Unraveling the genetic link: an umbrella review on HLA-B*15:02 and antiepileptic drug-induced Stevens-Johnson syndrome/toxic epidermal necrolysis.

PURPOSE: This umbrella review was conducted to summarize the association between HLA*1502 allele with antiepileptic induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). METHODS: Pubmed, Scopus and EMBASE were searched for eligible reviews in May 2023. Two authors independently screened titles and abstracts and assessed full-text reviews for eligibility. The quality of meta-analyses and case-control studies was appraised with Assessing the Methodological Quality of Systematic Reviews 2 and Newcastle-Ottawa Scale, respectively. Narrative summaries of each antiepileptic drug were analyzed. Preestablished protocol was registered on the International Prospective Register of Systematic Reviews Registry(ID: CRD42023403957). RESULTS: Included studies are systematic reviews, meta-analyses and case-control studies evaluating the association of HLA-B*1502 allele with the following antiepileptics. Seven meta-analyses for carbamazepine, three meta-analyses for lamotrigine (LTG), three case-control studies for oxcarbazepine, nine case-control studies for phenytoin and four case-control studies for phenobarbitone were included. The findings of this umbrella review suggest that there is a strong association between HLA-B-1502 with SJS/TEN for carbamazepine and oxcarbazepine and a milder association for lamotrigine and phenytoin. CONCLUSION: In summary, although HLA-B*1502 is less likely to be associated with phenytoin or lamotrigine-induced SJS/TEN compared to carbamazepine-induced SJS/TEN, it is a significant risk factor that if carefully screened, could potentially reduce the development of SJS/TEN. In view of potential morbidity and mortality, HLA-B*1502 testing may be beneficial in patients who are initiating lamotrigine/phenytoin therapy. However, further studies are required to examine the association of other alleles with the development of SJS/TEN and to explore the possibility of genome-wide association studies before initiation of treatment.

Rates of pulmonary vein reconnection at repeat ablation for recurrent atrial fibrillation and its impact on outcomes among females and males.

BACKGROUND: Several studies have demonstrated that females have a higher risk of arrhythmia recurrence after pulmonary vein (PV) isolation for atrial fibrillation (AF). There are limited data on sex-based differences in PV reconnection rates at repeat ablation. We aimed to investigate sex-based differences in electrophysiological findings and atrial arrhythmia recurrence after repeat AF ablation METHODS: We conducted a retrospective study of 161 consecutive patients (32% female, age 65 ± 10 years) who underwent repeat AF ablation after index PV isolation between 2010 and 2022. Demographics, procedural characteristics and follow-up data were collected. Recurrent atrial tachycardia (AT)/AF was defined as any atrial arrhythmia ≥30 s in duration. RESULTS: Compared to males, females tended to be older and had a significantly higher prevalence of prior valve surgery (10 vs. 2%; P = .03). At repeat ablation, PV reconnection was found in 119 (74%) patients. Males were more likely to have PV reconnection at repeat ablation compared to females (81 vs. 59%; P = .004). Excluding repeat PV isolation, there were no significant differences in adjunctive ablation strategies performed at repeat ablation between females and males. During follow-up, there were no significant differences in freedom from AT/AF recurrence between females and males after repeat ablation (63 vs. 59% at 2 years, respectively; P = .48). CONCLUSIONS: After initial PV isolation, significantly fewer females have evidence of PV reconnection at the time of repeat ablation for recurrent AF. Despite this difference, long-term freedom from AT/AF was similar between females and males after repeat ablation.

Activation of brain arousal networks coincident with eye blinks during resting state.

Eye-blinking has been implicated in arousal and attention. Here we test the hypothesis that blinking-moments represent arousal surges associated with activation of the ascending arousal network (AAN) and its thalamic projections. For this purpose, we explored the temporal relationship between eye-blinks and fMRI BOLD activity in AAN and thalamic nuclei, as well as whole brain cluster corrected activations during eyes-open, resting-state fMRI scanning. We show that BOLD activations in the AAN nuclei peaked prior to the eye blinks and in thalamic nuclei peaked prior to and during the blink, consistent with the role of eye blinking in arousal surges. Additionally, we showed visual cortex peak activation prior to the eye blinks, providing further evidence of the visual cortex's role in arousal, and document cerebellar peak activation post eye blinks, which might reflect downstream engagement from arousal surges.

