Association Of BCR-ABL Alternative Splice Variants with Disease Progression, Treatment Response and Survival in Chronic Myeloid Leukemia Patients Treated with Firstline imatinib Monotherapy

Background: Alternative RNA splicing has diverse biological effects in heath as well as disease. It also contributes to cancer onset and progression. Chronic Myeloid Leukemia (CML) results due to BCR-ABL fusion oncogene that is created due to chromosomal translocation t [9; 22] [q34; q11]). BCR-ABL is target of tyrosine kinase inhibitors (TKIs). BCR-ABL through alternative splicing can generate b2a2, b3a2 and some other rare splicing variants. BCR-ABL variants may vary in their response to TKI treatment and disease progression potential, which is a major factor contributing to dismal treatment outcome in CML. Objective: The objective of this study is to investigate correlation of BCR-ABL splice variants with TKI treatment outcome and survival in three phases of CML that has rarely been studied previously.Methods: BCR-ABL splice variants were studied using reverse transcriptase PCR (RT-PCR). in 70 CML patients from three phases of CML who were receiving imatinib (TKI) treatment.Results: Frequencies of different BCR/ABL splice variants like b3a2, b2a2 and b3a2+b2a2 were 49 (70%), 15 (21.4%) and 6 (8.6%), respectively. Splice variant b2a2 were more common (53.3%) in chronic phase CML (CP-CML) while b3a2 had higher frequency in advanced phases of CML (44.9%). CML patients with b2a2 transcript had better complete cytogenetic response and major molecular response to TKI treatment overall (100% vs. 24.5%) as well as in CP-CML (100% vs. 85.7%) and superior survival when compared to patients with b3a2 splice variant. All patients who died had male gender, less than 33 years age, b3a2 transcript, advanced phases of CML and imatinib resistance.Conclusions: Splice variant b3a2 was associated with CML progression, poorer survival and inferior treatment outcome as compared to b2a2. Further investigations on BCR-ABL splice variants and their roles in CML pathogenesis can provide deeper insights into CML biology and new targets for BCR-ABL positive leukemia treatment.          Keywords: CML; BCR-ABL splice variants; Progression; Survival; Treatment outcome 

Teledentistry-Knowledge, Practice, and Attitudes of Dental Practitioners in Saudi Arabia: A Nationwide Web-Based Survey

The present survey assessed the knowledge, attitudes, and practice of teledentistry (TD) among dental practitioners in Saudi Arabia. This questionnaire-based cross-sectional study was conducted with dental interns and practicing dentists in Saudi Arabia. An online questionnaire was sent to all potential respondents. Questions related to knowledge, practice, attitudes, and training regarding TD were presented. A total of 603 (227 dental interns, 376 practicing dentists) completed the questionnaire. Generally, the participants revealed poor knowledge and practice of TD, with only 38% having heard about TD and only one-quarter of the sample (23.2%) reporting practicing TD at their current workplace. However, most of the participants expressed positive attitudes and a willingness to practice TD in the future. Specialists and those in practice for >5 years showed significantly better knowledge and practice of TD than general dentists and those with lesser clinical experience (p > 0.01). While only one-fifth of the participants (20.2%) reported having attended a workshop/lecture about TD, the majority (69.7%) felt that they needed training on TD. The results revealed poor knowledge, practice, and training with regard to TD among practicing dentists in Saudi Arabia. However, the positive attitude expressed by most of the participants towards practicing TD in the future is an encouraging sign for dental educators and planners of oral health care. Continuous education through periodic workshops and training courses on TD is crucial to improve dentists’ knowledge, practice, and attitudes towards TD. Integration of TD topics into undergraduate/postgraduate curricula is highly recommended. Special attention should be directed to training general dental practitioners and junior dentists

Relationship between apical periodontitis and missed canals in mesio-buccal roots of maxillary molars: CBCT study

