Impact of intracardiac echocardiography versus transesophageal echocardiography guidance on left atrial appendage occlusion procedures: A meta-analysis.

BACKGROUND: Intracardiac echocardiography (ICE) is increasingly used during left atrial appendage occlusion (LAAO) as an alternative to transesophageal echocardiography (TEE). The objective of this study is to evaluate the impact of ICE versus TEE guidance during LAAO on procedural characteristics and acute outcomes, as well the presence of peri-device leaks and residual septal defects during follow-up. METHODS: All studies comparing ICE-guided versus TEE-guided LAAO were identified. The primary outcomes were procedural efficacy and occurrence of procedure-related complications. Secondary outcomes included lab efficiency (defined as a reduction in in-room time), procedural time, fluoroscopy time, and presence of peri-device leaks and residual interatrial septal defects (IASD) during follow-up. RESULTS: Twelve studies (n = 5637) were included. There were no differences in procedural success (98.3% vs. 97.8%; OR 0.73, 95% CI 0.42-1.27, p = .27; I2 = 0%) or adverse events (4.5% vs. 4.4%; OR 0.81 95% CI 0.56-1.16, p = .25; I2 = 0%) between the ICE-guided and TEE-guided groups. ICE guidance reduced in in-room time (mean-weighted 28.6-min reduction in in-room time) without differences in procedural time or fluoroscopy time. There were no differences in peri-device leak (OR 0.93, 95% CI 0.68-1.27, p = 0.64); however, an increased prevalence of residual IASD was observed with ICE-guided versus TEE-guided LAAO (46.3% vs. 34.2%; OR 2.23, 95% CI 1.05-4.75, p = 0.04). CONCLUSION: ICE guidance is associated with similar procedural efficacy and safety, but could result in improved lab efficiency (as established by a significant reduction in in-room time). No differences in the rate of periprocedural leaks were found. A higher prevalence of residual interatrial septal defects was observed with ICE guidance.

Assisted reality device to guide cardiac implantable device programming in distant rural areas.

BACKGROUND: Patients with cardiac implantable electronic devices (CIEDs) living in rural areas have difficulty obtaining follow-up visits for device interrogation and programming in specialized healthcare facilities. OBJECTIVE: To describe the use of an assisted reality device designed to provide front-line workers with real-time online support from a remotely located specialist (Realwear HTM-1; Realwear) during CIED assistance in distant rural areas. METHODS: This is a prospective study of patients requiring CIED interrogation using the Realwear HMT-1 in a remote rural population in Colombia between April 2021 and June 2022. CIED interrogation and device programming were performed by a general practitioner and guided by a cardiac electrophysiologist. Non-CIED-related medical interventions were allowed and analyzed. The primary objective was to determine the incidence of clinically significant CIED alerts. Secondary objectives were the changes medical interventions used to treat the events found in the device interrogations regarding non-CIED related conditions. RESULTS: A total of 205 CIED interrogations were performed on 139 patients (age 69 ± 14 years; 54% female). Clinically significant CIED alerts were reported in 42% of CIED interrogations, consisting of the detection of significant arrhythmias (35%), lead malfunction (3%), and device in elective replacement interval (3.9%). Oral anticoagulation was initiated in 8% of patients and general medical/cardiac interventions unrelated to the CIED were performed in 52% of CIED encounters. CONCLUSION: Remote assistance using a commercially available assisted reality device has the potential to provide specialized healthcare to patients in difficult-to-reach areas, overcoming current difficulties associated with RM, including the inability to change device programming. Additionally, these interactions provided care beyond CIED-related interventions, thus delivering significant social and clinical impact to remote rural populations.

Anatomical considerations and clinical interpretation of the 12-lead ECG in the prone position: a prospective multicentre study.

