Characterisation and mitigation of gas leaks at laparoscopy: an international prospective, multi-center cohort clinical trial.

INTRODUCTION: Gas leaks polluting the operating room are common in laparoscopy. Studies defining methods for sensitive leak characterisation and mechanical mitigation in real world settings are, however, lacking. METHODS: Mobile optical gas imagers (both a miniaturised Schlieren system and sensitive tripod-mounted near-infrared carbon dioxide camera (GF343, FLIR)) prospectively defined trocar-related gas leaks occurring either spontaneously or with instrumentation during planned laparoscopic surgery at three hospitals. A boutique Matlab-based analyser using sequential frame subtraction categorised leaks (class 0-no observable leak; class 1-marginally detectable leak; class 2-short-lived plume; class 3-energetic, turbulent jet). Concurrently, the usefulness of a novel vacuum-ring device (LeakTrap™, Palliare, Ireland) designed as a universal adjunct for existing standard laparoscopic ports at both abdominal wall and port valve level was determined similarly in a phase I/11 clinical trial along with the device's useability through procedural observation and surgeon questionnaire. RESULTS: With ethical and regulatory approval, 40 typical patients (mean age 58.6 years, 20 males) undergoing planned laparoscopic cholecystectomy (n = 36) and hernia repair (n = 4) were studied comprising both control (n = 20) and intervention (n = 20) cohorts. Dual optical gas imaging was successfully performed across all procedures with minimal impact on procedural flow. In total, 1643 trocar instrumentations were examined, 819 in the control group (mean 41 trocar instrumentations/procedure) and 824 in the intervention group (mean 41.2 trocar instrumentations/procedure). Gas leaks were detected during 948(62.6%) visualised trocar instrumentations (in 129-7.8%-the imaging was obscured). 14.8% (110/742) and 60% (445/742) of leaks in control patients were class 0 and 3, respectively, versus 59.1% (456/770) and 8.7% (67/772) in the interventional group (class 3 v non-class 3, p < 0.0001, χ2). The Leaktrap proved surgically acceptable without significant workflow disruption. CONCLUSION: Laparoscopic gas leaks can be sensitively detected and consistently, effectively mitigated using straightforward available-now technology with most impact on the commonest, highest energy instrument exchange leaks.

Intrapulmonary T Cells Are Sufficient for Schistosoma-Induced Pulmonary Hypertension.

BACKGROUND: Schistosomiasis is a parasitic infection that can cause pulmonary hypertension (PH). Th2 CD4 T cells are necessary for experimental Schistosoma-PH. However, if T cells migrate to the lung to initiate, the localized inflammation that drives vascular remodeling and PH is unknown. METHODS: Mice were sensitized to Schistosoma mansoni eggs intraperitoneally and then challenged using tail vein injection. FTY720 was administered, which blocks lymphocyte egress from lymph nodes. T cells were quantified using flow cytometry, PH severity via heart catheterization, and cytokine concentration through ELISA. RESULTS: FTY720 decreased T cells in the peripheral blood, and increased T cells in the mediastinal lymph nodes. However, FTY720 treatment resulted in no change in PH or type 2 inflammation severity in mice sensitized and challenged with S. mansoni eggs, and the number of memory and effector CD4 T cells in the lung parenchyma was also unchanged. Notably, intraperitoneal Schistosoma egg sensitization alone resulted in a significant increase in intravascular lymphocytes and T cells, including memory T cells, although there was no significant change in parenchymal cell density, IL-4 or IL-13 expression, or PH. CONCLUSION: Blocking T cell migration did not suppress PH following Schistosoma egg challenge. Memory CD4 T cells, located in the lung intravascular space following egg sensitization, appear sufficient to cause type 2 inflammation and PH.

Exhaled patient derived aerosol dispersion during awake tracheal intubation with concurrent high flow nasal therapy.

