An International Learning Collaborative Phase 2 Trial for Haploidentical Bone Marrow Transplant in Sickle Cell Disease.

In the setting of a learning collaborative, we conducted an international multicenter phase 2 clinical trial testing the hypothesis that non-myeloablative related haploidentical BMT with thiotepa and post-transplant cyclophosphamide (PTCy) will result in 2-year event-free survival (no graft failure or death) of at least 80%. A total of 70 participants (median age 19.1 (IQR 14.1 - 25.0) were evaluable based on the conditioning protocol. Graft failure occurred in 11.4% (8/70) and only in participants <18 years (p=0.001); all had autologous reconstitution. After a median follow-up of 2.4 years (IQR 1.5-3.9), the 2-year Kaplan-Meier-based probability of event-free survival was 82.6% (95% CI 71.4%-89.7%). The 2-year overall survival was 94.1% (95% CI 84.9%-97.7%) with no difference between the child and adult participants (p=0.889). After excluding participants with graft failure (n=8), participants with engraftment had median whole blood donor chimerism values at D+180 and D+365 post-transplant of 100.0% (IQR 99.8 - 100.0%; n=59) and 100.0% (IQR 100.0 - 100.0%; n=58), respectively, and 96.6% (57/59) were off immunosuppression at 1-year post-transplant. The 1-year grades III-IV acute graft versus host disease (GvHD) rate was 10.0% (95% CI 4.6 - 18.6%), and the 2-year moderate-severe chronic GvHD rate was 10.0% (95% CI 4.6 - 18.6%). Five participants (7.1%) died from infectious complications. We demonstrate that non-myeloablative haploidentical BMT with thiotepa and PTCy is a readily available curative therapy for most adults, even those with organ damage, instead of the more expensive myeloablative gene therapy and gene editing. Additional strategies are required for children to decrease graft failure rates (ClinicalTrials.gov identifier NCT01850108).

HLA-haploidentical stem cell transplantation in children with inherited bone marrow failure syndromes: A retrospective analysis on behalf of EBMT severe aplastic Anemia and pediatric diseases working parties.

Haploidentical stem cell transplantation (haplo-SCT) represents the main alternative for children with inherited bone marrow failure syndrome (I-BMF) lacking a matched donor. This retrospective study, conducted on behalf of the EBMT SAAWP and PDWP, aims to report the current outcomes of haplo-SCT in I-BMFs, comparing the different in vivo and ex vivo T-cell depletion approaches. One hundred and sixty-two I-BMF patients who underwent haplo-SCT (median age 7.4 years) have been registered. Fanconi Anemia was the most represented diagnosis (70.1%). Based on different T-cell depletion (TCD) approaches, four categories were identified: (1) TCRαß+ /CD19+ -depletion (43.8%); (2) T-repleted with post-transplant Cyclophosphamide (PTCy, 34.0%); (3) In-vivo T-depletion with ATG/alemtuzumab (14.8%); (4) CD34+ positive selection (7.4%). The cumulative incidences (CI) of neutrophil and platelet engraftment were 84% and 76% respectively, while that of primary and secondary graft failure was 10% and 8% respectively. The 100-day CI of acute GvHD grade III-IV(95% CI) was 13%, while the 24-month CI of extensive chronic GvHD was 4%. After a median follow-up of 43.4 months, the 2-year overall survival(OS) and GvHD/Rejection-free Survival (GRFS) probabilities are 67% and 53%, respectively. The TCR CD3+ αß+ /CD19+ depletion group showed a significantly lower incidence of both acute and chronic GvHD and higher OS (79%; p0.013) and GRFS (71%; p < .001), while no significant differences in outcomes have been observed by different diagnosis and conditioning regimens. This large retrospective study supports the safety and feasibility of haplo-SCT in I-BMF patients. TCRαß+ /CD19+ depletion offers higher chances of patients' survival, with a significantly lower risk of severe a- and c-GvHD in I-BMFs compared to other platforms.

Comparing between HLA-matched sibling donor allogenic HSCT and non-sibling matched related donor allogenic HSCT outcome in pediatric patients; single center retrospective study.

