Driving pressure-guided ventilation and postoperative pulmonary complications in thoracic surgery: a multicentre randomised clinical trial.

BACKGROUND: Airway driving pressure, easily measured as plateau pressure minus PEEP, is a surrogate for alveolar stress and strain. However, the effect of its targeted reduction remains unclear. METHODS: In this multicentre trial, patients undergoing lung resection surgery were randomised to either a driving pressure group (n=650) receiving an alveolar recruitment/individualised PEEP to deliver the lowest driving pressure or to a conventional protective ventilation group (n=650) with fixed PEEP of 5 cm H2O. The primary outcome was a composite of pulmonary complications within 7 days postoperatively. RESULTS: The modified intention-to-treat analysis included 1170 patients (mean [standard deviation, sd]; age, 63 [10] yr; 47% female). The mean driving pressure was 7.1 cm H2O in the driving pressure group vs 9.2 cm H2O in the protective ventilation group (mean difference [95% confidence interval, CI]; -2.1 [-2.4 to -1.9] cm H2O; P<0.001). The incidence of pulmonary complications was not different between the two groups: driving pressure group (233/576, 40.5%) vs protective ventilation group (254/594, 42.8%) (risk difference -2.3%; 95% CI, -8.0% to 3.3%; P=0.42). Intraoperatively, lung compliance (mean [sd], 42.7 [12.4] vs 33.5 [11.1] ml cm H2O-1; P<0.001) and Pao2 (median [inter-quartile range], 21.5 [14.5 to 30.4] vs 19.5 [13.5 to 29.1] kPa; P=0.03) were higher and the need for rescue ventilation was less frequent (6.8% vs 10.8%; P=0.02) in the driving pressure group. CONCLUSIONS: In lung resection surgery, a driving pressure-guided ventilation improved pulmonary mechanics intraoperatively, but did not reduce the incidence of postoperative pulmonary complications compared with a conventional protective ventilation. CLINICAL TRIAL REGISTRATION: NCT04260451.

Non-Invasive Risk Assessment and Prediction of Mortality in Patients Undergoing Coronary Artery Bypass Graft Surgery.

Objectives: Heart rate turbulence (HRT) and T-wave alternans (TWA), non-invasive markers of cardiac autonomic dysfunction, and ventricular repolarization abnormality, reportedly, predict the risk of cardiovascular death after myocardial infarction. We investigated whether pre-operative assessment of HRT and/or TWA could predict long-term mortality following coronary artery bypass graft (CABG) surgery. Methods: From May 2010 to December 2017, patients undergoing elective CABG and receiving 24 h ambulatory electrocardiogram monitoring 1 to 5 days prior to CABG surgery were prospectively enrolled. Pre-operative HRT and TWA were measured using a 24 h ambulatory electrocardiogram. The relative risk of cardiac or overall death was assessed according to abnormalities of HRT, TWA, or left ventricular ejection fraction (LV EF). Results: During the mean follow-up period of 4.6 ± 3.9 years, 40 adjudicated overall (5.9%/yr) and 5 cardiac deaths (0.9%/yr) occurred in 146 enrolled patients (64.9 ± 9.3 years; 108 males). Patients with abnormal HRT exhibited significantly higher relative risks of cardiac death (adjusted hazard ratio [HR] 24.9, 95% confidence interval [CI] 1.46-427) and all-cause death (adjusted HR 5.77, 95% CI 2.34-14.2) compared to those with normal HRT. Moreover, abnormal HRT plus abnormal TWA and LV EF < 50% was associated with a greater elevation in cardiac and overall mortality risk. The predictive role of abnormal HRT with/without abnormal TWA for all-cause death was likely more prominent in patients with mildly reduced (35 to 50%) or preserved (≥50%) LV EF. Abnormal HRT plus abnormal TWA and LV EF < 50% showed high negative predictive value in cardiac and overall mortality risk. Conclusions: Assessment of pre-operative HRT and/or TWA predicted mortality risk in patients undergoing elective CABG. Combined analysis of HRT, TWA, and LVEF enhanced the prognostic power. In particular, the predictive value of HRT was enhanced in patients with preserved or mid-range LV EF.

