Medicine and Health Sciences Commons^™

Improved Right Ventricular Systolic Function After Cardiac Resynchronization Therapy In Patients With Heart Failure, Hakimeh Sadeghian, Ali Kazemisaied, Mehrnaz Rezvanfard, Arash Jalali, Afsaneh Sadeghian, Haleh Ashraf, Farbod Semnani, Amirhossein Ghaseminejad Raeini

The Texas Heart Institute Journal

Background

Since the introduction of cardiac resynchronization therapy (CRT) to improve left ventricular function, the effect of CRT on the right ventricle in patients with heart failure has not been well described.

Methods

We evaluated the effect of CRT on right ventricular systolic function in 20 patients (80% men; mean [SD] age, 58.5 [9.8] y) with cardiomyopathy and right ventricular systolic dysfunction (New York Heart Association class III or IV, left ventricular ejection fraction ≤35%, and QRS interval ≥120 ms). The median follow-up time was 15 months. Right ventricular systolic function, defined as a tricuspid annular plane systolic excursion (TAPSE) …

Arrhythmia Burden And Heart Rate Response During Exercise In Anderson-Fabry Disease, Adam W Powell, Samuel G Wittekind, Wayne A Mays, Sean M Lang, Timothy K Knilans, Carlos E Prada, Robert J Hopkin, Clifford Chin

The Texas Heart Institute Journal

Patients with Anderson-Fabry disease (AFD) have an elevated incidence of resting arrhythmias and ischemic heart disease, but their exercise arrhythmia burden and ischemic changes are not well understood. In addition, little research has been done on heart rate recovery in these patients.

We retrospectively reviewed charts of patients with AFD who underwent maximal effort cardiopulmonary exercise testing (CPET) (n=44; 38.2 ± 13.8 yr; 23 men) from 2012 through 2018. Electrocardiographic, Holter monitoring, echocardiographic, cardiac magnetic resonance imaging, and patient demographic data were collected.

No patient had adverse events that necessitated CPET termination, whereas 25 (57%) had ectopy during CPET, including …

Hypertrophic Cardiomyopathy And Pregnancy: A Retrospective Analysis From A Tertiary Care Hospital, Pooja Sikka, Vanita Suri, Seema Chopra, Neelam Aggarwal, Subhas Chandra Saha, Ramandeep Bansal, Rajesh Vijayvergiya, Ajay Bahl

The Texas Heart Institute Journal

Pregnancy in women with hypertrophic cardiomyopathy is not well described. In this retrospective study, we analyzed data on pregnant women with hypertrophic cardiomyopathy who were under follow-up care in the cardiology department of a tertiary care hospital. We reviewed data on all women registered in the hypertrophic cardiomyopathy cohort and those who attended the cardio-obstetric clinic and delivered between January 2010 and June 2019. From these 2 groups, we identified 7 pregnant women with hypertrophic cardiomyopathy who delivered during this period. These 7 women (mean [SD] age, 25 [3.3] years) had a total of 15 pregnancies (range per woman,1–4). This …

Combined Disease Of The Quadricuspid Aortic Valve, Robert Blazekovic, Jasmina Catic, Stjepan Barisin, Marko Kusurin, Savica Gjorgjievska, Stanislav Glumbic

The Texas Heart Institute Journal

No abstract provided.

Transcatheter Aortic Valve Implantation For Severe Aortic Stenosis And Large Membranous Interventricular Septal Aneurysm, Maheedhar Gedela, Tomasz Stys, Terezia Petraskova, Adam Stys

The Texas Heart Institute Journal

No abstract provided.

Minimal Impact Of The Covid-19 Pandemic On Disease Activity And Health-Related Quality Of Life In Patients With Ankylosing Spondylitis Receiving Bimekizumab: Exploratory Analyses From A Phase 2b Open-Label Extension Study., Philip C Robinson, Pedro M Machado, Nigil Haroon, Lianne S Gensler, John D Reveille, Vanessa Taieb, Thomas Vaux, Carmen Fleurinck, Marga Oortgiesen, Natasha De Peyrecave, Atul Deodhar

Journal Articles

OBJECTIVE: The impact of the COVID-19 pandemic on patients with inflammatory rheumatic diseases, such as ankylosing spondylitis (AS), has been variable. Here, we assess disease activity and health-related quality of life (HRQoL) through the pandemic in patients with AS.

