Mitochondrial function, grip strength, and activity are related to recovery of mobility after a total knee arthroplasty.

Low muscle quality and a sedentary lifestyle are indicators for a slow recovery after a total knee arthroplasty (TKA). Mitochondrial function is an important part of muscle quality and a key driver of sarcopenia. However, it is not known whether it relates to recovery. In this pilot study, we monitored activity after TKA using a wrist mounted activity tracker and assessed the relation of mitochondrial function on the rate of recovery after TKA. Additionally, we compared the increase in activity as a way to measure recovery to traditional outcome measures. Patients were studied 2 weeks before TKA and up to 6 months after. Activity was monitored continuously. Baseline mitochondrial function (citrate synthase and complex [CP] 1-5 abundance of the electron transport chain) was determined on muscle tissue taken during TKA. Traditional outcome measures (Knee Injury and Osteoarthritis Outcome Score [KOOS], timed up-and-go [TUG] completion time, grip, and quadriceps strength) were performed 2 weeks before, 6 weeks after, and 6 months after TKA. Using a multivariate regression model with various clinical baseline parameters, the following were significantly related to recovery: CP5 abundance, grip strength, and activity (regression weights 0.13, 0.02, and 2.89, respectively). During recovery, activity correlated to the KOOS-activities of daily living (ADL) score (r = 0.55, p = 0.009) and TUG completion time (r = -0.61, p = 0.001). Mitochondrial function seems to be related to recovery, but so are activity and grip strength, all indicators of sarcopenia. Using activity trackers before and after TKA might give the surgeon valuable information on the expected recovery and the opportunity to intervene if recovery is low.

Postoperative pain reduction by pre-emptive N-acetylcysteine: an exploratory randomized controlled clinical trial.

BACKGROUND: A new potential target for multimodal pain management is the group-II metabotropic glutamate receptor subtypes, which can be activated by N-acetylcysteine. We investigated whether pre-emptive administration of N-acetylcysteine leads to a reduction in postoperative pain after laparoscopic inguinal hernia repair. METHODS: Sixty American Society of Anesthesiologists I-II patients scheduled for elective inguinal hernia repair were randomized to receive either N-acetylcysteine (150 mg/kg) or placebo intravenously 1 hour before surgery. The primary outcome was the visual analogue score during movement in the morning (approximately 24 hours) after surgery. Among secondary outcomes were postoperative opioid consumption and safety of intravenous N-acetylcysteine. RESULTS: In total, 23 patients were analyzed per group. Pain scores were similar at all timepoints with a 24 hours median score of 34 (IQR of 19.0 to 42.5) in the N-acetylcysteine group and a median score of 26 (16.0 to 50.0) in the placebo group. The percentage of patients using opioids after surgery was 22% versus 39% day 1 (p=0.63); 9% versus 26% day 2 (p=0.14); 9% versus 17% day 3 (p=0.35) in the N-acetylcysteine group compared with placebo group. Side effects resembling anaphylactoid reactions in response to the administration of N-acetylcysteine were present in more than half of the patients. CONCLUSIONS: Without finding important differences between N-acetylcysteine and placebo group in pain scores postoperatively, but with a high percentage of bothersome side effects for the N-acetylcysteine group, we would not recommend the use of pre-emptive intravenous N-acetylcysteine to reduce postoperative pain in laparoscopic inguinal hernia repair patients based on this study. TRIAL REGISTRATION NUMBER: NCT03354572.

A cost-effectiveness analysis after implementation of a fast-track protocol for total knee arthroplasty.

BACKGROUND: Since the introduction of arthroplasty fast-track protocols, many studies have investigated their effect on complications and length of hospital stay. However, few fast-track studies have examined the long-term effects on cost and health-related quality of life after total knee arthroplasty (TKA). This study aimed to specifically analyze, after implementation of fast-track TKA, cost-effectiveness with functional outcome, length of stay, thromboembolic complications, medical costs, and quality of life after 12 months. METHODS: A retrospective cohort of 403 TKA patients treated by a fast-track pathway were compared with 283 patients in a non-fast-track pathway. Length of stay and thromboembolic complications were registered postoperatively. Healthcare costs were based on hospital production costs and calculated on average. Costs were compared with EQ-5D questionnaires to derived quality-adjusted life year (QALY) scores. RESULTS: No between-protocol differences were found in functional outcome and quality of life after TKA. The fast-track protocol reduced the length of stay from a median five days to median three days, and did not influence the thromboembolic complication rate (2.6%). After one-year follow-up for fast-track pathway patients, QALY was 0.85 vs. 0.84 for non-fast-track. A reduction of 268,- euro per patient was calculated in favor of the fast-track protocol. CONCLUSION: Fast-track protocol implementation is a cost-effective strategy for patients undergoing TKA, with high QALY and reduced costs. Fast-track TKA treatment is safe, with low thromboembolic complications. This is the first study to measure fast-track implementation effects on functional outcome and quality of life up to 12 months postoperatively, and calculate equivalent QALYs for both groups. LEVEL OF EVIDENCE: Level III.

