT5 and VOMS postconcussion. While prior COVID-19 diagnosis did result in a significantly longer duration to symptom resolution when compared with individuals who did not have a prior COVID-19 diagnosis, prior COVID-19 did not significantly influence time to FMC by a healthcare provider. Clinicians should consider that individuals with a prior diagnosis of COVID-19 might experience prolonged symptoms postconcussion.

Sport-related concussions in baseball and softball: do mechanisms of injury affect recovery?

OBJECTIVE: Baseball and softball pose unique risks for sport-related concussion (SRC). Although these are not collision sports, concussions in baseball and softball can nonetheless involve high-speed impacts. In a regional, single-institution cohort of baseball and softball athletes who sustained an SRC, the current study sought to 1) describe the mechanisms of injury that led to SRC, and 2) compare initial symptom burden and recovery metrics across mechanisms, including time to return to learn (RTL), time to symptom resolution, and time to return to play (RTP) by mechanism of injury. METHODS: A retrospective cohort study was performed of baseball and softball athletes 12 to 23 years old who sustained an SRC between November 2017 and April 2022. Mechanisms of injury were divided into two categories: 1) contact mechanism (i.e., what initiated contact with the injured player, such as head-to-ball), and 2) player mechanism (i.e., the action the injured player was performing at the time of injury, such as fielding). The recovery outcomes of time to RTL, symptom resolution, and RTP were compared between mechanisms using bivariate analysis and multivariable regression analysis, controlling for sex, age, time to present to concussion clinic, and initial total symptom score. RESULTS: The sample included 58 baseball and softball players (60.3% female, mean age 16.0 ± 1.9 years). Most SRCs (62.1%) occurred during competition. Head-to-ball (50.0%) was the most common contact mechanism, followed by head-to-head/body (31.0%) and head-to-wall/ground/equipment (17.2%). Fielding (63.8%) was the most common player mechanism, followed by drills (20.7%) and running (13.8%). SRCs sustained in practice had significantly longer RTL (median 10.0 [interquartile range (IQR) 3.3-16.3] vs 4.0 [IQR 2.0-8.0] days; U = 421.5, p = 0.031) and symptom resolution (37.0 [IQR 18.0-90.0] vs 14.0 [IQR 7.0-41.0] days; U = 406.5, p = 0.025) compared with SRCs sustained in competition. Multivariable regression analysis revealed that head-to-wall/ground/equipment contact mechanism was associated with longer RTL (ß = 0.30, 95% CI 0.07-0.54, p = 0.013). CONCLUSIONS: The current study found that SRCs in baseball and softball occurred more often in competition than in practice. Head-to-ball and fielding were the most common contact and player mechanisms, respectively. SRCs sustained in practice were associated with longer time to RTL and symptom resolution, and head-to-wall/ground/equipment was associated with longer RTL in multivariable regression analysis. These results provide empirical data to improve concussion safety in baseball/softball.

The association between continuing to play, clinical domains, and recovery outcomes in collegiate athletes following concussion.

OBJECTIVE: Continued play following concussion can lead to worse outcomes and longer recoveries compared with athletes who immediately report. This has been well documented in youth athletes, while less attention has been paid to collegiate athletes despite differences in healthcare access, recovery trajectories, and additional pressures to play. Therefore, the purpose of this study was to determine if continuing to play immediately following a concussion influenced clinical outcomes and recovery time in collegiate athletes. METHODS: A prospective, repeated-measures design was used to compare clinical outcomes and recovery time between collegiate athletes who continued playing (n = 37) and those immediately removed (n = 56) after a concussion. Assessments were conducted within 5 days of the concussion and at full medical clearance (FMC; ± 3 days) using the Sport Concussion Assessment Tool-5th edition (SCAT5), Vestibular/Ocular Motor Screening assessment, and High-Level Mobility Assessment Tool. Mann-Whitney U-tests determined differences in clinical outcomes between groups. Cox proportional hazards regression models examined the relationship between factors associated with days to symptom resolution and days to FMC, and covariates were selected a priori based on previous literature. Hazard ratios with 95% CIs were reported for each predictor variable. RESULTS: Significant differences were found in SCAT5 concentration composite scores (p = 0.010) and SCAT5 delayed recall composite scores (p = 0.045) at the acute visit and near point of convergence average distance (cm; p = 0.005) at the FMC visit between the group who continued to play and those who were immediately removed. There were no differences between groups in days to symptom resolution (10 vs 7 days, p = 0.05) and days to clearance (13 vs 11.50 days, p = 0.13). The association between groups and days to symptom resolution (χ2[4] = 5.052, p = 0.282), and days to clearance (χ2[4] = 3.624, p = 0.459) were not significant when adjusting for covariates. CONCLUSIONS: Collegiate athletes who continued to play following concussion did not exhibit worse clinical outcomes or recovery times compared with athletes who were immediately removed. While the lack of differences found in this study could be supported by prior literature, including improved education, awareness, reporting attitudes, and concussion management at the collegiate level in recent years, the authors believe discrepancies are more likely due to study-specific differences (e.g., sample size, care setting, and timing). Therefore, these findings should not diminish the dangers of continued play and the importance of timely removal after concussion.

