In vitro evaluation of the potential immunosuppressive effect of panobinostat on cultured lymphocytes retrieved from childhood systemic lupus erythematosus patients.

Although many drugs are available for childhood systemic lupus erythematosus (SLE) treatment, the adverse effects and poor response in some cases make it crucial to find new drugs targeting various pathways in disease pathogenesis to improve overall outcomes. This study aimed to (i) investigate the effect of Panobinostat on cultured lymphocytes obtained from children with active SLE and (ii) to compare that effect with standard drugs used in SLE, such as Prednisone and hydroxychloroquine. The study included 24 SLE active patients, divided into four equal groups. Lymphocytes were isolated from blood samples of the study patients. According to the study group, cells were treated with either Panobinostat, Prednisolone, hydroxychloroquine, or not treated (control group). After cell culture, the response of lymphocytes upon drug treatment was analyzed in terms of the production of anti-dsDNA antibodies and levels of apoptosis as detected by flow cytometry using annexin V and propidium iodide (PI) staining. The Panobinostat group showed a significant decrease in the viable cell count (p < 0.001). Both Prednisone and hydroxychloroquine decreased anti-dsDNA expression more than the Panobinostat and control groups (p < 0.001 for both). PI was higher in the Prednisone group, and Annexin V was higher in the Panobinostat group compared to other groups; however, their increase did not reach statistically significant levels (p= 0.12 and 0.85, respectively). This is the first study of the Panobinostat effect on cultured lymphocytes of SLE. In conclusion, Panobinostat could be a prospective treatment for B-cell-driven autoimmune diseases such as SLE. However, its effect on autoantibodies levels and different clinical features of SLE still need a thorough evaluation.

The prognostic values of the IL-10 (G1082A) and TNF-α (G308A) polymorphisms in Egyptian patients with acute lymphoblastic leukemia: A single-center study.

Background: Interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-α) genes contribute to oncogenesis. We evaluated the influence of the IL-10 (G1082A) and TNF-α (G308A) polymorphisms on the prognosis and outcomes of Egyptian patients with acute lymphoblastic leukemia (ALL). Materials and Methods: We investigated 64 children and 76 adults with ALL, between 2016 and 2019, for the IL-10 (G1082A) and TNF-α (G308A) polymorphisms using allele-specific polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism. Survival analyses were performed using the Kaplan-Meier estimator and the log-rank test. Results: In children with ALL, the A allele of TNF-α and IL-10 polymorphisms was associated with older age (P = 0.04 and 0.03), more extramedullary disease (P = 0.02 and 0.001), positive breakpoint cluster region-Abelson (BCR-ABL) rearrangement (p190; P = 0.04 and 0.001), and more relapse (P = 0.002). The IL-10 GG genotype was associated with higher overall survival in children (P = 0.026). Adults carrying the TNF-α A allele showed more extramedullary disease (P = 0.009) and relapse (P = 0.003). We also found a higher frequency of IL-10 A allele in adults with older age (P = 0.03), lower hemoglobin level (P = 0.04), positive BCR-ABL rearrangement (P = 0.001), more extramedullary disease (P = 0.001), more relapse (P = 0.002), and a longer time for the first complete remission (P = 0.003). Conclusion: A possible association exists between the A allele of IL-10 and TNF-α polymorphisms and poor prognosis in Egyptian patients with ALL, while the IL-10 GG genotype may be associated with better survival in children with ALL.

Molecular Study of Torque Teno Virus in Patients with Acute Gastroenteritis.

BACKGROUND: Torque teno virus (TTV) is a single stranded non enveloped DNA virus. Various studies have found a high prevalence of TTV in different populations and in different human samples including blood and stool. OBJECTIVE: The aim of the present study was to evaluate the prevalence of TTV in adult patients with acute gastroenteritis in stool samples by semi-nested polymerase chain reaction (PCR). METHODS: This study was a retrospective, cross-sectional study carried out on 100 preserved stool samples from adult patients with simple community acquired diarrhea without dehydration. Stool samples were subjected to antigen detection of rotavirus and norovirus by enzyme linked immunosorbent assay (ELISA). Detection of TTV was performed by the use of semi- nested PCR. RESULTS: The detected viruses were TTV by semi-nested PCR in 83% of the patients, followed by both norovirus and rotavirus in 20% of patients each. TTV was present without any other studied virus in 52% of the samples, the norovirus antigen was detected as a single virus in 2%, and rotavirus was detected as a single virus in 3%. No viruses were detected in 11% of the stool samples. Norovirus was associated with TTV in 17 isolates and as a sole virus in three samples (p = 0.5). Rotavirus was associated with TTV in 17 isolates and alone in three. CONCLUSIONS: The data of the present study show a high prevalence of TTV in stool samples from adults with acute gastroenteritis. The presence of rotavirus and norovirus was also a common finding in these patients. There were no detected effects on the clinical features of gastroenteritis associated with the presence of TTV in acute gastroenteritis.

Comparison of Segmental Lordosis and Global Spinopelvic Alignment After Single-Level Lateral Lumbar Interbody Fusion or Transforaminal Lumbar Interbody Fusion.

BACKGROUND: Lateral lumbar interbody fusion (LLIF) has steadily increased in popularity. Compared with the traditional transforaminal lumbar interbody fusion (TLIF), LLIF is thought to allow for greater improvement in lordosis. However, there are limited direct comparison data on the degree of regional and global alignment change after single-level LLIF and TLIF procedures. This study compared the changes in spinal sagittal alignment in patients who underwent either procedure. METHODS: A retrospective analysis of patients who underwent LLIF or TLIF for lumbar degenerative disease at a single institution was performed. Twenty patients who underwent single-level LLIF were matched to 20 patients who underwent single-level TLIF by gender and level of interbody fusion. All included patients had preoperative and postoperative standing scoliosis radiographs. Changes in segmental lordosis (SL) at the fused level, lumbar lordosis (LL), sagittal vertical axis, and pelvic incidence-LL mismatch (PI-LL) were measured. Statistical analysis was performed using paired and unpaired Student's t-tests. Means were reported with standard error. RESULTS: Within each group, 2, 4, and 14 patients had cages placed at L2-3, L3-4, and L4-5, respectively. The LLIF group demonstrated significantly increased SL compared with the TLIF group (+4.9° ± 3.0 vs. +2.6° ± 1.7, P = 0.01). LL, sagittal vertical axis, and PI-LL changes did not differ significantly between groups. CONCLUSIONS: LLIF achieved greater improvements in SL than TLIF. However, regionally and globally, there were no significant differences with either procedure after a single-level intervention. The increased lordosis from LLIF compared with TLIF may be more impactful globally in multilevel fusions.