Determination of enzalutamide long-term safety and efficacy for castration-resistant prostate cancer patients after combined anti-androgen blockade followed by alternative anti-androgen therapy: a multicenter prospective DELC study.

BACKGROUND: Alternative anti-androgen therapy has been widely used as a first-line treatment for castration-resistant prostate cancer, and it may affect treatment outcome of subsequent agents targeting the androgen receptor axis. We conducted the prospective observational DELC (Determination of Enzalutamide Long-term safety and efficacy for Castration-resistant prostate cancer patients after combined anti-androgen blockade followed by alternative anti-androgen therapy) study to evaluate the efficacy of enzalutamide in patients with castration-resistant prostate cancer who underwent prior combined androgen blockade with bicalutamide and then alternative anti-androgen therapy with flutamide. METHODS: The DELC study enrolled 163 Japanese patients with castration-resistant prostate cancer who underwent alternative anti-androgen therapy with flutamide following failure of initial combined androgen blockade with bicalutamide in multiple institutions between January 2016 and March 2019. Primary endpoint was overall survival. Administration of enzalutamide was started at 160 mg orally once daily in all patients. RESULTS: The rate of decline of prostate-specific antigen by 50% or more was 72.2%, and median overall survival was 42.05 months. Multivariate analysis revealed that higher pretreatment serum levels of prostate-specific antigen (≥11.3 ng/mL; P = 0.004), neuron-specific enolase (P = 0.014) and interleukin-6 (≥2.15 pg/mL; P = 0.004) were independent risk factors for overall survival. Fatigue (30.0%), constipation (19.6%) and appetite loss (17.8%) were the most common clinically relevant adverse events. The enzalutamide dose was not reduced in any patient under the age of 70, but adherence was decreased in those over 70. CONCLUSIONS: In the DELC study, the safety of enzalutamide was comparable to that in previous reports. Serum levels of neuron-specific enolase and interleukin-6 were suggested as prognostic factors for castration-resistant prostate cancer with potential clinical utility.

Current status and future perspectives on robot-assisted kidney autotransplantation: A literature review.

This review presents the latest insights on robot-assisted kidney autotransplantation (RAKAT). RAKAT is a minimally invasive surgical procedure and represents a promising alternative to conventional laparoscopic nephrectomy followed by open kidney transplantation for the treatment of various complex urological and vascular conditions. RAKAT can be performed either extracorporeally or intracorporeally. Additionally, a single-port approach can be performed through one small incision without the need to reposition the patient. Of 86 patients undergoing RAKAT, 8 (9.3%) developed postoperative > Grade 2 Clavien-Dindo (CD) complications. Although the feasibility of RAKAT was established in 2014, the long-term efficacy and safety along with outcomes of this surgical approach are still being evaluated, and additional studies are needed. With improvements in the technology of RAKAT and as surgeons gain more experience, RAKAT should become increasingly used and further refined, thereby leading to improved surgical outcomes and improved patients' quality of life.

Quantitative Computed Tomography Analysis of the Longitudinal Change Between Centrilobular and Paraseptal Emphysema Subtypes: A Retrospective Study.

OBJECTIVE: This study aimed to investigate the difference between the extent of centrilobular emphysema (CLE) and paraseptal emphysema (PSE) on follow-up chest CT scans and their relationship to the cross-sectional area (CSA) of small pulmonary vessels. METHODS: Sixty-two patients (36 CLE and 26 PSE) who underwent 2 chest CT scans were enrolled in this study. The percentage of low attenuation volume (%LAV) and total CSA of the small pulmonary vessels <5 mm 2 (%CSA < 5) were measured at the 2 time points. Analysis of the initial %CSA < 5 and the change in the %LAV and %CSA < 5 on follow-up imaging was performed. RESULTS: The initial %CSA < 5 was not significantly different between the CLE and the PSE groups (CLE, 0.66 vs. PSE, 0.71; P = 0.78). There was no significant difference in the longitudinal change in the %LAV between the 2 groups (CLE, -0.048% vs. PSE, 0.005%; P = 0.26). The longitudinal change in the %CSA < 5 in patients with PSE significantly decreased compared with those with CLE (CLE, 0.025% vs. PSE, -0.018%; P = 0.02). CONCLUSIONS: The longitudinal change in the %CSA < 5 was significantly different for patients with CLE and PSE, demonstrating an important pathophysiological difference between the subtypes.

