Multiplex cytokine analysis for the identification of novel potential synovial fluid biomarkers for periprosthetic joint infections.

INTRODUCTION: Periprosthetic joint infections (PJIs) are a devastating complication of total hip (THA) and knee (TKA) arthroplasty. The use of novel techniques like multiplex cytokine analysis could contribute immensely to the identification of potential novel biomarkers. PATIENTS AND METHODS: This is a single-centre study of patients that were treated with revision TKA, THA or hemiarthroplasty. Serum's white blood cells (WBCs), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and synovial fluid's WBCs, percentage of polymorphonuclear neutrophils (%PMNs) and CRP were measured. Proteomic analysis targeting the secreted cytokines in synovial fluid was conducted using a 73-plex assay panel. The results were statistically compared between the septic and aseptic cases and ROC analysis to establish the area under the curve (AUC), sensitivity and specificity of each biomarker. RESULTS: The study included 30 patients (18 revision THA cases; 3 conversion of hemiarthroplasty to THA and 9 revision TKA cases); 14 cases were considered infected, 1 likely infected and 15 not infected. The results showed statistically significant differences (p < 0.05) between infected and not infected cases in serum's ESR, CRP and synovial fluid's%PMNs, growth-regulated oncogene alpha (GROA), interleukin-8, interleukin-5, S100-A8/calprotectin and resistin (RETN) with AUCs of 0.75, 0.72, 0.95, 0.75, 0.72, 0.95, 0.83, 0.73, 0.75, 0.81 and 0.76 respectively. CONCLUSIONS: In the present study, serum ESR and CRP as well as synovial %PMNs, GROA, IL-8, IL-5, calprotectin and RETN protein levels were identified as potential biomarkers. Further studies are needed to further investigate their diagnostic utility and optimal cut-off values.

Surgical management and functional outcomes of perilunate dislocations and fracture dislocations through the dorsal approach.

BACKGROUND: Perilunate dislocations and perilunate fracture dislocations (PLD/PLFDs) are rare injuries of the wrist, with surgical management leading to acceptable functional results. PURPOSE: The purpose of this study was to assess the functional outcomes of the patients of our department who were treated with surgical management of PLDs/PLFDs through dorsal approach, as well as to report any complications on their follow-up. PATIENTS AND METHODS: In this retrospective study, 52 patients with PLD/PLFD, fulfilling the inclusion and exclusion criteria of the study, underwent surgical management of their injury. All patients were followed up at 6 weeks, 12 weeks, 6 months, 1 year postoperatively with radiographic imaging as well as functional scores measured with the modified mayo wrist score and the QuickDASH questionnaire. RESULTS: The mean postoperative modified Mayo score was 76.8 ± 8.8 and the mean QuickDASH score was 1.52 ± 2.18. Of the 52 cases, 20% had excellent results, 42% had good results, 29% had fair results and 9% had poor results as per the modified Mayo wrist score. No patient signed any symptoms of median nerve neuropathy. CONCLUSION: In conclusion, open reduction and internal fixation through dorsal approach is a reliable technique to manage perilunate injuries in spite of radiological evidence of wrist arthritis, as it also provides consistently good results in terms of functional outcomes. LEVEL OF EVIDENCE IV: Retrospective case series study.

Intraoperative calprotectin lateral flow immunoassay can assist decision-making between one- and two-stage revision total hip arthroplasty for patients with suspected periprosthetic joint infection.

Aims: Accurate diagnosis of chronic periprosthetic joint infection (PJI) presents a significant challenge for hip surgeons. Preoperative diagnosis is not always easy to establish, making the intraoperative decision-making process crucial in deciding between one- and two-stage revision total hip arthroplasty (THA). Calprotectin is a promising point-of-care novel biomarker that has displayed high accuracy in detecting PJI. We aimed to evaluate the utility of intraoperative calprotectin lateral flow immunoassay (LFI) in THA patients with suspected chronic PJI. Methods: The study included 48 THAs in 48 patients with a clinical suspicion of PJI, but who did not meet European Bone and Joint Infection Society (EBJIS) PJI criteria preoperatively, out of 105 patients undergoing revision THA at our institution for possible PJI between November 2020 and December 2022. Intraoperatively, synovial fluid calprotectin was measured with LFI. Cases with calprotectin levels ≥ 50 mg/l were considered infected and treated with two-stage revision THA; in negative cases, one-stage revision was performed. At least five tissue cultures were obtained; the implants removed were sent for sonication. Results: Calprotectin was positive (≥ 50 mg/l) in 27 cases; out of these, 25 had positive tissue cultures and/or sonication. Calprotectin was negative in 21 cases. There was one false negative case, which had positive tissue cultures. Calprotectin showed an area under the curve of 0.917, sensitivity of 96.2%, specificity of 90.9%, positive predictive value of 92.6%, negative predictive value of 95.2%, positive likelihood ratio of 10.6, and negative likelihood ratio of 0.04. Overall, 45/48 patients were correctly diagnosed and treated by our algorithm, which included intraoperative calprotectin measurement. This yielded a 93.8% concordance with postoperatively assessed EBJIS criteria. Conclusion: Calprotectin can be a valuable tool in facilitating the intraoperative decision-making process for cases in which chronic PJI is suspected and diagnosis cannot be established preoperatively.

