Project description:BackgroundEthanol infusion has recently been described as a curative strategy for certain peri-mitral flutters by blocking electrical conduction across the mitral isthmus along with the Marshall bundle. The present case showed that a right jugular vein approach, less described, may be a good choice when performing an ethanol infusion in the vein of Marshall (VOM).Case summaryA 45-year-old man was admitted to our unit for dyspnoea associated with an atypical atrial flutter with a cycle length of 320 ms. The left atrial activation map showed a peri-mitral counter-clockwise circuit. The atrial flutter cycle length went up to 345 ms once an endocardial and epicardial point-by point-ablation of the mitral line was completed. At this stage, a new activation map showed that the mitral line was still permeable with an epicardial conduction bridge through the VOM. We decided to use an ethanol infusion for the ablation of the VOM. The coronary sinus could not be thoroughly catheterized due to a winding and angular shape so we decided to try a right jugular vein approach. A total of 9 mL of ethanol was injected into the VOM. A final venogram showed the diffusion of ethanol around the VOM. Sinus rhythm was restored during the last ethanol infusion. A new voltage map confirmed the completion of the mitral line, and we confirmed the bidirectional block.DiscussionThe present case showed that a right jugular vein approach may be a good choice when catheterizing and performing an ethanol infusion in the VOM.
Project description:ImportanceCatheter ablation of persistent atrial fibrillation (AF) has limited success. Procedural strategies beyond pulmonary vein isolation have failed to consistently improve results. The vein of Marshall contains innervation and AF triggers that can be ablated by retrograde ethanol infusion.ObjectiveTo determine whether vein of Marshall ethanol infusion could improve ablation results in persistent AF when added to catheter ablation.Design, setting, and participantsThe Vein of Marshall Ethanol for Untreated Persistent AF (VENUS) trial was an investigator-initiated, National Institutes of Health-funded, randomized, single-blinded trial conducted in 12 centers in the United States. Patients (N = 350) with persistent AF referred for first ablation were enrolled from October 2013 through June 2018. Follow-up concluded in June 2019.InterventionsPatients were randomly assigned to catheter ablation alone (n = 158) or catheter ablation combined with vein of Marshall ethanol infusion (n = 185) in a 1:1.15 ratio to accommodate for 15% technical vein of Marshall ethanol infusion failures.Main outcomes and measuresThe primary outcome was freedom from AF or atrial tachycardia for longer than 30 seconds after a single procedure, without antiarrhythmic drugs, at both 6 and 12 months. Outcome assessment was blinded to randomization treatment. There were 12 secondary outcomes, including AF burden, freedom from AF after multiple procedures, perimitral block, and others.ResultsOf the 343 randomized patients (mean [SD] age, 66.5 [9.7] years; 261 men), 316 (92.1%) completed the trial. Vein of Marshall ethanol was successfully delivered in 155 of 185 patients. At 6 and 12 months, the proportion of patients with freedom from AF/atrial tachycardia after a single procedure was 49.2% (91/185) in the catheter ablation combined with vein of Marshall ethanol infusion group compared with 38% (60/158) in the catheter ablation alone group (difference, 11.2% [95% CI, 0.8%-21.7%]; P = .04). Of the 12 secondary outcomes, 9 were not significantly different, but AF burden (zero burden in 78.3% vs 67.9%; difference, 10.4% [95% CI, 2.9%-17.9%]; P = .01), freedom from AF after multiple procedures (65.2% vs 53.8%; difference, 11.4% [95% CI, 0.6%-22.2%]; P = .04), and success achieving perimitral block (80.6% vs 51.3%; difference, 29.3% [95% CI, 19.3%-39.3%]; P < .001) were significantly improved in vein of Marshall-treated patients. Adverse events were similar between groups.Conclusions and relevanceAmong patients with persistent AF, addition of vein of Marshall ethanol infusion to catheter ablation, compared with catheter ablation alone, increased the likelihood of remaining free of AF or atrial tachycardia at 6 and 12 months. Further research is needed to assess longer-term efficacy.Trial registrationClinicalTrials.gov Identifier: NCT01898221.
