Medicine and Health Sciences Commons^™

Cyclophosphamide Induces Durable Molecular And Clinical Responses In Patients With Relapsed T-Lgl Leukemia., Zachary Braunstein, Eric Mclaughlin, Anjali Mishra, Jonathan E Brammer

Department of Medical Oncology Faculty Papers

No abstract provided.

Ocular Adnexal Lymphoma: A Single-Institution Retrospective Study, César A. Fernández, Roger K. Henry, Carol L. Shields, Jurij R. Bilyk, Sara E. Lally, Ralph C. Eagle, Tatyana Milman

Wills Eye Hospital Papers

PURPOSE: To characterize demographic, clinical, and histopathologic features of ocular adnexal lymphoma (OAL) at a single institution. METHODS: Retrospective review of all patients with pathologic diagnosis of OAL between 2015 and 2020. RESULTS: There were 133 patients with OAL, with a median age of 65 years (range 23-97) and a slight female predominance (male: female = 1:1.46), (n = 79, 59%). The majority of tumors were non-Hodgkin B-cell lymphomas (n = 131, 99%), most frequently Extranodal Marginal Zone B-Cell Lymphoma (EMZL, n = 93, 70%), followed by follicular lymphoma (n = 21, 16%), chronic lymphocytic leukemia/small lymphocytic lymphoma (n = …

Making Waves: How Ultrasound-Targeted Drug Delivery Is Changing Pharmaceutical Approaches., Lauren J Delaney, Selin Isguven, John R Eisenbrey, Noreen J Hickok, Flemming Forsberg

Department of Radiology Faculty Papers

Administration of drugs through oral and intravenous routes is a mainstay of modern medicine, but this approach suffers from limitations associated with off-target side effects and narrow therapeutic windows. It is often apparent that a controlled delivery of drugs, either localized to a specific site or during a specific time, can increase efficacy and bypass problems with systemic toxicity and insufficient local availability. To overcome some of these issues, local delivery systems have been devised, but most are still restricted in terms of elution kinetics, duration, and temporal control. Ultrasound-targeted drug delivery offers a powerful approach to increase delivery, therapeutic …

Anterior Segment Optical Coherence Tomography Features Of Netarsudil-Associated Reticular Corneal Edema, Ashley Kahlilil, Reza Razeghinejad, Zeba Syed

Wills Eye Hospital Papers

No abstract provided.

Postoperative Outcomes In Oesophagectomy With Trainee Involvement., Oesophago-Gastric Anastomosis Study Group (Ogaa) On Behalf Of The West Midlands Research Collaborative

Department of Surgery Faculty Papers

BACKGROUND: The complexity of oesophageal surgery and the significant risk of morbidity necessitates that oesophagectomy is predominantly performed by a consultant surgeon, or a senior trainee under their supervision. The aim of this study was to determine the impact of trainee involvement in oesophagectomy on postoperative outcomes in an international multicentre setting.

METHODS: Data from the multicentre Oesophago-Gastric Anastomosis Study Group (OGAA) cohort study were analysed, which comprised prospectively collected data from patients undergoing oesophagectomy for oesophageal cancer between April 2018 and December 2018. Procedures were grouped by the level of trainee involvement, and univariable and multivariable analyses were performed …

A Prospective Examination Of Sex Differences In Posttraumatic Autonomic Functioning., Antonia V Seligowski, Elizabeth R Steuber, Rebecca Hinrichs, Mariam H Reda, Charis N Wiltshire, Cassandra P Wanna, Sterling J Winters, Karlye A Phillips, Stacey L House, Francesca L Beaudoin, Xinming An, Jennifer S Stevens, Donglin Zeng, Thomas C Neylan, Gari D Clifford, Sarah D Linnstaedt, Laura T Germine, Kenneth A Bollen, Guia Guffanti, Scott L Rauch, John P Haran, Alan B Storrow, Christopher Lewandowski, Paul I Musey, Phyllis L Hendry, Sophia Sheikh, Christopher W Jones, Brittany E Punches, Michael C Kurz, Vishnu P Murty, Meghan E Mcgrath, Lauren A Hudak, Jose L Pascual, Mark J Seamon, Elizabeth M Datner, Anna Marie Chang, Claire Pearson, David A Peak, Roland C Merchant, Robert M Domeier, Niels K Rathlev, Brian J O'Neil, Leon D Sanchez, Steven E Bruce, Mark W Miller, Robert H Pietrzak, Jutta Joormann, Deanna M Barch, Diego A Pizzagalli, John F Sheridan, Beatriz Luna, Steven E Harte, James M Elliott, Karestan C Koenen, Ronald C Kessler, Samuel A Mclean, Kerry J Ressler, Tanja Jovanovic

