Novel mutation in alpha-spectrin gene in Saudi patients with hereditary spherocytosis.

Hereditary spherocytosis (HS) is the most common hereditary hemolytic disorder induced by red blood cell (RBC) membrane defect. This study was undertaken to determine mutations in genes associated with RBC membrane defect in patients with HS such as α-spectrin gene (SPTA1), ß-spectrin gene (SPTB), ankyrin gene (ANK1), band 3 anion transport gene (SLC4A1) and erythrocyte membrane protein band 4.1 gene (EPB41). Blood samples were collected from 23 unrelated patients with HS. Patients were diagnosed according to the guidelines from the British Society for Hematology. All hematological examinations for the determination of RBC abnormalities and osmotic fragility tests were conducted. Genomic DNA were extracted from peripheral blood cells and coding exons of known genes for hereditary spherocytosis were enriched using Roche/KAPA sequence capture technology and sequenced on an Illumina system via next-generation sequencing (NGS). The data showed that most of the HS patients confirmed splenomegaly and showed elevated reticulocytes and abnormal bilirubin values. NGS analysis identified the heterozygous variant c.5501G > A in the exon 39 of SPTA1 gene, resulted in a Trp1834*, which leads to a premature stop codon and subsequent mRNA degradation (nonsense- mediated decay) or truncation in α spectrin. Moreover, our data also revealed conventional mutations in genes SPTB, ANK, SLC4A1 and EBP41 in severe patients of HS. In short, this is the first report that determined a novel mutation c.5501G > A in SPTA1 gene in the Saudi population. To the best of our knowledge, this variant c.5501G > A has not been described in global literature so far. This novel mutation in SPTA1 gene is unique in the Saudi population.

Isolated benign neutropenia in healthy individuals from Saudi Arabia's central region: A comprehensive study.

Objectives: Neutrophils are the most common cell types in circulation and are considered the first line of defense in the immune system against microorganisms. This study was undertaken to investigate the occurrence of isolated benign neutropenia (IBN) among healthy individuals in the central region of Saudi Arabia. Methods: This retrospective study analyzed complete blood count tests as part of routine checkups for chronic health conditions from April to September 2022. The 10,442 participants were randomly selected and their medical records were reviewed for neutropenia and mean absolute neutrophil counts (ANCs) were calculated. Descriptive analysis was employed to assess the prevalence of IBN across various demographic factors, such as age, gender, and nationality. Results: The prevalence of IBN in the central region of Saudi Arabia was found to be 2.82% across the entire cohort of participants. The mean ANC among all participants was 4.55 × 109/L. The prevalence of neutropenia was higher in male participants compared with female. Male neutropenic had a lower mean ANC than female; however, the differences were not statistically different (P > 0.05). The prevalence of neutropenia was lower in Saudi participants compared with non-Saudis. While the mean ANC was lower among Saudis as compared with non-Saudi participants. However, the differences were not statistically different (P > 0.05). Conclusion: This is the first study from the central region of Saudi Arabia that determined the prevalence of chronic benign neutropenia among healthy individuals. The prevalence of IBN was found to be relatively low. Furthermore, neutropenia was more frequent in males than females. Moreover, male neutropenic individuals have a lower ANC.

Assessment of osteoporosis in patients with type 2 diabetes mellitus: A study from the central region of Saudi Arabia.

OBJECTIVES: To understand the impact of diabetes on bone mineral density and whether it increases the likelihood of osteoporosis. METHODS: This study was performed on 327 Saudis (aged >40 years) who were screened for osteoporosis and diabetes mellitus (DM). The levels of osteoporosis were determined by an estimation of Bone mineral density (BMD) using a DEXA scan examination. The data on BMD from diabetic subjects were compared with healthy nondiabetic controls. RESULTS: Out of 327 enrolled subjects, 38 (11.6%) were found to be osteoporotic, whereas 138 (42.2%) had DM. The data showed that the number of patients with osteoporosis in the DM group was 14 (36.8%), significantly lower than in nondiabetic patients, 21 (55.2%) (p=0.0015). Notably, the data showed no significant difference in the mean BMD of the femur in patients with DM (0.926 g/cm2) and non-diabetes (0.936 g/cm2) (p=0.280; T-score p=0.4746). The mean BMD levels in the spine of the DM study group (1.049 g/cm2) were significantly higher when compared with nondiabetic healthy controls (0.990 g/cm2) (p=0.0031). CONCLUSION: Patients with diabetes had higher lumbar BMD than nondiabetics, although femoral BMD was similar. Patients with diabetes have a lower osteoporosis risk than nondiabetics.