BACKGROUND: Extended family donor search other than siblings may yield an HLA matched donor in communities with high rate of consanguinity. The outcome of patients who are transplanted from non-sibling matched related donors (NS-MRD) including engraftment and graft versus host disease (GVHD) are scarce in comparison with matched sibling donor (MSD). METHODS: We retrospectively reviewed the outcome of all our pediatric hematopoietic stem cell transplantation (HSCT) patients who had non-sibling matched related donor and controlled them with matched sibling donor HSCT (based on age, indication of HSCT, conditioning regimen, GVHD prophylaxis, serotherapy, stem cell source and cytomegalovirus status). RESULTS: A total of 76 patients were reviewed during study period. Thirty patients (39.5%) in NS-MRD arm and 46 patients in MSD (60.5%) were identified after matching in age, disease, and conditioning regimens. All patients had similar approach including stem cell source and GVHD prophylaxis (CNI + 2nd agent). Out of the NS-MRD group, 18 patients (59%) had one of their parents as a donor and the rest as second degree relatives. Both groups were equally distributed and were homogeneous. Both groups had no statistically significant difference in outcome including engraftment, GVHD and Chimerism tests results. GVHD was seen in (13%) NS-MRD patients compared to (11%) in MSD patients. All patients remain alive with median follow up of 1249 days (431-3525). CONCLUSIONS: This study showed no significant difference in allogenic HSCT outcomes between matched sibling donors and non-sibling matched related donors and support using the same management approach in terms of conditioning therapy, GVHD prophylaxis, and serotherapy only if indicated.

The impact of child-specific characteristics on warfarin dosing requirements.

Background: The influence of child characteristics on warfarin dosing has been reported; however, there is no consensus on the nature and extent of this effect. Objectives: To investigate the impacts of the demographic and clinical characteristics of children on the warfarin dose required to achieve a therapeutic international normalization ratio (INR). Methods: This retrospective cohort study included children aged 3 months to 14 years old who were prescribed warfarin for 3 months or longer with a "stable INR." The primary outcome was the total daily dose (TDD) and total weekly dose of warfarin required to achieve a therapeutic INR target. Results: We included 127 patients with a mean age of 7.7 ± 3.7 years and a median weight of 22 (IQR, 16-33) kg. Of the sample, 55 patients (43.3%) required a TDD of ≤0.1 mg/kg. The TDD for children younger than 5 years, 5 to 10 years, and older than 10 years were 0.14 ± 0.06 mg/kg, 0.12 ± 0.05 mg/kg, and 0.096 ± 0.04 mg/kg, respectively (P = .002). Overweight and obese children required a smaller TDD than normal-weight children: 0.09 ± 0.05 vs 0.13 ± 0.05 mg/kg (P = .004), which was similar for underweight children. A lower body surface area (<0.5 m2) required a higher dose. All the other variables did not affect warfarin doses. The incidence of a subtherapeutic or supratherapeutic INR was independent of demographic or clinical variables. Conclusion: The study confirmed that the patient demographics affect the daily warfarin dose required to achieve the INR target. However, they do not have any predictive value for the incidence of out-of-range-INR.

Potential role of immunotherapy and targeted therapy in the treatment of cancer: A contemporary nursing practice.

Immunotherapy and targeted therapy have emerged as promising therapeutic options for cancer patients. Immunotherapies induce a host immune response that mediates long-lived tumor destruction, while targeted therapies suppress molecular mechanisms that are important for tumor maintenance and growth. In addition, cytotoxic agents and targeted therapies regulate immune responses, which increases the chances that these therapeutic approaches may be efficiently combined with immunotherapy to ameliorate clinical outcomes. Various studies have suggested that combinations of therapies that target different stages of anti-tumor immunity may be synergistic, which can lead to potent and more prolonged responses that can achieve long-lasting tumor destruction. Nurses associated with cancer patients should have a better understanding of the immunotherapies and targeted therapies, such as their efficacy profiles, mechanisms of action, as well as management and prophylaxis of adverse events. Indeed, this knowledge will be important in establishing care for cancer patients receiving immunotherapies and targeted therapies for cancer treatment. Moreover, nurses need a better understanding regarding targeted therapies and immunotherapies to ameliorate outcomes in patients receiving these therapies, as well as management and early detection of possible adverse effects, especially adverse events associated with checkpoint inhibitors and various other therapies that control T-cell activation causing autoimmune toxicity. Nurses practice in numerous settings, such as hospitals, home healthcare agencies, radiation therapy facilities, ambulatory care clinics, and community agencies. Therefore, as compared to other members of the healthcare team, nurses often have better opportunities to develop the essential rapport in providing effective nurse-led patient education, which is important for effective therapeutic outcomes and continuance of therapy. In this article, we have particularly focused on providing a detailed overview on targeted therapies and immunotherapies used in cancer treatment, management of their associated adverse events, and the impact as well as strategies of nurse-led patient education.