Examining for gender differences in return to learn following sport-related concussion in high school student athletes.

OBJECTIVE: Prior studies have investigated associations between gender, symptom resolution, and time to return to play following sport-related concussion (SRC). However, there is a notable gap in research regarding the association between gender and return to learn (RTL) in adolescents. Therefore, this study 1) compared the patterns of RTL between boys and girls who are high school student athletes, and 2) evaluated the possible association between gender and time to RTL after adjusting for covariates. METHODS: A retrospective cohort study of a prospective surveillance program that monitored concussion recovery of athletes in high schools throughout the state of Maine between February 2015 and January 2023 was performed. The primary independent variable was gender, dichotomized as boys and girls. The primary outcome was time to RTL, defined by the number of days for an athlete to return to school without accommodations. Mann-Whitney U-tests were used to compare RTL between the boys and girls. Each athlete's RTL status was dichotomized (i.e., returned vs had not returned) at several time points following injury (i.e., 1, 2, 3, and 4 weeks), and chi-square tests were performed to compare the proportions who achieved RTL between groups. Multivariable linear regression analyses were performed to evaluate the predictive value of gender on RTL. Covariates included age, number of previous concussions, history of learning disability or attention-deficit disorder or attention-deficit/hyperactivity disorder, history of a psychological condition, history of headaches or migraines, initial Sport Concussion Assessment Tool (SCAT3/SCAT5) score, and days to evaluation. RESULTS: Of 895 high school athletes, 488 (54.5%) were boys and 407 (45.5%) were girls. There was no statistically significant difference in median [IQR] days to RTL between genders (6.0 [3.0-11.0] vs 6.0 [3.0-12.0] days; U = 84,365.00, p < 0.375). A greater proportion of boys successfully returned to learn without accommodations by 3 weeks following concussion (93.5% vs 89.4%; χ2 = 4.68, p = 0.030), but no differences were found at 1, 2, or 4 weeks. A multivariable model predicting days to RTL showed that gender was not a significant predictor of RTL (p > 0.05). Longer days to evaluation (ß = 0.10, p = 0.021) and higher initial SCAT3/SCAT5 scores (ß = 0.15, p < 0.001) predicted longer RTL. CONCLUSIONS: In a cohort of high school athletes, RTL did not differ between boys and girls following SRC. Gender was not a significant predictor of RTL. Longer days to evaluation and higher initial symptom scores were associated with longer RTL.

Biofeedback combined with percutaneous electrical pudendal nerve stimulation for the treatment of low anterior rectal resection syndrome: a study protocol for a randomized controlled trial.

BACKGROUND: Low anterior resection syndrome (LARS) is a distressing condition that affects approximately 25-80% of patients following surgery for rectal cancer. LARS is characterized by debilitating bowel dysfunction symptoms, including fecal incontinence, urgent bowel movements, and increased frequency of bowel movements. Although biofeedback therapy has demonstrated effectiveness in improving postoperative rectal control, the research results have not fulfilled expectations. Recent research has highlighted that stimulating the pudendal perineal nerves has a superior impact on enhancing pelvic floor muscle function than biofeedback alone. Hence, this study aims to evaluate the efficacy of a combined approach integrating biofeedback with percutaneous electrical pudendal nerve stimulation (B-PEPNS) in patients with LARS through a randomized controlled trial (RCT). METHODS AND ANALYSIS: In this two-armed multicenter RCT, 242 participants with LARS after rectal surgery will be randomly assigned to undergo B-PEPNS (intervention group) or biofeedback (control group). Over 4 weeks, each participant will undergo 20 treatment sessions. The primary outcome will be the LARS score. The secondary outcomes will be anorectal manometry and pelvic floor muscle electromyography findings and the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal 29 (EORTC QLQ-CR29) scores. Data will be collected at baseline, post-intervention (1 month), and follow-up (6 months). DISCUSSION: We anticipate that this study will contribute further evidence regarding the efficacy of B-PEPNS in alleviating LARS symptoms and enhancing the quality of life for patients following rectal cancer surgery. TRIAL REGISTRATION: Chinese Clincal Trials Register ChiCTR2300078101. Registered 28 November 2023.

