Factors associated with adherence to noninvasive positive pressure ventilation in amyotrophic lateral sclerosis.

INTRODUCTION: This cohort study aimed to investigate the factors associated with noninvasive positive pressure ventilation adherence and assess the long-term effects of noninvasive positive pressure ventilation adherence in patients with amyotrophic lateral sclerosis (ALS). METHODS: The medical records of patients with ALS admitted to a tertiary hospital for noninvasive positive pressure ventilation initiation were retrospectively reviewed. Pulmonary function parameters, variables of blood gas analysis, the site of symptom onset, the time from onset and diagnosis to noninvasive positive pressure ventilation application, ALS Functional Rating Scale-Revised, neurophysiological index, and the length of hospital stay were evaluated. The adherence to noninvasive positive pressure ventilation was defined as the use of noninvasive positive pressure ventilation for ≥ 2 h/day or ≥ 4 h/day. The correlations between noninvasive positive pressure ventilation adherence or length of hospital stay and other clinical parameters were analyzed. RESULTS: Fifty-one patients with ALS were included in the study. The time from onset and diagnosis to NIPPV application was reduced by 16 months in the adherent group than that in the non-adherent group; however, the parameters of blood gas analysis and pulmonary function tests did not differ significantly between the groups. Furthermore, the neurophysiological index of the abductor digiti minimi muscle was higher by 4.05 in the adherent group than that in the non-adherent group. The adherence to noninvasive positive pressure ventilation prolonged tracheostomy-free survival compared to that of non-adherence. Desaturation events, lower forced vital capacity, last pCO2, bicarbonate, and base excess, and higher differences in pCO2, were associated with an increase in the length of hospital stay. CONCLUSIONS: Noninvasive positive pressure ventilation application shortly after symptom onset and ALS diagnosis in patients with CO2 retention and reduced forced vital capacity can be considered for successful adherence. Adherence to noninvasive positive pressure ventilation may result in reduced tracheostomy conversion rates and prolonged tracheostomy-free survival.

Factors affecting upper limb functional recovery after mastectomy with immediate breast reconstruction: a prospective study.

BACKGROUND: Little is known about the differences in postoperative shoulder function following two common approaches for immediate breast reconstruction (IBR): abdominal-based breast reconstruction and implant-based breast reconstruction (ABR and IMBR). It was hypothesized that postoperative upper limb function would differ between the ABR and IMBR due to incomplete detachment of the pectoral muscles. PURPOSE: This study aimed to investigate the factors for shoulder function recovery post-IBR and compare recovery outcomes between ABR and IMBR. METHODS: This single-center prospective follow-up study included 60 patients who underwent IBR for 4 months postoperatively. Patients were invited to complete functional measurements 1 and 4 months postoperatively. The primary outcome was improvement in upper limb disability based on the Q-DASH score. Secondary outcomes were functional shoulder recovery markers: shoulder flexibility, strength, movement accuracy, scapular alignment, body schema accuracy, and neuropathic pain. Repeated-measures analyzes of variance and linear regression were performed. RESULTS: Within-group differences were found for most variables (p < .05) except for neuropathic pain (p = .929). However, there was no overall main group effect (p > .05). Multivariate regression analysis established significant models for ABR and IMBR (R2 = 0.430, p = .002 and R2 = 0.442, p < .001, respectively). However, the variables included in the model showed between-group differences. CONCLUSION: Postoperative shoulder function was comparable between the two IBR approaches. However, different factors were associated with improved upper limb disability between ABR and IMBR. Acute rehabilitation focused on resolving muscle tightness and pain may help mitigate upper limb disabilities following IBR.Trial registration number: KCT 0006501.

Rejuvenating aged microglia by p16ink4a-siRNA-loaded nanoparticles increases amyloid-ß clearance in animal models of Alzheimer's disease.

