ABSTRACT
Allogeneic hematopoietic stem cell transplant (HSCT) for adults with severe sickle cell disease (SCD) is potentially curative but not commonly utilized therapy due to complications such as graft failure (GF) and organ toxicity. Herein, we are reporting our long-term outcome data of non-myeloablative (NMA) HSCT in adults with severe SCD with emphasis on factors predicting event free survival (EFS). Adults with severe SCD undergoing NMA match-related donor allogeneic HSCT from 2015 to 2021 with at least 12 months of follow-up were included. A total of 200 patients were included with a median age of 26 years (14-43) and 56% were male. The median infused CD34 dose was 13.7 (5.07-25.8), respectively. Median absolute neutrophil count engraftment was 19 (13-39) days with 51% of patients receiving GCSF to expedite recovery. A total of 17 patients experienced GF; 3 as primary and 14 as secondary within a median time of 204 days (40-905). A 76% successfully discontinued sirolimus at the last follow-up. Median follow-up for the cohort is 29.2 (2.1-71.4) months. Estimated 3-year EFS and OS were 88.2% (81.9-92.5) and 94.6% (89.2-97.3). At multivariable analysis, minor ABC incompatibility hazard ratio (HR) 4 (1.3-12.1; 0.014) and allo-antibody against non-ABO donor antigens HR 4.3 (1.3-14.1; 0.016) were significant for EFS. No clonal evolution or myeloid malignancies were seen. This largest single-center report of NMA HSCT in adults with severe SCD further delineated its feasibility, potential toxicities, and fertility outcomes. GF remains a major impediment and appears dependent on ABO matching and non-ABO antibodies.
Subject(s)
Anemia, Sickle Cell , Hematopoietic Stem Cell Transplantation , Humans , Adult , Male , Female , Anemia, Sickle Cell/therapy , Hematopoietic Stem Cell Transplantation/methods , Adolescent , Young Adult , Transplantation, Homologous , Treatment Outcome , Transplantation Conditioning/methods , Graft vs Host Disease/etiology , Follow-Up Studies , Retrospective Studies , AllograftsABSTRACT
Interferon-induced membrane proteins (IFITM) 3 gene variants are known risk factor for severe viral diseases. We examined whether IFITM3 variant may underlie the heterogeneous clinical outcomes of SARS-CoV-2 infection-induced COVID-19 in large Arab population. We genotyped 880 Saudi patients; 93.8% were PCR-confirmed SARS-CoV-2 infection, encompassing most COVID-19 phenotypes. Mortality at 90 days was 9.1%. IFITM3-SNP, rs12252-G allele was associated with hospital admission (OR = 1.65 [95% CI; 1.01-2.70], P = 0.04]) and mortality (OR = 2.2 [95% CI; 1.16-4.20], P = 0.01). Patients less than 60 years old had a lower survival probability if they harbor this allele (log-rank test P = 0.002). Plasma levels of IFNγ were significantly lower in a subset of patients with AG/GG genotypes than patients with AA genotype (P = 0.00016). Early identification of these individuals at higher risk of death may inform precision public health response.
