Rehabilitation in Acute COVID-19 Patients: A Japanese Retrospective, Observational, Multi-Institutional Survey.

OBJECTIVE: To investigate the changes in activities of daily living (ADLs) and the conditions of rehabilitation for acute COVID-19 patients in Japan. DESIGN: Retrospective, observational survey. SETTING: Four tertiary hospitals with intensive care units and one secondary hospital in Japan. PARTICIPANTS: COVID-19 patients (N=478) admitted to 5 hospitals INTERVENTIONS: : Not applicable. MAIN OUTCOME MEASURES: Walking ability and swallowing status were assessed using the FIM locomotion item and Food Intake Scale at admission and discharge. The physiatrists of each hospital were also surveyed regarding the factors that influenced decisions to provide rehabilitation. RESULTS: Excluding patients who died, the proportion of critical patients who could walk independently at discharge was 63%, and the proportion of those who were able to take 3 meals orally at discharge was 90%. Rehabilitation was provided to 13.4% of all patients and to 58.3% of patients with critical symptoms. CONCLUSIONS: After COVID-19 treatment, patients, especially those with critical symptoms, still have functional disabilities related to walking and swallowing. It is possible that sufficient rehabilitation could not be provided during the period studied.

Preoperative maximum phonation time as a predictor of pneumonia in patients undergoing esophagectomy.

PURPOSE: Esophagectomy is a highly invasive procedure, associated with several postoperative complications including pneumonia, anastomotic leakage, and sepsis, which may result in multiorgan failure. Pneumonia is considered a major predictor of poor long-term prognosis, so its prevention is important for patients undergoing surgery for esophageal cancer. METHODS: The subjects of this study were 137 patients who underwent esophagectomy at Keio University Hospital, Tokyo, Japan, between January, 2012 and December, 2016. Patients who underwent R0 or R1 resection or esophagectomy with organ excision were included. Patients who underwent salvage surgery or resection of recurrent laryngeal nerve, and those with preoperative recurrent laryngeal nerve palsy, were excluded. We investigated the effect of the maximum phonation time on the development of postoperative pneumonia. RESULTS: Pneumonia developed more frequently in patients with a long operative time, clinically left recurrent nerve lymph node metastasis, and a short preoperative maximum phonation time (p = 0.074, 0.046, and 0.080, respectively). Pneumonia was also more common in men with an abnormal maximum phonation time (p = 0.010). CONCLUSIONS: The maximum phonation time is a significant predictor of postoperative pneumonia after esophagectomy in men.

Resting Energy Expenditure in Patients with Stroke during the Subacute Phases - Relationships with Stroke Types, Location, Severity of Paresis, and Activities of Daily Living.

BACKGROUND: The energy demands in patients with stroke during the subacute phases are unclear. However, this information is essential for appropriate clinical and nutritional management. The aims of this study were to determine the resting energy expenditure (REE) during the subacute phases, examine its relationships with stroke types, location, severity of hemiparesis, and activities of daily living (ADL), and evaluate whether estimation of REE from the Harris-Benedict equation (HB) requires the addition of a 'stress factor' to capture possible additional REE imposed by stroke. METHODS: We measured REE in 95 patients with subacute stroke (53.5 ± 16.6 days post-stroke) with indirect calorimetry, and compared it with predicted values of energy expenditure estimated from the HB (expressed as percentage). Patients were admitted for rehabilitation of their first ischemic or nonsurgical hemorrhagic stroke. The severity of hemiparesis was assessed with the motor items of the Stroke Impairment Assessment Set (SIAS). The ADL was assessed with the Functional Independence Measure (FIM). We compared REE and %HB of the two groups divided by hemiparesis severity and ADL limitation using the Student's t-test, and those of the five groups divided by stroke location. The correlations between REE and the motor items of the SIAS and the FIM score were assessed with the Spearman rank correlation test. A multiple regression analysis for REE was conducted. RESULTS: The average body weight (BW) was 57.1 ± 11.3 kg. The average body mass index (BMI) was 22.5 ± 4.0. The mean REE (%HB) was 1,271 ± 284 kcal/day (106.0 ± 17.3%). REE and %HB of the low ADL group was less than that of the high ADL group (p < 0.05). The REE had a positive correlation with the FIM score (rs = 0.51, p < 0.01). The motor items of the SIAS were not significantly correlated with REE. BW, FIM, and stroke location were independent predictors of REE. CONCLUSIONS: Analysis of energy expenditure suggests that stroke patients are not hypermetabolic during the subacute phase. The 'stress factor' in stroke patients during the subacute phase was 1.0-1.1. This finding provides important information for improving nutritional management during the subacute phase in patients with stroke.