Repetitive transcranial magnetic stimulation promotes motor function recovery in mice after spinal cord injury via regulation of the Cx43-autophagy loop.

Spinal cord injury (SCI) is a severe condition with an extremely high disability rate. It is mainly manifested as the loss of motor, sensory and autonomic nerve functions below the injury site. High-frequency transcranial magnetic stimulation, a recently developed neuromodulation method, can increase motor function in mice with spinal cord injury. This study aimed to explore the possible mechanism by which transcranial magnetic stimulation (TMS) restores motor function after SCI. A complete T8 transection model of the spinal cord was established in mice, and the mice were treated daily with 15 Hz high-frequency transcranial magnetic stimulation. The BMS was used to evaluate the motor function of the mice after SCI. Western blotting and immunofluorescence were used to detect the expression of Connexin43 (CX43) and autophagy-related proteins in vivo and in vitro, and correlation analysis was performed to study the relationships among autophagy, CX43 and motor function recovery after SCI in mice. Western blotting was used to observe the effect of magnetic stimulation on the expression of mTOR pathway members. In the control group, the expression of CX43 was significantly decreased, and the expression of microtubule-associated protein 1 A/1b light chain 3 (LC3II) and P62 was significantly increased after 4 weeks of spinal cord transection. After high-frequency magnetic stimulation, the level of CX43 decreased, and the levels of LC3II and P62 increased in primary astrocytes. The BMS of the magnetic stimulation group was greater than that of the control group. High-frequency magnetic stimulation can inhibit the expression of CX43, which negatively regulates autophagic flux. HF-rTMS increased the expression levels of mTOR, p-mTOR and p-S6. Our experiments showed that rTMS can restore hindlimb motor function in mice after spinal cord injury via regulation of the Cx43-autophagy loop and activation of the mTOR signalling pathway.

Effects of ultrasound-guided serratus plane block combined with general anesthesia on postoperative early quality of recovery and analgesia in patients undergoing transapical transcatheter aortic valve implantation surgery: study protocol for a randomized controlled trial.

BACKGROUND: Compared to traditional thoracotomy, transapical transcatheter aortic valve implantation (TAVI) surgery offers reduced trauma and faster recovery, fostering the adoption of enhanced recovery after surgery (ERAS) protocols in cardiac surgery. Despite these advancements, postoperative pain management has received insufficient attention. The potential effects of multi-mode analgesia, including ultrasound-guided serratus anterior plane block (SAPB), on postoperative pain and early quality of recovery have not been widely studied, lacking comprehensive prospective evidence. Therefore, this study aims to investigate the impact of SAPB combined with general anesthesia on early recovery quality and analgesic efficacy in transapical TAVI patients. METHODS: This prospective, randomized controlled study will enroll 70 patients undergoing transapical TAVI, randomly allocated to either the SAPB group or the control group. The primary outcome, assessed using Quality of Recovery-40 (QOR-40) scale, focuses on the quality of recovery at 24 h and 48 h postoperatively. Secondary outcomes include the visual analog scale (VAS) pain scores at rest and during coughing at 6 h, 12 h, 24 h, and 48 h after surgery, frequency of patient-controlled analgesia (PCA) utilization at 24 h and 48 h, opioid consumption at 24 h and 48 h, time and frequency of rescue analgesia and severe pain at 24 h and 48 h, incidence of nausea and vomiting at 48 h after surgery, and dosage of antiemetic drugs. DISCUSSION: The purpose of our study is to evaluate the effects of ultrasound-guided SAPB combined with general anesthesia on postoperative early quality of recovery and analgesia in transapical TAVI patients. The results obtained may provide valuable insight for the implementation of multi-mode analgesia and enhanced ERAS in this specific patient population. TRIAL REGISTRATION: China Clinical Trial Register ChiCTR2300068584. Registered on 24 February 2023.

Integrating hydrogels manipulate ECM deposition after spinal cord injury for specific neural reconnections via neuronal relays.

