Cholesterol suppresses spontaneous activation of EGFR-mediated signal transduction.

Epidermal growth factor receptor (EGFR)-mediated signal transduction controls cell growth and proliferation. The signaling pathway is regulated so that it is activated only by external EGF stimuli, but the mechanisms that prevent EGF-independent spontaneous activation of EGFR-mediated signaling are unknown. Here we report cholesterol depletion activates EGFR-mediated signaling without EGF. We applied automated single-molecule imaging to EGFR and characterized the lateral diffusion and cluster formation on cholesterol-depleted and cholesterol-supplemented membranes. In cells in which cholesterol was depleted by methyl-ß-cyclodextrin (MßCD) treatment, EGFR exhibited a reduction in lateral diffusion, an acceleration of cluster formation, and autophosphorylation without EGF. Concurrently, extracellular signal-regulated kinase (ERK), which is regulated by EGFR-mediated signaling, exhibited phosphorylation and nuclear translocation without EGF. These cholesterol depletion-induced changes were similar, albeit less efficient, to those that occurred with EGF stimulation in normal cells without MßCD, indicating the spontaneous activation of EGFR signaling. The exogenous supplementation of cholesterol suppressed the MßCD-induced spontaneous activation of EGFR and ERK nuclear translocation. Single-molecule imaging of EGFR in a large number of cells revealed cell-to-cell heterogeneity, with a sub-population showing a high ability for spontaneous activation. These results provide evidence that EGFR-mediated signaling is properly regulated by cholesterol metabolism to prevent uncontrolled spontaneous activation.

Safe and promising outcomes of in-hospital preoperative rehabilitation for coronary artery bypass grafting after an acute coronary syndrome.

OBJECTIVE: In patients with stable hemodynamic status after an acute coronary syndrome (ACS), coronary artery bypass grafting (CABG) after preoperative investigations can provide outcomes comparable to those of emergency surgery. However, no established guidelines exist regarding the preparation period before surgery. We report the results of the use of an inpatient cardiac rehabilitation program followed by CABG after an ACS to improve post-operative outcomes and prognosis after discharge. METHODS: From 2005 to 2017, 471 patients underwent either isolated or combined CABG at our institution, and of those, the 393 who received isolated CABG were included in the analysis. Twenty-seven patients (6.9%) were admitted with ACS and underwent preoperative rehabilitation before undergoing CABG, with a subsequent review of surgical morbidity and mortality rates. Propensity score matching yielded a cohort of 26 patients who underwent preoperative rehabilitation (group A) and 26 controls (group B). Preoperative characteristics were similar between groups. RESULTS: The completion rate of the rehabilitation program was 96.3%. All programs were conducted with inpatients, with an average length of stay of 23 ± 12 days. All patients completed in-bed exercises, and 85% completed out-of-bed exercises. The 30-day postoperative mortality was 0% in both groups A and B, and the rate of postoperative major adverse cardiac or cerebrovascular events at 12 months did not differ significantly between groups (7.7% vs 3.9%, respectively; p = 1.0). The duration of mechanical ventilation (1.3 ± 0.3 vs 1.5 ± 0.3 days, respectively; p = 0.633), length of intensive care unit stay (4.4 ± 2.1 vs 4.8 ± 2.3 days, respectively; p = 0.584) and length of hospital stay (25 ± 13 vs 22 ± 9 days, respectively; p = 0.378) did not differ significantly between groups. CONCLUSIONS: No complications of preoperative rehabilitation were observed, suggesting that it is an acceptable option for patients who experience ACS and undergo CABG. These results are promising in offering more robust designs of future trials.

SALL4 deletion and kidney and cardiac defects associated with VACTERL association.