Diamond-like carbon coating to inner surface of polyurethane tube reduces Staphylococcus aureus bacterial adhesion and biofilm formation.

Staphylococcus aureus is one of the main causative bacteria for polyurethane catheter and artificial graft infection. Recently, we developed a unique technique for coating diamond-like carbon (DLC) inside the luminal resin structure of polyurethane tubes. This study aimed to elucidate the infection-preventing effects of diamond-like carbon (DLC) coating on a polyurethane surface against S. aureus. We applied DLC to polyurethane tubes and rolled polyurethane sheets with our newly developed DLC coating technique for resin tubes. The DLC-coated and uncoated polyurethane surfaces were tested in smoothness, hydrophilicity, zeta-potential, and anti-bacterial properties against S. aureus (biofilm formation and bacterial attachment) by contact with bacterial fluids under static and flow conditions. The DLC-coated polyurethane surface was significantly smoother, more hydrophilic, and had a more negative zeta-potential than did the uncoated polyurethane surface. Upon exposure to bacterial fluid under both static and flow conditions, DLC-coated polyurethane exhibited significantly less biofilm formation than uncoated polyurethane, based on absorbance measurements. In addition, the adherence of S. aureus was significantly lower for DLC-coated polyurethane than for uncoated polyurethane under both conditions, based on scanning electron microscopy. These results show that applying DLC coating to the luminal resin of polyurethane tubes may impart antimicrobial effects against S. aureus to implantable medical polyurethane devices, such as vascular grafts and central venous catheters.

Plasma circulating tumor DNA profiling in patients with chemo-refractory germ cell tumors.

OBJECTIVES: Molecular analysis of tumor tissues has been extensively analyzed in germ cell tumors. However, genetic analysis of plasma circulating tumor DNA has been limited. Our objective was to analyze genetic alterations in circulating tumor DNA as well as its impact on prognosis in patients with chemo-refractory germ cell tumors. METHODS: We included 13 patients with chemo-refractory germ cell tumors who relapsed after second-line or higher previous chemotherapy and performed targeted sequencing of plasma cell-free DNA using an AVENIO Expanded kit. RESULTS: Tumor-specific genetic alterations were identified in all patients. The most frequently mutated gene was TP53 (53.4%), followed by PTEN (23.1%), GNAS (15.4%) and MTOR (15.4%). Moreover, EGFR amplification (38.5%) and MET amplification (15.4%) were also identified. We defined two or more single nucleotide variants detected in plasma cell-free DNA as circulating tumor DNA-positive. Kaplan-Meier analysis revealed that overall survival was significantly shorter in circulating tumor DNA-positive patients than circulating tumor DNA negative-patients (median overall survival 3.13 vs. 8.73 months; p = 0.042). CONCLUSION: Analysis of plasma circulating tumor DNA could detect genetic alterations in patients with chemo-refractory GCT. Moreover, detectable circulating tumor DNA in plasma was associated with poor prognosis in those patients. These results suggest that liquid biopsy using analysis of plasma circulating tumor DNA may be clinically useful for germ cell tumor patients.

Radiomics model of diffusion-weighted whole-body imaging with background signal suppression (DWIBS) for predicting axillary lymph node status in breast cancer.

