A Structured Approach To Skin And Soft Tissue Infections (Sstis) In An Ambulatory Setting, Benjamin Silverberg

Faculty & Staff Scholarship

The skin is the largest, and arguably, the most vulnerable organ in the human body. Scratches and scrapes, bites and puncture wounds, impetigo and erysipelas—all these disruptions can lead to pain, swelling, and/or systemic symptoms. In this article, which is based on the Infectious Diseases Society of America’s 2014 guidelines and the World Society of Emergency Surgery and Surgical Infection Society of Europe’s 2018 consensus statement, a structured approach to skin and soft tissue infections (SSTIs) is reviewed, comparing treatment for suppurative and non-suppurative infections, and then discussing specific conditions commonly seen in Primary Care and Urgent Care facilities.

Postdischarge Opioid Use After Total Hip And Total Knee Arthroplasty, Keenan Atwood, Taylor Shackleford, Wesley Lemons, Jennifer L. Eicher, Brock A. Lindsey, Adam E. Klein

Faculty & Staff Scholarship

Background

Methods

Excision Of A Rare Triquetral Body Fracture Nonunion, Michael J. Niemann, William C. Brooks, Priscilla Cavanaugh, Andrea B. Lese, John S. Taras

Faculty & Staff Scholarship

Aside from the more common dorsal avulsion fractures, isolated triquetral body fractures are a rare injury and often missed. When they are identified, conservative treatment via immobilization is often the standard of care for initial treatment. Rarely, triquetral body fractures can develop into symptomatic nonunions, causing considerable pain and disability. Multiple classification schemes have been described to categorize triquetrum fractures; however, distal triquetrum fractures fit into none of the established models. There is scarce literature describing treatment of triquetral body fracture nonunions. The few reports that exist often use a variation of open reduction internal fixation with or without grafting …

Field Test Of A Passive Infrared Camera For Measuring Trail-Based Physical Activity, Christiaan G. Abildso, Vaike Haas, Shay M. Daily, Thomas K. Bias

Faculty & Staff Scholarship

Introduction: Trails are ubiquitous and far-reaching, but research on the impact trails have on physical activity is limited by the lack of resource-efficient, accurate, and practical systematic observation tools. Commonly used infrared trail sensors count trail use and may broadly differentiate activity (i.e., bicyclist vs. pedestrian), but cannot detect nuances needed for outcomes research such as frequency, intensity, time, and type of activity. Motion-activated passive infrared cameras (PICs), used in ecological research and visitor management in wildlife areas, have potential applicability as a systematic observation data collection tool.

Materials and Methods: We conducted a 7-month field test of a PIC …

Sublingual Buprenorphine/Naloxone And Multi-Modal Management For High-Risk Chronic Pain Patients, Shane Kaski, Patrick Marshalek, Jeremy Herschler, Sijin Wen, Wanhong Zheng

Faculty & Staff Scholarship

Patients with chronic pain managed with opioid medications are at high risk for opioid overuse or misuse. West Virginia University (WVU) established a High-Risk Pain Clinic to use sublingual buprenorphine/naloxone (bup/nal) plus a multimodal approach to help chronic pain patients with history of Substance Use Disorder (SUD) or aberrant drug-related behavior. The objective of this study was to report overall retention rates and indicators of efficacy in pain control from approximately six years of High-Risk Pain Clinic data. A retrospective chart review was conducted for a total of 78 patients who enrolled in the High-Risk Pain Clinic between 2014 and …

Prevalence Of Alcohol Use In Late Pregnancy, Amna Umer, Christa Lilly, Candice Hamilton, Aileen Baldwin, Janine Breyel, Amy Tolliver, Christina Mullins, Collin John, Stefan Maxwell

Faculty & Staff Scholarship

Background

Prenatal alcohol exposure (PAE) can result in detrimental developmental complications. The objective of this study was to estimate the most recent PAE prevalence data for the state of West Virginia (WV) and associated factors.

Method

In all, 1830 newborn residual dried blood spots (DBS) in the WV Newborn Screening Repository were analyzed for phosphatidylethanol (PETH). Data were matched with Project WATCH data (94% match, N = 1729).

