Effects of cardiac rehabilitation on cognitive function in patients with acute coronary syndrome: A systematic review.

Background: Construction of an intervention method for the cognitive dysfunction of patients with acute coronary syndrome (ACS) is needed. Exercise-based comprehensive cardiac rehabilitation is a potentially effective approach that can improve cognitive function in ACS patients. This study aimed to investigate the effect of cardiac rehabilitation on cognitive function in ACS patients through a systematic review. Methods: A systematic review was conducted of studies on PubMed, MEDLINE, Web of Science, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) on September 13, 2022, to identify those reporting the effects of cardiac rehabilitation on cognitive function in ACS patients. Data that reported exercise-based comprehensive cardiac rehabilitation and cognitive function (even if not main results and any type of cognitive function assessment was used) were extracted. Results: In total, six studies were included that comprised a total of 1085 ACS patients. Overall positive effects of cardiac rehabilitation on cognitive function in ACS patients were reported across the six studies. All studies included aerobic exercise, resistance exercise, and patient education in cardiac rehabilitation. Meta-analysis could not be undertaken because each dataset used different methods to evaluate cognitive function, and the outcomes were different. Conclusions: This systematic review showed that cardiac rehabilitation could have positive effects on cognitive function in ACS patients. Our results support the efficacy of cardiac rehabilitation for cognitive function in ACS patients. Additional well-designed clinical trials of exercise-based comprehensive cardiac rehabilitation should be conducted to clarify the true effect on cognitive function in ACS patients.

Impact of maximum phonation time on postoperative dysphagia and prognosis after cardiac surgery.

Objective: The incidence of postoperative complications, including dysphagia, increases as the population undergoing cardiovascular surgery ages. This study aimed to explore the potential of maximum phonation time (MPT) as a simple tool for predicting postextubation dysphagia (PED) and major adverse cardiac and cerebrovascular events (MACCEs). Methods: This retrospective study included 442 patients who underwent elective cardiac surgery at a university hospital. MPT was measured before surgery, and patients were stratified into 2 groups based on normal and abnormal MPTs. Postoperative complications, including PED and MACCEs, were also investigated. Swallowing status was assessed using the Food Intake Level Scale. Results: MPT predicted PED with prevalence of 11.0% and 18.0% in the normal and abnormal MPT groups, respectively (P = .01). During the follow-up period, MACCEs developed in 17.0% of patients. Frailty, European System for Cardiac Operative Risk Evaluation II score, PED, and MPT were markedly associated with MACCEs (adjusted hazard ratios: 2.25, 1.08, 1.96, and 0.96, respectively). Mediation analysis revealed that MPT positively influenced PED and MACCEs, whereas PED positively influenced MACCEs. The trend in restricted cubic spline analysis indicated that the hazard ratio for MACCEs increased sharply when MPT was <10 seconds. Conclusions: These findings underscore the potential of MPT as a valuable tool in the preoperative assessment and management of patients undergoing cardiac surgery. By incorporating MPT into routine preoperative evaluations, clinicians can identify patients at a higher risk of PED and MACCEs, allowing for targeted interventions and closer postoperative monitoring. This may improve patient outcomes and reduce the health care costs associated with these complications.

Effects of Group Exercise Intervention on Quality of Life and Physical Parameters in Patients with Childhood Cancer: A Systematic Review.

BACKGROUND: Although the survival rates of childhood cancer are increasing, children diagnosed as having cancer experience psychological and physical problems and a declining quality of life (QOL). METHODS: A systematic review of PubMed databases was conducted up to September 2023 to identify studies reporting the effects of group exercise intervention in children with cancer. The inclusion criteria were pre-specified, including children aged ≤19 years old who received group exercise intervention and interventional studies written in English. Studies involving non-exercise intervention or non-group intervention were excluded. RESULTS: Five studies were included in the present review. In three studies, QOL and physical parameters were improved after group exercise intervention, and in two studies, only physical parameters were improved. Improvements in QOL were achieved through psychosocial variables, improved scores of subscales of pain and hurt, nausea, and procedure-related anxiety, and reduced cancer-related fatigue. All studies had high numbers of participants who completed the intervention. However, all studies showed a high risk of bias regarding the selection of the reported results, and most studies showed a high risk of bias regarding deviations from the intended intervention and outcome measurement. CONCLUSION: The reviewed studies showed that group exercise intervention for children with cancer could improve their QOL and/or physical parameters.