Assessment of clinical miscoding errors and potential financial their implications on healthcare management - A case of local hospital in Najran, Saudi Arabia.

Background: Healthcare systems can potentially improve their safety, quality of service, and performance efficiency with a cost reduction, through the introduction and implementation of healthcare information management systems. This study aims to examine the frequency of miscoding errors in principal and secondary diagnoses, exploring demographic and coder-related factors contributing to these errors through the use of the QuadraMed system. The study also investigates the association of coding errors with patient safety and service quality to estimate the potential financial implications resulting from these inaccuracies in the healthcare system. Methods: This analytical cross-sectional retrospective study was conducted at a local hospital in Najran, Saudi Arabia, from July 2021 to February 2022 using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification (ICD-10-AM) coding system. The costing and financial data were collected from the reimbursement department for eligible 750 patient cases in terms of payment mode, services availed, and length of stay. The financial claims were evaluated to estimate the impact on the quality of service and patient safety. The reimbursement amount was calculated based on codes. The data were analyzed using SPSS and the odds ratio was calculated to estimate the risk of major coding errors in different departments. Results: Primary codes 240 (32%) and 40 (5.3) secondary codes were reviewed and percentages and inaccuracies were calculated after recording. The percentage of inaccurate medical codes in principal diagnosis was 57(26.8%) and the percentage of inaccurate medical codes in secondary diagnosis was 21 (9.9%). The primary diagnostic codes have more coding errors with a total number of 240 (32%) coding errors with a moderate level of agreement between the original coder and independent coder with a kappa value of 0.462. The identified recording was done by the independent coder, and the secondary diagnostic code showed 40 (5.3%) cases, with a poor kappa value of 0.128. The results showed the highest number of primary diagnostic codes was among surgery clinics 79 (63.2%). The highest number of secondary diagnostic codes were reported among consultant clinics 12 (9.6%). Conclusions: The study concludes that the identification of miscoding in the healthy population has a financial impact on the healthcare organization's infrastructure.

Total Number of Identified Parathyroid Glands During Total Thyroidectomy and Its Relation to Postoperative Hypoparathyroidism.

OBJECTIVES: To evaluate the correlation between the intraoperative number of identified parathyroid glands (PGs) and the risk of developing hypoparathyroidism postoperatively. Also, to determine the risks and prognostic factors in patients with postoperative hypoparathyroidism. METHODS: A retrospective study of 499 patients who underwent total thyroidectomy at two tertiary care institutions, King Saud University Medical City (KSUMC) and King Fahad Medical City (KFMC) in Riyadh, Saudi Arabia was included. Individual demographic characteristics with detailed clinical information were recorded, focusing mainly on operative reports for a total number of identified PGs intraoperatively and investigating the risk of developing hypoparathyroidism postoperatively. Factors such as age, gender, comorbidity, and number of excised and reimplanted parathyroid glands were investigated to determine the risks and prognostic factors in patients with postoperative hypoparathyroidism. RESULTS: The findings from the analysis showed that the number of identified PGs intraoperatively had a positive correlation with a higher postoperative risk of developing hypoparathyroidism. For zero, one, two, three, and four identified PGs, the risk of hypoparathyroidism in one-hour parathyroid hormone level postoperative was 6.6%, 7.3%, 34.4%, 34.4%, and 17.2% respectively. CONCLUSION: The greater the number of identified PGs intraoperatively, the less likely it was to prevent inadvertent hypoparathyroidism post-total thyroidectomy.

Utility of the Milan System for Reporting Salivary Gland Cytopathology in Parotid Gland Masses: The Experience of Two Tertiary Centers.