METHODS: In the open-label extension (OLE) of the phase 2b BE AGILE study, patients with AS received 160 mg of subcutaneous bimekizumab every 4 weeks. We assessed Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Quality of Life (ASQoL) scores in the OLE immediately before and during the COVID-19 pandemic …

Association Between Metabolic Overweight/Obesity Phenotypes And Readmission Risk In Patients With Lung Cancer: A Retrospective Cohort Study, Zinuo Yuan, Yiping Cheng, Junming Han, Dawei Wang, Hang Dong, Yingzhou Shi, Kyle L Poulsen, Xiude Fan, Jiajun Zhao

Journal Articles

BACKGROUND: Increased body mass index (BMI) and metabolic abnormalities are controversial prognostic factors of lung cancer. However, the relationship between metabolic overweight/obesity phenotypes and hospital readmission in patients with lung cancer is rarely reported.

METHODS: We established a retrospective cohort using the United States (US) Nationwide Readmissions Database (NRD). We included adult patients diagnosed with lung cancer from January 1, 2018 to November 30, 2018 and excluded patients combined with other cancers, pregnancy, died during hospitalization, low body weight, and those with missing data. The cohort was observed for hospital readmission until December 31, 2018. We defined and distinguished four …

Predominantly Persistent Intraretinal Fluid In The Comparison Of Age-Related Macular Degeneration Treatments Trials, Jason Q Core, Maxwell Pistilli, Peiying Hua, Ebenezer Daniel, Juan E Grunwald, Cynthia A Toth, Glenn J Jaffe, Daniel F Martin, Maureen G Maguire, Gui-Shuang Ying, Comparison Of Age-Related Macular Degeneration Treatments Trials (Catt) Research Group

Journal Articles

PURPOSE: To describe predominantly persistent intraretinal fluid (PP-IRF) and its association with visual acuity (VA) and retinal anatomic findings at long-term follow-up in eyes treated with pro re nata (PRN) ranibizumab or bevacizumab for neovascular age-related macular degeneration.

DESIGN: Cohort within a randomized clinical trial.

PARTICIPANTS: Participants in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT) assigned to PRN treatment.

METHODS: The presence of intraretinal fluid (IRF) on OCT scans was assessed at baseline and monthly follow-up visits by Duke OCT Reading Center. Predominantly persistent intraretinal fluid through week 12, year 1, and year 2 was defined as the …

Dockopathies: A Systematic Review Of The Clinical Pathologies Associated With Human Dock Pathogenic Variants, Adrienne Samani, Katherine G English, Michael A Lopez, Camille L Birch, Donna M Brown, Gurpreet Kaur, Elizabeth A Worthey, Matthew S Alexander

Journal Articles

The Dedicator of Cytokinesis (DOCK) family (DOCK1-11) of genes are essential mediators of cellular migration, growth, and fusion in a variety of cell types and tissues. Recent advances in whole-genome sequencing of patients with undiagnosed genetic disorders have identified several rare pathogenic variants in DOCK genes. We conducted a systematic review and performed a patient database and literature search of reported DOCK pathogenic variants that have been identified in association with clinical pathologies such as global developmental delay, immune cell dysfunction, muscle hypotonia, and muscle ataxia among other categories. We then categorized these pathogenic DOCK variants and their associated clinical …

Treating Phantom Limb Pain: Cryoablation Of The Posterior Tibial Nerve, Matthew Fiala, Abana Azariah, Jean Woo, Ahmed Kamel Abdel Aal, Alexa Levey

Journal Articles

Phantom limb pain (PLP) is a complex pathophysiologic process involving both the central and peripheral nervous system for which there is no definitive treatment. The number of individuals living with amputated limbs is predicted to increase to 3.5 million by 2050, and up to 80% of these patients will have PLP. In this case report, we will demonstrate successful reduction of PLP in a patient with bilateral phantom toe pain utilizing nerve blockade and subsequent cryoablation of the posterior tibial nerves.