Department of Emergency Medicine Faculty Papers

Background: Cross-sectional studies have found that individuals with posttraumatic stress disorder (PTSD) exhibit deficits in autonomic functioning. While PTSD rates are twice as high in women compared to men, sex differences in autonomic functioning are relatively unknown among trauma-exposed populations. The current study used a prospective design to examine sex differences in posttraumatic autonomic functioning.

Methods: 192 participants were recruited from emergency departments following trauma exposure (

Results: 2-week systolic BP was significantly higher in men, while 2-week HR was significantly higher in women, and a sex by PTSD interaction suggested that women who developed PTSD demonstrated the highest HR …

Therapeutic Resistance In Pancreatic Ductal Adenocarcinoma: Current Challenges And Future Opportunities, Aditi Jain, Phd, Vikas Bhardwaj

Kimmel Cancer Center Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancerrelated deaths in the United States. Although chemotherapeutic regimens such as gemcitabine+ nab-paclitaxel and FOLFIRINOX (FOLinic acid, 5-Fluroruracil, IRINotecan, and Oxaliplatin) significantly improve patient survival, the prevalence of therapy resistance remains a major roadblock in the success of these agents. This review discusses the molecular mechanisms that play a crucial role in PDAC therapy resistance and how a better understanding of these mechanisms has shaped clinical trials for pancreatic cancer chemotherapy. Specifically, we have discussed the metabolic alterations and DNA repair mechanisms observed in PDAC and current approaches in targeting …

Bone Mineral Density Changes Associated With Pregnancy, Lactation, And Medical Treatments In Premenopausal Women And Effects Later In Life., Nelson B Watts, Neil Binkley, Charlotte D Owens, Ayman Al-Hendy, Elizabeth E Puscheck, Mohamad Shebley, William Schlaff, Md, James A Simon

Department of Obstetrics and Gynecology Faculty Papers

Bone mineral density (BMD) changes during the life span, increasing rapidly during adolescence, plateauing in the third decade of life, and subsequently entering a phase of age-related decline. In women, menopause leads to accelerated bone loss and an increase in fracture risk. Between peak bone mass attainment and menopause, BMD is generally stable and the risk of fracture is typically low. This time period is marked by life events such as pregnancy and lactation, which transiently decrease BMD, yet their long-term effects on fracture risk are less certain. BMD may also be altered by exposure to medications that affect bone …

Engaging Patients With Late-Stage Non-Small Cell Lung Cancer In Shared Decision Making About Treatment., Ronald E. Myers, Phd, Dsw, Shailesh M Advani, Pamela Myers, Preethi Selvan Mph Student, Gregory Garber, Msw, Lcsw, Brooke Worster, Md, Neal Flomenberg, Md, Andrew Chapman, Do, Ralph Zinner

Department of Medical Oncology Faculty Papers

Few treatment decision support interventions (DSIs) are available to engage patients diagnosed with late-stage non-small cell lung cancer (NSCLC) in treatment shared decision making (SDM). We designed a novel DSI that includes care plan cards and a companion patient preference clarification tool to assist in shared decision making. The cards answer common patient questions about treatment options (chemotherapy, chemotherapy plus immunotherapy, targeted therapy, immunotherapy, clinical trial participation, and supportive care). The form elicits patient treatment preference. We then conducted interviews with clinicians and patients to obtain feedback on the DSI. We also trained oncology nurse educators to implement the prototype. …

A Review Of Fixed Drug Eruption With A Special Focus On Generalized Bullous Fixed Drug Eruption., Hannah J. Anderson, Jason B. Lee, Md