Congenital anomalies of the kidney and urinary tract (CAKUT) can be a part of the VACTERL association, which represents the non-random combination of the following congenital anomalies: vertebral anomalies, anal anomalies, cardiac anomalies, tracheal-esophageal anomalies, kidney anomalies, and limb anomalies. VACTERL association is generally considered to be a non-genetic condition. Exceptions include a patient with a heterozygous nonsense SALL4 variant and anal stenosis, tetralogy of Fallot, sacro-vertebral fusion, and radial and thumb anomalies. SALL4 encodes a transcription factor that plays a critical role in kidney morphogenesis. Here, we report a patient with VACTERL association and a heterozygous 128-kb deletion spanning SALL4 who presented with renal hypoplasia, radial and atrio-septal defects, and patent ductus arteriosus. The present report of SALL4 deletion, in addition to a previously reported patient with VACTERL association phenotype and SALL4 nonsense mutation, further supports the notion that SALL4 haploinsufficiency can lead to VACTERL association.

Cardiovascular risk assessments in patients with cortisol-producing adenoma: impact of clinical features and genetic characteristics.

The causes of adrenal Cushing's syndrome (CS) encompass a wide spectrum of adrenal cortisol proliferations that exhibit clinical and molecular heterogeneity. The aims of our study were to investigate whether clinical and molecular heterogeneity influences endothelial function and metabolic abnormalities in patients with cortisol-producing adenoma (CPA). We retrospectively enrolled 25 patients with CPA and 45 patients with essential hypertension (EH). All CPAs were studied by direct sequencing of PRKACA. Flow-mediated vasodilation (FMD), an index of vascular endothelial function, was significantly lower in CS and subclinical CS (SCS) groups than in the EH group. FMD impairment did not differ significantly between CS and SCS groups. No differences in FMD were seen between PRKACA mutant and wild-type groups. FMD correlated negatively with hemoglobin A1c (HbA1c) in both PRKACA mutant and wild-type groups, as well as in CS and SCS groups. After adrenalectomy, systolic blood pressure (SBP) and HbA1c decreased significantly from baseline in the CS group, and SBP and low-density lipoprotein cholesterol (LDL-C) decreased significantly from baseline in the SCS group. While SBP and LDL-C decreased significantly from baseline in patients with wild-type PRKACA, only HbA1c decreased from baseline in patients harboring PRKACA mutations. Our data showed that patients with CPA have impaired endothelial function compared with EH patients and suggest the need for strict monitoring of atherosclerosis, even in patients with SCS or without PRKACA mutation.

Sake yeast symbiosis with lactic acid bacteria and alcoholic fermentation.

The yeast Saccharomyces cerevisiae plays a pivotal role in the production of fermented foods by converting sugars in ingredients into ethanol through alcoholic fermentation. However, how accurate is our understanding of its biological significance? Although yeast is essential to produce alcoholic beverages and bioethanol, yeast does not yield ethanol for humankind. Yeast obtains energy in the form of ATP for its own vital processes through alcoholic fermentation, which generates ethanol as a byproduct. The production of ethanol may have more significance for yeast, since many other organisms do not produce ethanol, a highly toxic substance, to obtain energy. The key to address this issue has not been found using conventional microbiology, where yeasts are isolated and cultured in pure form. This review focuses on a possible novel role of yeast alcohol fermentation, which is revealed through our recent studies of microbial interactions.

Efficacy and safety of dupilumab with concomitant topical corticosteroids in Japanese pediatric patients with moderate-to-severe atopic dermatitis: A randomized, double-blind, placebo-controlled phase 3 study.

