Real-World Registry on the Pharmacotherapy of Multiple Myeloma and Associated Renal and Pulmonary Impairments in the Greater Gulf Region: Protocol for a Retrospective Real-World Data Study.

BACKGROUND: Multiple myeloma (MM) is the second-most common cancer among hematological malignancies. Patients with active disease may experience several comorbidities, including renal insufficiency and asthma, which may lead to treatment failure. The treatment of relapsed or refractory MM (RRMM) has been associated with multiple factors, causing a decline in progression-free survival as well as overall survival with subsequent lines of therapy. Data about the characteristics of this group of patients in the Greater Gulf region are lacking. OBJECTIVE: The primary objective of this study is to describe the disease characteristics and various treatment approaches or regimens used in the management of patients with RRMM in the Greater Gulf region. METHODS: We will conduct a regional, retrospective study collecting real-world and epidemiological data on patients with MM in countries of the Greater Gulf region. Medical records will be used to obtain the required data. Around 150 to 170 patients' records are planned to be retrospectively reviewed over 6 months without any cross-sectional or prospective intervention. Cases will be collected from Saudi Arabia, the United Arab Emirates, Kuwait, Oman, and Qatar. Descriptive as well as analytical statistics will be performed on the extracted data. The calculated sample size will allow us to estimate the percentages of RRMM cases with acceptable precision while complying with the challenges in light of data scarcity. We will obtain a comprehensive description of the demographic profile of patients with MM; treatment outcomes; the proportion of patients with MM with renal impairment and asthma, chronic obstructive pulmonary disease, or both at the time of diagnosis and any subsequent point; and data related to treatment lines, regimens, and MM-associated morbidities. RESULTS: Patient medical records were reviewed between June 2022 and January 2023 for eligibility and data extraction. A total of 148 patients were eligible for study inclusion, of whom 64.2% (n=95) were male and 35.8% (n=53) were female. The study is currently in its final stages of data analysis. The final manuscript is expected to be published in 2024. CONCLUSIONS: Although MM is a predominant hematological disease, data on its prevalence and patients' characteristics in the Greater Gulf region are scarce. Therefore, this study will give us real-world insights into disease characteristics and various management approaches of patients with MM in the Greater Gulf region. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49861.

International survey on complications of religious fasting after metabolic and bariatric surgery.

Religious fasting in Ramadan the 9th month of the lunar year is one of five pillars in Islam and is practiced for a full month every year. There may be risks with fasting in patients with a history of metabolic/bariatric surgery (MBS). There is little published evidence on the possible complications during fasting and needs stronger recommendations and guidance to minimize them. An international survey was sent to surgeons to study the types of complications occurring during religious fasting in patients with history of MBS to evaluate the risk factors to manage and prepare more evidence-based recommendations. In total, 21 centers from 11 countries participated in this survey and reported a total of 132 patients with complications occurring during religious fasting after MBS. The mean age of patients with complications was 36.65 ± 3.48 years and mean BMI was 43.12 ± 6.86 kg/m2. Mean timing of complication occurring during fasting after MBS was 14.18 months. The most common complications were upper GI (gastrointestinal) symptoms including [gastroesophageal reflux disease (GERD), abdominal pain, and dyspepsia], marginal ulcers and dumping syndrome in 24% (32/132), 8.3% (11/132) and 23% (31/132) patients respectively. Surgical management was necessary in 4.5% of patients presenting with complications (6/132) patients due to perforated marginal or peptic ulcer in Single Anastomosis Duodenoileostomy with Sleeve gastrectomy (SADI-S), one anastomosis gastric bypass (OAGB) and sleeve gastrectomy (SG), obstruction at Jejunojenostomy after Roux-en-Y gastric bypass (RYGB) (1/6) and acute cholecystitis (1/6). Patients after MBS should be advised about the risks while fasting including abdominal pain, dehydration, and peptic ulcer disease exacerbation, and a thorough review of their medications is warranted to minimize complications.

Religious Fasting of Muslim Patients After Metabolic and Bariatric Surgery: a Modified Delphi Consensus.