Awake Tracheal Intubation (ATI) can be performed in cases where there is potential for difficult airway management. It is considered an aerosol generating procedure and is a source of concern to healthcare workers due to the risk of transmission of airborne viral infections, such as SARS-CoV-2. At present, there is a lack of data on the quantities, size distributions and spread of aerosol particles generated during such procedures. This was a volunteer observational study which took place in an operating room of a university teaching hospital. Optical particle sizers were used to provide real time aerosol characterisation during a simulated ATI performed with concurrent high-flow nasal oxygen therapy. The particle sizers were positioned at locations that represented the different locations of clinical staff in an operating room during an ATI. The greatest concentration of patient derived aerosol particles was within 0.5-1.0 m of the subject and along their midline, 2242 #/cm3. As the distance, both radial and longitudinal, from the subject increased, the concentration decreased towards ambient levels, 36.9 ± 5.1 #/cm3. Patient derived aerosol particles < 5 µm in diameter remained entrained in the exhaled aerosol plume and fell to the floor or onto the subject. Patient derived particles > 5 µm in diameter broke away from the exhaled plume and spread radially throughout the operating room. Irrespective of distance and ventilation status, full airborne protective equipment should be worn by all staff when ATI is being performed on patients with suspected viral respiratory infections.

Impact of intra-abdominal insufflation pressure on gas leakage occurring during laparoscopy.

INTRODUCTION: The advent of the COVID-19 pandemic led to recommendations aimed at minimizing the risk of gas leaks at laparoscopy. As this has continuing relevance including regarding operating room pollution, we empirically quantified carbon dioxide (CO2) leak jet velocity (important for particle propulsion) occurring with different instruments inserted into differing trocars repeated across a range of intra-abdominal pressures (IAPs) and modern insufflators in an experimental model. METHOD: Laparoscopic gas plume leak velocity (metres/second) was computationally enumerated from schlieren optical flow videography on a porcine cadaveric laparoscopic model with IAPs of 4-5, 7-8, 12-15 and 24-25 mmHg (repeated with 5 different insufflators) during simulated operative use of laparoscopic clip appliers, scissors, energy device, camera and staplers as well as Veres needle (positive control) and trocar obturator (negative control) in fresh 5 mm and 12 mm ports. RESULTS: Close-fitting solid instruments (i.e. cameras and obturators) demonstrated slower gas leak velocities in both the 5 mm and 12 mm ports (p = 0.02 and less than 0.001) when compared to slimmer instruments, however, hollow instrument designs were seen to defy this pattern with the endoscopic linear stapler visibly inducing multiple rapid jests even when compared to similarly sized clip appliers (p = 0.03). However, on a per device basis the operating instrumentation displayed plume speeds which did not vary significantly when challenged with varying post size, IAP and a range of insufflators. CONCLUSION: In general, surgeon's selection of instrument, port or pressure does not usefully mitigate trocar CO2 leak velocity. Instead better trocar design is needed, helped by a fuller understanding of trocar valve mechanics via computational fluid dynamics informed by relevant surgical modelling.

Increased resource utilization and overall morbidity are associated with general versus regional anesthesia for carotid endarterectomy in data collected by the Michigan Surgical Quality Collaborative.