Department of Dermatology and Cutaneous Biology Faculty Papers

Fixed drug eruption (FDE) is a cutaneous adverse drug reaction characterized by the onset of rash at a fixed location on the body each time a specific medication is ingested. With each recurrence, the eruption can involve additional sites. Lesions can have overlying vesicles and/or bullae, and when they cover a significant percentage of body surface area, the eruption is referred to as generalized bullous fixed drug eruption (GBFDE). Due to the widespread skin denudation that can be seen in this condition, GBFDE may be confused clinically with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). While treatments described for GBFDE include supportive …

Preoperative Immunotherapy In The Multidisciplinary Management Of Oral Cavity Cancer., Ramez Philips, Md, Chihun Han, Brian Swendseid, Md, Joseph Curry, Athanassios Argiris, Adam Luginbuhl, Jennifer Johnson, Md

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Despite advances in multimodal treatment for oral cavity squamous cell carcinoma, recurrence rates remain high, providing an opportunity for new therapeutic modalities that may improve oncologic outcomes. Much recent attention has been paid to the molecular interactions between the tumor cells with the adjacent peritumoral microenvironment, in which immunosuppressive molecular changes create a landscape that promotes tumor progression. The rationale for the introduction of immunotherapy is to reverse the balance of these immune interactions in a way that utilizes the host immune system to attack tumor cells. In the preoperative setting, immunotherapy has the advantage of priming the unresected tumor …

Isomirmap-Fast, Deterministic, And Exhaustive Mining Of Isomirs From Short Rna-Seq Datasets., Phillipe Loher, Nestoras Karathanasis, Eric R Londin, Paul Bray, Venetia Pliatsika, Aristeidis G. Telonis, Isidore Rigoutsos

Computational Medicine Center Faculty Papers

MOTIVATION: MicroRNA (miRNA) precursor arms give rise to multiple isoforms simultaneously called "isomiRs." IsomiRs from the same arm typically differ by a few nucleotides at either their 5´ or 3´ termini, or both. In humans, the identities and abundances of isomiRs depend on a person's sex, population of origin, race/ethnicity, and on tissue type, tissue state, and disease type/subtype. Moreover, nearly half of the time the most abundant isomiR differs from the miRNA sequence found in public databases. Accurate mining of isomiRs from deep sequencing data is thus important.

RESULTS: We developed isoMiRmap, a fast, standalone, user-friendly mining tool that …

The Influence Of Axial Myopia On Optic Disc Characteristics Of Glaucoma Eyes., Jasmin Rezapour, Christopher Bowd, Jade Dohleman, Akram Belghith, James A Proudfoot, Mark Christopher, Leslie Hyman, Jost B Jonas, Massimo A Fazio, Robert N Weinreb, Linda M Zangwill

Wills Eye Hospital Papers

This study characterizes differences in glaucomatous eyes with and without high axial myopia using custom automated analysis of OCT images. 452 eyes of 277 glaucoma patients were stratified into non (n = 145 eyes), mild (n = 214 eyes), and high axial myopia (axial length (AL) > 26 mm, n = 93 eyes). Optic disc ovality index, tilt and rotation angle of Bruch´s membrane opening (BMO) and peripapillary choroidal thickness (PCT) were calculated using automated and deep learning strategies. High myopic optic discs were more oval and had larger BMO tilt than mild and non-myopic discs (both p < 0.001). Mean PCT was thinnest in high myopic eyes followed by mild and non-myopic eyes (p < 0.001). BMO rotation angle, global retinal nerve fiber layer (RNFL) thickness and BMO-minimum rim width (MRW) were similar among groups. Temporal RNFL was thicker and supranasal BMO-MRW was thinner in high myopic eyes. BMO tilt and PCT showed moderate and temporal RNFL and nasal BMO-MRW showed weak but significant associations with AL in multivariable analyses (all p < 0.05). Large BMO tilt angle and thin PCT are characteristics of highly myopic discs and were not associated with severity of glaucoma. Caution should be exercised when using sectoral BMO-MRW and RNFL thickness for glaucoma management decisions in myopic eyes.

A Shocking Case Of Far-Field Atrial Oversensing In Giant-Cell Myocarditis, Tanuka Datta, Md, S. Melnick, Do, Bharaniabirami Rajaram, Md, Behzad B. Pavri

Division of Cardiology Faculty Papers

We report a unique case of delivery of inappropriate implantable cardioverter-defibrillator therapies related to a “perfect storm”: presence of an integrated lead, insufficient lead slack related to right heart dilation resulting in shock coil misplacement, myocarditis with loss of R waves, and the concomitant occurrence of an incessant atrial tachycardia. (Level of Difficulty: Advanced.)