Reducing needle-to-balloon time by using a single guiding catheter during transradial primary coronary intervention.

OBJECTIVES AND BACKGROUND: It is unknown whether using a single guiding catheter for both nonculprit and culprit vessel angiography and intervention during transradial primary percutaneous coronary intervention (PCI) is feasible. METHODS: This single-center study enrolled 242 consecutive patients with ST segment elevation myocardial infarction (STEMI) who received primary PCI. Among them, 102 patients received primary PCI via transfemoral approach (TFI), 109 patients received primary PCI via transradial approach using conventional technique (Conventional TRI), and 31 underwent primary TRI using a single guiding catheter (Single Guiding TRI). The catheter used for this purpose was 6 Fr RM® 3.5 guiding catheter. RESULTS: Using a single guiding catheter, both coronary artery angiograms and intervention were successful in 30 of 31 patients (96.7%). Needle-to-balloon time (from puncture to first balloon) and door-to-balloon (D2B) time were similar between TFI and Conventional TRI groups and significantly lower in the Single Guiding TRI group (13.8 [TFI] and 14.1 [Conventional TRI] vs. 7.6 minutes, P < 0.001; 89.5 [TFI] and 91.0 [Conventional TRI] vs. 68.5 minutes, P = 0.008, respectively), whereas proportion of patients achieving D2B time within 90 minutes increased significantly in the Single Guiding TRI group from 51.0% for TFI and 49.5% for Conventional TRI to 74.2% (P = 0.023). CONCLUSIONS: Primary transradial PCI using a single guiding catheter is feasible and highly successful and might allow timely restoration of blood flow in infarct-related artery.

Comparison between GlideRite® rigid stylet and Parker Flex-It™ stylet to facilitate GlideScope intubation in simulated difficult intubation: a randomized controlled study.

BACKGROUND: The GlideScope® videolaryngoscope (GVL) is widely used in patients with difficult airways and provides a good glottic view. However, the acute angle of the blade can make insertion and advancement of an endotracheal tube (ETT) more difficult than direct laryngoscopy, and the use of a stylet is recommended. This randomized controlled trial compared Parker Flex-It™ stylet (PFS) with GlideRite® rigid stylet (GRS) to facilitate intubation with the GVL in simulated difficult intubations. METHODS: Fifty-four patients were randomly allocated to undergo GVL intubation using either GRS (GRS group) or PFS (PFS group). The total intubation time (TIT), 100-mm visual analog scale (VAS) for ease of intubation, success rate at the first attempt, use of laryngeal manipulation, tube advancement rate by assistant, and complications were recorded. RESULTS: There was no significant difference between the GRS and PFS groups regarding TIT (50.3 ± 12.0 s in the GRS group and 57.8 ± 18.8 s in the PFS group, P = 0.108). However, intubation was more difficult in the PFS group than in the GRS group according to VAS score (P = 0.011). Cases in which the ETT was advanced from the stylet by an assistant, were more frequent in the GRS group than in the PFS group (P = 0.002). The overall incidence of possible complications was not significantly different. CONCLUSIONS: In patients with a simulated difficult airway, there was no difference in TIT using either the PFS or GRS. However, endotracheal intubation with PFS is more difficult to perform than GRS.

Prognostic value of left ventricular apical four-chamber longitudinal strain after heart valve surgery in real-world practice.

BACKGROUND: Left ventricular longitudinal strain is an emerging marker of ventricular systolic function. However, the prognostic value of apical four-chamber longitudinal strain after heart valve surgery in real-world clinical practice is uncertain. The authors investigated whether left ventricular apical four-chamber longitudinal strain measured in real-world practice is helpful for predicting postoperative outcomes in patients undergoing heart valve surgery. METHODS: This observational cohort study was conducted in patients who underwent heart valve surgery between January 2014 and December 2018 at a tertiary hospital in South Korea. The exposure of interest was preoperative left ventricular apical four-chamber longitudinal strain. The primary outcome was postoperative all-cause mortality. RESULTS: Among 1,773 study patients (median age, 63 years; female, 45.9%), 132 (7.4%) died during a median follow-up of 27.2 months. Preoperative left ventricular apical four-chamber longitudinal strain was significantly associated with all-cause mortality (adjusted hazard ratio, 0.94 per 1% increment in absolute value; 95% CI [0.90, 0.99], P = 0.022), whereas left ventricular ejection fraction (LVEF) was not significantly associated with all-cause mortality (adjusted hazard ratio: 1.01, 95% CI [0.99, 1.03], P = 0.222). Moreover, combining left ventricular apical four-chamber longitudinal strain to the LVEF and conventional prognostic factors enhance the prognostic model for all-cause mortality (P = 0.022). CONCLUSIONS: In patients undergoing heart valve surgery without coronary artery disease, left ventricular apical four-chamber longitudinal strain measured in real-world clinical practice was independently associated with postoperative survival. Left ventricular longitudinal strain measurement may be helpful for outcome prediction after valve surgery.

