ABSTRACT
Sporadic inclusion body myositis (sIBM) is a muscle disease in older people and is characterized by inflammatory cell invasion into intact muscle fibers and rimmed vacuoles. The pathomechanism of sIBM is not fully elucidated yet, and controversy exists as to whether sIBM is a primary autoimmune disease or a degenerative muscle disease with secondary inflammation. Previously, we established a method of collecting CD56-positive myoblasts from human skeletal muscle biopsy samples. We hypothesized that the myoblasts derived from these patients are useful to see the cell-autonomous pathomechanism of sIBM. With these resources, myoblasts were differentiated into myotubes, and the expression profiles of cell-autonomous pathology of sIBM were analyzed. Myoblasts from three sIBM cases and six controls were differentiated into myotubes. In the RNA-sequencing analysis of these "myotube" samples, 104 differentially expressed genes (DEGs) were found to be significantly upregulated by more than twofold in sIBM, and 13 DEGs were downregulated by less than twofold. For muscle biopsy samples, a comparative analysis was conducted to determine the extent to which "biopsy" and "myotube" samples differed. Fifty-three DEGs were extracted of which 32 (60%) had opposite directions of expression change (e.g., increased in biopsy vs decreased in myotube). Apolipoprotein E (apoE) and transmembrane protein 8C (TMEM8C or MYMK) were commonly upregulated in muscle biopsies and myotubes from sIBM. ApoE and myogenin protein levels were upregulated in sIBM. Given that enrichment analysis also captured changes in muscle contraction and development, the triggering of muscle atrophy signaling and abnormal muscle differentiation via MYMK or myogenin may be involved in the pathogenesis of sIBM. The presence of DEGs in sIBM suggests that the myotubes formed from sIBM-derived myoblasts revealed the existence of muscle cell-autonomous degeneration in sIBM. The catalog of DEGs will be an important resource for future studies on the pathogenesis of sIBM focusing on primary muscle degeneration.
Subject(s)
Muscle Fibers, Skeletal , Myositis, Inclusion Body , Humans , Myositis, Inclusion Body/metabolism , Myositis, Inclusion Body/genetics , Myositis, Inclusion Body/pathology , Muscle Fibers, Skeletal/metabolism , Muscle Fibers, Skeletal/pathology , Cell Differentiation , Aged , Female , Male , Cells, Cultured , Transcriptome , Myoblasts/metabolism , Myoblasts/pathology , Biopsy , Gene Expression Profiling , Middle AgedABSTRACT
Background: This study aimed to evaluate the severity of adhesion between muscles in the shoulder joint using dynamic ultrasonography and to confirm whether adhesions cause range of motion (ROM) restrictions. Methods: Twenty-four shoulders from 15 frozen shoulder patients and 24 shoulders from 18 rotator cuff disorder patients were enrolled. We obtained ultrasound video sequences of the subscapularis (SSC) and deltoid muscles during shoulder external rotation. The mean stretching velocities of the deltoid and SSC were subsequently analyzed using a personal computer. If adhesions occurred between both muscles, the deltoid was stretched more vigorously, and we calculated mean stretching velocity of the deltoid / SSC as adhesion severity. The coracohumeral ligament thickness was measured using the same images. Shoulder ROM was measured by using a universal goniometer. Results: The intraclass correlation coefficients (1.1) and (2.1) of the adhesion severity measurements were 0.85 and 0.91, respectively. Multiple linear regression analysis revealed that the adhesion severity is a significant predictor for external rotation ROM in the rotator cuff disorder group (R2 = 0.44, F = 10.1, P < .01, t = -2.9), while coracohumeral ligament thickness predicts ROM in the frozen shoulder group (R2 = 0.28, F = 5.5, P = .01, t = -3.0). Conclusion: The proposed method is reliable. Muscle adhesion causes ROM restriction of the shoulder joint. The primary cause of shoulder ROM restriction differed between the diagnostic groups.