Evaluation of hematological parameters in dyspepsia patients infected with Helicobacter pylori: A retrospective study from the Central Region of Saudi Arabia.

OBJECTIVES: To evaluate the hematological parameters in dyspepsia patients infected with Helicobacter pylori (H. pylori) infection from Al Qassim province of Kingdom of Saudi Arabia (KSA). METHODS: This retrospective study was carried out in Dr. Sulaiman Al-Habib Hospital, Al Qassim, KSA. The data of dyspepsia and epigastric pain patients were derived from the hospital based registration system between 2020-2021. Logistic regression models were used to investigate the correlation between the onset of H. pylori infection and anemia. RESULTS: Among 810 enrolled patients, there were 202 (24.9%) patients with H. pylori infection and 144 (17.8%) with anemia. The prevalence of anemia in the H. pylori (+) group was not statistically higher than the H. pylori (-) group after adjusting age, red blood cell count, serum ferritin, mean corpuscular volume, platelet count, and mean corpuscular hemoglobin (p>0.05). The level of hemoglobin was almost identical in both the H. pylori (+) group and the H. pylori (-) group (p>0.05). CONCLUSION: The findings show that H. pylori infection may not be related to anemia in dyspepsia patients from the Central region of KSA.

Modulation of mice immune responses against Schistosoma mansoni infection with anti-schistosomiasis drugs: Role of interleukin-4 and interferon-gamma.

Objective: Schistosoma mansoni (S. mansoni) is endemic in Africa, the Middle East, South America, and the Caribbean. This study investigated the modulation of immune response against S. mansoni through estimation of interleukin-4 (IL-4) (Th2 cytokine) and interferon-gamma (INF-γ) (Th1 cytokine) under the effect of anti-schistosomal drugs. Methods: Laboratory bred female albino mice (n = 120) were divided into the following groups: untreated mice, S. mansoni infected mice, S. mansoni infected mice treated with artemisinin (ART), arachidonic acid (ARA), nifedipine or praziquantel (PZQ). Levels of IL-4 and INF-γ cytokines in the serum samples of treated and untreated mice were determined by enzyme-linked immunosorbent assay and the results were further validated by measuring the mRNA levels IL-4 and INF-γ using quantitative real-time polymerase chain reaction. Results: Anti-schistosomiasis drugs ART and ARA increased the levels of Th2 cytokine IL-4 (P < 0.05), whereas PZQ drug decreased the response of IL-4 (P < 0.05). However, nifedipine was found to be ineffective in modulating the response of IL-4 (P > 0.05). As far as Th-1 cytokine IFN γ was concerned, only PZQ increased its levels (P < 0.05), whereas other tested anti-schistosomiasis drugs; ART, ARA, and nifedipine were found to be infective (P > 0.05). Conclusions: These findings indicated that anti-schistosomiasis drugs ART, ARA, and PZQ play a role in the modulation of expression of Th2 cytokines. Whereas, only PZQ may play a role in the modulation of Th1 cytokines. These findings provide a scope for the formulation of novel anti-schistosomal drugs as well as in the therapeutic management of patients infected with S. mansoni.

Full Dose Cyclophosphamide with the Addition of Fludarabine for Matched Sibling Transplants in Severe Aplastic Anemia.

