Blood donation and migraine relief: A national population cohort study in Denmark.

INTRODUCTION: Migraine is a prevalent neurological headache disorder. Due to challenges associated with finding effective treatment, many individuals with migraine feel compelled to explore alternative treatment strategies, such as blood donation, hypothesized to provide migraine relief. METHODS: Through logistic, Poisson, and Cox regression methods, we examined the links between migraine and blood donation activities in two population cohorts: Danish blood donors in the Scandinavian Donations and Transfusions Database (SCANDAT-DK, N >1 million) and the Danish Blood Donor Study (N ~ 100,000). RESULTS: SCANDAT-DK analyses showed no link between migraine and the propensity to become a blood donor among males (odds ratio [OR]Males = 0.95 [95% Confidence Interval: 0.86-1.04], and a reduced propensity among females ORFemales = 0.88 [0.83-0.93]). The incidence of migraine was not reduced upon blood donation (standardized incidence ratio [SIR]Males = 0.94 [0.83-1.06]; SIRFemales = 1.04 [0.99-1.10]). Donors with migraine demonstrated longer intervals between donations (hazard ratio [HR]Males = 0.87 [0.85-0.91], HRFemales = 0.80 [0.78-0.82]), and an increased risk of donor lapse (ORMales = 1.23 [1.14-1.32]; ORFemales = 1.28 [1.22-1.33]). Results were corroborated in DBDS using self-reported migraine. Genetic predisposition to migraine associated with longer intervals in females (HRFemales = 0.98 [0.97-0.99]), but not in males. DISCUSSION: Our findings do not support the hypothesis that blood donation serves as a viable treatment strategy among migraine patients. Future prospective investigations may help to elucidate the underlying biological mechanisms by which blood donation may influence migraine pathology.

Genetic variants associated with syncope implicate neural and autonomic processes.

AIMS: Syncope is a common and clinically challenging condition. In this study, the genetics of syncope were investigated to seek knowledge about its pathophysiology and prognostic implications. METHODS AND RESULTS: This genome-wide association meta-analysis included 56 071 syncope cases and 890 790 controls from deCODE genetics (Iceland), UK Biobank (United Kingdom), and Copenhagen Hospital Biobank Cardiovascular Study/Danish Blood Donor Study (Denmark), with a follow-up assessment of variants in 22 412 cases and 286 003 controls from Intermountain (Utah, USA) and FinnGen (Finland). The study yielded 18 independent syncope variants, 17 of which were novel. One of the variants, p.Ser140Thr in PTPRN2, affected syncope only when maternally inherited. Another variant associated with a vasovagal reaction during blood donation and five others with heart rate and/or blood pressure regulation, with variable directions of effects. None of the 18 associations could be attributed to cardiovascular or other disorders. Annotation with regard to regulatory elements indicated that the syncope variants were preferentially located in neural-specific regulatory regions. Mendelian randomization analysis supported a causal effect of coronary artery disease on syncope. A polygenic score (PGS) for syncope captured genetic correlation with cardiovascular disorders, diabetes, depression, and shortened lifespan. However, a score based solely on the 18 syncope variants performed similarly to the PGS in detecting syncope risk but did not associate with other disorders. CONCLUSION: The results demonstrate that syncope has a distinct genetic architecture that implicates neural regulatory processes and a complex relationship with heart rate and blood pressure regulation. A shared genetic background with poor cardiovascular health was observed, supporting the importance of a thorough assessment of individuals presenting with syncope.

The effect of ferritin-guided iron supplementation among Danish female first-time blood donors.

BACKGROUND: The identification of blood donors at risk of developing low hemoglobin (Hb) and subsequent intervention is expected to reduce donation-induced iron deficiency and low Hb among blood donors. This study explores the effects of ferritin-guided iron supplementation for female first-time donors implemented in four of five administrative regions in Denmark. STUDY DESIGN AND METHODS: We included 45,919 female first-time donors in this study. Hb values were determined in donations of included donors during a 2-year follow-up period. For each region, an intervention group (after implementation) and a control group (before implementation) were defined. The primary outcome was Hb below the donation threshold (7.8 mmol/L ~ 12.5 g/dL) at the time of donation, in the control group, and the intervention group, using logistic regression. The secondary outcome was the number of donations per donor given during the follow-up period. RESULTS: We observed a statistically significant decrease in the risk of female first-time donors experiencing a donation with low Hb after ferritin-guided iron supplementation was introduced: Odds ratio, 0.82; 95% confidence interval (CI), 0.71-0.95. We found a statistically significant increase in the number of donations per donor during the follow-up period after intervention; rate ratio: 1.05, 95% CI: 1.02-1.08. DISCUSSION: Ferritin-guided iron supplementation led to a significant reduction in the occurrence of low hemoglobin (Hb) levels among Danish female first-time blood donors. The intervention was additionally associated with an increase in the number of donations per donor.

Genetic prediction of 33 blood group phenotypes using an existing genotype dataset.