A Diagnostic Dilemma Of Antiglutamic Acid Decarboxylase 65 (Anti-Gad 65) And Mycoplasma Pneumoniae Antibodies In A Girl Presenting With Acute-Onset Obsessive-Compulsive Disorder., Cecilia Freeman, Antanoid J Langeveldt, Robyn R Miller

Department of Pediatrics Faculty Papers

Acute-onset obsessive-compulsive disorder can be challenging, especially when triggered by an underlying disease process. Clinicians often turn to Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS), but it is important to consider a broad differential in these patients. We present a case of a 9-year-old girl with acute-onset obsessive-compulsive behavior likely triggered by a post-infectious phenomenon that ultimately resolved following treatment with plasmapheresis.

Global Point-Of-Care Ultrasound Education And Training In The Age Of Covid-19., Onyinyechi F Eke, Patricia C. Henwood, Grace W Wanjiku, Abiola Fasina, Sigmund J Kharasch, Hamid Shokoohi

Department of Emergency Medicine Faculty Papers

The COVID-19 pandemic has disrupted traditional global point-of-care ultrasound (POCUS) education and training, as a result of travel restrictions. It has also provided an opportunity for innovation using a virtual platform. Tele-ultrasound and video-conferencing are alternative and supportive tools to augment global POCUS education and training. There is a need to support learners and experts to ensure that maximum benefit is gained from the use of these innovative modalities.

Cytokine Storms, Evolution And Covid-19, Joe Alcock, Alix Masters

Department of Medicine Faculty Papers

Since the identification of severe illness caused by the novel coronavirus SARS-CoV-2, the role of the host immune system in causing disease has attracted widespread attention, along with intense interest in medical interventions that target the host immune response. A wide variety of agents have been proposed to treat a cytokine storm in coronavirus disease 2019 (COVID-19), but so far, only one class of medications, corticosteroids, has proved useful. In recent decades, experimental therapies for cytokine storms have been tried and mostly failed to help patients with severe sepsis and other infections. We summarize this history in order to frame …

White Paper On Ophthalmic Imaging For Choroidal Nevus Identification And Transformation Into Melanoma, Carol Shields, Sara E. Lally, Lauren Dalvin, Mandeep Sagoo, Marco Pellegrini, Swathi Kaliki, Ahmet Kaan Gündüz, Minoru Furuta, Prithvi Mruthyunjaya, Adrian T. Fung, Jay S. Duker, Sara M. Selig, Antonio Yaghy, Sandor R. Ferenczy, Malvina B. Eydelman, Mark S. Blumenkranz

Wills Eye Hospital Papers

Purpose: To discuss the evolution of noninvasive diagnostic methods in the identification of choroidal nevus and determination of risk factors for malignant transformation as well as introduce the novel role that artificial intelligence (AI) can play in the diagnostic process. Methods: White paper. Results: Longstanding diagnostic methods to stratify benign choroidal nevus from choroidal melanoma and to further determine the risk for nevus transformation into melanoma have been dependent on recognition of key clinical features by ophthalmic examination. These risk factors have been derived from multiple large cohort research studies over the past several decades and have garnered widespread use …

Algorithm For Cavo-Tricuspid Isthmus Flutter On Surface Ecgs: The Actions Study., Daniel Frisch, Eitan Frankel, Deanna Gill, Jad Al Danaf

Division of Cardiology Faculty Papers

OBJECTIVE: Cavo-tricuspid isthmus atrial flutter (CTI-AFL) is an important arrhythmia to recognise because there is a highly effective and relatively low-risk ablation strategy. However, clinical experience has demonstrated that providers often have difficulty distinguishing AFL from atrial fibrillation.

