9. Chronic knee pain.

INTRODUCTION: Chronic knee pain is defined as pain that persists or recurs over 3 months. The most common is degenerative osteoarthritis (OA). This review represents a comprehensive description of the pathology, diagnosis, and treatment of OA of the knee. METHODS: The literature on the diagnosis and treatment of chronic knee pain was retrieved and summarized. A modified Delphi approach was used to formulate recommendations on interventional treatments. RESULTS: Patients with knee OA commonly present with insidious, chronic knee pain that gradually worsens. Pain caused by knee OA is predominantly nociceptive pain, with occasional nociplastic and infrequent neuropathic characteristics occurring in a diseased knee. A standard musculoskeletal and neurological examination is required for the diagnosis of knee OA. Although typical clinical OA findings are sufficient for diagnosis, medical imaging may be performed to improve specificity. The differential diagnosis should exclude other causes of knee pain including bone and joint disorders such as rheumatoid arthritis, spondylo- and other arthropathies, and infections. When conservative treatment fails, intra-articular injections of corticosteroids and radiofrequency (conventional and cooled) of the genicular nerves have been shown to be effective. Hyaluronic acid infiltrations are conditionally recommended. Platelet-rich plasma infiltrations, chemical ablation of genicular nerves, and neurostimulation have, at the moment, not enough evidence and can be considered in a study setting. The decision to perform joint-preserving and joint-replacement options should be made multidisciplinary. CONCLUSIONS: When conservative measures fail to provide satisfactory pain relief, a multidisciplinary approach is recommended including psychological therapy, integrative treatments, and procedural options such as intra-articular injections, radiofrequency ablation, and surgery.

Complex regional pain syndrome of the knee after conventional radiofrequency ablation of the genicular nerves treated successfully with dorsal root ganglion stimulation: A case report.

BACKGROUND: Radiofrequency (RF) treatment of the genicular nerves offers pain relief in patients suffering from chronic knee pain including persistent post-surgical knee pain (PPSP). We present the first case report of the development of complex regional pain syndrome (CRPS) in a chronic knee pain patient after an RF ablation of the genicular nerves that was successfully treated with dorsal root ganglion (DRG) stimulation. CASE PRESENTATION: The patient developed increased pain, sympathetic and dysmorphic changes of the index knee 10 weeks after RF treatment for PPSP. Diagnosis of CRPS type II was made using positive clinical findings and the Budapest diagnostic tool. Laboratory workup and PET-CT were negative. The patient was refractory to usual care and she was treated successfully with dorsal ganglion root stimulation. CONCLUSIONS: Complex regional pain syndrome is a possible complication of RF ablation of the genicular nerves in patients with chronic knee pain, and DRG stimulation may be a treatment option. Physicians should be aware of this complication, especially when patients have a medical history of CRPS.

A retrospective study on patients with chronic knee pain treated with ultrasound-guided radiofrequency of the genicular nerves (RECORGEN trial).

INTRODUCTION: Radiofrequency (RF) treatment of the genicular nerves is a promising treatment for chronic osteoarthritic and persistent postsurgical knee pain (PPSP), refractory to conventional medical management. METHODS: The RECORGEN study is a retrospective single-center cohort study of patients treated with ultrasound-guided conventional RF of the genicular nerves for chronic knee pain in Hospital Oost-Limburg, Genk from September 2017 to June 2020. Subgroup analysis based on etiology of pain (PPSP and degenerative knee pain) was performed in addition to the total study population analysis. Outcome parameters were global perceived effect (GPE), Numeric Rating Scale for pain, consumption of strong opioids, and safety of the treatment at 6 weeks and cross-sectionally at a variable time point. Treatment success was defined as GPE≥50%. RESULTS: Sixty-eight cases were screened of which 59 (46 diagnosed with PPSP and 13 with degenerative knee pain) were included in the study. Treatment success at 6 weeks was achieved in 19 of 59 interventions (32.2%) and was similar in both groups. Seventeen responders were evaluated at follow-up. 45.1% (8/17) continued to have a positive effect at the second time point. The mean duration of effect of the RF treatment was 8.3 months. Safety analysis at 6 weeks and at the second time point showed a good safety profile of the treatment. CONCLUSION: Conventional RF of the genicular nerves was clinically successful in more than 30% of the study population refractory to conventional medical management. Overall, the treatment was well tolerated. The mean duration of effect was 8.3 months.