BACKGROUND: Fasting during Ramadan is one of the five pillars of the Muslim faith. Despite the positive effects of fasting on health, there are no guidelines or clear recommendations regarding fasting after metabolic/bariatric surgery (MBS). The current study reports the result of a modified Delphi consensus among expert metabolic/bariatric surgeons with experience in managing patients who fast after MBS. METHODS: A committee of 61 well-known metabolic and bariatric surgeons from 24 countries was created to participate in the Delphi consensus. The committee voted on 45 statements regarding recommendations and controversies around fasting after MBS. An agreement/disagreement ≥ of 70.0% was regarded as consensus. RESULTS: The experts reached a consensus on 40 out of 45 statements after two rounds of voting. One hundred percent of the experts believed that fasting needs special nutritional support in patients who underwent MBS. The decision regarding fasting must be coordinated among the surgeon, the nutritionist and the patient. At any time after MBS, 96.7% advised stopping fasting in the presence of persistent symptoms of intolerance. Seventy percent of the experts recommended delaying fasting after MBS for 6 to 12 months after combined and malabsorptive procedures according to the patient's situation and surgeon's experience, and 90.1% felt that proton pump inhibitors should be continued in patients who start fasting less than 6 months after MBS. There was consensus that fasting may help in weight loss, improvement/remission of non-alcoholic fatty liver disease, dyslipidemia, hypertension and type 2 diabetes mellitus among 88.5%, 90.2%, 88.5%, 85.2% and 85.2% of experts, respectively. CONCLUSION: Experts voted and reached a consensus on 40 statements covering various aspects of fasting after MBS.

Isolated Myeloperoxidase Immunohistochemical Expression in Bone Marrow Biopsy Depicts Clinical Outcomes in Adults with Typical B-Acute Lymphoblastic Leukemia.

INTRODUCTION: Recently, isolated myeloperoxidase expression (isoMPO) has been documented in B-acute lymphoblastic leukemia (B-ALL) and several contradictory studies addressed its clinical significance in pediatric patients. AIM: In this study, isoMPO was evaluated in bone marrow biopsies (BMB) from adults with B-ALL using immunohistochemistry (IHC) in relation to a number of risk-stratification factors and patients' outcomes. METHODS: Sixty B-ALL adult patients were selected upon electronic database search. Demographic, clinical, laboratory, therapy and survival data were reviewed and tabulated. Flowcytometry (FCM), histopathology and IHC available material were reviewed to confirm the diagnostic criteria according to our standard laboratory protocols. IHC was performed on BMB using antiMPO. Cases were divided into MPO+ve and MPO-ve based on a 3% blast cell staining threshold. RESULTS: Using IHC, 26.7% of B-ALLs were MPO+ve, in most of which ≥10% of blasts were stained. Among standard risk-stratification factors, isoMPO was associated with a mean WBC count above 30x109/L. MPO+ patients achieved therapeutic complete remission at lower rates and were more prone to progressive/refractory disease and relapse. There was a concordant expression of MPO in FCM and IHC. All of the aforementioned parameters reached the level of significance when compared to the MOP-ve group. Kaplan-Meier curves revealed a significantly lower survival probability for the MPO+ group than the MOP-ve one (p= 0.0066; Log-rank test) and also when separating MPO+ and -ve patients by gender (p= 0.0033; Log-rank test). CONCLUSION: isoMPO occur in a considerable percentage of B-ALL in adults contributing to misdiagnosis. It depicts poor outcomes and might be introduced as a B-ALL risk-stratification factor.
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Impact of Bone Marrow Natural Killer Cells (NK); Soluble TNF-α and IL-32 Levels in Myelodysplastic Syndrome Patients.

BACKGROUND: Myelodysplastic syndromes (MDS) are complex clonal hemopoietic progenitor cell disorders that result from the evolution of aberrant clones which lead to leukemia. Disorders of the immune system serve important functions in the pathophysiology and progression of this disorder. This study aimed to assess the bone marrow natural killer cells percentage as well as soluble TNF-α and sIL-32 concentration levels in MDS patients. METHODS: Bone marrow samples were obtained from 34 MDS; 12 MDS-AML and 10 controls. The percentage of total NK cells and mature NK cells were determined by flowcytometry. Bone Marrow soluble TNF-α and sIL-32 concentration levels were measured by ELISA. RESULTS: The percentage of total NK and mature NK cells were significantly lower in MDS patients as compared to controls (p.

Prognostic Value of CD200 Expression and Soluble CTLA-4 Concentrations in Intermediate and High-Risk Myelodysplastic Syndrome Patients.

OBJECTIVE: This study was designed in order to identify the prognostic relevance of CD200 expression and soluble Cytotoxic T-lymphocyte antigen-4 (CTLA-4) levels in myelodysplastic syndrome (MDS) patients. METHODS: The study included 57 MDS (37 intermediate and 20 high risk) patients and 10 controls. For all of included patients; CD200 expression was identified by flowcytometry on CD33 positive cells and soluble CTLA-4 (CD152) concentration was determined by ELISA. RESULTS: CD200 positive expression was detected in 32/57 (56.1%) of MDS cases, the mean serum CTLA-4 concentrations were significantly higher in MDS patients as compared to controls (P<0.01). Significant association between high CD200 positive expression; high CTLA-4   concentration levels and   MDS risk stages being higher in high risk MDS group as compared to intermediate risk one (P < 0.01).  After 36-month follow-up; the subgroup of MDS patients with high expression of CD200; and high serum CTLA-4 concentrations showed high death rate and high frequency of acute myeloid leukemia transformation. CONCLUSIONS: CD200 positive expression could be considered as a new prognostic marker for risk stratification of MDS patients. CD200 expression may exert its effect through upregulation of CTLA-4.
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Clinical Value of NOTCH1 Mutations Detection among Chronic Lymphocytic Leukemia Patients.

