Considerations for the Use of Phage Therapy in Clinical Practice.

Increasing antimicrobial resistance and medical device-related infections have led to a renewed interest in phage therapy as an alternative or adjunct to conventional antimicrobials. Expanded access and compassionate use cases have risen exponentially but have varied widely in approach, methodology, and clinical situations in which phage therapy might be considered. Large gaps in knowledge contribute to heterogeneity in approach and lack of consensus in many important clinical areas. The Antibacterial Resistance Leadership Group (ARLG) has convened a panel of experts in phage therapy, clinical microbiology, infectious diseases, and pharmacology, who worked with regulatory experts and a funding agency to identify questions based on a clinical framework and divided them into three themes: potential clinical situations in which phage therapy might be considered, laboratory testing, and pharmacokinetic considerations. Suggestions are provided as answers to a series of questions intended to inform clinicians considering experimental phage therapy for patients in their clinical practices.

The African Green Monkey Model of Pneumonic Plague and US Food and Drug Administration Approval of Antimicrobials Under the Animal Rule.

BACKGROUND: Additional treatment options for pneumonic plague, the most severe form of infection by Yersinia pestis, are needed, as past US Food and Drug Administration (FDA) approvals were not based on clinical trials that meet today's standards, and multiple drugs are sought to counter resistance or use in special populations. Due to the sporadic nature of outbreaks and the low number of pneumonic cases of disease, we sought FDA approval of antimicrobials for treatment under the Animal Efficacy Rule, where efficacy can be demonstrated in 1 or more well-characterized animal models that sufficiently represent human disease. METHODS: A model was developed in African green monkeys (AGMs) after challenge with a lethal dose of Y. pestis delivered as an aerosol, in 4 independent studies in 3 laboratories. The primary data points were bacteremia (daily), body temperature and heart rate (continuously monitored by telemetry), and survival. In antimicrobial efficacy studies, human-equivalent doses of gentamicin, ciprofloxacin, levofloxacin, and doxycycline were administered upon fever onset for 10 days. RESULTS: Disease in AGMs was similar to case reports of human disease. Fever was determined to be a reliable sign of disease and selected as a treatment trigger. Gentamicin was 60%-80% effective depending on the dose given to animals. Ciprofloxacin and levofloxacin were found to be >90% efficacious. These data were submitted to FDA and plague indications were approved. Doxycycline was less effective. CONCLUSIONS: The AGM model of pneumonic plague is reproducible, well-characterized, and mimics human disease. It has been used to support plague indications for fluoroquinolones and to test the efficacy of additional antimicrobials.

Effect of Delaying Treatment on Efficacy of Ciprofloxacin and Levofloxacin in the African Green Monkey Model of Pneumonic Plague.

BACKGROUND: Ciprofloxacin and levofloxacin, 2 fluoroquinolone antimicrobials, are ≥90% effective for the treatment of inhalational plague when administered within 2-6 hours of fever onset in African green monkeys (AGM). Based on data in the AGM model, these antimicrobials were approved under the Food and Drug Administration's Animal Efficacy Rule. However, that data did not address the issue of how long treatment with these antimicrobials would remain effective after fever onset. METHODS: The AGM model of pneumonic plague was used to explore the effect of delaying treatment with ciprofloxacin and levofloxacin on efficacy. In 2 studies, AGMs were challenged with inhaled lethal doses of Yersinia pestis. Treatment with ciprofloxacin and levofloxacin was initiated from 0 to up to 30 hours after fever onset. RESULTS: Challenged animals all developed fever within 78 hours and were treated with ciprofloxacin (n = 27) or levofloxacin (n = 29) at various predetermined time points postfever. When administered 10 hours after fever onset, 10 days of ciprofloxacin and levofloxacin treatment remained very effective (90 or 100%, respectively). The efficacy of both antimicrobials declined as treatment initiation was further delayed. Statistical analyses estimated the treatment delay times at which half of the AGMs were no longer expected to survive as 19.7 hours for ciprofloxacin and 26.5 hours for levofloxacin. CONCLUSIONS: This study demonstrates that there is a narrow window following fever onset during which ciprofloxacin and levofloxacin are fully effective treatment options for pneumonic plague in AGMs. Since the timing of disease is similar in humans and AGMs, these AGM data are reasonably likely to predict response times for treatment in humans.

