Regenerative Metaplastic Clones in COPD Lung Drive Inflammation and Fibrosis.

Chronic obstructive pulmonary disease (COPD) is a progressive condition of chronic bronchitis, small airway obstruction, and emphysema that represents a leading cause of death worldwide. While inflammation, fibrosis, mucus hypersecretion, and metaplastic epithelial lesions are hallmarks of this disease, their origins and dependent relationships remain unclear. Here we apply single-cell cloning technologies to lung tissue of patients with and without COPD. Unlike control lungs, which were dominated by normal distal airway progenitor cells, COPD lungs were inundated by three variant progenitors epigenetically committed to distinct metaplastic lesions. When transplanted to immunodeficient mice, these variant clones induced pathology akin to the mucous and squamous metaplasia, neutrophilic inflammation, and fibrosis seen in COPD. Remarkably, similar variants pre-exist as minor constituents of control and fetal lung and conceivably act in normal processes of immune surveillance. However, these same variants likely catalyze the pathologic and progressive features of COPD when expanded to high numbers.

Epigenetic regulation during cancer transitions across 11 tumour types.

Chromatin accessibility is essential in regulating gene expression and cellular identity, and alterations in accessibility have been implicated in driving cancer initiation, progression and metastasis1-4. Although the genetic contributions to oncogenic transitions have been investigated, epigenetic drivers remain less understood. Here we constructed a pan-cancer epigenetic and transcriptomic atlas using single-nucleus chromatin accessibility data (using single-nucleus assay for transposase-accessible chromatin) from 225 samples and matched single-cell or single-nucleus RNA-sequencing expression data from 206 samples. With over 1 million cells from each platform analysed through the enrichment of accessible chromatin regions, transcription factor motifs and regulons, we identified epigenetic drivers associated with cancer transitions. Some epigenetic drivers appeared in multiple cancers (for example, regulatory regions of ABCC1 and VEGFA; GATA6 and FOX-family motifs), whereas others were cancer specific (for example, regulatory regions of FGF19, ASAP2 and EN1, and the PBX3 motif). Among epigenetically altered pathways, TP53, hypoxia and TNF signalling were linked to cancer initiation, whereas oestrogen response, epithelial-mesenchymal transition and apical junction were tied to metastatic transition. Furthermore, we revealed a marked correlation between enhancer accessibility and gene expression and uncovered cooperation between epigenetic and genetic drivers. This atlas provides a foundation for further investigation of epigenetic dynamics in cancer transitions.

Microfluidics for Electrochemical Energy Conversion.

Electrochemical energy conversion is an important supplement for storage and on-demand use of renewable energy. In this regard, microfluidics offers prospects to raise the efficiency and rate of electrochemical energy conversion through enhanced mass transport, flexible cell design, and ability to eliminate the physical ion-exchange membrane, an essential yet costly element in conventional electrochemical cells. Since the 2002 invention of the microfluidic fuel cell, the research field of microfluidics for electrochemical energy conversion has expanded into a great variety of cell designs, fabrication techniques, and device functions with a wide range of utility and applications. The present review aims to comprehensively synthesize the best practices in this field over the past 20 years. The underlying fundamentals and research methods are first summarized, followed by a complete assessment of all research contributions wherein microfluidics was proactively utilized to facilitate energy conversion in conjunction with electrochemical cells, such as fuel cells, flow batteries, electrolysis cells, hybrid cells, and photoelectrochemical cells. Moreover, emerging technologies and analytical tools enabled by microfluidics are also discussed. Lastly, opportunities for future research directions and technology advances are proposed.

Not all roads lead to the immune system: the genetic basis of multiple sclerosis severity.

