Publications by authors named "Ronak Shah"

86 Publications

The Anterior Mediastinal Mass-the Challenging Management of Hypoxemia Despite Peripheral Cannulation for ECMO.

J Cardiothorac Vasc Anesth 2021 Mar 6. Epub 2021 Mar 6.

Division of Cardiothoracic Surgery, Department of Surgery, University of California San Diego, San Diego, CA.

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http://dx.doi.org/10.1053/j.jvca.2021.03.003DOI Listing
March 2021

Time-resolved photoelectron imaging of complex resonances in molecular nitrogen.

J Chem Phys 2021 Apr;154(14):144305

Elettra-Sincrotrone Trieste, SS 14, km 163.5, in Area Science Park, 34149 Basovizza, Trieste, Italy.

We have used the FERMI free-electron laser to perform time-resolved photoelectron imaging experiments on a complex group of resonances near 15.38 eV in the absorption spectrum of molecular nitrogen, N, under jet-cooled conditions. The new data complement and extend the earlier work of Fushitani et al. [Opt. Express 27, 19702-19711 (2019)], who recorded time-resolved photoelectron spectra for this same group of resonances. Time-dependent oscillations are observed in both the photoelectron yields and the photoelectron angular distributions, providing insight into the interactions among the resonant intermediate states. In addition, for most states, we observe an exponential decay of the photoelectron yield that depends on the ionic final state. This observation can be rationalized by the different lifetimes for the intermediate states contributing to a particular ionization channel. Although there are nine resonances within the group, we show that by detecting individual photoelectron final states and their angular dependence, we can identify and differentiate quantum pathways within this complex system.
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http://dx.doi.org/10.1063/5.0046577DOI Listing
April 2021

Continuous Fetal Monitoring During Electroconvulsive Therapy: A Prospective Observation Study.

Int J Womens Health 2021 6;13:1-7. Epub 2021 Jan 6.

University of Wisconsin School of Medicine and Public Health, Psychiatric Institute and Clinic, Madison, WI, USA.

Objective: The use of electroconvulsive therapy in pregnancy has been limited by concerns about its effects on fetal well-being, despite limited evidence that suggests it is safe and effective. No studies have utilized continuous fetal heart rate monitoring during electroconvulsive therapy sessions. We aimed to describe the fetal heart rate patterns of patients undergoing electroconvulsive therapy.

Design: This study is a prospective case series of pregnant patients undergoing electroconvulsive therapy with continuous fetal heart rate monitoring.

Setting: University-based hospital.

Population: Pregnant patients with a psychiatric indication for electroconvulsive therapy.

Methods: Patients underwent fetal heart rate monitoring immediately prior, during and immediately after ECT therapy.

Main Outcome Measures: Characterization of the fetal heart rate tracing.

Results: Five subjects underwent 44 electroconvulsive therapy sessions. Continuous fetal monitoring was performed on 34 of the sessions. Transient fetal heart rate decelerations occurred in 4 sessions, all self-resolved and none required intervention.

Conclusion: This case series is the first to report the results of continuous FHR monitoring during electroconvulsive therapy. The most common finding was a transient, self-resolving bradycardia that was not associated with adverse perinatal outcomes. This supports the opinion that electroconvulsive therapy is a safe treatment option in pregnancy in women with severe mental disease.
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http://dx.doi.org/10.2147/IJWH.S290934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797309PMC
January 2021

Adverse outcomes in COVID-19 and diabetes: a retrospective cohort study from three London teaching hospitals.

BMJ Open Diabetes Res Care 2021 01;9(1)

Imperial Centre for Endocrinology, Imperial College Healthcare NHS Trust, London, UK

Introduction: Patients with diabetes mellitus admitted to hospital with COVID-19 have poorer outcomes. However, the drivers of poorer outcomes are not fully elucidated. We performed detailed characterization of patients with COVID-19 to determine the clinical and biochemical factors that may be drivers of poorer outcomes.

Research Design And Methods: This is a retrospective cohort study of 889 consecutive inpatients diagnosed with COVID-19 between March 9 and April 22, 2020 in a large London National Health Service Trust. Unbiased multivariate logistic regression analysis was performed to determine variables that were independently and significantly associated with increased risk of death and/or intensive care unit (ICU) admission within 30 days of COVID-19 diagnosis.

