Evaluating the Differences of Wound Related Complications in Robotically Assisted Radical Cystectomy vs. Open Radical Cystectomy.

OBJECTIVE: To determine whether robotic assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) compared to open radical cystectomy (ORC) or RARC with extracorporeal urinary diversion (ECUD) would result in a decreased rate of surgical site complications. RARC has been shown to be non-inferior to ORC. Both RARC and ORC are complicated by a high rate of perioperative morbidity, including wound related complications, which may be decreased by a robotic approach with intracorporeal diversion. METHODS: A retrospective review of our bladder cancer database for patients undergoing radical cystectomy from 2013 to 2021. Patients were stratified by surgical technique as RARC with ICUD vs. ORC vs. RARC with ECUD. Surgical site complications were measured at both 30 and 90-day intervals. RESULTS: Of the 269 patients, 127 (47.2%) had RARC with ICUD, 118 (43.7%) had ORC, and 24 (8.9%) had RARC with ECUD (mean ages 71.0, 69.5, 67.5 respectively). A comparison of the three groups demonstrated statistical significance at both the 30-day (p<0.001) and 90-day (p<0.001) timeframes for total surgical site complications, with RARC with ICUD having the fewest amount of patients experience a surgical site complication (0.8%) followed by ORC (25.4%) and RARC with ECUD (29.2%). CONCLUSION: Overall, we observed lower surgical site complication rates among patients undergoing RARC with ICUD compared to patients who underwent ORC or RARC with ECUD. This study suggests that decreased surgical site complications may be one benefit of the minimally invasive approach particularly in patients at high risk for surgical site complications after radical cystectomy.

Surgical Approach and Dislocation Risk After Hemiarthroplasty in Geriatric Patients With Femoral Neck Fracture With and Without Cognitive Impairments-Does Cognitive Impairment Influence Dislocation Risk?

OBJECTIVES: To determine whether there is an association between surgical approach and dislocation risk in patients with cognitive impairment compared with those without cognitive impairment treated with hemiarthroplasty for femoral neck fracture. DESIGN: Retrospective study. SETTING: Large, multicenter health system. PATIENTS/PARTICIPANTS: One thousand four hundred eighty-one patients who underwent hemiarthroplasty for femoral neck fractures. 828 hips met inclusion criteria, 290 (35.0%) were cognitively impaired, and 538 (65.0%) were cognitively intact. INTERVENTION: Hemiarthroplasty. MAIN OUTCOME MEASURE: Prosthetic hip dislocation. RESULTS: The overall dislocation rate was 2.1% (17 of 828), 3.4% (10 of 290) in the cognitively impaired group, and 1.3% (7 of 538) in the cognitively intact group with a median time to dislocation of 20.5 days (range 2-326 days), 24.5 days (range 3-326 days), and 19.0 days (range 2-36 days), respectively. In the entire cohort, there were no dislocations (0 of 58) with the direct anterior approach (DA); 1.1% (6 of 553) and 5.1% (11 of 217) dislocated with the modified Hardinge (MH) and posterior approaches (PA), respectively. In the cognitively impaired group, there were no dislocations with the DA (0 of 19); 1.5% (3 of 202) and 10.1% (7 of 69) dislocated with the MH and PA, respectively. In the cognitively intact group, there were no dislocations (0 of 39) with the DA; 0.85% (3 of 351) and 2.7% (4 of 148) dislocated with the MH and PA, respectively. There were statistically significant associations between surgical approach and dislocation in the entire cohort and the cognitively impaired group when comparing the MH and PA groups. This was not observed in the cognitively intact group. Patients who dislocated had 3.2 times (95% CI 1.2, 8.7) ( P = 0.0226) the hazard of death compared with patients who did not dislocate. Dislocation effectively increased the risk of death by 221% (HR 3.2 95% CI 1.2, 8.7) ( P = 0.0226). CONCLUSIONS: In this patient population, the PA has a higher dislocation rate than other approaches and has an especially high rate of dislocation when the patients were cognitively impaired. The authors of this study suggest careful consideration of surgical approach when treating these injuries. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Primary Repair, Reconstruction, and Suture Tape Augmentation All Provide Excellent Outcomes for Lateral Ligament Instability: A Systematic Review.