Cooled versus conventional radiofrequency treatment of the genicular nerves for chronic knee pain: 12-month and cost-effectiveness results from the multicenter COCOGEN trial.

BACKGROUND: Radiofrequency (RF) treatment of the genicular nerves reduces chronic knee pain in patients with osteoarthritis (OA) or persistent postsurgical pain (PPSP) after total knee arthroplasty (TKA). The objective of this study is to compare long-term outcomes of cooled and conventional RF and perform an economic evaluation. METHODS: The COCOGEN trial is a double-blinded, non-inferiority, pilot, randomized controlled trial that compared the effects up to 12 months of cooled and conventional RF in patients with chronic knee pain suffering from OA or PPSP after TKA following a 1:1 randomization rate. Outcomes were knee pain, functionality, quality of life, emotional health, medication use, and adverse events. A trial-based economic evaluation was performed with a 12-month societal perspective. Here, the primary outcome was the incremental costs per quality-adjusted life year (QALY). RESULTS: 41 of the 49 included patients completed the 12-month follow-up. One patient in the PPSP cooled RF group had substantial missing data at 12-month follow-up. The proportion of patients with ≥50% pain reduction at 12 months was 22.2% (4/18) in patients treated with conventional RF versus 22.7% (5/22) in patients treated with cooled RF (p>0.05). There was a statistically significant difference in the mean absolute numerical rating scale at 12 months after cooled RF and conventional RF in patients with PPSP (p=0.02). Differences between other outcomes were not statistically significant. The health economic analysis indicated that cooled RF resulted in lower costs and improved QALYs compared with conventional RF in PPSP but not in OA. There were no serious adverse events. CONCLUSIONS: Both RF treatments demonstrated in approximately 22% of patients a ≥50% pain reduction at 12 months. In patients with PPSP, contrary to OA, cooled RF seems to be more effective than conventional RF. Additionally, cooled RF has in patients with PPSP, as opposed to OA, greater effectiveness at lower costs compared with conventional RF. TRIAL REGISTRATION NUMBER: NCT03865849.

Comparison of conventional and cooled radiofrequency treatment of the genicular nerves versus sham procedure for patients with chronic knee pain: protocol for a multicentre, double-blind, randomised controlled trial (COGENIUS).

INTRODUCTION: The prevalence of chronic knee pain is increasing. Osteoarthritis (OA) and persistent postsurgical pain (PPSP) are two important causes of knee pain. Chronic knee pain is primarily treated with medications, physiotherapy, life-style changes and intra-articular infiltrations. A radiofrequency treatment (RF) of the genicular nerves is a therapeutical option for refractory knee pain. This study investigates the effectiveness and cost-effectiveness of conventional and cooled RF in patients suffering from chronic, therapy resistant, moderate to severe knee pain due to OA and PPSP. METHODS AND ANALYSIS: The COGENIUS trial is a double-blinded, randomised controlled trial with 2-year follow-up. Patients and outcome assessors are blinded. Patients will be recruited and treated in Belgium and the Netherlands. All PPSP after a total knee prothesis and OA patients (grades 2-4) will undergo a run-in period of 1-3 months where conservative treatment will be optimised. After the run-in period, 200 patient per group will be randomised to conventional RF, cooled RF or a sham procedure following a 2:2:1 ratio. The analysis will include a comparison of the effectiveness of each RF treatment with the sham procedure and secondarily between conventional and cooled RF. All comparisons will be made for each indication separately. The primary outcome is the Western Ontario and McMaster Universities Osteoarthritis Index score at 6 months. Other outcomes include knee pain, physical functionality, health-related quality of life, emotional health, medication use, healthcare and societal cost and adverse events up to 24 months postintervention. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee of the University of Antwerp (Number Project ID 3069-Edge 002190-BUN B3002022000025), the Ethics committee of Maastricht University (Number NL80503.068.22-METC22-023) and the Ethics committee of all participating hospitals. Results of the study will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05407610.

Comparison of cooled versus conventional radiofrequency treatment of the genicular nerves for chronic knee pain: a multicenter non-inferiority randomized pilot trial (COCOGEN trial).