Pain management after total hip arthroplasty: comparative study of analgesic efficacy and tolerability between oral tramadol/dexketoprofen and injectable paracetamol + tramadol.

BACKGROUND: Multimodal analgesia for total hip arthroplasty (THA) is increasingly employed to reduce early postoperative pain and promote fast patient discharge. The aim of this study was to compare the efficacy and tolerability of tramadol/dexketoprofen (TRAM/DKP, Group A) versus paracetamol + tramadol (PARA+TRAM, Group B) in patients undergoing THA using minimally invasive direct anterior approach (DAA). METHODS: A single-centre, randomised, single-blind, parallel, interventional study conducted in 323 patients undergoing primary THA with DAA was performed. Group A consisted of 188 patients and Group B of 135. The primary endpoints were the change from baseline (measured 2 hours postoperatively) in pain intensity (PI) during the treatment period (48 hours), assessed by visual analogue scale (VAS) at pre-specified postoperative time-points (2, 8, 24, 48 hours) and the total rescue medication (RM) use during the first 24 hours postoperatively. RESULTS: As early as 2 hours after baseline, Group A showed a greater PI reduction from baseline compared to Group B (-26.24% vs. -6.87%; p < 0.001). A lower mean PI (VAS) score was consistently found over the entire observation period following treatment with TRAM/DKP than with PARA+TRAM as well as more than 2-fold higher proportion of responders at the end of treatment period. More patients in Group B required RM in comparison to those in Group A (15.6% vs. 3.7%, p < 0.001). Both treatments were well tolerated. CONCLUSIONS: After THA, oral TRAM/DKP provides faster and greater pain relief when compared to intravenous PARA+TRAM with limited consumption of RM and favourable tolerability profile. Our study expands the use of TRAM/DKP in the setting of major orthopaedic surgeries. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov (NCT04178109).

Fall risk question-based tools for fall screening in community-dwelling older adults: a systematic review of the literature.

Fall screening tools aim to accurately identify the high fall risk individuals. To increase ease of administration and cost-effectiveness many studies focus on question-based tools. The purpose of this systematic review was to identify question-based tools for fall risk assessment in community-dwelling older adults over the age of 60 and the risk factors that are covered by these tools. The PRISMA guidelines were followed. A literature search was conducted in PubMed/MEDLINE, Web of Science and Google Scholar. Data quality assessment was performed with the Ottawa-Newcastle scale. The results identified 20 studies that used 22 question-based tools to assess fall risk. The number of questions per tool varied from 1 to 41 questions. Data quality varied greatly, with values 3-9 for cohort and 2-7 for cross-sectional studies. The most commonly reported fall risk factors were fall history, feeling of unsteadiness, fear of falling, muscle strength, gait limitation and incontinence. Healthcare providers should use the above tools with caution regarding the limitations of each tool. Further studies should be designed to address individuals with high fall risk, such as individuals with cognitive impairment, as they are under-represented or excluded from most of the existing studies.

Development and validation of a fall risk Questionnaire in Greek community-dwelling individuals over 60 years old.

Objectives: The purpose of this study was to develop a questionnaire that can reliably recognize Greek individuals over the age of 60 with increased risk of falls. Methods: An 11-item self-reported Questionnaire (LRMS) was developed and delivered to 200 individuals. Collected data were compared to Timed Up and Go (TUG), Falls Efficacy Scale-International (FES-I), Tinetti Assessment Tool, Geriatric Depression Scale-15 (GDS-15) and Morse fall scale. The results were statistically analyzed. Results: Correlation between LRMS and the examined tools was high TUG (r=0.831), FES-I (r=-0.820), Tinetti balance (r=-0.812), Tinetti gait (r=-0.789), GDS-15 (r=-0.562), and Morse fall scale (r=0.795). Cronbach's alpha for LRMS total score was 0.807. ICC of the LRMS total score was 0.991. The area under the curve of LRMS was 0.930 (cut-off point 10.5, 95% C.I. 0.88 - 0.98, p<0.001, sensitivity=86%, specificity=98%) with TUG as gold standard, 0.919 (cut-off point 11.5, 95% C.I. 0.88 - 0.96, p<0.001, sensitivity=85%, specificity=89%) with FES-I and 0.947 (cut-off point 10.5, 95% C.I. 0.91 - 0.98, p<0.001, sensitivity=93%, specificity=91%) with Tinetti. Conclusions: The LRMS Questionnaire showed sufficient internal consistency, excellent test-retest reliability and high correlation with the already established tools for fall risk assessment. It is short and easy to use without assistance from specially trained personnel.

