Long-term Functional Impairment Research Articles

Effects of mTBI with loss of consciousness on neurobehavioral symptoms, depression, and insomnia in former collegiate and NFL football athletes

ABSTRACT Objective Considering that diagnostic decisions about mTBI are often predicated on clinical symptom criteria, it is imperative to determine which initial presentation features of mTBI have prognostic significance for identifying those at high risk for long-term functional impairment. Setting Zoom interview Participants: Male, former NCAA Division I, and professional-level National Football League (NFL) athletes (n = 177) between the ages of 27 and 85 (M = 54.1, SD = 14.7). Design Cross-sectional case-control. Main Measures: History of mild TBI, history of loss of consciousness (LOC), depression symptoms, insomnia, neurobehavioral symptoms. Results Number of mTBI exposures did not predict neurobehavioral symptoms (B = 0.21, SE = 0.18, p = 0.23), but number of mTBI + LOC events did (B = 2.27, SE = 0.64, p = <.001). Further analysis revealed that the number of mTBI + LOC events predicted neurobehavioral symptoms indirectly through both depression (B = 0.85, 95% CI = [0.27, 1.52) and insomnia (B = 0.81, 95% CI = [0.3, 1.4]). Further, the direct effect of mTBI + LOC events on neurobehavioral symptoms became non-significant when depression and insomnia were added to the model (B = 0.78, SE = 0.45, p = 0.08). Conclusions Findings support LOC at time of injury as an important predictor of long-term outcomes. Additionally, results suggest depression and insomnia as potential mediators in the association between mTBI + LOC and neurobehavioral symptoms. These findings provide justification for early depression and insomnia symptom monitoring following mTBI + LOC.

Neuromuscular electrical stimulation for physical function maintenance during hematopoietic stem cell transplantation: Study protocol.

Hematopoietic stem cell transplantation is a common life-saving treatment for hematologic malignancies, though can lead to long-term functional impairment, fatigue, muscle atrophy, with decreased quality of life. Although traditional exercise has helped reduce these effects, it is inconsistently recommended and infrequently maintained, and most patients remain sedentary during and after treatment. There is need for alternative rehabilitation strategies, like neuromuscular electrical stimulation, that may be more amenable to the capabilities of hematopoietic stem cell transplant recipients. Patients receiving autologous HCT are being enroled in a randomized controlled trial with 1:1 (neuromuscular electrical stimulation:sham) design stratified by diagnosis and sex. Physical function, body composition, quality of life, and fatigue are assessed prior to hematopoietic stem cell transplant (prior to initiating preparatory treatment) and 24±5 days post hematopoietic stem cell transplant (Follow-up 1); physical function and quality of life are also assessed 6-months post hematopoietic stem cell transplant (Follow-up 2). The primary outcome is between-group difference in the 6-minute walk test change scores (Follow-up 1-Pre-transplant; final enrolment goal N = 23/group). We hypothesize that 1) neuromuscular electrical stimulation will attenuate hematopoietic stem cell transplant-induced adverse effects on physical function, muscle mass, quality of life, and fatigue compared to sham at Follow-up 1, and 2) Pre-transplant physical function will significantly predict fatigue and quality of life at Follow-up 2. We will also describe feasibility and acceptability of neuromuscular electrical stimulation during hematopoietic stem cell transplant. This proposal will improve rehabilitative patient care and quality of life by determining efficacy and feasibility of a currently underutilized therapeutic strategy aimed at maintaining daily function and reducing the impact of a potent and widely used cancer treatment. This trial is registered with clinicaltrials.gov (NCT04364256).

Trunk control and acute-phase multifactorial predictors of community mobility after stroke: a longitudinal observational study.

