Enhanced efficacy of glycoengineered rice cell-produced trastuzumab.

For several decades, a plant-based expression system has been proposed as an alternative platform for the production of biopharmaceuticals including therapeutic monoclonal antibodies (mAbs), but the immunogenicity concerns associated with plant-specific N-glycans attached in plant-based biopharmaceuticals has not been completely solved. To eliminate all plant-specific N-glycan structure, eight genes involved in plant-specific N-glycosylation were mutated in rice (Oryza sativa) using the CRISPR/Cas9 system. The glycoengineered cell lines, PhytoRice®, contained a predominant GnGn (G0) glycoform. The gene for codon-optimized trastuzumab (TMab) was then introduced into PhytoRice® through Agrobacterium co-cultivation. Selected cell lines were suspension cultured, and TMab secreted from cells was purified from the cultured media. The amino acid sequence of the TMab produced by PhytoRice® (P-TMab) was identical to that of TMab. The inhibitory effect of P-TMab on the proliferation of the BT-474 cancer cell line was significantly enhanced at concentrations above 1 µg/mL (****P < 0.0001). P-TMab bound to a FcγRIIIa variant, FcγRIIIa-F158, more than 2.7 times more effectively than TMab. The ADCC efficacy of P-TMab against Jurkat cells was 2.6 times higher than that of TMab in an in vitro ADCC assay. Furthermore, P-TMab demonstrated efficient tumour uptake with less liver uptake compared to TMab in a xenograft assay using the BT-474 mouse model. These results suggest that the glycoengineered PhytoRice® could be an alternative platform for mAb production compared to current CHO cells, and P-TMab has a novel and enhanced efficacy compared to TMab.

Stability Engineering of Recombinant Secretory IgA.

Secretory IgA (SIgA) presents a promising avenue for mucosal immunotherapy yet faces challenges in expression, purification, and stability. IgA exists in two primary isotypes, IgA1 and IgA2, with IgA2 further subdivided into two common allotypes: IgA2m(1) and IgA2m(2). The major differences between IgA1 and IgA2 are located in the hinge region, with IgA1 featuring a 13-amino acid elongation that includes up to six O-glycosylation sites. Furthermore, the IgA2m(1) allotype lacks a covalent disulfide bond between heavy and light chains, which is present in IgA1 and IgA2m(2). While IgA1 demonstrates superior epitope binding and pathogen neutralization, IgA2 exhibits enhanced effector functions and stability against mucosal bacterial degradation. However, the noncovalent linkage in the IgA2m(1) allotype raises production and stability challenges. The introduction of distinct single mutations aims to facilitate an alternate disulfide bond formation to mitigate these challenges. We compare four different IgA2 versions with IgA1 to further develop secretory IgA antibodies against SARS-CoV-2 for topical delivery to mucosal surfaces. Our results indicate significantly improved expression levels and assembly efficacy of SIgA2 (P221R) in Nicotiana benthamiana. Moreover, engineered SIgA2 displays heightened thermal stability under physiological as well as acidic conditions and can be aerosolized using a mesh nebulizer. In summary, our study elucidates the benefits of stability-enhancing mutations in overcoming hurdles associated with SIgA expression and stability.

Utilizing the Frailty Index to Predict Long-term Mortality in Patients Undergoing Major Lower Extremity Amputation.