Selective Monofunctionalization Enabled by Reaction-History-Dependent Communication in Catalytic Rotaxanes.

Selective monofunctionalization of substrates with distant, yet equally reactive functional groups is difficult to achieve, as it requires the second functional group to selectively modulate its reactivity once the first functional group has reacted. We now show that mechanically interlocked catalytic rings can effectively regulate the reactivity of stoppering groups in rotaxanes over a distance of about 2 nm. Our mechanism of communication is enabled by a unique interlocked design, which effectively removes the catalytic rings from the substrates by fast dethreading as soon as the first reaction has taken place. Our method not only led to a rare example of selective monofunctionalization, but also to a "molecular if function". Overall, the study presents a way to get distant functional groups to communicate with each other in a reaction-history-dependent manner by creating linkers that can ultimately perform logical operations at the molecular level.

Software for designing rigorous and replicable preclinical research: The Experimental Design Accelerator.

In recent years, there have been concerns about research practices in basic and preclinical biomedical research. There have been problems with non-replicable results, and experimental designs lacking internal validity or external or translational validity. The Experimental Design Accelerator (XDA) is Internet-based, interactive software designed to help those trying to design, conduct and document rigorous, replicable and relevant experiments. It leads the investigator step-by-step through a series of decisions that will define the experimental design. It provides background regarding the significance of each decision and the advantages and disadvantages of each possible choice. For example, it leads the researcher to address issues such as choosing a research model, developing testable hypotheses, identifying extraneous variables, dealing with random and systematic error, picking appropriate sample size and picking appropriate statistical analyses. There are also sections to help conduct the experiment consistent with its design and to document the study to facilitate accurate replication. Helpful features include access to an online statistics book and provisions for rapid contact with consulting experts. A number of potential uses for such novel interactive software tools will be discussed.

Enantioselective Electrophilic Aromatic Nitration: A Chiral Auxiliary Approach.

Enantioselective electrophilic aromatic nitration methodology is needed to advance chirality-assisted synthesis (CAS). Reported here is an enantioselective aromatic nitration strategy operating with chiral diester auxiliaries, and it provides an enantioselective synthesis of a C3v -symmetric tribenzotriquinacene (TBTQ). These axially-chiral structures are much sought-after building blocks for CAS, but they were not accessible prior to this work in enantioenriched form without resolution of enantiomers. This nitration strategy controls the stereochemistry of threefold nitration reactions from above the aromatic rings with chiral diester arms. Dicarbonyl-to-arenium chelation rigidifies the reaction systems, so that remote stereocenters position the ester-directing groups selectively over specific atoms of the TBTQ framework. Closely guided by computational design, a more selective through-space directing arm was first predicted with density functional theory (DFT), and then confirmed in the laboratory, to outperform the initial structural design. This enantio- and regioselective TBTQ synthesis opens a new pathway to access building blocks for CAS.

Pseudoaneurysm of the left main coronary artery: A complication of orbital atherectomy.

Plaque modification devices are used to treat heavily calcified coronary artery lesions during percutaneous coronary artery interventions. As these devices have unique risk profiles, clinicians need to be aware of potential complications associated with their use. A case of a contained rupture (i.e., pseudoaneurysm) of the proximal left main coronary artery following orbital atherectomy is presented. This lesion was managed with coronary artery bypass grafting and oversewing of the left main coronary artery ostium. This case illustrates that lesion location and configuration may influence tracking of these devices, as well as the actual site of tissue ablation. This case underscores the importance of concurrent imaging during treatment and concern for potential unintended consequences of atherectomy.