BACKGROUND: We investigated the efficacy and safety of dupilumab in Japanese patients aged ≥6 months to <18 years old with moderate-to-severe atopic dermatitis not adequately controlled with existing therapies. METHODS: In this randomized, double-blind, phase 3 study, patients received dupilumab (n = 30) or placebo (n = 32) with concomitant topical corticosteroids for 16 weeks, then all patients received dupilumab from 16 to 52 weeks. The primary endpoint was the proportion of patients with ≥75% improvement in Eczema Area and Severity Index (EASI) score from baseline (EASI-75) to Week 16. Key secondary endpoints included changes in EASI score, proportion of patients with investigator global assessment (IGA) scores of 0/1, and changes in worst daily itch numerical rating scale (NRS) scores (evaluated in patients aged ≥6 to <12 years [n = 35]). RESULTS: At Week 16, more patients achieved EASI-75 with dupilumab than placebo (43.3% vs 18.8%; P = 0.0304), and the least squares mean (LSM) difference in percent change in EASI scores at Week 16 of dupilumab vs placebo was -39.4% (P = 0.0003). However, no significant difference in the proportion of patients achieving IGA scores of 0/1 at Week 16 with dupilumab versus placebo were seen (10.0% vs 9.4%; P = 0.8476). The percent change in worst daily itch NRS scores at Week 16 was higher with dupilumab (LSM difference: -33.3%; nominal P = 0.0117). Dupilumab was well tolerated; no new safety signals were identified. CONCLUSIONS: Dupilumab showed consistent efficacy and was well tolerated in Japanese patients aged ≥6 months to <18 years with moderate-to-severe atopic dermatitis previously insufficiently controlled with existing therapies.

[Left Atrial Appendage Closure with Various Types of Surgical Technique and Its Results].

BACKGROUND: Occlusion of the left atrial appendage( LAA) may prevent stroke in patients with atrial fibrillation. In this study, we reviewed various types of LAA occlusion techniques and results of patients underwent surgical LAA closure. METHODS: Between 2004 and 2022, 182 patients who underwent surgical LAA closure were enrolled in this study. RESULTS: The surgical LAA closure consisted of 90 cases of closure device, AtriCure, 63 cases of surgical excision, 13 cases of stapler excision, 3 cases of ligation, and 13 cases of internal suture ligation. During the follow-up period, there were no deaths owing to cardiogenic emboli and no cerebral infarctions. CONCLUSIONS: Regardless of the surgical techniques, LAA closure was effective in preventing cardiogenic stroke. The AtriClip is a safe, simple, and effective and thoracoscopic LAA closure using AtriClip is expected as a less-invasive LAA management.

Effects of Aliskiren Monotherapy versus Amlodipine Monotherapy in Hypertensive Patients with Obesity or Type 2 Diabetes Mellitus.

INTRODUCTION: Renin-angiotensin system inhibitors have been reported to exert protective effects against organ damage and failure; however, the impact of the direct renin inhibitor as monotherapy has not been assessed. Here, we investigated the effects of 24-week monotherapy with aliskiren compared to amlodipine in hypertensive patients with type 2 diabetes or obesity. METHODS: In this randomized intervention study, 62 adult hypertensive patients with visceral obesity (defined as a body mass index [BMI] greater than 25 kg/m2 and a visceral adipose tissue area [VFA] greater than 100 cm2) or type 2 diabetes mellitus (age 57 ± 13, 65% men, BMI 28.8 ± 4.8 kg/m2, VFA 134.8 ± 47.0 cm2, blood pressure 141 ± 16/86 ± 13 mm Hg) were randomized to receive 24-week treatment with aliskiren (max. 300 mg) or amlodipine (max. 10 mg). The primary outcome was the change in VFA at 24 weeks post-treatment. RESULTS: Change in VFA did not differ significantly from baseline in either group. Systolic blood pressure significantly decreased at 12 weeks (-10 mm Hg, p = 0.001) and 24 weeks (-10 mm Hg, p = 0.001) in the amlodipine group and at 24 weeks (-11 mm Hg, p = 0.001) in the aliskiren group. Diastolic blood pressure significantly decreased at 24 weeks (-6 mm Hg, p = 0.009) only in the amlodipine group. Although the estimated glomerular filtration rates did not significantly change in either group, the logarithm of urinary albumin excretion significantly decreased at 24 weeks only in the aliskiren group (-0.60, p < 0.001). The 24-week changes in the urinary albumin excretion significantly correlated with the changes in the plasma renin activity in the aliskiren group (r = 0.51, p = 0.008). CONCLUSION: Aliskiren monotherapy did not show any superiority to amlodipine monotherapy on VFA, estimated glomerular filtration rates, or urinary albumin excretion in obese or type 2 diabetic hypertensive patients.

