tbuckley/cabot-search huggingface dataset:
Clinical outcomes of transoral robot-assisted supraglottic laryngectomy: An experience of a French cooperative evaluation group of transoral robotic surgery.
Authors: Philippe Ceruse, Benjamin Lallemant, Karine Aubry, Sylvain Morinieres, Sebastien Vergez, Adil Benlyazid, Erwan De Mones del pujol, Olivier Malard
Journal: Journal of Clinical Oncology (2013)

6053 Background: Transoral, minimally invasive organ preservation surgeries are being increasingly used for laryngopharyngeal carcinomas to avoid the toxicities of combined chemotherapy and radiation therapy regimens. This study investigates the efficiency, safety, and functional outcomes of transoral robot assisted surgery (TORAS) for supraglottic laryngectomy. Methods: Experience of TORA supraglottic laryngectomy for patients with supraglottic carcinomas is presented in a multicentric study of a case series with planned data collection between 2009 and 2012. Results: Eighty-six of 262 patients underwent TORA supraglottic laryngectomy for supraglottic carcinomas. Thirty-three percent of patients were started an oral diet within 24 hours. For 77% of the other patients, the median use of a feeding tube was 8 days (0-10 months). Nine percent of them had a definitive percutaneous gastrostomy feeding. For 87% of patients no tracheotomy was performed, for 23% of the others patients, the median use of tracheotomy was 8 days, 3% of them had a definitive tracheotomy. Aspiration was observed in 22% of the patients in the postoperative course and was responsible for the death of one patient. Sixteen percent of the patients had a postoperative bleeding. Fifty percent of the patients received adjuvant radiation therapy based on pathology results. Conclusions: TORA supraglottic laryngectomy is a safe procedure with good functional outcomes and fast recovery but adverse events are possible. Consequently this technique needs a good selection of the patients to reduce the risk of postoperative complications.
Prospective comparison of uPA/PAI-1 and EndoPredict-clin score in ER-positive, HER2-negative breast cancer: Impact on risk stratification and treatment decisions.
Authors: Johannes Ettl, Kirsten Grosse Lackmann, Alexander Hapfelmeier, Evelyn Klein, Stefan Paepke, Christoph Petry, Katja Specht, Heinz Hoefler, Marion Kiechle
Journal: Journal of Clinical Oncology (2013)

581 Background: Adjuvant therapy decisions in breast cancer patients are based on accurate risk assessment. UPA/PAI-1 can be used for risk evaluation. Recently, the EndoPredict-clin score (EPclin), a second generation multigene test has been introduced into clinical practice. Aim of this prospective study is to compare risk assessment by uPA/PAI-1 and EPclin and to determine, how these parameters influence treatment decisions. Methods: 100 consecutive cases of ER-pos, HER2neg, intermediate risk breast cancer cases were enrolled in this study. EPclin and uPA/PAI-1 (for G2-tumors) were obtained by central pathology assessment of the patients´ surgical specimen. Type of adjuvant treatment was chosen after case discussion in an interdisciplinary tumor conference. Results: 94 Patients (pt) have been evaluated. Tumor grading within the presented cohort was as follows: G1: 15 pt (16%), G2: 66 pt (70%), G3: 13 pt (14%). 20 pt (21%) had positive axillary lymph node involvement. Tumor size was less than 1 cm in 27 pt (29%). EPclin could be assessed in 94 pt (100%). 32 pt (34%) were classified as “high risk” whereas 62 pt (66%) were classified as “low risk”. uPA/PAI was obtained from 54 pt (57%). 36 pt (67%) out of these 54 pt had high uPA/PAI-1 levels whereas 18 pt (33%) showed low uPA/PAI-1 levels. Only 2 pt (4%) with low uPA/PAI-1 levels were classified as “high risk” with EPclin, whereas 17 pt (32%) with high uPA/PAI-1 were classified as “low risk” via EPclin (p=0,003). In 29 cases (31%) treatment decision was influenced by EPclin: In 26 pt (28%) adjuvant chemotherapy (ctx) was omitted whereas in 3 pt (3%) ctx was added following the EPclin. Conclusions: This prospective study shows for the first time, that high risk status according to the EPclin score is strongly associated with a high risk status as defined by uPA/PAI-1. Providing analytically valid results for all patients evaluated EPclin’s clinical practicability was clearly superior to uPA/PAI-1. This finding, combined with the fact that EPclin assigns twice as many patients to the low risk group indicated that EPclin is a more versatile and powerful tool to help spare patients from chemotherapy than uPA/PAI-1.
UTILIZING LEFT ATRIAL STRAIN TO IDENTIFY PATIENTS AT RISK FOR DEVELOPING ATRIAL FIBRILLATION ON IBRUTINIB
Authors: Arushi Singh, Katherine McGee, Nadia El Hangouche, Robert Lentz, Sarah Hale, Lua Jafari, Joseph Feinglass, Nausheen Akhter
Journal: Journal of the American College of Cardiology (2020)
SEX- AND RACE-BASED DIFFERENCES AMONG MEDICARE BENEFICIARIES UNDERGOING TRANSCATHETER AND SURGICAL AORTIC VALVE REPLACEMENT IN THE UNITED STATES, 2012-2017
Authors: Aakriti Gupta, Yun Wang, Susheel K. Kodali, Torsten Vahl, Makoto Mori, Isaac George, Ajay Kirtane, Martin Leon, Harlan M. Krumholz
Journal: Journal of the American College of Cardiology (2020)
Retraction notice to “Endophthalmitis Occurring after Cataract Surgery: Outcomes of More Than 480 000 Cataract Surgeries, Epidemiologic Features, and Risk Factors” (Ophthalmology. 2016;123:295-301)
Authors: Mahmoud Jabbarvand, Hesam Hashemian, Mehdi Khodaparast, Mohammadkarim Jouhari, Ali Tabatabaei, Shadi Rezaei
Journal: Ophthalmology (2020)
HSR20-095: Progression-Free Survival, Overall Survival, and Tumor Response for Patients Diagnosed With Small Cell Lung Cancer Who Received First-Line Systemic Therapy
Authors: Junji Lin, Santosh Gautam, Nan Hu, Debra Wertz, Gboyega Adeboyeje, Sumesh Kachroo
Journal: Journal of the National Comprehensive Cancer Network (2020)