Crystal-Packing-Driven Enrichment of Atropoisomers.

Crystal-packing forces can have a significant impact on the relative stabilities of different molecules and their conformations. The magnitude of such effects is, however, not yet well understood. Herein we show, that crystal packing can completely overrule the relative stabilities of different stereoisomers in solution. Heating of atropoisomers (i.e. "frozen-out" conformational isomers) in solution leads to complex mixtures. In contrast, solid-state heating selectively amplifies minor (<25 mole %) components of these solution-phase mixtures. We show that this heating strategy is successful for compounds with up to four rotationally hindered σ bonds, for which a single stereoisomer out of seven can be amplified selectively. Our results demonstrate that common supramolecular interactions-for example, [methyl⋅⋅⋅π] coordination and [C-H⋅⋅⋅O] hydrogen bonding-can readily invert the relative thermodynamic stabilities of different molecular conformations. These findings open up potential new avenues to control the folding of macromolecules.

Validation and analysis of prognostic scoring systems for critically ill patients with cirrhosis admitted to ICU.

INTRODUCTION: The number of patients admitted to ICU who have liver cirrhosis is rising. Current prognostic scoring tools to predict ICU mortality have performed poorly in this group. In previous research from a single centre, a novel scoring tool which modifies the Child-Turcotte Pugh score by adding Lactate concentration, the CTP + L score, is strongly associated with mortality. This study aims to validate the use of the CTP + L scoring tool for predicting ICU mortality in patients admitted to a general ICU with cirrhosis, and to determine significant predictive factors for mortality with this group of patients. This study will also explore the use of the Royal Free Hospital (RFH) score in this cohort. METHODS: A total of 84 patients admitted to the Glasgow Royal Infirmary ICU between June 2012 and Dec 2013 with cirrhosis were included. An additional cohort of 115 patients was obtained from two ICUs in London (St George's and St Thomas') collected between October 2007 and July 2009. Liver specific and general ICU scoring tools were calculated for both cohorts, and compared using area under the receiver operating characteristic (ROC) curves. Independent predictors of ICU mortality were identified by univariate analysis. Multivariate analysis was utilised to determine the most predictive factors affecting mortality within these patient groups. RESULTS: Within the Glasgow cohort, independent predictors of ICU mortality were identified as Lactate (p < 0.001), Bilirubin (p = 0.0048), PaO2/FiO2 Ratio (p = 0.032) and PT ratio (p = 0.012). Within the London cohort, independent predictors of ICU mortality were Lactate (p < 0.001), PT ratio (p < 0.001), Bilirubin (p = 0.027), PaO2/FiO2 Ratio (p = 0.0011) and Ascites (p = 0.023). The CTP + L and RFH scoring tools had the highest ROC value in both cohorts examined. CONCLUSION: The CTP + L and RFH scoring tool are validated prognostic scoring tools for predicting ICU mortality in patients admitted to a general ICU with cirrhosis.

Handheld Devices and Video Modeling to Enhance the Learning of Self-Help Skills in Adolescents With Autism Spectrum Disorder.

The viewing of videos is a much-studied intervention to teach self-help, social, and vocational skills. Many of the studies to date looked at video modeling using televisions, computers, and other large screens. This study looked at the use of video modeling on portable handheld devices to teach hand washing to three adolescent students with an autism spectrum disorder. Three students participated in this 4-week study conducted by occupational therapists. Baseline data were obtained for the first student for 1 week, the second for 2 weeks, and the third for 3 weeks; videos were introduced when the participants each finished the baseline phase. Given the cognitive and motor needs of the participants, the occupational therapist set the player so that the participants only had to press the play button to start the video playing. The participants were able to hold the players and view at distances that were most appropriate for their individual needs and preferences. The results suggest that video modeling on a handheld device improves the acquisition of self-help skills.