Establishing Optimal Control Cohorts for Phase 1 Trials: Retrospective Analysis of Clinical and Biological Outcomes in Neonates and Infants Undergoing Two-Ventricle Repair.

Phase 1 trials are primarily conducted to evaluate the safety and feasibility of new interventions, usually without recruiting control patients. This retrospective study aims to characterize clinical and biological outcomes in historical and contemporary cases of neonates and infants undergoing two-ventricle repair to facilitate future secondary endpoint analyses for such trials. This retrospective study included neonates/infants (ages ≤ 6 months) who underwent two-ventricle repair between 2015 and 2021 using the same criteria as our phase 1 trial (n = 199). Patients were allocated into the ventricular septal defect (n = 61), the Tetralogy of Fallot (TOF, n = 88), and the transposition of the great arteries (n = 50) groups with an additional comparison between two eras (2015-2019 vs. 2020-2021). Patient characteristics and most variables assessed were different between the three diagnostic groups indicating the importance of diagnostic matching for secondary analyses. Although the era did not alter cerebral/somatic oxygenation, ventricular function, neuroimaging findings, and complication rates, we observed improvement of inotropic and/or vasoactive-inotropic scores in all groups during the more recent era. In 2020-2021, the age and the body weight at the operation were higher, and hospital stay was shorter in the TOF group, suggesting the possible impact of the pandemic. Results also indicated that matching altered characteristics such as age at operation that may limit the temporal effects and optimize secondary analyses. Using optimal contemporary cases and historical data based on this study will assist in developing a comprehensive study design for a future efficacy/effectiveness trial.

Early Stroke and Mortality After Percutaneous Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation.

BACKGROUND: Percutaneous endocardial left atrial appendage occlusion (LAAO) is an alternative therapy for stroke prevention in patients with atrial fibrillation who are poor candidates for oral anticoagulants. Oral anticoagulation is generally discontinued 45 days following successful LAAO. Real-world data on early stroke and mortality following LAAO are lacking. METHODS: Using International Classification of Diseases, Tenth Revision, Clinical-Modification codes, we performed a retrospective observational registry analysis to examine the rates and predictors of stroke, mortality, and procedural complications during index hospitalization and 90-day readmission among 42 114 admissions in the Nationwide Readmissions Database for LAAO between 2016 and 2019. Early stroke and mortality were defined as events occurring during index admission or 90-day readmission. Data on timing of early strokes post-LAAO were collected. Multivariable logistic regression modeling was used to ascertain predictors of early stroke and major adverse events. RESULTS: LAAO was associated with low rates of early stroke (0.63%), early mortality (0.53%), and procedural complications (2.59%). Among patients who had readmissions with strokes after LAAO, the median time from implant to readmission was 35 days (interquartile range, 9-57 days); 67% of readmissions with strokes occurred <45 days postimplant. Between 2016 and 2019, the rates of early stroke after LAAO significantly decreased (0.64% versus 0.46% P-for-trend <0.001), while early mortality and major adverse event rates were unchanged. Peripheral vascular disease and a history of prior stroke were independently associated with early stroke after LAAO. Early post-LAAO stroke rates were similar between low, medium, and high LAAO volume tertile centers. CONCLUSIONS: In this contemporary real-world analysis, the early stroke rate after LAAO was low, with the majority occurring within 45 days of device implantation. Despite an increase in LAAO procedures between 2016 and 2019, there with a significant decline in early strokes after LAAO during that period.

Initial experience with stylet-driven versus lumenless lead delivery systems for left bundle branch area pacing.