AIMS: The aim of this study is to provide guidance for the clinical interpretation of electrocardiograms (ECGs) in prone position and to establish the electroanatomic explanations for the possible differences to supine position ECGs that may be observed. Additionally, to determine if prone back ECG can be used as an alternative to standard ECG in patients who may benefit from prone position. METHODS AND RESULTS: The ECG in supine (standard ECG), prone back (precordial leads placed on the patient's back), and prone anterior position (precordial leads placed in the standard position with the subjects in prone position) were prospectively examined on 85 subjects. Comparisons of ECG parameters between these positions were performed. Computed tomography (CT) scans were performed in both positions to determine possible electroanatomic aetiologies for prone-associated ECG changes. There were significant differences in QRS amplitude in Leads V1-V5 between supine and prone positions. Q waves were more frequently observed in prone back position vs. supine position (V1: 74.1 vs. 10.6%, P < 0.0001; V2: 23.5 vs. 0%, P < 0.0001, respectively). Flat and inverted T waves were more common in prone back leads (V1: 98 vs. 66%, P < 0.0001; V2: 96 vs. 8%, P < 0.0001; V3: 45 vs. 7%, P < 0.0001). The 3D-CT reconstructions measurements corroborated the significant inverse correlation between QRS amplitude and the distance from the centre of the heart to the estimated lead positions. CONCLUSION: In prone back position ECG, low QRS amplitude should not be misinterpreted as low voltage conditions, neither should Q waves and abnormal T waves are considered anteroseptal myocardial infarction. These changes can be explained by an increased impedance (due to interposing lung tissue) and by the increased distance between the electrodes to the centre of the heart.

Current practice in transvenous lead extraction in Latin America: Latin American Heart Rhythm Association survey.

BACKGROUND: Transvenous lead extraction (TLE) is standard of care for the management of patients with cardiac implantable electronic device infection or lead-related complications. Currently, objective data on TLE in Latin America is lacking. OBJECTIVE: To describe the current practice standards in Latin American centers performing TLE. METHODS: An online survey was sent through the mailing list of the Latin American Heart Rhythm Society. Online reminders were sent through the mailing list; duplicate answers were discarded. The survey was available for 1 month, after which no more answers were accepted. RESULTS: A total of 48 answers were received, from 44 different institutions (39.6% from Colombia, 27.1% from Brazil), with most respondents (82%) being electrophysiologists. Twenty-nine institutions (66%) performed <10 lead extractions/year, with 7 (16%) institutions not performing lead extraction. Although most institutions in which lead extraction is performed reported using several tools, mechanical rotating sheaths were cited as the main tool (66%) and only 13% reported the use of laser sheaths. Management of infected leads was performed according to current guidelines. CONCLUSION: This survey is the first attempt to provide information on TLE procedures in Latin America and could provide useful information for future prospective registries. According to our results, the number of centers performing high volume lead extraction in Latin America is smaller than that reported in other continents, with most interventions performed using mechanical tools. Future prospective registries assessing acute and long-term success are needed.

Clinical and Toxicological Profile of NBOMes: A Systematic Review.

BACKGROUND: NBOMes are a new class of potent hallucinogens widely present in illicit drugs. Little is known about this class of drugs, regarding its detection and clinical manifestations of intoxication. OBJECTIVE: This study aims to enhance care involving NBOMes by reviewing the literature on their clinical manifestations and laboratorydetection. METHODS: A systematic review was performed on the clinical manifestations and laboratory tests of NBOMEs ingestion. Embase, Pubmed, PsycINFO, and Cochrane databases were employed in this analysis. RESULTS: Forty-five articles met the inclusion criteria out of the 2814 nonduplicated studies on the theme. Seventy case reports of intoxication were found in the analyzed articles (64.3% were men and 11.4% were women, mean age of 22.5). The technique most employed for NBOMes identification was chromatography of blood, urine, and oral fluids. Moreover, the studies identified 13 chemical structures differentfrom the NBOMes on their toxicological analyses.According to these studies, most of these drugs were ingested orally-nasal use was the second preferred administration route, followed by intravenous administration. CONCLUSION: Better identification of the clinicalmanifestations and laboratory profile of NBOMes is crucial to the recognition of intoxication as well as to its effective treatment.