ABSTRACT
Recently, patients with out-of-hospital cardiac arrest (OHCA) refractory to conventional resuscitation have started undergoing extracorporeal cardiopulmonary resuscitation (ECPR). However, the mortality rate of these patients remains high. This study aimed to clarify whether a center ECPR volume was associated with the survival rates of adult patients with OHCA resuscitated using ECPR. This was a secondary analysis of a retrospective multicenter registry study, the SAVE-J II study, involving 36 participating institutions in Japan. Centers were divided into three groups according to the tertiles of the annual average number of patients undergoing ECPR: high-volume (≥ 21 sessions per year), medium-volume (11-20 sessions per year), or low-volume (< 11 sessions per year). The primary outcome was survival rate at the time of discharge. Patient characteristics and outcomes were compared among the three groups. Moreover, a multivariable-adjusted logistic regression model was applied to study the impact of center ECPR volume. A total of 1740 patients were included in this study. The center ECPR volume was strongly associated with survival rate at the time of discharge; furthermore, survival rate was best in high-volume compared with medium- and low-volume centers (33.4%, 24.1%, and 26.8%, respectively; P = 0.001). After adjusting for patient characteristics, undergoing ECPR at high-volume centers was associated with an increased likelihood of survival compared to middle- (adjusted odds ratio 0.657; P = 0.003) and low-volume centers (adjusted odds ratio 0.983; P = 0.006). The annual number of ECPR sessions was associated with favorable survival rates and lower complication rates of the ECPR procedure.Clinical trial registration: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000041577 (unique identifier: UMIN000036490).
Subject(s)
Cardiopulmonary Resuscitation , Out-of-Hospital Cardiac Arrest , Adult , Humans , Out-of-Hospital Cardiac Arrest/therapy , Hospital Mortality , Treatment Outcome , Cardiopulmonary Resuscitation/methods , Retrospective StudiesABSTRACT
BACKGROUND: Chest computed tomography findings are helpful for understanding the pathophysiology of severe acute respiratory distress syndrome (ARDS). However, there is no large, multicenter, chest computed tomography registry for patients requiring veno-venous extracorporeal membrane oxygenation (V-V ECMO). The aim of this study was to describe chest computed tomography findings at V-V ECMO initiation and to evaluate the association between the findings and outcomes in severe ARDS. METHODS: This multicenter, retrospective cohort study enrolled patients with severe ARDS on V-V ECMO, who were admitted to the intensive care units of 24 hospitals in Japan between January 1, 2012, and December 31, 2022. RESULTS: The primary outcome was 90-day in-hospital mortality. The secondary outcomes were the successful liberation from V-V ECMO and the values of static lung compliance. Among the 697 registry patients, of the 582 patients who underwent chest computed tomography at V-V ECMO initiation, 394 survived and 188 died. Multivariate Cox regression showed that traction bronchiectasis and subcutaneous emphysema increased the risk of 90-day in-hospital mortality (hazard ratio [95% confidence interval] 1.77 [1.19-2.63], p = 0.005 and 1.97 [1.02-3.79], p = 0.044, respectively). The presence of traction bronchiectasis was also associated with decreased successful liberation from V-V ECMO (odds ratio: 0.27 [0.14-0.52], p < 0.001). Lower static lung compliance was associated with some chest computed tomography findings related to changes outside of pulmonary opacity, but not with the findings related to pulmonary opacity. CONCLUSIONS: Traction bronchiectasis and subcutaneous emphysema increased the risk of 90-day in-hospital mortality in patients with severe ARDS who required V-V ECMO.
