World Health Organization Diagnostic Criteria Research Articles

Prevalence of iron deficiency and anemia in pediatric heart transplant recipients.

The prevalence of iron deficiency and anemia in the setting of modern-day maintenance immunosuppression in pediatric heart transplant (HTx) recipients is unclear. The primary aim was to determine the prevalence of iron deficiency (serum ferritin<30ng/mL±transferrin saturation<20%) and anemia per World Health Organization diagnostic criteria and associated risk factors. Single-center, cross-sectional analysis of 200 consecutive pediatric HTx recipients(<21 years old) from 2005 to 2021. Data were collected at 1-year post-HTx at the time of annual protocol biopsy. Median age at transplant was 3 years (IQR.5-12.2). The median ferritin level was 32ng/mL with 46% having ferritin<30ng/mL. Median transferrin saturation (TSAT) was 22% with 47% having TSAT<20%. Median hemoglobin was 11g/dL with 54% having anemia. Multivariable analysis revealed lower absolute lymphocyte count, TSAT<20%, and estimated glomerular filtration rate<75mL/min/1.73m2 were independently associated with anemia. Ferritin<30ng/mL in isolation was not associated with anemia. Ferritin<30ng/mL may aid in detecting absolute iron deficiency while TSAT<20% may be useful in identifying patients with functional iron deficiency±anemia in pediatric HTx recipients. Iron deficiency and anemia are highly prevalent in pediatric HTx recipients. Future studies are needed to assess the impact of iron deficiency, whether with or without anemia, on clinical outcomes in pediatric HTx recipients.

Abstract 3497: Glioma Immune Microenvironment Composition Calculator (GIMiCC): A method of estimating the proportions of eighteen key cell types from human brain tissue assayed using Illumina DNA methylation microarray technology

Abstract Precise detection of both tumor subclass and immune composition is critical in the pursuit of personalized immunotherapeutic treatment strategies for glioma. DNA methylation (DNAm) biomarkers are promising on both fronts. DNAm-based biomarkers for molecular classification have been developed and integrated into World Health Organization (WHO) diagnostic criteria. However, prediction of the tumor microenvironment is not as well defined. To fill this gap, we present GIMiCC, an approach for cellular deconvolution of DNAm microarray data for four WHO 2021 tumor subclasses: glioblastoma, oligodendroglioma, grade 2/3 astrocytoma and grade 4 astrocytoma. Using data from 17 isolated cell types, we describe the derivation of the deconvolution libraries and test the method on independent datasets from the Cancer Genome Atlas (TCGA) and the DKFZ molecular neuropathology classifier (PMID: 29539639). We utilize GIMiCC to illustrate that DNAm-based glioma classification is unlikely to be biased by compositional variation. In addition, we utilize GIMiCC to identify composition independent DNAm alterations that are associated with high immune infiltration. Our future work aims to optimize GIMiCC and advance the clinical evaluation of glioma with this new tool. Citation Format: Steven C. Pike, John K. Wiencke, Ze Zhang, Annette M. Molinaro, Devin C. Koestler, Brock C. Christensen, Karl T. Kelsey, Lucas A. Salas. Glioma Immune Microenvironment Composition Calculator (GIMiCC): A method of estimating the proportions of eighteen key cell types from human brain tissue assayed using Illumina DNA methylation microarray technology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3497.

Clinical and prognostic characteristics of pediatric acute myeloid leukemia with myelodysplasia-related changes under different diagnostic criteria