The 5-factor modified Frailty Index (mFI-5) is a risk-stratification tool utilized to predict complications and mortality following major lower extremity (LE) amputation. However, its prognostic value for long-term mortality is unknown. The study aim was to assess whether a high mFI-5 score relates to long-term mortality following major LE amputation for chronic wounds. Patients ≥60 years who underwent major LE amputation from 2017 to 2021 were retrospectively reviewed. Data regarding demographics, comorbidities, perioperative factors, amputation type, and postoperative complications was collected and mFI-5 was calculated. Survival analysis was performed with Kaplan-Meier curves and differences were assessed with Log-Rank test. A total of 172 patients were identified. Mean age was 70.7 ± 8.0 years. Median time to ambulation was 3.7 months (IQR 4.0). By final follow-up of 17.5 ± 15.9 months, ambulatory rate was 51.7% (n = 89), overall mortality 36.0% (n = 62), 1-year mortality 14.0% (n = 24), and 3-year mortality 27.9% (n = 48). Patients with an mFI-5 of ≥4 (26.7%, n = 46) compared with patients with mFI-5 <4 (73.3%, n = 126) had a higher rate of prolonged postoperative LOS (34.8% vs 19.8%, p = .042), overall mortality (52.2% vs 30.2%, p = .008), 1-year mortality (23.9% vs 10.3%, p = .023), and 3-year mortality (45.7% vs 21.4%, p = .002). Multivariate analysis demonstrated mFI-5 was an independent predictor of 3-year mortality (OR 2.35, p = .043). At a threshold ≥4, the mFI-5 demonstrated utility in predicting long-term mortality. The value of this prognostic indicator is in its preoperative application of assessing risk of mortality, which should be utilized in conjunction with other measures.

Factors influencing intraoperative conversion from double- to single-incision mastectomy with free nipple grafts in 352 transgender and non-binary patients.

BACKGROUND: Double-incision mastectomy (DIM) with free nipple grafts (FNG) is a common technique employed in gender-affirming mastectomy (GAM), but is associated with a high scar burden. Intraoperatively, the surgeon may opt for a single-incision mastectomy (SIM) along the inframammary folds (IMF) to optimize aesthetic outcomes. This study sought to identify factors predictive of intraoperative conversion. METHODS: From February 2018 to November 2022, TGNB patients who underwent GAM at a single institution were retrospectively reviewed. Data regarding patient characteristics, perioperative details, postoperative complications, and aesthetic satisfaction were collected. RESULTS: A total of 352 patients were identified. Median age and body mass index (BMI) were 25.0 years (IQR: 9.0) and 28.5 kg/m2 (IQR: 8.5), respectively. Most patients received IMF incisions (n = 331, 94.0%); of whom, 66 (19.9%) underwent intraoperative conversion from DIM to SIM with FNG. Larger breast cup-size (p < 0.001) and a greater degree of ptosis (p = 0.002) preoperatively were significantly associated with intraoperative conversion to SIM. There was no significant association between intraoperative conversion and the ratio of intermammary distance to the width of the chest wall (p = 0.086). Overall complication rates were significantly higher among patients with diabetes mellitus (p = 0.015) and a greater degree of ptosis (p = 0.018). 77.8% (n = 274) of patients were satisfied with their aesthetic outcome. NPWT usage was associated with higher rates of aesthetic satisfaction (83.6% vs. 77.8%; p = 0.005). CONCLUSION: Patients with larger breast cup size and greater degree of ptosis should be counseled preoperatively that they may be at a higher risk of conversion to a singular incision.

Recombinant immune complexes as vaccines against infectious diseases.

New vaccine technologies are needed to combat many existing infections and prepare better for those that may emerge in the future. The conventional technologies that rely on protein-based vaccines are still severely restricted by the sparsity and poor accessibility of available adjuvants. One possible solution to this problem is to enhance antigen immunogenicity by a more natural means by complexing it with antibodies in the form of immune complexes (ICs). However, natural ICs are impractical as vaccines, and significant research efforts have been made to generate them in recombinant form, with plant bioengineering being at the forefront of these efforts. Here, we describe the challenges and progress made to date to make recombinant IC vaccines applicable to humans.

Piriformis syndrome.

