Prediction of the external work of the native heart from the dynamic H-Q curves of the rotary blood pumps during left heart bypass

The ventricular performance is dependent on the drainage effect of rotary blood pumps (RBPs) and the performance of RBPs is affected by the ventricular pulsation. In this study, the interaction between the ventricle and RBPs was examined using the pressure-volume (P-V) diagram of the ventricle and dynamic head pressure-bypass flow (H-Q) curves (H, head pressure: arterial pressure minus ventricular pressure vs. Q, bypass flow) of the RBPs. We first investigated the relationships in a mock loop with a passive fill ventricle, followed by validation in ex vivo animal experiments. An apical drainage cannula with a micro-pressure sensor was especially fabricated to obtain ventricular pressure, while three pairs of ultrasonic crystals placed on the heart wall were used to derive ventricular volume. The mock loop-configured ventricular apical-descending aorta bypass revealed that the external work of the ventricle expressed by the area inside the P-V diagrams (EW(Heart) ) correlated strongly with the area inside dynamic H-Q curves (EW(VAD)), with the coefficients of correlation being R2 = 0.869 ～ 0.961. The results in the mock loop were verified in the ex vivo studies using three Shiba goats (10-25 kg in body weight), showing the correlation coefficients of R2 = 0.802 ～ 0.817. The linear regression analysis indicated that the increase in the bypass flow reduced pulsatility in the ventricle expressed in EW(Heart) as well as in EW(VAD) . Experimental results, both mock loop and animal studies, showed that the interaction between cardiac external work and H-Q performance of RBPs can be expressed by the relationships "EW(Heart) versus EW(VAD) ." The pulsatile nature of the native heart can be expressed in the area underneath the H-Q curves of RBPs EW(VAD) during left heart bypass indicating the status of the level of assistance by RBPs and the native heart function.     

Effect of graft adaptation of the internal mammary artery on longitudinal phasic blood flow velocity characteristics after surgery

Left internal mammary artery (LIMA) bypass conduits undergo gradual longitudinal flow transition from the proximal to distal segments, and the diastolic/systolic (D/S) ratios of the flow indices can diagnose graft patency. However, the influence of graft adaptation on this has not been studied. We examined 46 patients with LIMA graft to the left anterior descending artery using a Doppler-tipped guidewire in the proximal, middle, and distal segments; 34 had patent LIMAs (group A: new LIMAs; <1 month postoperatively; n = 22 and group B: old LIMAs; ≥1 month postoperatively; n = 12), and 12 had new LIMAs with distal stenosis (group C). In diastole, the time-averaged peak velocities, maximum peak velocities, and velocity–time integrals in each segment were significantly greater in group A than in groups B or C; however, in systole, they did not differ significantly among the three groups. The D/S ratios of the indices in all segments in group A were significantly greater than those in groups B or C; however, they did not differ between groups B and C in any of the segments. Graft adaptation of a patent LIMA, itself, affects the longitudinal flow transition pattern. The D/S ratio of the three indices in the patent old LIMAs did not differ from those in the LIMAs with distal stenosis early after surgery. The timing of LIMA flow assessment must be considered during assessment of the graft patency from the flow velocity patterns.     

Development of a Disposable Maglev Centrifugal Blood Pump Intended for One-Month Support in Bridge-to-Bridge Applications: In Vitro and Initial In Vivo Evaluation

MedTech Dispo, a disposable maglev centrifugal blood pump with two degrees of freedom magnetic suspension and radial magnetic coupling rotation, has been developed for 1-month extracorporeal circulatory support. As the first stage of a two-stage in vivo evaluation, 2-week evaluation of a prototype MedTech Dispo was conducted. In in vitro study, the pump could produce 5 L/min against 800 mm Hg and the normalized index of hemolysis was 0.0054 ± 0.0008 g/100 L. In in vivo study, the pump, with its blood-contacting surface coated with biocompatible 2-methacryloyloxyethyl phosphorylcholine polymer, was implanted in seven calves in left heart bypass. Pump performance was stable with a mean flow of 4.49 ± 0.38 L/min at a mean speed of 2072.1 ± 64.5 rpm. The maglev control revealed its stability in rotor position during normal activity by the calves. During 2 weeks of operation in two calves which survived the intended study period, no thrombus formation was seen inside the pump and levels of plasma free hemoglobin were maintained below 4 mg/dL. Although further experiments are required, the pump demonstrated the potential for sufficient and reliable performance and biocompatibility in meeting the requirements for cardiopulmonary bypass and 1-week circulatory support.     

