SARC-F Predicts Mortality Risk of Older Adults during Hospitalization.

OBJECTIVES: To determine the association between SARC-F scores and the in-hospital mortality risk among older patients admitted to acute care hospitals. DESIGN: Single-center retrospective study. SETTING: A university hospital. PARTICIPANTS: All consecutive patients aged older than 65 were admitted and discharged from the study hospital between July 2019 and September 2019. MEASUREMENTS: Relevant patient data included age, sex, body mass index, nutritional status, fat-free mass, disease, activities of daily living (ADL), duration of hospital stay, SARC-F, and occurrence of death within 30 days of hospitalization. The diseases that caused hospitalization and comorbidities (Charlson Comorbidity Index; CCI) were obtained from medical records. The Eastern Cooperative Oncology Group-performance status (PS) was used to determine ADL, and the in-hospital mortality rate within 30 days of hospitalization as the outcome. RESULTS: We analyzed 2,424 patients. The mean age was 75.9±6.9 and 55.5% were male. Fifty-three in-hospital mortalities occurred among the participants within the first 30 days of hospitalization. Patients who died in-hospital were older, had poorer nutritional status and severer PS scores, and more comorbidities than those who did not. A SARC-F score of ≥4 predicted a higher mortality risk within those 30 days with the following precision: sensitivity 0.792 and specificity 0.805. There were significantly more deaths in Kaplan-Meier curves regarding a score of SARC-F≥4 than a score of SARC-F<4 (p<0.001). Cox proportional hazard analysis was used to identify the clinical indicators most associated with in-hospital mortality. SARC-F≥4 (Hazard Ratio: HR 5.65, p<0.001), CCI scores (HR1.11, p=0.004), and infectious and parasitic diseases (HR3.13, p=0.031) were associated with in-hospital mortality. The SARC-F items with significant in-hospital mortality effects were assistance with walking (HR 2.55, p<0.001) and climbing stairs (HR 2.46, p=0.002). CONCLUSION: The SARC-F questionnaire is a useful prognostic indicator for older adults because a SARC-F ≥4 score during admission to an acute care hospital predicts in-hospital mortality within 30 days of hospitalization.

The SARC-F Score on Admission Predicts Falls during Hospitalization in Older Adults.

OBJECTIVES: Community-dwelling older adults with sarcopenia are likely to fall. However, few studies have investigated whether sarcopenia is associated with falls during hospitalization in older adults. The purpose of this study was to determine whether the SARC-F when used as a simple screening tool for sarcopenia at the time of admission, predicts in-hospital falls. DESIGN: A retrospective, observational study. SETTING: A 900-bed university hospital. PARTICIPANTS: A total of 9,927 patients aged 65 years and older were hospitalized at the hospital between April 2019 and March 2020. MEASUREMENTS: The SARC-F contains five items: strength, assistance in walking, rise from a chair, climb stairs, and falls were evaluated at hospital admission. To investigate the relationship between the SARC-F score and falls, a ROC curve analysis was performed. Multivariate analysis adjusted for fall-related confounding factors such as age, gender, ADL, and disease were performed. RESULTS: Mean age: 75.9±6.7 years; male: 56.2% were analyzed, and 159 patients (1.6%) fell during hospitalization. SARC-F scores at admission were significantly higher in the fall group than in the control group (3 [1-6] points vs. 0 [¬0-2] point, p<0.001). Statistical association was observed between the SARC-F and in-hospital fall (area under the curve = 0.721 [0.678-0.764], p < 0.001). The cut-off value for the highest sensitivity and specificity of the SARC-F score for in-hospital falls was two (sensitivity = 0.679, specificity = 0.715). Among the subitem of the SARC-F, the hazard ratios for climbing stairs were significantly higher (HR = 1.52 [1.10-2.09], p = 0.011) and for a history of fall was significantly higher (HR = 1.41 [1.02-1.95], p = 0.036). A SARC-F score ≥ 2 had a significantly higher incidence of in-hospital falls compared to a SARC-F score <2 (3.7% vs. 0.7%, p < 0.001). Also, a SARC-F score ≥ 2 had a significantly higher hazard ratio for falls (2.11 [1.37-3.26], p < 0.001). CONCLUSION: SARC-F can help predict falls among hospitalized older adults.