Age-dependent accumulation of amyloid plaques in patients with sporadic Alzheimer's disease (AD) is associated with reduced amyloid clearance. Older microglia have a reduced ability to phagocytose amyloid, so phagocytosis of amyloid plaques by microglia could be regulated to prevent amyloid accumulation. Furthermore, considering the aging-related disruption of cell cycle machinery in old microglia, we hypothesize that regulating their cell cycle could rejuvenate them and enhance their ability to promote more efficient amyloid clearance. First, we used gene ontology analysis of microglia from young and old mice to identify differential expression of cyclin-dependent kinase inhibitor 2A (p16ink4a), a cell cycle factor related to aging. We found that p16ink4a expression was increased in microglia near amyloid plaques in brain tissue from patients with AD and 5XFAD mice, a model of AD. In BV2 microglia, small interfering RNA (siRNA)-mediated p16ink4a downregulation transformed microglia with enhanced amyloid phagocytic capacity through regulated the cell cycle and increased cell proliferation. To regulate microglial phagocytosis by gene transduction, we used poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles, which predominantly target microglia, to deliver the siRNA and to control microglial reactivity. Nanoparticle-based delivery of p16ink4a siRNA reduced amyloid plaque formation and the number of aged microglia surrounding the plaque and reversed learning deterioration and spatial memory deficits. We propose that downregulation of p16ink4a in microglia is a promising strategy for the treatment of Alzheimer's disease.

Long-term effects of lumbar flexion versus extension exercises for chronic axial low back pain: a randomized controlled trial.

This study aimed to compare the long-term effects of flexion- and extension-based lumbar exercises on chronic axial low back pain (LBP). This was a 1-year follow-up of a prospective, assessor-blind, randomized controlled trial. Patients with axial LBP (intensity ≥ 5/10) for > 6 months allocated to the flexion or extension exercise group. Patients underwent four sessions of a supervised treatment program and were required to perform their assigned exercises daily at home. Clinical outcomes were obtained at baseline, 1, 3, 6 months, and 1-year. A total of 56 patients (age, 54.3 years) were included, with 27 and 29 in the flexion and extension groups, respectively. Baseline pain and functional scales were similar between both groups. The mean (± standard deviation) baseline average back pain was 6.00 ± 1.00 and 5.83 ± 1.20 in the flexion and extension groups, respectively. At 1-year, the average pain was 3.78 ± 1.40 and 2.26 ± 2.62 (mean between-group difference, 1.52; 95% confidence interval 0.56-2.47; p = 0.002), favoring extension exercise. The extension group tended to have more improvements in current pain, least pain, and pain interference than the flexion group at 1-year. However, there was no group difference in worst pain and functional scales. In this controlled trial involving patients with chronic axial LBP, extension-based lumbar exercise was more effective in reducing pain than flexion-based exercises at 1-year, advocating lumbar extension movement pattern as a component for therapeutic exercise for chronic LBP.Clinical Trial Registration No.: NCT02938689 (Registered on www.clinicaltrial.gov ; first registration date was 19/10/2016).

Evaluating the Surgical Outcome of Lymphovenous Anastomosis in Breast Cancer-Related Lymphedema Using Tc-99m Phytate Lymphoscintigraphy: Preliminary Results.

Background: Breast cancer-related lymphedema (BCRL) remains a significant postcancer treatment challenge with no definitive cure. Recent supermicrosurgical treatments, such as lymphovenous anastomosis (LVA), have shown promise but lack established objective indicators for outcome evaluation. We investigated the utility of Technetium-99m (Tc-99m) lymphoscintigraphy, an imaging technique providing objective information on lymphatic fluid flow, for assessing LVA surgical outcomes. Methods and Results: A retrospective cohort analysis of patients undergoing LVA for BCRL was conducted. Lymphoscintigraphy images pre- and 1-year postsurgery were compared to determine changes in lymphatic fluid flow of 18 patients based on newly defined parameters "uptake ratio" and "washout rates." Statistically significant reduction in the uptake ratio was observed in the forearm at 30 and 60 minutes postinjection phases. In addition, the forearm showed higher washout rate, indicating an improved lymphatic function in the forearm. Conclusion: Tc-99m lymphoscintigraphy can provide valuable objective data for evaluating LVA surgical outcomes in BCRL patients. However, site-specific differences in outcomes highlight the need for individualized surgical planning. Further large-scale studies are necessary to validate these preliminary findings and develop a standardized approach for LVA assessment.

Peptide-mediated targeted delivery of SOX9 nanoparticles into astrocytes ameliorates ischemic brain injury.

