Subacute Period Research Articles

Acute Versus Subacute Endovascular Repair for Uncomplicated Type B Aortic Dissections

Uncomplicated type B aortic dissection (TBAD) was historically managed nonoperatively with strict impulse control and close monitoring owing to the high morbidity and mortality of open repair. However, thoracic endovascular aortic repair (TEVAR) has recently emerged as a viable option due to the potential for inducing more favorable aortic remodeling. The aim of this study is to compare outcomes of uncomplicated TBAD treated medically or with TEVAR in either the acute (1-14 days) or subacute period (2 weeks to 3 months).

155. What are the risk factors for continued opioid use in patients following spine surgery?

BACKGROUND CONTEXT Although studies have explored acute opioid use within 30 days after surgery and chronic opioid use longer than 90 days after surgery, the impact of opioid use within the subacute phase of 31-90 days after surgery has not been studied. However, this subacute postoperative period has been identified as a potential predictor of chronic opioid use. PURPOSE This study aims to identify factors common in opioid-naïve patients who are at a high risk of opioid use during the subacute phase of 31-90 days after discharge. STUDY DESIGN/SETTING Retrospective analysis. PATIENT SAMPLE Adult opioid-naïve patients who underwent spine surgeries at a quaternary medical care center from June 2012 to December 2019. OUTCOME MEASURES Opioid refills in the subacute postoperative period of 31-90 days following discharge. METHODS In this retrospective cohort study, the electronic medical record of adult opioid-naïve patients who underwent spine surgeries at a quaternary medical care center from June 2012 to December 2019 were analyzed. Opioid refills in the subacute postoperative period of 31-90 days following discharge were the primary study outcome. RESULTS Of the study cohort consisting of 3,024 patients, 2,685 (89%) required inpatient opioids in the last 24 hours before discharge, 733 (26%) required an opioid refill 1-30 days after discharge, and 579 (19%) required opioid refill 31-90 days after discharge. Moreover, a postoperative opioid refill 1-30 days after discharge conferred the strongest risk of an opioid refill 31-90 days after discharge (OR 4.66, 95% CI 3.84-5.64). Other factors associated with the increased risk of an opioid refill 31-90 days after discharge were gabapentinoid use, discharge disposition to facilities other than home or self-care, reoperation, and female gender. Meanwhile, Asian American race was associated with the reduced risk. Those requiring opioid refills were noted to be younger, underwent longer surgeries, had extended inpatient hospital stays, required higher doses of inpatient opioids, and required higher doses of discharge opioid prescriptions for longer durations. CONCLUSIONS In opioid-naïve postoperative spine patients, opioid refills 1-30 days after discharge were strongly associated with an increased risk of opioid refills 31-90 days after discharge. Factors associated with opioid refill requirements also included longer surgeries and inpatient hospital stays as well as higher doses of inpatient opioids. Overall, this study enables physicians to identify patients at a higher risk of opioid use and to intervene early during the postoperative course. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs. Although studies have explored acute opioid use within 30 days after surgery and chronic opioid use longer than 90 days after surgery, the impact of opioid use within the subacute phase of 31-90 days after surgery has not been studied. However, this subacute postoperative period has been identified as a potential predictor of chronic opioid use. This study aims to identify factors common in opioid-naïve patients who are at a high risk of opioid use during the subacute phase of 31-90 days after discharge. Retrospective analysis. Adult opioid-naïve patients who underwent spine surgeries at a quaternary medical care center from June 2012 to December 2019. Opioid refills in the subacute postoperative period of 31-90 days following discharge. In this retrospective cohort study, the electronic medical record of adult opioid-naïve patients who underwent spine surgeries at a quaternary medical care center from June 2012 to December 2019 were analyzed. Opioid refills in the subacute postoperative period of 31-90 days following discharge were the primary study outcome. Of the study cohort consisting of 3,024 patients, 2,685 (89%) required inpatient opioids in the last 24 hours before discharge, 733 (26%) required an opioid refill 1-30 days after discharge, and 579 (19%) required opioid refill 31-90 days after discharge. Moreover, a postoperative opioid refill 1-30 days after discharge conferred the strongest risk of an opioid refill 31-90 days after discharge (OR 4.66, 95% CI 3.84-5.64). Other factors associated with the increased risk of an opioid refill 31-90 days after discharge were gabapentinoid use, discharge disposition to facilities other than home or self-care, reoperation, and female gender. Meanwhile, Asian American race was associated with the reduced risk. Those requiring opioid refills were noted to be younger, underwent longer surgeries, had extended inpatient hospital stays, required higher doses of inpatient opioids, and required higher doses of discharge opioid prescriptions for longer durations. In opioid-naïve postoperative spine patients, opioid refills 1-30 days after discharge were strongly associated with an increased risk of opioid refills 31-90 days after discharge. Factors associated with opioid refill requirements also included longer surgeries and inpatient hospital stays as well as higher doses of inpatient opioids. Overall, this study enables physicians to identify patients at a higher risk of opioid use and to intervene early during the postoperative course.

