Transtracheal Pressure for Evaluation of Decannulation Readiness.

BACKGROUND: Pediatric tracheostomy decannulation protocols vary among institutions and may include toleration of Passy Muir Valve (PMV), microlaryngoscopy and bronchoscopy (MLB) findings, and polysomnography evaluation. Transtracheal pressure (TTP) is an objective measurement utilized to evaluate PMV toleration. We aimed to investigate the role of TTP in decannulation candidates and compare TTP measurements with polysomnography and MLB findings. METHODS: A retrospective cohort study of children who underwent TTP measurement during PMV trial between December 2012 and November 2022. RESULTS: A total of 79 patients underwent TTP measurement and MLB evaluation; of these, 16 (20.3%) patients had a capped polysomnography. Twenty-eight (35.4%) patients had TTPs ≤10 cm H2O, and 51 (64.6%) patients had TTPs >10 cm H2O. The most common indication for tracheostomy was upper airway obstruction (n = 41, 51.9%), followed by a need for mechanical ventilation (n = 24, 30.4%). Twenty-five (31.6%) patients were decannulated. Patients with TTPs ≤10 cm H2O had a mean Apnea-Hypopnea Index of 0.17 ± 0.26/h compared with 6.93 ± 7.67/h in those with TTPs >10 cm H2O, p = 0.0365. Patients with TTPs >10 cm H2O were found to have a significantly higher occurrence of airway obstruction (96.1% vs. 46.4%, p < 0.0001) and multilevel airway obstruction (70.6% vs. 21.4%, p < 0.0001) on MLB. Neither TTP measured at time of PMV assessment nor capped polysomnography was associated with successful decannulation. CONCLUSIONS: TTP measurements at time of PMV evaluation are associated with polysomnography and MLB findings. One-time PMV measurements were not indicative of decannulation success. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3377-3383, 2024.

Pharmacological modelling of dissociation and psychosis: an evaluation of the Clinician Administered Dissociative States Scale and Psychotomimetic States Inventory during nitrous oxide ('laughing gas')-induced anomalous states.

RATIONALE: A significant obstacle to an improved understanding of pathological dissociative and psychosis-like states is the lack of readily implemented pharmacological models of these experiences. Ketamine has dissociative and psychotomimetic effects but can be difficult to use outside of medical and clinical-research facilities. Alternatively, nitrous oxide (N2O) - like ketamine, a dissociative anaesthetic and NMDAR antagonist - has numerous properties that make it an attractive alternative for modelling dissociation and psychosis. However, development and testing of such pharmacological models relies on well-characterized measurement instruments. OBJECTIVES: To examine the factor structures of the Clinician Administered Dissociative States Scale (CADSS) and Psychotomimetic States Inventory (PSI) administered during N2O inhalation in healthy volunteers. METHODS: Secondary analyses of data pooled from three previous N2O studies with healthy volunteers. RESULTS: Effect sizes for N2O-induced dissociation and psychotomimesis were comparable to effects reported in experimental studies with sub-anaesthetic ketamine in healthy volunteers. Although, like ketamine, a three-factor representation of N2O-induced dissociation was confirmed, and a more parsimonious two-factor model might be more appropriate. Bayesian exploratory factor analysis suggested that N2O-induced psychosis-like symptoms were adequately represented by two negative and two positive symptom factors. Hierarchical cluster analysis indicated minimal item overlap between the CADSS and PSI. CONCLUSION: N2O and ketamine produce psychometrically similar dissociative states, although parallels in their psychosis-like effects remain to be determined. The CADSS and PSI tap largely non-overlapping experiences under N2O and we propose the use of both measures (or similar instruments) to comprehensively assess anomalous subjective states produced by dissociative NMDAR antagonists.

QRS morphology in lead V1 for the rapid localization of idiopathic ventricular arrhythmias originating from the left ventricular papillary muscles: A novel electrocardiographic criterion.

BACKGROUND: Twelve-lead electrocardiogram (ECG) criteria have been developed to identify idiopathic ventricular arrhythmias (VAs) from the left ventricular (LV) papillary muscles (PAPs), but accurate localization remains a challenge. OBJECTIVE: The purpose of this study was to develop ECG criteria for accurate localization of LV PAP VAs using lead V1 exclusively. METHODS: Consecutive patients undergoing mapping and ablation of VAs from the LV PAPs guided by intracardiac echocardiography from 2007 to 2018 were reviewed (study group). The QRS morphology in lead V1 was compared to patients with VAs with a "right bundle branch block" morphology from other LV locations (reference group). Patients with structural heart disease were excluded. RESULTS: One hundred eleven patients with LV PAP VAs (mean age 54 ± 16 years; 65% men) were identified, including 64 (55%) from the posteromedial PAP and 47 (42%) from the anterolateral PAP. The reference group included patients with VAs from the following LV locations: fascicles (n = 21), outflow tract (n = 36), ostium (n = 37), inferobasal segment (n = 12), and apex (5). PAP VAs showed 3 distinct QRS morphologies in lead V1 93% of the time: Rr (53%), R with a slurred downslope (29%), and RR (11%). Sensitivity, specificity, positive predictive value, and negative predictive value for the 3 morphologies combined are 93%, 98%, 98%, and 93%, respectively. The intrinsicoid deflection of PAP VAs in lead V1 was shorter than that of the reference group (63 ± 13 ms vs 79 ± 24 ms; P < .001). An intrinsicoid deflection time of <74 ms best differentiated the 2 groups (sensitivity 79%; specificity 87%). CONCLUSION: VAs originating from the LV PAPs manifest unique QRS morphologies in lead V1, which can aid in rapid and accurate localization.

