Cross-Sectional and Longitudinal Associations of Creatinine-to-Cystatin C Ratio with Sarcopenia Parameters in Older Adults.

OBJECTIVES: Accumulating evidence from cross-sectional studies suggests that the serum creatinine-to-cystatin C ratio (CCR) may be a useful biomarker for sarcopenia. This study aimed to assess the cross-sectional and longitudinal associations of CCR with sarcopenia and its parameters in community-dwelling older adults. DESIGN: Cross-sectional and longitudinal study. SETTING AND PARTICIPANTS: This 6-year prospective cohort study included the repeated measurement data from 1,253 Japanese residents (662 males and 591 females) aged ≥65 years who underwent medical checkups in Kusatsu and Hatoyama, Japan. A total of 4,421 observations were collected. MEASUREMENTS: The CCR was grouped into quartiles by sex (Q1-Q4) using Q4 as the reference category. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019 algorithm. Skeletal muscle mass index (SMI) measured using segmental multifrequency bioelectrical impedance analysis, handgrip strength (HGS), usual gait speed (UGS), and maximal gait speed (MGS) were measured repeatedly as sarcopenia parameters. The association of the CCR with changes in sarcopenia, SMI, HGS, UGS, and MGS during the 6-year period were analyzed using a generalized linear mixed-effects model. RESULTS: The prevalence of sarcopenia at baseline was 13.1% (11.9% in males and 14.5% in females). In a cross-sectional analysis, the CCR quartile was inversely associated with sarcopenia and was positively associated with SMI, HGS, and MGS (P for trend < 0.001). In a longitudinal analysis during the 6 years, a significant increase in sarcopenia in Q2 (B = 1.1% point/year; P = 0.026 for group-by-time interaction) and significant declines in SMI (B = -0.01 kg/m2/year; P = 0.044 for group-by-time interaction) and MGS (B = -0.008 m/sec/year; P = 0.041 for group-by-time interaction) in Q1 were observed compared with Q4. However, the dose-response relationship was significant only for MGS (P = 0.033 for trend). No significant group-by-time interaction was observed for HGS. CCR was not significantly associated with UGS either cross-sectionally or longitudinally. CONCLUSIONS: CCR is a useful biomarker regarding the status of sarcopenia. It may be used for sarcopenia screening even in older adults whose physical function is difficult to assess. However, further longitudinal studies are needed to determine whether CCR can be a predictor of future sarcopenia.

A Combined Assessment Method of Phase Angle and Skeletal Muscle Index to Better Predict Functional Recovery after Acute Stroke.

OBJECTIVES: We aimed to investigate whether combination assessment of phase angle (PhA) and skeletal muscle index (SMI), was a possible predictor of physical function at discharge from the hospital in patients with acute stroke. RESEARCH METHODS AND PROCEDURES: In this retrospective cohort study that was conducted from May 2020 and July 2021, we determined PhA and SMI using bioimpedance analysis (BIA) in patients with acute stroke. Patients were classified as normal, low PhA + SMI group, pre-sarcopenia (low SMI only), and dynapenia (low PhA only) using cut-off points (men: SMI < 7.0 kg/m2, PhA < 4.05 degrees; women: SMI < 5.7 kg/m2, PhA < 3.55 degrees). The main outcome was physical function based on functional independence measure motor (FIM-motor) score at discharge. Multiple regression analysis was used to determine the association between low PhA + SMI and FIM-motor score. RESULTS: We included 244 patients (161 men; mean age, 73.9 years). low PhA + SMI was found in 21 (8.6%) patients. Multiple regression analysis showed that low PhA + SMI was independently associated with the FIM-motor score at discharge (ß= -0.099, 95%CI: -0.193,-0.005, p = 0.039). The PhA cutoff values for determining good functional results using receiver operating characteristic (ROC) curves were 5.36 for men (sensitivity = 0.769, specificity = 0.586, area under the curve [AUC] = 0.682), and 3.85 for women (sensitivity = It was 0.881, specificity = 0.481, AUC). Further, pearson correlation coefficient showed that PhA was significantly related to FIM-motor score in patients with mild or moderately severe stroke (mild: r = 0.472, p < 0.001; moderate: r = 0.524, p < 0.001). CONCLUSIONS: Combination of low PhA and SMI values at baseline, was an independent predictor of physical function at discharge in patients with acute stroke. The findings highlighted the importance of measuring PhA and SMI using BIA in patients with acute stroke.

