The Association of Post-Lung Transplant Pulmonary Embolism With the Development of Chronic Lung Allograft Dysfunction.

Background: Pulmonary embolism (PE) is a rare yet serious postoperative complication for lung transplant recipients (LTRs). The association between timing and severity of PE and the development of chronic allograft lung dysfunction (CLAD) has not been described. Methods: A single-center, retrospective cohort analysis of first LTRs included bilateral or single lung transplants and excluded multiorgan transplants and retransplants. PEs were confirmed by computed tomography angiography or ventilation/perfusion (VQ) scans. Infarctions were confirmed on computed tomography angiography by a trained physician. The PE severity was defined by the Pulmonary Embolism Severity Index (PESI) score, a 30-d post-PE mortality risk calculator, and stratified by low I and II (0-85), intermediate III and IV (85-125), and high V (>125). PE and PESI were analyzed in the outcomes of overall survival, graft failure, and chronic lung allograft dysfunction (CLAD). Results: We identified 57 of 928 patients (6.14%) who had at least 1 PE in the LTR cohort with a median follow-up of 1623 d. In the subset with PE, the median PESI score was 85 (75.8-96.5). Most of the PESI scores (32/56 available) were in the low-risk category. In the CLAD analysis, there were 49 LTRs who had a PE and 16 LTRs (33%) had infarction. When treating PE as time-dependent and adjusting for covariates, PE was significantly associated with death (hazard ratio [HR] 1.8; 95% confidence interval [CI], 1.3-2.5), as well as increased risk of graft failure, defined as retransplant, CLAD, or death (HR 1.8; 95% CI, 1.3-2.5), and CLAD (HR 1.7; 95% CI, 1.2-2.4). Infarction was not associated with CLAD or death. The PESI risk category was not a significant predictor of death or CLAD. Conclusions: PE is associated with decreased survival and increased hazard of developing CLAD. PESI score was not a reliable predictor of CLAD or death in this lung transplant cohort.

Comparing preoperative fasting and ultrasound-measured intravascular volume status in elective surgery, enhanced recovery patients versus inpatient, urgent surgery patients and the ability of IVC collapsibility to predict post-induction hypotension.

Hypotension following induction of general anaesthesia has been shown to result in increased complications and mortality postoperatively. Patients admitted to the hospital undergoing urgent surgery are often fasted from fluids for significant periods compared to elective patients subject to Enhanced Recovery After Surgery protocols despite guidelines stating that a two-hour fast is sufficient. The aim of this prospective, observational study was to compare fasting times and intravascular volume status between elective surgery patients subject to enhanced recovery protocols and inpatient, urgent surgery patients and to assess differences in the incidence of post-induction hypotension. Fasting data was obtained by questionnaire in the preoperative area in addition to inferior vena cava collapsibility index, a non-invasive measure of intravascular volume. Blood pressure readings and drug administration for the ten minutes following induction were obtained from patients' charts. Inpatients undergoing urgent surgery were fasted significantly longer than enhanced recovery patients and had lower intravascular volume. However, no difference was found in the incidence of post-induction hypotension.

Venous Excess Ultrasound (VExUS Grading to Assess Perioperative Fluid Status for Noncardiac Surgeries: a Prospective Observational Pilot Study.

Objectives: Perioperative fluid administration impacts the rate of complications following surgery. VExUS grading system is a standardized point of care ultrasound (POCUS)-based, comprehensive method to assess volume status. VExUS could serve as a tool to guide fluid management, if validated perioperatively. The primary aim was to assess the success rate of obtaining required windows for VExUS grading , as well as the feasibility within a perioperative setting among noncardiac surgery. Further, this study describes the incidence of perioperative venous congestion and associations with 30-day postoperative complications. Methods: This observational study was conducted in non-critically ill adults undergoing noncardiac surgery. Patients were scanned preoperatively, in the post anesthesia care unit (PACU), and 24 hours postoperatively for venous congestion. Researchers retrospectively captured 30-day complications for multivariate analyses. Results: The cohort included 69 participants. Ninety-one percent of scans over all timepoints were successfully completed. Pre-operatively, 57 (83%) scans were Grade 0, and 11 (16%) were Grade 1. Venous congestion was observed in 29 (44%) patients in the PACU (n=66). 22 (33%) patients were Grade 1, while 7 (11%) were Grade 2. At 24 hours (n=63), 31 patients (49%) had venous congestion: 20 (32%) Grade 1 and 11 (17%) Grade 2. Of the pre-operative Grade 0, 28 (50%) had at least one postoperative scan with venous congestion. No patients were Grade 3 at any timepoint. The 30-day complication rate was 32% (n=22). Eleven (16%) patients developed acute kidney injury (AKI). There was no statistically significant association between VExUS grading and all-cause complications or AKI. Conclusion: This study demonstrates that perioperative VExUS scoring is a feasible tool among a variety of noncardiac surgeries. We highlight that venous congestion is common and increases postoperatively within non-ICU populations. Larger studies are needed to assess the relationship between VExUS grading and postoperative complications.