Piriformis syndrome is a condition that is proposed to result from compression of the sciatic nerve, either in whole or in part, in the deep gluteal space by the piriformis muscle. The prevalence of piriformis syndrome depends upon the diagnostic criteria being used and the population studied but is estimated by some to be 5%-6% in all cases of low back, buttock, and leg pain and up to 17% of patients with chronic low back pain. While the sciatic nerve may pierce the piriformis muscle in about 16% of healthy individuals, this frequency is no different in those with the syndrome; thus, the relationship to this anatomic finding is unclear. The most common symptoms are buttock pain, external tenderness over the greater sciatic notch, and aggravation of the pain through sitting. Many clinical signs are reported for piriformis syndrome, but the sensitivity and specificity are unclear, in part because of the lack of a uniformly accepted case definition. In the majority of cases in the literature, it appears that the diagnosis is more ascribed to a myofascial condition rather than a focal neuropathy. Electrodiagnostic studies can be useful to exclude other causes of symptoms, but there is no well-accepted test to confirm the presence of piriformis syndrome. Ultrasound imaging may show thickening of the piriformis muscle, but further research is required to confirm that this is correlated with the clinical diagnosis. Magnetic resonance imaging and neurography may hold promise in the future, but there are not yet sufficient data to support adopting these methods as a standard diagnostic tool. The initial treatment of piriformis syndrome is typically conservative management with the general rehabilitation principles similar to other soft tissue musculoskeletal conditions. Local anesthetic, botulinum toxin, and/or corticosteroid injections have been reported by some to be beneficial for diagnostic or treatment purposes. Surgical interventions have also been used with variable success.

Cryoablation of atrial fibrillation in "very severe" obese patients (BMI ≥ 40): Indications, feasibility, procedural safety and efficacy, and clinical outcome (the ICE-Obese Extreme).

BACKGROUND: Management of atrial fibrillation (AF) in very severe obese patients is challenging. Cryoballoon ablation (CBA) represents an effective rhythm control strategy. However, data in this patient group were limited. METHODS: Highly symptomatic AF patients with body mass index (BMI) ≥ 40 kg/m2 who had failed antiarrhythmic drug therapy and electrocardioversion and failure to achieve targeted body-weight-reduction underwent CBA. RESULTS: Data of 72 very severe obese AF patients (Group A) and 129 AF patients with normal BMI (Group B, BMI < 25 kg/m2) were consecutively collected. Group A had significantly younger age (60.6 ± 10.4 vs. 69.2 ± 11.2 years), higher BMI (44.3 ± 4.3 vs. 22.5 ± 1.6 kg/m2). Procedural pulmonary vein isolation (PVI) was successful in all patients (2 touch-up ablation in Group A). Compared to Group B, Group A had similar procedural (61.3 ± 22.6 vs. 57.5 ± 19 min), similar fluoroscopy time (10.1 ± 5.5 vs. 9.2 ± 4.8 min) but significantly higher radiation dose (2852 ± 2095 vs. 884 ± 732 µGym2). We observed similar rates of real-time-isolation (78.6% vs. 78.5%), single-shot-isolation (86.5% vs. 88.8%), but significantly longer time-to-sustained-isolation (53.5 ± 33 vs. 43.2 ± 25 s). There was significantly higher rate of puncture-site-complication (6.9% vs. 1.6%) in Group A. One-year clinical success in paroxysmal AF was (Group A: 69.4% vs. Group B: 80.2%; p < .001), in persistent AF was (Group A: 58.1% vs. Group B: 62.8%; p = .889). In Re-Do procedures Group A had a numerically lower PVI durability (75.0% vs. 83.6%, p = .089). CONCLUSION: For very severe obese AF patients, CBA appears feasible, leads to relatively good clinical outcome.

Phased nanopore assembly with Shasta and modular graph phasing with GFAse.

Reference-free genome phasing is vital for understanding allele inheritance and the impact of single-molecule DNA variation on phenotypes. To achieve thorough phasing across homozygous or repetitive regions of the genome, long-read sequencing technologies are often used to perform phased de novo assembly. As a step toward reducing the cost and complexity of this type of analysis, we describe new methods for accurately phasing Oxford Nanopore Technologies (ONT) sequence data with the Shasta genome assembler and a modular tool for extending phasing to the chromosome scale called GFAse. We test using new variants of ONT PromethION sequencing, including those using proximity ligation, and show that newer, higher accuracy ONT reads substantially improve assembly quality.

Oxidative damage in the gastrocnemius predicts long-term survival in patients with peripheral artery disease.

