Introduction. Hypoalbuminemia has previously been identified as an independent predictor of postoperative complications following total knee arthroplasty (TKA). Given the morbidity and financial burden associated with TKA complications, significant effort has gone into identifying patients at increased risk for perioperative complications. The American Society of Anesthesiologists (ASA) physical status score has been utilized for risk stratification of surgical patients for many years and is a measure of overall health. However, it is unclear how measures like albumin compare to the prognostic ability of this type of global health measure. This study aims to elucidate the utility of preoperative albumin compared with that of the ASA score in predicting complications following TKA. Methods. Patients undergoing TKA between 2005 and 2015 were identified using the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database. Patients were stratified based on preoperative hypoalbuminemia (<3.5 g/dL) and ASA score (≤ 2 vs. > 2). Multivariable regression analysis adjusted for age, sex, BMI, and smoking status was utilized to determine predictive potential of hypoalbuminemia and ASA score on each postoperative complication. Results. Of the 79,661 patients included in the cohort, 4.3% had preoperative hypoalbuminemia. Univariate regression analysis found significant predictive abilities of both serum albumin and ASA score on numerous postoperative complications, such as superficial infection, deep infection, MI, pneumonia, renal insufficiency, reintubation, transfusion, readmission, reoperation, and death. Interestingly, multivariable regression analysis demonstrated that hypoalbuminemia more robustly predicted postoperative deep infection than ASA. Discussion and Conclusion. Hypoalbuminemia and ASA each individually predict numerous postoperative complications following TKA. However, this study suggests that while ASA score more accurately predicts post-operative medical complications, hypoalbuminemia may be a more accurate predictor of periprosthetic infection following TKA. Ultimately, preoperative albumin should be incorporated in the pre-operative work-up routine to stratify patient risk, especially regarding postoperative infection

Malnutrition is a potentially modifiable risk factor that may contribute to complications following geriatric hip fracture surgery. The purpose of this study was to investigate the association between preoperative hypoalbuminemia, a marker for malnutrition, and complications during the thirty days following surgery for geriatric hip fracture. The American College of Surgeons National Surgical Quality Improvement Program was used to conduct a retrospective cohort study of geriatric patients (>65 years) undergoing surgery for hip fracture. Patients without preoperative serum albumin concentration were excluded. Outcomes were compared between patients with and without hypoalbuminemia (defined as serum albumin concentration <3.5g/dL). All comparisons were adjusted for baseline differences between populations. 17,651 Patients were identified. Of these, 8,272 (46.9%) underwent hemiarthroplasty, 759 (4.3%) total joint arthroplasty, 324 (1.9%) percutaneous fixation, 2,445 (13.9%) plate/screw fixation, and 5,833 (33.1%) intramedullary fixation. The prevalence of hypoalbuminemia was 45.9% (Figure 1). The risk for death was strongly associated with serum albumin concentration, with a linear increase in risk observed as albumin fell below 3.5 g/dL (p<0.001; Figure 2). Following adjustment for all demographic, comorbidity, and procedural characteristics, patients with hypoalbuminemia had higher rates of death (9.94% versus 5.53%, adjusted relative risk [RR]=1.54, p<0.001), pneumonia (5.30% versus 3.77%, adjusted RR=1.20, p=0.012), sepsis (1.19% versus 0.53%, adjusted RR=1.90, p<0.001), and hospital readmission (10.91% versus 9.03%, adjusted RR=1.11, p<0.036; Table 1). The present study suggests that hypoalbuminemia is a powerful independent risk factor for death following surgery for geriatric hip fracture. This association persists over-and-above any associations of death with age, sex, body mass index, and comorbidities. Based on these data, we propose that the nutritional status of hip fracture patients should receive greater attention, and that randomized trials testing for efficacy of aggressive postoperative nutritional interventions may be warranted. For any figures or tables, please contact the authors directly by clicking on ‘Info & Metrics’ above to access author contact details

Hip fractures are a significant cause of mortality and morbidity in the elderly. Malnutrition is a major element of this but no consensus exists as to the detection or management of this condition. Reported incidence in elderly hip fracture patients varies widely between 9.0% and 88.6%. The aim of this study was to evaluate the nutritional status of 415 patients with operatively managed hip fractures and determine the prognostic relevance of admission serum albumin and total lymphocyte count (TLC) assays. Protein-energy malnutrition (PEM) was defined as serum albumin < 3.5g/dl and a TLC < 1,500 cells/mm3. Delay to operation, duration of in-patient stay, re-admission (< 3 months) and in-patient, 3- and 12-month mortality were assessed as outcome variables. Survival data was available for 377 patients at 12 months. Of 377 patients, 53% (n=200) had both a serum albumin and TLC levels taken at admission, while 47% (n=177) had not. The incidence of PEM was 51%. Inhospital mortality for PEM patients was 9.8%, compared with 0% for patients with normal values of both laboratory parameters. Older patients were more likely to have lower albumin (p=0.017) and TLC (p=0.023). Nursing home patients were also more likely to have lower albumin (p=0.033). Multivariate analysis revealed a significant difference in 12-month mortality, with patients who had both a low albumin and a low TLC 4.6 times (95% CI: 1.0–21.3) more likely to die within 12 months postoperatively than patients who had normal values of both laboratory parameters. This was significant after adjusting for age, gender and domicile (p=0.049). Serum albumin and TLC in combination are accurate predictors of 12-month mortality in hip fracture patients. These results highlight the relevance of assessing the nutritional status of patients with hip fractures at the time of admission and emphasises the relationship between nutrition and outcome

