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Background & Aims: DNA methylation alterations may provide important insights into gene-environment interaction in cancer, aging, and complex diseases, such as inflammatory bowel disease (IBD). We aim first to determine whether the circulating DNA methylome in patients requiring surgery may predict Crohn’s disease (CD) recurrence following intestinal resection; and second to compare the circulating methylome seen in patients with established CD with that we had reported in a series of inception cohorts. Methods: TOPPIC was a placebo-controlled, randomized controlled trial of 6-mercaptopurine at 29 UK centers in patients with CD undergoing ileocolic resection between 2008 and 2012. Genomic DNA was extracted from whole blood samples from 229 of the 240 patients taken before intestinal surgery and analyzed using 450KHumanMethylation and Infinium Omni Express Exome arrays (Illumina, San Diego, CA). Coprimary objectives were to determine whether methylation alterations may predict clinical disease recurrence; and to assess whether the epigenetic alterations previously reported in newly diagnosed IBD were present in the patients with CD recruited into the TOPPIC study. Differential methylation and variance analysis was performed comparing patients with and without clinical evidence of recurrence. Secondary analyses included investigation of methylation associations with smoking, genotype (MeQTLs), and chronologic age. Validation of our previously published case-control observation of the methylome was performed using historical control data (CD, n = 123; Control, n = 198). Results: CD recurrence in patients following surgery is associated with 5 differentially methylated positions (Holm P < .05), including probes mapping to WHSC1 (P = 4.1 × 10-9, Holm P = .002) and EFNA3 (P = 4.9 × 10-8, Holm P = .02). Five differentially variable positions are demonstrated in the group of patients with evidence of disease recurrence including a probe mapping to MAD1L1 (P = 6.4 × 10-5). DNA methylation clock analyses demonstrated significant age acceleration in CD compared with control subjects (GrimAge + 2 years; 95% confidence interval, 1.2–2.7 years), with some evidence for accelerated aging in patients with CD with disease recurrence following surgery (GrimAge +1.04 years; 95% confidence interval, -0.04 to 2.22). Significant methylation differences between CD cases and control subjects were seen by comparing this cohort in conjunction with previously published control data, including validation of our previously described differentially methylated positions (RPS6KA2 P = 1.2 × 10-19, SBNO2 = 1.2 × 10-11) and regions (TXK [false discovery rate, P = 3.6 × 10-14], WRAP73 [false discovery rate, P = 1.9 × 10-9], VMP1 [false discovery rate, P = 1.7 × 10-7], and ITGB2 [false discovery rate, P = 1.4 × 10-7]). Conclusions: We demonstrate differential methylation and differentially variable methylation in patients developing clinical recurrence within 3 years of surgery. Moreover, we report replication of the CD-associated methylome, previously characterized only in adult and pediatric inception cohorts, in patients with medically refractory disease needing surgery.

Abstract Ferric derisomaltose (FDI; Monofer) is used in clinical practice to treat iron deficiency, but the safety and efficacy of FDI has not been robustly evaluated in a large real-world study. This retrospective, multicentre, audit-based, observational study provides pragmatic information about safety and clinical responses with FDI across therapy areas and patient populations, helping to facilitate treatment decisions. Participating sites provided data from the medical records of adults who had received ≥ 1 FDI infusion. The primary outcome was the incidence of adverse reactions within 24 hours of the FDI infusion. Secondary outcomes included the change from baseline in haemoglobin and ferritin up to 12 months post infusion. In total, 19 sites provided data for a total of 7354 FDI-treated patients; 64.3% of patients were female, and 42.2% were aged ≥ 70 years. Surgery was the main hospital specialty (34.5%). The incidence of any recorded adverse reactions, hypersensitivity reactions, and anaphylaxis were 1.7%, 0.4%, and

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

Summary: Background: Patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy exhibit attenuated humoral immune responses to vaccination against SARS-CoV-2. The gut microbiota and its functional metabolic output, which are perturbed in IBD, play an important role in shaping host immune responses. We explored whether the gut microbiota and metabolome could explain variation in anti-SARS-CoV-2 vaccination responses in immunosuppressed IBD patients. Methods: Faecal and serum samples were prospectively collected from infliximab-treated patients with IBD in the CLARITY-IBD study undergoing vaccination against SARS-CoV-2. Antibody responses were measured following two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccine. Patients were classified as having responses above or below the geometric mean of the wider CLARITY-IBD cohort. 16S rRNA gene amplicon sequencing, nuclear magnetic resonance (NMR) spectroscopy and bile acid profiling with ultra-high-performance liquid chromatography mass spectrometry (UHPLC-MS) were performed on faecal samples. Univariate, multivariable and correlation analyses were performed to determine gut microbial and metabolomic predictors of response to vaccination. Findings: Forty-three infliximab-treated patients with IBD were recruited (30 Crohn's disease, 12 ulcerative colitis, 1 IBD-unclassified; 26 with concomitant thiopurine therapy). Eight patients had evidence of prior SARS-CoV-2 infection. Seventeen patients (39.5%) had a serological response below the geometric mean. Gut microbiota diversity was lower in below average responders (p = 0.037). Bilophila abundance was associated with better serological response, while Streptococcus was associated with poorer response. The faecal metabolome was distinct between above and below average responders (OPLS-DA R2X 0.25, R2Y 0.26, Q2 0.15; CV-ANOVA p = 0.038). Trimethylamine, isobutyrate and omega-muricholic acid were associated with better response, while succinate, phenylalanine, taurolithocholate and taurodeoxycholate were associated with poorer response. Interpretation: Our data suggest that there is an association between the gut microbiota and variable serological response to vaccination against SARS-CoV-2 in immunocompromised patients. Microbial metabolites including trimethylamine may be important in mitigating anti-TNF-induced attenuation of the immune response. Funding: JLA is the recipient of an NIHR Academic Clinical Lectureship (CL-2019-21-502), funded by Imperial College London and The Joyce and Norman Freed Charitable Trust. BHM is the recipient of an NIHR Academic Clinical Lectureship (CL-2019-21-002). The Division of Digestive Diseases at Imperial College London receives financial and infrastructure support from the NIHR Imperial Biomedical Research Centre (BRC) based at Imperial College Healthcare NHS Trust and Imperial College London. Metabolomics studies were performed at the MRC-NIHR National Phenome Centre at Imperial College London; this work was supported by the Medical Research Council (MRC), the National Institute of Health Research (NIHR) (grant number MC_PC_12025) and infrastructure support was provided by the NIHR Imperial Biomedical Research Centre (BRC). The NIHR Exeter Clinical Research Facility is a partnership between the University of Exeter Medical School College of Medicine and Health, and Royal Devon and Exeter NHS Foundation Trust. This project is supported by the National Institute for Health Research (NIHR) Exeter Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the NIHR or the UK Department of Health and Social Care.

Crohn’s disease (CD) is a chronic inflammation of the digestive tract that significantly impairs patients’ quality of life and well-being. Anti-TNF biologicals revolutionised the treatment of CD, yet many patients do not adequately respond to such therapy. Previous studies have demonstrated a pro-inflammatory pattern in the composition of CD patients’ immunoglobulin G (IgG) N-glycome compared to healthy individuals. Here, we utilised the high-throughput UHPLC method for N-glycan analysis to explore the longitudinal effect of the anti-TNF drugs infliximab and adalimumab on N-glycome composition of total serum IgG in 198 patients, as well as the predictive potential of IgG N-glycans at baseline to detect primary non-responders to anti-TNF therapy in 1315 patients. We discovered a significant decrease in IgG agalactosylation and an increase in monogalactosylation, digalactosylation and sialylation during the 14 weeks of anti-TNF treatment, regardless of therapy response, all of which suggested a diminished inflammatory environment in CD patients treated with anti-TNF therapy. Furthermore, we observed that IgG N-glycome might contain certain information regarding the anti-TNF therapy outcome before initiating the treatment. However, it is impossible to predict future primary non-responders to anti-TNF therapy based solely on IgG N-glycome composition at baseline.

