In Vitro and In Vivo Testing of an Implantable Motor-Driven Left Ventricular Assist Device

Abstract: A totally implantable motor-driven left ventricular assist device (LVAD) has been developed and tested. The performance of this LVAD was tested in a mock circulatory system. This pump provided 8 L/min of output against a mean afterload of 120 mm Hg with a filling pressure of 20 mm Hg when the pump was operated in the fill/empty mode. The right and left pumps were tested in a mock loop. The right pump afterload was kept in the range from 23–32 mm Hg. With increase in the left pump afterload, the pump power output varied from 1.64 to 2.37 W. The instantaneous motor power input varied from 22.6 to 30.6 W with the total system efficiency ranging from 6.7 to 9.4%. To date, 4 in vivo studies have been conducted for up to 12 h. Two animals survived 12 and 10 h, respectively. Termination was due to bleeding in 1 animal, vent tube obstruction in 1, and respiratory failure in 2. All animals died of technical failure. Another experiment is to be undertaken, and a newly designed cannula is now being manufactured.     

Clinical characteristics and risk factors for septic shock in patients receiving emergency drainage for acute pyelonephritis with upper urinary tract calculi

Background

Guideline recommendations on therapy in urinary tract infections are based on antibiotic resistance rates. Due to a lack of surveillance data, little is known about resistance rates in uncomplicated urinary tract infection (UTI) in general practice in Germany. In a prospective observational study, urine cultures of all women presenting with urinary tract infections in general practice were analysed. Resistance rates against antibiotics recommended in German guidelines on UTI are presented.

Methods

In a prospective, multi-center observational study general practitioner included all female patients?≥?18 years with clinically suspected urinary tract infection. Only patients receiving an antibiotic therapy within the last two weeks were excluded.

Results

40 practices recruited 191 female patients (mean age 52 years; range 18–96) with urinary tract infections. Main causative agent was Escherichia coli (79%) followed by Enterococcus faecalis (14%) and Klebsiella pneumoniae (7.3%). Susceptibiliy of E.coli as the main causative agent was highest against fosfomycin and nitrofurantoin, with low resistance rates of 4,5%; 2,2%. In 17,5%, E.coli was resistant to trimethoprim and in 8,5% to ciprofloxacin.

Conclusions

Resistance rates of uropathogens from unselected patients in general practice differ from routinely collected laboratory data. These results can have an impact on antibiotic prescribing and treatment recommendations.     

Local hypothermia in the treatment of idiopathic sudden sensorineural hearing loss

Objective

The additive effects of local hypothermia and restricted activity in the treatment of idiopathic sudden sensorineural hearing loss (ISSHL) were investigated by case-matched study as a multicenter (13 hospitals) pilot trial.

Patients and methods

In a preliminary experiment, we evaluated the effects of cooled water pillow (15 °C). Cooling the neck and mastoid with the pillow decreased the tympanic membrane temperature for 1.4 °C in 2 h without causing uncomfortable sensation or frostbite. In this study, 86 patients with ISSHL were enrolled in the hypothermic group, which received hypothermic treatment with restricted activity in addition to medication, and 86 ISSHL patients constituted the control group, which received the same medication but without cooling and rest. Control patients were selected retrospectively from case records by matching the experimental patients with respect to age, gender, days until the start of treatment, hearing loss, shape of the audiogram, and accompanying vertigo. The patients in the hypothermic group were admitted and treated with a cooled water pillow for 48 h, in addition to conventional drug treatment (e.g., 60 mg of prednisone) for 7 days. The water pillow was cooled to 15 °C and was changed 4–5 times per day. The patients used the water pillow for the first 48 h after admission, with restricted activity. The control patients received only the medications.

Results

Hearing results were evaluated using criteria proposed by the Sudden Sensorineural Hearing Loss Research Group of the Japanese Ministry of Health and Welfare. The recovery rates were judged 6 months after onset. The recovery rate in the hypothermic group was significantly (p < 0.05) better than that in the control group. When the comparison was limited to younger patients, the use of the cooled water pillow was effective in facilitating the recovery of hearing.

Conclusions

Hearing restoration in ISSHL may be improved by adding mild hypothermia and restricted activity to the conventional treatment.     

Plasma KL-6 predicts the development and outcome of bronchopulmonary dysplasia

Circulating KL-6 is a specific indicator of pulmonary injury affecting the alveolar epithelium and interstitium. Our preliminary study suggested the usefulness of plasma KL-6 as a marker of bronchopulmonary dysplasia (BPD). To confirm the diagnostic value of KL-6 for BPD as well as to determine the reference range, we conducted a larger prospective study in 135 preterm infants <32 wk GA. Among the infants without oxygen dependence at a postconceptional age of 36 wk, the plasma KL-6 level showed no significant association with GA at any time. Among 42 infants <28 wk GA, plasma KL-6 levels were significantly higher in those with moderate/severe BPD compared with those with no/mild BPD. A plasma level of 199 U/mL at 1 wk or 232 U/mL at 2 wk was an excellent predictor of moderate/severe BPD <28 wk GA (positive predictive value of 83% and 80%, respectively). Unlike nonspecific markers of inflammation or fibrosis, KL-6 objectively reflects the severity of pulmonary injury irrespective of the treatment or the radiographic changes. Therefore, not only as a good marker, measurement of KL-6 may also help to provide new insights into the pathogenesis of BPD.     