Results

The prevalence of late pregnancy PAE was 8.10% (95%CI: 6.81, 9.38) for all births, 7.61% (95%CI: 6.26, 8.97) for WV residents only, and ranged from 2.27 to 17.11% by region. The …

A Medial Congruent Polyethylene Offers Satisfactory Early Outcomes And Patient Satisfaction In Total Knee Arthroplasty, Benjamin M. Frye, Caitlyn Patton, Jason A. Kinney, T. Ryan Murphy, Adam E. Klein, Matthew J. Dietz

Faculty & Staff Scholarship

Background

Although a successful operation, almost 20% of patients are dissatisfied with total knee arthroplasty (TKA). The purpose of this retrospective cohort study was to see if a medial congruent (MC) polyethylene would offer satisfactory early outcomes and patient satisfaction after TKA.

Methods

We reviewed prospectively collected data on 327 TKAs using multiple bearings within the same implant system. Ninety-six received an MC bearing, 70 received a cruciate-retaining (CR) bearing, and 161 received a posterior-stabilized (PS) bearing. We evaluated the visual analog scale pain scores and range of motion (ROM) at 2 weeks, 6 weeks, 3 months, and 1 year; …

Localized Cytokine Responses To Total Knee Arthroplasty And Total Knee Revision Complications, Nicole Prince, Julia A. Penatzer, Matthew J. Dietz, Jonathan W. Boyd

Faculty & Staff Scholarship

Background

The study of localized immune-related factors has proven beneficial for a variety of conditions, and one area of interest in the field of orthopaedics is the impact of implants and localized infections on immune response. Several cytokines have shown increased systemic concentrations (in serum/plasma) in response to implants and infection, but tissue-level cytokines have not been investigated as thoroughly.

Methods

This exploratory study investigated tissue-level cytokines in a cohort of patients (N = 17) in response to total knee arthroplasty and total knee revision to better understand the immune response to implants and localized infection (e.g., prosthetic joint infection). …

Orofacial Granulomatosis In A Child, Reena Razdan, Maxwell D. Newby, Michele M. Carr

Faculty & Staff Scholarship

Orofacial granulomatosis (OFG) is a rare, idiopathic disorder of the orofacial region. It is clinically characterized by persistent and/or recurrent enlargement of the soft tissues of the oral and maxillofacial region, often manifesting as labial enlargement and swelling of intraoral sites such as the gingiva, tongue, and buccal mucosa. Full-thickness mucosal biopsy reveals noncaseating granulomatous inflammation, similar to Crohn’s disease and sarcoidosis. Thus, OFG must be distinguished from other chronic granulomatous disorders. We report a case of a young female patient who presented with labial and maxillary gingival enlargement without any identifiable systemic causes, with suggested involvement of environmental triggers.

Retrospective Review Of The Patient Cases At A Major Trauma Center In Nairobi, Kenya And Implications For Emergency Care Development, Julie Saleeby, Justin G. Myers, Karen Ekernas, Katherine Hunold, Ali Wangara, Alice Maingi, Peyton Wilson, Vincent Mutiso, Sarah Zamamiri, Daniel Bacon, Wes Davis, John Suder, Yash Agrawal, Ogar Ogar, Ian B.K. Martin, Stephen Dunlop

Faculty & Staff Scholarship

Introduction

Low- and middle-income countries (LMICs) are continuing to experience a “triple burden” of disease - traumatic injury, non-communicable diseases (NCDs), and communicable disease with maternal and neonatal conditions (CD&Ms). The epidemiology of this triad is not well characterised and poses significant challenges to resource allocations, administration, and education of emergency care providers. The data collected in this study provide a comprehensive description of the emergency centre at Kenya's largest public tertiary care hospital.

Methods

This study is a retrospective chart review conducted at Kenyatta National Hospital of all patient encounters over a four-month period. Data were collected from financial …

Mutations In Arl2bp, A Protein Required For Ciliary Microtubule Structure, Cause Syndromic Male Infertility In Humans And Mice, Abigal R. Moye, Nicola Bedoni, Jessica G. Cunningham, Urikhan Sanzhaeva, Eric S. Tucker, Peter Mathers, Virginie G. Peter, Mathieu Quinodoz, Liliana P. Paris, Luisa Coutinho-Santos, Pedro Camacho, Madeleine G. Purcell, Abbie C. Winkelmann, James A. Foster, Elena N. Pugacheva, Carlo Rivolta, Visvanathan Ramamurthy