Subject(s)
COVID-19/genetics , Genetic Predisposition to Disease , Membrane Proteins/genetics , RNA-Binding Proteins/genetics , SARS-CoV-2/genetics , Adult , Aged , Aged, 80 and over , COVID-19/mortality , COVID-19/virology , Female , Genetic Association Studies , Genotype , Humans , Interferons/genetics , Male , Middle Aged , Polymorphism, Single Nucleotide/genetics , SARS-CoV-2/pathogenicityABSTRACT
AIM: Chemotherapy-induced peripheral neuropathy (CIPN) is a long-term neurological health issue in patients diagnosed with multiple myeloma (MM). The aim of this study was to assess CIPN symptoms and health-related quality of life (HRQOL) among MM patients. METHODS: A cross-sectional survey was conducted among patients diagnosed with MM in a tertiary care hospital using a self-reported Arabic questionnaire, European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire for CIPN scale (QLQ-CIPN20). The HRQOL was assessed using EORTC multiple myeloma module (QLQ-MY20). Categorical variables were reported in frequency tables and percentages. Age and duration of MM diagnosis were reported as mean and standard deviation. Survey responses were presented using descriptive statistics. RESULTS: In total, 62 patients had participated. Males were 60%. The average age was 58.74 ± 11.49 years. On sensory scale, 20% reported "quite a bit"/"very much" tingling in fingers/hands, 23% in toes/feet, 39% numbness in fingers/hands, 37% in toes/feet, and 43% reported trouble standing or walking. On motor scale, 40% reported trouble walking and 60% had difficulty in climbing stairs/standing up from chair. On autonomic scale, 27% reported orthostatic hypotension and only 13/37 (46%) males reported erectile dysfunction. For HRQOL, 50% reported bone aches/pain, 42% reported back pain, 57% reported feeling ill, 33% reported lost hair, 35% had been thinking about their illness, whereas 28% were worried about future health and 22% had reported being worried about dying. CONCLUSION: MM patients encounter CIPN symptoms with impaired HRQOL. Capturing CIPN as a patient-reported outcome needs to be considered in routine clinical practice.
ABSTRACT
B-cells of the high-grade non-Hodgkin lymphoma Burkitt's lymphoma (BL) overexpress survival oncoproteins, including the proviral integration site for Moloney murine leukaemia virus kinase (Pim)-1, and become apoptosis resistant. Activated death receptor CD95 after ligation with anti-CD95 monoclonal antibody (mAb) resulted in the regression of BL via induction of apoptosis, suggesting a decrease of survival protein expression. Here, CD95-mediated apoptotic pathways in BL B-cell lines (Raji and Daudi) following treatment with anti-CD95 mAb was investigated with the cause-and-effects on pim-1 gene expression, in comparison with leukemic cell line (K562) used as CD95-negative cells. Immunohistochemical staining for CD95 and Pim-1 was performed, and the effects of anti-CD95 mAb on apoptotic signalling using western blotting, on caspase activity and cell survival of BL B-cell and leukemic cell lines were determined. We showed that Raji cells expressed more CD95 receptors than Daudi cells. Half of each population underwent apoptosis accompanied by decreased cell viability after anti-CD95 mAb treatment. Distinct extrinsic and intrinsic CD95-mediated apoptotic pathways in Raji and Daudi cells were revealed by high caspase activity and mitochondrial outer membrane permeabilization, respectively. We observed decreased Pim-1 transcript and protein expression levels with increased heat-shock protein (Hsp)70 and decreased Hsp90 expression in anti-CD95 mAb-treated cells. Throughout the study, K562 cells did not undergo apoptosis upon anti-CD95 mAb treatment. Pim-1 knockdown following to stable transfection with plasmid vectors induced apoptosis and decreased viability of BL and K562 cells. Therefore, CD95-mediated apoptosis induces Pim-1 down-regulation in BL B-cells, but Pim-1 down-regulation cannot fully eradicate BL and leukaemia.