Objective: To evaluate the clinical and prognostic differences in acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) children under different diagnostic criteria (World Health Organization (WHO) 2016 and WHO 2022 criteria). Methods: In this retrospective cohort study, clinical characteristics and prognosis information of 260 acute myeloid leukemia (AML) children admitted to Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from August 2017 to August 2021 were analyzed retrospectively. According to WHO 2016 and WHO 2022 diagnostic criteria, patients were divided into AML-MRC group and non-AML-MRC group, the prognostic and genetic differences between two groups were compared respectively. Meanwhile, the characteristics of children with 8 MRC-related genes defined in WHO 2022 diagnostic criteria were described. Mann-Whitney U test, chi-square test were used for comparison between groups. Survival curve was plotted by Kaplan-Meier method, and comparison between groups was performed by Log-Rank method. Results: Among the 260 children, there were 148 males and 112 females. The follow-up time was 26 (16, 38) months. A total of 28 children (10.8%) were diagnosed with AML-MRC according to the WHO 2016 diagnostic criteria. Compared with non-AML-MRC children, the frequency of PTPN11, RUNX11, SH2B3, MPL and STAG2 mutations was higher in AML-MRC children (25.0% (7/28) vs.4.3% (10/232), 14.3% (4/28) vs.3.9% (9/232), 10.7% (3/28) vs.2.2% (5/232), 10.7% (3/28) vs.2.2% (5/232), 10.7% (3/28) vs.0.9% (2/232), all P<0.05). The 2-year overall survival (OS) and events free survival (EFS) rate of 28 AML-MRC children under WHO 2016 diagnostic criteria were worse than those of 232 non-AML-MRC children ((62.1±10.8)% vs. (94.5±1.6)%, χ2=22.1,P<0.001;(48.0±10.6)% vs. (70.9±3.2)%, χ2=6.33,P=0.012). Twenty-seven children (10.4%) were eventually diagnosed with AML-MRC according to WHO 2022 criteria, their 2-year OS rate were worse than 233 non-AML-MRC children ((60.8±11.1)% vs. (94.5±1.6)%, χ2=24.49,P<0.001), and there was no statistically significant difference in EFS rate between two groups at 2 years ((55.1±10.8)% vs. (70.1±3.2)%, χ2=2.44, P=0.119). Conclusions: Compared with the 2022 WHO diagnostic criteria, the survival rates of children with AML-MRC under the 2016 WHO diagnostic criteria were worse than that of children without MRC.The new version of the AML-MRC diagnostic criteria emphasizes the importance of genes.

High-grade HER2-positive mucoepidermoid carcinoma of the breast: a case report and review of the literature

BackgroundMucoepidermoid carcinoma of the breast is a rare special type of salivary gland-like tumor of the breast, usually displaying triple-negative phenotype. To date, only 64 cases have been reported in the English literature. Herein, we report the first case of mucoepidermoid carcinoma of the breast with human epidermal growth factor receptor 2 gene amplification.Case presentationA 58-year-old Caucasian woman treated with breast-conserving surgery, radiotherapy, and chemotherapy for an invasive breast carcinoma of no special type, relapsed 20 years later in the ipsilateral left breast. Histological examination of the core needle biopsy of the relapse deferred to the surgical specimen for the definitive diagnosis, because of the broad differential diagnosis. On the resected specimen we observed the presence of a poorly differentiated carcinoma with mucoepidermoid carcinoma of the breast typical features consisting of epidermoid, intermediate and mucinous cells lacking true keratinization, in keeping with the latest World Health Organization diagnostic criteria. The mucoepidermoid carcinoma of the breast was weakly estrogen receptor and androgen receptor positive and progesterone receptor negative, but exceptionally showed human epidermal growth factor receptor 2 gene amplification. Mastermind-like transcriptional coactivator 2 gene translocations were not detected by fluorescent in situ hybridization. The patient received adjuvant chemotherapy with anti-human epidermal growth factor receptor 2 therapy but no endocrine therapy. After 61 months of follow-up, no signs of local or distant recurrence were observed.ConclusionsMucoepidermoid carcinoma of the breast is a very rare entity. Despite being most frequently triple negative, the standard evaluation of receptor status is mandatory, as well as strict application of World Health Organization diagnostic criteria for correct patient management.

Diagnostic Performance of Red Blood Cell Indices, Serum Erythropoietin, and JAK2 Mutation Testing for the Evaluation of Polycythemia Vera at High Altitude