SARC-F as a Screening Tool for Sarcopenia and Possible Sarcopenia Proposed by AWGS 2019 in Hospitalized Older Adults.

OBJECT: The SARC-F questionnaire is a sarcopenia screening tool. However, the validity of the SARC-F score ≥4 (SARC-F≥4) for the evaluation of sarcopenia in the hospital setting has not been investigated. This study investigated the validity of SARC-F≥4 as a screening tool for sarcopenia among hospitalized older adults. DESIGN: Cross-sectional retrospective study. SETTING: A university hospital. PARTICIPANTS: This study included older adult patients (age ≥65 years) who were hospitalized at, and subsequently discharged from, the hospital between April and September 2019 and underwent a nutritional assessment by the nutrition support team during their hospitalization. MEASUREMENTS: SARC-F was recorded at the time of admission, and the criteria specified by the Asia Working Group for Sarcopenia in 2019 (AWGS 2019) were applied to diagnose sarcopenia and possible sarcopenia. Appendicular muscle mass was estimated through validated equations, and three different models were developed for sarcopenia diagnosis. The sensitivity, specificity, and positive/negative likelihood ratios were calculated to analyze the accuracy of the SARC-F≥4 for sarcopenia and possible sarcopenia. Receiver-operating characteristic analyses were conducted to calculate the area under the curve (AUC). RESULTS: In total, 1,689 patients (mean age: 77.2±7.3 years; male: 54.4%) were analyzed, and 636 patients (37.7%) had SARC-F≥4. Patients with SARC-F≥4 had a statistically significant higher prevalence of AWGS 2019-defined sarcopenia than patients with SARC-F <4 in the models (65.4-78.9% vs 40.9-45.2%, p<0.001). The sensitivity, specificity, and positive/negative likelihood ratios of SARC-F≥4 for sarcopenia and possible sarcopenia were 49.1-51.3%, 73.9-81.2%, and 1.88-2.72/0.60-0.69 and 48.0%, 84.5%, and 3.11/0.62, respectively. The AUC for sarcopenia and possible sarcopenia were 0.644-0.695 and 0.708, respectively. The AUC of SARC-F for possible sarcopenia was equivalent to or larger than that for sarcopenia (DeLong test p=0.438, 0.088, and <0.001 vs the three models). CONCLUSIONS: SARC-F≥4 is suitable as a screening tool for sarcopenia in hospitalized older adults. SARC-F assessment could facilitate the detection and exclusion of sarcopenia at hospitalization and may lead to early adoption of a therapeutic and preventive approach.

Burden of Premorbid Consumption of Texture Modified Diets in Daily Life on Nutritional Status and Outcomes of Hospitalization.

OBJECTIVES: Due to the water-rich cooking process required to soften texture modified diets (TMDs), TMDs may have poorer nutrition. The aim of this study was to investigate the associations between daily premorbid TMD consumption and nutritional status at the time of hospitalization, and its burden on hospitalization outcomes. DESIGN: Retrospective observational study. SETTING: An academic hospital. PARTICIPANTS: The cohort comprised 3,594 older adult patients aged ≥65 years admitted to the hospital. MEASUREMENTS: Patients were interviewed on admission using a premorbid daily consumption meal form to determine whether the patient ate a TMD. Nutritional status was examined using nutritional screening tools (Mini-Nutritional Assessment Short Form [MNA-SF], Malnutrition Universal Screening Tool [MUST], Geriatric Nutritional Risk Index [GNRI]) and the European Society of Clinical Nutrition and Metabolism (ESPEN)-defined criteria of malnutrition at admission. Length of hospital stay (LOS) and in-hospital mortality were considered outcomes of hospitalization. Multivariate analyses were performed to detect associations between premorbid TMD consumption and nutritional status and outcomes. RESULTS: The mean age of the subjects was 75.9±7.0 years, including 58% males. Overall, 110 (3.1%) patients consuming a premorbid TMD were identified. They were older (p<0.001), had poor nutritional status (lower MNA-SF score [p<0.001] and GNRI value [p<0.001], higher MUST score [p<0.001], and more prevalent ESPEN-defined malnutrition [61.8% vs. 14.0%, p<0.001] than did patients without a TMD. The mortality rate and LOS of patients with TMD was higher (7.3% vs. 2.9%, p=0.017) and longer (19 days vs. 8 days, p<0.001) than those without TMD. Multivariate analyses showed that TMD consumption was independently associated with poor nutritional status and prolonged LOS after adjusting confounders. CONCLUSION: Daily consumption of a TMD during the premorbid period affects nutritional status at the time of hospitalization and outcomes. Further studies are necessary to investigate whether nutritional intervention can improve outcomes for people on a TMD.