Gut microbial stability in older Japanese populations: insights from the Mykinso cohort.

Gut microbiota imbalance plays an important role in the pathogenesis of various diseases. Here, we determined microbe-microbe interactions and gut microbiome stability in a Japanese population with varying body mass indices (BMIs) and enterotypes. Using 16S ribosomal RNA gene sequencing, we analyzed gut microbial data from fecal samples obtained from 3,365 older Japanese individuals. The individuals were divided into lean, normal, and obese groups based on their BMIs. They were further categorized according to their gut microbiota enterotypes: Bacteroides (enterotype B), Prevotella (enterotype P), and Ruminococcus (enterotype R). We obtained data on different host factors, such as age, BMI, and disease status, using a survey questionnaire evaluated by the Mykinso gut microbiome testing service. Subsequently, we evaluated the co-occurrence network. Individual differences in BMI were associated with differences in co-occurrence networks. By exploring the network topology based on BMI status, we observed that the network density was lower in the lean group than that in the normal group. Furthermore, a simulation-based stability analysis revealed a lower resistance index in the lean group than those in the other two groups. Our results provide insights into various microbe-microbe interactions and gut microbial stability and could aid in developing appropriate therapeutic strategies targeting gut microbiota modulation to manage frailty.

Activity of Daily Living and Walking Ability of Patients with Severe COVID-19 at Discharge from an Acute Care Hospital.

Objectives: The effectiveness of acute rehabilitation treatment for severe coronavirus disease 2019 (COVID-19) has not yet been established. This study examined the efficacy of treatment provided to patients with severe COVID-19 in an acute care facility. Methods: A total of 98 patients with severe COVID-19 requiring inpatient management in our intensive care unit (ICU) were included between December 2020 and October 2021. They were divided into two groups: those who received physiotherapy (PT group; n=44) and those who did not receive physiotherapy (non-PT group; n=54). Their backgrounds, clinical characteristics, and activities of daily life (ADL) at discharge were compared to examine factors that influenced the need for physiotherapy (PT). We also evaluated the effect of PT on ADL by comparing the Barthel Index (BI) before PT and at discharge. Results: The PT group patients were significantly older, had longer hospital and ICU stays, and used invasive mechanical ventilators (IMV) more frequently than those in the non-PT group. More patients in the non-PT group were able to walk at discharge than in the PT group. The PT group patients showed significant improvement in BI and ADL at discharge when compared with BI at the start of PT, regardless of whether an IMV was used. Conclusions: Older patients with severe COVID-19 with prolonged hospitalization or ICU stay or on an IMV are prone to a decline in ADL and may need to be considered for early PT.

Relationship between nutritional status and clinical outcomes among older individuals using long-term care services: A systematic review and meta-analysis.

BACKGROUND & AIMS: Nutritional status is a significant issue in an aging society; however, the impact of the nutritional status of older individuals using long-term care services on the caregiving burden remains unclear. This systematic review and meta-analysis aimed to investigate the impact of nutritional issues on adverse outcomes in older individuals using long-term care services. METHODS: We used data from the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Web of Science, CINAHL, and Ichu-shi Web databases. Original articles published in English or Japanese between January 2000 and July 2022 were included. The inclusion criteria were interventional and observational studies on individuals using long-term care services with aged ≥65 years and a focus on body weight or weight loss. Data on adverse outcomes related to caregiving burden, including the number of people requiring care, mortality, complications, activities of daily living (ADL), and quality of life, were collected. RESULTS: The literature search yielded 7873 studies, of which 35 were ultimately included. Seven observational studies investigated mortality outcomes, and seven examined ADL outcomes. The meta-analysis revealed significantly higher mortality rates in individuals classified as underweight (BMI <18.5 kg/m2) than in those with BMI ≥18.5 kg/m2 (risk ratio [RR] 1.49; 95 % confidence interval [CI] 1.31 to 1.73, 0.22; I2 93 %). Further, on categorising the participants based on a BMI cutoff of 25 kg/m2, those with a BMI of <25 kg/m2 had a significantly increased mortality rate (RR 1.21; 95 % CI 1.04-1.40; I2 = 98 %). BMI and weight loss did not affect ADL. CONCLUSIONS: Our findings indicate that underweight and weight loss are significantly associated with increased mortality in older individuals using long-term care services. Therefore, appropriate weight management is recommended for this population. However, further research is necessary owing to the high heterogeneity observed in this study.