Results: 62% of patients in our cohort were of non-white ethnic background and the prevalence of diabetes was 38%. 323 (36%) patients met the primary outcome of death/admission to the ICU within 30 days of COVID-19 diagnosis. Male gender, lower platelet count, advancing age and higher Clinical Frailty Scale (CFS) score (but not diabetes) independently predicted poor outcomes on multivariate analysis. Antiplatelet medication was associated with a lower risk of death/ICU admission. Factors that were significantly and independently associated with poorer outcomes in patients with diabetes were coexisting ischemic heart disease, increasing age and lower platelet count.

Conclusions: In this large study of a diverse patient population, comorbidity (ie, diabetes with ischemic heart disease; increasing CFS score in older patients) was a major determinant of poor outcomes with COVID-19. Antiplatelet medication should be evaluated in randomized clinical trials among high-risk patient groups.
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http://dx.doi.org/10.1136/bmjdrc-2020-001858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789097PMC
January 2021

Barrier Devices, Intubation, and Aerosol Mitigation Strategies: Personal Protective Equipment in the Time of Coronavirus Disease 2019.

Anesth Analg 2021 01 15;132(1):38-45. Epub 2020 Sep 15.

From the Department of Anesthesiology, Perioperative & Pain Medicine.

Background: Numerous barrier devices have recently been developed and rapidly deployed worldwide in an effort to protect health care workers (HCWs) from exposure to coronavirus disease 2019 (COVID-19) during high-risk procedures. However, only a few studies have examined their impact on the dispersion of droplets and aerosols, which are both thought to be significant contributors to the spread of COVID-19.

Methods: Two commonly used barrier devices, an intubation box and a clear plastic intubation sheet, were evaluated using a physiologically accurate cough simulator. Aerosols were modeled using a commercially available fog machine, and droplets were modeled with fluorescein dye. Both particles were propelled by the cough simulator in a simulated intubation environment. Data were captured by high-speed flash photography, and aerosol and droplet dispersion were assessed qualitatively with and without a barrier in place.

Results: Droplet contamination after a simulated cough was seemingly contained by both barrier devices. Simulated aerosol escaped the barriers and flowed toward the head of the bed. During barrier removal, simulated aerosol trapped underneath was released and propelled toward the HCW at the head of the bed. Usage of the intubation sheet concentrated droplets onto a smaller area. If no barrier was used, positioning the patient in slight reverse Trendelenburg directed aerosols away from the HCW located at the head of the bed.

Conclusions: Our observations imply that intubation boxes and sheets may reduce HCW exposure to droplets, but they both may merely redirect aerosolized particles, potentially resulting in increased exposure to aerosols in certain circumstances. Aerosols may remain within the barrier device after a cough, and manipulation of the box may release them. Patients should be positioned to facilitate intubation, but slight reverse Trendelenburg may direct infectious aerosols away from the HCW. Novel barrier devices should be used with caution, and further validation studies are necessary.
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http://dx.doi.org/10.1213/ANE.0000000000005249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523478PMC
January 2021

Intraoperative aerosol box use: does an educational visual aid reduce contamination?

Korean J Anesthesiol 2021 04 17;74(2):158-164. Epub 2020 Nov 17.

Department of Anesthesiology, Perioperative & Pain Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: The aerosol box was rapidly developed and disseminated to minimize viral exposure during aerosolizing procedures during the COVID-19 pandemic, yet users may not understand how to use and clean the device. This could potentially lead to increased viral exposure to subsequent patients and practitioners. We evaluated intraoperative contamination and aerosol box decontamination and the impact of a preoperative educational visual aid.

Methods: Using a double-blinded randomized design, forty-four anesthesiology trainees and faculty completed a simulated anesthetic case using an aerosol box contaminated with a fluorescent marker; half of the subjects received a visual aid prior to the simulation. Intraoperative contamination was evaluated at 10 standardized locations using an ultraviolet (UV) light. Next, subjects were instructed to clean the aerosol box for use on the next patient. Following cleaning, the box was evaluated for decontamination using an UV light.

Results: Median total contamination score was significantly reduced in the experimental group (5.0 vs. 10.0, P < 0.001). The aerosol box was completely cleaned by 36.4% of subjects in the experimental group compared to 4.5% in the control group (P = 0.009).