Introduction: Polycythemia vera (PV) is a clonal myeloproliferative neoplasm associated with mutation of Janus kinase 2 ( JAK2) in virtually all patients. Patients with PV typically present with constitutional symptoms and thrombotic complications related to myeloproliferation but can present with only mild or no symptoms. In 2016, the World Health Organization (WHO) diagnostic criteria for PV were revised to use lower hemoglobin and hematocrit cut-off levels in order to avoid missing masked polycythemia. Accordingly, a hemoglobin concentration of more than 16 g/dL (HCT&amp;gt;48%) for females and 16.5 g/dL (HCT&amp;gt;49%) for males can be considered for PV evaluation (previously &amp;gt;18.5 g/dL for men and &amp;gt;16.5 g/dL for women). In conjunction, concerns arise about the unnecessary evaluation of individuals with otherwise high-normal hemoglobin levels, more so for those living at high altitude. Altitude exposure, amongst others, decreases plasma volume to increase [Hb] which may accordingly muddle the diagnosis of PV at altitude. Nonetheless, Red Cell Mass (RCM) is seldom assessed in clinical practice. In addition, red blood cell count, related indices, and serum erythropoietin may also be affected by high altitude, and their diagnostic performance in the evaluation of PV at altitude has not been prospectively assessed. Method: We collected lab records for all JAK2 requests over three years (2020-2022) in two referral hospitals serving a population residing at an altitude of 2,270-3,000 meters above sea level. Indications for requests, as well as laboratory data and imaging, were gathered. Complete blood count (CBC) and other laboratory values were collected when ordered within one week of JAK2 testing. For CBC, EDTA anticoagulated samples were processed using Sysmex XN-3100. For JAK2 testing, RNA isolated from peripheral blood samples (using the MagNA Pure System) was reverse-transcribed, amplified, and sequenced for any mutations involving exons 12, 13, 14, or 15 using an ABI 3730 XL genetic analyzer. For serum EPO, frozen serum samples were outsourced to Bio Scientia Labs, Germany. Reference values for serum erythropoietin were lab generated at 4.3-29 mIU/ml and were not validated for our altitude. . Results:Of the 208 JAK2 tests performed during the reviewed period, 132 (63.4%) were for polycythemia (Table 1). The JAK2 V617F mutation was found in 22 (16.7%) patients, with 10 (45.5%) of them being men. No JAK2 mutation other than the exon 14 V617F substitution was found. JAK2-positive patients had a median age of 61 years, while JAK2-unmutated patients had a median age of 47 years. Overt polycythemia, according to the WHO 2016 classification, was identified in 15 (68.2%) , while the remainder had masked PV ( defined as increased RBCs with normal hemoglobin/ HCT). Patients with PV had significantly higher RBCs and lower MCV/MCH/MCHC compared to those with JAK2-unmutated polycythemia. They also exhibited significant elevation of RDW-CW and significant neutrophilia, basophilia, thrombocytosis, and splenomegaly. All PV patients with available serum EPO tests had low values (median 2 mIU/ml). Conclusion: At altitude, patients with PV show the same age and sex characteristics as those living at low elevations. Patients with PV have higher RBCs and lower MCV/MCH/MCHC compared to those with JAK-unmutated (secondary) polycythemia. RDW is significantly increased in patients with PV, reflecting an associated iron deficiency. Serum EPO performed well at altitude to suggest the presence of PV. The low rate of positive JAK2 mutation in our high-altitude cohort may reflect poor selection of subjects and over-workup of otherwise altitude-associated erythrocytosis. Isolated mild polycythemia at altitude remains common. Using hemoglobin/hematocrit alone to select patients for PV evaluation has a low positive predictive value and may be associated with unnecessary workup. RBC indices and RDW, along with an evaluation for iron status, might help select those more likely to have PV and could decrease unnecessary workups.

Determinants of outcomes of childhood severe Malaria: A multi-centric study

BackgroundsSevere malaria (SM) has remained a major global health challenge, disproportionately affecting children in endemic areas. Understanding the factors that influence childhood SM outcomes is critical for developing contextualized early warning scores, effective prevention, and treatment strategies. MethodsThis is a retrospective, multicenter study conducted between year 2019 and 2022 involving children diagnosed with SM based on World Health Organization (WHO) diagnostic criteria. Multivariate logistic regression was used to identify the determinants of in-hospital mortality from significantly associated factors on bivariate analysis. ResultsOf the 7765 children admitted to emergency rooms, 997 (12.8%) had SM, with a median age of 4 (IQR: 2.7). M: F ratio of 1.2:1. Anemia (353: 35.4%), hemoglobinuria (348: 34.9%), cerebral malaria (331: 33.1%), and prostration (325: 32.6%) were the most common manifestations of SM. Half (494, 49.5%) of the children had only one form of SM, followed by a combination of three forms (270: 27.1%) of SM. Nine of 43 children with severe acute kidney injury received peritoneal dialysis, while 19 received haemodialysis. Severe shock (75.0%) and a patient with respiratory distress syndrome received mechanical ventilation support. The determinants of increased mortality included the first day of admission [OR (95% CI):24.44 (9.792, 61.007)], and manifestations of shock with a 17-fold [OR (95% CI): 17.682 (4.159, 75.196)] increased mortality. ConclusionSM still carries a significant risk of increased mortality, the need for dialysis, and mechanical ventilation support. The first 24 h after admission, as well as the shock, are determinants of increased mortality.

The Use of Bone Density Scan in Monitoring Treatment Response in Patients Diagnosed with Osteoporosis: A Retrospective Cohort Study.