Faculty & Staff Scholarship

Cilia are evolutionarily conserved hair-like structures with a wide spectrum of key biological roles, and their dysfunction has been linked to a growing class of genetic disorders, known collectively as ciliopathies. Many strides have been made towards deciphering the molecular causes for these diseases, which have in turn expanded the understanding of cilia and their functional roles. One recently-identified ciliary gene is ARL2BP, encoding the ADP-Ribosylation Factor Like 2 Binding Protein. In this study, we have identified multiple ciliopathy phenotypes associated with mutations in ARL2BP in human patients and in a mouse knockout model. Our research demonstrates that spermiogenesis …

Investigational Monoclonal Antibodies In The Treatment Of Multiple Myeloma: A Systematic Review Of Agents Under Clinical Development, Ahmad Iftikhar, Hamza Hassan, Nimra Iftikhar, Adeela Mushtaq, Atif Sohail, Nathaniel Rosko, Rajshekhar Chakraborty, Faryal Razzaq, Sonia Sandeep, Jason Neil Valent, Abraham Sebastian Kanate, Faiz Anwer

Faculty & Staff Scholarship

Background: Immunotherapy for multiple myeloma (MM) has been the focus in recent years due to its myeloma-specific immune responses. We reviewed the literature on non-Food and Drug Administration (FDA) approved monoclonal antibodies (mAbs) to highlight future perspectives. We searched PubMed, EMBASE, Web of Science, Cochrane Library and ClinicalTrials.gov to include phase I/II clinical trials. Data from 39 studies (1906 patients) were included. Of all the agents, Isatuximab (Isa, anti-CD38) and F50067 (anti-CXCR4) were the only mAbs to produce encouraging results as monotherapy with overall response rates (ORRs) of 66.7% and 32% respectively. Isa showed activity when used in combination with …

Eustachian Tube Foreign Body With Endoscopic-Assisted Surgical Removal, Phillip R. Purnell, Adam Bender Heine, Habib Zalzal, Abdul R. Tarabishy, Adam Casis

Faculty & Staff Scholarship

Abstract

Objectives. Foreign bodies of the external and middle ear are not uncommon; however, foreign bodies in the eustachian tube are rare. Here we describe the presentation, imaging, and endoscopic-assisted surgical management of a case of eustachian tube foreign body. Methods. A 34-year-old male was seen for evaluation of foreign body of the left eustachian tube while working with metal at a machine shop. Imaging and surgical management are highlighted and review of available literature regarding foreign bodies of the eustachian tube is presented. Results. A CT scan revealed a foreign body present approximately 1 cm into …

Traumatic Bladder Ruptures: A Ten-Year Review At A Level 1 Trauma Center, John Barnard, Tyler Overholt, Ali Hajiran, Chad Crigger, Morris Jessop, Jennifer Knight, Chad Morley

Faculty & Staff Scholarship

Abstract

Bladder rupture occurs in only 1.6% of blunt abdominopelvic trauma cases. Although rare, bladder rupture can result in significant morbidity if undiagnosed or inappropriately managed. AUA Urotrauma Guidelines suggest that urethral catheter drainage is a standard of care for both extraperitoneal and intraperitoneal bladder rupture regardless of the need for surgical repair. However, no specific guidance is given regarding the length of catheterization. The present study seeks to summarize contemporary management of bladder trauma at our tertiary care center, assess the impact of length of catheterization on bladder injuries and complications, and develop a protocol for management of bladder …

Melatonin Prevents Osteoarthritis-Induced Cartilage Degradation Via Targeting Microrna-140, Yijian Zhang, Jun Lin, Xinfeng Zhou, Xi Chen, Angela Carley Chen, Bin Pi, Guoquing Pan, Ming Pei, Huilin Yang, Tao Liu, Fan He

Faculty & Staff Scholarship

Abstract

Osteoarthritis (OA) is characterized by the progressive destruction of articular cartilage, which is involved in the imbalance between extracellular matrix (ECM) synthesis and degradation. MicroRNA-140-5p (miR-140) is specifically expressed in cartilage and plays an important role in OA-induced matrix degradation. The aim of this study was to investigate (1) whether intra-articular injection of melatonin could ameliorate surgically induced OA in mice and (2) whether melatonin could regulate matrix-degrading enzymes at the posttranscriptional level by targeting miR-140. In an in vitro OA environment induced by interleukin-1 beta (IL-1β), melatonin treatment improved cell proliferation of human chondrocytes, promoted the …