Conclusions: The use of a visual aid significantly decreased intraoperative contamination and improved box cleaning. Despite these findings, a potentially clinically significant amount of viral exposure may exist. Thorough evaluation of the risks and benefits of the aerosol box should be completed prior to use. If an aerosol box is used, a visual aid should be considered to remind practitioners how to best use and clean the box.
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http://dx.doi.org/10.4097/kja.20511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024202PMC
April 2021

Using Simulation to Develop Solutions for Ventilator Shortages From the Epicenter.

Simul Healthc 2021 Feb;16(1):78-79

From the Department of Anesthesiology, Perioperative & Pain Medicine (G.W.B., A.S., E.A.F., C.Y.L., M.L.), Icahn School of Medicine at Mount Sinai; and Department of Anesthesiology & Critical Care Medicine (R.S.), Memorial Sloan Kettering Cancer Center, New York, NY.

Summary Statement: The COVID-19 pandemic threatened to overwhelm the medical system of New York City, and the threat of ventilator shortages was real. Using high-fidelity simulation, a variety of solutions were tested to solve the problem of ventilator shortages including innovative designs for safely splitting ventilators, converting noninvasive ventilators to invasive ventilators, and testing and improving of ventilators created by outside companies. Simulation provides a safe environment for testing of devices and protocols before use on patients and should be vital in the preparation for emergencies such as the COVID-19 pandemic.
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http://dx.doi.org/10.1097/SIH.0000000000000523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853722PMC
February 2021

Aortic Dissection During Cardiac Surgery.

J Cardiothorac Vasc Anesth 2021 Jan 23;35(1):323-331. Epub 2020 Aug 23.

Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL. Electronic address:

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http://dx.doi.org/10.1053/j.jvca.2020.08.042DOI Listing
January 2021

Differential Ventilation Using Flow Control Valves as a Potential Bridge to Full Ventilatory Support during the COVID-19 Crisis.

Anesthesiology 2020 10;133(4):892-904

Background: During the COVID-19 pandemic, ventilator sharing was suggested to increase availability of mechanical ventilation. The safety and feasibility of ventilator sharing is unknown.

Methods: A single ventilator in pressure control mode was used with flow control valves to simultaneously ventilate two patients with different lung compliances. The system was first evaluated using high-fidelity human patient simulator mannequins and then tested for 1 h in two pairs of COVID-19 patients with acute respiratory failure. Patients were matched on positive end-expiratory pressure, fractional inspired oxygen tension, and respiratory rate. Tidal volume and peak airway pressure (PMAX) were recorded from each patient using separate independent spirometers and arterial blood gas samples drawn at 0, 30, and 60 min. The authors assessed acid-base status, oxygenation, tidal volume, and PMAX for each patient. Stability was assessed by calculating the coefficient of variation.

Results: The valves performed as expected in simulation, providing a stable tidal volume of 400 ml each to two mannequins with compliance ratios varying from 20:20 to 20:90 ml/cm H2O. The system was then tested in two pairs of patients. Pair 1 was a 49-yr-old woman, ideal body weight 46 kg, and a 55-yr-old man, ideal body weight 64 kg, with lung compliance 27 ml/cm H2O versus 35 ml/cm H2O. The coefficient of variation for tidal volume was 0.2 to 1.7%, and for PMAX 0 to 1.1%. Pair 2 was a 32-yr-old man, ideal body weight 62 kg, and a 56-yr-old woman, ideal body weight 46 kg, with lung compliance 12 ml/cm H2O versus 21 ml/cm H2O. The coefficient of variation for tidal volume was 0.4 to 5.6%, and for PMAX 0 to 2.1%.

Conclusions: Differential ventilation using a single ventilator is feasible. Flow control valves enable delivery of stable tidal volume and PMAX similar to those provided by individual ventilators.

Editor’s Perspective:
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http://dx.doi.org/10.1097/ALN.0000000000003473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359901PMC
October 2020

Plasma Oxalate as a Predictor of Kidney Function Decline in a Primary Hyperoxaluria Cohort.

Int J Mol Sci 2020 May 20;21(10). Epub 2020 May 20.

Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA.