OBJECTIVE: Advocates for performing carotid endarterectomy (CEA) under regional anesthesia (RA) cite reduction in hemodynamic instability and the ability for neurologic monitoring, but many still prefer general anesthesia (GA) as benefits of RA have not been clearly demonstrated, reliable RA may not be available in all centers, and a certain amount of movement by the patient during the procedure may not be uniformly tolerated. We evaluated the association of anesthesia type and perioperative morbidity and mortality as well as resource utilization in patients undergoing CEA using the Michigan Surgical Quality Collaborative (MSQC) database. METHODS: Between 2012 and 2014, 4558 patients underwent CEA among the MSQC participating hospitals. Of these patients, 4008 underwent CEA under GA and 550 underwent CEA under RA. Data points were collected for each procedure, and a review of 30-day perioperative outcomes was conducted using the χ2 test. Propensity score regression adjusted for case mix preoperative conditions as fixed effects, and a mixed model adjusted for site as a random effect. RESULTS: The two groups were similar in gender and incidence of hypertension, diabetes, congestive heart failure, and smoking history. The RA group tended to be of better functional status. After GA, there was a greater than twofold higher percentage of any morbidity (8.7% vs 4.2%). Further analysis demonstrated that patients undergoing GA had higher unadjusted rates for mortality (1.0% vs 0.0%), unplanned intubations (2.1% vs 0.6%), pneumonia (1.3% vs 0.0%), sepsis (0.8% vs 0.0%), and readmissions (9.2% vs 6.1%). Adjusting for case mix and random effect, there was statistically significantly higher overall morbidity (P = .0002), unplanned intubation (P = .0196), extended length of stay (P = .0007), emergency department visits (P = .0379), and readmissions (P = .0149) in the GA group. There was no statistically significant difference in incidence of myocardial infarction or cerebrovascular accident. CONCLUSIONS: Based on this analysis from the MSQC database, there is an associated increased morbidity and resource utilization with GA vs RA for CEA. This has implications for enterprise resource planning initiatives and the CEA value proposition in general, which is of special interest to both hospitals and payers.

Pursuing the Triple Aim: The First 7 Years.

UNLABELLED: POLICY POINTS: In 2008, researchers at the Institute for Healthcare Improvement (IHI) proposed the Triple Aim, strategic organizing principles for health care organizations and geographic communities that seek, simultaneously, to improve the individual experience of care and the health of populations and to reduce the per capita costs of care for populations. In 2010, the Triple Aim became part of the US national strategy for tackling health care issues, especially in the implementation of the Patient Protection and Affordable Care Act (ACA) of 2010. Since that time, IHI and others have worked together to determine how the implementation of the Triple Aim has progressed. Drawing on our 7 years of experience, we describe 3 major principles that guided the organizations and communities working on this endeavor: creating the right foundation for population management, managing services at scale for the population, and establishing a learning system to drive and sustain the work over time. CONTEXT: In 2008, researchers at the Institute for Healthcare Improvement (IHI) described the Triple Aim as simultaneously "improving the individual experience of care; improving the health of populations; and reducing the per capita costs of care for populations." IHI and its close colleagues had determined that both individual and societal changes were needed. METHODS: In 2007, IHI began recruiting organizations from around the world to participate in a collaborative to implement what became known as the Triple Aim. The 141 participating organizations included health care systems, hospitals, health care insurance companies, and others closely tied to health care. In addition, key groups outside the health care system were represented, such as public health agencies, social services groups, and community coalitions. This collaborative provided a structure for observational research. By noting the contrasts between the contexts and structures of those sites in the collaborative that progressed and those that did not, we were able to develop an ex post theory of what is needed for an organization or community to successfully pursue the Triple Aim. FINDINGS: Drawing on our 7 years of experience, we describe the 3 major principles that guided the organizations and communities working on the Triple Aim: creating the right foundation for population management, managing services at scale for the population, and establishing a learning system to drive and sustain the work over time. CONCLUSIONS: The concept of the Triple Aim is now widely used, because of IHI's work with many organizations and also because of the adoption of the Triple Aim as part of the national strategy for US health care, developed during the implementation of the Patient Protection and Affordable Care Act of 2010. Even those organizations working on the Triple Aim before IHI coined the term found our concept to be useful because it helped them think about all 3 dimensions at once and organize their work around them.

Experimental Schistosoma haematobium pulmonary hypertension.

Whether all Schistosoma species cause pulmonary hypertension (PH) is unclear. Experimentally exposing mice to Schistosoma haematobium eggs caused PH, which was less severe than that induced by S. mansoni exposure. These findings align with the relatively uncommon reports of pulmonary arterial hypertension associated with S. haematobium.

Interstitial macrophage phenotypes in Schistosoma-induced pulmonary hypertension.