A Trigger Warning: Red Flag Laws are Still Constitutionally Permissible and Could Reduce the Suicide Rates in the Country's Most Vulnerable States.

Montana, Alaska, and Wyoming lead the United States in a category coveted by no one: the suicide rate. Firearm ownership drives the rate to the disproportionate level it reaches year after year and the states are left with little recourse. This article argues the usefulness and constitutionality of narrowly tailored red-flag laws aimed exclusively at reducing the rate of suicide in these mountain states. The article follows Supreme Court jurisprudence leading up to New York Rifle and Pistol Association v. Bruen and offers an analysis that complies with the hyper textualist history and tradition test laid out by Scalia in District of Columbia v. Heller and McDonald v. City of Chicago. The analysis demonstrates that narrowly tailored red flag laws are a constitutional means of reducing the suicide rate in these at-risk states and references statutory and cultural avenues for the implementation of the legislation.

Bilateral Inferior Rectus Schwannoma and Strabismus: A Case Report.

Schwannomas, also known as neurilemomas, are peripheral nerve sheath neoplasms. They can be sporadic or associated with genetic syndromes including neurofibromatosis type 2 (NF2). Schwannomas may lead to symptoms by exerting pressure on nearby structures, such as nerve and muscle fibers. In this study, we present the case of a 22-year-old female with a history of NF2 who, upon examination, presented with a visibly enlarged salmon-colored mass involving the left inferior rectus that she had since the age of 12 years. Ocular examinations revealed a small left hypertropia and exotropia in all gazes. Magnetic resonance imaging confirmed bilateral involvement of the inferior rectus muscles. She had a partial excisional biopsy of the mass involving the left inferior rectus muscle that confirmed the presence of schwannoma. This case highlights the importance of comprehensive evaluation of sensory and motor functions as well as considering orbital schwannomas in cases of strabismus, especially within the context of neurofibromatosis.

GRL-0519, a novel oxatricyclic ligand-containing nonpeptidic HIV-1 protease inhibitor (PI), potently suppresses replication of a wide spectrum of multi-PI-resistant HIV-1 variants in vitro.

We report that GRL-0519, a novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) containing tris-tetrahydrofuranylurethane (tris-THF) and a sulfonamide isostere, is highly potent against laboratory HIV-1 strains and primary clinical isolates (50% effective concentration [EC50], 0.0005 to 0.0007 µM) with minimal cytotoxicity (50% cytotoxic concentration [CC50], 44.6 µM). GRL-0519 blocked the infectivity and replication of HIV-1NL4-3 variants selected by up to a 5 µM concentration of ritonavir, lopinavir, or atazanavir (EC50, 0.0028 to 0.0033 µM). GRL-0519 was also potent against multi-PI-resistant clinical HIV-1 variants isolated from patients who no longer responded to existing antiviral regimens after long-term antiretroviral therapy, highly darunavir (DRV)-resistant variants, and HIV-2ROD. The development of resistance against GRL-0519 was substantially delayed compared to other PIs, including amprenavir (APV) and DRV. The effects of nonspecific binding of human serum proteins on GRL-0519's antiviral activity were insignificant. Our analysis of the crystal structures of GRL-0519 (3OK9) and DRV (2IEN) with protease suggested that the tris-THF moiety, compared to the bis-THF moiety present in DRV, has greater water-mediated polar interactions with key active-site residues of protease and that the tris-THF moiety and paramethoxy group effectively fill the S2 and S2' binding pockets, respectively, of the protease. The present data demonstrate that GRL-0519 has highly favorable features as a potential therapeutic agent for treating patients infected with wild-type and/or multi-PI-resistant variants and that the tris-THF moiety is critical for strong binding of GRL-0519 to the HIV protease substrate binding site and appears to be responsible for its favorable antiretroviral characteristics.

Cilia-mimetic hairy surfaces based on end-immobilized nanocellulose colloidal rods.

