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1. A novel lossless encoding algorithm for data compression–genomics data as an exemplar

Author

Anas Al-okaily and Abdelghani Tbakhi

Subjects
compression, Huffman encoding, LZ, genomics, BWT, Computer applications to medicine. Medical informatics, R858-859.7
Abstract

Data compression is a challenging and increasingly important problem. As the amount of data generated daily continues to increase, efficient transmission and storage have never been more critical. In this study, a novel encoding algorithm is proposed, motivated by the compression of DNA data and associated characteristics. The proposed algorithm follows a divide-and-conquer approach by scanning the whole genome, classifying subsequences based on similarities in their content, and binning similar subsequences together. The data is then compressed into each bin independently. This approach is different than the currently known approaches: entropy, dictionary, predictive, or transform-based methods. Proof-of-concept performance was evaluated using a benchmark dataset with seventeen genomes ranging in size from kilobytes to gigabytes. The results showed a considerable improvement in the compression of each genome, preserving several megabytes compared to state-of-the-art tools. Moreover, the algorithm can be applied to the compression of other data types include mainly text, numbers, images, audio, and video which are being generated daily and unprecedentedly in massive volumes.

Published
2025
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2. Implementation of Universal Pan-Cancer Germline Genetic Testing in an Arab Population: The Jordanian Exploratory Cancer Genetics Study

Author

Hikmat Abdel-Razeq, Baha' Sharaf, Hira Bani Hani, Ramiz Abu Hijlih, Mais Alkyam, Khansa Al-Azzam, Shatha Elemian, Abdelghani Tbakhi, Areej Al-Atary, Rachel E. Ellsworth, Emily M. Russell, Edward D. Esplin, Malek Horani, Zeidan Zeidan, Abdulla Alzibdeh, Brandie Heald, Sarah M. Nielsen, and Robert L. Nussbaum

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

PURPOSEGermline genetic testing (GGT) significantly affects cancer care. While universal testing has been studied in Western societies, less is known about adoption elsewhere.MATERIALS AND METHODSIn this study, 3,319 unselected, pan-cancer Jordanian patients diagnosed between April 2021 and September 2022 received GGT. Pathogenic germline variant (PGV) frequency among patients who were in-criteria (IC) or out-of-criteria (OOC; 2020 National Comprehensive Cancer Network criteria) and changes in clinical management in response to GGT results were evaluated. Statistical analysis was performed using two-tailed Fisher's exact test with significance level P < .05.RESULTSThe cohort was predominantly female (69.9%), with a mean age of 53.7 years at testing, and 53.1% were IC. While patients who were IC were more likely than patients who were OOC to have a PGV (15.8% v 9.6%; P < .0001), 149 (34.8%) patients with PGVs were OOC. Clinical management recommendations in response to GGT, including changes to treatment and/or follow-up, were made for 57.3% (161 of 281) of patients with high- or moderate-risk PGVs, including 26.1% (42 of 161) of patients who were OOC.CONCLUSIONUniversal GGT of patients with newly diagnosed cancer was successfully implemented in Jordan and led to identification of actionable PGVs that would have been missed with guidelines-based testing.

Published
2024
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3. Impact of the SARS‐CoV‐2 pandemic on the overall respiratory viruses' transmission in a cancer care setting

Author

Sawsan Mubarak, Osama Alsmadi, Abdelghani Tbakhi, Osama Abu Ata, Ala'a Hassan, and Hadeel AlGhawrie

Subjects
COVID‐19, flu viruses, joint point regression, respiratory viruses, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Introduction and Objective The emergence of the COVID‐19 pandemic raised questions about the interaction between severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and other respiratory viruses. The objective of this study is to validate the impact of the SARS‐CoV‐2 pandemic and its interventional measures on the respiratory viruses' transmission/infection rates. Methods A retrospective chart review was conducted for cancer patients who underwent laboratory‐confirmed respiratory virus polymerase chain reaction (PCR) testing from January 2018 to June 2022. COVID‐19 PCR tests from March 2020 to June 2022 were also included. Joinpoint regression analysis was applied to evaluate trends in respiratory virus rates. Statistical analysis was performed using Statistical Package for Social Science software. Results A total of 6298 respiratory virus PCRs and 40,000 COVID‐19 PCRs were performed. Data showed a significant decrease in respiratory viruses' positive cases, total respiratory tests, and respiratory viruses' activity during the pandemic period compared with the pre‐pandemic period (p = .0209, .026, and .028, respectively). The joinpoint regression analysis showed a significant decrease of 13.85% in the tested positive cases of respiratory viruses between the years 2018 and 2022. Monthly, the analysis indicated a significant decrease in the positive cases by 13.46% from December 2019 to May 2021. Weekly analysis following lockdown initiation showed a reduction in respiratory virus cases. Conclusion This study provides valuable insights into the interplay between COVID‐19 and other respiratory viruses, suggesting that the measures taken for COVID‐19 were effective in reducing the spread of viral respiratory infections, aiding future infection control strategies to protect vulnerable populations, including cancer patients, from seasonal respiratory infections.

Published
2023
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4. Flow cytometric signature of CD371-positive B-cell acute lymphoblastic leukemia

Author

Hind Shakah, Abdelghani Tbakhi, Saleh Khudirat, Ruba Al Abweh, Nabil Hasasna, Alaa Alwhaidi, Abdallah Khoujah, and Fareed Barakat

Subjects
Medicine (General), R5-920
Abstract

Objectives Multiparametric flow cytometry (MFC) aids in the diagnosis and management of B-cell acute lymphoblastic leukemia (B-ALL) by establishing a baseline immunophenotype for leukemic cells and measuring minimal residual disease (MRD) throughout the course of treatment. Aberrant expression patterns of myeloid markers in B-ALL are also examined during long-term surveillance. Here, we investigated the utility of the newly described myeloid marker cluster of differentiation (CD)371 in MRD surveillance via MFC in patients with CD371-positive B-ALL. Methods Eight-color MFC with standard panels (including CD371) was used to evaluate 238 patients with newly diagnosed B-ALL. Expression levels of key markers were retrospectively assessed at diagnosis, as well as days 15 and 33 of therapy. Results CD371 was expressed in 8.4% of patients with B-ALL. CD371 positivity was associated with older age at diagnosis, higher expression levels of CD34 and CD38, and lower expression levels of CD10 and CD20. Residual leukemic cells demonstrated decreased CD10 expression and increased CD45 expression after therapy, whereas CD371 expression remained stable. Conclusions Patients with CD371-positive B-ALL exhibit a specific signature that merits further analysis, particularly because it has been associated with DUX4 rearrangement.

Published
2023
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5. BRAF V600E mutation in papillary thyroid carcinoma: it’s relation to clinical features and oncologic outcomes in a single cancer centre experience

Author

Mahmoud Al-Masri, Tawfiq Al-Shobaki, Hani Al-Najjar, Rafal Iskanderian, Enas Younis, Niveen Abdallah, Abdelghani Tbakhi, Hussam Haddad, Mohammad Al-Masri, Zeinab Obeid, and Awad Jarrar

Subjects
thyroid cancer, papillary, neoplasms, mutation, middle east, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Purpose: This study focuses on the oncologic influence of BRAF V600E mutations in a cohort of Middle Eastern papillary thyroid carcinoma (PTC) patients treated at a single centre. We tested the association of BRAF V600E mutation with papillary thyroid carcinoma at King Hussein Cancer Center. Methods: Patients with histologically confirmed PTC who underwent surgic al treatment between 2006 and 2015 were included in this study. Oncological outcomes, both short-and long-termed, were collected. Results: A total of 128 patients (68% females) were included in this st udy with a mean age of 38 years (±13.8). The median follow-up period was 50 mon ths. The BRAF V600E mutation was found in 71% of patients. The tumour size for pati ents with a negative BRAF V600E mutation was significantly larger in comparison to pa tients who tested positive for the mutation (3.47 cm vs 2.31 cm, respectively, P = 0.009). The two groups showed similar disease-free survival (DFS) rates; positive = 75% (median 43 months (0–168)) compared to 78% for the negative BRAF V600E mutation (median 38 months (3–142)) (P = 0.162, HR = 0.731) Furthermore, both groups showed similar overall surviva l rates, positive = 94.5% (median 56 months (0–228)) compared to 94.6% for the neg ative BRAF V600E mutation (median 43 months (3–157)) (P = 0.941, HR = 0.940). Conclusion: BRAF V600E mutation had no effect on loco-regional recurrence, distant metastasis, overall survival, or DFS. These findings may be attr ibuted to geographic variations or reflect that BRAF V600E may only serve as an indicator of poor prognosis in high-risk group as such.

Published
2021
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6. Early post‐induction augmented therapy improves outcome in children and adolescents with T‐cell acute lymphoblastic leukemia

Author

Mayada Abu Shanap, Haytham Al Jabour, Rawad Rihani, Hasan Hashem, Amal Abu Ghosh, Abdelghani Tbakhi, Nazmi Kamal, Iyad Sultan, and Faris Madanat

Subjects
children, cranial radiation, intensification therapy, relapse, T‐cell acute leukemia, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Introduction T‐cell acute lymphoblastic leukemia (T‐ALL) accounts for approximately 15% of all newly diagnosed ALL in children and adolescents and is associated with worse outcomes compared to pre‐B ALL. We aimed to decrease T‐ALL relapses by intensifying our regimen. Methods Patients with T‐ALL were treated using two different regimens; before September 2014, patients were treated per St. Jude Total XV protocol; subsequently, a major change was adopted by adding two intensive blocks: FLAG and Reintensification. Cranial radiation was limited to patients with WBC ≥ 100 k/μl at diagnosis and/or patients with CNS2/CNS3 status. Results Between June 2005 and April 2020, a total of 100 patients (76 males) were treated and followed up for a median of 70 months (range 14–181). Median age at diagnosis was 9 years (range 0.5–17.8). Forty‐eight patients were diagnosed after September 2014 and received the augmented regimen; their median follow up was 46 months (range 14–74). The 5‐year‐EFS estimates for patients who received the augmented regimen versus standard regimen were 87% ± 4.9% versus 67% ± 6.8% (p = .03); and the 5‐year‐OS estimates were 87% ± 5.1% versus 71% ± 6.3% (p = .06), respectively. Treatment related mortality (TRM) was reported in two patients treated per standard regimen but none for patients who received the augmented regimen. Conclusions We implemented a novel approach with early intensification added to a backbone of modified St. Jude Total‐XV regimen for patients with T‐ALL that resulted in improved outcome with no treatment related mortality.

Published
2023
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7. Burden of tracheal, bronchus, and lung cancer in North Africa and Middle East countries, 1990 to 2019: Results from the GBD study 2019

Author

Shaghayegh Khanmohammadi, Sahar Saeedi Moghaddam, Sina Azadnajafabad, Negar Rezaei, Zahra Esfahani, Nazila Rezaei, GBD 2019 NAME Tracheal, Bronchus and Lung Cancer Collaborators, Mohsen Naghavi, Bagher Larijani, Farshad Farzadfar, Mohsen Abbasi-Kangevari, Zeinab Abbasi-Kangevari, Meriem Abdoun, Zahra Abrehdari-Tafreshi, Ahmed Abu-Zaid, Aqeel Ahmad, Sepideh Ahmadi, Hanadi Al Hamad, Rumailah Hospital, Saleh Ali Alessy, Syed Mohamed Aljunid, Mehrdad Amir-Behghadami, Alireza Ansari-Moghaddam, Jalal Arabloo, Mohammadreza Azangou-Khyavy, Nayereh Baghcheghi, Khuloud Bajbouj, Ali Bijani, Mariah Malak Bilalaga, Souad Bouaoud, Daniela Calina, William C S Cho, Omar B Da’ar, Shirin Djalalinia, Hesham Elghazaly, Muhammed Elhadi, Rana Ezzeddini, Alireza Feizkhah, Ahmad Ghashghaee, Mohamad Golitaleb, Atlas Haddadi Avval, Nima Hafezi-Nejad, Randah R Hamadeh, Mahsa Jalili, Elham Jamshidi, Amirali Karimi, Yousef Saleh Khader, Javad Khanali, Farzad Kompani, Hamid Reza Koohestani, Burcu Kucuk Bicer, Ahmad R Mafi, Ata Mahmoodpoor, Mohammad-Reza Malekpour, Ahmad Azam Malik, Reza Mirfakhraie, Esmaeil Mohammadi, Sara Momtazmanesh, Rahmatollah Moradzadeh, Paula Moraga, Zuhair S Natto, Maryam Noori, Simone Perna, Raffaele Pezzani, AIROB (Associazione Italiana Ricerca Oncologica di Base), Majid Pirestani, Ashkan Pourabhari Langroudi, Mohammad Rabiee, Navid Rabiee, Shayan Rahmani, Elrashdy Moustafa Mohamed Redwan, Nima Rezaei, Gholamreza Roshandel, Erfan Sadeghi, Amir Salek Farrokhi, Abdallah M Samy, Brijesh Sathian, Saeed Shahabi, Javad Sharifi-Rad, Sara Sheikhbahaei, Zahra Shokri Varniab, Seyed Afshin Shorofi, Moslem Taheri Soodejani, Abdelghani Tbakhi, Arash Tehrani-Banihashemi, Sahel Valadan Tahbaz, Seyed Hossein Yahyazadeh Jabbari, Zabihollah Yousefi, Maryam Zamanian, Iman Zare, Armin Zarrintan, and Mohammad Zoladl

Subjects
tracheal cancer, bronchus cancer, lung neoplasms, global burden of disease, attributable risks, tobacco use, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

ObjectiveTo provide estimates on the regional and national burden of tracheal, bronchus, and lung (TBL) cancer and its attributable risk factors from 1990 to 2019 in the North Africa and Middle East (NAME) region.Methods and materialsThe Global Burden of Disease (GBD) 2019 data were used. Disability-adjusted life years (DALYs), death, incidence, and prevalence rates were categorized by sex and age groups in the NAME region, in 21 countries, from 1990 to 2019. Decomposition analysis was performed to calculate the proportion of responsible factors in the emergence of new cases. Data are presented as point estimates with their 95% uncertainty intervals (UIs).ResultsIn the NAME region, TBL cancer caused 15,396 and 57,114 deaths in women and men, respectively, in 2019. The age-standardized incidence rate (ASIR) increased by 0.7% (95% UI -20.6 to 24.1) and reached 16.8 per 100,000 (14.9 to 19.0) in 2019. All the age-standardized indices had a decreasing trend in men and an increasing trend in women from 1990 to 2019. Turkey (34.9 per 100,000 [27.6 to 43.5]) and Sudan (8.0 per 100,000 [5.2 to 12.5]) had the highest and lowest age-standardized prevalence rates (ASPRs) in 2019, respectively. The highest and lowest absolute slopes of change in ASPR, from 1990 to 2019, were seen in Bahrain (-50.0% (-63.6 to -31.7)) and the United Arab Emirates (-1.2% (-34.1 to 53.8)), respectively. The number of deaths attributable to risk factors was 58,816 (51,709 to 67,323) in 2019 and increased by 136.5%. Decomposition analysis showed that population growth and age structure change positively contributed to new incident cases. More than 80% of DALYs could be decreased by controlling risk factors, particularly tobacco use.ConclusionThe incidence, prevalence, and DALY rates of TBL cancer increased, and the death rate remained unchanged from 1990 to 2019. All the indices and contribution of risk factors decreased in men but increased in women. Tobacco is still the leading risk factor. Early diagnosis and tobacco cessation policies should be improved.