Parkinsonism and progressive atypical psychiatric symptoms in the post-stroke subacute period

Parkinsonism and progressive atypical psychiatric symptoms in the post-stroke subacute period

A study of dynamic hand orthosis combined with unilateral task-oriented training in subacute stroke: A functional near-infrared spectroscopy case series.

BackgroundMotor dysfunction in the upper extremities after stroke prohibits people with stroke from being independent in daily living. The application of fNIRS to explore brain activity under rehabilitation intervention is a research focus on neurorehabilitation.ObjectiveThe purpose of this study was to explore, using a grip-release ring motor task, the activated changes of regions of interest and changes in motor function utilizing fNIRS technology and test scales on persons with stroke who received unilateral task-oriented therapy with a hand orthosis in the early subacute stroke period before and after intervention. The study aimed to find a sensitive motor task and region of interest first, then to evaluate the feasibility and mechanism of this rehabilitation method by utilizing fNIRS technology in the next randomized controlled trial.MethodsIn this case series, eight right-handed, right hemiplegia subacute stroke persons (6 males,2 females from age 47 to 72) were enrolled. They received 30 min of unilateral task-oriented therapy without orthosis and 30 min of unilateral task-oriented therapy with orthosis (5 days/week) for 4 weeks. Activated channel numbers and beta values based on oxygenated hemoglobin concentration change using a grip-release ring motor task were estimated with fNIRS. Clinical outcome measures, including grip strength evaluation, action research arm test, and Fugl-Meyer assessment of the arm, were evaluated at the same time.ResultsIndividual activation analysis showed that, after intervention, Subjects 1, 2, 6, 7, and 8 had the maximum mean beta value located in the left premotor cortex, while Subjects 4 and 5 had the maximum mean beta value located in the left sensorimotor cortex. The activation analysis of Subject 3 showed the maximum mean beta value located in the right premotor cortex. Deactivations of left sensorimotor cortex, left premotor cortex, and bilateral prefrontal cortex were observed after intervention which were different from other cases. Group activation analysis showed that bilateral cerebral hemispheres were activated in all eight participants, with right hemisphere and right supplementary motor cortex activated dominantly. After the intervention, the activation of bilateral hemispheres decreased but in different brain regions; there was a trend that the activation intensity of left sensorimotor cortex, right premotor cortex, and right prefrontal cortex decreased while activation intensity of left premotor cortex and left prefrontal cortex increased. Each participant demonstrated improvements in all the clinical test scales after intervention.ConclusionsLeft premotor cortex, left sensorimotor cortex, and right supplementary motor cortex may be the primary regions of interest. Grasp-release ring task was not appropriate to achieve our fNIRS research objective and a more sensitive motor task or more sensitive evaluating indicator should be used in further studies.

