Search

Evidence on polypharmacy in patients with sarcopenia is lacking. We aimed to examine the association of polypharmacy with swallowing function and nutritional risk in post-stroke patient with sarcopenia. This retrospective cohort study included hospitalized patients diagnosed with sarcopenia who needed convalescent rehabilitation following stroke onset. Study outcomes were the Food Intake Level Scale (FILS) as dysphagia assessment and geriatric nutritional risk index (GNRI) as nutritional status at hospital discharge, respectively. To examine the impact of admission polypharmacy, multivariate linear regression analyses were used to determine whether the number of drugs prescribed at hospital admission was associated with these outcomes. As a result, of the 586 patients enrolled, 257 (mean age 79.3 years, 44.0% male) were diagnosed with sarcopenia and were finally analyzed high admission drug prescription numbers were independently associated with FILS (β = −0.133, p = 0.017) and GNRI (β = −0.145, p = 0.003) at hospital discharge, respectively. Polypharmacy is associated with dysphagia and malnutrition in post-stroke patients with sarcopenia. In addition to the combination of nutritional and exercise therapies, review and optimization of prescription medications may be warranted to treat sarcopenia in order to maximize improvement in outcomes for these patients.

To investigate the effect of trunk and appendicular skeletal muscle mass on the swallowing function at discharge in acute stroke patients.This retrospective cohort study included patients hospitalized after acute strokes. Skeletal muscle mass was measured by bioelectrical impedance analysis within 5 days of admission. The primary outcome was swallowing function at acute hospital discharge, assessed using the Functional Oral Intake Scale (FOIS). Secondary outcomes were Functional Independence Measure-eating (FIM-eating) scores and length of hospital stay.Data from 231 patients (age 72.2 years; 151 men) were included in the analysis. The median trunk muscle mass index (TMI) was 8.2 and 6.8 kg/mSkeletal muscle mass had site-specific impacts on swallowing function and eating activities. This finding may contribute to the design of more individualized rehabilitation programs.

The aim of this study was to evaluate the effects of trunk muscle mass on functional prognosis, including activities of daily living (ADLs), at hospital discharge in patients with acute stroke.This retrospective cohort study included hospitalized patients with acute stroke. Trunk muscle mass was measured using bioelectrical impedance analysis within 5 d of admission. The primary outcome was ADLs at hospital discharge, assessed using the Functional Independence Measure-motor items (FIM-motor). The secondary outcomes were hospital length of stay and discharge to home. Multivariate analyses were performed to determine the association between trunk muscle mass and FIM subitems.Data from 212 patients (mean age 72.7 y; 143 men) were included in the analysis. The median trunk muscle mass index (TMI) was 8.2 kg/msup2/supin men and 6.7 kg/msup2/supin women. Patients in the high TMI group were younger and had a higher FIM-motor score at discharge (Plt; 0.001). In multivariate analyses, TMI was positively associated with the FIM-motor score at discharge (β = 0.240, Plt; 0.001). FIM-self-care (β = 0.351, Plt; 0.001) and locomotion (β = 0.331, Plt; 0.001) were positively associated with the TMI.Trunk muscle mass is associated with ADLs at hospital discharge after acute stroke. TMI is important for evaluating functional prognosis in patients with acute stroke.