Subject(s)
Apoptosis , Burkitt Lymphoma/genetics , Down-Regulation , Gene Expression Regulation, Neoplastic , Proto-Oncogene Proteins c-pim-1/genetics , fas Receptor/metabolism , Antibodies, Monoclonal/pharmacology , Antineoplastic Agents, Immunological/pharmacology , Apoptosis/drug effects , B-Lymphocytes/drug effects , B-Lymphocytes/metabolism , B-Lymphocytes/pathology , Burkitt Lymphoma/drug therapy , Burkitt Lymphoma/metabolism , Burkitt Lymphoma/pathology , Cell Line, Tumor , Cell Survival , Down-Regulation/drug effects , Gene Expression Regulation, Neoplastic/drug effects , HumansABSTRACT
AIM: This study aimed to (i) assess the level of patient satisfaction and its association with different sociodemographic and healthcare characteristics in an emergency care centre (ECC) in Saudi Arabia and (ii) to identify the predictors of patients' satisfaction. METHODS: A prospective cohort study of 390 adult patients with Canadian triage category III and IV who visited ECC at King Abdulaziz Medical City, Riyadh, Saudi Arabia, between 1 July and end of September 2011 was conducted. All patients were followed up from the time of arrival at the front desk of ECC until being seen by a doctor, and were then interviewed. Patient satisfaction was measured using a previously validated interview-questionnaire, within two domains: clarity of medical information and relationship with staff. Patient perception of health status after as compared with before the visit, and overall life satisfaction were also measured. Data on patient characteristics and healthcare characteristics were collected. Multiple linear regression analysis was used, and significance was considered at p≤0.05. RESULTS: One-third (32.8%) of patients showed high level of overall satisfaction and 26.7% were unsatisfied, with percentage mean score of 70.36% (17.40), reflecting moderate satisfaction. After adjusting for all potential confounders, lower satisfaction with the ED visit was significantly associated with male gender (p<0.001), long waiting time (p=0.032) and low perceived health status compared with status at admission (p<0.001). Overall life satisfaction was not a significant predictor of patient satisfaction. CONCLUSIONS: An appreciation of waiting time as the only significant modifiable risk factor of patient satisfaction is essential to improve the healthcare services, especially at emergency settings.
Subject(s)
Emergency Service, Hospital/standards , Patient Satisfaction , Adult , Female , Humans , Interviews as Topic , Male , Professional-Patient Relations , Prospective Studies , Saudi Arabia , Surveys and Questionnaires , Triage , Waiting ListsABSTRACT
BACKGROUND: Individuals living with sickle cell disease (SCD) have significantly increased emergency department (ED) use compared to the general population. In Saudi Arabia, health care is free for all individuals and therefore has no bearing on increased ED visits. However, little is known about the relationship between quality of life (QoL) and frequency of acute care utilization in this patient population. METHODS: A cross-sectional study was conducted on 366 patients with SCD who attended the outpatient department at King Fahad Hospital, Hofuf, Saudi Arabia. Data were collected through self-administered surveys, which included: demographics, SCD-related ED visits, clinical issues, and QoL levels. We assessed the ED use by asking for the number of SCD-related ED visits within a 6-month period. RESULTS: The self-report survey of ED visits was completed by 308 SCD patients. The median number of SCD-related ED visits within a 6-month time period (IQR) was four (2-7 visits). According to the unadjusted negative binomial model, the rate of SCD-related ED visits increased by (46, 39.3, 40, and 53.5 %) for patients with fever, skin redness with itching, swelling, and blood transfusion, respectively. Poor QoL tends to increase the rate of SCD-related ED visits. Well education and poor general health positively influenced the rate of SCD-related ED visits. Well education tends to increase the rate of SCD-related ED visits by 50.2 %. The rate of SCD-related ED visits decreased by 1.4 % for every point increase in general health. CONCLUSION: Saudi patients with sickle cell disease reported a wide range of SCD-related ED visits. It was estimated that six of 10 SCD patients had at least three ED visits within a 6-month period. Well education and poor general health resulted in an increase in the rate of SCD-related ED visits.