BACKGROUND: The data about the clinical impact of NOTCH1 mutations among Egyptians B - cell chronic lymphocytic patients is not previously identified. We herein, evaluate the prevalence and the prognostic significance of neurogenic locus notch homolog protein-1 (NOTCH1) mutations in B- cell lymphocytic leukemia (B-CLL). METHODS: A cohort of 105 Egyptian B-CLL patients aging from 43 to 86 years. PCR products including NOTCH1 exon 26, 27, and distal part of exon 34 expanding the sequences encoding transcription activation domain (TAD) and a peptide sequence rich in proline (P), glutamic acid (E), serine (S), threonine (T) (PEST domains) were sequenced by direct DNA Sanger sequencing. RESULTS: NOTCH1 mutations were detected in 48/105 of patients (45.7%). Mutations in B-CLL patients are insertions (n=21), point mutations (n=18) and deletions (n=12). NOTCH1 mutations showed significant impact on prognosis of B-CLL patients as they were associated with increased bone marrow lymphocytes, more relapse and  high incidence of mortality, shortened overall survival and progression free survival, and lymphocytes doubling time, when compared with NOTCH1 wild type B-CLL patients (P= 0.001; 0,005; 0.042; 0.049; 0.008; 0.049 respectively). CONCLUSION: NOTCH1 mutations were considered as bad prognostic marker in B-CLL and suggested to be included in risk stratification of B-CLL patients at diagnosis.

From diabetes remedy to diabetes remission; could single-anastomosis gastric bypass be a safe bridge to reach target in non-obese patients?

BACKGROUND/AIMS: Type 2 diabetes mellitus (T2DM) is considered a chronic progressive incurable metabolic disease. Single-anastomosis gastric bypass (SAGB) has proved to be effective in obese patients, yet its impact on non-obese diabetics is not extensively studied. The aim is to determine the anthropometric and glycemic outcomes of SAGB as a proposed line of treatment for T2DM patients with body mass index (BMI) 25-30 kg/m2. METHODS: From November 2013 to March 2016, a prospective study has been conducted at Ain-Shams University Hospitals on 17 consecutive patients who have undergone SAGB. The demographic and anthropometric data, as well as the relevant laboratory results, were reported. Complete T2DM remission is considered if glycosylated hemoglobin (HbA1c) <6 % for at least 1 year without medication, whereas partial remission is considered if HbA1c<6.5%. RESULTS: The mean age was 42.6 ±13.8 years, mean BMI was 26.7 ± 2.3 kg/m2 and mean duration of DM was 6.3 ± 2.7 years. The mean baseline values of HbA1c, FPG (fasting plasma glucose), and 2-hours postprandial glucose (2-H PPG) were 9.9%, 176.3 mg/dl, and 310.3 mg/dl respectively. These values significantly dropped at the 18th month to reach 5.8%, 93.4 mg/dl, and 156.2 mg/dl, with 13/17 patients became off-treatment (complete remission rate 76.4%). CONCLUSION: T2DM patients with BMI 25-30 kg/m2 are considered the most controversial group. SAGB is an efficient metabolic procedure and could be integrated into the treatment algorithm of T2DM. Such line of treatment opens new horizons to change the concept of treatment from diabetes remedy to diabetes remission.

Prevalence and Prognostic Value of IDH1 R132 Mutation in Newly Diagnosed AML Egyptian Patients with Normal Karyotype.

Mutation in IDH1 gene was suggested to be associated with bad prognosis in cytogenetically normal AML (CN-AML). However, there are conflicting data about its prognostic impact. Besides, its prevalence and prognostic significance in Egyptian patients still not fully stated. We aimed to assess the prevalence of IDH1R132 mutation in Egyptian CN-AML patients, its correlation with FAB subtypes, and clinical outcome of those patients. Sequencing of amplified IDH1 gene exon four from 50 patients was performed to detect codon R132 point mutation. High prevalence of IDH1 mutation was detected in our patients (9/50, 18 %). Mutated IDH1R132 was associated with older age and higher platelets count (p = 0.04 and 0.01 respectively). The most common FAB subtype associated with mutated IDH1R132 was AML-M2 followed by M4. In multivariate analysis, IDH1R132 mutation was found as independent prognostic variable. It was significantly associated with lower CR and shorter OS (p = 0.06 and 0.009 respectively).