Calcitriol-mediated hypercalcemia secondary to granulomatous disease caused by soft-tissue filler injection: a case report.

Soft-tissue filler (STF) injections have been used worldwide for cosmetic reasons. In most cases, they are not approved by the United States Food and Drug Administration (FDA). Regulatory boards in Latin American countries do not allow the medical use of STF injections; however, these injections are still widely used. A case of calcitriol-mediated hypercalcemia with ectopic calcifications, chronic kidney disease, nephrolithiasis and calcinosis is presented. The reported case highlights the consequences of STF use, including calcitriol-mediated hypercalcemia secondary to granulomatous reactions years after an esthetic procedure.

Immunological characterization of compensatory anti-inflammatory response syndrome in patients with severe sepsis: a longitudinal study*.

OBJECTIVES: To perform a complete immunological characterization of compensatory anti-inflammatory response syndrome in patients with sepsis and to explore the relationship between these changes and clinical outcomes of 28-day mortality and secondary infections. DESIGN: Prospective single-center study conducted between April 2011 and December 2012. SETTING: ICUs from Hospital Universitario San Vicente Fundación at Medellin, Colombia. PATIENTS: One hundred forty-eight patients with severe sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: At days 0, 1, 3, 5, 10, and 28, we determined the expression of HLA-DR in monocytes and the apoptosis and the proliferation index in T lymphocytes, as well as the levels of tumor necrosis factor-α, interleukin-6, interleukin-1ß, interleukin-10, and transforming growth factor-ß in both plasma and cell culture supernatants of peripheral blood mononuclear cells. The mean percentage of HLA-DR was 60.7 at enrollment and increased by 0.9% (95% CI, 0.7-1.2%) per day. The mean percentage of CD4 T cells and CD8 T cells AV+/7-AAD- at enrollment was 37.2% and 20.4%, respectively, but it diminished at a rate of -0.5% (95% CI, -0.7% to -0.3%) and -0.3% (95% CI, -0.4% to -0.2%) per day, respectively. Plasma levels of interleukin-6 and interleukin-10 were 290 and 166 pg/mL and decreased at a rate of -7.8 pg/mL (95% CI, -9.5 to -6.1 pg/mL) and -4 pg/mL (95% CI, -5.1 to -2.8 pg/mL) per day, respectively. After controlling for confounders, only sustained plasma levels of interleukin-6 increase the risk of death (hazard ratio 1.003; 95% CI, 1.001-1.006). CONCLUSIONS: We found no evidence to support a two-phase model of sepsis pathophysiology. However, immunological variables did behave in a mixed and time-dependent manner. Further studies should evaluate changes over time of interleukin-6 plasma levels as a prognostic biomarker for critically ill patients.

Intracardiac Echocardiography-guided Left Atrial Appendage Occlusion.

Left atrial appendage occlusion (LAAO) is a suitable alternative to oral anticoagulant therapy to prevent stroke in patients with AF. Most procedures are performed under transoesophageal echocardiography (TOE) guidance, which facilitates transseptal puncture, reduces the risk of procedurerelated complications and provides an additional method for device selection and real-time monitoring during device deployment. However, TOE has significant shortcomings, including the need for general anaesthesia/deep sedation as well as a significant risk of procedure-related adverse events. More recently, intracardiac echocardiography has been proposed as an alternative to TOE guidance during LAAO procedures. In this review, we summarise the available evidence as well as providing a step-by-step approach for intracardiac echocardiography-guided LAAO.

Left Bundle Branch Pacing vs Left Ventricular Septal Pacing vs Biventricular Pacing for Cardiac Resynchronization Therapy.

