Prevention and Management of Infectious Complications of Retrograde Intrarenal Surgery.

Kidney stone disease (KSD) is a commonly encountered ailment in urologic practice. Urinary tract infection (UTI) is commonly associated with KSD, both as an etiology (e.g., struvite and carbonate apatite stones), and as a complication (i.e., obstructive pyelonephritis and post-operative UTI). Indeed, a significant portion of the economic burden of KSD is skewed toward stones associated with infection. UTI is the most common post-operative complication related to stone intervention with progression to urosepsis as a rare but serious consequence. Risk for infection is influenced by a variety of factors including co-morbid conditions, anatomic abnormalities, prior surgical procedures, and local anti-microbial susceptibility. Understanding these risks and the proper steps to mitigate them is an essential component in reducing post-operative morbidity and mortality. Retrograde intrarenal surgery is routinely used for the treatment of KSD. The objective of this review article is to examine the current literature and guidelines for the prevention and management of stone-related infectious complications associated with retrograde intrarenal surgery. Special attention will be given to the incidence, etiology, and antibiotic prophylaxis choice in the management of stone-related infections. Intraoperative risk mitigation techniques will be discussed in conjunction with the management of post-operative infections. Antibiotic stewardship and the potential benefits of reduced empiric antibiotic treatment will also be discussed.

A pilot biomechanical study comparing a novel, intramedullary Nail/Plate construct to standard Dual-Plate fixation of intra-articular C2.3 distal humerus fractures.

BACKGROUND: The gold-standard treatment for intra-articular distal humerus fractures (DHFs) is dual-plate/dual-column fixation, though optimal orientation is not yet established. With a superior method not yet identified, we propose a load-sharing construct, combining absolute stability (extramedullary plate fixation) for distal articular fragments and relative stability (load-sharing intramedullary nail) for the metaphyseal segment. The purpose of this pilot study was to evaluate the biomechanical performance of a novel implant compared to orthogonal dual-plating. MATERIALS AND METHODS: Ten fresh-frozen matched-pairs of human cadaveric upper extremities with no prior elbow pathology/surgery were used. Pairs were randomized into two groups: Dual-Plate (medial and posterolateral) or novel Nail/Plate (cross-locked medial nail and posterolateral plate). AO/ASIF type 13-C2.3 multifragmentary fractures with simulated metaphyseal comminution. Biomechanical testing included stiffness (MPa) and load to failure (Newtons) in axial (100 cycles at 3 Hz at 20 N increments from 20 to 100 N) and coronal (varus/valgus; 4,000 cycles from 50N-100 N at 3 Hz) planes. Failed specimens were not analyzed and mechanisms were identified. For all failures, mechanisms were identified and reviewed by three consultant surgeons for revision vs. immobilization, to attempt to recreate a real-world scenario. All outcomes were compared between groups. RESULTS: During stiffness testing, zero Nail/Plate specimens failed, but two (20%) Dual-Plate specimens failed (mechanisms: fracture diastasis; bone collapse and intussusception into osteotomy, yielding articular congruency loss). For remaining samples, Nail/Plate (n = 10) coronal (varus/valgus) stiffness was comparable to Dual-Plate (n = 8) constructs (41.5 vs. 39.0 MPa, p = 0.440). Remaining Dual-Plate constructs had greater axial overall stiffness than Nail/Plate (118.3 ± 48.3 vs. 95.6 ± 34.7 MPa, p = 0.020). Failure loads were comparable between Nail/Plate and Dual-Plate constructs (1,327.8 vs. 1,032.4 N, p = 0.170). Individual nail yield strength ranged from 1,101.1-1,124.4 N (n = 2). In review of all failures, the most common overall mechanism was fracture/osteotomy site posterolateral plate bending. Revision recommendation rate was comparable between constructs (Nail/Plate, 22.2% vs. Dual-Plate, 44.4%, p>0.05). CONCLUSIONS: The novel Nail/Plate construct demonstrated non-inferior coronal (varus/valgus) stiffness, despite producing lower axial stiffness than orthogonal dual-plating, potentially due to the load-sharing cross-locked design. Considering comparable biomechanical performance, with no failures and comparable recommendations for revision, this novel construct warrants further evaluation as an alternative to the gold-standard, dual-plate fixation method for intra-articular distal humerus fractures. LEVEL OF EVIDENCE: N/A.

Design and Characterization of Biosensors for the Screening of Modular Assembled Naringenin Biosynthetic Library in Saccharomyces cerevisiae.

A common challenge in the assembly and optimization of plant natural product biosynthetic pathways in recombinant hosts is the identification of gene orthologues that will result in best production titers. Here, we describe the modular assembly of a naringenin biosynthetic pathway in Saccharomyces cerevisiae that was facilitated by optimized naringenin-inducible prokaryotic transcription activators used as biosensors. The biosensors were designed and developed in S. cerevisiae by a multiparametric engineering strategy, which further was applied for the in vivo, high-throughput screening of the established yeast library. The workflow for assembling naringenin biosynthetic pathways involved Golden gate-directed combinatorial assembly of genes and promoters, resulting in a strain library ideally covering 972 combinations in S. cerevisiae. For improving the performance of our screening biosensor, a series of fundamental components was optimized, affecting the efficiency of the biosensor such as nuclear localization signal (NLS), the detector module and the effector module. One biosensor (pTDH3_NLS_FdeR-N_tPGK1-pGPM1-fdeO_mcherry_tTDH1-MV2) showed better performance, defined as better dynamic range and sensitivity than others established in this study as well as other previously reported naringenin biosensors. Using this biosensor, we were able to identify a recombinant S. cerevisiae strain as the most efficient candidate for the production of naringenin from the established naringenin biosynthetic library. This approach can be exploited for the optimization of other metabolites derived from the flavonoid biosynthetic pathways and more importantly employed in the characterization of putative flavonoid biosynthetic genes.