Astrocytes are highly activated following brain injuries, and their activation influences neuronal survival. Additionally, SOX9 expression is known to increase in reactive astrocytes. However, the role of SOX9 in activated astrocytes following ischemic brain damage has not been clearly elucidated yet. Therefore, in the present study, we investigated the role of SOX9 in reactive astrocytes using a poly-lactic-co-glycolic acid (PLGA) nanoparticle plasmid delivery system in a photothrombotic stroke animal model. We designed PLGA nanoparticles to exclusively enhance SOX9 gene expression in glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes. Our observations indicate that PLGA nanoparticles encapsulated with GFAP:SOX9:tdTOM reduce ischemia-induced neurological deficits and infarct volume through the prostaglandin D2 pathway. Thus, the astrocyte-targeting PLGA nanoparticle plasmid delivery system provides a potential opportunity for stroke treatment. Since the only effective treatment currently available is reinstating the blood supply, cell-specific gene therapy using PLGA nanoparticles will open a new therapeutic paradigm for brain injury patients in the future.

Application of 3D scanner to measure physical size and improvement of hip brace manufacturing technology in severe cerebral palsy patients.

This prospective pilot study aimed to develop a personalized hip brace for treating hip subluxation in children with cerebral palsy. Nineteen children, aged 1-15, with severe cerebral palsy participated in the study. Customized hip braces were created based on 3D scanner measurements and worn for 7 days. The primary outcome, Hip Migration Index (MI), and secondary outcomes, including range of motion (ROM) in the hip and knee joints, pain intensity, satisfaction, discomfort scores, CPCHILD, and wearability test, were assessed. The MI and ROM were assessed at screening and at Visit 1 (when the new hip brace was first worn), while other indicators were evaluated at screening, Visit 1, and Visit 2 (7 days after wearing the new hip brace). The study demonstrated significant improvements in the MI for the right hip, left hip, and both sides. However, there were no statistically significant differences in hip and knee joint ROM. Other indicators showed significant changes between screening, Visit 1, and Visit 2. The study suggests that customized hip braces effectively achieved immediate correction, positively impacting the quality of life and satisfaction in children with cerebral palsy. Furthermore, the hip braces have the potential to enhance compliance and prevent hip subluxation.Clinical Trial Registration number: NCT05388422.

Effects of hip brace on coxa valga in nonambulatory children with cerebral palsy: A randomized controlled trial.

BACKGROUND: Coxa valga, measured as the neck-shaft angle (NSA) or head-shaft angle (HSA), is regarded as a potential risk factor for hip dislocation in patients with cerebral palsy. We investigated the effects of a novel hip brace on coxa valga. METHODS: A prospective, multicenter, assessor-blinded, randomized controlled trial was conducted from July 2019 to November 2021. Children with cerebral palsy aged 1 to 10 years with Gross Motor Function Classification System levels IV and V were recruited. The study group wore a hip brace for at least 12 hour a day. A lower strap of the hip brace was designed to prevent coxa valga biomechanically. The effectiveness of the hip brace on coxa valga was assessed by measurement of the NSA and head-shaft angle at enrollment and 6 and 12 months after enrollment. RESULTS: Sixty-six participants were enrolled, and 33 patients were assigned to each group. Changes in the mean NSA of both sides and the NSA of left side showed significant differences between the 2 groups over 12 months (mean NSA of both sides, -1.12 ± 3.64 in the study group and 1.43 ± 3.75 in the control group, P = .023; NSA of the left side, -1.72 ± 5.38 in the study group and 2.01 ± 5.22 in the control group, P = .008). CONCLUSIONS: The hip brace was effective in preventing the progression of coxa valga and hip displacement, suggesting that the prevention of coxa valga using hip brace is a contributing factor in prevention of hip displacement.

Outcome Analysis of Combined Surgical Approaches in Advanced-stage Upper Extremity Breast Cancer-related Lymphedema.