Miniscrew implants (MSIs) are widely used to provide absolute anchorage for the orthodontic treatment. However, the application of MSIs is limited by the relatively high failure rate (22.86%). In this study, we wished to investigate the effects of amorphous and crystalline biomimetic calcium phosphate coating on the surfaces of MSIs with or without the incorporated BSA for the osteointegration process with an aim to facilitate the early loading of MSIs. Amorphous and crystalline coatings were prepared on titanium mini-pin implants. Characterizations of coatings were examined by Scanning electron microscopy (SEM), Confocal laser-scanning dual-channel-fluorescence microscopy (CLSM) and Fourier-transform infrared spectroscopy (FTIR). The loading and release kinetics of bovine serum albumin (BSA) were evaluated by Enzyme linked immunosorbent assay (ELISA). Activity of alkaline phosphate (ALP) was measured by using the primary osteoblasts. In vivo, a model of metaphyseal tibial implantation in rats was used (n=6 rats per group). We had 6 different groups: no coating no BSA, no coating but with surface adsorption of BSA and incorporation of BSA in the biomimetic coating in the amorphous and crystalline coatings. Time points were 3 days, 1, 2 and 4 weeks. Histological and histomorphometric analysis were performed and the bone to implant contact (BIC) of each group was compared. In vitro, the incorporation of BSA changed the crystalline coating from sharp plates into curly plates, and the crystalline coating showed slow-release profile. The incorporation of BSA in crystalline coating significantly decreased the activity of ALP in vitro. In vivo study, the earliest significant increase of BIC appeared in crystalline coating group at one week. The crystalline coating can serve as a carrier and slow release system for the bioactive agent and accelerate osteoconductivity at early stage in vivo. The presence of BSA is not favorable for the early establishment of osteointegration

Purpose: One of the major concerns regarding metal-on-metal prostheses is the biological and biochemical activities of chromium (Cr) ions. Previous studies showed that Cr3+ ions form nanostructures in cell culture media and to date, there has been little attempt to understand the nature of implant-derived metal ions in adjacent tissues or in biofluid. The aim of this work was to determine the nature of proteins present in serum involved in the formation of Cr nanostuctures. Methods: RPMI 1640 and DMEM media supplemented with 5% human serum (HS) or 5% foetal bovine serum (FBS) were incubated for 1h at 37°C in the presence of 50 ppm of Cr3+ (CrCl3). Structures were then isolated and separated by SDS-PAGE. Proteins were stained by Coomassie blue and analyzed by liquid chromatography-quadrupole-time of flight-mass spectrometer (LC-Q-Tof-MS). Data were submitted to Mascot software for a search against the NCBI nonredundant database. Results: Results show that Cr-nanostructures can interact with proteins from both human and bovine serums. On SDS-PAGE, the molecular weights of the proteins were between 40 to 90 kDa. The LC-Q-Tof-MS results suggest that Cr-nanostructures are the result of the interaction with numerous proteins present in serum. However, the complete analysis of results demonstrates that only two proteins (in both RPMI and DMEM) are implicated in these nanostructures: albumin and trans-ferrin. For both proteins, at least 40 peptides matched to the complete sequence of the proteins. The ion scores (“peptide identity score”) were between 79 and 108. Ion scores > 45 indicate identity or extensive homology. Conclusions: Human serum contains more than 400 different proteins. Albumin, the major protein of human serum, has been shown to play a scavenger role by binding and transporting injected and ingested Cr. Albumin could also play an immunological role by addressing signals to defense cells, such as macrophages. Trans-ferrin, known as an iron-carrying protein, also plays a scavenger role for Cr. This suggests that the binding of Cr to these proteins may protect cells from the cytotoxic effect of Cr ions. However, the relation with Cr nano-structures in vivo remains to be determined

Background: Protein energy malnutrition (PEM) is an accepted predictor of poor outcome in hip fracture patients. There is no universally accepted definition of PEM. Admission screening for PEM is not routinely performed for hip fracture patients. The reported incidence in elderly hip fracture patients varies widely between 9.0% and 88.6%. Aims: To determine the prognostic relevance of admission serum albumin and total lymphocyte count (TLC), as clinical markers of PEM and predictors of outcome for hip fracture patients. Methods: Retrospective review of 415 patients with operatively managed hip fracture. Protein-energy malnutrition was defined as albumin < 3.5g/dl and TLC < 1,500cells/mm3. Delay to operation, duration of in-patient stay, readmission (< 3 months) and in-patient, 3- and 12-month mortality were assessed as outcome variables. Results: Survival data was available for 377 patients at 12 months. Of 377 patients, 53% (n=200) had both a serum albumin and TLC levels taken at admission (study), while 47% (n=177) had not (control). Incidence of PEM was 51%. Older patients were more likely to have lower albumin (p=0.03) and TLC (p=0.012). Nursing home patients were also more likely to have lower albumin (p=0.049). In-hospital mortality for PEM patients was 9.8%, compared with 0% for patients with normal values of both laboratory parameters. Patients with PEM had a higher 12-month mortality compared to patients who had normal values of both laboratory parameters (Odds Ratio=4.52; p=0.049). Conclusion: Serum albumin and TLC in combination are accurate predictors of 12-month mortality in hip fracture patients. These results underscore the clinical relevance of assessing the nutritional status of patients with hip fractures at the time of admission and emphasises the relationship between nutrition and outcome in these patients