Background The application of fine needle aspiration (FNA) in parotid masses via the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) enhances the diagnosis of these lesions alongside radiological investigations.  Objectives Our objective was to assess the risk of malignancy, sensitivity, specificity, and false positive and negative results for each category of the MSRSGC. Additionally, we assessed the level of agreement between the FNA results using MSRSGC and post-resection histopathological diagnosis. Methods We conducted a retrospective chart review of parotid gland masses that received FNA and postoperative pathological diagnosis at King Saud University Medical City and King Fahad Medical City between 2018 and 2022. We summarized the categorical variables using frequencies and percentages. Results A total of 172 cases met the inclusion criteria. Males encompassed 102 patients (59.3%) of the study sample, and 89 (51.7%) of parotid masses were on the left side. The risk of malignancy for the MSRSGC categories was 37.5% (Category I), 9.0% (II), 50.0% (III), 4.7% (IVa), 50.0% (IVb), 100.0% (V), and 71.0% (VI). FNA had an overall success rate of 81%. The sensitivity was 64% and specificity was 94% for non-neoplastic masses. For benign masses, the sensitivity was 91% and specificity was 66%; however, the sensitivity was 40% and specificity was 97% for malignant lesions. We found that the percentage of agreement between the FNA and final pathology was 80%. Conclusion FNA using MSRSGC is a valuable preoperative clinical tool. However, the low sensitivity rates based on the diagnosis of malignant lesions should alert clinicians not to be overly reliant on biopsy results and instead defer to definitive surgical management.

Human leucocyte antigen-matched related haematopoietic stem cell transplantation using low-dose cyclophosphamide, fludarabine and thymoglobulin in children with severe aplastic anaemia.

When human leucocyte antigen-matched related donors are available, haematopoietic stem cell transplantation (HSCT) in children with severe aplastic anaemia (SAA) represents the standard of care. Cyclophosphamide (Cy) 200 mg/kg and anti-thymocyte globulin (ATG) are frequently administered, but to-date, no standard conditioning regimen exists. In this study, we investigated the efficacy of a unified HSCT conditioning protocol consisting of low-dose Cy 80 mg/kg, fludarabine and ATG. Data were reviewed from children aged ≤14 years with either acquired SAA or non-Fanconi anaemia inherited bone marrow failure syndrome (IBMFS) between 2011 and 2022 at various Saudi institutions. Graft-versus-host disease (GVHD) prophylaxis included mycophenolate mofetil and calcineurin inhibitors. HSCT was performed in 32 children (17 females and 15 males). Nine patients had deleterious mutations (two ERCC6L2, two ANKRD26, two TINF2, one LZTFL1, one RTEL1 and one DNAJC21). Four patients had short telomeres. All 32 patients engrafted successfully. At 3 years post-transplant, the event-free survival was 93% and overall survival was 95%. Two patients experienced secondary graft failure or myelodysplastic syndrome. A low probability of GVHD was observed (one acute GVHD II and one mild chronic GVHD). These data highlight how HSCT using low-dose Cy as part of a fludarabine-based regimen is safe and effective in SAA/non-Fanconi anaemia IBMFS.

Management of fever and acute painful crises in children with sickle cell disease in emergency departments: a tertiary hospital experience.

Sickle Cell Disease (SCD) is highly prevalent in Saudi Arabia with variable demographics and access to health care facilities including emergency departments. Literature reviews for locally published articles are deficient in the in-depth evaluation of current emergency practices in managing patients with SCD. The study aims to assess the current emergency practice in managing SCD patients in tertiary hospitals. We reviewed data of 212 visits by patients with SCD over three years and assessed the current emergency department practices in managing common SCD crises, such as vaso-occlusive (VOC) and febrile episodes. Our findings revealed that 47.2%, 37.7%, and 15% of the patients presented with pain, fever, or both, respectively. The patients were triaged level III according to the Canadian triage and acuity scale system in 89% of the visits. The Median time for patients to see healthcare providers was 22 min. In the first 2 h, 86% of the patients received at least one fluid bolus and 79% of them received appropriate analgesia for pain crises. Approximately 41.5% of the patients with fever were admitted and received ceftriaxone as single intravenous antimicrobial agent. However, none of the patients had bacteremia. Only 2.4% of the patients had either urinary tract infection or osteomyelitis based on imaging. ED management is a key factor in the successful management of patients with SCD in a timely manner by providing fluids, analgesia, and antibiotics. Adopting evidence-based guidelines and avoiding unnecessary admissions are suggested in clinically well patients with fever in the era of completed vaccination, antibiotic prophylaxis, and good access to care for patients with a clear viral infection focus.