Osteoporosis is characterized as a metabolic bone disease defined by low bone mineral density (BMD) and bone tissue degeneration, particularly a reduction in the number of trabeculae and a drop in cortical bone thickness, and a rise in porosity, which is mainly due to an imbalance between bone resorption and formation. As a result, it increases bone fragility, and the susceptibility to fracture increases, especially among the elderly. The objective is to assess the effectiveness of dual-energy X-ray absorptiometry (DXA) scan in monitoring the response to osteoporosis treatment and compare the scan's response to different osteoporosis treatments. This retrospective cohort study included 51 adults selected from 300 patients diagnosed with osteoporosis based on World Health Organization (WHO) diagnostic criteria of a T-score of -2.5. Data were acquired from the electronic medical records between 2016 and 2019 from a private hospital in Dubai, United Arab Emirates (UAE). The study included sociodemographic characteristics, biomedical parameters, comorbidities, history of fracture, medications, laboratory, and DXA scan results. Ninety-four percent of the patients were females; the mean (±SD) age was 58.1 ± 11.5 years. Most patients were expatriates (84.3%), of which Asian ethnicity was 66.7%. The mean (±SD) duration of osteoporosis was 2.82 ± 1.8 years. Eleven (21.6%) patients had a history of fragility fracture. Ninety-six percent of the patients had vitamin D deficiency. One-third (29.4%) of the patients had hyperparathyroidism. Alendronate/cholecalciferol, received by nine patients (17.6%), showed a significant improvement (p = 0.018) in the BMD of the femoral neck among the study group. In conclusion, the DXA scan as a monitoring tool has shown a significant improvement in the BMD of the femoral neck among patients taking alendronate/cholecalciferol treatment compared to other medications.

Prevalence of Low Bone Mass and Osteoporosis in Ireland: the Dual-Energy X-Ray Absorptiometry (DXA) Health Informatics Prediction (HIP) Project.

Osteoporosis is a common disease that has a significant impact on patients, healthcare systems, and society. World Health Organization (WHO) diagnostic criteria for postmenopausal women were established in 1994 to diagnose low bone mass (osteopenia) and osteoporosis using dual-energy X-ray absorptiometry (DXA)-measured bone mineral density (BMD) to help understand the epidemiology of osteoporosis, and identify those at risk for fracture. These criteria may also apply to men ≥50 years, perimenopausal women, and people of different ethnicity. The DXA Health Informatics Prediction (HIP) project is an established convenience cohort of more than 36,000 patients who had a DXA scan to explore the epidemiology of osteoporosis and its management in the Republic of Ireland where the prevalence of osteoporosis remains unknown. In this article we compare the prevalence of a DXA classification low bone mass (T-score < -1.0) and of osteoporosis (T-score ≤ -2.5) among adults aged ≥40 years without major risk factors or fractures, with one or more major risk factors, and with one or more major osteoporotic fractures. A total of 33,344 subjects met our study inclusion criteria, including 28,933 (86.8%) women; 9362 had no fractures or major risk factors, 14,932 had one or more major clinical risk factors, and 9050 had one or more major osteoporotic fractures. The prevalence of low bone mass and osteoporosis increased significantly with age overall. The prevalence of low bone mass and osteoporosis was significantly greater among men and women with major osteoporotic fractures than healthy controls or those with clinical risk factors. Applying our results to the national population census figure of 5,123,536 in 2022 we estimate between 1,039,348 and 1,240,807 men and women aged ≥50 years have low bone mass, whereas between 308,474 and 498,104 have osteoporosis. These data are important for the diagnosis of osteoporosis in clinical practice, and national policy to reduce the illness burden of osteoporosis. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Contribution of lowered hemoglobin threshold value in the diagnosis of polycythemia vera: Comparison of 2016 and 2008 WHO criteria.

Polycythemia vera (PV) diagnosis remains a difficult task despite various updates in the 2016 World Health Organization (WHO) diagnostic criteria compared to 2008 criteria. This study aimed to examine the biochemical and clinical features of patients diagnosed with PV using the WHO 2016 criteria but would have been missed by the WHO 2008 criteria, and to ascertain the impact of the lowered thresholds on PV diagnosis. A total of 229 patients with suspected myeloproliferative neoplasms were included in this cross sectional study. The study group was divided with regard to hemoglobin values. Group A consisted of 126 patients with hemoglobin values of ≤ 18.5 g/dL in males and ≤ 16.5 g/dL in females. Group B comprised 103 patients with hemoglobin values of > 18.5 g/dL in males and > 16.5 g/dL in females. The number of PV diagnoses increased to 145 from 87 (increased by 66.67%) when the 2016 diagnostic criteria were employed rather that the 2008 criteria. Mean age and the frequency of female subjects were lower in Group A compared to Group B. The groups were similar in terms of chronic obstructive pulmonary disease/obstructive sleep apnea syndrome, spleen status, smoking status, and mean corpuscular volume, white blood count, neutrophil, eosinophil and platelet values. red blood cells and lactate dehydrogenase values were significantly higher, while lymphocyte counts were significantly lower in Group B. With the introduction of WHO 2016 criteria, we found a significant increase in the number of patients who were candidates for PV testing and were ultimately diagnosed with PV. These findings support the diagnostic value of the 2016 WHO criteria, and by extension, the lowered thresholds for detection of patients requiring further analysis.