Background: Protein energy malnutrition (PEM) is an accepted predictor of poor outcome in hip fracture patients. There is no universally accepted definition of PEM. Admission screening for PEM is not routinely performed for hip fracture patients. The reported incidence in elderly hip fracture patients varies widely between 9.0% and 88.6%. Aims: To determine the prognostic relevance of admission serum albumin and total lymphocyte count (TLC), as clinical markers of PEM and predictors of outcome for hip fracture patients. Methods: Retrospective review of 415 patients with operatively managed hip fracture. Protein-energy malnutrition was defined as albumin < 3.5g/dl and TLC < 1,500 cells/ mm3. Delay to operation, duration of in-patient stay, readmission (< 3 months) and in-patient, 3- and 12-month mortality were assessed as outcome variables. Results: Survival data was available for 377 patients at 12 months. Of 377 patients, 53% (n=200) had both a serum albumin and TLC levels taken at admission (study), while 47% (n=177) had not (control). Incidence of PEM was 51%. Older patients were more likely to have lower albumin (p=0.03) and TLC (p=0.012). Nursing home patients were also more likely to have lower albumin (p=0.049). In-hospital mortality for PEM patients was 9.8%, compared with 0% for patients with normal values of both laboratory parameters. Patients with PEM had a higher 12-month mortality compared to patients who had normal values of both laboratory parameters (Odds Ratio=4.52; p=0.049). Conclusion: Serum albumin and TLC in combination are accurate predictors of 12-month mortality in hip fracture patients. These results underscore the clinical relevance of assessing the nutritional status of patients with hip fractures at the time of admission and emphasises the relationship between nutrition and outcome in these patients

Malnutrition is considered a risk factor for postoperative complications in total hip and knee arthroplasty, though prospective studies investigating this assumption are lacking. The aim of this study was to prospectively analyse the 90-day postoperative complications, postoperative length of stay (LOS) and readmission rates of patients undergoing primary total hip and total kneearthroplasty using albumin, total lymphocyte count (TLC) and transferrin as serum markers of potential malnutrition. 603 primary hip and 823 primary knee arthroplasties over a 3-year period from a single centre wereprospectively analysed. BMI, demographic and comorbidity data were recorded. Complications werecategorised as surgical site infection, venous thromboembolism (deep vein thrombosis andpulmonary embolus), implant related (such as dislocation), and non-implant related (such aspneumonia). Outcomes were compared between groups, with malnutrition defined as serumalbumin <3.5g/dL, transferrin <200 mg/dL, or TLC <1,500 cells/mm³. Potential malnutrition was present in 9.3% of the study population. This group experienced a longeraverage LOS at 6.5 days compared to the normal albumin group at 5.0 days (p=0.003). Surgical siteinfection rate was higher in the malnourished group (12.5 vs 7.8%, p=0.02). There was no differencebetween the two groups in implant related complications (0.8 vs 1.0%, p=0.95) medicalcomplications (7.8 vs 13.3%, p=0.17), rate of venous thromboembolism (2.3 vs 2.7%) or 90-dayreadmission rate (14.1 vs 17.0%, p=0.56). TLC and transferrin were not predictive of any of theprimary outcomes measured (p<0.05). Pacific Island (p<0.001), Indian (p=0.02) and Asian (p=0.02) patients had lower albumin than NZ European. This study demonstrates an association between low albumin levels and increased postoperativeLOS and surgical site infection in total joint arthroplasty, providing rationale for consideration ofpreoperative nutritional screening and optimisation

Sarcopenia has been observed to be a predictor of mortality in international studies of patients with metastatic disease of the spine. This study aimed to validate sarcopenia as a prognostic tool in a New Zealand setting. A secondary aim of this study was to assess the intra-observer reliability of measurements of psoas and vertebral body cross sectional areas on computed tomography imaging. A cohort of patients who had presented to Waikato Hospital with secondary neoplasia in the spinal column from 2014 to 2018 was selected. Cross sectional psoas and vertebral body areas were measured at the mid-pedicle L3 level, followed by calculation of the psoas to vertebral body cross sectional area ratio. Psoas to vertebral body cross sectional area ratio was compared with survivorship. The strength of the correlation between sarcopenia and survivorship was compared with the correlation between serum albumin and survivorship, as well as the correlation between the Metastatic Spine Risk Index (MSRI) and survivorship. A total of 110 patients who received operative (34) and non-operative (76) were included. The results demonstrate that psoas to vertebral body cross sectional area ratio is not statistically significantly correlated with survivorship (p=0.53). Serum albumin is significantly correlated with survivorship (p<0.0001), as was the MSRI. There is good intra-observer and inter-observer reliability for measurements of psoas to vertebral body cross sectional area. This study failed to demonstrate the utility for the psoas to vertebral body cross sectional area ratio that other studies have demonstrated in estimating survivorship. Serum albumin levels remain a useful prognostic indicator in patients with secondary tumours in the vertebral column