BACKGROUND: Left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP) are considered to be acceptable as LBBAP strategies. Differences in clinical outcomes between LBBP and LVSP are yet to be determined. OBJECTIVES: The purpose of this study was to compare the outcomes of LBBP vs LVSP vs BIVP for CRT. METHODS: In this prospective multicenter observational study, LBBP was compared with LVSP and BIVP in patients undergoing CRT. The primary composite outcome was freedom from heart failure (HF)-related hospitalization and all-cause mortality. Secondary outcomes included individual components of the primary outcome, postprocedural NYHA functional class, and electrocardiographic and echocardiographic parameters. RESULTS: A total of 415 patients were included (LBBP: n = 141; LVSP: n = 31; BIVP: n = 243), with a median follow-up of 399 days (Q1-Q3: 249.5-554.8 days). Freedom from the primary composite outcomes was 76.6% in the LBBP group and 48.4% in the LVSP group (HR: 1.37; 95% CI: 1.143-1.649; P = 0.001), driven by a 31.4% absolute increase in freedom from HF-related hospitalizations (83% vs 51.6%; HR: 3.55; 95% CI: 1.856-6.791; P < 0.001) without differences in all-cause mortality. LBBP was also associated with a higher freedom from the primary composite outcome compared with BIVP (HR: 1.43; 95% CI: 1.175-1.730; P < 0.001), with no difference between LVSP and BIVP. CONCLUSIONS: In patients undergoing CRT, LBBP was associated with improved outcomes compared with LVSP and BIVP, while outcomes between BIVP and LVSP are similar.

Improved all-cause mortality with left bundle branch area pacing compared to biventricular pacing in cardiac resynchronization therapy: a meta-analysis.

BACKGROUND: Left bundle branch area pacing (LBBAP) has emerged as a physiological alternative pacing strategy to biventricular pacing (BIVP) in cardiac resynchronization therapy (CRT). We aimed to assess the impact of LBBAP vs. BIVP on all-cause mortality and heart failure (HF)-related hospitalization in patients undergoing CRT. METHODS: Studies comparing LBBAP and BIVP for CRT in patients with HF with reduced left ventricular ejection fraction (LVEF) were included. The coprimary outcomes were all-cause mortality and HF-related hospitalization. Secondary outcomes included procedural and fluoroscopy time, change in QRS duration, and change in LVEF. RESULTS: Thirteen studies (12 observational and 1 RCT, n = 3239; LBBAP = 1338 and BIVP = 1901) with a mean follow-up duration of 25.8 months were included. Compared to BIVP, LBBAP was associated with a significant absolute risk reduction of 3.2% in all-cause mortality (9.3% vs 12.5%, RR 0.7, 95% CI 0.57-0.86, p < 0.001) and an 8.2% reduction in HF-related hospitalization (11.3% vs 19.5%, RR 0.6, 95% CI 0.5-0.71, p < 0.00001). LBBAP also resulted in reductions in procedural time (mean weighted difference- 23.2 min, 95% CI - 42.9 to - 3.6, p = 0.02) and fluoroscopy time (- 8.6 min, 95% CI - 12.5 to - 4.7, p < 0.001) as well as a significant reduction in QRS duration (mean weighted difference:- 25.3 ms, 95% CI - 30.9 to - 19.8, p < 0.00001) and a greater improvement in LVEF of 5.1% (95% CI 4.4-5.8, p < 0.001) compared to BIVP in the studies that reported these outcomes. CONCLUSION: In this meta-analysis, LBBAP was associated with a significant reduction in all-cause mortality as well as HF-related hospitalization when compared to BIVP. Additional data from large RCTs is warranted to corroborate these promising findings.

Sex Differences in Left Bundle Branch Area Pacing Versus Biventricular Pacing for Cardiac Resynchronization Therapy.