INTRODUCTION: Left bundle branch area pacing (LBBP) has emerged as an alternative method for conduction system pacing. While initial experience with delivery systems for stylet-driven and lumenless lead implantation for LBBP has been described, data comparing outcomes of stylet-driven versus lumenless lead implantation for LBBP are limited. In this study, we compare success rates and outcomes of LBBP with stylet-driven versus lumenless lead delivery systems. METHODS: Eighty-three consecutive patients (mean age 74.1 ± 11.2 years; 56 [68%] male) undergoing attempted LBBP at a single institution were identified. Cases were grouped by lead delivery systems used: stylet-driven (n = 53) or lumenless (n = 30). Baseline characteristics and procedural findings were recorded and compared between the cohorts. Intermediate term follow-up data on ventricular lead parameters were also compared. RESULTS: Baseline characteristics were similar between groups. Successful LBBP was achieved in 77% of patients, with similar success rates between groups (76% in stylet-driven, 80% in lumenless, p = 0.79), and rates of adjudicated LBB capture and other paced QRS parameters were also similar. Compared with the lumenless group, the stylet-driven group had significantly shorter procedure times (90 ± 4 vs. 112 ± 31 min, p = 0.004) and fluoroscopy times (10 ± 5 vs. 15 ± 6 min, p = 0.003). Ventricular lead parameters at follow-up were similar, and rates of procedural complications and need for lead revision were low in both groups. CONCLUSION: Delivery systems for stylet-driven and for lumenless leads for LBBP have comparable acute success rates. Long-term follow-up of lead performance following use of the various delivery systems is warranted.

Contemporary outcomes after treatment of aberrant subclavian artery and Kommerell's diverticulum.

OBJECTIVE: Aberrant subclavian artery (ASA) and Kommerell's diverticulum (KD) are rare vascular anomalies that may be associated with lifestyle-limiting and life-threatening complications. The aim of this study is to report contemporary outcomes after invasive treatment of ASA/KD using a large international dataset. METHODS: Patients who underwent treatment for ASA/KD (2000-2020) were identified through the Vascular Low Frequency Disease Consortium, a multi-institutional collaboration to investigate uncommon vascular disorders. We report the early and mid-term clinical outcomes including stroke and mortality, technical success, and other operative outcomes including reintervention rates, patency, and endoleak. RESULTS: Overall, 285 patients were identified during the study period. The mean patient age was 57 years; 47% were female and 68% presented with symptoms. A right-sided arch was present in 23%. The mean KD diameter was 47.4 mm (range, 13.0-108.0 mm). The most common indication for treatment was symptoms (59%), followed by aneurysm size (38%). The most common symptom reported was dysphagia (44%). A ruptured KD was treated in 4.2% of cases, with a mean diameter of 43.9 mm (range, 18.0-100.0 mm). An open procedure was performed in 101 cases (36%); the most common approach was ASA ligation with subclavian transposition. An endovascular or hybrid approach was performed in 184 patients (64%); the most common approach was thoracic endograft and carotid-subclavian bypass. A staged operative strategy was employed more often than single setting repair (55% vs 45%). Compared with endovascular or hybrid approach, those in the open procedure group were more likely to be younger (49 years vs 61 years; P < .0001), female (64% vs 36%; P < .0001), and symptomatic (85% vs 59%; P < .0001). Complete or partial symptomatic relief at 1 year after intervention was 82.6%. There was no association between modality of treatment and symptom relief (open 87.2% vs endovascular or hybrid approach 78.9%; P = .13). After the intervention, 11 subclavian occlusions (4.5%) occurred; 3 were successfully thrombectomized resulting in a primary and secondary patency of 95% and 96%, respectively, at a median follow-up of 39 months. Among the 33 reinterventions (12%), the majority were performed for endoleak (36%), and more reinterventions occurred in the endovascular or hybrid approach than open procedure group (15% vs 6%; P = .02). The overall survival rate was 87.3% at a median follow-up of 41 months. The 30-day stroke and death rates were 4.2% and 4.9%, respectively. Urgent or emergent presentation was independently associated with increased risk of 30-day mortality (odds ratio [OR], 19.8; 95% confidence interval [CI], 3.3-116.6), overall mortality (OR, 3.6; 95% CI, 1.2-11.2) and intraoperative complications (OR, 8.3; 95% CI, 2.8-25.1). Females had a higher risk of reintervention (OR, 2.6; 95% CI, 1.0-6.5). At an aneurysm size of 44.4 mm, receiver operator characteristic curve analysis suggested that 60% of patients would have symptoms. CONCLUSIONS: Treatment of ASA/KD can be performed safely with low rates of mortality, stroke and reintervention and high rates of symptomatic relief, regardless of the repair strategy. Symptomatic and urgent operations were associated with worse outcomes in general, and female gender was associated with a higher likelihood of reintervention. Given the worse overall outcomes when symptomatic and the inherent risk of rupture, consideration of repair at 40 mm is reasonable in most patients. ASA/KD can be repaired in asymptomatic patients with excellent outcomes and young healthy patients may be considered better candidates for open approaches versus endovascular or hybrid modalities, given the lower likelihood of reintervention and lower early mortality rate.