Multiple sclerosis is a leading cause of neurological disability in adults. Heterogeneity in multiple sclerosis clinical presentation has posed a major challenge for identifying genetic variants associated with disease outcomes. To overcome this challenge, we used prospectively ascertained clinical outcomes data from the largest international multiple sclerosis registry, MSBase. We assembled a cohort of deeply phenotyped individuals of European ancestry with relapse-onset multiple sclerosis. We used unbiased genome-wide association study and machine learning approaches to assess the genetic contribution to longitudinally defined multiple sclerosis severity phenotypes in 1813 individuals. Our primary analyses did not identify any genetic variants of moderate to large effect sizes that met genome-wide significance thresholds. The strongest signal was associated with rs7289446 (ß = -0.4882, P = 2.73 × 10-7), intronic to SEZ6L on chromosome 22. However, we demonstrate that clinical outcomes in relapse-onset multiple sclerosis are associated with multiple genetic loci of small effect sizes. Using a machine learning approach incorporating over 62 000 variants together with clinical and demographic variables available at multiple sclerosis disease onset, we could predict severity with an area under the receiver operator curve of 0.84 (95% CI 0.79-0.88). Our machine learning algorithm achieved positive predictive value for outcome assignation of 80% and negative predictive value of 88%. This outperformed our machine learning algorithm that contained clinical and demographic variables alone (area under the receiver operator curve 0.54, 95% CI 0.48-0.60). Secondary, sex-stratified analyses identified two genetic loci that met genome-wide significance thresholds. One in females (rs10967273; ßfemale = 0.8289, P = 3.52 × 10-8), the other in males (rs698805; ßmale = -1.5395, P = 4.35 × 10-8), providing some evidence for sex dimorphism in multiple sclerosis severity. Tissue enrichment and pathway analyses identified an overrepresentation of genes expressed in CNS compartments generally, and specifically in the cerebellum (P = 0.023). These involved mitochondrial function, synaptic plasticity, oligodendroglial biology, cellular senescence, calcium and G-protein receptor signalling pathways. We further identified six variants with strong evidence for regulating clinical outcomes, the strongest signal again intronic to SEZ6L (adjusted hazard ratio 0.72, P = 4.85 × 10-4). Here we report a milestone in our progress towards understanding the clinical heterogeneity of multiple sclerosis outcomes, implicating functionally distinct mechanisms to multiple sclerosis risk. Importantly, we demonstrate that machine learning using common single nucleotide variant clusters, together with clinical variables readily available at diagnosis can improve prognostic capabilities at diagnosis, and with further validation has the potential to translate to meaningful clinical practice change.

Mycorrhizal colonization and Streptomyces viridosporus HH1 synergistically up-regulate the polyphenol biosynthesis genes in wheat against stripe rust.

BACKGROUND: Stripe rust is considered one of the most devastating diseases of wheat all over the world, resulting in a high loss in its production. In this study, time-course changes in expression of the polyphenol biosynthesis pathways genes in wheat against stripe rust were investigated. The defense mechanisms triggered by mycorrhizal colonization and/or spraying with Streptomyces viridosporus HH1 against this disease were also investigated. RESULTS: Results obtained revealed that C3H, which is considered the key gene in lignin biosynthesis, was the most expressed gene. Furthermore, most of the chlorogenic acid and flavonoid biosynthesis genes were also overexpressed. Volcano plots of the studied genes reveal that the dual treatment led to a high significant overexpression of 10 out of the 13 studied genes. Heatmap of these genes showed that the most frequent expressed gene in response to all applied treatments along the study period was DFR, the key gene in the biosynthesis of anthocyanidins. Gene co-expression network of the studied genes showed that HQT was the most central gene with respect to the other genes, followed by AN2 and DFR, respectively. Accumulation of different flavonoids and phenolic acids were detected in response to the dual treatment, in particular, cinnamic acid, coumarin, and esculetin, which recorded the highest elevation level recording 1000, 488.23, and 329.5% respectively. Furthermore, results from the greenhouse experiment showed that application of the dual treatment led to an 82.8% reduction in the disease severity, compared with the control treatment. CONCLUSIONS: We can conclude that the biosynthesis of lignin, chlorogenic acid, and flavonoids contributed to the synergistic triggering effect of the dual treatment on wheat resistance to stripe rust.

