Impact of High-Power Short-Duration Radiofrequency Ablation on Esophageal Temperature Dynamic

Background: High-power short-duration (HP-SD) radiofrequency ablation (RFA) has been proposed as a method for producing rapid and effective lesions for pulmonary vein isolation. The underlying hypothesis assumes an increased resistive heating phase and decreased conductive heating phase, potentially reducing the risk for esophageal thermal injury. The objective of this study was to compare the esophageal temperature dynamic profile between HP-SD and moderate-power moderate-duration (MP-MD) RFA ablation strategies. Methods: In patients undergoing pulmonary vein isolation, RFA juxtaposed to the esophagus was delivered in an alternate sequence of HP-SD (50 W, 8–10 s) and MP-MD (25 W, 15–20 s) between adjacent applications (distance, ≤4 mm). Esophageal temperature was recorded using a multisensor probe (CIRCA S-CATH). Temperature data included magnitude of temperature rise, maximal temperature, time to maximal temperature, and time return to baseline. In swine, a similar experimental design compared the effect of HP-SD and MP-MD on patterns of esophageal injury. Results: In 20 patients (68.9±5.8 years old; 60% persistent atrial fibrillation), 55 paired HP-SD and MP-MD applications were analyzed. The esophageal temperature dynamic profile was similar between HP-SD and MP-MD ablation strategies. Specifically, the magnitude of temperature rise (2.1 °C [1.4–3] versus 2.0 °C [1.5–3]; P =0.22), maximal temperature (38.4 °C [37.8–39.3] versus 38.5 °C [37.9–39.4]; P =0.17), time to maximal temperature (24.9±7.5 versus 26.3±6.8 s; P =0.1), and time of temperature to return to baseline (110±23.2 versus 111±25.1 s; P =0.86) were similar between HP-SD and MP-MD ablation strategies. In 6 swine, esophageal injury was qualitatively similar between HP-SD and MP-MD strategies. Conclusions: Esophageal temperature dynamics are similar between HP-SD and MP-MD RFA strategies and result in comparable esophageal tissue injury. Therefore, when using a HP-SD RFA strategy, the shorter application duration should not prompt shorter intervals between applications.

Can ISO GPS and ASME Tolerancing Systems Define the Same Functional Requirements?

Geometrical tolerances are defined in the ISO Geometrical Product Specification system that is used worldwide, but on the other hand, the ASME Y14.5 standard is used in American companies to define how far actual parts may be away from their nominal geometry. This paper aimed to investigate whether specifications defining acceptable geometrical deviations in one system can be transformed to specifications in the other system. Twelve selected cases are discussed in the paper. Particularly, two cases of size tolerance, three cases of form tolerances, one case of orientation tolerance, four cases of position tolerance (including position tolerance with MMR for the pattern of five holes) and, finally, two cases of surface profile tolerance (unequally disposed tolerance zone and dynamic profile tolerance). The issue is not only in the several different symbols and a set of different defaults, but also in the different meanings and different application contexts of some symbols that have the same graphical form. The answer to the question raised in the paper title is yes for the majority of indications specified according to ASME Y14.5 when new tools from the 2017 edition of ISO 1101 are applied.

Dynamic profile of SARS-CoV-2 infection among hospitalized patients in Kuwait: a descriptive study

Background The coronavirus induced disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan (China) in December 2019 is currently spreading rapidly worldwide. This study aimed to analyze the dynamic profile of SARS-CoV-2 infection among hospitalized patients that would characterize the period of viral shedding and detection among patients. Methods Retrospectively, 103 confirmed SARS-CoV-2 patients hospitalized at Jaber hospital in Kuwait were included. Demographic and clinical characteristics of the patients were collected. Nasopharyngeal swabs were obtained at different time intervals and analyzed by Real-Time RT-PCR for SARS-CoV-2 infection. Results Of 103 hospitalized patients with SARS-CoV-2 infection, the median age was 41 years, and 64% were male. The median period from admission to the positive SARS-CoV-2 RT-PCR test was 19 days (IQR, 13–22). The median period from admission to active negative SARS-CoV-2 RT-PCR test result was 22 days (IQR, 16–26). Older patients, patients with comorbidities, and patients with symptoms were more likely to have extended viral shedding. Conclusion For the first time, this descriptive study conducted in Kuwait on SARS-CoV-2 RT-PCR test results from 103 patients positive for SARS-provided solid proof and a good understanding of the dynamic profile of SARS-CoV-2 infection among patients in Kuwait. This information will further enrich the global knowledge on the emerging SARS-CoV-2.