International Multi-Institutional Experience with Presentation and Management of Aortic Arch Laterality in Aberrant Subclavian Artery and Kommerell's Diverticulum.

BACKGROUND: Aberrant subclavian artery (ASA) with or without Kommerell's diverticulum (KD) is a rare anatomic aortic arch anomaly that can cause dysphagia and/or life-threatening rupture. The objective of this study is to compare outcomes of ASA/KD repair in patients with a left versus right aortic arch. METHODS: Using the Vascular Low Frequency Disease Consortium methodology, a retrospective review was performed of patients ≥18 years old with surgical treatment of ASA/KD from 2000 to 2020 at 20 institutions. RESULTS: 288 patients with ASA with or without KD were identified; 222 left-sided aortic arch (LAA), and 66 right-sided aortic arch (RAA). Mean age at repair was younger in LAA 54 vs. 58 years (P = 0.06). Patients in RAA were more likely to undergo repair due to symptoms (72.7% vs. 55.9%, P = 0.01), and more likely to present with dysphagia (57.6% vs. 39.1%, P < 0.01). The hybrid open/endovascular approach was the most common repair type in both groups. Rates of intraoperative complications, death within 30 days, return to the operating room, symptom relief and endoleaks were not significantly different. For patients with symptom status follow-up data, in LAA, 61.7% had complete relief, 34.0% had partial relief and 4.3% had no change. In RAA, 60.7% had complete relief, 34.4% had partial relief and 4.9% had no change. CONCLUSIONS: In patients with ASA/KD, RAA patients were less common than LAA, presented more frequently with dysphagia, had symptoms as an indication for intervention, and underwent treatment at a younger age. Open, endovascular and hybrid repair approaches appear equally effective, regardless of arch laterality.

Defining the optimal historical control group for a phase 1 trial of mesenchymal stromal cell delivery through cardiopulmonary bypass in neonates and infants.

OBJECTIVE: The Mesenchymal Stromal Cell Delivery through Cardiopulmonary Bypass in Pediatric Cardiac Surgery study is a prospective, open-label, single-centre, dose-escalation phase 1 trial assessing the safety/feasibility of delivering mesenchymal stromal cells to neonates/infants during cardiac surgery. Outcomes will be compared with historical data from a similar population. We aim to define an optimal control group for use in the Mesenchymal Stromal Cell Delivery through Cardiopulmonary Bypass in Pediatric Cardiac Surgery trial. METHODS: Consecutive patients who underwent a two-ventricle repair without aortic arch reconstruction within the first 6 months of life between 2015 and 2020 were studied using the same inclusion/exclusion criteria as the Phase 1 Mesenchymal Stromal Cell Delivery through Cardiopulmonary Bypass in Pediatric Cardiac Surgery trial (n = 169). Patients were allocated into one of three diagnostic groups: ventricular septal defect type, Tetralogy of Fallot type, and transposition of the great arteries type. To determine era effect, patients were analysed in two groups: Group A (2015-2017) and B (2018-2020). In addition to biological markers, three post-operative scoring methods (inotropic and vasoactive-inotropic scores and the Pediatric Risk of Mortality-III) were assessed. RESULTS: All values for three scoring systems were consistent with complexity of cardiac anomalies. Max inotropic and vasoactive-inotropic scores demonstrated significant differences between all diagnosis groups, confirming high sensitivity. Despite no differences in surgical factors between era groups, we observed lower inotropic and vasoactive-inotropic scores in group B, consistent with improved post-operative course in recent years at our centre. CONCLUSIONS: Our studies confirm max inotropic and vasoactive-inotropic scores as important quantitative measures after neonatal/infant cardiac surgery. Clinical outcomes should be compared within diagnostic groupings. The optimal control group should include only patients from a recent era. This initial study will help to determine the sample size of future efficacy/effectiveness studies.