SIRT1 controls lipolysis in adipocytes via FOXO1-mediated expression of ATGL.

Recent studies have established SIRT1 as an important regulator of lipid metabolism, although the mechanism of its action at the molecular level has not been revealed. Here, we show that knockdown of SIRT1 with the help of small hairpin RNA decreases basal and isoproterenol-stimulated lipolysis in cultured adipocytes. This effect is attributed, at least in part, to the suppression of the rate-limiting lipolytic enzyme, adipose triglyceride lipase (ATGL), at the level of transcription. Mechanistically, SIRT1 controls acetylation status and functional activity of FoxO1 that directly binds to the ATGL promoter and regulates ATGL gene transcription. We have also found that depletion of SIRT1 decreases AMP-dependent protein kinase (AMPK) activity in adipocytes. To determine the input of AMPK in regulation of lipolysis, we have established a stable adipose cell line that expresses a dominant-negative α1 catalytic subunit of AMPK under the control of the inducible TET-OFF lentiviral expression vector. Reduction of AMPK activity does not have a significant effect on the rates of lipolysis in this cell model. We conclude, therefore, that SIRT1 controls ATGL transcription primarily by deacetylating FoxO1.

Forward Left Ventricular Ejection Fraction as a Predictor of Postoperative Left Ventricular Dysfunction in Patients with Degenerative Mitral Regurgitation.

BACKGROUND: Left ventricular dysfunction (LVD) can occur immediately after mitral valve repair (MVr) for degenerative mitral regurgitation (DMR) in some patients with normal preoperative left ventricular ejection fraction (LVEF). This study investigated whether forward LVEF, calculated as left ventricular outflow tract stroke volume divided by left ventricular end-diastolic volume, could predict LVD immediately after MVr in patients with DMR and normal LVEF. METHODS: Echocardiographic and clinical data were retrospectively evaluated in 234 patients with DMR ≥ moderate and preoperative LVEF ≥ 60%. LVD and non-LVD were defined as LVEF < 50% and ≥50%, respectively, as measured by echocardiography after MVr and before discharge. RESULTS: Of the 234 patients, 52 (22.2%) developed LVD at median three days (interquartile range: 3-4 days). Preoperative forward LVEF in the LVD and non-LVD groups were 24.0% (18.9-29.5%) and 33.2% (26.4-39.4%), respectively (p < 0.001). Receiver operating characteristic (ROC) analyses showed that forward LVEF was predictive of LVD, with an area under the ROC curve of 0.79 (95% confidence interval: 0.73-0.86), and an optimal cut-off was 31.8% (sensitivity: 88.5%, specificity: 58.2%, positive predictive value: 37.7%, and negative predictive value: 94.6%). Preoperative forward LVEF significantly correlated with preoperative mitral regurgitant volume (correlation coefficient [CC] = -0.86, p < 0.001) and regurgitant fraction (CC = -0.98, p < 0.001), but not with preoperative LVEF (CC = 0.112, p = 0.088). CONCLUSION: Preoperative forward LVEF could be useful in predicting postoperative LVD immediately after MVr in patients with DMR and normal LVEF, with an optimal cut-off of 31.8%.

Dry sauna therapy is beneficial for patients with low back pain.