Purpose: To analyze the literature to compare outcomes and complications following primary lateral ankle ligament repair compared with lateral ankle ligament reconstruction and the suture tape augmentation in patients with lateral ankle instability. Methods: Following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) criteria, a systematic literature review using the PubMed/Ovid Medline database was performed (October 11, 1947, to October 1, 2019). Clinical trials that included all the following criteria were considered eligible; published in the English language; patients undergoing primary lateral ankle repair or reconstruction with/without autograft or allograft (anterior talofibular ligament, anterior talofibular ligament + calcaneofibular ligament) or suture tape augmentation; a follow-up at least 1 year; reported least 1 of the measured outcomes (The American Orthopaedic Foot Ankle Score, Karlsson Score, return to sport [RTS], complications, skin wound complications, reoperation). Surgical techniques were evaluated, and studies were subdivided by the following categories: primary repair (PR), reconstruction with graft (GR), and suture tape augmentation (STA). Complications, radiographic outcomes, functional outcome scores, and RTS were analyzed. Results: A total of 41 of 1,991 studies met the criteria for final analysis. This included 1,920 patients who underwent surgical intervention for chronic lateral instability with at least a 1-year follow-up. There were 350 patients who had GR, 1,486 who underwent the PR, and 84 who had STA. GR group appeared to have the lowest rate of complications: GR 3.1% (11 of 350), PR 4.2% (63 of 1486), and STA 10.7% (9 of 84). Postoperative American Orthopaedic Foot Ankle Score ranged from 89.0 to 95.1 for GR and 90.0 to 98.8 for PR. Postoperative Karlsson scores ranged from 80.9 to 94.4 for GR and from 89.2 to 94.1 for PR. Anterior drawer postoperative scores ranged from 1.4 to 30.3 mm for GR, 2.7 to 8.6 mm for PR, and 4.1 to 4.2 mm for STA. Postoperative talar tilt ranged from 2.4 to 7.3° for GR, 1.9 to 6.0° for PR, and 3.6 to 4.5° for STA. RTS ranged from 9.5 to 20.4 weeks for the PR group; one study reported a RTS of 10.6 weeks for STA. Conclusions: Excellent outcomes were noted across all intervention groups. Current literature may suggest there is no difference in functional outcomes between patients treated with PR versus GR. However, there may be a potential improvement in functional outcomes with PR versus STA. Level of Evidence: Level IV, systematic review of Level I to Level IV studies.

Clinical predictors of invasive fungal rhinosinusitis in a tertiary pediatric hospital.

OBJECTIVES: Invasive fungal rhinosinusitis (IFRS) is a potentially fatal disease that affects the severely immunocompromised and requires aggressive treatment. The objective of this study is to better describe predictors of biopsy positivity in patients at high risk of IFRS at a pediatric hospital. METHODS: This was a single-center case-control study of 36 patients (37 total biopsies) ≤ 21 years old with one of five high-risk oncologic/hematologic diagnoses who underwent operative endoscopy for clinical suspicion for IFRS. IFRS positivity was defined histologically. Collected information included patient demographics, primary diagnosis, oncologic relapses, time from diagnosis to biopsy, clinical characteristics, and endoscopic findings. These data were used to create a simple predictive scoring system. RESULTS: 17 patients had biopsy-proven IFRS (IFRS(+)) for an overall incidence of 2.1% in the designated high-risk population. Average time from most recent oncologic development (diagnosis, relapse, or hematopoietic stem-cell transplant) to biopsy in the IFRS(+) group was 2.09 months (SD = 2.26), and 7.28 months in the IFRS(-) group (SD = 9.17) (p = 0.009). Clinical characteristics did not differentiate between IFRS(+) and IFRS(-). Bedside endoscopy performed poorly, as it was interpreted as normal in 42.8% of IFRS(+) and 53.8% of IFRS(-). In contrast, the presence of any positive endoscopic finding intra-operatively was highly specific for IFRS(+) (94%) with moderate sensitivity (70%), and the difference in rate of positivity between groups was statistically significant (p < 0.001). CONCLUSION: Operative endoscopy with biopsy remains the gold-standard to rule-out IFRS in the setting of high clinical suspicion. Time elapsed from most recent oncologic development to clinical concern for IFRS may influence the likelihood of disease, though this requires further study. Clinical symptoms and bedside endoscopy were not predictive and should be used with caution in decision-making.

Programmable RNA targeting with the single-protein CRISPR effector Cas7-11.

CRISPR-Cas interference is mediated by Cas effector nucleases that are either components of multisubunit complexes-in class 1 CRISPR-Cas systems-or domains of a single protein-in class 2 systems1-3. Here we show that the subtype III-E effector Cas7-11 is a single-protein effector in the class 1 CRISPR-Cas systems originating from the fusion of a putative Cas11 domain and multiple Cas7 subunits that are derived from subtype III-D. Cas7-11 from Desulfonema ishimotonii (DiCas7-11), when expressed in Escherichia coli, has substantial RNA interference effectivity against mRNAs and bacteriophages. Similar to many class 2 effectors-and unique among class 1 systems-DiCas7-11 processes pre-CRISPR RNA into mature CRISPR RNA (crRNA) and cleaves RNA at positions defined by the target:spacer duplex, without detectable non-specific activity. We engineered Cas7-11 for RNA knockdown and editing in mammalian cells. We show that Cas7-11 has no effects on cell viability, whereas other RNA-targeting tools (such as short hairpin RNAs and Cas13) show substantial cell toxicity4,5. This study illustrates the evolution of a single-protein effector from multisubunit class 1 effector complexes, expanding our understanding of the diversity of CRISPR systems. Cas7-11 provides the basis for new programmable RNA-targeting tools that are free of collateral activity and cell toxicity.

Early Versus Delayed Mobilization Post-Operative Protocols for Primary Lateral Ankle Ligament Reconstruction: A Systematic Review and Meta-Analysis.