Evidence is scarce for potentially inappropriate medications (PIMs) in rehabilitation medicine.To examine the effect of PIMs on functional recovery in older patients with sarcopenia after stroke.We conducted a retrospective cohort study in a post-acute rehabilitation hospital. All patients diagnosed with sarcopenia aged ≥ 65 years among all post-stroke patients hospitalized from 2015 to 2020 were included. PIMs were defined based on the 2019 Beers criteria. Sarcopenia was diagnosed using handgrip strength (HG) and skeletal muscle mass index (SMI), according to the criteria of the Asian Working Group for Sarcopenia 2019. The outcomes included functional independence measure motor (FIM-motor), HG, and SMI values at discharge. Multiple linear regression analyses were used to determine whether PIMs used at admission were independently associated with outcomes.Of the eligible patients, 361 were 65 years or older, of whom 196 (mean age 81.0 years, 44.4% male) presented with sarcopenia and were included in the analysis. Of these, 131 (66.8%) were prescribed PIMs at admission. The most frequently prescribed PIMs were proton pump inhibitors, antipsychotics, benzodiazepines, and nonsteroidal anti-inflammatory drugs. The number of PIMs on admission was independently associated with FIM-motor (β = - 0.132, P = 0.001) and HG (β = - 0.091, P = 0.048) at discharge, but not with SMI (β = - 0.055, P = 0.256).High admission PIMs prescription numbers are negatively associated with favorable discharge functional status and muscle strength in older patients with sarcopenia after stroke.

Currently, there is a lack of evidence to show that exercise therapy improves sarcopenia in older patients in clinical practice. We therefore conducted a retrospective cohort study to clarify the effects of chair-stand exercise on improving sarcopenia among patients diagnosed with sarcopenia undergoing convalescent rehabilitation after stroke. According to the latest Asian criteria, sarcopenia was diagnosed when both skeletal muscle mass index (SMI) and handgrip strength (HGS) were low. Patients were asked to perform a repeated chair-stand exercise as whole-body resistance training, in addition to the rehabilitation program. Outcomes included sarcopenia rates, SMI, HGS, and physical function at hospital discharge. Multivariate analyses were used to examine whether the frequency of daily chair-stand exercise was independently associated with the outcomes after adjustment for potential confounders. After enrollment, 302 patients with sarcopenia (mean age: 78.6 years; 46.4% male) were analyzed. Overall, sarcopenia prevalence decreased by 21.9%, from 100% at admission to 78.1% at discharge. Multivariate analyses showed that the frequency of the exercise was significantly associated with the presence of sarcopenia (odds ratio: 0.986, p = 0.010), SMI (β = 0.181, p < 0.001), and HGS (β = 0.101, p = 0.032) at discharge, respectively. The chair-standing exercise was effective in improving sarcopenia in these patients.

Energy intake and rehabilitation time individually contribute to the improvement of activities of daily living (ADL). This study aimed to investigate the additive effect of energy intake and rehabilitation time on ADL improvement in acute stroke patients with sarcopenia. The study included 140 patients (mean age 82.6 years, 67 men) with stroke. Energy intake during the first week of hospitalization was classified as “Sufficiency” or “Shortage” based on the reported cutoff value and rehabilitation time was classified as “Long” or “Short” based on the median. The study participants were categorized into four groups based on the combination of energy intake and rehabilitation time. The primary outcome was the gain of functional independence measure (FIM) motor during hospitalization. The secondary outcomes were length of stay and home discharge rates. Multivariate analysis was performed with primary/secondary outcomes as the dependent variable, and the effect of each group on the outcome was examined. Multivariate analysis showed that “long rehabilitation time and sufficient energy intake” (β = 0.391, p < 0.001) was independently associated with the gain of FIM motor items. The combination of high energy intake and sufficient rehabilitation time was associated with ADL improvement in acute stroke patients with sarcopenia.