ABSTRACT
BACKGROUND: Risk stratification is important in patients with post-cardiac arrest syndrome. The Post-Cardiac Arrest Syndrome for Therapeutic Hypothermia (CAST) and revised CAST (rCAST) scores have been well validated for predicting neurological outcomes, particularly for conventionally resuscitated patients with post-cardiac arrest syndrome. However, no studies have evaluated patients undergoing extracorporeal cardiopulmonary resuscitation. METHODS AND RESULTS: Adult patients with out-of-hospital cardiac arrest who underwent extracorporeal cardiopulmonary resuscitation were analyzed in this retrospective observational multicenter cohort study. We validated the accuracy of the CAST/rCAST scores for predicting neurological outcomes at 30 days. Moreover, we compared the predictive performance of these scores with the TiPS65 risk score derived from patients with out-of-hospital cardiac arrest who were resuscitated using extracorporeal cardiopulmonary resuscitation. A total of 1135 patients were analyzed. The proportion of patients with favorable neurological outcomes was 16.6%. In the external validation, the area under the receiver operating characteristic curve of the CAST score was significantly higher than that of the rCAST score (area under the receiver operating characteristic curve 0.677 versus 0.603; P<0.001), but there was no significant difference with that of the TiPS65 score (versus 0.633; P=0.154). Both CAST/rCAST risk scores showed good calibration (Hosmer-Lemeshow test: P=0.726 and 0.674), and the CAST score showed significantly better predictability in net reclassification compared with the rCAST (P<0.001) and TiPS65 scores (P=0.001). CONCLUSIONS: The prognostic accuracy of the CAST score was significantly better than that of other risk scores in net reclassification. The CAST score may help to predict neurological outcomes in patients with out-of-hospital cardiac arrest who undergo extracorporeal cardiopulmonary resuscitation. However, the predictive value of the CAST score was not sufficiently high for clinical application. REGISTRATION: URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000041577; Unique identifier: UMIN000036490.
Subject(s)
Cardiopulmonary Resuscitation , Out-of-Hospital Cardiac Arrest , Post-Cardiac Arrest Syndrome , Adult , Humans , Out-of-Hospital Cardiac Arrest/diagnosis , Out-of-Hospital Cardiac Arrest/therapy , Cohort Studies , Retrospective Studies , Prognosis , Cardiopulmonary Resuscitation/methodsABSTRACT
INTRODUCTION: While limiting the tidal volume to 6 mL/kg during veno-venous extracorporeal membrane oxygenation (V-V ECMO) to ameliorate lung injury in patients with acute respiratory distress syndrome (ARDS) is widely accepted, the best setting for positive end-expiratory pressure (PEEP) is still controversial. This study is being conducted to investigate whether a higher PEEP setting (15 cmH2O) during V-V ECMO can decrease the duration of ECMO support needed in patients with severe ARDS, as compared with a lower PEEP setting. METHODS AND ANALYSIS: The study is an investigator-initiated, multicentre, open-label, two-arm, randomised controlled trial conducted with the participation of 20 intensive care units (ICUs) at academic as well as non-academic hospitals in Japan. The subjects of the study are patients with severe ARDS who require V-V ECMO support. Eligible patients will be randomised equally to the high PEEP group or low PEEP group. Recruitment to the study will continue until a total of 210 patients with ARDS requiring V-V ECMO support have been randomised. In the high PEEP group, PEEP will be set at 15 cmH2O from the start of V-V ECMO until the trials for liberation from V-V ECMO (or until day 28 after the allocation), while in the low PEEP group, the PEEP will be set at 5 cmH2O. Other treatments will be the same in the two groups. The primary endpoint of the study is the number of ECMO-free days until day 28, defined as the length of time (in days) from successful libration from V-V ECMO to day 28. The secondary endpoints are mortality on day 28, in-hospital mortality on day 60, ventilator-free days during the first 60 days and length of ICU stay. ETHICS AND DISSEMINATION: Ethics approval for the trial at all the participating hospitals was obtained on 27 September 2022, by central ethics approval (IRB at Hiroshima University Hospital, C2022-0006). The results of this study will be presented at domestic and international medical congresses, and also published in scientific journals. TRIAL REGISTRATION NUMBER: The Japan Registry of Clinical Trials jRCT1062220062. Registered on 28 September 2022. PROTOCOL VERSION: 28 March 2023, version 4.0.
