Development of a novel classification system for anatomical variants of the puboprostatic ligaments with expert validation

Introduction: We propose a novel classification system with a validation study to help clinicians identify and typify commonly seen variants of the puboprostatic ligaments (PPL). Methods: A preliminary dissection of 6 male cadavers and a prospective dataset of over 300 robotic-assisted laparoscopic radical prostatectomies (RARP) recorded on video were used to identify 4 distinct ligament types. Then the prospectively collected database of surgical videos was used to isolate images of the PPL from RARP. Over 300 surgical videos were reviewed and classified with 1 to 5 pictures saved for reference of the type of PPL. To validate the new classification system, we selected 5 independent, blinded expert robotic surgeons to classify 100 ligaments based on morphology into a 4-type system: parallel, V-shaped, inverted V-shape, and fused. One week later, a subset of 25 photographs was sent to the same experts and classified. Statistical analyses were performed to determine both the intra-rater and inter-rater reliability of the proposed system. Results: Inverted V-shaped ligaments were noted most frequently (29.97%), parallel and V-shaped ligaments were found at 19.19% and 11.11%, respectively and fused ligaments were noted less frequently (6.06%). There was good intra-rater agreement (ê = 0.66) and inter-rater agreement (ê = 0.67) for the classification system. Conclusions: This classification system provided standardized descriptions of ligament variations that could be adopted universally to help clinicians categorize the variants. The system, validated by several blinded expert surgeons, demonstrated that surgeons were able to learn and correctly classify the variants. The system may be useful in helping to predict peri- and postoperative outcomes; however, this will require further study

Psychology and aggression

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68264/2/10.1177_002200275900300301.pd

AVONET: morphological, ecological and geographical data for all birds

Functional traits offer a rich quantitative framework for developing and testing theories in evolutionary biology, ecology and ecosystem science. However, the potential of functional traits to drive theoretical advances and refine models of global change can only be fully realised when species‐level information is complete. Here we present the AVONET dataset containing comprehensive functional trait data for all birds, including six ecological variables, 11 continuous morphological traits, and information on range size and location. Raw morphological measurements are presented from 90,020 individuals of 11,009 extant bird species sampled from 181 countries. These data are also summarised as species averages in three taxonomic formats, allowing integration with a global phylogeny, geographical range maps, IUCN Red List data and the eBird citizen science database. The AVONET dataset provides the most detailed picture of continuous trait variation for any major radiation of organisms, offering a global template for testing hypotheses and exploring the evolutionary origins, structure and functioning of biodiversity

Lateral subvastus approach: A cadaveric examination of its potential for total knee arthroplasty

© 2020 Elsevier B.V. Background: Lateral approaches to total knee arthroplasty (TKA) provide good surgical exposure and may provide greater ease of soft tissue balancing in patients with a valgus deformity; however, little is known about the versatility in non-valgus knees. The present study evaluated if a lateral subvastus approach can achieve adequate surgical exposure while maintaining less soft tissue damage compared with the medial parapatellar approach in knees without any significant deformity. Methods: Using paired fresh-frozen cadaveric knees, the present study provides the first specimen-matched, side-by-side comparison of the lateral subvastus approach to the standard medial parapatellar approach to TKA. Ten knees were selected to undergo a lateral subvastus approach; the contralateral knee had a medial parapatellar approach as control. Incision length, surgical exposure and iatrogenic soft tissue damage were compared between the two approaches. Results: The lateral subvastus approach was successfully performed using an incision length that was not different from that used in the medial parapatellar approach (p \u3e 0.05). The resultant surgical exposure was comparable between approaches (p \u3e 0.05). The risk of the approach included tearing of the vastus lateralis fibers, and/or abrasion of the iliotibial tract/patellar ligament. Conclusions: The lateral subvastus approach to TKA provided a comparable method to the standard medial parapatellar approach. Despite adequate exposure, the approach did risk soft tissue injury. Caution needs to be exercised to reduce the risk of iatrogenic injury to the vastus lateralis and surrounding ligaments. The successful implementation in this cadaveric study substantiates the need for further consideration of this approach in clinical practice

Peptide Mimetics of Gamma Interferon Possess Antiviral Properties against Vaccinia Virus and Other Viruses in the Presence of Poxvirus B8R Protein

We have developed peptide mimetics of gamma interferon (IFN-γ) that play a direct role in the activation and nuclear translocation of STAT1α transcription factor. These mimetics do not act through recognition by the extracellular domain of IFN-γ receptor but rather bind to the cytoplasmic domain of the receptor chain 1, IFNGR-1, and thereby initiate the cellular signaling. Thus, we hypothesized that these mimetics would bypass the poxvirus virulence factor B8R protein that binds to intact IFN-γ and prevents its interaction with the receptor. Human and murine IFN-γ mimetic peptides were introduced into an adenoviral vector for intracellular expression. Murine IFN-γ mimetic peptide was also expressed via chemical synthesis with an attached lipophilic group for penetration of cell plasma membrane. In contrast to intact human IFN-γ, the mimetics did not bind poxvirus B8R protein, a homolog of the IFN-γ receptor extracellular domain. Expression of B8R protein in WISH cells did not block the antiviral effect of the mimetics against encephalomyocarditis or vesicular stomatitis virus, while the antiviral activity of human IFN-γ was neutralized. Consistent with the antiviral activity, the upregulation of MHC class I molecules on WISH cells by the IFN-γ mimetics was not affected by B8R protein, while IFN-γ-induced upregulation was blocked. Finally, the mimetics, but not IFN-γ, inhibited vaccinia virus replication in African green monkey kidney BSC-40 cells. The data presented demonstrate that small peptide mimetics of IFN-γ can avoid the B8R virulence factor for poxviruses and, thus, are potential candidates for antivirals against smallpox virus