Background Evidence is scarce regarding polypharmacy and potentially inappropriate medications (PIMs) in rehabilitation medicine. Aim To investigate the prevalence of polypharmacy and PIMs and their association with outcomes in stroke rehabilitation. Method A retrospective cohort study was conducted with 849 older inpatients post-stroke. Polypharmacy was defined as six or more medications, and PIMs were defined based on Beers criteria 2019. Study outcomes included functional independence measure (FIM)-motor, FIM-cognitive, energy intake, dysphagia, length of hospital stay, and the rate of home discharge. To consider the effect of pharmacotherapy during rehabilitation, multivariate analyses were used to determine whether the presence of polypharmacy or PIMs at discharge was associated with outcomes. Results After enrollment, 361 patients (mean age 78.3 ± 7.7 years; 49.3% male) were analyzed. Polypharmacy was observed in 43.8% and 62.9% of patients, and any PIMs were observed in 64.8% and 65.4% of patients at admission and discharge, respectively. The most frequently prescribed PIMs included antipsychotics, benzodiazepines, and proton pump inhibitors. Polypharmacy was negatively associated with FIM-motor score (β = - 0.062, P = 0.049), FIM-cognitive score (β = - 0.076, P = 0.014), energy intake (β = - 0.143, P = 0.005), and home discharge (OR: 0.458; 95% CI: 0.248, 0.847; P = 0.013). PIMs were negatively associated with home discharge (OR: 0.375; 95% CI: 0.195, 0.718; P = 0.003). Conclusion Polypharmacy and PIMs are commonly found among older patients undergoing stroke rehabilitation. Moreover, polypharmacy was negatively associated with activities of daily living (ADL) but not with PIMs and ADLs, and both were associated with home discharge.

Sarcopenic obesity is of growing research and clinical interest; however, validated diagnostic criteria are lacking. We therefore aimed to examine the prevalence of sarcopenic obesity as diagnosed by the criteria recently proposed by the European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO), and its association with outcomes among patients after stroke. This study was based on a cohort of 760 Japanese patients after stroke admitted to a post-acute rehabilitation hospital. Sarcopenic obesity was diagnosed at admission according to the ESPEN and EASO criteria using reference values specific to Asians. Outcomes included the motor domain of the functional independence measure (FIM-motor) and the food intake level scale (FILS) at discharge. Multivariate linear regression models were used to assess the associations between sarcopenic obesity and outcomes. Among 760 patients (median age, 73 years; 352 women and 408 men), sarcopenic obesity was diagnosed in 34 patients (4.5%; 5.4% of women and 4.1% of men). In multivariate analyses, sarcopenic obesity was independently and negatively associated with FIM-motor (β = −0.048, p = 0.031) and FILS at discharge (β = −0.095, p = 0.046) in women. In contrast, in men, sarcopenic obesity showed an independent negative association with FIM-motor at discharge (β = −0.117, p < 0.001) but no statistically significant association with FILS at discharge (β = −0.004, p = 0.323). In conclusion, the prevalence of sarcopenic obesity diagnosed by the ESPEN and EASO-defined criteria was as low as 4.5% among Japanese patients after stroke. Furthermore, sarcopenic obesity was negatively associated with improvements in activities of daily living and dysphagia.

Evidence regarding the effect of sarcopenic obesity on recovery in stroke patients is scarce in rehabilitation medicine. The aim of this study was to examine the association between changes in muscle strength and functional outcomes in patients with sarcopenic obesity undergoing rehabilitation after stroke.This study was a retrospective cohort study of stroke patients, consecutively admitted to post-acute rehabilitation wards of a single hospital, of which, only those diagnosed with sarcopenic obesity at admission were included in the final analysis. Bioimpedance analysis was used to measure skeletal muscle mass and body fat mass. Sarcopenic obesity was defined as the presence of both sarcopenia and obesity. Sarcopenia was diagnosed using muscle mass index and handgrip strength. Obesity was diagnosed using body fat percentage (men ≥30%, women ≥35%). The evaluated outcomes were Functional Independence Measure (FIM)-motor score at discharge and its gain. Multiple regression analysis was used to verify whether changes in hand grip strength during hospitalization were associated with functional outcomes.Sixty-two patients (29 men) with a mean age of 78 years, were analyzed. The mean change in the hand grip strength was 3.9 kg. In multiple regression analysis, changes in the hand grip strength were significantly associated with FIM-motor at discharge (β = 0.34, P0.01) and FIM-motor gain (β = 0.58, P0.01).Muscle strength gain was associated with improved functional recovery in stroke patients with sarcopenic obesity.