Stroke is a detrimental condition associated with long-term functional impairments that restrict community reintegration, which is an indicator of successful post-stroke functional recovery and rehabilitation. Additionally, trunk control is an understudied factor that may contribute to community mobility and participation after stroke. This study aimed to identify predictors of community mobility among stroke survivors in the acute phase, with a primary focus on trunk control, in addition to exploring the mediating and moderating role of predictive factors. A longitudinal observational study included 61 participants with acute stroke. Trunk control test (TCT) during sitting, stroke severity, quality of life, fear of falls, depression, and age was assessed during the acute phase as potential predictors. The community mobility outcome measure was assessed 3 months after baseline using the Reintegration to Normal Living Index (RNLI). Statistical analyses included correlation, linear regression, mediation, and moderation analyses. Trunk control test was the strongest predictor of RNLI among all factors (β = 0.72; 95%CI = 0.004-0.007; p ≤ 0.0001). Stroke severity, quality of life, fear of falls, and age significantly predicted RNLI (p < 0.01). Higher age was a significant moderator of the relationship between TCT and RNLI (β = 0.002; p < 0.001; 95% CI = 0.0001-0.0003). The findings highlight sitting trunk control impairment during the acute stage as a crucial predictor of reduced community mobility after stroke, where age over 60 years can moderate this relationship. The study emphasizes that addressing trunk control during early stroke rehabilitation may enhance community reintegration prospects.

Advancing nerve regeneration: Peripheral nerve injury (PNI) chip empowering high-speed biomaterial and drug screening

Peripheral nerve injuries (PNIs) represent a significant challenge in regenerative medicine, often leading to long-term functional impairments. In this study, we introduce the peripheral nerve injury-on-a-chip (PNI chip), a cutting-edge platform designed for high-speed screening of biomaterials and drugs to enhance peripheral nerve regeneration. The PNI chip combines aligned nanofibers as topographical cues with microfluidic technology to create a controlled and versatile environment for investigating key factors influencing axonal growth and regeneration. Our study reveals that density of aligned nanofibers plays a pivotal role in axonal regeneration regarding regeneration velocity and the recovery of damaged axonal areas. Additionally, we investigate the dynamic interactions between regenerating axons and aligned nanofibers, shedding light on the adaptability of axonal growth cones to topographical cues. Moreover, the PNI chip serves as a potent tool for drug screening, as demonstrated by our evaluation of paclitaxel and M1. Paclitaxel exhibits concentration-dependent effects, while M1, a mitochondria fusion promoter, substantially enhances axonal growth velocity, emphasizing the potential of mitochondria dynamics as a target for improving nerve regeneration. The PNI chip represents a breakthrough in peripheral nerve regeneration research, offering the means to systematically explore nanofiber parameters and drug interventions in a controlled and high-throughput manner.

Open reduction and internal fixation using suture anchors for an isolated lesser tuberosity fracture: description of technique and a case report

Isolated fractures of the lesser tuberosity (LT) of the humerus are uncommon and pose diagnostic challenges. This case study explores a distinctive treatment for a displaced and angulated LT fracture in a 27-year-old female skier. Emphasizing open reduction and internal fixation with suture anchors, the study addresses the scarcity of consensus on optimal treatments and the difficulties in accurate diagnosis. The successful application of suture anchors highlights their potential advantages, including biodegradability, improved vascularity, optimized intraoperative workflow without the need for fluoroscopy, and minimized risk of collateral bone damage. This case underscores the importance of surgical intervention for preventing long-term functional impairments in displaced LT fractures and advocates for considering alternative surgical techniques. By contributing insights into the rationale and advantages of using suture anchors, this study aims to enrich the discourse on optimal management strategies for these rare fractures, potentially informing future treatment decisions.

Long-Term Neuropsychiatric, Neurocognitive, and Functional Outcomes of Patients Receiving ECMO: A Systematic Review and Meta-Analysis

