Urinary Titin N-Fragment as a Biomarker of Muscle Atrophy, Intensive Care Unit-Acquired Weakness, and Possible Application for Post-Intensive Care Syndrome

Titin is a giant protein that functions as a molecular spring in sarcomeres. Titin interconnects the contraction of actin-containing thin filaments and myosin-containing thick filaments. Titin breaks down to form urinary titin N-fragments, which are measurable in urine. Urinary titin N-fragment was originally reported to be a useful biomarker in the diagnosis of muscle dystrophy. Recently, the urinary titin N-fragment has been increasingly gaining attention as a novel biomarker of muscle atrophy and intensive care unit-acquired weakness in critically ill patients, in whom titin loss is a possible pathophysiology. Furthermore, several studies have reported that the urinary titin N-fragment also reflected muscle atrophy and weakness in patients with chronic illnesses. It may be used to predict the risk of post-intensive care syndrome or to monitor patients’ condition after hospital discharge for better nutritional and rehabilitation management. We provide several tips on the use of this promising biomarker in post-intensive care syndrome

Urinary titin as a biomarker for muscle atrophy

Objective: Although skeletal muscle atrophy is common in critically ill patients, biomarkers associated with muscle atrophy have not been identified reliably. Titin is a spring-like protein found in muscles and has become a measurable biomarker for muscle breakdown. We hypothesized that urinary titin is useful for monitoring muscle atrophy in critically ill patients. Therefore, we investigated urinary titin level and its association with muscle atrophy in critically ill patients. Design: Two-center, prospective observational study Setting: Mixed medical/surgical intensive care unit (ICU) in Japan Patients: Nonsurgical adult patients who were expected to remain in ICU for >5 days Interventions: None Methods: Urine samples were collected on days 1, 2, 3, 5, and 7 of ICU admission. To assess muscle atrophy, rectus femoris cross-sectional area and diaphragm thickness were measured with ultrasound on days 1, 3, 5, and 7. Secondary outcomes included its relationship with ICU-acquired weakness (ICU-AW), ICU Mobility Scale (IMS), and ICU mortality. Measurements and Main Results: Fifty-six patients and 232 urinary titin measurements were included. Urinary titin (normal range: 1–3 pmol/mg Cr) was 27.9 (16.8–59.6), 47.6 (23.5–82.4), 46.6 (24.4–97.6), 38.4 (23.6–83.0), and 49.3 (27.4–92.6) pmol/mg Cr on days 1, 2, 3, 5, and 7, respectively. Cumulative urinary titin level was significantly associated with rectus femoris muscle atrophy on days 3–7 (p < 0.03), although urinary titin level was not associated with change in diaphragm thickness (p = 0.31–0.45). Furthermore, cumulative urinary titin level was associated with incidence of ICU-AW (p = 0.01) and ICU mortality (p = 0.02) but not with IMS (p = 0.18). Conclusions: In nonsurgical critically ill patients, urinary titin level increased 10–30 times compared with the normal level. The increased urinary titin level was associated with lower limb muscle atrophy, incidence of ICU-AW, and ICU mortality

Electrical muscle stimulation on upper and lower limb muscles in critically ill patients

Objectives: Electrical muscle stimulation (EMS) is widely used to enhance lower limb mobilization. Although upper limb muscle atrophy is common in critically ill patients, EMS application for the upper limbs has been rarely reported. The purpose of this study was to investigate whether EMS prevents upper and lower limb muscle atrophy and improves physical function. Design: Randomized controlled trial. Setting: Two-center, mixed medical/surgical intensive care unit (ICU). Patients: Adult patients who were expected to be mechanically ventilated for >48 h and stay in the ICU for >5 days. Interventions: Forty-two patients were randomly assigned to the EMS (n = 17) or control group (n = 19). Measurements and Main Results: Primary outcomes were change in muscle thickness and cross-sectional area of the biceps brachii and rectus femoris from day 1 to 5. Secondary outcomes included incidence of ICU-acquired weakness (ICU-AW), ICU mobility scale (IMS), length of hospitalization, and amino acid levels. The change in biceps brachii muscle thickness was −1.9% vs. −11.2% in the EMS and control (p = 0.007) groups, and the change in cross-sectional area was −2.7% vs. −10.0% (p = 0.03). The change in rectus femoris muscle thickness was −0.9% vs. −14.7% (p = 0.003) and cross-sectional area was −1.7% vs. −10.4% (p = 0.04). No significant difference was found in ICU-AW (13% vs. 40%; p = 0.20) and IMS (3 vs. 2; p = 0.42) between the groups. The length of hospitalization was shorter in the EMS group (23 [19–34] vs. 40 [26–64] days) (p = 0.04). On day 3, the change in the branched-chain amino acid level was lower in the EMS group (40.5% vs. 71.5%; p = 0.04). Conclusion: In critically ill patients, EMS prevented upper and lower limb muscle atrophy and attenuated proteolysis and decreased the length of hospitalization