"HSR20-095: Progression-Free Survival, Overall Survival, and Tumor Response for Patients Diagnosed With Small Cell Lung Cancer Who Received First-Line Systemic Therapy" published on 20 Mar 2020 by National Comprehensive Cancer Network.
Norrin mediates tumor-promoting and -suppressive effects in glioblastoma via Notch and Wnt
Authors: Ahmed El-Sehemy, Hayden Selvadurai, Arturo Ortin-Martinez, Neno Pokrajac, Yasin Mamatjan, Nobuhiko Tachibana, Katherine Rowland, Lilian Lee, Nicole Park, Kenneth Aldape, Peter Dirks, Valerie A. Wallace
Journal: Journal of Clinical Investigation (2020)

Glioblastoma multiforme (GBM) contains a subpopulation of cells, GBM stem cells (GSCs), that maintain the bulk tumor and represent a key therapeutic target. Norrin is a Wnt ligand that binds Frizzled class receptor 4 (FZD4) to activate canonical Wnt signaling. Although Norrin, encoded by NDP, has a well-described role in vascular development, its function in human tumorigenesis is largely unexplored. Here, we show that NDP expression is enriched in neurological cancers, including GBM, and its levels positively correlated with survival in a GBM subtype defined by low expression of ASCL1, a proneural factor. We investigated the function of Norrin and FZD4 in GSCs and found that it mediated opposing tumor-suppressive and -promoting effects on ASCL1lo and ASCL1hi GSCs. Consistent with a potential tumor-suppressive effect of Norrin suggested by the tumor outcome data, we found that Norrin signaling through FZD4 inhibited growth in ASCL1lo GSCs. In contrast, in ASCL1hi GSCs Norrin promoted Notch signaling, independently of WNT, to promote tumor progression. Forced ASCL1 expression reversed the tumor-suppressive effects of Norrin in ASCL1lo GSCs. Our results identify Norrin as a modulator of human brain cancer progression and reveal an unanticipated Notch-mediated function of Norrin in regulating cancer stem cell biology. This study identifies an unanticipated role of Norrin in human brain cancer progression. In addition, we provide preclinical evidence suggesting Norrin and canonical Wnt signaling as potential therapeutic targets for GBM subtype-restricted cancer stem cells.
Characteristics and Outcome of Chronic Myeloid Leukemia (CML) Patients with E255K and E255V BCR-ABL Kinase Domain Mutations.
Authors: Kiran Naqvi, Hagop Kantarjian, Alfonso Quintás-Cardama, Elias Jabbour, Susan O'Brien, William G. Wierda, Gautam Borthakur, Tapan Kadia, Elizabeth Burton, Jorge E. Cortes
Journal: Blood (2010)
SAFETY AND EFFECTIVENESS OF MANTA VASCULAR CLOSURE DEVICE AFTER LARGE BORE ARTERIAL ACCESS FOR MECHANICAL CIRCULATORY SUPPORT - INITIAL REAL WORLD EXPERIENCE
Authors: Ankur Gupta, Lina Fouad, Mir Basir, Saroj Neupane, Mohammad Zaidan, Gerald Koenig, Mohammad Alqarqaz, Pedro Villablanca, William W. O'Neill, Khaldoon Alaswad
Journal: Journal of the American College of Cardiology (2020)
Primary hormonal therapy for patients with localized or locally advanced prostate cancer
Authors: Z. Shklar, R. Rubinov, M. Steiner, A. Rabkin, M. Leviov, S. Keren, K. Sinatzky
Journal: Journal of Clinical Oncology (2006)