Subject(s)
Anemia, Sickle Cell/physiopathology , Anemia, Sickle Cell/psychology , Emergency Service, Hospital/statistics & numerical data , Quality of Life , Adult , Cross-Sectional Studies , Female , Humans , Male , Risk Factors , Saudi Arabia , Severity of Illness Index , Young AdultABSTRACT
BACKGROUND: There is a lack of research concerning health-related quality of life (HRQoL) in Saudi patients with sickle cell disease (SCD), particularly among adult populations. The aim of the current study was to describe the characteristics of SCD patients and their impact on their quality of life (QoL). METHODS: Six hundred twenty-nine adult SCD patients who attended King Fahad Hospital in Hofuf and King Fahad Central Hospital in Jazan were included in the analysis. Demographic/clinical data were collected and an Arabic version of the Medical Outcomes 36-Item Short-Form Health Survey (SF-36) questionnaire was used to assess QoL. RESULTS: SCD patients who hold a university degree reported positive impacts on the following domains of SF-36: physical role function, vitality, emotional well being, social function, pain reduction, and general health (P = .002, P = .001, P = .001, P = .003, P = .004, and P = .001, respectively). In general, patients with fever, skin redness, swelling, or history of blood transfusion tended to impair the health status of the SF-36. A multivariate analysis revealed that patients with a university degree tended to report high scores of physical role functions, emotional role function, and vitality. Patients with regular exercise tend to increase vitality, social function, general health, and reduce pain. Unemployment tends to lessen vitality and worsen pain. On average, pain, social function, and physical function scores tended to worsen in patients with swelling or history of blood transfusion. CONCLUSIONS: This study highlighted that poor education, fever, skin redness, and swelling were negatively associated with specific components of SF-36. SCD patients with a history of blood transfusion found their QoL poorer, whereas regular exercise tended to improve QoL.
Subject(s)
Anemia, Sickle Cell/psychology , Attitude to Health , Health Status , Psychometrics/instrumentation , Quality of Life/psychology , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Reproducibility of Results , Saudi Arabia , Socioeconomic Factors , Surveys and Questionnaires , Young AdultABSTRACT
BACKGROUND: In the Kingdom of Saudi Arabia, breast cancer (BC) usually presents at advanced stages and more frequently in young pre-menopausal women in comparison to western countries. There is controversy surrounding the efficacy of breast self examination (BSE) for early detection of BC in countries where other methods are available. This study aims to explore the perception towards breast cancer and towards BSE among Saudi women, using the Health Belief Model (HBM). METHODS: A convenient sample of adult Saudi female employees, working at King Abdulaziz Medical City, Riyadh, Saudi Arabia (n = 225), and their non-working adult female family members (n = 208), were subjected to the Arabic version of revised Champion's Health Belief Model Scale (CHBMS) and the Arabic version of Breast Cancer Awareness Measure (CAM), to assess their knowledge and attitude on BC respectively. Percentage mean score (PMS) for each HBM domain was calculated. Significant predictors of BSE practice were identified using logistic regression analysis and significance was considered at p < 0.05. RESULTS: The majority of women heard about BSE (91.2 %), only 41.6 % reported ever practicing BSE and 21 % performed it regularly. Reported reasons for not doing BSE were: not knowing how to examine their breast (54.9 %), or untrusting themselves able to do it (24.5 %). Women were less knowledgeable about BC in general, its risk factors, warning signs, nature and screening measures (PMS:54.2 %, 44.5 %, 61.4 %, 53.2 %, 57.6 % respectively). They reported low scores of; perceived susceptibility, seriousness, confidence and barriers (PMS: 44.8 %, 55.6 %, 56.5 % & 41.7 % respectively), and high scores of perceived benefits and motivation (PMS: 73 % & 73.2 % respectively) to perform BSE. Significant predictors of BSE performance were: levels of perceived barriers (p = 0.046) and perceived confidence (p = 0.001) to BSE, overall knowledge on BC (p < 0.001), work status (p = 0.032) and family history of BC (p = 0.011). CONCLUSIONS: Saudi women had poor knowledge on BC, reported negative attitude towards BSE and their practice was poor. Working women and those with family history of BC, higher perceived confidence and lower perceived barriers on HBM, and those with high level of knowledge on BC were more likely to perform BSE. Breast awareness as an alternative to BSE needs further investigations. HBM was shown as a valid tool to predict BSE practice among Saudi women.