Subject(s)
Extracorporeal Membrane Oxygenation , Respiratory Distress Syndrome , Humans , Positive-Pressure Respiration/methods , Respiratory Distress Syndrome/therapy , Tidal Volume , Ventilators, Mechanical , Randomized Controlled Trials as Topic , Multicenter Studies as TopicABSTRACT
PURPOSE: The objective of the present study was to examine the relationship between anxiety and sleep disorder during the COVID-19 pandemic and to evaluate whether sleep disorder is mediated by the decreased frequency of going out. METHODS: The data of a total of 1976 residents aged 18 years and over who had responded to a self-reported questionnaires at a health survey in 2020 were analyzed. The subjects were divided into four groups based on their response to the questionnaire on anxiety about the COVID-19 pandemic. Sleep disorder was measured using the Athens Insomnia Scale (AIS). A cross-sectional analysis was performed to examine the association between anxiety about the COVID-19 pandemic and AIS scores. Mediation analysis was used to calculate the association between anxiety and AIS scores during the COVID-19 pandemic, with decreased frequency of going out as a potential mediating variable. RESULTS: In the cross-sectional study, the level of anxiety about the COVID-19 pandemic was significantly associated with the AIS score (p < 0.001). On mediation analysis, the direct effect of the relationship showed that anxiety positively influenced AIS scores (ß = 0.283, p < 0.01). The indirect effect of the relationship showed that the decreased frequency of going out positively mediated the relationship between anxiety and AIS scores (ß = 0.342, p < 0.05). The decreased frequency of going out accounted for almost 10% of the AIS score. CONCLUSION: The present study found that anxiety about the COVID-19 pandemic was significantly associated with sleep disorder, with the decreased frequency of going out mediating this association.
ABSTRACT
Low back pain (LBP) and neck pain (NP) are common health problems worldwide. LBP often coexists with NP; however, the association between these pains remains unclear. The purpose of this study was to clarify the association between LBP and NP, focusing on dose-dependent effects. This study used a 3-year longitudinal cohort data of people living in disaster-stricken areas after the Great East Japan Earthquake (n = 2,118). LBP and NP were assessed at 4, 5, 6, and 7 years after the disaster. LBP was categorized according to its frequency. Multivariate logistic regression analyses were performed to assess the association between LBP and NP, and the effect of preceding LBP on the subsequent onset of NP, according to the frequency of LBP. LBP was significantly associated with NP, and the association was stronger with increased frequency of LBP. Adjusted odds ratios (95% confidence intervals) were 2.40 (1.71-3.37) for "1", 3.99 (2.82-5.66) for "2", and 6.08 (4.40-8.41) for "≥ 3" in frequency when the absence of LBP was used as a reference (p for trend < 0.001). Furthermore, preceding LBP was significantly associated with subsequent onset of NP, and the effect was stronger with increased frequency of LBP. Adjusted odds ratios (95% confidence intervals) were 2.44 (1.62-3.68) for "1" and 2.68 (1.77-4.05) for "≥ 2" in frequency when the absence of LBP was used as a reference (p for trend < 0.001). LBP is associated with NP in a dose-dependent manner. The association between LBP and NP should be considered to effectively treat these pains.
Subject(s)
Earthquakes , Low Back Pain , Humans , Longitudinal Studies , Neck Pain/epidemiology , Low Back Pain/epidemiology , Japan/epidemiology , SurvivorsABSTRACT
BACKGROUND: Atraumatic rotator cuff tears (ARCTs) are frequently concomitant with adduction restriction of the glenohumeral joint (GHJ). Adduction manipulation (AM) removes the restriction and relieves pain. The present study aimed to investigate the clinical efficacy of AM versus physiotherapy (PT) in ARCTs. METHODS: Eighty-eight patients with adduction restriction were allocated to the AM and PT groups (n = 44 per group). The glenohumeral adduction angle (GAA) was calculated using X-rays at the first and last follow-up appointments. We recorded pain severity (visual analog scale, VAS), flexion, abduction, external rotation (ER), internal rotation (IR), and American Shoulder and Elbow Society (ASES) and Constant scores at baseline and at 1-, 3-, 6-, and 12- month follow-ups. RESULTS: Forty-three patients (23 males, average age 71.3 years) in the AM group and 41 (16 males, average age 70.7 years) in the PT group were consequently analyzed. At the 1-month follow-up, VAS, shoulder motion except ER, ASES and Constant scores were much better in the AM group than in the PT group, whereas those in the PT group improved gradually up to 12 months. At the final follow-up, flexion, abduction, and Constant score were significantly better in the AM group than in the PT group. The GAA at the initial and final examinations was -21.6° and -3.2°, respectively, in the AM group, and -21.1° and -14.4°, respectively, in the PT group. CONCLUSIONS: The AM procedure, which had better clinical efficacy than PT, is recommended as the first conservative treatment option for ARCTs.