Published
2023
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8. Factors that predict severity of infection and seroconversion in immunocompromised children and adolescents with COVID-19 infection

Author

Mayada Abu Shanap, Maher Sughayer, Osama Alsmadi, Ismail Elzayat, Abeer Al-Nuirat, Abdelghani Tbakhi, and Iyad Sultan

Subjects
SARS-CoV-2, immunocompromised, COVID 19, cancer, children, stem cell transplant, Immunologic diseases. Allergy, RC581-607
Abstract

ObjectivesWe aimed to study the outcomes, severity, and seroconversion post SARS-CoV-2 infection in immunocompromised children and adolescents treated at our center.MethodFor this observational study, all pediatric patients who had COVID-19 infection from Sep-22-2020 to Nov-10-2021were identified by reviewing our laboratory records. Their charts were reviewed to determine clinical severity and outcome. Blood samples were drawn for anti-SARS-CoV-2 antibody assay. Serious COVID-19 infection (SVI) was defined if the patient had moderate, severe, or critical illness. A cutoff of 100 U/mL anti-SARS-CoV-2 antibodies was used to categorize low and high titer seroconversion.ResultsWe identified 263 pediatric patients with COVID-19; most (68%) were symptomatic: 5% had severe or critical infection, 25% were hospitalized, 12 required respiratory support, 12 were admitted to the ICU, and five patients (2%) died. Multivariable analysis revealed several factors that predict SVI: Age above 12 years (p=0.035), body mass index above 95th percentile (p=0.034), comorbid conditions (p=0.025), absolute neutrophil count ≤500(p=0.014) and absolute lymphocyte count ≤300 (p=0.022). Levels of anti-SARS-CoV-2 spike antibodies were obtained for 173 patients at a median of 94 days (range, 14–300) after PCR diagnosis; of them 142 (82%) patients seroconverted; the lowest seroconversion rate was observed in patients with hematological malignancies (79%). Our univariable model showed that the following factors were predictive of low titer: lower ANC, p=0.01; hematologic malignancy, p=0.023; receiving steroids in the last 14 days, p=0.032; time since last chemotherapy or immunosuppressive therapy less than 30 days, p=0.002; and being on active chemotherapy in the last 3 months prior to infection, p

Published
2022
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9. Obstacles and Considerations Related to Clinical Trial Research During the COVID-19 Pandemic

Author

Hasan Hashem, Mohammad Abufaraj, Abdelghani Tbakhi, and Iyad Sultan

Subjects
COVID-19, SARS-CoV-2, clinical research, clinical trials, ethics, misinformation, Medicine (General), R5-920
Abstract

The response to the COVID-19 pandemic from the research and science community has been vigorous, with information being released faster than that of any other event in human history. Articles related to the virus were being rapidly published by January 2020. A small fraction of these publications comprised reports of prospective clinical trials (0.25%), and many of these trials have imparted conflicting conclusions, leading to confusion among the public and the scientific community. Additionally, the pandemic has raised many serious scientific and ethical concerns related to clinical research. In this review, we divided the conduct of clinical research trials into three steps and critically reviewed each step, along with the challenges and obstacles arising amid the ongoing crisis. The clinical research steps we reviewed include (1) clinical trial design factors such as social and scientific value, feasibility, single vs. multicenter trials, randomization, control groups, endpoints, off-label and compassionate use of medications, data analysis, and verifying the integrity of data; (2) ethical issues such as committee approvals, efficiency, virtual visits and remote monitoring, informed consent, shipping investigational products, and external monitoring and audits; and (3) publication and sharing of preprints, press releases, social media, and misinformation. The COVID-19 pandemic is adversely affecting existing clinical trials for other ailments and diseases, including cancer, with most trials being delayed or deferred. Although urgency is needed to communicate effective treatment and prevention strategies for COVID-19, research efforts should maintain the same high-quality core ethical principles that governed human subject research before the pandemic. Despite the catastrophic devastation caused by the pandemic, the adoption of more flexible, cost-effective methods of conducting clinical trials (without compromising ethical conduct, safety, or data integrity, while maintaining research efficiency) represents a potential silver lining. Streamlining clinical research will help to congruently address other important health issues, despite the ongoing COVID-19 crisis.

Published
2020
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10. Quantitative Comparison of Immunohistochemical Staining Intensity in Tissues Fixed in Formalin and Histochoice

Author

D. Geoffrey Vince, Abdelghani Tbakhi, Ajeetkumar Gaddipati, Robert M. Cothren, J. Fredrick Cornhill, and Raymond R. Tubbs

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cytology, QH573-671
Abstract

Formaldehyde fixatives have traditionally been used to preserve tissues as they impart excellent morphological preservation. Formaldehyde fixes tissue by cross linking, a process which can reduce the antigenicity of tissue and weakens the intensity of immunohistochemical stains. Preliminary studies have shown that Histochoice tissue fixative offers equal or greater staining intensity than neutral buffered formalin (NBF). This study compares these fixatives quantitatively and presents the results in unambiguous statistical terms.

Published
1997
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13. Fludarabine or cyclophosphamide in combination with total body irradiation as myeloablative conditioning prior to allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia: an analysis by the Acute Leukemia Working Party of the EBMT

Author

Sebastian Giebel, Myriam Labopin, Gerard Socié, Mahmoud Aljurf, Urpu Salmenniemi, Hélène Labussière-Wallet, Micha Srour, Nicolaus Kröger, Mohsen Al Zahrani, Bruno Lioure, Péter Reményi, Mutlu Arat, Jean Henri Bourhis, Grzegorz Helbig, Abdelghani Tbakhi, Edouard Forcade, Anne Huynh, Eolia Brissot, Alexandros Spirydonidis, Bipin N. Savani, Zinaida Peric, Arnon Nagler, and Mohamad Mohty

Subjects
Transplantation, Hematology
Published
2023
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15. Global, regional, and national burden of colorectal cancer and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Author

Rajesh Sharma, Mohsen Abbasi-Kangevari, Rami Abd-Rabu, Hassan Abidi, Eman Abu-Gharbieh, Juan Manuel Acuna, Sangeet Adhikari, Shailesh M Advani, Muhammad Sohail Afzal, Mohamad Aghaie Meybodi, Bright Opoku Ahinkorah, Sajjad Ahmad, Ali Ahmadi, Sepideh Ahmadi, Haroon Ahmed, Luai A Ahmed, Muktar Beshir Ahmed, Hanadi Al Hamad, Fares Alahdab, Fahad Mashhour Alanezi, Turki M Alanzi, Fadwa Alhalaiqa Naji Alhalaiqa, Yousef Alimohamadi, Vahid Alipour, Syed Mohamed Aljunid, Motasem Alkhayyat, Sami Almustanyir, Rajaa M Al-Raddadi, Saba Alvand, Nelson Alvis-Guzman, Saeed Amini, Robert Ancuceanu, Amir Anoushiravani, Ali Arash Anoushirvani, Alireza Ansari-Moghaddam, Jalal Arabloo, Armin Aryannejad, Mohammad Asghari Jafarabadi, Seyyed Shamsadin Athari, Floriane Ausloos, Marcel Ausloos, Atalel Fentahun Awedew, Mamaru Ayenew Awoke, Tegegn Mulatu Ayana, Sina Azadnajafabad, Hiva Azami, Mohammadreza Azangou-Khyavy, Amirhossein Azari Jafari, Ashish D Badiye, Sara Bagherieh, Saeed Bahadory, Atif Amin Baig, Jennifer L Baker, Maciej Banach, Amadou Barrow, Alemshet Yirga Berhie, Sima Besharat, Devidas S Bhagat, Akshaya Srikanth Bhagavathula, Neeraj Bhala, Krittika Bhattacharyya, Vijayalakshmi S Bhojaraja, Sadia Bibi, Ali Bijani, Antonio Biondi, Tone Bjørge, Belay Boda Abule Bodicha, Dejana Braithwaite, Hermann Brenner, Daniela Calina, Chao Cao, Yin Cao, Giulia Carreras, Felix Carvalho, Ester Cerin, Raja Chandra Chakinala, William C S Cho, Dinh-Toi Chu, Joao Conde, Vera Marisa Costa, Natália Cruz-Martins, Omid Dadras, Xiaochen Dai, Lalit Dandona, Rakhi Dandona, Anna Danielewicz, Feleke Mekonnen Demeke, Getu Debalkie Demissie, Rupak Desai, Deepak Dhamnetiya, Mostafa Dianatinasab, Daniel Diaz, Mojtaba Didehdar, Saeid Doaei, Linh Phuong Doan, Milad Dodangeh, Fatemeh Eghbalian, Debela Debela Ejeta, Michael Ekholuenetale, Temitope Cyrus Ekundayo, Iman El Sayed, Muhammed Elhadi, Daniel Berhanie Enyew, Tahir Eyayu, Rana Ezzeddini, Ildar Ravisovich Fakhradiyev, Umar Farooque, Hossein Farrokhpour, Farshad Farzadfar, Ali Fatehizadeh, Hamed Fattahi, Nima Fattahi, Masood Fereidoonnezhad, Eduarda Fernandes, Getahun Fetensa, Irina Filip, Florian Fischer, Masoud Foroutan, Peter Andras Gaal, Mohamed M Gad, Silvano Gallus, Tushar Garg, Tamiru Getachew, Seyyed-Hadi Ghamari, Ahmad Ghashghaee, Nermin Ghith, Maryam Gholamalizadeh, Jamshid Gholizadeh Navashenaq, Abraham Tamirat Gizaw, James C Glasbey, Mahaveer Golechha, Pouya Goleij, Kebebe Bekele Gonfa, Giuseppe Gorini, Avirup Guha, Sapna Gupta, Veer Bala Gupta, Vivek Kumar Gupta, Rasool Haddadi, Nima Hafezi-Nejad, Arvin Haj-Mirzaian, Rabih Halwani, Shafiul Haque, Sanam Hariri, Ahmed I Hasaballah, Soheil Hassanipour, Simon I Hay, Claudiu Herteliu, Ramesh Holla, Mohammad-Salar Hosseini, Mehdi Hosseinzadeh, Mihaela Hostiuc, Mowafa Househ, Junjie Huang, Ayesha Humayun, Ivo Iavicoli, Olayinka Stephen Ilesanmi, Irena M Ilic, Milena D Ilic, Farhad Islami, Masao Iwagami, Mohammad Ali Jahani, Mihajlo Jakovljevic, Tahereh Javaheri, Ranil Jayawardena, Rime Jebai, Ravi Prakash Jha, Tamas Joo, Nitin Joseph, Farahnaz Joukar, Jacek Jerzy Jozwiak, Ali Kabir, Rohollah Kalhor, Ashwin Kamath, Neeti Kapoor, Ibraheem M Karaye, Amirali Karimi, Joonas H Kauppila, Asma Kazemi, Mohammad Keykhaei, Yousef Saleh Khader, Himanshu Khajuria, Rovshan Khalilov, Javad Khanali, Maryam Khayamzadeh, Mahmoud Khodadost, Hanna Kim, Min Seo Kim, Adnan Kisa, Sezer Kisa, Ali-Asghar Kolahi, Hamid Reza Koohestani, Jacek A Kopec, Rajasekaran Koteeswaran, Ai Koyanagi, Yuvaraj Krishnamoorthy, G Anil Kumar, Manoj Kumar, Vivek Kumar, Carlo La Vecchia, Faris Hasan Lami, Iván Landires, Caterina Ledda, Sang-woong Lee, Wei-Chen Lee, Yeong Yeh Lee, Elvynna Leong, Bingyu Li, Stephen S Lim, Stany W Lobo, Joana A Loureiro, Raimundas Lunevicius, Farzan Madadizadeh, Ata Mahmoodpoor, Azeem Majeed, Mohammad-Reza Malekpour, Reza Malekzadeh, Ahmad Azam Malik, Fariborz Mansour-Ghanaei, Lorenzo Giovanni Mantovani, Miquel Martorell, Sahar Masoudi, Prashant Mathur, Jitendra Kumar Meena, Entezar Mehrabi Nasab, Walter Mendoza, Alexios-Fotios A Mentis, Tomislav Mestrovic, Junmei Miao Jonasson, Bartosz Miazgowski, Tomasz Miazgowski, Gelana Fekadu Worku Mijena, Seyyedmohammadsadeq Mirmoeeni, Mohammad Mirza-Aghazadeh-Attari, Hamed Mirzaei, Sanjeev Misra, Karzan Abdulmuhsin Mohammad, Esmaeil Mohammadi, Saeed Mohammadi, Seyyede Momeneh Mohammadi, Abdollah Mohammadian-Hafshejani, Shafiu Mohammed, Teroj Abdulrahman Mohammed, Nagabhishek Moka, Ali H Mokdad, Zeinab Mokhtari, Mariam Molokhia, Sara Momtazmanesh, Lorenzo Monasta, Ghobad Moradi, Rahmatollah Moradzadeh, Paula Moraga, Joana Morgado-da-Costa, Sumaira Mubarik, Francesk Mulita, Mohsen Naghavi, Mukhammad David Naimzada, Hae Sung Nam, Zuhair S Natto, Biswa Prakash Nayak, Javad Nazari, Ehsan Nazemalhosseini-Mojarad, Ionut Negoi, Cuong Tat Nguyen, Son Hoang Nguyen, Nurulamin M Noor, Maryam Noori, Seyyed Mohammad Ali Noori, Virginia Nuñez-Samudio, Chimezie Igwegbe Nzoputam, Bogdan Oancea, Oluwakemi Ololade Odukoya, Ayodipupo Sikiru Oguntade, Hassan Okati-Aliabad, Andrew T Olagunju, Tinuke O Olagunju, Sokking Ong, Samuel M Ostroff, Alicia Padron-Monedero, Reza Pakzad, Adrian Pana, Anamika Pandey, Fatemeh Pashazadeh Kan, Urvish K Patel, Uttam Paudel, Renato B Pereira, Navaraj Perumalsamy, Richard G Pestell, Zahra Zahid Piracha, Richard Charles G Pollok, Akram Pourshams, Naeimeh Pourtaheri, Akila Prashant, Mohammad Rabiee, Navid Rabiee, Amir Radfar, Sima Rafiei, Mosiur Rahman, Amir Masoud Rahmani, Vahid Rahmanian, Nazanin Rajai, Aashish Rajesh, Vajiheh Ramezani-Doroh, Kiana Ramezanzadeh, Kamal Ranabhat, Sina Rashedi, Amirfarzan Rashidi, Mahsa Rashidi, Mohammad-Mahdi Rashidi, Mandana Rastegar, David Laith Rawaf, Salman Rawaf, Reza Rawassizadeh, Mohammad Sadegh Razeghinia, Andre M N Renzaho, Negar Rezaei, Nima Rezaei, Saeid Rezaei, Mohsen Rezaeian, Sahba Rezazadeh-Khadem, Gholamreza Roshandel, Maha Mohamed Saber-Ayad, Bahar Saberzadeh-Ardestani, Basema Saddik, Hossein Sadeghi, Umar Saeed, 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H., Yang, L., Yazdanpanah, F., Yu, C., Yuce, D., Yunusa, I., Zadnik, V., Zahir, M., Zare, I., Zhang, Z. -J., Zoladl, M., Epidemiologie, RS: NUTRIM - R3 - Respiratory & Age-related Health, and Bill & Melinda Gates Foundation

Subjects
Adult, MED/42 - IGIENE GENERALE E APPLICATA, IMPACT, colorectal cancer, Colorectal Neoplasm, GBD 2019 Colorectal Cancer Collaborators, HEREDITARY, Global Burden of Disease, Cancer screening, DISPARITIES, SDG 3 - Good Health and Well-being, Cancer treatment strategies, Risk Factors, Quality-Adjusted Life Year, COLON, Global studies, DALY, GBD, colorectal cancer, risk factors, Humans, Global Burden of Disease Study, Early Detection of Cancer, Hepatology, MORTALITY, Gastroenterology, Cancer incidence rates, Middle Aged, Cancer burden, SURVIVAL, SEX, GENDER, Quality-Adjusted Life Years, Colorectal Neoplasms, Human
Abstract

Correction to Lancet Gastroenterol Hepatol 2022; 7: 627-47. Lancet Gastroenterol Hepatol. 2022 Aug;7(8):704. doi: 10.1016/S2468-1253(22)00210-2. PMID: 35809605. Background: Colorectal cancer is the third leading cause of cancer deaths worldwide. Given the recent increasing trends in colorectal cancer incidence globally, up-to-date information on the colorectal cancer burden could guide screening, early detection, and treatment strategies, and help effectively allocate resources. We examined the temporal patterns of the global, regional, and national burden of colorectal cancer and its risk factors in 204 countries and territories across the past three decades. Methods: Estimates of incidence, mortality, and disability-adjusted life years (DALYs) for colorectal cancer were generated as a part of the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019 by age, sex, and geographical location for the period 1990-2019. Mortality estimates were produced using the cause of death ensemble model. We also calculated DALYs attributable to risk factors that had evidence of causation with colorectal cancer. Findings: Globally, between 1990 and 2019, colorectal cancer incident cases more than doubled, from 842 098 (95% uncertainty interval [UI] 810 408-868 574) to 2·17 million (2·00-2·34), and deaths increased from 518 126 (493 682-537 877) to 1·09 million (1·02-1·15). The global age-standardised incidence rate increased from 22·2 (95% UI 21·3-23·0) per 100 000 to 26·7 (24·6-28·9) per 100 000, whereas the age-standardised mortality rate decreased from 14·3 (13·5-14·9) per 100 000 to 13·7 (12·6-14·5) per 100 000 and the age-standardised DALY rate decreased from 308·5 (294·7-320·7) per 100 000 to 295·5 (275·2-313·0) per 100 000 from 1990 through 2019. Taiwan (province of China; 62·0 [48·9-80·0] per 100 000), Monaco (60·7 [48·5-73·6] per 100 000), and Andorra (56·6 [42·8-71·9] per 100 000) had the highest age-standardised incidence rates, while Greenland (31·4 [26·0-37·1] per 100 000), Brunei (30·3 [26·6-34·1] per 100 000), and Hungary (28·6 [23·6-34·0] per 100 000) had the highest age-standardised mortality rates. From 1990 through 2019, a substantial rise in incidence rates was observed in younger adults (age

Published
2022
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16. Supplement 1 from The Wilms' Tumor Antigen Is a Novel Target for Human CD4+ Regulatory T Cells: Implications for Immunotherapy

Author

Said Dermime, Mahmoud Aljurf, Abdelghani Tbakhi, Hazza Al-Zahrani, Fahad Alsharif, Naeem Chaudhri, Fahad Almohareb, Khaled Al-Hussein, Ghofran Al Qudaihi, Abdullah Al-Sulaiman, Hazem Ghebeh, and Cynthia Lehe