Hepatic Circadian And Differentiation Factors Control Liver Susceptibility For Fatty Liver Disease And Tumorigenesis, Baharan Fekry, Aleix Ribas-Latre, Rachel Van Drunen, Rafael Bravo Santos, Samay Shivshankar, Yulin Dai, Zhongming Zhao, Seung-Hee Yoo, Zheng Chen, Kai Sun, Frances M Sladek, Mamoun Younes, Kristin Eckel-Mahan

Journal Articles

Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths, and the most common primary liver malignancy to present in the clinic. With the exception of liver transplant, treatment options for advanced HCC are limited, but improved tumor stratification could open the door to new treatment options. Previously, we demonstrated that the circadian regulator Aryl Hydrocarbon-Like Receptor Like 1 (ARNTL, or Bmal1) and the liver-enriched nuclear factor 4 alpha (HNF4α) are robustly co-expressed in healthy liver but incompatible in the context of HCC. Faulty circadian expression of HNF4α- either by isoform switching, or loss of expression- results in an increased …

Modulation Of The Association Between Age And Death By Risk Factor Burden In Critically Ill Patients With Covid-19, Ashwin Sunderraj, Chloe Cho, Xuan Cai, Shruti Gupta, Rupal Mehta, Tamara Isakova, David E Leaf, Anand Srivastava

Journal Articles

UNLABELLED: Older age is a key risk factor for adverse outcomes in critically ill patients with COVID-19. However, few studies have investigated whether preexisting comorbidities and acute physiologic ICU factors modify the association between age and death.

DESIGN: Multicenter cohort study.

SETTING: ICUs at 68 hospitals across the United States.

PATIENTS: A total of 5,037 critically ill adults with COVID-19 admitted to ICUs between March 1, 2020, and July 1, 2020.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: The primary exposure was age, modeled as a continuous variable. The primary outcome was 28-day inhospital mortality. Multivariable logistic regression tested the association …

Primary Sjögren's Syndrome Presenting As Cerebral Venous Thrombosis: A Rare Case, Mohan Sonu Chandra, Monisha G A, Ravi Kiran M

Journal Articles

Sjogren's syndrome is a late-onset, slowly progressing autoimmune disease characterized by the destruction of the exocrine glands by lymphocytic infiltration, resulting in dry mouth (xerostomia) and dry eyes (keratoconjunctivitis sicca). Sjögren's syndrome may be associated with various autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis. We report a case of a 34-year-old female who delivered a live baby 20 days ago. She presented in a postictal state after two episodes of tonic-clonic movements of limbs with altered sensorium with a history of headache for seven days. Further evaluation revealed that the subject had a history of multiple …

Coronary-To-Coronary Bypass Grafting In Aortoarteritis: A Case Report, Immaneni Sathyamurthy, Narra Lavanya, Kanthallu Narayanamoorthy Srinivasan, Maligail Ramkrishna Girinath

Journal Articles

Takayasu's arteritis (TA) is an idiopathic vasculitis affecting the aorta and its major branches. In TA, coronary artery involvement is rare and it mainly consists of stenosis or occlusion of the coronary ostia. In TA, as the arterial tree is diseased, often, arterial grafts are unsuitable for grafting so the saphenous vein grafts (SVG) are commonly used. We present a case of a young female with TA with an ostial left main stenosis who has undergone a right coronary-to-left anterior descending artery SVG and put on immunosuppression and steroids. She was asymptomatic with a patent graft during 7 years follow-up.

Ugrc 2021 Recommendations On Gme Transition: Pros And Cons, Opportunities And Limitations, John R Gimpel, Jennifer L Swails, Jessica L Bienstock, Grant L Lin, Michelle A Roett, Juhee K Patel, Daniel W Giang

Journal Articles

The Coalition for Physician Accountability's Undergraduate Medical Education-Graduate Medical Education (UME-GME) Review Committee (UGRC): Recommendations for Comprehensive Improvement of the UME-GME Transition final report includes a total of 34 recommendations and outlines opportunities to transform the current processes of learner transition from a US-based MD- or DO-granting medical school or international medical education pathway into residency training in the United States. This review provides a reflection on the recommendations from the authors, all members of the UGRC, describing the pros and cons and the opportunities and limitations, in the hopes that they might inspire readers to dig deeper into the …