ABSTRACT
BACKGROUND: Knee is the most commonly injured part of the body in young athletes. Knee pain in several studies have been seen to be more prevalent in active adolescents compared to inactive, although common in both groups. Nevertheless, few studies with large sample size have been published reporting the difference of the prevalence of knee pain for each sport among young sports players. This study investigated the point prevalence of knee pain among young sports players aged 6-15 years old according to age, sex, and sports discipline. Furthermore, this study investigated the association between knee pain and sports discipline among young sports players. METHODS: A cross-sectional study was conducted using a self-reported questionnaire on young sports players aged 6-15 years from the Miyagi Amateur Sports Association. Multivariable logistic regression models were used to examine the association between knee pain and sports discipline and were adjusted for age, sex, body mass index (BMI), training days per week, and training hours per weekday and weekend. RESULTS: A total of 7234 young sports players were included. The point prevalence of knee pain was 10.9%. Females (13.3%) had more knee pain than males (9.8%). Young, 13-year-old sports players had the highest prevalence of knee pain (19.1%). The multivariable analysis showed that the highest odds ratio [95% confidence interval] was observed for handball players (2.42 [1.01-5.81]). In addition, hand ball, mini-basketball (odds ratio 1.85; 95% CI 1.38-2.47), and basketball (odds ratio 1.66; 95% CI 1.23-2.26) were significantly associated with knee pain, compared with football. The lowest odds ratio was observed for swimming (0.34 [0.05-2.54]), followed by karate (odds ratio 0.38; 95% CI 0.16-0.89) and baseball (odds ratio 0.47; 95% CI 0.35-0.64). CONCLUSION: The prevalence of knee pain among young athletes differed according to age, sex, and sports discipline. Their parents and clinicians should recognize this information to manage knee pain among young sports players.
ABSTRACT
Lacosamide is an antiepileptic drug that acts on voltage-gated sodium channels and was approved as an antiepileptic by the Food and Drug Administration in 2008. Although the efficacy and safety of lacosamide have been established in many previous trials, some case reports have shown that it may lead to cardiovascular side effects, especially in patients with electrical conduction system disorders. We herein report a case of life-threatening cardiac arrhythmia caused by lacosamide intoxication that was successfully treated with veno-arterial extracorporeal membrane oxygenation.
Subject(s)
Extracorporeal Membrane Oxygenation , Humans , Lacosamide , Anticonvulsants/therapeutic use , TachycardiaABSTRACT
Joint immobilization, which ensures rest and accelerates tissue recovery in musculoskeletal disorders, often causes joint contracture, for which there is still no effective prevention. To address this, we investigated the effects of extracorporeal shockwave therapy (ESWT) in preventing joint contracture, in a unilaterally immobilized knee rat model. Under general anesthesia, ESWT (0.25 mJ/mm2 , 3000 shot, 4 Hz, 3 days/week) was administered from 1 day after immobilization up to 2, 4, and 6 weeks. The immobilized control group received general anesthesia without ESWT. We evaluated joint angle, tissue elasticity, and gene and protein expression related to fibrosis, inflammation, and angiogenesis in the joint capsule. Relative to the control, the ESWT group had greater joint angle at 4 and 6 weeks, and lower posterior-capsule elasticity at 6 weeks. In the ESWT group, at 6 weeks, gene expression of collagen type I (col1α1), connective tissue growth factor (CTGF), and α-smooth muscle actin (α-SMA) was significantly downregulated, whereas interleukin-6 (IL-6) and hypoxia-inducible factor-1α (HIF-1α) gene expression was upregulated, relative to that in the control. Compared with that in the control, at 4 and 6 weeks, the ratio of CTGF+ cells was significantly lower in the ESWT group; at 4 weeks, the ESWT group had significantly fewer CD68+ cells in the adhesion area, and at 6 weeks, significantly more blood vessels. Statement of Clinical Significance: In a rat model, ESWT counteracted fibrosis, suppressed macrophage infiltration, and promoted neovascularization, reducing elasticity, and increasing joint range-ofmotion. ESWT offers a potential new strategy to prevent progression in joint contracture.
