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Over the past decade, studies on microRNA (miRNA) and cancer quickly became known. miRNAs are small non-coding RNAs that play a vital role in regulation of gene expression. In the present study, the expression of miR-27b, miR-29a, and miR-155, their prognostic roles, and their potential targets in chronic lymphocytic leukemia (CLL) and breast cancer (BC) by qRT-PCR were investigated. In two case-control studies, qRT-PCR was used to analyze the peripheral blood serum of 15 CLL patients and tissue samples of 15 BC patients for the expression of miR-27b, miR-29a, and miR-155. miRNA expression levels were calculated using the qRT-PCR method. The results revealed a significant increase in the expression of all miRNAs in patients with BC and CLL compared with respective healthy groups (p < 0.001). In BC patients, there was a significant difference between the expression of miR-155 and miR-29a (p < 0.05), miR-155 and miR-27b (p < 0.01), and miR-27b and miR-29a (p < 0.001). In CLL patients, a significant difference between expression of both miR-27b and miR-29a compared with expression of miR-155 (p < 0.001) was found. Furthermore, a significant association between miR-155 and prevascular invasion was found. Significantly, elevated circulating miRNAs were shown to be BC specific and could differentiate BC tissues from the controls. It was demonstrated that miRNAs used in this study and their expression profiles can be developed as biomarkers for early diagnosis and prognosis of CLL and BC. Further studies utilizing a larger test group of patients would provide identification of miRNAs as key players in intercellular interactions. Keywords: CLL, breast cancer, miRNAs, biomarker, qRT-PCR

Introduction: Despite the significant advances in treatment of patients with multiple myeloma, therapy of patients with high risk disease remains challenging. Maintenance treatment with Lenalidomide following autologous stem cell transplant (ASCT) is the standard of care in patients with multiple myeloma; however its efficacy in patients with high risk features is conflicting. The efficacy of proteasome inhibitors (PI) ± lenalidomide (Len) maintenance in high risk patients has been evaluated in other studies with discrepant results with respect to improvement in long term outcomes. In this study we sought to assess the impact of various maintenance strategies on outcomes of transplant eligible newly diagnosed myeloma patients in the real world setting. Methods: This is a retrospective, single center Canadian cohort study (London, Canada) with the primary objective to compare the PFS in the high risk transplant eligible (TE) newly diagnosed multiple myeloma (NDMM) patients receiving maintenance treatment versus no maintenance post ASCT, diagnosed from January 1,2007 to April 30,2021. Secondary objectives are comparison of PFS, OS and overall response rate (ORR) based on risk group and various maintenance strategies. ORR is defined as partial response or better. To investigate the effect of different variables on survival outcomes we used Kaplan-Meier curves, univariate and multivariate cox regression analysis. Results: In total, 155 TE- NDMM patients were included. 61 (39%) were high risk defined as: deletion 17p, t (4; 14), t (14; 16), 1q amp. One hundred and thirty (84%) patients received PI or Len-based induction therapy. Of the entire cohort, 53 (34%) patients received maintenance treatment post ASCT: 41 Len to progression, 12 Len+Pi. In the entire cohort, ORR was 71% (38 of 53) for patients who received maintenance and 53% (55 of 102) for those who did not receive maintenance (p=0.7). In the 61 high risk patients, 33 received maintenance: 11 Len+PI and 22 Len single agent. ORR was significantly better for maintenance, 63% (21 of 33) compared to 11% (3 of 27) for no maintenance (p=0.0054). Maintenance therapy also influenced PFS. In total, median PFS was significantly higher in patients who received maintenance; with 63% of patients alive and on therapy at 60 months, compared to no maintenance with median PFS of 40 months (HR 0.46,95% CI(025-0.85),p= 0.011). A subgroup analysis of the impact of maintenance between the standard and high risk groups suggested excellent PFS for both: 56.8% for standard and 67.1% for high risk at 60 months. On the other hand, median PFS was dismal for the high risk no maintenance group: only 19 months versus 45.5 months in the standard group ( HR=0.14,95% CI(0.05-0.38), p In the entire cohort there was no difference in the median OS, NYR in both groups at 60 months; 51% in maintenance, 53% in no maintenance (p=0.25). Similarly in the high risk patients median OS was not different, 61 months in maintenance vs NYR in no maintenance (45% vs 52% at 60 months, p=0.38). OS was also not different in high risk patients who received Len+PI vs Len single agent maintenance, NYR vs 61 months (p= 0.68). In the standard risk group