The Descriptive Features of Primary Spontaneous Pneumothorax Patients in King Abdulaziz Medical City, Riyadh, Saudi Arabia.

Background Primary spontaneous pneumothorax (PSP) is a fairly prevalent disorder in emergency medicine. PSP most frequently affects tall, thin male smokers and is most prevalent during adolescence. Published literature contains a wide range of Primary Spontaneous Pneumothorax (PSP) recurrence rates, but there is limited information on the variables affecting recurrence. Objective To identify the descriptive features of PSP in King Abdulaziz Medical City, Riyadh, Saudi Arabia. Methods This retrospective cross-sectional study was conducted in Surgery King Abdulaziz Medical City, Riyadh, Saudi Arabia. Including all PSP patients from 2016-2021, excluding pediatric and geriatric patients. Participants were selected using a simple random sampling technique, and data were collected from hospital records. Data analysis was conducted by using SPSS. Results In this study, we included a total of 131 participants. Most were males (93.1%), and most were aged between 21-30 years. Our findings showed that most PSP events occurred in winter (28.6%). Followed by fall (25.7%), summer (25.0%), and spring (20.7%). Concerning the smoking status of our respondents, our results revealed that most of them were active smokers (72.5%). Left-PSP was the most commonly reported type of PSP (43.5 %), followed by right-PSP (38.9%), non-simultaneous bilateral PSP (14.5%), and bilateral simultaneous PSP (3.1%). Moreover, we found that the recurrence rate of PSP was 42%. Regarding the management of PSP, almost half of the respondents were managed initially by Chest tube. The most frequently used surgical option was VATS- Bullectomy with Abrasion Pleurodesis. Finally, the recurrence rate of PSP was 42% among the patients. The percentage of patients with one recurrence only was 65.5% among the patients with recurrent PSP, second recurrence at 29.1%. Third, Fourth, and Fifth had the same recurrence percentage of 1.8%, and these percentages came to be statistically significant. (P value < 0.001) Conclusion Our study concluded that PSP was more prevalent in tall, thin, young male smokers. Almost half of the respondents suffered from at least one recurrence attack of PSP. The majority of the patients with recurrences experienced one recurrence only, and the second recurrence was estimated to be almost one-third. There is no significant association between the occurrence and seasons of the attack at a time. Most of the participants were managed initially by a chest tube. The most frequently used surgical option was Video Assisted Thoracoscopic Surgery (VATS) with abrasion pleurodesis.

Acquired Brown Syndrome After a Fist Punch: A Case Report.

A 15-year-old male presented with double vision in the left and upward gaze following a hit in the right orbital region. The orthoptic assessment revealed -2 limitation of elevation in the adduction position of the right eye and right hypotropia of 20 prism diopter (PD) in the left gaze and right hypotropia of 10 PD in the upward gaze. He was diagnosed with traumatic Brown syndrome and planned for superior oblique lengthening surgery for the right eye. Two months postoperatively, the patient has a normal extra-ocular motor function with the elimination of diplopia and significant improvement of elevation of the right eye in the adduction position. Herein, we discuss the clinical features, etiologies, tailored evaluation, and management for the patient with traumatic Brown syndrome.

Chronic Kidney Disease Education Class Improves Rates of Early Access Creation and Peritoneal Dialysis Enrollment.

Background Most patients with end-stage kidney disease begin hemodialysis (HD) in an unplanned fashion at a late stage, necessitating the commencement of HD with a temporary venous catheter, the least favorable option. Alternative modalities of kidney replacement therapy (KRT), peritoneal dialysis (PD), and preemptive transplant offer similar or better outcomes than HD at a lower overall cost, and yet they remain underutilized in Saudi Arabia. Early education may help prepare patients with advanced chronic kidney disease (CKD IV and V) to accept their disease and choose a KRT modality that minimizes complications and matches their lifestyle. The aim of the study is to assess the impact of a pilot educational class on therapy choices and outcomes. Methodology In a cross-sectional study, we conducted phone interviews and reviewed medical records of 81 attendees of the multidisciplinary monthly educational class about KRT that was held at the King Abdulaziz Medical City (KAMC) from January 2017 to October 2021. The interview was conducted at least one year after the participants attended the class. The study proposal, consent, and questionnaire were approved by the King Abdulaziz International Medical Research Center. Patient data was retrieved from KAMC electronic medical record system. Results Volunteer participation in the survey was high (62/81). For the respondents, a preemptive kidney transplant was the most preferred (48/62, 77%) option for KRT. Among the preferred fallback options, HD was the most frequently chosen (29/62, 47%) compared to PD (26/62, 41.9%). At the time of the interview, a great majority of the patients (54/62, 87%) was already on KRT, including about half (26/54, 48%) on HD via a catheter, and the rest about equally divided between those on HD via an arteriovenous (AF) fistula (13/54, 24%) and those on PD (15/54, 28%). Thus, half of the respondents on KRT (28/54, 51%) avoided urgent HD catheter commencement. However, because of an unfortunate shortage of donors, only a small minority (2/62, 3%) of patients received preemptive transplantation. Conclusion The KAMC CKD education class helped boost the fraction of patients, significantly above the national average, who accepted the diagnosis of kidney failure and pursued preemptive native HD access or enrolled in PD.