Genotype and Phenotype of Adenosine Deaminase 2 Deficiency: a Report from Saudi Arabia.

Adenosine deaminase 2 deficiency (DADA2), a rare and potentially fatal systemic autoinflammatory disease, is characterized by low or lack of ADA2 activity due to ADA2 mutations. DADA2 symptoms are variable and include vasculitis, immunodeficiency, and cytopenia. Minimal data are available from Saudi Arabia. This retrospective study conducted at seven major tertiary medical centers examined the phenotypic and genotypic variabilities, clinical and diagnostic findings, and treatment outcomes among 20 Saudi patients with DADA2 from 14 families. The median age of the study cohort was 9.5 years (4-26 years). The clinical presentation was before the age of 5 months in 25% of patients. Homozygous c.1447-1451del mutation was the most frequent ADA2 alteration (40%), followed by c.882-2A:G (30%). All tested patients exhibited absent or near-absent ADA2 activity. Phenotypic manifestations included stroke (40%), hematological abnormalities (95%), lymphoproliferation (65%), and recurrent infection (45%). Five and three patients had extracranial vasculitis features and Hodgkin lymphoma, respectively. Atypical manifestations included growth retardation (30%) and transverse myelitis. Anti-tumor necrosis factor (anti-TNF) therapy was the main treatment. Some patients underwent blood transfusion, splenectomy, cyclosporine and colony-stimulating factor therapies, and hematopoietic stem cell transplantation due to anti-TNF therapy failure. Fulminant hepatitis and septic multiorgan failure caused mortality in three patients. Thus, this study revealed the variability in the molecular and clinical characteristics of DADA2 in the study cohort with predominant aberrant hematological and immunological characteristics. Consensus diagnostic criteria will facilitate early diagnosis and treatment. Additionally, disease registries or large prospective studies are needed for evaluating rare disease complications, such as cancer.

Antimicrobial prophylaxis and the rate of blood stream infections and Clostridioides difficile in pediatric stem cell transplantation: A single-center retrospective study.

BACKGROUND: The use of prophylactic antibiotics in the pre-engraftment period to minimize the risk of bacteremia is debatable given concerns of Clostridioides difficile (C. diff), antibiotics resistance, and disruption of gut microbiota. METHODS: We retrospectively reviewed the rate and characteristics of bacteremia and C. diff infections within the first 100 days post-HSCT in all pediatric patients who received routine antibacterial prophylaxis during HSCT from 2015 to 2018. C. diff infection was defined by the presence of three or more unformed stools in 24 h and positive stool test for C. diff or its toxins. RESULTS: One hundred and thirty-five (100 allogeneic and 35 autologous) transplants in 123 patients were eligible for analysis. Median age at transplant was 7.1 (range 0.2-13.7), 67 (55%) were women, and diagnosis was malignant condition in 68 patients. Median time to neutrophil engraftment was 18 days (13-23). Cefepime or piperacillin-tazobactam prophylaxis was used in 105 (78%) and 28 (21%) of patients, respectively. Only five (3%) patients had bacteremia during the pre-engraftment period, and 13 (11%) patients developed bacteremia postengraftment. Septic shock was present in only one patient pre-engraftment and was due to gram-negative bacteria. All patients who developed bacteremia received MAC. Thirteen patients (10%) of patients fulfilled C. diff infection definition. There was no mortality related to bacterial infections among our patients. CONCLUSIONS: The use of antibiotic prophylaxis was associated with low rate of bacteremia in the pre-engraftment period and a 10% risk of C. diff infections. More studies are needed to better evaluate the efficacy of antibiotic prophylaxis in HSCT patients.

Atrial fibrillation/atrial flutter related mortality trends in the US population 2010-2020: Regional, racial, sex variations.