Subject(s)
Contracture , Extracorporeal Shockwave Therapy , Rats , Animals , Knee Joint/pathology , Joint Capsule/pathology , Contracture/prevention & control , Contracture/metabolism , FibrosisABSTRACT
BACKGROUND: Functional disability is a major health issue in an aging population. Low back pain (LBP) is a common health concern that can lead to functional disability in the elderly; nonetheless, their association has not yet been clarified. This study aimed to examine the association between LBP and functional disability in the elderly, with a focus on its dose-dependent effects. METHODS: This study used the 4-year longitudinal data of people living in disaster-affected areas after the Great East Japan Earthquake (aged â§65, n = 914). LBP and physical function were assessed at 2, 4, and 6 years after the disaster. Multivariate logistic regression analyses were performed to assess the association between LBP and low physical function, as well as the effect of preceding LBP on the onset of low physical function. RESULTS: LBP was significantly associated with low physical function, and the association became stronger as the duration of LBP increased. Adjusted odds ratios (95% confidence intervals) were 1.27 (0.79-2.06) in "< 2 years," 1.95 (1.01-3.77) in "≥2 years and <4 years," and 2.34 (1.35-4.06) in "≥4 years" (p for trend = 0.009). Additionally, preceding LBP was significantly associated with the onset of low physical function, and the effect became prominent as the duration of LBP increased. Adjusted odds ratios (95% confidence intervals) were 2.28 (1.19-4.37) in "< 2 years" and 2.82 (1.35-5.90) in "≥2 years" (p for trend = 0.003). CONCLUSIONS: LBP is associated with physical disability among the elderly in a dose-dependent manner. Therefore, prevention and treatment of LBP are important for preventing functional disability.
Subject(s)
Disasters , Earthquakes , Low Back Pain , Aged , Humans , Longitudinal Studies , Low Back Pain/diagnosis , Low Back Pain/epidemiology , Japan/epidemiologyABSTRACT
BACKGROUND: Low back pain and sleep disturbance are common health problems worldwide which are also commonly observed among people after natural disasters. These symptoms are well known to coexist, and recent reports have indicated that sleep disturbance is a risk factor for low back pain. However, the influence of low back pain on sleep disturbance has rarely been assessed; therefore, this study aimed to clarify the association of low back pain with sleep disturbance, especially focusing on the frequency of low back pain, using 3-year cohort data after the Great East Japan Earthquake. METHODS: This study used the data obtained from people living in the disaster-affected areas after the Great East Japan Earthquake (n = 2,097). Low back pain and sleep disturbance were assessed at 4, 5, 6, and 7 years after the disaster. The frequency of low back pain was defined as the number of low back pain episodes at and before the evaluation time point and categorized into five groups such as absence, 1, 2, 3, and 4 at the fourth time point and four groups such as absence, 1, 2, and 3 at the third time point. Multivariate logistic regression analyses were conducted to assess the association of low back pain with sleep disturbance. RESULTS: Low back pain was significantly associated with sleep disturbance, and the association was stronger in participants with more frequent low back pain (adjusted odds ratios [95% confidence intervals],1.46 [1.10-1.95] in "1"; 2.02 [1.49-2.74] in "2"; 2.38 [1.67-3.40] in "3"; and 4.08 [2.74-6.06] in "4" in the frequency of low back pain) (P for trend < 0.001). Furthermore, antecedent low back pain was significantly associated with new-onset sleep disturbance, and the association was robust in more frequent low back pain (adjusted odds ratios [95% confidence intervals],1.60 [1.05-2.44] in "1"; 1.96 [1.20-3.21] in "2"; and 2.17 [1.14-4.14] in "3" in the frequency of low back pain) (P for trend = 0.007). CONCLUSION: Our study showed that low back pain is strongly associated with sleep disturbance. Attention should be paid to low back pain to prevent and treat sleep disturbance, especially focusing on chronicity of low back pain.