Multisystem inflammatory syndrome in children during the COVID-19 waves: data from the Juvenile Inflammatory Rheumatism cohort.

Multisystem inflammatory syndrome in children (MIS-C) is a new condition that first appeared in children and adolescents during the COVID-19 pandemic. We aimed to describe the diagnostic course, clinical and biological manifestations, and treatment of MIS-C during the first three COVID-19 waves. We extracted patient data from the Juvenile Inflammatory Rheumatism (JIR) cohort. We analyzed data for patients meeting the World Health Organization diagnostic criteria for MIS-C from the start of the COVID-19 pandemic from March 2020 to June 30, 2021. We then compared data for patients in wave one to those in waves two and three. We identified 136 patients with MIS-C. The median age decreased but not significantly during the waves, from 9.9 years to 7.3 years (p = 0.105). Boys represented 52.2% (n = 71) of patients, and 46% (n = 41) of patients originated from sub-Saharan Africa (p < 0.001). Patients presented less diarrhea (p = 0.004), respiratory distress (p < 0.001), and myocarditis (p < 0.001) with progressive waves. Biological inflammation also decreased, namely, C-reactive protein level (p < 0.001), neutrophil count (p = 0.004), and albumin level (p < 0.001). Patients received more corticosteroids (p < 0.001) and required less ventilation support (p < 0.01) and less inotrope treatment (p < 0.001) in the later waves. The duration of hospitalization gradually decreased (p < 0.001), as did critical care unit admissions (p = 0.002). Over the three COVID-19 waves, with a change in the management of MIS-C, children in the JIR cohort in France showed a less severe disease course, in particular, a greater use of corticosteroids. This observation may reflect the impact of both improved management and different SARS-CoV-2 variant.

VEGFA rs3025039 is associated with phenotype severity of myelofibrosis-type megakaryocyte dysplasia.

VEGFA rs3025039 is associated with phenotype severity of myelofibrosis-type megakaryocyte dysplasia.

Association between different behavioral factors and dental caries among children attending the dental clinics in a sample from Saudi Arabia

BackgroundThis study aimed to assess the association between different behavioral factors and the prevalence of dental caries among children attending the dental clinic in a sample from the Hail and Tabuk regions, Saudi Arabia.MethodA cross-sectional study design was employed to determine the burden of dental caries in teeth and key associated factors among 6-12-year-old children who attended different dental clinics. The data was recruited from Hail and Tabuk districts, Saudi Arabia. The study included only Saudi nationals, whose parents could fill out the self-administered questionnaire and provide informed consent for their child’s dental examination at clinics. Children underwent a simple dental examination based on the World Health Organization diagnostic criteria for oral health surveys. The Decayed, Missed, Filled Tooth (DMFT) index developed by the World Health Organization (WHO) was utilized to assess dental caries. Descriptive statistics were performed to describe categorical variables. The mean DMFT was compared between girls’ and boys’ and the children from Hail and Tabuk regions using the Mann-Whitney U-test. The chi-square test was used to examine the association between different behavioral factors and the prevalence of dental caries.ResultsOf the total 399 children examined, 203 (50.9%) were boys, whilst 196 (49.1%) were girls. The prevalence of dental caries was correlated with the cleaning tool, parental educational level, dental visits, and sugar consumption (p < 0.05). However, brushing frequency failed to demonstrate a correlation with the prevalence of dental caries (p > 0.05). The total mean DMFT for the studied sample was 7.81 (SD ± 1.9). Caries’ experience was made up mainly of decayed teeth. Decayed teeth made up an average of 3.30 (SD ± 1.07). The total mean of missing and filling teeth was 2.51 (SD ± 0.99) and 1.99 (SD ± 1.26) respectively. There was no statistically significant difference in the mean DMFT and gender or between Hail and Tabuk (p < 0.05).ConclusionSaudi Arabia continues to have a high prevalence of dental caries compared to the global norm.

Triple-Negative Primary Myelofibrosis: A Bone Marrow Pathology Group Study

Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm driven by canonical gene mutations in JAK2, CALR, or MPL in >80% of the cases. PMF that lacks these canonical alterations is termed triple-negative PMF (TN-PMF). The pathologic and genetic characteristics of TN-PMF compared with those of conventional PMF with canonical driver mutations (DM-PMF) have not been well studied. We aimed to identify clinicopathologic and molecular genetic differences between patients with TN-PMF (n = 56) and DM-PMF (n = 89), all of whom fulfilled the 2016 World Health Organization diagnostic criteria for PMF. Compared with the control group, patients in the TN-PMF group were more likely to have thrombocytopenia and less likely to have organomegaly. The bone marrow in patients with TN-PMF showed fewer granulocytic elements and more frequent dyserythropoiesis. Cytogenetic analysis showed a higher incidence of trisomy 8. Targeted next-generation sequencing revealed a lower frequency of ASXL1 mutations but enrichment of ASXL1/SRSF2 comutations. Our findings demonstrated several clinicopathologic and molecular differences between TN-PMF and DM-PMF. These findings, particularly the observed mutation profile characterized by a higher frequency of ASXL1 and SRSF2 comutation, suggest that at least a subset of TN-PMF may be pathogenetically different from DM-PMF, with potential prognostic implications.