Background: This study aimed to discuss several surgical approaches for advanced-stage breast cancer-related lymphedema and compared their treatment outcomes. Methods: The patients who underwent surgery with International Society of Lymphology stage III lymphedema were included in this study. The three surgical methods used here were (1) suction-assisted lipectomy with lymphovenous anastomosis, (2) autologous breast reconstruction with muscle-sparing transverse rectus abdominis muscle flap combined with inguinal lymph node transfer, and (3) vascularized lymph node transfer with free omental flap. Analysis of the postoperative outcomes in the patients was based on the difference in volume between patients pre- and postoperatively, LYMPH-Q questionnaire, and bioelectrical impedance analysis. Results: Eighty-seven patients with stage IIb or higher disease underwent surgery. 38 patients underwent suction-assisted lipectomy + lymphovenous anastomosis, 23 underwent autologous breast reconstruction with vascularized lymph node transfer + lymphovenous anastomosis, and 26 underwent right gastroepiploic omental vascularized lymph node transfer with lymphovenous anastomosis. The LYMPH-Q questionnaire, which evaluates patients' subjective satisfaction, showed that the autologous breast reconstruction group showed the greatest improvement, whereas in bioimpedance analysis, the omental flap group demonstrated the greatest postoperative improvement compared with preoperative values. However, suction-assisted lipectomy was considered the most effective surgical method for reducing limb volume in patients with high-stage lymphedema accompanied by fibrosis and volume increase. Conclusions: We observed slightly different clinical effects for each surgical method; however, all surgical methods demonstrated a reduction in the degree of edema and an increase in patient satisfaction.

Utilization of Noncontrast Magnetic Resonance Lymphangiography for Selection of Effective Surgical Method in Breast Cancer-Related Lymphedema.

Background and Objectives: When considering surgery for patients with breast cancer-related lymphedema (BCRL), it is crucial to determine which surgery will be most effective for the patient and establish the indications for each surgery. Our study retrospectively compared the results of preoperative noncontrast MR lymphangiography (NMRL) performed on the lymphedematous limb of patients before surgery, with the aim of analyzing whether preoperative NMRL can be used as a criterion for determining the type of surgery. Materials and Methods: From January 2020 to June 2022, a total of 138 patients with lymphedema underwent surgery at Seoul National University Bundang Hospital. All patients underwent preoperative NMRL imaging and were classified into stages 1-3 based on the MRI severity index using the authors' previous reference. Three types of surgery, LVA, LVA + liposuction, and LVA + VLNT, were conducted on all patients. The effectiveness of the surgery was evaluated one year postoperatively using the interlimb volume difference before and after surgery, the fluid volume of the edematous limb measured by bioimpedance spectroscopy, and the subjective satisfaction of the patients through the Lymph Q questionnaire. Results: In this study, out of a total of 138 patients, 26 (19%) were MRI stage 1, 62 (45%) were stage 2, and 50 (36%) were stage 3. Of the 83 patients who underwent LVA surgery, the greatest decrease in interlimb volume difference was observed in stage 2 patients, and subjective satisfaction was also the most effective in stage 2. In the case of LVA + liposuction patients, a significant volume decrease and a high satisfaction were observed in stage 3 patients. In the case of LVA + VLNT patients, there was no difference in volume decrease according to the stage, but a greater decrease in body fluid volume was observed as the MRI severity index score increased through BIA. Conclusions: In conclusion, this study demonstrates that NMRL imaging is a useful modality for determining the most effective surgical method and predicting the surgical outcome in patients with lymphedema. This highlights the importance of using NMRL in the treatment planning of lymphedema patients.

Effectiveness and clinical application of multidisciplinary combined exercise and nutrition intervention for sarcopenic older adults with metabolic syndrome: study protocol for a multicentre randomised controlled trial.

INTRODUCTION: Among chronic diseases affecting older adults, metabolic syndrome (MetS) is known to be closely related to sarcopenia. Insulin resistance may play a key role in the increased frequency of sarcopenia associated with metabolic disorders. To date, an exercise-nutrition combined intervention has been the treatment of choice for sarcopenia. However, trials of combined interventions for individuals with sarcopenia and MetS are still lacking. This study aims to develop and conduct a standardised intervention, named the Multidisciplinary combined Exercise and Nutrition inTervention fOR Sarcopenia (MENTORS), for sarcopenic older patients with MetS. METHODS AND ANALYSIS: This multicentre, randomised controlled trial includes 168 community-dwelling older adults with sarcopenia and MetS. The 12-week MENTORS comprises an exercise intervention consisting of an introductory phase (3 weeks; twice-weekly visits), an expanded phase (3 weeks; twice-weekly visits) and a maintenance phase (6 weeks; once-weekly visits); and a nutrition intervention tailored to the nutritional status of individual subjects. Outcomes will be measured at 0-week, 12-week and 24-week postintervention. The data will be analysed using the intention-to-treat and per-protocol principle. ETHICS AND DISSEMINATION: Before screening, all participants will be provided with oral and written information. Ethical approval has already been obtained from all participating hospitals. The study results will be disseminated in peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT04948736.