Evidence is scarce regarding the polypharmacy in patients with sarcopenia. The aim of this study was to investigate the effect of deprescribing for polypharmacy on the improvement of nutritional intake and sarcopenia in older patients with sarcopenia. A retrospective cohort study was conducted with hospitalized older patients with sarcopenia undergoing rehabilitation after stroke. Study outcomes included energy intake, protein intake, handgrip strength (HG) and skeletal muscle mass index (SMI) at hospital discharge. To consider the effects of deprescribing for polypharmacy, we used multivariate analyses to examine whether the change in the number of medications during hospitalization was associated with outcomes. Of 361 patients after enrollment, 91 (mean age 81.0 years, 48.4% male) presented with sarcopenia and polypharmacy and were eligible for analysis. The change in the number of medications was independently associated with energy intake (β = −0.237, p = 0.009) and protein intake (β = −0.242, p = 0.047) at discharge, and was not statistically significantly associated with HG (β = −0.018, p = 0.768) and SMI (β = 0.083, p = 0.265) at discharge, respectively. Deprescribing was associated with improved nutritional intake in older sarcopenic patients with polypharmacy undergoing stroke rehabilitation.

A supervised machine learning algorithm, which is qualified for image classification and analyzing similarities, is based on multiple discriminative morphological features that are automatically assembled during the learning processes. The algorithm is suitable for population-based analysis of images of biological materials that are generally complex and heterogeneous. Here we used the algorithm wndchrm to quantify the effects on nucleolar morphology of the loss of the components of nuclear envelope in a human mammary epithelial cell line. The linker of nucleoskeleton and cytoskeleton (LINC) complex, an assembly of nuclear envelope proteins comprising mainly members of the SUN and nesprin families, connects the nuclear lamina and cytoskeletal filaments. The components of the LINC complex are markedly deficient in breast cancer tissues. We found that a reduction in the levels of SUN1, SUN2, and lamin A/C led to significant changes in morphologies that were computationally classified using wndchrm with approximately 100% accuracy. In particular, depletion of SUN1 caused nucleolar hypertrophy and reduced rRNA synthesis. Further, wndchrm revealed a consistent negative correlation between SUN1 expression and the size of nucleoli in human breast cancer tissues. Our unbiased morphological quantitation strategies using wndchrm revealed an unexpected link between the components of the LINC complex and the morphologies of nucleoli that serves as an indicator of the malignant phenotype of breast cancer cells.

Background/aim Chemotherapy is an important first-line treatment for oesophageal squamous cell carcinoma (ESCC). However, there are few secondary options. Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, enhances the cytotoxicity of various anticancer drugs and has been used to treat advanced ovarian and breast cancers. This study examined the effect of olaparib on the cytotoxicity of anticancer drugs in ESCC cell lines. Materials and methods ESCC KYSE70 and KYSE140 cells were grown in Dulbecco's modified Eagle's medium and treated with 5-fluorouracil (5-FU), cisplatin, docetaxel, doxorubicin, SN-38, or temozolomide without or with olaparib. Results Olaparib enhanced the cytotoxicity of all tested anticancer drugs and increased the effects of cisplatin, doxorubicin, SN-38, and temozolomide synergistically. These anticancer drugs caused the accumulation of phospho-histone H2AX Ser139 (γH2AX), a biomarker of DNA damage, and olaparib increased this accumulation. Conclusion PARP inhibitors may potentiate the anticancer activity of DNA-damaging agents in ESCC patients synergistically.

