Low and high body mass index and lower numbers of screws in the articular segment are risk factors for non-union of distal humeral fractures in the elderly: A multi-center retrospective study (TRON study).

Background: Distal humerus fracture in the elderly is a challenging fracture for orthopedic surgeons. Non-union is one of the serious complications of distal humerus fracture after surgery. This retrospective multicenter study aimed to estimate the incidence of distal humeral non-union after open reduction and internal fixation, determine factors related to non-union, and compare the postoperative results of cases with non-union to cases with the union. Methods: Among 423 patients diagnosed with distal humeral fracture and who were treated by surgical therapy in 2010-2020 from our database called TRON. Only 190 subjects met the inclusion criteria. We performed a logistic regression analysis with the presence of non-union as the response variable to examine risk factors. We compare the Mayo Elbow Performance Scores of cases with non-union to cases with the union. Results: Non-union occurred after surgery in 15 patients (7.9%). The logistic regression analysis showed that body mass index<20 kg/m2 and ≥25 kg/m2, and ≤3 screws in the articular segment were significant explanatory factors for non-union (odds ratio 10.4 and 47.8, respectively). The Mayo Elbow Performance Scores were significantly worse in patients with non-union. Discussion: Low and high body mass index and three or fewer screws in the articular segment might be risk factors for non-union of distal humerus fracture in the elderly. Non-union is associated with poor clinical outcomes.

Reliability of Binocular Esterman Visual Field Test in Patients with Glaucoma and Other Ocular Conditions.

The binocular Esterman visual field test (EVFT) of 120 points was the first method to quantify the defects in the binocular visual field. It is used in many parts of the world as a standard test to determine whether an individual has the visual capabilities to drive safely. In Japan, it is required for the grading and issuance of visual disability certificates. The purpose of this study was to determine the reliability of the EVFT results. We studied 104 patients who had undergone the binocular EVFT at Mie University Hospital. Their mean age was 68.0 ± 11.4 years, and the best-corrected visual acuity of the better eye was 0.18 ± 0.38 logMAR units. The EVFT was performed twice on the same day, and the results of the first and second tests were compared. The mean Esterman scores for the first and second test were 89.3 ± 30.5 and 89.1 ± 30.2, respectively, and the test times were 338.9 ± 86.8 and 336.7 ± 76.4 s, respectively. The differences were not significant (p = 0.69 and p = 0.33). In the Bland-Altman analyses (second-first test) of the Esterman scores, the mean difference was 0.38 without significant fixed errors (p = 0.20) or proportional errors (p = 0.27). The limits of agreement within the 1.96 standard deviation were -8.96 to +9.45 points. The agreement rate for the most peripheral 24 test points was significantly lower than the agreement rate for the other 96 test points (p < 0.01). The agreement rate of the upper visual field was significantly lower than that of the lower field (p < 0.01). The overall reliability rate of the EVFT is acceptable, but the peripheral and upper test points have relatively low reliability rates. These findings are important for interpretations of the EVFT results.

Exceptionally preserved stomach contents of a young tyrannosaurid reveal an ontogenetic dietary shift in an iconic extinct predator.

Tyrannosaurids were large carnivorous dinosaurs that underwent major changes in skull robusticity and body proportions as they grew, suggesting that they occupied different ecological niches during their life span. Although adults commonly fed on dinosaurian megaherbivores, the diet of juvenile tyrannosaurids is largely unknown. Here, we describe a remarkable specimen of a juvenile Gorgosaurus libratus that preserves the articulated hindlimbs of two yearling caenagnathid dinosaurs inside its abdominal cavity. The prey were selectively dismembered and consumed in two separate feeding events. This predator-prey association provides direct evidence of an ontogenetic dietary shift in tyrannosaurids. Juvenile individuals may have hunted small and young dinosaurs until they reached a size when, to satisfy energy requirements, they transitioned to feeding on dinosaurian megaherbivores. Tyrannosaurids occupied both mesopredator and apex predator roles during their life span, a factor that may have been key to their evolutionary success.

Instruments to assess post-intensive care syndrome assessment: a scoping review and modified Delphi method study.