Malnutrition is an important consideration during the perioperative period and albumin is the most common laboratory surrogate for nutritional status. The purpose of this study is to identify if preoperative serum albumin measurements are predictive of infection following arthroscopic procedures. Patients undergoing knee, shoulder or hip arthroscopy between 2006–2016 were identified in the American College of Surgeons National Surgical Quality Improvement Program database. Patients with an arthroscopic current procedural terminology code and a preoperative serum albumin measurement were included. Patients with a history of prior infection, including a non-clean wound class, pre-existing wound infection or systemic sepsis were excluded. Independent t-tests where used to compare albumin values in patients with and without the occurrence of a postoperative infection. Pre-operative albumin levels were subsequently evaluated as predictors of infection with logistic regression models. There were 31,906 patients who met the inclusion criteria. The average age was 55.7 years (standard deviation (SD) 14.62) and average BMI was 31.7 (SD 7.21). The most prevalent comorbidities were hypertension (49.2%), diabetes (18.4%) and smoking history (16.9%). The average preoperative albumin was 4.18 (SD 0.42). There were 45 cases of superficial infection (0.14%), 10 cases of wound dehiscence (0.03%), 17 cases of deep infection (0.05%), 27 cases of septic arthritis or other organ space infection (0.08%) and 95 cases of any infection (0.30%). The preoperative albumin levels for patients who developed septic arthritis (mean difference (MD) 0.20, 95% CI, 0.038, 0.35, P = 0.015) or any infection (MD 0.14, 95% CI 0.05, 0.22, P = 0.002) were significantly lower than the normal population. Additionally, disseminated cancer, Hispanic race, inpatient status and smoking history were significant independent risk factors for infection, while female sex and increasing albumin were protective towards developing any infection. Rates of all infections were found to increase exponentially with decreasing albumin. The relative risk of infection with an albumin of 2 was 3.46 (95% CI, 2.74–4.38) when compared to a normal albumin of 4. For each albumin increase of 0.69, the odds of developing any infection decreases by a factor of 0.52. This study suggests that preoperative serum albumin is an independent predictor of septic arthritis and all infection following elective arthroscopic procedures. Although the effect of albumin on infection is modest, malnutrition may represent a modifiable risk factor with regard to preventing infection following arthroscopy

Introduction. Rates of readmission and reoperation following primary total knee arthroplasty (TKA) are under scrutiny due to new payment models, which penalize these negative outcomes. Many prior studies have demonstrated the risk of perioperative complications among patients with obesity. However, an elevated complication rate among patients with poor nutrition, as measured by hypoalbuminemia, has also been reported. We sought to determine whether controlling for hypoalbuminemia would mitigate the effect that prior authors had identified in patients with obesity. In addition, we hoped to identify an albumin threshold above which risk of readmission and reoperation would be minimized. Materials and Methods. We reviewed the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database for the period of 2008–2016 to evaluate the rates of perioperative complications among primary TKA patients by obesity category and albumin level. Patients were divided into groups according to World Health Organization obesity category and continuous as well as dichotomous albumin level. The primary outcomes were readmission and reoperation within 30 days of surgery. Patients without BMI or albumin data were excluded, as were patients undergoing surgery for the treatment of fracture or bone tumor. Univariate logistic regression compared predictive value of body mass index and albumin on incidence of these outcomes, using the normal weight and albumin > 3.5 g/dL groups as controls. Multivariate logistic regression modeling controlled for age, gender, and comorbidity status. Receiver operator curves (ROC) were generated to determine if an albumin threshold could be determined, above which risk for these complications would be minimized. Results. Outcome data was available 108,601 patients. Overall, 3,508 patients (3.46%) were readmitted and 1,219 patients (1.19%) underwent reoperation within 30 days. Hypoalbuminemia was present in 4,327 patients (4.11%), lowest in the Overweight group (3.16%) and highest in the Obese Type III (6.72%) and Underweight (12.62%) groups (p <0.001). Readmission and reoperation rates were highest among patients categorized as Obesity Class III (4.15 and 1.73%, respectively) compared with Normal Weight (3.59 and 1.14%, respectively, p <0.001). Readmission and reoperation rates were higher among patients with hypoalbuminemia (6.10 and 1.96%, respectively) compared with normal albumin (3.34 and 1.16%, respectively, p <0.001). After controlling for covariates of interest using multivariate regression including continuous albumin, odds ratio of readmission among the highest obesity category no longer differed from the Normal Weight control group. Odds ratio of reoperation among the highest obesity category declined from 1.52 to 1.38 after controlling for albumin and other covariates (p = 0.022). A subanalysis was performed excluding all patients with albumin < 3.5 g/dL, but results did not differ significantly from the multivariate model. ROC modeling was unable to identify a threshold for continuous BMI or albumin that would adequately mitigate risk for readmission or reoperation. Discussion. Albumin and obesity remain significant independent risk factors for reoperation following primary TKA procedures. However, after controlling for hypoalbuminemia and other important covariates, readmission rates did not significantly differ between patients with Normal Weight and any other obesity category. Controlling for albumin alone does not mitigate all risk imposed by obesity on perioperative outcomes. Future studies may assess whether preoperative albumin repletion or weight loss may improve outcomes for patients with hypoalbuminemia and obesity. For figures, tables, or references, please contact authors directly