A bioinspired hydrogel composed of hyaluronic acid-graft-dopamine (HADA) and a designer peptide HGF-(RADA)4-DGDRGDS (HRR) was presented to enhance tissue integration following spinal cord injury (SCI). The HADA/HRR hydrogel manipulated the infiltration of PDGFRß+ cells in a parallel pattern, transforming dense scars into an aligned fibrous substrate that guided axonal regrowth. Further incorporation of NT3 and curcumin promoted axonal regrowth and survival of interneurons at lesion borders, which served as relays for establishing heterogeneous axon connections in a target-specific manner. Notable improvements in motor, sensory, and bladder functions resulted in rats with complete spinal cord transection. The HADA/HRR + NT3/Cur hydrogel promoted V2a neuron accumulation in ventral spinal cord, facilitating the recovery of locomotor function. Meanwhile, the establishment of heterogeneous neural connections across the hemisected lesion of canines was documented in a target-specific manner via neuronal relays, significantly improving motor functions. Therefore, biomaterials can inspire beneficial biological activities for SCI repair.

Visual restoration with KPro after face allotransplantation with a grade III phthisical eye.

The Boston Keratoprosthesis type I (KPro-I) has been shown to be successful in restoring vision after severe ocular burns; however, its long-term outcomes in phthisical eyes have rarely been reported. A monocular woman with a history of severe alkali chemical injury necessitating facial transplantation presented with a light perception left eye after a complicated course, including failed KPro-I, therapeutic penetrating keratoplasty, endophthalmitis, hypotony, total retinal detachment, and structural changes, including a shrunken 18 mm axial length and eye wall thickening. The patient underwent a combined vitrectomy with silicone oil and KPro-I implantation, resulting in her regaining ambulatory visual acuity (20/250) at 3 years' follow-up.

Time to surgical management of distal radius fractures: effects on health care utilization and functional outcomes.

BACKGROUND: Distal radius fractures are common injuries. Open reduction and internal fixation with volar locking plates is the most common approach for surgical fixation. This study investigated the association between time to surgery and health care utilization, income, and functional outcomes among patients undergoing open reduction and internal fixation for distal radius fracture. METHODS: We conducted a retrospective review of patients who underwent open reduction and internal fixation for isolated acute distal radius fracture between 2009 and 2019. Time to surgery was grouped as early (≤ 14 d) and delayed (> 14 d). We performed χ2 (or Fisher exact) and Wilcoxon rank sum (or Kruskal-Wallis) tests to provide statistical comparison of time to surgery by health care utilization and functional outcomes. Univariable and multivariable logistic regression analyses were performed to identify factors significantly associated with time to surgery. We included all significant univariables in the multivariable logistic regression model, which identified factors based on significant adjusted odds ratios (95% confidence intervals excluding the null) after we adjusted for confounding variables. RESULTS: We included 106 patients, with 36 (34.0%) in the group receiving early treatment and 70 (66.0%) in the group receiving delayed treatment. Patients in the delayed-treatment group attended significantly more clinic visits and postoperative hand therapy sessions. The group with delayed treatment demonstrated significantly lower degrees of wrist flexion at the first follow-up, but this difference did not persist. Patients with higher estimated income (> $39 405 per annum) had lower odds of delayed surgery than those with lower estimated income (≤ $39 405). CONCLUSION: Delayed time to surgery was associated with greater health care utilization and lower degrees of early wrist flexion. Access to care for lower-income patients warrants further evaluation.

Loss of miR-145 promotes remyelination and functional recovery in a model of chronic central demyelination.

Strategies for treating progressive multiple sclerosis (MS) remain limited. Here, we found that miR-145-5p is overabundant uniquely in chronic lesion tissues from secondary progressive MS patients. We induced both acute and chronic demyelination in miR-145 knockout mice to determine its contributions to remyelination failure. Following acute demyelination, no advantage to miR-145 loss could be detected. However, after chronic demyelination, animals with miR-145 loss demonstrated increased remyelination and functional recovery, coincident with altered presence of astrocytes and microglia within the corpus callosum relative to wild-type animals. This improved response in miR-145 knockout animals coincided with a pathological upregulation of miR-145-5p in wild-type animals with chronic cuprizone exposure, paralleling human chronic lesions. Furthermore, miR-145 overexpression specifically in oligodendrocytes (OLs) severely stunted differentiation and negatively impacted survival. RNAseq analysis showed altered transcriptome in these cells with downregulated major pathways involved in myelination. Our data suggest that pathological accumulation of miR-145-5p is a distinctive feature of chronic demyelination and is strongly implicated in the failure of remyelination, possibly due to the inhibition of OL differentiation together with alterations in other glial cells. This is mirrored in chronic MS lesions, and thus miR-145-5p serves as a potential relevant therapeutic target in progressive forms of MS.