METHODS: We developed a novel ECG-based three-step algorithm to identify CTI-AFL based on established CTI flutter characteristics and verified on consecutive ablation cases of typical flutter, atypical flutter and atrial fibrillation. The algorithm assesses V1/inferior lead F-wave concordance, consistency of P-wave morphology and the presence of isoelectric intervals in the inferior leads. In this observation study, the algorithm was validated on a …

International Evidence-Based Consensus Diagnostic And Treatment Guidelines For Unicentric Castleman Disease., Frits Van Rhee, Eric Oksenhendler, Gordan Srkalovic, Peter Voorhees, Megan Lim, Angela Dispenzieri, Makoto Ide, Sophia Parente, Stephen Schey, Matthew Streetly, Raymond Wong, David Wu, Ivan Maillard, Joshua Brandstadter, Nikhil Munshi, Wilbur Bowne, Kojo S Elenitoba-Johnson, Alexander Fössa, Mary Jo Lechowicz, Shanmuganathan Chandrakasan, Sheila K Pierson, Amy Greenway, Sunita Nasta, Kazuyuki Yoshizaki, Razelle Kurzrock, Thomas S Uldrick, Corey Casper, Amy Chadburn, David C Fajgenbaum

Department of Surgery Faculty Papers

Castleman disease (CD) includes a group of rare and heterogeneous disorders with characteristic lymph node histopathological abnormalities. CD can occur in a single lymph node station, which is referred to as unicentric CD (UCD). CD can also involve multicentric lymphadenopathy and inflammatory symptoms (multicentric CD [MCD]). MCD includes human herpesvirus-8 (HHV-8)-associated MCD, POEMS-associated MCD, and HHV-8-/idiopathic MCD (iMCD). The first-ever diagnostic and treatment guidelines were recently developed for iMCD by an international expert consortium convened by the Castleman Disease Collaborative Network (CDCN). The focus of this report is to establish similar guidelines for the management of UCD. To this purpose, …

Caring For Aml Patients During The Covid-19 Crisis: An American And Italian Experience., Lindsay Wilde, Md, Alessandro Isidori, Gina Keiffer, Md, Neil D. Palmisiano, Md, Margaret Kasner

Department of Medical Oncology Faculty Papers

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the subsequent pandemic have impacted every aspect of oncology care worldwide. Healthcare systems have been forced to rapidly change practices in order to maximize the safety of patients and healthcare providers and preserve scare resources. Patients with acute myeloid leukemia are at increased risk of complications from SARS-CoV-2 not only due to immune compromise related to the malignancy but also due to the acuity of the disease and intensity of treatment. These issues have created unique challenges during this difficult time. In this article, we present the approaches taken …

Blood-Brain Barrier: Mechanisms Governing Permeability And Interaction With Peripherally Acting Μ-Opioid Receptor Antagonists., Eugene R. Viscusi, Andrew R Viscusi

Department of Anesthesiology Faculty Papers

The blood-brain barrier (BBB) describes the unique properties of endothelial cells (ECs) that line the central nervous system (CNS) microvasculature. The BBB supports CNS homeostasis via EC-associated transport of ions, nutrients, proteins and waste products between the brain and blood. These transport mechanisms also serve as physiological barriers to pathogens, toxins and xenobiotics to prevent them from contacting neural tissue. The mechanisms that govern BBB permeability pose a challenge to drug design for CNS disorders, including pain, but can be exploited to limit the effects of a drug to the periphery, as in the design of the peripherally acting μ-opioid …

Reply: There Are Limits To Autonomy., John W C Entwistle, Kathleen N Fenton

Department of Surgery Faculty Papers

No abstract provided.

A Foldable Nonpenetrating Keratoprosthesis: Medium To Long-Term Clinical Results In Patients With Corneal Blindness Due To Noninflammatory Anterior Cornea Disease., Jose M Vargas, Eric Shiuey

Department of Medicine Faculty Papers

PURPOSE: To report the medium to long-term safety and performance outcomes of the KeraKlear nonpenetrating artificial cornea (KeraKlear) as the primary procedure in patients with corneal blindness due to noninflammatory anterior cornea disease.