Background: Schistosomiasis is a common cause of pulmonary hypertension (PH) worldwide. Type 2 inflammation contributes to the development of Schistosoma-induced PH. Specifically, interstitial macrophages (IMs) derived from monocytes play a pivotal role by producing thrombospondin-1 (TSP-1), which in turn activates TGF-ß, thereby driving the pathology of PH. Resident and recruited IM subpopulations have recently been identified. We hypothesized that in Schistosoma-PH, one IM subpopulation expresses monocyte recruitment factors, whereas recruited monocytes become a separate IM subpopulation that expresses TSP-1. Methods: Mice were intraperitoneally sensitized and then intravenously challenged with S. mansoni eggs. Flow cytometry on lungs and blood was performed on wildtype and reporter mice to identify IM subpopulations and protein expression. Single-cell RNA sequencing (scRNAseq) was performed on flow-sorted IMs from unexposed and at day 1, 3 and 7 following Schistosoma exposure to complement flow cytometry based IM characterization and identify gene expression. Results: Flow cytometry and scRNAseq both identified 3 IM subpopulations, characterized by CCR2, MHCII, and FOLR2 expression. Following Schistosoma exposure, the CCR2+ IM subpopulation expanded, suggestive of circulating monocyte recruitment. Schistosoma exposure caused increased monocyte-recruitment ligand CCL2 expression in the resident FOLR2+ IM subpopulation. In contrast, the vascular pathology-driving protein TSP-1 was greatest in the CCR2+ IM subpopulation. Conclusion: Schistosoma-induced PH involves crosstalk between IM subpopulations, with increased expression of monocyte recruitment ligands by resident FOLR2+ IMs, and the recruitment of CCR2+ IMs which express TSP-1 that activates TGF-ß and causes PH.

The Cognitive Control Model of Work-related Flow.

Although several models of flow have been proposed that include environmental and trait-based antecedents of the state, elements of cognitive control that enable workers to experience flow and its subsequent outcomes at work have largely been overlooked. This research proposes and provides empirical support for the "Cognitive Control Model of Work-related Flow," which integrates antecedents of flow at work related to the ability to focus concentration of cognitive resources toward experiencing flow at work. Along with flow at work, the model includes the antecedents of grit, flow metacognition, and mindfulness at work and the outcomes of work performance, engagement, and burnout. Findings across three studies (a cross-sectional, a time-lagged, and a one-day experience sampling method study) utilizing MTurk participants provided support for the model, as grit, mindfulness, and flow metacognition predicted flow, and flow predicted subjective performance, engagement, and burnout. Theoretical implications and the potential for developing flow interventions at work are discussed.

Understanding surgical smoke in laparoscopy through Lagrangian Coherent Structures.

In laparoscopic surgery, one of the main byproducts is the gaseous particles, called surgical smoke, which is found hazardous for both the patient and the operating room staff due to their chemical composition, and this implies a need for its effective elimination. The dynamics of surgical smoke are monitored by the underlying flow inside the abdomen and the hidden Lagrangian Coherent Structures (LCSs) present therein. In this article, for an insufflated abdomen domain, we analyse the velocity field, obtained from a computational fluid dynamics model, first, by calculating the flow rates for the outlets and then by identifying the patterns which are responsible for the transportation, mixing and accumulation of the material particles in the flow. From the finite time Lyapunov exponent (FTLE) field calculated for different cross-sections of the domain, we show that these material curves are dependent on the angle, positions and number of the outlets, and the inlet. The ridges of the backward FTLE field reveal the regions of vortex formation, and the maximum accumulation, details which can inform the effective placement of the instruments for efficient removal of the surgical smoke.

Dexamethasone prophylaxis protects from acute high-altitude illness by modifying the peripheral blood mononuclear cell inflammatory transcriptome.