BACKGROUND: There is an evolving need to evaluate atrial fibrillation/atrial flutter (AF/AFL) mortality trends across races, sexes, geographic regions and urbanization statuses to better understand management inequalities. METHODS: This observational study utilized the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database. Mortality rates due to AF/AFL as underlying and contributing causes of death between 2010 and 2020 were investigated. Mortality trends due to AF/AFL as contributing causes of death for different races, sexes, census regions and urbanization statuses were analyzed using annual percentage change (APC), and Joinpoint regression analysis. RESULTS: Mortality from AF/AFL as the underlying cause was increasing across the US until 2016 (APC 4.8%), followed by a plateau 2016-2020 (APC 0.0 %). Conversely, the mortality rate due to AF/AFL as a contributing cause increases 2010-2020 (APC 3.3%). The mortality rate in both sexes significantly increased in almost all groups, with the largest increase seen in Non-Hispanic Black males. Rural areas had a higher mortality rate (36.9 and 22.9 per 100,000 for males and females in 2020, respectively) and higher slope of increase than urban areas in total US population. Non-Hispanic White people had greater mortality than Non-Hispanic Black people; however, Non-Hispanic Black mortality rates are increasing at a faster rate in urban areas. CONCLUSION: AF/AFL as the underlying cause of death has plateaued from 2016 across the US 2010-2020; whilst AF/AFL as contributing cause of death is increasing. Significant discrepancies in mortality rates are identified between races and urbanization status.

Efficacy and Safety of Rituximab Therapy for Lupus Nephritis Among SLE Female Patients; a Retrospective Hospital-Based Study.

Background: Renal affection in systemic lupus erythematosus (SLE) is a high-risk manifestation in which novel treatment strategies are required, particularly in patients who show lower response to conventional therapy. Rituximab has been used as an off-label treatment for lupus nephritis (LN) for the last ten years. This study aims to assess the outcome of the use of rituximab to treat LN patients. Methods: A retrospective cross-sectional study included 40 LN patients on Rituximab therapy who attended the Rheumatology clinic at Omdurman Military Hospital, Khartoum, Sudan. Between January to July 2020. Data were collected from the hospital records and included demographic, duration of disease and Rituximab doses. Renal biopsy, renal function parameters, albumin-creatinine ratio, hematological parameters and inflammatory markers. Assessment of the outcomes was conducted by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI score). Data were analyzed by using Statistical Package for Social Studies Program (SPSS, V. 21.0. IBM; Chicago). Chi-square test was used as significance test, the P. value was considered as significant at level 0.05 and akk continues variables had a normal distribution with Kolmogorov-Smirnov test. Results: Renal function test showed significant improvement after 6 months of treatment with Rituximab. In addition, the mean of the SLE Activity Index 2000 (SLEDAI 2K) was significantly decreased with remarkable improvement in the histological degree of LN. The histology of renal biopsy of the patients commonly was diffuse proliferative nephritis followed by minimal mesangial glomerulonephritis, mesangial proliferative LN then membranous nephritis respectively. Improvement was common among the patients aged 20-39 years, those with disease duration less than 5 years, who received 4 doses and rituximab as the initial modality. Conclusion: Rituximab therapy is effectively managing patients with lupus nephritis, after 6 months of follow-up, Patients showed remarkable clinical and laboratory improvement.

First Report on Comparative Essential Oil Profile of Stem and Leaves of Blepharispermum hirtum Oliver and Their Antidiabetic and Anticancer Effects.