Abstract

Supplement 1 from The Wilms' Tumor Antigen Is a Novel Target for Human CD4+ Regulatory T Cells: Implications for Immunotherapy

Published
2023
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17. Supplement 4 from The Wilms' Tumor Antigen Is a Novel Target for Human CD4+ Regulatory T Cells: Implications for Immunotherapy

Author

Said Dermime, Mahmoud Aljurf, Abdelghani Tbakhi, Hazza Al-Zahrani, Fahad Alsharif, Naeem Chaudhri, Fahad Almohareb, Khaled Al-Hussein, Ghofran Al Qudaihi, Abdullah Al-Sulaiman, Hazem Ghebeh, and Cynthia Lehe

Abstract

Supplement 4 from The Wilms' Tumor Antigen Is a Novel Target for Human CD4+ Regulatory T Cells: Implications for Immunotherapy

Published
2023
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18. Supplement 3 from The Wilms' Tumor Antigen Is a Novel Target for Human CD4+ Regulatory T Cells: Implications for Immunotherapy

Author

Said Dermime, Mahmoud Aljurf, Abdelghani Tbakhi, Hazza Al-Zahrani, Fahad Alsharif, Naeem Chaudhri, Fahad Almohareb, Khaled Al-Hussein, Ghofran Al Qudaihi, Abdullah Al-Sulaiman, Hazem Ghebeh, and Cynthia Lehe

Abstract

Supplement 3 from The Wilms' Tumor Antigen Is a Novel Target for Human CD4+ Regulatory T Cells: Implications for Immunotherapy

Published
2023
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19. Supplement 5 from The Wilms' Tumor Antigen Is a Novel Target for Human CD4+ Regulatory T Cells: Implications for Immunotherapy

Author

Said Dermime, Mahmoud Aljurf, Abdelghani Tbakhi, Hazza Al-Zahrani, Fahad Alsharif, Naeem Chaudhri, Fahad Almohareb, Khaled Al-Hussein, Ghofran Al Qudaihi, Abdullah Al-Sulaiman, Hazem Ghebeh, and Cynthia Lehe

Abstract

Supplement 5 from The Wilms' Tumor Antigen Is a Novel Target for Human CD4+ Regulatory T Cells: Implications for Immunotherapy

Published
2023
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20. Supplement 2 from The Wilms' Tumor Antigen Is a Novel Target for Human CD4+ Regulatory T Cells: Implications for Immunotherapy

Author

Said Dermime, Mahmoud Aljurf, Abdelghani Tbakhi, Hazza Al-Zahrani, Fahad Alsharif, Naeem Chaudhri, Fahad Almohareb, Khaled Al-Hussein, Ghofran Al Qudaihi, Abdullah Al-Sulaiman, Hazem Ghebeh, and Cynthia Lehe

Abstract

Supplement 2 from The Wilms' Tumor Antigen Is a Novel Target for Human CD4+ Regulatory T Cells: Implications for Immunotherapy

Published
2023
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21. Data from The Wilms' Tumor Antigen Is a Novel Target for Human CD4+ Regulatory T Cells: Implications for Immunotherapy

Author

Said Dermime, Mahmoud Aljurf, Abdelghani Tbakhi, Hazza Al-Zahrani, Fahad Alsharif, Naeem Chaudhri, Fahad Almohareb, Khaled Al-Hussein, Ghofran Al Qudaihi, Abdullah Al-Sulaiman, Hazem Ghebeh, and Cynthia Lehe

Abstract

Compelling evidences indicate a key role for regulatory T cells (Treg) on the host response to cancer. The Wilms' tumor antigen (WT1) is overexpressed in several human leukemias and thus considered as promising target for development of leukemia vaccine. However, recent studies indicated that the generation of effective WT1-specific cytotoxic T cells can be largely affected by the presence of Tregs. We have generated T-cell lines and clones that specifically recognized a WT1-84 (RYFKLSHLQMHSRKH) peptide in an HLA-DRB1*0402–restricted manner. Importantly, they recognized HLA-DRB1*04–matched fresh leukemic cells expressing the WT1 antigen. These clones exerted a T helper 2 cytokine profile, had a CD4+CD25+Foxp3+GITR+CD127− Treg phenotype, and significantly inhibited the proliferative activity of allogeneic T cells independently of cell contact. Priming of alloreactive T cells in the presence of Tregs strongly inhibited the expansion of natural killer (NK), NK T, and CD8+ T cells and had an inhibitory effect on NK/NK T cytotoxic activity but not on CD8+ T cells. Furthermore, priming of T cells with the WT1-126 HLA-A0201–restricted peptide in the presence of Tregs strongly inhibited the induction of anti–WT1-126 CD8+ CTL responses as evidenced by both very low cytotoxic activity and IFN-γ production. Moreover, these Treg clones specifically produced granzyme B and selectively induced apoptosis in WT1-84–pulsed autologous antigen-presenting cells but not in apoptotic-resistant DR4-matched leukemic cells. Importantly, we have also detected anti–WT1-84 interleukin-5+/granzyme B+/Foxp3+ CD4+ Tregs in five of eight HLA-DR4+ acute myeloid leukemia patients. Collectively, our in vitro and in vivo findings strongly suggest important implications for the clinical manipulation of Tregs in cancer patients. [Cancer Res 2008;68(15):6350–9]

Published
2023
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22. PIK3CA Mutational Profiling in a Patient Cohort with HR+/HER2- Advanced Metastatic Breast Cancer at a Tertiary Cancer Center

Author

OSAMA ALSMADI, Hikmat Abdel-Razeq, Yazan Talab, Hazem Abdulelah, Zeena Shaheen, and Abdelghani Tbakhi

Abstract

Common PIK3CA gene activating mutations can be found in 20–30% of all breast cancer cases, and regarded as predictive markers for therapeutic response to PI3K inhibitors. The therascreen PIK3CA mutation companion assay and the alpha-specific PI3K inhibitor, Alpelisib, are FDA-approved for selecting and treating patients with advanced PIK3CA-mutated metastatic breast cancer. The main objective behind this report was to investigate the composition and proportion of PIK3CA mutations using a PIK3CA mutation Therascreen RT-PCR assay, in a patient cohort with receptor-positive/HER2-negative (HR+/HER2) metastatic breast cancer, who were diagnosed and treated at King Hussein Cancer Center (KHCC). Patients with PIK3CA-mutated tumors represented 39.4% (91/231) of all patients. Four PIK3CA mutations comprised 86.8% of all PIK3CA mutations; mainly H1047R (33.3%), E545K (20.9%), E542K (24.2%), and H1047L (8.8%). The four main mutations map to the helical and kinase domains of the PIK3CA encoded protein. C420R was found in only one patient, and E545A was found in two patients. Nine of the 91 mutated patients had shown double PIK3CA mutations (9.9%). In conclusion, PIK3CA is frequently mutated in multiple types of cancers at known ‘Hot-spots’, mainly in the kinase and helical modular domains, which was found consistent with our findings. PIK3CA mutational signature in our metastatic breast cancer cohort varied with a 39.4% (91/231) positivity rate. The PIK3CA mutational screening panel did not capture mutations in the remaining 140 (60.6%) cases; these patients may be mutated in other genes related to breast cancer, or in PIK3CA loci not covered by the Therascreen assay. Survival and clinical outcomes in association with PIK3CA mutational profiles shall be addressed in a follow-up investigation for this patients’ cohort.

Published
2023
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23. HLA-Haploidentical Stem Cell Transplantation in Children with Inherited Bone Marrow Failure Syndromes: A Retrospective Analysis on Behalf of EBMT Severe Aplastic Anemia Working Party

Author

Stefano Giardino, Dirk-Jan Eikema, Brian Piepenbroek, Mattia Algeri, Mouhab Ayas, Maura Faraci, Abdelghani Tbakhi, Marco Zecca, Mohammed Essa, Bénédicte Neven, Yves Bertrand, Gaurav Kharya, Tatiana A Bykova, Sarah Lawson, Mario Petrini, Alexander Mohseny, Fanny Rialland, Beki James, Anca Colita, Mony Fahd, Simone Cesaro, Ansgar Schulz, Carlo Dufour, Antonio Risitano, and Régis Peffault de Latour

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022
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24. Specific Cytogenetic Abnormalities at Diagnosis Predict Survival after Hematopoietic Cell Transplant in Poor-Risk Pediatric Acute Myeloid Leukemia: A PDWP/EBMT Study

Author

Akshay Sharma, Jacques-Emmanuel Galimard, Angharad Pryce, Senthil Bhoopalan, Arnaud Dalissier, Jean-Hugues Dalle, Franco Locatelli, Charlotte Jubert, Oana Mirci-Danicar, Vassiliki Kitra-Roussou, Yves Bertrand, Franca Fagioli, Fanny Rialland, Alessandra Biffi, Robert F Wynn, Gerard Michel, Francesco Paolo P Tambaro, Ali Abdallah Ahmari, Abdelghani Tbakhi, Caroline Furness, Miguel Ángel Díaz Pérez, Petr Sedlacek, Ivana Bodova, Maura Faraci, Kanchan Rao, Marie Thérèse Rubio, Brenda Gibson, Neel S. Bhatt, and Selim Corbacioglu

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022
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25. Outcome of Haematopoietic Cell Transplantation in 813 Children with Fanconi Anaemia: A Study on Behalf of the EBMT Severe Aplastic Anaemia Working Party and Paediatric Disease Working Party

Author

Su Han Lum, Sujith Samarasinghe, Dirk-Jan Eikema, Brian Piepenbroek, Arnaud Dalissier, Mouhab Ayas, Ashrafsadat Mousavi, Rose-Marie Hamladji, Akif Yesilipek, Jean-Hugues Dalle, Savas Kansoy, Franco Locatelli, Duygu Çetinkaya, Marc Bierings, O. Alphan Kupesiz, Abdelghani Tbakhi, Elena Skorobogatova, Gülyüz Öztürk, Maura Faraci, Yves Bertrand, Pamela Evans, Selim Carbacioglu, Carlo Dufour, Antonio Risitano, Robert F Wynn, and Régis Peffault de Latour

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022
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26. Allogeneic hematopoietic cell transplantation for myelodysplastic syndrome unclassifiable – a retrospective study on behalf of the Chronic Malignancies Working Party of the EBMT

Author

Joanna Drozd-Sokolowska, Luuk Gras, Nienke Zinger, Mohsen Al Zahrani, Jakob Passweg, Jenny Byrne, Aloysius Ho, Xiao-jun Huang, Nicolaus Kröger, Jiri Mayer, Domenico Russo, Ann De Becker, Abdelghani Tbakhi, Aspasia Stamatoullas, Thomas Valerius, Patrick Hayden, Donal P. McLornan, Francesco Onida, Christof Scheid, Marie Robin, Ibrahim Yakoub-Agha, Hematology, and Faculty of Medicine and Pharmacy

Subjects
Transplantation, myelodysplastic syndrome unclassifiable, Hematology, Allogeneic hematopoietic cell transplantation
Published
2023
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27. ERAMER: A Novel In silico Tool for Prediction of ERAP1 Enzyme Trimming

Author

Anas Al-okaily, Razan Abu Khashabeh, Osama Alsmadi, Yazan Ahmad, Iyad Sultan, Ion Mandoiu, Abdelghani Tbakhi, and Pramod Srivast

Abstract

Somatic mutations in tumors can generate neoantigens that are presented on the cell surface through MHC molecules. As these mutations are expected to be unique to each tumor and as these generated (and presented) neoantigens play a significant role in mediating immune response against the tumor through tumor-specific T-cells, personalized cancer immunotherapy for each tumor can be designed, formed, and effective in curing cancer. MHC class I pathway consists of four main steps: proteasomal cleavage in the cytosol in which proteins are cleaved into smaller peptides, precursors are then transported into the endoplasmic reticulum by the transporter associated with antigen processing (TAP), next further processing (trimming) at the N-terminal region is undertaken by an ER resident aminopeptidases 1 (ERAP1) enzyme to generate optimal lengths (8-10 amino acids) to produce a stable MHCI: peptide association, and finally the trimmed precursors are loaded into MHCI molecule to be transited via the Golgi apparatus to the cell surface for presentation to the cellualar immune system. Several studies reported specificities related to the ERAP1 trimming process and yet there is no in silico tool for the prediction of the trimming process of the ERAP1 enzyme. In this paper, we provide and implement a prediction model for the trimming process of the ERAP1 enzyme.

Published
2023
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28. BRAF V600E mutation in papillary thyroid carcinoma: it’s relation to clinical features and oncologic outcomes in a single cancer centre experience

Author

Awad Jarrar, Enas Younis, Rafal Iskanderian, Tawfiq Al-Shobaki, Abdelghani Tbakhi, Mahmoud Al-Masri, Hussam Haddad, Hani Al-Najjar, Niveen Abdallah, Zeinab Obeid, and Mohammad AlMasri

Subjects
medicine.medical_specialty, Poor prognosis, endocrine system diseases, Endocrinology, Diabetes and Metabolism, neoplasms, Gastroenterology, Diseases of the endocrine glands. Clinical endocrinology, Thyroid carcinoma, Middle East, Endocrinology, papillary, Internal medicine, Cancer centre, Internal Medicine, medicine, thyroid cancer, Thyroid cancer, business.industry, Research, Cancer, medicine.disease, RC648-665, BRAF V600E, Cohort, Mutation (genetic algorithm), mutation, business
Abstract

Purpose This study focuses on the oncologic influence of BRAF V600E mutations in a cohort of Middle Eastern papillary thyroid carcinoma (PTC) patients treated at a single centre. We tested the association of BRAF V600E mutation with papillary thyroid carcinoma at King Hussein Cancer Center. Methods Patients with histologically confirmed PTC who underwent surgical treatment between 2006 and 2015 were included in this study. Oncological outcomes, both short- and long-termed, were collected. Results A total of 128 patients (68% females) were included in this study with a mean age of 38 years (±13.8). The median follow-up period was 50 months. The BRAF V600E mutation was found in 71% of patients. The tumour size for patients with a negative BRAF V600E mutation was significantly larger in comparison to patients who tested positive for the mutation (3.47 cm vs 2.31 cm, respectively, P = 0.009). The two groups showed similar disease-free survival (DFS) rates; positive = 75% (median 43 months (0–168)) compared to 78% for the negative BRAF V600E mutation (median 38 months (3–142)) (P = 0.162, HR = 0.731) Furthermore, both groups showed similar overall survival rates, positive = 94.5% (median 56 months (0–228)) compared to 94.6% for the negative BRAF V600E mutation (median 43 months (3–157)) (P = 0.941, HR = 0.940). Conclusion BRAF V600E mutation had no effect on loco-regional recurrence, distant metastasis, overall survival, or DFS. These findings may be attributed to geographic variations or reflect that BRAF V600E may only serve as an indicator of poor prognosis in high-risk group as such.

Published
2021

29. The O

Author

Samer, Salah, Walid, Naser, Omar, Jaber, Yacob, Saleh, Rawan, Mustafa, Ramiz, Abuhijlih, Fawzi, Abuhijla, Taleb, Ismaeel, Sameer, Yaser, Iyad, Sultan, Nour, Mustafa, and Abdelghani, Tbakhi

Abstract

There remains an unmet need to identify molecular biomarkers in Ewing sarcoma (ES). We sought to assess the influence of the OData of advanced ES patients, treated with IT were retrospectively collected. Patients were required to have progression after prior VDC-IE.A total of 20 ES patients underwent

Published
2022

30. Impact of RB1 gene mutation type in retinoblastoma patients on clinical presentation and management outcome

Author

Ibrahim Al-Nawaiseh, Imad Jaradat, Mohammad Mosallam, Reem AlJabari, Abdelghani Tbakhi, Ala Saab, Iyad Sultan, Maysa Al-Hussaini, Mustafa Mehyar, Mona Mohammad, Yacoub A. Yousef, and Rasha Deebajah

Subjects
Oncology, Male, medicine.medical_specialty, Adolescent, Germline, Ubiquitin-Protein Ligases, Nonsense mutation, medicine.disease_cause, Malignancy, lcsh:RC254-282, Frameshift mutation, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Internal medicine, medicine, Humans, Child, Germ-Line Mutation, Sanger sequencing, RB1 gene, Mutation, Retinoblastoma, business.industry, lcsh:RC633-647.5, Eye Neoplasms, Hematology, General Medicine, lcsh:Diseases of the blood and blood-forming organs, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Stop codon, eye diseases, Retinoblastoma Binding Proteins, 030220 oncology & carcinogenesis, Child, Preschool, symbols, Female, business, 030215 immunology
Abstract

Objective/background Retinoblastoma (RB), the most common intraocular malignancy in children, is caused by biallelic inactivation of the human retinoblastoma susceptibility gene (RB1). We are evaluating the impact of the type of RB1 gene mutation on clinical presentation and management outcome. Methods A retrospective case series of 50 patients with RB. Main outcomes were clinical and pathologic features and types of RB1 gene mutations detected using quantitative multiplex polymerase chain reaction (PCR), allele-specific PCR, next-generation sequencing analysis, and Sanger sequencing. Results Twenty (40%) patients had unilateral RB and 30 (60%) had bilateral RB. Overall, 36 (72%) patients had germline disease, 17 (47%) of whom inherited the disease. Of these 17 inherited cases, paternal origin of the RB1 mutation was seen in 15 (88%). The overall eye salvage rate was 74% (n = 49/66; 100% for Groups A + B + C, and 79% for Group D eyes). The most frequent type of mutation was a nonsense mutation generating a stop codon (15/36, 42%). Other mutations that result in a premature stop codon due to deletions or insertions with donor splice site or receptor splice site mutations were detected in 7/36 (19%), 10/36 (28%), and 2/26 (6%) patients, respectively. The remaining two (6%) patients had frameshift mutation. Patients with deletion, acceptor splice site, and frameshift mutations presented with more advanced ICRB (International Classification of Retinoblastoma) stage (75% diagnosed with Group D or E), even though there was no significant difference in eye salvage rate or tumor invasiveness between patients with different types of mutations. Conclusion Despite the heterogeneous nature of RB1 gene mutations, tumor stage remains the most important predictive factor for clinical presentation and outcome. Furthermore, acceptor splice site and frameshift mutations are associated with more advanced tumor stage at diagnosis.

