Right Heart Reserve Function Assessed With Fluid Loading Predicts Late Right Heart Failure After Left Ventricular Assist Device Implantation.

BACKGROUND: A left ventricular assist device (LVAD) is an effective therapeutic option for advanced heart failure. Late right heart failure (LRHF) is a complication after LVAD implantation that is associated with increasing morbidity and mortality; however, the assessment of right heart function, including right heart reserve function after LVAD implantation, has not been established. We focused on a fluid-loading test with right heart catheterization to evaluate right heart preload reserve function and investigate its impact on LRHF. METHODS: Patients aged > 18 years who received a continuous-flow LVAD between November 2007 and December 2022 at our institution, and underwent right heart catheterization with saline loading (10 mL/kg for 15 minutes) 1 month after LVAD implantation, were included. RESULTS: Overall, 31 cases of LRHF or death (right heart failure [RHF] group) occurred in 149 patients. In the RHF vs the non-RHF groups, the pulmonary artery pulsatility index (PAPi) at rest (1.8 ± 0.89 vs 2.5 ± 1.4, P = 0.02) and the right ventricular stroke work index (RVSWi) change ratio with saline loading (0.96 ± 0.32 vs 1.1 ± 0.20, P = 0.03) were significantly different. The PAPi at rest and the RVSWi change ratio with saline loading were identified as postoperative risks for LRHF and death. The cohort was divided into 3 groups based on whether the PAPi at rest and the RVSWi change ratio were low. The event-free curve differed significantly among the 3 groups (P < 0.001). CONCLUSIONS: Hemodynamic assessment with saline loading can evaluate the right ventricular preload reserve function of patients with an LVAD. A low RVSWi change with saline loading was a risk factor for LRHF following LVAD implantation.

Prophylactic negative pressure wound therapy is not effective for preventing driveline infection following left ventricular assist device implantation.

BACKGROUND: Driveline infection (DLI) following left ventricular assist device (LVAD) implantation remains an unresolved problem. Negative pressure wound therapy (NPWT) promotes wound healing by applying negative pressure on the surface of the wound. Recently, the prophylactic application of NPWT to closed surgical incisions has decreased surgical site infections in various postsurgical settings. Therefore, we evaluated the efficacy and safety of prophylactic NPWT for preventing DLI in patients with LVAD implantation. METHODS: Prophylactic NPWT was provided to 50 patients who received continuous-flow LVADs as bridge-to-transplant therapy at our institution between May 2018 and October 2020 (NPWT group). The negative pressure dressing was applied immediately after surgery and retained on the driveline exit site for 7 days with a continuous application of -125 mm Hg negative pressure. The primary outcome was DLI within 1 year of LVAD implantation. We compared the rate of DLI incidence in the NPWT group with that in the historical control cohort (50 patients) treated with the standard dressing (SD) who received LVAD implantation between July 2015 and April 2018 (SD group). RESULTS: No severe complications were associated with the NPWT. During the follow-up period, DLI was diagnosed in 16 participants (32%) in the NPWT group and 21 participants (42%) in the SD group. The rates of DLI incidence and freedom from DLI did not differ between groups (p = 0.30 and p = 0.63). CONCLUSIONS: Prophylactic NPWT at the driveline exit site was safe following LVAD implantation. However, it did not significantly reduce the risk of DLI.

Sarcopenia and risk of infection in adult heart transplant recipients in Japan.

