Clinical Characteristics and Outcomes of CML in Adolescents and Young Adults.

BACKGROUND: While Chronic Myeloid Leukemia (CML) is a disease of older adults, there is a growing population of adolescent and young adults (AYAs) with CML. This study evaluated the clinical characteristics and outcomes of CML in AYAs. PATIENTS AND METHODS: Data from medical records of adults with chronic phase CML diagnosed and treated at our center from 2011until 2021were retrospectively analyzed. Age between 18 and 29 years was used to define AYAs. Response to tyrosine kinase inhibitors (TKIs), progression to accelerated phase (AP) or blast crisis (BC), event-free survival (EFS) and overall survival (OS) were compared between AYAs and older adults. RESULTS: Among 163 patients included, 41 (25.1%) were AYAs. AYAs were more likely to be males (P = .02), to present with symptoms (P = .004), had a higher median white blood cell count (P = .007), neutrophil count (P = .029), eosinophil count (P = 0.01), low-risk Sokal (P = .033) and Hasford (P = .005) groups. TKI-sensitivity as well as median times for achievement of complete cytogenetic and major molecular response were comparable between both groups. After a median follow-up of 76 (range: 11-235) months, there was no difference in OS (P = .528), or cumulative incidence of transformation to accelerated phase or blast crisis (P = .11). On the other hand, AYA had an inferior EFS (P = .034). CONCLUSION: A quarter of the patients diagnosed with CML in our population were AYAs. Despite being characterized as "lower-risk," they presented with a greater disease burden, had a shorter EFS but comparable OS. Further studies are needed to better understand the disease biology of this group.

Clinical Characteristics, Prognostic Factors and Treatment Outcomes of Patients with Bone-Only Metastatic Breast Cancer.

Introduction: Bone is the most frequent site of breast cancer metastasis. Differences between those who present with de novo bone-only metastasis (BOM) and those who progress to bone-only disease following a diagnosis of early-stage breast cancer are not clear. Such differences in clinical course might have an impact on the aggressiveness of treatment. This study presents the clinical and pathological features, along with treatment outcomes, of breast cancer patients with BOM in relation to the timing and type of bone metastasis. Patients and Methods: Patients with breast cancer and BOM were retrospectively reviewed. De novo BOM was defined as bone metastasis diagnosed at presentation or within the first 4 months of follow-up. Treatment outcomes of patients with de novo, compared to those with subsequent BOM, are presented. Results: 242 patients, median age (range) at diagnosis was 52 (27-80) years were enrolled. The majority of the patients (77.3%) had de novo BOM with multiple sites of bone involvement (82.6%). At a median follow-up of 37.7 months, the median overall survival (OS) for patients with de novo BOM disease was significantly shorter than those who developed so subsequently; 40.8 months (95% CI, 51.1-184.1) compared to 80.9 months (95% CI, 36.4-47.9), p < 0.001. Tumor grade, hormone receptor status and type of bone lesions (lytic versus sclerotic) had a significant impact on survival outcomes. Conclusion: Breast cancer with de novo BOM is a distinct clinical entity with unfavorable prognosis and is associated with shorter survival. Several risk factors for poor outcomes were identified and might inform treatment plans.

Genomic Epidemiology of SARS-CoV-2 in Seychelles, 2020-2021.

Seychelles, an archipelago of 155 islands in the Indian Ocean, had confirmed 24,788 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the 31st of December 2021. The first SARS-CoV-2 cases in Seychelles were reported on the 14th of March 2020, but cases remained low until January 2021, when a surge was observed. Here, we investigated the potential drivers of the surge by genomic analysis of 1056 SARS-CoV-2 positive samples collected in Seychelles between 14 March 2020 and 31 December 2021. The Seychelles genomes were classified into 32 Pango lineages, 1042 of which fell within four variants of concern, i.e., Alpha, Beta, Delta and Omicron. Sporadic cases of SARS-CoV-2 detected in Seychelles in 2020 were mainly of lineage B.1 (lineage predominantly observed in Europe) but this lineage was rapidly replaced by Beta variant starting January 2021, and which was also subsequently replaced by the Delta variant in May 2021 that dominated till November 2021 when Omicron cases were identified. Using the ancestral state reconstruction approach, we estimated that at least 78 independent SARS-CoV-2 introduction events occurred in Seychelles during the study period. The majority of viral introductions into Seychelles occurred in 2021, despite substantial COVID-19 restrictions in place during this period. We conclude that the surge of SARS-CoV-2 cases in Seychelles in January 2021 was primarily due to the introduction of more transmissible SARS-CoV-2 variants into the islands.