Fracture Liaison Service in Korea: 2022 Position Statement of the Korean Society for Bone and Mineral Research.

Osteoporosis and osteoporotic fractures cause socioeconomic concerns, and medical system and policies appear insufficient to prepare for these issues in Korea, where the older adult population is rapidly increasing. Many countries around the world are already responding to osteoporosis and osteoporotic fractures by adopting fracture liaison service (FLS), and such an attempt has only begun in Korea. In this article, we introduce the operation methods for institutions implementing FLS and characteristics of services, and activities of the FLS Committee for FLS implementation in the Korean Society for Bone and Mineral Research. In addition, we hope that the current position statement will contribute to the implementation of FLS in Korea and impel policy changes to enable a multidisciplinary and integrated FLS operated under the medical system.

Factors predictive of functional outcomes and quality of life in patients with fragility hip fracture: A retrospective cohort study.

To determine the predictors of functional outcomes and quality of life (QoL) of patients who were surgically treated for fragility hip fracture. This was a retrospective cohort study performed in the 3 tertiary rehabilitation facilities. A total of 165 patients who had undergone surgery for fragility hip fracture were followed up to 6 months postoperatively. The factors expected to be related to the functional outcomes and QoL at 6 months post-surgery were as follows: baseline demographics, fracture site, operation type, fall characteristics including fall location and fall direction, comorbidities, and initial functional status. The following were comorbidities: hypertension, diabetes mellitus, dementia, cerebrovascular accident, and osteoporosis. Functional outcome and QoL measures were represented using the Koval grade, functional ambulatory category (FAC), Berg balance scale, 4-m walking speed test, the Korean version of Mini-Mental State Examination, EuroQol 5-dimension (EQ-5D) questionnaire, the Korean version of Modified Barthel Index, and the Korean version of instrumental activities of daily living (K-IADL). For all tests, each patient was assessed immediately after transfer and at 6 months post-surgery. Multivariable regression analyses adjusting for factors mentioned above were as follows. Old age led to a significantly less favorable outcome on FAC and K-IADL at 6 months. Intertrochanteric fracture had a significantly positive impact on Koval at 6 months compared to femur neck and intertrochanteric fractures. Total hip replacement arthroplasty and bipolar hemiarthroplasty had a significantly positive impact on EQ-5D and FAC at 6 months respectively compared to other operation types. Fall characteristics didn't reveal any significant impact on functional outcomes and QoL. Patients with hypertension and diabetes mellitus had a significantly negative outcome on EQ-5D and K-IADL respectively. Among initial assessments of function and QoL, initial 4-m walking speed test, Korean version of Mini-Mental State Examination, K-IADL, and Korean version of Modified Barthel Index were independent predictors of function and QoL at 6 months. This study confirmed that age, fracture site, operation type, comorbidities, and initial physical and cognitive function significantly influenced recovery of function and QoL at 6 months in patients with fragility hip fractures.

Efficacy of a Hip Brace for Hip Displacement in Children With Cerebral Palsy: A Randomized Clinical Trial.

Importance: There is no consensus on interventions to slow the progress of hip displacement in patients with cerebral palsy. Objective: To investigate the efficacy of a novel hip brace in preventing progressive hip displacement in patients with cerebral palsy. Design, Setting, and Participants: This 2-group randomized clinical trial was conducted at 4 tertiary hospitals in South Korea from July 2019 to November 2021. Participants included children aged 1 to 10 years with nonambulatory cerebral palsy (Gross Motor Function Classification System level IV or V). Block randomization was used to assign an equal number of patients to the study and control groups via computerized random allocation sequences. Data were analyzed from November to December 2021. Interventions: The intervention group wore the hip brace for at least 12 hours a day for the study duration (ie, 12 months). Follow-up evaluations were performed after 6 and 12 months of wearing the brace. Both groups proceeded with conventional rehabilitation therapy during the trial. Main Outcomes and Measures: The primary outcome was the Reimers migration index (MI) on radiography, as assessed by 3 blinded investigators. Primary outcome variables were analyzed using linear mixed models. Secondary outcomes include change in the Caregiver Priorities & Child Health Index of Life with Disabilities, on which lower scores indicate better quality of life. Results: A total of 66 patients were included, with 33 patients (mean [SD] age, 68.7 [31.6] months; 25 [75.8%] boys) randomized to the intervention group and 33 patients (mean [SD] age, 60.7 [24.9] months; 20 [60.6%] boys) randomized to the control group. The baseline mean (SD) MI was 37.4% (19.3%) in the intervention group and 30.6% (16.3%) in the control group. The mean difference of the MI between the intervention group and control group was -8.7 (95% CI, -10.2 to -7.1) percentage points at 6 months and -12.7 (95% CI, -14.7 to -10.7) percentage points at 12 months. The changes in the Caregiver Priorities & Child Health Index of Life with Disabilities were favorable in the study group and reached statistical significance at the 6-month follow-up compared with the control group (difference, -14.2; 95% CI, -25.2 to -3.3). Conclusions and Relevance: In this randomized clinical trial, the novel hip brace was significantly effective in preventing the progression of hip displacement, compared with the control group. It effectively improved quality of life in patients with nonambulatory cerebral palsy. Therefore, hip brace use could be a promising treatment method to delay hip surgery and improve the quality of life of patients with nonambulatory cerebral palsy. Trial Registration: ClinicalTrials.gov Identifier: NCT04033289.