Aims. While preoperative bloodwork is routinely ordered, its value in determining which patients are at risk of postoperative readmission following total knee arthroplasty (TKA) and total hip arthroplasty (THA) is unclear. The objective of this study was to determine which routinely ordered preoperative blood markers have the strongest association with acute hospital readmission for patients undergoing elective TKA and THA. Methods. Two population-based retrospective cohorts were assembled for all adult primary elective TKA (n = 137,969) and THA (n = 78,532) patients between 2011 to 2018 across 678 North American hospitals using the American College of Surgeons National Quality Improvement Programme (ACS-NSQIP) registry. Six routinely ordered preoperative blood markers - albumin, haematocrit, platelet count, white blood cell count (WBC), estimated glomerular filtration rate (eGFR), and sodium level - were queried. The association between preoperative blood marker values and all-cause readmission within 30 days of surgery was compared using univariable analysis and multivariable logistic regression adjusted for relevant patient and treatment factors. Results. The mean TKA age was 66.6 years (SD 9.6) with 62% being females (n = 85,163/137,969), while in the THA cohort the mean age was 64.7 years (SD 11.4) with 54% being female (n = 42,637/78,532). In both cohorts, preoperative hypoalbuminemia (< 35 g/l) was associated with a 1.5- and 1.8-times increased odds of 30-day readmission following TKA and THA, respectively. In TKA patients, decreased eGFR demonstrated the strongest association with acute readmission with a standardized odds ratio of 0.75 per two standard deviations increase (p < 0.0001). Conclusion. In this population level cohort analysis of arthroplasty patients, low albumin demonstrated the strongest association with acute readmission in comparison to five other commonly ordered preoperative blood markers. Identification and optimization of preoperative hypoalbuminemia could help healthcare providers recognize and address at-risk patients undergoing TKA and THA. This is the most comprehensive and rigorous examination of the association between preoperative blood markers and readmission for TKA and THA patients to date. Cite this article: Bone Jt Open 2021;2(6):388–396

Aims. The incidence of limb fractures in patients living with HIV (PLWH) is increasing. However, due to their immunodeficiency status, the operation and rehabilitation of these patients present unique challenges. Currently, it is urgent to establish a standardized perioperative rehabilitation plan based on the concept of enhanced recovery after surgery (ERAS). This study aimed to validate the effectiveness of ERAS in the perioperative period of PLWH with limb fractures. Methods. A total of 120 PLWH with limb fractures, between January 2015 and December 2023, were included in this study. We established a multidisciplinary team to design and implement a standardized ERAS protocol. The demographic, surgical, clinical, and follow-up information of the patients were collected and analyzed retrospectively. Results. Compared with the control group, the ERAS group had a shorter operating time, hospital stay, preoperative waiting time, postoperative discharge time, less intraoperative blood loss, and higher albumin and haemoglobin on the first postoperative day. The time to removal of the urinary catheter/drainage tube was shortened, and the drainage volume was also significantly reduced in the ERAS group. There was no significant difference in the visual analogue scale (VAS) scores on postoperative return to the ward, but the ERAS group had lower scores on the first, second, and third postoperative days. There were no significant differences in the incidence of complications, other than 10% more nausea and vomiting in the control group. The limb function scores at one-year follow-up were similar between the two groups, but time to radiological fracture union and time to return to physical work and sports were significantly reduced in the ERAS group. Conclusion. The implementation of a series of perioperative nursing measures based on the concept of ERAS in PLWH with limb fracture can significantly reduce the operating time and intraoperative blood loss, reduce the occurrence of postoperative pain and complications, and accelerate the improvement of the functional status of the affected limb in the early stage, which is worthy of applying in more medical institutions. Cite this article: Bone Joint Res 2024;13(11):647–658

