The impact of primary total hip and knee replacement on frailty: an observational prospective analysis.

BACKGROUND: Osteoarthritis is a prevalent condition in frail older adults that requires hip or knee replacement in many patients. The aim of the study was to determine the impact of hip and knee arthroplasty on frailty. METHODS: In this prospective short-term study, we used data from 101 participants of the ongoing Special Orthopaedic Geriatrics (SOG) trial, funded by the German Federal Joint Committee (GBA). Frailty, measured by Fried's Physical Frailty Phenotype (PFP), was assessed preoperatively, 7 days postoperatively, 4-6 weeks and 3 months after hip and knee arthroplasty. ANOVA with repeated measures and post-hoc tests for the subgroups were used for the statistical analysis. RESULTS: Of the 101 participants, 50 were pre-frail (1-2 PFP criteria) and 51 were frail (≥ 3 PFP criteria) preoperatively. In the pre-frail group, the PFP score decreased from 1.56 ± 0.50 (median 2) preoperatively to 0.53 ± 0.73 (median 0) 3 months after surgery (p < 0.001). The PFP score in the frail cohort decreased from 3.39 ± 1.45 (median 3) preoperatively to 1.27 ± 1.14 (median 1) 3 months postoperatively (p < 0.001). While the PFP score of the pre-frail participants increased 7 days after surgery, the PFP score of the frail group decreased significantly. CONCLUSION: Pre-frail individuals often regain robustness and patients with frailty are no longer assessed as frail after surgery. Joint replacement is an effective intervention to improve frailty in hip and knee osteoarthritis. TRIAL REGISTRATION: This study is part of the Special Orthopaedic Geriatrics (SOG) trial, German Clinical Trials Register DRKS00024102. Registered on 19 January 2021.

[Structured approach for infected prosthesis]. / Strukturiertes Vorgehen bei infizierter Prothese.

BACKGROUND: Endoprosthesis infections represent a major challenge for doctors and patients. Due to the increase in endoprosthesis implantation because of the increasing life expectancy, an increase in endoprosthesis infections is to be expected. In addition to infection prophylaxis, methods of infection control become highly relevant, especially in the group of geriatric and multimorbid patients. The aim is to reduce the high 1­year mortality from prosthesis infections through a structured algorithm. ALGORITHM FOR PROSTHESIS INFECTIONS: Prosthesis infections can basically be divided into early and late infections. According to the criteria of the International Consensus Meeting, a late infection is defined as the occurrence more than 30 days after implantation. With respect to the planned approach, the (p)TNM classification offers an orientation. In the early postoperative interval the clinical appearance is crucial as in this phase neither laboratory parameters nor an analysis of synovial fluid show a high sensitivity. It is fundamental that, apart from patients with sepsis, environment diagnostics should be initiated. If a late infection is suspected, in addition to radiological diagnostics (X-ray, skeletal scintigraphy and if necessary, computed tomography, CT), laboratory (C-reactive protein, CRP, leukocytes, blood sedimentation, and if necessary, interleukin­6, procalcitonin) and microbiological diagnostics (arthrocentesis with synovial analysis and microbiology) are indicated; however, in addition to the arthrocentesis result, the clinical appearance is crucial in cases where an exclusion cannot be confirmed by laboratory parameters. If an infection is confirmed, the treatment depends on the spectrum of pathogens, the soft tissue situation and the comorbidities, including a multistage procedure with temporary explantation and, if necessary, implantation of an antibiotic-containing spacer is necessary. A prosthesis preservation using the debridement, antibiotics and implant retention (DAIR) regimen is only appropriate in an acute infection situation. Basically, radical surgical debridement should be carried out to reduce the pathogen load and treatment of a possible biofilm formation for both early and late infections. The subsequent antibiotic treatment (short or long interval) should be coordinated with the infectious disease specialists. CONCLUSION: A structured approach for prosthesis infections oriented to an evidence-based algorithm provides a sufficient possibility of healing. An interdisciplinary approach involving cooperation between orthopedic and infectious disease specialists has proven to be beneficial. Surgical treatment with the aim of reducing the bacterial load by removing the biofilm with subsequent antibiotic treatment is of intrinsic importance.

No Success without Effort: Follow-Up at Six Years after Implementing a Benchmarking and Feedback Concept for Postoperative Pain after Total Hip Arthroplasty.