We show a simple method toward nanoscale cilia-like structures, i.e., functional hairy surfaces, upon topochemically functionalizing nanorods of cellulose nanocrystals (CNCs) with thiol end groups (CNC-SHs), which leads to their immobilization onto a gold surface from one end, still allowing their orientational mobility. CNCs having a lateral dimension of 3-5 nm and length of 50-500 nm incorporate the native crystalline structure with hydrogen-bonded cellulose chains in the parallel configuration. This facilitates asymmetric, selective chemical modification of the reducing ends through reductive amination. Successful thiol functionalization is demonstrated using cryo transmission electron microscopy based on selective attachment of silver nanoparticles to the CNC-SH ends to form Janus-like colloidal rod-sphere adducts. The extent of thiol modification of CNC-SHs is quantified using X-ray photoelectron spectroscopy. The promoted binding of CNC-SHs on gold surfaces is shown by atomic force microscopy and quartz crystal microbalance, where the high dissipation suggests pronounced orientational mobility due to flexible joints at one rod end onto the surfaces. That the joints are flexible is also shown by the bending and realignment of the CNC-SH rods using a receding triple-phase evaporation front of a drying drop of water. The ability of the hairy surface to size-selectively resist particle binding was also investigated. As the CNCs are piezoelectric and allow magnetic functionalization by nanoparticles, we foresee a general platform for nanosized artificial cilia for fluid manipulation and controlled adsorption/desorption.

Pimavanserin reverses multiple measures of anxiety in a rodent model of post-traumatic stress disorder.

Pimavanserin is a highly selective 5-HT2A inverse agonist in current medical use. Prior studies suggest that 5-HT2A serotonin receptors may play a role in anxiety and emotional memory. Therefore, pimavanserin was tested in a rat model of PTSD to determine whether it might ameliorate PTSD-like symptoms. The lifetime prevalence of PTSD is estimated to be 125% higher in women than men. Consequently, in an effort to create a robust model of PTSD that was more representative of human PTSD prevalence, 20-week old female rats of the emotionally hyperreactive Lewis strain were used for these studies. The rats were single-housed and exposed twice to restraint stress coupled with predator odor or to a sham-stressed condition. Twenty days after the second stress or sham-stress exposure, rats were injected with saline alone or with 0.3 or 1.0 mg/kg pimavanserin, doses that were confirmed to substantially block 5-HT2A receptor activity in this study without causing any non-specific behavioral or adverse effects. One hour later, rats were tested for anxiety through acoustic startle response, the elevated plus-maze and three parameters of open field behavior. Five days later, blood was sampled for plasma corticosterone. The stressed/saline-injected rats had higher anxiety scores and corticosterone levels than sham-stressed/saline-injected rats. Pimavanserin significantly and generally dose-dependently reversed these persistent stress effects, but had no significant effect on the behavioral measures in normal, non-stressed rats. These results, consistent with a role for the 5-HT2A receptor, suggest that pimavanserin might have potential to reduce some consequences of traumatic stress.

The Prevalence, Magnitude, and Reversibility of Elevated Liver Enzyme Activities in Hyperthyroid Cats Presenting for Iodine-131 Treatment.

OBJECTIVES: The primary objective of this study was to report the prevalence and magnitude of elevated liver enzyme activity in feline hyperthyroidism using a large cohort of cats presenting for iodine-131 treatment. The secondary objective was to determine if elevated liver enzyme activity was a reversible process following successful iodine-131 treatment. METHODS: Cases that presented for a single iodine-131 treatment were retrospectively reviewed. Short-term and long-term follow-up clinicopathologic data was then reviewed for the secondary objective. RESULTS: Two hundred seventeen hyperthyroid cats met the inclusion criteria for the primary objective. In total, 123/217 (56.7%) of the cats had at least one liver enzyme elevation on their chemistry panel, with alanine transaminase activity being the most common. All cats who were successfully treated with iodine-131 had liver enzyme activity within the reference range at short-term follow-up and long-term follow-up points. CONCLUSION AND RELEVANCE: Our study demonstrates that elevated liver values are common in cats presenting for iodine-131 treatment. Additionally, our study demonstrates that even when liver values are markedly elevated prior to treatment, the liver enzyme activity will return to normal after successful resolution of hyperthyroidism using iodine-131 treatment. Investigation into hepatobiliary disease and liver function tests for cats with a diagnosis of hyperthyroidism may be unnecessary as the liver values will likely return to normal with successful iodine-131 treatment.

