The Impact of Tracheal Stenosis on Distal Airway Pressure with Jet Ventilation.

OBJECTIVE: This study investigates the effects of tracheal stenosis on distal airway pressure during low-frequency jet ventilation (LFJV) in tracheal stenosis resection procedures, focusing on variables like stenosis size, depth, scope type, and inlet pressure. METHODS: A 3D-printed human airway model was employed, featuring inserted tracheal stenoses of varied sizes and depths. Distal airway pressure was measured with 16 pressure transducers, and data were processed via MATLAB. The study varied stenosis size, depth, scope type, and inlet pressure during five sequential jet bursts under LFJV. RESULTS: Using a subglottiscope resulted in significantly reduced distal airway pressure compared to a laryngoscope. Interestingly, neither stenosis size nor depth significantly influenced distal airway pressure. However, increased distance between the scope and stenosis raised normalized pressure. A linear rise in normalized distal airway pressure was noted with increased inlet pressure, regardless of stenosis dimensions. CONCLUSION: In this model, scope type and inlet pressure were noted to be significant determinants of distal airway pressure, while stenosis size and depth were not. The distance between the scope and the stenosis did influence distal pressures. These findings may have clinical implications for managing airway pressures in patients undergoing LFJV, potentially reducing the risk of ventilator-induced lung injury. LEVEL OF EVIDENCE: NA (Basic Research) Laryngoscope, 134:2300-2305, 2024.

Extracorporeal membrane oxygenation in obstetric patients: An Israeli nationwide study.

BACKGROUND: The leading causes of maternal mortality include respiratory failure, cardiovascular events, infections, and hemorrhages. The use of extracorporeal membrane oxygenation (ECMO) as rescue therapy in the peripartum period for cardiopulmonary failure is expanding in critical care medicine. METHODS: This retrospective observational study was conducted on a nationwide cohort in Israel. During the 3-year period, between September 1, 2019, and August 31, 2022, all women in the peripartum period who had been supported by ECMO for respiratory or circulatory failure at 10 large Israeli hospitals were identified. Indications for ECMO, maternal and neonatal outcomes, details of ECMO support, and complications were collected. RESULTS: During the 3-year study period, in Israel, there were 540 234 live births, and 28 obstetric patients were supported by ECMO, with an incidence of 5.2 cases per 100 000 or 1 case per 19 000 births (when excluding patients with COVID-19, the incidence will be 2.5 cases per 100 000 births). Of these, 25 were during the postpartum period, of which 16 (64%) were connected in the PPD1, and 3 were during pregnancy. Eighteen patients (64.3%) were supported by V-V ECMO, 9 (32.1%) by V-A ECMO, and one (3.6%) by a VV-A configuration. Hypoxic respiratory failure (ARDS) was the most common indication for ECMO, observed in 21 patients (75%). COVID-19 was the cause of ARDS in 15 (53.7%) patients. The indications for the V-A configuration were cardiomyopathy (3 patients), amniotic fluid embolism (2 patients), sepsis, and pulmonary hypertension. The maternal and fetal survival rates were 89.3% (n = 25) and 100% (n = 28). The average ECMO duration was 17.6 ± 18.6 days and the ICU stay was 29.8 ± 23.8 days. Major bleeding complications requiring surgical intervention were observed in one patient. CONCLUSIONS: The incidence of using ECMO in the peripartum period is low. The maternal and neonatal survival rates in patients treated with ECMO are high. These results show that ECMO remains an important treatment option for obstetric patients with respiratory and/or cardiopulmonary failure.

Spatial and seasonal variation in thermal sensitivity within North American bird species.

Responses of wildlife to climate change are typically quantified at the species level, but physiological evidence suggests significant intraspecific variation in thermal sensitivity given adaptation to local environments and plasticity required to adjust to seasonal environments. Spatial and temporal variation in thermal responses may carry important implications for climate change vulnerability; for instance, sensitivity to extreme weather may increase in specific regions or seasons. Here, we leverage high-resolution observational data from eBird to understand regional and seasonal variation in thermal sensitivity for 21 bird species. Across their ranges, most birds demonstrated regional and seasonal variation in both thermal peak and range, or the temperature and range of temperatures when observations peaked. Some birds demonstrated constant thermal peaks or ranges across their geographical distributions, while others varied according to local and current environmental conditions. Across species, birds typically demonstrated either geographical or seasonal adaptation to climate. Local adaptation and phenotypic plasticity are likely important but neglected aspects of organismal responses to climate change.