Hemorrhagic activity and muscle damaging effect of Pseudomonas aeruginosa metalloproteinase (elastase).

Pseudomonas aeruginosa elastase, a Bacillus subtilis thermolysin-like zinc-proteinase was examined for hemorrhagic activity and its effect on muscle and endothelial cells. Subcutaneous and intramuscular injections of elastase into mice caused severe hemorrhage with an acute increase of creatine phosphokinase activity in serum. The elastase also possessed fibrinogenolytic and fibrinolytic activities. The Aalpha and Bbeta chains of fibrinogen were completely hydrolyzed as demonstrated by their electrophoretic disappearance on SDS polyacrylamide gels. The pathological study indicates that elastase induces changes in the structure of the vascular wall and causes leakage of the plasma component and red and white blood cells into the extravascular tissue. This is further supported by results showing injury to cultured endothelial cells and macrophages. These data indicate that P. aeruginosa elastase directly affects endothelial cells and destroys the basement membrane of blood vessels to cause hemorrhage. Since fibrinogenolytic activity is an additional component of this elastase and this activity induces the hemorrhagic tendency, the damage in tissues could become increasingly severe.

Morphological changes in mouse accessory sex glands following neonatal estrogen treatment.

A single injection of beta-estradiol 17-cypionate into the mice within 5 hr after birth induced inflammation in all prostate lobes and the seminal vesicles. Neutrophils emigrated into the lumen through the basal lamina and epithelium of the seminal vesicle and the anterior prostate. Local infiltration of lymphocytes was observed in the stroma and epithelium of ventral prostates. Lymphocytes penetrated through smooth muscle cells into epithelium. This could support the hypothesis that smooth muscle cells are the target of the estrogen action of prostates in estrogenized animals.

An autopsy case of hepatitis B (HB) antigen-positive polyarteritis nodosa, with reference to immunopathological studies of vascular lesions.

Abstract An autopsy case of an 11-year-old boy with polyarteritis nodosa is described in which the onset of the disease was associated with the presence of hepatitis B (HB) antigens (Ag) in the cytoplasm and nuclei of hepatocytes as detected by immunohistological methods. Deposits of HBsAg, HBeAg, IgG, IgM, C3, and C1q were demonstrated in systemic vascular lesions. It is considered that the arteritis was due to deposition in the arteries of immune complexes formed by HBAg and HB antibodies.

Partial amino acid sequence and biological characterization of elegatoxin, hemorrhagic toxin from Trimeresurus elegans (Sakishimahabu) venom.

A hemorrhagic toxin, designated Elegatoxin, was isolated from the venom of Trimeresurus elegans using HW-55, DEAE-Sephacel, CM-Cellulose and Mono S column chromatographies. The purified toxin was shown to be homogeneous by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, isoelectric electrophoresis, and Ouchterlony immunodiffusion. Elegatoxin has a molecular weight of 26,000 with an isoelectric point of 8.6. The toxin demonstrated both hemorrhagic and proteolytic activities. Hemorrhagic activity was inhibited by ethylenediaminetetraacetic acid (EDTA), ethyleneglycol-bis-(2-amino-ethylether)N,N'-tetraacetic acid (EGTA), o-phenanthroline, and N-bromosuccinimide, but not by amidinophenylmethanesulfonyl fluoride hydrochloride (APMSF). The minimum hemorrhagic dose was found to be 0.8 microgram/mouse. Elegatoxin possesses proteolytic activity as evidenced by hydrolyzing type IV collagen, actin and the A alpha, B beta, and gamma chains of bovine fibrinogen. This purified toxin contains 1 mol of zinc and 2 mols of calcium per mol of protein and a partial amino acid sequence was determined. The pathological and biochemical properties of Elegatoxin were investigated, and these results are reported in this paper.