Evaluation of the usefulness of culture of induced sputum and the optimal timing for the collection of a good-quality sputum sample to identify causative pathogen of community-acquired pneumonia in young children: A prospective observational study.

BACKGROUND: The usefulness of an induced sputum in the identification of causative bacteria of community-acquired pneumonia (CAP) in young children is controversial. This study aimed to investigate the significance of the implementation of an induced sputum culture among children with CAP and the impact of prior use of antimicrobial agents on the quality of the sample and result of the culture. METHODS: This prospective study included 96 children hospitalized for acute bacterial CAP whose sputum samples were collected by suctioning from the hypopharynx through the nose. The samples were evaluated for their quality using Geckler classification, and the result of this conventional culture method was compared to that of a clone library analysis of the bacterial 16S rRNA gene sequence for each sample. RESULTS: The concordance between bacteria isolated by sputum culture and the most predominant bacteria identified by a clonal library analysis was significantly higher in the samples judged as a good quality (Geckler 5, 90%) than in others (70%). The rate of good-quality sputum sample was significantly higher in samples collected from patients without prior antimicrobial therapy (70%) than in those from patients with it (41%). The concordance between the two methods was significantly higher in the former (88%) than in the latter population (71%). CONCLUSION: Bacteria isolated by the culture using good-quality sputum samples collected from children with CAP were more likely to be causative pathogens. Sputum samples collected before starting antimicrobial therapy showed better quality and higher probability of the identification of causative pathogens.

Predictors of Activities of Daily Living in Intensive Care Unit Survivors: A Propensity Score Matching Analysis.

Objectives: Increased long-term impairment is common among intensive care unit (ICU) survivors. However, predictors of activities of daily living (ADL) in ICU survivors are poorly understood. We aimed to focus on the trajectory of physical function and explore the clinical variables that affect ADL at hospital discharge. Methods: We enrolled 411 patients admitted to the ICU from April 2018 to October 2020. Physical function was evaluated at ICU admission, ICU discharge, and hospital discharge. We assessed physical function (grip strength, arm and calf circumference, quadriceps thickness, and Barthel index). Patients were assigned to the high or low ADL group based on their Barthel index at discharge. Propensity score matching analysis was performed to minimize selection biases and differences in clinical characteristics. Results: After matching propensity scores, 114 of the 411 patients (aged 65±15 years) were evaluated. The high ADL group showed better physical function at ICU discharge and hospital discharge than the low ADL group. An overall decreasing trend in muscle mass was observed over time; the rates of decline were lower in the high ADL group than in the low ADL group. The cutoff values for relative changes in calf circumference and quadriceps thickness to predict high ADL were -7.89% (sensitivity: 77.8%, specificity: 55.6%) and -28.1% (sensitivity: 81.0%, specificity: 58.8%), respectively. Conclusions: The relative decreases in calf circumference and quadriceps thickness during hospitalization were lower in patients who maintained their ADL. Assessment of the trajectory of physical function can predict ADL status at hospital discharge among ICU survivors.

Reliability and Validity of Quadriceps Muscle Thickness Measurements in Ultrasonography: A Comparison with Muscle Mass and Strength.

Objectives: Measurement of skeletal muscle using ultrasonography (US) has received considerable attention as an alternative method of muscle assessment. However, intra- and inter-rater reliability remains controversial. Furthermore, there is no consensus regarding the relationship between muscle assessment using US and muscle mass or physical assessment. We aimed to verify the validity and reliability of muscle measurements using US and its relationships with muscle strength and physical assessment. Methods: The 22 participants were all healthy men. Quadriceps muscle thickness was measured by US by three different raters. Intraclass correlation coefficient (ICC) was used to assess inter- and intra-rater reliability. The maximum isokinetic strength of the quadriceps and handgrip strength were used as measures of lower and upper muscle strength, respectively. Leg muscle mass was assessed using the leg skeletal muscle index (SMI), measured by body impedance analysis, and calf circumference. Results: The intra-rater reliability was excellent which the ICC(1,1) ranges 0.957-0.993, and ICC(1,3) ranges 0.985-0.998. For inter-rater reliability, the values of 0.904 for ICC(2,1) and 0.966 for ICC(2,3) indicated excellent reliability. Leg SMI was significantly correlated with quadriceps thickness (r=0.36). Maximum isokinetic strength and handgrip strength showed weak but statistically significant correlations with quadriceps thickness (r=0.20, r=0.30, respectively). The correlation between quadriceps thickness and calf circumference was not statistically significant. Conclusions: Quadriceps muscle assessment using US is a valid and reliable technique for healthy individuals. Quadriceps muscle thickness was significantly positively correlated with upper and lower muscle strength and leg SMI. Muscle thickness assessment could replace full body muscle assessment in clinical settings.