INTRODUCTION: Lateral ankle instability represents a common orthopaedic diagnosis. Nonoperative treatment through focused physical therapy provides satisfactory results in most patients. However, some patients experience persistent chronic lateral ankle instability despite appropriate nonoperative treatment. These patients may require stabilization, which can include primary lateral ligament reconstruction with a graft to restore ankle stability. Optimal post-operative rehabilitation of lateral ankle ligament reconstruction remains unknown, as surgeons vary in how long they immobilize their patients post-operatively. The aim of this review was to provide insight into early mobilization (EM) versus delayed mobilization (DM) post-operative protocols in patients undergoing primary lateral ankle ligament reconstructions to determine if an optimal evidence-based post-operative rehabilitation protocol exists in the literature. METHODS: Following PRIMSA criteria, a systematic review/meta-analysis using the PubMed/Ovid Medline database was performed (10/11/1947 - 1/28/2020). Manuscripts that were duplicates, non-lateral ligament repair, biomechanical, and non-English language were excluded. Protocols were reviewed and divided into two categories: early mobilization (within three weeks of surgery) and delayed mobilization (after three weeks of surgery). Functional outcome scores (American Orthopedic Foot and Ankle Society Score (AOFAS), Karlsson scores), radiographic measurements (anterior drawer, talar tilt), and complications were evaluated using weighted mean differences (pre- and post-operative scores) and mixed-effect models. RESULTS: After our search, twelve out of 1,574 studies met the criteria for the final analysis, representing 399 patients undergoing lateral ankle reconstruction. Using weighted mean differences the DM group showed superior AOFAS functional scores compared to the EM group (28.0 (5.5) vs. 26.3 (0.0), respectively; p < 0.001), although sample size was small. Conversely, no significant differences were found for Karlsson functional score (p = 0.246). With regards to radiographic outcome, no significant differences were observed; anterior drawer was p = 0.244 and talar tilt was p = 0.937. A meta-analysis using mixed-effects models confirmed these results, although heterogeneity was high. CONCLUSIONS: While there are some conflicting results, the findings indicated the timing of post-operative mobilization made no difference in functional outcomes or post-operative stability for patients undergoing lateral ankle ligament reconstruction. Because heterogeneity was high, future studies are needed to evaluate these protocols in less diverse patient groups and/or more consistent techniques for lateral ankle ligament reconstruction.

Total Elbow Arthroplasty for Distal Humerus Fractures.

Distal humerus fractures in elderly patients are challenging due to poor bone quality and may threaten the independence of elderly patients due to loss of functional range of motion. Total elbow arthroplasty has gained popularity in the treatment of these injuries. This video demonstrates total elbow arthroplasty in an elderly patient with a comminuted distal humerus fracture.

Collaborative interactions of heterogenous ribonucleoproteins contribute to transcriptional regulation of sterol metabolism in mice.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a group of functionally versatile proteins that play critical roles in the biogenesis, cellular localization and transport of RNA. Here, we outline a role for hnRNPs in gene regulatory circuits controlling sterol homeostasis. Specifically, we find that tissue-selective loss of the conserved hnRNP RALY enriches for metabolic pathways. Liver-specific deletion of RALY alters hepatic lipid content and serum cholesterol level. In vivo interrogation of chromatin architecture and genome-wide RALY-binding pattern reveal insights into its cooperative interactions and mode of action in regulating cholesterogenesis. Interestingly, we find that RALY binds the promoter region of the master metabolic regulator Srebp2 and show that it directly interacts with coactivator Nuclear Transcription Factor Y (NFY) to influence cholesterogenic gene expression. Our work offers insights into mechanisms orchestrating selective promoter activation in metabolic control and a model by which hnRNPs can impact health and disease states.

Allergy in Irish adults: a survey of referrals and outcomes at a major centre.

BACKGROUND: There is an increasing demand for specialist public allergy services across Ireland. Little data exist on the patterns of allergic disease in Irish adults. The limited resources available require innovative strategies to ensure quality care delivery. AIMS: This study aimed to review the types of allergy referrals and diagnostic outcomes at a major Irish centre, and to establish an efficient method of communication with non-specialist practitioners. METHODS: Demographic data, referral characteristics and diagnostic outcomes from one hundred consecutive new allergy referrals were identified. Additionally, communications to a pilot email service were reviewed over a 12-month period and user satisfaction assessed. RESULTS: Requests for the investigation of food allergy accounted for 71% of referrals. Despite this, the main diagnostic outcome in this cohort was a non-allergic condition, chronic spontaneous urticaria (56%). immunoglobulin E (IgE)-mediated food allergy was definitively diagnosed in only 9% of patients, with the majority of these presenting with anaphylaxis. The allergy advice email service received 43 requests for assistance over 12 months, mainly for help in the interpretation of an allergy clinical history. Feedback on the email service was universally positive. CONCLUSIONS: The majority of patients in this cohort did not have IgE-mediated allergic disease. Increased awareness of the features that differentiate allergy from non-allergic conditions such as food intolerance or chronic spontaneous urticaria is required. The allergy advice email service should be developed further to play a key role in education and care delivery in partnership primary care.