Frequency- and orientation-dependent effects of mexiletine and quinidine on conduction in the intact dog heart

Myocardial conduction depends on the magnitude of the fast inward sodium current as well as on cardiac fiber orientation, with more rapid propagation along myocardial fibers than across them. Although antiarrhythmic drugs depress the sodium current in a frequency-dependent fashion in vitro, their effects on conduction in the intact ventricle have been less well studied. We therefore evaluated the frequency- and orientation-dependent actions of mexiletine, quinidine, and their combination on epicardial conduction in 24 pentobarbital-anesthetized dogs. These interventions were chosen because the time constant of recovery from sodium-channel blockade by mexiletine in vitro is shorter than that from blockade by quinidine, and because we have previously shown that the combination of these drugs is often clinically effective when single-agent therapy fails. An electrode array that permitted measurement of conduction times in multiple orientations over short segments of epicardium without contamination by rapid Purkinje fiber propagation or by latency or virtual cathode effects at the stimulus site was developed for these studies. In all animals, the atrioventricular node was destroyed by injection of formalin to permit measurements over a wide range of cycle lengths (250 to 1500 msec). In the absence of drugs, conduction in any direction was frequency independent. In the presence of mexiletine, however, frequency-dependent increases in conduction times were found at cycle lengths of 600 msec or less; these changes were significantly greater in orientations for which baseline conduction was rapid. Quinidine, on the other hand, increased conduction times at all tested cycle lengths without significant orientation-dependent effects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Flexible Thin-Film PVDF-TrFE Based Pressure Sensor for Smart Catheter Applications

We demonstrate the design of thin flexible pressure sensors based on piezoelectric PVDF-TrFE (polyvinyledenedifluoride-tetrafluoroethylene) co-polymer film, which can be integrated onto a catheter, where the compact inner lumen space limit the dimensions of the pressure sensors. Previously, we demonstrated that the thin-film sensors of one micrometer thickness were shown to have better performance compared to the thicker film with no additional electrical poling or mechanical stretching due to higher crystallinity. The pressure sensors can be mass producible using standard lithography process, with excellent control of film uniformity and thickness down to one micrometer. The fabricated pressure sensors were easily mountable on external surface of commercial catheters. Elaborate experiments were performed to demonstrate the applicability of PVDF sensors towards catheter based biomedical application. The resonant frequency of the PVDF sensor was found to be 6.34 MHz. The PVDF sensors can operate over a broad pressure range of 0–300 mmHg. The average sensitivity of the PVDF sensor was found to be four times higher (99 μV/mmHg) than commercial pressure sensor while the PVDF sensor (0.26 s) had fivefold shorter response time than commercial pressure sensor (1.30 s), making the PVDF sensors highly suitable for real-time pressure measurements using catheters.     

Reporting of dose–volume specifications for “Martinez Universal Perineal Interstitial Template–based interstitial high-dose-rate brachytherapy for gynecological cancers” according to International Commission on Radiation Units and Measurements 58 with early clinical outcomes

PurposeThe study is an audit of reporting dose and volume specifications as per the ICRU 58 for MUPIT-based interstitial brachytherapy in gynecological cancers. Correlation between total reference air kerma (TRAK) and isodose surface was also evaluated to understand the intensity of treatment in interstitial brachytherapy.Methods and MaterialsForty-two patients underwent HDR MUPIT-based interstitial brachytherapy 20 Gy in five fractions after EBRT during 2017–2019. Treated volume, high and low-dose regions, mean central dose, Dose Homogeneity Index (DHI), organ at risk doses, and TRAK values were computed.ResultsHigh-dose regions V150 mean was 12.4 cc and V200 was 4.58 cc; and low-dose region was 75.92 cc. The mean treated volume was 59.8 cc. The mean central dose was 3.7 Gy. DHI was 79%. The mean D2cm³ bladder and rectum were 2.9 Gy and 2.8 Gy. The mean TRAK was 0.16 cGy per fraction per hour at 1 m. TRAK values showed significant correlation with various isodose volumes (TRAK and V100: r = 0.943 p < 0.0005; and TRAK and V50: r = 0.953; p < 0.0005). A positive correlation was observed between TRAK and the number of needles (r = 0.746; p < 0.0005). At a median followup of 16 months, 4 of 42 patients (9.5%) had local recurrences.ConclusionsOur study shows compliance with ICRU 58 recommendations along with certain deviations. Local recurrence rate is acceptable. TRAK shows correlation with surface isodose in MUPIT-based brachytherapy and should to be evaluated in future studies.     