Neurostimulation for Chronic Pain: A Systematic Review of High-Quality Randomized Controlled Trials With Long-Term Follow-Up.

OBJECTIVE: This study aimed to review the best evidence on the long-term efficacy of neurostimulation for chronic pain. MATERIALS AND METHODS: We systematically reviewed PubMed, CENTRAL, and WikiStim for studies published between the inception of the data bases and July 21, 2022. Randomized controlled trials (RCTs) with a minimum of one-year follow-up that were of high methodologic quality as ascertained using the Delphi list criteria were included in the evidence synthesis. The primary outcome was long-term reduction in pain intensity, and the secondary outcomes were all other reported outcomes. Level of recommendation was graded from I to III, with level I being the highest level of recommendation. RESULTS: Of the 7119 records screened, 24 RCTs were included in the evidence synthesis. Therapies with recommendations for their usage include pulsed radiofrequency (PRF) for postherpetic neuralgia, transcutaneous electrical nerve stimulation for trigeminal neuralgia, motor cortex stimulation for neuropathic pain and poststroke pain, deep brain stimulation for cluster headache, sphenopalatine ganglion stimulation for cluster headache, occipital nerve stimulation for migraine, peripheral nerve field stimulation for back pain, and spinal cord stimulation (SCS) for back and leg pain, nonsurgical back pain, persistent spinal pain syndrome, and painful diabetic neuropathy. Closed-loop SCS is recommended over open-loop SCS for back and leg pain. SCS is recommended over PRF for postherpetic neuralgia. Dorsal root ganglion stimulation is recommended over SCS for complex regional pain syndrome. CONCLUSIONS: Neurostimulation is generally effective in the long term as an adjunctive treatment for chronic pain. Future studies should evaluate whether the multidisciplinary management of the physical perception of pain, affect, and social stressors is superior to their management alone.

Atrial fibrillation ablation in chronic kidney disease-Lessons from large datasets.

Outcomes data regarding atrial fibrillation treatment in chronic kidney disease are lacking. Available data and unanswered questions in this realm will be discussed, along with how the present manuscript fits into the overall literature of this field.

Chronic headaches related to post-dural puncture headaches: a scoping review.

Post-dural puncture headache (PDPH) is a well-recognised complication of neuraxial procedures. Although it is generally considered to be self-limiting, there is mounting evidence suggesting an association between PDPH and chronic headaches. In this review, chronic headache after dural puncture was defined as the reporting of persistent headaches more than 1 month after the index dural puncture. This scoping review aims to: (1) review the relationship between PDPH and chronic headaches, (2) explore the pathophysiology of chronic headache arising from a dural puncture, and (3) make recommendations about the follow-up and treatment of these patients. The pooled relative risk of chronic headache from 15 863 patients reported in 12 cohort studies in patients with an accidental dural puncture compared with those without accidental dural puncture were 1.9 (95% confidence interval [CI], 1.2-2.9), 2.5 (95% CI, 2.0-3.2), and 3.6 (95% CI, 1.9-7.1) at 2, 6, and 12 months, respectively. We also identified 20 case reports of 49 patients who developed chronic headache after a dural puncture. Epidural blood patch and fibrin glue injection and surgery have been used to treat chronic postural headaches. Overall, the level of evidence is low for all reported outcomes (aetiology, intervention and outcome) by virtue of the type of studies available (cohort and case reports) and significant risk of bias in the cohort studies. Based on findings from this review, we recommend that the risk of chronic headache is included in the informed consent discussion for all neuraxial procedures. Patients with PDPH should be closely followed up after hospital discharge.