Safety and microbiological activity of phage therapy in persons with cystic fibrosis colonized with Pseudomonas aeruginosa: study protocol for a phase 1b/2, multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Bacteriophages (phages) are a promising anti-infective option for human disease. Major gaps remain in understanding their potential utility. METHODS: This is a randomized, placebo-controlled, double-blind study of a single dose of intravenous phage in approximately 72 clinically stable adult cystic fibrosis volunteers recruited from up to 20 US sites with Pseudomonas aeruginosa airway colonization. The single dose of phage consists of a mixture of four anti-pseudomonal phages. Six sentinel participants will be sequentially enrolled with dose escalation of the phage mixture by one log10 beginning with 4 × 107 plaque-forming units in an unblinded stage 1. If no serious adverse events related to the study product are identified, the trial will proceed to a double-blinded stage 2. In stage 2a, 32 participants will be randomly assigned to one of three phage dosages or placebo in a 1:1:1:1 allocation. An interim analysis will be performed to determine the phage dosage with the most favorable safety and microbiological activity profile to inform phage dosing in stage 2b. During stage 2b, up to 32 additional volunteers will be randomized 1:1 to the phage or placebo arm. Primary outcomes include (1) the number of grade 2 or higher treatment-emergent adverse events, (2) change in log10 P. aeruginosa total colony counts in sputum, and (3) the probability of a randomly selected subject having a more favorable outcome ranking if assigned to receive phage therapy versus placebo. Exploratory outcomes include (1) sputum and serum phage pharmacokinetics, (2) the impact of phage on lung function, (3) the proportion of P. aeruginosa isolates susceptible to the phage mixture before and after study product administration, and (4) changes in quality of life. DISCUSSION: This trial will investigate the activity of phages in reducing P. aeruginosa colony counts and provide insights into the safety profile of phage therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT05453578. Registered on 12 July 2022.

Outcomes of Combined Transcatheter Aortic Valve Replacement and Peripheral Vascular Intervention in the United States.

OBJECTIVES: The aim of this study was to compare the prevalence and real-world outcomes of patients who require peripheral vascular intervention during the same hospitalization as transcatheter aortic valve replacement (TAVR) compared with TAVR alone. BACKGROUND: There are limited data on the prevalence and outcomes of combined TAVR and percutaneous peripheral vascular intervention. METHODS: All patients who underwent TAVR in 2016 and 2017 were identified using the Nationwide Readmissions Database. Outcomes of patients undergoing TAVR alone were compared with those of patients undergoing combined TAVR and peripheral intervention, TAVR and peripheral intervention with and without a history of peripheral artery disease, and alternative-access TAVR with transfemoral TAVR in individuals undergoing peripheral intervention. The primary outcome was in-hospital mortality. RESULTS: A total of 99,654 hospitalizations were identified, among which 4,397 patients (4.42%) underwent peripheral intervention during the same admission as TAVR. Patients who required peripheral intervention had increased mortality (4.2% vs 1.5%; P < 0.001), stroke (3.5% vs 1.8%; P < 0.001), acute kidney injury (17.6% vs 10.8%; P < 0.001), blood transfusion (16.0% vs 11.3%; P < 0.001), 30-day readmission (16.3% vs 12.1%; P < 0.001), median length of stay (4 days [IQR: 2-8 days] vs 3 days [IQR: 2-5 days]; P < 0.001), and hospitalization charges. Compared with patients undergoing peripheral intervention to facilitate transfemoral TAVR, alternative-access TAVR was associated with increased mortality (4.6% vs 3.0%; P = 0.036), acute kidney injury (22.7% vs 14.3%; P < 0.001), median length of stay (5 days [IQR: 3-10 days] vs 4 days [IQR: 2-7 days]; P < 0.001), and 30-day readmission (18.1% vs 15.5%; P = 0.012). CONCLUSIONS: Peripheral vascular intervention may be used to facilitate transfemoral access or as a bailout for vascular complications during TAVR. Combined TAVR and peripheral intervention is associated with an increased risk for adverse events, though outcomes are better compared with alternative-access TAVR using a nonfemoral approach.