Impact of serum immunoglobulins level and IL-18 promoter gene polymorphism among Egyptian patients with idiopathic thrombocytopenic purpura.

OBJECTIVES: Based on the concept of immune dysregulation in immune thrombocytopenic purpura (ITP) and that Interleukin-18 (IL-18) is an inflammatory cytokine that plays an important role in autoimmune disease by inducing interferon-γ secretion; this study aimed to assess a possible association between the IL-18 promoter polymorphisms (-607 C/A site) and genetic susceptibility to ITP and the impact of the immunoglobulins (Igs) concentrations level on disease severity and response to therapy. METHODS: A cross-section study was done on 105 patients' age range from 10 to 28 years, with newly diagnosed ITP at the Oncology Center Mansoura University over the past 2 years and 100 healthy subjects as a control group. For all patients and controls, the IL-18 promoter polymorphism (-607 C/A site) as well as serum Ig (IgG, IgM, IgA) concentration was determined. RESULTS: The IL-18 promoter polymorphism (-607 C/A site) was not significantly different between ITP patients and normal controls. The number of patients respond to standard line of therapy was significantly higher in those with low IgA levels as compared to those with high IgA levels (P = 0.02). On the other hand, the number of patients respond to standard therapy was significantly higher in those patients with high IgM levels as compared to those with low IgM levels (54.7 vs. 36.5%) (P < 0.05). The number of patients with bleeding manifestation was significantly higher among those with high IgA as compared to those with low IgA (43 of 79, 54.4%; vs. 36 of 79, 45.6%; P = 0.04). A change in IgG levels was not associated with response to treatment, bleeding tendency, or platelet counts. CONCLUSION: There is no association between IL-18 promoter polymorphisms (-607 C/A site) and genetic susceptibility to ITP. High IgA and low IgM levels are a bad index for treatment response to standard therapy.

Telomerase reverse transcriptase (TERT) A1062T mutation as a prognostic factor in Egyptian patients with acute myeloid leukemia (AML).

This study aimed to evaluate the incidence and clinical and prognostic impact of TERT A1062T mutation in AML patients treated at Mansoura Oncology Center. Screening for TERT A1062T mutation in exon 15 of the TERT gene was performed on diagnostic DNA samples from 153 AML patients and 197 healthy subjects as a control group by using sequence-specific primers. TERT A1062T mutation was detected in 18 cases out of 153 patients (11.8 %) and in one out of 197 control group subjects (0.51 %). The achievement of complete remission was significantly higher in AML group with wild type as compared to that in the mutant one (53.3 vs 16.7 %, respectively). In addition, the relapse rate was significantly higher in the mutant patients as compared to those with wild type (62.5 vs 28.2 %, respectively). The AML patients with TERT (A1062T) mutation had shorter overall survival than patients with wild type (P = 0.001). In a multivariable analysis, TERT (A1062T) mutational status is independently worse predictor factor (P = 0.007) when controlling for cytogenetic status (P = <0.001), performance status (P = <0.001) and bone marrow blast cells (P = 0.001). In conclusion, TERT A1062T mutation is an independent negative prognostic factor in AML patients. Therefore, molecular testing for TERT A1062T mutation in patients with AML is recommended in order to delineate their prognostic status.

Prevalence and impact of colony stimulating factor 3 receptor (CSF3R) mutations among Egyptian acute myeloid leukemia patients.

Granulocyte-colony stimulating factor receptor (G-CSFR) mutations have been implicated in the progression of severe congenital neutropenia (SCN) to leukemia. This study aimed to investigate the prevalence of colony stimulating factor 3 receptor (CSF3R) mutations among Egyptian acute myeloid leukemia and their clinic-pathological impact. The study was conducted on 179 adult patients (156 de novo AML and 23 secondary AML on top of SCN). CSF3R mutations were analyzed by sequencing of the PCR products. CSF3R mutations were detected in 2 cases out of 156 de novo AML patients (1.2%) and eighteen cases out of 23 secondary AML patients (78.2%). It was noticed that most of the mutant cases are of younger age, have a high white blood cells count, high bone marrow blasts, bad performance status, and absence of extra medullary disease and with low rate induction remission. Also the overall survival of AML patient's secondary to CSF3R mutations was shorter as compared to those with wild type AML cases. In conclusion the frequency of CSF3R mutations is highly prevalent among AML patients secondary to SCN compared to de novo AML.