The current research was designed to explore the Blepharispermum hirtum Oliver (Asteraceae) stem and leaves essential oil (EO) composition extracted through hydro-distillation using gas chromatography-mass spectrometry (GC-MS) analysis for the first time. The EOs of the stem and leaves of B. hirtum were comparatively studied for the in vitro antidiabetic and anticancer potential using in vitro α-glucosidase and an MTT inhibition assay, respectively. In both of the tested samples, the same number of fifty-eight compounds were identified and contributed 93.88% and 89.07% of the total oil composition in the EOs of the stem and leaves of B. hirtum correspondingly. However, camphene was observed as a major compound (23.63%) in the stem EO, followed by ß-selinene (5.33%) and ß-elemene (4.66%) and laevo-ß-pinene (4.38%). While in the EO of the leaves, the dominant compound was found to be 24-norursa-3,12-diene (9.08%), followed by ß-eudesmol (7.81%), ß-selinene (7.26%), thunbergol (5.84%), and caryophyllene oxide (5.62%). Significant antidiabetic potential was observed with an IC50 of 2.10 ± 0.57 µg/mL by the stem compared to the EO of the leaves of B. hirtum, having an IC50 of 4.30 ± 1.56 µg/mL when equated with acarbose (IC50 = 377.71 ± 1.34 µg/mL). Furthermore, the EOs offered considerable cytotoxic capabilities for MDA-MB-231. However, the EO of the leaves presented an IC50 = 88.4 ± 0.5 µg/mL compared to the EO of the stem of B. hirtum against the triple-negative breast cancer (MDA-MB-231) cell lines with an IC50 = 123.6 ± 0.8 µg/mL. However, the EOs were also treated with the human breast epithelial (MCF-10A) cell line, and from the results, it has been concluded that these oils did not produce much harm to the normal cell lines. Hence, the present research proved that the EOs of B. hirtum might be used to cure diabetes mellitus and human breast cancer. Moreover, further studies are considered to be necessary to isolate the responsible bioactive constituents to devise drugs for the observed activities.

Outcomes of blinatumomab based therapy in children with relapsed, persistent, or refractory acute lymphoblastic leukemia: a multicenter study focusing on predictors of response and post-treatment immunoglobulin production.

The management of Refractory/Relapsed B-cell Acute Lymphoblastic Leukemia (R/R ALL) remains challenging. Incorporating blinatumomab in R/R ALL treatment has shown encouraging results. We describe the outcome and predictors of response in children receiving blinatumomab as a bridge to definitive therapy. Immunoglobulin (Ig) G and viral serology before and after therapy were evaluated. Thirty-three patients that failed standard first-line treatments due to relapsed ALL (n = 22), persistent minimal residual disease (MRD) (n = 8), or refractory disease (n = 3) received blinatumomab. Grade 2 toxicity occurred in 27.2% of patients. MRD remission (<0.01%) was achieved in 72.7% of patients. Pre-blinatumomab absolute lymphocyte count (ALC) and MRD/ALC ratio significantly associated with MRD-response. Patients with t(1;19) translocation had lower response rate, compared to all other cytogenetic categories (p = 0.013). One-year event-free survival (EFS) and overall survival (OS) were 69.2% and 79.7%, respectively. Analysis of OS and EFS showed pre-blinatumomab MRD level, ALC, MRD/ALC ratio, t(1;19), and post-blinatumomab MRD remission associated with survival. Following blinatumomab, 83% (15/18) of tested patients had low IgG levels. IgG seronegative status was observed in 83% (12/15) for varicella zoster, 35% (6/17) for herpes zoster, 18% (3/17) for cytomegalovirus, and 26% (5/17) for Epstein Barr virus. Blinatumomab produced encouraging results in children with R/R ALL and low disease burden bridging to definitive therapy. Incorporating baseline genetics and biomarkers may help identify subgroups likely to be responsive/resistant to therapy. Viral serological testing pre- and post-blinatumomab is recommended to optimize supportive and preemptive therapy.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2022.2049936 .

Influencing factors of vision-threatening disease among patients with diabetes in the central region of Saudi Arabia: A case-control study.

Aims: Diabetic retinopathy is called as vision threatening disease. It affects retina very severely. DR is a common public health problem in Worldwide. Our main objective was to identify significant risk factors for diabetic retinopathy among diabetes mellitus patients. Materials and Methods: The present retrospective Case-Control study was conducted with 404 DM patients' records were collected from King Abdulaziz Medical City, Riyadh, Saudi Arabia. Statistical analysis used: Data were presented as descriptive statistics, multivariate logistic regression, association between variables was using odds ratio and 95% confidence interval. Results: Among 404 diabetes patients, 192 (47.5%) were Cases and 212 (52.5%) Controls. In multivariate regression analysis showed that male gender also had a higher likelihood in the development of DR, OR: 1. 68 [95% CI: (1.04 - 2.71); p<0.05]. Patients with poor glycaemic control, OR: 4. 86 [95% CI: (2.21-10.66); p<0.001]. Similarly, HbA1C, Low LDL was prominent risk factor in the progression of DR except age, hypocholesterolaemia, nephropathy wasn't significant. Conclusions: From our study findings, male gender, tobacco habit, poor glycaemic control, and Low HDL were appeared independently associated with the development of vision-threatening disease. By regular check-up, reducing risk factors or retain their stages in the same stage or to prolong the DR incidents among DM patients.