Learning needs assessment for multi-stakeholder implementation science training in LMIC settings: findings and recommendations.

BACKGROUND: Despite significant progress in the field of implementation science (IS), current training programs are inadequate to meet the global need, especially in low-and middle-income countries (LMICs). Even when training opportunities exist, there is a "knowledge-practice gap," where implementation research findings are not useful to practitioners in a field designed to bridge that gap. This is a critical challenge in LMICs where complex public health issues must be addressed. This paper describes results from a formal assessment of learning needs, priority topics, and delivery methods for LMIC stakeholders. METHODS: We first reviewed a sample of articles published recently in Implementation Science to identify IS stakeholders and assigned labels and definitions for groups with similar roles. We then employed a multi-step sampling approach and a random sampling strategy to recruit participants (n = 39) for a semi-structured interview that lasted 30-60 min. Stakeholders with inputs critical to developing training curricula were prioritized and selected for interviews. We created memos from audio-recorded interviews and used a deductively created codebook to conduct thematic analysis. We calculated kappa coefficients for each memo and used validation techniques to establish rigor including incorporating feedback from reviewers and member checking. RESULTS: Participants included program managers, researchers, and physicians working in over 20 countries, primarily LMICs. The majority had over 10 years of implementation experience but fewer than 5 years of IS experience. Three main themes emerged from the data, pertaining to past experience with IS, future IS training needs, and contextual issues. Most respondents (even with formal training) described their IS knowledge as basic or minimal. Preferences for future training were heterogeneous, but findings suggest that curricula must encompass a broader set of competencies than just IS, include mentorship/apprenticeship, and center the LMIC context. CONCLUSION: While this work is the first systematic assessment of IS learning needs among LMIC stakeholders, findings reflect existing research in that current training opportunities may not meet the demand, trainings are too narrowly focused to meet the heterogeneous needs of stakeholders, and there is a need for a broader set of competencies that moves beyond only IS. Our research also demonstrates the timely and unique needs of developing appropriately scoped, accessible training and mentorship support within LMIC settings. Therefore, we propose the novel approach of intelligent swarming as a solution to help build IS capacity in LMICs through the lens of sustainability and equity.

Dietary inflammatory index and odds of breast cancer: A case-control study.

Breast cancer (BrCA) is one of the most commonly diagnosed cancers and is the leading cause of cancer deaths in women worldwide. This study aimed to examine the association between the dietary inflammatory index (DII®) and BrCA among Jordanian women. A total of 400 adult women were enrolled into this case-control study. Cases were 200 women recently diagnosed with BrCA selected from the two hospitals that provide cancer therapy in Jordan. They were matched on age, income, and marital status with 200 BrCA-free controls. DII scores were calculated from dietary data that were collected in a face-to-face interview conducted between October 2016 and September 2017 using a validated food frequency questionnaire. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% CIs. The study results revealed no significant associations between DII scores in relation to the odds of developing BrCA after multivariable adjustment including age, education, total energy, BMI, number of pregnancy, contraceptive use, lactation, smoking, and family history of BrCA. Stratified analyses by obesity status showed that overweight/obese participants in the highest DII tertile had a >75% increased BrCA risk (OR of 1.77 [95% CI, 1.01-3.12]) compared with participants in the lowest tertile, after adjusting for age. The results from this study showed no significant relationship between the proinflammatory potential of the diet and BrCA risk in the overall study population. However, results stratified by weight category indicated an effect of diet-associated inflammation on BrCA risk in the overweight/obese group. Results of the study are consistent with a recommendation aimed at maintaining higher diet quality, that is, adopting healthy diets characterized by low DII scores in order to reduce the risk for BrCA.

Analysis of FLT3-Activating Mutations in Patients With Acute Myelogenous Leukemia in Jordan: Association With FAB Subtypes and Identification of Subgroups With Poor Prognosis.