Gastrocnemius Venous Aneurysm-A Diagnostic Dilemma, Akiko Tanaka, Taha Syed Zaidi, S Keisin Wang, Arash Keyhani, Kourosh Keyhani

Journal Articles

A 63-year-old man with multiple previous orthopedic procedures in both lower extremities had presented to us for a third opinion regarding the point-specific pain in his right lateral calf. The initial diagnosis had been venous reflux at two other institutions. However, repeat imaging studies demonstrated an aneurysmal gastrocnemius vein without any other abnormalities, such as venous reflux or thrombosis. The patient had received compression stocking therapy for 6 months but had continued to experience increasing pain at night, especially when lying in bed. The patient was reexamined in the supine position, which showed a prominent bulge in the lateral calf. …

New Sedatives And Analgesic Drugs For Gastrointestinal Endoscopic Procedures, Jae Min Lee, Yehyun Park, Jin Myung Park, Hong Jun Park, Jun Yong Bae, Seung Young Seo, Jee Hyun Lee, Hyung Ku Chon, Jun-Won Chung, Hyun Ho Choi, Jun Kyu Lee, Byung-Wook Kim

Journal Articles

Procedural sedation has become increasingly common in endoscopy. Sedatives and analgesics induce anxiolysis and amnesia. In addition, an appropriate level of sedation is necessary for safe procedures including therapeutic endoscopy. Midazolam and propofol are the most commonly used drugs in sedative endoscopy. In recent years, the need to ascertain the safety and effectiveness of sedation has increased in practice. Therefore, new sedatives and analgesic drugs for optimal sedative endoscopy, have recently emerged. This article reviews the characteristics of sedatives and analgesics, and describes their clinical use in gastrointestinal endoscopy.

Apoptotic Brown Adipocytes Enhance Energy Expenditure Via Extracellular Inosine, Birte Niemann, Saskia Haufs-Brusberg, Laura Puetz, Martin Feickert, Michelle Y Jaeckstein, Anne Hoffmann, Jelena Zurkovic, Markus Heine, Eva-Maria Trautmann, Christa E Müller, Anke Tönjes, Christian Schlein, Azin Jafari, Holger K Eltzschig, Thorsten Gnad, Matthias Blüher, Natalie Krahmer, Peter Kovacs, Joerg Heeren, Alexander Pfeifer

Journal Articles

Brown adipose tissue (BAT) dissipates energy

The Effect Of Biologic Therapy For Immune-Mediated Inflammatory Diseases On Clinical Outcomes Of Covid-19 In The Greater Houston Area: A Retrospective Chart Review, Kevin P Lee, Misha V Koshelev, D3code Team, Omar Pacha

Journal Articles

No abstract provided.

A Case Of Perifollicular Macular Amyloidosis, Imran T Baig, Jamael L Thomas, Misha V Koshelev

Journal Articles

Macular amyloidosis is a common type of primary localized cutaneous amyloidosis. We present a case report of a 74-year-old patient with no significant past medical history who was evaluated for dark macules and pruritus for over a year. On exam, follicular-based brown macules on the upper and lower back, bilateral shoulders, and bilateral dorsal upper arms were noted. The morphology and distribution of follicular-based macules was unusual, so the differential included follicular lichen planus, follicular eczema, and macular amyloidosis. Punch biopsy showed deposits of eosinophilic fibrillary material along with pigmentary incontinence in the papillary dermis, consistent with macular amyloidosis. Additionally, …

Dynamic S-Acylation Of The Er-Resident Protein Stromal Interaction Molecule 1 (Stim1) Is Required For Store-Operated Ca2+ Entry, Goutham Kodakandla, Savannah J West, Qiaochu Wang, Ritika Tewari, Michael X Zhu, Askar M Akimzhanov, Darren Boehning

Journal Articles

Many cell surface stimuli cause calcium release from endoplasmic reticulum (ER) stores to regulate cellular physiology. Upon ER calcium store depletion, the ER-resident protein stromal interaction molecule 1 (STIM1) physically interacts with plasma membrane protein Orai1 to induce calcium release-activated calcium (CRAC) currents that conduct calcium influx from the extracellular milieu. Although the physiological relevance of this process is well established, the mechanism supporting the assembly of these proteins is incompletely understood. Earlier we demonstrated a previously unknown post-translational modification of Orai1 with long-chain fatty acids, known as S-acylation. We found that S-acylation of Orai1 is dynamically regulated in a …