High Proliferation Rate and a Compromised Spindle Assembly Checkpoint Confers Sensitivity to the MPS1 Inhibitor BOS172722 in Triple-Negative Breast Cancers.

BOS172722 (CCT289346) is a highly potent, selective, and orally bioavailable inhibitor of spindle assembly checkpoint kinase MPS1. BOS172722 treatment alone induces significant sensitization to death, particularly in highly proliferative triple-negative breast cancer (TNBC) cell lines with compromised spindle assembly checkpoint activity. BOS172722 synergizes with paclitaxel to induce gross chromosomal segregation defects caused by MPS1 inhibitor-mediated abrogation of the mitotic delay induced by paclitaxel treatment. In in vivo pharmacodynamic experiments, BOS172722 potently inhibits the spindle assembly checkpoint induced by paclitaxel in human tumor xenograft models of TNBC, as measured by inhibition of the phosphorylation of histone H3 and the phosphorylation of the MPS1 substrate, KNL1. This mechanistic synergy results in significant in vivo efficacy, with robust tumor regressions observed for the combination of BOS172722 and paclitaxel versus either agent alone in long-term efficacy studies in multiple human tumor xenograft TNBC models, including a patient-derived xenograft and a systemic metastasis model. The current target indication for BOS172722 is TNBC, based on their high sensitivity to MPS1 inhibition, the well-defined clinical patient population with high unmet need, and the synergy observed with paclitaxel.

First experience with zero-fluoroscopic ablation for supraventricular tachycardias using a novel impedance and magnetic-field-based mapping system.

AIMS: Zero- and near-zero-fluoroscopic ablation techniques reduce the harmful effects of ionizing radiation during invasive electrophysiology procedures. We aimed to test the feasibility and safety of a zero-fluoroscopic strategy using a novel integrated magnetic and impedance-based electroanatomical mapping system for radiofrequency ablation (RFA) of supraventricular tachycardias (SVTs). METHODS: We retrospectively studied 92 consecutive patients undergoing electrophysiology studies with/without RFA for supraventricular tachycardia (SVT) performed by a single operator at a single center. The first 42 (Group 1) underwent a conventional fluoroscopic-guided approach and the second 50 (Group 2) underwent a zero-fluoroscopic approach using the Ensite Precision™ 3-D magnetic and impedance-based mapping system (Abbott Inc). RESULTS: Group 1 comprised 14 AV-nodal re-entrant tachycardia (AVNRT), 12 typical atrial flutter, 4 accessory pathway (AP), 2 atrial tachycardia (AT), and 9 diagnostic EP studies (EPS). Group 2 comprised 16 AVNRT, 17 atrial flutter, 6 AP, 3 AT, 2 AV-nodal ablations, and 7 EPS. A complete zero-fluoroscopic approach was achieved in 94% of Group 2 patients. All procedures were acutely successful, and no complications occurred. There was a significant reduction in fluoroscopy dose, dose area product, and time (p < 0.0001, for all), with no difference in procedure times. Ablation time for typical atrial flutter was shorter in Group 2 (p = 0.006). CONCLUSIONS: A zero-fluoroscopic strategy for diagnosis and treatment of SVTs using this novel 3D-electroanatomical mapping system is feasible in majority of patients, is safe, reduces ionizing radiation exposure, and does not compromise procedural times, success rates, or complication rates.

Relationship of the lungs to the left atrium of particular relevance for ablation of atrial fibrillation.