Summary: Gut dysmotility is associated with constipation, diarrhea, and functional gastrointestinal disorders like irritable bowel syndrome (IBS), although its molecular underpinnings are poorly characterized. We studied stool frequency (defined by the number of bowel movements per day, based on questionnaire data) as a proxy for gut motility in a GWAS meta-analysis including 167,875 individuals from UK Biobank and four smaller population-based cohorts. We identify 14 loci associated with stool frequency (p ≤ 5.0 × 10−8). Gene set and pathway analyses detected enrichment for genes involved in neurotransmitter/neuropeptide signaling and preferentially expressed in enteric motor neurons controlling peristalsis. PheWAS identified pleiotropic associations with dysmotility syndromes and the response to their pharmacological treatment. The genetic architecture of stool frequency correlates with that of IBS, and UK Biobank participants from the top 1% of stool frequency polygenic score distribution were associated with 5× higher risk of IBS with diarrhea. These findings pave the way for the identification of actionable pathological mechanisms in IBS and the dysmotility syndromes.

Abstract Background Many genome- and epigenome-wide association studies (GWAS and EWAS) and studies of promoter methylation of candidate genes for inflammatory bowel disease (IBD) have demonstrated significant associations between genetic and epigenetic changes and IBD. Independent GWA studies have identified genetic variants in the BACH2, IL6ST, LAMB1, IKZF1, and MGAT3 loci to be associated with both IBD and immunoglobulin G (IgG) glycosylation. Methods Using bisulfite pyrosequencing, we analyzed CpG methylation in promoter regions of these five genes from peripheral blood of several hundred IBD patients and healthy controls (HCs) from two independent cohorts, respectively. Results We found significant differences in the methylation levels in the MGAT3 and BACH2 genes between both Crohn’s disease and ulcerative colitis when compared to HC. The same pattern of methylation changes was identified for both genes in CD19+ B cells isolated from the whole blood of a subset of the IBD patients. A correlation analysis was performed between the MGAT3 and BACH2 promoter methylation and individual IgG glycans, measured in the same individuals of the two large cohorts. MGAT3 promoter methylation correlated significantly with galactosylation, sialylation, and bisecting GlcNAc on IgG of the same patients, suggesting that activity of the GnT-III enzyme, encoded by this gene, might be altered in IBD. The correlations between the BACH2 promoter methylation and IgG glycans were less obvious, since BACH2 is not a glycosyltransferase and therefore may affect IgG glycosylation only indirectly. Conclusions Our results suggest that epigenetic deregulation of key glycosylation genes might lead to an increase in pro-inflammatory properties of IgG in IBD through a decrease in galactosylation and sialylation and an increase of bisecting GlcNAc on digalactosylated glycan structures. Finally, we showed that CpG methylation in the promoter of the MGAT3 gene is altered in CD3+ T cells isolated from inflamed mucosa of patients with ulcerative colitis from a third smaller cohort, for which biopsies were available, suggesting a functional role of this glyco-gene in IBD pathogenesis.

Background: The fabella is a sesamoid bone that is a normal anatomic variant yet a rare cause of pathology in the posterolateral portion of the knee. The fabella can cause chronic knee pain in patients with knee osteoarthritis and athletes at all levels and in rare cases can cause neuropathy. Initially, treatment for a painful fabella includes conservative measures, with surgical intervention after conservative treatments have failed. This technique describes our arthroscopic-assisted fabella removal technique with a concomitant medial meniscus revision repair. Indications: The goal of treatment is to relieve pain and numbness. Conservative measures (i.e., nonsteroidal anti-inflammatory drugs [NSAIDs], range of motion exercises, heel cord stretching, etc.) are the initial step in treatment. Patients are treated surgically after conservative measures have failed. The surgical approach involves an open incision, arthroscopy, or a combination. Technique Description: With the patient in the supine position, a physical examination is performed under anesthesia to compare to validate clinical findings. An open lateral knee approach helps to locate the fabella which is grasped with an Alice clap. An arthroscopy is performed, and viewing posterolaterally will confirm that the fabella is within the grips of the Alice clamp. After repair of the meniscus, the surgical bed is repositioned to identify the fabella properly. Excision of the fabella is performed sharply from the lateral gastrocnemius tendon, and palpation is demonstrated to ensure complete removal. Caution is essential to avoid complications including damage to nearby anatomic structures, such as the lateral gastrocnemius tendon, and incomplete fabella removal. Results: A clinical study by Dekker et al reported that 80% of patients were able to return to full activities and postoperative patient-reported outcomes improved from preoperative to postoperative. Fabella excision is recommended for patients with fabella pain who do not respond to conservative treatment. Discussion: We describe a technique for removing the fabella with arthroscopic assistance. Patients who have not responded appropriately to conservative treatment for a painful fabella should consider surgical intervention. With the early initiation of rehabilitation, patients will have an increased likelihood of decreased pain, resolution of symptoms, and reduced knee stiffness. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

How is new information organized in memory? According to latent state theories, this is determined by the level of surprise, or prediction error, generated by the new information: a small prediction error leads to the updating of existing memory, large prediction error leads to encoding of a new memory. We tested this idea using a protocol in which rats were first conditioned to fear a stimulus paired with shock. The stimulus was then gradually extinguished by progressively reducing the shock intensity until the stimulus was presented alone. Consistent with latent state theories, this gradual extinction protocol (small prediction errors) was better than standard extinction (large prediction errors) in producing long-term suppression of fear responses, and the benefit of gradual extinction was due to updating of the conditioning memory with information about extinction. Thus, prediction error determines how new information is organized in memory, and latent state theories adequately describe the ways in which this occurs.