Clinicopathological and survival profile of patients with salivary gland myoepithelial carcinoma: A systematic review.

In this systematic review, we aimed to evaluate the clinicopathological and prognosis data of patients with myoepithelial carcinoma (MC) of the salivary glands. MEDLINE/PubMed, Scopus, and Embase search was performed with the keywords "myoepithelial carcinoma", "malignant myoepithelioma", and "salivary glands". Only primary salivary glands MC that fulfilled the World Health Organization diagnostic criteria were included. The Joanna Briggs Institute tool was used to assess the risk of bias. Forty-three studies (comprising data from 71 cases) met the inclusion criteria. The patients having MC showed a mean age of 56.4 ± 19.6 years with no sex predilection. The parotid was the most affected gland (49.3%) (49.3%). Clinically, the MC presented as an asymptomatic (65.1%) mass (84%). The most common histological findings were the presence of clear tumor cells (39.7%) and multinodular growth patterns (60.7%). Multivariate analysis showed plasmacytoid cell type (p=0.010) and solid growth pattern (p=0.003) were related to decreased disease-free survival (DFS). Surgery alone was the most used treatment (53.5%). Patients with a combination of treatments (surgery, radiation therapy with/without chemotherapy) showed a longer DFS (p=0.049). The 2-year and 5-year overall survival rates were 67.5% and 46.1% respectively. Salivary gland MC is a rare salivary cancer with no sex predilection, with a higher incidence in the parotid gland. Cell type, growth pattern, and treatment type may be related to a lower DFS. Overall, salivary gland MC presented low recurrence and metastasis rates.

Direct image to subtype prediction for brain tumors using deep learning.

Deep Learning (DL) can predict molecular alterations of solid tumors directly from routine histopathology slides. Since the 2021 update of the World Health Organization (WHO) diagnostic criteria, the classification of brain tumors integrates both histopathological and molecular information. We hypothesize that DL can predict molecular alterations as well as WHO subtyping of brain tumors from hematoxylin and eosin-stained histopathology slides. We used weakly supervised DL and applied it to three large cohorts of brain tumor samples, comprising N = 2845 patients. We found that the key molecular alterations for subtyping, IDH and ATRX, as well as 1p19q codeletion, were predictable from histology with an area under the receiver operating characteristic curve (AUROC) of 0.95, 0.90, and 0.80 in the training cohort, respectively. These findings were upheld in external validation cohorts with AUROCs of 0.90, 0.79, and 0.87 for prediction of IDH, ATRX, and 1p19q codeletion, respectively. In the future, such DL-based implementations could ease diagnostic workflows, particularly for situations in which advanced molecular testing is not readily available.

Pharmacist-lead screening for diabetic peripheral neuropathy using Michigan Neuropathy Screening Instrument (MNSI)

Background Diabetic peripheral neuropathy (DPN) is highly prevalent among Jordanian patients, mostly are asymptomatic. Early recognition and appropriate management of neuropathy is important to improve symptoms, reduce sequelae, and improve quality of life. This study aims at exploring the role of pharmacists in the early recognition of DPN and providing quick screening for the presence of it among diabetic patients. Material and Methods A cross-sectional study was conducted at multi-pharmacy settings, in Irbid, Jordan. Twenty trained pharmacists who had bachelor’s degrees in pharmacy participated in data collection. A total of 400 patients with confirmed diagnosis of type 2 diabetes mellitus (DM) according to the World Health Organization diagnostic criteria were recruited. DPN was assessed using the translated Arabic version of Michigan Neuropathy Screening Instrument (MNSI) history version. Results The mean MNSI questionnaire score for all participants was 4.40 ± 3.00. Mean age of the patients was 62.6 ± 10.7 years old and duration of diabetes was 8.25 ± 6.9. DN was present in 23.7% of the population. Diabetic patients with neuropathy were older than patients without neuropathy (p < 0.05) and had had diabetes longer (p < 0.05). Poor glycemic control, hypertension and gender, were significantly risk factors for DN (p < 0.05). Conclusions In addition to delivering medications, this study suggests that pharmacists can have a role in screening and counseling about diabetic peripheral neuropathy using a simple objective, and non-invasive tool and also can determine level of damage and risk.