α-Clustering in atomic nuclei from first principles with statistical learning and the Hoyle state character.

A long-standing crucial question with atomic nuclei is whether or not α clustering occurs there. An α particle (helium-4 nucleus) comprises two protons and two neutrons, and may be the building block of some nuclei. This is a very beautiful and fascinating idea, and is indeed plausible because the α particle is particularly stable with a large binding energy. However, direct experimental evidence has never been provided. Here, we show whether and how α(-like) objects emerge in atomic nuclei, by means of state-of-the-art quantum many-body simulations formulated from first principles, utilizing supercomputers including K/Fugaku. The obtained physical quantities exhibit agreement with experimental data. The appearance and variation of the α clustering are shown by utilizing density profiles for the nuclei beryllium-8, -10 and carbon-12. With additional insight by statistical learning, an unexpected crossover picture is presented for the Hoyle state, a critical gateway to the birth of life.

A multicenter cohort study of osimertinib compared with afatinib as first-line treatment for EGFR-mutated non-small-cell lung cancer from practical dataset: CJLSG1903.

BACKGROUND: FLAURA, the prospective trial of osimertinib as a first-line therapy compared with first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), did not show superior survival benefit for osimertinib in either the subgroup of Asians or the subgroup with the L858R mutation. In addition, the superiority of osimertinib compared with second-generation EGFR-TKI is thus far unclear. PATIENTS AND METHODS: We reviewed the clinical data of all consecutive patients who were treated with osimertinib or afatinib as first-line therapy between May 2016 and October 2019 from 15 institutions in Japan. We defined the groups based on first-line EGFR-TKI as the afatinib group and the osimertinib group. Outcomes included time to discontinuation of any EGFR-TKI (TD-TKI), overall survival (OS), and time to treatment failure, with propensity score analysis carried out as an exploratory analysis in the survival and subgroup analyses. RESULTS: A total of 554 patients were enrolled. Data on 326 patients in the osimertinib group, and 224 patients in the afatinib group were analyzed. TD-TKI adjusted by propensity score in the afatinib and osimertinib groups was 18.6 months (95% confidence interval 15.8 to 22.0) and 20.5 months (95% confidence interval 13.8 to not reached), respectively, without significant difference (P = 0.204). OS adjusted by propensity score favored the afatinib group with a significant difference (P = 0.018). Subgroup analysis with propensity score showed that patients with L858R and without brain metastasis had superior survival benefit with afatinib compared with osimertinib (P < 0.001). CONCLUSIONS: TD-TKI in the afatinib group was not significantly prolonged compared with the osimertinib group in the practical data. In the exploratory analysis of patients with L858R-mutated non-small-cell lung cancer without brain metastasis, afatinib showed more benefit in OS over osimertinib.

Daytime Dynamo Electrodynamics With Spiral Currents Driven by Strong Winds Revealed by Vapor Trails and Sounding Rocket Probes.

We investigate the forces and atmosphere-ionosphere coupling that create atmospheric dynamo currents using two rockets launched nearly simultaneously on 4 July 2013 from Wallops Island (USA), during daytime Sq conditions with ΔH of -30 nT. One rocket released a vapor trail observed from an airplane which showed peak velocities of >160 m/s near 108 km and turbulence coincident with strong unstable shear. Electric and magnetic fields and plasma density were measured on a second rocket. The current density peaked near 110 km exhibiting a spiral pattern with altitude that mirrored that of the winds, suggesting the dynamo is driven by tidal forcing. Such stratified currents are obscured in integrated ground measurements. Large electric fields produced a current opposite to that driven by the wind, believed created to minimize the current divergence. Using the observations, we solve the dynamo equation versus altitude, providing a new perspective on the complex nature of the atmospheric dynamo.