Investigating the accuracy of blood oxygen saturation measurements in common consumer smartwatches.

Blood oxygen saturation (SpO2) is an important measurement for monitoring patients with acute and chronic conditions that are associated with low blood oxygen levels. While smartwatches may provide a new method for continuous and unobtrusive SpO2 monitoring, it is necessary to understand their accuracy and limitations to ensure that they are used in a fit-for-purpose manner. To determine whether the accuracy of and ability to take SpO2 measurements from consumer smartwatches is different by device type and/or by skin tone, our study recruited patients aged 18-85 years old, with and without chronic pulmonary disease, who were able to provide informed consent. The mean absolute error (MAE), mean directional error (MDE) and root mean squared error (RMSE) were used to evaluate the accuracy of the smartwatches as compared to a clinical grade pulse oximeter. The percent of data unobtainable due to inability of the smartwatch to record SpO2 (missingness) was used to evaluate the measurability of SpO2 from the smartwatches. Skin tones were quantified based on the Fitzpatrick (FP) scale and Individual Typology Angle (ITA), a continuous measure of skin tone. A total of 49 individuals (18 female) were enrolled and completed the study. Using a clinical-grade pulse oximeter as the reference standard, there were statistically significant differences in accuracy between devices, with Apple Watch Series 7 having measurements closest to the reference standard (MAE = 2.2%, MDE = -0.4%, RMSE = 2.9%) and the Garmin Venu 2s having measurements farthest from the reference standard (MAE = 5.8%, MDE = 5.5%, RMSE = 6.7%). There were also significant differences in measurability across devices, with the highest data presence from the Apple Watch Series 7 (88.9% of attempted measurements were successful) and the highest data missingness from the Withings ScanWatch (only 69.5% of attempted measurements were successful). The MAE, RMSE and missingness did not vary significantly across FP skin tone groups, however, there may be a relationship between FP skin tone and MDE (intercept = 0.04, beta coefficient = 0.47, p = 0.04). No statistically significant difference was found between skin tone as measured by ITA and MAE, MDE, RMSE or missingness.

Evaluating Patterns of Injectate Spread After Rectus Sheath Block: A Cadaveric Dissection Study.

INTRODUCTION: This cadaveric dye study assesses the effect of volume and number of injections on the spread of solution after ultrasound-guided rectus sheath injections. In addition, this study evaluates the impact of the arcuate line on solution spread. MATERIALS AND METHODS: Ultrasound-guided rectus sheath injections were performed on seven cadavers on both sides of the abdomen, for a total of 14 injections. Three cadavers received one injection of 30 mL of a solution consisting of bupivacaine and methylene blue at the level of the umbilicus. Four cadavers received two injections of 15 mL of the same solution, one midway between the xiphoid process and umbilicus and one midway between the umbilicus and pubis. RESULTS: Six cadavers were successfully dissected and analyzed for a total of 12 injections, while one cadaver was excluded due to poor tissue quality that was inadequate for dissection and analysis. There was a significant spread of solution with all injections caudally to the pubis without limitation by the arcuate line. However, a single 30 mL injection showed inconsistent spread to the subcostal margin in four of six injections, including in a cadaver with an ostomy. A double injection of 15 mL showed consistent spread from xiphoid to pubis in five of six injections, except in a cadaver with a hernia. CONCLUSIONS: Injections deep to the rectus abdominis muscle, using the same technique as an ultrasound-guided rectus sheath block, achieve spread along a large and continuous fascial plane without limitation by the arcuate line and may provide coverage of the entire anterior abdomen. A large volume is necessary for complete coverage and spread is improved with multiple injections. We suggest that two injections with a total volume of at least 30 mL per side may be needed to achieve adequate coverage in the absence of preexisting abdominal abnormalities.