This retrospective analysis investigated plasma oxalate (POx) as a potential predictor of end-stage kidney disease (ESKD) among primary hyperoxaluria (PH) patients. PH patients with type 1, 2, and 3, age 2 or older, were identified in the Rare Kidney Stone Consortium (RKSC) PH Registry. Since POx increased with falling estimated glomerular filtration rate (eGFR), patients were stratified by chronic kidney disease (CKD) subgroups (stages 1, 2, 3a, and 3b). POx values were categorized into quartiles for analysis. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for risk of ESKD were estimated using the Cox proportional hazards model with a time-dependent covariate. There were 118 patients in the CKD1 group (nine ESKD events during follow-up), 135 in the CKD 2 (29 events), 72 in CKD3a (34 events), and 45 patients in CKD 3b (31 events). During follow-up, POx Q4 was a significant predictor of ESKD compared to Q1 across CKD2 (HR 14.2, 95% CI 1.8-115), 3a (HR 13.7, 95% CI 3.0-62), and 3b stages (HR 5.2, 95% CI 1.1-25), < 0.05 for all. Within each POx quartile, the ESKD rate was higher in Q4 compared to Q1-Q3. In conclusion, among patients with PH, higher POx concentration was a risk factor for ESKD, particularly in advanced CKD stages.
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http://dx.doi.org/10.3390/ijms21103608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279271PMC
May 2020

Novel insights into breast cancer copy number genetic heterogeneity revealed by single-cell genome sequencing.

Elife 2020 05 13;9. Epub 2020 May 13.

Cold Spring Harbor Laboratory, Cold Spring Harbor, United States.

Copy number alterations (CNAs) play an important role in molding the genomes of breast cancers and have been shown to be clinically useful for prognostic and therapeutic purposes. However, our knowledge of intra-tumoral genetic heterogeneity of this important class of somatic alterations is limited. Here, using single-cell sequencing, we comprehensively map out the facets of copy number alteration heterogeneity in a cohort of breast cancer tumors. Ou/var/www/html/elife/12-05-2020/backup/r analyses reveal: genetic heterogeneity of non-tumor cells (i.e. stroma) within the tumor mass; the extent to which copy number heterogeneity impacts breast cancer genomes and the importance of both the genomic location and dosage of sub-clonal events; the pervasive nature of genetic heterogeneity of chromosomal amplifications; and the association of copy number heterogeneity with clinical and biological parameters such as polyploidy and estrogen receptor negative status. Our data highlight the power of single-cell genomics in dissecting, in its many forms, intra-tumoral genetic heterogeneity of CNAs, the magnitude with which CNA heterogeneity affects the genomes of breast cancers, and the potential importance of CNA heterogeneity in phenomena such as therapeutic resistance and disease relapse.
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http://dx.doi.org/10.7554/eLife.51480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220379PMC
May 2020

Coronavirus Disease 2019 (COVID-19) Complicated by Acute Respiratory Distress Syndrome: An Internist's Perspective.

Cureus 2020 Mar 31;12(3):e7482. Epub 2020 Mar 31.

Hospital Medicine, Cleveland Clinic - Fairview Hospital, Cleveland, USA.

A pandemic outbreak of a novel coronavirus disease (COVID-19) that began in Wuhan, China, in December 2019 has spread rapidly to multiple countries. In the United States, the first confirmed case was reported on January 20, 2020, and since then, the number of cases is rising exponentially on a daily basis. We report a case of COVID-19 infection that presented with symptoms suggestive of pneumonia. Due to the major backlog with an immense number of pending tests, it took 48 hours for the result to come back positive, while the patient went into acute respiratory distress syndrome. We provide an internist's perspective of the difficulties encountered in terms of the available management options, as the patient progressively deteriorated on the regular medical floor prompting transfer to the intensive care unit.
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http://dx.doi.org/10.7759/cureus.7482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188448PMC
March 2020

Utilization of a Voice-Based Virtual Reality Advanced Cardiac Life Support Team Leader Refresher: Prospective Observational Study.

J Med Internet Res 2020 03 12;22(3):e17425. Epub 2020 Mar 12.

Department of Anesthesiology, Pain, & Perioperative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

Background: The incidence of cardiac arrests per year in the United States continues to increase, yet in-hospital cardiac arrest survival rates significantly vary between hospitals. Current methods of training are expensive, time consuming, and difficult to scale, which necessitates improvements in advanced cardiac life support (ACLS) training. Virtual reality (VR) has been proposed as an alternative or adjunct to high-fidelity simulation (HFS) in several environments. No evaluations to date have explored the ability of a VR program to examine both technical and behavioral skills and demonstrate a cost comparison.

Objective: This study aimed to explore the utility of a voice-based VR ACLS team leader refresher as compared with HFS.