BACKGROUND: Women respond more favorably to biventricular pacing (BIVP) than men. Sex differences in atrioventricular and interventricular conduction have been described in BIVP studies. Left bundle branch area pacing (LBBAP) offers advantages due to direct capture of the conduction system. We hypothesized that men could respond better to LBBAP than BIVP. OBJECTIVES: This study aims to describe the sex differences in response to LBBAP vs BIVP as the initial cardiac resynchronization therapy (CRT). METHODS: In this multicenter prospective registry, we included patients with left ventricular ejection fraction ≤35% and left bundle branch block or a left ventricular ejection fraction ≤40% with an expected right ventricular pacing exceeding 40% undergoing initial CRT with LBBAP or BIVP. The composite primary outcome was heart failure-related hospitalization and all-cause mortality. The primary safety outcome included all procedure-related complications. RESULTS: There was no significant difference in the primary outcome when comparing men and women receiving LBBAP (P = 0.46), whereas the primary outcome was less frequent in women in the BIVP group than men treated with BIVP (P = 0.03). The primary outcome occurred less frequently in men undergoing LBBAP (29.9%) compared to those treated with BIVP (46.5%) (P = 0.004). In women, the incidence of the primary endpoint was 24.14% in the LBBAP group and 36.2% in the BIVP group; however, this difference was not statistically significant (P = 0.23). Complication rates remained consistent across all groups. CONCLUSIONS: Men and women undergoing LBBAP for CRT had similar clinical outcomes. Men undergoing LBBAP showed a lower risk of heart failure-related hospitalizations and all-cause mortality compared to men undergoing BIVP, whereas there was no difference between LBBAP and BIVP in women.

Chlorhexidine gluconate pocket lavage to prevent cardiac implantable electronic device infection in high-risk procedures.

BACKGROUND: Infection is the most dreaded complication of cardiac implantable electronic devices (CIEDs), particularly in patients undergoing high-risk procedures (eg, generator change, device upgrade, lead/pocket revision). OBJECTIVE: The purpose of this study was to describe the impact of chlorhexidine gluconate (CHG) pocket lavage in high-risk procedures. METHODS: Patients from a prospective multicenter registry undergoing high-risk procedures were included. CHG lavage was performed by irrigating the generator pocket with 20 cc of 2% CHG without alcohol followed by and normal saline (NS) irrigation. Only NS irrigation was performed in the comparison group. The primary efficacy outcome was CIED-related infection at 12 months. The primary safety outcome was any CHG-associated adverse event. The secondary outcome was CIED infection during long-term follow-up. Propensity score matching (PSM) analysis was performed for the primary efficacy outcome. RESULTS: A total of 1504 patients were included. At 12-month follow-up, the primary efficacy outcome occurred in 4 of 904 CHG (0.4%) and 14 of 600 NS (2.3%) subjects (log-rank P = .005). On multivariate analysis, the use of CHG irrigation was associated with a lower risk of infection at 1-year follow-up (Cox proportional hazard ratio [HR] 0.138; 95% confidence interval [CI] 0.04-0.45; P = .001). This effect persisted during long-term follow-up. PSM demonstrated a significant reduction in CIED-related infection for the CHG group (0.2% vs 2.5%; Cox proportional HR 0.08; 95% CI 0.01-0.59; P = .014). No adverse events were associated with the use of CHG. CONCLUSION: CHG lavage during high-risk procedures was associated with a reduction in CIED-related infections without any adverse events reported. The benefits of CHG lavage were observed even during long-term follow up and in PSM analysis.

The Emerging Role of Left Bundle Branch Area Pacing for Cardiac Resynchronisation Therapy.