Despite the common occurrence of neurologic complications during extracorporeal membrane oxygenation (ECMO) support, data on long-term neuropsychiatric, neurocognitive, and functional outcomes are sparse. We aimed to determine the prevalence of long-term neuropsychiatric symptoms, neurocognitive and functional impairment, and favorable neurologic outcomes in adult patients who receive ECMO. PubMed, Embase, Cochrane, Web of Science, and Scopus were searched for text related to ECMO and neuropsychiatric, neurocognitive, and functional outcomes from inception to May 3, 2023. Our primary outcome was the prevalence of neuropsychiatric symptoms (pain/discomfort, anxiety, depression, posttraumatic stress disorder [PTSD], and sleep disturbance) at long-term (≥6 months) follow-up. Our secondary outcomes were the prevalence of neurocognitive impairment (memory, attention, and reasoning), functional impairment (daily activities, physical activity/mobility, and personal/self-care), and favorable neurologic outcomes (Cerebral Performance Category ≤2, modified Rankin scale ≤3, or Glasgow Outcome Scale ≥4). This study was registered in PROSPERO (CRD42023420565). We included 59 studies with 3,280 patients (median age 54 years, 69% male). The cohort consisted of 86% venoarterial (VA)-ECMO (n = 2,819) and 14% venovenous (VV)-ECMO (n = 461) patients. More than 10 tools were used to assess neuropsychiatric and neurocognitive outcomes, indicating a lack of standardization in assessment methodologies. The overall prevalence of neuropsychiatric symptoms was 41% (95% CI 33%-49%): pain/discomfort (52%, 95% CI 42%-63%), sleep disturbance (37%, 95% CI 0%-98%), anxiety (36%, 95% CI 27%-46%), depression (31%, 95% CI 22%-40%), and PTSD (18%, 95% CI 9%-29%). The prevalence of neurocognitive impairment was 38% (95% CI 13%-65%). The prevalence of functional impairment was 52% (95% CI 40%-64%): daily activities (54%, 95% CI 41%-66%), mobility (41%, 95% CI 28%-54%), and self-care (21%, 95% CI 13%-31%). The prevalence of neuropsychiatric symptoms in VV-ECMO patients was higher than that in VA-ECMO patients (55% [95% CI 34%-75%] vs 32% [95% CI 23%-41%], p = 0.01), though the prevalence of neurocognitive and functional impairment was not different between the groups. The prevalence of favorable neurologic outcomes was not different at various follow-ups: 3 months (23%, 95% CI 12%-36%), 6 months (25%, 95% CI 16%-35%), and ≥1 year (28%, 95% CI 21%-36%, p = 0.68). A substantial proportion of ECMO patients seemed to experience neuropsychiatric symptoms and neurocognitive and functional impairments at long-term follow-up. Considerable heterogeneity in methodology for gauging these outcomes exists, warranting the need for standardization. Multicenter prospective observational studies are indicated to further investigate risk factors for these outcomes in ECMO-supported patients.

Geriatric Pain Protocol: Impact of Multimodal Pain Care for Elderly Orthopedic Trauma Patients

ABSTRACT Hip fractures are costly, and associated complications are the leading cause of injury-related deaths in persons 65 years or older. Uncontrolled pain leads to increased hospital length of stay (LOS), delayed physical therapy, and long-term functional impairment. The Geriatric Pain Protocol (GPP) is Cedars-Sinai's multimodal pain management solution, addressing the needs of older adult inpatients who have suffered fractures. Study participants included hip fracture patients admitted between February 1, 2019, and March 5, 2021. Inclusion criteria were patients 65 years or older with a hip fracture sustained from a ground-level fall and surgical candidate. Participants were divided into 2 categories: Geriatric Fracture Program (GFP) and non-GFP, with physician participation in the GFP being the differentiating factor. End points included postoperative pain, postoperative opioid utilization, LOS, complications, and 30-day readmission rates. The GPP decreased morphine milligram equivalent (MME) daily totals on days 1 and 2 and improved pain management compared with non-GPP patients. MMEs were lower in the GPP group than in the non-GPP group for both postoperative day 1 (POD1) (P = 0.007) and POD2 (P = 0.043); the Numerical Rating Scale (NRS) pain score on POD1 was lower in the GPP group (vs non-GPP, P = 0.013). There were no group differences in NRS POD2 pain or complications (all Ps &gt; 0.1). The study sample (N = 453) had no significant difference between sex and LOS (all Ps &gt; 0.3). Although not statistically significant, the 30-day readmission rate trended lower in patients treated in accordance with the GPP. Use of the GPP reduced pain levels and MME totals.

Anti-N-methyl-D-aspartate receptor-associated encephalitis: A review of clinicopathologic hallmarks and multimodal imaging manifestations.