BACKGROUND: Total hip arthroplasty (THA) is still ranked among the operations with the highest postoperative pain scores. Uncontrolled postsurgical pain leads to prolongated hospital stays, causes more frequent adverse reactions and can induce chronical pain syndromes. In 2014, we implemented a standardized, multidisciplinary pain management concept with continuous benchmarking at our tertiary referral center by using the "Quality Improvement in Postoperative Pain Management" (QUIPS) program with excellent results over a period of two years. The initial study ended in 2016 and we aimed to evaluate if it was possible to obtain the excellent short-term results over a period of six years without any extra effort within the daily clinical routine. MATERIALS AND METHODS: In a retrospective study design, we compared postoperative pain, side effects and functional outcome after primary THA for 2015 and 2021, using validated questionnaires from the QUIPS project. In contrast to the implementation of the pain management concept in 2014, the weekly meetings of the multidisciplinary health care team and special education for nurses were stopped in 2021. Data assessment was performed by an independent pain nurse who was not involved in pain management. RESULTS: Altogether, 491 patients received primary THA in 2015 and 2021 at our tertiary referral center. Collected data revealed significantly worse maximum and activity-related pain (both p < 0.001) in combination with significantly higher opioid consumption in comparison to implementation in 2015. Though the patients reported to be less involved in pain management (p < 0.001), the worse pain scores were not reflected by patient satisfaction which remained high. While the participation rate in this benchmarking program dropped, we still fell behind in terms of maximum and activity-related pain in comparison to 24 clinics. CONCLUSION: Significantly worse pain scores in combination with higher opioid usage and a lower hospital participation rate resemble a reduced awareness in postoperative pain management. The significantly lower patient participation in pain management is in line with the worse pain scores and indirectly highlights the need for special education in pain management. The fact patient satisfaction appeared to remain high and did not differ significantly from 2015, as well as the fact we still achieved an acceptable ranking in comparison to other clinics, highlight the value of the implemented multidisciplinary pain management concept.

Special orthopaedic geriatrics (SOG) - a new multiprofessional care model for elderly patients in elective orthopaedic surgery: a study protocol for a prospective randomized controlled trial of a multimodal intervention in frail patients with hip and knee replacement.

BACKGROUND: Due to demographic change, the number of older people in Germany and worldwide will continue to rise in the coming decades. As a result, the number of elderly and frail patients undergoing total hip and knee arthroplasty is projected to increase significantly in the coming years. In order to reduce risk of complications and improve postoperative outcome, it can be beneficial to optimally prepare geriatric patients before orthopaedic surgery and to provide perioperative care by a multiprofessional orthogeriatric team. The aim of this comprehensive interventional study is to assess wether multimorbid patients can benefit from the new care model of special orthopaedic geriatrics (SOG) in elective total hip and knee arthroplasty. METHODS: The SOG study is a registered, monocentric, prospective, randomized controlled trial (RCT) funded by the German Federal Joint Committee (GBA). This parallel group RCT with a total of 310 patients is intended to investigate the specially developed multimodal care model for orthogeriatric patients with total hip and knee arthroplasty (intervention group), which already begins preoperatively, in comparison to the usual orthopaedic care without orthogeriatric co-management (control group). Patients ≥70 years of age with multimorbidity or generally patients ≥80 years of age due to increased vulnerability with indication for elective primary total hip and knee arthroplasty can be included in the study. Exclusion criteria are age < 70 years, previous bony surgery or tumor in the area of the joint to be treated, infection and increased need for care (care level ≥ 4). The primary outcome is mobility measured by the Short Physical Performance Battery (SPPB). Secondary outcomes are morbidity, mortality, postoperative complications, delirium, cognition, mood, frailty, (instrumental) activities of daily living, malnutrition, pain, polypharmacy, and patient reported outcome measures. Tertiary outcomes are length of hospital stay, readmission rate, reoperation rate, transfusion rate, and time to rehabilitation. The study data will be collected preoperative, postoperative day 1 to 7, 4 to 6 weeks and 3 months after surgery. DISCUSSION: Studies have shown that orthogeriatric co-management models in the treatment of hip fractures lead to significantly reduced morbidity and mortality rates. However, there are hardly any data available on the elective orthopaedic care of geriatric patients, especially in total hip and knee arthroplasty. In contrast to the care of trauma patients, optimal preoperative intervention is usually possible. TRIAL REGISTRATION: German Clinical Trials Register DRKS00024102. Registered on 19 January 2021.

Early Tumor Size Reduction of at least 10% at the First Follow-Up Computed Tomography Can Predict Survival in the Setting of Advanced Melanoma and Immunotherapy.

RATIONALE AND OBJECTIVES: Early tumor size reduction (TSR) has been explored as a prognostic factor for survival in patients with advanced melanoma in clinical trials. The purpose of this analysis is to validate, in a routine clinical milieu, the predictive capacity of TSR by 10% for overall survival (OS) and progression-free survival (PFS) and to compare its predictive performance with the RECIST 1.1 criteria. MATERIALS AND METHODS: This retrospective study was approved by the local ethics committee. A total of 152 patients with both CT before immunotherapy initiation and at first response evaluation after immunotherapy initiation were included. Prior to statistical analysis, treatment response was trichotomized as follows: Complete response and/or partial response, stable disease and progressive disease. Furthermore, response was dichotomized regarding TSR (TSR ≥ 10% and TSR < 10%). Kaplan-Meier survival estimates, Cox regression and Harrel's concordance index (C-index) were computed for prediction of overall survival and progression-free survival. RESULTS: Tumor size reduction by at least 10% significantly differentiated between patients with increased survival from the ones with decreased survival (median OS: TSR ≥ 10%: 2137 days vs. TSR < 10%: 263 days) (p < 0.001) (median PFS: TSR ≥ 10%: 590 days vs. TSR < 10%: 11 days) (p < 0.001). RECIST 1.1. criteria had a slightly higher C-index for overall survival reflecting a slight superior predictive capacity (RECIST: 0.69 vs TSR: 0.64) but a similar predictive capacity regarding progression-free survival (both: 0. 63). CONCLUSION: Early tumor size reduction serves as a simple-to-use metric which can be implemented on the first follow-up CT. Tumor size reduction by at least 10% can be considered an additional biomarker predictive of overall survival and progression-free survival in routine clinical care and not only in the context of clinical trials in patients with advanced melanoma undergoing immunotherapy. Nevertheless, RECIST-based criteria should remain the main tool of treatment response assessment until results of prospective studies validating the TSR method are available.