Published
2020

31. Prognostic impact of Epstein-Barr virus serostatus in patients with nonmalignant hematological disorders undergoing allogeneic hematopoietic cell transplantation: the study of Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation

Author

Jan Styczynski, Gloria Tridello, Lidia Gil, Per Ljungman, Malgorzata Mikulska, Steffie van der Werf, Nina Simone Knelange, Diana Averbuch, Gerard Socié, Hendrik Veelken, Jean-Hugues Dalle, Mahmoud Aljurf, Alphan Kupesiz, Yves Bertrand, Abdelghani Tbakhi, Boris Afanasyev, Bruno Lioure, Hélène Labussière-Wallet, Xavier Poiré, Johan Maertens, Eefke Petersen, Patrice Chevallier, Noel Milpied, John A. Snowden, Ibrahim Yakoub-Agha, Jan Cornelissen, Nicolaas Schaap, Carlo Dufour, Regis Peffault de Latour, Arjan Lankester, and Simone Cesaro

Subjects
Oncology, medicine.medical_specialty, Acute leukemia, business.industry, Incidence (epidemiology), Bone marrow failure, Hematology, Disease, medicine.disease, Lymphoma, Transplantation, 03 medical and health sciences, 0302 clinical medicine, Graft-versus-host disease, hemic and lymphatic diseases, 030220 oncology & carcinogenesis, Internal medicine, medicine, Serostatus, business, 030215 immunology
Abstract

BackgroundIn patients with acute leukemia, lymphoma and chronic malignancies, donor and/or recipient Epstein-Barr virus (EBV) seropositive status increases the risk of development of chronic graft-versus-host disease (cGVHD) after allo-hematopoietic cell transplantation (allo-HCT), while it has no influence on other transplant outcomes. No data are available on the impact of EBV serostatus on transplant outcomes in patients with nonmalignant hematological disorders.ObjectiveWe analyzed the influence of the recipient's (R) and donor's (D) EBV serostatus on transplant outcomes (overall survival (OS); relapse-free survival (RFS); relapse incidence (RI); nonrelapse mortality (NRM); acute graft-versus-host disease (aGVHD); cGVHD) in patients with nonmalignant hematological disorders undergoing allo-HCT.Patients and MethodsA total of 2,355 allo-HCTs performed between 1997 and 2016 for acquired bone marrow failure or hemoglobinopathies were included in this retrospective Registry megafile Infectious Diseases Working Party of the European Society of Blood and Marrow Transplantation (IDWP-EBMT) study.ResultsDemographics: The median age of recipient was 17.7 years (range: 0–77), and 50.8% were children. 79.0% of recipients and 75.4% of donors were EBV-seropositive. 67.8% had HCT from a matched family donor, 4.6% from a mismatched family donor, and 27.6% from an unrelated donor (UD). T-cell depletion was performed in vivo and ex vivo in 82.2% and 6.6% of patients, respectively. Conditioning regimen was myeloablative in 63.7% and reduced intensity conditioning (RIC) in 36.3% of patients. The median follow-up was 4.7 years. Transplant outcomes: EBV-seropositive recipients in comparison with EBV-seronegative recipients had lower OS (85.4% vs. 88.4%, p = 0.035) and higher NRM (10.0% vs. 6.4%, p = 0.018). No other significant differences were found for: RI, RFS, and aGVHD or cGVHD with respect to EBV pretransplant serostatus donor and/or recipient. Multivariate analysis: A trend toward higher risk of development of cGVHD (HR = 1.31; p = 0.081) and better survival (HR = 0.78; p = 0.087) in allo-HCT from EBV-seropositive donors was found. Allo-HCT in EBV-seropositive recipients had a trend toward lower risk of development of cGVHD (HR = 0.75; p = 0.065). When four subgroups (R−/D−, R−/D+, R+/D−, R+/D+ EBV serology) were analyzed, the EBV serostatus had no significant impact on OS, RFS, RI, NRM and development of aGVHD or cGVHD.ConclusionsAllo-HCT from EBV-seropositive versus EBV-seronegative donors are at 31% higher risk of cGVHD in patients with nonmalignant hematological disorders undergoing allo-HCT; however this difference is nonsignificant in multivariate analysis.

Published
2020
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32. Global, regional, and national burden of colorectal cancer and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Author

Sharma, R, Abbasi-Kangevari, M, Abd-Rabu, R, Abidi, H, Abu-Gharbieh, E, Manuel Acuna, J, Adhikari, S, M Advani, S, Sohail Afzal, M, Aghaie Meybodi, M, Opoku Ahinkorah, B, Ahmad, S, Ahmadi, A, Ahmadi, S, Ahmed, H, A Ahmed, L, Beshir Ahmed, M, Al Hamad, H, Alahdab, F, Mashhour Alanezi, F, M Alanzi, T, Alhalaiqa Naji Alhalaiqa, F, Alimohamadi, Y, Alipour, V, Mohamed Aljunid, S, Alkhayyat, M, Almustanyir, S, M Al-Raddadi, R, Alvand, S, Alvis-Guzman, N, Amini, S, Ancuceanu, R, Anoushiravani, A, Arash Anoushirvani, A, Ansari-Moghaddam, A, Arabloo, J, Aryannejad, A, Asghari Jafarabadi, M, Shamsadin Athari, S, Ausloos, F, Ausloos, M, Fentahun Awedew, A, Ayenew Awoke, M, Mulatu Ayana, T, Azadnajafabad, S, Azami, H, Azangou-Khyavy, M, Azari Jafari, A, D Badiye, A, Bagherieh, S, Bahadory, S, Amin Baig, A, L Baker, J, Banach, M, Barrow, A, Yirga Berhie, A, Besharat, S, S Bhagat, D, Srikanth Bhagavathula, A, Bhala, N, Bhattacharyya, K, S Bhojaraja, V, Bibi, S, Bijani, A, Biondi, A, Bj??rge, T, Boda Abule Bodicha, B, Braithwaite, D, Brenner, H, Calina, D, Cao, C, Cao, Y, Carreras, G, Carvalho, F, Cerin, E, Chandra Chakinala, R, S Cho, W, Chu, D, Conde, J, Marisa Costa, V, Cruz-Martins, N, Dadras, O, Dai, X, Dandona, L, Dandona, R, Danielewicz, A, Mekonnen Demeke, F, Debalkie Demissie, G, Desai, R, Dhamnetiya, D, Dianatinasab, M, Diaz, D, Didehdar, M, Doaei, S, Phuong Doan, L, Dodangeh, M, Eghbalian, F, Debela Ejeta, D, Ekholuenetale, M, Cyrus Ekundayo, T, El Sayed, I, Elhadi, M, Berhanie Enyew, D, Eyayu, T, Ezzeddini, R, Ravisovich Fakhradiyev, I, Farooque, U, Farrokhpour, H, Farzadfar, F, Fatehizadeh, A, Fattahi, H, Fattahi, N, Fereidoonnezhad, M, Fernandes, E, Fetensa, G, Filip, I, Fischer, F, Foroutan, M, Andras Gaal, P, M Gad, M, Gallus, S, Garg, T, Getachew, T, Ghamari, S, Ghashghaee, A, Ghith, N, Gholamalizadeh, M, Gholizadeh Navashenaq, J, Tamirat Gizaw, A, C Glasbey, J, Golechha, M, Goleij, P, Bekele Gonfa, K, Gorini, G, Guha, A, Gupta, S, Bala Gupta, V, Kumar Gupta, V, Haddadi, R, Hafezi-Nejad, N, Haj-Mirzaian, A, Halwani, R, Haque, S, Hariri, S, I Hasaballah, A, Hassanipour, S, I Hay, S, Herteliu, C, Holla, R, Hosseini, M, Hosseinzadeh, M, Hostiuc, M, Househ, M, Huang, J, Humayun, A, Iavicoli, I, Stephen Ilesanmi, O, M Ilic, I, D Ilic, M, Islami, F, Iwagami, M, Ali Jahani, M, Jakovljevic, M, Javaheri, T, Jayawardena, R, Jebai, R, Prakash Jha, R, Joo, T, Joseph, N, Joukar, F, Jerzy Jozwiak, J, Kabir, A, Kalhor, R, Kamath, A, Kapoor, N, M Karaye, I, Karimi, A, H Kauppila, J, Kazemi, A, Keykhaei, M, Saleh Khader, Y, Khajuria, H, Khalilov, R, Khanali, J, Khayamzadeh, M, Khodadost, M, Kim, H, Seo Kim, M, Kisa, A, Kisa, S, Kolahi, A, Reza Koohestani, H, A Kopec, J, Koteeswaran, R, Koyanagi, A, Krishnamoorthy, Y, Anil Kumar, G, Kumar, M, Kumar, V, La Vecchia, C, Hasan Lami, F, Landires, I, Ledda, C, Lee, S, Lee, W, Yeh Lee, Y, Leong, E, Li, B, S Lim, S, W Lobo, S, A Loureiro, J, Lunevicius, R, Madadizadeh, F, Mahmoodpoor, A, Majeed, A, Malekpour, M, Malekzadeh, R, Azam Malik, A, Mansour-Ghanaei, F, Mantovani, L, Martorell, M, Masoudi, S, Mathur, P, Kumar Meena, J, Mehrabi Nasab, E, Mendoza, W, A Mentis, A, Mestrovic, T, Miao Jonasson, J, Miazgowski, B, Miazgowski, T, Fekadu Worku Mijena, G, Mirmoeeni, S, Mirza-Aghazadeh-Attari, M, Mirzaei, H, Misra, S, Abdulmuhsin Mohammad, K, Mohammadi, E, Mohammadi, S, Momeneh Mohammadi, S, Mohammadian-Hafshejani, A, Mohammed, S, Abdulrahman Mohammed, T, Moka, N, H Mokdad, A, Mokhtari, Z, Molokhia, M, Momtazmanesh, S, Monasta, L, Moradi, G, Moradzadeh, R, Moraga, P, Morgado-da-Costa, J, Mubarik, S, Mulita, F, Naghavi, M, David Naimzada, M, Sung Nam, H, S Natto, Z, Prakash Nayak, B, Nazari, J, Nazemalhosseini-Mojarad, E, Negoi, I, Tat Nguyen, C, Hoang Nguyen, S, M Noor, N, Noori, M, Mohammad Ali Noori, S, Nu??ez-Samudio, V, Igwegbe Nzoputam, C, Oancea, B, Ololade Odukoya, O, Sikiru Oguntade, A, Okati-Aliabad, H, T Olagunju, A, O Olagunju, T, Ong, S, M Ostroff, S, Padron-Monedero, A, Pakzad, R, Pana, A, Pandey, A, Pashazadeh Kan, F, K Patel, U, Paudel, U, B Pereira, R, Perumalsamy, N, G Pestell, R, Zahid Piracha, Z, G Pollok, R, Pourshams, A, Pourtaheri, N, Prashant, A, Rabiee, M, Rabiee, N, Radfar, A, Rafiei, S, Rahman, M, Masoud Rahmani, A, Rahmanian, V, Rajai, N, Rajesh, A, Ramezani-Doroh, V, Ramezanzadeh, K, Ranabhat, K, Rashedi, S, Rashidi, A, Rashidi, M, Rastegar, M, Laith Rawaf, D, Rawaf, S, Rawassizadeh, R, Sadegh Razeghinia, M, N Renzaho, A, Rezaei, N, Rezaei, S, Rezaeian, M, Rezazadeh-Khadem, S, Roshandel, G, Mohamed Saber-Ayad, M, Saberzadeh-Ardestani, B, Saddik, B, Sadeghi, H, Saeed, U, Sahebazzamani, M, Sahebkar, A, Salek Farrokhi, A, Salimi, A, Salimzadeh, H, Samadi, P, Samaei, M, M Samy, A, Sanabria, J, M Santric-Milicevic, M, Arif Nadeem Saqib, M, Sarveazad, A, Sathian, B, Satpathy, M, Jayce Ceola Schneider, I, ??ekerija, M, G Sepanlou, S, Seylani, A, Sha, F, Mohammad Shafiee, S, Shaghaghi, Z, Shahabi, S, Shaker, E, Sharifian, M, Sharifi-Rad, J, Sheikhbahaei, 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Biondi, Tone Bj??rge, Belay Boda Abule Bodicha, Dejana Braithwaite, Hermann Brenner, Daniela Calina, Chao Cao, Yin Cao, Giulia Carreras, Felix Carvalho, Ester Cerin, Raja Chandra Chakinala, William C S Cho, Dinh-Toi Chu, Joao Conde, Vera Marisa Costa, Nat??lia Cruz-Martins, Omid Dadras, Xiaochen Dai, Lalit Dandona, Rakhi Dandona, Anna Danielewicz, Feleke Mekonnen Demeke, Getu Debalkie Demissie, Rupak Desai, Deepak Dhamnetiya, Mostafa Dianatinasab, Daniel Diaz, Mojtaba Didehdar, Saeid Doaei, Linh Phuong Doan, Milad Dodangeh, Fatemeh Eghbalian, Debela Debela Ejeta, Michael Ekholuenetale, Temitope Cyrus Ekundayo, Iman El Sayed, Muhammed Elhadi, Daniel Berhanie Enyew, Tahir Eyayu, Rana Ezzeddini, Ildar Ravisovich Fakhradiyev, Umar Farooque, Hossein Farrokhpour, Farshad Farzadfar, Ali Fatehizadeh, Hamed Fattahi, Nima Fattahi, Masood Fereidoonnezhad, Eduarda Fernandes, Getahun Fetensa, Irina Filip, Florian Fischer, Masoud Foroutan, Peter Andras Gaal, Mohamed M Gad, Silvano Gallus, Tushar 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Jennifer L Baker, Maciej Banach, Amadou Barrow, Alemshet Yirga Berhie, Sima Besharat, Devidas S Bhagat, Akshaya Srikanth Bhagavathula, Neeraj Bhala, Krittika Bhattacharyya, Vijayalakshmi S Bhojaraja, Sadia Bibi, Ali Bijani, Antonio Biondi, Tone Bj??rge, Belay Boda Abule Bodicha, Dejana Braithwaite, Hermann Brenner, Daniela Calina, Chao Cao, Yin Cao, Giulia Carreras, Felix Carvalho, Ester Cerin, Raja Chandra Chakinala, William C S Cho, Dinh-Toi Chu, Joao Conde, Vera Marisa Costa, Nat??lia Cruz-Martins, Omid Dadras, Xiaochen Dai, Lalit Dandona, Rakhi Dandona, Anna Danielewicz, Feleke Mekonnen Demeke, Getu Debalkie Demissie, Rupak Desai, Deepak Dhamnetiya, Mostafa Dianatinasab, Daniel Diaz, Mojtaba Didehdar, Saeid Doaei, Linh Phuong Doan, Milad Dodangeh, Fatemeh Eghbalian, Debela Debela Ejeta, Michael Ekholuenetale, Temitope Cyrus Ekundayo, Iman El Sayed, Muhammed Elhadi, Daniel Berhanie Enyew, Tahir Eyayu, Rana Ezzeddini, Ildar Ravisovich Fakhradiyev, Umar Farooque, Hossein Farrokhpour, Farshad Farzadfar, Ali Fatehizadeh, Hamed Fattahi, Nima Fattahi, Masood Fereidoonnezhad, Eduarda Fernandes, Getahun Fetensa, Irina Filip, Florian Fischer, Masoud Foroutan, Peter Andras Gaal, Mohamed M Gad, Silvano Gallus, Tushar Garg, Tamiru Getachew, Seyyed-Hadi Ghamari, Ahmad Ghashghaee, Nermin Ghith, Maryam Gholamalizadeh, Jamshid Gholizadeh Navashenaq, Abraham Tamirat Gizaw, James C Glasbey, Mahaveer Golechha, Pouya Goleij, Kebebe Bekele Gonfa, Giuseppe Gorini, Avirup Guha, Sapna Gupta, Veer Bala Gupta, Vivek Kumar Gupta, Rasool Haddadi, Nima Hafezi-Nejad, Arvin Haj-Mirzaian, Rabih Halwani, Shafiul Haque, Sanam Hariri, Ahmed I Hasaballah, Soheil Hassanipour, Simon I Hay, Claudiu Herteliu, Ramesh Holla, Mohammad-Salar Hosseini, Mehdi Hosseinzadeh, Mihaela Hostiuc, Mowafa Househ, Junjie Huang, Ayesha Humayun, Ivo Iavicoli, Olayinka Stephen Ilesanmi, Irena M Ilic, Milena D Ilic, Farhad Islami, Masao Iwagami, Mohammad Ali Jahani, Mihajlo Jakovljevic, Tahereh Javaheri, Ranil Jayawardena, Rime Jebai, Ravi Prakash Jha, Tamas Joo, Nitin Joseph, Farahnaz Joukar, Jacek Jerzy Jozwiak, Ali Kabir, Rohollah Kalhor, Ashwin Kamath, Neeti Kapoor, Ibraheem M Karaye, Amirali Karimi, Joonas H Kauppila, Asma Kazemi, Mohammad Keykhaei, Yousef Saleh Khader, Himanshu Khajuria, Rovshan Khalilov, Javad Khanali, Maryam Khayamzadeh, Mahmoud Khodadost, Hanna Kim, Min Seo Kim, Adnan Kisa, Sezer Kisa, Ali-Asghar Kolahi, Hamid Reza Koohestani, Jacek A Kopec, Rajasekaran Koteeswaran, Ai Koyanagi, Yuvaraj Krishnamoorthy, G Anil Kumar, Manoj Kumar, Vivek Kumar, Carlo La Vecchia, Faris Hasan Lami, Iv??n Landires, Caterina Ledda, Sang-woong Lee, Wei-Chen Lee, Yeong Yeh Lee, Elvynna Leong, Bingyu Li, Stephen S Lim, Stany W Lobo, Joana A Loureiro, Raimundas Lunevicius, Farzan Madadizadeh, Ata Mahmoodpoor, Azeem Majeed, Mohammad-Reza Malekpour, Reza Malekzadeh, Ahmad Azam Malik, Fariborz Mansour-Ghanaei, Lorenzo Giovanni Mantovani, Miquel Martorell, Sahar Masoudi, Prashant Mathur, Jitendra Kumar Meena, Entezar Mehrabi Nasab, Walter Mendoza, Alexios-Fotios A Mentis, Tomislav Mestrovic, Junmei Miao Jonasson, Bartosz Miazgowski, Tomasz Miazgowski, Gelana Fekadu Worku Mijena, Seyyedmohammadsadeq Mirmoeeni, Mohammad Mirza-Aghazadeh-Attari, Hamed Mirzaei, Sanjeev Misra, Karzan Abdulmuhsin Mohammad, Esmaeil Mohammadi, Saeed Mohammadi, Seyyede Momeneh Mohammadi, Abdollah Mohammadian-Hafshejani, Shafiu Mohammed, Teroj Abdulrahman Mohammed, Nagabhishek Moka, Ali H Mokdad, Zeinab Mokhtari, Mariam Molokhia, Sara Momtazmanesh, Lorenzo Monasta, Ghobad Moradi, Rahmatollah Moradzadeh, Paula Moraga, Joana Morgado-da-Costa, Sumaira Mubarik, Francesk Mulita, Mohsen Naghavi, Mukhammad David Naimzada, Hae Sung Nam, Zuhair S Natto, Biswa Prakash Nayak, Javad Nazari, Ehsan Nazemalhosseini-Mojarad, Ionut Negoi, Cuong Tat Nguyen, Son Hoang Nguyen, Nurulamin M Noor, Maryam Noori, Seyyed Mohammad Ali Noori, Virginia Nu??ez-Samudio, Chimezie Igwegbe Nzoputam, Bogdan Oancea, Oluwakemi Ololade Odukoya, Ayodipupo Sikiru Oguntade, Hassan Okati-Aliabad, Andrew T Olagunju, Tinuke O Olagunju, Sokking Ong, Samuel M Ostroff, Alicia Padron-Monedero, Reza Pakzad, Adrian Pana, Anamika Pandey, Fatemeh Pashazadeh Kan, Urvish K Patel, Uttam Paudel, Renato B Pereira, Navaraj Perumalsamy, Richard G Pestell, Zahra Zahid Piracha, Richard Charles G Pollok, Akram Pourshams, Naeimeh Pourtaheri, Akila Prashant, Mohammad Rabiee, Navid Rabiee, Amir Radfar, Sima Rafiei, Mosiur Rahman, Amir Masoud Rahmani, Vahid Rahmanian, Nazanin Rajai, Aashish Rajesh, Vajiheh Ramezani-Doroh, Kiana Ramezanzadeh, Kamal Ranabhat, Sina Rashedi, Amirfarzan Rashidi, Mahsa Rashidi, Mohammad-Mahdi Rashidi, Mandana Rastegar, David Laith Rawaf, Salman Rawaf, Reza Rawassizadeh, Mohammad Sadegh Razeghinia, Andre M N Renzaho, Negar Rezaei, Nima Rezaei, Saeid Rezaei, Mohsen Rezaeian, Sahba Rezazadeh-Khadem, Gholamreza Roshandel, Maha Mohamed Saber-Ayad, Bahar Saberzadeh-Ardestani, Basema Saddik, Hossein Sadeghi, Umar Saeed, Maryam Sahebazzamani, Amirhossein Sahebkar, Amir Salek Farrokhi, Amir Salimi, Hamideh Salimzadeh, Pouria Samadi, Mehrnoosh Samaei, Abdallah M Samy, Juan Sanabria, Milena M Santric-Milicevic, Muhammad Arif Nadeem Saqib, Arash Sarveazad, Brijesh Sathian, Maheswar Satpathy, Ione Jayce Ceola Schneider, Mario ??ekerija, Sadaf G Sepanlou, Allen Seylani, Feng Sha, Sayed Mohammad Shafiee, Zahra Shaghaghi, Saeed Shahabi, Elaheh Shaker, Maedeh Sharifian, Javad Sharifi-Rad, Sara Sheikhbahaei, Jeevan K Shetty, Reza Shirkoohi, Parnian Shobeiri, Sudeep K Siddappa Malleshappa, Diego Augusto Santos Silva, Guilherme Silva Julian, Achintya Dinesh Singh, Jasvinder A Singh, Md Shahjahan Siraj, Gholam Reza Sivandzadeh, Valentin Yurievich Skryabin, Anna Aleksandrovna Skryabina, Bogdan Socea, Marco Solmi, Mohammad Sadegh Soltani-Zangbar, Suhang Song, Vikt??ria Szerencs??s, Mikl??s Sz??cska, Rafael Tabar??s-Seisdedos, Elnaz Tabibian, Majid Taheri, Yasaman TaheriAbkenar, Amir Taherkhani, Iman M Talaat, Ker-Kan Tan, Abdelghani Tbakhi, Bekele Tesfaye, Amir Tiyuri, Daniel Nigusse Tollosa, Mathilde Touvier, Bach Xuan Tran, Biruk Shalmeno Tusa, Irfan Ullah, Saif Ullah, Marco Vacante, Sahel Valadan Tahbaz, Massimiliano Veroux, Bay Vo, Theo Vos, Cong Wang, Ronny Westerman, Melat Woldemariam, Seyed Hossein Yahyazadeh Jabbari, Lin Yang, Fereshteh Yazdanpanah, Chuanhua Yu, Deniz Yuce, Ismaeel Yunusa, Vesna Zadnik, Mazyar Zahir, Iman Zare, Zhi-Jiang Zhang, and Mohammad Zoladl