Gastro-intestinal function and quality of life are favorable in adolescent and adult gastroschisis patients.

BACKGROUND AND AIMS: Studies on long-term sequelae of gastroschisis are scarce. The limited data suggest increased abdominal complaints in young children. To provide proper counseling for both parents and patients, more information on long-term outcome is needed. This study aims to evaluate long-term outcome regarding GI function, gastroesophageal reflux (GER), health-related quality of life (HRQoL) and cosmetic satisfaction. METHODS: An observational longitudinal cohort study was performed. All patients (N = 43) born between 1982 and 2008 with gastroschisis that were admitted to the University Medical Centre Utrecht, Wilhelmina Children's Hospital were invited to fill in a survey. Data of included patients were compared to validated Dutch reference standards. RESULTS: Fourteen patients responded to the survey. The median follow-up was 18 years. Abdominal pain on weekly basis was present in two patients (14%) and feeding difficulties were present in one patient. Presence of a complication during gastroschisis treatment led to more GI symptoms (80% versus 22%). One patient experienced moderate complaints of regurgitation or dyspepsia. Although the overall HRQoL was lower in teenage gastroschisis patients as compared to healthy controls (73/100 versus 83/100, respectively), we found no relevant difference in overall HRQoL in the other age groups. Seven patients (50%) were satisfied with the cosmetic result of the scar. CONCLUSIONS: GI function and HRQoL in gastroschisis patients seem similar to healthy controls at adolescent and adult age. Complications during gastroschisis treatment led to an increase of abdominal complaints later in life. The surgical technique had no significant effect on the cosmetic results.

Does early anterior cruciate ligament reconstruction prevent development of meniscal damage? Results from a secondary analysis of a randomised controlled trial.

OBJECTIVES: To determine development of new and worsening meniscal damage over 5 years after acute anterior cruciate ligament (ACL) injury comparing rehabilitation plus early ACL reconstruction ('early-ACLR') versus rehabilitation with optional delayed ACL reconstruction ('optional-delayed-ACLR'). METHODS: We used knee MRIs from the only randomised controlled trial in the field including 121 young adults. One musculoskeletal radiologist read baseline and 5-year follow-up images using the Anterior Cruciate Ligament Osteoarthritis Score (ACLOAS). We defined development (ie, new and worsening) of meniscal damage both dichotomously and as a sum score representing severity (based on the reclassified ACLOAS meniscus grades). In the full analysis set, we analysed development of meniscal damage (yes/no) with logistic regression and severity with zero-inflated Poisson regression and adjusted for age, sex and baseline meniscal damage. RESULTS: Over 5 years, new or worsening meniscal damage developed in 45% of subjects with early-ACLR and in 53% of subjects with optional-delayed-ACLR. The relative risk for development of meniscal damage on knee level was 1.3 (95% CI 0.9 to 1.9) in optional-delayed-ACLR versus early-ACLR. For medial and lateral meniscal damage, respectively, the relative risks were 2.1 (95% CI 1.1 to 3.9) and 1.0 (95% CI 0.6 to 1.5). The mean severity score was 1.5 higher (more severe damage) on knee level in optional-delayed-ACLR versus early-ACLR (95% CI 1.1 to 1.9) among those with meniscal damage at 5 years. For medial and lateral meniscal damage, respectively, the corresponding scores were 1.7 (95% CI 1.2 to 2.5) and 1.1 (95% CI 0.8 to 1.4). CONCLUSION: A strategy of early-ACLR may reduce development of medial meniscal damage following acute ACL injury. For the lateral meniscus, ACLR seems neither to be protective nor to increase the risk of damage. TRIAL REGISTRATION NUMBER: ISRCTN 84752559.

Combined intravenous, topical and oral tranexamic acid administration in total knee replacement: Evaluation of safety in patients with previous thromboembolism and effect on hemoglobin level and transfusion rate.

BACKGROUND: The aims of this study were to investigate the safety of combined intravenous, oral and topical tranexamic acid (TXA) in primary total knee replacement. We assessed dose-related efficacy on hemoglobin level, transfusion, length of stay and thromboembolic complications. In addition, TXA safety in patients with previous history of thromboembolism >12months ago was monitored specifically. METHODS: From January 2013 until January 2016, 922 patients were included who received TXA after primary total knee replacement. Patients without TXA administration or with thromboembolic events <12months ago were excluded. TXA dosage groups were divided into ≤10mg/kg, >10-25mg/kg and >25-50mg/kg. RESULTS: Between the three TXA groups no significant difference was found in thromboembolic complications (deep venous thrombosis (DVT) and pulmonary embolism (PE)), wound leakage and transfusion rate. For patients with DVT or PE in their history >12months ago specifically, no more complications were noted in higher-TXA-dosage groups compared to the low-dosage group. Length of stay was shorter in the highest-TXA-dosage group compared with lower-dosage groups (median two vs three days). With high TXA dose a smaller difference between pre- and postoperative Hb was found: the >25-50mg/kg TXA group had a 0.419mmol/l smaller decrease in postoperative hemoglobin compared to the lowest-dosage group (P<0.05). CONCLUSION: Combined intravenous, oral and topical TXA is effective in knee replacement and can safely be given to patients with a thromboembolic history >12months ago. High dosage (>25-50mg/kg) TXA resulted in the smallest decrease in postoperative hemoglobin.

