Optimization of personalized immuno-oncology requires integration of several technologies and selection of those best suited for an individual patient. Advances in immuno-oncology are also attributed to technologies for targeted delivery of anticancer therapeutics such as antigen-capturing nanoparticles for precision targeting and selective delivery. A breakthrough in cell therapy of cancer is a chimeric antigen receptors-T cell, which combines the antigen-binding site of a MAb with the signal activating machinery of a T cell, freeing antigen recognition from major histocompatibility complex restriction. Gene-editing tools such as clustered regularly interspaced short palindromic repeats have a promising application for removing alloreactivity and decreasing immunogenicity of third-party T cells. In conclusion, personalized immuno-oncology is one of the most promising approaches to management of cancer.

Large variability in neonatal amoxicillin dosing recommendations may reflect uncertainty about appropriate efficacy and toxicity targets.

The aim of this study was to model efficacious and safe exposure for current neonatal amoxicillin dosing regimens, given a range of assumptions for minimal inhibitory concentration (MIC), targeted %fT > MIC, and potential for aminopenicillin-related neurotoxicity.

Individual intravenous amoxicillin exposures based on 6 international and 9 Swiss neonatal dosing recommendations, reflecting the range of current dosing approaches, were assessed by a previously developed population pharmacokinetic model informed by neonatal data from an international cohort. Exposure was simulated by attributing each dosing regimen to each patient cohort. End points of interest were %fT > MIC and potential neurotoxicity using Cmax > 140 mg/L as threshold.

None of the dosing regimens achieved targets of ≥100%fT > MIC at any of the relevant MICs for a desired probability of tarlecting optimal dosing regimens in this understudied population.

There are several electrocardiographic algorithms to predict the origin of idiopathic outflow tract ventricular arrhythmias (OT-VAs). This study aimed to develop a more accurate and efficient stepwise electrocardiographic algorithm to discriminate left ventricular outflow tract (LVOT) from right ventricular outflow tract (RVOT) origin.

We analyzed 12-lead electrocardiographic characteristics of 173 consecutive OT-VAs patients who underwent successful radiofrequency catheter ablation in the RVOT (n = 124) or LVOT (n = 49). Based on the areas under the receiver operating characteristic curves, the combination of transitional zone (TZ) index <0 and V2S/V3R index ≤1.5 exhibited 93.5% sensitivity, 85.9% specificity, and 87.3% accuracy. A further analysis was performed in the 71 OT-VAs with a V3-lead precordial transition. The sensitivity, specificity, and accuracy of the integration of V2S/V3R index ≤1.5 and R-wave deflection interval in lead V3 >80 ms were 91.7, 83.1, and 85.9%, respectively. In the prospective evaluation, the combination of TZ index and V2S/V3R index could identify the correct origin sites with 91.2% accuracy in the overall analysis, and the integration of V2S/V3R index ≤1.5 and R-wave deflection interval in lead V3 >80 ms exhibited 94% accuracy in V3-lead precordial transition.

The combination of TZ index <0 and V2S/V3R index ≤1.5 is a simple and efficient stepwise electrocardiographic algorithm for predicting LVOT origin. For the OT-VAs with a V3-lead precordial transition, the integration of V2S/V3R index ≤1.5 and R-wave deflection interval in lead V3 >80 ms would be a better choice.

80 ms would be a better choice.

Lusutrombopag, a small-molecule thrombopoietin receptor agonist, is used to treat thrombocytopenia based on the results of a phase 3 trial, including data for single-use administration in patients with chronic liver disease (CLD) undergoing invasive procedures. anti-PD-1 monoclonal antibody We aimed to evaluate the efficacy and safety of repeated lusutrombopag use.

Lusutrombopag was administered repeatedly in patients undergoing multi-cycle invasive procedures at intervals >1 month.

Data from 8 patients (median platelet count at baseline, 44.0 [range, 35-49] × 109/L) and 25 cycles of invasive procedures, including 2 cycles in 3 patients, 3 cycles in 4 patients, and 7 cycles in 1 patient, were retrospectively evaluated. The procedures included 18 transarterial chemoembolizations, 5 radiofrequency ablations, and 2 liver needle biopsies. Platelet counts increased significantly compared with baseline, and median changes in platelet counts were 46.0 × 109/L (p = 0.012) in cycle 1, 44.0 × 109/L (p = 0.012) in cycle 2, and 42.0 × 109/L (p = 0.008) in cycles 3-7. No severe adverse events, including portal vein thrombus or bleeding, were observed.

Repeated use of lusutrombopag might be safe and effective against thrombocytopenia in patients with CLD undergoing multi-cycle invasive procedures, although long-term data from more patients are required.

Repeated use of lusutrombopag might be safe and effective against thrombocytopenia in patients with CLD undergoing multi-cycle invasive procedures, although long-term data from more patients are required.

Symptomatic idiopathic ventricular arrhythmias (VA), including premature beats (VPB) and nonsustained ventricular tachycardia (VT) are commonly encountered arrhythmias. Although these VA are usually benign, their treatment can be a challenge to primary and secondary health care providers. Mainstay treatment is comprised of antiarrhythmic drugs (AAD) and, in case of drug intolerance or failure, patients are referred for catheter ablation to tertiary health care centers. These patients require extensive medical attention and drug regimens usually have disappointing results. A direct comparison between the efficacy of the most potent AAD and primary catheter ablation in these patients is lacking. The ECTOPIA trial will evaluate the efficacy of 2 pharmacological strategies and 1 interventional approach to suppress the VA burden, improve the quality of life (QoL), and safety.

We hypothesize that flecainide/verapamil combination and catheter ablation are both superior to sotalol in suppressing VA in patients with symptomatic idiopathic VA.