Techniques improving electrical cardioversion success for patients with atrial fibrillation: a systematic review and meta-analysis.

AIMS: Electrical cardioversion is commonly used to restore sinus rhythm in patients with atrial fibrillation (AF), but procedural technique and clinical success vary. We sought to identify techniques associated with electrical cardioversion success for AF patients. METHODS AND RESULTS: We searched MEDLINE, EMBASE, CENTRAL, and the grey literature from inception to October 2022. We abstracted data on initial and cumulative cardioversion success. We pooled data using random-effects models. From 15 207 citations, we identified 45 randomized trials and 16 observational studies. In randomized trials, biphasic when compared with monophasic waveforms resulted in higher rates of initial [16 trials, risk ratio (RR) 1.71, 95% CI 1.29-2.28] and cumulative success (18 trials, RR 1.10, 95% CI 1.04-1.16). Fixed, high-energy (≥200 J) shocks when compared with escalating energy resulted in a higher rate of initial success (four trials, RR 1.62, 95% CI 1.33-1.98). Manual pressure when compared with no pressure resulted in higher rates of initial (two trials, RR 2.19, 95% CI 1.21-3.95) and cumulative success (two trials, RR 1.19, 95% CI 1.06-1.34). Cardioversion success did not differ significantly for other interventions, including: antero-apical/lateral vs. antero-posterior positioned pads (initial: 11 trials, RR 1.16, 95% CI 0.97-1.39; cumulative: 14 trials, RR 1.01, 95% CI 0.96-1.06); rectilinear/pulsed biphasic vs. biphasic truncated exponential waveform (initial: four trials, RR 1.11, 95% CI 0.91-1.34; cumulative: four trials, RR 0.98, 95% CI 0.89-1.08) and cathodal vs. anodal configuration (cumulative: two trials, RR 0.99, 95% CI 0.92-1.07). CONCLUSIONS: Biphasic waveforms, high-energy shocks, and manual pressure increase the success of electrical cardioversion for AF. Other interventions, especially pad positioning, require further study.

Effect of osteoarthritis on alveolar bone loss in experimental periodontitis in rats.

BACKGROUND: There is scarce information about the relationship between periodontal disease and osteoarthritis. This study investigated the effect of surgically induced osteoarthritis on alveolar bone loss in experimental periodontitis in rats. METHODS: 12 rats were divided into test and control groups. On day 1, the animals were anaesthetized, and silk ligatures were ligated around 6 maxillary posterior teeth in each animal from both groups. Surgical induction of osteoarthritis was performed on the left knees in the test group. No knee surgeries were performed in the control group. The ligatures were kept in place for 30 days, at which time the animals were euthanatized, and the maxillae and knee joints were harvested and processed for histological analysis. The alveolar bone loss was assessed using a zoom stereomicroscope. RESULTS: The knee joint histologic sections of the control group showed normal joint features, whereas in the test group there were substantial changes typical of osteoarthritis, including wide joint spaces, prominent monocytic infiltration of the synovium, invasion of periarticular bone, and decreased chondrocyte density. Comparison of the bone height between the groups showed a significantly higher bone loss in the test than in the control group The marginal mean bone height, adjusted for covariates and the intraclass correlation between sites, was 1.19 and 0.78 mm in the test and control groups, respectively (p < .0001). CONCLUSIONS: Surgically induced osteoarthritis leads to greater alveolar bone loss in the experimental periodontitis model in rats.

Artemisia annua Extract Attenuate Doxorubicin-Induced Hepatic Injury via PI-3K/Akt/Nrf-2-Mediated Signaling Pathway in Rats.