Usefulness of Cervical Computed Tomography Hounsfield Units to Differentiate Kawasaki Disease From a Deep-neck Abscess.

We measured the Hounsfield units (HUs) value of cervical plain computed tomography images to differentiate between Kawasaki disease (KD) and a deep-neck abscess (DNA). The HUs value was significantly lower in KD than in DNA, making it a useful marker for differentiating between these 2 diseases.

Postoperative dysphagia as a predictor of functional decline and prognosis after undergoing cardiovascular surgery.

AIMS: Post-extubation dysphagia (PED), an often overlooked problem, is a common and serious complication associated with mortality and major morbidity after cardiovascular surgery. Dysphagia is considered an age-related disease, and evaluating its long-term effects is a pressing issue with rapidly progressing ageing worldwide. Therefore, we examined the effect of PED on functional status and long-term cardiovascular events in patients undergoing cardiovascular surgery. METHODS AND RESULTS: This single-centre, retrospective cohort study included 712 patients who underwent elective cardiovascular surgery and met the inclusion criteria. Patients were divided into PED and non-PED groups based on their post-operative swallowing status. The swallowing status was assessed using the Food Intake Level Scale. Functional status was evaluated as hospital-associated disability (HAD), defined as a decrease in activities of daily living after hospital discharge compared with preoperative values. The patients were subsequently followed up to detect major adverse cardiac and cerebrovascular events (MACCEs). Post-extubation dysphagia was present in 23% of the 712 patients and was independently associated with HAD (adjusted odds ratio, 2.70). Over a 3.5-year median follow-up period, MACCE occurred in 14.1% of patients. Multivariate Cox proportional hazard analysis revealed HAD to be independently associated with an increased risk of MACCE (adjusted hazard ratio, 1.85), although PED was not significantly associated with MACCE. CONCLUSION: Post-extubation dysphagia was an independent HAD predictor, with the odds of HAD occurrence being increased by 2.7-fold due to PED. Hospital-associated disability accompanied by PED is a powerful predictor of poor prognosis. Perioperative evaluation and management of the swallowing status, and appropriate therapeutic interventions, are warranted.

Rehabilitation Nutrition in Patients with Chronic Kidney Disease and Cachexia.

Rehabilitation nutrition is a proposed intervention strategy to improve nutritional status and physical function. However, rehabilitation nutrition in patients with cachexia and protein-energy wasting (PEW), which are the main nutrition-related problems in patients with chronic kidney disease (CKD), has not been fully clarified. Therefore, this review aimed to summarize the current evidence and interventions related to rehabilitation nutrition for cachexia and PEW in patients with CKD. CKD is a serious condition worldwide, with a significant impact on patient prognosis. In addition, CKD is easily complicated by nutrition-related problems such as cachexia and PEW owing to disease background- and treatment-related factors, which can further worsen the prognosis. Although nutritional management and exercise therapy are reportedly effective for cachexia and PEW, the effectiveness of combined nutrition and exercise interventions is less clear. In the future, rehabilitation nutrition addressing the nutritional problems associated with CKD will become more widespread as more scientific evidence accumulates. In clinical practice, early intervention in patients with CKD involving both nutrition and exercise after appropriate assessment may be necessary to improve patient outcomes.

Impact of Frailty on Postoperative Dysphagia in Patients Undergoing Elective Cardiovascular Surgery.