Subject(s)
Breast Neoplasms/diagnosis , Breast Self-Examination , Health Knowledge, Attitudes, Practice , Adolescent , Adult , Awareness , Female , Humans , Logistic Models , Middle Aged , Motivation , Risk Factors , Saudi Arabia , Young AdultABSTRACT
BACKGROUND: Public cord blood banks (CBBs) store cord blood unit (CBU) donations for anyone in need. However, strict regulations need to be followed to build up high-quality bank products that can be used worldwide. We established a public CBB at a tertiary hospital in Saudi Arabia. Here, we investigated the reasons behind rejecting or not collecting CBUs over 2 years (2011-2012) and which steps were implemented to improve the number and quality of storable units. STUDY DESIGN AND METHODS: A total of 2891 mothers were evaluated. Reasons for rejecting donors, not collecting, and rejecting units before or after collection were analyzed and compared for the years 2011 and 2012. RESULTS: A total of 1157 (40%) CBUs were not collected, mainly due to staff availability, and 564 (20%) CBUs were rejected. The main reason for rejecting donations was the mother's or neonate's health. Rejecting CBUs after collection was due to low volume. A total of 1170 (40%) CBUs were successfully collected for potential banking and sent for processing; however, 58% were rejected in the laboratory due to low total nucleated cell counts. Several changes were implemented during the 2 years including physician education and awareness, in utero collection, cesarean collection, and staff recruitment. These changes positively affected the numbers of our collected units. Out of the initially eligible mothers in 2011, only 17% were banked; this was increased to 33% in 2012. CONCLUSIONS: We identified the problems with collecting CBUs for banking and will keep improving our selection process of recruiting more CBUs of high quality.
Subject(s)
Blood Banking/methods , Blood Donors , Fetal Blood , Tertiary Healthcare , Adult , Blood Banks/standards , Female , Humans , Pregnancy , Quality Control , Retrospective StudiesABSTRACT
BACKGROUND: The essential oil (EO) of Artemisia vulgaris L. has been traditionally used worldwide for treating a large number of diseases. Although major components in A. vulgaris EO have been shown to inhibit growth of different cancer cells, as pure compounds or part of other plants extracted oil, no information is known about its anti-proliferative activities. Therefore, the current investigation has evaluated the toxicity of the plant extracted oil from buds (AVO-b) and leaves (AVO-l) and characterized their growth inhibitory effects on cancer cells. METHODS: AVO-b and AVO-l from A. vulgaris L. were extracted by hydrodistillation, and their effect on the viability of human HL-60 promyelocytic leukemia and various other cancer cell lines was tested using MTT assay. Flow cytometric analysis of apoptosis, DNA fragmentation assay, caspases enzymatic activities and Western blotting were used to determine the apoptotic pathway triggered by their action on HL-60 cells. RESULTS: Low concentrations of AVO-b and AVO-l inhibited the growth of HL-60 cells in a dose- and time-dependent manner. Employing flow cytometric, DNA fragmentation and caspase activation analyses, demonstrated that the cytotoxic effect of the oils is mediated by a caspase-dependent apoptosis. Kinetic studies in the presence and absence specific caspase inhibitors showed that activation of caspase-8 was dependent and subsequent to the activation of caspases-9 and -3. In addition, the essential oil caused a disruption of the mitochondrial transmembrane potential (ΔΨm), increased the release of cytochrome c to the cytosol, and altered the expression of certain members of Bcl-2 family (Bcl-2, Bax and Bid), Apaf-1 and XIAP. Interestingly, low doses of AVO-b and AVO-1 also induced apoptosis in various cancer cell lines, but not in noncancerous cells. CONCLUSIONS: The results demonstrate that the EO-induced apoptosis in HL-60 cells is mediated by caspase-dependent pathways, involving caspases-3, -9, and -8, which are initiated by Bcl-2/Bax/Bid-dependent loss of ΔΨm leading to release of cytochrome c to the cytoplasm to activate the caspase cascade. The finding that AVO-b and AVO-l are more efficient to induce apoptosis in different cancer cell lines than noncancerous cells, suggests that A. vulgaris might be a promising source for new anticancer agents.