14630 Background: During 1998–2000, 68 patients with localized or locally advanced prostate carcinoma who were not suitable for radical therapy received primary hormonal therapy as the only treatment modality. The group consisted 15.8% of all prostate cancer patients referred to our center during the three years period. Methods: Their median age was 76.7 years (65–89). 42.4% had T1c disease, 30.3% T2a, 15.2% stage T2b and 12.1% T3. 78.4% had Gleason score 4–6, 10.8% Gleason 7 and 10.8% Gleason 8–10 prostate cancer. Median serum PSA level before starting therapy was 15.8 ng/ml (3.4–289). 76% received LHRH agonists monotherapy while 24% had complete androgen blockade. Patients were followed using repeated serum PSA level during 39–95 months (median 79.5). Results: 32/68 patients (47%) experienced PSA recurrence during the study period. Median time to PSA failure was 38.9 months (13–77). No clinical difference was observed between recurrent and non recurrent patients as regarding stage of disease or type of hormonal therapy. In relapsing patients high Gleason score (7–10) was more common (32.3% vs 11.6%) and median initial serum PSA value was higher (22.4 vs 14.5 ng/ml) than in the non recurrent group. During the study period, only 4/68 patients (5.9%) developed clinical disease, 10/68 patients (14.7%) died of unrelated causes and no patient died of prostate cancer. Conclusions: We conclude that primary hormonal therapy is a safe option for prostate cancer patients not suitable for more radical procedures. As expected, high Gleason score and higher initial serum PSA value are predictive for earlier relapse. No significant financial relationships to disclose.
NOVEL METHOD FOR ASSESSING PLATELET RESPONSE TO ADP: TECHNICAL VALIDATION STUDY OF THE AGGREGUIDE A-100 ADP ASSAY
Authors: Paul A. Gurbel, Kevin Bliden, Udaya Tantry, Rischard Fisher, Sivaprasad Sukavaneshvar, Jeffrey Dahlen, Philip Speros
Journal: Journal of the American College of Cardiology (2020)
When it all comes down to pressure: right ventricular ejection fraction at cardiac catheterisation
Authors: Robert Naeije, Manuel J. Richter, Rebecca Vanderpool, Khodr Tello
Journal: European Respiratory Journal (2020)