Acute high-altitude (HA) exposure can induce several pathologies. Dexamethasone (DEX) can be taken prophylactically to prevent HA disease, but the mechanism by which it acts in this setting is unclear. We studied the transcriptome of peripheral blood mononuclear cells (PBMCs) from 16 subjects at low altitude (LA, 225 m) and then 3 days after acute travel to HA (3500 m) during the India-Leh-Dexamethasone-Expedition-2020 (INDEX2020). Half of the participants received oral DEX prophylaxis 4 mg twice daily in an unblinded manner, starting 1 day prior to travel to HA, and 12 h prior to the first PBMC collection. PBMC transcriptome data were obtained from 16 subjects, half of whom received DEX. The principal component analysis demonstrated a clear separation of the groups by altitude and treatment. HA exposure resulted in a large number of gene expression changes, particularly in pathways of inflammation or the regulation of cell division, translation, or transcription. DEX prophylaxis resulted in changes in fewer genes, particularly in immune pathways. The gene sets modulated by HA and DEX were distinct. Deconvolution analysis to assess PBMC subpopulations suggested changes in B-cell, T-cell, dendritic cell, and myeloid cell numbers with HA and DEX exposures. Acute HA travel and DEX prophylaxis induce significant changes in the PBMC transcriptome. The observed benefit of DEX prophylaxis against HA disease may be mediated by suppression of inflammatory pathways and changing leukocyte population distributions.

Airborne particle dispersion by high flow nasal oxygen: An experimental and CFD analysis.

High Flow Nasal Oxygen (HFNO) therapy offers a proven means of delivering respiratory support to critically ill patients suffering from viral illness such as COVID-19. However, the therapy has the potential to modify aerosol generation and dispersion patterns during exhalation and thereby put healthcare workers at increased risk of disease transmission. Fundamentally, a gap exists in the literature with regards to the effect of the therapy on the fluid dynamics of the exhalation jet which is essential in understanding the dispersion of aerosols and hence quantifying the disease transmission risk posed by the therapy. In this paper, a multi-faceted approach was taken to studying the aerosol-laden exhalation jet. Schlieren imaging was used to visualise the flow field for a range of expiratory activities for three healthy human volunteers receiving HFNO therapy at flow rates of 0-60 L/min. A RANS turbulence model was implemented using the CFD software OpenFOAM and used to perform a parametric study on the influence of exhalation velocity and duration on the dispersion patterns of non-evaporating droplets in a room environment. A dramatic increase in the turbulence of the exhalation jet was observed when HFNO was applied. Quantitative analysis indicated that the mean exhalation velocity was increased by 2.2-3.9 and 2.3-3 times that for unassisted breathing and coughing, respectively. A 1-2 second increase was found in the exhalation duration. The CFD model showed that small droplets (10-40 µm) were most greatly affected, where a 1 m/s increase in velocity and 1 s increase in duration caused an 80% increase in axial travel distance.

Aerosol release, distribution, and prevention during aerosol therapy: a simulated model for infection control.

Aerosol therapy is used to deliver medical therapeutics directly to the airways to treat respiratory conditions. A potential consequence of this form of treatment is the release of fugitive aerosols, both patient derived and medical, into the environment and the subsequent exposure of caregivers and bystanders to potential viral infections. This study examined the release of these fugitive aerosols during a standard aerosol therapy to a simulated adult patient. An aerosol holding chamber and mouthpiece were connected to a representative head model and breathing simulator. A combination of laser and Schlieren imaging was used to non-invasively visualize the release and dispersion of fugitive aerosol particles. Time-varying aerosol particle number concentrations and size distributions were measured with optical particle sizers at clinically relevant positions to the simulated patient. The influence of breathing pattern, normal and distressed, supplemental air flow, at 0.2 and 6 LPM, and the addition of a bacterial filter to the exhalation port of the mouthpiece were assessed. Images showed large quantities of fugitive aerosols emitted from the unfiltered mouthpiece. The images and particle counter data show that the addition of a bacterial filter limited the release of these fugitive aerosols, with the peak fugitive aerosol concentrations decreasing by 47.3-83.3%, depending on distance from the simulated patient. The addition of a bacterial filter to the mouthpiece significantly reduces the levels of fugitive aerosols emitted during a simulated aerosol therapy, p≤ .05, and would greatly aid in reducing healthcare worker and bystander exposure to potentially harmful fugitive aerosols.

