New findings regarding the influence of assistants on surgical outcomes in penile prosthesis implantation.

Penile prosthesis implantation is the definitive treatment for refractory erectile dysfunction, yet exposure to this procedure during training of urology residents is often limited. To assess the effects of resident participation in penile prosthesis surgery, we compared surgical outcomes in a retrospective case series of 253 penile prosthesis surgeries by a single surgeon at the same institution between 2017 and 2020 with the assistance of either a registered nurse first assistant (RNFA) or a resident. Pertinent patient characteristics and surgical complications including device complications, surgical site infection, postoperative bleeding, iatrogenic injury, cardiovascular events, pulmonary events, and urinary retention were documented.

Do commonly used prostate medications alter prostate MRI and fusion biopsy performance?

Aims: To determine whether phosphodiesterase inhibitors (PDEi) or α-antagonists (AA) were associated with differences in region of interest (ROI) characteristics or prostate cancer detection on fusion biopsy (FB).

Materials And Methods: Records from 847 consecutive patients undergoing FB at three separate institutions over a period of 2 years were retrospectively reviewed. Associations between medication use, Prostate Imaging Reporting & Data System (PIRADS) scores, and ROI locations were assessed with ordinal logistic regression.

Androgen Suppression Therapy Is Associated with Lower Recurrence of Non-muscle-invasive Bladder Cancer.

Background: The challenge of managing non-muscle-invasive bladder cancer (NMIBC) is its high recurrence rate. Clinical investigations have begun to explore the role of androgen suppression as an adjunct to bladder cancer (BC) treatment.

Objective: To examine the effect of androgen suppression therapy (AST) on recurrence and progression rate of risk-stratified NMIBC.

Prevalence of refractive errors in children with retinoblastoma.

Purpose: The main purpose of this study was to investigate refractive errors in children with unilateral and bilateral retinoblastoma (RB).

Methods: An institutional review board-approved consecutive retrospective cohort study was undertaken. Subjects underwent examination under general anesthesia as part of their RB follow-up, which included evaluation by a single pediatric ophthalmologist.

Optical Coherence Tomography Angiography of Combined Central Retinal Artery and Vein Occlusion.

Optical coherence tomography angiography (OCTA) is a new, noninvasive technology that enables detailed evaluation of flow in the retinal and choroidal vasculature. The authors believe this to be the first report to describe the optical coherence tomography angiography findings associated with combined central retinal artery occlusion (CRAO) and central retinal vein occlusion (CRVO).

Inhibition of mTORC1/C2 signaling improves anti-leukemia efficacy of JAK/STAT blockade in rearranged and/or driven Philadelphia chromosome-like acute B-cell lymphoblastic leukemia.

Patients with cytokine receptor-like factor 2 rearranged (-re) subgroup Philadelphia chromosome-like B-cell acute lymphoblastic leukemia (Ph-like B-ALL) have a high relapse rate and poor clinical outcomes. -re Ph-like B-ALL is characterized by heightened activation of multiple signaling pathways, including the JAK/STAT and PI3K/AKT/mTOR pathways. We hypothesized that the combined inhibition by JAK2 and mTOR inhibitors would induce an additive antileukemia effect in -re Ph-like B-ALL.

The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice.

More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe).

Activity of the Type II JAK2 Inhibitor CHZ868 in B Cell Acute Lymphoblastic Leukemia.

A variety of cancers depend on JAK2 signaling, including the high-risk subset of B cell acute lymphoblastic leukemias (B-ALLs) with CRLF2 rearrangements. Type I JAK2 inhibitors induce paradoxical JAK2 hyperphosphorylation in these leukemias and have limited activity. To improve the efficacy of JAK2 inhibition in B-ALL, we developed the type II inhibitor CHZ868, which stabilizes JAK2 in an inactive conformation.

Mutations in G protein β subunits promote transformation and kinase inhibitor resistance.

Activating mutations in genes encoding G protein α (Gα) subunits occur in 4-5% of all human cancers, but oncogenic alterations in Gβ subunits have not been defined. Here we demonstrate that recurrent mutations in the Gβ proteins GNB1 and GNB2 confer cytokine-independent growth and activate canonical G protein signaling. Multiple mutations in GNB1 affect the protein interface that binds Gα subunits as well as downstream effectors and disrupt Gα interactions with the Gβγ dimer.

Triplication of a 21q22 region contributes to B cell transformation through HMGN1 overexpression and loss of histone H3 Lys27 trimethylation.

Down syndrome confers a 20-fold increased risk of B cell acute lymphoblastic leukemia (B-ALL), and polysomy 21 is the most frequent somatic aneuploidy among all B-ALLs. Yet the mechanistic links between chromosome 21 triplication and B-ALL remain undefined. Here we show that germline triplication of only 31 genes orthologous to human chromosome 21q22 confers mouse progenitor B cell self renewal in vitro, maturation defects in vivo and B-ALL with either the BCR-ABL fusion protein or CRLF2 with activated JAK2.

Improved spatial learning in aged rats by genetic activation of protein kinase C in small groups of hippocampal neurons.

Age-related decline in human cognition is well known, and there are correlative changes in the function of neocortical and hippocampal neurons. Similarly, age-related decline in learning has been observed in rodents, including deficits in a hippocampal-dependent learning paradigm, the Morris water maze. Furthermore, there are correlative deficits in specific signaling pathways, including protein kinase C (PKC) pathways, in cerebellar, hippocampal, or neocortical neurons.