Shifting Trends in Prostate Treatment: A Systematic Review Comparing Transurethral Resection of the Prostate and Holmium Laser Enucleation of the Prostate.

Our systematic review aimed to assess the effectiveness and suitability of holmium laser enucleation of the prostate (HoLEP) as a treatment for benign prostatic hyperplasia (BPH) in comparison to transurethral resection of the prostate (TURP). We analyzed 12 studies involving male participants aged 45-85 years, all of whom had BPH. In our analysis, we compared HoLEP and TURP, with a focus on several primary outcomes, including postoperative International Prostate Symptom Score (IPSS), postvoid residual (PVR) volume, maximum flow rate (Qmax), and changes in sexual function post-treatment. HoLEP demonstrated advantages in certain aspects when compared to TURP. HoLEP generally resulted in an improved postoperative IPSS in some studies, but not all studies showed a significant difference when compared to TURP. HoLEP was associated with improved Qmax in most studies, but one study found no significant difference between HoLEP and TURP. Patients who underwent HoLEP showed improvement in the PVR volume in some studies, while others found no significant change in the PVR volume with either HoLEP or TURP. Some studies reported a reduction in orgasm and ejaculatory scores following TURP, while no significant changes were observed in erectile function, intercourse satisfaction, and overall satisfaction scores. It is worth noting that previous reviews and meta-analyses had limited data on the effects of HoLEP and TURP on sexual dysfunction. TURP is associated with a higher risk of morbidity and mortality, which has led to its replacement with HoLEP as the gold standard for treating BPH, particularly due to its size-independent applicability. HoLEP also demonstrated greater efficacy in the postoperative period.

High-throughput screening for developability during early-stage antibody discovery using self-interaction nanoparticle spectroscopy.

The discovery of monoclonal antibodies (mAbs) that bind to a particular molecular target is now regarded a routine exercise. However, the successful development of mAbs that (1) express well, (2) elicit a desirable biological effect upon binding, and (3) remain soluble and display low viscosity at high concentrations is often far more challenging. Therefore, high throughput screening assays that assess self-association and aggregation early in the selection process are likely to yield mAbs with superior biophysical properties. Here, we report an improved version of affinity-capture self-interaction nanoparticle spectroscopy (AC-SINS) that is capable of screening large panels of antibodies for their propensity to self-associate. AC-SINS is based on concentrating mAbs from dilute solutions around gold nanoparticles pre-coated with polyclonal capture (e.g., anti-Fc) antibodies. Interactions between immobilized mAbs lead to reduced inter-particle distances and increased plasmon wavelengths (wavelengths of maximum absorbance), which can be readily measured by optical means. This method is attractive because it is compatible with dilute and unpurified mAb solutions that are typical during early antibody discovery. In addition, we have improved multiple aspects of this assay for increased throughput and reproducibility. A data set comprising over 400 mAbs suggests that our modified assay yields self-interaction measurements that are well-correlated with other lower throughput assays such as cross-interaction chromatography. We expect that the simplicity and throughput of our improved AC-SINS method will lead to improved selection of mAbs with excellent biophysical properties during early antibody discovery.

High throughput detection of antibody self-interaction by bio-layer interferometry.

Self-interaction of an antibody may lead to aggregation, low solubility or high viscosity. Rapid identification of highly developable leads remains challenging, even though progress has been made with the introduction of techniques such as self-interaction chromatography (SIC) and cross-interaction chromatography (CIC). Here, we report a high throughput method to detect antibody clone self-interaction (CSI) using bio-layer interferometry (BLI) technology. Antibodies with strong self-interaction responses in the CSI-BLI assay also show delayed retention times in SIC and CIC. This method allows hundreds of candidates to be screened in a matter of hours with minimal material consumption.

High throughput solution-based measurement of antibody-antigen affinity and epitope binning.

Advances in human antibody discovery have allowed for the selection of hundreds of high affinity antibodies against many therapeutically relevant targets. This has necessitated the development of reproducible, high throughput analytical techniques to characterize the output from these selections. Among these characterizations, epitopic coverage and affinity are among the most critical properties for lead identification. Biolayer interferometry (BLI) is an attractive technique for epitope binning due to its speed and low antigen consumption. While surface-based methods such as BLI and surface plasmon resonance (SPR) are commonly used for affinity determinations, sensor chemistry and surface related artifacts can limit the accuracy of high affinity measurements. When comparing BLI and solution equilibrium based kinetic exclusion assays, significant differences in measured affinity (10-fold and above) were observed. KinExA direct association (k(a)) rate constant measurements suggest that this is mainly caused by inaccurate k(a) measurements associated with BLI related surface phenomena. Based on the kinetic exclusion assay principle used for KinExA, we developed a high throughput 96-well plate format assay, using a Meso Scale Discovery (MSD) instrument, to measure solution equilibrium affinity. This improved method combines the accuracy of solution-based methods with the throughput formerly only achievable with surface-based methods.