Trial Sequential Analysis and Meta-Analysis of Olanzapine in Pediatric Patients for Chemotherapy-Induced Nausea and Vomiting (CINV).

Background and Objective: Olanzapine (OLZ) containing regimens are approved in adults for chemotherapy-induced nausea and vomiting (CINV) receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC), and the same has not been approved in the pediatric population. In order to generate data regarding the efficacy and safety of OLZ as an adjunct to the standard of care (SoC) for CINV in pediatric patients receiving HEC/MEC, the review authors performed this systematic review and meta-analysis. Methods: A systematic literature search was performed through the databases Cochrane Library, Pub Med, and clinicaltrials.gov, from inception to September 2023, using keywords: "chemotherapy" and "olanzapine," "nausea" and "vomiting." Randomized clinical trials published in English that analyzed the efficacy and safety of olanzapine as an adjunct to SoC were included. The essential outcomes included in this study were the proportion of patients with no emesis in the acute and delayed phase, patients with no nausea in the acute and delayed phase, the proportion of patients requiring rescue medication, and the proportion of patients with reduced CNS arousal. Results: In the OLZ group, a greater number of patients had no emesis both in the acute and delayed phase (RR = 1.22; 95% CI = 1.09-1.37; P = .0004); and (RR = 1.23; 95% CI = 0.92-1.63; P = .16) respectively. Similarly, a higher number of patients showed no nausea both in the acute and delayed phase (RR = 1.08; 95% CI = 0.78-1.48; P = .66) and (RR = 1.12; 95% CI = 0.79-1.61; P = .52) respectively. The use of rescue medication was significantly less in the OLZ group (RR = 0.62; 95% CI = 0.42-0.91; P = .01). More patients experienced reduced CNS arousal in the OLZ group (RR = 2.97; 95% CI = 2.02-4.38; P < .0001). Conclusions: Olanzapine as an adjunct to the SoC may be effective in acute emesis, which may also reduce the use of rescue medication. Reduced CNS alertness was the significant adverse effect observed. For other endpoints, more studies are required to substantiate its role in CINV.

Prevalence and Clinical Outcome of FMS-Like Tyrosine Kinase Mutations Among Patients With Core Binding Factor-Acute Myeloid Leukemia: Systematic Review and Meta-Analysis.

BACKGROUND: Core binding factor acute myeloid leukemia (CBF-AML) belongs to favorable risk group in AML. However, approximately 50% of patients with CBF-AML remain incurable and their outcomes are also determined by the various co-occurring mutations. Though, FMS-like tyrosine kinase-3(FLT3) mutation in AML is associated with poor survival, the prevalence and prognostic significance of FLT3 mutations among CBF-AML is unknown. PATIENTS AND METHODS: We performed a systematic review and meta-analysis to assess the prevalence of FLT3 mutations (ITD and TKD) among patients with CBF-AML. The pooled prevalence of FLT3 mutations was estimated for patients with CBF-AML, t(8;21) and Inv(16). Pooled odds ratio was calculated to compare the prevalence of various FLT3 mutations within the 2 subsets of CBF-AML. A random effects model was adopted for analysis when heterogenicity existed (Pheterogenicity< 0.05 or I2 > 50%). Otherwise, a fixed effects model was used. RESULTS: The pooled prevalence of any FLT3 mutations among patients with CBF-AML was available from 18 studies and was 13% (95% CI: 10%-16%; I2 = 79%). Comparison of prevalence of FLT3 mutations between the 2 subgroups of CBF-AML showed that patients with t(8;21) had a higher prevalence of FLT3-ITD [pooled odds ratio(OR): 2.23 (95% CI:1.41-3.53, P < .01)] and lower prevalence of FLT3-TKD [pooled OR: 0.29 (95% CI:0.19-0.44; P < .01)] compared to patients with Inv(16). Additionally, we have discussed the prognostic significance of FLT3 mutations in CBF-AML patients. CONCLUSION: The prevalence of FLT3-TKD mutation was commoner among Inv(16) AML while FLT3-ITD mutation was commoner among t(8;21) AML. Uniform reporting of outcomes is essential to understand the prognostic significance of FLT3 mutations among CBF-AML.

Systemic Therapy in Thyroid Cancer.