In the present issue of the European Respiratory Journal , Heerdt et al. [1] report on the validation of right ventricularejection fraction (RVEF) calculated from a pressure curve at cardiac catheterisation. This is of great interest as right ventricular (RV) function is the main determinant of symptomatology and outcome in pulmonary hypertension [2], and RVEF accordingly adds significantly to risk stratification in these patients [3]. However, ejection fraction (EF) is a ratio of stroke volume (SV) to end-diastolic volume (EDV), with no pressure in the equation. So, how is it possible to calculate a volume ratio from pressure measurements? Right ventricular ejection fraction can be calculated from a pressure curve <http://bit.ly/2tjE37Q>
ATRIAL FIBRILLATION AND SEPSIS
Authors: Saima Shikari-Dossaji, Anusha Ganapati Bhat, Muhammad Khan, Anisha Contractor, Anthony Esposito, Munther Maouh Queisi, Joshua Allgaier, Fotis Katsikeris, Tara Lagu, Peter St. Marie, Aixa Perez-Caraballo
Journal: Journal of the American College of Cardiology (2020)
SEX AND PERMANENT DRUG DISCONTINUATION IN CLINICAL TRIALS: INSIGHTS FROM THE TIMI TRIALS
Authors: Emily Lau, Eugene Braunwald, David A. Morrow, Robert Giugliano, Elliott M. Antman, C. Michael Gibson, Benjamin M. Scirica, Erin Ann Bohula, Deepak Bhatt, Christopher P. Cannon, KyungAh Im, Jianping Guo, Marc Steven Sabatine, Michelle O’Donoghue
Journal: Journal of the American College of Cardiology (2020)
Correlation of short telomeres (ST) with vulnerability, toxicity, and early death in elderly AOC patients receiving carboplatin: A multicenter GINECO trial.
Authors: Claire Falandry, Béatrice Horard, Jerome Alexandre, Gael Deplanque, Oana Cojocarasu, Jacques Salvat, Eric Legouffe, Jacques Cretin, Jérome Meunier, Raymonde Maraval-Gaget, Douglas Micheau-Bonnier, Eric Gilson, Gilles Freyer
Journal: Journal of Clinical Oncology (2012)

9011 Background: Age induces a progressive decline in the functional reserve and interferes with cancer treatments. As aging is heterogeneous, this decline has to be assessed individually. Telomere attrition leads to tissue senescence. We tested the hypothesis that telomere lenght (TL) could predict pts vulnerability and outcome during cancer treatment. Methods: This study was performed in the “Elderly women” GINECO trial designed to evaluate the impact of geriatric covariates on survival in AOC pts over 70 receiving 6 courses of carboplatin. TL was estimated in duplicate using standard Terminal Restriction Fragment analysis from peripheral blood cells at inclusion and tested for its correlation with geriatric covariates and pts outcomes (TC and tolerance, overall survival: OS). Results: TL (in base pair) was estimated for 109/111 pts (median 5997; extremes [4517-8333]). No significant correlation was found with any pts characteristics. With a cutoff of 5770 bp, TL discriminated two groups with significantly different Treatment Completion (TC) rates: 0.80 (95CI[0.71-0.89]) and 0.59 (95CI[0.41-0.76]), OR=2.8, p=0.02 for long telomere (LT) and short telomere groups, respectively . ST pts were at higher risk of severe adverse events (SAE, OR=2.7; p&lt;0.02) and tended to have more unplanned hospital admissions (OR=2.1; p&lt;0.08). Considering OS, after adjustment on FIGO stage, TL shorter than the median was a nearly significant risk factor of premature death (HR=1.57; p=0.06. Finally, we addressed if TL correlated with our previously validated geriatric vulnerability score (GVS)c including ADL score&lt;6, IADL score&lt;25, albuminemia&lt;35g/l, lymphopenia&lt;1G/L, HADS score£15 as risk factors of poorer survival. Despite no significant correlation with any of these factors, GVS³3) and ST tended to be correlated (OR=2.1; p=0.08). Conclusions: This exploratory study identifies TL as predictive factor of decreased TC, SAE risk, unplanned hospital admissions and OS after adjustment on FIGO stage.
LOW-DENSITY NON-CALCIFIED PLAQUE ON CORONARY CT ANGIOGRAPHY IS THE STRONGEST INDEPENDENT PREDICTOR OF FUTURE MYOCARDIAL INFARCTION
Authors: Michelle Williams, Jacek Kwiecinski, Mhairi Doris, Priscilla McElhinney, Michelle S. D'Souza, Sebastien J. Cadet, Philip D. Adamson, Alastair Moss, Shirjel Alam, Amanda Hunter, Anoop Shah, Nicholas L. Mills, Tania Pawade, Chengjia Wang, Jonathan Weir-McCall, Giles Roditi, Edwin Van Beek, Leslee J. Shaw, Edward David Nicol, Daniel S. Berman, Piotr Slomka, David E. Newby, Marc Dweck, Damini Dey
Journal: Journal of the American College of Cardiology (2020)
Modern Security Screening and Electromagnetic Interference With Cardiac Implantable Electronic Devices
Authors: Carsten Lennerz, Matthew J. O’Connor, Patrick Blažek, Severin Weigand, Christian Grebmer, Sebastian Reif, Lena Friedrich, Tilko Reents, Felix Bourier, Heribert Schunkert, Isabel Deisenhofer, Christof Kolb
Journal: Journal of the American College of Cardiology (2020)
LONG-TERM CLINICAL OUTCOMES OF SEVERE TRICUSPID REGURGITATION WITHOUT LEFT-SIDE VALVE DISEASE
Authors: Naoki Nishiura, Takeshi Kitai, Akiko Masumoto, Norihisa Miyawaki, Yutaro Miyoshi, Yuta Tsujisaka, Hiroyuki Kono, Mison Paku, Toshiaki Toyoda, Yasuhiro Sasaki, Kitae Kim, Natsuhiko Ehara, Atsushi Kobori, Makoto Kinoshita, Shuichiro Kaji, Yutaka Furukawa
Journal: Journal of the American College of Cardiology (2020)
AIR POLLUTION AND TRANSPORTATION NOISE COMBINE TO INCREASE MACE RISK
Authors: Nicki Naddaf, Michael Thomas Osborne, Shady Abohashem, Azar Radfar, Tomas Patrich, Brian Tung, Blake Oberfeld, Parastou Ghazi, Jaffer James, Tawseef Ahmad Dar, Nehal Mehta, Ahmed Tawakol
Journal: Journal of the American College of Cardiology (2020)
1. METAGENOMIC ANALYSIS OF MICROBIOTA IN PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION 2. ORAL, GUT, AND THROMBUS MICROBIOME IN ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION
Authors: Ju Seung Kwun, Si-Hyuck Kang, Hyo-Jung Lee, Chang-Hwan Yoon, Jung-Won Suh, Young-Seok Cho
Journal: Journal of the American College of Cardiology (2020)
Effect of inhibition of nuclear protein export using a novel CRM1 inhibitor on the apoptotic response to SN38 in preclinical colon cancer models.
Authors: Hye Won Chung, Roberto A. Salas Fragomeni, Sharon Shacham, Michael Kauffman, James C. Cusack
Journal: Journal of Clinical Oncology (2012)