Managing COVID-19 in a Novel, Rapidly Deployable Community Isolation Quarantine Facility.

Singapore is one of the most densely populated small island-states in the world. During the coronavirus disease 2019 (COVID-19) pandemic, Singapore implemented large-scale institutional isolation units called Community Care Facilities (CCFs) to combat the outbreak in the community by housing low-risk COVID-19 patients from April to August 2020. The CCFs were created rapidly by converting existing public spaces and used a protocolized system, augmented by telemedicine to enable a low health care worker-patient ratio (98 health care workers for 3200 beds), to operate these unique facilities. In the first month, a total of 3758 patients were admitted to 4 halls, 4929 in-house medical consults occurred, 136 patients were transferred to a hospital, 1 patient died 2 weeks after discharge, and no health care workers became infected. This article shares the authors' experience in operating these massive-scale isolation facilities while prioritizing safety for all and ensuring holistic patient care in the face of a public health crisis and lean health care resources.

Functional connectivity during language processing in 3-month-old infants at familial risk for autism spectrum disorder.

Auditory statistical learning (ASL) plays a role in language development and may lay a foundation for later social communication impairment. As part of a longitudinal study of infant siblings, we asked whether electroencephalography (EEG) measures of connectivity during ASL at 3 months of age-differentiated infants who showed signs of autism spectrum disorder (ASD) at age 18 months. We measured spectral power and phase coherence in the theta (4-6 Hz) and alpha (6-12 Hz) frequency bands within putative language networks. Infants were divided into ASD-concern (n = 14) and No-ASD-concern (n = 49) outcome groups based on their ASD symptoms at 18 months, measured using the Autism Diagnostic Observation Scale Toddler Module. Using permutation testing, we identified a trend toward reduced left fronto-central phase coherence at the electrode pair F9-C3 in both theta and alpha frequency bands in infants who later showed ASD symptoms at 18 months. Across outcome groups, alpha coherence at 3 months correlated with greater word production at 18 months on the MacArthur-Bates Communicative Development Inventory. This study introduces signal processing and analytic tools that account for the challenges inherent in infant EEG studies, such as short duration of recordings, considerable movement artifact, and variable volume conduction. Our results indicate that connectivity, as measured by phase coherence during 2.5 min of ASL, can be quantified as early as 3 months and suggest that early alternations in connectivity may serve as markers of resilience for neurodevelopmental impairments.

Preliminary evidence on abatacept safety and efficacy in refractory juvenile localized scleroderma.

OBJECTIVE: To evaluate the safety and efficacy of abatacept treatment for refractory juvenile localized scleroderma (jLS) in a retrospective study. METHODS: A multicentre cohort study was performed to evaluate jLS subjects treated with abatacept with follow-up for 12 months to maximum of 24 months. Assessments at 6-month intervals included skin activity measures and physician global assessment of activity (PGA-A). Descriptive statistical analysis was performed. RESULTS: Eighteen subjects were studied with median age of 13.4 years, the majority had linear scleroderma subtype, and musculoskeletal involvement. All had previously failed MTX and/or mycophenolate mofetil treatment and glucocorticoids. Abatacept was added to the subject's maintenance DMARD treatment; 13 also received glucocorticoids at start of abatacept. No serious adverse events occurred. Skin activity and PGA-A scores declined in nearly all by 6 months and continued to improve from 6 to 12 months. At 12 months, 15 (83%) subjects were considered responders, two (11%) treatment failures, and one dropped out for adverse event. Response was sustained for 11 (61%) subjects to 18 months and eight (44%) to 24 months. Overall, four (22%) subjects were treatment failures and three (16.7%) discontinued abatacept for adverse event. Active musculoskeletal problems improved in most affected subjects. Ten subjects were able to discontinue initial glucocorticoid and six concomitant DMARD treatment. CONCLUSION: Abatacept was found to be safe and effective for jLS subjects refractory to standard of care treatment. Subjects experienced improvement in both skin and musculoskeletal activity. Prospective studies should be performed to more fully evaluate abatacept's efficacy.