Aim. This study seeks to outline the clinical, laboratory, and imaging features of patients with pyogenic spondylitis. It aims to define a novel imaging sign that could indicate the severity of suppurative spondylitis, aiding in its early diagnosis and treatment. Method. This retrospective study included 137 patients from 2013 to 2023. Through the analysis and summary of imaging characteristics among all patients, we identified a distinct MRI sign known as ‘the Disc Penetration sign’ (DP). This sign is defined as an image finding on sagittal MRI depicting the anterior and posterior penetration of an abscess through the intervertebral disc space, affecting both the anterior margin of the vertebrae and the structures within the spinal canal. Observational parameters included WBC, ESR, CRP, hemoglobin, and albumin levels. Documentation of the study included location and segment of the lesion, presence or absence of spinal cord compression, and paravertebral abscesses. Results. 56 patients presented with the Disc Penetration sign(DP) and 81 did not. In both groups, there were no significant differences in gender ratio or age (P > 0.05). However, significant differences were observed in the presence of comorbid diabetes and chronic kidney disease (p < 0.05). The DP group had a significantly greater ESR level (74.30±33.79 mm/h vs. 51.46±30.46 mm/h, P < 0.001) and CRP level (47.28 mg/L vs. 26.18 mg/L, P = 0.003). Additionally, the DP group had a significantly lower Hb (100.66±19.82 g/L vs. 116.99±19.99g/L,P < 0.001) and the serum albumin level (28.81±6.59 g/L vs. 34.09±6.17 g/L,P < 0.001). Imaging results showed no significant differences in affected spinal segments or parts (p>0.05). Patients in the DP group showed a higher likelihood of developing paravertebral abscesses compared to those in the non-DP group (n = 54 [96.4%] vs. n = 33 [40.7%], P < 0.001), and also exhibited a higher incidence of spinal cord compression(n = 32 [57.1%] vs. n = 17 [21.0%], P < 0.001). Conclusions. The study suggests that the Disc Penetration sign in pyogenic spondylitis patients correlates with more severe inflammation and higher incidence of paraspinal abscess, pointing to worse stability of the spine, longer bone restructuring time, and potentially poorer prognosis. These findings enable clinicians to rapidly assess the severity of the disease and prognosticate outcomes more effectively We emphasize the need for early, pathogen-specific diagnosis and treatment, particularly considering surgical intervention for patients demonstrating substantial paraspinal abscesses or spinal instability

Aims. Advances in treatment have extended the life expectancy of patients with metastatic bone disease (MBD). Patients could experience more skeletal-related events (SREs) as a result of this progress. Those who have already experienced a SRE could encounter another local management for a subsequent SRE, which is not part of the treatment for the initial SRE. However, there is a noted gap in research on the rate and characteristics of subsequent SREs requiring further localized treatment, obligating clinicians to extrapolate from experiences with initial SREs when confronting subsequent ones. This study aimed to investigate the proportion of MBD patients developing subsequent SREs requiring local treatment, examine if there are prognostic differences at the initial treatment between those with single versus subsequent SREs, and determine if clinical, oncological, and prognostic features differ between initial and subsequent SRE treatments. Methods. This retrospective study included 3,814 adult patients who received local treatment – surgery and/or radiotherapy – for bone metastasis between 1 January 2010 and 31 December 2019. All included patients had at least one SRE requiring local treatment. A subsequent SRE was defined as a second SRE requiring local treatment. Clinical, oncological, and prognostic features were compared between single SREs and subsequent SREs using Mann-Whitney U test, Fisher’s exact test, and Kaplan–Meier curve. Results. Of the 3,814 patients with SREs, 3,159 (83%) patients had a single SRE and 655 (17%) patients developed a subsequent SRE. Patients who developed subsequent SREs generally had characteristics that favoured longer survival, such as higher BMI, higher albumin levels, fewer comorbidities, or lower neutrophil count. Once the patient got to the point of subsequent SRE, their clinical and oncological characteristics and one-year survival (28%) were not as good as those with only a single SRE (35%; p < 0.001), indicating that clinicians’ experiences when treating the initial SRE are not similar when treating a subsequent SRE. Conclusion. This study found that 17% of patients required treatments for a second, subsequent SRE, and the current clinical guideline did not provide a specific approach to this clinical condition. We observed that referencing the initial treatment, patients in the subsequent SRE group had longer six-week, 90-day, and one-year median survival than patients in the single SRE group. Once patients develop a subsequent SRE, they have a worse one-year survival rate than those who receive treatment for a single SRE. Future research should identify prognostic factors and assess the applicability of existing survival prediction models for better management of subsequent SREs. Cite this article: Bone Joint Res 2024;13(9):497–506

Low back pain is strongly associated with degeneration of the intervertebral disc (IVD). During degeneration, altered matrix synthesis and increased matrix degradation, together with accompanied cell loss is seen particularly in the nucleus pulposus (NP). It has been proposed that notochordal (NC) cells, embryonic precursors for the cells within the NP, could be utilized for mediating IVD regeneration. However, injectable biomaterials are likely to be required to support their phenotype and viability within the degenerate IVD. Therefore, viability and phenotype of NC cells were analysed and compared within biomaterial carriers subjected to physiological oxygen conditions over a four-week period were investigated. Porcine NC cells were incorporated into three injectable hydrogels: NPgel (a L-pNIPAM-co-DMAc hydrogel), NPgel with decellularized NC-matrix powder (dNCM) and Albugel (an albumin/ hyaluronan hydrogel). The NCs and biomaterials constructs were cultured for up to four weeks under 5% oxygen (n=3 biological repeats). Histological, immunohistochemical and glycosaminoglycans (GAG) analysis were performed to investigate NC viability, phenotype and extracellular matrix synthesis and deposition. Histological analysis revealed that NCs survive in the biomaterials after four weeks and maintained cell clustering in NPgel, Albugel and dNCM/NPgel with maintenance of morphology and low caspase 3 staining. NPgel and Albugel maintained NC cell markers (brachyury and cytokeratin 8/18/19) and extracellular matrix (collagen type II and aggrecan). Whilst Brachyury and Cytokeratin were decreased in dNCM/NPgel biomaterials, Aggrecan and Collagen type II was seen in acellular and NC containing dNCM/NPgel materials. NC containing constructs excreted more GAGs over the four weeks than the acellular controls. NC cells maintain their phenotype and characteristic features in vitro when encapsulated into biomaterials. NC cells and biomaterial construct could potentially become a therapy to treat and regenerate the IVD