The recommended therapy for severe aplastic anemia (SAA) in younger patients with a matched sibling donor (MSD) is allogeneic hematopoietic cell transplantation (allo-HCT). A number of conditioning regimens and protocols have been used for these patients. Here we report a homogeneous cohort of SAA patients receiving a uniform transplantation protocol. This study is a retrospective analysis of 82 consecutive patients with SAA who underwent MSD allo-HCT at a single center. The median duration of follow-up for survivors was 100 months, the 10-year overall survival (OS) was 87.5%, and the 10-year event-free survival was 75.3%. The OS was 97.4% for "mobilized" bone marrow (BM) graft recipients and 78.9% for "nonmobilized" BM graft recipients (P = .01. The cumulative incidence of acute graft-versus-host disease (GVHD) was 25.6%, that of chronic GVHD was 27.16%, and that of graft failure was 16.2%. Recipient age ≥30 years and transplantation at >6 months after SAA diagnosis were associated with a increased risk of events. In the presence of a fully matched sibling donor, allo-HCT with a mobilized BM graft and fludarabine-cyclophosphamide conditioning is an efficacious and safe approach. Early transplantation is associated with a better outcome, emphasizing the importance of not delaying transplantation in these patients. Prospective trials are needed to determine the optimal regimen.

Philadelphia chromosome-positive lymphoblastic lymphoma-Is it rare or underdiagnosed?

Lymphoblastic lymphomas (LBLs) are neoplasms of precursor B and T cells; they are considered in the same spectrum as precursor B and T cell acute lymphoblastic leukemia (ALL). The World Health Organization classification classifies both LBL and ALL as one disease entity. While chromosome abnormalities are well defined with all of their therapeutic and prognostic implications in ALL, these are not well studied in LBL. Here, we describe a case of Philadelphia chromosome-positive LBL and review the available literature regarding this entity.

Outcomes of allogeneic hematopoietic cell transplant for acute myeloid leukemia in adolescent patients.

Patients between 14 and 22 years old are underrepresented in both adult and pediatric studies. We analyzed the outcomes of 94 consecutive patients aged between 14 and 22 who underwent myeloablative matched related-donor transplant while in first or second complete remission. We studied the impact of disease type, remission status, ELN risk group, ABO mismatch, time from diagnosis to transplant, patient and donor age, conditioning type, stem cell source, and the year of transplant on transplant outcomes. The cumulative incidences of relapse, NRM, OS, and DFS at 5 years were 42%, 10%, 59%, and 48%, respectively. Absence of ABO mismatch and donor age > 20 were associated with better OS and DFS on univariate and multivariate analysis. The cumulative incidence of aGVHD and cGVHD were 18% and 44%, respectively. Donor age > 20 and peripheral blood stem cell source were significantly associated with higher incidence of cGVHD on univariate and multivariate analysis. Younger patient age was significantly associated with higher incidence of aGVHD. In this age group, the determinants of survival seem to be dependent on donor variables rather on the traditional disease and patient related variables. Relapse still a significant factor for transplant failure while NRM was low.

Early and late effects of therapeutic plasma exchange in patients with systemic lupus erythematosus and antineutrophil cytoplasmic antibody-associated vasculitis: A single-center experience.

Therapeutic plasma exchanges (TPE) is considered as one of the treatment modalities that is used in systemic autoimmune diseases. This study aimed to describe the early and late effect of TPE in patients with systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) presented with acute kidney injury (AKI). Retrospective study comprised patients with SLE and AAV with AKI seen between January 2000 and June 2014 at King Faisal Specialist Hospital and Research Center in Riyadh. All patients underwent TPE. Retrospectively, all patients were assessed for early and late renal outcome at 12- month and 24-month intervals. Renal outcome was assessed according to serum creatinine level, glomerular filtration rate, active urine sediment, and proteinuria. P <0.05 was considered significant. A total of 68 patients were included, 58 patients (51 females) had SLE and 10 patients (7 females) had AAV completed TPE. All patients had active disease and had AKI. At the first 12 months, 18 patients (17 SLE and 1 AAV) showed complete response and 14 patients had partial response while 22 patients did not show therapeutic benefit. The nonresponders (22 patients) entered the late assessment interval (24 months) without any therapeutic response. Statistically, there was no significant difference between the patient's response to TPE at the first and second assessment intervals and the baseline serum creatinine level. TPE might be an alternative rescue treatment in lupus nephritis with AKI.

Nephrotic syndrome is a rare manifestation of IGA nephropathy.

Nephrotic syndrome is a rare presentation of IgA nephropathy. The degree of proteinuria in IgA nephropathy predicts poor prognosis. We herein report a teenager with IGA nephropathy, the nephrotic syndrome and segmental glomerular scars who after developing complications from high dose corticosteroid therapy was successfully treated with tacrolimus and low dose prednisone.