BACKGROUND: Dry sauna has been very popular as an alternative therapy for promoting health among people who want to improve their health condition without relying on pharmaceuticals. The aim of this study was to investigate whether dry sauna therapy improved quality of life and reduced pain in participants with low back pain. METHODS: Study participants comprised a total of 37 consecutive patients who were over 20 years of age with low back pain. Dry sauna therapy was performed twice per day for 5 consecutive days over the course of 1 week, thus comprising a total of 10 sessions each of 15 min of exposure to a 90°C dry sauna. RESULTS: The verbal numerical rating scale (VNRS) and Oswestry disability index (ODI) scores were significantly reduced after dry sauna therapy (P < 0.001 for both). VNRS pain scores had a median (range) of 5 (2-8) before dry sauna therapy and 3 (0-8) after dry sauna therapy. ODI scores had a median (range) of 12 (2-24) before dry sauna therapy and 8 (1-17) after dry sauna therapy. The proportion of participants who reported successful treatment (excellent + good) was 70%. No adverse effects were observed related to dry sauna therapy. CONCLUSIONS: Our results suggest that dry sauna therapy may be useful to improve quality of life and reduce pain in patients with low back pain. Therefore, pain physicians can recommend dry sauna therapy as an alternative and complimentary therapy for patients with low back pain.

Scabies mimicking graft versus host disease in a hematopoietic cell transplant recipient.

Scabies is a highly contagious skin infestation caused by the mite, Sarcoptes scabiei var. hominis. Complex responses to scabies mites in the innate, humoral, and cellular immune systems can cause skin inflammation and pruritus. Diagnosis can be challenging because scabies resembles other common skin conditions. We report the first Korean case of scabies in a hematopoietic cell transplant (HCT) recipient, initially suspected of skin graft versus host disease (GVHD). A T-cell acute lymphocytic leukemia patient underwent a sibling-matched allogeneic HCT and developed pruritus after cell engraftment. Treatment for GVHD did not improve the symptoms. He was diagnosed with scabies 30 days after the onset of symptoms.

It Is Not Mandatory to Use Triple Rather Than Dual Anti-Platelet Therapy After a Percutaneous Coronary Intervention With a Second-Generation Drug-Eluting Stent.

It has been shown that triple antiplatelet therapy with cilostazol results in better clinical outcomes than dual therapy in patients treated with a first-generation drug-eluting stent (DES); however, it is unclear whether triple antiplatelet therapy has a similar efficacy after the implantation of second-generation DES.In the COACT (Cath Olic medical center percutAneous Coronary in Tervention) registry, 1248 study subjects who underwent percutaneous coronary intervention with an everolimus- or zotarolimus-eluting stent (Endeavor, Xience V, or Promus) were analyzed. The patients were divided into 2 groups after propensity score matching (n = 724; M = 422 [58.3%]; mean age = 66.1 ±â€Š11.0 years): Group 1: patients treated with dual antiplatelet drugs (aspirin and clopidogrel; n = 362; M = 213 [58.8%]; mean age = 65.6 ±â€Š11.7 years); Group 2: patients treated with triple antiplatelet drugs (aspirin, clopidogrel, and cilostazol; n = 362; M = 209 [57.7%]; mean age = 65.6 ±â€Š11.7 years). The mean follow-up duration was 13 ±â€Š10 months, and the cumulative incidence of major cardiovascular events (MACE) was 6.3% in Group 1 and 7.7% in Group 2. There were no significant differences in MACE (death, nonfatal myocardial infarction, and stroke) between the 2 groups (OR, 1.210; 95% CI: 0.772-1.898; P = 0.406). Kaplan-Meier curves for MACE did not show any survival benefit for triple antiplatelet therapy, even in patients with acute coronary syndrome.In patients treated with a second-generation DES implantation, there is no added clinical benefit to using triple rather than dual antiplatelet therapy.

Carotid intima-media thickness is not related with clinical outcomes in young hypertensives.