Mir-486 Is Essential For Muscle Function And Suppresses A Dystrophic Transcriptome, Adrienne Samani, Rylie M Hightower, Andrea L Reid, Katherine G English, Michael A Lopez, J Scott Doyle, Michael J Conklin, David A Schneider, Marcas M Bamman, Jeffrey J Widrick, David K Crossman, Min Xie, David Jee, Eric C Lai, Matthew S Alexander

Journal Articles

miR-486 is a muscle-enriched microRNA, or “myomiR,” that has reduced expression correlated with Duchenne muscular dystrophy (DMD). To determine the function of miR-486 in normal and dystrophin-deficient muscles and elucidate miR-486 target transcripts in skeletal muscle, we characterized mir-486 knockout mice (mir-486 KO). mir-486 KO mice developed disrupted myofiber architecture, decreased myofiber size, decreased locomotor activity, increased cardiac fibrosis, and metabolic defects were exacerbated in mir-486 KO:mdx5cv (DKO) mice. To identify direct in vivo miR-486 muscle target transcripts, we integrated RNA sequencing and chimeric miRNA eCLIP sequencing to identify key transcripts and pathways that contribute towards mir-486 …

Informed Consent For Placebo-Controlled Trials: Do Ethics And Science Conflict?, Hope A Feldman, James A Feldman, Charles C Miller, Garrett Walsh, Jon E Tyson

Journal Articles

The use of a placebo has been considered the best method for controlling bias in a prospective randomized clinical trial and provides the most rigorous test of treatment efficacy for evaluating a medical therapy. Placebos commonly produce clinically important effects particularly in studies where the primary outcomes are subjective. Yet the potential beneficial or harmful effects of placebos are often not addressed in designing a clinical trial, calculating the sample size, seeking consent, or interpreting clinical trial results. In this manuscript, we use an actual study to indicate three approaches that might be considered in seeking informed consent for placebo-controlled …

Covid-19 And Blood Clots: A Report Of Massive Pulmonary Embolism In Covid-19 Patient Supported On Veno-Venous Ecmo And The Utility Of Thrombolysis, Bindu Akkanti, Joseph Zwischenberger, Mark T Warner, Kha Dinh, Rahat Hussain, Farah Kazzaz, Pascal Kingah, Lisa M Janowiak, Biswajit Kar, Igor D Gregoric

Journal Articles

COVID-19 morbidity and mortality are not equivalent to other etiologies of acute respiratory distress syndrome (ARDS) as fulminant activation of coagulation can occur, thereby resulting in widespread microvascular thrombosis and consumption of coagulation factors. A 53-year-old female presented to an emergency center on two occasions with progressive gastrointestinal and respiratory symptoms. She was diagnosed with COVID-19 pneumonia and admitted to a satellite intensive care unit with hypoxemic respiratory failure. She was intubated and mechanically ventilated, but her ARDS progressed over the next 48 hours. The patient was emergently cannulated for veno-venous extracorporeal membrane oxygenation (V-V ECMO) and transferred to our …

Post-Lung Transplantation Outcomes And Ex Vivo Histopathological Findings In Severe Post-Covid-19 Pulmonary Disease-A Single-Center Experience, Hana Javaid, Masayuki Nigo, Bihong Zhao, Daniel Ocazionez Trujillo, Rodrigo Hasbun, Luis Ostrosky-Zeichner, Manish Patel, Soma Jyothula

Journal Articles

BACKGROUND: A significant proportion of patients with severe and persistent coronavirus disease 2019 (COVID-19) require continuous ventilatory support and occasional extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS). Lung transplantation is a treatment option for patients who develop severe ARDS.