CLINICAL VALIDATION OF ANKRD36 MUTATIONS AS A NOVEL BIOMARKER FOR MONITORING EARLY PROGRESSION AND TIMELY CLINICAL INTERVENTIONS IN BLAST CRISIS CML.

Background: Chronic Myeloid Leukemia (CML) is initiated in the bone marrow due to the chromosomal translocation t(9;22), resulting in the fusion oncogene BCR-ABL. Tyrosine kinase inhibitors (TKIs) targeting BCR-ABL have transformed fatal CML into an almost curable disease. However, TKIs lose efficacy during disease progression, and the mechanism of CML progression remains to be fully understood. Additionally, common molecular biomarkers for CML progression are lacking. Our studies previously detected ANKRD36 (c.1183_1184 delGC and c.1187_1188 dupTT) associated exclusively with advanced phase CML. However, clinical validation of this finding was pending. Therefore, this study aimed to clinically validate mutated ANKRD36 as a novel biomarker of CML progression. Materials and Methods: The study enrolled 124 patients in all phases of CML, recruited from Mayo Hospital and Hameed Latif Hospital in Lahore, Punjab, between January 2019 and August 2021. All response criteria were adopted from the European LeukemiaNet guideline 2020. Informed consent was obtained from all study subjects. The study was approved by scientific and ethical review committees of all participating centers.Sanger sequencing was employed to detect ANKRD36 mutations in CML patients in accelerated phase (AP) (n=11) and blast crisis (BC) (n=10), with chronic-phase CML (CP-CML) patients as controls (n=103). Samples were processed using Big Dye Terminator Cycle Sequencing Ready Reaction kits and sequenced using ABI Prism 3730 Genetic Analyzer, and sequencing using forward and reverse primers for ANKRD36. Results: During our study, 17% of CML patients progressed to advanced phases AP-CML n=11 (8.9%) and BC-CML n=10 (8.1%). The chronic- and advanced-phase patients showed significant difference with respect to male-to-female ratio, hemoglobin level, WBC count, and platelet count. Sanger sequencing detected ANKRD36 mutations c. 1183 1184 delGC and c. 1187 1185 dupTT exclusively in all AP- and BC-CML patients but in none of the CP-CML patients. Nevertheless, mutations status was not associated with male-to-female ratio, hemoglobin level, WBC count, and platelet count, which makes ANKRD32 as an independent predictor of early and terminal disease progression in CML. Conclusions: The study confirms ANKRD36 as a novel genomic biomarker for early and late CML progression. Further prospective studies should be carried out in this regard. ANKRD36, although fully uncharacterized in humans, shows the highest expression in bone marrow, particularly myeloid cells. Functional integrated genomic studies are recommended to further explore the role of ANKRD36 in the biology and pathogenesis of CML.

A 3D cone beam computed tomography (CBCT) investigation of mandibular condyle morphometry: Gender determination, disparities, asymmetry assessment and relationship with mandibular size.

OBJECTIVE: CBCT (cone beam computed tomography) analysis of condyle morphometry, to investigate the gender differences, symmetry and relationship with mandibular size. MATERIALS AND METHODS: This is a retrospective study. 800 CBCT scan obtained for the measurement of condyle in anterior-posterior and medio-lateral aspect using OnDemand 3D software. Participants were Saudi nationals of age above 18 years. 395 Males and 405 Females with the mean age of 38.2 ± 10.5 years. Right and left anterior-posterior width and medio-lateral width of the condyle were measured. Condyles were not isolated on the CBCT for volume measurement. RESULTS: Mean right and anterior-posterior condyle width was 9.02 mm and 8.74 mm in males whereas in females it was 9.01 mm 8.69 mm respectively. For males mean medio-lateral width of the condyle in right and left side was 17.40 mm and 16.95 mm. For females, mean medio-lateral width of the condyle in right and left side was 17.14 mm and 16.93 mm. The prediction rate of gender was 57.2% for males and 53.3% for females. Statistically significant differences (p < 0.05) were found in the anterior-posterior and medio-lateral width of right and left condyles among males and females. Left anterior-posterior and medio-lateral width of average vs small mandible shows statistically significant difference (p < 0.05). CONCLUSION: Condyle morphometry is a weak predictor for gender. Irrespective of gender, right and left condyle are asymmetrical in relation to condyle morphometry of anterior-posterior and medio-lateral aspect. Left mandibular condyle morphometry is different in relation to the mandible size.