BACKGROUND: In breast cancer diagnosis and treatment, non-invasive prediction of axillary lymph node (ALN) metastasis can help avoid complications related to sentinel lymph node biopsy. OBJECTIVE: This study aims to develop and evaluate machine learning models using radiomics features extracted from diffusion-weighted whole-body imaging with background signal suppression (DWIBS) examination for predicting the ALN status. METHODS: A total of 100 patients with histologically proven, invasive, clinically N0 breast cancer who underwent DWIBS examination consisting of short tau inversion recovery (STIR) and DWIBS sequences before surgery were enrolled. Radiomic features were calculated using segmented primary lesions in DWIBS and STIR sequences and were divided into training (n = 75) and test (n = 25) datasets based on the examination date. Using the training dataset, optimal feature selection was performed using the least absolute shrinkage and selection operator algorithm, and the logistic regression model and support vector machine (SVM) classifier model were constructed with DWIBS, STIR, or a combination of DWIBS and STIR sequences to predict ALN status. Receiver operating characteristic curves were used to assess the prediction performance of radiomics models. RESULTS: For the test dataset, the logistic regression model using DWIBS, STIR, and a combination of both sequences yielded an area under the curve (AUC) of 0.765 (95% confidence interval: 0.548-0.982), 0.801 (0.597-1.000), and 0.779 (0.567-0.992), respectively, whereas the SVM classifier model using DWIBS, STIR, and a combination of both sequences yielded an AUC of 0.765 (0.548-0.982), 0.757 (0.538-0.977), and 0.779 (0.567-0.992), respectively. CONCLUSIONS: Use of machine learning models incorporating with the quantitative radiomic features derived from the DWIBS and STIR sequences can potentially predict ALN status.

Deep learning approach of diffusion-weighted imaging as an outcome predictor in laryngeal and hypopharyngeal cancer patients with radiotherapy-related curative treatment: a preliminary study.

OBJECTIVES: This preliminary study aimed to develop a deep learning (DL) model using diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps to predict local recurrence and 2-year progression-free survival (PFS) in laryngeal and hypopharyngeal cancer patients treated with various forms of radiotherapy-related curative therapy. METHODS: Seventy patients with laryngeal and hypopharyngeal cancers treated by radiotherapy, chemoradiotherapy, or induction-(chemo)radiotherapy were enrolled and divided into training (N = 49) and test (N = 21) groups based on presentation timeline. All patients underwent MR before and 4 weeks after the start of radiotherapy. The DL models that extracted imaging features on pre- and intra-treatment DWI and ADC maps were trained to predict the local recurrence within a 2-year follow-up. In the test group, each DL model was analyzed for recurrence prediction. Additionally, the Kaplan-Meier and multivariable Cox regression analyses were performed to evaluate the prognostic significance of the DL models and clinical variables. RESULTS: The highest area under the receiver operating characteristics curve and accuracy for predicting the local recurrence in the DL model were 0.767 and 81.0%, respectively, using intra-treatment DWI (DWIintra). The log-rank test showed that DWIintra was significantly associated with PFS (p = 0.013). DWIintra was an independent prognostic factor for PFS in multivariate analysis (p = 0.023). CONCLUSION: DL models using DWIintra may have prognostic value in patients with laryngeal and hypopharyngeal cancers treated by curative radiotherapy. The model-related findings may contribute to determining the therapeutic strategy in the early stage of the treatment. KEY POINTS: • Deep learning models using intra-treatment diffusion-weighted imaging have prognostic value in patients with laryngeal and hypopharyngeal cancers treated by curative radiotherapy. • The findings from these models may contribute to determining the therapeutic strategy at the early stage of the treatment.

Dietary oleamide attenuates obesity induced by housing mice in small cages.

Physical inactivity due to prolonged sedentary behavior induces obesity. Therefore, we investigated whether housing mice in small cages to mimic sedentary behavior induced obesity and whether dietary oleamide (cis-9,10-octadeceneamide) suppressed the induced obesity. A single oral administration of oleamide (50 mg/kg) to mice resulted in the accumulation of the exogenous oleamide in abdominal visceral fat. Next, mice were housed in small cages and oleamide (50 mg/kg/d) was orally administered for 12 weeks. Housing mice in small cages impaired glucose tolerance and increased food efficiency. It also increased body weight and abdominal fat mass. Dietary oleamide improved the impairment and inhibited their increase in mice housed in small cages. Furthermore, dietary oleamide suppressed the mRNA expression of inflammation-related factors in the abdominal fat of mice housed in small cages. Hence, these results indicate that although housing mice in small cages induces obesity and increases abdominal fat mass, dietary oleamide suppresses the obesity.