Total hip arthroplasty through the direct anterior approach in morbidly obese patients.

AIMS: There is evidence that morbidly obese patients have more intra- and postoperative complications and poorer outcomes when undergoing total hip arthroplasty (THA) with the direct anterior approach (DAA). The aim of this study was to determine the efficacy of DAA for THA, and compare the complications and outcomes of morbidly obese patients with nonobese patients. METHODS: Morbidly obese patients (n = 86), with BMI ≥ 40 kg/m2 who underwent DAA THA at our institution between September 2010 and December 2017, were matched to 172 patients with BMI < 30 kg/m2. Data regarding demographics, set-up and operating time, blood loss, radiological assessment, Harris Hip Score (HHS), International Hip Outcome Tool (12-items), reoperation rate, and complications at two years postoperatively were retrospectively analyzed. RESULTS: No significant differences in blood loss, intra- and postoperative complications, or implant position were observed between the two groups. Superficial wound infection rate was higher in the obese group (8.1%) compared to the nonobese group (1.2%) (p = 0.007) and relative risk of reoperation was 2.59 (95% confidence interval 0.68 to 9.91). One periprosthetic joint infection was reported in the obese group. Set-up time in the operating table and mean operating time were higher in morbidly obese patients. Functional outcomes and patient-related outcome measurements were superior in the obese group (mean increase of HHS was 52.19 (SD 5.95) vs 45.1 (SD 4.42); p < 0.001), and mean increase of International Hip Outcome Tool (12-items) was 56.8 (SD 8.88) versus 55.2 (SD 5.85); p = 0.041). CONCLUSION: Our results suggest that THA in morbidly obese patients can be safely and effectively performed via the DAA by experienced surgeons. Cite this article: Bone Jt Open 2022;3(1):4-11.

Effect of Calcium and Vitamin D Supplementation With and Without Collagen Peptides on Volumetric and Areal Bone Mineral Density, Bone Geometry and Bone Turnover in Postmenopausal Women With Osteopenia.

Collagen peptides (CPs) have been shown to potentially have a role as a treatment option in osteopenia. In the present randomized prospective study, we examined the effect of calcium, vitamin D with and without CPs supplementation on changes in volumetric bone mineral density (vBMD) and bone geometry assessed by peripheral quantitative computed tomography at the tibia, areal bone mineral density (aBMD) assessed by dual-energy X-ray absorptiometry at the lumbar spine and the hip and bone turnover markers over 12-mo. Fifty-one postmenopausal women with osteopenia were allocated to Group A who received orally 5 g CPs, 500 mg calcium and 400 IU vitamin D3 and Group B who received the same dose of calcium and vitamin D3 per day. The primary endpoint was the change of trabecular bone mineral content (BMC) and vBMD after 12-mo supplementation in Groups A and B. At the trabecular site (4% of the tibia length), Group A had a significant increase of total BMC by 1.96 ± 2.41% and cross-sectional area by 2.58 ± 3.91%, trabecular BMC by 5.24 ± 6.48%, cross-sectional area by 2.58 ± 3.91% and vBMD by 2.54 ± 3.43% and a higher % change of these parameters at 12 mo in comparison to Group B (p < 0.01, p = 0.04, p < 0.01, p = 0.04, p = 0.02, respectively). At the cortical site (38% of the tibia length), total and cortical vBMD increased by 1.01 ± 2.57% and 0.67 ± 1.71%. Furthermore, the mean aBMD at the spine was higher (p = 0.01), while bone markers decreased in Group A compared to Group B. The present study shows improvement of trabecular and cortical parameters as assessed by peripheral quantitative computed tomography at the tibia, prevention of aBMD decline and decrease of bone turnover after 12-mo supplementation with calcium, vitamin D with CPs.

Management of femoral neck fractures with the ALMIS approach in elderly patients: Outcomes compared to posterior approach.