Background: Postextubation dysphagia (PED) is a serious postoperative complication following cardiovascular surgery that can lead to a worse prognosis. On the other hand, frailty is a prognostic factor in patients who undergo cardiac surgery. Objectives: This study investigated the effect of frailty status on PED and impact of PED on postoperative complications. Methods: This single-center retrospective cohort study included 644 consecutive patients who underwent elective cardiovascular surgery between May 1, 2014, and December 31, 2020; they were assigned to the PED or non-PED group based on postoperative swallowing status, and postoperative complications were investigated. Frailty status and physical functions, including walking speed, grip strength, Short Physical Performance Battery, and 6-minute walking distance, were preoperatively assessed; the frailty-status cutoff for predicting PED was determined from the receiver-operating characteristic curve. Results: In this study cohort (mean age 67.7 years), the overall PED prevalence was 14.8%; preoperative frailty had a significantly higher prevalence in the PED group (50.0%) than in the non-PED group (20.3%; P < 0.001). PED correlated with a higher incidence of postoperative pneumonia and prolonged intensive care unit or hospital stay (P < 0.05 for all). After adjustment for confounders, multiple regression analysis revealed that preoperative frailty was independently associated with PED (P < 0.001). Conclusions: PED occurred commonly after cardiovascular surgery and increased the risk of postoperative complications. Preoperative frailty was independently associated with PED. The 6-minute walking distance was the most powerful predictor of PED. Evaluation of preoperative frailty status is important for risk stratification and prevention of postoperative morbidity in patients undergoing surgery.

Impact of body mass index on in-hospital mortality for six acute cardiovascular diseases in Japan.

Body mass index (BMI) distribution and its impact on cardiovascular disease (CVD) vary between Asian and western populations. The study aimed to reveal time-related trends in the prevalence of obesity and underweight and safe ranges of BMI in Japanese patients with CVD. We analyzed 5,020,464 records from the national Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination dataset over time (2012-2019) and evaluated BMI trends and the impact on in-hospital mortality for six acute CVDs: acute heart failure (AHF), acute myocardial infarction (AMI), acute aortic dissection (AAD), ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). Patients were categorized into five groups using the WHO Asian-BMI criteria: underweight (< 18.5 kg/m2), normal (18.5-22.9 kg/m2), overweight at risk (23.0-24.9 kg/m2), obese I (25.0-29.9 kg/m2), and obese II (≥ 30.0 kg/m2). Age was significantly and inversely related to high BMI for all diseases (P < 0.001). The proportion of BMI categories significantly altered over time; annual BMI trends showed a significant and gradual increase, except AAD. In adjusted mixed models, underweight was significantly associated with a high risk of in-hospital mortality in all CVD patients (AHF, OR 1.41, 95% CI 1.35-1.48, P < 0.001; AMI, OR 1.27, 95% CI 1.20-1.35, P < 0.001; AAD, OR 1.23, 95% CI 1.16-1.32, P < 0.001; IS, OR 1.45, 95% CI 1.41-1.50, P < 0.001; ICH, OR 1.18, 95% CI 1.13-1.22, P < 0.001; SAH, OR 1.17, 95% CI 1.10-1.26, P < 0.001). Moreover, obese I and II groups were significantly associated with a higher incidence of in-hospital mortality, except AHF and IS. Age was associated with in-hospital mortality for all BMI categories in six CVD patients. BMI increased annually in patients with six types of CVDs. Although underweight BMI was associated with high mortality rates, the impact of obesity on in-hospital mortality differs among CVD types.

Hospital-associated disability and hospitalization costs for acute heart failure stratified by body mass index- insight from the JROAD/JROAD-DPC database.

BACKGROUND: The impact of body mass index (BMI) on hospital mortality in patients with acute heart failure has been well documented in Asian populations. However, the relationship between BMI, hospital-associated disability (HAD), and hospitalization costs in patients with heart failure is poorly understood. This study aimed to explore the impact of BMI on HAD and hospitalization costs for acute heart failure in Japan. METHODS: From April 2012 to March 2020, the Japanese Registry of All Cardiac and Vascular Disease Diagnosis Procedure Combination (JROAD-DPC) database was used to identify patients with acute heart failure. All patients were categorized into five groups according to the World Health Organization Asian BMI criteria. The hospitalization costs and HAD were evaluated. RESULTS: Among the 238,160 eligible patients, 15.7% were underweight, 42.2% were normal, 16.7% were overweight, 19.3% were obese I, and 6.0% were obese II, according to BMI. The prevalence of HAD was 7.43% in the total cohort, and the risk of HAD increased with a lower BMI. Restricted cubic spline analysis showed a U-shaped relationship between BMI and hospitalization costs for all ages. Furthermore, developing HAD was associated with greater costs compared with non-HAD, regardless of BMI category. CONCLUSIONS: We found that the lower the BMI, the higher the incidence of HAD. A U-shaped association was confirmed between BMI and hospitalization costs, indicating that hospitalization costs increased for both lower and higher BMI regardless of age. BMI could be an important and informative risk stratification tool for functional outcomes and economic burdens.