Effects of Model-Based Iterative Reconstruction in Low-Dose Paranasal Computed Tomography: A Comparison with Filtered Back Projection and Hybrid Iterative Reconstruction.

Iterative reconstruction (IR) improves image quality compared with filtered back projection (FBP). This study investigated the usefulness of model-based IR (forward-projected model-based iterative reconstruction solution [FIRST]) in comparison with FBP and hybrid IR (adaptive iterative dose reduction three-dimensional processing [AIDR 3D]) in low-dose paranasal CT. Twenty-four patients with paranasal sinusitis who underwent standard-dose CT (120 kV) and low-dose CT (100 kV) scanning before and after medical treatment were enrolled. Standard-dose CT scans were reconstructed with FBP (FBP120), and low-dose CT scans with FBP (FBP100), AIDR 3D, and FIRST. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in three anatomical structures and effective doses were compared using Mann-Whitney U test. Two radiologists independently evaluated the visibility of 16 anatomical structures, overall image quality, and artifacts. Effective doses in lowdose CT were significantly reduced compared with those in standard-dose CT (0.24 vs 0.43 mSv, p<0.001). FIRST achieved significantly higher SNR (p<0.01, respectively) and CNR (p<0.001, respectively) of evaluated structures and significant improvement in overall image quality (p<0.001), artifacts (p<0.001), and visibility related to muscles (p<0.05) compared to FBP120, FBP100, and AIDR 3D. FIRST allowed radiation-dose reduction, while maintaining objective and subjective image quality in low-dose paranasal CT.

Robot-assisted partial nephrectomy with minimum follow-up of 5 years: A multi-center prospective study in Japan.

OBJECTIVES: Robot-assisted partial nephrectomy is widely performed for small renal masses, achieving excellent perioperative and intermediate oncological outcomes. However, long-term oncological, functional, and quality of life outcomes after robot-assisted partial nephrectomy remain unclear. In this study, we aimed to evaluate quality of life at 1 year and oncological and functional outcomes of robot-assisted partial nephrectomy after a minimum follow-up of 5 years. METHODS: Personal, perioperative, postoperative, functional, oncological, and quality of life data were evaluated. The EQ-5D-5L tool, which incorporates health profiles and a EuroQol Visual Analog Scale, was used to assess quality of life preoperatively and 365 days postoperatively. Regarding oncological and functional outcomes, overall survival, recurrence-free survival, and changes in estimated glomerular filtration rate were calculated. RESULTS: There were few changes in levels between the two time points for all EQ-5D dimensions. The mean change in EQ-5D-5L was 0.020 (95% confidence interval 0.006-0.033, P = 0.006), and in EuroQol Visual Analog Scale score 4.60 (95% confidence interval 2.17-7.02, P = 0.0003). Overall and recurrence-free survival 5 years after robot-assisted partial nephrectomy were 97.9% and 92.8%, respectively. After an early postoperative decrease, the estimated glomerular filtration rate remained stable over time. CONCLUSIONS: Robot-assisted partial nephrectomy in patients with a T1 renal tumor is safe, feasible, and effective from the perspective of quality of life and survival, even after 5 years. When making treatment decisions, perioperative and quality of life outcomes should be considered together with long-term oncological outcomes.

Phase II trial of nivolumab monotherapy and biomarker screening in patients with chemo-refractory germ cell tumors.