Deep learning with citizen science data enables estimation of species diversity and composition at continental extents.

Effective solutions to conserve biodiversity require accurate community- and species-level information at relevant, actionable scales and across entire species' distributions. However, data and methodological constraints have limited our ability to provide such information in robust ways. Herein we employ a Deep-Reasoning Network implementation of the Deep Multivariate Probit Model (DMVP-DRNets), an end-to-end deep neural network framework, to exploit large observational and environmental data sets together and estimate landscape-scale species diversity and composition at continental extents. We present results from a novel year-round analysis of North American avifauna using data from over nine million eBird checklists and 72 environmental covariates. We highlight the utility of our information by identifying critical areas of high species diversity for a single group of conservation concern, the North American wood warblers, while capturing spatiotemporal variation in species' environmental associations and interspecific interactions. In so doing, we demonstrate the type of accurate, high-resolution information on biodiversity that deep learning approaches such as DMVP-DRNets can provide and that is needed to inform ecological research and conservation decision-making at multiple scales.

Extracorporal Membrane Oxygenation in Nonintubated Patients (Awake ECMO) With COVID-19 Adult Respiratory Distress Syndrome: The Israeli Experience.

In this retrospective multicenter observational study, we describe the Israeli experience with veno-venous extracorporeal membrane oxygenation (VV ECMO) for the treatment of COVID-19-induced severe adult respiratory distress syndrome (ARDS), in which ECMO cannulation was done while the patients were awake and spontaneously breathing without endotracheal tube, namely "awake ECMO." We enrolled all adult patients with severe ARDS due to COVID-19, treated with VV ECMO between March 1, 2020, and November 30, 2021, in which cannulation was done while the patient was awake and spontaneously breathing. During the study period, 365 COVID-19 ARDS patients were treated with VV ECMO. Of these, 25 (6.8%) were treated as awake ECMO. The patient's mean age was 52 years, and 80% were male. Nine of the 25 patients (36%) remained awake throughout their intensive care unit stay and were not sedated and mechanically ventilated at all. Sixteen (64%) were eventually intubated while being on ECMO. Six months survival was 76%. Median mechanical ventilation-free days on ECMO was 8 (interquartile range 5-12) days. This hypothesis-generating study suggests that treating COVID-19 ARDS patients with VV ECMO without sedation and mechanical ventilation is feasible, yet, additional research will be required in order to determine if this modality offers a survival benefit and to identify who are the patients most likely to benefit from it.

Is Thyrohyoid Space Palpation a Reliable and Useful Clinical Tool Within Diagnostic Protocol for Voice Disorders?

OBJECTIVES: Palpation of the extrinsic laryngeal muscles is a common part of examination performed by otolaryngologists and speech-language pathologists on individuals presenting with voice complaints, thought to aid in diagnosis and treatment planning. While research has identified a significant relationship between thyrohyoid tension and hyperfunctional voice disorders, we are not aware of any studies exploring correlations between thyrohyoid posture during palpation and the full spectrum of voice disorders. This study aims to identify whether patterns in thyrohyoid posture at rest and during phonation can be related to stroboscopic findings and voice disorder diagnoses. METHODS: A multidisciplinary team of three laryngologists and three speech-language pathologists participated in data collection during 47 new patient visits for voice complaints. Each patient underwent neck palpation and evaluation of thyrohyoid space at rest and during phonation by two independent raters. Clinicians then used stroboscopy to rate glottal closure and supraglottic activity as part of determining primary diagnosis. RESULTS: Strong inter-rater agreement was found for ratings of thyrohyoid space posture both at rest (κ = 0.93) and during phonation (κ = 0.80). Findings revealed no significant correlations between patterns of thyrohyoid posture and laryngoscopic findings or primary diagnoses. CONCLUSIONS: Findings suggest that the presented method of laryngeal palpation is a reliable measure for assessing thyrohyoid posture at rest and during phonation. Lack of significant correlation between palpation ratings and other collected measures suggests that this method of palpation is not a useful tool for predicting laryngoscopic findings or voice diagnoses. Laryngeal palpation may still be useful in predicting extrinsic laryngeal muscle tension and guiding treatment planning; however, further research exploring the validity of laryngeal palpation as a measure of extrinsic laryngeal muscle tension is needed, as well as studies that include patient-reported measures and repeated measurements of thyrohyoid posture over time to explore whether thyrohyoid posture is impacted by other factors.

Comparative Treatment Outcomes for Idiopathic Subglottic Stenosis: 5-Year Update.