Side Effects of COVID-19 Vaccines in Patients with Inflammatory Bowel Disease in Japan.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are recommended to receive the coronavirus disease 2019 (COVID-19) vaccine. However, a recent survey showed that patients with IBD are more hesitant to receive the vaccine than the general population. Detailed information on the side effects of the COVID-19 vaccine is necessary to encourage vaccination among patients with IBD. AIM: To investigate the frequency of side effects following COVID-19 vaccination in patients with IBD in Japan. STUDY DESIGN: a cross-sectional survey was conducted using a questionnaire administered to adult patients with IBD in a tertiary medical facility. RESULTS: Among the participants who answered the questionnaire, 92.6%, 91.5%, and 41.5% of the participants had received their first, second, and third doses of the COVID-19 vaccine, respectively. Of the vaccinated participants, 88.3%, 86.3%, and 89.0% experienced side effects after receiving the first, second, and third doses of the vaccine, respectively. The incidences of fever, chills, and headaches were significantly higher among female participants than among male participants (p < 0.05). However, the frequencies of most side effects were comparable between the BNT162b2 mRNA and mRNA-1273 vaccines. CONCLUSION: The findings of our survey can help encourage patients with IBD to receive the COVID-19 vaccine.

Prenatal Torsion of Radial Polydactyly: A Gangrenous Mass at the Base of the Thumb.

A patient was born with a mass at the base of the thumb approximately 1.5 cm in diameter on the radial side of the fingers. The mass had globular swelling filled with hemorrhagic fluid and was dark red. X-rays and histology of the excised specimen suggested the diagnosis of gangrene and torsion of polydactyly. Prenatal torsion of polydactyly is not a common occurrence; moreover, prenatal torsion of polydactyly has only been found in ulnar polydactyly. Our case is a novel case of radial polydactyly that was gangrenous at birth owing to prenatal torsion. Diagnosing such a mass at the base of the thumb is important.

Therapeutic Effectiveness of Needle Injection Versus Needle-Free Jet Injector System for Botulinum Toxin Type A in Palmar Hyperhidrosis.

BACKGROUND: The most important problem with local injections of botulinum toxin type A (BTX-A) in palmar hyperhidrosis is pain during the injections. OBJECTIVES: We evaluated therapeutic effectiveness and pain of local injections of BTX-A using needle-free direct administration system. METHODS: We performed BTX-A local injection therapy using a conventional injection needle in the left hand and a needle-free direct administration system in the right hand. RESULTS: A reduction in the quantity of perspiration was observed 4 weeks after administration of both Needle and Needle-free BTX-A, and reduction was maintained throughout 28 weeks observation period. Both hyperhidrosis Disease Severity Scale scores and Dermatology Life Quality Index for hands treated with Needle BTX-A and hands treated with Needle-free BTX-A had decreased significantly by 4 weeks after treatment. Pain visual analog scale scores and the degree of pain were significantly lower in hands treated with Needle-free BTX-A than in hands treated with Needle BTX-A. CONCLUSIONS: When the trigger of the pressurized needle-free injector device is activated, the gas powered driving pressure propels BTX-A through an orifice (0.13 mm) about four times narrower than a 30 G needle at very high speed. As most pain occurs during the needle prick itself, the advantage of a small orifice coupled with high-speed penetration of BTX-A through the pressurized device results in reduced pain during administration. The needle-free direct administration system administers the injectate under the skin without a visible needle.

Spontaneous Attenuation of Alcoholic Fermentation via the Dysfunction of Cyc8p in Saccharomyces cerevisiae.