BACKGROUND: The assessment of post-intensive care syndrome (PICS) is challenging due to the numerous types of instruments. We herein attempted to identify and propose recommendations for instruments to assess PICS in intensive care unit (ICU) survivors. METHODS: We conducted a scoping review to identify PICS follow-up studies at and after hospital discharge between 2014 and 2022. Assessment instruments used more than two times were included in the modified Delphi consensus process. A modified Delphi meeting was conducted three times by the PICS committee of the Japanese Society of Intensive Care Medicine, and each score was rated as not important (score: 1-3), important, but not critical (4-6), and critical (7-9). We included instruments with ≥ 70% of respondents rating critical and ≤ 15% of respondents rating not important. RESULTS: In total, 6972 records were identified in this scoping review, and 754 studies were included in the analysis. After data extraction, 107 PICS assessment instruments were identified. The modified Delphi meeting reached 20 PICS assessment instrument recommendations: (1) in the physical domain: the 6-min walk test, MRC score, and grip strength, (2) in cognition: MoCA, MMSE, and SMQ, (3) in mental health: HADS, IES-R, and PHQ-9, (4) in the activities of daily living: the Barthel Index, IADL, and FIM, (5) in quality of life: SF-36, SF-12, EQ-5D-5L, 3L, and VAS (6), in sleep and pain: PSQI and Brief Pain Inventory, respectively, and (7) in the PICS-family domain: SF-36, HADS, and IES-R. CONCLUSION: Based on a scoping review and the modified Delphi method, 20 PICS assessment instruments are recommended to assess physical, cognitive, mental health, activities of daily living, quality of life, sleep, and pain in ICU survivors and their families.

A narrow gene encoding an extracellular matrix is involved in the formation of the footpad hairs in Drosophila melanogaster.

Drosophila melanogaster is an insect that can walk on smooth surfaces, and its tarsal segments bear a pair of footpads that are equipped with spatulate-shaped hairs (setae). We found that narrow B ( nw B ) mutants, an allele of the nw gene, were unable to climb smooth surfaces, due to the destruction of the footpad hair tips. The mutant hair tips were damaged during molting from the pupal cuticle at eclosion. Thus, the nw gene encoding a secretory protein that serves as an extracellular matrix is implicated in the formation of the footpad hairs.

Anion-π Interactions in Monolayers Formed by Amphiphilic Electron-Deficient Aromatic Compounds at Air/Water Interfaces.

Biological systems precisely and selectively control ion binding through various chemical reactions, molecular recognition, and transport by virtue of effective molecular interactions with biological membranes and proteins. Because ion binding is inhibited in highly polar media, recognition systems for anions in aqueous media, which are relevant to biological and environmental systems, are still limited. In this study, we explored the anion binding of Langmuir monolayers formed by amphiphilic naphthalenediimide (NDI) derivatives with a series of substituents at air/water interfaces via anion-π interactions. Density functional theory (DFT) simulations revealed that the binding of anions originating from anion-π interactions is related to the electron density of the anions. At the air/water interfaces, amphiphilic NDI derivatives formed Langmuir monolayers, and the addition of anions caused expansion of the Langmuir monolayers. The anions with larger hydration energies related to electron density showed larger binding constants (Ka) for 1:1 stoichiometry with the NDI derivatives. The loosely packed monolayer formed by the amphiphilic NDI derivatives with bromine groups showed a better anion response. In contrast, the binding of NO3- was significantly enhanced in the highly packed monolayer. These results indicate that the packing of NDI derivatives with rigid aromatic rings influenced the binding of the anions. These results provide insight into ion binding using the air/water interface as a promising recognition site for mimicking biological membranes. In future, sensing devices can be developed using Langmuir-Blodgett films on electrodes. Furthermore, the capture of anions on electron-deficient aromatic compounds can lead to doping or composition technologies for n-type semiconductors.

The impact of acute skeletal muscle loss after gastrointestinal cancer surgery on physical function.