Accelerometer-Determined Intensity and Duration of Habitual Physical Activity and Walking Performance in Well-Functioning Middle-Aged and Older Women: A Cross-Sectional Study.

BACKGROUND: The association of physical activity (PA) intensities and duration spent in those activities with different walking tasks remains unclear. OBJECTIVES: To examine the association between the duration of PA intensities and three walking speeds (usual walking speed, maximal walking speed and zig-zag walking speed). DESIGN: Multiple linear regression analysis was used to estimate the association of age, BMI, maximum knee extension strength, light PA, moderate PA and vigorous PA with walking speeds. SETTING: University lab. PARTICIPANTS: Eighty-six older women (67 ± 7 years). MEASUREMENTS: PA was measured for 30 consecutive days using the Lifecorder-EX accelerometer. Exercise intensity was categorized as light (levels 1-3), moderate (levels 4-6) and vigorous (levels 7-9) based on the manufacturer algorithms. Usual straight walking speed (20 m), maximal straight walking speed (20 m) and zig-zag walking speed tests (10 m) were performed by each participant. RESULTS: For the usual straight walking speed model (R2 = 0.296, SEE = 0.15 m/s), the significant predictors were BMI, knee extension strength, light PA and vigorous PA. For the maximal straight walking speed model (R2 = 0.326, SEE = 0.20 m/s), only age was a significant predictor. For the zig-zag walking speed model (R2=0.417, SEE = 0.14 m/s), age and maximum knee strength were significant predictors in the model. CONCLUSIONS: Overall, the results of this study suggest that vigorous PA and maximal knee extension strength are two important factors that are associated with different walking speeds in older women.

Gastrectomy with or without omentectomy for cT3-4 gastric cancer: a multicentre cohort study.

BACKGROUND: Omentectomy is performed widely for locally advanced gastric cancer to prevent disease recurrence. However, its clinical benefit is unknown. METHODS: This retrospective cohort study compared the outcome of gastrectomy with preservation of the omentum (GPO) and gastrectomy with resection of the omentum (GRO) among patients with cT3-T4 gastric cancer who underwent gastrectomy between 2006 and 2012 in one of five participating institutions. A consensus conference identified 28 variables potentially associated with outcome after gastrectomy for the estimation of propensity scores, and propensity score matching (PSM) was undertaken to control for possible confounders. Postoperative surgical outcomes, overall survival and disease recurrence were compared between GPO and GRO. RESULTS: A total of 1758 patients were identified, of whom 526 remained after PSM, 263 in each group. Median follow-up was 4·9 (i.q.r. 3·1-5·9) years in the GRO group and 5·0 (2·5-6·8) years in the GPO group. The incidence of postoperative complications of Clavien-Dindo grade III or more was significantly higher in the GRO group (17·5 versus 10·3 per cent; P = 0·016). Five-year overall survival rates were 77·1 per cent in the GRO group and 79·4 per cent in the GPO group (P = 0·749). There were no significant differences in recurrence rate or pattern of recurrence between the groups. CONCLUSION: Overall survival and disease recurrence were comparable in patients with cT3-4 gastric cancer who underwent GPO or GRO.