The linker of nucleoskeleton and cytoskeleton (LINC) complex, containing the proteins SUN and nesprin, is the fundamental structural unit of the nuclear envelope. The neoplastic-based regulation of the LINC complex in cancer tissues has become increasingly recognized in recent years, including the altered expression, somatic mutation, and methylation of genes. However, precisely how mutations and deregulated expression of the LINC complex contribute to the pathogenic mechanisms of tumorigenesis remain to be elucidated, mainly because of several technical difficulties. First, both the SUN and SYNE (encoding nesprin) genes give rise to a vast number of splicing variants. Second, immunoprecipitation experiments of endogenous SUN and nesprin proteins are difficult owing to the lack of suitable reagents as well as the limited solubility of these proteins in mild extraction conditions. Here, we describe three protocols to investigate these aspects: (1) immunohistochemistry to determine the expression levels and localization of the LINC complex in cancer tissue, (2) detection of SUN1 splicing variants at the mRNA level, and (3) detection of SUN1 splicing variants and binding partners at the protein level.

Acute kidney injury (AKI) is associated with prolonged hospitalization and high mortality, and it predisposes individuals to chronic kidney disease. To date, no effective AKI treatments have been established. Here we show that the apoptosis inhibitor of macrophage (AIM) protein on intraluminal debris interacts with kidney injury molecule (KIM)-1 and promotes recovery from AKI. During AKI, the concentration of AIM increases in the urine, and AIM accumulates on necrotic cell debris within the kidney proximal tubules. The AIM present in this cellular debris binds to KIM-1, which is expressed on injured tubular epithelial cells, and enhances the phagocytic removal of the debris by the epithelial cells, thus contributing to kidney tissue repair. When subjected to ischemia-reperfusion (IR)-induced AKI, AIM-deficient mice exhibited abrogated debris clearance and persistent renal inflammation, resulting in higher mortality than wild-type (WT) mice due to progressive renal dysfunction. Treatment of mice with IR-induced AKI using recombinant AIM resulted in the removal of the debris, thereby ameliorating renal pathology. We observed this effect in both AIM-deficient and WT mice, but not in KIM-1-deficient mice. Our findings provide a basis for the development of potentially novel therapies for AKI.

Cancer cells exhibit a variety of features indicative of atypical nuclei. However, the molecular mechanisms underlying these phenomena remain to be elucidated. The linker of nucleoskeleton and cytoskeleton (LINC) complex, a nuclear envelope protein complex consisting mainly of the SUN and nesprin proteins, connects nuclear lamina and cytoskeletal filaments and helps to regulate the size and shape of the nucleus. Using immunohistology, we found that a nuclear lamina component, lamin A/C and all of the investigated LINC complex components, SUN1, SUN2, and nesprin-2, were downregulated in human breast cancer tissues. In the majority of cases, we observed lower expression levels of these analytes in samples' cancerous regions as compared to their cancer-associated noncancerous regions (in cancerous regions, percentage of tissue samples exhibiting low protein expression: lamin A/C, 85% [n = 73]; SUN1, 88% [n = 43]; SUN2, 74% [n = 43]; and nesprin-2, 79% [n = 53]). Statistical analysis showed that the frequencies of recurrence and HER2 expression were negatively correlated with lamin A/C expression (P

Apoptosis inhibitor of macrophage (AIM, encoded by cd5l) is a multi-functional circulating protein that has a beneficial role in the regulation of a broad range of diseases, some of which are ameliorated by AIM administration in mice. In blood, AIM is stabilized by association with IgM pentamers and maintains its high circulating levels. The mechanism regulating the excessive accumulation of blood AIM remains unknown, although it is important, since a constitutive increase in AIM levels promotes chronic inflammation. Here we found a physiological AIM-cleavage process that induces destabilization of AIM and its excretion in urine. In blood, IgM-free AIM appeared to be cleaved and reduced in size approximately 10 kDa. Cleaved AIM was unable to bind to IgM and was selectively filtered by the glomerulus, thereby excreted in urine. Amino acid substitution at the cleavage site resulted in no renal excretion of AIM. Interestingly, cleaved AIM retained a comparable potency with full-length AIM in facilitating the clearance of dead cell debris in injured kidney, which is a key response in the recovery of acute kidney injury. Identification of AIM-cleavage and resulting functional modification could be the basis for designing safe and efficient AIM therapy for various diseases.