Abstract

Background: Colorectal cancer is the third leading cause of cancer deaths worldwide. Given the recent increasing trends in colorectal cancer incidence globally, up-to-date information on the colorectal cancer burden could guide screening, early detection, and treatment strategies, and help effectively allocate resources. We examined the temporal patterns of the global, regional, and national burden of colorectal cancer and its risk factors in 204 countries and territories across the past three decades. Methods: Estimates of incidence, mortality, and disability-adjusted life years (DALYs) for colorectal cancer were generated as a part of the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019 by age, sex, and geographical location for the period 1990–2019. Mortality estimates were produced using the cause of death ensemble model. We also calculated DALYs attributable to risk factors that had evidence of causation with colorectal cancer. Findings: Globally, between 1990 and 2019, colorectal cancer incident cases more than doubled, from 842 098 (95% uncertainty interval [UI] 810 408–868 574) to 2·17 million (2·00–2·34), and deaths increased from 518 126 (493 682–537 877) to 1·09 million (1·02–1·15). The global age-standardised incidence rate increased from 22·2 (95% UI 21·3–23·0) per 100 000 to 26·7 (24·6–28·9) per 100 000, whereas the age-standardised mortality rate decreased from 14·3 (13·5–14·9) per 100 000 to 13·7 (12·6–14·5) per 100 000 and the age-standardised DALY rate decreased from 308·5 (294·7–320·7) per 100 000 to 295·5 (275·2–313·0) per 100 000 from 1990 through 2019. Taiwan (province of China; 62·0 [48·9–80·0] per 100 000), Monaco (60·7 [48·5–73·6] per 100 000), and Andorra (56·6 [42·8–71·9] per 100 000) had the highest age-standardised incidence rates, while Greenland (31·4 [26·0–37·1] per 100 000), Brunei (30·3 [26·6–34·1] per 100 000), and Hungary (28·6 [23·6–34·0] per 100 000) had the highest age-standardised mortality rates. From 199

Published
2022

33. Distinct Vaccine Efficacy Rates Among Health Care Workers During a COVID-19 Outbreak in Jordan

Author

Iyad Sultan, Abdelghani Tbakhi, Osama Abuatta, Sawsan Mubarak, Osama Alsmadi, Adib Edilbi, Ruba Al-Ani, Manar Makhlouf, Rawan Hajir, Omar Khreisat, Majeda A. Al-Ruzzieh, Hikmat Abdelrazeq, and Asem Mansour

Abstract

BACKGROUNDWe aimed to assess the efficacy of 3 COVID-19 vaccines in a population of health care workers at a tertiary cancer center in Amman, Jordan.METHODSWe evaluated the records of 2855 employees who were fully vaccinated with 1 of 3 different vaccines and those of 140 employees who were not vaccinated. We measured the number of SARS-CoV-2 infections that occurred at least 14 days after the second vaccine dose.RESULTSThe 100-day cumulative incidence of PCR-confirmed SARS-CoV-2 infections was 19.3% ± 3.3% for unvaccinated employees and 1.7% ± 0.27% for fully vaccinated employees. The 100-day cumulative infection rates were 0.7% ± 0.22% in BNT162b2 vaccine recipients (n = 1714), 3.6% ± 0.77% in BBIBP-CorV recipients (n = 680), and 2.3% ± 0.73% in ChAdOx1 recipients (n = 456). We used Cox regression analyses to compare the risks of SARS-CoV-2 infection among the different vaccine recipient groups and found a significantly higher infection risk in BBIBP-CorV (hazard ratio [HR] = 2.9 ± 0.31) and ChAdOx1 recipients (HR = 3.0 ± 0.41) compared to BNT162b2 recipients (P = .00039 and .0074, respectively). Vaccinated employees who had no previously confirmed SARS-CoV-2 infections were at a markedly higher risk for breakthrough infections than those who experienced prior infections (HR = 5.7 ± 0.73, P = .0178).CONCLUSIONSOur study offers a real-world example of differential vaccine efficacy among a high-risk population during a national outbreak. We also show the important synergism between a previous SARS-CoV-2 infection and vaccination.FundingNone

Published
2022
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34. Global, regional, and national burden of hepatitis B, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Author