BACKGROUND: Radiofrequency (RF) treatment of the genicular nerves has the potential to reduce chronic knee pain due to osteoarthritis or persistent postsurgical pain, however, a direct comparison between the two main modalities used, conventional and cooled, is lacking. METHODS: This double blind, non-inferiority, pilot, randomized controlled trial compared the effects of cooled and conventional RF in chronic knee pain patients suffering from osteoarthritis or persistent postsurgical pain after total knee arthroplasty. Patients were randomized following a 1:1 rate. The primary outcome was the proportion of patients with ≥50% pain reduction at 3 months postintervention. Other outcomes were knee pain, functionality, quality of life, emotional health, and adverse events up to 6 months postintervention. Conventional RF treatment was tested for non-inferiority to cooled in reducing knee pain at 3 months follow-up. RESULTS: Forty-nine of 70 patients were included, of which 47 completed a 3-month follow-up. The primary outcome was achieved in 4 of 23 patients treated with conventional RF (17%) vs in 8 of 24 with cooled (33%) (p=0,21). Results from the non-inferiority comparison were inconclusive in relation to the non-inferiority margin. There was no statistically significant difference between secondary outcomes. There were no serious adverse events. CONCLUSIONS: Both conventional and cooled RF treatment reduced pain in the osteoarthritis and persistent postsurgical pain population. This pilot study did not demonstrate statistically significant differences in the proportion of patients experiencing ≥50% pain reduction between techniques. The non-inferiority analysis was inconclusive. These results warrant further research. TRIAL REGISTRATION NUMBER: NCT03865849.

Role of resuscitation ratio in monitoring burn patients.

INTRODUCTION: Efforts with the utilization of an Input/Output ratio (I/O ratio) are done with success for analyzing and moving forward the treatment in the resuscitation phase of the burn patient. The need for conducting this research is to apply the I/O ratio in our cohort as a helpful index for classifying the resuscitation response of the burn patients. Our prespecified hypothesis is if it matters the analysis of the I/O ratio at 8 h of fluid resuscitation period. MATERIAL AND METHOD: This prospective observational study was performed in 50 patients (22 adults and 28 children) admitted in the Intensive Care of the Service of Burns in Tirana, Albania in the period January to December 2016. We calculated the I/O ratio at 8 h and the end of the 1st 24 h based on the stratification of patients according to the ratio in respective groups. In the adult population we did an analysis whereby the ratio I/O at 8 h has a relationship with the 24 h results as well as with ICU-free days. RESULTS: The 24 h fluid resuscitation was done with the majority clustered in the range 2-4 ml/kg/% TBSA with fluid-weight score (ml/kg) correlated with % TBSA. After calculation of the I/O ratio at 8 h, 29 patients were assigned in over-responders (<0.166), 16 patients in the expected group(0.166-0.334), and 5 patients were assigned in under-responders (>0.334). There is a strong correlation between the I/O ratio at 8 h and the I/O ratio at 24 h and I/O ratio predict better the longer ICU-free days. CONCLUSIONS: The I/O ratio is a very useful parameter not only at 12 h and 24 h but also at 8 h after burns. By classifying the patients into outcome groups that reflect not only the volume given but moreover the physiologic reactions to the resuscitation volume gotten, we were more attentive to patients in under-responders at 8 h. This parameter fulfills the criteria for better classifying patients and a better understanding of the physiology of burns.

Effectiveness of maintenance therapy with methotrexate compared with leflunomide for patients with RA having achieved disease control with both these drugs: results of a predefined sub-analysis of CareRA, a pragmatic RCT.