Buprenorphine: Far Beyond the “Ceiling”

Chronic pain, including neuropathic pain, represents an untreated disease with important repercussions on the quality of life and huge costs on the national health system. It is well known that opioids are the most powerful analgesic drugs, but they represent the second or third line in neuropathic pain, that remain difficult to manage. Moreover, these drugs show several side effects that limit their use. In addition, opioids possess addictive properties that are associated with misuse and drug abuse. Among available opioids compounds, buprenorphine has been suggested advantageous for a series of clinical reasons, including the effectiveness in neuropathic pain. Some properties are partly explained by its unique pharmacological characteristics. However, questions on the dynamic profile remain to be answered. Pharmacokinetics optimization strategies, and additional potentialities, are still to be explored. In this paper, we attempt to conceptualize the potential undiscovered dynamic profile of buprenorphine.

Serial circulating tumor DNA (ctDNA) monitoring in metastatic colorectal cancer (mCRC) reveals dynamic profile of actionable alterations.

3572 Background: Serial ctDNA can measure dynamic changes in disease burden over time, however utility of serial profiling to detect changes in actionable alterations remains unclear. Methods: We evaluated 501 patients with ≥3 serial Guardant360 assays performed between 09/2016 and 11/2020 and compared MSI, fusion, amplification and single nucleotide variant (SNV) detection over time. This comprised 2147 assays with a median of 4 assays per patient (min 3, max 18) occurring an average of 163 days apart (+/- SD of 147 days). Maximum detected variant allele frequency in samples (maxVAF) was assessed for relation to changes in detected alterations as a surrogate for tumor volume. Results: Among 406 patients with assays assessable for MSI-status, 17 (4.2%) had MSI detected. New MSI detection on a subsequent assay always occurred with a rising maxVAF (3/3) that was also ≥0.7%, while loss of detectable MSI between assays always associated with falling maxVAFs (7/7) with 6/7 occurring when maxVAF fell below 0.4%. Fusions were noted in 9/501 (2%) patients. Among 3 patients who lost a detectable fusion, maxVAF decreased in 1 patient and changed ≤0.2% between assays in 2, while 2/3 patients with new fusions had rising maxVAFs and 1 patient had a falling maxVAF. Amplifications were detected in 242/501 patients (48%). While most genes had highly variable amplification detection between assays (9% serially detected), ERBB2 amplifications were more consistent and serially detected in 39% of detected cases (P < 0.0001). New detection of amplifications occurred more commonly in cases with rising maxVAF (OR 11.70, 95% CI 7.61-18.00, P < 0.0001) and loss of detectable amplifications occurred more between samples with falling maxVAF (OR 12.37, 95% CI 8.35-18.66, P < 0.0001). Change in maxVAF correlated with change in number of detected amplifications (r = 0.62, P < 0.0001), but only partially explained changes seen (R2= 0.39). Between serial assays, SNVs changed a median of 0 variants (IQR -1 to 1), however some patients had significant changes (max gain 21/max loss 18). Among 1646 serial time points, 454 (28%) had no change in SNVs, 674 (41%) gained SNVs, and 518 (31%) lost SNVs on subsequent assays. Gains were more common in samples with rising maxVAF (OR 7.76, 95% CI 6.18-9.73, P < 0.0001) while losses were more common when maxVAF fell (OR 6.90, 95% CI 5.47-8.66, P < 0.0001). The correlation between maxVAF change and SNV change was significant (r = 0.29, P < 0.0001), but minimally explained SNV changes (R2= 0.086) and was a much weaker association than noted for amplification changes. Conclusions: We noted significant differences in detection of actionable alterations across serial ctDNA assays. Increased ctDNA volume (higher maxVAF) due to tumor progression may explain some variation over time, but variability also occurs outside these changes, likely reflecting clonal evolution following therapy.