Anti-N-methyl-D-aspartate receptor-associated encephalitis (NMDARE) is a rare immune-mediated neuroinflammatory condition characterized by the rapid onset of neuropsychiatric symptoms and autonomic dysfunction. The mechanism of pathogenesis remains incompletely understood, but is thought to be related to antibodies targeting the GluN1 subunit of the NMDA receptor with resultant downstream dysregulation of dopaminergic pathways. Young adults are most frequently affected; the median age at diagnosis is 21 years. There is a strong female predilection with a female sex predominance of 4:1. NMDARE often develops as a paraneoplastic process and is most commonly associated with ovarian teratoma. However, NMDARE has also been described in patients with small cell lung cancer, clear cell renal carcinoma, and other benign and malignant neoplasms. Diagnosis is based on correlation of the clinical presentation, electroencephalography, laboratory studies, and imaging. Computed tomography, positron emission tomography, and magnetic resonance imaging are essential to identify an underlying tumor, exclude clinicopathologic mimics, and predict the likelihood of long-term functional impairment. Nuclear imaging may be of value for prognostication and to assess the response to therapy. Treatment may involve high-dose corticosteroids, intravenous immunoglobulin, and plasma exchange. Herein, we review the hallmark clinicopathologic features and imaging findings of this rare but potentially devastating condition and summarize diagnostic criteria, treatment regimens, and proposed pathogenetic mechanisms.

Long-term functional outcomes of upper extremity civilian vascular trauma

ObjectiveCivilian analyses of long-term outcomes of upper extremity vascular trauma (UEVT) are limited. Our goal was to evaluate the management of UEVT in the civilian trauma population and explore the long-term functional consequences. MethodsA retrospective review and analysis was performed of patients with UEVT at an urban Level 1 trauma center (2001-2022). Management and long-term functional outcomes were analyzed. ResultsThere were 150 patients with UEVT. Mean age was 34 years, and 85% were male. There were 42% Black and 27% White patients. Mechanism was penetrating in 79%, blunt in 20%, and multifactorial in 1%. Within penetrating trauma, mechanism was from firearms in 30% of cases. Of blunt injuries, 27% were secondary to falls, 13% motorcycle collisions, 13% motor vehicle collisions, and 3% crush injuries. Injuries were isolated arterial in 62%, isolated venous in 13%, and combined in 25% of cases. Isolated arterial injuries included brachial (34%), radial (27%), ulnar (27%), axillary (8%), and subclavian (4%). The majority of arterial injuries (92%) underwent open repair with autologous vein bypass (34%), followed by primary repair (32%), vein patch (6.6%), and prosthetic graft (3.3%). There were 23% that underwent fasciotomies, 68% of which were prophylactic. Two patients were managed with endovascular interventions; one underwent covered stent placement and the other embolization. Perioperative reintervention occurred in 12% of patients. Concomitant injuries included nerves (35%), bones (17%), and ligaments (16%). Intensive care unit admission was required in 45%, with mean intensive care unit length of stay 1.6 days. Mean hospital length of stay was 6.7 days. Major amputation and in-hospital mortality rates were 1.3% and 4.6% respectively. The majority (72%) had >6-month follow-up, with a median follow-up period of 197 days. Trauma readmissions occurred in 19%. Many patients experienced chronic pain (56%), as well as motor (54%) and sensory (61%) deficits. Additionally, 41% had difficulty with activities of daily living. Of previously employed patients (57%), 39% experienced a >6-month delay in returning to work. Most patients (82%) were discharged with opioids; of these, 16% were using opioids at 6 months. ConclusionsUEVT is associated with long-term functional impairments and opioid use. It is imperative to counsel patients prior to discharge and ensure appropriate follow-up and therapy.

Patterns and predictors of dental hospitalizations in patients with acquired brain injury from pre-injury to acute and post-acute injury.

Acquired brain injury (ABI) can cause long-term disability and functional impairment. This study aims to determine the prevalence of dental hospitalizations in an ABI cohort across different phases of injury and identify factors associated with such hospitalizations. The cohort comprises patients with ABI (n = 683), traumatic (n = 282) and non-traumatic (n = 401) who were admitted to a neurorehabilitation service in Western Australia between 1991 and 2016. De-identified patient data were linked to the Hospital Morbidity Data Collection. The incidence of dental hospitalizations was calculated per 1,000 person-years (PY), and associated factors were investigated using multilevel mixed-effects logistic regression. Dental hospitalizations significantly increased from pre-injury (3.35/1,000PY) to acute injury (302.65, Δ+299.3) and remained elevated in the post-acute phase (23.98, Δ+20.63). Dental caries had the highest incidence rate among all diagnoses in the pre-injury and post-acute phases (0.68 and 8.93, respectively), followed by gingivitis and periodontal diseases (3.60) in the post-acute phase. Tooth extractions were performed more often than restorative and preventive treatment in the pre-and post-injury phase, p < 0.001. Dental hospitalizations were associated with the type of ABI, age at injury, remoteness, and history of pre-injury hospitalization. Implementing comprehensive preventive dental care can reduce potentially preventable dental hospitalization among ABI patients.