A case of intractable hepatic encephalopathy successfully treated by oral administration of vancomycin hydrochloride, with subsequent improvement of hepatic function reserve enabling transcatheter arterial chemoembolization against hepatocellular carcinoma

We report a case of an 80-year-old male who suffered from intractable hepatic encephalopathy and hepatocellular carcinoma( HCC), associated with hepatitis type C-related liver cirrhosis. He was unable to receive HCC treatment due to the deterioration of his liver. His hepatic encephalopathy was resistant to oral administration of laxatives, lactulose, and kanamycin sulfate, etc. His blood ammonia concentration averaged about 130 mg/dL, and often exceeded 200 mg/dL(normal range: <80 mg/dL). Later, an oral administration of vancomycin hydrochloride, 0. 5 g once every 3 days, was initiated. Soon after ward, his blood ammonia concentration declined to the normal range(about 50 mg/dL), and the clinical symptoms of hepatic encephalopathy showed a remarkable improvement. By the continuation of vancomycin administration, the normalization of his state of consciousness was achieved, improving his quality of life, and his activities of daily living. Three months after beginning treatment, he was able to receive transcatheter arterial chemoembolization for the treatment of HCC, because his liver function reserve improved(Child-Pugh score decreased from 10 to 7).     

Sensitivity to previous irinotecan treatment does not predict the efficacy of combination chemotherapy with cetuximab plus irinotecan for wild-type KRAS metastatic colorectal cancer

The aim of this study was to evaluate the association of sensitivity to previous irinotecan-based chemotherapy with efficacy of cetuximab plus irinotecan therapy in metastatic colorectal cancer (MCRC) patients with wild-type KRAS. We analysed a pooled data set consisting of data from 87 MCRC patients from two previous phase II studies (n = 60) and a group given off-protocol treatment (n = 27) following irinotecan-, oxaliplatin-, and fluoropyrimidine-based chemotherapy. Overall objective response rate to cetuximab plus irinotecan was 28.7%, median progression-free survival (PFS) was 5.3 months, and median overall survival was 12.2 months. Objective response rate did not significantly differ between patients with a favourable response to previous irinotecan (n = 23), stable disease (n = 38), or progressive disease (n = 26), with observed rates of 29.2%, 31.6%, and 23.1%, respectively. Additionally, the non-parametric Spearman rank correlation coefficients (ρ) between the PFS of previous irinotecan-based chemotherapy and that of cetuximab plus irinotecan were quite low (ρ = 0.067 and 0.057 in patients with previous irinotecan as first- and second-line therapies, respectively). Although exploratory nature and small sample size may be limitations of this study, these findings indicate that the efficacy of irinotecan plus cetuximab in MCRC patients with wild-type KRAS did not differ by previous sensitivity to irinotecan.     

Development of a reflected optical fiber system for measuring oxygen saturation in an integrated artificial heart-lung system

Abstract:  The purpose of this study was to develop a blood oxygen saturation (OS) monitoring system for use with an integrated artificial heart–lung system (IAHLS). The OS monitoring system consists of two paired optical fiber probes (OFPs) and a measurement system. To investigate the effect of the OFP configuration and incident light wavelength on the relationship between OS and the reflectance ratio for wavelengths of 810 and 645 nm, we performed theoretical analyses of the relationship between OS and R810/R645 using a diffusion equation. The prototype OFP located on the blood outlet port of our IAHLS housing was evaluated using an in vitro test. An OS range of 65–100% was adjusted to supply oxygen and nitrogen gas to the IAHLS. The blood flow rate was maintained at 3 L/min by the rotational speed of an impeller in the IAHLS. The OS-corrected blood from the IAHLS was measured using a commercial gas analyzer. The correlation coefficients ( r ²) between the theoretical ratio of R810/R645 and OS, and between measured OS and the reflectance ratio of R810/R645 were 0.97 and 0.78, respectively. In conclusion, we confirmed that the development of this oximetry system is applicable for IAHLS.       