Malnutrition diagnosed by the Global Leadership Initiative on Malnutrition criteria as a predictor of gait ability in patients with hip fracture.

AIM: Malnutrition is common in patients with hip fractures and is associated with poor clinical outcomes. The Global Leadership Initiative on Malnutrition (GLIM) and the European Society for Clinical Nutrition and Metabolism (ESPEN) criteria are widely used to diagnose malnutrition. However, the criteria regarding the prediction of gait ability in patients with hip fractures during the acute phase remain unclear. We aimed to determine whether GLIM or ESPEN criteria were more appropriate for predicting gait ability at discharge from an acute hospital. METHODS: This retrospective observational study included hip fracture patients aged ≥ 65 years. Patients were classified as malnourished or non-malnourished according to the GLIM and ESPEN criteria at admission. The primary outcome was gait ability, which was evaluated using functional ambulation categories (FAC) at discharge. We categorized into those with (FAC score ≥ 3 points) and without (< 3 points) improved gait ability. Logistic regression analysis for FAC was performed to determine whether GLIM or ESPEN was predictive of gait ability at discharge. RESULTS: Overall 157 patients were included; the median age was 84 years, and 75.3% were female. The prevalence of malnutrition was 73.9% and 25.5% according to the GLIM and ESPEN criteria, respectively. Logistic regression analysis showed that malnutrition evaluated using the GLIM criteria were predictive of lower FAC at discharge (odds ratio, 0.394; 95% CI, 0.164-0.946), while ESPEN criteria did not show statistically significant differences (odds ratio, 0.625; 95% CI, 0.292-1.335). CONCLUSION: GLIM criteria are useful for predicting gait ability at discharge during acute hospitalization in patients with hip fractures.

Relationship between Nutrition-Related Problems and Falls in Hemodialysis Patients: A Narrative Review.

Falls are a social problem that increase healthcare costs. Hemodialysis (HD) patients need to avoid falling because fractures increase their risk of death. Nutritional problems such as frailty, sarcopenia, undernutrition, protein-energy wasting (PEW), and cachexia may increase the risk of falls and fractures in patients with HD. This review aimed to summarize the impact of frailty, sarcopenia, undernutrition, PEW, and cachexia on falls in HD patients. The reported global incidence of falls in HD patients is 0.85-1.60 falls per patient per year. HD patients fall frequently, but few reports have investigated the relationship between nutrition-related problems and falls. Several studies reported that frailty and undernutrition increase the risk of falls in HD patients. Nutritional therapy may help to prevent falls in HD patients. HD patients' falls are caused by nutritional problems such as iatrogenic and non-iatrogenic factors. Falls increase a person's fear of falling, reducing physical activity, which then causes muscle weakness and further decreased physical activity; this cycle can cause multiple falls. Further research is necessary to clarify the relationships between falls and sarcopenia, cachexia, and PEW. Routine clinical assessments of nutrition-related problems are crucial to prevent falls in HD patients.

Lysosome­targeted drug combination induces multiple organelle dysfunctions and non­canonical death in pancreatic cancer cells.