Cardiac resynchronisation therapy (CRT) reduces the risk of heart failure-related hospitalisations and all-cause mortality, as well as improving quality of life and functional status in patients with persistent heart failure symptoms despite optimal medical treatment and left bundle branch block. CRT has traditionally been delivered by implanting a lead through the coronary sinus to capture the left ventricular epicardium; however, this approach is associated with significant drawbacks, including a high rate of procedural failure, phrenic nerve stimulation, high pacing thresholds and lead dislodgement. Moreover, a significant proportion of patients fail to derive any significant benefit. Left bundle branch area pacing (LBBAP) has recently emerged as a suitable alternative to traditional CRT. By stimulating the cardiac conduction system physiologically, LBBAP can result in a more homogeneous left ventricular contraction and relaxation, thus having the potential to improve outcomes compared with conventional CRT strategies. In this article, the evidence supporting the use of LBBAP in patients with heart failure is reviewed.

Sustained Apnea for Epicardial Access With Right Ventriculography: The SAFER Epicardial Approach.

BACKGROUND: Epicardial access (EA) has emerged as an increasingly important approach for the treatment of ventricular arrhythmias and to perform other interventional cardiology procedures. EA is frequently underutilized because the current approach is challenging and carries a high risk of life-threatening complications. OBJECTIVE: The purpose of this study was to determine the efficacy and safety of the SAFER (Sustained Apnea for Epicardial Access With Right Ventriculography) epicardial approach. METHODS: Consecutive patients who underwent EA with the SAFER technique were included in this multicenter study. The primary efficacy outcome was the successful achievement of EA. The primary safety outcomes included right ventricular (RV) perforation, major hemorrhagic pericardial effusion (HPE), and bleeding requiring surgical intervention. Secondary outcomes included procedural characteristics and any complications. Our results were compared with those from previous studies describing other EA techniques to assess differences in outcomes. RESULTS: A total of 105 patients undergoing EA with the SAFER approach from June 2021 to February 2023 were included. EA was used for ventricular tachycardia ablation in 98 patients (93.4%), left atrial appendage closure in 6 patients (5.7%), and phrenic nerve displacement in 1 patient (0.9%). EA was successful in all subjects (100%). The median time to EA was 7 minutes (IQR: 5-14 minutes). No cases of RV perforation, HPE, or need of surgical intervention were observed in this cohort. Comparing our results with previous studies about EA, the SAFER epicardial approach resulted in a significant reduction in major pericardial bleeding. CONCLUSIONS: The SAFER epicardial approach is a simple, efficient, effective, and low-cost technique easily reproducible across multiple centers. It is associated with lower complication rates than previously reported techniques for EA.

Left Bundle Branch Area Pacing Versus Biventricular Pacing as Initial Strategy for Cardiac Resynchronization.

BACKGROUND: Left bundle branch area pacing (LBBAP) for cardiac resynchronization therapy (CRT) is an alternative to biventricular pacing (BiVp). OBJECTIVES: The purpose of this study was to compare the outcomes between LBBAP and BiVp as an initial implant strategy for CRT. METHODS: In this prospective multicenter, observational, nonrandomized study, first-time CRT implant recipients with LBBAP or BiVp were included. The primary efficacy outcome was a composite of heart failure (HF)-related hospitalization and all-cause mortality. The primary safety outcomes were acute and long-term complications. Secondary outcomes included postprocedural New York Heart Association functional class and electrocardiographic and echocardiographic parameters. RESULTS: A total of 371 patients (median follow-up of 340 days [IQR: 206-477 days]) were included. The primary efficacy outcome occurred in 24.2% in the LBBAP vs 42.4% in the BiVp (HR: 0.621 [95% CI: 0.415-0.93]; P = 0.021) group, driven by a reduction in HF-related hospitalizations (22.6% vs 39.5%; HR: 0.607 [95% CI: 0.397-0.927]; P = 0.021) without significant difference in all-cause mortality (5.5% vs 11.9%; P = 0.19) or differences in long-term complications (LBBAP: 9.4% vs BiVp: 15.2%; P = 0.146). LBBAP resulted in shorter procedural (95 minutes [IQR: 65-120 minutes] vs 129 minutes [IQR: 103-162 minutes]; P < 0.001) and fluoroscopy times (12 minutes [IQR: 7.4-21.1 minutes] vs 21.7 minutes [IQR: 14.3-30 minutes]; P < 0.001), shorter QRS duration (123.7 ± 18 milliseconds vs 149.3 ± 29.1 milliseconds; P < 0.001), and higher postprocedural left ventricular ejection fraction (34.1% ± 12.5% vs 31.4% ± 10.8%; P = 0.041). CONCLUSIONS: LBBAP as an initial CRT strategy resulted in a lower risk of HF-related hospitalizations compared to BiVp. A reduction in procedural and fluoroscopy times, shorter paced QRS duration, and improvements in left ventricular ejection fraction compared with BiVp were observed.