Background: Anterior cruciate ligament reconstructions (ACLRs) are performed to restore knee biomechanics, increase knee stability, and slow the progression of osteoarthritis. After ACLRs, many patients still have residual anterolateral instability which is a risk factor for ACL graft failure. An anterolateral ligament reconstruction (ALLR) attempts to restore the native function of the anterolateral complex to augment the ACL. Performing an ALLR with an ACLR has been reported to reduce symptoms of instability and improve clinical outcomes. Indications: While no definitive indication for an ALLR has been set, current considerations include high posterior tibial slope >12°, revision ACLR, high-grade pivot shift, skeletally immature patients, hyperlaxity, and patients in high-level sports. Technique Description: The preoperative assessment includes a thorough physical examination with special attention paid to rotational laxity assessed via the pivot-shift examination. Imaging should include standard radiographic series (anteroposterior, posteroanterior flexion, lateral, and sunrise views), long-leg mechanical axis views to assess coronal plane alignment and standing lateral ACL stress radiographs to assess sagittal alignment and objective instability. The iliotibial band ALLR graft is harvested first. An 8-cm long by 1-cm wide strip of the inferior iliotibial band is harvested in a standard fashion, leaving the distal aspect attached to Gerdy’s tubercle. An anchor is placed centered upon the native ALL distal tibial insertion. The native ALL femoral origin is identified at 4.7 mm posterior and proximal to the fibular collateral ligament, and a second suture anchor is placed at this point. Final fixation is performed after the final fixation of the ACLR graft. Results: A study by Pioger et al reported that patients with ACLR and ALLR had significantly less reoperation rate than patients with isolated ACLR, 8.9% versus 20.5% respectively. Lee et al found that a revision ACLR in combination with an ALLR was effective in reducing rotational laxity, which was assessed by the pivot-shift test. Discussion: We describe a technique for a new anatomic ALLR using the iliotibial band that attempts to restore the native ALL anatomy. This surgical technique effectively restores rotational laxity and improves knee stability. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Background: Symptomatic genu recurvatum is defined as greater than 5° of knee hyperextension and can be caused by osseous deformity, soft tissue laxity, or a combination. Common symptoms include pain, weakness, instability, decreased range of motion, leg length discrepancy, and stretching of the posterior capsuloligamentous structures of the knee. In instances where the genu recurvatum is caused by reverse tibial slope, literature supports the use of anterior opening-wedge proximal tibial osteotomy (OW PTO) to treat genu recurvatum by increasing tibial slope. Correction of anterior slope to a more anatomic, posterior orientation allows any stressed ligaments to return to their normal tension and restores the native biomechanics of the knee. Indications: The primary indication for OW PTO is genu recurvatum that is nonresponsive to physical therapy or genu recurvatum with concurrent ligamentous injury. The heel-height test provides an objective assessment for the identification and measurement of knee hyperextension. Technique Description: 2 guide pins are placed parallel to the tibial plateau, engaging the posterior cortex. A small micro sagittal saw is used to cut the anterior cortex. Osteotomes are used to complete the osteotomy, preserving a posterior hinge. An opening spreader device is placed and opened slowly while keeping the posterior cortex intact. The new slope is maintained by use of an opening wedge osteotomy plate and screws. Allograft bone graft is packed thoroughly into the osteotomy site. Fluoroscopy is used throughout the case to assess appropriate orientation and depth of the osteotomy, as well as the final opening width. Results: A review of 5 studies demonstrated adequate reduction in hyperextension, with a mean knee hyperextension ranging from 17° to 32° preoperatively and 0° to 7° postoperatively. Patients had significantly improved postoperative clinical outcomes compared with the preoperative state. Discussion/Conclusion: Anterior OW PTO has been shown to be a safe method of accurately correcting tibial plateau slope for the treatment of genu recurvatum. Patients can expect correction of knee hyperextension, restoration of anatomic posterior tibial slope, decreased posterior tibial translation, and increased subjective outcome scores. Patient Consent Disclosure Statement: The author(s) attest that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Introduction Characterised by chronic inflammation of the gastrointestinal tract, inflammatory bowel disease (IBD) symptoms including diarrhoea, abdominal pain and fatigue can significantly impact patient’s quality of life. Therapeutic developments in the last 20 years have revolutionised treatment. However, clinical trials and real-world data show primary non-response rates up to 40%. A significant challenge is an inability to predict which treatment will benefit individual patients.Current understanding of IBD pathogenesis implicates complex interactions between host genetics and the gut microbiome. Most cohorts studying the gut microbiota to date have been underpowered, examined single treatments and produced heterogeneous results. Lack of cross-treatment comparisons and well-powered independent replication cohorts hampers the ability to infer real-world utility of predictive signatures.IBD-RESPONSE will use multi-omic data to create a predictive tool for treatment response. Future patient benefit may include development of biomarker-based treatment stratification or manipulation of intestinal microbial targets. IBD-RESPONSE and downstream studies have the potential to improve quality of life, reduce patient risk and reduce expenditure on ineffective treatments.Methods and analysis This prospective, multicentre, observational study will identify and validate a predictive model for response to advanced IBD therapies, incorporating gut microbiome, metabolome, single-cell transcriptome, human genome, dietary and clinical data. 1325 participants commencing advanced therapies will be recruited from ~40 UK sites. Data will be collected at baseline, week 14 and week 54. The primary outcome is week 14 clinical response. Secondary outcomes include clinical remission, loss of response in week 14 responders, corticosteroid-free response/remission, time to treatment escalation and change in patient-reported outcome measures.Ethics and dissemination Ethical approval was obtained from the Wales Research Ethics Committee 5 (ref: 21/WA/0228). Recruitment is ongoing. Following study completion, results will be submitted for publication in peer-reviewed journals and presented at scientific meetings. Publications will be summarised at www.ibd-response.co.uk.Trial registration number ISRCTN96296121.

Background: Anatomically, native posterior tibial slope (PTS) ranges from 6° to 10° and have significant effects on cruciate ligament stability. PTS

Background: The popliteus tendon is a primary stabilizer of external knee rotation and has been described as the “fifth ligament of the knee.” Injuries involving the posterolateral corner of the knee commonly involve the popliteus tendon; isolated injury to the popliteus tendon is relatively rare and usually involves a rotatory injury mechanism and symptoms of instability and pain. In this patient, there was a concomitant injury to the proximal tibiofibular joint. Indications: Popliteus tendon reconstruction is indicated for patients with abnormal external rotation on examination and symptoms of pain and instability. Proximal tibiofibular joint reconstruction is indicated for patients with instability of the tibiofibular joint. Technique Description: Preoperative examination under anesthesia is essential to determine the extent of external rotation and assess for additional posterolateral pathology. The popliteus tendon procedure begins with a meticulous common peroneal nerve neurolysis to minimize nerve irritation and decrease the risk of a postoperative foot drop. Semitendinosus and gracilis graft harvest is performed with at least 16 cm of graft length followed by tunnel reaming of the popliteus tendon femoral attachment and tibia tunnel identification and reaming. The femoral attachment of the popliteus tendon is secured, and the semitendinosus graft is anatomically oriented along the native path and passed from posterior to anterior through the femoral tunnel. The gracilis graft for anatomic proximal tibiofibular joint reconstruction requires an anterior to posterior tunnel through the fibular head. Finally, both grafts are secured in the tibial tunnel with the application of an anterior traction force. Results: A cadaveric study by LaPrade et al reported that an anatomic popliteus tendon reconstruction with a semitendinosus autograft significantly reduced external rotation laxity compared with the sectioned state. In addition, popliteus tendon reconstruction resulted in significantly decreased varus laxity, anterior tibial translation, and internal rotation. Discussion: This is a technique that effectively restores external rotation knee stability utilizing an anatomically oriented reconstruction of the popliteus tendon and tibiofibular joint. The popliteus tendon serves as a primary stabilizer to external rotation and facilitates static function of the knee. The proximal tibiofibular joint reconstruction restores the function of the posterior proximal tibiofibular joint ligaments. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Background: Contributors to knee degeneration include mechanical axis malalignment, patellar maltracking, meniscal deficiency, and tibiofemoral instability. Full-thickness osteochondral defects in young, active patients can lead to significant pain and instability. The gold standard treatment for large (>2 cm 2 ) osteochondral defects is an osteochondral allograft (OCA) which addresses the pathologic articular cartilage loss and underlying bone deficiency. While biologic failure of fresh OCAs is reported, the majority of early failures are attributed to unaddressed mechanical malalignment in the coronal plane. Proximal tibial osteotomy (PTO) corrects malalignment thereby unloading the affected medial compartment and the newly placed OCA, improving long-term survivability. Indications: OCAs are indicated for isolated osteochondral defects and lesions in active young patients. PTO is indicated for patients with varus malalignment who risk potential graft failure of the affected medial compartment. Technique Description: The articular cartilage defect is identified, and a guide pin is drilled in the center. The defect is templated and scored around the margins. A reamer is used to drill to a total depth of 7 to 8 mm. The recipient site is then dilated for graft insertion. On the donor graft, the harvest site is outlined and drilled to the proper diameter. Careful measurement is utilized to ensure graft depth measurements match the recipient site. Once sized, the graft is tapped into place obtaining an anatomic fit along its entire periphery. The osteotomy is performed by using guide pins to delineate the plane cutting the tibia. Fluoroscopy confirmed the osteotomy site and angle. A spacing plate was securely inserted with screws, with placement confirmed by fluoroscopy. Results: Fresh OCAs can restore osteochondral defects. PTO corrects malalignment and unloads the affected medial compartment, decreasing the risk of revision graft failure or total knee arthroplasty. Discussion: Clinical and biomechanical studies that compared isolated and concomitant procedures demonstrated that OCA with PTOs had significantly greater survival rates. Significant malalignment increases the risk of graft failure. It remains unclear whether concomitant osteotomy with osteoarticular allografts leads to increased complication risk; inherent risks remain associated with individual procedures. In adolescents, simultaneous corrective osteotomy along with fresh OCA may delay arthroplasty and associated ambulatory restrictions. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Background: Fibular collateral ligament (FCL) injuries commonly present in a multiligament knee injury pattern. These injuries are associated with significant instability leading to altered tibiofemoral biomechanics and therefore require surgical intervention. Similarly, grade 3 posterior cruciate ligament (PCL) injuries may disrupt normal tibiofemoral and patellofemoral biomechanics and increase the risk of secondary osteoarthritis. Therefore, concomitant reconstruction of the FCL and PCL should be performed to decrease knee laxity and optimize functional outcomes. Indications: Early operative treatment is indicated for patients with combined grade 3 FCL injuries and complete PCL tears. Contraindications to this procedure include patients who have significant osteoarthritis, open knee dislocations, or medical comorbidities making them unfit for surgery. Technique Description: The fundamental idea behind this technique is a stepwise treatment starting with open aspects of the procedure and followed by arthroscopic work. The technique is initiated with a lateral approach, common peroneal neurolysis, fibular and femoral FCL reconstruction tunnel preparation, and a gracilis or semitendinosus tendon autograft harvest. After that, focus shifts to intra-articular work such as associated meniscal assessment and treatment, PCL femoral and tibial tunnel preparation, graft passage, and PCL femoral tunnel fixation. Final graft fixation order is as follows: anterolateral bundle of PCL, posteromedial bundle of PCL, and finally FCL. Results: Multiple studies have reported that an anatomic FCL reconstruction in the setting of multiligament injury results in improved patient outcomes. In a prospective study of 20 patients, LaPrade et al reported −0.4 mm difference in side-to-side lateral compartment gapping and significant postoperative improvement of symptom and functional scores at a minimum 2 year postoperative follow-up after anatomic reconstruction of the FCL. Similarly, Moulton et al reported significant improvement in the average Western Ontario and Lysholm scores at 2.7 years follow-up. LaPrade et al also reported significant improvement in function and objective outcome scores at 3 years’ follow-up from anatomic double-bundle PCL reconstruction. Discussion: Anatomic FCL and PCL reconstructions successfully restore near native knee objective stability and provide superior clinical outcomes when compared to nonanatomic-based FCL reconstructions that continue to be performed. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Background: Complete meniscal root tears disrupt dispersion of axial loading forces through hoop stresses. This increases point-loading on tibiofemoral cartilage and leads to chondromalacia and accelerated osteoarthritis (OA). Posterior root tears may be treated successfully with a transtibial pullout repair. Varus malalignment also leads to increased medial compartment pressures, increasing the risk of early OA and putting increased stress on the meniscus and stabilizing knee ligaments. In particular, revision medial meniscal root repairs without correction of varus malalignment are at increased risk of failure. Genu varum may be corrected with a medial opening-wedge proximal tibial osteotomy (OW PTO). Indications: Meniscal root repairs are indicated for acute or chronic tears in active patients with healthy cartilage. OW PTO is indicated for varus malalignment in ambulatory patients with healthy cartilage, or who are at risk for failure of meniscal or ligamentous procedures. Technique Description: After exposure of the osteotomy site, arthroscopy is performed through the incision and the revision posterior meniscus root repair is performed via a double-tunnel transtibial pullout technique. The positioning of these tunnels is modified superiorly so as to not cross the planned osteotomy site. The osteotomy is then performed by drilling 2 guide pins under fluoroscopy to delineate the plane of the cut. An OW plate is placed, and the root repair is tensioned last. Results: Double-tunnel transtibial pullout repairs increase meniscal fixation contact surface and have been shown to be biomechanically superior to all-inside fixation techniques. Medial OW PTO restores knee alignment and reduces supra-anatomic stresses in the medial compartment, additionally decreasing the risk of a revision medial meniscus repair failure. Discussion: Biomechanical studies have shown that meniscal root tears are functionally equivalent to complete meniscectomy. Varus malalignment increases the risk of medial meniscal tears, and reduces the risk of a successful long-term repair. We describe a technique for a revision transosseous posterior root repair with concomitant proximal tibial osteotomy, with discussion of surgical pearls and pitfalls. This technique restores anatomic position and native function of the medial meniscus while correcting tibiofemoral malalignment that could jeopardize the repair. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form.