Total knee arthroplasty (TKA) is the most commonly performed elective orthopaedic procedure. With an increasingly aging population, the number of TKAs performed is expected to be ∼2,900 per 100,000 by 2050. Surgical Site Infections (SSI) after TKA can have significant morbidity and mortality. The purpose of this study was to construct a risk prediction model for acute SSI (classified as either superficial, deep and overall) within 30 days of a TKA based on commonly ordered pre-operative blood markers and using audited administrative data from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. All adult patients undergoing an elective unilateral TKA for osteoarthritis from 2011–2016 were identified from the NSQIP database using Current Procedural Terminology (CPT) codes. Patients with active or chronic, local or systemic infection/sepsis or disseminated cancer were excluded. Multivariate logistic regression was conducted to estimate coefficients, with manual stepwise reduction to construct models. Bootstrap estimation was administered to measure internal validity. The SSI prediction model included the following co-variates: body mass index (BMI) and sex, comorbidities such as congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), smoking, current/previous steroid use, as well as pre-operative blood markers, albumin, alkaline phosphatase, blood urea nitrogen (BUN), creatinine, hematocrit, international normalized ratio (INR), platelets, prothrombin time (PT), sodium and white blood cell (WBC) levels. To compare clinical models, areas under the receiver operating characteristic (ROC) curves and McFadden's R-squared values were reported. The total number of patients undergoing TKA were 210,524 with a median age of 67 years (mean age of 66.6 + 9.6 years) and the majority being females (61.9%, N=130,314). A total of 1,674 patients (0.8%) had a SSI within 30 days of the index TKA, of which N=546 patients (33.2%) had a deep SSI and N=1,128 patients (67.4%) had a superficial SSI. The annual incidence rate of overall SSI decreased from 1.60% in 2011 to 0.68% in 2016. The final risk prediction model for SSI contained, smoking (OR=1.69, 95% CI: 1.31 – 2.18), previous/current steroid use (OR=1.66, 95% CI: 1.23 – 2.23), as well as the pre-operative lab markers, albumin (OR=0.46, 95% CI: 0.37 – 0.56), blood urea nitrogen (BUN, OR=1.01, 95% CI: 1 – 1.02), international normalized ratio (INR, OR=1.22, 95% CI:1.05 – 1.41), and sodium levels (OR=0.94, 95% CI: 0.91 – 0.98;). Area under the ROC curve for the final model of overall SSI was 0.64. Models for deep and superficial SSI had ROC areas of 0.68 and 0.63, respectively. Albumin (OR=0.46, 95% CI: 0.37 – 0.56, OR=0.33, 95% CI: 0.27 – 0.40, OR=0.75, 95% CI: 0.59 – 0.95) and sodium levels (OR=0.94, 95% CI: 0.91 – 0.98, OR=0.96, 95% CI: 0.93 – 0.99, OR=0.97, 95% CI: 0.96 – 0.99) levels were consistently significant in all prediction models for superficial, deep and overall SSI, respectively. Overall, hypoalbuminemia and hyponatremia are both significant risk factors for superficial, deep and overall SSI. To our knowledge, this is the first prediction model for acute SSI post TKA whereby hyponatremia (and hypoalbuminemia) are predictive of SSI. This prediction model can help fill an important gap for predicting risk factors for SSI after TKA and can help physicians better optimize patients prior to TKA

Introduction. We aimed to identify genes associated with the development of ALVAL at relatively low levels of wear. Methods. At our unit all patients undergoing revision of a MoM hip prosthesis have periprosthetic tissue samples graded for ALVAL. Explants undergo volumetric wear testing of the bearing and taper surfaces. We identified patients with moderate/severe ALVAL who had been exposed to lower than the median wear rate of all recorded patients who had developed ALVAL (<3mm. 3. /year). This was termed the “ALVAL” group. We then identified all patients whose tissues had shown no signs of ALVAL. The patients in the two groups were sent buccal DNA collection kits. DNA was examined using next generation sequencing. Alleleic frequencies in the two groups were compared using Fisher's test and compared to a background UK population group (n=8514). We then conducted binary logistic regression with patient age, sex, primary source of debris (taper/bearing) and HLA genotype as the predictors. With the hypothesis that a cobalt/albumin metalloprotein acts as the epitope, we used validated binding prediction software to determine the relative affinities of the binding grooves created by different DQA1/DQB1 genetic combinations for albumin derived peptides. Given the protection that male sex and younger age appears to confer against ALVAL, we hypothesized that testosterone peptides may compete for these binding sites. Results. 28 ALVAL and 37 non ALVAL patients returned their samples for testing. The frequencies of DQA1∗05:05 and DQB1∗03:01 were significantly greater in the ALVAL groups(p=0.018). The variables positively associated with ALVAL were female sex(0.021), increasing age(0.003) and DQA1/DQB1 combinations with greater binding affinity for albumin fragments(0.03). Greater binding affinities for testosterone peptides were inversely related to ALVAL(0.05). Discussion. Common immune genotypes are associated with a greater risk of ALVAL. Conclusion. The evidence base on which MoM follow up protocols are based should be re-evaluated in light of these findings and future studies designed accordingly