Patients with peripheral artery disease (PAD) have increased mortality rates and a myopathy in their affected legs which is characterized by increased oxidative damage, reduced antioxidant enzymatic activity and defective mitochondrial bioenergetics. This study evaluated the hypothesis that increased levels of oxidative damage in gastrocnemius biopsies from patients with PAD predict long-term mortality rates. Oxidative damage was quantified as carbonyl adducts in myofibers of the gastrocnemius of PAD patients. The oxidative stress data were grouped into tertiles and the 5-year, all-cause mortality for each tertile was determined by Kaplan-Meier curves and compared by the Modified Peto test. A Cox-regression model was used to control the effects of clinical characteristics. Results were adjusted for age, sex, race, body mass index, ankle-brachial index, smoking, physical activity, and comorbidities. Of the 240 study participants, 99 died during a mean follow up of 37.8 months. Patients in the highest tertile of oxidative damage demonstrated the highest 5-year mortality rate. The mortality hazard ratios (HR) from the Cox analysis were statistically significant for oxidative damage (lowest vs middle tertile; HR = 6.33; p = 0.0001 and lowest vs highest; HR = 8.37; p < 0.0001). Survival analysis of a contemporaneous population of PAD patients identifies abundance of carbonyl adducts in myofibers of their gastrocnemius as a predictor of mortality rate independently of ankle-brachial index, disease stage and other clinical and myopathy-related covariates.

The variation and evolution of complete human centromeres.

Human centromeres have been traditionally very difficult to sequence and assemble owing to their repetitive nature and large size1. As a result, patterns of human centromeric variation and models for their evolution and function remain incomplete, despite centromeres being among the most rapidly mutating regions2,3. Here, using long-read sequencing, we completely sequenced and assembled all centromeres from a second human genome and compared it to the finished reference genome4,5. We find that the two sets of centromeres show at least a 4.1-fold increase in single-nucleotide variation when compared with their unique flanks and vary up to 3-fold in size. Moreover, we find that 45.8% of centromeric sequence cannot be reliably aligned using standard methods owing to the emergence of new α-satellite higher-order repeats (HORs). DNA methylation and CENP-A chromatin immunoprecipitation experiments show that 26% of the centromeres differ in their kinetochore position by >500 kb. To understand evolutionary change, we selected six chromosomes and sequenced and assembled 31 orthologous centromeres from the common chimpanzee, orangutan and macaque genomes. Comparative analyses reveal a nearly complete turnover of α-satellite HORs, with characteristic idiosyncratic changes in α-satellite HORs for each species. Phylogenetic reconstruction of human haplotypes supports limited to no recombination between the short (p) and long (q) arms across centromeres and reveals that novel α-satellite HORs share a monophyletic origin, providing a strategy to estimate the rate of saltatory amplification and mutation of human centromeric DNA.

Implications of O-glycan modifications in the hinge region of a plant-produced SARS-CoV-2-IgA antibody on functionality.

Introduction: Prolyl-4-hydroxylases (P4H) catalyse the irreversible conversion of proline to hydroxyproline, constituting a common posttranslational modification of proteins found in humans, plants, and microbes. Hydroxyproline residues can be further modified in plants to yield glycoproteins containing characteristic O-glycans. It is currently unknown how these plant endogenous modifications impact protein functionality and they cause considerable concerns for the recombinant production of therapeutic proteins in plants. In this study, we carried out host engineering to generate a therapeutic glycoprotein largely devoid of plant-endogenous O-glycans for functional characterization. Methods: Genome editing was used to inactivate two genes coding for enzymes of the P4H10 subfamily in the widely used expression host Nicotiana benthamiana. Using glycoengineering in plants and expression in human HEK293 cells we generated four variants of a potent, SARS-CoV-2 neutralizing antibody, COVA2-15 IgA1. The variants that differed in the number of modified proline residues and O-glycan compositions of their hinge region were assessed regarding their physicochemical properties and functionality. Results: We found that plant endogenous O-glycan formation was strongly reduced on IgA1 when transiently expressed in the P4H10 double mutant N. benthamiana plant line. The IgA1 glycoforms displayed differences in proteolytic stability and minor differences in receptor binding thus highlighting the importance of O-glycosylation in the hinge region of human IgA1. Discussion: This work reports the successful protein O-glycan engineering of an important plant host for recombinant protein expression. While the complete removal of endogenous hydroxyproline residues from the hinge region of plant-produced IgA1 is yet to be achieved, our engineered line is suitable for structure-function studies of O-glycosylated recombinant glycoproteins produced in plants.