Doxorubicin (DOX), which is used to treat cancer, has harmful effects that limit its therapeutic application. Finding preventative agents to thwart DOX-caused injuries is thus imperative. Artemisia annua has numerous biomedical uses. This study aims to investigate the attenuative effect of Artemisia annua leaf extract (AALE) treatment on DOX-induced hepatic toxicity in male rats. A phytochemical screening of AALE was evaluated. Forty male rats were used; G1 was a negative control group, G2 was injected with AALE (150 mg/kg) intraperitoneally (i.p) daily for a month, 4 mg/kg of DOX was given i.p to G3 once a week for a month, and G4 was injected with DOX as G3 and with AALE as G2. Body weight changes and biochemical, molecular, and histopathological investigations were assessed. The results showed that AALE contains promising phytochemical constituents that contribute to several potential biomedical applications. AALE mitigated the hepatotoxicity induced by DOX in rats as evidenced by restoring the alterations in the biochemical parameters, antioxidant gene expression, and hepatic histopathological alterations in rats. Importantly, the impact of AALE against the hepatic deterioration resulting from DOX treatment is through activation of the PI-3K/Akt/Nrf-2 signaling, which in turn induces the antioxidant agents.

Pre-treatment with antiarrhythmic drugs for elective electrical cardioversion of atrial fibrillation: a systematic review and network meta-analysis.

AIMS: Our objective was to compare the efficacy of pre-treatment with different classes of anti-arrhythmic drugs (AADs) in patients with atrial fibrillation (AF) undergoing electrical cardioversion. METHODS AND RESULTS: We performed a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing different AADs in patients with AF undergoing electrical cardioversion. We grouped AADs into five network nodes: no treatment or rate control, Class Ia, Class Ic, Class III, and amiodarone. Outcomes were (i) acute restoration and (ii) maintenance of sinus rhythm. We searched MEDLINE and EMBASE from inception until June 2020. We used Python 3.8.3 and R 3.6.2 for data analysis. We evaluated the overall certainty of evidence with the GRADE framework. We included 28 RCTs. Compared with no treatment or rate control, Class III AADs [odds ratio (OR): 2.41; 95% credible interval (CrI): 1.37 to 4.62, high certainty] and amiodarone (OR: 2.58; 95% CrI: 1.54 to 4.37, high certainty) improved restoration of sinus rhythm. Amiodarone improved long-term maintenance of sinus rhythm when compared with no treatment or rate control (OR: 5.37; 95% CrI: 4.00-7.39, high certainty), Class Ic (OR: 1.89; 95% CrI: 1.05-3.45, moderate certainty) and Class III AADs (OR: 2.19; 95% CrI: 1.39-3.26, high certainty). CONCLUSION: Before electrical cardioversion of AF, treatment with Class III AADs or amiodarone improves the acute restoration of sinus rhythm. Amiodarone is most likely to improve the maintenance of sinus rhythm after electrical cardioversion, but Class Ic and Class III AADs are also effective.

Visual health and prevalence of dry eye syndrome among university students in Iraq and Jordan.

Dry eye syndrome (DES), is a multifactorial disease that affects the ocular surface and contributes to the ocular symptoms. The COVID-19 pandemic influenced the general population and university students' health in different ways. The pandemic forced many people including university students around the world to use virtual platforms on their digital devices, such as computers and smartphones, to work from a distance. This study aimed to explore the visual health and prevalence of dry eye syndrome among university students in Iraq and Jordan. This was a cross-sectional study that was conducted in Iraq and Jordan using online questionnaire tool for the duration between November 2021 and January 2022. University students in Jordan and Iraq were invited to participate in this study and formed the study population. No restrictions on study level or field of study were applied. A previously developed and validated questionnaire tools were used in this study (National Eye Institute Visual Functioning Questionnaire - 25 (VFQ-25) and the Women's Health Study Questionnaire (WHS), which was developed by Schaumberg et al.). A total of 1,431 university students were involved in this study (1,018 students from Iraq, 71.1%). Around one third the study participants (29.0%) reported that have been diagnosed by a clinician as having dry eye syndrome. Around15.3% of the total study participants reported that they feel their eyes are dry (not wet enough) and 17.3% reported that they feel their eyes are irritated. Based on Women's Health Study Questionnaire (WHS) criteria, a total of 479 participants (33.4%) are symptomatically diagnosed with DES. Students aged 27-29 years, those at their fifth year of study, and those who wear contact lenses are at higher risk of developing DYS compared to others. Dry eye syndrome is common health problem among university students. Further studies are required to identify other risk factors associated with DES. Future research should focus on identifying strategies that could help reduce the risk of developing DES as a result of the inevitability of long-term use of digital devices among many categories of society, including university students.