Subject(s)
Earthquakes , Low Back Pain , Sleep Wake Disorders , Humans , Longitudinal Studies , Japan/epidemiology , Low Back Pain/diagnosis , Low Back Pain/epidemiology , Low Back Pain/complications , Surveys and Questionnaires , Survivors , Sleep Wake Disorders/epidemiology , Sleep Wake Disorders/etiology , SleepABSTRACT
The physiological significance of skeletal muscle as a secretory organ is now well known but we can only speculate as to the existence of as-yet-unidentified myokines, especially those upregulated in response to muscle contractile activity. We first attempted to establish an "insert-chamber based in vitro exercise model" allowing the miniature but high cell-density culture state enabling highly developed contractile human myotubes to be readily obtained by applying electric pulse stimulation (EPS). By employing this in vitro exercise model, we identified R-spondin 3 (RSPO3) as a novel contraction-inducible myokine produced by cultured human myotubes. Contraction-dependent muscular RSPO3 mRNA upregulation was confirmed in skeletal muscles of mice subjected to sciatic nerve mediated in situ contraction as well as those of mice after 2 h of running. Pharmacological in vitro experiments demonstrated a relatively high concentration of metformin (millimolar range) to suppress the contraction-inducible mRNA upregulation of human myokines including RSPO3, interleukin (IL)-6, IL-8 and CXCL1. Our data also suggest human RSPO3 to be a paracrine factor that may positively participate in the myogenesis processes of myoblasts and satellite cells. Thus, the "insert chamber-based in vitro exercise model" is a potentially valuable research tool for investigating contraction-inducible biological responses of human myotubes usually exhibiting poorer contractility development even in the setting of EPS treatment.
Subject(s)
Muscle Contraction , Muscle Fibers, Skeletal , Thrombospondins , Animals , Electric Stimulation , Humans , Interleukin-6/genetics , Mice , Muscle Contraction/physiology , Muscle Fibers, Skeletal/physiology , Muscle, Skeletal/physiology , RNA, Messenger/genetics , Thrombospondins/geneticsABSTRACT
BACKGROUND: The prevalence of extracorporeal cardiopulmonary resuscitation (ECPR) in patients with out-of-hospital cardiac arrest (OHCA) has been increasing rapidly worldwide. However, guidelines or clinical studies do not provide sufficient data on ECPR practice. The aim of this study was to provide real-world data on ECPR for patients with OHCA, including details of complications. METHODS: We did a retrospective database analysis of observational multicenter cohort study in Japan. Adult patients with OHCA of presumed cardiac etiology who received ECPR between 2013 and 2018 were included. The primary outcome was favorable neurological outcome at hospital discharge, defined as a cerebral performance category of 1 or 2. RESULTS: A total of 1644 patients with OHCA were included in this study. The patient age was 18-93 years (median: 60 years). Shockable rhythm in the initial cardiac rhythm at the scene was 69.4%. The median estimated low flow time was 55 min (interquartile range: 45-66 min). Favorable neurological outcome at hospital discharge was observed in 14.1% of patients, and the rate of survival to hospital discharge was 27.2%. The proportions of favorable neurological outcome at hospital discharge in terms of shockable rhythm, pulseless electrical activity, and asystole were 16.7%, 9.2%, and 3.9%, respectively. Complications were observed during ECPR in 32.7% of patients, and the most common complication was bleeding, with the rates of cannulation site bleeding and other types of hemorrhage at 16.4% and 8.5%, respectively. CONCLUSIONS: In this large cohort, data on the ECPR of 1644 patients with OHCA show that the proportion of favorable neurological outcomes at hospital discharge was 14.1%, survival rate at hospital discharge was 27.2%, and complications were observed during ECPR in 32.7%.