ANTECEDENTES: La omentectomía se realiza ampliamente en el cáncer gástrico localmente avanzado para prevenir la recidiva de la enfermedad. Sin embargo, se desconoce su beneficio clínico. MÉTODOS: Este estudio retrospectivo comparó el resultado de la gastrectomía con preservación del omento (gastrectomy with preservation of the omentum, GPO) con la gastrectomía con resección del omento (gastrectomy with resection of the omentum, GRO) para el cáncer gástrico con estadio clínico T3/T4. Se incluyeron pacientes sometidos a gastrectomía por cáncer gástrico clínico T3/T4 (2006-2012) y se recogieron datos relevantes de 5 hospitales participantes. A través de una conferencia de consenso se identificaron 28 variables potencialmente asociadas con el resultado tras la gastrectomía, mediante las cuales se estimaron las puntuaciones de propensión, utilizándose el emparejamiento por puntuación de propensión (propensity score matching, PSM) para el control de posibles factores de confusión. Los resultados quirúrgicos postoperatorios, la supervivencia global y la recidiva de la enfermedad se compararon entre las gastrectomías con GPO y GRO. RESULTADOS: En total, se identificaron 1.758 pacientes, seleccionándose 526 (263 GRO y 263 GPO) tras el PSM. La mediana (rango intercuartílico) de seguimiento fue de 4,9 años (3,1-5,9) en el grupo GRO y de 5,0 años (2,5-6,8) en el grupo GPO. La incidencia de complicaciones postoperatorias de Clavien-Dindo grado III o más alto fue significativamente más elevada en el grupo GRO que en el grupo GPO (17,1% versus 9,1%; P = 0,010). La supervivencia global a los 5 años fue del 77,1% para el grupo GRO y del 79,4% para el grupo GPO (P = 0,749). No hubo diferencias estadísticamente significativas en la tasa de recidiva o patrón de recidiva entre ambos grupos. CONCLUSIÓN: La supervivencia global y la recidiva de la enfermedad son comparables en pacientes con cáncer gástrico estadio clínico T3-4 sometidos a GPO o GRO.

Impact of Fat-Free Adipose Tissue on the Prevalence of Low Muscle Mass Estimated Using Calf Circumference in Middle-Aged and Older Adults.

Previous studies proposed calf circumference cutoff values for predicting dual-energy X-ray absorptiometry (DXA)-derived low muscle mass. However, DXA-derived appendicular lean mass (aLM) includes non-skeletal muscle components such as the appendicular fat-free component of adipose tissue fat cells (aFFAT). The purpose of this study was to compare the calf circumference method of classification before (Model #1) and after (Model #2) eliminating the influence of FFAT in healthy Japanese adults (50 to 79 years; mean age 70 (SD 7) years). Model 1, and Model 2 for classifying low muscle mass had a sensitivity of 78% and 64%, specificity of 76% and 75%, positive predictive value of 31% and 28%, and negative predictive value of 96% and 93%, respectively. Appendicular fat-free component of adipose tissue has the potential to influence the ability of calf circumference to accurately classify individuals with low muscle mass. Consideration should be made when using this as a screening tool for low muscle mass.

Influence of an SGLT2 inhibitor, tofogliflozin, on the resting heart rate in relation to adipose tissue insulin resistance.

AIMS: To examine the effects of a sodium-glucose co-transporter 2 (SGLT2) inhibitor, tofogliflozin, on resting heart rate by exploring baseline factors that independently influenced changes in the resting heart rate. METHODS: Data on 419 participants in tofogliflozin phase 2/3 trials were analysed. Changes in resting heart rate from baseline to week 24 were analysed using an analysis of covariance (ANCOVA) model with groups (tofogliflozin/placebo) as a fixed effect and baseline values as covariates. The antilipolytic effect was evaluated as adipose tissue insulin resistance (Adipo-IR) and was calculated as the product of fasting insulin and free fatty acid. Multivariate analysis evaluated independent factors for changes in resting heart rate from baseline to week 24. RESULTS: Of the participants, 58% were men, and mean age, HbA1c , BMI and resting heart rate were 57.6 years, 65 mmol/mol (8.1%), 25.5 kg/m2 and 66 bpm, respectively. At week 24, adjusted mean difference vs. placebo in the change from baseline was -2.3 bpm [95% confidence interval (CI) -4.6, -0.1] with tofogliflozin. Changes in resting heart rate were positively correlated with changes in Adipo-IR, whereas reductions in HbA1c , body weight and blood pressure were similar independent of changes in resting heart among quartiles of resting heart rate change. On multivariate analysis, higher baseline resting heart rates and Adipo-IR values were significantly associated with greater reductions in resting heart rate. CONCLUSIONS: Tofogliflozin corrected resting heart rate levels in accordance with baseline levels. Correction of high resting heart rates may be attributed to improved adipose tissue insulin resistance, leading to correction of hyperinsulinaemia.