Discovery and Protein Modeling Studies of Novel Compound Mutations Causing Resistance to Multiple Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia.

OBJECTIVE: BCR-ABL fusion oncogene is the hallmark of chronic myeloid leukemia (CML), causing genomic instability which leads to accumulation of mutations in BCR-ABL as well as other genes. BCR-ABL mutations are the cause of tyrosine kinase inhibitors (TKIs) resistance in CML. Recently, compound BCR-ABL mutations have been reported to resist all FDA approved TKIs. Therefore, finding novel compound BCR-ABL mutations can help and clinically manage CML. Therefore, our objective was to find out novel drug-resistant compound BCR-ABL mutations in CML and carry out their protein modelling studies. METHODOLOGY: Peripheral blood samples were collected from ten imatinib resistant CML patients receiving nilotinib treatment. BCR-ABL transcript mutations were investigated by employing capillary sequencing. Patient follow-up was carried out using European LeukemiaNet guidelines. Protein modeling  studies were carried out for new compound mutations using PyMol to see the effects of mutations at structural level. RESULTS: A novel compound mutation (K245N mutation along with G250W mutation) and previously known T351I utation was detected in two of the nilotinib resistance CML patients respectively while in the rest of 8 nilotinib responders, no resistant mutations were detected. Protein modelling studies indicated changes in BCR-ABL mutant protein which may have negatively impacted its binding with nilotinib leading to drug resistance. CONCLUSION: We report a novel nilotinib resistant BCR-ABL compound mutation (K245N along with G250W mutation) which impacts structural modification in BCR-ABL mutant protein leading to drug resistance. As compound mutations pose a new threat by causing resistance to all FDA approved tyrosine kinase inhibitors in BCR-ABL+ leukemias, our study opens a new direction for in vitro characterization of novel BCR-ABL compound mutations and their resistant to second  generation and third generation TKIs.

Whole exome sequencing identifies a novel FANCD2 gene splice site mutation associated with disease progression in chronic myeloid leukemia: Implication in targeted therapy of advanced phase CML.

Tyrosine Kinase Inhibitors (TKIs) have significantly improved the clinical outcome of BCR-ABL+ Chronic Phase-Chronic Myeloid Leukemia (CP-CML). Nonetheless, approximately one-third of the CP-CML patient's progress to advanced phases of CML (accelerated and blast phase). Impaired DNA repair including mutations in Fanconi anemia (FA) pathway genes are responsible for progression of many cancers. Nevertheless, FA-pathways genes have never been reported in myeloid cancers. Hence, this study was aimed to discover DNA repair genes associated with CML progression. AP-CML patients were subjected to whole exome sequencing along with appropriate controls. A novel splice site FANCD2 mutation was detected. FANCD2 is a well-known FA-pathway gene with established role in DNA repair. This is first report of FA-pathway DNA repair genes in myeloid cancers that can serve as a novel marker of CML progression to clinically intervene CML progression. Further studies are needed to establish the functional role of FANCD2 in CML progression that can provide novel insights into CML pathogenesis. This study also indicates that a combination TKIs and Poly (ADP-ribose) polymerase (PARP) inhibitors like Olaparib (FDA approved anti-cancer drug for FA-pathway gene mutations) could improve the clinical outcome CML patients in accelerated and blast-crisis phases of the disease.

Dental Students' Knowledge and Attitudes towards Antibiotic Prescribing Guidelines in Riyadh, Saudi Arabia.

Background: The use of antibiotics prophylactically and therapeutically in dentistry has become common practice. Inappropriate prescription may lead to adverse side effects and bacterial resistance. During clinical training, dental students in Saudi Arabia are authorized to prescribe antibiotics. Aim: To evaluate dental students’ knowledge and attitudes regarding antibiotic prescription in Riyadh, Saudi Arabia. Methods: A cross-sectional study based on a validated questionnaire consisting of 34 questions focusing on antibiotic indications in dentistry, antibiotic regimens, and knowledge regarding resistance was distributed amongst dental students in five leading dental colleges in Riyadh. Results: A large proportion of students (71.7%) were familiar with the concept of antibiotic resistance. When comparing junior and senior dental students’ knowledge with regards to indications of antibiotic use in commonly encountered conditions, it was found that there was no significant difference in antibiotic prescription frequency between these groups. Most dental students choose to prescribe amoxicillin as their first-choice of antibiotic (88.4%), and most also chose to use it for a duration of 3⁻5 days (69.2%). Conclusions: This study concludes that dental students may prescribe antibiotics inappropriately to manage various conditions when not indicated. This may indicate a defect in education of students with regards to current antibiotic guidelines.