Efficacy and tolerability of isocitrate dehydrogenase inhibitors in patients with acute myeloid leukemia: A systematic review of clinical trials.

BACKGROUND: Acute myeloid leukemia (AML) is a hematological malignancy due to anomalous differentiation and proliferation of hematopoietic stem cells with myeloid blast buildup. Induction chemotherapy is considered the first line of treatment in most patients with AML. However, targeted therapy in the form of FLT-3, IDH, BCL-2, and immune checkpoint inhibitors, can be considered as the first line depending on their molecular profile, resistance to chemotherapy, comorbidities, etc. This review aims to assess the tolerability and efficacy of isocitrate dehydrogenase (IDH) inhibitors in AML. METHODS: We searched Medline, WOS, Embase, and clinicaltrials.gov. PRISMA guidelines were followed in this systematic review. 3327 articles were screened, and 9 clinical trials (N = 1119) were included. RESULTS: In randomized clinical trials (RCTs), objective response (OR) was reported in 63-74% of the patients with IDH inhibitors + azacitidine as compared to 19-36 % of the patients with azacitidine monotherapy in newly diagnosed (ND) medically unfit patients. Survival rates were significantly improved with the use of ivosidenib. OR was reported in 39.1-46 % of the patients who relapsed/refractory to chemotherapy. ≥Grade 3 IDH differentiation syndrome and QT prolongation were reported in 3.9-10 % and 2-10 % of the patients, respectively. CONCLUSION: IDH inhibitors (ivosidenib for IDH-1 and enasidenib for IDH-2) are safe and effective in treating ND medically unfit or relapsed refractory patients with IDH mutation. However, no survival benefit was reported with enasidenib. More randomized multicenter double-blinded clinical studies are needed to confirm these results and compare them with other targeting agents.

Incidence of Microalbuminuria and Factors Affecting It in Patients With Type 2 Diabetes Mellitus.

Background and objectives Microalbuminuria prevalence is high in patients with type 2 diabetes mellitus (T2DM) all over the world and its prevalence is affected by several factors. In Pakistan, microalbuminuria and factors that play a role in its development in patients with T2DM are under-researched. This study aimed to determine the incidence of microalbuminuria and the factors affecting it in patients with T2DM. Material and methods This descriptive cross-sectional study was performed on 129 diagnosed patients with T2DM in the outpatient department of Benazir Bhutto Hospital, Rawalpindi, for approximately six months from August 2021 to January 2022. Patients were recruited in the study through a non-probability consecutive sampling technique and established inclusion and exclusion criteria. Ethical approval was obtained from the relevant hospital ethical review board (ERB). After explaining the study's aims, informed consent was also taken from all patients before the start of data collection. A self-structured and interview-based questionnaire was used for the collection of data. Descriptive statistics and a chi-square test were applied for the data analysis using Statistical Package for the Social Sciences (SPSS) version 25 (Armonk, NY: IBM Corp.). Results The incidence of microalbuminuria in the study population was 31.78%. The association between microalbuminuria and age (p = 0.002), gender (p = 0.003), duration of diabetes mellitus (p = 0.001), therapy type (p = 0.03), control of diabetes mellitus, (p = 0.001), and hypertension (p = 0.002) was statistically significant. Higher age group, male gender, longer duration of diabetes mellitus, oral hypoglycemic agents, poorly controlled diabetes mellitus, and history of hypertension, all were found to raise the incidence of microalbuminuria. Even though being overweight was also found to raise the incidence of microalbuminuria, the association between microalbuminuria and nutritional status was statistically insignificant (p = 0.05). Conclusion Microalbuminuria incidence is significantly high in the study population. The factors such as increasing age, male gender, longer duration of the diabetes mellitus, oral hypoglycemic agents, poorly controlled diabetes mellitus, and history of hypertension, all raise the incidence of microalbuminuria in patients with T2DM to a statistically significant extent. Screening of microalbuminuria patients with T2DM should be added to the routine investigations for diabetes mellitus for the early detection of renal and cardiovascular complications.

Risk Factors of Nephrolithiasis in a Tertiary Care Hospital in Rawalpindi: A Descriptive Cross-Sectional Study.

Background Nephrolithiasis (renal stones) is the most common urological disease. Its prevalence is high in every part of the world. Several factors lead to renal stone formation. In Pakistan, nephrolithiasis prevalence is also high as Pakistan is located in a region which is known as the salt belt. However, nephrolithiasis and its possible risk factors are under-researched in Pakistan. Objective This study aims to identify the risk factors for nephrolithiasis among admitted patients with renal stones. This may lead to a reduction in renal stone incidence and its allied complications by the prevention of risk factors that would have a major role in renal stone formation. Material and methods This descriptive cross-sectional study was performed among the 143 admitted patients with renal stones in the urology ward of Benazir Bhutto Hospital, Rawalpindi, for approximately six months from November 2021 to April 2022. Non-probability convenient sampling and developed inclusion and exclusion criteria were used for the recruitment of patients. After elaborating on the objectives, the study data were collected by interviewers through a self-structured questionnaire. Descriptive analysis was carried out using SPSS version 25.0 (IBM Corp., Armonk, NY). Results Nephrolithiasis was more prevalent among patients who had an age group range of 15-30 years (47.55%), male gender (56.65%), illiterate educational status (53.14%), lower socioeconomic status (66.43%), inadequate intake of water (61.53%), used tap water (56.64%), a habit of daily vegetable intake (65.04%), sedentary lifestyle (51.74%), family history of renal stones (57.34%), no diabetes mellitus (62.94%), no hypertension (52.45%), and overweight (48.23%). Conclusion In brief, the age group of 15-30 years, male gender, illiteracy, lower socioeconomic status, insufficient water intake, tap water, high vegetables, inactive lifestyle, family history of nephrolithiasis, and a high BMI all increase the risk of nephrolithiasis.