The North American Airway Collaborative (NoAAC) previously published a 3-year multi-institutional prospective cohort study showing variation in treatment effectiveness between 3 primary surgical techniques for idiopathic subglottic stenosis (iSGS). In this report, we update these findings to include 5 years of data evaluating treatment effectiveness. Patients in the NoAAC cohort were re-enrolled for 2 additional years and followed using the prespecified published protocol. Consistent with prior data, prospective observation of 487 iSGS patients for 5 years showed treatment effectiveness differed by modality. Cricotracheal resection maintained the lowest rate of recurrent operation (5%), followed by endoscopic resection with adjuvant medical therapy (30%) and endoscopic dilation (50%). These data support the initial observations and continue to provide value to providers and patients navigating longitudinal decision-making. Level of evidence: 2-prospective cohort study.

Nontuberculous Mycobacterial Infection of Larynx and Cervical Trachea.

OBJECTIVES: To present a patient with the first case of NTM (nontuberculous mycobacteria) infection of the larynx extending to cervical trachea, and the first case of subglottic stenosis associated with an NTM infection. METHODS: Case report and review of the literature. RESULTS: A 68-year-old female with history of prior smoking, gastroesophageal reflux disease, asthma, bronchiectasis, and tracheobronchomalacia presented with a 3-month history of shortness of breath, exertional inspiratory stridor, and hoarseness. Flexible laryngoscopy demonstrated ulceration of medial aspect of right vocal fold and subglottic tissue abnormality with crusting and ulceration extending through the upper trachea. Microdirect laryngoscopy with tissue biopsies and carbon dioxide (CO2) laser ablation of disease completed, and intraoperative culture revealed positive Aspergillus and acid-fast bacilli with Mycobacterium abscessus (type of NTM). Patient began antimicrobial treatment of cefoxitin, imipenem, amikacin, azithromycin, clofazimine, and itraconazole. Fourteen months after initial presentation, patient developed subglottic stenosis with limited extension into the proximal trachea prompting CO2 laser incision, balloon dilation, and steroid injection of the subglottic stenosis. Patient remains disease free without further subglottic stenosis. CONCLUSION: Laryngeal NTM infections are exceedingly rare. Failure to consider NTM infection in the differential diagnosis when presented with an ulcerative, exophytic mass in patients with increased risk factors (structural lung disease, Pseudomonas colonization, chronic steroid use, prior NTM positivity) may result in insufficient tissue evaluation, delayed diagnosis, and disease progression.

The Predictive Value of Decisive and Soft Ultrasound Criteria for Ectopic Pregnancy Identification in 321 Preoperative Cases.

PURPOSE: To define the predictive value of morphological types (MTs) and further criteria in diagnosing ectopic pregnancy (ECP) by transvaginal sonography (TVS) prior to operative confirmation and treatment. MATERIALS AND METHODS: Retrospective cohort analysis of 321 consecutive patients with suspected ECP who were advised to undergo operation. RESULTS: ECP was investigated by TVS in all 321 patients. Application of the five selected MTs (blob sign, bagel sign, yolk sac, embryo, heart action) resulted in 85 % of cases receiving a conclusive diagnosis and 12 % receiving a presumed ECP diagnosis. 3 % remained nondiagnostic due to large or multiple ovarian cysts, large myoma, extended hemoperitoneum, or severe pain. ECP diagnosis was confirmed intraoperatively in 97 % of cases and was otherwise (3 %) immediately followed by curettage (CUR). The assessment of free fluid by TVS was achieved in most cases and correlated significantly with free blood. In the majority of cases, free blood was not bound to transmural ECP rupture. Histology confirmed the ECP diagnosis directly or by exclusion in 99 % of cases. Three cases of tubal ECP were diagnosed by TVS but not confirmed by LSC (1 %) and, finally, histology from CUR proved miscarriage (false-positive rate 1 %). CONCLUSION: We confirm the high accuracy of TVS diagnosis of ECP relying on five clearly different MTs, independent of its location. The blob and bagel sign emerged as important types (75 % of all ECPs). Histology from CUR was needed when ECP could not be visualized in LSC. Assessment of free fluid was essential and accurate in predicting free blood.

Virtual Reality in Biomedical Education in the sense of the 3Rs.