METHODS: Our lung transplant database was retrospectively reviewed for patients who underwent lung transplantation for COVID-19 pulmonary disease at Memorial Hermann Hospital, Texas Medical Center, Houston, Texas, from January 2020 to March 2022. We evaluated outcomes of patients who were followed in our clinic at least 6 months post-transplant. Pretransplant patient characteristics, COVID-19-related treatment, histopathology results, and postdischarge …

Short Signature Rpob Gene Sequence To Differentiate Species In Mycobacterium Abscessus Group, Jian R Bao, Kileen L Shier, Ronald N Master, Robert S Jones, Richard B Clark

Journal Articles

Mycobacterium abscessus group (MAG) are rapidly growing acid-fast bacteria that consist of three closely related species: M. abscessus (Ma), M. bolletii (Mb), and M. massiliense (Mm). Differentiation of these species can be difficult but is increasingly requested owing to recent infectious outbreaks and their differential drug resistance. We developed a novel and rapid pyrosequencing method using short signature sequences (35 to 45 bp) at a hypervariable site in the rpoB gene to differentiate the three MAG species, along with M. chelonae (Mc), and M. immunogenum (Mi). This method was evaluated …

Comparative Risks Of Initial Aortic Events Associated With Genetic Thoracic Aortic Disease, Ellen S Regalado, Shaine A Morris, Alan C Braverman, Ellen M Hostetler, Julie De Backer, Ruosha Li, Reed E Pyeritz, Anji T Yetman, Elena Cervi, Sherene Shalhub, Richmond Jeremy, Scott Lemaire, Maral Ouzounian, Arturo Evangelista, Catherine Boileau, Guillaume Jondeau, Dianna M Milewicz

Journal Articles

BACKGROUND: Pathogenic variants in 11 genes predispose individuals to heritable thoracic aortic disease (HTAD), but limited data are available to stratify the risk for aortic events associated with these genes.

OBJECTIVES: This study sought to compare the risk of first aortic event, specifically thoracic aortic aneurysm surgery or an aortic dissection, among 7 HTAD genes and variant types within each gene.

METHODS: A retrospective cohort of probands and relatives with rare variants in 7 genes for HTAD (n = 1,028) was assessed for the risk of first aortic events based on the gene altered, pathogenic variant type, sex, proband status, …

Fiber Bragg Grating Array For Shape Reconstruction In Structural Elements, Edson A Souza, Leandro C Macedo, Anselmo Frizera, Carlos Marques, Arnaldo Leal-Junior

Journal Articles

This paper presents the development, analysis and application of a fiber Bragg grating (FBG) array for two-dimensional (2D) shape reconstruction in a cantilever beam. The structural elements made of Pinus wood and Nylon 6.0 were numerically analyzed using the finite element method for the strain distribution when constant loading is applied at the free end of the beam. In addition, the temperature compensation method is proposed to decouple the temperature cross-sensitivity in the deflection analysis. In this case, the temperature sensitivities of all sensing elements of the 5-FBG array were obtained. An additional FBG was encapsulated in a silicone mold …

Generalization In Quantum Machine Learning From Few Training Data, Matthias C Caro, Hsin-Yuan Huang, M Cerezo, Kunal Sharma, Andrew Sornborger, Lukasz Cincio, Patrick J Coles

Journal Articles

Modern quantum machine learning (QML) methods involve variationally optimizing a parameterized quantum circuit on a training data set, and subsequently making predictions on a testing data set (i.e., generalizing). In this work, we provide a comprehensive study of generalization performance in QML after training on a limited number N of training data points. We show that the generalization error of a quantum machine learning model with T trainable gates scales at worst as [Formula: see text]. When only K ≪ T gates have undergone substantial change in the optimization process, we prove that the generalization error improves to [Formula: see …

Mixed-Phenotype Acute Leukemia: Clinical Diagnosis And Therapeutic Strategies, Binsah S George, Binoy Yohannan, Anneliese Gonzalez, Adan Rios

Journal Articles

Mixed-phenotype acute leukemia (MPAL) comprises a heterogenous group of leukemias that are genetically, immunophenotypically, and clinically, diverse. Given the rarity of the disease, the diagnosis and treatment of MPAL is extremely challenging. Recent collaborative efforts have made significant progress in understanding the complex genomic landscape of MPAL. Some retrospective studies support starting ALL-type induction followed by an allogeneic stem cell transplant(allo-sct) in the first complete remission; however, due to the inherent bias of retrospective data and small case series, a prospective validation of AML- and ALL-based regimen, and the incorporation of targeted therapies based on genetics and immunophenotype are warranted. …