Fructosamine is a valuable marker for glycemic control and predicting adverse outcomes following total hip arthroplasty: a prospective multi-institutional investigation

Recently, fructosamine has shown promising results in predicting adverse outcomes following total knee arthroplasty. The purpose of this study was to assess the utility of fructosamine to predict adverse outcomes following total hip arthroplasty (THA). A prospective multi-center study involving four institutions was conducted. All primary THA were evaluated for glycemic control using fructosamine levels prior to surgery. Adverse outcomes were assessed at a minimum 1 year from surgery. Primary outcome of interest was periprosthetic joint infection (PJI) based on the International Consensus Meeting (ICM) criteria. Secondary outcomes assessed were superficial infections, readmissions and death. Based on previous studies on the subject, fructosamine levels above 293 µmol/L were used to define inadequate glycemic control. Overall 1212 patients were enrolled in the present study and were available for follow up at a minimum 1 year from surgery. Of those, 54 patients (4.5%) had elevated fructosamine levels (\u3e 293 µmol/L) and these patients were 6.7 times more likely to develop PJI compared to patients with fructosamine levels below 293 µmol/L (p = 0.002). Patients with elevated fructosamine were also associated with more readmissions (16.7% vs. 4.4%, p \u3c 0.007) and a higher mortality rate (3.7% vs. 0.6%, p = 0.057). These associations remained statistically significant in a multi-regression analysis after adjusting for age, comorbidities and length of stay; Adjusted odds ratio were 6.37 (95% confidence interval 1.98-20.49, p = 0.002) for PJI and 2.68 (95% confidence interval 1.14-6.29, p = 0.023) for readmissions. Fructosamine is a good predictor of adverse outcomes in patients undergoing THA and should be used routinely to mitigate morbidity and mortality risk

Hyperimmune immunoglobulin for hospitalised patients with COVID-19 (ITAC): a double-blind, placebo-controlled, phase 3, randomised trial

BACKGROUND: Passive immunotherapy using hyperimmune intravenous immunoglobulin (hIVIG) to SARS-CoV-2, derived from recovered donors, is a potential rapidly available, specific therapy for an outbreak infection such as SARS-CoV-2. Findings from randomised clinical trials of hIVIG for the treatment of COVID-19 are limited. METHODS: In this international randomised, double-blind, placebo-controlled trial, hospitalised patients with COVID-19 who had been symptomatic for up to 12 days and did not have acute end-organ failure were randomly assigned (1:1) to receive either hIVIG or an equivalent volume of saline as placebo, in addition to remdesivir, when not contraindicated, and other standard clinical care. Randomisation was stratified by site pharmacy; schedules were prepared using a mass-weighted urn design. Infusions were prepared and masked by trial pharmacists; all other investigators, research staff, and trial participants were masked to group allocation. Follow-up was for 28 days. The primary outcome was measured at day 7 by a seven-category ordinal endpoint that considered pulmonary status and extrapulmonary complications and ranged from no limiting symptoms to death. Deaths and adverse events, including organ failure and serious infections, were used to define composite safety outcomes at days 7 and 28. Prespecified subgroup analyses were carried out for efficacy and safety outcomes by duration of symptoms, the presence of anti-spike neutralising antibodies, and other baseline factors. Analyses were done on a modified intention-to-treat (mITT) population, which included all randomly assigned participants who met eligibility criteria and received all or part of the assigned study product infusion. This study is registered with ClinicalTrials.gov, NCT04546581. FINDINGS: From Oct 8, 2020, to Feb 10, 2021, 593 participants (n=301 hIVIG, n=292 placebo) were enrolled at 63 sites in 11 countries; 579 patients were included in the mITT analysis. Compared with placebo, the hIVIG group did not have significantly greater odds of a more favourable outcome at day 7; the adjusted OR was 1·06 (95% CI 0·77–1·45; p=0·72). Infusions were well tolerated, although infusion reactions were more common in the hIVIG group (18·6% vs 9·5% for placebo; p=0·002). The percentage with the composite safety outcome at day 7 was similar for the hIVIG (24%) and placebo groups (25%; OR 0·98, 95% CI 0·66–1·46; p=0·91). The ORs for the day 7 ordinal outcome did not vary for subgroups considered, but there was evidence of heterogeneity of the treatment effect for the day 7 composite safety outcome: risk was greater for hIVIG compared with placebo for patients who were antibody positive (OR 2·21, 95% CI 1·14–4·29); for patients who were antibody negative, the OR was 0·51 (0·29–0·90; pinteraction=0·001). INTERPRETATION: When administered with standard of care including remdesivir, SARS-CoV-2 hIVIG did not demonstrate efficacy among patients hospitalised with COVID-19 without end-organ failure. The safety of hIVIG might vary by the presence of endogenous neutralising antibodies at entry. FUNDING: US National Institutes of Health