median OS was NYR at 60 months in both maintenance and no maintenance groups (p=0.57) Conclusion: In this Canadian single center retrospective cohort study we compared PFS and OS in patients with TE-NDMM who received maintenance compared to those with no maintenance treatment post ASCT. We found PFS was significantly improved in the high risk patients who received maintenance treatment but we found no impact on dual versus single maintenance strategy. This further validates the findings of large phase 3 clinical trials illustrating a positive impact of maintenance treatment post ASCT irrespective of the cytogenetics risk in the real world setting. Although the maintenance treatment could not entirely overcome the worse outcome in the high risk group, more than 40% of the high risk patients who received maintenance were still alive at 60 months. The question of the best maintenance strategy for high risk myeloma patients remains open and further studies are warranted Figure 1 Figure 1. Disclosures Lam: Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees; SeaGen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Hoffmann-La Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees. Phua: Amgen: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria. Louzada: Pfizer: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Celgene: Honoraria.

Introduction: Febrile neutropenia (FN) is a serious potential adverse event of myelosuppressive chemotherapy. Dose-adjusted EPOCH-R (DA-EPOCH-R: etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab, with doses adjusted to induce neutropenia of < 0.5 x 10 9/L) is a chemoimmunotherapy regimen used for aggressive lymphomas including diffuse large B-cell lymphoma, double/triple hit, Burkitt, primary mediastinal, and HIV-associated large cell lymphoma. It is associated with high rates of FN (13-25% of cycles) despite use of prophylactic Septra and granulocyte colony stimulating factor (G-CSF). Fluoroquinolone antibiotics have been used in various hematological malignancies to reduce infection rates while on chemotherapy, but this strategy has never been reported with DA-EPOCH-R. This study was conducted to assess the impact of adding routine Levofloxacin prophylaxis on FN and infection rates in patients receiving DA-EPOCH-R. Methods: This is a combined cohort study comparing the patients who received DA-EPOCH-R for newly diagnosed aggressive lymphoma at the London Regional Cancer Program in London, Ontario, Canada before and after the initiation of routine Levofloxacin prophylaxis in July 2020. The prospective cohort received Levofloxacin 500 mg x 7 days with each cycle starting on cycle day 8 in addition to standard supportive care with Septra and G-CSF. The primary objective was the rate of febrile neutropenia. Secondary objectives included days hospitalized, deaths related to infections, and adverse events secondary to Levofloxacin. Results: Thirty patients who received DA-EPOCH-R in the 5 years preceding the initiation of routine prophylactic Levofloxacin were included in the retrospective cohort. Median age was 58 (range 18-79), 66% were male, and 90% had stage III/IV disease. Total number of cycles of DA-EPOCH-R received was 110, with a median of 4 cycles per patient (range: 1-6). FN developed in 14 patients (46%), and complicated a total of 20 cycles (18%) of DA-EPOCH-R. There were 19 hospital admissions due to FN, with a median duration of hospitalization of 12 days (range 3-120). Two patients died, both due to infection. Thirteen patients have been treated so far in the prospective cohort, 12 of whom received levofloxacin prophylaxis. Median age was 59 (range 23-69), 66% were male, and 76% had stage III/IV disease. Total number of cycles of DA-EPOCH-R received was 60, with a median of 5 cycles per patient (range: 1-6 ). Only 1 patient (8%) developed FN, which complicated a total of 3 cycles (5%) of chemotherapy. All 3 episodes of FN resulted in hospitalization for a median duration of 30 days (range 20-49). There have been no deaths due to infection in this cohort thus far. No concerning adverse effects from Levofloxacin have been observed. Conclusions: Although enrollment in the prospective cohort is ongoing, preliminary data are highly encouraging, with significantly lower rates of FN and death due to infection observed since the introduction of routine Levofloxacin prophylaxis. The addition of Levofloxacin to standard prophylaxis with Septra and G-CSF seems to be an effective way to mitigate the risks to patients on DA-EPOCH-R for aggressive lymphomas, and this strategy is worthy of further study. Disclosures Lam: Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Hoffmann-La Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Honoraria, Membership on an entity's Board of Directors or advisory committees; SeaGen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Phua: NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria.