AIMS: Heart transplantation (HT) is an effective therapeutic option for end-stage heart failure. Infection is a major cause of morbidity and mortality after HT. Sarcopenia, defined as the loss of muscle mass and strength, is a common comorbidity in HT candidates with end-stage heart failure. However, the effects of sarcopenia on the occurrence of post-HT infections are not well understood. Therefore, we explored the association between the skeletal muscle mass and post-transplant infections in adult HT recipients. METHODS AND RESULTS: We retrospectively examined the records of 135 patients who underwent HT between August 2007 and November 2019 at our institution. Pre-transplant computed tomography was used to calculate the skeletal muscle index (SMI) at the level of the third lumbar vertebra. Muscle wasting was defined as the SMI of the lowest sex-based tertiles. The primary endpoint was infections within 6 months of HT. The study included 109 patients (80 men, mean age: 41.6 ± 12.0 years): 37 patients in the muscle wasting group and 72 patients in the non-muscle wasting group. The mean SMI values in the muscle wasting and non-muscle wasting groups were 29.9 ± 4.8 cm2 /m2 and 40.7 ± 6.7 cm2 /m2 , respectively. Prior to HT, 108 (99.1%) patients were on left ventricular assist device support, and during that support, the rate of late right heart failure was significantly higher in the muscle wasting group than non-muscle wasting group (P = 0.012). Sixteen infections occurred within 6 months of HT. The most common infection sites included the respiratory tract (n = 5) and the upper gastrointestinal tract (n = 5), followed by the urinary tract (n = 4). Overall, 10 patients experienced infections in the muscle wasting group (27.0%) and 6 in the non-muscle wasting group (8.3%) (P = 0.009). Two patients in the muscle wasting group required intensive care unit admission, compared to none in the non-muscle wasting group. Low skeletal muscle mass was associated with infections in the univariate and multivariate logistic regression models (hazard ratio: 3.68, 95% confidence interval: 1.19-11.3; P = 0.023). However, the duration of all-cause mortality within 3 years did not differ between the groups (P = 0.56). CONCLUSIONS: Low skeletal muscle mass is a predictor of post-HT infections within 6 months of HT.

Carbon Monoxide Diffusing Capacity Predicts Cardiac Readmission in Patients Undergoing Left Ventricular Assist Device Implantation in Japan.

Carbon monoxide diffusion capacity (DLCO) is impaired in heart failure patients; however, its clinical impact has not been well investigated in the left ventricular assist device (LVAD) population. We explored the predictive value of preoperative DLCO in the survival and cardiac readmission rates after LVAD implantation. Seventy-six patients who received continuous-flow LVAD as bridge-to-transplant therapy from November 2007 to September 2018 and underwent pulmonary function test before LVAD implantation were included. The primary study endpoints were death and readmission for heart failure or arrhythmia (cardiac readmission). Patients were stratified into two groups according to the percent of predicted DLCO (%DLCO). Pulmonary vascular resistance (PVR) was equivocal between the groups preoperatively, whereas the low DLCO group (%DLCO < 80%) showed significantly high PVR postoperatively. The mortality rate was not different between the groups. The 2 year cardiac readmission rate was 33.5% in the low DLCO group and 8.7% in the high DLCO group (%DLCO ≥ 80%) (P = 0.028). The %DLCO was associated with cardiac readmission in univariate and multivariate analyses (hazard ratio: 4.32; 95% CI: 1.50-15.9; P = 0.005). Low %DLCO was associated with high PVR postoperatively and was a risk factor for cardiac readmission after LVAD implantation.

Differences in the prognoses of patients referred to an advanced heart failure center from hospitals with different bed volumes.

Few reports have discussed appropriate strategies for patient referrals to advanced heart failure (HF) centers with available left ventricular assist devices (LVADs). We examined the association between the characteristics and prognoses of referred patients with advanced HF and the bed volume of the referring hospitals. This retrospective analysis evaluated 186 patients with advanced HF referred to our center for consultation about the indication of LVAD between January 1, 2015, and August 31, 2018. We divided the patients into two groups according to the bed volume of their referring hospital (high bed volume hospitals (HBHs): ≥ 500 beds in the hospital; low bed volume hospitals (LBHs): < 500 beds). We compared the primary outcome measure, a composite of LVAD implantation and all-cause death, between the patients referred from HBHs and patients referred from LBHs. The 186 patients with advanced HF referred to our hospital, who were referred from 130 hospitals (87 from LBHs and 99 from HBHs), had a mean age of 43.0 ± 12.6 years and a median left ventricular ejection fraction of 22% [15-33%]. The median follow-up duration of the patients was 583 days (119-965 days), and the primary outcome occurred during follow-up in 42 patients (43%) in the HBH group and 20 patients (23%) in the LBH group. Patients referred from HBHs tended to require catecholamine infusion on transfer more often than those referred from LBLs (36.5% (HBH), 20.2% (LBL), P = 0.021). Kaplan-Meier analysis indicates that the occurrence of the primary outcome was significantly higher in the HBH patients than in the LBH patients (log-rank P = 0.0022). Multivariate Cox proportional hazards analysis revealed that catecholamine support on transfer and long disease duration were statistically significant predictors of the primary outcome. Patients from HBHs had a greater risk of the primary outcome. However, the multivariate analysis did not indicate an association between referral from an HBH and the primary outcome. In contrast, catecholamine support on transfer, long duration of disease, and low blood pressure were independent predictors of the primary outcome. Therefore, these should be considered when determining the timing of a referral to an advanced HF center, irrespective of the bed volume of the referring hospital.