Mylox-1: An Open-Label, Phase IIa Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral LOXL2 Inhibitor, GB2064, in Myelofibrosis

Background: GB2064 is a high-affinity, selective, pseudo-irreversible, small-molecule inhibitor of LOXL2, a secreted glycoprotein that crosslinks extracellular matrix collagens and elastin which contributes to stiffness and loss of function of fibrotic organs. GB2064 is being developed as an oral treatment for myelofibrosis (MF), a rare myeloproliferative disease with high morbidity and mortality. Janus kinase (JAK) inhibitor therapy has brought significant advancements in the treatment of MF, but a significant proportion of patients would eventually discontinue treatment, predominantly due to the development of cytopenias (Kyukendall et al.,Ann Hematol. 2018). Thus, a substantial unmet need to develop well-tolerated disease-modifying treatments that reduce bone marrow fibrosis to improve haematological parameters, splenomegaly, symptom burden and quality of life remains. Aims: To assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and clinical effects of oral GB2064 (1000 mg twice daily [BID]), which was administered to participants with primary or secondary myelofibrosis (PMF/SMF) for 9 months. Methods: Open-label study in 16 adult participants diagnosed with PMF or SMF in accordance with World Health Organization diagnostic criteria (Barbui et al., Blood Cancer 2018; Cruz et al.,Expert Rev Hematol. 2020), who are not taking a JAK inhibitor and therefore are likely to be refractory, intolerant or ineligible for such inhibitors; participants had Eastern Cooperative Oncology Group performance status 0-2, and the clinical laboratory parameters were within appropriate limits per protocol. Primary endpoint is safety and tolerability. Safety and tolerability, PK, PD and appropriate MF-specific assessments will take place at all visits except Day 7, Day 15 and Month 4 when only safety and tolerability will be assessed (Fig A). Bone marrow biopsies, magnetic resonance imaging of spleen and quality of life measures, MPN-10 and EQ-5D-5L are performed at prespecified timepoints within the protocol. Exploratory endpoints include LOXL2 binding assay in the circulation, relationships between PK plasma exposure, PD markers, and markers of clinical activity, fibrosis and inflammation biomarkers (YKL-40, PAI-1, PDGF, CCN2, collagen formation and degradation neoepitopes). The study is not formally powered. Participants who derive benefit may continue therapy for an additional 3 years (Fig B). Results: At least half of the intended participants have been enrolled and are on GB2064 treatment as of June 2022. One participant successfully completed the study in May 2022 and moved to the extension phase. GB2064 was detected in bone marrow biopsies at concentrations close to those in the plasma and demonstrated LOXL2 target engagement in the systemic compartment using a LOXL2 binding assay in plasma. No significant safety concerns were observed at a dose of 1000 mg BID to date. Conclusions: MYLOX-1 is designed to explore the safety and clinical effects of GB2064, a novel small-molecule LOXL-2 inhibitor, addressing bone marrow fibrosis as a main element of MF, with the aim to decrease extramedullary haematopoiesis and improve haematological parameters, symptom burden and the quality of life for patients with MF. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

IMMUNIZATION STRESS-RELATED RESPONSES DURING SKIN TESTING AND CHALLENGE TO COVID-19 VACCINES: A CASE SERIES

<h3>Introduction</h3> While IgE-mediated hypersensitivity to COVID-19 vaccines may occur, many adverse reactions (ARs) to COVID-19 vaccination are non-immunologic in nature and meet criteria for immunization stress-related response (ISRR). <h3>Methods</h3> Patients were referred to our allergy clinic for skin testing (prick with undiluted vaccine, intradermal with 1:100, 1:10, and undiluted vaccine) and graded challenge with COVID-19 vaccines (Pfizer, Moderna, or Johnson and Johnson) between July 2021 and June 2022. ARs were documented and treated accordingly. ARs were characterized as ISRR based on the World Health Organization diagnostic criteria or non-ISRR if symptoms were outside those criteria. <h3>Results</h3> 83 patients underwent skin testing (ST) and/or graded challenge (GC) with COVID-19 vaccines in our office. Twenty-six (31.3%) patients had one or more symptoms of AR in the immediate period following ST/GC while 57 patients completed vaccination without any AR. 15 patients (1 to ST, 14 to challenge dose) had symptoms consistent with ISRR. 14 of these patients completed full vaccine dose. No patients had any significant objective changes in physical exam. 11 patients had ARs not meeting ISRR criteria. The most reported symptom in this cohort was subjective pruritus. 6 of these patients were able to complete full vaccination dose. <h3>Conclusion</h3> Most patients with AR consistent with ISRR successfully completed full COVID-19 vaccine administration. Some patients with symptoms suggestive of histamine-mediated reaction had no objective findings and were also able to complete vaccination. Our experience highlights the need to consider ISRR in evaluation of vaccine reactions and supports the safety of COVID-19 vaccination in patients with ISRR.