INTRODUCTION: Significant skeletal muscle loss occurs commonly after cancer surgery; however, the impact of postoperative acute skeletal muscle loss on physical function remains poorly understood. OBJECTIVE: To determine the impact of surgery-associated acute skeletal muscle wasting on physical function in the early postoperative period in patients with gastrointestinal cancer. DESIGN: A single-center retrospective observational study. SETTING: General hospital. PATIENTS: Hospitalized patients with gastrointestinal cancer who were admitted for surgery. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: The main outcome was the partial correlation between postoperative changes in skeletal muscle index (SMI) and physical function such as handgrip strength, gait speed, and 6-minute walk test. RESULTS: A total of 69 patients (41 male and 28 female) with a mean age of 70.5 years were included. SMI was significantly correlated with physical function, such as handgrip strength (r = 0.757, p < .001), maximum gait speed (r = 0.318, p = .008), and 6-minute walk test (r = 0.365, p = .002) before surgery. In contrast, partial correlation analysis between the absolute changes in SMI and physical function after controlling for SMI and each physical function before surgery showed no significant correlation. Multivariable linear regression analyses also showed that postoperative change in SMI was not significantly associated with the postoperative change in physical function but it was associated with the length of stay after surgery, SMI at admission, and absolute change in body fat percentage. CONCLUSIONS: The absolute change in SMI during the early postoperative period was not linearly correlated with the degree of decline in physical function. Further studies are necessary to investigate the effects of the respective changes in skeletal muscle mass and physical function on clinical outcomes.

A less invasive operative method using a medial cannulated cancellous screw and single plate fixation for the treatment of transcondylar fracture of the humerus in elderly patients in multicenter (TRON group) study.

BACKGROUND: Double plate fixation for transcondylar fracture (TCF) tends to be more invasive to the soft tissue, and often carries a higher risk of postoperative complications, including ulnar nerve neuropathy. This study presents the outcomes of TCF of the distal humerus between patients treated with a single plate and cannulated cancellous screw fixation and patients treated with double plate fixation. METHODS: Between 2011 and 2021, 371 cases involving treatment of distal humeral fracture were recorded in our multicenter (named TRON group) database. Patients of ≥ 65 years of age with TCF treated with opeb n reduction and internal fixation were included. Clinical outcomes were assessed by the Mayo elbow performance score, range of motion, and total elbow arc joint. Complications included fracture-related infection (FRI) and ulnar neuropathy. RESULTS: There were significant differences in the average operative time (CCS group vs. Plate group: 119.0 min vs. 186.5 min; p < 0.001) and average tourniquet time (CCS group vs. Plate group: 91.5 min vs. 121.0 min; p < 0.001). FRI occurred as a complication in the Plate group (n = 6). The rates of FRI did not differ to a statistically significant extent (CCS group vs. Plate group: 0% vs. 9.2%; p = 0.477). No patients underwent reoperation. The rate of sensory symptoms in the Plate group was higher than that in the CCS group (CCS group: none [n = 25], numbness [n = 1] vs. Plate group: none [n = 57], numbness [n = 15], sensory depression [n = 2]; p = 0.039). DISCUSSION: Among patients of ≥ 65 years of age with TCF, the clinical outcomes of patients treated with medial CCS and lateral/posterolateral plate did not differ from those of patients who received double plate fixation, and the former treatment was associated with significantly fewer complications, including ulnar nerve palsy. In addition to double plate fixation, this less invasive method of medial CCS and single plate fixation should be considered as a treatment option for TCF in elderly patients.

Clinical comparison of double-plate fixation by the perpendicular plate method versus parallel plate method for distal humeral fracture: a multicenter (TRON group) study.

INTRODUCTION: Double-plating methods are popular, with perpendicular and parallel plate methods being widely used surgical method for the rigid fixation of distal humeral fracture (DHF). However, which plate method is better for DHF remains controversial. The aim of this study was to compare patient outcomes including the incidences of complications and reoperation between the two plate methods. METHODS: We extracted 383 patients with DHF undergoing surgery between 2011 and 2020 from our multicenter database, which is named TRON. We divided the subjects into two groups: perpendicular plating group (Group A) and parallel plating group (Group B). To adjust for baseline differences between the groups, patients were matched for age, sex, olecranon osteotomy, AO type, and type of injury. We assessed the Mayo Elbow Performance Score (MEPS) at 3 and 6 months and the last follow-up month as the clinical outcome. We investigated the incidences of complications and reoperations in both groups. RESULTS: After matching, each group comprised 50 patients. There was no significant difference between Group A versus Group B in MEPS score at each time point. The incidence of implant removal in Group B was higher than that in Group A (26.5% vs 50%, p = 0.023). DISCUSSION: Although there were no significant differences in clinical outcomes or complications between the two groups, the incidence of implant removal was higher in Group B than in Group A. In the parallel plate technique, where the plates have to be placed in areas with thin subcutaneous soft tissue, the incidence of implant removal might be high due to the discomfort caused by the implant.