To the question of the main of acute urinary retention development during myocardial infarction in young and middle-aged men predictors

BACKGROUND: Importance in assessing the course and prognosis of myocardial infarction is given to the study of a combination of two or more chronic diseases in one patient, interconnected by a single pathogenetic mechanism. Urological diseases are not among the most common in myocardial infarction, but during this period they significantly worsen the quality of life, increase the cost of treatment and are also associated with a worse prognosis.
 AIM: To study the development of acute urinary retention during the acute and subacute periods of myocardial infarction risk factors in men under 60 years old to improve prevention and outcomes.
 MATERIALS AND METHODS: The study included men aged 1960 years with type I myocardial infarction. Patients were divided into two age-comparable groups: I study group, with acute urinary retention 22 patients; II control, without urination disorders 644 patients. A comparative analysis of the main and additional cardiovascular risk factors observation frequency, the features of the clinical course in the selected groups were performed. Pearsons Chi-square method was used to analyze the risks of developing acute urinary retention.
 RESULTS: The structure of cardiovascular risk factors in the study group differed from the control group in a higher frequency of coronary artery bypass surgery in the medical history (I: 31.8%; II: 8.4%; p = 0.0002) and pacing (9.1 and 0.5%; respectively; p 0.0001), as well as fibrillation and/or atrial flutter in the medical history (27.3 and 9.2%; p = 0.005), chronic cerebrovascular insufficiency (77.3 and 51.3%; p = 0.02), alcohol abuse (63.6 and 25.2%; p 0.0001), frequent (four and more per year) colds (27.3 and 12.6%; p = 0.04), cardiac arrhythmias and conduction disorders at the onset of coronary artery disease (61.9 and 24.9%; p = 0.0007), smoking for 20 years or more (36.4 and 16.8%; p = 0.003), chronic kidney disease (46.7 and 16.2%; p = 0.02), chronic infection foci of internal organs (77.3 and 39.4%; p = 0.002), urinary (27.3 and 8.6%; p = 0.006) and cholelithiasis (13.6 and 5.4%; p = 0.006). Among the features of the clinical course of the disease, the study group was distinguished by a higher incidence of multiple complications of myocardial infarction (100 and 44.0%; p 0.0001), severe and extremely severe condition of patients (59.0 and 19.6%; p 0.0001). Asystole (absolute risk: 42.1%; relative: 18.0; p 0.0001), hydrothorax (absolute risk: 41.7%; relative: 15.9; p 0.0001), the patients severe condition in the first hours of illness (absolute risk: 100%; relative: 36.5; p 0.0001), alcohol abuse (8.0%; 4.9; p 0.0001), smoking (absolute risk: 4.4%; relative: 8.0; p = 0.01) and onset of CHD with heart rhythm and conduction disturbances (7.7%; 4.6; p = 0.0001) were the most significant predictors of acute urinary retention.
 CONCLUSIONS: Patients with acute urinary retention are characterized by a more severe course of myocardial infarction. Combinations of listed above factors indicate an increased risk of developing this complication. It is advisable to use them for predictive modeling and the formation of risk groups for early prevention.

Altered amyloid precursor protein, tau-regulatory proteins, neuronal numbers and behaviour, but no tau pathology, synaptic and inflammatory changes or memory deficits, at 1month following repetitive mild traumatic brain injury.

Repetitive mild traumatic brain injury, commonly experienced following sports injuries, results in various secondary injury processes and is increasingly recognised as a risk factor for the development of neurodegenerative conditions such as chronic traumatic encephalopathy, which is characterised by tau pathology. We aimed to characterise the underlying pathological mechanisms that might contribute to the onset of neurodegeneration and behavioural changes in the less-explored subacute (1-month) period following single or repetitive controlled cortical impact injury (five impacts, 48 h apart) in 12-week-old male and female C57Bl6 mice. We conducted motor and cognitive testing, extensively characterised the status of tau and its regulatory proteins via western blot and quantified neuronal populations using stereology. We report that r-mTBI resulted in neurobehavioural deficits, gait impairments and anxiety-like behaviour at 1 month post-injury, effects not seen following a single injury. R-mTBI caused a significant increase in amyloid precursor protein, an increased trend towards tau phosphorylation and significant changes in kinase/phosphatase proteins that may promote a downstream increase in tau phosphorylation, but no changes in synaptic or neuroinflammatory markers. Lastly, we report neuronal loss in various brain regions following both single and repeat injuries. We demonstrate herein that repeated impacts are required to promote the initiation of a cascade of biochemical events that are consistent with the onset of neurodegeneration subacutely post-injury. Identifying the timeframe in which these changes occur and the pathological mechanisms involved will be crucial for the development of future therapeutics to prevent the onset or mitigate the progression of neurodegeneration following r-mTBI.