Postoperative recurrence detection using individualized circulating tumor DNA in upper tract urothelial carcinoma

Biomarkers that could detect the postoperative recurrence of upper tract urothelial carcinoma (UTUC) have not been established. In this prospective study, we aim to evaluate the utility of individualized circulating tumor DNA (ctDNA) monitoring using digital PCR (dPCR) as a tumor recurrence biomarker for UTUC in the perioperative period. Twenty-three patients who underwent radical nephroureterectomy (RNU) were included. In each patient, whole exome sequencing by next-generation sequencing and TERT promoter sequencing of tumor DNA were carried out. Case-specific gene mutations were selected from sequencing analysis to examine ctDNA by dPCR analysis. We also prospectively collected plasma and urine ctDNA from each patient. The longitudinal variant allele frequencies of ctDNA during the perioperative period were plotted. Case-specific gene mutations were detected in 22 cases (96%) from ctDNA in the preoperative samples. Frequently detected genes were TERT (39%), FGFR3 (26%), TP53 (22%), and HRAS (13%). In all cases, we obtained plasma and urine samples for 241 time points and undertook individualized ctDNA monitoring for 2 years after RNU. Ten patients with intravesical recurrence had case-specific ctDNA detected in urine at the time of recurrence. The mean lead time of urinary ctDNA in intravesical recurrence was 60 days (range, 0–202 days). Two patients with distal metastasis had case-specific ctDNA in plasma at the time of metastasis. In UTUC, tumor-specific gene mutations can be monitored postoperatively as ctDNA in plasma and urine. Individualized ctDNA might be a minimally invasive biomarker for the early detection of postoperative recurrence.     

Eating Perception,Nutrition Knowledge and Body Image among Para-Athletes: Practical Challenges in Nutritional Support

Limited information exists on dietary practices in para-athletes. The aim of this study was to clarify the actual situation of para-athletes’ dietary practice and to sort out the factors (i.e., eating perception, nutrition knowledge, and body image), that may hinder their dietary practices, and explored the practical challenges in nutritional support and improving nutrition knowledge for para-athletes. Thirty-two Japanese para-athletes (22 men) and 45 collegiate student athletes without disabilities (27 men) participated in the online survey. The questionnaire included demographic characteristics, eating perception, dietary practices, and nutrition knowledge. The Japanese version of the body appreciation scale was used to determine their body image. Para-athletes who answered that they knew their ideal amount and way of eating showed significantly higher body image scores (r = 0.604, p < 0.001). However, mean score for nutrition knowledge of para-athletes were significantly lower than collegiate student athletes (19.4 ± 6.8 vs. 24.2 ± 6.1 points, p = 0.001). Both groups did not identify a dietitian as the source of nutrition information or receiving their nutrition advice. The results indicate para-athletes have unique eating perceptions and inadequate nutrition knowledge. Future interventions are needed to examine nutritional supports and education in relation to the role of dietitians.     

Establishment and characterization of a novel Hodgkin lymphoma cell line,AM‐HLH,carrying the Epstein‐Barr virus genome integrated into the host chromosome

We describe the establishment and characterization of a cell line, AM‐HLH, obtained from a patient with Epstein‐Barr virus–positive (EBV⁺) nodular sclerosis–type Hodgkin lymphoma (HL). The cells were positive for CD2 and CD30 and negative for CD15. The immunoglobulin heavy‐ and κ light–chain genes were rearranged. The karyotype was of the triploid range. Southern blotting using the EBV terminal repeat probe detected 3 hybridizing bands that were identical to those of the parental HL material. The cells expressed EBV‐encoded RNAs as well as latent genes (EBNA1, EBNA2, LMP1, and LMP2A) and lytic genes (BZLF1 and BALF2). Fluorescence in situ hybridization (FISH) with the cosmid pJB8 clone containing a fragment of EBV DNA as a probe revealed multiple hybridization signals at a marker chromosome. Additional FISH using whole chromosome painting and centromere probes in combination with multicolor FISH determined that multiple EBV copies were clustered within the chromosome 20 materials of the marker chromosome. Culture supernatants of AM‐HLH contained IL‐10 as measured by the bead‐based immunoassay. It is possible that an integrated EBV genome and cellular genes on chromosome 20 were coamplified, leading to the enhanced expression of genes involved in cell growth control. The AM‐HLH cell line will be useful to clarify the role of cytokines in the development of EBV⁺ HL.