METHODS: Fifteen patients with corneal blindness (preoperative visual acuity [VA] of ≥20/200) due to a non-inflammatory anterior corneal condition were included in this prospective, single-center study. Preoperative diagnoses included corneal scars, keratoconus, and corneal dystrophies. Diseased corneas were implanted with the KeraKlear (KeraMed Inc., Irvine, California, USA) by a single surgeon (JMV) using a femtosecond laser to create all incisions. Participants were followed up with for as …

Telemedicine For The Spine Surgeon In The Age Of Covid-19: Multicenter Experiences Of Feasibility And Implementation Strategies., Daniel Franco, Thiago Montenegro, Glenn A Gonzalez, Kevin Hines, Aria Mahtabfar, Melvin D Helgeson, Rakesh Patel, James Harrop

Department of Neurosurgery Faculty Papers

STUDY DESIGN: Multicenter study.

OBJECTIVES: The COVID-19 pandemic has obligated physicians to recur to additional resources and make drastic changes regarding the standard physician-patient encounter. In the last century, there has been a substantial improvement in technology, which over the years has opened the door to a new form of medical practicing known as telemedicine.

METHODS: Healthcare workers from three hospitals involved in the care for COVID-19 patients in the united states were invited to share their experience using telemedicine to deliver clinical care to their patients.

RESULTS: Since the appearance of this worldwide outbreak, social distancing has been a …

Conditions For Combining Gene Therapy With Bone Marrow Transplantation In Murine Krabbe Disease., Mohammad Rafi, Paola Luzi, David A Wenger

Department of Neurology Faculty Papers

No abstract provided.

Targeting Homologous Recombination Addicted Tumors: Challenges And Opportunities, Talia Golan, Jonathan Brody, Md

Kimmel Cancer Center Faculty Papers

Recent advances in next generation sequencing (NGS) and molecular subtyping of tumors have opened the door to clinically available targeted therapies. Although the treatment of many solid tumors still rely on a steady regimen of non-targeted chemotherapeutic agents, it is becoming increasingly more apparent that certain tumors with defects in DNA damage repair (DDR) genes may be exquisitely sensitive to DNA damaging agents or therapies targeting key elements of this pathway such PARP1, ATR, or ATM. Still, for tumors with DDR defects the challenges are multi-fold including: (I) identifying these tumors in patients in time for a window of opportunity …

Download Entire Issue: Gibbon Surgical Review, Volume 2, Issue 1, 2019

Gibbon Surgical Review

Table of Contents

4 - The Gibbon Surgical Externship: A Student’s Perspective

6 - Invited Article: The PCOM Wisely Surgical Association and the Philadelphia Surgery Conference

8 - Interview With Thomas Jefferson Cardiothoracic Surgeon, H. Todd Massey, MD

12 - The Life of a Rwandan Surgical Resident

14 - Role Of Technological Advancement In The Context Of Surgical Planning And Execution: Perspective Of Jefferson Surgical Faculty

16 - Interview with William B. Hughes, MD, Director of the Thomas Jefferson University Hospital Burn Center

19 - Women in Surgery: An Interview with Dr. Karen Chojnacki, Vice Chair of Surgical Education at …

Utilizing Livers From Donors Older Than 65: A Single Center Experience, Krishnaraj Mahendraraj, Jorge H. Castro, Sean Devitt, Chad Gorn, Cataldo Doria, Adam Frank, Warren Maley, Carlo G. Ramirez

Adam M. Franks, MD

Conclusions:

Use of liver grafts from older donors presents similar survival outcomes as grafts from younger donor age. Therefore, it offers a viable option to expand the donor pool and increase number of OLTs.

However, there is higher incidence of retransplantation due to primary graft non-function, and longer hospital length of stay observed in the older donor age group.

Further studies using larger patient populations are needed to validate our results.

Racial Disparities In Head And Neck Cancers In An Urban Hospital, Jessica Kraus-Lavy, Charnita Zeigler-Johnson, Scott W Keith, Frances Guiles, David Cognetti, Voichita Bar-Ad, Rita S. Axelrod, Md

Phase 1

Introduction: Head and neck cancer incidence rates are higher for white residents in Philadelphia, while related mortality rates are highest for black residents. It is unclear how risk factors like HPV and smoking contribute to these disparities. The goal of this study is to determine which factors are associated with head and neck cancers in a diverse patient population from a Philadelphia hospital.

Methods: Cancer registry data from Thomas Jefferson University was used to obtain records from 922 head and neck cancer patients. One patient of other race was excluded. Twenty in-situ cancer cases were excluded. Chi-square tests were used …