A Pragmatic Approach to Weaning Temporary Mechanical Circulatory Support: A State-of-the-Art Review.

Temporary mechanical circulatory support (TMCS) provides short-term support to patients with or at risk of refractory cardiogenic shock. Although indications, contraindications, and complications of TMCS may guide device selection, optimal strategies for device weaning and explant remain poorly defined. Under the revised adult heart allocation policy implemented by the United Nations for Organ Sharing in October 2018, rejustification of heart transplant listing status includes demonstrating TMCS dependency with attempted device wean trials. However, standardized device-specific weaning and explant protocols have not been proposed or evaluated. This review highlights when to use percutaneous TMCS in cardiogenic shock, with a focus on weaning and explant considerations. Terminology for important concepts that guide device escalation, de-escalation, and explantation have been defined. Clinical, hemodynamic, metabolic, and imaging features have been defined, which can guide a tailored approach to TMCS weaning and explant based on the approach used at the Cleveland Clinic. A narrative review of published studies that have reported TMCS weaning protocols and survey results of member centers from CS-MCS working group centers is also provided. Future research is needed to better understand optimal timing and implementation of standardized protocols to achieve successful TMCS weaning and explant.

Characteristics and Outcomes of Patients With Acute Coronary Syndrome Who Received Percutaneous Coronary Intervention During Snowy Days.

BACKGROUND: Acute coronary syndrome (ACS) is affected by several weather conditions. Studies from different geographical locations have yielded mixed results regarding the outcomes of patients presenting with ACS during snowy days, and we aim to report the Cleveland Clinic experience. METHODS: Patients who presented with an ACS and underwent percutaneous coronary intervention (PCI) from July 1, 2009 to September 30, 2017 were divided into ST-segment elevation myocardial infarction (STEMI), and non-ST segment elevation ACS (NSTE-ACS). According to snowy day arrival, we compared in-hospital mortality, culprit lesion anatomy, and door-to-balloon (DTB) time (in STEMI patients). Findings were confirmed in propensity-score matched cohorts. RESULTS: A total of 6878 patients were included: 1608 patients with STEMI (139 snowy-day vs 1469 non-snowy day PCIs) and 5270 NSTE-ACS (419 snowy-day vs 4851 non-snowy day PCIs). Right coronary artery territories accounted for most of the stented culprit lesions in all STEMI and NSTE-ACS snowy-day PCIs. While left anterior descending artery lesions were predominant in NSTE-ACS non-snowy day PCIs. There was no difference in in-hospital mortality between the snowy-day vs non-snowy day groups (4.3% vs 4.5% in the STEMI group [P=.92] and 1.2% vs 1.7% in the NSTE-ACS group [P=41]). In STEMI patients, mean DTB times were similar (43 ± 55.1 minutes vs 46.7 ± 59.6 minutes; P=.61), which remained true after hours, during weekends and holidays. Outcomes were similar in propensity-score matched cohorts. CONCLUSION: At our institution, snowy days do not seem to affect in-patient mortality. In STEMI patients, DTB times were similar in those who underwent PCI regardless of the snowfall.