OBJECTIVES: Germ cell tumors are highly susceptible to chemotherapy; however, there is a lack of established treatments for consistently relapsing germ cell tumor. Therefore, in this phase II study, we evaluated the efficacy and safety of nivolumab for relapsed germ cell tumor. METHODS: Seventeen adult patients (median age 34 years) with refractory primary germ cell tumor after second-line or higher chemotherapy were enrolled. Nivolumab was administered over 30 min at 240 mg/body every 2 weeks until disease progression or intolerable adverse event occurrence. The primary endpoint was the overall response rate. RESULT: We performed a biomarker analysis of programmed death ligand-1 expression and genomic sequencing. Tumor histology revealed nonseminoma and seminoma in 14 and three patients, respectively. Patients were pretreated with a median of three chemotherapy lines, and three patients received high-dose chemotherapy. The median number of nivolumab doses was 3 (range 2-46). One patient showed a partial response and three showed stable disease. Responses were durable in one patient with a partial response and one patient with stable disease (median 90 and 68 weeks, respectively). Nivolumab was well-tolerated, with only two Grade 3 adverse events observed. Programmed death ligand-1 expression was not associated with objective responses. Genomic sequencing revealed a high tumor mutation burden in a patient with a durable partial response. While a small subset of chemorefractory germ cell tumors may respond to nivolumab, programmed death ligand-1 is unreliable to measure response. CONCLUSIONS: Tumor mutation burden is a potential biomarker for future testing of germ cell tumor response.

Immunomodulatory Properties and Osteogenic Activity of Polyetheretherketone Coated with Titanate Nanonetwork Structures.

Polyetheretherketone (PEEK) is a potential substitute for conventional metallic biomedical implants owing to its superior mechanical and chemical properties, as well as biocompatibility. However, its inherent bio-inertness and poor osseointegration limit its use in clinical applications. Herein, thin titanium films were deposited on the PEEK substrate by plasma sputtering, and porous nanonetwork structures were incorporated on the PEEK surface by alkali treatment (PEEK-TNS). Changes in the physical and chemical characteristics of the PEEK surface were analyzed to establish the interactions with cell behaviors. The osteoimmunomodulatory properties were evaluated using macrophage cells and osteoblast lineage cells. The functionalized nanostructured surface of PEEK-TNS effectively promoted initial cell adhesion and proliferation, suppressed inflammatory responses, and induced macrophages to anti-inflammatory M2 polarization. Compared with PEEK, PEEK-TNS provided a more beneficial osteoimmune environment, including increased levels of osteogenic, angiogenic, and fibrogenic gene expression, and balanced osteoclast activities. Furthermore, the crosstalk between macrophages and osteoblast cells showed that PEEK-TNS could provide favorable osteoimmunodulatory environment for bone regeneration. PEEK-TNS exhibited high osteogenic activity, as indicated by alkaline phosphatase activity, osteogenic factor production, and the osteogenesis/osteoclastogenesis-related gene expression of osteoblasts. The study establishes that the fabrication of titanate nanonetwork structures on PEEK surfaces could extract an adequate immune response and favorable osteogenesis for functional bone regeneration. Furthermore, it indicates the potential of PEEK-TNS in implant applications.

Carotenoid transporter CD36 expression depends on hypoxia-inducible factor-1α in mouse soleus muscles.

Dietary ß-carotene induces muscle hypertrophy and prevents muscle atrophy in red slow-twitch soleus muscles, but not in white fast-twitch extensor digitorum longus (EDL) muscles and gastrocnemius muscles. However, it remains unclear why these beneficial effects of ß-carotene are elicited in soleus muscles. To address this issue, we focused on carotenoid transporters in skeletal muscles. In mice, Cd36 mRNA levels were higher in red muscle than in white muscle. The siRNA-mediated knockdown of CD36 decreased ß-carotene uptake in C2C12 myotubes. In soleus muscles, CD36 knockdown inhibited ß-carotene-induced increase in muscle mass. Intravenous injection of the hypoxia marker pimonidazole produced more pimonidazole-bound proteins in soleus muscles than in EDL muscles, and the hypoxia-inducible factor-1 (HIF-1) α protein level was higher in soleus muscles than in EDL muscles. In C2C12 myotubes, hypoxia increased the expression of CD36 and HIF-1α at the protein and mRNA levels, and HIF-1α knockdown reduced hypoxia-induced increase in Cd36 mRNA level. In soleus muscles, HIF-1α knockdown reduced Cd36 mRNA level. These results indicate that CD36 is predominantly involved in ß-carotene-induced increase in soleus muscle mass of mice. Furthermore, we demonstrate that CD36 expression depends on HIF-1α in the soleus muscles of mice, even under normal physiological conditions.