Glucokinase is located in secretory granules of pancreatic D-cells.

We immunohistochemically examined the distribution of glucokinase in rat pancreatic islets. Glucokinase immunoreactivity under light microscopy was detected in the cytoplasm of somatostatin cells as well as in that of insulin cells. No specific immunoreactivity was detected in glucagon and pancreatic polypeptide cells. In somatostatin cells, glucokinase immunoreactivity was located by electron microscopy exclusively within secretory granules.

[Diffuse bronchiolo-alveolar cell carcinoma that produced both amylase and CA19-9].

A 68-year-old man who worked as an editor was admitted to Aichi Medical University Hospital due to dyspnea on exertion and emaciation. The patient had noticed rapid weight loss during diet therapy for diabetes mellitus that started in the beginning of July, 1993. Laboratory examinations revealed elevated levels of LDH and amylase in serum. Ultrasonography disclosed minimal ascites. Dyspnea on exertion developed in September, 1993. Chest roentgenography showed diffuse bilateral small nodular or reticular opacities. CT-guided percutaneous needle aspiration was done and cytologic examination of a specimen of lung tissue revealed papillary adenocarcinoma. The diagnosis was bronchiolo-alveolar carcinoma. Serum levels of amylase were elevated. The amylase isozyme pattern was of the salivary type. Serum levels of CA19-9 and CEA were also elevated. The patient died of respiratory failure on December 4, 1993. Postmortem examination revealed diffuse small nodules in both lungs. Examination of the nodules showed bronchiolo-alveolar cell carcinoma. The tumor cells stained positively for amylase (salivary type, not pancreatic type) CA19-9, and CEA by the avidin biotin complex method, but they were immunohistologically negative for AFP. We conclude that this lung cancer produced amylase, CA19-9, and CEA. We know of only a few reports of cases in which lung cancer produced both amylase and CA19-9.

Role of enteric bacteria in the pathogenesis of rheumatoid arthritis: evidence for antibodies to enterobacterial common antigens in rheumatoid sera and synovial fluids.

OBJECTIVE: To study antibodies to Escherichia coli O:14, which expresses large amounts of enterobacterial common antigen (ECA), and their corresponding antigen molecules in serum and synovial fluid samples from patients with rheumatoid arthritis (RA). METHODS: Enzyme linked immunosorbent assay (ELISA) was used to measure antibodies to heat killed E coli O:14 in serum and synovial fluid samples from patients with RA and control subjects including healthy donors and patients with osteoarthritis. ELISA was also used to perform absorption analyses of antibodies to E coli O:14 with several enteric bacteria and their lipopolysaccharide (LPS). In addition, antigenic molecules reacting with E coli O:14 antibodies from patients with RA were examined using immunoblot analysis and N-terminal amino acid analysis. RESULTS: Compared with control subjects, patients with RA showed significantly increased titres of antibodies against heat killed E coli O:14 in 33 of 83 serum samples (39.8%) and 38 of 58 joint fluid samples (65.5%). Absorption analyses with enteric bacteria and their LPS resulted in the reduction of antibody titres to heat killed E coli O:14 in serum and synovial fluid samples from the RA patients. In addition, immunoblot analysis of the samples from RA patients revealed not only a ladder-like banding pattern equivalent to ECA associated with LPS, but also two clear bands of bacterial outer membrane proteins of 35 kDa (Omp A) and 38 kDa (Omp C), having amino acid sequence homology with those of other Enterobacteriaceae. CONCLUSION: These results suggest that some patients with RA are sensitised to antigens common to Enterobacteriaceae, and this may prove relevant to the future development of immunotherapy for RA. Furthermore, this sensitisation to antigens found commonly in Enterobacteriaceae may have a key role in the pathogenesis of human RA similar to that described previously in our animal model.