INTRODUCTION: Careful observations of long- and short-term outcomes associated with carotid intima-media thickness (IMT) are relatively limited. METHODS: A total of 2,972 patients (male:female = 1,960:1,012; mean age = 62 ± 12 years) who underwent carotid IMT measurements from September 2003 to March 2009 were divided into four groups. Group I (n = 271; mean age, 42 ± 7.8 years) included normotensive younger subjects (males, <45 years and females <55 years), group II (n = 992; mean age, 63 ± 9 years) included normotensive elderly subjects, group III (n = 177; mean age, 46 ± 7.8 years) was hypertensive younger subjects, and group IV (n = 1,532; mean age, 63 ± 10.2 years) was hypertensive elderly subjects. We analyzed the clinical and cardiovascular events in the younger hypertensive subjects based on IMT measurements. RESULTS: The baseline characteristics of the subjects showed that carotid IMT increased in the elderly subjects and in patients with hypertension. Poor clinical outcomes, such as all-cause death and major adverse cardiac events, were related with age, not with hypertension. Among the conventional risk factors, age and the highest quartile level of right maximum carotid IMT were related with major adverse events (young: odds ratio [OR], 0.47; 95% confidence interval [CI], 0.25 to 0.9 vs. OR, 1.73; 95% CI, 1.20 to 2.49). The patients in the highest quartile of carotid IMT had worse survival outcomes than those with the lowest IMT (p = 0.03). DISCUSSION: Subjects with hypertension had increased carotid IMT levels. Controlling hypertension and carefully evaluating carotid IMT are important to prevent cardiovascular events even in younger subjects with hypertension.

Acetyl-CoA carboxylase beta expression mediated by MyoD and muscle regulatory factor 4 is differentially affected by retinoic acid receptor and retinoid X receptor.

Mammals have two major isoforms of acetyl-CoA carboxyase (ACC). The 275 kDa beta-form (ACCbeta) is predominantly in heart and skeletal muscle while the 265 kDa alpha-form (ACCalpha) is the major isoform in lipogenic tissues such as liver and adipose tissue. ACCbeta is thought to control fatty acid oxidation by means of the ability of malonyl-CoA to inhibit carnitine palmitoyl-CoA transferase-1 (CPT-1), which is a rate-limiting enzyme of fatty acid oxidation in mitochondria. Previously, it was reported that MyoD and other muscle regulating factors (MRFs) up-regulate the expression of ACCbeta by interactions between these factors and several cis-elements of ACCbeta promoter. We described here that ACCbeta expression mediated by MRFs is regulated by retinoic acids. Endogenous expression of ACCbeta in differentiated H9C2 myotube was significantly increased by retinoic acid treatment. However, on transient transfection assay in H9C2 myoblast, ACCbeta promoter activity was suppressed by RXRalpha and more severely by RARalpha. These effects on ACCbeta expression in myoblasts and myotubes by RXRalpha and RARalpha seem to be mediated by their interactions with MRFs because no consensus sequence for RXRalpha and RARalpha has been found in ACCbeta promoter and retinoic acid receptors did not affect this promoter activities by itself. In transient transfection in NIH3T3 fibroblast, the activation of ACCbeta promoter by MyoD, main MRF in myoblast, was significantly suppressed by RARalpha and to a less extent by RXRalpha while the RXRalpha drastically augmented the activation by MRF4, major MRF in myotube. These results explained that retinoic acids differentially affected the action of MRFs according to their types and RXRalpha specially elevates the expression of muscle specific genes by stimulating the action of MRF4.

Entrapment of a kinked catheter in the radial artery during transradial coronary angiography.

The transradial approach is currently popular for vascular access during percutaneous coronary angiography and intervention. Catheter kinking during catheter manipulation is not uncommon, but mostly the kinked catheter can be unraveled by gentle rotation of catheter in the opposite direction. We describe a case in which the diagnostic catheter was kinked and entrapped in the small radial artery during transradial angiography. Attempts to withdraw or to unravel the catheter with gentle rotation were unsuccessful. We were able to catch the catheter tip with a 6 Fr Amplatz goose-neck snare kit (ev3, Inc.) guided by an 8 Fr guiding catheter via right femoral approach. We pulled the kinked catheter up into the brachial artery with large diameter where successful unraveling was possible, allowing for its successful removal through the radial sheath.

A primary neuron culture system for the study of herpes simplex virus latency and reactivation.