EEG Based Resting State Connectivity Changes in the Motor Cortex Associated with Upper Limb Motor Recovery in the Subacute Period Post-Stroke.

Stroke is a heterogeneous condition that would benefit from valid biomarkers of recovery for research and in the clinic. We evaluated the change in resting state connectivity (RSC) via electroencephalography (EEG) in motor areas, as well as motor recovery of the affected upper limb, in the subacute phase post-stroke. Fifteen participants who had sustained a subcortical stroke were included in this study. The group made significant gains in upper limb impairment as measured by the Upper Extremity Fugl-Meyer Assessment (UEFMA) from baseline to four months post-stroke (24.78 (SD 5.4)). During this time, there was a significant increase in RSC in the beta band from contralesional M1 to ipsilesional M1. We propose that this change in RSC may have contributed to the motor recovery seen in this group. Clinical Relevance- This study evaluates resting state connectivity measured via EEG as a neural biomarker of recovery post-stroke. Biomarkers can help clinicians understand the potential for recovery after stroke and thus help them to establish therapy goals and determine treatment plans.

Evaluation of Changes in Kinematic Measures of Three Dimensional Reach to Grasp Movements in the Early Subacute Period of Recovery from Stroke.

This study examines longitudinal data of subjects initially examined in the early subacute period of recovery following a stroke with a test of reach to grasp (RTG) kinematics in an attempt to identify changes in movement patterns during the period of heightened neural recovery following a stroke. Subjects (n=8) were a convenience sample of persons with stroke that participated in an intervention trial. Baseline Upper Extremity Fugl Meyer Assessment (UEFMA) scores ranged between 31 and 52 and ages were between 49 and 83. The UEFMA and RTG test were collected prior to intervention, immediately after the intervention (approximately 18 days later post baseline) and one month after the intervention. RTG data for the uninvolved UE was collected at the one-month session. Subjects reached for objects placed on a table 10 cm from their sternums, picking them up and placing them on a target 30 cm from their acromioclavicular joints. Data was collected using an optical motion capture system. Active makers were placed on each fingertip, metacarpophalangeal, and proximal interphalangeal joint. Four additional passive markers were placed on the dorsum of the hand, the elbow, the shoulder, and the sternum. Subjects demonstrated statistically significant improvements in reaching duration, reaching trajectory smoothness, time after peak velocity and peak grip aperture. All of these measures correlated significantly with improvements in UEFMA. Clinical Relevance- Kinematic measures of reaching and grasping collected early in the subacute period of recovery from stroke may offer insight into specific aspects of the recovery of upper extremity motor function that differ from the information gleaned from clinical scales.

Incidence and Risk Factors for Spinal Cord Stimulator Lead Migration With or Without Loss of Efficacy: A Retrospective Review of 91 Consecutive Thoracic Lead Implants

ObjectiveLead migration after spinal cord stimulator (SCS) implant is a commonly reported complication and the most common reason for revision surgery in cases of loss of efficacy. The primary aims of this study are to describe the incidence and degree of lead migration in the subacute postoperative period after SCS implant and to report potential risk factors for lead migration. Materials and MethodsWe performed a retrospective chart review of all patients at a single academic center who received an SCS implant from January 1, 2020, to December 31, 2020. Information on patient (age, sex, weight, and height) and operative factors (device manufacturer, epidural access level and method, and implantable pulse generator location) were extracted from medical records. Intraoperative imaging was compared to subacute follow-up imaging obtained less than 20 days postimplant to measure lead migration distance. Regression models were fitted to determine associations between lead migration distance and potential clinical risk factors. ResultsA total of 91 cases (182 leads) were included in the study. Within 20 days of implantation, 88.5% of leads had migrated (86.3% caudal and 2.2% cephalad). Mean migration distance for leads with caudal migration only was 12.34 ± 12.19 mm based on anteroposterior radiographs and 16.95 ± 15.68 mm on lateral radiographs. There was an association of greater caudal lead migration as patient body mass index increased (β-coefficient 0.07 [95% confidence interval 0.01–0.13], p = 0.031). Within the entire cohort, one patient (1.1%) required lead revision for loss of efficacy. ConclusionsIn the subacute postoperative period after SCS implant, the majority of SCS leads migrated caudally with an average of two lead contacts. Knowledge of this expected migration and risk factors can better inform implanting physicians intraoperatively when deciding final lead placement location. The finding of high likelihood of caudal lead migration in the subacute postoperative period brings the need for a well-designed prospective study to the forefront of our field. This will allow implanting providers to make well-informed decisions for intraoperative lead placement.