Prdm6 drives ductus arteriosus closure by promoting ductus arteriosus smooth muscle cell identity and contractility.

Based upon our demonstration that the smooth muscle cell-selective (SMC-selective) putative methyltransferase, Prdm6, interacts with myocardin-related transcription factor-A, we examined Prdm6's role in SMCs in vivo using cell type-specific knockout mouse models. Although SMC-specific depletion of Prdm6 in adult mice was well tolerated, Prdm6 depletion in Wnt1-expressing cells during development resulted in perinatal lethality and a completely penetrant patent ductus arteriosus (DA) phenotype. Lineage tracing experiments in Wnt1Cre2 Prdm6fl/fl ROSA26LacZ mice revealed normal neural crest-derived SMC investment of the outflow tract. In contrast, myography measurements on DA segments isolated from E18.5 embryos indicated that Prdm6 depletion significantly reduced DA tone and contractility. RNA-Seq analyses on DA and ascending aorta samples at E18.5 identified a DA-enriched gene program that included many SMC-selective contractile associated proteins that was downregulated by Prdm6 depletion. Chromatin immunoprecipitation-sequencing experiments in outflow tract SMCs demonstrated that 50% of the genes Prdm6 depletion altered contained Prdm6 binding sites. Finally, using several genome-wide data sets, we identified an SMC-selective enhancer within the Prdm6 third intron that exhibited allele-specific activity, providing evidence that rs17149944 may be the causal SNP for a cardiovascular disease GWAS locus identified within the human PRDM6 gene.

Transcriptional and posttranscriptional regulation of the SMC-selective blood pressure-associated gene, ARHGAP42.

We previously showed that ARHGAP42 is a smooth muscle cell (SMC)-selective, RhoA-specific GTPase activating protein that regulates blood pressure and that a minor allele single nucleotide variation within a DNAse hypersensitive regulatory element in intron1 (Int1DHS) increased ARHGAP42 expression by promoting serum response factor binding. The goal of the current study was to identify additional transcriptional and posttranscriptional mechanisms that control ARHGAP42 expression. Using deletion/mutation, gel shift, and chromatin immunoprecipitation experiments, we showed that recombination signal binding protein for immunoglobulin κ-J region (RBPJ) and TEA domain family member 1 (TEAD1) binding to a conserved core region was required for full IntDHS transcriptional activity. Importantly, overexpression of the notch intracellular domain (NICD) or plating SMCs on recombinant jagged-1 increased IntDHS activity and endogenous ARHGAP42 expression while siRNA-mediated knockdown of TEAD1 inhibited ARHGAP42 mRNA levels. Re-chromatin immunoprecipitation experiments indicated that RBPJ and TEAD1 were bound to the Int1DHS enhancer at the same time, and coimmunoprecipitation assays indicated that these factors interacted physically. Our results also suggest TEAD1 and RBPJ bound cooperatively to the Int1DHS and that the presence of TEAD1 promoted the recruitment of NICD by RBPJ. Finally, we showed that ARHGAP42 expression was inhibited by micro-RNA 505 (miR505) which interacted with the ARHGAP42 3'-untranslated region (UTR) to facilitate its degradation and by AK124326, a long noncoding RNA that overlaps with the ARHGAP42 transcription start site on the opposite DNA strand. Since siRNA-mediated depletion of AK124326 was associated with increased H3K9 acetylation and RNA Pol-II binding at the ARHGAP42 gene, it is likely that AK124326 inhibits ARHGAP42 transcription.NEW & NOTEWORTHY First, RBPJ and TEAD1 converge at an intronic enhancer to regulate ARHGAP42 expression in SMCs. Second, TEAD1 and RBPJ interact physically and bind cooperatively to the ARHGAP42 enhancer. Third, miR505 interacts with the ARHGAP42 3'-UTR to facilitate its degradation. Finally, LncRNA, AK124326, inhibits ARHGAP42 transcription.