Pretreatment metastatic growth rate determines clinical outcome of advanced melanoma patients treated with anti-PD-1 antibodies: a multicenter cohort study.

BACKGROUND: Checkpoint inhibitors revolutionized the treatment of metastatic melanoma patients. Although tumor burden and lactate dehydrogenase (LDH) are associated with overall survival (OS), the impact of tumor growth kinetics remains elusive and in part contradictory. The aims of this study were to develop a novel simple and rapid method that estimates pretreatment metastatic growth rate (MGR) and to investigate its prognostic impact in melanoma patients treated with antiprogrammed death receptor-1 (PD-1) antibodies. METHODS: MGR was assessed in three independent cohorts of a total of 337 unselected consecutive metastasized stage IIIB-IV melanoma patients (discovery cohort: n=53, confirmation cohort: n=126, independent multicenter validation cohort: n=158). MGR was computed during the pretreatment period before initiation of therapy with anti-PD-1 antibodies nivolumab or pembrolizumab by measuring the increase of the longest diameter of the largest target lesion. Tumor doubling time served as quality control. Kaplan-Meier analysis and univariable as well as multivariable Cox regression were used to examine the prognostic impact of MGR. RESULTS: Pretreatment MGR >3.9 mm/month was associated with impaired OS in the discovery cohort (HR 6.19, 95% CI 2.92 to 13.10, p<0.0001), in the confirmation cohort (HR 3.62, 95% CI 2.19 to 5.98, p<0.0001) and in the independent validation cohort (HR 2.57, 95% CI 1.56 to 4.25, p=0.00023). Prior lines of systemic treatment did not influence the significance of MGR. Importantly, the prognostic impact of MGR was independent of total tumor burden, diameter of the largest metastasis, number of prior lines of systemic treatment, LDH, as well as liver and brain metastasis (discovery and confirmation cohorts: both p<0.0001). Superiority of MGR compared with these variables was confirmed in the independent multicenter validation cohort (HR 2.92, 95% CI 1.62 to 5.26, p=0.00036). CONCLUSIONS: High pretreatment MGR is an independent strong prognostic biomarker associated with unfavorable survival of melanoma patients receiving anti-PD-1 antibodies. Further investigations are warranted to assess the predictive impact of MGR in distinct systemic therapeutic regimens.

Baseline clinical and imaging predictors of treatment response and overall survival of patients with metastatic melanoma undergoing immunotherapy.

PURPOSE: We aimed to identify predictive clinical and CT imaging biomarkers and assess their predictive capacity regarding overall survival (OS) and treatment response in patients with metastatic melanoma undergoing immunotherapy. METHODS: The local institutional ethics committee approved this retrospective study and waived informed patient consent. 103 patients with immunotherapy for metastatic melanoma were randomly divided into training (n = 69) and validation cohort (n = 34). Baseline tumor markers (LDH, S100B), baseline CT imaging biomarkers (tumor burden, Choi density) and CT texture parameters (Entropy, Kurtosis, Skewness, uniformity, MPP, UPP) of the largest target lesion were extracted. To identify treatment response predictors, binary logistic regression analysis was performed in the training cohort and tested in the validation cohort. For OS, Cox regression and Kaplan Maier analyses were performed in the training cohort. Bivariate and multivariate models were established. Goodness of fit was assessed with Harrell's C-index. Potential predictors were tested in the validation cohort also using Cox-regression and Kaplan-Meier analyses. RESULTS: Baseline S100B (Hazard ratio(HR) = 2.543, p0.018), tumor burden (HR = 1.657, p = 0.002) and Kurtosis (HR = 2.484, p < 0.001) were independent predictors of OS and were confirmed in the validation cohort (p < 0.048). Tumor burden and Kurtosis showed incremental predictive capacity allowing a good predictive model when combined with baseline S100B levels (C-index = 0.720). Only S100B was predictive of treatment response (OR ≤ 0.630, p ≤ 0.022). Imaging biomarkers did not predict treatment response. CONCLUSION: We identified easily obtainable baseline clinical (S100B) and CT predictors (tumor burden and Kurtosis) of OS in patients with metastatic melanoma undergoing immunotherapy. However, imaging predictors did not predict treatment response.