Assessment and prediction of affective disorders in patients after cerebral stroke using modern measurement scales

Objective — to analyze the results of scale‑based assessments of post‑stroke depression (PSD) and post‑stroke anxiety disorders (PSAD) in different phases of cerebral stroke (CS) as well as to determine independent predictors of PSD at discharge from the Stroke Center (StC), and to evaluate the characteristics of the respective predictive models. Methods and subjects. Two hundred patients, including 92 (46.0 %) women and 108 (54.0 %) men with the median age of 65.6 years (IQR 58.2 — 75.1) were enrolled. The health status of all patients was assessed after hospitalization using the National Institutes of Health Stroke Scale (NIHSS), Barthel Index, Modified Rankin Scale, Mini‑Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA). 172 (86.0 %) patients were diagnosed with ischemic stroke (IS), 28 (14.0 %) — intracerebral hemorrhage. Among patients with IS, 58 (33.7 %) had an atherothrombotic subtype, 85 (49.4 %) had a cardioembolic subtype, 16 (9.3 %) had a lacunar subtype, 13 (7.6 %) had another or unknown subtype. The PSD and PSAD were assessed using the Hospital Anxiety and Depression Scale (HADS) and the Patient Health Questionnaire (PHQ‑9) before discharge from the Stroke Center. The impact of factors was assessed by odds ratio (OR) and its 95 % confidence interval (95 % CI). The method of constructing and analyzing logistic regression models was used to determine independent predictors of PSD at discharge. Results. The baseline NIHSS score ranged from 1 to 29. The mRS scores upon admission were from 1 to 5, and the BI scores from 0 to 100. Forty‑one (20.5 %) patients were admitted in the hyperacute period, 55 (27.5 %) in the acute period, 68 (34.0 %) in the early subacute period, 13 (6.5 %) in the late subacute period, and 23 (11.5 %) in the chronic phase of stroke. The HADS‑D score ranged from 0 to 18, and the HADS‑A score from 0 to 15. PHQ‑9 scores ranged from 0 to 21. Based on the HADS score, 19 (9.5 %) of the patients had clinically significant PSD and 16 (8.0 %) of the participants had clinically significant PSAD. According to the total HADS score, 22 (11.0 %) of the patients had clinically significant affective disorders. With PHQ‑9 showed that clinically significant PSD was detected in 45 (22.5 %) patients. The HADS and PHQ‑9 scores had a strong positive significant correlation, but neither of them correlated with the age or sex of the patients, the subtype or severity of CS. However, univariate analysis showed that the risk of clinically significant PSD at discharge (according to HADS‑D) was significantly directly related to age and atrial fibrillation in addition to inverse relationship with the BI, MMSE and MoCA scores, LA subtype of IS and ICH. The risk of moderate to severe PSD (according to PHQ‑9) had a statistically significant direct corelation with the initial NIHSS score, as well as an inverse corelation with the baseline BI, MMSE, and MoCA scores. In multivariate analysis, 4 features were independently associated with PSD (HADS‑D > 10) at discharge: initial MMSE score (OR 0.93; 95 % CI 0.88 — 0.98, on average, for each additional point, p = 0.006), arterial hypertension (OR 8.5; 95 % CI 0.9 — 76.3; p = 0.057) or obesity (OR 0.23; 95 % CI 0.05 — 1.14; p = 0.072) as well as hospitalization after 30 days from CS onset. The predictive model based on these 4 variables had excellent sensitivity (94.7 %) and satisfactory specificity (73.3 %) and could assess the risk of developing PSD with good accuracy (AUC = 0.847). Furthermore, three factors were independent predictors of moderate or severe PSD (PHQ‑9 > 9) at discharge: age (OR 1.04; 95 % CI 1.00 — 1.08, on average, for each additional year, p = 0.028), the baseline MoCA score (OR 0.94; 95 % CI 0.91 — 0.98, on average, with an increase in the score for each additional point, p = 0.005) and UN subtype of IS. The prognostic model based on the latter 3 variables had satisfactory sensitivity (65.1 %) and specificity (75.5 %), but good accuracy of PSD prediction (AUC = 0.735). Conclusions. The HADS and PHQ‑9 scores in CS patients varied widely, and indicated high prevalence of clinically significant PSD and PSAD. HADS and PHQ‑9 scores correlated with each other, but not with age, sex, subtype, or severity of stroke. Elderly patients with significant cognitive impairment on admission were at a higher risk of affective disorders. The prognostic models allow accurate PSD prediction, which can contribute to the timely detection and initiation of PSD treatment in patients at risk.