Project description:BackgroundThe Vein of Marshall Ethanol for Untreated Persistent AF (VENUS) trial demonstrated that adding vein of Marshall (VOM) ethanol infusion to catheter ablation (CA) improves ablation outcomes in persistent atrial fibrillation (AF). There was significant heterogeneity in the impact of VOM ethanol infusion on rhythm control.ObjectiveThe purpose of this study was to assess the association between outcomes and (1) achievement of bidirectional perimitral conduction block and (2) procedural volume.MethodsThe VENUS trial randomized patients with persistent AF (N = 343) to CA combined with VOM ethanol or CA alone. The primary outcome (freedom from AF or atrial tachycardia [AT] lasting longer than 30 seconds after a single procedure) was analyzed by 2 categories: (1) successful vs no perimitral block and (2) high- (>20 patients enrolled) vs low-volume centers.ResultsIn patients with perimitral block, the primary outcome was reached 54.3% after VOM-CA and 37% after CA alone (P = .01). Among patients without perimitral block, freedom from AF/AT was 34.0% after VOM-CA and 37.0% after CA (P = .583). In high-volume centers, the primary outcome was reached in 56.4% after VOM-CA and 40.2% after CA (P = .01). In low-volume centers, freedom from AF/AT was 30.77% after VOM-CA and 32.61% after CA (P = .84). In patients with successful perimitral block from high-volume centers, the primary outcome was reached in 59% after VOM-CA and 39.1% after CA (P = .01). Tests for interaction were significant (P = .002 for perimitral block and P = .04 for center volume).ConclusionAdding VOM ethanol infusion to CA has a greater impact on outcomes when associated with perimitral block and performed in high-volume centers. Perimitral block should be part of the VOM procedure.
Project description:Although 22q11.2 deletion syndrome (22q11.2DS) is the most recurrent human microdeletion syndrome associated with a highly variable phenotype, little is known about the condition's true incidence and the phenotype at diagnosis. We performed a multicenter, retrospective analysis of postnatally diagnosed patients recruited by members of the Association des Cytogénéticiens de Langue Française (the French-Speaking Cytogeneticists Association). Clinical and cytogenetic data on 749 cases diagnosed between 1995 and 2013 were collected by 31 French cytogenetics laboratories. The most frequent reasons for referral of postnatally diagnosed cases were a congenital heart defect (CHD, 48.6%), facial dysmorphism (49.7%) and developmental delay (40.7%). Since 2007 (the year in which array comparative genomic hybridization (aCGH) was introduced for the routine screening of patients with intellectual disability), almost all cases have been diagnosed using FISH (96.1%). Only 15 cases (all with an atypical phenotype) were diagnosed with aCGH; the deletion size ranged from 745 to 2904?kb. The deletion was inherited in 15.0% of cases and was of maternal origin in 85.5% of the latter. This is the largest yet documented cohort of patients with 22q11.2DS (the most commonly diagnosed microdeletion) from the same population. French cytogenetics laboratories diagnosed at least 108 affected patients (including fetuses) per year from among a national population of ?66 million. As observed for prenatal diagnoses, CHDs were the most frequently detected malformation in postnatal diagnoses. The most common CHD in postnatal diagnoses was an isolated septal defect.
Project description:Chest wall and mediastinal wounds may be life-threatening. Although modern reconstruction methods with various muscle flaps have reduced morbidity and mortality, chest wall reconstruction presents unique challenges. Major categories of adverse outcomes include (1) persistent infection; (2) interference with respiratory mechanics; (3) functional deficits of the shoulder; and (4) hernias. Persistent infection may be resolved by providing coverage via muscle or omental flap, performing thorough debridement, filling the "dead space" with adequate volume, buttressing repair of visceral fistulae, and covering exposed prosthetic material with vascularized flaps. Potential deficits in respiratory mechanics and shoulder function may be avoided by stabilizing the chest wall skeleton and decreasing donor muscle functional loss. Hernias may be minimized by maintaining visceral "right of domain" to the chest and abdominal cavities. Complex reconstructive cases represent an intricate interplay of physiology, structural protection, and aesthetic considerations and require integration of several management principles.
Project description:Hydroclimate variations since 1300 in central and monsoonal Asia and their interplay on interannual and interdecadal timescales are investigated using the tree-ring based Palmer Drought Severity Index (PDSI) reconstructions. Both the interannual and interdecadal variations in both regions are closely to the Pacific Decadal Oscillation (PDO). On interannual timescale, the most robust correlations are observed between PDO and hydroclimate in central Asia. Interannual hydroclimate variations in central Asia are more significant during the warm periods with high solar irradiance, which is likely due to the enhanced variability of the eastern tropical Pacific Ocean, the high-frequency component of PDO, during the warm periods. We observe that the periods with significant interdecadal hydroclimate changes in central Asia often correspond to periods without significant interdecadal variability in monsoonal Asia, particularly before the 19th century. The PDO-hydroclimate relationships appear to be bridged by the atmospheric circulation between central North Pacific Ocean and Tibetan Plateau, a key area of PDO. While, in some periods the atmospheric circulation between central North Pacific Ocean and monsoonal Asia may lead to significant interdecadal hydroclimate variations in monsoonal Asia.