Thyroid cancer is the most common endocrine malignancy. While surgery remains the mainstay of the treatment of all different histologies, for differentiated thyroid cancers, radioactive iodine also plays an important role in management. Once tumor becomes radio-iodine refractory, it needs systemic therapy. Earlier, these tumors had very dismal prognosis. However, with the advancement of technology and research, it has become clear now that thyroid cancer cells are driven by various mutations. Targeting these oncogenic drivers by various molecules have proven to be effective therapeutic strategy in thyroid cancer. Besides, as in other solid tumors, immunotherapy is also being evaluated in thyroid cancer. While these new therapeutic approaches have revolutionized the treatment on advanced/metastatic thyroid cancer, there are definite challenges which limit their use in common clinical practice. These challenges include higher treatment cost and lack of testing to identify the driver mutations. Moreover, there is still need for further research in thyroid cancers to identify oncogenic targets and agent to act upon them.

Pre-transplant use of tyrosine kinase inhibitors and transplant associated thrombotic microangiopathy - a single centre analysis of incidence, risk factors and outcomes.

Transplant associated thrombotic microangiopathy (TA-TMA) is life-threatening complication post allogeneic stem cell transplant (ASCT). Risk factors and prognosis of TA-TMA are not well defined. We retrospectively studied consecutive ASCT patients with AML, ALL, and CML from January 2008 to March 2019 to study the incidence, risk factors, and outcomes of TMA. Definitive and probable TA-TMA was defined using Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) and Cho criteria, respectively. Risk factors explored were age, gender, diagnosis, type of transplant, use of tyrosine kinase inhibitors (TKI) pre transplant, conditioning regimen, and acute GVHD. Standard statistical methods were used. Total 241 patients, 179 (74.2 %) males, median age of 29 years were studied. Diagnoses were AML in 104, ALL in 85 (Ph+ve 23) and CML 52. Total 26 (10.7%) patients (22 males) developed TA-TMA at median of day+102. On multivariate analysis, pre-HSCT TKI (OR 2.7, p = 0.028), haplo-HSCT (OR 3.16, p = 0.018) and presence of acute GVHD (OR 4.17, p = 0.003) were significant risk factors. With a median follow up of 60 months, median OS with and without TA-TMA was 18 and 97 months respectively (p = 0.021). The association of pre-HSCT with TKI with TA-TMA merits further exploration in prospective studies.

Dunite carbonation in batch-tubular reactor.

For geological carbon sequestration, the reaction of aqueous CO2 with silicate rock permits carbonate formation, achieving permanent carbon sequestration. The fractures available in silicate rock provide significant surface area for the precipitation of carbonates. The experiments were performed in a batch tubular reactor under diffusion-limited condition, with a special arrangement of a narrow tube filled with a 2800 g/L dunite slurry. The tube was kept open from the top, standing vertically filled with a CO2-rich bulk solution under 1 barg CO2 and temperatures ranging from 25 to 75 oC for 7-30 days. After 7 days of the experiment, magnesite precipitation was seen inside the tube and the precipitation was continued for up to 30 days. The magnesite precipitation was identified by micro-Raman spectroscopy, X-ray diffraction, and scanning electron microscopy. Additionally, SiO2 formation was seen in relative close vicinity to the magnesite precipitation. The precipitation on the surface of silicate rock might cover the fractures and pore spaces available, which may over time reduce the dissolution rate of dunite. Graphical Abstract.

Olivine dissolution from Indian dunite in saline water.

The rate and mechanism of olivine dissolution was studied using naturally weathered dunite FO98.21(Mg1.884Fe0.391SiO4) from an Indian source, that also contains serpentine mineral lizardite. A series of batch dissolution experiments were carried out to check the influence of temperature (30-75 ∘C), initial dunite concentration (0.5 and 20 g/L), and salinity (0-35 g/L NaCl) under fixed head space CO2 pressure (P[Formula: see text] = 1 barg) on dunite dissolution. Dissolved Mg, Si, and Fe concentrations were determined by inductive coupled plasma atomic emission spectroscopy. End-product solids were characterized by scanning electron microscopy and X-ray diffraction. Initially, rates of dissolution of Si and Mg were observed to be in stoichiometric proportion. After 8 h, the dissolution rate was observed to decline. At the end of the experiment (504 h), an amorphous silica-rich layer was observed over the dunite surface. This results in decay of the dissolution rate. The operating conditions (i.e., salinity, temperature, and mineral loading) affect the dissolution kinetics in a very complex manner because of which the observed experimental trends do not exhibit a direct trend.