INTRODUCTION: Over the last 2 decades, several minimally invasive surgical techniques and approaches have been introduced for hip arthroplasty, including anterolateral minimally invasive surgery (ALMIS) introduced by Röttinger in 2004. As described, this muscle sparing approach promises faster recovery and lower dislocation rates. Although there has been a peaked recent interest in minimally invasive surgery (MIS) hip arthroplasty, few studies support the superiority of ALMIS compared to the more traditional posterior approach. The present study examines the safety and early complications of elderly patients undergoing ALMIS compared to a posterior approach for hemiarthroplasty of displaced femoral neck fractures. METHODS: In a retrograde level III case-control study, 100 consecutive elderly patients with primary hip arthroplasty were divided into two groups. The first group consisted of 50 consecutive cases operated with the ALMIS approach and the second group of 50 consecutive cases operated through a posterior approach. Operative time, postoperative complication rates, length of hospitalization, blood loss, and leg-length discrepancy, were reviewed retrospectively. RESULTS: No differences were observed in post-operative complications. Overall, the operative time was significantly greater in the ALMIS group compared to the posterior approach group (75 ± 12 vs 67.5 ± 16 min, respectively; p ≤ 0.01). However, the operating time of the second half of the ALMIS cohort (N = 25), did not differ from the posterior approach group (72.7 ± 10.5 vs 67.5 ± 16, respectively; p = 0.19). Leg length discrepancy was significantly less in the ALMIS group compared to the posterior exposure group (1.5 ± 3.2 vs 3.2 ± 3.3, respectively; P≤0.1). CONCLUSIONS: The results of the retrograde analysis, although limited in sample size, shows no major differences in ALMIS compared to a more traditional posterior approach in terms of immediate post-operative complications. Although the overall operating time was longer in the patients treated with ALMIS, the second cohort of patients treated with this method had an operating time that was similar to that observed with posterior approach. Leg-length discrepancies were significantly less in patients treated with ALMIS.

Effect of calcium and vitamin D supplementation with and without collagen peptides on bone turnover in postmenopausal women with osteopenia.

OBJECTIVES: Collagen peptides (CPs) seem to exert beneficial effects on bone and may have a role as a treatment option. In the present randomized prospective study, we aimed to examine the efficacy, as expressed by changes in P1NP and CTX, and the tolerability of 3-month supplementation of calcium, vitamin D with or without bioactive CPs in postmenopausal women with osteopenia. METHODS: Fifty-one female, postmenopausal women with osteopenia were allocated to two groups: Group A received a sachet containing 5 g CPs, 3.6 g calcium lactate (equivalent to 500 mg of elemental calcium) and 400 IU vitamin D3 and group B received a chewable tablet containing 1.25 g calcium carbonate (equivalent to 500 mg of elemental calcium) and 400 IU vitamin D3 daily. RESULTS: In group A, the P1NP levels significantly decreased by 13.1% (p<0.001) and CTX levels decreased by 11.4% (p=0.058) within 3 months of supplementation. In group B, P1NP and CTX did not change. Group A presented better compliance in comparison to group B and no adverse events contrary to group B. CONCLUSIONS: These findings may reflect the reduction of the increased bone turnover in postmenopausal women with the use of calcium, vitamin D and CPs supplements. The addition of CPs in a calcium and vitamin D supplement may enhance its already known positive effect on bone metabolism. Clinical Trial ID: NCT03999775.

Program death-1 immune checkpoint and tumor microenvironment in malignant liver tumors.

Hepatic malignancies are one of the leading causes of cancer death globally. Considering the limited efficacy of current standard treatments in management of patients with advanced liver cancers, there has been a growing interest in identifying novel therapies. Despite achieving promising results in initial clinical trials, the therapeutic benefit of immunotherapy is limited due to strong immune-tolerogenic characteristics of liver tumors. Therapeutic regimens that impede tumor immunosuppressive mechanisms or elaborate tumor-specific immunity may improve clinical outcomes of patients with liver malignancies. Programmed cell death 1 (PD-1), an inhibitory checkpoint molecule, and its ligands (PD-L1 and -L2) are the main mediators of immunosuppression within the tumor microenvironment. The expression level of PD-1/PD-L1 may act as a biomarker to predict disease progression, as well as long-term survival. Furthermore, early trials have demonstrated the efficacy and safety of targeting PD-1/PD-L1 as an emerging field in the management of patients with advanced hepatocellular carcinoma. We herein review the role of PD-1/PD-L1 in the pathogenesis of liver malignancies, as well as its potential diagnostic and therapeutic implications.

Postoperative Abdominal Adhesions: Clinical Significance and Advances in Prevention and Management.