Mutational Landscape of Patients Referred for Elevated Hemoglobin Level.

Background: Since the identification of JAK2 V617F and exon 12 mutations as driver mutations in polycythemia vera (PV) in 2005, molecular testing of these mutations for patients with erythrocytosis has become a routine clinical practice. However, the incidence of myeloid mutations other than the common JAK2 V617F mutation in unselected patients referred for elevated hemoglobin is not well studied. This study aimed to characterize the mutational landscape in a real-world population of patients referred for erythrocytosis using a targeted next-generation sequencing (NGS)-based assay. Method: A total of 529 patients (hemoglobin levels >160 g/L in females or >165 g/L in males) were assessed between January 2018 and May 2021 for genetic variants using the Oncomine Myeloid Research Assay (ThermoFisher Scientific, Waltham, MA, USA) targeting 40 key genes with diagnostic and prognostic implications in hematological conditions (17 full genes and 23 genes with clinically relevant “hotspot” regions) and a panel of 29 fusion driver genes (>600 fusion partners). Results: JAK2 mutations were detected in 10.9% (58/529) of patients, with 57 patients positive for JAK2 V617F, while one patient had a JAK2 exon 12 mutation. Additional mutations were detected in 34.5% (20/58) of JAK2-positive patients: TET2 (11; 19%), DNMT3A (2;3.4%), ASXL1 (2; 3.4%), SRSF2 (2; 3.4%), BCOR (1; 1.7%), TP53 (1; 1.7%), and ZRSR2 (1; 1.7%). Diagnosis of PV was suspected in 2 JAK2-negative patients based on the 2016 World Health Organization (WHO) diagnostic criteria. Notably, one patient carried mutations in the SRSF2 and TET2 genes, and the other patient carried mutations in the SRSF2, IDH2, and ASXL1 genes. Three JAK2-negative patients with elevated hemoglobin who tested positive for BCR/ABL1 fusion were diagnosed with chronic myeloid leukemia (CML) and excluded from further analysis. The remaining 466 JAK2-negative patients were diagnosed with secondary erythrocytosis and mutations were found in 6% (28/466) of these cases. Conclusion: Mutations other than JAK2 mutations were frequently identified in patients referred for erythrocytosis, with mutations in the TET2, DNMT3A, and ASXL1 genes being detected in 34.5% of JAK2-positive PV patients. The presence of additional mutations, such as ASXL1 mutations, in this population has implications for prognosis. Both the incidence and mutation type identified in patients with secondary erythrocytosis likely reflects incidental, age-associated clonal hematopoiesis of indeterminate potential (CHIP).

Serum Homocysteine Levels and Blood Pressure in Type 2 Diabetic Patients in Zaria, Northern Nigeria.

Hyperhomocysteinaemia and hypertension are established cardiovascular risk factors for cardiovascular diseases. However, knowledge on the contributions of these risk factors in diabetic patients is limited. The purpose of this study was to assess serum homocysteine concentrations and blood pressures in Type 2 diabetic patients in Zaria, Kaduna State, Northern Nigeria. In this cross-sectional study, serum homocysteine levels and blood pressures were assessed in 140 men and women with type 2 diabetes aged 20-60 years in Ahmadu Bello University Teaching Hospital (ABUTH), Zaria, Nigeria. Diabetes mellitus status was confirmed biochemically according to World Health Organization diagnostic criteria for classification of diabetes mellitus. Hypertension was confirmed according to World Health Organization diagnostic criteria. Serum homocysteine concentration was measured using ELISA method. Data for selected clinical/demographic variables were obtained from fasting blood samples using an interviewer-administered questionnaire. The mean values of serum homocysteine, Waist circumference (WC), Hip circumference (HC), WC: HC, Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) in diabetic patients were significantly higher (p=0.000) than those of controls, whereas the mean values of age, weight (WT), height (H) and Body Mass Index (BMI) in diabetic patients were similar to those of controls (p=0.972, p=0.271 and p=0.825 respectively). We observed that that High levels of homocysteine and high blood pressures all contributes to the (WT), height (H) and Body Mass Index (BMI) in diabetic patients were similar to those of controls (p=0.972, p=0.271 and p=0.825 respectively). We observed that that High levels of homocysteine and high blood pressures all contributes to the development of cardiovascular complications in people with type 2 diabetic mellitus.