Detecting Meniscal Tears in Primary Care: Reproducibility and Accuracy of 2 Weight-Bearing Tests and 1 Non-Weight-Bearing Test.

STUDY DESIGN: Diagnostic accuracy study using a cross-sectional design. OBJECTIVES: To determine the interexaminer reliability and the diagnostic accuracy in primary care of 1 existing weight-bearing meniscal test, the Thessaly test, 1 new weight-bearing test, the deep squat test, and 1 non-weight-bearing test, the joint-line tenderness test. BACKGROUND: Meniscal tears are difficult to detect in primary care. Although valuable in secondary care, weight-bearing physical examination tests require validation in primary care in unselected patients. METHODS: Between October 2009 and December 2013, 121 patients (age range, 18-65 years) seen in primary care and suspected of having internal derangement of the knee of less than 6 months in duration were included in the study. Diagnostic accuracy of the 3 meniscal tests was determined based on assessment with magnetic resonance imaging. The meniscal tests were performed by 3 trained physical therapists, who were not informed about the patient history and magnetic resonance imaging results. Each test was performed independently by 2 of the 3 trained physical therapists in alternating pairs. RESULTS: The Thessaly test and the deep squat test had a moderate level of interexaminer reliability, with kappas of 0.54 and 0.46, respectively. The joint-line tenderness test had poor interexaminer reliability and was therefore not assessed for diagnostic accuracy. The following results are reported separately for both examiners. The Thessaly test had a sensitivity of 66.7% (95% confidence interval [CI]: 53.0%, 78.0%) and 51.2% (95% CI: 36.8%, 65.4%), a specificity of 37.9% (95% CI: 27.2%, 50.0%) and 43.5% (95% CI: 30.2%, 57.8%), a positive likelihood ratio of 1.07 (95% CI: 0.82, 1.41) and 0.91 (95% CI: 0.62, 1.33), and a negative likelihood ratio of 0.88 (95% CI: 0.54, 1.45) and 1.12 (95% CI: 0.72, 1.76). Similarly, the deep squat test had a sensitivity of 74.5% (95% CI: 61.1%, 84.5%) and 76.7% (95% CI: 62.3%, 86.9%), a specificity of 42.4% (95% CI: 31.2%, 54.4%) and 36.2% (95% CI: 24.0%, 50.5%), a positive likelihood ratio of 1.29 (95% CI: 0.97, 1.68) and 1.20 (95% CI: 0.92, 1.58), and a negative likelihood ratio of 0.60 (95% CI: 0.35, 1.04) and 0.64 (95% CI: 0.33, 1.25). CONCLUSION: Although the Thessaly and deep squat tests have a moderate level of reliability, neither test is sufficiently accurate to help in the diagnosis of meniscal tears in primary care. Future research should focus on other relevant patient variables instead of on physical examination tests in the detection of meniscal tears. LEVEL OF EVIDENCE: Diagnosis, level 3b.

Risk factors for meniscal tears: a systematic review including meta-analysis.

STUDY DESIGN: Systematic review with meta-analysis. OBJECTIVES: To review and critically appraise the literature for factors that increase the risk for meniscal tears. BACKGROUND: Meniscal tears are an important cause of disability and time lost from work, and are associated with a 4-fold increase in the long-term risk of knee osteoarthritis. Knowledge of the risk factors that lead to meniscal tears can help to correctly diagnose knee injuries and is important to the development of prevention strategies for knee osteoarthritis. METHODS: A search of the Cochrane Database of Systematic Reviews, MEDLINE, and Embase, from 1950 to January 2012, and a hand search of reference lists of all initially selected studies, without restriction on language or date of publication, were conducted. Prospective, retrospective, and case-control studies that included individuals over 16 years of age, who had no previous meniscal injuries or surgeries, were selected. A meta-analysis for 17 risk factors was performed. Where considerable heterogeneity among studies was present or the data did not provide sufficient information to perform a meta-analysis, a qualitative synthesis was conducted. RESULTS: Eleven studies, with a total of 7358 participants, were selected for systematic review. Data were available for meta-analysis for 10 of the 11 studies. Qualitative analysis was conducted using data from 3 of the 11 studies. Results showed strong evidence that age (older than 60 years), gender (male), work-related kneeling and squatting, and climbing stairs (greater than 30 flights) were risk factors for degenerative meniscal tears. We also found strong evidence that playing soccer and playing rugby were strong risk factors for acute meniscal tears. Waiting longer than 12 months between the anterior cruciate ligament injury and reconstructive surgery was a strong risk factor for a medial meniscal tear but not for a lateral meniscal tear. CONCLUSION: The literature indicates a number of risk factors leading to either degenerative or acute meniscal tears, with some of these factors being potentially modifiable. LEVEL OF EVIDENCE: Prognosis, level 2a.