Postoperative adhesions remain one of the more challenging issues in surgical practice. Although peritoneal adhesions occur after every abdominal operation, the density, time interval to develop symptoms, and clinical presentation are highly variable with no predictable patterns. Numerous studies have investigated the pathophysiology of postoperative adhesions both in vitro and in vivo. Factors such as type and location of adhesions, as well as timing and recurrence of adhesive obstruction remain unpredictable and poorly understood. Although the majority of postoperative adhesions are clinically silent, the consequences of adhesion formation can represent a lifelong problem including chronic abdominal pain, recurrent intestinal obstruction requiring multiple hospitalizations, and infertility. Moreover, adhesive disease can become a chronic medical condition with significant morbidity and no effective therapy. Despite recent advances in surgical techniques, there is no reliable strategy to manage postoperative adhesions. We herein review the pathophysiology and clinical significance of postoperative adhesions while highlighting current techniques of prevention and treatment.

Hepatocellular carcinoma development in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Is it going to be the "Plague" of the 21st century? A literature review focusing on pathogenesis, prevention and treatment.

Liver carcinogenesis in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) is a subject of intense research nowadays, since NAFLD is the most common chronic liver disease, affecting a great percentage of the population worldwide, while hepatocellular carcinoma (HCC), which represents the most common primary liver malignancy, is the third leading cause of cancer-related mortality. The underlying pathogenic pathways of both NAFLD and HCC are not completely understood, but there is growing evidence that they share many common pathophysiologic mechanisms and risk factors. Due to lack of solid evidence, though, the ultimate goal of designing effective diagnostic tools, treatment options and screening policies remain unmet for the time being. This review article aims to present recent data available regarding pathogenesis, diagnosis and management of HCC and NAFLD, as well as to highlight the importance of the development of HCC in the setting of NAFLD and NASH.

Tailoring the 'Perfect Fit' for Renal Transplant Recipients with End-stage Polycystic Kidney Disease: Indications and Timing of Native Nephrectomy.

BACKGROUND: The ideal timing of native nephrectomy in relation to kidney transplantation in patients with autosomal-dominant polycystic kidney disease (ADPKD) can be a very puzzling decision for transplant surgeons and remains a matter of debate. This review article aims to present current literature regarding this highly controversial issue. MATERIALS AND METHODS: The MEDLINE/PubMed database was searched using "polycystic kidney disease", "renal/kidney transplantation" and "native nephrectomy" as key words. Our search was focused on the optimal timing of and indications for native nephrectomy in renal transplant recipients with ADPKD. RESULTS: In symptomatic cases, pre-transplant unilateral or bilateral native nephrectomy seems appropriate, in order to alleviate symptoms. In cases that are provided with the option of living-donor transplantation, the performance of the simultaneous procedure could be of benefit. When the principal indication of native nephrectomy is the creation of space for the renal allograft, various studies highlight the safety of the simultaneous approach of either unilateral or bilateral nephrectomy. CONCLUSION: No consensus exists on the appropriate timing for native nephrectomy in patients with ADPKD. Several issues to be addressed in the decision-making process are the importance of residual diuresis, the longer operative time along with the associated prolonged ischemia time and higher complication rate of the combined procedure.

De Novo Renal Cell Carcinoma of Native Kidneys in Renal Transplant Recipients: A Single-center Experience.

BACKGROUND: The risk of renal cell carcinoma (RCC) development in renal transplant recipients is 15-100 times higher than in the general population. The majority of RCCs found in renal transplant recipients develop in the recipient's native kidneys, only 9% of tumors develop in the allograft itself. The mechanisms of development of RCC in native kidneys and renal allografts are not completely understood. We present our experience in renal transplant recipients with RCC of native kidneys providing valuable and clinically applicable treatment and follow-up data. PATIENTS AND METHODS: The records of 2,173 patients who underwent renal transplantation in our Department between March 1983 and December 2015 were retrospectively reviewed. Using these data, we analyzed the incidence and types of post-transplant RCCs, as well as their clinical courses, focusing on native malignancies. RESULTS: We found 11 RCCs (0.5%) during the observation period in native kidneys. The mean (±SD) follow-up period was 50.54±32.80 months. Four patients died during this period (36.4%). CONCLUSION: Most RCCs in renal transplant recipients are low-stage, low-grade tumors with a favorable prognosis. Their diagnosis is usually incidental. RCC development in the native kidney of renal transplant recipients is an early event, frequently observed within 4 to 5 years after transplantation. The different natural history of these tumors is still undefined. Further research is needed to determine whether these differences are due to particular molecular pathways or to biases in relation to the mode of diagnosis.