Single-dose oral anti-arrhythmic drugs for cardioversion of recent-onset atrial fibrillation: a systematic review and network meta-analysis of randomized controlled trials.

AIMS: Single oral dose anti-arrhythmic drugs (AADs) are used to cardiovert recent-onset atrial fibrillation (AF); however, the optimal agent is uncertain. METHODS: We performed a systematic review and network meta-analysis of randomized trials testing single oral dose AADs vs. any comparator to cardiovert AF <7 days duration. We searched MEDLINE, Embase, and CENTRAL to April 2020. The primary outcome was successful cardioversion at timepoint nearest 8 h after administration. RESULTS: From 12 712 citations, 22 trials (2320 patients) were included. Thirteen trials included patients with some degree of heart failure; 19 included patients with some degree of ischaemic heart disease vs. placebo or rate-control (32% success) at 8 h, flecainide [73%, network odds ratio (OR) 7.6, 95% credible interval (CrI) 4.4-14.0], propafenone (70%, OR 4.6, CrI 2.9-7.3), and pilsicainide (59%, OR 10.0, CrI 1.8-69.0), but not amiodarone (28%, OR 1.0, CrI 0.4-2.8) were superior. Flecainide (OR 7.5, CrI 2.6-24.0) and propafenone (OR 4.5, CrI 1.6-13.0) were superior to amiodarone; propafenone vs. flecainide did not statistically differ (OR 0.6, CrI 0.3-1.1). At longest follow-up, amiodarone was superior to placebo (OR 11.0, CrI 3.2-41.0), flecainide vs. amiodarone (OR 0.79, CrI 0.19-3.1), and propafenone vs. amiodarone (OR 0.36, CrI 0.092-1.4) were not statistically different, and flecainide was superior to propafenone (OR 2.2, CrI 1.1-4.8). Atrial and ventricular tachyarrhythmias, bradyarrhythmias, and hypotension were rare with PO AADs. CONCLUSION: Single oral dose Class 1C AADs are effective and safe for cardioversion of recent-onset AF. Flecainide may be superior to propafenone. Amiodarone is a slower acting alternative.

Incidence and recurrence of new-onset atrial fibrillation detected during hospitalization for non-cardiac surgery: a systematic review and meta-analysis.

PURPOSE: This systematic review aimed to summarize reports of the incidence and long-term recurrence of new-onset atrial fibrillation (AF) associated with non-cardiac surgery. SOURCES: We searched CENTRAL, MEDLINE and EMBASE from inception to November 2019. We included studies that reported on the incidence of new-onset perioperative AF during hospitalization for non-cardiac surgery and/or AF recurrence in such patients following discharge. Reviewers screened articles and abstracted data independently and in duplicate. We assessed study quality by appraising methodology for collecting AF history, incident AF during hospitalization, and AF recurrence after discharge. PRINCIPAL FINDINGS: From 39,233 citations screened, 346 studies that enrolled a total of 5,829,758 patients met eligibility criteria. Only 27 studies used prospective, continuous inpatient electrocardiographic (ECG) monitoring to detect incident AF. Overall, the incidence of postoperative AF during hospitalization ranged from 0.004 to 50.3%, with a median [interquartile range] of 8.7 [3.8-15.0]%. Atrial fibrillation incidence varied with type of surgery. Prospective studies using continuous ECG monitoring reported significantly higher incidences of AF than those that did not (13.9% vs 1.9%, respectively; P < 0.001). A total of 13 studies (25,726 patients) with follow-up up to 5.4 years reported on AF recurrence following hospital discharge; only one study used a prospective systematic monitoring protocol. Recurrence rates ranged from 0 to 37.3%. CONCLUSIONS: Rates of AF incidence first detected following non-cardiac surgery and long-term AF recurrence vary markedly. Differences in the intensity of ECG monitoring and type of surgery may account for this variation. TRIAL REGISTRATION: PROSPERO (CRD42017068055); registered 1 September 2017.