Combination of compressed sensing and parallel imaging for T2-weighted imaging of the oral cavity in healthy volunteers: comparison with parallel imaging.

OBJECTIVE: Compressed sensing (CS) and parallel imaging (PI) are magnetic resonance (MR) imaging acceleration techniques. Image quality of two-dimensional fast spin echo imaging of the oral cavity using CS or combined CS and PI has not been evaluated. The aim of this study was to compare the acquisition time and image quality between T2-weighted imaging (T2WI) with CS and PI (CSPI-T2WI) and T2WI with PI (PI-T2WI) of the oral cavity. MATERIALS AND METHODS: Twenty healthy volunteers who underwent CSPI-T2WI and PI-T2WI of the oral cavity on a 3 T MR scanner were enrolled in the study. Contrast ratios of fat/muscle and bone/muscle on CSPI-T2WI and PI-T2WI were measured. Overall image quality, 4 kinds of artifacts, and visualization of 18 anatomical structures were independently evaluated by two radiologists with grading scales. The quantitative and qualitative measurements were compared between CSPI-T2WI and PI-T2WI by using the Wilcoxon signed-rank test. RESULTS: Mean acquisition time of CSPI-T2WI and PI-T2WI was 72 s and 136 s, respectively (p < .001). CSPI-T2WI showed a significantly higher contrast ratio of fat/muscle than PI-T2WI (p < .01). There were no significant differences in the overall image quality, artifacts, and visualization of anatomical structures between CSPI-T2WI and PI-T2WI. CONCLUSIONS: CSPI-T2WI of the oral cavity in healthy volunteers can provide a reduction in acquisition time without impaired image quality compared to PI-T2WI. KEY POINTS: • The acquisition time of T2WI with the combined CS and PI provided a 47% reduction in acquisition time compared with T2WI with PI. • T2WI with the combined CS and PI did not show impaired image quality compared with T2WI with PI. • Combined CS and PI can be a useful technology to evaluate the oral cavity with high-speed acquisition.

Oleamide rescues tibialis anterior muscle atrophy of mice housed in small cages.

Skeletal muscle atrophy causes decreased physical activity and increased risk of metabolic diseases. We investigated the effects of oleamide (cis-9,10-octadecanamide) treatment on skeletal muscle health. The plasma concentration of endogenous oleamide was approximately 30 nm in male ddY mice under normal physiological conditions. When the stable isotope-labelled oleamide was orally administered to male ddY mice (50 mg/kg), the plasma concentration of exogenous oleamide reached approximately 170 nm after 1 h. Male ddY mice were housed in small cages (one-sixth of normal size) to enforce sedentary behaviour and orally administered oleamide (50 mg/kg per d) for 4 weeks. Housing in small cages decreased tibialis anterior (TA) muscle mass and the cross-sectional area of the myofibres in TA muscle. Dietary oleamide alleviated the decreases in TA muscle and resulted in plasma oleamide concentration of approximately 120 nm in mice housed in small cages. Housing in small cages had no influence on the phosphorylation levels of Akt serine/threonine kinase (Akt), mechanistic target of rapamycin (mTOR) and ribosomal protein S6 kinase (p70S6K) in TA muscle; nevertheless, oleamide increased the phosphorylation levels of the proteins. Housing in small cages increased the expression of microtubule-associated protein 1 light chain 3 (LC3)-II and sequestosome 1 (p62), but not LC3-I, in TA muscle, and oleamide reduced LC3-I, LC3-II and p62 expression levels. In C2C12 myotubes, oleamide increased myotube diameter at ≥100 nm. Furthermore, the mTOR inhibitor, Torin 1, suppressed oleamide-induced increases in myotube diameter and protein synthesis. These results indicate that dietary oleamide rescued TA muscle atrophy in mice housed in small cages, possibly by activating the phosphoinositide 3-kinase/Akt/mTOR signalling pathway and restoring autophagy flux.