Striatal correlates of Bayesian beliefs in self-efficacy in adolescents and their relation to mood and autonomy: a pilot study.

Major depressive disorder often originates in adolescence and is associated with long-term functional impairment. Mechanistically characterizing this heterogeneous illness could provide important leads for optimizing treatment. Importantly, reward learning is known to be disrupted in depression. In this pilot fMRI study of 21 adolescents (16-20years), we assessed how reward network disruption impacts specifically on Bayesian belief representations of self-efficacy (SE-B) and their associated uncertainty (SE-U), using a modified instrumental learning task probing activation induced by the opportunity to choose, and an optimal Hierarchical Gaussian Filter computational model. SE-U engaged caudate, nucleus accumbens (NAcc), precuneus, posterior parietal and dorsolateral prefrontal cortex (PFWE < 0.005). Sparse partial least squares analysis identified SE-U striatal activation as associating with one's sense of perceived choice and depressive symptoms, particularly anhedonia and negative feelings about oneself. As Bayesian uncertainty modulates belief flexibility and their capacity to steer future actions, this suggests that these striatal signals may be informative developmentally, longitudinally and in assessing response to treatment.

Abstract PO-049: The neural landscape is associated with functional outcomes for patients with oropharyngeal squamous cell carcinoma

Abstract Despite the excellent prognosis of patients with oropharyngeal squamous cell carcinoma (OPSCC), long-term functional impairment (e.g., dysphagia) is a major burden for many patients. Recent studies have explored the role of pharyngeal constrictors and muscle fibrosis in dysphagia. However, to date, no study has examined the association between the OPSCC neural microenvironment and posttreatment functional impairment. We hypothesized that cancer-related neuronal changes in the OPSCC tumor microenvironment (TME) would affect patients’ prognoses. Therefore, in the present study, we investigated whether cancer-related changes in the tumor neuronal microenvironment influence functional outcomes in patients with OPSCC. Prospectively collected, patient-reported outcomes (i.e., from the MD Anderson Symptom Inventory [MDASI] and the MD Anderson Dysphagia Inventory [MDADI]) and functional outcomes from the Dynamic Imaging Grade of Swallowing Toxicity [DIGEST] for patients with OPSCC were collected (n=29). OPSCC tissue samples were obtained from surgically treated patients, and multiplex/high-plex immunofluorescence and machine learning techniques were used to correlate neuronal changes with prospectively collected patient data. Electromyography was performed to assess the neuronal populations involved in neuropathies after treatment. A murine animal model of dysphagia was also used to correlate the neuronal changes. The results showed that sensory nerves with adrenergic features (CGRP+TH+) were associated with perineural and lymphovascular invasion. In addition, we found that human papillomavirus associated OPSCC was associated with an enrichment of parasympathetic progenitors (VIP+DCX+). Poor MDASI scores were associated with CGRP+, adrenergic (TH+), or CGRP+TH+ innervation, and growing progenitor neurons (GAP43+DCX+) were associated with improved oral symptoms. Swallowing, measured by MDADI scale revealed that patients with tumors enriched with growing (GAP43+), parasympathetic (VIP+), and neuronal progenitor (DCX+) neurons reported poor swallowing perception; subgroup electromyography analysis confirmed our findings. Quantitative swallowing assessment with DIGEST by speech language pathologists revealed that TMEs innervated by CGRP+, TH+, and MBP+ neurons were associated with poor swallowing functions. Finally, using a murine model of dysphagia we confirmed that sensory (CGRP+), myelinated (MBP+), and cholinergic parasympathetic (CHAT+) or progenitor (CHAT+DCX+) enrichment was associated with denervation and downstream dysphagia. In conclusion, our results show that neuronal changes are correlated with clinical features in OPSCC patients. Patients’ functional outcomes after therapy completion are influenced by distinct nerve populations in the TME. These benchmark data should be further evaluated as a potential target for cancer survivors with dysphagia and as a biomarker for patients who might need escalated swallowing rehabilitation during and after treatment for OPSCC. Citation Format: Shajedul Islam, Frederico O. Gleber-Netto, Collin F. Mulcahy, Mica D. E. Glaun, Patrick J. Hunt, Michelle D. Williams, Carly E. Barbon, Weilu Zhao, Adewale Adebayo, Shamima Akhter, Tongxin Xie, Ismail Yaman, Jared K. Burks, Javier Gomez, Karin Woodman, Teresa E. Lever, Katherine A. Hutcheson, Moran Amit. The neural landscape is associated with functional outcomes for patients with oropharyngeal squamous cell carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-049.