RéSUMé: OBJECTIF: Cette revue systématique visait à résumer les comptes rendus sur l'incidence et la récurrence à long terme de la fibrillation auriculaire (FA) de novo associée à une chirurgie non cardiaque. SOURCES: Nous avons effectué des recherches dans les bases de données CENTRAL, MEDLINE et EMBASE de leur création à novembre 2019. Nous avons inclus les études ayant examiné l'incidence de nouvelle FA périopératoire pendant l'hospitalisation pour une chirurgie non cardiaque et/ou la récurrence de la FA chez de tels patients après leur congé. Les chercheurs ont passé en revue les articles et les données extraites de manière indépendante et en double. Nous avons estimé la qualité des études en évaluant la méthodologie de collecte des antécédents de FA, de l'incident de FA pendant l'hospitalisation et de la récurrence de FA après le congé. CONSTATATIONS PRINCIPALES: Sur les 39 233 citations examinées, 346 études portant sur un total de 5 829 758 patients ont répondu à nos critères d'admissibilité. Seulement 27 études ont utilisé un monitorage électrocardiographique (ECG) continu prospectif et des patients hospitalisés pour détecter les incidents de FA. Dans l'ensemble, l'incidence de FA postopératoire pendant l'hospitalisation allait de 0,004 à 50,3 %, avec une médiane [écart interquartile] de 8,7 [3,8-15,0] %. L'incidence de fibrillation auriculaire variait en fonction du type de chirurgie. Des études prospectives utilisant un monitorage continu par ECG ont fait état d'incidences significativement plus élevées de FA que celles sans monitorage continu (13,9 % vs 1,9 %, respectivement; P < 0,001). Au total, 13 études (25 726 patients) avec un suivi allant jusqu'à 5,4 ans ont rapporté leurs données sur la récurrence de FA après le congé de l'hôpital; seule une étude a utilisé un protocole de monitorage prospectif systématique. Les taux de récurrence allaient de 0 à 37,3 %. CONCLUSION: Les taux d'incidence de nouvelle FA détectés après une chirurgie non cardiaque et la récurrence à long terme de FA varient considérablement. Les différences du degré de monitorage par ECG et le type de chirurgie pourraient expliquer cette variation. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42017068055); enregistrée le 1er septembre 2017.

Saliva as a comparable-quality source of DNA for Whole Exome Sequencing on Ion platforms.

BACKGROUND: Whole Exome Sequencing (WES) utilises overlapping fragments prone to sequencing artefacts. Saliva, a non-invasive source of DNA, has been successfully used in WES studies on various platforms. This study explored the validity and quality of DNA sourced from saliva compared to whole blood on an Ion Platform. METHODS: DNA was extracted from both sample types from four individuals. WES, performed on the Ion Proton platform was assessed for quality metrics (Depth, Genotyping Quality, etc.) and variant identification for the same source sample-pairs. RESULTS: No significant differences in quality metrics were identified between data obtained from whole blood and saliva samples, with several saliva samples demonstrating higher coverage depth. Variants within the same sample, from the two genomic DNA sources, had an average concordance similar to other studies and platforms with different chemistry. CONCLUSION: Saliva-extracted DNA provides comparable sequencing quality to whole blood for WES on Ion Torrent Platforms.

Treatment of Recurrent Respiratory Papillomatosis: Case Series and Review of Technique.