Cardiac repolarization of black athletes has a distinctive pattern. During an episode of pericarditis, this pattern may evolve into a "pseudonormalized" electrocardiography (ECG). On resolution of the pericardial inflammation, the ECG may return to the normal variant for a black athlete, sounding the alarms of extended disease to the myocardium. Recognizing the normal variant for a black athlete will reduce the need for unnecessary further testing or treatments. The case is discussed in detail.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.To synthesize data on the worldwide prevalence and severity of COPD by geographical region, age groups, and smoking status in a systematic review.A systematic search was performed following Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. International databases including PubMed, Scopus and Web of Science were searched for population- based studies published between January 2004 and May 2015 that reported the prevalence of COPD anywhere in the world. The prevalence of COPD was calculated based on World Health Organization (WHO) regions and sex and severity stages using metaprop. Meta-regression and subgroup analysis were applied to determine the sources of heterogeneity.Sixty papers were screened with a combined subject sample size of 127 598. The prevalence of post-bronchodilator COPD was 12.16% (10.91-13.40%). The pooled prevalence of COPD was 15.70% (13.80-18.59%) in men and 9.93% (8.73- 11.13%) in women. Among all WHO regions, the highest prevalence was recorded in the Region of the Americas (14.53%), and the lowest was recorded in the South-East Asia Region/Western Pacific Region (8.80%). Meta-regression model variables were: sample size, WHO region, study quality score, level of gathering data, publication year, and sampling methods that justified 29.82% of heterogeneity detected among COPD prevalence rates worldwide.Global prevalence of COPD among men is about 5% higher than among women. The most prevalent stage of COPD is stage 1.معدل الانتشار العالمي لمرض الانسداد الرئوي المزمن: استعراض منهجي وتحليل تلوي.مهدي ورمقاني، مينا دهقاني، إلهام حيدري، فارشاد شريفي، سحر سعيدي مقدم، فرشاد فرزادفر.يُعَدُّ مرض الانسداد الرئوي المزمن أحد الأسباب الرئيسية التي تسبب المراضة والوفيات على مستوى العالم.هدفت هذه الدراسة إلى جمع البيانات حول معدل الانتشار العالمي لمرض الانسداد الرئوي المزمن ومدى شدته حسب المنطقة الجغرافية والفئات العمرية وحالة التدخين، وذلك من خلال استعراض منهجي للمواد الطبية المنشورة.أُجري بحث منظَّم اتبع التحليل التلوي للمبادئ التوجيهية الخاصة بالدراسات الرصدية في علم الوبائيات. وتم البحث في قواعد البيانات الدولية، بما في ذلك PubMed و Scopus و Web of Science ، عن الدراسات القائمة على السكان التي أبلغت عن معدل انتشار مرض الانسداد الرئوي المزمن في أي مكان بالعالم، والمنشورة في الفترة بين يناير/كانون الثاني 2004 ومايو/أيار 2015. وتم حساب معدل انتشار مرض الانسداد الرئوي المزمن بناءً على أقاليم منظمة الصحة العالمية والجنس ومراحل شدة المرض باستخدام برنامج Metaprop الإحصائي. وطُبِقت أساليب التحوف التلوي وتحليل المجموعات الفرعية لتحديد مصادر عدم التباين.