Roles of monocarboxylate transporter subtypes in promotion and suppression of osteoclast differentiation and survival on bone.

Monocarboxylate transporters (MCTs) provide transmembrane transport of monocarboxylates such as lactate and pyruvate. The present results showed that α-cyano-4-hydroxycinnamic acid (CHC), an inhibitor of MCTs, promoted osteoclast differentiation from macrophages at lower concentrations (0.1-0.3 mM) and suppressed that at a higher concentration (1.0 mM). On the other hand, CHC reduced the number of mature osteoclasts on the surface of dentin in a concentration-dependent manner. Additionally, macrophages and osteoclasts were found to express the Mct1, Mct2, and Mct4 genes, with Mct1 and Mct4 expression higher in macrophages, and that of Mct2 higher in osteoclasts. Although Mct1 gene knockdown in macrophages enhanced osteoclast formation induced by RANKL, Mct2 gene knockdown suppressed that. Finally, Mct2 gene silencing in mature osteoclasts decreased their number and, thereby, bone resorption. These results suggest that MCT1 is a negative regulator and MCT2 a positive regulator of osteoclast differentiation, while MCT2 is required for bone resorption by osteoclasts.

Monocarboxylate transporter-1 promotes osteoblast differentiation via suppression of p53, a negative regulator of osteoblast differentiation.

Monocarboxylate transporter-1 (MCT-1) is a transmembrane transporter for monocarboxylates including lactate and pyruvate. Silencing Mct1 by its small interfering RNA (siRNA) suppressed the expression of marker genes for osteoblast differentiation, namely, Tnap, Runx2, and Sp7, induced by BMP-2 in mouse myoblastic C2C12 cells. Mct1 siRNA also suppressed alkaline phosphatase activity, as well as expressions of Tnap and Bglap mRNAs in mouse primary osteoblasts. On the other hand, Mct1 siRNA did not have effects on the Smad1/5 or ERK/JNK pathways in BMP-2-stimulated C2C12 cells, while it up-regulated the mRNA expression of p53 (Trp53) as well as nuclear accumulation of p53 in C2C12 cells in a BMP-2-independent manner. Suppression of osteoblastic differentiation by Mct1 siRNA in C2C12 cells was abolished by co-transfection of Trp53 siRNA. Together, these results suggest that MCT-1 functions as a positive regulator of osteoblast differentiation via suppression of p53.

[Two autopsy cases in which previous surgery facilitated the positive identification of decomposed bodies]. / Dve pitvy, ve kterých predchozí operace usnadnila ztotoznení posmrtne dekomponovaných tel.

The positive identification of decomposed corpses is often difficult. We describe two autopsy cases in which medical materials, which had been implanted during previous surgical treatments, facilitated positive identification. The discovery of decomposed corpses is increasingly common in Japan, due to the increasing number of lonely deaths. Implanted medical materials and devices may be a useful tool for personal identification in the near future.

An autopsy case of complete adipocere formation.