Association between postextubation dysphagia and physical function in survivors of critical illness: A retrospective study.

BACKGROUND & AIMS: Dysphagia following endotracheal intubation, also known as postextubation dysphagia (PED), is generally observed in survivors of critical illness. However, its association with physical function remains relatively unexplored. This study aimed to investigate the association between PED and physical function in patients after intensive care. METHODS: This is a single-center retrospective observational study. Medical records of adult patients who required emergency admission and were intubated and mechanically ventilated were retrospectively reviewed. Swallowing and physical function were assessed using the Food Intake Level Scale (FILS) and functional status score for the intensive care unit (FSS-ICU) at discharge, respectively. Multivariable linear and logistic regression analyses were used to analyze the association between dysphagia and physical dysfunction at discharge. RESULTS: A total of 103 patients (63 men and 40 women) with a mean age of 67.3 years were enrolled. PED was observed in 20 patients (19.4%) at hospital discharge. The FILS score at hospital discharge was significantly and independently associated with the FSS-ICU (ß = 0.458, p < 0.001); however, the FILS score was not an independent risk factor for non-home discharge (95% confidence interval, 0.547-1.160). CONCLUSIONS: PED is significantly associated with physical dysfunction at discharge in survivors of critical illness. PED should be considered as a component of post-intensive care syndrome, and early intervention to prevent and improve swallowing dysfunction may be necessary.

Parametrized topological complexity of poset-stratified spaces.

In this paper, parametrized motion planning algorithms for a fiberwise space X → P over a poset P are studied. Such an algorithm assigns paths in a space X decomposed into subspaces with the index set P, that do not cross the boundaries of the separated regions. We compute the parametrized topological complexity of X → P , which is one less than the minimal number of local parametrized motion planning algorithms used for designing non-cross-border robot motions in X.

Identifying Protein-Drug Interactions in Cell Lysates Using Histidine Hydrogen Deuterium Exchange.

Identifying the targets of a drug is critical to understand the mechanism of action and predicts possible side effects. The conventional approach is capturing interacting proteins by affinity purification. However, it requires drugs to be immobilized to a solid support or derivatized with chemical moieties used for pulling down interacting proteins. Such covalent modifications to drugs may mask a critical recognition site for or alter the binding affinity to their targets. To overcome the drawback, several methods that do not require covalent modifications to drugs have been developed. These methods identify targets by detecting proteins whose thermodynamic stability is enhanced in the presence of drugs. Although the utility of these methods has been demonstrated, the difficulty in identifying low abundant targets is the common problem of these methods. We have developed a new target identification method that increases the likelihood of identifying low abundant targets. The method uses histidine-hydrogen deuterium exchange (His-HDX) as a readout technique to probe the changes in protein stability induced by drugs. The workflow involves incubating cell lysates in various concentrations of a protein denaturant in the presence and absence of a drug in D2O followed by digestion of the proteins, enrichment of His-containing peptides, and analysis of the enriched His-peptides by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The developed method was successfully applied to identify the interaction between endogenously expressed MAPK14 and its inhibitor in HEK293 cell lysates. The implementation of selective enrichment of histidine-containing peptides in the workflow was a key that enabled identifying the MAPK14-inhibitor interaction.

A new carcharodontosaurian theropod dinosaur occupies apex predator niche in the early Late Cretaceous of Uzbekistan.

Carcharodontosauria is a group of medium to large-sized predatory theropods, distributed worldwide during the Cretaceous. These theropods were probably the apex predators of Asiamerica in the early Late Cretaceous prior to the ascent of tyrannosaurids, although few Laurasian species are known from this time due to a poor rock record. Here, we describe Ulughbegsaurus uzbekistanensis gen. et sp. nov. from the early Late Cretaceous (Turonian) of Central Asia, which represents the first record of a Late Cretaceous carcharodontosaurian from the region. This new taxon is represented by a large, isolated maxilla from the Bissekty Formation of the Kyzylkum Desert, the Republic of Uzbekistan, a formation yielding a rich and diverse assemblage of dinosaurs and other vertebrates from fragmentary remains. Comparison of the maxilla with that of other allosauroids indicates Ulughbegsaurus was 7.5-8 m in body length and greater than 1000 kg in body mass, suggesting it was the previously unrecognized apex predator of the Bissekty ecosystem while smaller known tryannosauroids and dromaeosaurids were probable mesopredators. The discovery of Ulughbegsaurus records the geologically latest stratigraphic co-occurrence of carcharodontosaurid and tyrannosauroid dinosaurs from Laurasia, and evidence indicates carcharodontosaurians remained the dominant predators relative to tyrannosauroids, at least in Asia, as late as the Turonian.