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P < 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P < 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Arrhythmia and death following percutaneous revascularization in ischemic left ventricular dysfunction: Prespecified analyses from the REVIVED-BCIS2 trial

BACKGROUND: Ventricular arrhythmia is an important cause of mortality in patients with ischemic left ventricular dysfunction. Revascularization with coronary artery bypass graft or percutaneous coronary intervention is often recommended for these patients before implantation of a cardiac defibrillator because it is assumed that this may reduce the incidence of fatal and potentially fatal ventricular arrhythmias, although this premise has not been evaluated in a randomized trial to date. METHODS: Patients with severe left ventricular dysfunction, extensive coronary disease, and viable myocardium were randomly assigned to receive either percutaneous coronary intervention (PCI) plus optimal medical and device therapy (OMT) or OMT alone. The composite primary outcome was all-cause death or aborted sudden death (defined as an appropriate implantable cardioverter defibrillator therapy or a resuscitated cardiac arrest) at a minimum of 24 months, analyzed as time to first event on an intention-to-treat basis. Secondary outcomes included cardiovascular death or aborted sudden death, appropriate implantable cardioverter defibrillator (ICD) therapy or sustained ventricular arrhythmia, and number of appropriate ICD therapies. RESULTS: Between August 28, 2013, and March 19, 2020, 700 patients were enrolled across 40 centers in the United Kingdom. A total of 347 patients were assigned to the PCI+OMT group and 353 to the OMT alone group. The mean age of participants was 69 years; 88% were male; 56% had hypertension; 41% had diabetes; and 53% had a clinical history of myocardial infarction. The median left ventricular ejection fraction was 28%; 53.1% had an implantable defibrillator inserted before randomization or during follow-up. All-cause death or aborted sudden death occurred in 144 patients (41.6%) in the PCI group and 142 patients (40.2%) in the OMT group (hazard ratio, 1.03 [95% CI, 0.82–1.30]; P =0.80). There was no between-group difference in the occurrence of any of the secondary outcomes. CONCLUSIONS: PCI was not associated with a reduction in all-cause mortality or aborted sudden death. In patients with ischemic cardiomyopathy, PCI is not beneficial solely for the purpose of reducing potentially fatal ventricular arrhythmias. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01920048

Ceramic-on-ceramic total hip arthroplasty in patients younger than 55 years.

PURPOSE: To review the outcomes of 65 patients younger than 55 years who underwent uncemented total hip arthroplasty (THA) using third-generation ceramic-on-ceramic prostheses. METHODS: Medical records of 30 men and 35 women (80 hips) aged 18 to 55 (mean, 39) years who underwent uncemented THA using third-generation ceramic-onceramic prostheses by a single surgeon were reviewed. 61 THAs used the Reflection cup with the Synergy stem (n=49), Spectron stem (n=7), or Anthology stem (n=5), and 19 THAs used the Trident cup with the Secur-Fit stem. Outcomes were assessed based on the UCLA Activity Score and Harris Hip Score, as well as radiolucency around the implants, malposition, and subsidence on radiographs. Patients were asked about their satisfaction with current activity level (yes/no), activity limitation (no limitation, musculoskeletal limitation, psychological impediments and lack of motivation, and pain or disability of the operative hip), and change in occupational activity level (same or similar, more active, and less active or disability). RESULTS: The mean follow-up period was 54 (range, 24-110) months. Six patients were excluded from the analysis owing to prosthetic failure secondary to ceramic liner fracture after falling (n=2), acetabular component loosening (n=1), intolerable squeak (n=1), periprosthetic fracture (n=1), and instability (n=1). The mean UCLA Activity Score improved from 4.0 (range, 1-10) to 7.7 (range, 2-10) [p CONCLUSION: Ceramic-on-ceramic THA achieved acceptable clinical and radiographic outcomes

A case of bilateral hip mechanically assisted crevice corrosion after staged total hip arthroplasty

