Response to pazopanib-based combination regimen in a case of FGFR3 amplified gastric adenocarcinoma.

Angiogenesis inhibitors (AGI) are not presently used for the treatment of gastric cancers. This report demonstrates that angiogenesis inhibitor can be safely and effectively used in combination with cytotoxic anti-cancer agents for treatment of Gastric cancers.

Development and validation of a multigene variant profiling assay to guide targeted and immuno therapy selection in solid tumors.

We present data on analytical validation of the multigene variant profiling assay (CellDx) to provide actionable indications for selection of targeted and immune checkpoint inhibitor (ICI) therapy in solid tumors. CellDx includes Next Generation Sequencing (NGS) profiling of gene variants in a targeted 452-gene panel as well as status of total Tumor Mutation Burden (TMB), Microsatellite instability (MSI), Mismatch Repair (MMR) and Programmed Cell Death-Ligand 1 (PD-L1) respectively. Validation parameters included accuracy, sensitivity, specificity and reproducibility for detection of Single Nucleotide Alterations (SNAs), Copy Number Alterations (CNAs), Insertions and Deletions (Indels), Gene fusions, MSI and PDL1. Cumulative analytical sensitivity and specificity of the assay were 99.03 (95% CI: 96.54-99.88) and 99.23% (95% CI: 98.54% - 99.65%) respectively with 99.20% overall Accuracy (95% CI: 98.57% - 99.60%) and 99.7% Precision based on evaluation of 116 reference samples. The clinical performance of CellDx was evaluated in a subsequent analysis of 299 clinical samples where 861 unique mutations were detected of which 791 were oncogenic and 47 were actionable. Indications in MMR, MSI and TMB for selection of ICI therapies were also detected in the clinical samples. The high specificity, sensitivity, accuracy and reproducibility of the CellDx assay is suitable for clinical application for guiding selection of targeted and immunotherapy agents in patients with solid organ tumors.

Oral Paracetamol vs Oral Ibuprofen in Patent Ductus Arteriosus: A Randomized, Controlled, Noninferiority Trial.

OBJECTIVE: To test the hypothesis that oral paracetamol is non-inferior to oral ibuprofen in closing hemodynamically significant patent ductus arteriosus (hsPDA) with an a priori noninferiority (NI) margin of 15%. STUDY DESIGN: Multicenter, randomized, controlled, NI trial conducted in level III neonatal intensive care units. Consecutively inborn preterm neonates of <32 weeks of gestation with hsPDA were included. Those with structural heart disease, major malformations, and contraindications for enteral feeding or for administration of study drugs were excluded. Interventions included oral paracetamol in the experimental arm and oral ibuprofen in the active control arm. The primary outcome was closure of hsPDA by 24 hours from the last dose of the study drug. Secondary outcome measures included closure of hsPDA by 24 hours after the first course of the study drug, rate of reopening after the first course, and adverse events associated with the study drug. RESULTS: Out of 1250 neonates screened, 161 were randomized. Oral paracetamol was noninferior to oral ibuprofen in closure of hsPDA by both per protocol analysis (62 [95.4%] vs 63 [94%]; relative risk [RR], 1.01 [95% CI, 0.94-1.1]; risk difference [RD], 1.4 [95% CI, -6 to 9]; P = .37) and intention-to-treat analysis (63 [89%] vs 65 [89%]; RR, 0.99 [95% CI, 0.89-1.12]; RD, -0.3 [95% CI, -11 to 10]; P = .47). All adverse events were comparable in the 2 study arms. CONCLUSIONS: Oral paracetamol is noninferior to oral ibuprofen for the closure of hsPDA in preterm neonates of <32 weeks of gestation. No difference was observed in the adverse events studied.

Mucosal bridges (MB): a 9-year retrospective study of their incidence with a third variant proposed.

BACKGROUND: Mucosal bridges (MBs) are rare laryngeal lesions that may cause dysphonia of varying degrees. We propose the existence of a third variant of MB besides thin and thick MBs, and have termed this as an incomplete mucosal bridge (IMB). The concept of an IMB has not been previously discussed in literature. Thin and thick MBs are attached anteriorly and posteriorly on the membranous vocal fold and may cause dysphonia because of their separate vibratory characteristics from the main vocal fold. We propose the presence of an entity named as IMB, which is typically identified by palpation of a slit on the superior surface of the membranous vocal fold. AIM: To propose and describe the existence of IMBs. Furthermore, to study the percentage of various types of MBs found while performing microlaryngeal surgeries (MLS) for benign glottic lesions, over a 9-year period at our Voice Clinic. METHOD: An IMB may be described as a MB that does not open at its medial edge. Thus it appears as an epithelial slit on the surface of the vocal fold. On palpating this slit with a microflap elevator, a flat pocket lying just below and parallel to the vocal fold epithelium is identified. These pockets are always directed medially (never laterally) and just stop short of opening up at the medial edge. These IMBs differ from sulci and focal pit as sulci and focal pits are not covered with a hood of epithelium. Our operative records of all MLS performed for benign glottic lesions were audited from 2009 to 2017 for cases of MBs. RESULTS: A total of 1728 MLS for benign glottic lesions were performed from 2009 to 2017 and 27 MBs were identified in 23 patients, 16 being male. A total of 11 IMBs were identified in 10 patients, with 1 case revealing a bilateral IMB. Other associated lesions were cysts, sulci, and polyps. A total of 14 thin MBs were identified in 11 patients with 3 cases revealing these bilaterally. Two thick MBs were identified in two separate cases, with one case having a bilobed hemorrhagic polyp attached to the thick MB. CONCLUSION: Our study found MBs in 1.33% of patients being operated for benign glottic lesions. The incidence of MBs in this group was 1.56% with IMBs accounting for 0.63%, thin MBs accounting for 0.81% and thick MBs in 0.11%. We recommend all patients undergoing MLS be actively palpated for the presence of mucosal bridges including IMBs especially if a small slit is found on the surface of the vocal fold. This is vital for accurate identification and documentation of all the lesions responsible for the patients voice quality. Ours is an ongoing study and we propose to analyze the vocal outcomes associated with surgical management of these IMBs.

Optimization of Ex Vivo Murine Bone Marrow Derived Immature Dendritic Cells: A Comparative Analysis of Flask Culture Method and Mouse CD11c Positive Selection Kit Method.

12-14 days of culturing of bone marrow (BM) cells containing various growth factors is widely used method for generating dendritic cells (DCs) from suspended cell population. Here we compared flask culture method and commercially available CD11c Positive Selection kit method. Immature BMDCs' purity of adherent as well as suspended cell population was generated in the decreasing concentration of recombinant-murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF) in nontreated tissue culture flasks. The expression of CD11c, MHCII, CD40, and CD86 was measured by flow cytometry. We found significant difference (P < 0.05) between the two methods in the adherent cells population but no significant difference was observed between the suspended cell populations with respect to CD11c+ count. However, CD11c+ was significantly higher in both adhered and suspended cell population by culture method but kit method gave more CD11c+ from suspended cells population only. On the other hand, using both methods, immature DC expressed moderate level of MHC class II molecules as well as low levels of CD40 and CD86. Our findings suggest that widely used culture method gives the best results in terms of yield, viability, and purity of BMDCs from both adherent and suspended cell population whereas kit method works well for suspended cell population.