Subject(s)
Apoptosis/drug effects , Artemisia/chemistry , Mitochondria/drug effects , Oils, Volatile/pharmacology , Caspases/metabolism , Cell Survival/drug effects , Cytochromes c/metabolism , HL-60 Cells , Humans , Oils, Volatile/chemistry , Proto-Oncogene Proteins c-bcl-2/metabolismABSTRACT
A selected set of substituted pyridone-annelated isoindigos 3a-f has been synthesized via interaction of 5- and 6-substituted oxindoles 2a-f with 6-ethyl-1,2,9-trioxopyrrolo[3,2-f]quinoline-8-carboxylic acid (1) in acetic acid at reflux. Among these isoindigos, the 5'-chloro and 5'-bromo derivatives 3b and 3d show strong and selective antiproliferative activities against a panel of human hematological and solid tumor cell-lines, but not against noncancerous cells, suggesting their potential use as anticancer agents. In all the tested cell lines, compound 3b was a 25%-50% more potent inhibitor of cell growth than 3d, suggesting the critical role of the substitution at 5'-position of the benzo-ring E. The IC50 values after 48 hours incubation with the 5'-chloro compound 3b were 6.60 µM in K562, 8.21 µM in THP-1, 8.97 µM in HepG2, 11.94 µM in MCF-7 and 14.59 µM in Caco-2 cancer cells, while the IC50 values in noncancerous HEK-293 and L-929 were 30.65 µM and 40.40 µM, respectively. In addition, compound 3b induced higher levels apoptosis in K562 cells than 3d, as determined by annexin V/7-AAD flowcytometry analysis. Therefore, further characterization of the antitproliferative mechanisms of compounds 3b and 3d may provide a novel chemotherapeutic agents.
Subject(s)
Cell Proliferation/drug effects , Neoplasms/drug therapy , Pyridones/chemistry , Structure-Activity Relationship , Apoptosis/drug effects , Caco-2 Cells , HEK293 Cells , Humans , Indoles/chemical synthesis , Indoles/chemistry , Indoles/pharmacology , K562 Cells , Oxindoles , Pyridones/pharmacologyABSTRACT
BACKGROUND: Discontinuation of TKI therapy and treatment-free remission (TFR) have become new goals for chronic-phase chronic myeloid leukemia (CP-CML). The aim of this study was to estimate the TFR post discontinuation of TKI therapy at 3 tertiary-care centers. PATIENTS AND METHODS: CP-CML patients aged ≥16 years who had an attempt to discontinue TKI therapy till June 2022, were eligible. The collected data included patients' demographics, prognostic score, type and duration of TKI therapy, response dates, relapse dates, response to re-initiation of TKI therapy, and risk factors for relapse. RESULTS: Fifty-five patients (35, 63.6% females) with a median age of 40 (range 16-74) years at diagnosis discontinued therapy. Forty-eight (87.3%) patients received imatinib as first line therapy. Twenty-nine (52.7%) patients were receiving imatinib at the time of TKI-discontinuation. Median time from diagnosis to TKI discontinuation was 86 months (IQR 60;132) and median duration of TKI therapy after achieving DMR was 66 months (IQR 47;114). After a median follow up of 34 (IQR 12;68) months, 15 (27.3%) patients relapsed. Median time to relapse was 5 months (range 2-38). Most of the relapses occurred during the first 6 months except 3 (20%) patients. All the relapsed patients achieved MMR after a median of 3 (range 2-6) months after restarting TKI therapy. None of the patients progressed to advanced-phase. CONCLUSION: Our experience confirms that discontinuation of TKI therapy in CP-CML patients is feasible and safe in routine clinical practice, and can achieve TFR in more than two-third of carefully selected patients.