Methods: This prospective observational study performed at an academic institution consisted of 25 postgraduate year 2 residents. Participants were randomized to HFS or VR training and then crossed groups after a 2-week washout. Participants were graded on technical and nontechnical skills. Participants also completed self-assessments about the modules. Proctors were assessed for fatigue and task saturation, and cost analysis based on local economic data was performed.

Results: A total of 23 of 25 participants were included in the scoring analysis. Fewer participants were familiar with VR compared with HFS (9/25, 36% vs 25/25, 100%; P<.001). Self-reported satisfaction and utilization scores were similar; however, significantly more participants felt HFS provided better feedback: 99 (IQR 89-100) vs 79 (IQR 71-88); P<.001. Technical scores were higher in the HFS group; however, nontechnical scores for decision making and communication were not significantly different between modalities. VR sessions were 21 (IQR 19-24) min shorter than HFS sessions, the National Aeronautics and Space Administration task load index scores for proctors were lower in each category, and VR sessions were estimated to be US $103.68 less expensive in a single-learner, single-session model.

Conclusions: Utilization of a VR-based team leader refresher for ACLS skills is comparable with HFS in several areas, including learner satisfaction. The VR module was more cost-effective and was easier to proctor; however, HFS was better at delivering feedback to participants. Optimal education strategies likely contain elements of both modalities. Further studies are needed to examine the utility of VR-based environments at scale.
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http://dx.doi.org/10.2196/17425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099400PMC
March 2020

Transcatheter Mitral Valve Repair and Replacement: Analysis of Recent Data and Outcomes.

J Cardiothorac Vasc Anesth 2020 Oct 15;34(10):2793-2806. Epub 2020 Jan 15.

Division of Cardiovascular and Thoracic Anesthesiology, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN. Electronic address:

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http://dx.doi.org/10.1053/j.jvca.2020.01.009DOI Listing
October 2020

Severe Vasoplegic Shock During Coronary Artery Bypass Surgery: Therapeutic challenges and Dilemmas in Hemodynamic Rescue.

J Cardiothorac Vasc Anesth 2020 May 10;34(5):1341-1347. Epub 2020 Feb 10.

Department of Anesthesiology and Critical Care, Cardiovascular and Thoracic Section, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. Electronic address:

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http://dx.doi.org/10.1053/j.jvca.2020.01.058DOI Listing
May 2020

Simulation Training for Critical Care Airway Management: Assessing Translation to Clinical Practice Using a Small Video-Recording Device.

Chest 2020 07 28;158(1):272-278. Epub 2020 Feb 28.

Division of Pulmonary, Critical Care, and Sleep Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, New Hyde Park, NY.

Background: Critical care airway management (CCAM) is a key skill for critical care physicians. Simulation-based training (SBT) may be an effective modality in training intensivists in CCAM.

Research Question: Is SBT of critical care fellows an effective means of providing training in CCAM, in particular in urgent endotracheal intubation?

Study Design And Methods: Thirteen first-year pulmonary critical care medicine (PCCM) fellows at an academic training program underwent SBT with a computerized patient simulator (CPS) in their first month of fellowship training. At the end of the training period, the fellows underwent video-based scoring using a 46-item checklist (of which 40 points could be scored) while performing a complete CCAM sequence on the CPS. They were then tested, using video-based scoring on their first real-life CCAM. Maintenance of skill at CCAM was assessed during the fellows' second and third year of training, using the same scoring method.

Results: For the first-year fellows, the score on the CPS was 38.3 ± 0.75 SD out of a maximum score of 40. The score on their first real-life patient CCAM was 39.0 ± 0.81 SD (P = .003 for equivalence; 95% CI for difference between real-life patient CCAM and CPS scores, 0.011-1.373). Sixteen second- and third-year fellows were tested at a real-life CCAM event later in their fellowship to examine for maintenance of skill. The mean maintenance of skill score of this group was 38.7 ± 1.14 SD.

Interpretation: Skill acquired through SBT of critical care fellows for CCAM transfers effectively to the real-life patient care arena. Second- and third-year fellows who had initially received SBT maintained skill at CCAM.
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http://dx.doi.org/10.1016/j.chest.2020.01.047DOI Listing
July 2020

Genome-wide Association Study of 24-Hour Urinary Excretion of Calcium, Magnesium, and Uric Acid.