Identifying biomarkers for epilepsy after cerebral malaria in Zambian children: rationale and design of a prospective observational study

IntroductionMalaria affecting the central nervous system (CM) is a major contributor to paediatric epilepsy in resource-poor settings, with 10%–16% of survivors developing epilepsy within 2 years of infection. Despite high...

Right frontal lobe AVM rupture with the formation of an intraparenchymal hematoma of the medial sections of the right fronto-parietal region and the corpus callosum. Clinical case of staged treatment and literature review

In the article, we report on a case of a 13‑year-old teenager with a verified intracranial hemorrhage resulting from an arteriovenous malformation (AVM) rupture in the right frontal lobe. Staged combined surgical treatment was carried out. The article discusses the features of diagnosis and tactics of surgical treatment of children with arteriovenous malformations in the acute and subacute periods of intracranial hemorrhage (ICH). Purpose of the study: Presentation and assessment of a clinical case and the combined treatment of the spontaneously ruptured AVM of the medial parts of the right frontal lobe with the formation of intracerebral hematoma of the medial parts of the fronto-parietal region and the corpus callosum in the ICH acute and subacute periods.

Modern capabilities of the computed tomography in orbital traumatic injuries diagnosis

BACKGROUND: Nowadays the problem of orbital trauma remains extremely relevant. Combined damage of several anatomical structures, globe injury, various clinical manifestations, the necessity of optimal surgical treatment require high-quality, timely diagnostics. Considering the current development of diagnostic equipment, postprocessing of CT data acquires the key role in order to obtain objective diagnostic information in patients with orbital trauma.
 AIM: Evaluation of the effectiveness of the developed methods for CT data assessing in patients with orbital trauma.
 MATERIALS AND METHODS: From 2016 to 2021 a total of 107 patients (100%) with orbital injuries were examined in Sechenov University clinics. All patients were distributed depending on the injury occurrence time: 50 patients (47%) in acute and subacute periods, 30 patients (28%) in the period of formation of post-traumatic deformities, 27 patients (25%) in the period of formed post-traumatic deformities. All patients (n = 107; 100%) underwent CT data analysis according to the developed protocol: analysis of bone and soft tissue trauma using a specialized algorithm, assessment of orbital volumes, evaluation of defects in the inferior orbital wall, examination of the globe position and of changes in the density of the orbital soft tissues.
 RESULTS: In the preoperative period the developed algorithm for orbital volumes measuring additionally revealed a post-traumatic increase in orbital volume in 21 patients (19%). The technique for the globe position assessing additionally revealed the risk of enophthalmos in 9 patients (8.1%), and in 1 case (0.9%) the suspicion of globe displacement was not confirmed. The defects of the inferior orbital wall were classified into small (n = 18; 17%), medium (n = 31; 29%) and large/total (n = 38; 35% and n = 20; 19%, respectively). In 88 patients (82%), the ratio of the defect to the entire inferior orbital wall was more than 6.65%, in 19 patients (18%) less than 6.65%. Changes in the density of the orbital soft tissues were as follows: soft tissue edema n = 60 (56%), soft tissue atrophy n = 28 (27%), hematoma of the orbital soft tissues n = 10 (9%), density was not changed n = 9 (8%). In the postoperative period, the developed methods for CT data processing revealed incomplete restoration of the orbital volume in 31 cases (29%), incomplete coverage of the inferior orbital wall defect in 38 cases (35%), globe displacement in 14 cases (13%), which was not determined by the standard CT data assessment without the specialized technique. In 7 cases (6%), a suspicion of an increase in the orbital volume was not confirmed by the developed methodology.
 CONCLUSION: The developed methods for measuring orbit volumes, assessing defects in the lower orbital wall, the globe position, and the condition of the orbital soft tissues provide statistically reliable additional diagnostic information about the patients condition and personalized approach for preoperative planning for each patient.