Cecal Perforation In The Setting Of Campylobacter Jejuni Infection, Seema Jain, Weston Betrner, Dane Olevian, Dhiraj Yadav

Faculty & Staff Scholarship

Campylobacter infection is the leading cause of bacterial gastroenteritis worldwide, yet life-threatening complications are extremely rare. We present a 32-year-old previously healthy man who presented with dysentery from Campylobacter jejuni, which was complicated by cecal perforation and secondary bacterial peritonitis.

Acute Levodopa Dosing Around-The-Clock Ameliorates Rem Sleep Without Atonia In Hemiparkinsonian Rats, Vishakh Iyer, Quynh Vo, Anthony Mell, Siven Chinniah, Ashley Zenerovitz, Kala Venkiteswaran, Allen R. Kunselman, Jidong Fang, Thyagarajan Subramanian

Faculty & Staff Scholarship

• Article
• Open Access
• Published: 29 November 2019

Acute levodopa dosing around-the-clock ameliorates REM sleep without atonia in hemiparkinsonian rats

• Vishakh Iyer,
• Quynh Vo,
• Anthony Mell,
• Siven Chinniah,
• Ashley Zenerovitz,
• Kala Venkiteswaran,
• Allen R. Kunselman,
• Jidong Fang &
• Thyagarajan Subramanian

npj Parkinson's Disease volume 5, Article number: 27 (2019) Cite this article

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Abstract

Rapid-eye-movement (REM) sleep without atonia (RSWA), a marker of REM sleep behavior disorder (RBD), is frequently comorbid with Parkinson’s disease (PD). Although rodent models are commonly used for studying PD, the neurobiological and behavioral correlates of …

Impact Of Fibronectin Knockout On Proliferation And Differentiation Of Human Infrapatellar Fat Pad-Derived Stem Cells, Yiming Wang, Yawen Fu, Zuoqin Yan, Xiao-Bing Zhang, Ming Pei

Faculty & Staff Scholarship

Fibronectin plays an essential role in tissue development and regeneration. However, the effects of fibronectin knockout (FN1-KO) on stem cells’ proliferation and differentiation remain unknown. In this study, CRISPR/Cas9 generated FN1-KO in human infrapatellar fat pad-derived stem cells (IPFSCs) was evaluated for proliferation ability including cell cycle and surface markers as well as stemness gene expression and for differentiation capacity including chondrogenic and adipogenic differentiation. High passage IPFSCs were also evaluated for proliferation and differentiation capacity after expansion on decellularized ECM (dECM) deposited by FN1-KO cells. Successful FN1-KO in IPFSCs was confirmed by Sanger sequencing and Inference of CRISPR Edits …

Improving Exposure For Transoral Oropharyngeal Surgery With The Floor Of Mouth Window: A Cadaveric Feasibility Study, Jefferson Chung, Adam Bender-Heine, H. Wayne Lambert

Faculty & Staff Scholarship

Background: Transoral robotic and laser surgery is rising in popularity due to the increasing incidence of Human Papilloma Virus (HPV) related oropharyngeal cancer. However, adequate exposure of the tongue base remains a major hurdle in many cases. This study introduces a novel surgical technique called the Floor of Mouth Window, which can be used to improve tongue base exposure at the time of transoral surgery. Methods: This is a preclinical anatomic cadaver study. Seven fresh cadavers were used for this study. Exposure of the tongue base was compared between conventional mouth gags – the Feyh-Kastenbauer and McIvor – and our …

Safety And Long-Term Efficacy Of Thoracoscopic Epicardial Ablation In Patients With Paroxysmal Atrial Fibrillation: A Retrospective Study, John Johnkoski, Bryan Miles, Anna Sudbury, Mohammed Osman, Muhammad Bilal Munir, Sudarshan Balla, Mina M. Benjamin