Resistance Exercise After Laparoscopic Surgery Enhances Improvement in Exercise Tolerance in Geriatric Patients With Gastrointestinal Cancer.

INTRODUCTION:  Early mobilization after cancer surgery is generally recommended. However, the effects of postoperative resistance exercise during a hospital stay have been rarely investigated. This study aimed to clarify the effects of resistance exercise after laparoscopic surgery on exercise tolerance and skeletal muscle mass in geriatric patients with gastrointestinal cancer. METHODS: This single-center retrospective observational study included patients with gastrointestinal cancer who admitted for laparoscopic surgery. Exercise tolerance and skeletal muscle mass were assessed using a six-minute walking test (6MWT) and skeletal muscle index (SMI) at admission and discharge, respectively. Intergroup comparisons of absolute changes in 6MWT and SMI were analyzed by the unpaired t-test or Mann-Whitney U test according to whether resistance exercise was performed or not. Multivariable linear regression analyses were used to analyze the association of resistance exercise with changes in 6MWT and SMI. The analyses were adjusted for age, sex, cancer stage, postoperative complication, and preoperative exercise tolerance and skeletal muscle mass. RESULTS: Altogether, 66 patients (mean age 69.9 years; 60.6% men) were recruited. Of them, 72.7% performed the resistance exercise and started at a median of 4.5 postoperative days. There were no significant intergroup differences in absolute changes in the 6MWT and the SMI (p = 0.153, p = 0.476, respectively). Multivariable linear regression analysis showed that resistance exercise was independently and positively associated with the 6MWT at discharge (ß = 1.70, 95% confidence interval, 1.88 to 71.09) and did not significantly contribute to the SMI at discharge (95% confidence interval, -0.21 to 0.27). CONCLUSION: Resistance exercise may enhance the improvement in postoperative exercise tolerance in geriatric patients with gastrointestinal cancer who underwent laparoscopic surgery.

Interaction between spatial neglect and attention deficit in patients with right hemisphere damage.

Unilateral spatial neglect (USN) was originally regarded as a parietal syndrome, but it has become evident that USN is a disturbance in the widespread attention network. Here, we focused on an interaction between spatial neglect and non-spatial aspect of attention deficit, and aimed to establish a novel evaluation approach based on the characteristics of the spatial distribution of reaction times. We tested 174 patients with right hemisphere damage and divided them based on their prescreening scores on the Behavioral Inattention Test (BIT): (1) USN++ (n = 79: BIT<131), (2) USN+ (n = 47: BIT≥131 with history of USN), and (3) RHD (n = 48: without neglect symptom). The patients were asked to conduct a touch panel-based pointing task toward 2D-arranged (seven columns × five rows) circular targets on a PC monitor, and the reaction time to each object was recorded. To evaluate aspects of attention deficit and neglect symptoms, we calculated the total average of the reaction time for all objects (RTmean) and the ratios of the right and left space (L/Rratio), respectively. The results revealed that RTmean and L/Rratio can be regarded as independent evaluation parameters for attention deficit and neglect symptoms, respectively. Voxel-based lesion-symptom mapping based on RTmean and L/Rratio values revealed relevant lesions with attention-related brain areas (middle temporal gyrus, angular gyrus, and inferior frontal gyrus), and neglect-related brain areas (superior temporal gyrus and superior longitudinal fascicules). A cluster analysis with Gaussian mixture model detected six different states of USN with an interaction between neglect symptoms and attention deficit. Interestingly, the recovery process after USN can be properly explained by the transition pattern from one cluster to another. Our results suggest that a novel evaluation approach to distinguish between neglect symptoms and attention deficit, namely the characterization of the interaction between RTmean and L/Rratio, provides useful information for understanding pathological features of USN.

Measuring and Monitoring Skeletal Muscle Mass after Stroke: A Review of Current Methods and Clinical Applications.