Distorted body schema after mastectomy with immediate breast reconstruction: a 4-month follow up study.

Background: After breast cancer, some patients report residual pain-related upper limb disability without physical impairment. Although pain and altered proprioception are known to affect the working body schema (WBS), there is little available evidence investigating the WBS of breast cancer survivors (BrCS). WBS-body representations in the brain-affect the "neuromatrix" that modulates pain sensitivity and the threshold for threatening stimuli. The aim of this study was to investigate whether WBS was disrupted after mastectomy with immediate breast reconstruction (IBR) for breast cancer and whether pain and proprioceptive changes affected WBS. Methods: Thirty-five BrCS participated in the 4-month follow-up study. They were observed at 1 and 4 months postoperatively. The main outcome measures were the left right judgement test (LRJT) results, absolute angle error, pectoralis minor length index (PMI), pain, and Quick-Disabilities of the Arm, Shoulder, and Hand (Q-DASH) score. They were measured at each observation, and parametric tests were performed to identify the nature of WBS. Results: Both the reaction time and accuracy of the hand LRJT were poorer than those of the foot and back LRJT (p < 0.001). The hand LRJT reaction time and accuracy were unchanged over the total follow-up period (p = 0.77 and p = 0.47, respectively). There was a weak correlation between the LRJT reaction time and PMI (r = -0.26, p = 0.07), pain severity (r = 0.37, p = 0.02), and Q-DASH score (r = 0.37, p = 0.02). There was also a weak correlation between LRJT accuracy and Q-DASH score (r = -0.31, p = 0.04). The LRJT accuracy of BrCS who underwent surgery on their dominant side was higher than that of BrCS who underwent surgery on their non-dominant side (p = 0.002). Regression analysis found a weak but significant relationship between the early hand LRJT results and late pain severity (adjusted R2 = 0.179, p = 0.007). A similar relationship was found between early hand LRJT results and Q-DASH score (adjusted R2 = 0.099, p = 0.039). Conclusion: To the best of our knowledge, this is the first study providing the nature of WBS after mastectomy with IBR. In this population, it is necessary to postoperatively preserve WBS integrity for pain and upper limb disability.

Comprehensive Rehabilitation in Severely Ill Inpatients With COVID-19: A Cohort Study in a Tertiary Hospital.