A cell population characterized by the release of glucose repression and known as [GAR+] emerges spontaneously in the yeast Saccharomyces cerevisiae. This study revealed that the [GAR+] variants exhibit retarded alcoholic fermentation when glucose is the sole carbon source. To identify the key to the altered glucose response, the gene expression profile of [GAR+] cells was examined. Based on RNA-seq data, the [GAR+] status was linked to impaired function of the Cyc8p-Tup1p complex. Loss of Cyc8p led to a decrease in the initial rate of alcoholic fermentation under glucose-rich conditions via the inactivation of pyruvate decarboxylase, an enzyme unique to alcoholic fermentation. These results suggest that Cyc8p can become inactive to attenuate alcoholic fermentation. These findings may contribute to the elucidation of the mechanism of non-genetic heterogeneity in yeast alcoholic fermentation.

[Surgical Treatment of Extensive Annular Defects by Aortic Valve Infective Endocarditis Using Stentless Bioprosthesis].

BACKGROUND: The optimal surgical technique and valve prosthesis in patients with active aortic valve infective endocarditis with annular abscess is controversial. If extensive annular defects occur after debridement, standard techniques are difficult;more complex aortic root replacement is inevitable. The SOLO SMART stentless bioprosthesis is specially designed for supra-annular implantation without annular stitches. METHODS: Since 2016, 15 patients with active aortic valve infective endocarditis underwent aortic valve surgery. Of these, we performed aortic valve replacement using the SOLO SMART valve in six patients with extensive annular destruction and complex aortic root pathologies requiring reconstruction. RESULTS: Although more than two-thirds of the annular structure was missing after radical debridement of infected tissues, supra-annular aortic valve replacement with the SOLO SMART valve could be performed successfully in all six patients. All patients are doing well without prosthetic valve dysfunction and/or recurrent infection. CONCLUSIONS: The supraannular aortic valve replacement using the SOLO SMART valve is considered to be a useful alternative to standard aortic valve replacement in patients complicated with extensive annular defect. It is a simple and technically less demanding alternative to aortic root replacement.

Crystal structures of EfeB and EfeO in a bacterial siderophore-independent iron transport system.

EfeUOB is a siderophore-independent iron uptake mechanism in bacteria. EfeU, EfeO, and EfeB are a permease, an iron-binding or electron-transfer protein, and a peroxidase, respectively. A Gram-negative bacterium, Sphingomonas sp. strain A1, encodes EfeU, EfeO, EfeB together with alginate-binding protein Algp7, a truncated EfeO-like protein (EfeOII), in the genome. The typical EfeO (EfeOI) consists of N-terminal cupredoxin and C-terminal M75 peptidase domains. Here, we detail the structure and function of bacterial EfeB and EfeO. Crystal structures of strain A1 EfeB and Escherichia coli EfeOI were determined at 2.30 Å and 1.85 Å resolutions, respectively. A molecule of heme involved in oxidase activity was bound to the C-terminal Dyp peroxidase domain of EfeB. Two domains of EfeOI were connected by a short loop, and a zinc ion was bound to four residues, Glu156, Glu159, Asp173, and Glu255, in the C-terminal M75 peptidase domain. These residues formed tetrahedron geometry suitable for metal binding and are well conserved among various EfeO proteins including Algp7 (EfeOII), although the metal-binding site (HxxE) is proposed in the C-terminal M75 peptidase domain. This is the first report on structure of a typical EfeO with two domains, postulating a novel metal-binding motif "ExxE-//-D-//-E" in the EfeO C-terminal M75 peptidase domain.

Compound heterozygous variants of the NARS2 gene in siblings with developmental delay, epilepsy, and neonatal diabetes syndrome.