OBJECTIVES: Muscle mass at admission is important to survive stroke, and stroke-induced sarcopenia is a serious problem because of its poor prognosis. Muscle mass measurement and monitoring are essential for appropriate rehabilitation and nutrition management. However, few reviews are available about the muscle mass measurement and monitoring after stroke. MATERIAL AND METHODS: Several methods are used to assess skeletal muscle mass in stroke, such as computed tomography (CT), ultrasound, bioelectrical impedance analysis, dual-energy X-ray absorptiometry, biomarkers, and anthropometrics. We summarized the current methods and clinical applications in stroke. RESULTS: In stroke, a head CT is used to estimate muscle mass by measuring the temporal muscle. However, it can be conducted retrospectively due to radiation exposure. After stroke, limb muscle atrophy and diaphragm dysfunction are observed using ultrasound. However, ultrasound requires an understanding of the methods and skill. A bioelectrical impedance analysis can be used to assess muscle mass in patients after a stroke unless they have dynamic fluid changes. Dual-energy X-ray absorptiometry is used for follow-up after hospital discharge. Urinary titin N-fragment and serum C-terminal agrin fragment reflect muscle atrophy after stroke. Anthropometrics may be useful with limited resources. CONCLUSIONS: We summarized the features of each measurement and proved the recent evidence to properly measure and monitor skeletal muscle mass after stroke.

The associations between nutritional status, physical function and skeletal muscle mass of geriatric patients with colorectal cancer.

BACKGROUND & AIMS: Nutritional status is associated with physical function and body composition. However, these relationships in patients with colorectal cancer remain poorly understood. This study aimed to investigate the association between nutritional status, physical function, and skeletal muscle mass in geriatric patients with colorectal cancer. METHODS: Preoperative patients diagnosed with colorectal cancer were recruited for this cross-sectional observational study. The correlations were calculated using Spearman's rank correlation coefficient, and the intergroup differences in physical function and skeletal muscle mass between categories according to nutritional assessment were analyzed using the Mann-Whitney U test or Kruskal-Wallis test. RESULTS: We recruited 127 patients (median age 71.0 years). Hand grip strength was correlated with geriatric nutritional risk index (GNRI) (male: p = 0.033; female: p = 0.014), albumin (male: p = 0.014; female: p = 0.003), and controlling nutritional status (CONUT) score (male: p = 0.004; female: p = 0.011) in both gender, and correlated with body mass index (BMI) (p = 0.027) in male patients. Psoas volume index (PVI) was positively correlated with BMI (male: p = 0.005; female: p < 0.001). In addition, intergroup comparisons for categories according to BMI showed PVI was significantly lower in the malnutrition category (male: p = 0.017; female: p < 0.001). Albumin and CONUT score were correlated with five-times sit-to-stand test (male: p = 0.011; female: p = 0.049, male: p = 0.031; female: p = 0.012, respectively) and short physical performance battery (male: p = 0.065; female: p = 0.028, male: p = 0.002; female: p = 0.006, respectively). Moreover, patients in lower albumin category had longer time on 5-times sit-to-stand test (male: p = 0.018; female: p = 0.009) and had lower scores on short physical performance battery (male: p = 0.027; female: p = 0.039). CONCLUSIONS: Hand grip strength correlated with various nutritional assessment tools, and PVI was correlated with BMI in particular. Five-times sit-to-stand test and short physical performance battery were correlated with serum albumin concentration and CONUT score. Physical function and skeletal muscle mass are associated with nutritional status, and hand grip strength might be more strongly associated with nutritional status.

Ultrasound Measurement of Septic Shock-induced Acute Skeletal Muscle Atrophy in Intensive Care Unit.