Management of ventricular tachycardias: insights on centre settings, procedural workflow, endpoints, and implementation of guidelines-results from an EHRA survey.

Ventricular tachycardia (VT), and its occurrence, is still one of the main reasons for sudden cardiac death and, therefore, for increased mortality and morbidity foremost in patients with structural heart [Kahle A-K, Jungen C, Alken F-A, Scherschel K, Willems S, Pürerfellner H et al. Management of ventricular tachycardia in patients with ischaemic cardiomyopathy: contemporary armamentarium. Europace 2022;24:538-51]. Catheter ablation has become a safe and effective treatment option in patients with recurrent VT [Cronin EM, Bogun FM, Maury P, Peichl P, Chen M, Namboodiri N et al. 2019 HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias. Heart Rhythm 2020;17:e2-154]. Previous and current guidelines provide guidance on indication for VT ablation and risk assessment and evaluation of underlying disease. However, no uniform recommendation is provided regarding procedural strategies, timing of ablation, and centre setting. Therefore, these specifics seem to differ largely, and recent data are sparse. This physician-based European Heart Rhythm Association survey aims to deliver insights on not only infrastructural settings but also procedural specifics, applied technologies, ablation strategies, and procedural endpoints. Therefore, these findings might deliver a real-world scenario of VT management and potentially are of guidance for other centres.

A Qualitative Study of Factors Influencing Hospital Participation in the Healthcare Equality Index.

ABSTRACT: Gender and sexual minority individuals experience higher rates of mistreatment and discrimination in healthcare compared with their non-lesbian, gay, bisexual, transgender, queer, and other nonheterosexual (LGBTQ+) peers. The Healthcare Equality Index (HEI) aims to create more inclusive environments and to provide metrics for quality improvement. Currently, only one adult hospital in the District of Columbia has earned the highest recognition from the HEI. Our institution is part of the same regional health system as this hospital, yet has never been evaluated by the HEI. This study explores the knowledge, attitudes, and perceptions surrounding the HEI at our institution to assess the feasibility of its participation. During the study period of July 2021 to June 2022, a total of 12 physicians, administrators, and educators from both hospitals and our affiliated school of medicine were interviewed. All participants expressed support after HEI requirements and improving inclusivity for LGBTQ+ patients. Participants at the other hospital cited unanimous support amongst hospital administrators as key for successful HEI implementation. Participants also mentioned cost, staff shortages, and the school of medicine's religious affiliation as potential barriers to this goal. Ultimately, hospital implementation of HEI guidelines is feasible despite shifting institutional priorities and resource limitations through greater stakeholder buy-in and streamlining a systemwide approach.

Marked enhancement of the immunogenicity of plant-expressed IgG-Fc fusion proteins by inclusion of cholera toxin non-toxic B subunit within the single polypeptide.

Immunoglobulin G (IgG)-based fusion proteins have been widely exploited as a potential vaccine delivery platform but in the absence of exogenous adjuvants, the lack of robust immunity remains an obstacle. Here, we report on a key modification that overcomes that obstacle. Thus, we constructed an IgG-Fc vaccine platform for dengue, termed D-PCF, which in addition to a dengue antigen incorporates the cholera toxin non-toxic B subunit (CTB) as a molecular adjuvant, with all three proteins expressed as a single polypeptide. Following expression in Nicotiana benthamiana plants, the D-PCF assembled as polymeric structures of similar size to human IgM, a process driven by the pentamerization of CTB. A marked improvement of functional properties in vitro and immunogenicity in vivo over a previous iteration of the Fc-fusion protein without CTB [1] was demonstrated. These include enhanced antigen presenting cell binding, internalization and activation, complement activation, epithelial cell interactions and ganglioside binding, as well as more efficient polymerization within the expression host. Following immunization of mice with D-PCF by a combination of systemic and mucosal (intranasal) routes, we observed robust systemic and mucosal immune responses, as well as systemic T cell responses, significantly higher than those induced by a related Fc-fusion protein but without CTB. The induced antibodies could bind to the domain III of the dengue virus envelope protein from all four dengue serotypes. Finally, we also demonstrated feasibility of aerosolization of D-PCF as a prerequisite for vaccine delivery by the respiratory route.