Standard toxicity study of clinical-grade allogeneic human bone marrow-derived clonal mesenchymal stromal cells

IntroductionMesenchymal stromal cells (MSCs) have opened a new window to treat inflammatory and non-inflammatory diseases. Nonetheless, their clinical applications require rigorous control and monitoring procedures to ensure full compliance with the principles of good manufacturing practice (GMP). Various evaluations should be passed in conjunction with the development of these newly emerging therapeutic products from bench-to-bedside. These evaluations include in vitro characterization, preclinical studies, and clinical trials to ensure product safety and efficacy. Therefore, a robust and well-designed preclinical study is critical to confirm product safety. This study aims to determine the probable toxicity effects of local and systemic injections of cryopreserved human bone marrow-derived clonal MSCs (BM-cMSCs) during subacute and subchronic periods of time.MethodsBM-cMSCs were characterized according to the International Society for Cell and Gene Therapy (ISCT) criteria for MSCs. Both safety and toxicity of the BM-cMSCs population produced under GMP-compatible conditions were assessed in both sexes of Sprague Dawley (SD) rats via systemic intravenous (IV) administration and local injection in intervertebral disc (IVD). Behavioral changes, clinical signs of toxicity, and changes in body weight, water and food consumption were the important variables for product toxicity testing over 14 consecutive days during the subacute period and 90 consecutive days during the subchronic period. At the end of the assessment periods, the rats were killed for histopathology analysis of the target tissues. The BM-cMSCs potential for tumorigenicity was checked in nude mice.ResultsSingle IV and IVD injections of BM-cMSCs did not cause significant signs of clinical toxicity, or changes in laboratory and histopathology data during the subacute (14 day) and subchronic (90 day) periods. Ex vivo-expanded and cryopreserved BM-cMSCs did not induce tumor formation in nude mice.ConclusionThe results suggest that local and systemic administrations of xenogeneic BM-cMSCs in both sexes of SD rats do not cause toxicity during the subacute and subchronic periods of time. Also, BM-cMSCs were non-tumorigenic in nude mice.

Acute and 28-day repeated dose toxicity evaluations of cold pressed Pinus halepensis Mill. seed oil in mice and rats

Pinus halepensis Mill. seed (Pinaceae), popularly known as ‘Zgougou’, is widely consumed in the Mediterranean countries and used traditionally in the treatment of some diseases such as bronchitis, rheumatism, infection, and inflammation. The present study aimed to evaluate the oral safety of cold pressed oil of Pinus halepensis Mill. seeds (COPHS) by acute and 28-day repeated dose toxicities studies in Wistar mice and rats, respectively. In the acute toxicity study, oral administration of COPHS to mice did not provoke mortality or any toxic signs at doses up to 5000 mg/kg bw. After administration of COPHS at doses of 250, 500, and 1000 mg/kg bw/day for 28 days, no abnormal changes were observed in body weight, water intake, food consumption, organ weight, blood haematological, serum biochemistry parameters, and histology profile. Furthermore, there was no animal death or any symptom of toxicity in any group during sub-acute toxicity test period. Our findings demonstrate that COPHS is relatively non-toxic and has a large safety margin (>5000 mg/kg). The results of the present research provide basic reference data for food consumption and for future in vivo screening of biological and pharmacological properties of cold pressed oil of Pinus halepensis Mill. seeds.

A Brief Measure Assessing Adolescents' Daily In-Hospital Function Predicts Pain and Health Outcomes at Home After Major Surgery.

