Sporadic inclusion body myositis-derived myotube culture revealed muscle cell-autonomous expression profiles.

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.

Quantitative evaluation of adhesion severity around subscapularis and its relationship with shoulder range of motion in frozen shoulder and rotator cuff disorder: an observational study using dynamic ultrasonography.

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.

Impact of center volume on in-hospital mortality in adult patients with out­of­hospital cardiac arrest resuscitated using extracorporeal cardiopulmonary resuscitation: a secondary analysis of the SAVE-J II study.

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).

Chest CT findings in severe acute respiratory distress syndrome requiring V-V ECMO: J-CARVE registry.

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.

External Validation of the CAST and rCAST Score in Patients With Out-of-Hospital Cardiac Arrest Who Underwent Extracorporeal Cardiopulmonary Resuscitation: A Secondary Analysis of the SAVE-J II Study.

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.