Article 23(2) of EU Directive 2010/63 on the protection of animals used for scientific purposes requires staff involved in the care and use of animals to be adequately educated and trained before carrying out procedures. Therefore, the 3Rs (refinement, reduction, and replacement) and knowledge of alternative methods should be part of the education and training itself. For this purpose, the digital learning concept "Virtual Reality (VR) in Biomedical Education" evolved, which successfully combines VR components with classical learning content. Procedures, such as anesthesia induction, substance application, and blood sampling in rats, as well as aspects of the laboratory environment were recorded in 360° videos. The generated VR teaching/learning modules (VR modules) were used to better prepare participants for hands-on training (refinement) or as a complete replacement for a live demonstration; thus, reducing the number of animals used for hands-on skills training (reduction). The current study evaluated users' experience of the VR modules. Despite little previous VR experience, participants strongly appreciated the VR modules and indicated that they believed VR has the potential to enhance delivery of procedures and demonstrations. Interestingly, participants with previous experience of laboratory animal science were more convinced about VR's potential to support the 3Rs principle, and endorsed its use for further educational purposes. In conclusion, VR appeared to be highly accepted as a learning/teaching method, indicating its great potential to further replace and reduce the use of animals in experimental animal courses.

Thoracic surgery in Israel.

During the past 74 years since its establishment, Israel has evolved into a modernized country with well-established and effective public health care system. Thoracic surgeons in Israel play a central role in the diagnosis and treatment of patients with diseases of the chest wall, diaphragm, mediastinum, airways, Lung, and esophagus as well are taking part in designated trauma teams. Between 2,500-3,000 cases are being performed in 16 designated thoracic surgical units and departments across the country annually, the majority of them being performed in a minimally invasive fashion. Lung cancer is the leading cause of cancer related mortality in Israel and the second most common cancer in Israel. All types of thoracic oncologic cases are being presented routinely during designated multi-disciplinary conferences and treatment plans are designed according to the most up to date international guidelines. Each surgeon undergoes at least 6 years of formal training, followed by certifying exams. Advanced training is usually obtained overseas in centers of excellence. Israeli thoracic surgeons are part of an international societies and are actively involved in academic research. Despite the advancement of the Israeli health care system, thoracic surgeons in Israel are still facing few challenges that are limiting the early diagnosis of thoracic surgical malignancies such as lack of established national lung cancer screening program in Israel although a pilot program is being tested during these days. Tasked with taking care of diseases of the chest, and in order to remain at the forefront of diagnosis and treatment similar to our colleagues across the globe, Thoracic surgeons in Israel are continuously seeking to learn and evolve in order to improve and provide better care to our patients.

Isolated laryngeal Mucormycosis requiring laryngectomy.

We report a case of isolated laryngeal mucormycosis in a patient who presented in diabetic ketoacidosis (DKA). The patient was managed with antifungal therapy and eventual total laryngectomy. To our knowledge, this is the first case presented of mucormycosis with isolated laryngeal involvement.

A favorable outcome in an infantile-onset Pompe patient with cross reactive immunological material (CRIM) negative disease with high dose enzyme replacement therapy and adjusted immunomodulation.

Infantile onset Pompe disease (IOPD) is a rare devastating disease that presents in early infancy with rapidly progressive hypertrophic cardiomyopathy, severe generalized myopathy and death within the first year of life. The emergence of enzyme replacement therapy (ERT) with recombinant human acid alpha glucosidase (rhGAA) has improved the natural course of IOPD with a significant impact on cardiomyopathy but has a more limited effect on the progression of myopathy and consequently the later deterioration of the disease. Possible reasons for reduced ERT efficacy include insufficient enzyme, partial targeting of skeletal muscle and the development of IgG rhGAA antibodies especially in patients who are cross-reactive immunological material (CRIM) negative. We report a CRIM-negative IOPD female patient who started treatment upon diagnosis at 4.5 months with ERT at 20 mg/kg every other week and a course of combined immunomodulation with rituximab, methotrexate and IVIG according to the published Duke protocol and increased ERT within a month to 40 mg/kg/week. Despite initial good clinical response to ERT and immunomodulation, monthly monitoring identified a gradual increase of serum antibody titers to rhGAA necessitating a second course of immunomodulation with bortezomib and maintenance rituximab and methotrexate. A gradual reduction in frequency of immunotherapy was instituted and over a period of 14 months was discontinued. Serum anti-rhGAA antibody titers remained negative for 5 months since cessation of immunomodulation and the patient is now immune tolerant with recovery of CD19. At the age of 30 months the patient is walking independently and has normal cardiac function and anatomy. We recommend initiating ERT at 40 mg/kg/week in CRIM-negative IOPD patients, concomitant with immunomodulation and monthly monitoring of serum anti-rhGAA IgG titers upon confirmation of the diagnosis.