Brittney S Sheena, Lindsey Hiebert, Hannah Han, Helen Ippolito, Mohsen Abbasi-Kangevari, Zeinab Abbasi-Kangevari, Hedayat Abbastabar, Amir Abdoli, Hiwa Abubaker Ali, Mesafint Molla Adane, Oyelola A Adegboye, Qorinah Estiningtyas Sakilah Adnani, Shailesh M Advani, Muhammad Sohail Afzal, Saira Afzal, Mohamad Aghaie Meybodi, Bahman Ahadinezhad, Bright Opoku Ahinkorah, Sajjad Ahmad, Tauseef Ahmad, Sepideh Ahmadi, Haroon Ahmed, Muktar Beshir Ahmed, Tarik Ahmed Rashid, Gizachew Taddesse Akalu, Addis Aklilu, Tayyaba Akram, Hanadi Al Hamad, Fares Alahdab, Adugnaw Zeleke Alem, Dejene Tsegaye Alem, Fadwa Alhalaiqa Naji Alhalaiqa, Robert Kaba Alhassan, Liaqat Ali, Muhammad Ashar Ali, Yousef Alimohamadi, Vahid Alipour, Motasem Alkhayyat, Sami Almustanyir, Rajaa M Al-Raddadi, Haya Altawalah, Saeed Amini, Hubert Amu, Robert Ancuceanu, Catalina Liliana Andrei, Tudorel Andrei, Amir Anoushiravani, Adnan Ansar, Anayochukwu Edward Anyasodor, Jalal Arabloo, Morteza Arab-Zozani, Ayele Mamo Argaw, Zeleke Gebru Argaw, Muhammad Arshad, Anton A Artamonov, Tahira Ashraf, Daniel Atlaw, Floriane Ausloos, Marcel Ausloos, Sina Azadnajafabad, Mohammadreza Azangou-Khyavy, Amirhossein Azari Jafari, Ghasem Azarian, Sayna Bagheri, Saeed Bahadory, Atif Amin Baig, Maciej Banach, Nastaran Barati, Amadou Barrow, Abdul-Monim Mohammad Batiha, Diana Fernanda Bejarano Ramirez, Uzma Iqbal Belgaumi, Alemshet Yirga Berhie, Devidas S Bhagat, Nikha Bhardwaj, Pankaj Bhardwaj, Krittika Bhattacharyya, Vijayalakshmi S Bhojaraja, Ali Bijani, Antonio Biondi, Belay Boda Abule Bodicha, Hunduma Amensisa Bojia, Archith Boloor, Cristina Bosetti, Dejana Braithwaite, Nikolay Ivanovich Briko, Zahid A Butt, Luis Alberto Cámera, Raja Chandra Chakinala, Promit Ananyo Chakraborty, Jaykaran Charan, Shu Chen, Jee-Young Jasmine Choi, Sonali Gajanan Choudhari, Fazle Rabbi Chowdhury, Dinh-Toi Chu, Sheng-Chia Chung, Paolo Angelo Cortesi, Benjamin C Cowie, Garland T Culbreth, Omid Dadras, Xiaochen Dai, Lalit Dandona, Rakhi Dandona, Fernando Pio De la Hoz, Sisay Abebe Debela, Mohammed Gebre Dedefo, Feleke Mekonnen Demeke, Takele Gezahegn G Demie, Getu Debalkie Demissie, Meseret Derbew Molla, Abebaw Alemayehu Desta, Deepak Dhamnetiya, Mandira Lamichhane Dhimal, Meghnath Dhimal, Mojtaba Didehdar, Linh Phuong Doan, Fariba Dorostkar, Thomas M Drake, Fatemeh Eghbalian, Michael Ekholuenetale, Iman El Sayed, Maysaa El Sayed Zaki, Muhammed Elhadi, Mohamed A Elmonem, Aisha Elsharkawy, Shymaa Enany, Daniel Berhanie Enyew, Ryenchindorj Erkhembayar, Sharareh Eskandarieh, Firooz Esmaeilzadeh, Sayeh Ezzikouri, Hossein Farrokhpour, Getahun Fetensa, Florian Fischer, Masoud Foroutan, Mohamed M Gad, Abhay Motiramji Gaidhane, Shilpa Gaidhane, Natalie C Galles, Silvano Gallus, Teferi Gebru Gebremeskel, Eyob Alemayehu Gebreyohannes, Keyghobad Ghadiri, Kazem Ghaffari, Mansour Ghafourifard, Seyyed-Hadi Ghamari, Ahmad Ghashghaee, Ali Gholami, Abdolmajid Gholizadeh, Aima Gilani, Amit Goel, Mahaveer Golechha, Pouya Goleij, Davide Golinelli, Giuseppe Gorini, Yitayal Ayalew Goshu, Max G Griswold, Mohammed Ibrahim Mohialdeen Gubari, Bhawna Gupta, Sapna Gupta, Veer Bala Gupta, Vivek Kumar Gupta, Rasool Haddadi, Rabih Halwani, Saeed S Hamid, Samer Hamidi, Asif Hanif, Shafiul Haque, Harapan Harapan, Arief Hargono, Sanam Hariri, Ahmed I Hasaballah, S M Mahmudul Hasan, Soheil Hassanipour, Hadi Hassankhani, Simon I Hay, Khezar Hayat, Golnaz Heidari, Claudiu Herteliu, Demisu Zenbaba Heyi, Kamal Hezam, Ramesh Holla, Mohammad-Salar Hosseini, Mostafa Hosseini, Mehdi Hosseinzadeh, Mihaela Hostiuc, Mowafa Househ, Junjie Huang, Nawfal R Hussein, Ivo Iavicoli, Segun Emmanuel Ibitoye, Olayinka Stephen Ilesanmi, Irena M Ilic, Milena D Ilic, Lalu Muhammad Irham, Jessica Y Islam, Nahlah Elkudssiah Ismail, Kathryn H Jacobsen, Farhad Jadidi-Niaragh, Amirreza Javadi Mamaghani, Shubha Jayaram, Ranil Jayawardena, Rime Jebai, Ravi Prakash Jha, Nitin Joseph, Farahnaz Joukar, Billingsley Kaambwa, Ali Kabir, Zubair Kabir, Rohollah Kalhor, Himal Kandel, Tesfaye K Tesfaye Kanko, Rami S Kantar, Ibraheem M Karaye, Bekalu Getnet Kassa, Phillip M Kemp Bohan, Mohammad Keykhaei, Yousef Saleh Khader, Himanshu Khajuria, Gulfaraz Khan, Imteyaz A Khan, Junaid Khan, Moien AB Khan, Javad Khanali, Amir M Khater, Mahalaqua Nazli Khatib, Mahmoud Khodadost, Abdullah T Khoja, Omid Khosravizadeh, Jagdish Khubchandani, Gyu Ri Kim, Hanna Kim, Min Seo Kim, Yun Jin Kim, Jonathan M Kocarnik, Ali-Asghar Kolahi, Rajasekaran Koteeswaran, G Anil Kumar, Carlo La Vecchia, Dharmesh Kumar Lal, Iván Landires, Savita Lasrado, Jeffrey V Lazarus, Caterina Ledda, Doo Woong Lee, Sang-woong Lee, Yeong Yeh Lee, Miriam Levi, Jiarui Li, Stephen S Lim, Stany W Lobo, Platon D Lopukhov, Joana A Loureiro, Jennifer H MacLachlan, Hassan Magdy Abd El Razek, Muhammed Magdy Abd El Razek, Azeem Majeed, Alaa Makki, Mohammad-Reza Malekpour, Reza Malekzadeh, Ahmad Azam Malik, Fariborz Mansour-Ghanaei, Mohammad Ali Mansournia, Francisco Rogerlândio Martins-Melo, Philippa C Matthews, Walter Mendoza, Ritesh G Menezes, Tuomo J Meretoja, Amanual Getnet Mersha, Tomislav Mestrovic, Ted R Miller, Le Huu Nhat Minh, Andreea Mirica, Seyyedmohammadsadeq Mirmoeeni, Erkin M Mirrakhimov, Sanjeev Misra, Prasanna Mithra, Babak Moazen, Ashraf Mohamadkhani, Mokhtar Mohammadi, Shafiu Mohammed, Nagabhishek Moka, Ali H Mokdad, Jalal Moludi, Sara Momtazmanesh, Lorenzo Monasta, Ghobad Moradi, Maliheh Moradzadeh, Rahmatollah Moradzadeh, Paula Moraga, Ebrahim Mostafavi, Sumaira Mubarik, Malaisamy Muniyandi, Christopher J L Murray, Mohsen Naghavi, Mukhammad David Naimzada, Sreenivas Narasimha Swamy, Zuhair S Natto, Biswa Prakash Nayak, Javad Nazari, Ionut Negoi, Serban Mircea Negru, Seyed Aria Nejadghaderi, Sandhya Neupane Kandel, Huong Lan Thi Nguyen, Che Henry Ngwa, Robina Khan Niazi, Chukwudi A Nnaji, Jean Jacques Noubiap, Ali Nowroozi, Virginia Nuñez-Samudio, Bogdan Oancea, Chimedsuren Ochir, Oluwakemi Ololade Odukoya, In-Hwan Oh, Andrew T Olagunju, Babayemi Oluwaseun Olakunde, Ahmed Omar Bali, Emad Omer, Stanislav S Otstavnov, Bilcha Oumer, Jagadish Rao Padubidri, Adrian Pana, Anamika Pandey, Eun-Cheol Park, Fatemeh Pashazadeh Kan, Urvish K Patel, Uttam Paudel, Ionela-Roxana Petcu, Zahra Zahid Piracha, Richard Charles G Pollok, Maarten J Postma, Akram Pourshams, Hossein Poustchi, Mohammad Rabiee, Navid Rabiee, Alireza Rafiei, Sima Rafiei, Pavan Manibettu Raghuram, Mosiur Rahman, Amir Masoud Rahmani, Setyaningrum Rahmawaty, Aashish Rajesh, Priyanga Ranasinghe, Chythra R Rao, Sowmya J Rao, Mahsa Rashidi, Mohammad-Mahdi Rashidi, David Laith Rawaf, Salman Rawaf, Reza Rawassizadeh, Negar Rezaei, Aziz Rezapour, Sahba Rezazadeh-Khadem, Jefferson Antonio Buendia Rodriguez, Godfrey M Rwegerera, Siamak Sabour, Basema Saddik, Mohammad Reza Saeb, Umar Saeed, Amirhossein Sahebkar, KM Saif-Ur-Rahman, Sarvenaz Salahi, Hamideh Salimzadeh, Chethan Sampath, Abdallah M Samy, Juan Sanabria, Francesco Sanmarchi, Milena M Santric-Milicevic, Arash Sarveazad, Brijesh 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Woldemariam, Suowen Xu, Seyed Hossein Yahyazadeh Jabbari, Mehdi Yaseri, Yigizie Yeshaw, Vahit Yiğit, Birhanu Wubale Yirdaw, Naohiro Yonemoto, Chuanhua Yu, Ismaeel Yunusa, Mazyar Zahir, Leila Zaki, Mohammad Zamani, Maryam Zamanian, Mikhail Sergeevich Zastrozhin, Theo Vos, John W Ward, M Ashworth Dirac, Value, Affordability and Sustainability (VALUE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Microbes in Health and Disease (MHD), Sheena, Brittney S, Hiebert, Lindsey, Han, Hannah, Ippolito, Helen, Abbasi-Kangevari, Mohsen, Abbasi-Kangevari, Zeinab, Abbastabar, Hedayat, Abdoli, Amir, Abubaker Ali, Hiwa, Adane, Mesafint Molla, Adegboye, Oyelola A, Adnani, Qorinah Estiningtyas Sakilah, Advani, Shailesh M, Afzal, Muhammad Sohail, Afzal, Saira, Aghaie Meybodi, Mohamad, Ahadinezhad, Bahman, Ahinkorah, Bright Opoku, Ahmad, Sajjad, Ahmad, Tauseef, Ahmadi, Sepideh, Ahmed, Haroon, Ahmed, Muktar Beshir, Ahmed Rashid, Tarik, Akalu, Gizachew Taddesse, 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Subjects
Liver Cirrhosis, Hepatology, Seroepidemiologic Studies, 3121 General medicine, internal medicine and other clinical medicine, Liver Neoplasms, Gastroenterology, Humans, Bayes Theorem, HBV, Global burden of diseases, HCC, Cirrhosis, Child, Hepatitis B, Global Burden of Disease
Abstract

Publisher Copyright: © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Combating viral hepatitis is part of the UN Sustainable Development Goals (SDGs), and WHO has put forth hepatitis B elimination targets in its Global Health Sector Strategy on Viral Hepatitis (WHO-GHSS) and Interim Guidance for Country Validation of Viral Hepatitis Elimination (WHO Interim Guidance). We estimated the global, regional, and national prevalence of hepatitis B virus (HBV), as well as mortality and disability-adjusted life-years (DALYs) due to HBV, as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. This included estimates for 194 WHO member states, for which we compared our estimates to WHO elimination targets. Methods: The primary data sources were population-based serosurveys, claims and hospital discharges, cancer registries, vital registration systems, and published case series. We estimated chronic HBV infection and the burden of HBV-related diseases, defined as an aggregate of cirrhosis due to hepatitis B, liver cancer due to hepatitis B, and acute hepatitis B. We used DisMod-MR 2.1, a Bayesian mixed-effects meta-regression tool, to estimate the prevalence of chronic HBV infection, cirrhosis, and aetiological proportions of cirrhosis. We used mortality-to-incidence ratios modelled with spatiotemporal Gaussian process regression to estimate the incidence of liver cancer. We used the Cause of Death Ensemble modelling (CODEm) model, a tool that selects models and covariates on the basis of out-of-sample performance, to estimate mortality due to cirrhosis, liver cancer, and acute hepatitis B. Findings: In 2019, the estimated global, all-age prevalence of chronic HBV infection was 4·1% (95% uncertainty interval [UI] 3·7 to 4·5), corresponding to 316 million (284 to 351) infected people. There was a 31·3% (29·0 to 33·9) decline in all-age prevalence between 1990 and 2019, with a more marked decline of 76·8% (76·2 to 77·5) in prevalence in children younger than 5 years. HBV-related diseases resulted in 555 000 global deaths (487 000 to 630 000) in 2019. The number of HBV-related deaths increased between 1990 and 2019 (by 5·9% [–5·6 to 19·2]) and between 2015 and 2019 (by 2·9% [–5·9 to 11·3]). By contrast, all-age and age-standardised death rates due to HBV-related diseases decreased during these periods. We compared estimates for 2019 in 194 WHO locations to WHO-GHSS 2020 targets, and found that four countries achieved a 10% reduction in deaths, 15 countries achieved a 30% reduction in new cases, and 147 countries achieved a 1% prevalence in children younger than 5 years. As of 2019, 68 of 194 countries had already achieved the 2030 target proposed in WHO Interim Guidance of an all-age HBV-related death rate of four per 100 000. Interpretation: The prevalence of chronic HBV infection declined over time, particularly in children younger than 5 years, since the introduction of hepatitis B vaccination. HBV-related death rates also decreased, but HBV-related death counts increased as a result of population growth, ageing, and cohort effects. By 2019, many countries had met the interim seroprevalence target for children younger than 5 years, but few countries had met the WHO-GHSS interim targets for deaths and new cases. Progress according to all indicators must be accelerated to meet 2030 targets, and there are marked disparities in burden and progress across the world. HBV interventions, such as vaccination, testing, and treatment, must be strategically supported and scaled up to achieve elimination. Funding: Bill & Melinda Gates Foundation.

Published
2022

35. Programmed Death Ligand-1 is Frequently Expressed in Primary Acute Myeloid Leukemia and B-Acute Lymphoblastic Leukemia

Author

Sara Hamdan, Maher Sugayer, Majd Khader, Abdelghani Tbakhi, Saleh Khudirat, Ala Hejazi, Saifaldeen AlRyalat, Nadwa Bustami, and Tariq Aladily

Subjects
Adult, Leukemia, Myeloid, Acute, Acute Disease, Humans, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Child, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, B7-H1 Antigen, General Biochemistry, Genetics and Molecular Biology
Abstract

The introduction of checkpoint inhibitors in solid cancer therapy showed successful results. The role of Programmed Death-1/Programmed Death-Ligand 1 (PD1/PD-L1) in hematologic malignancies is currently being investigated and clinical trials are ongoing. Preliminary findings showed conflicting results. In this study, we examined the degree of PD-L1 and PD-L2 expression in primary acute leukemia patients.Flow cytometry expression of PD-L1 and PD-L2 was evaluated in de novo acute leukemia in the collaborating institutions between 2018 - 2020.One hundred forty patients were identified. PD-L1 was positive in 34/70 (49%) of AML, 25/50 (50%) of B-ALL, and none (0/20) of T-ALL patients. In contrast, PD-L2 was solely expressed in eight (19%) AML patients. The expression of PD-L1 showed statistically significant correlation with the type of acute leukemia (AML and B-ALLT-ALL, p0.001) and with age group (adultschildren, p = 0.048), but not with blast count, immunophenotype or cytogenetic mutations. The positivity for PD-L1 was associated with worse overall survival in AML, but not in B-ALL.The expression of PD-L1 is common among newly diagnosed AML and B-ALL patients and is not restricted to relapsed cases as previously described. PD-L2 is less commonly expressed and is accompanied by PD-L1 expression. Positive PD-L1 patients may benefit from treatment with immune checkpoint inhibitors, especially in AML. Further studies are recommended.

Published
2022
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36. The global burden of adolescent and young adult cancer in 2019: a systematic analysis for the Global Burden of Disease Study 2019

Author

Elysia M Alvarez, Lisa M Force, Rixing Xu, Kelly Compton, Dan Lu, Hannah Jacqueline Henrikson, Jonathan M Kocarnik, James D Harvey, Alyssa Pennini, Frances E Dean, Weijia Fu, Martina T Vargas, Theresa H M Keegan, Hany Ariffin, Ronald D Barr, Yana Arturovna Erdomaeva, D Sanjeeva Gunasekera, Yetunde O John-Akinola, Tyler G Ketterl, Tezer Kutluk, Marcio Henrique Malogolowkin, Prashant Mathur, Venkatraman Radhakrishnan, Lynn Ann Gloeckler Ries, Carlos Rodriguez-Galindo, Garik Barisovich Sagoyan, Iyad Sultan, Behzad Abbasi, Mohsen Abbasi-Kangevari, Zeinab Abbasi-Kangevari, Hedayat Abbastabar, Michael Abdelmasseh, Sherief Abd-Elsalam, Amir Abdoli, Haimanot Abebe, Aidin Abedi, Hassan Abidi, Hassan Abolhassani, Hiwa Abubaker Ali, Eman Abu-Gharbieh, Basavaprabhu Achappa, Juan Manuel Acuna, Isaac Akinkunmi Adedeji, Oyelola A Adegboye, Qorinah Estiningtyas Sakilah Adnani, Shailesh M Advani, Muhammad Sohail Afzal, Mohamad Aghaie Meybodi, Bahman Ahadinezhad, Bright Opoku Ahinkorah, Sajjad Ahmad, Sepideh Ahmadi, Muktar Beshir Ahmed, Tarik Ahmed Rashid, Yusra Ahmed Salih, Wajeeha Aiman, Gizachew Taddesse Akalu, Hanadi Al Hamad, Fares Alahdab, Abdulhadi A AlAmodi, Fahad Mashhour Alanezi, Turki M Alanzi, Adugnaw Zeleke Alem, Dejene Tsegaye Alem, Yosef Alemayehu, Fadwa Naji Alhalaiqa, Robert Kaba Alhassan, Saqib Ali, Gianfranco Alicandro, Vahid Alipour, Syed Mohamed Aljunid, Motasem Alkhayyat, Sunitha Alluri, Nihad A Almasri, Sadeq Ali Al-Maweri, Sami Almustanyir, Rajaa M Al-Raddadi, Nelson Alvis-Guzman, Edward Kwabena Ameyaw, Saeed Amini, Hubert Amu, Robert Ancuceanu, Catalina Liliana Andrei, Tudorel Andrei, Fereshteh Ansari, Alireza Ansari-Moghaddam, Davood Anvari, Anayochukwu Edward Anyasodor, Jalal Arabloo, Morteza Arab-Zozani, Ayele Mamo Argaw, Muhammad Arshad, Judie Arulappan, Armin Aryannejad, Zatollah Asemi, Mohammad Asghari Jafarabadi, Mohammad Reza Atashzar, Prince Atorkey, Alok Atreya, Sameh Attia, Avinash Aujayeb, Marcel Ausloos, Leticia Avila-Burgos, Atalel Fentahun 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Chao Cao, Yin Cao, Giulia Carreras, Ferrán Catalá-López, Francieli Cembranel, Ester Cerin, Raja Chandra Chakinala, Promit Ananyo Chakraborty, Vijay Kumar Chattu, Pankaj Chaturvedi, Akhilanand Chaurasia, Prachi P Chavan, Odgerel Chimed-Ochir, Jee-Young Jasmine Choi, Devasahayam J Christopher, Dinh-Toi Chu, Michael T Chung, Joao Conde, Vera Marisa Costa, Omar B Da'ar, Omid Dadras, Saad M A Dahlawi, Xiaochen Dai, Giovanni Damiani, Emanuele D'Amico, Lalit Dandona, Rakhi Dandona, Parnaz Daneshpajouhnejad, Amira Hamed Darwish, Ahmad Daryani, Fernando Pio De la Hoz, Sisay Abebe Debela, Takele Gezahegn G Demie, Getu Debalkie Demissie, Zeleke Geto Demissie, Edgar Denova-Gutiérrez, Meseret Derbew Molla, Rupak Desai, Abebaw Alemayehu Desta, Deepak Dhamnetiya, Samath Dhamminda Dharmaratne, Mandira Lamichhane Dhimal, Meghnath Dhimal, Mostafa Dianatinasab, Mojtaba Didehdar, Mengistie Diress, Shirin Djalalinia, Huyen Phuc Do, Saeid Doaei, Fariba Dorostkar, Wendel Mombaque dos Santos, Thomas M Drake, Michael Ekholuenetale, Iman El Sayed, Maysaa El Sayed Zaki, Maha El Tantawi, Hassan El-Abid, Mostafa Ahmed Elbahnasawy, Iffat Elbarazi, Hala Rashad Elhabashy, Muhammed Elhadi, Shaimaa I El-Jaafary, Daniel Berhanie Enyew, Ryenchindorj Erkhembayar, Babak Eshrati, Sharareh Eskandarieh, Mohammed Faisaluddin, Jawad Fares, Umar Farooque, Abidemi Omolara Fasanmi, Wafa Fatima, José Miguel P Ferreira de Oliveira, Simone Ferrero, Lorenzo Ferro Desideri, Getahun Fetensa, Irina Filip, Florian Fischer, James L Fisher, Masoud Foroutan, Takeshi Fukumoto, Peter Andras Gaal, Mohamed M Gad, Piyada Gaewkhiew, Silvano Gallus, Tushar Garg, Teferi Gebru Gebremeskel, Belete Negese Belete Gemeda, Tamiru Getachew, Mansour Ghafourifard, Seyyed-Hadi Ghamari, Ahmad Ghashghaee, Fariba Ghassemi, Nermin Ghith, Ali Gholami, Jamshid Gholizadeh Navashenaq, Syed Amir Gilani, Themba G Ginindza, Abraham Tamirat Gizaw, James C Glasbey, Amit Goel, Mahaveer Golechha, Pouya Goleij, Davide Golinelli, Sameer Vali Gopalani, 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Foundation, NIH - National Cancer Institute (NCI) (Estados Unidos), Epidemiologie, and RS: NUTRIM - R3 - Respiratory & Age-related Health