Faculty & Staff Scholarship

Background: The aim of this study is to report the long-term efficacy and safety of thoracoscopic epicardial left atrial ablation (TELA) in patients with paroxysmal atrial fibrillation (AF). Methods: This was a retrospective review of medical records. We included all patients diagnosed with paroxysmal AF who underwent TELA at our institution between 04/2011 and 06/2017. TELA included pulmonary vein isolation, LA dome lesions and LA appendage exclusion. All (n = 55) patients received an implantable loop recorder (ILR), 30 days post-operatively. Antiarrhythmic and anticoagulation therapy were discontinued at 90 and 180 days postoperatively, respectively, if patients were free of AF …

Surgical Correction Of Aortic Regurgitation Using A Haart 300™ Rigid Aortic Ring: A Novel Method To Standardize Aortic Valve Repair, Radoslaw Gocol, Marek Jasiński, Damian Hudziak, Jaroslaw Bis, Aleksandra Żak, Piotr Duraj, Magdalena Mizia, J. Scott Rankin, Marek A. Deja

Faculty & Staff Scholarship

No abstract provided.

Increased Dementia Mortality In West Virginia Counties With Mountaintop Removal Mining?, A. K. Salm, Michael J. Benson

Faculty & Staff Scholarship

(MTM), a practice that has been ongoing in some counties of West Virginia (WV) USA since the 1970s. PM inhalation has been linked to central nervous system pathophysiology, including cognitive decline and dementia. Here we compared county dementia mortality statistics in MTM vs. non-MTM WV counties over a period spanning 2001–2015. We found significantly elevated age-adjusted vascular or unspecified dementia mortality/100,000 population in WV MTM counties where, after adjusting for socioeconomic variables, dementia mortality was 15.60 (±3.14 Standard Error of the Mean (S.E.M.)) times higher than that of non-MTM counties. Further analyses with satellite imaging data revealed a highly significant …

Unusual Presentation Of Recurrent Gallstone Ileus: A Case Report And Literature Review, Osayande Osagiede, Paula Pacurari, Dorin Colibaseanu, Nezar Jrebi

Faculty & Staff Scholarship

Background. Gallstone ileus (GSI) is a rare form of small bowel obstruction (SBO) in patients with cholelithiasis, which is often poorly managed. Enhanced abdominal computed tomography (CT) with contrast is considered the most helpful diagnostic tool, as it is highly sensitive, specific, and accurate. We report an interesting case of recurrent GSI that was not detected by CT but diagnosed intraoperatively. Case Presentation. A 49-year-old female with a previous history of choledocholithiasis and ERCP presented to the emergency department following episodes of sudden cramping, epigastric pain, and nausea. An abdominal CT revealed evidence of SBO with clear evidence of GSI …

Unforeseen Computed Tomography Resimulation For Initial Radiation Planning: Associated Factors And Clinical Impact, April Metzger, Paul Renz, Shaakir Hasan, Stephen Karlovits, Jason Sohn, Steven Gresswell

Faculty & Staff Scholarship

Purpose: Repeat computed tomography (CT) simulation is problematic because of additional expense of clinic resources, patient inconvenience, additional radiation exposure, and treatment delay. We investigated the factors and clinical impact of unplanned CT resimulations in our network. Methods and Materials: We used the billing records of 18,170 patients treated at 5 clinics. A total of 213 patients were resimulated before their first treatment. The disease site, location, use of 4- dimensional CT (4DCT), contrast, image fusion, and cause for resimulation were recorded. Odds ratios determined statistical significance. Results: Our total rate of resimulation was 1.2%. Anal/colorectal (P < .001) and head and neck (P < .001) disease sites had higher rates of resimulation. Brain (P Z .001) and lung/thorax (P Z .008) had lower rates of resimulation. The most common causes for resimulation were setup change (11.7%), change in patient anatomy (9.8%), and rectal filling (8.5%). The resimulation rate for 4DCTs was 3.03% compared with 1.0% for non-4DCTs (P < .001). Median time between simulations was 7 days. Conclusions: The most common sites for resimulation were anal/colorectal and head and neck, largely because of change in setup or changes in anatomy. The 4DCT technique correlated with higher resimulation rates. The resimulation rate was 1.2%, and median treatment delay was 7 days. Further studies are warranted to limit the rate of resimulation.