Functional analysis of lysosomes during mouse preimplantation embryo development.

Lysosomes are acidic and highly dynamic organelles that are essential for macromolecule degradation and many other cellular functions. However, little is known about lysosomal function during early embryogenesis. Here, we found that the number of lysosomes increased after fertilization. Lysosomes were abundant during mouse preimplantation development until the morula stage, but their numbers decreased slightly in blastocysts. Consistently, the protein expression level of mature cathepsins B and D was high from the one-cell to morula stages but low in the blastocyst stage. One-cell embryos injected with siRNAs targeted to both lysosome-associated membrane protein 1 and 2 (LAMP1 and LAMP2) were developmentally arrested at the two-cell stage. Pharmacological inhibition of lysosomes also caused developmental retardation, resulting in accumulation of lipofuscin. Our findings highlight the functional changes in lysosomes in mouse preimplantation embryos.

Impact of early postoperative factors on changes in skeletal muscle mass after esophagectomy in older patients with esophageal cancer.

BACKGROUND: Loss of skeletal muscle mass, measured by the skeletal muscle mass index (SMI), after esophagectomy negatively impacts prognosis. However, the information to develop novel supportive care options for preventing loss of skeletal muscle mass is limited. The purpose of this retrospective cohort study was to investigate the impact of early postoperative factors on change in SMI 4 months after curative esophagectomy in older patients with esophageal cancer. METHODS: This study included 113 subjects who underwent esophagectomy between 2015 and 2020. Preoperative and postoperative SMI (cm2/m2) were calculated from computed tomography images. The percentage change in SMI 4 months after surgery (SMI%) was calculated as follows: ([postoperative SMI - preoperative SMI] ÷ preoperative SMI) × 100. Potential factors affecting percentage change of SMI after surgery were analyzed by multiple regression. RESULTS: The mean SMI% was - 5.6%. The percentage change (per 1%) in quadriceps muscle strength in the first month after surgery (standardized ß = 0.190, p = 0.048) impacted the SMI%, which was independent of age, sex, preoperative SMI, comorbidity, pathological stage, and neoadjuvant chemotherapy. CONCLUSION: Quadriceps muscle weakness in the first month after esophagectomy impacted the SMI% in a dose-dependent relationship.

Relationship Between Pneumonia and Dysphagia in Patients With Multiple System Atrophy.

Introduction: Dysphagia is one of the most clinically significant disabilities in patients with multiple system atrophy (MSA), because it can cause aspiration pneumonia, which is potentially fatal. In this study, the Neuromuscular disease Swallowing Status Scale (NdSSS), which was developed to evaluate dysphagia in patients with neuromuscular diseases, was used to evaluate patients with MSA. In addition, correlation between a history of pneumonia and swallowing function was evaluated. Methods: Study 1: Reliability, concurrent validity, and responsiveness of the NdSSS in patients with MSA. In 81 patients for whom evaluation items could be collected, the NdSSS was tested for its interrater and intrarater reliability using weighted kappa statistics. Concurrent validity was assessed by correlating the NdSSS with existing scales (Functional Oral Intake Scale (FOIS), Functional Intake LEVEL Scale (FILS), and the unified MSA rating scale (UMSARS)) using Spearman's rank correlation coefficients. Sixty-three patients were evaluated by videofluorographic (VF) swallowing examination. To evaluate concurrent validity, Spearman's rank correlation coefficients were calculated between the NdSSS and VF swallowing assessments. Additionally, scale responsiveness was determined using the standardized response mean (SRM) in 23 patients who could be followed up to assess their long-term course. Study 2: Cross-sectional survey of swallowing function and history of pneumonia. Data regarding history of pneumonia, UMSARS, NdSSS, age, sex, MSA subtype, and disease duration were retrospectively obtained from the medical records of 113 patients with MSA. Differences in these parameters and NdSSS stage between those with and without a history of pneumonia were examined using the Mann-Whitney test or chi-squared test. Furthermore, clinical factors related to a history of pneumonia were examined by binomial logistic regression analysis. Results: The NdSSS showed satisfactory reliability, concurrent validity, and responsiveness. A history of pneumonia was related to the severity of MSA, age, MSA subtype, and NdSSS stage. Binomial logistic regression analysis showed that NdSSS stage (odds ratio (OR), 0.490; 95% confidence interval (CI), 0.301-0.797, p = 0.001) and MSA subtype (OR, 4.031; 95% CI, 1.225-13.269, p = 0.021) were significantly associated with a history of pneumonia. Conclusions: In patients with MSA, the NdSSS has sufficient reliability, concurrent validity, and responsiveness for assessing dysphagia. Patients with a history of pneumonia have more severe dysphagia. We found that the pneumonia risk was related to NdSSS stage and MSA-p (predominantly parkinsonism). Meticulous care to prevent aspiration is needed from early stages of the disease.