Pain-related function is not routinely assessed in the hospital. This prospective cohort study examined whether patients' daily pain-related function during hospitalization, based on the validated Youth Acute Pain Functional Ability Questionnaire (YAPFAQ), is associated with pain and quality of life. The YAPFAQ is a 12-item measure assessing functional parameters of recovery related to pain and has been validated in children and adolescents with sickle cell disease and after surgery. Adolescents undergoing major musculoskeletal surgery (n = 93) completed the YAPFAQ daily for up to 3 days after surgery. Adolescents self-reported health-related quality of life on the Pediatric Quality of Life Inventory and pain intensity on a numeric rating scale at home 2weeks after surgery. Higher YAPFAQ scores, representing poorer function, were associated with higher pain intensity (β = 0.2, P = 0.04) and poorer health-related quality of life (β = -0.3, P = 0.01) at home 2 weeks after surgery. This functional measure could be clinically relevant to providers to identify adolescents at risk of difficulty with pain and recovery at home after surgery who might need further intervention to minimize functional impairment and delayed recovery. This article provides conceptual validation of a functional score for pediatric pain, the YAPFAQ, to assess pain intensity and health-related quality of life in the subacute period.

Use of Mayer Wave Activity to Identify Discordant Cardiovascular Autonomic Function during the Subacute Period of Spinal Cord Injury as a Potential Means to Identify Co-Occurring Traumatic Brain Injury (P1-1.Virtual)

Use of Mayer Wave Activity to Identify Discordant Cardiovascular Autonomic Function during the Subacute Period of Spinal Cord Injury as a Potential Means to Identify Co-Occurring Traumatic Brain Injury (P1-1.Virtual)

Is There a Time-Sensitive Window in Patients With Stroke to Enhance Arm Recovery With Higher Intensity Motor Therapy?

Is There a Time-Sensitive Window in Patients With Stroke to Enhance Arm Recovery With Higher Intensity Motor Therapy?

The use of an adhesive balm with magnetic polymers, hexethydine, cytylpyridinium chloride and hyaluronic acid in the treatment of inflammatory periodontal diseases

The article presents the results of a study of an adhesive balm with magnetic polymers, hexethidine, cytylpyridinium chloride and hyaluronic acid in the treatment of inflammatory periodontal diseases. Revealed and scientifically proven its effectiveness in acute and subacute periods of the course of gingivitis and periodontitis. The study involved 40 patients aged 20 to 60 years, in whom the anti-inflammatory and hemostatic effect of the adhesive balm on the inflamed periodontal soft tissues was studied. During the monitoring of index indicators, it was revealed that the PMA index decreased from 50,72 to 16,31 by the end of the study. After 14 days, the hemostatic efficiency was 56,25%. Local allergic reactions and irritation were not observed during the study. It has been proven that an adhesive paste with magnetic polymers, hexethydine, cytylpyridinium chloride and hyaluronic acid has a bactericidal effect on the microflora of the oral cavity.

Upper Limb Training with a Dynamic Hand Orthosis in Early Subacute Stroke: A Pilot Randomized Trial.

To investigate the effect of the addition of a dynamic hand orthosis to unilateral task-oriented training in early subacute stroke. Pilot randomized trial with concealed allocation, measurer blinding, and intention-to-treat analysis. Rehabilitation hospital. Thirty subacute stroke patients with moderate-to-severe upper limb disability. All participants received 4 weeks (60 min per day, 5 days a week) of unilateral task-oriented training. The experimental group (n = 15) wore a dynamic hand orthosis during half of the training time (i.e. 30 min per day). Primary outcome was the upper limb activity measured using the Action Research Arm Test (ARAT) measured at baseline and 4 weeks. Secondary outcomes were the Nine-hole Peg Test, Fugl-Meyer Assessment for upper extremity, grip strength, modified Ashworth Scale, Barthel Index and EuroQol-5D. No difference between groups was found for the primary outcome ARAT (mean difference 4/57, 95% confidence interval (95% CI) -5 to 13) nor for any secondary outcome. No additional benefit was found of wearing a dynamic hand orthosis during unilateral taskoriented training in the early subacute period.