The CIP2A-TOPBP1 complex safeguards chromosomal stability during mitosis.

The accurate repair of DNA double-strand breaks (DSBs), highly toxic DNA lesions, is crucial for genome integrity and is tightly regulated during the cell cycle. In mitosis, cells inactivate DSB repair in favor of a tethering mechanism that stabilizes broken chromosomes until they are repaired in the subsequent cell cycle phases. How this is achieved mechanistically is not yet understood, but the adaptor protein TOPBP1 is critically implicated in this process. Here, we identify CIP2A as a TOPBP1-interacting protein that regulates TOPBP1 localization specifically in mitosis. Cells lacking CIP2A display increased radio-sensitivity, micronuclei formation and chromosomal instability. CIP2A is actively exported from the cell nucleus in interphase but, upon nuclear envelope breakdown at the onset of mitosis, gains access to chromatin where it forms a complex with MDC1 and TOPBP1 to promote TOPBP1 recruitment to sites of mitotic DSBs. Collectively, our data uncover CIP2A-TOPBP1 as a mitosis-specific genome maintenance complex.

Upper Esophageal Sphincter Compression Device as an Adjunct to Proton Pump Inhibition for Laryngopharyngeal Reflux.

BACKGROUND: The Reflux Band, an external upper esophageal sphincter (UES) compression device, reduces esophago-pharyngeal reflux events. This study aimed to assess device efficacy as an adjunct to proton pump inhibitor (PPI) therapy in patients with laryngopharyngeal reflux (LPR). METHODS: This two-phase prospective clinical trial enrolled adults with at least 8 weeks of laryngeal symptoms (sore throat, throat clearing, dysphonia) not using PPI therapy at two tertiary care centers over 26 months. Participants used double dose PPI for 4 weeks in Phase 1 and the external UES compression device nightly along with PPI for 4 weeks in Phase 2. Questionnaire scores and salivary pepsin concentration were measured throughout the study. The primary endpoint of symptom response was defined as reflux symptom index (RSI) score ≤ 13 and/or > 50% reduction in RSI. RESULTS: Thirty-one participants completed the study: 52% male, mean age 47.9 years (SD 14.0), and mean body mass index (BMI) 26.2 kg/m2 (5.1). Primary endpoint was met in 11 (35%) participants after Phase 1 (PPI alone) and 17 (55%) after Phase 2 (Device + PPI). Compared to baseline, mean RSI score (24.1 (10.9)) decreased at end of Phase 1 (PPI alone) (21.9 (9.7); p = 0.06) and significantly decreased at end of Phase 2 (Device + PPI) (15.5 (10.3); p < 0.01). Compared to non-responders, responders to Device + PPI had a significantly lower BMI (p = 0.02) and higher salivary pepsin concentration (p = 0.01). CONCLUSION: This clinical trial highlights the potential efficacy of the external UES compression device (Reflux Band) as an adjunct to PPI for patients with LPR (ClinicalTrials.Gov NCT03619811).

Jet flow rate and needle position govern distal airway pressures during low-frequency jet ventilation.

OBJECTIVES: Although jet ventilation is frequently used during surgery for airway stenosis, little is known about distal airway pressures during jet ventilation. The objective of the study is to determine how jet pressure, flow rate, and position of the ventilation needle relate to distal airway pressure magnitude and homogeneity. METHODS: Two 3D models of the first five generations of the human airway tree were created. One is a duplicate of a human airway from a 15-year-old healthy male's computed tomography scan, and the other is an idealized symmetric model of human lung morphometry. Pressure transducers measured fifth-generation distal airway pressures in both models. A computer-controlled jet needle positioning system was used to ventilate the lung casts. The effects of jet needle position, jet pressure, and jet flow rate on distal airway pressure and homogeneity were measured. RESULTS: Total entrained jet flow rate was the most reliable predictor of distal airway pressure. Pressure supplied to the jet ventilation needle had a positive linear relationship with distal airway pressure; however, this relationship was dependent on the jet needle flow resistance. As the ventilation needle moved closer to the tracheal wall, ventilation homogeneity decreased. Depth into the trachea was positively correlated with sensitivity of the needle to the tracheal wall. CONCLUSION: In this model, total entrained jet flow rate is a more robust predictor of distal airway pressure than jet inlet pressure. More homogeneous ventilation was observed in our model with the ventilation needle centered in the proximal region of the trachea.