Assessment of dysarthria with Frenchay dysarthria assessment (FDA-2) in patients with Duchenne muscular dystrophy.

PURPOSE: The purpose of this study was to test the psychometric properties of the Japanese version of Frenchay Dysarthria Assessment (FDA-2) and to use this tool to describe the features of speech in patients with Duchenne muscular dystrophy (DMD). MATERIALS AND METHODS: The Japanese version of FDA-2 was culturally adapted, and reliability and validity were examined in 22 and 50 patients, respectively. The Japanese version of FDA-2 was administered to 51 patients with DMD. Multiple regression analysis was performed to identify factors related to FDA-2 scores. RESULTS: Inter-/intra-rater reliabilities (ICCs) and internal consistency (Cronbach's α) for total scores were 0.76, 0.97, and 0.94 respectively. For construct validity, two-way ANOVA showed a significant interaction between the disorders and FDA-2 sections (p < 0.05). In DMD patients, the item of tongue at rest was most severely affected, reflecting tongue hypertrophy. Multiple regression analysis identified age, swallowing status, and ventilator use as significantly related. CONCLUSIONS: The results showed that the Japanese version of FDA-2 has satisfactory reliability and validity. The present study demonstrated the features of dysarthria and related factors in patients with DMD.Implications for rehabilitationIn Duchenne muscular dystrophy (DMD), an absent or defective dystrophin protein causes progressive weakness of respiratory and oropharyngeal muscles, both of which are crucial contributors to speech production.This study shows that the Japanese version of FDA-2 has satisfactory reliability and validity compared to original version.The Japanese version of FDA-2 characterizes dysarthria in patients with DMD in this cohort.

A comparison of swallowing dysfunction in Becker muscular dystrophy and Duchenne muscular dystrophy.

PURPOSE: Swallowing dysfunction has been reported in Duchenne muscular dystrophy (DMD), but has not been studied in Becker muscular dystrophy (BMD). The aims of this study were to report the characteristics of swallowing dysfunction in BMD compared with DMD. MATERIALS AND METHODS: The study participants were 18 patients with BMD and 18 patients with DMD. All the patients were examined using videofluorography during swallowing of 5 mL of fluid. The penetration-aspiration scale (P-A scale) and the videofluorographic dysphagia scale (VDS) were used to evaluate dysphagia. RESULTS: Swinyard functional ability stage was not significantly different between the BMD and DMD groups. Rate of aspiration, P-A scale score, and total VDS score did not differ across groups, but the VDS item score for laryngeal elevation was lower in the BMD group than in the DMD group (median scores 4.5 and 9, respectively; p < 0.001). In the BMD group, total VDS score significantly correlated with Swinyard stage (r = 0.78, p < 0.001), but not with age or lung function. CONCLUSION: Patients with BMD have swallowing problems similar to those observed in patients with DMD when matched according to physical functional status. These patients should be evaluated and followed-up for the duration of their disease. Implications for rehabiliation Dysphagia is one of the most critical problems in patients with progressive neuromuscular disease but dysphagia in patients with Becker muscular dystrophy (BMD) was not well known. Eighteen patients with BMD and 18 patients with Duchenne muscular dystrophy were examined with videofluorography. Patients with BMD have swallowing problems similar to those observed in patients with DMD.

Feasibility of a Respiratory Movement Evaluation Tool to Quantify Thoracoabdominal Movement for Neuromuscular Diseases.