الملخص: أهداف البحث: تتضمن أهداف الدراسة: ١) تقييم مدى انتشار القنوات المفقودة في الجذور البوغية الوسطى للأسنان الطواحين العلوية المعالجة عن طريق العلاج الجذري والعلاقة بينها وبين التهاب اللثة المحيط بالجذر، ٢) دراسة العلاقة بين وجود قناة البوغية الوسطى الثانية المفقودة المندمجة أو المنفصلة ومعدل انتشار التهاب اللثة المحيط بالجذر، ٣) دراسة العلاقة بين الجودة التقنية للعلاج الجذري في قناة البوغية الوسطى الأولى ومعدل انتشار التهاب اللثة المحيط بالجذر. طرق البحث: تم الحصول على ودراسة ٨٠٠ صورة من التصوير بالأشعة المقطعية المخروطية من سجلات ٨٠٠ مريض على مدى ستة أشهر. تضمنت المعلمات الملاحظة لكل سن: أ) رقم السن، ب) وجود قناة مفقودة في الجذر البوغي الوسطي، ج) تشكيل القناة البوغية الوسطى الثانية المفقودة (مندمجة أو منفصلة)، د) قبولية العلاج الجذري من الناحية التقنية للقنوات البوغية الوسطى الأولى المعالجة، هـ) نتيجة المؤشر الشعاعي الجذري على التصوير بالأشعة المقطعية المخروطية. النتائج: تم اختيار ٢٠٣ طاحنة علوية من ١٤٨ صورة من التصوير بالأشعة المقطعية المخروطية. كانت معدلات انتشار القناة البوغية الوسطى الثانية ٨٨,٢٪ في الأسنان الطواحين العلوية الأولى و٦٢,٧٪ في الأسنان الطواحين العلوية الثانية. تم العثور على القناة البوغية الوسطى الثانية في ١٦٤ من الأسنان الطواحين العلوية المعالجة من خلال العلاج الجذري. خلال العلاج، تم تفويتها في ١٥٠ سن (٩١,٥٪) وتم علاجها في ١٤ سن (٨,٥٪). أظهرت الدراسة أن 100% من الأسنان التي تم تفويتها في العلاج الجذري لها التهاب لثة محيط بالجذر، بينما ٣٥,٧٪ من الأسنان التي تم علاجها تحتوي على التهاب لثة محيط بالجذر. ظهرت الفروق في الانتشار كفروق ذات دلالة إحصائية. كانت القناة البوغية الوسطى الثانية المفقودة المندمجة أكثر انتشارا (٥٥,٢٪) من القناة البوغية الوسطى الثانية المفقودة المنفصلة (٣٣,٥٪). كان معدل انتشار التهاب اللثة المحيط بالجذر أعلى في الأسنان التي كانت تحتوي على قناة بوغية وسطى ثانية مندمجة (١٠٠٪) مقارنة بالأسنان التي كانت تحتوي على قناة بوغية وسطى ثانية منفصلة (٤٠٪). كانت الفروق في الانتشار تحمل دلالة إحصائية. الاستنتاجات: يبدو أن هناك علاقة قوية بين تفويت القناة البوغية الوسطى الثانية في أسنان الطواحين العلوية المعالجة عن طريق العلاج الجذري ووجود التهاب اللثة المحيط بالجذر. يتطلب الكشف والعلاج الصحيح للقناة البوغية الوسطى الثانية مهارة ومعرفة كبيرتين من قبل أطباء الأسنان لتجنب التهاب اللثة المحيط بالجذر. Abstract: Objectives: The objectives of this study were to: (1) assess the frequency of missed canals in the mesiobuccal root (MB) of endodontically treated maxillary molars and its association with apical periodontitis (AP); (2) examine the correlation between the presence of a confluent or separate missed MB2 canal and the prevalence of AP; and (3) examine the correlation between the technical quality of endodontic treatment in the MB1 canal and the prevalence of AP. Methods: We obtained and examined 800 cone-beam computed tomography (CBCT) scans from 800 patient records over 6 months. The parameters noted for each tooth included the tooth number; presence of missed canals in the MB root; configuration of missed MB2 canals (confluent or separate); technical acceptability of root canal treatment (RCT) of treated MB1 canals; and the CBCT periapical index score. Data were analyzed in SPSS version 24. Results: A total of 203 maxillary molars from 148 CBCT scans were included. The MB2 canal prevalence was 88.2% in maxillary first molars and 62.7% in maxillary second molars. MB2 was found in 164 endodontically treated maxillary molars. During treatment, MB2 was missed in 150 (91.5%) and treated in 14 (8.5%) teeth. A total of 103 teeth (50.73%) had AP, which was observed in 67.3% of teeth with a missed MB2 canal but only 14.3% of teeth with a treated MB2 canal. The prevalence of AP was 43.7% in teeth with confluent MB2 canals and 80.9% in teeth with separate MB2 canals. Conclusion: The MB2 canal frequency was significantly higher in the examined maxillary first molars than the maxillary second molars. The MB2 canal was missed in most teeth that underwent endodontic treatment. The AP prevalence was relatively higher in endodontically treated maxillary molars with missed MB2 canals

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population