Predictors of one year chronic post-surgical pain trajectories following thoracic surgery.

PURPOSE: Chronic post-surgical pain (CPSP) is a highly prevalent complication following thoracic surgery. This is a prospective cohort study that aims to describe the pain trajectories of patients undergoing thoracic surgery beginning preoperatively and up to 1 year after surgery METHODS: Two hundred and seventy nine patients undergoing elective thoracic surgery were enrolled. Participants filled out a preoperative questionnaire containing questions about their sociodemographic information, comorbidities as well as several psychological and pain-related statuses. They were then followed-up during their immediate postoperative period and at the three, six and 12 month time-points to track their postoperative pain, complications and pain-related outcomes. Growth mixture modeling was used to construct pain trajectories. RESULTS: The first trajectory is characterized by 185 patients (78.1%) with mild pain intensity across the 12 month period. The second is characterized by 32 patients (7.5%) with moderate pain intensity immediately after surgery which decreases markedly by 3 months and remains low at the 12 month follow-up. The final trajectory is characterized by 20 patients (8.4%) with moderate pain intensity immediately after surgery which persists at 12 months. Patients with moderate to severe postoperative pain intensity were much more likely to develop CPSP compared to patients with mild pain intensity. Initial pain intensity levels immediately following surgery as well as levels of pain catastrophizing at baseline were predicting pain trajectory membership. None of the surgical or anesthetic-related variables were significantly associated with pain trajectory membership. CONCLUSION: Patients who undergo thoracic surgery can have postoperative pain that follows one of the three different types of trajectories. Higher levels of immediate postoperative pain and preoperative pain catastrophizing were associated with moderately severe CPSP.

Improved Discrimination of Asymmetric and Symmetric Arginine Dimethylation by Optimization of the Normalized Collision Energy in Liquid Chromatography-Mass Spectrometry Proteomics.

Protein arginine methylation regulates diverse biological processes including signaling, metabolism, splicing, and transcription. Despite its important biological roles, arginine dimethylation remains an understudied post-translational modification. Partly, this is because the two forms of arginine dimethylation, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), are isobaric and therefore indistinguishable by traditional mass spectrometry techniques. Thus, there exists a need for methods that can differentiate these two modifications. Recently, it has been shown that the ADMA and SDMA can be distinguished by the characteristic neutral loss (NL) of dimethylamine and methylamine, respectively. However, the utility of this method is limited because the vast majority of dimethylarginine peptides do not generate measurable NL ions. Here, we report that increasing the normalized collision energy (NCE) in a higher-energy collisional dissociation cell increases the generation of the characteristic NLs that distinguish ADMA and SDMA. By analyzing both synthetic and endogenous methyl-peptides, we identify an optimal NCE value that maximizes NL generation and simultaneously improves methyl-peptide identification. Using two orthogonal methyl-peptide enrichment strategies, high pH strong cation-exchange and immunoaffinity purification, we demonstrate that the optimal NCE improves NL-based ADMA and SDMA annotation and dimethyl-peptide identifications by 125% and 17%, respectively, compared to the standard NCE. This simple parameter change will greatly facilitate the identification and annotation of ADMA and SDMA in mass spectrometry-based methyl-proteomics to improve our understanding of how these modifications differentially regulate protein function. All raw data have been deposited in the PRIDE database with accession number PXD017193.

Robotics for catheter ablation of cardiac arrhythmias: Current technologies and practical approaches.