BACKGROUND: An objective method to evaluate thoracoabdominal movement is needed in daily clinical practice to detect patients at risk of hypoventilation and to allow for timely interventions in neuromuscular diseases. The clinical feasibility, reliability, and validity of a newly developed method for quantifying respiratory movement using fiber grating sensors, called the Respiratory Movement Evaluation Tool (RMET), was evaluated. METHODS: The time needed to measure respiratory movement and the usability of the measurement were determined by 5 clinicians using the Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST) 2.0 questionnaire. Thoracoabdominal movement was measured using RMET 3 times in 10 healthy subjects to evaluate intraclass correlation coefficients (ICC). The subjects were encouraged to breathe 10 times while voluntarily changing the amount of air during ventilation simultaneously with the RMET and a spirometer, and their correlations were evaluated to test validity using Pearson's product-moment correlation coefficients. The same measurements were also performed in 10 subjects with Duchenne muscular dystrophy. RESULTS: Real-time recordings of thoracoabdominal movements were obtained over a mean time of 374 ± 23.9 s. With QUEST 2.0, the median score of each item exceeded 3 (more or less satisfied). In healthy subjects, ICC(1,1) ranged from 0.82 to 0.99, and ICC(2,1) ranged from 0.83 to 0.97. Significant correlations were observed between the respiratory amplitudes measured with RMET, and the amount of air during ventilation was measured with a spirometer (r = 0.995, P < .001). In subjects with Duchenne muscular dystrophy, ICC(1,1) ranged from 0.87 to 0.97, and ICC(2,1) ranged from 0.84 to 0.99. The respiratory amplitudes measured with RMET correlated significantly with the amount of air during ventilation with a spirometer (r = 0.957, P < .001). CONCLUSIONS: We developed a novel method of quantifying respiratory movement called RMET that was feasible to use in daily clinical practice.

Development of a new scale for dysphagia in patients with progressive neuromuscular diseases: the Neuromuscular Disease Swallowing Status Scale (NdSSS).

Dysphagia is one of the most critical problems in patients with progressive neuromuscular diseases. However, clinically useful and practical scales to evaluate dysphagia are limited. Therefore, the aim of this study was to develop such a scale. An 8-stage Neuromuscular Disease Swallowing Status Scale (NdSSS) was developed and tested for its inter- and intrarater reliabilities, concurrent validity, and responsiveness. The NdSSS was used to evaluate 134 patients with Duchenne muscular dystrophy (DMD) and 84 patients with amyotrophic lateral sclerosis (ALS). Inter- and intrarater reliabilities were examined with weighted kappa statistics. Concurrent validity was assessed by correlating the NdSSS with the existing scales [Functional Oral Intake Scale (FOIS), Functional Intake LEVEL Scales (FILS), and ALS Functional Rating Scale-Revised Swallow (ALSFRS-R Sw)], using Spearman's correlation coefficients. Responsiveness was determined with the standardized response mean (SRM). For inter- and intrarater reliabilities, the weighted kappas were 0.95 and 1.00, respectively, for DMD; and 0.98 and 0.98, respectively, for ALS. The NdSSS showed strong correlations with the FOIS (rs = 0.87 for DMD, rs = 0.93 for ALS, p < 0.001), FILS (rs = 0.89 for DMD, rs = 0.92 for ALS, p < 0.001), and ALSFRS-R SW (rs = 0.93, p < 0.001). SRMs were 0.65 for DMD and 1.21 for ALS. The SRM was higher in DMD patients for the NdSSS than for the other scales, while it was similar in ALS patients and the other scales. Our originally developed NdSSS demonstrated sufficient reliability, validity, and responsiveness in patients with DMD and ALS. It is also useful in evaluating dysphagia in patients with progressive neuromuscular diseases.

The metaphor and sarcasm scenario test: a new instrument to help differentiate high functioning pervasive developmental disorder from attention deficit/hyperactivity disorder.

It is sometimes difficult to discriminate high functioning pervasive developmental disorders (HFPDD) from attention deficit/hyperactivity disorders (AD/HD) in young children because of the behavioral similarities between the two. For adequate diagnosis, understanding fundamental differences in their social cognitive abilities might become significant. In order to detect the differences in social cognitive abilities between AD/HD and HFPDD, a new test, the Metaphor and Sarcasm Scenario Test (MSST) was developed. One hundred and ninety-nine normal school children (the control group), 29 AD/HD children and 54 HFPDD children were involved. The results showed that the inability to understand a sarcastic situation was specific to children with HFPDD, both children with AD/HD and HFPDD could not equally understand metaphor. The correlation between the comprehension of sarcasm and success in the theory of mind task was remarkably high but not for comprehension of metaphor. In conclusion, the MSST has the potential to discriminate HFPDD from AD/HD in young children.