Knee extension contracture is a common postinjury and postsurgical complication, which decreases knee joint flexion. Many techniques have been described in the literature to restore knee flexion, with the most common one being an arthroscopic lysis of adhesions. However, in severe cases, additional intra- and extra-articular procedures are needed to restore full knee flexion. Manipulation under anesthesia (MUA) is one of them. Unfortunately, it may lead to devastating complications, such as iatrogenic rupture of the patellar tendon or fractures of the patella or tibial tuberosity. Therefore, the purpose of this report is to present a safer modification of MUA for knee extension contracture in cases in which excessive force is demanded to achieve flexion. The key aim of the “patellar base support” technique (PBS technique) is to stretch the contracted quadriceps muscle with controlled and decreased tension on the patella, patellar tendon, and tibial tuberosity.

Arthroscopic visualization and access of the posterior knee are limited when using standard anterior and posterior portals. The creation of a trans-septal portal allows for complete access to the posterior compartment as arthroscopic instruments are able to be passed back and forth between the posteromedial and posterolateral compartments. Due to the close proximity of the popliteal artery and its branches, precise portal placement and safe orientation of arthroscopic instruments are critical to avoid iatrogenic injury. The conventional technique of trans-septal portal creation, involving a posterolateral portal, can be difficult in some cases. To overcome these obstacles, a posteromedial technique of trans-septal portal creation is presented. By using the medial parapatellar portal as the viewing portal, our technique allows for direct visualization of the posterior septum on each step of creation of the trans-septal portal, eliminating the need for “blind” maneuvers. What is more, no posterolateral portal is needed, decreasing the risk of potential complications. Using the posterior cruciate ligament fibers as a main landmark for trans-septal portal placement, preservation of the posterior part of the septum is achieved. This ensures optimal safe-margin distance away from the popliteal neurovascular bundle and making the technique safe and reproducible.

Abstract 58‐year‐old male presented with knee extension contracture (25°) with iatrogenic fixed anterior tibial subluxation. Consecutive arthroscopic arthrolysis, manipulation under anesthesia, and quadriceps‐Z‐plasty during one surgery failed to restore flexion. Therefore, shortened posterior cruciate ligament was released, which eliminated subluxation and allowed 115° flexion. Despite physiotherapy, flexion progressively decreased to 70° postoperatively. Revision quadricepsplasty by transverse incisions restored 120° of flexion maintained at 31‐months follow‐up. International Knee Documentation Committee increased 4/87‐ > 50/87, Knee injury and Osteoarthritis Outcome 7/100‐ > 68/100 at follow‐up. Posterior cruciate ligament release and repeated quadricepsplasty could be a viable salvage option in severe extension contracture with fixed anterior tibial subluxation.

Stable quantum bits, capable both of storing quantum information for macroscopic time scales and of integration inside small portable devices, are an essential building block for an array of potential applications. We demonstrate high-fidelity control of a solid-state qubit, which preserves its polarization for several minutes and features coherence lifetimes exceeding 1 second at room temperature. The qubit consists of a single \(^{13}C\) nuclear spin in the vicinity of a nitrogen-vacancy color center within an isotopically purified diamond crystal. The long qubit memory time was achieved via a technique involving dissipative decoupling of the single nuclear spin from its local environment. The versatility, robustness, and potential scalability of this system may allow for new applications in quantum information science., Physics

Purpose: To quantitatively determine whether there is an added risk of orthopaedic injury attributable to the collision forces that athletes participating in collision-contact (CC) sports regularly encounter. Methods: The National Electronic Injury Surveillance System was used to collect data on patients presenting to an emergency department with a contact sports-related injury between 2014 and 2020. Select contact sports were classified as either belonging to a CC or noncollision-contact (NCC) sports group based on involvement of frequent and intentional player-to-player collisions. Results: From 2014 to 2020, 25,784 patients with team-based sports related injuries presented to an emergency department, of whom 7,591 sustained an injury during a CC sport and 18,193 during a NCC sport. The CC group was associated with significantly increased odds of sustaining at least 1 fracture (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.35-1.52) (P < .001), dislocation (OR 1.2, 95 % CI 1.06-1.33) (P < .001), and being admitted into the hospital (OR 1.6, 95% CI 1.34-1.86) (P < .001), compared with the NCC group. Conclusions: We found that frequent and intentional high-energy collisions associated with CC sports significantly increase the risk of sustaining fractures and dislocations. Furthermore, we found that that the injuries sustained by players engaging in CC sports required hospitalization at a significantly greater rate than those sustained in contact sports that do not involve frequent and intentional player-to-player collisions. Level of Evidence: Level III, prognostic (retrospective cohort study).