A car containing a male corpse with complete adipocere formation was found at the bottom of a lake. The deceased had presumably driven into the lake 7 years earlier. The surface of the deceased was unusually hard and firm like a gypsum board, and the entire internal viscera had turned into adipocere. Since the time required for adipocerous changes depends largely on environmental conditions, we considered the key conditions, namely, water temperature, pH, and oxygen content. In our case, cold, acidic water may have delayed adipocere formation, thus necessitating a long period of time for completeness. On the other hand, anoxic conditions and the peculiar environment of a lake bottom presumably contributed to complete adipocere formation.

Changes of fructose concentrations in seminal plasma and glucose and testosterone concentrations in blood plasma in rams over the course of a year.

The present study was performed to examine seasonal changes in the fructose concentrations of seminal plasma and glucose and testosterone concentrations of blood plasma over the course of a year (from November 2004 to November 2005) using 5 Suffolk rams. Osmolality of the seminal plasma was also measured. The fructose concentrations in the seminal plasma increased as the breeding season approached, with the maximum in October (179.8 mg/dl) and the minimum in May (6.9 mg/dl), although there were no significant differences during the year. Osmolality of the seminal plasma in February (304 mOsm) was significantly (P<0.05) lower than in January (325 mOsm), July (327 mOsm), and August (325 mOsm). It was also significantly (P<0.05) lower in November (308 mOsm) than in January and August. The blood plasma glucose concentration in October (79.3 mg/dl) was significantly (P<0.05) higher than in January and February (43.2 and 43.7 mg/dl, respectively). The blood plasma testosterone (T) concentrations were significantly (P<0.05) higher in September (8.5 ng/ml) and October (10.2 ng/ml) than in other months. The fructose concentrations in the seminal plasma appeared to be related to the glucose and T concentrations in the blood plasma. These results show that fructose concentrations in the seminal plasma and blood plasma glucose and T concentrations tended to increase during the breeding season, with the highest concentrations in October.

Effects of bovine serum albumin and trehalose in semen diluents for improvement of frozen-thawed ram spermatozoa.

In this study, two following experiments were performed to improve post-thaw motility and viability of frozen-thawed ram spermatozoa. We examined i) the effects of different concentrations of bovine serum albumin (0, 0.3, 1, 5, 10 and 15% BSA) in semen diluents lacking egg yolk and ii) the effects of four semen diluents, fructose (F: control) and trehalose (T) in semen diluents containing egg yolk, 15% BSA in semen diluents without egg yolk (BSA), and modified phosphate buffered saline (m-PBS). Frozen-thawed spermatozoa were examined for progressive sperm motility, viability, morphological abnormality, sperm tail swelling test, and sperm acrosome integrity. In Experiment 1, the rates of sperm motility immediately after thawing (0 h) were significantly (P<0.05) higher in the 10 and 15% BSA groups (55.0 +/- 2.9 and 58.3 +/- 6.7%, respectively) than in the positive control (F) group (41.7 +/- 4.4%). The rate of sperm viability in the negative control (0% BSA) group (80.2 +/- 3.3%) was significantly (P<0.05) lower than in the positive control (F) group (89.8 +/- 1.5%), but when compared with the F group, no significant differences were found among the 0.3, 1, 5, 10 and 15% BSA groups at 0 h. The rates of sperm morphological abnormality of the 10 and 15% BSA groups (6.5 +/- 1.3 and 6.3 +/- 1.1%, respectively) were significantly (P<0.05) lower at 0 h than that in the 1% BSA group (16.3 +/- 5.2%). In Experiment 2, T addition improved (P<0.05) the post-thaw motility compared with the F and BSA groups. Furthermore, at 3 and 6 h, the post-thaw motility of the T group (36.3 +/- 2.4 and 25.0 +/- 2.0%, respectively) was significantly (P<0.05) higher than in the BSA (26.3 +/- 2.4 and 18.8 +/- 1.3%, respectively) and F (28.8 +/- 3.8 and 18.8 +/- 2.4%, respectively) groups. The post-thaw sperm motility and viability in the m-PBS group were significantly (P<0.05) lower than those of the control (F), T, and BSA groups throughout all observation points. These results indicate that 10 and 15% BSA can be substituted for egg-yolk for ram semen diluent and that the addition of trehalose enhances motility and viability of ram spermatozoa after freezing and thawing.