Subjects
adolescent cancer, global burden of disease, epidemiology, Adult, Male, Adolescent, 3122 Cancers, UNITED-STATES, Disability-Adjusted Life Year, Adolescents, Socioeconomic Factor, Global Health, Global Burden of Disease, Young Adult, Life Expectancy, SDG 3 - Good Health and Well-being, Risk Factors, WORLDWIDE, Neoplasms, Cause of Death, Prevalence, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Mortality, Cancer burden analyses, Cancer, ACUTE LYMPHOBLASTIC-LEUKEMIA, disease, Global burden, OUTCOMES, CHILDHOOD-CANCER, Incidence, Risk Factor, the GBD 2019 methodology, Disability-Adjusted Life Years, GBD 2019 Adolescent Young Adult Cancer Collaborators, CARE, Cancer control efforts, Socioeconomic Factors, Oncology, Neoplasm, Female, Young adults, Human
Abstract

Funding: J A Loureiro acknowledges support from Base Funding UIDB/00511/2020 of the LEPABE funded by national funds through the FCT/MCTES (PIDDAC) and Scientific Employment Stimulus (FCT) [CEECINST/00049/2018]. Background: In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15–39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods: Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15–39 years to define adolescents and young adults. Findings: There were 1·19 million (95% UI 1·11–1·28) incident cancer cases and 396 000 (370 000–425 000) deaths due to cancer among people aged 15–39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59·6 [54·5–65·7] per 100 000 person-years) and high-middle SDI countries (53·2 [48·8–57·9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14·2 [12·9–15·6] per 100 000 person-years) and middle SDI (13·6 [12·6–14·8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23·5 million (21·9–25·2) DALYs to the global burden of disease, of which 2·7% (1·9–3·6) came from YLDs and 97·3% (96·4–98·1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation: Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Funding: Bill & Melinda Gates Foundation, American Lebanese Syrian Associated Charities, St Baldrick's Foundation, and the National Cancer Institute. publishersversion published

Published
2022
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37. Early post-induction Augmented therapy improves outcome in children and adolescents with T-cell acute lymphoblastic leukemia

Author

Mayada Abu Shanap, Haytham Aljbour, Rawad Rihani, Hasan Hashem, Amal Abu Ghosh, Abdelghani Tbakhi, Nazmi Kamal, Iyad Sultan, and Faris Madanat

Abstract

Introduction: T-cell acute lymphoblastic leukemia (T-ALL) accounts for approximately 15% of all newly diagnosed ALL in children and adolescents and is associated with worse outcomes compared to pre-B ALL. We aimed to decrease T-ALL relapses by intensifying our regimen. Methods: Patients with T-ALL were treated using two different regimens; before September 2014, patients were treated per St. Jude Total XV protocol; subsequently, a major change was adopted by adding two intensive blocks: FLAG and Re-Intensification (fludarabine, dexamethasone, cytarabine, etoposide and asparaginase). Cranial radiation was limited to patients with WBC >=100k/µl at diagnosis and/or patients with CNS2/CNS3 status. Results: Between June 2005 and April 2020, a total of 100 patients (76 males) were treated and followed for a median of 70 months (range, 14-181 months). Median age at diagnosis was 9 years (range,0.5-17.8 years). Forty-eight patients were diagnosed after September 2014 and received the augmented regimen; their median follow up was 46 months (range,14-74 months). The 5-yr-EFS estimates for patients who received the augmented regimen vs. standard regimen were 87%±4.9% vs 67%±6.8% (p=0.03); and the 5-yr-OS estimates were 87%±5.1% vs. 71%±6.3% (p=0.06) respectively. Treatment related mortality (TRM) were reported in 2 patients treated using our standard regimen but none for patients who received the augmented regimen. Conclusions: We implemented a novel approach with early intensification added to a backbone of modified St. Jude Total-XV regimen for patients with T-ALL that resulted in improved outcome with no treatment related mortality.

Published
2021
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38. Transplantation for Congenital Sideroblastic Anaemia Is Feasible and Offers Outcomes Comparable to Other Transfusion Dependent Anaemias. a Joint Retrospective Study of the Paediatric Diseases and Severe Aplastic Anaemia Working Parties (PDWP/SAAWP) of EBMT

Author

Régis Peffault de Latour, Carlo Dufour, Miguel Angel Diaz, Vassiliki Kitra-Roussou, John Moppett, Antonio M. Risitano, Abdelghani Tbakhi, John G. Gribben, Antonio Martinez, Tessa Kerre, Tobias Gedde-Dahl, Henrik Sengeloev, Muhlis Cem Ar, Josu de la Fuente, Cristina Díaz de Heredia, Paul Bosman, Mohamed Salaheldin Mohamed, Dominique Bron, Stig Lenhoff, José M. Moraleda, Hendrik Veelken, Giuseppe Visani, Selim Corbacioglu, Peter J. Shaw, Amal Al-Seraihy, Brenda Gibson, Dirk-Jan Eikema, Rupert Handgretinger, Estelle Verburgh, and Robert Wynn

Subjects
Pediatrics, medicine.medical_specialty, business.industry, Incidence (epidemiology), education, Immunology, Retrospective cohort study, Cell Biology, Hematology, Treosulfan, medicine.disease, Biochemistry, Fludarabine, Transplantation, Regimen, medicine, Alemtuzumab, Reticulocytopenia, business, health care economics and organizations, medicine.drug
Abstract

Congenital sideroblastic anaemias (CSA) are a rare group of disorders characterized by the presence of pathologic iron deposits within the mitochondria of erythroid precursors (ring sideroblasts) in the bone marrow due to heterogenous germline mutations leading to defects in mitochondrial heme synthesis, iron-sulfur (Fe-S) cluster biogenesis, or protein synthesis. Patients present with anaemia and relative reticulocytopenia, and systemic iron overload secondary to chronic ineffective erythropoiesis, leading to end-organ damage. The disease is heterogenous underlying the genetic variability and the variable response to treatment. Although a number of CSA patients have received a bone marrow transplant, the outcomes and toxicities are not known. This status makes it very difficult to understand the role of BMT in the management of CSA. A search in the EBMT database identified 28 patients receiving a HSCT for CSA between 1998 to 2018 by 24 participating centres. The median year of transplantation was 2014 (IQR 2004-2016). The distribution was equal between males (n=14) and females (n=14). The median age at transplantation was 7 years of age (3-10 years). Fifteen patients had a sibling HSCT (88%), one a family matched donor HSCT (6%) and one an unrelated matched (6%), the type of transplant being unknown in others (n=11). The source of stem cells was bone marrow in 20 cases (74%), peripheral blood in 4 cases (15%), cord blood in 2 (7%) and combined bone marrow and cord in one (4%). Five cases had a Bu/Cy based conditioning regimen, 4 had Bu/fludarabine based regimen and three fludarabine/treosulfan based conditioning with the rest having a variety of approaches. Eighty-six percent of cases had serotherapy with ATG or alemtuzumab. The median follow-up was 31.6 months (95% CI, 12.2-74.1%). The overall survival at 12 and 24 months was 88% (76-100) and 82% (66-99), respectively (figure 1). The median neutrophil engraftment was 18 (15-21) days and platelet engraftment >20 x 109/L was 29 (20-51) days, with a graft failure incidence of 7% (0-17) at 12 months. Two patients suffered from VOD. There were four deaths, three of which were related to transplant complications. The event free survival (survival without graft failure, relapse and second transplant) at 12 and 24 months was 85% (72-99) (figure 2). Six patients developed acute GvHD grade II and one case grade III; giving a grade II/III incidence of 28% (10-46). There was one case of limited and one of chronic GvHD, giving an incidence of 11% (0-26%) at 12 months and 24 months. In conclusion, whilst HSCT for CSA is a rare occurrence, these data demonstrate that HSCT for this condition is feasible and the outcomes are in keeping with those obtained for transplantation for transfusion dependent anaemias during the same time-period. Disclosures Handgretinger: Amgen: Honoraria. Moraleda:Gilead: Consultancy, Other: Travel Expenses; Jazz Pharmaceuticals: Consultancy, Research Funding; Novartis: Consultancy, Other: Travel Expenses; Sandoz: Consultancy, Other: Travel Expenses; Takeda: Consultancy, Other: Travel Expenses. Risitano:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Alnylam: Research Funding; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Jazz: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Samsung: Membership on an entity's Board of Directors or advisory committees; Amyndas: Consultancy; RA pharma: Research Funding; Biocryst: Membership on an entity's Board of Directors or advisory committees; Apellis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Achillion: Membership on an entity's Board of Directors or advisory committees; Pfizer: Speakers Bureau. Peffault De Latour:Amgen: Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Apellis: Membership on an entity's Board of Directors or advisory committees; Alexion Pharmaceuticals Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Published
2020
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39. Abstract P2-09-06: Genetic counseling and genetic testing for germline BRCA1/2 mutations among high risk breast cancer patients in Jordan: A study of 500 patients

Author

Dima Jadaan, Hikmat Abdel-Razeq, Lama Abujamous, Abdelghani Tbakhi, and Amal Al-Omari

Subjects
Oncology, Cancer Research, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Genetic counseling, medicine.disease, Germline, Breast cancer, Internal medicine, Medicine, business, Genetic testing
Abstract

Introduction: Breast Cancer is the most common cancer worldwide and so in our region. In Jordan, almost 50% of patients are diagnosed before the age of 50. Knowledge of BRCA1/2 mutations has significant clinical impact on the management and prevention of breast cancer. In this study, we evaluate the prevalence of germline mutations in BRCA1/2 among high-risk Jordanian patients selected as per the updated NCCN guidelines. Methods: Jordanian breast cancer patients, stages I-IV, with a selected high-risk profile treated at our institution were invited to participate. Blood samples were obtained for DNA extraction, and BRCA sequencing and dosage analysis were performed at Leeds Cancer Center, Leeds-United Kingdom. BRCA1/2 mutations were classified as pathogenic/likely pathogenic and variant of uncertain significance (VUS). Clinical and pathological data were obtained from patients' medical records and a detailed 3-generation family history was also obtained by a genetic counselor. Results: A total of 517 patients were enrolled, genetic testing and counseling have been completed for all. Median age at diagnosis was 39 (range: 20-78) years. Among the whole group, 72 (13.9%) patients had pathogenic or likely pathogenic BRCA1 (n=24, 4.6%) or BRCA2 (n=48, 9.3%) mutations, while 53 (10.3%) others had VUS. Among 333 younger (≤40 years) patients, pathogenic/likely pathogenic mutations were observed in 44 (13.2%) patients and 36 (10.8%) others had VUS. Among 242 patients who had one or more close relatives with breast cancer, diagnosed at age 50 years or younger, 40 (16.5%) had pathogenic/likely pathogenic mutations (Table). Twenty (35.1%) of the 57 patients with triple-negative (TN) disease had pathogenic/likely pathogenic mutations; 16 (28.1%) were in BRCA1. Rate was significantly higher (55.6%, p Conclusions: BRCA1/2 mutations are not uncommon and may contribute to the pathogenesis of familial breast cancer among Jordanians. Young age, per se, has the weakest association with positive BRCA1/2 mutations while TN-disease, especially when associated with positive family history, has significantly higher mutation rate. The establishment of Clinical Cancer Genetics program made running such culturally-sensitive genetic testing and counseling more acceptable even in societies like ours. Table: Rates of positive BRCA1/2 mutation across different indications for testingVariableTotalPositive BRCA mutations*BRCA1BRCA2BRCA1/2P-ValueAge (years)≤4033315 (4.5%)29 (8.7%)44 (13.2%)0.53>401849 (4.9%)19 (10.3%)28 (15.2%)Age ≤ 50 years with one or more close relative with breast cancer at any ageYes2428 (3.3%)32 (13.2%)40 (16.5%)0.1No27516 (5.8%)16 (5.8%)32 (11.6%)Age ≤ 60 with triple negative diseaseYes5716 (28.1%)4 (7.0%)19 (35.1%) Citation Format: Hikmat Abdel-Razeq, Lama Abujamous, Amal Al-Omari, Abdelghani Tbakhi, Dima Jadaan. Genetic counseling and genetic testing for germline BRCA1/2 mutations among high risk breast cancer patients in Jordan: A study of 500 patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-09-06.

Published
2020
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40. Worldwide Network for Blood and Marrow Transplantation Recommendations for Establishing a Hematopoietic Stem Cell Transplantation Program in Countries with Limited Resources, Part II: Clinical, Technical, and Socioeconomic Considerations

Author

Mouhab Ayas, Salman Naseem Adil, Shinichiro Okamoto, Mary M. Horowitz, Mohamed A. Kharfan-Dabaja, Daniel J. Weisdorf, Asma El Quessar, Tarek Ben Othman, Wael Saber, Dennis L. Confer, Ardeshir Ghavamzadeh, Eliane Gluckman, Mahmoud Aljurf, Amr Nassar, Fazal Hussain, Hassan El Solh, David Dennison, Alok Srivastava, Yoshihisa Kodera, Ali Bazarbachi, Saleh Ladeb, Hossam K. Mahmoud, Peihua Lu, Greinix Hildegard, Nickolas Novitzky, Syed Osman Ahmed, Parvez Ahmed, Doug Rizzo, Dietger Niederwieser, Jeff Szer, Parameswaran Hari, Mehdi Hamadani, Rose Marie Hamladji, Abdelghani Tbakhi, Amir Ali Hamidieh, Mohamed Amine Bekadja, Navneet S. Majhail, Adriana Seber, Alaa Elhaddad, Mohamad Mohty, Yoshiko Atsuta, Salman Alkindi, Marcelo C. Pasquini, Shahrukh K. Hashmi, Moosa Patel, Ayman Alhejazi, and Usama Gerges

Subjects
medicine.medical_specialty, Transplantation Conditioning, Cost effectiveness, medicine.medical_treatment, Population, Developing country, Hematopoietic stem cell transplantation, Transplantation, Autologous, Health care, medicine, Humans, Transplantation, Homologous, Intensive care medicine, education, Developing Countries, Societies, Medical, health care economics and organizations, Transplantation, Government, education.field_of_study, business.industry, Hematopoietic Stem Cell Transplantation, Hematology, surgical procedures, operative, Socioeconomic Factors, Practice Guidelines as Topic, business
Abstract

The development of hematopoietic stem cell transplantation (HSCT) programs can face significant challenges in most developing countries because such endeavors must compete with other government health care priorities, including the delivery of basic services. Although this is may be a limiting factor, these countries should prioritize development of the needed expertise to offer state-of-the-art treatments, including transplantation, by providing financial, technological, legal, ethical, and other needed support. This would prove beneficial in providing successful programs customized to the needs of their population and potentially provide long-term cost savings by circumventing the need for their citizens to seek care abroad. The costs of establishing an HSCT program and the costs of the HSCT procedure itself can be substantial barriers in developing countries. In addition, socioeconomic factors intrinsic to specific countries can influence access to HSCT, patient eligibility for HSCT, and timely utilization of HSCT center capabilities. This report describes recommendations from the Worldwide Network for Blood and Marrow Transplantation for establishing HSCT programs, with a specific focus on developing countries, and identifies challenges and opportunities for providing this specialized procedure in resource-constrained settings.

Published
2019
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41. A Novel Lossless Encoding Algorithm for Data Compression

Author

Anas Al-okaily and Abdelghani Tbakhi

Subjects
Lossless compression, Computer science, Encoding algorithm, Data_CODINGANDINFORMATIONTHEORY, Algorithm, Data compression
Abstract

Data compression is a challenging and increasingly important problem. As the amount of data generated daily continues to increase, efficient transmission and storage has never been more critical. In this study, a novel encoding algorithm is proposed, motivated by the compression of DNA data and associated characteristics. The proposed algorithm follows a divide-and-conquer approach by scanning the whole genome, classifying subsequences based on similarity patterns, and binning similar subsequences together. The data are then compressed in each bin independently. This approach is different than the currently known approaches: entropy, dictionary, predictive, or transform based methods. Proof-of-concept performance was evaluated using a benchmark dataset with seventeen genomes ranging in size from kilobytes to gigabytes. The results showed considerable improvement in the compression of each genome, preserving several megabytes compared with state-of-art tools. Moreover, the algorithm can be applied to the compression of other data types include mainly text, numbers, images, audio, and video which are being generated daily and unprecedentedly in massive volumes.