INTRODUCTION/OBJECTIVES: Evidence regarding the effectiveness of step-down strategies for patients with well-controlled early rheumatoid arthritis (RA) on a combination of methotrexate (MTX) and leflunomide (LEF) is currently lacking. METHOD: The Care in early RA (CareRA) trial is a 2-year randomized pragmatic trial comparing different remission induction strategies in treatment-naïve patients with early RA. For this study, we included participants who achieved low disease activity (LDA) (DAS28-CRP ≤ 3.2) between 40 to 52 weeks after starting a combination of MTX, LEF, and a prednisone bridging scheme followed by a treat-to-target approach. Patients were re-randomized to a maintenance monotherapy of either MTX 15 mg weekly or LEF 20 mg daily. Remission rates (DAS28-CRP < 2.6) at week 65 counted from re-randomization, as well as drug retention rates and safety during the 65 weeks of follow-up, were compared. RESULTS: Remission rates at week 65 after re-randomization were numerically higher in patients assigned to MTX (29/32; 90.6%) compared with patients on LEF (20/27; 74.1%) (p = 0.091). Of patients assigned to MTX, 60% (19/32) maintained LDA while continuing their assigned monotherapy until week 65 after re-randomization versus 44% (12/27) in the LEF group (p = 0.25). Patients re-randomized to MTX were more frequently in LDA measured by Clinical Disease Activity Index (32/32; 100%) compared with patients on LEF (23/27; 85.2%) (p = 0.024) 65 weeks after re-randomization. According to survival analyses, the probability of maintaining MTX monotherapy was higher (81%) than maintaining LEF monotherapy (55%) for 65 weeks (p = 0.025) after re-randomization. Safety analysis after re-randomization showed a good safety profile in both groups. CONCLUSION: MTX monotherapy seems not significantly more efficacious as maintenance treatment compared with LEF monotherapy but has a better retention rate and is well tolerated in early RA patients in LDA after combination therapy with both. TRIAL REGISTRATION: Clinical trials NCT01172639 Key points • Methotrexate should be preferred over leflunomide as maintenance therapy after an initial intensive combination of these two drugs. • Methotrexate shows a better retention rate to leflunomide as maintenance therapy in this context.

Epidemiology and outcome analysis of sepsis and organ dysfunction/failure after burns.

BACKGROUND: The aim of this prospective study in adult population is to give frequency data (prevalence, incidence) of burn wound sepsis and its consequences (organ dysfunction/failure); to analyze the evolution of the SOFA cumulative score during the disease and relationship between the SOFA score in the 3rd, 7th, 14th and 21th day after burn with mortality. METHOD: A prospective cohort study was performed among adult patients (age ≥20 years) admitted in the ICU, with major and moderate burns. Sepsis, organ dysfunction, organ failure and mortality were calculated as Cumulative Incidence (CI) and as Incidence rate (IR). Data from patients with sepsis were compared with those without sepsis. Evaluation of SOFA evolution was done with delta score and the influence of the SOFA score in mortality was calculated with AUC of the ROC curve. RESULTS AND CONCLUSIONS: Period prevalence of sepsis in our adult burned population was 26%. Incidence proportion as CI was 0.3 or 30 patients per 100 adults. Incidence rate (IR) was 6 patients with sepsis per 100 patient-years. Overall morbidity was 88.1% while overall mortality was 11.9%. Mortality in patients with sepsis was 34.4%. Incidence of MOD was 63% while incidence of MOF was 37%. Respective mortality as CI was 7% and 81% while mortality rate as IR was 1.4 per 100 patient-years in patients with MOD and 16.2 per 100 patient-years in patients with MOF. SOFA-3 should be considered a "reliable indicator" at separating survivors from non survivors and SOFA 7, 14, and 21 should be considered excellent in predicting mortality.

Epidemiology of infections in a burn unit, Albania.

BACKGROUND: Many types of nosocomial infections (NIs) can be present in the burned patient. The purpose of this study is to calculate the rates for NI in the Intensive Care Unit of the Service of Burns and Plastic Surgery in University Hospital Centre (UHC) in Tirana, Albania. METHOD: The study is prospective, clinical and analytical. The study is continued/longitudinal because monitors all patients with severe burns during a specified time period (1year). For data analysis was used SPSS 19.0. RESULTS: The infection prevalence rate was 12 infected patients per 100 patients. The colonisation prevalence rate was 43 colonised patients for 100 patients. The most frequent infection microorganisms were Pseudomonas aeruginosa and Staphylococcus aureus (67% and 24%). Incidence of BSI was 3 BSI for 1000 hospitalization days. Incidence of catheter-related bloodstream infection (CRBSI) was 11.7 BSI for 1000 catheter days. Colonisation of the tip of the central catheter (CTC) was 15.6 for 1000 catheter days. CONCLUSIONS: The epidemiology of burn wound infections as well as the definitions have changed due to important changes in burn wound treatment but further studies should be done documented the factors that can reduce the burn wound infection rates.