BACKGROUND: This study aimed to investigate the effects of comprehensive rehabilitation management on functional recovery and examine the correlation between clinical parameters and improvements in functional outcomes in severe-to-critical inpatients with coronavirus disease 2019 (COVID-19) in a tertiary hospital. METHODS: Post-acute COVID-19 patients who had a World Health Organization (WHO) ordinal scale of 5-7, underwent intensive care, and received comprehensive rehabilitation management, including exercise programs, nutritional support, dysphagia evaluation, and psychological care were included. The appendicular skeletal muscle mass index (SMI), Medical Research Council sum score, handgrip strength, number of repetitions in the 1-minute sit-to-stand test, gait speed, Berg Balance Scale (BBS), and Functional Ambulation Classification (FAC) were evaluated at hospital stay, discharge, and 1-month follow-up. The correlation between the rehabilitation dose and improvement in each outcome measure was analyzed. RESULTS: Overall, 37 patients were enrolled, of whom 59.5% and 32.4% had a score of 6 and 7 on the WHO ordinal scale, respectively. Lengths of stay in the intensive care unit and hospital were 33.6 ± 23.9 and 63.8 ± 36.5 days. Outcome measures revealed significant improvements at discharge and 1-month follow-up. The SMI was significantly increased at the 1-month follow-up (6.13 [5.24-7.76]) compared with that during the hospital stay (5.80 [5.39-7.05]). We identified dose-response associations between the rehabilitation dose and FAC (ρ = 0.46) and BBS (ρ = 0.50) scores. Patients with older age, longer hospitalization, longer stay at the intensive care unit, longer duration of mechanical ventilation, tracheostomy, a more depressive mood, and poorer nutritional status revealed poorer improvement in gait speed at the 1-month follow-up. CONCLUSION: Comprehensive rehabilitation management effectively improved muscle mass, muscle strength, and physical performance in severe-to-critical COVID-19 patients. Dose-response relationship of rehabilitation and functional improvement emphasizes the importance of intensive post-acute inpatient rehabilitation in COVID-19 survivors. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05104411.

p16INK4a-siRNA nanoparticles attenuate cartilage degeneration in osteoarthritis by inhibiting inflammation in fibroblast-like synoviocytes.

In osteoarthritis (OA), chondrocytes in cartilage undergo phenotypic changes and senescence, restricting cartilage regeneration and favoring disease progression. Although senescence biomarker p16INK4a expression is known to induce aging by halting the cell cycle, therapeutic applications for p16INK4a targeting are limited. Here, we aimed to reduce cartilage damage and alleviate pain using p16INK4a nanoparticles in OA. The p16INK4a expression of human OA chondrocytes and synoviocytes from patients with knee OA was measured and the levels of p16INK4a, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and matrix metalloproteinase (MMP) 13 were examined. p16INK4a siRNA was encapsulated into poly (lactic-co-glycolic acid) (PLGA) nanoparticles and characterized. The partial medial meniscectomy (pMMx) model was performed for the OA model which was investigated by molecular analysis and behavioral tests. The expression of p16INK4a was increased in the synovium and articular cartilage from OA patients. p16INK4a siRNA-loaded PLGA nanoparticles (p16 si_NP) reduced the levels of TNF-α, IL-1ß, and IL-6 especially in fibroblast-like synoviocytes (FLSs), and MMP13 in chondrocytes. Rhodamine-tagged NPs injected into the mouse knee joints were found mainly in the synovium. p16 si_NP injection in the pMMx model alleviated pain-associated behavior, and reduced cartilage damage and p16INK4a in the synovium, and MMP13, collagen X, and NITEGE in cartilage. The preferential reduction of p16INK4a in FLSs by the application of RNAi nanomedicine could contribute to the recovery of osteoarthritic cartilage and relieve pain, suggesting that p16INK4a may be a viable future therapeutic candidate.

Reference Standards for Nerve Conduction Studies of Individual Nerves of Lower Extremity With Expanded Uncertainty in Healthy Korean Adults.

OBJECTIVE: To develop a set of reference standards for tibial motor, common peroneal motor, sural sensory, and superficial peroneal sensory nerve conduction studies (NCSs) with expanded uncertainty in a healthy Korean population. METHODS: Standardized procedures were conducted for individual lower extremity NCSs of 199 healthy participants in their 20s (n=100) and 50s (n=99). Mean values and expanded uncertainties for parameters were analyzed with thorough consideration of multiple uncertainty factors under the International Guide to the Expression of Uncertainty in Measurement. In addition, side-to-side differences in onset latency, amplitude, and nerve conduction velocity (NCV) were analyzed. RESULTS: Mean (reference range) for distal onset latency, baseline to negative peak amplitude, NCV of tibial motor nerve in males in their 20s were 4.3 ms (3.1-5.4 ms), 7.1 mV (3.4-10.9 mV), and 50.7 m/s (42.2-59.3 m/s), respectively; sural sensory nerve baseline to negative peak amplitude in males in their 20s was 21.7 µV (8.3-35.2 µV). Including the aforementioned data, we present a vast dataset of normative mean values and expanded uncertainties for NCSs of the leg in a healthy Korean population. Furthermore, upper limits for normal side-to-side differences for onset latency, amplitude, and NCV of each nerve are suggested. CONCLUSION: To our knowledge, this is the first study to present the reference standards of leg NCSs with consideration for multifactorial uncertainties in an Asian population. We expect these results to help practitioners make reliable and reproducible clinical decisions.