Problematic consumption of online pornography during the COVID-19 pandemic: clinical recommendations.

The coronavirus disease (COVID-19) pandemic is one of the greatest contemporary challenges. Feelings of fear and uncertainty triggered by this pandemic have had noxious effects on people's mental health. This seems to have increased during quarantine and there is evidence of an intensification of rewarddirected behavior. Nevertheless, there are few studies dealing with pornography consumption during this period. The aim of this manuscript is to contextualize this phenomenon during the pandemic and suggest some clinical recommendations on the matter.

Author Correction: Characterization of Sex-Based Dna Methylation Signatures in the Airways During Early Life.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Characterization of Sex-Based Dna Methylation Signatures in the Airways During Early Life.

Human respiratory conditions are largely influenced by the individual's sex resulting in overall higher risk for males. Sex-based respiratory differences are present at birth suggesting a strong genetic component. Our objective was to characterize early life sex-based genomic signatures determined by variable X-chromosome methylation in the airways. We compared male versus female genome-wide DNA methylation in nasal airway samples from newborns and infants aged 1-6 months (N = 12). We analyzed methylation signals across CpG sites mapped to each X-linked gene using an unsupervised classifier (principal components) followed by an internal evaluation and an exhaustive cross-validation. Results were validated in an independent population of children (N = 72) following the same algorithm. X-linked genes with significant sex-based differential methylation in the nasal airway of infants represented only about 50% of the unique protein coding transcripts. X-linked genes without significant sex-based differential methylation included genes with evidence of escaping X-inactivation and female-biased airway expression. These genes showed similar methylation patterns in males and females suggesting unbalanced X-chromosome dosage. In conclusion, we identified that the human airways have already sex-based DNA methylation signatures at birth. These early airway epigenomic marks may determine sex-based respiratory phenotypes and overall predisposition to develop respiratory disorders later in life.

Antibiotics has more impact on mortality than other early goal-directed therapy components in patients with sepsis: An instrumental variable analysis.

PURPOSE: To estimate the effect of each of the EGDT components, as well as of the antibiotics, on length-of-stay and mortality. METHODS: Prospective cohort in three hospitals. Adult patients admitted by the Emergency Rooms (ER) with infection and any of systolic blood pressure < 90 mmHg or lactate >4 mmol/L. An instrumental analysis with hospital of admission as the instrumental variable was performed to estimate the effect of each intervention on hospital mortality and secondary outcomes. RESULTS: Among 2587 patients evaluated 884 met inclusion criteria, with a hospital mortality rate of 17% (n = 150). In the instrumental analysis, the only intervention associated with an absolute reduction in mortality (21%) was the use of antibiotics in the first 3 h. In patients with lactate values ≥4 mmol/L in the ER, a non-decrease of at least 10% at six hours was independently associated with mortality (OR = 3.1; 95%CI = 1.5-6.2). CONCLUSIONS: Among patients entering ER with infection and shock or hypoperfusion criteria, the use of appropriate antibiotics in the first 3 h is the measure that has the greatest impact on survival. In addition, among patients with hyperlactatemia >4 mmol/L, the clearance of >10% of lactate during resuscitation is associated with better outcomes.