Herpes simplex virus type-1 (HSV-1) establishes a life-long latent infection in peripheral neurons. This latent reservoir is the source of recurrent reactivation events that ensure transmission and contribute to clinical disease. Current antivirals do not impact the latent reservoir and there are no vaccines. While the molecular details of lytic replication are well-characterized, mechanisms controlling latency in neurons remain elusive. Our present understanding of latency is derived from in vivo studies using small animal models, which have been indispensable for defining viral gene requirements and the role of immune responses. However, it is impossible to distinguish specific effects on the virus-neuron relationship from more general consequences of infection mediated by immune or non-neuronal support cells in live animals. In addition, animal experimentation is costly, time-consuming, and limited in terms of available options for manipulating host processes. To overcome these limitations, a neuron-only system is desperately needed that reproduces the in vivo characteristics of latency and reactivation but offers the benefits of tissue culture in terms of homogeneity and accessibility. Here we present an in vitro model utilizing cultured primary sympathetic neurons from rat superior cervical ganglia (SCG) (Figure 1) to study HSV-1 latency and reactivation that fits most if not all of the desired criteria. After eliminating non-neuronal cells, near-homogeneous TrkA(+) neuron cultures are infected with HSV-1 in the presence of acyclovir (ACV) to suppress lytic replication. Following ACV removal, non-productive HSV-1 infections that faithfully exhibit accepted hallmarks of latency are efficiently established. Notably, lytic mRNAs, proteins, and infectious virus become undetectable, even in the absence of selection, but latency-associated transcript (LAT) expression persists in neuronal nuclei. Viral genomes are maintained at an average copy number of 25 per neuron and can be induced to productively replicate by interfering with PI3-Kinase / Akt signaling or the simple withdrawal of nerve growth factor(1). A recombinant HSV-1 encoding EGFP fused to the viral lytic protein Us11 provides a functional, real-time marker for replication resulting from reactivation that is readily quantified. In addition to chemical treatments, genetic methodologies such as RNA-interference or gene delivery via lentiviral vectors can be successfully applied to the system permitting mechanistic studies that are very difficult, if not impossible, in animals. In summary, the SCG-based HSV-1 latency / reactivation system provides a powerful, necessary tool to unravel the molecular mechanisms controlling HSV1 latency and reactivation in neurons, a long standing puzzle in virology whose solution may offer fresh insights into developing new therapies that target the latent herpesvirus reservoir.

Differential regulation of human and mouse orphan nuclear receptor small heterodimer partner promoter by sterol regulatory element binding protein-1.

Small heterodimer partner (SHP; NR0B2) is an unusual orphan nuclear receptor that lacks a conventional DNA-binding domain and acts as a modulator of transcriptional activities of a number of nuclear receptors. Herein, we report that the human SHP promoter (hSHP) is activated by sterol regulatory element-binding protein-1 (SREBP-1), which regulates the expression of various genes involved in cholesterol and fatty acid synthesis. Overexpression of SREBP-1 activated the human but not mouse SHP promoter, although SREBP-2 had little effect on the SHP promoter in CV-1 cells. Serial deletion reporter assays revealed that SREBP-1-responsive region is located within the sequences from -243 to -120 bp in the hSHP promoter. DNase I footprinting, gel shift assays, and chromatin immunoprecipitation assays demonstrated that SREBP-1 binds directly to the hSHP promoter. Site-directed mutagenesis made it clear that the hSHP promoter activation by SREBP-1 is mostly mediated by the SRE1 (-186 to -195 bp) in the hSHP promoter, which is not conserved in the mouse SHP promoter. Moreover, adenovirus-mediated overexpression of SREBP-1c/ADD-1 induced SHP mRNA expression and repressed CYP7A1 expression in HepG2 cells. Finally, we found that a four-nucleotide deletion (-195CT-GAdel) in the hSHP promoter, which is reported to be associated with altered body weight and insulin secretion in human, coincides with the SRE1. This mutation strongly decreased both basal and SREBP-1 dependent activities of the hSHP promoter, because of the reduced binding of SREBP-1 to the mutated SRE1. Overall, our results demonstrate a differential regulation of human and mouse SHP promoters by SREBP-1. We propose a possible role of SREBP-1 in the species differential regulation of cholesterol and bile acid homeostasis via a novel mechanism of up-regulation of the hSHP gene expression.