Neonatal diabetes mellitus (NDM) with developmental delay and epilepsy is classified as developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome. The majority of DEND syndrome are due to severely damaging variants of K-ATP channels, and few mitochondria-related genes have been reported. We report here two Japanese siblings who were clinically diagnosed with DEND syndrome in whom NARS2 compound heterozygous variants were detected. Patient 1 was a 3-year-old girl and presented with diabetes ketoacidosis at 3 months old. Patient 2 was a 1-year-old boy who presented with severe hyperglycemia and started insulin therapy at 3 days old. After the first episodes, they both presented with severe developmental delay, hearing loss and treatment-resistant epilepsy accompanied by progressive brain atrophy. Whole-exome sequencing revealed compound heterozygous NARS2 p.R159C and p.L217V variants, and the GATA4 p.P407Q variant in both patients. They were treated by mitochondrial supportive therapy of vitamin B1, L-carnitine, and coenzyme Q10. Patient 2 was withdrawn from insulin therapy at 6 months old. This is the first report of NDM in which variants of the NARS2 gene coding mitochondrial protein were detected. Genetic analysis including mitochondrial genes should be considered in patients with neonatal onset diabetes associated with neurogenic symptoms.

Feasibility of assessing male osteoporosis using MRI IDEAL-IQ sequence of proximal femur in prostate cancer patients.

Osteoporosis is often accompanied by bone loss with fat accumulation of the red marrow. A novel technique for quantification of iron and fat content by MRI IDEAL-IQ can visualize hematopoietic areas and fatty deposits in bone marrow; however, the relationship between these indices and total hip bone mineral density (BMD) remains unclear. In this study, the proximal femur of 104 men who underwent pelvic MRI and bone densitometry prior to treatment for non-metastatic prostate cancer was retrospectively examined to investigate the R2* value to quantify iron and proton density fat fraction (PDFF) to assess bone marrow fat content. R2* was significantly positively correlated with BMD (r = 0.6017, p < 0.0001), and PDFF was not correlated with BMD (r = -0.1302, p = 0.0512). Patients with BMD T-score ≤ -2.5 had significantly lower R2* than patients with BMD T-score > -2.5; however, there was no significant difference in PDFF. In the ROC analysis, which examined the predictive ability of R2* with BMD T-score ≤ -2.5 as an outcome, the cut-off value of R2* was 50.7 s-1 (AUC 0.817). These results show R2* correlated with BMD. R2* may be a non-invasive surrogate marker for diagnosing male osteoporosis.

Efficacy and predictor of anti-TNFα agents in patients with intestinal Behçet's disease.

BACKGROUND: Behçet's disease (BD) is a recurrent multisystem inflammatory disease. Anti-tumor necrosis factor (TNF) α agents have been used to treat patients with intestinal BD with severe disease activity or those who are resistant to conventional treatments; however, the long-term efficacy of anti-TNFα agents in intestinal BD remains unclear. In the present study, we investigated the clinical outcomes and predictors of discontinuation of anti-TNFα agents in patients with intestinal BD. METHODS: We reviewed the medical records of patients with intestinal BD who received first-line anti-TNFα agents between January 2009 and June 2020. The primary outcome was the percentage of patients who continued anti-TNFα therapy for 48 weeks. Secondary outcomes included the percentage of patients who achieved marked improvement, complete remission, and mucosal healing, as well as predictors of discontinuation of anti-TNFα agents. RESULTS: A total of 29 patients were included in the study. Twenty-two (75.9%) patients continued anti-TNFα therapy for 48 weeks. The percentage of patients who achieved marked improvement, complete remission, and mucosal healing at week 48 was 48.3%, 37.9%, and 48.3%, respectively. At week 96, 11 (37.9%) patients achieved marked improvement, complete remission, and mucosal healing. A higher C-reactive protein level (CRP; ≥ 1 mg/dL) at baseline was a predictor of discontinuation of anti-TNFα agents. CONCLUSIONS: The 48-week continuation rate of anti-TNFα agents was 75.9% in bio-naïve patients with intestinal BD. However, a higher baseline CRP level (≥ 1 mg/dL) was associated with discontinuation of anti-TNFα agents.

Ultrasonographic evaluation reveals thinning of cervical nerve roots and peripheral nerves in spinal and bulbar muscular atrophy.