Monitoring of muscle mass in critically ill patients : comparison of ultrasound and two bioelectrical impedance analysis devices

Background: Skeletal muscle atrophy commonly occurs in critically ill patients, and decreased muscle mass is associated with worse clinical outcomes. Muscle mass can be assessed using various tools, including ultrasound and bioelectrical impedance analysis (BIA). However, the effectiveness of muscle mass monitoring is unclear in critically ill patients. This study was conducted to compare ultrasound and BIA for the monitoring of muscle mass in critically ill patients. Methods: We recruited adult patients who were expected to undergo mechanical ventilation for > 48 h and to remain in the intensive care unit (ICU) for > 5 days. On days 1, 3, 5, 7, and 10, muscle mass was evaluated using an ultrasound and two BIA devices (Bioscan: Malton International, England; Physion: Nippon Shooter, Japan). The influence of fluid balance was also evaluated between each measurement day. Results: We analyzed 93 images in 21 patients. The age of the patients was 69 (interquartile range, IQR, 59–74) years, with 16 men and 5 women. The length of ICU stay was 11 days (IQR, 9–25 days). The muscle mass, monitored by ultrasound, decreased progressively by 9.2% (95% confidence interval (CI), 5.9–12.5%), 12.7% (95% CI, 9.3–16.1%), 18.2% (95% CI, 14.7–21.6%), and 21.8% (95% CI, 17.9–25.7%) on days 3, 5, 7, and 10 (p < 0.01), respectively, with no influence of fluid balance (r = 0.04, p = 0.74). The muscle mass did not decrease significantly in both the BIA devices (Bioscan, p = 0.14; Physion, p = 0.60), and an influence of fluid balance was observed (Bioscan, r = 0.37, p < 0.01; Physion, r = 0.51, p < 0.01). The muscle mass assessment at one point between ultrasound and BIA was moderately correlated (Bioscan, r = 0.51, p < 0.01; Physion, r = 0.37, p < 0.01), but the change of muscle mass in the same patient did not correlate between these two devices (Bioscan, r = − 0.05, p = 0.69; Physion, r = 0.23, p = 0.07). Conclusions: Ultrasound is suitable for sequential monitoring of muscle atrophy in critically ill patients. Monitoring by BIA should be carefully interpreted owing to the influence of fluid change

Arduinoを用いたマイコン制御の入門教育

The programming language used in information processing education from 2011 in mechanical engineering department was changed to C from Fortran. Not only the numerical computation but also the study of the control using the microcomputer was thereby enabled and a new subject has been initiated in 2013. The name of this 4th grader's subject is "microcomputer control" and is compulsory in half year. Each individual student is using Arduino purchased by oneself, is taking the lesson and doing a programming training. The aim of this subject is to have a student understand next. (1) what is made with a microcomputer ? (2) what kind of program is necessary for it ? Inexpensive sensors and equipment were being used, were prepared subject to feel that there is interest to students. In this report, the contents of the lecture are reported including the later application around an item to treat by a lecture

Urinary titin reflects muscle atrophy in critical ill patients

Skeletal muscle atrophy is a serious problem in critically ill patients. After intensive care unit （ICU）admission, muscle atrophy starts within ３ days and progressively worsens thereafter. We have previously reported that upper and lower limb muscle mass of critically ill patients decreased by １３%‐２１% within ７ days of admission. Muscle atrophy in the ICU is associated with long-term functional impairment and weakness in ICU survivors. Although monitoring of muscle mass is important, there have been no reliable biomarkers associated with muscle atrophy in critically ill patients. In this study, we have focused on urinary titin, which is the biggest giant sarcomere protein and functions as a spring for muscle extension and viscoelasticity. We have clarified that urinary titin level reflected muscle breakdown correlated with limb muscle atrophy in non-surgical critically ill patients. The cumulative urinary titin level associated with the incidence of ICU-AW and ICU mortality. Our study indicates urinary titin can be the noble biomarker to evaluate the catabolism and muscle atrophy in critically ill patients

Lymphangioma of the Small Intestine : A Case Report

Lymphangiomas of the small intestine are rare tumors arising from masses of dilated lymphatic vessels in the submucosa. There are 11 cases of lymphangioma of the small intestine in the Japanese literature. We report a case of lymphangioma of the jejunum seen in a 76-year-old female and discuss with clinical feature