The effect of robot-assisted versus standard training on motor function following subacute rehabilitation after ischemic stroke - protocol for a randomised controlled trial nested in a prospective cohort (RoboRehab).

BACKGROUND: Body weight unloaded treadmill training has shown limited efficacy in further improving functional capacity after subacute rehabilitation of ischemic stroke patients. Dynamic robot assisted bodyweight unloading is a novel technology that may provide superior training stimuli and continued functional improvements in individuals with residual impairments in the chronic phase after the ischemic insult. The aim of the present study is to investigate the effect of dynamic robot-assisted versus standard training, initiated 6 months post-stroke, on motor function, physical function, fatigue, and quality of life in stroke-affected individuals still suffering from moderate-to-severe disabilities after subacute rehabilitation. METHODS: Stroke-affected individuals with moderate to severe disabilities will be recruited into a prospective cohort with measurements at 3-, 6-, 12- and 18-months post-stroke. A randomised controlled trial (RCT) will be nested in the prospective cohort with measurements pre-intervention (Pre), post-intervention (Post) and at follow-up 6 months following post-intervention testing. The present RCT will be conducted as a multicentre parallel-group superiority of intervention study with assessor-blinding and a stratified block randomisation design. Following pre-intervention testing, participants in the RCT study will be randomised into robot-assisted training (intervention) or standard training (active control). Participants in both groups will train 1:1 with a physiotherapist two times a week for 6 months (groups are matched for time allocated to training). The primary outcome is the between-group difference in change score of Fugl-Meyer Lower Extremity Assessment from pre-post intervention on the intention-to-treat population. A per-protocol analysis will be conducted analysing the differences in change scores of the participants demonstrating acceptable adherence. A priori sample size calculation allowing the detection of the minimally clinically important between-group difference of 6 points in the primary outcome (standard deviation 6 point, α = 5% and ß = 80%) resulted in 34 study participants. Allowing for dropout the study will include 40 participants in total. DISCUSSION: For stroke-affected individuals still suffering from moderate to severe disabilities following subacute standard rehabilitation, training interventions based on dynamic robot-assisted body weight unloading may facilitate an appropriate intensity, volume and task-specificity in training leading to superior functional recovery compared to training without the use of body weight unloading. TRIAL REGISTRATION: ClinicalTrials.gov. NCT06273475. TRIAL STATUS: Recruiting. Trial identifier: NCT06273475. Registry name: ClinicalTrials.gov. Date of registration on ClinicalTrials.gov: 22/02/2024.

PEMOCS: Evaluating the effects of a concept-guided, PErsonalised, MOtor-Cognitive exergame training on cognitive functions and gait in chronic Stroke-study protocol for a randomised controlled trial.

BACKGROUND: Many stroke survivors remain with residual cognitive and motor impairments despite receiving timely acute and sub-acute rehabilitation. This indicates that rehabilitation following stroke should be continuous to meet the needs of individual stroke patients. Both cognitive and motor functions are essential for mastering daily life and, therefore, should be aimed at with rehabilitation. Exergames, motor-cognitive exercises performed using video games, are an auspicious method to train both motor and cognitive functions and at the same time may foster the long-term motivation for training. This study aims to assess the effect of concept-guided, personalised, motor-cognitive exergame training on cognitive and motor functions in chronic stroke survivors. METHODS: This study is a single-blinded, randomised controlled trial. Assessments are performed at baseline, after a 12-week intervention, and at a 24-weeks follow-up. Chronic stroke patients (≥ 18 years old, ≥ 6 months post-stroke) able to stand for 3 min, independently walk 10 m, follow a two-stage command, and without other neurological diseases apart from cognitive deficits or dementia are included. Participants in the intervention group perform the exergame training twice per week for 30 (beginning) up to 40 (end) minutes additionally to their usual care programme. Participants in the control group receive usual care without additional intervention(s). Global cognitive functioning (total Montreal Cognitive Assessment (MoCA) score) is the primary outcome. Secondary outcomes include health-related quality of life, specific cognitive functions, single- and dual-task mobility, and spatiotemporal gait parameters. The target sample size for this trial is 38 participants. Linear mixed models with the post-outcome scores as dependent variables and group and time as fixed effects will be performed for analysis. DISCUSSION: Superior improvements in global cognitive functioning and in the abovementioned secondary outcomes in the intervention group compared to the control group are hypothesised. The results of this study may guide future design of long-term rehabilitation interventions after stroke. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05524727). Registered on September 1, 2022.