Published
2021
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42. Haploidentical Hematopoietic Cell Transplantation Using Post-transplant Cyclophosphamide for Children With Non-malignant Diseases

Author

Iyad Sultan, Rawad Rihani, Rula Najjar, Eman Khattab, Mayada Abu-Shanap, Abdelghani Tbakhi, and Hasan Hashem

Subjects
Adult, Male, Oncology, medicine.medical_specialty, Adolescent, Cyclophosphamide, Primary Immunodeficiency Diseases, Immunology, Graft vs Host Disease, Young Adult, Medical microbiology, Metabolic Diseases, immune system diseases, Internal medicine, medicine, Humans, Immunology and Allergy, Cumulative incidence, Child, Retrospective Studies, business.industry, Incidence (epidemiology), Hematopoietic Stem Cell Transplantation, Bone marrow failure, Infant, medicine.disease, Hematologic Diseases, Transplantation, Hemoglobinopathy, surgical procedures, operative, Child, Preschool, Transplantation, Haploidentical, Primary immunodeficiency, Female, business, Immunosuppressive Agents, medicine.drug
Abstract

Haploidentical hematopoietic cell transplantation (HCT) is a valuable curative option for children with non-malignant diseases. Haploidentical HCT using post-transplant cyclophosphamide (PTCy) is a readily available option in the absence of an HLA- matched donor. We conducted a retrospective single-center study on the outcome of haploidentical HCT in children with non-malignant diseases. We gathered data from 44 patients underwent HCT in the period 2015 to 2020. The indications for HCT were bone marrow failure, primary immunodeficiency, metabolic disorders, and hemoglobinopathy. Median age at HCT was 4 years (range 0.7-20).The conditioning regimens were myeloablative (n=16), or reduced intensity (n=26). After a median follow-up of 20 months (range 4-71), 2-year overall survival was 89% and 2 year GvHD-free relapse-free survival (GRFS) was 66%. Incidence of primary graft failure was 13.6%. Cumulative incidence of grade II-IV acute and moderate/severe chronic GvHD were 20% and 6.4%, respectively. Younger age at HCT (p

Published
2021
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43. Implementation of universal, pan-cancer germline genetic testing in patients with cancer in Jordan

Author

Hikmat Abdel-Razeq, Abdelghani Tbakhi, Ramiz Abuhijlih, Lama Abujamous, Mahmoud Al Masri, Razan Abukhashabeh, Asia Mitchell, Brandie Heald, Sarah M. Nielsen, Robert Luke Nussbaum, and Edward D. Esplin

Subjects
Cancer Research, Oncology
Abstract

10580 Background: Detection of pathogenic germline variants (PGVs) has a significant and growing impact on the management of patients with many types of cancer. Most research to date evaluated individuals of European background, which can result in skewed genetic testing criteria and variant interpretation. Additional data are needed from diverse populations. This study aimed to investigate a universal germline testing strategy and the pattern and frequency of PGVs among all newly diagnosed cancer patients at a single center in Jordan. Methods: In this prospective, observational study, consecutive patients newly diagnosed with cancer were classified as meeting or not meeting National Comprehensive Cancer Network (NCCN) germline genetic testing criteria. All patients underwent an 84-gene panel test, independent of age, stage or family history. Demographics and clinical history were collected and analyzed from information provided by the clinicians on the test requisition form. Descriptive statistics were employed, and statistical significance was determined by two-tailed Fisher’s exact test and unpaired t test. Results: In total, 1377 cancer patients of Arabic background were enrolled, of which 831 (60.3%) met NCCN criteria (Table). PGVs were identified in 210 (15.3%). Excluding the 29 patients who were carriers for autosomal recessive conditions, 192 PGVs were identified in 181 (13.1%) patients. PGVs were most commonly identified in APC (p.I1307K variant, 55, 28.6%), BRCA2 (35, 18.2%), BRCA1 (21, 10.9%), and TP53 (12, 6.3%). While patients who met NCCN testing criteria were more likely to have a PGV (p95% of whom might qualify for increased screening, targeted therapies, and/or clinical trials. [Table: see text]

Published
2022
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44. Novel conditioning regimen for upfront haploidentical hematopoietic cell transplantation in children with severe aplastic anemia and donor-specific anti-HLA antibodies

Author

Eman Khattab, Mayada Abu Shanap, Rawad Rihani, Hasan Hashem, Iyad Sultan, and Abdelghani Tbakhi

Subjects
Transplantation, Transplantation Conditioning, Hematopoietic cell, business.industry, Hematopoietic Stem Cell Transplantation, Anemia, Aplastic, Graft vs Host Disease, Hematology, Severe Aplastic Anemia, Conditioning regimen, Immunology, Humans, Medicine, Hla antibodies, Child, business
Published
2021
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45. Linear Approximate Pattern Matching Algorithm

Author

Abdelghani Tbakhi and Anas Al-okaily

Subjects
FOS: Computer and information sciences, Matching (statistics), Computer science, Process (computing), Structure (category theory), Databases (cs.DB), String searching algorithm, Space (mathematics), Data structure, Computer Science - Databases, Computer Science - Data Structures and Algorithms, Data Structures and Algorithms (cs.DS), Pattern matching, Algorithm, Time complexity, Mathematics
Abstract

Pattern matching is a fundamental process in almost every scientific domain. The problem involves finding the positions of a given pattern (usually of short length) in a reference stream of data (usually of large length). The matching can be an exact or as an approximate (inexact). Exact matching is to search for the pattern without allowing for mismatches (or insertions and deletions) of one or more characters in the pattern), while approximate matching is the opposite. For exact matching, several data structures that can be built in linear time and space are used and in practice nowadays. For approximate matching, the solutions proposed to solve this matching are non-linear and currently impractical. In this paper, we designed and implemented a structure that can be built in linear time and space ($O(n)$) and solves the approximate matching problem in $O(m + \frac {log_2n {(log_\Sigma n)} ^{k+1}}{k!} + occ)$ search costs, where $m$ is the length of the pattern, $n$ is the length of the reference, and $k$ is the number of tolerated mismatches (and insertion and deletions)., Comment: 15 pages double spaced

Published
2021
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46. Outcomes of Unmanipulated Haploidentical Transplantation Using Post-Transplant Cyclophosphamide (PT-Cy) in Pediatric Patients With Acute Lymphoblastic Leukemia

Author

Selim Corbacioglu, Arnaud Dalissier, Annalisa Ruggeri, Akif Yesilipek, Mikael Sundin, José M. Fernández Navarro, Franco Locatelli, Rose-Marie Hamladji, Vanderson Rocha, Maura Faraci, Concepción Herrera, O.V. Paina, Jose Rifón, E V Skorobogatova, Jacques-Emmanuel Galimard, Abdelghani Tbakhi, Franca Fagioli, and Amal Al-Seraihy

Subjects
medicine.medical_specialty, Transplantation Conditioning, Haploidentical transplantation, Disease, Acute lymphoblastic leukemia, Gastroenterology, Internal medicine, medicine, Immunology and Allergy, Humans, Cumulative incidence, Post-transplantation cyclophosphamide, Child, Childhood Acute Lymphoblastic Leukemia, Cyclophosphamide, Retrospective Studies, Transplantation, business.industry, Hazard ratio, Cell Biology, Hematology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Childhood, surgical procedures, operative, medicine.anatomical_structure, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Transplantation, Haploidentical, Molecular Medicine, Bone marrow, Stem cell, business
Abstract

HLA-haploidentical transplantation (haplo-HCT) using post-transplantation-cyclophosphamide (PT-Cy) is a feasible procedure in children with malignancies. However, large studies on Haplo-HCT with PT-Cy for childhood acute lymphoblastic leukemia (ALL) are lacking. We analyzed haplo-HCT outcomes in 180 children with ALL. Median age was 9 years, and median follow-up was 2.7 years. Disease status was CR1 for 24%, CR2 for 45%, CR+3 for 12%, and active disease for 19%. All patients received PT-Cy day +3 and +4. Bone marrow (BM) was the stem cell source in 115 patients (64%). Cumulative incidence of 42-day engraftment was 88.9%. Cumulative incidence of day-100 acute graft-versus-host disease (GVHD) grade II-IV was 28%, and 2-year chronic GVHD was 21.9%. At 2 years, cumulative incidence of nonrelapse mortality (NRM) was 19.6%. Cumulative incidence was 41.9% for relapse and 25% for patients in CR1. Estimated 2-year leukemia free survival was 65%, 44%, and 18.8% for patients transplanted in CR1, CR2, CR3+ and 3% at 1 year for active disease. In multivariable analysis for patients in CR1 and CR2, disease status (CR2 [hazard ratio {HR} = 2.19; P = .04]), age at HCT older than 13 (HR = 2.07; P = .03) and use of peripheral blood stem cell (PBSC) (HR = 1.98; P = .04) were independent factors associated with decreased overall survival. Use of PBSC was also associated with higher NRM (HR = 3.13; P = .04). Haplo-HCT with PT-Cy is an option for children with ALL, namely those transplanted in CR1 and CR2. Age and disease status remain the most important factors for outcomes. BM cells as a graft source is associated with improved survival.

Published
2021

47. BRAF V600E Mutations in Papillary Thyroid Carcinoma: Their Relation to Clinical Features and Oncologic Outcomes in A Single Cancer Centre Experience

Author

Mahmoud Al-Masri, Tawfiq Al-Shobaki, Hani Al-Najjar, Rafal Iskanderian, Enas Younis, Niveen Abdallah, Abdelghani Tbakhi, Hussam Haddad, Awad Jarrar, and Mohammad Al-Masri

Subjects
endocrine system diseases
Abstract

Introduction BRAF V600E is one of the most common mutations in Papillary Thyroid Cancer (PTC). Its clinical correlation has been extensively studied with contradictory results. The aim of this study is to evaluate the oncological impact of BRAF V600E mutation on a cohort of Middle Eastern PTC patients treated at a single institute.Methods Patients with histologically confirmed PTC that were treated surgically between 2006 to 2015 were included in the study. Formalin fixed paraffin embedded tumor blocks were sectioned and tested for BRAF V600E mutation. Short- and long-term oncological outcomes were collected. Results 128 patients (68% females) were included with a mean age of 38 years (±13.8). Median follow-up was 50 months. BRAF V600E mutation was found in 71% of patientsIThe BRAF negative tumors were significantly larger than the BRAF positive (3.47 cm versus 2.31 cm respectively, P = 0.009). All other clinicopathological characteristics were comparable between BRAF V600E mutation positive and negative groups. The two groups showed similar 5-year Disease-free (P= 0.37) and Overall survival rates (P = 0.94).Conclusion BRAF V600E mutation did not affect loco-reginal recurrence, distant metastasis, overall and disease-free survival. These results support the diversity of BRAF V600E significance among various ethnicities.

Published
2020
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48. A Novel Encoding Algorithm for Textual Data Compression

Author

Anas Al-okaily and Abdelghani Tbakhi

Subjects
Transmission (telecommunications), Computer science, Compression (functional analysis), Encoding algorithm, Data_CODINGANDINFORMATIONTHEORY, Coding theory, Algorithm, Data compression
Abstract

Data compression is a fundamental problem in the fields of computer science, information theory, and coding theory. The need for compressing data is to reduce the size of the data so that the storage and the transmission of them become more efficient. Motivated from resolving the compression of DNA data, we introduce a novel encoding algorithm that works for any textual data including DNA data. Moreover, the design of this algorithm paves a novel approach so that researchers can build up on and resolve better the compression problem of DNA or textual data.

Published
2020
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49. Outcome of patients with Fanconi anemia developing myelodysplasia and acute leukemia who received allogeneic hematopoietic stem cell transplantation: A retrospective analysis on behalf of EBMT group

Author

Charlotte Jubert, Wolfgang Holter, Mahmoud Aljurf, Bénédicte Bruno, Claudia Rossig, Miguel Angel Diaz, Maura Faraci, Duygu Uckan-Cetinkaya, Birgit Burkhardt, Marco Zecca, Marie Robin, Peter Bader, Paul Bosman, Antonio M. Risitano, Katharine Patrick, Dirk-Jan Eikema, Edoardo Lanino, Luiz Guilherme Darrigo Junior, Gérard Michel, Vanderson Rocha, Franco Locatelli, Arnold Ganser, Carlo Dufour, Filomena Pierri, Maurizio Miano, Nicolaus Kröger, Abdelghani Tbakhi, Stefano Giardino, Amal Al-Seraihy, Maija Itälä-Remes, Mouhab Ayas, Boris V. Afanasyev, Yves Bertrand, Peter J. Shaw, Régis Peffault de Latour, Martin Bornhäuser, Giardino, S., de Latour, R. P., Aljurf, M., Eikema, D. -J., Bosman, P., Bertrand, Y., Tbakhi, A., Holter, W., Bornhauser, M., Rossig, C., Burkhardt, B., Zecca, M., Afanasyev, B., Michel, G., Ganser, A., Alseraihy, A., Ayas, M., Uckan-Cetinkaya, D., Bruno, B., Patrick, K., Bader, P., Itala-Remes, M., Rocha, V., Jubert, C., Diaz, M. A., Shaw, P. J., Junior, L. G. D., Locatelli, F., Kroger, N., Faraci, M., Pierri, F., Lanino, E., Miano, M., Risitano, A., Robin, M., and Dufour, C.

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Hematopoietic stem cell transplantation, Gastroenterology, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Fanconi anemia, Internal medicine, medicine, Humans, Cumulative incidence, Survival rate, Retrospective Studies, Acute leukemia, Leukemia, business.industry, Myelodysplastic syndromes, Bone marrow failure, Hematopoietic Stem Cell Transplantation, Hematology, medicine.disease, Allografts, Survival Rate, surgical procedures, operative, Fanconi Anemia, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, leukemia, stem cell transplantation, 030220 oncology & carcinogenesis, Myelodysplastic Syndromes, Acute Disease, Female, business, 030215 immunology, Follow-Up Studies
Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is curative for bone marrow failure in patients with Fanconi anemia (FA), but the presence of a malignant transformation is associated with a poor prognosis and the management of these patients is still challenging. We analyzed outcome of 74 FA patients with a diagnosis of myelodysplastic syndrome (n = 35), acute leukemia (n = 35) or with cytogenetic abnormalities (n = 4), who underwent allo-HSCT from 1999 to 2016 in EBMT network. Type of diagnosis, pre-HSCT cytoreductive therapies and related toxicities, disease status pre-HSCT, donor type, and conditioning regimen were considered as main variables potentially influencing outcome. The 5-year OS and EFS were 42% (30-53%) and 39% (27-51%), respectively. Patients transplanted in CR showed better OS compared with those transplanted in presence of an active malignant disease (OS:71%[48-95] vs 37% [24-50],P = .04), while none of the other variables considered had an impact. Twenty-two patients received pre-HSCT cytoreduction and 9/22 showed a grade 3-4 toxicity, without any lethal event or negative influence on survival after HSCT(OS:toxicity pre-HSCT 48% [20-75%] vs no-toxicity 51% [25-78%],P = .98). The cumulative incidence of day-100 grade II-IV a-GvHD and of 5-year c-GvHD were 38% (26-50%) and 40% (28-52%). Non-relapse-related mortality and incidence of relapse at 5-years were 40% (29-52%) and 21% (11-30%) respectively, without any significant impact of the tested variables. Causes of death were transplant-related events in most patients (34 out of the 42 deaths, 81%). This analysis confirms the poor outcome of transformed FA patients and identifies the importance of achieving CR pre-HSCT, suggesting that, in a newly diagnosed transformed FA patient, a cytoreductive approach pre-HSCT should be considered if a donor have been secured.

Published
2020

50. Drug Repositioning Suggests a Role for the Heat Shock Protein 90 Inhibitor Geldanamycin in Treating COVID-19 Infection

Author

Iyad Sultan, Abdelghani Tbakhi, and Scott C. Howard

Subjects
Drug repositioning, chemistry.chemical_compound, Coronavirus disease 2019 (COVID-19), chemistry, business.industry, Heat shock protein, Medicine, Pharmacology, Geldanamycin, business
Abstract

Drug repositioning offers an unmatched opportunity to offer novel therapeutics to treat SARS family of coronaviruses (SARS-FCoVs); an issue that became extremely urgent with the spreading of a novel virus with potential to threaten the lives of millions of people. Hereby, we analyzed a dataset of patients who presented with SARS during the 2003 outbreak. We established a gene signature that defines differential gene expression in patients who were sick with SARS vs. healthy controls and convalescent patients. We used a robust platform to conduct drug repositioning based on clustered gene expression and pathway enrichment to identify best matching drugs. We identified 55 agents of potential benefit. In most of these drugs we were able to establish a link to previous related research, use as antiviral, or at least a hypothetical role in treating SARS-FCoVs. Most notably, the heat shock protein 90 (hsp90) emerged as a major component that enables viruses to hijack infected cells through the process of autophagy. Almost half of the drugs identified could be linked to hsp90. As such, we propose using hsp90 inhibitors, mainly geldanamycin and its derivatives, to treat COVID-19.

Published
2020
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