Mayo Clin Proc Innov Qual Outcomes 2019 Dec 22;3(4):448-460. Epub 2019 Nov 22.

Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN.

Objectives: The urinary excretion of organic and inorganic substances and their concentrations have attracted extensive attention for their role in the pathogenesis of urinary stone disease. The urinary excretion of specific factors associates with sex and age and seems to have a hereditary component, but the precise genomic determinants remain ill-defined.

Methods: Genome-wide association studies previously conducted in 3 cohorts (Genetic Epidemiology Network of Arteriopathy study, January 1, 2006, through December 31, 2012; the combined Nurses' Health Study (NHS), NHS II, and Health Professionals Follow-up Study, January 1, 1994, through December 31, 2003; and the Prevention of Renal and Vascular End-stage Disease study, January 1, 1997, through December 31, 1998) were combined into meta-analyses to evaluate genetic associations with available urinary phenotypes relevant to stone pathogenesis (calcium, magnesium, and uric acid excretion; total urine volume).

Results: One region on chromosome 9q21.13 showed strong evidence of an association with urinary magnesium excretion. The strongest signal in this region was near , whose protein product mediates magnesium transport in the colon and kidney, and , , , and (rs1176815; 1.70×10, with each copy of the A allele corresponding to a daily 5.29-mg decrease in magnesium excretion). The single nucleotide polymorphism (SNP) that achieved genome-wide significance for calcium excretion (rs17216707 on chromosome 20; 1.12×10) was previously associated with fibroblast growth factor 23 levels, which regulate phosphorus and vitamin D metabolism. Urine volume and uric acid excretion did not have any genome-wide significant SNPs.

Conclusion: Common variants near genes important for magnesium metabolism and bone health associate with urinary magnesium and calcium excretion.
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http://dx.doi.org/10.1016/j.mayocpiqo.2019.08.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978610PMC
December 2019

Precision oncology: lessons learned and challenges for the future.

Cancer Manag Res 2019 7;11:7525-7536. Epub 2019 Aug 7.

The Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences, New York, NY, USA.

The decreasing cost of and increasing capacity of DNA sequencing has led to vastly increased opportunities for population-level genomic studies to discover novel genomic alterations associated with both Mendelian and complex phenotypes. To translate genomic findings clinically, a number of health care institutions have worked collaboratively or individually to initiate precision medicine programs. These precision medicine programs involve designing patient enrollment systems, tracking electronic health records, building biobank repositories, and returning results with actionable matched therapies. As cancer is a paradigm for genetic diseases and new therapies are increasingly tailored to attack genetic susceptibilities in tumors, these precision medicine programs are largely driven by the urgent need to perform genetic profiling on cancer patients in real time. Here, we review the current landscape of precision oncology and highlight challenges to be overcome and examples of benefits to patients. Furthermore, we make suggestions to optimize future precision oncology programs based upon the lessons learned from these "first generation" early adopters.
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http://dx.doi.org/10.2147/CMAR.S201326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698584PMC
August 2019

Simulation-Based Education and Team Training.

Otolaryngol Clin North Am 2019 Dec 13;52(6):995-1003. Epub 2019 Sep 13.

Department of Anesthesiology, Perioperative and Pain Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, Klingenstein Clinical Center 8th Floor, PO Box 1010, New York, NY 10029, USA.

Simulation-based education (SBE) has become pervasive in health care training and medical education, and is even more important in subspecialty training whereby providers such as otolaryngologists and anesthesiologists share overlapping patient concerns because of the proximity of the surgical airway. Both these subspecialties work in a fast-paced environment involving high-stakes situations and life-changing events that necessitate critical thinking and timely action, and have an exceedingly small bandwidth for error. Team training in the form of interprofessional education and learning involving surgeons, anesthesiologists, and nursing is critical for patient safety in the operating room in general, but more so in otolaryngology surgery.
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http://dx.doi.org/10.1016/j.otc.2019.08.002DOI Listing
December 2019

Selective Autophagy of Mitochondria on a Ubiquitin-Endoplasmic-Reticulum Platform.

Dev Cell 2019 09 25;50(5):627-643.e5. Epub 2019 Jul 25.