BACKGROUND: FLT3 mutations are common in acute myeloid leukemia (AML), particularly in French-American-British M2 subtype AML and in cytogenetically normal (CN) AML; however, its incidence in Jordan is poorly studied. An FLT3 mutation implies poor prognosis in AML patients. We aimed to assess the incidence and prognostic value of FLT3 mutations in AML in Jordan. PATIENTS AND METHODS: One hundred thirty-two newly diagnosed unselected AML patients were included. Patient data were collected, including demographics as well as morphologic, cytogenetic, and molecular testing results. FLT3 mutations were detected by real-time reverse transcriptase PCR, next-generation sequencing, or both. Survival analysis and comparisons of incidence, remission rate, relapse, and survival outcomes between FLT3-mutated and wild-type groups were done and prognostic factors identified. RESULTS: FLT3 mutation was detected in 40% of AML patients. The highest incidence was associated with M2 subtype AML (47%) and CN-AML (50%). There was a significant negative association between FLT3 mutations and overall survival (OS), as well as a trend toward improved relapse-free survival, with 3-year OS being 19.17% vs 34.16% (P < .0001) and 33.6% vs 71.0% (P = .085), respectively. Patients with FLT3 mutation had a significantly better complete remission rate after induction (67.9% vs 63.3%, P = .001). Also, OS improved in patients with complete remission (P = .0015) and who then continued to allogeneic hematopoietic cell transplantation compared to FLT3 wild-type patients (P < .001). CONCLUSION: FLT3 mutation is common in Jordanian AML patients, with the highest incidence occurring in patients with M2 or CN disease. It implies a poor prognosis, with poor OS and relapse-free survival, which may be abrogated by early allogeneic transplantation and/or peritransplantation provision of FLT3 inhibitors.

External quality assessment for HIV rapid tests: challenges and opportunities in Haiti.

HIV rapid diagnostic tests (RDTs) are instrumental in scaling-up HIV testing services (HTS) in low-income and middle-income countries (LMICs). HIV misdiagnosis is a growing concern in the era of expanded and decentralised access to HTS. External quality assurance (EQA) programme including proficiency testing (PT) for HIV RDTs is a priority to guarantee the accuracy and reliability of the patients' result. Here we are sharing Haiti's 11 years' experience in implementing HIV RDTs EQA programme to help address some of the challenges faced by other LMICs. HTS is expanding beyond laboratory walls and HIV RDTs are increasingly performed by non-laboratory personnel and closer to the community. EQA programmes for HIV RDTs in Haiti have faced significant challenges. In expanded HTS settings, non-laboratory personnel (nurses, aid-nurses) involved in HIV RDT are usually undertrained and participate poorly in PT programs. In more than half of the lab enrolled in the PT programme in Haiti, the panels are always tested by the most experienced technician, defying the purpose of the program which is to evaluate the performance of the technician performing the test daily. EQA programme in Haiti and other LMICs are usually not tailored to address community HIV testing challenges. With decreased funding and absence of government financial commitment to HIV RDTs EQA programmes, more innovative and cost-efficient strategies are sought to ensure the quality of HIV diagnosis in LMICs. Qualified human resources, continuous training, supervision and community-tailored PT programmes remain key components for the success of HIV RDT quality management.

Four cycles of adriamycin and cyclophosphamide followed by four cycles of docetaxel (NSABP-B27) with concomitant trastuzumab as neoadjuvant therapy for high-risk, early-stage, HER2-positive breast cancer patients.

BACKGROUND: The majority of breast cancer patients in Jordan are diagnosed at a young age and present with metastatic or locally advanced disease. The National Surgical Adjuvant Breast and Bowel Project Protocol B27 (NSABP-B27) (four cycles of adriamycin and cyclophosphamide [AC] followed by four cycles of docetaxel) is a standard neoadjuvant regimen in our institution. In this study, we report the efficacy of adding trastuzumab to docetaxel in this regimen for high-risk human epidermal growth factor receptor 2 (HER2)-positive early-stage disease. PATIENTS AND METHODS: Consecutive HER2-positive breast cancer patients treated with this regimen were included. Treatment was given at standard doses and schedules as reported in NSABP-B27. Trastuzumab was given with docetaxel and then continued for 1 year. RESULTS: A total of 121 patients (mean age 45.4 years) were included. The majority had high-risk features including large tumor size, positive axillary lymph nodes, and grade III disease. Three patients did not complete the planned cycles of AC due to a lack of response. Eight (6.6%) patients missed at least one cycle of docetaxel. Following neoadjuvant therapy, 119 patients underwent surgery, of whom 59 (49.6%) patients achieved pathological complete response. The response was higher in node-negative patients (64.0 vs 45.7%; P=0.03) and in hormone receptor-negative disease patients (69.7 vs 41.9%; P=0.018). Breast-conserving surgery was performed in 21.5% of the patients. The median disease-free survival (DFS) for the whole group was not reached while the 3- and 5-year DFS rates were 84.2 and 74.1%, respectively. CONCLUSION: Trastuzumab added to the NSABP-B27 regimen is a unique combination. When used in high-risk patients, as in our study, outcomes similar to reported data were achieved without unexpected toxicities.