Objectives. Low back pain is strongly associated with degeneration of the intervertebral disc (IVD). During degeneration, altered matrix synthesis and increased matrix degradation, together with accompanied cell loss is seen particularly in the nucleus pulposus (NP). It has been proposed that notochordal (NC) cells, embryonic precursors for the cells within the NP, could be utilized for mediating IVD regeneration. However, injectable biomaterials are likely to be required to support their phenotype and viability within the degenerate IVD. Therefore, viability and phenotype of NC cells were analysed and compared within biomaterial carriers subjected to physiological oxygen conditions over a four-week period were investigated. Methodology. Porcine NC cells were incorporated into three injectable hydrogels: NPgel (a L-pNIPAM-co-DMAc hydrogel), NPgel with decellularized NC-matrix powder (dNCM) and Albugel (an albumin/ hyaluronan hydrogel). The NCs and biomaterials constructs were cultured for up to four weeks under 5% oxygen (n=3 biological repeats). Histological, immunohistochemical and glycosaminoglycans (GAG) analysis were performed to investigate NC viability, phenotype and extracellular matrix synthesis and deposition. Results. Histological analysis revealed that NCs survive in the biomaterials after four weeks and maintained cell clustering in NPgel, Albugel and dNCM/NPgel. NPgel and Albugel maintained NC cell markers and extracellular matrix. NC containing constructs excreted more GAGs over the four weeks than the acellular controls. Conclusion. NC cells maintain their phenotype and characteristic features in vitro when encapsulated into biomaterials. NC cells and biomaterial construct could potentially become a therapy to treat and regenerate the IVD. Conflicts of interest: No conflicts of interest. Sources of funding: This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 825925

Introduction. Ink engineering can advance 3D-printability for better therapeutics, with optimized proprieties. Herein, we describe a methodology for yielding 3D-printable nanocomposite inks (NC) using low-viscous matrices, via the interaction between the organic and inorganic phases by chemical coupling. Method. Natural photocurable matrices were synthesized: a protein – bovine serum albumin methacrylate (BSAMA), and a polysaccharide – hyaluronic acid methacrylate (HAMA). Bioglass nanoparticles (BGNP) were synthesized and functionalized via aminosilane chemistry. The functionalization of BSAMA, HAMA, and BGNP were quantified via NMR. To arise extrudable inks, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-Hydroxysuccinimide (NHS) chemistry was used to link innate carboxylic groups of BSAMA/HAMA and amine-functionalized BGNP. Different crosslinker and BGNP amounts were tested. Visible light photopolymerization is performed, using lithium phenyl-2,4,6-trimethylbenzoylphosphinate. The NC's rheological, mechanical, and biological behavior was evaluated before 3D extrusion printability. Result. All composite formulations effectively immobilized and homogeneously dispersed the BGNP, turning low-viscous materials (< 1 Pa) into shear-thinning formulations with tunable increased elastic/viscous moduli (50-500 Pa). More pronounced increments were found with increasing EDC/NHS and BGNP concentrations. The resulting inks produce robust and stable scaffolds successfully retrieved after post-print photocrosslinking (1-5 kPa). Bioactivity in simulated body fluid and in vitro assays using adipose-derive stem cells revealed a similar calcium/phosphate ratio to that of hydroxyapatite, and increased viability and metabolic activity. BSAMA and HAMA demonstrated distinct natures not only in printability but also in overall cellular performance and mechanical properties, making these ideal for interfacial tissue engineering. Conclusion. This strategy demonstrated being effective and reproducible to advance nanocomposites for 3D printing using different types of biomaterials. Further, we envision using both inks to produce hierarchical constructs via extrusion printing, better mimicking bone-to-cartilage interfaces. Acknowledgements. FCT grants (DOI:10.54499/2022.04605.CEECIND/CP1720/CT0021), (BI/UI89/10303/2022), (PRT/BD/154735/2023); EU's Horizon 2020 research and innovation programs InterLynk (Nº953169) and SUPRALIFE (Nº101079482) projects; CICECO-Aveiro Institute of Materials projects (DOI:10.54499/UIDB/50011/2020), (DOI:10.54499/UIDP/50011/2020), and (DOI:10.54499/LA/P/0006/2020), financed by FCT/MCTES(PIDDAC)