Asymmetric skull deformity in children with cerebral palsy: frequency and correlation with postural abnormalities and deformities.

OBJECTIVE: Asymmetrical skull deformity is frequently seen in children with cerebral palsy, and may contribute to postural abnormalities and deformities. The aim of this cross-sectional- survey was to determine the frequency of asymmetrical skull deformity and its correlation with clinical parameters. METHODS: A 10-item checklist for asymmetrical skull deformity, postural abnormalities, and deformities was developed, and its inter-rater reliability was tested. A total of 110 participants aged 1-18 years (mean age 9.3 years (standard deviation 4.7)) was assessed using the checklist. The frequency of asymmetrical skull deformity was analysed and related to the Gross Motor Function Classification System (GMFCS), postural abnormalities, and deformities. RESULTS: The reliability of the checklist was satisfactory (κ > 0.8). Asymmetrical skull deformity was observed in 44 children, 24 showing right and 20 showing left flat occipital deformity. Its frequency was significantly related to GMFCS and with the patterns of asymmetrical posture and deformities (p < 0.05). Children with right flat occipital asymmetrical skull deformity showed predominantly rightward facial direction and right-side-dominant asymmetrical tonic neck reflex, left convex scoliosis, right-side-elevated pelvic obliquity, and left-sided hip dislocation. Those with left flat occipital asymmetrical skull deformity demonstrated the reverse tendency. CONCLUSION: Asymmetrical skull deformity is frequent in cerebral palsy and closely related to asymmetrical posture and deformities. This information will be useful to manage these problems.

Morphology and neurophysiology of tarsal vibration receptors in the water strider Aquarius paludum (Heteroptera: Gerridae).

Substrate vibratory information receptors are extensively studied in insects and spiders, however for water surface dwelling species little data is available. We studied the vibration receptive organs in tarsi of the water strider Aquarius paludum, using light, transmission and scanning electron microscopes, and recorded the neural activity of the organs in response to vibrational stimuli, which were afterwards analysed with a custom made spike sorting program. We found that the tarsal chordotonal organ has one set of three scoloparia: one in the tarsomere I and two in the tarsomere II, all of which consisted of a few scolopidia. The chordotonal organ clearly responded to vibratory stimulation. Furthermore, we found that a pair of large subapical emergent dorsal setae, which had been deemed mechanosensory by previous authors, are not so. In turn, four ventral subapical trichobothria that are in direct contact with the water surface during locomotion, proved to be mechanosensory. The anatomical and ultrastructural observations support these electro-physiological results.

Pharmaceutical approach to HIV protease inhibitor atazanavir for bioavailability enhancement based on solid dispersion system.

Atazanavir (ATV) is a low oral bioavailability (BA) compound and, clinically, is generally coadministrated with ritonavir (RTV), which boosts the oral BA of ATV by inhibiting cytochrome P450 (CYP) 3A, and P-glycoprotein (Pgp) via the same metabolic pathway. However, depending on pharmacokinetic interaction, RTV-boosted ATV has great potential for other comedication. In this study we demonstrated the pharmaceutical approach to BA improvement of ATV without RTV in rats, based on the solid dispersion system using sodium lauryl sulfate (SLS) as a carrier and Gelucire 50/13 as an absorption enhancer. ATV solid dispersions in SLS were prepared by a conventional solvent method and, at ratios of ATV to SLS of 1 : 2 and 1 : 3, were demonstrated to form an amorphous state in powder X-ray diffraction (PXRD) analysis and exhibited 2.26- and 2.36-fold improvement in a dissolution test in comparison to bulk ATV, respectively. After oral administration to rats, ATV solid dispersion in SLS at a ratio of 1 : 2 showed a 3.5-fold increase in BA compared with bulk ATV. Moreover, the addition of Gelucire 50/13 to ATV solid dispersion, at a total ratio of Gelucire 50/13, ATV and SLS 1 : 1 : 2 gave 7.0- and 4.7-fold increase in Cmax and BA compared with bulk ATV, respectively, when the relative BA to RTV-boosted ATV reached 93%. The results in this study proved that a pharmaceutical approach could improve the bioavailability of ATV without pharmacokinetic interaction with RTV.