Robotic technology has emerged as an important tool to facilitate catheter ablation of arrhythmias. Robotic cardiac electrophysiology technology includes remote magnetic navigation and manual robotic navigation. Robotics can confer advantages with respect to ease of catheter manipulation in anatomically challenging spaces, minimization of fluoroscopic exposure to both patients and operators, and reduction in operator fatigue. This review provides a comprehensive summary of robotic electrophysiology technology, its practical applications and its safety and efficacy for targeting cardiac arrhythmias.

Outcomes and mortality associated with atrial arrhythmias among patients hospitalized with COVID-19.

INTRODUCTION: The impact of atrial arrhythmias on coronavirus disease 2019 (COVID-19)-associated outcomes are unclear. We sought to identify prevalence, risk factors and outcomes associated with atrial arrhythmias among patients hospitalized with COVID-19. METHODS: An observational cohort study of 1053 patients with severe acute respiratory syndrome coronavirus 2 infection admitted to a quaternary care hospital and a community hospital was conducted. Data from electrocardiographic and telemetry were collected to identify atrial fibrillation (AF) or atrial flutter/tachycardia (AFL). The association between atrial arrhythmias and 30-day mortality was assessed with multivariable analysis. RESULTS: Mean age of patients was 62 ± 17 years and 62% were men. Atrial arrhythmias were identified in 166 (15.8%) patients, with AF in 154 (14.6%) patients and AFL in 40 (3.8%) patients. Newly detected atrial arrhythmias occurred in 101 (9.6%) patients. Age, male sex, prior AF, renal disease, and hypoxia on presentation were independently associated with AF/AFL occurrence. Compared with patients without AF/AFL, patients with AF/AFL had significantly higher levels of troponin, B-type natriuretic peptide, C-reactive protein, ferritin and d-dimer. Mortality was significantly higher among patients with AF/AFL (39.2%) compared to patients without (13.4%; p < .001). After adjustment for age and co-morbidities, AF/AFL (adjusted odds ratio [OR]: 1.93; p = .007) and newly detected AF/AFL (adjusted OR: 2.87; p < .001) were independently associated with 30-day mortality. CONCLUSION: Atrial arrhythmias are common among patients hospitalized with COVID-19. The presence of AF/AFL tracked with markers of inflammation and cardiac injury. Atrial arrhythmias were independently associated with increased mortality.

Inpatient hospital procedural volume and outcomes following catheter ablation of atrial fibrillation.

INTRODUCTION: The real-world distribution of hospital atrial fibrillation (AF) ablation volume and its impact on outcomes are not well-established. We sought to examine patient characteristics, complications, and readmissions after AF ablation stratified by hospital procedural volume. METHODS AND RESULTS: Using the nationally representative inpatient Nationwide Readmissions Database, we evaluated 54 597 admissions for AF ablation between 2010 and 2014. Hospitals were categorized according to tertiles of annual AF ablation volume. Index complications, 30-day readmissions, and early mortality were examined. Multivariable logistic regression was performed to assess the predictors of adverse outcomes. Between 2010 and 2014, low volume tertile hospitals accounted for 79.3% of hospitals performing AF ablations. When stratified by first, second, and third volume tertiles, complication and early mortality rates were higher in low volume centers (8.9% and 0.67% vs 6.1% and 0.33%, vs 4.5% and 0.16%, respectively; P < .001). Patients undergoing AF ablation at low volume centers were older and had a higher prevalence of congestive heart failure, coronary artery disease, and other comorbidities. Low volume hospitals were associated with increased cardiac perforation (adjusted odds ratio [aOR], 4.79; P < .001), vascular complications (aOR 1.49; P < .001), and any complication (aOR 2.06; P < .001) during index admission as well as increased early mortality (aOR 2.43; P = .039). CONCLUSIONS: Among patients hospitalized for AF ablation, low inpatient AF ablation hospital volume was associated with worse outcomes following ablation, which was exacerbated by a greater comorbidity burden among patients at these centers.