استُعرضت 60 ورقة بحثية إجمالاً، وبلغ مجموع حجم العينة 127.598 شخصًا. وبلغ معدل انتشار مرض الانسداد الرئوي المزمن ما بعد إعطاء موسع للقصبات 12.16% (10.91 – 13.40%). وبلغ مجموع معدل انتشار مرض الانسداد الرئوي المزمن 15.70% (13.80 – 18.59%) بين الرجال، و 9.93% (8.73 – 11.13%) بين النساء. ومن بين أقاليم منظمة الصحة العالمية، سُجِّل أعلى معدل انتشار في إقليم الأمريكتين (14.53 %)، وأقل معدل انتشار في إقليم جنوب شرق آسيا/إقليم غرب المحيط الهادئ (8.80 %). وفي نموذج التحوف التلوي، شملت المتغيرات ما يلي: حجم العينة، والأقاليم، ومستوى جودة الدراسة للبيانات المُجمَّعة، وسنة النشر، وأساليب أخذ العينات، والتي توضح 29.82% من عدم التباين المكتشف بين معدلات انتشار مرض الانسداد الرئوي المزمن على مستوى العالم.يبدو أن معدل الانتشار العالمي لمرض الانسداد الرئوي المزمن بين الذكور أعلى بنسبة 5% تقريبًا عنه بين النساء. وأكثر المراحل انتشارًا من المرض هو المرحلة الأولى.Prévalence mondiale de la bronchopneumopathie chronique obstructive : analyse systématique et méta-analyse.La bronchopneumopathie chronique obstructive (BPCO) est l’une des principales causes de morbidité et de mortalité dans le monde.Réaliser une synthèse des données relatives à la prévalence et à la gravité de la BPCO par régions géographiques, tranches d’âges et statut tabagique à partir d’une analyse systématique de la littérature médicale disponible.Une recherche systématique a été réalisée conformément aux lignes directrices pour la méta-analyse des études observationnelles (MOOSE). Des recherches ont été lancées dans des bases de données internationales, notamment PubMed, Scopus et Web of Science, afin d’identifier les études populationnelles, publiées entre janvier 2004 et mai 2015, faisant état de la prévalence de la BPCO partout dans le monde. La prévalence de la BPCO a été calculée à l’aide du programme Metaprop en fonction des régions définies par l’Organisation mondiale de la Santé (OMS), du sexe et du stade de sévérité. Des méthodes de méta-régression et d’analyse de sous-groupes ont été appliquées afin d’identifier les sources d’hétérogénéité.Au total, 60 articles ont été analysés portant sur un échantillon composite de 127 598 sujets. La prévalence de la BPCO après utilisation d’un bronchodilatateur était de 12,16 % (10,91 à 13,40 %). La prévalence globale de la BPCO était de 15,70 % (13,80 à 18,59 %) chez les hommes et de 9,93 % (8,73 à 11,13 %) chez les femmes. Sur l’ensemble des régions OMS, la prévalence la plus forte était enregistrée pour les Amériques (14,53 %) et la plus faible pour l’Asie du Sud-Est/le Pacifique occidental (8,80 %). Les variables du modèle de méta-régression utilisé incluaient la taille de l’échantillon, la région, le score de la qualité de l’étude, le niveau des données recueillies, l’année de publication et la méthode d’échantillonnage, justifiant ainsi l’hétérogénéité de 29,82 % associée aux taux de prévalence de la BPCO à travers le monde.La prévalence mondiale de la BPCO chez les hommes s’avère supérieure d’environ 5 % à celle observée chez les femmes. Le stade 1 de la BPCO est celui ayant la prévalence la plus élevé.