Recombinant neutralizing secretory IgA antibodies for preventing mucosal acquisition and transmission of SARS-CoV-2.

Passive delivery of antibodies to mucosal sites may be a valuable adjunct to COVID-19 vaccination to prevent infection, treat viral carriage, or block transmission. Neutralizing monoclonal IgG antibodies are already approved for systemic delivery, and several clinical trials have been reported for delivery to mucosal sites where SARS-CoV-2 resides and replicates in early infection. However, secretory IgA may be preferred because the polymeric complex is adapted for the harsh, unstable external mucosal environment. Here, we investigated the feasibility of producing neutralizing monoclonal IgA antibodies against SARS-CoV-2. We engineered two class-switched mAbs that express well as monomeric and secretory IgA (SIgA) variants with high antigen-binding affinities and increased stability in mucosal secretions compared to their IgG counterparts. SIgAs had stronger virus neutralization activities than IgG mAbs and were protective against SARS-CoV-2 infection in an in vivo murine model. Furthermore, SIgA1 can be aerosolized for topical delivery using a mesh nebulizer. Our findings provide a persuasive case for developing recombinant SIgAs for mucosal application as a new tool in the fight against COVID-19.

Age is just a number: The role of advanced age in predicting complications following ventral hernia repair with component separation.

BACKGROUND: While advanced age is often considered a risk factor for complications following abdominal surgery, its impact on outcomes after complex open ventral hernia repair (VHR) with component separation technique (CST) remains unclear. METHODS: A single-center retrospective review of patients who VHR with CST from November 2008 to January 2022 was performed and cohorts were stratified by presence of advanced age (≥60 years). RESULTS: Of 219 patients who underwent VHR with CST, 114 patients (52.1 â€‹%) were aged ≥60 years. Multivariate analysis demonstrated BMI to be an independent predictor for any complication (OR 1.1, p â€‹= â€‹0.002) and COPD was positively associated with seroma development (OR 20.1, p â€‹= â€‹0.012). Advanced age did not independently predict postoperative outcomes, including hernia recurrence (OR 0.8, p â€‹= â€‹0.766). CONCLUSIONS: VHR with CST is generally safe to perform in patients of advanced age. Every patient's comorbidity profile should be thoroughly assessed preoperatively for risk stratification regardless of age.

Sex differences in growth and mortality in pregnancy-associated hypertension.

BACKGROUND: It is hypothesized that male fetuses prioritize growth, resulting in increased mortality, whereas females reduce growth in the presence of adversity. Preeclampsia reflects a chronic condition, in which fetuses have the opportunity to adjust growth. If females reduce their growth in response to preeclampsia, but males attempt to maintain growth at the cost of survival, we predict that differences in birthweight between preeclamptic and non-preeclamptic pregnancies will be greater among females, whereas differences in mortality will be greater among males. METHODS: We analysed data from the Centers for Disease Control and Prevention. We compared pregnancies with pregnancy-associated hypertension (PAH) and controls. RESULTS: The difference in birthweight between pregnancies affected by PAH and controls varied by fetal sex and gestational age. Among pregnancies of White individuals, at 34-35 weeks, the difference between PAH and controls was higher among females, as predicted. However, this pattern was reversed earlier in pregnancy and around term. Such variation was not significant in Black pregnancies. In both Black and White pregnancies, early in gestation, males had lower odds of death in PAH pregnancies, but higher odds of death in control pregnancies, counter to our prediction. Later, males had higher odds of death in PAH and controls, although the increased odds of death in males was not higher in PAH pregnancies than in controls. Overall, the difference in birthweight between surviving and non-surviving infants was greater in males than in females, opposite to our prediction. CONCLUSIONS: The impact of PAH on birthweight and survival varies widely throughout gestation. Differences in birthweight and survival between male and female PAH and controls are generally not consistent with the hypothesis that males prioritize fetal growth more than females, and that this is a cause of increased mortality in males.