Post-coronavirus disease 2019 functional impairments, limitations, and restrictions: A prospective cohort study based on the international classification of functioning, disability, and health.

Current knowledge regarding coronavirus disease 2019 (COVID-19) is constantly evolving, and the long-term functional impairments, limitations, and restrictions have not yet been well established. to evaluate the impact of post-COVID condition on the human functioning through the International Classification of Functioning, Disability and Health (ICF) classification. This is a prospective cohort study with 53 individuals with post-COVID condition at 3 time points: 0 to 3 (baseline), 3 to 6, and 6-12months (follow-up). Outcomes were organized in dichotomous variable: No impairment (0); presence of impairment (≥1) in body function, structure, activities, and participation domains according to the ICF checklist. Chi-square test was used to determine the differences of 3 time points, and association with persistent symptoms. A statistically significant difference was observed between the periods, with greater disabilities at 6-12 than at 0-3months in mental, sensory, pain, and movement-related functions; cardiovascular, immunological, and respiratory systems. In terms of activity and participation, a greater limitation at 6-12months was observed than at 0-3months in learning and applying knowledge, general tasks, and mobility. In the domain of interpersonal interactions and relationships, there was a statistically significant difference between the 6-12 and 3-6months groups. Associations between COVID-19 symptoms and ICF components at the first follow-up were: anosmia and dysgeusia with weight maintenance, fatigue and irritability with pain, brain fog with watching and listening, walking difficulty with pain, and headache with pain, watching, and listening. At the second follow-up were: anosmia and dysgeusia with energy and drive functions, attention, memory, and emotional functions; dizziness with watching and listening; fatigue with emotional function, pain, undertaking multiple tasks, lifting and carrying objects, and driving; irritability with energy and drive, emotional function, undertaking multiple tasks, lifting and carrying objects, and walking; walking difficulty with energy and driving, emotional function, respiration, muscle power, cardiovascular system, undertaking multiple tasks, lifting and carrying objects, and walking; and headache with emotional function, watching, and listening. Individuals with COVID-19 persistent symptoms showed impairments in structure and function, activity limitations, and participation restrictions during the 1-year follow-up period.

Oligodendrocytes in human induced pluripotent stem cell-derived cortical grafts remyelinate adult rat and human cortical neurons.

Neuronal loss and axonal demyelination underlie long-term functional impairments in patients affected by brain disorders such as ischemic stroke. Stem cell-based approaches reconstructing and remyelinating brain neural circuitry, leading to recovery, are highly warranted. Here, we demonstrate the invitro and invivo production of myelinating oligodendrocytes from a human induced pluripotent stem cell (iPSC)-derived long-term neuroepithelial stem (lt-NES) cell line, which also gives rise to neurons with the capacity to integrate into stroke-injured, adult rat cortical networks. Most importantly, the generated oligodendrocytes survive and form myelin-ensheathing human axons in the host tissue after grafting onto adult human cortical organotypic cultures. This lt-NES cell line is the first human stem cell source that, after intracerebral delivery, can repair both injured neural circuitries and demyelinated axons. Our findings provide supportive evidence for the potential future use of human iPSC-derived cell lines to promote effective clinical recovery following brain injuries.

Geriatric Pain Protocol: Impact of Multimodal Pain Care for Elderly Orthopaedic Trauma Patients.