Multiligament knee injuries (MLKIs) are severe injuries that involve complete or partial tear to multiple ligaments of the knee, such as the cruciate ligaments, collateral ligaments, as well as structures such as the posteromedial and posterolateral corners. These injuries often occur as a result of high-energy trauma in motor vehicle accidents, but can also occur during sports activities such as a fall or collision while skiing or snowboarding. Diagnosis of an MLKI can be challenging due to the multifaceted nature of these injuries, and a comprehensive evaluation, including a thorough history, physical examination, and imaging studies, is necessary. Imaging methods, such as plain and stress radiographs and magnetic resonance imaging, are often used to confirm the diagnosis and assist in the establishment of a treatment plan. Treatment of MLKIs commonly involves surgical repair or reconstruction of torn ligaments and capsular structures, followed by lengthy rehabilitation focused on mobility, strength, and improving knee function. Return to sport is a concern, especially for those with many ligaments torn and those involving both cruciate ligaments and/or those involving the posterolateral corner. Prevention of MLKIs in skiing and snowboarding is important, and proper technique, equipment, risk awareness, and strengthening exercises can help reduce the risk of injury. While much is known about knee injuries in skiers, further research is needed to better understand MLKIs in ski and snowboard athletes, including the incidence, optimal management, and return to sport rates.

Background: Chronic posterior cruciate ligament (PCL) insufficiency leads to instability of the knee, resulting in increased loading of the medial and patellofemoral compartments. Chronic PCL insufficiency progressively damages the menisci and chondral surfaces and can accentuate and worsen varus malalignment. Biplanar proximal tibial opening-wedge osteotomy (BPTO) is a treatment option for chronic PCL tears with medial compartment arthritis which concurrently treats sagittal (flat slope) and varus coronal alignment. Indications: Opening-wedge BPTO is indicated in active patients who present with varus malalignment and flat slope with concomitant degenerative medial compartment osteoarthritis and PCL insufficiency. In general, BPTO is contraindicated in patients with a significantly elevated body mass index (BMI), smokers, or in those who have advanced tricompartmental osteoarthritis. Technique Description: Preoperative long-leg radiographs are essential to preoperative evaluation. Ideal coronal alignment following correction would have the mechanical axis pass through the apex of the lateral tibial eminence to properly off-load the medial compartment. Magnetic resonance imaging (MRI) studies are also useful for determining the presence and extent of concomitant soft tissue and chondral injury, especially in the lateral compartment. This video demonstrates the senior author’s preferred technique for a biplanar proximal tibial opening (PTO) with concomitant chondroplasty and partial medial meniscectomy (PMM). The senior author’s preferred order of operations is also displayed and involves first performing an arthroscopy, then proceeding with the open portions of the case, including the medial approach and subsequent osteotomy. Results: Past studies have supported PTO as a reliable treatment option for varus malalignment. Bode et al reported a 5-year survival rate of 96% of patients with an overall complication rate of 8.6%. The authors also reported that Lysholm scores were also significantly improved at 60-month follow-up compared with preoperative scores. Discussion: This is a technique for the correction of a varus malalignment with concomitant flat slope and PCL insufficiency with biplanar open-wedge PTO. This operation corrects the mechanical axis and sagittal slope of the knee and restores proper load distribution across the tibiofemoral articulation. In conclusion, a biplanar open-wedge PTO is a useful alternative to joint arthroplasty for active patients with a chronic PCL tear, medial compartment arthritis, and varus malalignment. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Background: Injuries to the fibular collateral ligament (FCL) seldom occur in isolation and may present with a concomitant injury to the biceps femoris tendon and anterior cruciate ligament (ACL). Injuries to structures of the posterolateral corner (PLC) lead to varus and rotational instability of the knee, subjecting the cruciate ligaments to increased forces that may result in graft failure. Therefore, reconstruction of these structures should be performed concurrently with the ACL. Indications: Grade III FCL injuries heal poorly without operative treatment and often result in residual varus instability of the knee that increases medial knee compartment forces, and forces on both the native ACL and the graft status post ACL reconstruction. Therefore, preservation of biomechanical stability and long-term health of the knee are reliant on addressing injuries to the PLC surgically. Technique Description: A key concept of this surgical technique is a meticulous peroneal nerve neurolysis in the setting of altered biceps femoris anatomy, and the proper order of the surgical steps for tunnel creation, graft passage, and fixation and suture anchor insertion to achieve optimal patient outcomes. The described technique involves a lateral surgical approach, peroneal neurolysis, and preparation of fibular and femoral FCL tunnels, followed by a Bone-patellar tendon-bone graft (BTB) graft harvest. Attention is then turned to intra-articular work including the diagnostic arthroscopy, femoral and tibial tunnel preparation, passage of the ACL graft, and fixation of the grafts in femoral tunnels. Last, fixation is achieved in the following order: FCL graft on fibula, ACL graft on tibia, and biceps femoris tendon to fibular head. Results: Compared with the preoperative state, Moulton et al reported significant improvements in the average Lysholm and Western Ontario scores at 2.7 years postoperatively following anatomic FCL reconstrution. Furthermore, Thompson et al reported on primary suture anchor repair of distal biceps femoris in 22 elite athletes and reported that all patients had returned to their preinjury level of sporting activity at 2-year follow-up. Discussion: Anatomic reconstructions of the FCL and ACL, such as the one described in our technique, effectively restore near native knee biomechanics and offer superior clinical outcomes compared with nonanatomic-based FCL reconstructions. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Background: Valgus malalignment leads to excessive loading of the lateral compartment and has been associated with lateral compartment meniscal injuries and early-onset knee osteoarthritis. Distal femoral osteotomy (DFO) is a treatment option that allows correction of the mechanical access to offload the lateral compartment. Lateral opening-wedge distal femoral osteotomy and medial meniscal root repairs are both aimed to address the pathologic biomechanics of the tibiofemoral joint and when successful can delay or even prevent progression to end-stage osteoarthritic changes in the lateral and medial compartment, respectively. Indications: Distal femoral osteotomy is indicated for patients with normal metabolic bone health and valgus malalignment who may present with concurrent lateral meniscal injury, symptomatic lateral compartment arthritis, or a chronic medial collateral ligament tear/laxity. Technique Description: Long-leg alignment radiographs and preoperative magnetic resonance images are required to evaluate the degree of mechanical access deviation and to evaluate for soft tissue injury, as there is often concomitant lateral meniscal or cartilage pathology present. This technique demonstrates the optimal order of surgical steps for DFO with a concurrent medial meniscal root repair. The senior author’s preferred order is to first perform the open lateral approach and expose the lateral cortex for the placement of plate prior to arthroscopic work and excess fluid extravasation. Intra-articular work is then performed with a diagnostic arthroscopy followed by medial meniscal root repair. Finally, the osteotomy and subsequent internal fixation are performed. Results: The literature on opening-wedge DFO outcomes is heterogeneous, with variable rates of successful outcomes and complications. Saithna et al reported that International Knee Documentation Committee and the pain subdomain of Knee injury and Osteoarthritis Outcome Scores significantly improved postoperatively following lateral opening-wedge DFOs in patients with lateral compartment osteoarthritis. The 10-year success rate of varus-producing DFO has been reported to be 64% to 85%. Discussion: We describe a technique for correction of a valgus deformity with opening-wedge DFO and concurrent meniscal root repair. This surgical technique effectively restores the native femoral and tibial axis with appropriate load distribution and also concurrently restores the appropriate function of the medial meniscus which allows axial force dispersion via hoop stresses for the medial compartment. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Background: Anterior cruciate ligament (ACL) reconstructions in skeletally immature patients have an increased risk of graft failure and a decreased rate of successful return to sports. Anterior cruciate ligament reconstructions (ACLRs) combined with lateral extra-articular tenodesis (LET) procedures are reported to limit anterolateral rotary instability of the knee, decreasing tension on the ACL graft. However, the open physes found in pediatric patients present unique challenges for ACLR. This video demonstrates a technique to avoid the femoral physis and necessary precautions for performing an ACLR with LET in a skeletally immature patient. Indications: The indications for combined ACLR and LET, as opposed to ACLR alone, mainly center on the risk factors for graft failure. These include the following: posterior tibial slope >12°, revision ACLR, high-grade pivot shift on physical examination, meniscal deficiency, generalized ligamentous hyperlaxity, and—especially pertinent to this procedure—skeletally immature patients. Technique Description: Standard plain radiographs and long-leg alignment films, along with a magnetic resonance imaging (MRI) study, are necessary to assess for malalignment, bone age, and concomitant meniscal and chondral pathology. This technique describes the senior author’s preferred technique for pediatric ACLR with LET. The senior author’s preferred order of operations includes performing the autologous hamstring graft harvest and LET before performing the diagnostic arthroscopy. This is followed by the intra-articular work including the ACLR. It is also the senior author’s preference to perform physeal-sparing femoral tunnels, using fluoroscopy for tunnel placement. Results: Getgood et al reported that an ACLR with an LET in young patients with a high risk of graft failure had a significant reduction in graft rupture compared to an ACLR alone. Furthermore, Noyes et al reported a significantly lower rate of graft failure and a higher rate of return to sports in those who received LET in addition to ACLR compared with those who received ACLR alone. Discussion: An ACLR combined with an LET has been reported to reduce graft failure rates and improve clinical outcomes in high-risk patients. An ACLR with LET may also be considered in skeletally immature patients with appropriate indications and extra precautions to avoid growth arrest or deformity. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Background: Lateral meniscal root tears often occur in the acute setting in concert with anterior cruciate ligament (ACL) tears. Severe changes in tibiofemoral biomechanics and joint degeneration are encountered when these injuries are either unrecognized or are treated with meniscectomy; therefore, meniscal root surgical repair is now preferred for longer-term benefits. The most common repair techniques include side-to-side and transtibial pull-out repair, which may be performed via single or double transtibial tunnel techniques. Indications: The primary indication for lateral meniscal root repair with double transtibial tunnels is suspicion for a lateral meniscal root tear based upon injury mechanism, physical examination findings, magnetic resonance imaging findings, and confirmation with diagnostic arthroscopy. Technique Description: The root attachment site is decorticated. Adhesions that cause lateral meniscal root retraction are arthroscopically released. Two separate transtibial tunnels are drilled 5 mm apart from the anterolateral tibia, entering the anterolateral tibia distal to Gerdy’s tubercle and entering the joint at the decorticated lateral root attachment site. Two suture tapes are passed through the torn lateral meniscal root in a vertical mattress configuration and shuttled with a passing suture through the tibial tunnels. The suture tapes are tied over a surgical button on the anterolateral tibia with the knee flexed to approximately 90° while the repair is viewed arthroscopically. Results: Lateral meniscal root repairs are safe and have very low reoperation rates. It has been reported that the transtibial pullout repair technique of the lateral meniscus significantly decreases lateral meniscus extrusion compared with other repair techniques in patients with combined ACL reconstruction. Zhuo et al also reported significantly improved postoperative clinical outcomes compared with the preoperative state in patients who underwent pullout repair for posterior lateral meniscal root avulsion tears. Discussion/Conclusion: The biomechanical and clinical evidence supports concomitant lateral meniscal root repair in the setting of concurrent ACL injury, and no studies to date have demonstrated a clear harm associated with this procedure. In addition, failure to repair the lateral meniscal root places supraphysiologic loads on the ACL graft and may increase the risk of graft failure. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Recent interest has uncovered the importance of understanding meniscal root anatomy, its effect on biomechanics of the knee joint, and appropriate treatment modalities. Meniscal root tears may account for up to one-fifth of all meniscal tears and have downstream consequences that can be as severe as total meniscectomy due to the unique force-dispersing properties of the meniscus. Meniscal biomechanics rely heavily upon the integrity of root attachments, and this historically overlooked etiology of knee pain and early onset osteoarthritis plays a vital role in maintaining the longevity of the knee joint. As meniscal root pathology becomes more commonly known and clinically assessed, an understanding of classifications, repair methods, and indications is important for surgeons.