Asymmetrical activation and asymmetrical weakness as two different mechanisms of adolescent idiopathic scoliosis.

There have been many studies on adolescent idiopathic scoliosis related abnormal muscle contractions of the spine. However, previous studies using surface electromyography to investigate paraspinal muscle asymmetry are controversial, lacking in clarity of results, and hindered by methodological limitations. The purpose of this study was to investigate the relationship between imbalance factors including surface electromyography activity according to the scoliosis curve type and leg length discrepancy and adolescent idiopathic scoliosis curve types. Seventy-nine patients with scoliosis were prospectively enrolled and were divided into five types: single thoracic, thoracolumbar, lumbar, double thoracic, and double major. Cobb angle and structural variables were measured. Surface electromyography examinations were conducted at the 7th, 12th thoracic erector spinae, 3rd lumbar erector spinae, and multifidus muscles during the superman position keeping prone spinal extension to lift the arms and legs off the floor. Whole spine radiographs were obtained to measure the Cobb angle, coronal imbalance, pelvic height and angle, and femoral head height. In the double major, thoracolumbar, and lumbar types, the mean root mean squared (RMS) EMG amplitudes were significantly higher on the convex side than the concave side (P < 0.005). In the DM type, the mean RMS EMG amplitudes of EST7 and ESL3 where the apex was located were significantly higher at the convex side than those of the concave side (P < 0.005, effect size (Cohen's d) for EST7/ESL3: 0.517/0.573). The TL and L types showed a similar pattern. The mean RMS EMG amplitudes of the EST12 concave side and MuL3 and ESL3 concave sides were significantly lower than those of the convex side in the TL and L types, respectively (P < 0.008, effect size (Cohen's d) for EST12/MuL3/ESL3: 0.960/0.264/0.448). Conversely, there were no significant differences in the single thoracic and double thoracic types. All structural variables (coronal imbalance, pelvic height and angle, and femur head height) were higher in the lumbar type, but only coronal imbalance was significantly different (P < 0.05). Different patterns of asymmetry of paraspinal muscles and structural variables were described based on the curvature of the spine. L type showed that EMG activity was asymmetric in the paraspinalis muscles where the apex was located and that structural asymmetry, such as coronal imbalance was significantly greater than other types. DM type showed similar paraspinalis asymmetry pattern to the ST type but there was no structural asymmetry in DM and ST types. TL type has the features of both thoracic and lumbar origins. Understanding these could contribute to the management in correcting scoliosis.

Clinical Practice Guideline for Postoperative Rehabilitation in Older Patients With Hip Fractures.

OBJECTIVE: The incidence of hip fractures is increasing worldwide with the aging population, causing a challenge to healthcare systems due to the associated morbidities and high risk of mortality. After hip fractures in frail geriatric patients, existing comorbidities worsen and new complications are prone to occur. Comprehensive rehabilitation is essential for promoting physical function recovery and minimizing complications, which can be achieved through a multidisciplinary approach. Recommendations are required to assist healthcare providers in making decisions on rehabilitation post-surgery. Clinical practice guidelines regarding rehabilitation (physical and occupational therapies) and management of comorbidities/complications in the postoperative phase of hip fractures have not been developed. This guideline aimed to provide evidence-based recommendations for various treatment items required for proper recovery after hip fracture surgeries. METHODS: Reflecting the complex perspectives associated with rehabilitation post-hip surgeries, 15 key questions (KQs) reflecting the complex perspectives associated with post-hip surgery rehabilitation were categorized into four areas: multidisciplinary, rehabilitation, community-care, and comorbidities/complications. Relevant literature from four databases (PubMed, EMBASE, Cochrane Library, and KoreaMed) was searched for articles published up to February 2020. The evidence level and recommended grade were determined according to the grade of recommendation assessment, development, and evaluation method. RESULTS: A multidisciplinary approach, progressive resistance exercises, and balance training are strongly recommended. Early ambulation, weigh-bearing exercises, activities of daily living training, community-level rehabilitation, management of comorbidities/complication prevention, and nutritional support were also suggested. This multidisciplinary approach reduced the total healthcare cost. CONCLUSION: This guideline presents comprehensive recommendations for the rehabilitation of adult patients after hip fracture surgery.