Project description:We describe a zero-fluoroscopy ablation of a left atrial re-entry tachycardia in a patient with a previous atrial fibrillation ablation procedure. The critical isthmus was demonstrated to use an epicardial connection via the ligament of Marshall after failed endocardial and epicardial ablation along the mitral isthmus line. (Level of Difficulty: Intermediate.).
Project description:MOTIVATION:Accurate identification of peptides binding to specific Major Histocompatibility Complex Class II (MHC-II) molecules is of great importance for elucidating the underlying mechanism of immune recognition, as well as for developing effective epitope-based vaccines and promising immunotherapies for many severe diseases. Due to extreme polymorphism of MHC-II alleles and the high cost of biochemical experiments, the development of computational methods for accurate prediction of binding peptides of MHC-II molecules, particularly for the ones with few or no experimental data, has become a topic of increasing interest. TEPITOPE is a well-used computational approach because of its good interpretability and relatively high performance. However, TEPITOPE can be applied to only 51 out of over 700 known HLA DR molecules. METHOD:We have developed a new method, called TEPITOPEpan, by extrapolating from the binding specificities of HLA DR molecules characterized by TEPITOPE to those uncharacterized. First, each HLA-DR binding pocket is represented by amino acid residues that have close contact with the corresponding peptide binding core residues. Then the pocket similarity between two HLA-DR molecules is calculated as the sequence similarity of the residues. Finally, for an uncharacterized HLA-DR molecule, the binding specificity of each pocket is computed as a weighted average in pocket binding specificities over HLA-DR molecules characterized by TEPITOPE. RESULT:The performance of TEPITOPEpan has been extensively evaluated using various data sets from different viewpoints: predicting MHC binding peptides, identifying HLA ligands and T-cell epitopes and recognizing binding cores. Among the four state-of-the-art competing pan-specific methods, for predicting binding specificities of unknown HLA-DR molecules, TEPITOPEpan was roughly the second best method next to NETMHCIIpan-2.0. Additionally, TEPITOPEpan achieved the best performance in recognizing binding cores. We further analyzed the motifs detected by TEPITOPEpan, examining the corresponding literature of immunology. Its online server and PSSMs therein are available at http://www.biokdd.fudan.edu.cn/Service/TEPITOPEpan/.
Project description:Spillage of gallstones into the abdominal cavity, referred to as "dropped gallstones" (DGs), occurs commonly during laparoscopic cholecystectomy. The majority of these spilled stones remain clinically silent; however, if uncomplicated DGs are not correctly identified on subsequent imaging, they may mimic peritoneal implants and cause unduly concern. A small percentage of DGs cause complications, including abscess and fistula formation. Recognising the DG within the abscess is critical for definitive treatment. This pictorial review illustrates the imaging appearances and complications of DGs on CT, MRI and ultrasound and emphasises pitfalls in diagnosis.
Project description:Background:High adrenergic tone appears to be associated with mortality in septic shock, while adrenergic antagonism may improve survival. In preparation for a randomized trial, we conducted a prospective, single-arm pilot study of esmolol infusion for patients with septic shock and tachycardia that persists after adequate volume expansion. Methods:From April 2016 to March 2017, we enrolled patients admitted to an intensive care unit with sepsis who were receiving vasopressor infusion and were tachycardic despite adequate volume expansion. All patients received a continuous intravenous infusion of esmolol, targeted to heart rate 80-90/min, while receiving vasopressors. The feasibility outcomes were proportion of eligible patients consented, compliance with pre-infusion safety check, and compliance with the titration protocol. The primary clinical outcome was organ-failure-free days (OFFD) at 28 days. Results:We enrolled 7 of 10 eligible patients. Mean age was 46 (±?19) years, and mean admission APACHE II was 28 (±?8). Median norepinephrine infusion rate at the initiation of esmolol infusion was 0.20 (0.14-0.23) ?g/kg/min. Compliance with the safety check was 100%; compliance with components of the titration protocol was 98-100%. OFFD were 26 (24.5-26); all patients survived to day 90. Median peak esmolol infusion was 50 (25-50) ?g/kg/min. Median peak norepinephrine infusion rate during esmolol infusion was 0.46 (0.13-0.50) ?g/kg/min. Four patients achieved target heart rate. Protocol-defined stop events, suggesting possible intolerance to a given infusion rate, occurred in three patients, all of whom were receiving at least 50 ?g/kg/min of esmolol. Conclusions:In a pilot, single-arm study, we report the first published experience with esmolol infusion in tachycardic patients with septic shock in the United States. These findings support a phase 2 trial of esmolol infusion for septic shock. Lower infusion rates of esmolol infusion may be better tolerated and more feasible than higher infusion rates for such a trial. Trial registration:This study was retrospectively registered at ClinicalTrials.gov (NCT02841241) on 19 July 2016.