Predictors of failure after fecal microbiota transplantation for recurrent Clostridioides difficile infection: a systematic review and meta-analysis

Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection (CDI), with ~15% 1-year recurrence rate. Small studies have identified variable risk factors associated with FMT failure. We, therefore, performed a systematic review and meta-analysis to evaluate the predictors of FMT failure. A systematic search of Medline, Embase, and Web of Science was performed from January 2013 up to June 2020. Meta-analyses were performed using random-effects models and pooled adjusted odds ratios for risk factors reported in ≥2 studies were calculated. Overall, 2671 patients with recurrent CDI who underwent FMT in 12 studies were included. FMT failure occurred in 454 patients (16.9%) with median follow-up of 3 months (range 2–7.7 months). A total of 9 risk factors were identified in ≥2 studies. Meta-analysis showed that use of non- CDI antibiotics, presence of inflammatory bowel disease, poor quality of bowel preparation, CDI-related hospitalization before FMT, inpatient FMT, and severe CDI were associated with statistically significant increased risk of failure after FMT. Increasing age, female gender, and immunocompromised status were not associated with increased risk for FMT failure. Several risk factors (both modifiable and non-modifiable) are associated with FMT failure. Lower use of antibiotics in the post-FMT period and good bowel preparation at the time of FMT are associated with lower risk of failure after FMT. Additionally, patients with non-modifiable risk factors should be counseled to be particularly alert about recurrent symptoms after FMT.

     

Diagnostic accuracy of quantitative flow ratio (QFR) and vessel fractional flow reserve (vFFR) estimated retrospectively by conventional radiation saving X-ray angiography

Background

Angiography derived FFR reveals good performance in assessing intermediate coronary stenosis. However, its performance under contemporary low X-ray frame and pulse rate settings is unknown. We aim to validate the feasibility and performance of quantitative flow ratio (QFR) and vessel fractional flow reserve (vFFR) under such angiograms.

Methods

This was an observational, retrospective, single center cohort study. 134 vessels in 102 patients, with angiograms acquired under 7.5fps and 7pps mode, were enrolled. QFR (fQFR and cQFR) and vFFR were validated with FFR as the gold standard. A conventional manual and a newly developed algorithmic exclusion method (M and A group) were both evaluated for identification of poor-quality angiograms.

Results

Good agreement between QFR/vFFR and FFR were observed in both M and A group, except for vFFR in the M group. The correlation coefficients between fQFR/cQFR/vFFR and FFR were 0.6242, 0.5888, 0.4089 in the M group, with r_vFFR significantly lower than r_fQFR (p?=?0.0303), and 0.7055, 0.6793, 0.5664 in the A group, respectively. AUCs of detecting lesions with FFR?≤?0.80 were 0.852 (95% CI 0.722–0.913), 0.858 (95% CI 0.778–0.917), 0.682 (95% CI 0.586–0.768), for fQFR/cQFR/vFFR in the M group, while vFFR performed poorer than fQFR (p?=?0.0063) and cQFR (p?=?0.0054). AUCs were 0.898 (95% CI 0.811–0.945), 0.892 (95% CI 0.803–0.949), 0.843 (95% CI 0.746–0.914) for fQFR/cQFR/vFFR in the A group. AUC_vFFR was significantly higher in the A group than that in the M group (p?=?0.0399).

Conclusions

QFR/vFFR assessment is feasible under 7.5fps and 7pps angiography, where cQFR showed no advantage compared to fQFR. Our newly developed algorithmic exclusion method could be a better method of selecting angiograms with adequate quality for angiography derived FFR assessment.

     

<Emphasis Type="Italic">Urtica dioica</Emphasis> modulates hippocampal insulin signaling and recognition memory deficit in streptozotocin induced diabetic mice

Diabetes mellitus has been associated with functional abnormalities in the hippocampus and performance of cognitive function. Urtica dioica (UD) has been used in the treatment of diabetes. In our previous report we observed that UD extract attenuate diabetes mediated associative and spatial memory dysfunction. The present study aimed to evaluate the effect of UD extract on mouse model of diabetes-induced recognition memory deficit and explore the possible mechanism behind it. Streptozotocin (STZ) (50 mg/kg, i.p. consecutively for 5 days) was used to induce diabetes followed by UD extract (50 mg/kg, oral) or rosiglitazone (ROSI) (5 mg/kg, oral) administration for 8 weeks. STZ induced diabetic mice showed significant decrease in hippocampal insulin signaling and translocation of glucose transporter type 4 (GLUT4) to neuronal membrane resulting in cognitive dysfunction and hypolocomotion. UD treatment effectively improved hippocampal insulin signaling, glucose tolerance and recognition memory performance in diabetic mice, which was comparable to ROSI. Further, diabetes mediated oxidative stress and inflammation was reversed by chronic UD or ROSI administration. UD leaves extract acts via insulin signaling pathway and might prove to be effective for the diabetes mediated central nervous system complications.