The Patient Selection Criteria For Veno-Arterial Extracorporeal Mechanical Oxygenation, Sandeep Banga, Abhiram Challa, Avani R. Patel, Shantanu Singh, Vamsi K. Emani

Faculty & Staff Scholarship

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) plays a crucial role in the management of patients with refractory cardiac and pulmonary dysfunction by providing temporary mechanical hemodynamic and respiratory support. However, the paucity of guidelines on indications for administering it and the failure to timely initiate VA-ECMO often result in a high in-hospital mortality rate and poor six-month outcomes after VA-ECMO deployment. Due to ethical issues, randomized controlled studies with VA-ECMO have not been conducted so that no recommended evidence-based guidelines exist for VA-ECMO patientselection criteria. Therefore, the indication for administering the device depends solely on expert opinion after reviewing the literature. …

Acute Psychosis Following 1,1-Difluoroethane Inhalation, Clara B. Novotny, Sarah Irvin, Eduardo D. Espiridion

Faculty & Staff Scholarship

Inhalants are often abused due to their ability to acutely induce feelings of euphoria. Difluoroethane is a toxic lipophilic hydrocarbon that crosses the blood-brain barrier and inhibits the central nervous system. Studies have shown the cardiac, renal, and respiratory effects it has when abused; however, our literature review yielded no previous report of acute psychosis after difluoroethane inhalation. In order to prevent poor outcomes by missed diagnosis, we present a case of difluoroethane-induced acute psychosis.

Consistent Technique Limits Suspension Laryngoscopy Complications, Sean P. Larner, Rick A. Fornelli, Shane D. Griffith

Faculty & Staff Scholarship

ntroduction Suspension laryngoscopy (SL) is a commonly performed procedure among otolaryngologists. Several studies have shown that adverse effects occur regularly with SL.

Objective To evaluate the postoperative complications of SL, and to determine if protecting the dentition and the oral mucosa and limiting suspension times decrease the overall incidence of oral cavity and pharyngeal complications of SL.

Methods All of the cases of SL performed by 1 surgeon from November 2008 through September 2014 were retrospectively reviewed. A consistent technique for dental and mucosal protection was utilized, and suspension times were strictly limited to 30 consecutive minutes. The incidence of …

Cardiac Prostheses‐Related Hemolytic Anemia, Mohamad Alkhouli, Ali Farooq, Ronald S. Go, Sudarshan Balla, Chalak Berzingi

Faculty & Staff Scholarship

Hemolysis is an unintended sequel of temporary or permanent intracardiac devices. However, limited data exist on the characteristics and treatment of hemolysis in patients with cardiac prostheses. This entity, albeit uncommon, often poses significant diagnostic and management challenges to the clinical cardiologist. In this article, we aim to provide a contemporary overview of the incidence, mechanisms, diagnosis, and management of cardiac prosthesis-related hemolysis.

A Pedunculated Skin Lesion In A Case Of Clear Cell Renal Carcinoma, Meghana Kesireddy, Amit Correa, Raoul Correa, Rohit Venkatesan

Faculty & Staff Scholarship

Clear cell type renal carcinoma accounts for about 80% of all renal cell carcinomas. We present a 39-year-old male with clear cell renal carcinoma of the right kidney, stage I: T1 b (5 cm) N0 M0, who developed cutaneous metastases in the right submandibular region 28 months after nephrectomy. Our case is unique as i) the patient with stage I cancer (at the time of nephrectomy) presented with an isolated cutaneous nodule in a location distant from the primary site; ii) cutaneous nodule developed while being treated with pazopanib for metastatic lesions in the lung and adrenal; and iii) nivolumab …

Trial Sequential Analysis Comparing Bleeding And Major Adverse Cardiovascular Events In Patients With Atrial Fibrillation And Acute Coronary Syndrome On Dual Versus Triple Therapy, Muhamad B. Munir, Khansa Osman, Maryam Saleem, Kinjan Patel, Sudarshan Balla

Faculty & Staff Scholarship

Objective To assess efficacy and safety of dual therapy (DT) and triple therapy (TT) in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) with or without percutaneous coronary intervention (PCI) and evaluate the quality of evidence with respect to said outcomes based on contemporary randomized trials (RCTs). The efficacy outcome taken was major adverse cardiovascular events (MACE) while safety outcome was major bleeding events. Introduction Appropriate anti-thrombotic therapy is still controversial in patients with AF and concomitant ACS or PCI. We conducted a conventional meta-analysis pooling data from major RCTs to assess the efficacy and safety of DT …