Hip fractures are costly, and associated complications are the leading cause of injury-related deaths in persons 65 years or older. Pain medications in this population can be more potent, have a longer duration of action, and have serious side effects (Chau et al., 2008). Hip fractures are projected to reach 6.26 million worldwide by 2050 (Gullberg et al., 1997; Kannus et al., 1996). Morrison et al. (2003) report that uncontrolled pain leads to increased hospital length of stay (LOS), delayed physical therapy, and long-term functional impairment. The Geriatric Pain Protocol (GPP) is Cedars-Sinai's multimodal pain management solution, addressing the needs of older adult inpatients who have suffered fractures. Can the implementation of GPP reduce the morphine milligram equivalents (MMEs) used, LOS, and postoperative outcomes compared with non-GPP patients? Study participants included hip fracture patients admitted between February 1, 2019, and March 5, 2021; data were collected prospectively from electronic medical records. Inclusion criteria were patients 65 years or older with a hip fracture sustained from a ground-level fall and surgical candidate. Participants were divided into two categories: Geriatric Fracture Program (GFP) and non-GFP, with physician participation in the GFP being the differentiating factor. End points included postoperative pain, postoperative opioid utilization, LOS, complications, and 30-day readmission rates. The Mann-Whitney U test and Fisher's exact test were used for data analysis. Spearman's rank-based correlation coefficient was used to assess associations. The GPP decreased MME daily totals on Days 1 and 2 and improved pain management compared with non-GPP patients. The MMEs were lower in the GPP group than in the non-GPP group for both Postoperative Day 1 (POD1) (p = .007) and POD2 (p = .043); Numerical Rating Scale (NRS) Pain on POD1 was lower in the GPP group (vs. non-GPP, p = .013). There were no group differences in NRS POD2 Pain or complications (all ps > .1). The study sample (N = 453) had no significant difference between sex and LOS (all ps > .3). Although not statistically significant, the 30-day readmission rate trended lower in patients treated in accordance with the GPP. Use of the multimodal GPP reduced pain levels and MME totals for older adult hip fracture inpatients. More data are needed to evaluate the efficiency of the proposed protocol. Future studies should explore the possibilities of using the GPP across the geriatric orthopaedic patient care continuum.

Comparative study of the functional outcome of semitendinosus graft versus peroneus longus graft in arthroscopic reconstruction surgeries of anterior cruciate ligament

Background: ACL disruption is the commonest ligamentous knee injury among active adults, invariably leading to changes in knee kinematics which are most likely to result in secondary degenerative changes and long-term functional impairment. Thus, due to the ACL's crucial role as the primary restraint against anterior tibial translation, its reconstruction using varying graft options are being extensively studied for better functional outcome. Methods: In this prospective study, we analysed 30 patients having ACL tear (clinically and radiographically) and treated with arthroscopic reconstruction of ACL. Among these, 15 cases were operated using semitendinosus graft and 15 cases by using peroneus longus tendon graft. The study was conducted in a tertiary care hospital from January 2021 to June 2022 with minimum follow up of 6 months and maximum follow up of 15 months. Results: Mean Lysholm score (post op) in Group ST was 90.6±3.18 and in Group PLT was 92.2±2.65. The Lysholm Score and IKDC grading between the two groups was comparable and showed no significant difference. Post-Op laxity assessed using the Lachman’s grading showed normal findings in 70% patients, and of the remaining 30% (9 patients), 5 patients from ST group and 4 patients from PLT group showed 1+ laxity at follow up examination. Conclusions: Arthroscopy assisted ACL reconstruction with peroneus longus tendon autograft provides a steady knee, reduces postoperative donor site morbidity and enables early rehabilitation, similar to the traditional semitendinosus tendon autograft.

Delayed cortical thinning in children and adolescents with prenatal alcohol exposure.