Risk factors for poor neurological recovery after anterior cervical discectomy and fusion: imaging characteristics.

BACKGROUND: Poor neurological recovery in patients after anterior cervical discectomy and fusion has been frequently reported; however, no study has analyzed the preoperative imaging characteristics of patients to investigate the factors affecting surgical prognosis. The purpose of this study was to investigate the factors that affect the preoperative imaging characteristics of patients and their influence on poor neurologic recovery after anterior cervical discectomy and fusion. METHODS: We retrospectively analyzed the clinical data of 89 patients who met the criteria for anterior cervical discectomy and fusion for the treatment of single-level cervical spondylotic myelopathy and evaluated the patients' neurological recovery based on the recovery rate of the Japanese Orthopaedic Association (JOA) scores at the time of the final follow-up visit. Patients were categorized into the "good" and "poor" groups based on the JOA recovery rates of ≥ 50% and < 50%, respectively. Clinical information (age, gender, body mass index, duration of symptoms, preoperative JOA score, and JOA score at the final follow-up) and imaging characteristics (cervical kyphosis, cervical instability, ossification of the posterior longitudinal ligament (OPLL), calcification of herniated intervertebral discs, increased signal intensity (ISI) of the spinal cord on T2-weighted imaging (T2WI), and degree of degeneration of the discs adjacent to the fused levels (cranial and caudal) were collected from the patients. Univariate and binary logistic regression analyses were performed to identify risk factors for poor neurologic recovery. RESULTS: The mean age of the patients was 52.56 ± 11.18 years, and the mean follow-up was 26.89 ± 11.14 months. Twenty patients (22.5%) had poor neurological recovery. Univariate analysis showed that significant predictors of poor neurological recovery were age (p = 0.019), concomitant OPLL (p = 0.019), concomitant calcification of herniated intervertebral discs (p = 0.019), ISI of the spinal cord on T2WI (p <0.05), a high grade of degeneration of the discs of the cranial neighboring levels (p <0.05), and a high grade of discs of the caudal neighboring levels (p <0.05). Binary logistic regression analysis showed that ISI of the spinal cord on T2WI (p = 0.001 OR = 24.947) and high degree of degeneration of adjacent discs on the cranial side (p = 0.040 OR = 6.260) were independent risk factors for poor neurological prognosis. CONCLUSION: ISI of the spinal cord on T2WI and high degree of cranial adjacent disc degeneration are independent risk factors for poor neurological recovery after anterior cervical discectomy and fusion. A comprehensive analysis of the patients' preoperative imaging characteristics can help in the development of surgical protocols and the management of patients' surgical expectations.

Guideline-Directed Medical Therapy and Survival After TEER for Secondary Mitral Regurgitation With Right Ventricular Impairment.

BACKGROUND: Right ventricular impairment is common among patients undergoing transcatheter edge-to-edge repair for secondary mitral regurgitation (SMR). Adherence to guideline-directed medical therapy (GDMT) for heart failure is poor in these patients. OBJECTIVES: The aim of this study was to evaluate the impact of GDMT on long-term survival in this patient cohort. METHODS: Within the EuroSMR (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation) international registry, we selected patients with SMR and right ventricular impairment (tricuspid annular plane systolic excursion ≤17 mm and/or echocardiographic right ventricular-to-pulmonary artery coupling <0.40 mm/mm Hg). Titrated guideline-directed medical therapy (GDMTtit) was defined as a coprescription of 3 drug classes with at least one-half of the target dose at the latest follow-up. The primary outcome was all-cause mortality at 6 years. RESULTS: Among 1,213 patients with SMR and right ventricular impairment, 852 had complete data on medical therapy. The 123 patients who were on GDMTtit showed a significantly higher long-term survival vs the 729 patients not on GDMTtit (61.8% vs 36.0%; P < 0.00001). Propensity score-matched analysis confirmed a significant association between GDMTtit and higher survival (61.0% vs 43.1%; P = 0.018). GDMTtit was an independent predictor of all-cause mortality (HR: 0.61; 95% CI: 0.39-0.93; P = 0.02 for patients on GDMTtit vs those not on GDMTtit). Its association with better outcomes was confirmed among all subgroups analyzed. CONCLUSIONS: In patients with right ventricular impairment undergoing transcatheter edge-to-edge repair for SMR, titration of GDMT to at least one-half of the target dose is associated with a 40% lower risk of all-cause death up to 6 years and should be pursued independent of comorbidities.