Examination of the Relationship and Dissociation Between Minimum Minute Ventilation/Carbon Dioxide Production and Minute Ventilation vs. Carbon Dioxide Production Slope.

BACKGROUND: Minute ventilation/carbon dioxide production (V̇E/V̇CO2) is a variable of cardiopulmonary exercise testing (CPET), which is evaluated by arterial CO2pressure and ventilation-perfusion mismatch via invasive methods. This study evaluated substitute non-invasively obtained variables for minimum V̇E/V̇CO2(Min) and V̇E vs. V̇CO2slope (Slope) and the relationship between Min and Slope.Methods and Results:This study enrolled 1,052 patients with heart disease who underwent CPET and impedance cardiography simultaneously. At first, the correlations between the end-tidal CO2pressure (PETCO2), tidal volume/respiratory rate (TV/RR) ratio, V̇E and V̇CO2Y-intercept (Y-int), and cardiac index (CI) and the Min and Slope were investigated. Second, the correlation between Min and Slope was investigated. PETCO2showed the largest correlation value among the 4 variables. These 4 variables could reveal 84.2% and 81.9% of Min and Slope, respectively. Although Slope correlated with Min (R=0.868) and predicted 78.9% of Min, considering these 4 variables, Slope+Y-int was more strongly correlated with Min (R=0.940); the Slope+Y-int revealed 90.6% of the Min relationship in the multiple regression analysis. CONCLUSIONS: Over 80% of the Min and Slope values were revealed with the above-mentioned 4 variables collected non-invasively. The formula, Min∝Slope+Y-int, can reveal >90% of the Min/Slope relationships, and the Y-int may be a crucial factor to clarify the relationship between Min and Slope.

Sodium Restriction Counseling Reduces Cardiac Events in Patients With Heart Failure.

BACKGROUND: Many heart failure (HF) guidelines recommend sodium restriction for patients with HF, but the outcome of sodium restriction counseling (SRC) for HF patients is still unknown. We wanted to clarify whether SRC reduces cardiac events in patients with HF.Methods and Results:Overall, 800 patients (77±12 years) who were hospitalized for HF were enrolled. During HF hospitalization, patients received SRC; patients were required to have a salt intake of <6 g/day. After discharge, death or HF rehospitalization events were investigated. During a mean follow-up of 319±252 days, 83 patients died, and 153 patients were rehospitalized for HF. SRC significantly decreased all-cause death (odds ratio, 0.42; 95% confidence interval [CI], 0.23-0.76; P<0.01), especially cardiac death of hospitalized HF patients after discharge. In the multivariate analysis adjusted for age, sex, SRC, body mass index, hypertension, dyslipidemia, ß-blockers, and mineralocorticoid receptor antagonist intake, cardiac rehabilitation, and the type of HF, SRC remained a significant predictor of death. Kaplan-Meier analysis showed that SRC significantly reduced deaths and the combined outcome of HF rehospitalization and death. In patients with reduced left ventricular ejection fraction, SRC significantly decreased the mortality rate (odds ratio, 0.27; 95% CI, 0.10-0.71; P<0.01). CONCLUSIONS: SRC reduced the mortality rate after discharge of hospitalized HF patients.

Long-term ureteroscopic management of upper tract urothelial carcinoma: 28-year single-centre experience.