ABSTRACT
This international questionnaire survey aimed to explore the current incidence, diagnostic policies, management, and outcomes of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) among healthcare providers involved in the management of these patients. A questionnaire was e-mailed to practitioners with an interest in allogeneic hematopoietic cell transplantation (allo-HCT). Of the respondents, 144 of 215 (67.0%) felt that early detection or diagnosis of VOD/SOS was difficult. Regarding diagnostic criteria, 142 (66.1%) already declared using the 2023 EBMT refined criteria. Most respondents (163/215, 75.8%) found these recent refined EBMT criteria useful for diagnosis, and 193 (89.8%) found the severity criteria easy to use. The major risk factors identified for VOD/SOS were a second allo-HCT (41.4%), pre-existing liver disease (54.9%), and prior use of antibody-drug conjugates (49.8%). Preferences for starting VOD/SOS treatment varied, with 61 (28.4%) preferring initiating therapy at a mild stage, and 122 (56.7%) preferring the moderate stage. In summary, this survey provided valuable insight into the challenges and opportunities of the identification and management of VOD/SOS. By improving current knowledge and increasing collaboration among healthcare professionals, early detection, management, and clinical outcomes for patients with this potentially serious complication can also be improved.
ABSTRACT
COVID-19 has resulted in a pandemic that aggravated the world's healthcare systems, economies, and education, and caused millions of global deaths. Until now, there has been no specific, reliable, and effective treatment to combat the virus and its variants. The current standard tedious PCR-based tests have limitations in terms of sensitivity, specificity, turnaround time, and false negative results. Thus, an alternative, rapid, accurate, and sensitive diagnostic tool that can detect viral particles, without the need for amplification or viral replication, is central to infectious disease surveillance. Here, we report MICaFVi (Magnetic Immuno-Capture Flow Virometry), a novel precise nano-biosensor diagnostic assay for coronavirus detection which combines the MNP-based immuno-capture of viruses for enrichment followed by flow-virometry analysis, enabling the sensitive detection of viral particles and pseudoviruses. As proof of concept, virus-mimicking spike-protein-coated silica particles (VM-SPs) were captured using anti-spike-antibody-conjugated MNPs (AS-MNPs) followed by detection using flow cytometry. Our results showed that MICaFVi can successfully detect viral MERS-CoV/SARS-CoV-2-mimicking particles as well as MERS-CoV pseudoviral particles (MERSpp) with high specificity and sensitivity, where a limit of detection (LOD) of 3.9 µg/mL (20 pmol/mL) was achieved. The proposed method has great potential for designing practical, specific, and point-of-care testing for rapid and sensitive diagnoses of coronavirus and other infectious diseases.
Subject(s)
COVID-19 , Middle East Respiratory Syndrome Coronavirus , Humans , COVID-19/diagnosis , SARS-CoV-2 , COVID-19 Testing , Magnetic PhenomenaABSTRACT
Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life-threatening complication that can develop after hematopoietic cell transplantation (HCT). A new definition for diagnosis, and a severity grading system for SOS/VOD in adult patients, was reported a few years ago on behalf of the European Society for Blood and Marrow Transplantation (EBMT). The aim of this work is to update knowledge regarding diagnosis and severity assessment of SOS/VOD in adult patients, and also its pathophysiology and treatment. In particular, we now propose to refine the previous classification and distinguish probable, clinical and proven SOS/VOD at diagnosis. We also provide an accurate definition of multiorgan dysfunction (MOD) for SOS/VOD severity grading based on Sequential Organ Failure Assessment (SOFA) score.