609 Background: Resistance to conventional chemotherapy remains a major challenge in Stage IV colon cancer. CRM1 inhibition leads to nuclear sequestration of proteins such as tumor suppressor p53, growth regulatory proteins, and chemotherapy targets such as topoisomerase I/II. We examined the effects of combination use of KPT185 (a novel CRM1 inhibitor) with SN38 (active metabolite of irinotecan) and the effect of drug administration sequence in human colon cancer cell lines to determine if CRM1 inhibition enhances the cytotoxic effect of chemotherapy. Methods: We evaluated the combination effect of KPT185 with SN-38 on both Lovo (KPT-sensitive, IC 50 = ∼ 500nM) and HT29 cells (KPT-resistant, IC 50 = 1000 ∼ 3000nM) by the Chou-Talalay method, an MTT-based assay that interrogates response across a spectrum of drug dosages: KPT185 (0, 1, 10, 100, 1000, 10000 nM) and SN38 (0, 100, 500, 1000 nM). Cell cycle analysis by FACS with propidium iodide (PI) staining was performed. Effects on apoptosis were determined by FACS (Annexin V/PI staining) and Cell Death Detection ELISA assay. Results: The Chou-Talalay method determined that there is a synergistic effect when KPT185 is combined with SN38 in both Lovo and HT29 cells (combination index &gt; 1). FACS analysis demonstrated combination use of KPT185 and SN38 induced an increase in the apoptotic sub-G1 fraction and a shift toward G2/M arrest. Combination treatment also significantly increased the Annexin V/PI-positive fraction compared with SN38 alone case (P &lt; 0.05). Treatment sequence studies demonstrated that pretreatment of SN38 followed by KPT185 (KPT-post) produced the maximum synergistic effect compared with pretreatment of KPT185 followed by SN38 (KPT-pre) or concurrent use (KPT-con); Cell Death Detection ELISA assay showed KPT-post increased apoptosis most (4.3-fold) compared with KPT-pre (4.2-fold), KPT-con (3.8-fold) and SN38 alone (1-fold). Conclusions: Our results show KPT185, a novel CRM1 inhibitor, sensitizes the response to SN38 in KPT-sensitive as well as KPT-resistant colon cancer cells. This method of sensitizing colon cancer cells warrants further evaluation in preclinical models of colon cancer.
Abstract 13269: Artificial Intelligence (AI) Clinical Decision-Supporting System (CDSS) for Diagnosis of Heart Failure: Concordance With Expert Decision
Authors: Dong-Ju Choi, Jin Joo Park, Youngjin Cho, Sungyoung Lee, Taqdir Ali
Journal: Circulation (2018)