Background: The posterolateral corner (PLC) of the knee is a complex anatomic region of the knee comprising the popliteus tendon, the popliteofibular ligament (PFL), and the fibular collateral ligament (FCL). Treatment of PLC injuries is based on the degree of varus and rotational instability on preoperative examination and is recommended in grade 3 injuries. 1,6 Technique Description: The key concept of this new surgical technique is to use adjustable loop cortical suspensory fixation implants for initial femoral fixation of the popliteus and the FCL grafts. This allows for individual tensioning of the grafts prior to definitive fixation with an interference screw. An anatomic fibular tunnel is initially created, followed by popliteus and FCL anatomic femoral socket drilling. A TightRope RT implant is attached to the popliteus end of the graft and secured through a bone tunnel on the medial femoral cortex initially. The popliteus end of the graft is then pulled into the femoral socket before tunneling the graft through the fibular tunnel. A second TightRope RT implant is secured to the FCL end of the graft before securing it to the medial femoral cortex through a bone tunnel and pulling the graft into the drilled femoral socket. An interference screw is first used to secure the graft at the fibular tunnel. The knee is then taken to 60° where the TightRope device is used to remove residual creep and optimize final tensioning prior to final fixation with interference screw in femoral socket. With the knee at 30° of flexion, neutral rotation, and slight valgus, the same steps are repeated for FCL graft. A posterolateral capsular shift is completed for additional stability. Results: Residual posterolateral corner instability or failure after reconstruction surgery has been reported in 6% to 9.4% of surgical reconstruction case. 2,3,5 The use of cortical suspensory devices in PLC reconstructions allows independent dialing of optimal graft tension for both the popliteus and FCL reconstruction before final interference screw fixation, therefore presumably limiting any residual creep and allowing for a double femoral fixation of the graft. Discussion: We describe a novel technique for posterolateral corner reconstruction which allows for optimal and individual tensioning of the structures of the posterolateral corner. Given the technique still uses well-described and validated graft choices and anatomic landmarks for reconstruction, we expect this new technique to allow for similar if not improved outcomes when compared with current gold standard. 4

Introduction Acute severe ulcerative colitis (ASUC) traditionally requires inpatient hospital management for intravenous therapies and/or colectomy. Ambulatory ASUC care has not yet been evaluated in large cohorts.Aims We used data from PROTECT, a UK multicentre observational COVID-19 inflammatory bowel disease study, to report the extent, safety and effectiveness of ASUC ambulatory pathways.Methods Adults (≥18 years old) meeting Truelove and Witts criteria between 1 January 2019–1 June 2019 and 1 March 2020–30 June 2020 were recruited to PROTECT. We used demographic, disease phenotype, treatment outcomes and 3-month follow-up data. Primary outcome was rate of colectomy during the index ASUC episode. Secondary outcomes included corticosteroid response, time to and rate of rescue or primary induction therapy, response to rescue or primary induction therapy, time to colectomy, mortality, duration of inpatient treatment and hospital readmission and colectomy within 3 months of index flare. We compared outcomes in three cohorts: (1) patients treated entirely in inpatient setting; ambulatory patients subdivided into; (2) patients managed as ambulatory from diagnosis and (3) patients hospitalised and subsequently discharged to ambulatory care for continued intravenous steroids.Results 37% (22/60) participating hospitals used ambulatory pathways. Of 764 eligible patients, 695 (91%) patients received entirely inpatient care, 15 (2%) patients were managed as ambulatory from diagnosis and 54 (7%) patients were discharged to ambulatory pathways. Aside from younger age in patients treated as ambulatory from diagnosis, no significant differences in disease or patient phenotype were observed. The rate of colectomy (15.0% (104/695) vs 13.3% (2/15) vs 13.0% (7/54), respectively, p=0.96) and secondary outcomes were similar among all three cohorts. Stool culture and flexible sigmoidoscopy were less frequently performed in ambulatory cohorts. Forty per cent of patients treated as ambulatory from diagnosis required subsequent hospital admission.Conclusions In a post hoc analysis of one of the largest ASUC cohorts collected to date, we report an emerging UK ambulatory practice which challenges treatment paradigms. However, our analysis remains underpowered to detect key outcome measures and further studies exploring clinical and cost-effectiveness as well as patient and physician acceptability are needed.Trial registration number NCT04411784.