Comparative Efficacy of Targeted Systemic Therapies for Moderate-to-Severe Atopic Dermatitis without Topical Corticosteroids: An Updated Network Meta-analysis

Abstract Introduction The treatment landscape for moderate-to-severe atopic dermatitis (AD) continues to expand. This network meta-analysis (NMA) updates a previously conducted NMA to include data from the most recent phase 3 trials to assess the comparative efficacy of targeted systemic therapies without the addition of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI) in adults with moderate-to-severe AD. Methods Data from recent phase 3 monotherapy trials of lebrikizumab, ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967), were included in the analyses, along with other eligible phase 3/4 randomized placebo-controlled trials for abrocitinib, baricitinib, dupilumab, tralokinumab, and upadacitinib identified through a systemic literature review in Silverberg et al. (Dermatol Ther (Heidelb) 12(5):1181–1196, 2022). The proportion of patients achieving Eczema Area and Severity Index (EASI) improvement ≥ 90% from baseline (EASI-90), EASI improvement ≥ 75% from baseline (EASI-75), ≥ 4-point improvement on Pruritus Numerical Rating Scale from baseline (ΔNRS ≥ 4), and Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) and reduction of ≥ 2 points from baseline (IGA 0/1) were evaluated using a Bayesian network meta-analysis. Results The updated NMA analyzed 13 unique placebo-controlled trials involving 7105 patients in 32 arms across 6 targeted therapies. Upadacitinib 30 mg was the most efficacious therapy across all endpoints at the primary timepoint (week 12 or 16) and at earlier timepoints, generally followed by abrocitinib 200 mg, upadacitinib 15 mg, dupilumab 300 mg, and lebrikizumab 250 mg or abrocitinib 100 mg. Baricitinib 2 mg and tralokinumab were generally ranked lower across outcomes. Conclusions Many factors need to be considered for treatment selection for AD, especially as new treatments continue to emerge. After incorporating recent placebo-controlled phase 3 data of lebrikizumab, upadacitinib 30 mg, upadacitinib 15 mg, and abrocitinib 200 mg remain the most efficacious targeted systemic therapies over 12–16 weeks of therapy in AD. These updated findings can help healthcare providers when creating a patient’s personalized treatment plan

Comparative Efficacy of Targeted Systemic Therapies for Moderate to Severe Atopic Dermatitis without Topical Corticosteroids: Systematic Review and Network Meta-analysis

INTRODUCTION: The comparative efficacy of targeted systemic therapies for moderate to severe atopic dermatitis (AD) has not been systematically assessed using recent phase 3 data. This network meta-analysis assesses the comparative efficacy of targeted systemic therapies without the addition of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI) in adults with moderate to severe AD. METHODS: The systematic literature review searched through 17 May 2021 for phase 3/4 trials with upadacitinib, interleukin-4 (IL-4), interleukin-13 (IL-13), or JAK inhibitors compared with placebo or active intervention for adults and adolescents with moderate to severe AD with inadequate response to TCS/TCI or for whom TCS/TCI was medically inadvisable, without restrictions on year or region. Researchers assessed data using PRISMA guidelines. The proportion of patients achieving trial co-primary endpoints [Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) and reduction of ≥ 2 points from baseline; proportion of patients achieving Eczema Area and Severity Index (EASI) improvement ≥ 75% from baseline (EASI-75)]; EASI improvement ≥ 90% from baseline (EASI-90); and ≥ 4-point improvement on Pruritus Numerical Rating Scale from baseline (ΔNRS ≥ 4) were evaluated using Bayesian network meta-analysis. RESULTS: Of 3415 initially identified records, network meta-analysis (NMA) ultimately included 6 records representing 9 unique studies. Two upadacitinib trials were also included. Eleven clinical trials including 6254 patients were analyzed. Upadacitinib 30 mg daily was the most efficacious therapy across all endpoints at the primary endpoint (week 12 or 16) and at earlier timepoints, followed by upadacitinib 15 mg daily and abrocitinib 200 mg daily. DISCUSSION: Many factors need to be considered for treatment selection for AD. These findings can help healthcare providers when personalizing a patient\u27s treatment. CONCLUSION: Upadacitinib 30 mg daily, upadacitinib 15 mg daily, and abrocitinib 200 mg daily may be the most efficacious targeted systemic therapies over 12-16 weeks of therapy in AD