Mechanically assisted crevice corrosion (MACC), also known as trunnionosis, and adverse local tissue reaction (ALTR) are entities that can lead to pain and necessitate revision in total hip arthroplasty (THA). We present a case of a 75-year-old female who received a bilateral staged primary THA with metal on cross-linked polyethylene implants and had subsequent bilateral revisions for MACC and ALTR. In both instances, she presented with anterior thigh pain, weakness, and difficulty ambulating, and she was revised to ceramic on cross-linked polyethylene implants. This case may suggest a biologic predisposition or systemic immunogenic reaction to metal debris in some patients with ALTR or represent an implant-specific complication. To our knowledge, this is the first case reported of a patient having bilateral MACC from staged THA performed by 2 different surgeons using the same brand implant. Keywords: Mechanically assisted crevice corrosion, Adverse local tissue reaction, Revision hip arthroplasty, Immune reactio

A risk-stratification algorithm to reduce superficial surgical site complications in primary hip and knee arthroplasty

Background: Surgical site complications (SSCs) are the most common cause for readmission after total joint arthroplasty (TJA), increasing costs while predisposing to inferior long-term outcomes. Prophylactic use of closed-incision negative pressure therapy (ciNPT) may lower the risk of these complications, especially in high-risk populations, but appropriate-use guidelines are lacking for patients undergoing primary TJA. We sought to develop a risk-stratification algorithm to guide use of ciNPT dressings and test its use in normalizing the rate of superficial SSCs among high-risk groups. Methods: We reviewed 323 consecutive primary TJAs, where 38% of those patients considered at elevated risk were risk-stratified to receive ciNPT dressings. An individual risk score was developed, assigning points based on patient-specific risk factors. We identified a historical control population of 643 patients who all received the same postoperative dressing to test the impact of this risk score. Results: Compared with historical controls, we observed a modest but significant improvement in superficial SSCs after implementation of risk-stratification (12.0% vs 6.8%; P = .013). Among high-risk patients, there was a marked improvement in SSCs when treated prophylactically with ciNPT dressings as compared with historical controls (26.2% vs 7.3%; P < .001). Low-risk patients, who continued to be treated with standard postoperative dressings, demonstrated no significant improvement (8.6% vs 6.5%; P = .344). Conclusions: ciNPT dressings are effective at reducing and normalizing risks of superficial SSCs among high-risk primary arthroplasty patients. The proposed risk-stratification algorithm may help identify those patients who benefit most from these dressings. Keywords: Closed-incision negative pressure therapy, Surgical dressing, Surgical site complications, Total hip arthroplasty, Total knee arthroplast

A comparison of pin site complications between large and small pin diameters in robotic‐assisted total knee arthroplasty

Abstract Purpose Robotic‐assisted total knee arthroplasty typically necessitates use of tracking pins, which can vary in diameter. Complications such as infections and fractures at the pin‐site have been observed, but clarification of the effect of pin diameter on complication is needed. The aim of this study is to compare the pin‐related complication rates following robotic‐assisted total knee arthroplasty between 4.5 mm and 3.2 mm diameter pins. Methods In this retrospective cohort study, 90‐day pin‐site complication rates after robotic‐assisted total knee arthroplasty were compared between 4.5 mm diameter and 3.2 mm diameter groups. In total, 367 patients were included: 177 with large pin diameter and 190 with small pin diameter. All four pin sites were evaluated using postoperative radiographs. Cases without orthogonal views or visualization of all four pin tracts were noted. Multivariate logistic regression was used to control for age, which differed between the two cohorts. Results The rate of pin‐site complications was 5.6% in the large pin diameter cohort and 2.6% in the small pin diameter cohort, with no statistically significant difference between the groups. The adjusted odds ratio for complications in small compared to large diameter group was 0.48, with a p‐value of 0.18. The most common pin‐site complication was infection/persistent drainage, found in 1.9% of patients, followed by intraoperative fracture of the second cortex in 1.4%. Intraoperative fracture could not be ruled out in 96 cases due to inadequate radiographic visualization of all pin sites. There was one postoperative pin‐site fracture in the large diameter cohort, which required operative fixation. Conclusion This study demonstrates no statistically significant difference in pin‐site complication rates after robotic‐assisted total knee arthroplasty between 4.5 mm and 3.2 mm pin diameter cohorts, although there was a trend towards increased intraoperative and postoperative pin‐site fractures in the 4.5 mm group