Subject(s)
Hematopoietic Stem Cell Transplantation , Hepatic Veno-Occlusive Disease , Vascular Diseases , Humans , Adult , Hepatic Veno-Occlusive Disease/diagnosis , Hepatic Veno-Occlusive Disease/etiology , Hepatic Veno-Occlusive Disease/drug therapy , Bone Marrow , Syndrome , Hematopoietic Stem Cell Transplantation/adverse effectsABSTRACT
BACKGROUND: The outcomes of Pediatric acute lymphoblastic leukemia (ALL) have improved dramatically whereas outcomes for ALL amongst adolescents and young adults (AYA) have lagged behind. The introduction of pediatric-like regimens to manage adult ALL has shown promising outcomes across several analyses. MATERIALS AND METHODS: In this analysis, we aimed to retrospectively compare the differences in outcomes among patients aged 14-40 years with Philadelphia-negative ALL treated with a Hyper-CVAD protocol versus a modified pediatric protocol. RESULTS: A total of 103 patients were identified with 58 (56.3%) in the modified ABFM group and 45 (43.7%) in the hyper-CVAD group. The median duration of follow-up for the cohort was 39 months (range 1-93). There were significantly lower rates of MRD persistence after consolidation (10.3% vs. 26.7%, P = 0.031) and transplantation (15.5% vs. 46.6%, P < 0.001) in the modified ABFM group. 5-year OS rates (83.9% vs. 65.3%, P = 0.036) and DFS rates (67.4% vs. 44%, P = 0.014) were higher in the modified ABFM groups. The incidence of grade 3 and 4 hepatotoxicity (24.1% vs. 13.3%, P < 0.001) and osteonecrosis (20.6% vs. 2.2%, P = 0.005) were higher in the modified ABFM group. CONCLUSION: Our analysis demonstrates that the use of a pediatric modified ABFM protocol demonstrated superior outcomes compared to the hyper-CVAD regimen in the treatment of Philadelphia-negative ALL amongst AYA patients. However, the modified ABFM protocol was associated with an increased risk of certain toxicities including high grade liver toxicity and osteonecrosis.
Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Adolescent , Young Adult , Child , Retrospective Studies , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Doxorubicin/therapeutic use , Cyclophosphamide/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Dexamethasone/adverse effects , Vincristine/therapeutic use , Multicenter Studies as TopicABSTRACT
Introduction: Hematological parameters are critical in disease diagnosis, management, and monitoring; however, complete blood count (CBC) reference intervals vary across populations. The aim of the current study was to provide the reference ranges of hematological parameters/indices in the healthy adult Saudi population. Methods: A multicenter retrospective cross-sectional study was conducted with a sample of employees who were screened pre-employment from January 2015 to December 2019, at tertiary care hospitals in three regions. Demographic and CBC data were extracted from the electronic health system. The 2.5th and 97.5th percentiles were used to determine the reference intervals. Results: Of a total of 1,388 participants, 53.82% were male. The majority 96% was less than 40 years old, and 85% were from the Central region. Gender-related differences were observed for the RBC count, Hb, HCT, MCV, MCH, MCHC, and the platelet count. Age-related differences were observed for the RBC, Hb, HCT, and eosinophils. The WBC parameters did not differ by gender or age categories. Region-related differences were observed for the RBC, hemoglobin, HCT, MCV, WBC, and basophils. The platelet count was higher in the female group, the age group 40 years and above, and in the Western region. The prevalence of anemia was high in the female group and the Eastern region. The overall neutropenia rate was 12.8%. Conclusion: The data from this study provide hematological parameter reference ranges for the adult Saudi population by gender, age, and region. Gender and age-related differences were observed for the hematological parameters. Anemia was more frequent in the female group and the Eastern region. Caution must be taken when comparing or interpreting results from different age groups, gender, region of origin, and ethnicity.
ABSTRACT
OBJECTIVES: To find any correlation between the clinical response as per International Working Myeloma Group (IWMG) response criteria and the radiological response at the end of treatment. METHODS: A retrospective cohort study was conducted, total of 39 patients whom diagnosed with multiple myeloma (MM) between January 2010 and December 2018 and fulfilled the study criteria were included. RESULTS: The high sensitivity and specificity of positron emission tomography/computed tomography (PET/CT) in detecting osteolytic myeloma lesions in the bones was strongly emphasized in our study. Follow up PET/CT, we found that while 17 patients showed complete remission in PET/CT, and 14 of these of patients demonstrated a complete clinical response at end of therapy assessment. CONCLUSION: Although we did not find a statistically significant correlation between the response versus metabolic activity and the number of bone/bone marrow lesions, however, our study was limited by the absence of clear criteria for defining disease response in PET/CT in MM patients. Further prospective analysis would be needed to establish a defined criterion.