Prenatal alcohol exposure (PAE) is associated with abnormalities in cortical structure and maturation, including cortical thickness (CT), cortical volume, and surface area. This study provides a longitudinal context for the developmental trajectory and timing of abnormal cortical maturation in PAE. We studied 35 children with PAE and 30 nonexposed typically developing children (Comparisons), aged 8-17 at enrollment, who were recruited from the University of Minnesota FASD Program. Participants were matched on age and sex. They underwent a formal evaluation of growth and dysmorphic facial features associated with PAE and completed cognitive testing. MRI data were collected on a Siemens Prisma 3T scanner. Two sessions, each including MRI scans and cognitive testing, were spaced approximately 15 months apart on average. Change in CT and performance on tests of executive function (EF) were examined. Significant age-by-group (PAE vs. Comparison) linear interaction effects in CT were observed in the parietal, temporal, occipital, and insular cortices suggesting altered developmental trajectories in the PAE vs. Comparison groups. Results suggest a pattern of delayed cortical thinning in PAE, with the Comparison group showing more rapid thinning at younger ages and those with PAE showing accelerated thinning at older ages. Overall, children in the PAE group showed reduced cortical thinning across time relative to the Comparison participants. Symmetrized percent change (SPC) in CT in several regions was significantly correlated with EF performance at 15-month follow-up for the Comparison group but not the group with PAE. Regional differences were seen longitudinally in the trajectory and timing of CT change in children with PAE, suggesting delayed cortical maturation and an atypical pattern of development compared with typically developing individuals. In addition, exploratory correlation analyses of SPC and EF performance suggest the presence of atypical brain-behavior relationships in PAE. The findings highlight the potential role of altered developmental timing of cortical maturation in contributing to long-term functional impairment in PAE.

Preclinical evaluation of ZL006-05, a new antistroke drug with fast-onset antidepressant and anxiolytic effects

BackgroundPoststroke depression and anxiety, independent predictor of poor functional outcomes, are common in the acute phase of stroke. Up to now, there is no fast-onset antidepressive and anxiolytic agents suitable...

Long-term functional impairment in pediatric OCD after and during treatment: An analysis of distinct trajectories

The present study aimed to: (a) identify latent class trajectories of OCD-related functional impairment, before, during and over three years after stepped-care treatment in children and adolescents with OCD; (b) describe these classes according to pretreatment characteristics; (c) identify predictors of trajectory class membership and (d) examine the relationship of functional impairment trajectory classes with OCD symptom severity trajectory classes. The sample consisted of 266 children and adolescents (aged 7–17 years) with OCD, participating in the Nordic long-term OCD treatment study. Latent class growth analysis was conducted using Child Obsessive-Compulsive Impact Scale-Revised (COIS-R) data from children and parents on seven assessment points over a three-year period. A 3-class solution was identified. The largest class (70.7%) initiated treatment with lower functional impairment and obtained moderate reduction which was maintained over time. The second class (24.4%) initiated with higher functional impairment which rapidly diminished over time. The third and smallest class (4.9%), initiated with moderate functional impairment which remained stable over time. The classes differed on measures of OCD severity and comorbid symptoms. Most participants improved with treatment and maintained low levels of impairment. However, a subgroup distinguished by higher levels of ADHD symptoms, remained at pretreatment levels of impairment throughout.

Exploration of muscle–tendon biomechanics one year after Achilles tendon rupture and the compensatory role of flexor hallucis longus

Achilles tendon (AT) rupture leads to long-term structural and functional impairments. Currently, the predictors of good recovery after rupture are poorly known. Thus, we aimed to explore the interconnections between structural, mechanical, and neuromuscular parameters and their associations with factors that could explain good recovery in patients with non-surgically treated AT rupture. A total of 35 patients with unilateral rupture (6 females) participated in this study. Muscle-tendon structural, mechanical, and neuromuscular parameters were measured 1-year after rupture. Interconnections between the inter-limb differences (Δ) were explored using partial correlations, followed by multivariable linear regression to find associations between the measured factors and the following markers that indicate good recovery: 1) tendon length, 2) tendon non-uniform displacement, and 3) flexor hallucis longus (FHL) normalized EMG amplitude difference between limbs. Δmedial gastrocnemius (MG) (β = −0.12, p = 0.007) and Δlateral gastrocnemius (β = −0.086, p = 0.030) subtendon lengths were associated with MG tendon Δstiffness. MG (β = 11.56, p = 0.003) and soleus (β = 2.18, p = 0.040) Δsubtendon lengths explained 48 % of variance in FHL EMG amplitude. Regression models for tendon length and non-uniform displacement were not significant. Smaller inter-limb differences in Achilles subtendon lengths were associated with smaller differences in the AT stiffness between limbs, and a smaller contribution of FHL muscle to the plantarflexion torque. In the injured limb, the increased contribution of FHL appears to partially counteract a smaller contribution from MG due to the elongated tendon, however the role of FHL should not be emphasized during rehabilitation to allow recovery of the TS muscles.