Background: Technologically integrated healthcare environments can be realized if physicians are encouraged to use smart systems for the creation and sharing of knowledge used in clinical decision ...
GLYCEMIA, CORONARY MICROVASCULAR DYSFUNCTION AND CARDIOVASCULAR RISK
Authors: Navkaranbir S. Bajaj, Navkaranbir S. Bajaj, Muthiah Vaduganathan, Wunan Zhou, Viviany R. Taqueti, Sharmila Dorbala, Ron Blankstein, Scott D. Solomon, Marcelo Di Carli
Journal: Journal of the American College of Cardiology (2020)
TAKOTSUBO SYNDROME IN OCTOGENARIANS AND NONAGENARIANS
Authors: Yuki Nishimura, Takako Fujita, Junya Komatsu, Sho-ichi Kubokawa, Ryu-ichiro Imai, Yoko Nakaoka, Koji Nishida, Satoshi Yamamoto, Shu-ichi Seki, Kazuya Kawai, Naohisa Hamasige, Yoshinori L. Doi
Journal: Journal of the American College of Cardiology (2020)
Personality traits in Turkish patients with cancer.
Authors: Nazim S. Turhal, Celal Satici, Caner Cinar, Abdullah Kinar, Salih Demirhan
Journal: Journal of Clinical Oncology (2013)

e20502 Background: This study was planned to investigate the personality traits of cancer patients in different treatment settings, and to correlate the demographics with the personality features. Methods: A total of 237 patients referred either to Marmara University School of Medicine (MUSM) Oncology Outpatient Unit or to the private office of the faculty between March 10 th and April 22 nd , 2010 were enrolled in the study. Big Five Mini Test was used to evaluate the 40 personality traits filled by patients. Results: The study group consisted of 98 males (41.35%) and 139 females (58.65%) with a mean age of 51. Out of 237 patients, 73.9% had an educational level beyond the junior high school, and 47.3% of all patients reported a positive family history for cancer. A significant difference in terms of reconcilability, extraversion, and responsibility was observed between patients admitting to the university outpatient clinic and the private office (p&lt;0.05). Reconcilability and extraversion were found to differ between genders significantly (p&lt;0.05). The description of the patient by him/herself or by its relatives displayed a significant difference in terms of openness (p&lt;0.05). Parameters such as educational level, family history of cancer, age and marital status showed no relevance with their characters. No discordance was observed between the self-analysis of the patient and the patient’s relatives. Conclusions: This is the first such study conducted in Turkish cancer patients and they found to be typically highly reconcilable and responsible, moderately stable, open and extraverted.
FREQUENCY: VERY LOW YIELD OF FETAL ECHOCARDIOGRAPHY IN HIGH-RISK PREGNANCIES WITH A NORMAL OBSTETRICAL SECOND-TRIMESTER ULTRASOUND
Authors: Mikhail-Paul Cardinal, Camille Noël, Marie-Hélène Gagnon, Cassandre Têtu, Alain Vanasse, Marie-Ève Roy-Lacroix, Thomas G. Poder, Ariane Marelli, Tiscar Cavalle-Garrido, Laurence Vaujois, Jean-Luc Bigras, Frédéric Dallaire
Journal: Journal of the American College of Cardiology (2020)
gscreend: modelling asymmetric count ratios in CRISPR screens to decrease experiment size and improve phenotype detection
Authors: Katharina Imkeller, Giulia Ambrosi, Michael Boutros, Wolfgang Huber
Journal: Genome biology (2020)

Abstract Pooled CRISPR screens are a powerful tool to probe genotype-phenotype relationships at genome-wide scale. However, criteria for optimal design are missing, and it remains unclear how experimental parameters affect results. Here, we report that random decreases in gRNA abundance are more likely than increases due to bottle-neck effects during the cell proliferation phase. Failure to consider this asymmetry leads to loss of detection power. We provide a new statistical test that addresses this problem and improves hit detection at reduced experiment size. The method is implemented in the R package gscreend, which is available at http://bioconductor.org/packages/gscreend .