Signalling Programme, Babraham Institute, Cambridge, UK. Electronic address:

The dynamics and coordination between autophagy machinery and selective receptors during mitophagy are unknown. Also unknown is whether mitophagy depends on pre-existing membranes or is triggered on the surface of damaged mitochondria. Using a ubiquitin-dependent mitophagy inducer, the lactone ivermectin, we have combined genetic and imaging experiments to address these questions. Ubiquitination of mitochondrial fragments is required the earliest, followed by auto-phosphorylation of TBK1. Next, early essential autophagy proteins FIP200 and ATG13 act at different steps, whereas ULK1 and ULK2 are dispensable. Receptors act temporally and mechanistically upstream of ATG13 but downstream of FIP200. The VPS34 complex functions at the omegasome step. ATG13 and optineurin target mitochondria in a discontinuous oscillatory way, suggesting multiple initiation events. Targeted ubiquitinated mitochondria are cradled by endoplasmic reticulum (ER) strands even without functional autophagy machinery and mitophagy adaptors. We propose that damaged mitochondria are ubiquitinated and dynamically encased in ER strands, providing platforms for formation of the mitophagosomes.
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http://dx.doi.org/10.1016/j.devcel.2019.06.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739445PMC
September 2019

Analysis of the 2019 ACC/AATS/AHA/ASE/ASNC/HRS/SCAI/SCCT/SCMR/STS Appropriate Use Criteria for Multimodal Imaging in the Assessment of Structural Heart Disease.

J Cardiothorac Vasc Anesth 2020 Mar 21;34(3):805-818. Epub 2019 May 21.

Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Phoenix, AZ. Electronic address:

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http://dx.doi.org/10.1053/j.jvca.2019.05.018DOI Listing
March 2020

Efficacy and Usability of a Novel Barrier Device for Preventing Injection Port Contamination: A Pilot Simulation Study.

Anesth Analg 2020 03;130(3):e45-e48

From the Department of Anesthesiology, Perioperative and Pain Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.

Contamination of intravenous (IV) ports and stopcocks has been associated with postoperative infections. We tested the usability and efficacy of a novel passive shielding device to prevent such contamination even in the absence of hand hygiene or port disinfection. In a desktop setting with deliberately contaminated hands, qualitative port contamination was detected after 5/60 (8.3%; 95% confidence interval [CI], 2.8-18.4) control port injections versus 0/60 (0%; 95% CI, 0-6.0) shielded injections (P = .025). In clinical simulations with a quantitative bioburden assay (measured in relative light units [RLUs]), median (interquartile range [IQR]) postsimulation bioburden was 46 (32-53) vs 27 (21-42) RLU for the control versus intervention groups (P = .036), yielding a median shift of -13 RLU (95% CI, -2 to -26) in favor of the shielding. Usability of the device was acceptable to practitioners.
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http://dx.doi.org/10.1213/ANE.0000000000004235DOI Listing
March 2020

Mentoring Fellows in Adult Cardiothoracic Anesthesiology for Academic Practice in the Contemporary Era-Perspectives From Mentors Around the United States.

J Cardiothorac Vasc Anesth 2020 Feb 9;34(2):521-529. Epub 2019 Jan 9.

Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. Electronic address:

This special article presents perspectives on the mentoring of fellows for academic practice in adult cardiothoracic anesthesiology. A comprehensive mentoring model should address the areas of clinical care, educational expertise and exposure to scholarly activity. The additional value of educational exposure to patient safety, quality improvement and critical care medicine in this model is also explored.
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http://dx.doi.org/10.1053/j.jvca.2019.01.024DOI Listing
February 2020

Real-Time Genomic Characterization of Metastatic Pancreatic Neuroendocrine Tumors Has Prognostic Implications and Identifies Potential Germline Actionability.

JCO Precis Oncol 2018 19;2018. Epub 2018 Apr 19.

Memorial Sloan Kettering Cancer Center; Columbia University College of Physicians and Surgeons, New York, NY.

Purpose: We assessed the usefulness of real-time molecular profiling through next-generation sequencing (NGS) in predicting the tumor biology of advanced pancreatic neuroendocrine tumors (panNETs) and in characterizing genomic evolution.

Methods: Patients with metastatic panNETs were recruited in the routine clinical practice setting (between May 2014 and March 2017) for prospective NGS of their tumors as well as for germline analysis using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) sequencing platform. When possible, NGS was performed at multiple time points.