BACKGROUND: Skeletal muscle wasting progresses rapidly during critical care. However, the effect of skeletal muscle changes on physical function during intensive care remain poorly understood. OBJECTIVE: To examine the changes in skeletal muscle thickness of patients admitted to the intensive care unit (ICU) for septic shock and the relationship between skeletal muscle thickness and physical function following intensive care. DESIGN: Longitudinal observational study. SETTING: Single emergency hospital. PATIENTS: Ten septic shock patients who were mechanically ventilated in the ICU were recruited. INTERVENTIONS: Not applicable. METHODS: Ultrasound measurements of thickness of rectus femoris (RF) were conducted within 24 hours after admission and repeated every two days until the 14th hospital day. The correlations between TRF and various parametric data (i.e., age, severity classification, mechanically ventilated period, length of stay (LOS) at the ICU, and physical function) correlations were assessed with Pearson's product moment coefficient of correlation. MAIN OUTCOME MEASURE(S): Curve estimation for best fit for chronological changes in TRF with respect to the HD and the correlation between TRF and clinical indicators. RESULTS: Eight septic shock patients were observed completely for 14 days. TRF decreased linearly by 30.6% (IQR: 23.9-45.7) during the first 14 days. The correlation between TRF at admission and physical function at the 30th hospital day was close to significant. The TRF at the 14th hospital day was negatively correlated with disease severity and age. A positive correlation was observed between the decrease in rate of TRF and LOS at the ICU. CONCLUSION: Skeletal muscle thickness of septic shock patients rapidly decreased in a linear manner over 14 days and may predict physical function after critical care.

Perioperative physical and nutritional therapy for tongue cancer-induced malnutrition and muscle atrophy: A case report.

Malnutrition is a common complication in patients with tongue cancer who experience dysphagia and can steadily lead to skeletal muscle atrophy. Additionally, skeletal muscle loss commonly occurs in patients after invasive surgery. Therefore, patients with tongue cancer are at high risk of skeletal muscle atrophy during the perioperative phase of treatment. Over time, physical and nutritional therapy are expected to increase skeletal muscle mass and improve nutritional status. However, immediate benefits for patients in the perioperative phase of treatment are largely unknown. This case report aimed to evaluate the combined effects of physical and nutritional therapy for a patient in the perioperative phase of treatment for tongue cancer. We describe a 48-year-old woman diagnosed with tongue cancer. Her increasing difficulty with eating and swallowing led to malnutrition. After hospital admission for oral surgery, physical and nutritional therapy were initiated. Skeletal muscle mass measured by body composition analyzer and ultrasound apparatus showed increases, whereas blood tests to indicate nutritional status showed no improvement. This case suggests that physical and nutritional therapy are effective for increasing skeletal muscle during perioperative phase treatment in malnourished patients with tongue cancer and assessment of skeletal muscle mass is a reliable method for clinical evaluation.

ONO-7475, a Novel AXL Inhibitor, Suppresses the Adaptive Resistance to Initial EGFR-TKI Treatment in EGFR-Mutated Non-Small Cell Lung Cancer.

PURPOSE: Currently, an optimal therapeutic strategy comprising molecularly targeted agents for treating EGFR-mutated non-small cell lung cancer (NSCLC) patients with acquired resistance to osimertinib is not available. Therefore, the initial therapeutic intervention is crucial for the prolonged survival of these patients. The activation of anexelekto (AXL) signaling is known to be associated with intrinsic and acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). In this study, we investigated the best therapeutic strategy to combat AXL-induced tolerance to EGFR-TKIs using the novel AXL inhibitor ONO-7475. EXPERIMENTAL DESIGN: We examined the efficacy of ONO-7475 in combination with EGFR-TKIs in EGFR-mutated NSCLC cells using in vitro and in vivo experiments. We investigated the correlation between AXL expression in tumors and clinical outcomes with osimertinib for EGFR-mutated NSCLC patients with acquired resistance to initial EGFR-TKIs. RESULTS: ONO-7475 sensitized AXL-overexpressing EGFR-mutant NSCLC cells to the EGFR-TKIs osimertinib and dacomitinib. In addition, ONO-7475 suppressed the emergence and maintenance of EGFR-TKI-tolerant cells. In the cell line-derived xenograft models of AXL-overexpressing EGFR-mutated lung cancer treated with osimertinib, initial combination therapy of ONO-7475 and osimertinib markedly regressed tumors and delayed tumor regrowth compared with osimertinib alone or the combination after acquired resistance to osimertinib. AXL expression in EGFR-TKI refractory tumors did not correlate with the sensitivity of osimertinib. CONCLUSIONS: These results demonstrate that ONO-7475 suppresses the emergence and maintenance of tolerant cells to the initial EGFR-TKIs, osimertinib or dacomitinib, in AXL-overexpressing EGFR-mutated NSCLC cells, suggesting that ONO-7475 and osimertinib is a highly potent combination for initial treatment.