Background: Autologous stem cell transplantation (ASCT) as consolidation post induction is standard of care for eligible multiple myeloma patients. Multiple strategies are employed for mobilization of stem cells in ASCT. Cyclophosphamide/GCSF is an effective standard regimen. However there are reported toxicities associated with cyclophosphamide including risk of febrile neutropenia. Since plerixafor was introduced in Canada, this mobilization agent has been increasingly used as needed with GCSF at Kingston Health Science Centre (KHSC), with elimination of cyclophosphamide. There is however high cost associated with plerixafor. To date, there is no standard mobilization regimen across Canada. This retrospective study evaluates mobilization and ASCT outcomes of multiple myeloma patients who had undergone stem cell mobilization with GCSF+/-plerixafor (GP) vs cyclophosphamide/GCSF+/-plerixafor (CyGP) at KHSC. The goal is to analyze the efficacy of each regimen balanced with adverse events to guide optimal mobilization regimen choice. Method: Patient with multiple myeloma who had ASCT at KHSC were selected consecutively based on date of ASCT in a reverse chronological order starting from Jan 2019. From Oct 2015 to March 2018, CyGP was the mobilization regimen used at KHSC. From March 2017 to January 2019, cyclophosphamide was eliminated and GP was used. Both groups could have received plerixafor as needed based on Cancer Care Ontario funding criteria such as failure to achieve target CD34+ cell count. Retrospective chart review was conducted to collect data on demographics, plerixafor use, days of apheresis, total cell collected, rate of febrile neutropenia, length of transplant hospital stay, time to engraftment, and transfusion requirement. Chi-Square, t-test, or Mann Whitney methods were used for test of statistical significance where appropriate. Results: Total 97 patients were included with 47 in the GP group and 50 in the CyGP group (Table 1). Average age was 64 and 63 respectively. 32% of patients in GP group and 36% of CyGP group required plerixafor rescue. No difference in the number of apheresis days were noted in the two groups. Total cell collection was significantly higher in the CyGP group (P Conclusions: Stem cell mobilization with CyGP resulted in significantly higher total collection cell count, and more efficient collection with higher yield on the first 2 days of apheresis. However, there was no difference in the total number of apheresis days. It also did not lead to less plerixafor usage and was associated with possibly higher rate of febrile neutropenia. There was no clinically significant difference in transplant outcomes in terms of transfusion support required, days to engraftment, or length of hospitalization for ASCT. Mobilization with GCSF+/-plerixafor without cyclophosphamide is a non-inferior regimen. Disclosures Bhella: Celgene: Consultancy, Honoraria.

Background: While psychological and behavioral symptoms are a major challenging aspect of dementia, they have not been considered as an important mental health issue in developing countries. The aim of the current study was to explore the prevalence and possible associated factors of psychiatric symptoms seen in patients with dementia. Methods: In a cross sectional study, 101 patients diagnosed with dementia were selected. Appropriated world-wide instruments, such as the Neuropsychiatry Inventory (NPI), Clinical Dementia Rating scale (CDR), barthel index and Cummulative Illmess Rating Scale (CIRS) were used to detect behavioral disturbance, severity of dementia, disability and burden of medical conditions, separately. In this study, the correlation between Behavioral and Psychological Symptoms of Dementia (BPSD) and severity of dementia, activity of daily living, organic dysfunction and type of dementia was also evaluated. Results: Behavioral and Psychological Symptoms of Dementia were frequent in about 70% of the study sample. The most common problematic behaviours were night time behaviours followed by delusion (58%), disinhibition (57%), anxiety (57%), irritability (56%), depression (55%), agitation (55%), and apathy (55%). The least frequent symptom was elation. These behavioral symptoms were significantly correlated with the severity of dementia, greater disability, higher burden of medical conditions, and the level of distress in both patients and their caregivers. Mood symptoms such as depression, anxiety, and elation were not increased with the severity of the dementia. Conclusions: The findings of this study suggested that the three main cluster symptoms were psychosis, behavioral disturbances such as disinhibition, irritability agitation and, mood symptoms including anxiety and depression.