Pancreatic cancer is one of the leading causes of cancer­related mortality and has the lowest 5­year survival rate. Therefore, novel strategies are urgently required to treat pancreatic cancer. Pancreatic ductal adenocarcinoma (PDAC) cells rely on enhanced lysosomal function for survival and proliferation to facilitate the degradation of contents accumulated via autophagy and macropinocytosis. Previously, we have reported that the combination of epidermal growth factor receptor/HER2 inhibitor lapatinib and sphingosine analog fingolimod (FTY720) confers a significant cytostatic effect in lung cancer cells. In the present study, the combined effects of these drugs on PDAC cell lines, BxPC­3, KP­4, PANC­1 and MIA PaCa­2, were examined. It was observed that FTY720 enhanced the lapatinib­induced cytotoxic effect and caused non­canonical and lysosome­dependent death in PDAC cells. Lapatinib and FTY720 induced lysosomal swelling and inhibited lysosomal acidification. Combination treatment with lapatinib and FTY720 increased lysosomal membrane permeability, induced mitochondrial depolarization, induced endoplasmic reticulum stress and disturbed intracellular calcium homeostasis. Additionally, the cytotoxic effect of lapatinib was enhanced by hydroxychloroquine or the CDK4/6 inhibitor abemaciclib, both of which induce lysosomal dysfunction. Collectively, these results indicated that the lysosome­targeted drug combination induces multiple organelle dysfunction and exerts a marked cytotoxic effect in PDAC cells.

Ultimate Load Measuring System for Fixation of Soft Tissue to Bone.

BACKGROUND: The initial ultimate load for graft fixation is one of the essential factors in the reconstruction of lateral ankle ligaments. Several anchoring devices have been developed to fix the substitute ligament into the bone. A fair comparison of these fixation methods warrant a reproducible examination system. The purpose of this study was to make an experimental animal model and to compare the initial ultimate loads of 3 graft fixation methods, including the use of EndoButton (EB), interference screw (IFS), and a novel socket anchoring (SA) technique. METHODS: Porcine calcaneus bones and 5-mm-wide split bovine Achilles tendons were used as fixation bases and graft materials, respectively. Both ends were firmly sutured side-by-side, using the circumferential ligation technique as a double-strand substitute that was 45 mm in length. Porcine calcanei with similar characteristics to adult human calcanei were mounted on a tensile testing machine, and substitutes were fixed into bones using the 3 fixation methods. A polyester tape was passed through the tendon loop and connected to a crosshead jig of the testing machine. The initial ultimate loads were measured in 15 specimens for each fixation method to simulate a lateral ankle ligament (LAL) injury. RESULTS: The ultimate loads (ULs) were 223.6 ± 52.7 N for EB, 229.7 ± 39.7 N for SA, and 208.8 ± 65.3 N for IFS. No statistically significant difference was observed among the 3 groups (P = .571). All failures occurred at the bone-ligament substitute interface. CONCLUSION: The initial ULs in all 3 fixation methods were sufficient for clinical usage. These values were larger than the UL of the anterior talofibular ligament; however, these were smaller than the UL of the calcaneofibular ligament. CLINICAL RELEVANCE: In an experimental animal model, ULs for SA, EB, and IFS techniques showed no significant difference. All failures were observed in the fixation site of the calcaneus and were overwhelmingly related to suture fixation failure.

Impact of mild cognitive impairment on unplanned readmission in patients with coronary artery disease.

AIMS: To investigate the effect of mild cognitive impairment (MCI) on unplanned readmission in patients with coronary artery disease (CAD). METHODS AND RESULTS: From 2132 CAD patients, MCI was estimated with the Japanese version of the Montreal Cognitive Assessment (MoCA-J) in 243 non-dementia patients who met the study criteria. The primary outcome was unplanned hospital readmission after discharge. The incidence of MCI in this cohort was 33.3%, and 51 patients (21.0%) had unplanned readmission during a mean follow-up period of 418.6 ± 203.5 days. After adjusting for the covariates, MCI (hazard ratio, 2.28; 95% confidence interval: 1.09-4.76; P = 0.03) was independently associated with unplanned readmission in the multivariable Cox proportional hazard regression analysis. In the Kaplan-Meier analysis, the cumulative incidence of unplanned readmission for the MCI group was significantly higher than that for the non-MCI group (log-rank test, P < 0.001). Even after exclusion of the patients readmitted within 30 days of discharge, the main results did not change (log-rank test, P < 0.001). CONCLUSION: Mild cognitive impairment was independently associated with unplanned readmission after adjustment for many independent variables in CAD patients. In addition to its short-term effects, the adverse effects of MCI had a persistent, long-term impact on CAD patients. Assessment of cognitive function should be conducted by health professionals prior to hospital discharge and during follow-up. To prevent readmission of CAD patients, it will be necessary to support solutions to the problems that inhibit secondary prevention behaviours based on the assessment of the patients' cognitive function.