BACKGROUND: Symptoms of possible lung and pleural injury such as chest pain and hemoptysis occur during and after radiofrequency ablation (RFA) and cryoablation (CA) of the left atrium (LA) for treatment of atrial fibrillation (AF). We determined the anatomical relationship of the lungs to the LA with particular reference to areas commonly targeted during AF ablation. METHODS: Distances from the LA endocardium to the lungs were measured from pre-procedure CT angiograms of 100 consecutive patients (71 males, age 60 ± 8 years) who underwent AF ablation. RESULTS: In 97% of the patients, the posterior right pulmonary vein antrum was <5 mm from the lower lobe of the right lung (RLL) over a supero-inferior distance of 3.6 ± 1.5 cm (minimum distance 1.2 ± 0.7 mm). The right inferior pulmonary vein (RIPV) ostium was <5 mm from the RLL in 94% (mean 2.7 ± 1.9 mm). The right superior pulmonary vein ostium was <5 mm from the RLL in 29% (mean 7.1 ± 3.8 mm). The medial segment of the right middle lobe was <5 mm from the carina between right pulmonary veins in 83% (mean 3.6 ± 1.9 mm). The mitral isthmus was <5 mm from the lingula in 5% (mean 9.4 ± 3.6 mm). The inferior lobe of the left lung was <5 mm from the posterior aspect of the ostia of the left inferior and superior pulmonary veins in 9 and 0%, respectively. The bronchi were <5 mm from the LA in 5%. CONCLUSIONS: The lungs are intimately related to sites of the LA commonly targeted during AF RFA. Whether this anatomical proximity translates into clinically significant potential for collateral lung damage during RFA merits further study.

Soluble epoxide hydrolase inhibition and peroxisome proliferator activated receptor γ agonist improve vascular function and decrease renal injury in hypertensive obese rats.

Cardiometabolic syndrome occurs with obesity and consists of pathophysiological factors that increase the risk for cardiovascular events. Soluble epoxide hydrolase inhibition (sEHi) is a novel therapeutic approach that exerts renal and cardiovascular protection. Although sEHi as a therapeutic approach is promising, it could be more effective for the treatment of cardiometabolic syndrome when combined with peroxisome proliferator activated receptor γ (PPARγ) agonists. We hypothesized that the PPARγ agonist, rosiglitazone in combination with a sEHi (tAUCB) will provide synergistic actions to decrease blood pressure, improve vascular function, decrease inflammation, and prevent renal damage in spontaneously hypertensive obese rats (SHROB). SHROB were treated with rosiglitazone, tAUCB or the combination of tAUCB and rosiglitazone for four-weeks and compared with spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Blood pressure increased in SHROB (164 ± 7 mmHg) and decreased 10 mmHg when treated with rosiglitazone, tAUCB, or tAUCB and rosiglitazone. Mesenteric artery dilation to the K(ATP) channel opener pinacidil was attenuated in SHROB (E(Max) = 77 ± 7%), compared with WKY (E(Max) = 115 ± 19) and SHR (E(Max) = 93 ± 12%). Vasodilation to pinacidil was improved by rosiglitazone (E(Max) = 92 ± 14%) but not tAUCB. Renal macrophage infiltration increased in SHROB and significantly decreased with rosiglitazone or tAUCB and rosiglitazone treatment. Albuminuria was increased in SHROB (90 ± 20 mg/d) and was significantly decreased by the combination of tAUCB and rosiglitazone (37 ± 9 mg/d). Glomerular injury in SHROB was also significantly decreased by tAUCB and rosiglitazone. These results indicate that even though sEHi or PPARγ agonist have benefits when used individually, the combination is more beneficial for the multidisease features in cardiometabolic syndrome.

A neurosurgical presentation of patent foramen ovale with atrial septal aneurysm.

We describe a case of cerebral abscess in a 53-year-old lady with a background of congenital heart defect. She has an atrial septal defect with atrial septal aneurysm, which remained undiagnosed until this clinical presentation. She presented with a short history of right-sided hemiplaegia and neuroimaging revealed a heterogeneous lesion in the left frontoparietal region. Neuronavigation-guided left frontoparietal craniotomy was performed to debulk the lesion and preoperatively frank pus was drained, which grew Streptococcus constellatus. She was successfully treated with antibiotics for 6 weeks and her clinical condition improved. We believe that the patients' previous dental extraction has possibly resulted in a paradoxical embolism through the atrial septal defect bypassing the pulmonary circulation. The MRI scan picture was misleading, as it was initially thought to be a high-grade brain tumour.

Wnts induce migration and invasion of myeloma plasma cells.

Multiple myeloma is an incurable form of lymphoid cancer characterized by accumulation of neoplastic plasma cells in the bone marrow cavity. Little is known about the mechanisms regulating myeloma cell movement within the bone marrow and metastasis to secondary sites. Herein, we identify multiple members of the wingless/int (Wnt) family as promoters of myeloma cell migration/invasion. Wnt-mediated migration was associated with the Wnt/RhoA pathway and did not necessitate signaling through beta-catenin. Activation of both RhoA and members of the protein kinase C (PKC) family, including PKCalpha, PKCbeta, and PKCmu, were required for induction of migration. Activated RhoA and PKCalpha, PKCbeta, and PKCmu appear to assemble in macromolecular signaling complexes that are associated with the cell membrane. These results suggest that Wnt responsiveness of myeloma plasma cells may be a significant factor in disease progression.