Prevalence of vitamin D deficiency, insufficiency and secondary hyperparathyroidism in the elderly inpatients and living in the community of the city of São Paulo, Brazil

The occurrence of osteoporotic fractures in the elderly is associated with reduced levels of vitamin D and resulting secondary hyperparathyroidism, and inpatients are the ones at a higher risk. In Brazil, given its high level of insolation, the populations large amount of vitamin D is inferred to be adequate. In this study we aimed to assess the serum levels of 25-hydroxivitamin D (25OHD), parathormone (PTH) and ionized calcium (Cai), as well as to analyze the prevalence of both hypovitaminosis D and secondary hyperparathyroidism in the elderly living in the city of S?o Paulo. We studied 177 inpatients (125 women and 52 men) with mean age (SD) 76.6 (9.0) years, and 243 outpatients (168 women and 75 men) aged 79.1 (5.9) years. In this assessment 71.2% in the inpatients group and 43.8% in the outpatients group had 25OHD levels below the minimum recommended (50 nmol/l), with the women presenting with levels considerably lower than the men. Secondary hyperparathyroidism occurred in 61.7% of the inpatients and in 54% of the outpatients. Considering the results achieved, we recommend vitamin D supplementation in effective doses for the Brazilian elderly population, in addition to suggesting a discussion for the implementation of vitamin D-enhanced food policies, particularly oriented to the ones at a greater risk.     

Gene expression profiling of epidermal growth factor receptor/KRAS pathway activation in lung adenocarcinoma

We examined the genome-wide expression profiles of 86 primary lung adenocarcinomas and compared them with the mutation status of the four key molecules (EGFR, ERBB2, KRAS and BRAF) in the EGFR/KRAS/BRAF pathway. Unsupervised classification revealed two subtypes (the bronchial type and the alveolar type) of lung adenocarcinoma. Mutually exclusive somatic mutations of the epidermal growth factor receptor (EGFR) gene (36/86, 41.8%), K-ras gene (11/86, 12.8%) and BRAF gene (1/86, 1.1%) were detected. KRAS mutations were observed significantly frequently in bronchial-type tumors, whereas the frequencies of EGFR mutations were similar in both the alveolar and bronchial types. Twenty-seven genes showed increased expression in EGFR-mutated tumors and these included molecules that function in the EGFR/KRAS/BRAF pathway (EGFR, AKT1 and BCR). In particular, expression of BCR, which is required for EGFR protein degradation, was induced by EGF stimulation, suggesting a negative feedback loop in lung cancer. A subgroup of the alveolar type tumors showed significantly better prognosis than other tumors. Integrated analysis of genetic and gene expression profiling aimed to delineate inherent oncogenic pathways in cancer will be valuable not only for the understanding of molecular pathogenesis, but also for discovering novel biomarkers and predicting clinical outcome.     

Characterization of skin infiltrating cells in adult T-cell leukaemia/lymphoma (ATLL): clinical, histological and immunohistochemical studies on eight cases

Eight cases of adult T-cell leukaemia/lymphoma (ATLL) with cutaneous involvement were studied. The clinical and histological features of these cases were recorded and immunohistochemistry carried out using a panel of monoclonal antibodies to T-cell differentiation antigens. Patients with ATLL showed distinct differences from patients with mycosis fungoides (MF) and Sézary syndrome (SS). Patients tended to have papulonodular and purpuric skin eruptions with pleomorphic lymphoid infiltrates, and often a degree of vasculitis. There was a high level of expression of activated T-cell antigens, CD25, CD30, CD38, T9 and Leu 8.