Pancreatic calculi superimposed upon slow growing pancreatic cancer.

We report on a 59 year old male patient with cancer of the head of the pancreas, upon which pancreatic calculi were superimposed during the 3 year clinical course. Pancreatic calculi were noted in the main pancreatic duct (MPD) on both computed tomographic scans and ultrasonographs of the abdomen approximately 10 months after the recognizable dilatation of the MPD. Existence of the calculi was confirmed by autopsy. Elemental analysis and infrared spectrophotometry of the calculi demonstrated that the main constituent of the calculi was calcium carbonate. Histopathological examination showed that the pancreatic cancer was moderately differentiated adenocarcinoma. Immunohistochemical studies revealed that pancreatic stone protein (lithostathine) was present in the cytoplasm of tumour cells. In this case, pancreatic cancer progressed to obstruct the MPD unusually slowly, resulting in stagnation of pancreatic secretion and subsequent formation of the calculi.

Changes in subcellular and zonal distribution of glucokinase in rat liver during postnatal development.

Subcellular and zonal distribution of glucokinase in rat liver during postnatal development was examined immunohistochemically. Before day 11 after birth, only some hepatocytes were immunostained, and a positive immunostaining was found in the cytoplasm but not in the nucleus. No zonal distribution of glucokinase was observed in livers of such pups. From day 15, at which time a dietary change from milk to laboratory chow begins to take place, glucokinase immunoreactivity increased; this increase was associated with increases in glucokinase activity and in glucokinase protein, and also the immunostaining was observed mainly in the nuclei. At day 21, the glucokinase immunoreactivity was found almost exclusively in the perivenous zone. At day 30, an intense immunostaining was seen both in the perivenous zone and in the periportal zone, being slightly predominant in the former. The present results indicate that dramatic changes in the distribution of glucokinase in developing rat liver may be related to dietary change.

Tissue and subcellular distribution of glucokinase in rat liver and their changes during fasting-refeeding.

The distribution of glucokinase in rat liver under both normal feeding and fasting-refeeding conditions was investigated immunohistochemically. Under normal feeding conditions, glucokinase immunoreactivity was observed in both nuclei and cytoplasm of parenchymal cells. The nuclei were stained intensely and evenly, whereas the cytoplasm showed weak immunoreactivity of different degrees of staining intensity depending on the location of the cells. The cytoplasm of perivenous hepatocytes was stained more intensely, though not so much more, than that of periportal hepatocytes. The cytoplasm of hepatocytes surrounding the terminal hepatic venule (THV), of hepatocytes surrounding the portal triad, and of some other hepatocytes showed a stronger immunoreactivity than that of residual hepatocytes. The nuclear immunoreactivity in hepatocytes surrounding the portal triad and in some other hepatocytes was weak or absent, and positive immunoreactivity was detected at the plasma membrane of some of these cells. After 72 h of fasting, glucokinase immunoreactivity was markedly decreased in all hepatocytes. After the start of refeeding, the cytoplasmic immunoreactivity began to increase first in the parenchymal cells surrounding the THV and extended to those in the intermediate zone followed by those in the periportal zone. In contrast, the increase in nuclear immunoreactivity started in hepatocytes situated in the intermediate zone adjacent to the perivenous zone and then extended to those in the perivenous zone followed by those in the periportal zone. Hepatocytes surrounding either THV or portal triad showed a distinctive change in immunoreactivity during the refeeding period. After 10 h of refeeding, strong immunoreactivity was observed in both the cytoplasm and the nuclei of all hepatocytes, and appreciable glucokinase immunoreactivity was detected at the plasma membrane of some hepatocytes. These findings are discussed from the standpoint of a functional role of glucokinase in hepatic glucose metabolism.

Prenatally diagnosed female prune belly syndrome associated with tetralogy of Fallot.