Adult Recurrent Respiratory Papillomatosis (RRP) is a rare disease caused by the human papilloma virus in which papilloma grows from the respiratory epithelium. Patients can suffer from significant respiratory distress secondary to tracheal or bronchial obstruction by papilloma and the mainstay of treatment is bronchoscopic debridement. There are a variety of techniques to resect the endoluminal tumor, including CO2 or YAG laser, argon plasma coagulation, microdebrider and cold forceps. There have been documented cases of healthcare workers contracting HPV after exposure to surgical smoke during ablation of papilloma and measures should be taken to avoid inhalation of the smoke plume. For proximal lesions that are accessible to a microdebrider, this appears to be a safe and effective technique that does not generate heat or surgical smoke. The rate of recurrence of adult-onset respiratory papilloma after initial debulking varies and adjuvant medical therapy including intralesional cidofovir, interferon, or oral indole-3-carbinol has been used to slow recurrence. Malignant transformation of adult-onset RRP to squamous cell carcinoma has been reported to occur in 3-7% of cases. Therefore, ongoing surveillance is needed to monitor for disease progression and malignant transformation. Here we describe three patients whose tracheal disease was managed with an Nd-YAG laser and microdebrider. One patient was treated with adjuvant systemic indole-3 carbinol and another was maintained with serial debridement only. The third patient presented with obstructing squamous cell carcinoma of the trachea and was treated with definitive chemoradiation. She presented with a new left mainstem lesion 6 months later which was diagnosed as RRP. She was started on indole-3 carbinol, but unfortunately it transformed to squamous cell carcinoma 8 months later.

Safety of Laser and Thermal Therapy During Rigid Bronchoscopy Using Manual Hand Jet Ventilation.

INTRODUCTION: Thermal ablative therapies (laser, radiofrequency ablation, electrocautery, argon plasma coagulation) are often used during rigid bronchoscopy for the treatment of central airway obstructions (CAO). An airway fire is a feared complication that can occur during endobronchial thermal ablation. MATERIALS AND METHODS: This was a single-center, retrospective, observational study. A total of 175 patients were reviewed undergoing rigid bronchoscopy in the operating room and bronchoscopy suite requiring manual hand jet ventilation and thermal therapy between September 2014 and September 2018. The study objective was to determine the safety of manual hand jet ventilation during endobronchial thermal therapies with rigid bronchoscopy. RESULTS: Over a five-year period, 175 patients underwent endobronchial thermal therapy during rigid bronchoscopy with manual hand jet ventilation for the treatment CAOs. Immediately prior to thermal therapy activation, jet ventilation was paused. No incidences (0/175) of airway fires occurred despite immediate delivery of thermal energy following a jet ventilation hold. CONCLUSIONS: Results of our study show that performing thermal ablative therapy during rigid bronchoscopy with jet ventilation using a breath-hold technique is safe.

Repetitive Transcranial Magnetic Stimulation For The Treatment of Chronic Tinnitus: A Preliminary Study of The Influence of Traumatic Brain Injury on Treatment Response.

This study aims to test whether the efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) differs between patients who developed tinnitus following a traumatic brain injury (TBI), and those without a history of TBI. This was a parallel pilot, open-label, non-randomized, clinical trial to compare the efficacy of low frequency rTMS on tinnitus symptoms in patients with and without a TBI history. Patients with moderate to severe tinnitus symptoms based on the Tinnitus Handicap Inventory (THI) and the Tinnitus Functional Index (TFI) were enrolled in the study. Validated questionnaires (THI and TFI) were used to quantify the severity of tinnitus symptoms and hearing impairment (Hearing Handicap Index - HHI) before and after ten sessions of rTMS of the left primary auditory cortex. Hearing threshold levels as well as speech reception and speech discrimination thresholds were also compared. The number of patients who experienced a reduction in their subjective tinnitus symptoms was greater and sustained longer in patients without a history of TBI. The same was seen with subjective symptoms of hearing impairment. In conclusion, our preliminary results suggest tinnitus patients without a history of TBI respond better to low frequency rTMS than those with a history of TBI, suggesting that treatments could be more effective if tailored to tinnitus etiology.