BACKGROUND: Ultrasonography (US) is a noninvasive and patient-friendly tool for the evaluation of peripheral nerves. In motor neuron diseases, amyotrophic lateral sclerosis (ALS) has been reported to show the atrophy of peripheral nerves on US. However, the US findings are still unclear in spinal and bulbar muscular atrophy (SBMA), an adult-onset lower motor neuron disease caused by an abnormal CAG repeat expansion in the androgen receptor gene. METHODS: We prospectively recruited and evaluated 11 patients with genetically confirmed SBMA and 9 patients with ALS diagnosed according to the revised El Escorial ALS criteria or the Awaji electrodiagnostic criteria. The C5-C7 cervical nerve roots and the median and ulnar nerves were evaluated ultrasonographically. RESULTS: The cross-sectional areas (CSAs) of the C6 and C7 nerve roots, the median nerve in the upper arm and forearm, and the ulnar nerve in the upper arm were smaller in patients with SBMA than those in patients with ALS (p < 0.05), whereas the CSAs of the C5 nerve root and the ulnar nerve in the forearm were not smaller. CONCLUSIONS: US showed that the peripheral nerves in patients with SBMA were thinner than those in patients with ALS despite similar degrees of weakness and motor neuron loss. Possible causes include additional sensory nerve involvement and longer disease duration in patients with SBMA than those in patients with ALS.

Discharge disposition and 1-year readmission in acute-phase hospitalized patients with heart failure: a retrospective observational multi-center study.

Patients hospitalized for acute heart failure (HF) tend to experience declines in physical function and activities of daily living (ADL) due to bed rest and restricted mobilization. This could result in some patients being transferred to rehabilitation hospitals. This study aims to examine the relationship between discharge disposition and 1-year readmission and mortality rates in HF patients. Nine hundred fifty six consecutive HF patients who were hospitalized for acute decompensated HF and underwent rehabilitation were divided into two groups: home (returned home) or transfer (transferred to rehabilitative or long-term care hospital units due to decline in physical function and/or ADL) groups. The primary and secondary outcomes were 1-year readmission and mortality rates after discharge, respectively. Of the 956 patients, 8.6% (n = 82) were transferred to rehabilitative or long-term care hospital units. Over a 1-year follow-up period, all-cause and HF readmission rates were 50.1% (n = 479) and 27.2% (n = 260), respectively. The transfer group had significantly lower readmission rates compared to home group after adjusting for the pre-existing risk factors (hazard ratio for all-cause and HF readmission: 0.600 and 0.552, 95% CI 0.401-0.897 and 0.314-0.969; P = 0.013 and P = 0.038, respectively). There was no significant relationship between discharge disposition and all-cause mortality rate. Low ADL defined as Barthel index < 60 points was identified as a predictor of all-cause and HF readmission among the home group (odds ratio for all-cause and HF readmission rates: 2.156 and 1.847, 95% CI 1.026-4.531 and 1.036-2.931; P = 0.043 and P = 0.037, respectively). This multi-center study demonstrated that HF patients transferred to rehabilitative or long-term care hospital units after an acute hospitalization had a significantly decreased 1-year all-cause and HF readmission rates compared to patients who returned to their home. These findings may help in selecting a discharge disposition for older HF patients with ADL decline.

Constrictive pericarditis caused by pericardial substitution using expanded polytetrafluoroethylene.

BACKGROUND: Expanded polytetrafluoroethylene (ePTFE) is commonly used as a pericardial substitute during cardiac surgery to prevent cardiac injury during re-sternotomy. However, although rare, constrictive pericarditis associated with ePTFE has been reported. MATERIAL, METHODS AND RESULTS: Here, we report a rare case of constrictive pericarditis developed due to severe restriction of cardiac motion associated with the ePTFE membrane used as a pericardial substitute. Hemodynamic improvement has been achieved by surgical removal of the ePTFE membrane and exudates within the overlapped portion of the ePTFE membranes, and dissection of the epicardial fibrous thickening. CONCLUSION: Considering the risk of constrictive pericarditis, we believe that the use of ePTFE membranes as a pericardial substitute should be carefully indicated for only selected patients.