Tongue surface model can predict radiation tongue mucositis due to intensity-modulated radiation therapy for head and neck cancer.

Acute radiation tongue mucositis has a profound effect on talking and eating. We examined whether the dose-volume histogram obtained from the tongue surface model correlates with mucositis severity, and whether it is useful for predicting acute radiation tongue mucositis in patients with head and neck cancer treated with intensity-modulated radiation therapy. Thirty-six patients who received intensity-modulated radiation therapy for head and neck cancer were analysed for acute radiation tongue mucositis according to the Common Terminology Criteria for Adverse Events, version 4.0, as well as the Radiation Therapy Oncology Group scoring systems. The corresponding high-dose locations in anatomical sub-regions in the tongue surface model and the development of high-grade acute radiation tongue mucositis were compared. The mucositis sites coincided with the high-dose anatomical sub-regions in the tongue surface model. There was a clear dose-response relationship between the mean dose to the tongue and the acute radiation tongue mucositis Radiation Therapy Oncology Group grade. According to the dose-volume histogram, patients receiving 16.0-73.0 Gy to the tongue were susceptible to grade 2-3 toxicity. The tongue surface model can predict the site and severity of acute radiation tongue mucositis. In future, radiation treatment plans ccould be optimized using this model.

Underlying Structure of Collective Bands and Self-Organization in Quantum Systems.

The underlying structure of low-lying collective bands of atomic nuclei is discussed from a novel perspective on the interplay between single-particle and collective degrees of freedom, by utilizing state-of-the-art configuration interaction calculations on heavy nuclei. Besides the multipole components of the nucleon-nucleon interaction that drive collective modes forming those bands, the monopole component is shown to control the resistance against such modes. The calculated structure of ^{154}Sm corresponds to the coexistence between prolate and triaxial shapes, while that of ^{166}Er exhibits a deformed shape with a strong triaxial instability. Both findings differ from traditional views based on ß/γ vibrations. The formation of collective bands is shown to be facilitated from a self-organization mechanism.

Blood flow restriction augments the skeletal muscle response during very low-load resistance exercise to volitional failure.

The purpose of this study was to compare the acute muscular response with resistance exercise between the following conditions [labeled (% one-repetition maximum/% arterial occlusion pressure)]: high-load (70/0), very low-load (15/0), very low-load with moderate (15/40), and high (15/80) blood flow restriction pressures. Twenty-three participants completed four sets of unilateral knee extension to failure (up to 90 repetitions) with each condition, one condition per leg, each day. Muscle thickness and maximal voluntary contraction (MVC) were measured before (Pre), immediately after (Post-0), and 15 min after (Post-15) exercise and electromyography (EMG) amplitude during exercise. Pre to Post-0 muscle thickness changes in cm [95% CI] were greater with 15/40 [0.57 (0.41, 0.73)] and 15/80 [0.49 (0.35, 0.62)] compared to 70/0 [0.33 (0.25, 0.40)]. Pre to Post-0 MVC changes in Nm [95% CI] were higher with 15/40 [-127.0 (-162.1, -91.9)] and 15/80 [-133.6 (-162.8, -104.4)] compared to 70/0 [-48.4 (-70.1, -26.6)] and 15/0 [-98.4 (-121.9, -74.9)], which were also different. Over the first three repetitions, EMG increased across sets, whereas in the last three repetitions it did not. EMG was also different between conditions and was generally greater during 70/0. Repetitions decreased across sets reaching the lowest for 70/0, and for very low loads decreased with increased pressure. In trained participants exercising to failure, lower load and the application of restriction pressure augment changes in muscle thickness and torque. The EMG amplitude was augmented by load. Training studies should compare these conditions, as the results herein suggest some muscular adaptations may differ.