BACKGROUND: Long-term survival outcomes of patients who undergo endoscopic management of non-invasive upper tract urothelial carcinoma remain uncertain. The longest mean follow-up period in previous studies was 6.1 years. This study reports the long-term outcomes of patients with upper tract urothelial carcinoma who underwent ureteroscopic ablation at a single institution over a 28-year period. METHODS: We identified all patients who underwent ureteroscopic management of upper tract urothelial carcinoma as their primary treatment at our institution between January 1991 and April 2011. Survival outcomes, including overall survival, cancer-specific survival, upper-tract recurrence-free survival and renal unit survival, were estimated using Kaplan-Meier methodology. RESULTS: A total of 15 patients underwent endoscopic management, with a mean age at diagnosis of 66 years. All patients underwent ureteroscopy, and biopsy-confirmed pathology was obtained. Median (range; mean) follow-up was 11.7 (2.3-20.9, 11.9) years. Upper tract recurrence occurred in 87% (n = 13) of patients. Twenty percent (n = 3) of patients proceeded to nephroureterectomy. The estimated cancer-specific survival rate was 93% at 5, 10, 15 and 20 years. Estimated overall survival rates were 86, 80, 54 and 20% at 5, 10, 15 and 20 years. Only one patient experienced cancer-specific mortality. The estimated mean and median overall survival times were 14.5 and 16.6 years, respectively. The estimated mean cancer-specific survival time was not reached. CONCLUSIONS: Although upper tract recurrence is common, endoscopic management of non-invasive upper tract urothelial carcinoma provides a 90% cancer-specific survival rate at 20 years in selected patients.

Ex vivo evaluation of the biventricular cardiac function for donation after circulatory death model: An experimental study.

Few reports on a biventricular working heart model with ex vivo perfusion exist owing to the complexity of establishing a circuit. Hence, we investigated it for donation after circulatory death. The heart in six juvenile pigs (~20 kg) was arrested by asphyxiation. After 30 minutes of global ischemia, the heart was harvested, reperfused with normoxemic blood cardioplegia for 20 minutes, and subsequently perfused with hyperxemic blood. After 70 minutes of controlled reperfusion, the system was switched to the biventricular working mode. Cardiac function was assessed before anoxia and during the biventricular mode. Left and right ventricular functions worsened during the biventricular mode, as compared to those before anoxia (dP/dtmax , 673 ± 120 vs. 283 ± 95 and 251 ± 35 vs. 141 ± 21 mm Hg/s, respectively; P < .001). Systemic (resistance/100 g net heart weight) and pulmonary vascular resistance indexes during the biventricular mode were similar to those before anoxia (829 ± 262 vs. 759 ± 359, P = .707, and 167 ± 57 vs. 158 ± 83 dynes·sec·cm-5 - l-100-g net heart weight, P = .859, respectively). The biventricular working heart model with ex vivo perfusion was feasible, exhibited stable hemodynamics, and has the potential to be a powerful tool for direct cardiac function assessment.

Assessment of the right ventricle in donation after circulatory death hearts.

In donation after circulatory death heart transplantation, the donor heart is exposed to circulatory load. The right ventricle, due to its structure, has high compliance for volume load but is particularly vulnerable to increased pressure load. This study used a porcine model to conduct a functional assessment of the hemodynamics of the heart, with a focus on the right ventricle. Six pigs weighing 24.6 ± 1.4 kg were used. Circulatory death was induced by asphyxiation after median sternotomy. After 30 minutes in the state of global warm ischemia, the ascending aorta was clamped, followed by a 20-minute reperfusion of the heart with a 20°C blood cardioplegia solution. Systemic circulation was established by cardiopulmonary bypass after aortic cross-clamping. After initial reperfusion, the blood cardioplegia solution was replaced with blood. The blood was then rewarmed while the heart was still in a non-working state. Cardiac function was assessed twice in situ, first by the thermodilution method, and then, by the pressure-volume measurement both at preischemia and at three hours after initiation of reperfusion. The recovery rate of cardiac output was 75%. End-systolic elastance (P = .02) and pulmonary arterial elastance significantly increased (P = .03), but the ratio of arterial elastance to end-systolic elastance was preserved (P = .91) in the right ventricle. Despite a decrease in cardiac output after reperfusion from warm ischemia, the right ventricle had a potential to respond the elevated afterload. It is important that donations after circulatory death heart transplantation should be performed with attention to avoiding right ventricular distension.