The title compounds, [Mo(C5H5)(COCH3)(C6H12N3P)(CO)2], (1), and [Mo(C5H5)(COCH3)(C9H16N3O2P)(C6H5)2))(CO)2], (2), have been prepared by phosphine-induced migratory insertion from [Mo(C5H5)(CO)3(CH3)]. The molecular structures of these complexes are quite similar, exhibiting a four-legged piano-stool geometry with trans-disposed carbonyl ligands. The extended structures of complexes (1) and (2) differ substantially. For complex (1), the molybdenum acetyl unit plays a dominant role in the organization of the extended structure, joining the molecules into centrosymmetrical dimers through C—H...O interactions with a cyclopentadienyl ligand of a neighboring molecule, and these dimers are linked into layers parallel to (100) by C—H...O interactions between the molybdenum acetyl and the cyclopentadienyl ligand of another neighbor. The extended structure of (2) is dominated by C—H...O interactions involving the carbonyl groups of the acetamide groups of the DAPTA ligand, which join the molecules into centrosymmetrical dimers and link them into chains along [010]. Additional C—H...O interactions between the molybdenum acetyl oxygen atom and an acetamide methyl group join the chains into layers parallel to (101).

Background: Patellofemoral instability is due to a combination of bony and soft tissue factors. While recurrent patellar dislocations are rare, evaluation and treatment of these conditions require addressing patellar height and lateralization of the tibial tubercle (TT), restraint to lateral patellar subluxation, and trochlear dysplasia. Other factors to consider are coronal limb-length alignment outside of the physiologic 5 to 8° of valgus, which may significantly alter the Q angle and contribute to lateral instability. Other ligaments around the patella contribute to soft-tissue restraint, including the medial and lateral patellotibial ligaments, patellomeniscal ligaments, and the medial quadriceps tendon femoral ligament. Patellar tilt is assessed with and without quadriceps contraction to further evaluate the patella’s relationship to the trochlear groove. The Caton-Deschamps Index, as well as patellar trochlear index (PTI), are used to measure patellar height for patella alta or baja. Technique Description: The technique is to surgically manage a patient in neutral mechanical alignment on standing limb radiographs, with moderate-to-severe DeJour type B trochlear dysplasia and a trochlear sulcus angle of around 145°, patella alta with a Caton-Deschamps Index of 1.6 and PTI of 0.22, a TT to trochlear groove (TT-TG) distance of 8 mm, and a deficient medial patellofemoral ligament (MPFL). The MPFL reconstruction is done first, with harvesting of the ipsilateral quadriceps tendon and maintenance of its distal attachment on the superior patellar pole. The quadriceps tendon graft is folded medially upon its distal attachment and fixed in this position with suture anchors. Tibial tubercle osteotomy is accomplished by spacing drill holes 2 mm apart, medially and laterally, on the TT and connecting the drill holes with an osteotome and reciprocating saw. A distalized location to secure the TT is selected and superficial bone is excised. A medial parapatellar arthrotomy is performed, and bur attachments are used to drill into the subchondral bone beneath the femoral articular surface to create a V-shaped flap of trochlear cartilage. An arthroscope is inserted under the trochlear flap during this process to visualize the appropriate depth. The trochlear flap is then secured with screws passed over guide pins to secure the flap to the desired location. Cannulated screws and washers are then used to secure the TT to its distalized and/or medialized position, with fluoroscopic verification of screw depth and location. The arthrotomy is then closed with the knee at 45°. The quadriceps graft is passed through a subretinacular channel and secured with suture anchors, adjacent to the adductor tubercle, to complete the MPFL reconstruction. Before closure, appropriate tracking and translation of the patella is verified. Results: Sulcus-deepening trochleoplasty, with or without MPFL reconstruction, has been reported to obtain satisfactory outcomes at 2 years, with close to 85% return to sport and 100% return to work, with improvements in International Knee Documentation Committee (IKDC) scores from 50.8 to 79.1 in some studies. MPFL reconstruction with tibial tubercle osteotomy (TTO) has yielded a 94.5% patient satisfaction rate in the literature. Discussion/Conclusion: In patients with recurrent patellar instability and DeJour types B-D trochlear dysplasia, MPFL reconstruction with TTO and sulcus-deepening trochleoplasty provides excellent subjective outcomes and restores patellar tracking with elimination of recurrent subluxation.

Background: At the outset of the COVID-19 pandemic, there was no routine comprehensive hospital medicines data from the UK available to researchers. These records can be important for many analyses including the effect of certain medicines on the risk of severe COVID-19 outcomes. With the approval of NHS England, we set out to obtain data on one specific group of medicines, “high-cost drugs” (HCD) which are typically specialist medicines for the management of long-term conditions, prescribed by hospitals to patients. Additionally, we aimed to make these data available to all approved researchers in OpenSAFELY-TPP. This report is intended to support all studies carried out in OpenSAFELY-TPP, and those elsewhere, working with this dataset or similar data. Methods: Working with the North East Commissioning Support Unit and NHS Digital, we arranged for collation of a single national HCD dataset to help inform responses to the COVID-19 pandemic. The dataset was developed from payment submissions from hospitals to commissioners. Results: In the financial year (FY) 2018/19 there were 2.8 million submissions for 1.1 million unique patient IDs recorded in the HCD. The average number of submissions per patient over the year was 2.6. In FY 2019/20 there were 4.0 million submissions for 1.3 million unique patient IDs. The average number of submissions per patient over the year was 3.1. Of the 21 variables in the dataset, three are now available for analysis in OpenSafely-TPP: Financial year and month of drug being dispensed; drug name; and a description of the drug dispensed. Conclusions: We have described the process for sourcing a national HCD dataset, making these data available for COVID-19-related analysis through OpenSAFELY-TPP and provided information on the variables included in the dataset, data coverage and an initial descriptive analysis.

Growing evidence has revealed the pivotal role of inflammatory biomarkers in the pathogenesis of osteoarthritis. There is significant interest in the prognostic value of select biomarkers, given the potential for early identification and treatment of patients at risk of osteoarthritis prior to the development of irreversible clinical disease. Clinical trials of novel therapeutics that disrupt the inflammatory pathways of osteoarthritis are also ongoing. The purpose of this review is to summarize the current literature on key biomarkers within the context of osteoarthritis pathogenesis, clinical symptom development, and treatment capabilities. Multiple recent studies have established biomarkers that signal the existence of osteoarthritis pathology and the development of clinical symptomology. However, prior to implementation in clinical practice, additional research is required to precisely define the prognostic value for numerous biomarkers and standardize their measurement. Biomarker-driven investigations represent a promising avenue for the early diagnosis and treatment of osteoarthritis.

Arthroscopic assessment of posterior compartments of the knee and the posterior aspect of the proximal tibial and fibula is challenging because of the relative proximity of the neurovascular bundle. This Technical Note describes a reproducible arthroscopic surgical approach in a cadaveric model that aims to identify and expose the popliteus tendon, posterior fibular head, fibular collateral ligament popliteal fibular ligament, biceps femoris tendon, and peroneal nerve.