Outcome of maintenance systemic chemotherapy with drug-free interval for metastatic urothelial carcinoma.

OBJECTIVE: Aiming to achieve long-term disease control, maintenance systemic chemotherapy (MSC) with a 1-3-month drug-free interval is continued in selected patients. We report our experience of MSC for metastatic urothelial carcinoma (UC). METHODS: Of 228 metastatic UC patients treated with systemic chemotherapy, 40 (17.5%, 40/228) had continuously undergone MSC. Data on the regimen, cycle number, and reason for the discontinuation of MSC were also collected. We analyzed OS from the initiation of MSC until death or the last follow-up, using the log-rank test to assess the significance of differences. RESULTS: The median number of cycles of chemotherapy was 6, and the responses were CR in 6, PR in 20, SD in 13, and PD in 1 before MSC. Gemcitabine plus CDDP or carboplatin was mainly performed as MSC (70%, 28/40). MSC was repeated quarterly in 30 (75%, 30/40), every two months in 8 (20%, 8/40), and with other intervals in 2 (5%, 2/40). Overall, a median of 3.5 cycles (range: 1-29) of MSC was performed. The reason for the discontinuation of MSC was PD in 24 (60%, 24/40), favorable disease control in 9 (22.5%, 9/40), and myelosuppression in 3 (7.5%, 3/40), and for other reasons in 2 (5%, 2/40). MSC was ongoing in 2 (5%, 2/40). The median OS was 27 months from the initiation of MSC. PS0 (P = 0.0169), the absence of lung metastasis (P = 0.0387), and resection of the primary site (P = 0.0495) were associated with long-term survival after MSC. CONCLUSIONS: In selected patients, long-term systemic chemotherapy could be performed with a drug-free interval. Our maintenance strategy with cytotoxic drugs may become one of the treatment options for long-term disease control.

An Ultrasound Prediction Equation to Estimate DXA-Derived Body Fatness for Middle-Aged and Older Caucasian Adults.

BACKGROUND AND OBJECTIVES: Currently, only one study has used dual-energy X-ray absorptiometry (DXA)-derived percent body fat (BF%) as the criterion measure to develop ultrasound prediction equations to estimate BF% in adults between the ages of 50 and 80 years. The aim of this study was to examine the relationship between BF% estimated from subcutaneous fat thickness using a previously published Japanese-based prediction equation and DXA-derived BF% in Caucasian middle-aged and older adults. A secondary aim was to develop a new prediction equation for Caucasian adults if the previously published equation did not predict BF% well in Caucasians. DESIGN: Cross-sectional study. PARTICIPANTS AND MEASUREMENTS: One-hundred and two Caucasian adults aged 50-76 years (59 men and 43 women) had ultrasound fat thickness and DXA values measured. A new BF% prediction model was developed using ordinary least squares multiple linear regression. RESULTS: There was a strong correlation between ultrasound predicted and DXA-derived BF% (r = 0.882, p<0.001). Bland-Altman analysis did not indicate a bias in the prediction of BF% for Caucasian adults (r = -0.092, p>0.05). However, the predicted BF% was significantly higher compared to DXA-derived BF% (approximately 4%). A newly developed nonlinear prediction model used to estimate BF% was significant [F(17,84) = 33.44, p<0.001] with an R2 of 0.871 and an adjusted R2 of 0.845. When examining the stability of the model, bootstrapping (n=1000) resulted in an optimism value of 0.1135 so that the corrected R2 was 0.758. After removing an outlier, the model was significant [F(17,83) = 34.82, p<0.001] and it's R2 was 0.877 and adjusted R2 was 0.852. CONCLUSION: The developed equation was stable with a high degree of variance compared to results from previous studies. The results of this study also suggest that ethnicity should be considered when choosing which prediction equations should be used to estimate BF%.