Results: NGS was performed in 96 tumor samples from 80 patients. Somatic alterations were identified in 76 of 80 patients (95%). The most commonly altered genes were (56%), (40%), (25%), and (25%). Alterations could be defined in pathways that included chromatin remodeling factors, histone methyltransferases, and mammalian target of rapamycin pathway genes. Somatic loss of heterozygosity was particularly prevalent (50 of 96 samples [52%]), and the presence of loss of heterozygosity resulted in inferior overall survival ( < .01). Sequencing of pre- and post-treatment samples revealed tumor-grade progression; clonal evolution patterns were also seen (molecular resistance mechanisms and chemotherapy-associated mutagenesis). Germline genetic analysis identified clinically actionable pathogenic or likely pathogenic variants in 14 of 88 patients (16%), including mutations in high-penetrance cancer susceptibility genes (, , and ).

Conclusion: A clinical NGS platform reveals pertubations of biologic pathways in metastatic panNETs that may inform prognosis and direct therapies. Repeat sequencing at disease progression reveals increasing tumor grade and genetic evolution, demonstrating that panNETs adopt a more aggressive behavior through time and therapies. In addition to frequent somatic mutations in and , germline mutations in these same genes underlie susceptibility to panNETs and highlight the need to re-evaluate whether germline genetic analysis should be performed for all patients with panNETs.
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http://dx.doi.org/10.1200/PO.17.00267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345401PMC
April 2018

Tracking tumour evolution in glioma through liquid biopsies of cerebrospinal fluid.

Nature 2019 01 23;565(7741):654-658. Epub 2019 Jan 23.

Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Diffuse gliomas are the most common malignant brain tumours in adults and include glioblastomas and World Health Organization (WHO) grade II and grade III tumours (sometimes referred to as lower-grade gliomas). Genetic tumour profiling is used to classify disease and guide therapy, but involves brain surgery for tissue collection; repeated tumour biopsies may be necessary for accurate genotyping over the course of the disease. While the detection of circulating tumour DNA (ctDNA) in the blood of patients with primary brain tumours remains challenging, sequencing of ctDNA from the cerebrospinal fluid (CSF) may provide an alternative way to genotype gliomas with lower morbidity and cost. We therefore evaluated the representation of the glioma genome in CSF from 85 patients with gliomas who underwent a lumbar puncture because they showed neurological signs or symptoms. Here we show that tumour-derived DNA was detected in CSF from 42 out of 85 patients (49.4%) and was associated with disease burden and adverse outcome. The genomic landscape of glioma in the CSF included a broad spectrum of genetic alterations and closely resembled the genomes of tumour biopsies. Alterations that occur early during tumorigenesis, such as co-deletion of chromosome arms 1p and 19q (1p/19q codeletion) and mutations in the metabolic genes isocitrate dehydrogenase 1 (IDH1) or IDH2, were shared in all matched ctDNA-positive CSF-tumour pairs, whereas growth factor receptor signalling pathways showed considerable evolution. The ability to monitor the evolution of the glioma genome through a minimally invasive technique could advance the clinical development and use of genotype-directed therapies for glioma, one of the most aggressive human cancers.
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http://dx.doi.org/10.1038/s41586-019-0882-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457907PMC
January 2019

Endoscopic optical coherence tomography angiography using a forward imaging piezo scanner probe.

J Biophotonics 2019 04 30;12(4):e201800382. Epub 2019 Jan 30.

Gisela and Erwin Sick Chair of Micro-optics, Department of Microsystems Engineering, University of Freiburg, Freiburg, Germany.

A forward imaging endoscope for optical coherence tomography angiography (OCTA) featuring a piezoelectric fiber scanner is presented. Imaging is performed with an optical coherence tomography (OCT) system incorporating an akinetic light source with a center wavelength of 1300 nm, bandwidth of 90 nm and A-line rate of 173 kHz. The endoscope operates in contact mode to avoid motion artifacts, in particular, beneficial for OCTA measurements, and achieves a transversal resolution of 12 μm in air at a rigid probe size of 4 mm in diameter and 11.3 mm in length. A spiral scan pattern is generated at a scanning frequency of 360 Hz to sample a maximum field of view of 1.3 mm. OCT images of a human finger as well as visualization of microvasculature of the human palm are presented both in two and three dimensions. The combination of morphological tissue contrast with qualitative dynamic blood flow information within this endoscopic imaging approach potentially enables improved early diagnostic capabilities of internal organs for diseases such as bladder cancer.
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http://dx.doi.org/10.1002/jbio.201800382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065608PMC
April 2019
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