Prevention of venous thromboembolism in right heart-sided electrophysiological procedures: results of an European Heart Rhythm Association survey.

Limited data are available regarding venous thromboembolism (VTE), specifically deep vein thrombosis (DVT) and pulmonary embolism (PE), following right-sided ablations and electrophysiological (EP) studies. Compared to left-sided procedures, no guidelines on antithrombotic management strategies for the prevention of DVT and PE are available. The main purpose of the present European Heart Rhythm Association (EHRA) survey is to report the current management of right-sided EP procedures, focusing on anticoagulation and prevention of VTE. An online survey was conducted using the EHRA infrastructure. A total of 244 participants answered a 19-items questionnaire on the periprocedural management of EP studies and right-sided catheter ablations. The right femoral vein is the most common access for EP studies and right-sided procedures. An ultrasound-guided approach is employed by more than 2/3 of respondents. Intravenous heparin is not commonly given by the majority of participants. About 1/3 of participants (34%) routinely prescribe VTE prophylaxis during (mostly aspirin and low molecular weight heparin) and 1/4 of respondents (25%) commonly prescribe VTE prophylaxis after discharge (mostly aspirin). Of note, respectively 13% and 9% of participants observed at least one DVT and one PE related to right-sided ablation or EP study within the last year in their center. The present survey shows that only a minority of operators routinely gives intraprocedural intravenous heparin and prescribes VTE prophylaxis after right-sided EP procedures. Compared to left-sided procedures like atrial fibrillation (AF) ablation, there are no consistent systematic antithrombotic management strategies.

Anterior cruciate ligament repair versus reconstruction: A clinical, MRI and patient-reported outcome comparison.

BACKGROUND: There has been a resurgence in anterior cruciate ligament (ACL) repair for proximal tears using modern surgical techniques and technology. This study aims to compare ACL repair with reconstruction using MRI, clinician-measured and patient-reported outcome measures (PROMs). METHODS: A post-hoc analysis was performed on prospectively collected data from 20 consecutive primary ACL repairs by the senior author. This was compared with an age and sex-matched cohort of 20 ACL reconstructions by the same surgeon using PROMs, return-to-sport (RTS) testing, and MRI signal noise quotient (SNQ). RESULTS: Repairs demonstrated equivalent post-operative PROMs to reconstructions as measured by International Knee Documentation Committee subjective score (78.5 ± 17.1 vs. 83.7 ± 13.3, P = 0.333), Tegner Activity Scale (5.9 ± 1.8 vs. 6.1 ± 2.6, P = 0.646) and Lysholm score (89.8 ± 10.0 vs. 89.6 ± 10.4, P = 0.762). There was no difference in repairs and reconstructions passing quadriceps strength criteria (50% vs. 53%, P = 0.097). A greater proportion of repairs passed hamstrings strength criteria (86% vs. 60%, P = 0.023) and hamstrings-to-quadriceps ratio (71% vs. 20%, P = 0.003). There were no differences across hop and Y-balance testing. Repairs had earlier RTS assessment (8.2 ± 2.8 months vs. 10.6 ± 1.4 months, P = 0.020). On 12-month MRI, repairs demonstrated higher femoral (8.8 ± 5.7 vs. 4.6 ± 2.9, P = 0.009) and tibial SNQ (10.0 ± 5.7 vs. 4.3 ± 4.2, P = 0.001), with no mid-substance difference (12.3 ± 8.5 vs. 7.6 ± 5.2, P = 0.074). There were no graft failures. CONCLUSIONS: When patient selection is optimized for proximal tears, ACL repairs demonstrate equivalent PROMs and better objective outcomes to reconstructions at an earlier timepoint. Repair tissue quality on MRI shows higher signal at tibial and femoral attachments.