Orthodontic camouflage versus orthodontic-orthognathic surgical treatment in borderline class III malocclusion: a systematic review.

OBJECTIVE: This systematic review evaluated the available evidence regarding the skeletal, dentoalveolar, and soft tissue effects of orthodontic camouflage (OC) versus orthodontic-orthognathic surgical (OOS) treatment in borderline class III malocclusion patients. METHODS: Eligibility criteria. The included studies were clinical trials and/or follow-up observational studies (retrospective and prospective). Information sources. PubMed, Scopus, Science Direct, Web of Science, Cochrane, and LILACS were searched up to October 2021. Risk of bias. Downs and Black quality assessment checklist was used. Synthesis of results. The outcomes were the skeletal, dentoalveolar, and soft tissue changes obtained from pre- and post-cephalometric measurements. RESULTS: Included studies. Out of 2089 retrieved articles, 6 were eligible and thus included in the subsequent analyses. Their overall risk of bias was moderate. Outcome results. The results are presented as pre- and post-treatment values or mean changes in both groups. Two studies reported significant retrusion of the maxillary and mandibular bases in OC, in contrast to significant maxillary protrusion and mandibular retrusion with increased ANB angle in OOS. Regarding the vertical jaw relation, one study reported a significant decrease in mandibular plane inclination in OC and a significant increase in OOS. Most of the included studies reported a significant proclination in the maxillary incisors in both groups. Three studies reported a significant proclination of the mandibular incisors in OOS, while four studies reported retroclination in OC. CONCLUSION: Interpretation. The OSS has a protrusive effect on the maxillary base, retrusive effect on the mandibular base, and thus improvement in the sagittal relationship accompanied with a clockwise rotational effect on the mandibular plane. The OC has more proclination effect on the maxillary incisors and retroclination effect on the mandibular incisors compared to OOS. Limitation. Meta-analysis was not possible due to considerable variations among the included studies. Owing to the fact that some important data in the included studies were missing, conducting further studies with more standardized methodologies is highly urgent. Registration. The protocol for this systematic review was registered at the International Prospective Register of Systematic Reviews (PROSPERO, No.: CRD42020199591). CLINICAL RELEVANCE: The common features including skeletal, dental, and soft tissue characteristics of borderline class III malocclusion cases make it more difficult to select the most appropriate treatment modality that can be either OC or OOS. The availability of high-level evidence-systematic reviews-makes the clinical decision much more clear and based on scientific basis rather than personal preference.

The effect of intensity of conditioning regimen on the outcome of HSCT in children with sickle cell disease.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) provides a cure for patients with sickle cell disease (SCD). This study describes the effect of conditioning regimen intensity on HSCT outcomes among children younger than 14 years with SCD. METHODS: Transplants from HLA-matched related donors (MRD) and unrelated donors (MUD) using either myeloablative conditioning (MAC) regimens or reduced intensity conditioning (RIC) regimens were considered. Event-free survival (EFS) was the primary endpoint. Secondary endpoints included overall survival (OS) and occurrence of GVHD. RESULTS: 48 SCD patients underwent HSCT, 45 (93.8%) patients had MRD, 1 (2.1%) had 9/10 related donor, and 2 (4.1%) had MUD. The median age at transplant was 8.6 years (range, 3.1-13.8). Conditioning regimens were myeloablative (MAC) in 41 (85.4%) patients and of reduced intensity in 7 (14.6%) patients. EFS at 2 years was 100% among MAC group compared to 29% in the RIC group (p < .001). The median follow-up was 43.4 months (range 26.8-134). All events in the RIC group were secondary graft failure. However, OS was 100% in both groups at 2 years. Acute GVHD II-IV was diagnosed in 2 (4.1%) patients. Chronic GVHD occurred in 2 (4.1%) patients. GVHD did not occur in patients who underwent MUD HSCT. CONCLUSIONS: MAC in children with SCD is well tolerated and associated with an excellent outcome for HLA-matched HSCT in SCD. There was a high rate of secondary graft failure with the use of RIC. Future studies are needed to optimize RIC regimens in HSCT of children with SCD.