Patient generated aerosol in the context of ophthalmic surgery.

OBJECTIVE: To assess the patterns of patient generated aerosol in the context of ophthalmic surgery and ophthalmic examinations. To inform medical teams regarding potential hazards and suggest mitigating measures. METHODS: Qualitatively, real-time time videography assessed exhalation patterns from simulated patients under different clinical scenarios using propylene glycol from an e-cigarette. Quantitatively, high-speed Schlieren imaging was performed to enable high resolution recordings analysable by MATLAB technical computing software. RESULTS: Without a face mask, the standard prior to COVID 19, vapour was observed exiting through the opening in the drape over the surgical field. The amount of vapour increased when a surgical mask was worn. With a taped face mask, the amount of vapour decreased and with inclusion of a continuous suction device, the least amount of vapour was seen. These results were equivocal when the patient was supine or sitting upright. High-speed Schlieren imaging corroborated these findings and in addition showed substantial increase in airflow egress during coughing and with ill-fitting face masks. CONCLUSION: Advising patients to wear a surgical mask at the time of ophthalmic interventions potentially contaminants the ocular field with patient generated aerosol risking endophthalmitis. Surgeon safety can be maintained with personal protective equipment to mitigate the increased egress of vapour from the surgical drape and taping, with or without suction is advisable, whilst meticulous hygiene around lenses is required at the time of slit lamp examination.

TIN-a combinatorial compound collection of synthetically feasible multicomponent synthesis products.

The synthetic feasibility of any compound library used for virtual screening is critical to the drug discovery process. TIN, a recursive acronym for 'TIN Is Not commercial', is a virtual combinatorial database enumeration of diversity-orientated multicomponent syntheses (MCR). Using a 'one-pot' synthetic technique, 12 unique small molecule scaffolds were developed, predominantly styrylisoxazoles and bis-acetylenic ketones, with extensive derivatization potential. Importantly, the scaffolds were accessible in a single operation from commercially available sources containing R-groups which were then linked combinatorially. This resulted in a combinatorial database of over 28 million product structures, each of which is synthetically feasible. These structures can be accessed through a free Web-based 2D structure search engine or downloaded in SMILES, MOL2, and SDF formats. Subsets include a 10% diversity subset, a drug-like subset, and a lead-like subset that are also freely available for download and virtual screening ( http://mmg.rcsi.ie:8080/tin ).

Ryanodine receptor type 1 gene mutations found in the Canadian malignant hyperthermia population.

PURPOSE: Malignant hyperthermia (MH) is an autosomal dominant pharmacogenetic disorder that is manifested on exposure of susceptible individuals to halogenated anesthetics or succinylcholine. Since MH is associated primarily with mutations in the ryanodine receptor type 1 (RYR1) gene, the purpose of this study was to determine the distribution and frequency of MH causative RyR1 mutations in the Canadian MH susceptible (MHS) population. METHODS: In this study, we screened a representative cohort of 36 unrelated Canadian MHS individuals for RYR1 mutations by sequencing complete RYR1 transcripts and selected regions of CACNA1S transcripts. We then analyzed the correlation between caffeine-halothane contracture test (CHCT) results and RYR1 genotypes within MH families. RESULTS: Eighty-six percent of patients had at least one RyR1 mutation (31 out of 36), five of which were unrelated individuals who were double-variant carriers. Fifteen of the 27 mutations identified in RYR1 were novel. Eight novel mutations, involving highly conserved amino acid residues, were predicted to be causal. Two of the mutations co-segregated with the MHS phenotype within two large independent families (a total of 79 individuals). Fourteen percent of MHS individuals (five out of 36) carried neither RYR1 nor known CACNA1S mutations. CONCLUSIONS: The distribution and frequency of MH causative RyR1 mutations in the Canadian MHS population are close to those of European MHS populations. Novel mutations described in this study will contribute to the worldwide pool of MH-associated mutations in the RYR1 gene, ultimately increasing the value of MH genetic diagnostic testing.