Female prune belly syndrome and tetralogy of Fallot were diagnosed in obstetric ultrasound screening at 13 and 28 weeks of gestation, respectively. The baby was born at 38 weeks showing abdominal distension, hypoplasia of abdominal muscles, vaginal atresia, imperforate anus and clubfeet. Radiologic and ultrasound examinations confirmed our prenatal diagnosis and revealed other abnormalities of patent ductus arteriosus, major aortopulmonary collateral arteries, bilateral vesicoureteral reflux, rectourethral fistula and hypoplasia of the right kidney. Urination has been smooth, but cystitis was observed repeatedly once a month. The infant was discharged in good condition and has been followed in the outpatient clinic.

Evidence for glucokinase translocation by glucose in rat hepatocytes.

By an immunohistochemical technique, we examined changes in the subcellular distribution of rat liver glucokinase in response to external stimuli. Glucokinase immunoreactivity was found predominantly in the nucleus of hepatocytes. In situ perfusion of the liver with 20 mM glucose for 10 min caused a marked decrease in nuclear immunoreactivity and an increase in cytoplasmic immunoreactivity. Insulin (10 nmol/l) potentiated this glucose effect. However, no change took place when 5 mM glucose was perfused. These results indicate that glucokinase is translocated from the nucleus to the cytoplasm in response to a high concentration of glucose.

Developmental blockage of mouse embryos caused by fatty acids.

PURPOSE: It has been shown that lipid peroxides derived from polyunsaturated fatty acids (PUFAs) inhibit the proliferation of various cells. In the meantime, it has been suggested that oxidative stress is closely related to the developmental blockage of mammalian embryos cultured in vitro. In this study, we investigated the effects by various fatty acids on mouse embryo development in vitro, and the reversal of these effects by various antioxidants such as superoxide dismutase, ascorbic acid, alpha-tocopherol, uric acid, and ethylenediaminetetraacetic acid. METHODS: Pronuclear and two-cell stage mouse (ICR) embryos were cultured in Biggers-Whitten-Whittingham medium with 0.3% bovine serum albumin alone or complexed with one of the following fatty acids: palmitic, stearic, oleic, linoleic, linolenic, or arachidonic acid. We also measured the fluorescence emission of embryos in media containing various fatty acids in order to investigate the involvement of H2O2 or lipid peroxidation in embryo development. RESULTS: Palmitic acid and PUFAs including linoleic acid inhibited the embryo development. The inhibitory effect of PUFAs was attenuated by adding antioxidants into the media, while the inhibitory effect of palmitic acid was not. Both pronuclear and two-cell stage embryos with PUFAs showed markedly more intensive emissions than those under other conditions. CONCLUSIONS: These results suggest that lipid radicals can easily be generated in early stage embryos and that blastomeres are among the cells vulnerable to the damage by lipid peroxidation.

The fate of embryos transferred into the uterus.

PURPOSE: The purpose of this study is to elucidate the fate of embryos transferred into the uterus. METHODS: Implantation rates were compared between synchronous and asynchronous intrauterine embryo transfers in mice. Then transferred embryos were recovered from the uterus and examined morphologically 24 hr after transfer. Moreover, the same transfer-recovery experiments were performed after ligation of the uterus two-thirds from the uterotubal junction immediately before transfer. RESULTS: The implantation rate was high (58.4% per embryo, 87.5% per recipient) when blastocysts were transferred into the uteri of recipients of pseudopregnant Day 4, but it was very low (0-2.4% per embryo, 0-8.3% per recipient) when blastocysts were transferred to recipients of pseudopregnant Day 2, or two-cell embryos into recipients of pseudopregnant Days 2 and 4. When transferred embryos were recovered from the uterus 24 hr after transfer, few embryos (1.4%) were recovered in asynchronous transfers, while 66.3% of the embryos were recovered in synchronous transfers. However, from recipients in which the lower portions of uteri were ligated, embryos at more advanced stages were recovered even in asynchronous transfers. CONCLUSIONS: These results suggest that discharge from the uterus is one of the major causes of the low implantation rate for asynchronous transfer.