Bronchoscope-Guided Percutaneous Endoscopic Gastrostomy Tube Placement by Interventional Pulmonologists: A Feasibility and Safety Study.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) tube placement is a procedure frequently done in the intensive care unit. The use of a traditional endoscope can be difficult in cases of esophageal stenosis and theoretically confers an increased risk of infection due to its complex architecture. We describe a technique using the bronchoscope, which allows navigation through stenotic esophageal lesions and also minimizes the risk of endoscopy-associated infections. METHODS: Prospective series of patients who had PEG tube placement guided by a bronchoscope. Procedural outcomes including successful placement, duration of the entire procedure, time needed for passage of the bronchoscope from the oropharynx to the major curvature, PEG tube removal rate, and mortality were collected. Procedural adverse events, including infections and long-term PEG-related complications, were recorded. RESULTS: A total of 84 patients underwent bronchoscope-guided PEG tube placement. Percutaneous endoscopic gastrostomy tube insertion was completed successfully in 82 (97.6%) patients. Percutaneous endoscopic gastrostomy tube placement was performed immediately following percutaneous tracheostomy in 82.1%. Thirty-day mortality and 1-year mortality were 11.9% and 31%, respectively. Overall, minor complications occurred in 2.4% of patients, while there were no major complications. No serious infectious complications were identified and no endoscope-associated hospital acquired infections were documented. CONCLUSIONS: The use of the bronchoscope can be safely and effectively used for PEG tube placement. The use of bronchoscope rather than a gastroscope has several advantages, which include the ease of navigating through complex aerodigestive disorders such as strictures and fistulas as well as decreased health-care utilization. In addition, it may have a theoretical advantage of minimizing infections related to complex endoscopes.

Adjuvant ß-Lactam Therapy Combined with Vancomycin for Methicillin-Resistant Staphylococcus aureus Bacteremia: Does ß-Lactam Class Matter?

We analyzed the impact of vancomycin (VAN) combined with adjuvant ß-lactam therapy (Combo) on persistent (≥5 days) methicillin-resistant Staphylococcus aureus bacteremia versus VAN alone by using pooled data from two previously published observational studies (n = 156). Combo was inversely associated with persistent bacteremia (adjusted odds ratio, 0.460; 95% confidence interval, 0.229 to 0.923). Acute kidney injury was more common with Combo than with VAN (18.9% and 7.6%, respectively; P = 0.062).

Atrial fibrillation in elderly patients with implantable loop recorders for unexplained syncope.

BACKGROUND: An implantable loop recorder (ILR) assists in the diagnosis of unexplained syncope and atrial fibrillation (AF). Both become prevalent with age. Limited data exist describing the incidence of AF as the diagnostic rhythm underlying syncope in the elderly. This study aims to report the incidence of AF in older adults with ILRs for unexplained syncope and identify clinical characteristics associated with AF in this population. METHODS: Retrospective observational study on patients with unexplained syncope seen in syncope clinics from two Canadian centers. Participants were ≥65 years old, without a history of AF, and received an ILR for unexplained syncope. Data were collected from patient's clinic charts. Arrhythmia diagnosis was based on ILR electrocardiogram reading during syncope (symptom-rhythm correlation). Fisher's exact test and the Student's t test were used to compare participants with and without AF. RESULTS: In our cohort of 222 patients, 124 were females and 98 were males. Mean age at implant was 80 ± 8 years. Arrhythmia was diagnosed in 98 patients (44.1%). Median time to diagnosis was 18 months. AF was diagnosed in 17 (7.7%) participants. There were fewer males in the AF group than the no AF group (11.8%, 46.8%, p = 0.01). Age, baseline EKG, and prevalence of hypertension, diabetes, stroke, or ischemic heart disease were not statistically different between patients with AF and without AF. CONCLUSIONS: Atrial fibrillation was a common diagnostic rhythm in this cohort of adults, aged 65 and older, with ILRs for unexplained syncope. It was observed more frequently in females.