Posterolateral corner injuries are complex injuries, and their therapeutic management varies from one individual to another. Biomechanical studies demonstrate that anatomic posterolateral corner reconstruction restores knee kinematics better than nonanatomic reconstruction. The purpose of this report is to describe an all-arthroscopic procedure for anatomic posterolateral corner reconstruction.

In the title compound, C40H36B2N4O5, the B—O—B bond angle is 132.75 (13) and the dihedral angle between the benzodiazborole rings is 73.02 (5)°. In the crystal, weak C—H...O interactions link the molecules.

Quadriceps tendinopathy in an increasingly recognized diagnosis can lead to quadriceps tendon rupture, especially in the older population. It can be caused by repeated micro trauma or also predisposed by systemic diseases such as diabetes mellitus and connective tissue disorders that can in turn lead to extensor mechanism deficits. Although a trial of conservative treatment is advocated, operative treatment should be performed in cases of persistent pain, extension deficit, or complete rupture of the tendon. The purpose of this Technical Note is to describe in detail a procedure for open repair of a quadriceps tendon, with significant degeneration due to quadriceps tendinopathy, using suture anchors and semitendinosus tendon allograft augmentation.

Meniscal injuries and meniscal loss are associated with changes in knee kinematics and loading, ultimately leading to poor functional outcomes and increased risk of progression to osteoarthritis. Biomechanical studies have shown restored knee function, and clinical studies have reported improved outcomes and decreased risk of osteoarthritis after meniscal repair. This has led orthopaedic surgeons to try and save the meniscus by repair whenever possible, as shown by increasing incidence of meniscal repair surgeries. Historically, meniscal lesions, particularly those greater in size and located in the white-white region of the meniscus, have been shown to have poor healing. In recent years, there has been an increasing interest in the use of biologic agents to help stimulate and expedite healing in traditionally more avascular tissue. Preliminary results for biologic therapeutic agents, such as platelet rich plasma and bone marrow aspirate concentrate, have been encouraging. However, these options are more demanding in regard to time, financial burden, resources, and regulations than some more classic agents such as fibrin clots. Fibrin clot is readily available, easy to use, affordable, and minimally invasive. This Technical Note describes a step-by-step and reproducible technique for harvesting, preparation, and using a fibrin clot to augment healing of meniscal repairs.

The use of ankle stress radiographs is common to evaluate ankle instability. However, the majority of the studies report the use of a manual method to apply the stress, increasing radiation exposure to the physician. Furthermore, as reported in other studies, the force applied during the stress may vary between examiners according the strength and experience. In this Technical Note, we describe our preferred method to evaluate ankle instability, either using an inversion or eversion stress, avoiding the necessity of a physician in the radiographic room.

The medial collateral ligament is the most commonly injured knee ligament. Valgus stress radiographs are reported to be an effective way to quantify the medial compartment opening. However, most of the techniques require the presence of a physician in the radiograph room to apply a manual valgus stress force, and can only be performed in 1 knee at a time. These techniques, although extremely effective, increase radiation exposure to physicians, are time consuming, and require additional radiographs to compare the side-to-side difference. The purpose of this Technical Note is to describe our preferred valgus stress radiographic technique to evaluate medial side laxity, which offers several advantages compared with conventional manual techniques.

Posterolateral corner injuries are a severe and often unrecognized pathology. Injuries to these structures are difficult to identify using magnetic resonance images. Physical examination tests including the dial test, frog-leg test, and varus stress test can be difficult to perform. In addition it is difficult to correctly evaluate the results in a multiligament injury setting. The correct diagnosis of this pathology is essential to determine the proper treatment and improve outcomes. Furthermore, failure to recognize this pathology is associated with a high risk of failure following isolated anterior cruciate ligament reconstructions. The purpose of this Technical Note is to present an alternative method for the evaluation of posterolateral corner injuries using radiographic images.

Anterior cruciate ligament reconstruction is one of the most commonly performed procedures in orthopaedics, with more than 125,000 performed in the United States per year. There are several reconstruction graft choices that can be used to reconstruct the native anterior cruciate ligament, with autograft hamstring tendons being one of the most commonly used. Preparation of a hamstring autograft varies depending on patient characteristics and physician preference. The purpose of this Technical Note is to describe in detail different variants of hamstring graft preparation techniques that are commonly used in practice.

Focal articular cartilage injuries in the knee are common and can cause severe morbidity and reduced function. The articular cartilage is avascular and has limited ability to heal, and hence, patients with cartilage injuries have increased risk of progressing to osteoarthritis. Most of the cartilage injuries are located on the femoral condyles. Engaging focal cartilage injuries involving the trochlea are challenging because of the morbidity caused by these injuries and the limited treatment options. Osteochondral allograft transplantation is emerging as a promising treatment for full-thickness articular cartilage defects. Recent studies have reported high success rates with the use of osteochondral allografts. This article reports our technique of osteochondral allograft transplantation for the treatment of a focal full-thickness defect of the trochlea.

Advanced glenohumeral osteoarthritis can transform glenoid morphology and, in some cases, is found in association with severe glenoid retroversion. The associated glenoid retroversion leads to difficulty in fixation of the glenoid component in reverse total shoulder arthroplasty. In the context of extreme glenoid wear, structural grafts can be used to restore glenoid volume and version in order for the glenoid component of the reverse total shoulder arthroplasty to be more easily implanted. Nevertheless, literature regarding structural grafts remains limited, with optimal graft choice and technique still controversial at best. This article details our technique for humeral head autograft transplantation before reverse total shoulder arthroplasty in the context of extreme glenoid retroversion with advanced osteoarthritis.

With a range of tear characteristics such as chronicity, degree of fatty atrophy, and number of tendons involved as well as varying patient-specific characteristics including age, injury mechanism, and expectations after treatment to consider, proper and successful treatment of a rotator cuff tear is multifactorial and, consequently, challenging. Although conservative management of a rotator cuff tear may be successful, a more severe tear with involvement of more tendons may warrant surgical intervention. Furthermore, additional pathology including biceps tendinopathy may result in greater patient morbidity and an even more complex treatment decision-making process and surgical technique. The purpose of this Technical Note is to describe our preferred surgical technique for the treatment of a rotator cuff tear involving 2 rotator cuff tendons in conjunction with a lesion of the long head of the biceps tendon.

Massive rotator cuff tears are particularly challenging to treat and severely limit the function of the shoulder. Compared with a small rotator cuff tear, massive tears are more unpredictable and usually present with low tendon quality. When performing an anatomical repair of the rotator cuff, the surgical treatment is often associated with failure of the construct. An alternative procedure that can be performed in the setting of a massive tear is superior capsular reconstruction (SCR), using an autograft or allograft. This procedure has been shown to be effective and is associated with positive treatment outcomes. Moreover, the combination of an SCR with an anatomic repair of the rotator cuff tendon may provide a stronger fixation for the rotator cuff and ultimately lead to a lower likelihood of retear and failure. The purpose of this Technical Note is to describe our preferred procedure for the treatment of a massive rotator cuff tear through SCR with superimposition of the repair of the native rotator cuff tendons.

Coracoid fractures are rare injuries, which may occur in isolation or in association with other shoulder pathology. The mechanism of trauma consists of a strong contraction of the conjoint tendon as a result of direct trauma. The diagnosis is usually difficult and many times overlooked, thereby requiring a high level of suspicion. In many cases, standard trauma series shoulder radiographs are unable to provide a definitive and reliable diagnosis. Therefore, other imaging modalities may be necessary to confirm the diagnosis. Although uncommon, if left untreated, a coracoid fracture will result in chronic pain and shoulder disability. Both conservative and surgical techniques have been previously reported and shown positive outcomes. In regard to the surgical technique, most reports describe the use of screw fixation, which has been associated with full recovery and high patient satisfaction. Nevertheless, the purpose of this Technical Note is to describe our preferred method to treat an isolated type II displaced coracoid process fracture through suture anchor fixation.