BACKGROUND: Accurate blood type data are essential for blood bank management, but due to costs, few of 43 blood group systems are routinely determined in Danish blood banks. However, a more comprehensive dataset of blood types is useful in scenarios such as rare blood type allocation. We aimed to investigate the viability and accuracy of predicting blood types by leveraging an existing dataset of imputed genotypes for two cohorts of approximately 90,000 each (Danish Blood Donor Study and Copenhagen Biobank) and present a more comprehensive overview of blood types for our Danish donor cohort. STUDY DESIGN AND METHODS: Blood types were predicted from genome array data using known variant determinants. Prediction accuracy was confirmed by comparing with preexisting serological blood types. The Vel blood group was used to test the viability of using genetic prediction to narrow down the list of candidate donors with rare blood types. RESULTS: Predicted phenotypes showed a high balanced accuracy >99.5% in most cases: A, B, C/c, Coa /Cob , Doa /Dob , E/e, Jka /Jkb , Kna /Knb , Kpa /Kpb , M/N, S/s, Sda , Se, and Yta /Ytb , while some performed slightly worse: Fya /Fyb , K/k, Lua /Lub , and Vel ~99%-98% and CW and P1 ~96%. Genetic prediction identified 70 potential Vel negatives in our cohort, 64 of whom were confirmed correct using polymerase chain reaction (negative predictive value: 91.5%). DISCUSSION: High genetic prediction accuracy in most blood groups demonstrated the viability of generating blood types using preexisting genotype data at no cost and successfully narrowed the pool of potential individuals with the rare Vel-negative phenotype from 180,000 to 70.

A Danish national, multicentre evaluation of the new donor vigilance system among different staff groups.

BACKGROUND AND OBJECTIVES: Two years after implementing a new national donor vigilance system, the Danish Haemovigilance Committee conducted a nationwide survey to evaluate the implementation among different staff groups. We present the results here. MATERIALS AND METHODS: The study was designed as an anonymous online survey to evaluate the satisfaction with the new registration, understanding of the parameters used and the user-friendliness. The REDCap platform was used. The questionnaire consisted of 22 questions. Ordinal variables were answered using five-point Likert scale (1 = strongly disagree to 5 = strongly agree). The data were analysed using descriptive statistics. Successful implementation was defined as mean overall satisfaction ≥4 and mean understanding of the individual components (adverse reaction category, severity and imputability) in the registration ≥4. RESULTS: In all, 104 staff members (77.9% donation staff) participated. The mean (SD) overall satisfaction among all participants was 3.96 (0.94), highest among medical doctors (4.43 (0.78)) and lowest for administrative or other personnel (2.78 (1.09)). The mean scores for understanding the adverse reaction categories, severity and imputability were 3.92 (0.94), 3.92 (0.94) and 3.88 (1.00), respectively. Experience with a previous donor vigilance system was associated with lower scores. The most successful implementation programme included a medical doctor for introduction and a contact person. CONCLUSION: The goal for successful implementation was not met. However, the overall attitude towards the new registration was positive and indicates that the system is suitable for different staff groups. Our results suggest that implementation could benefit from special attention to administrative staff and those accustomed to another donor vigilance system.

Clinical, functional, and patient-reported outcome of traumatic knee dislocations: a retrospective cohort study of 75 patients with 6.5-year follow-up.

INTRODUCTION: At present, limited knowledge regarding clinical, functional, and patient-reported outcomes at mid- and long-terms after surgical treatment of traumatic knee dislocations is available. This study aimed to investigate the mid-term recovery regarding clinical, functional, and patient-reported outcomes in patients following knee dislocation with associated multi-ligament injuries. MATERIALS AND METHODS: The study design was a cross-sectional cohort study. Data were collected by retrospective chart review, clinical examination, and interview of patients. All patients treated surgically following a knee dislocation between January 2000 and December 2011 were included. The surgical technique was up to the decision of the individual surgeon. The main outcome was the Lysholm knee score. Secondary outcomes consist of clinical knee examination, functional performance test, pain, and patient-reported outcome across several domains in function, sport, pain, and quality of life. RESULTS: Seventy-five patients (66.3%) accepted the invitation to participate. The mean age at the time of knee dislocation was 33.5 years, with a range of 16-65 years of age. The mean follow-up time was 78 months (R: 17-147). 75% of patient a Schenck's type 1 lesion and 23% a type 3. The median Lysholm knee score was 83 (R: 18-100). The mean KOOS for the five subscales were pain 84.5 (95% CI 80.5-88.5), symptoms 75.1 (95% CI 70.7-79.4), ADL 87.0 (95% CI 83.1-90.9), sport 59.9 (95% CI 53.3-66.4), and QOL 71.3 (95% CI 67.0-75.6). The mean Tegner activity level was 5.1 (95% CI 4.5-5.7). The median single assessment numeric evaluation (SANE) was 93 (R: 0-100). The pain intensity score for pain (VAS) during activity was reported with a mean of 2.7 (95% CI 2.1-3.3). The objective IKDC examination showed 76% of patients grouped by Grade A (normal knee function) or Grade B (nearly normal). CONCLUSION: With a mean follow-up of 6.5 years, combined repair and reconstruction surgery following a knee dislocation shows good to excellent patient-reported outcome and more than 75% of patients experiencing normal knee functioned evaluated by the IKDC score.

The new donor vigilance system in Denmark reveals regional differences in adverse reactions supposedly caused by variation in the registration.

BACKGROUND AND OBJECTIVES: In recent years, there has been an increased focus among blood bank professionals on the health and safety of blood donors. In 2019, the Danish Haemovigilance Committee designed a national donor vigilance system to improve the registration of adverse reactions (AR) in blood donors. The new donor vigilance system was implemented on 1 January 2020 and we here present the results from the first year of registration. MATERIALS AND METHODS: AR categories, severity level and imputability score were defined based on the definitions from the International Society of Blood Transfusion, AABB and the European Commission directive 2005/61/EC, respectively. RESULTS: Across all severity levels, AR in Danish blood donors were found to be rare (1498 per 100,000 donations). Only 0.2% of the registered reactions were classified as serious (2.7 per 100,000 donations). Large regional differences were seen in the registration of citrate reactions and haematomas. CONCLUSION: Significant differences across regions in what to categorize as an AR were persistent even when including a severity score in the reporting. The Danish Haemovigilance Committee will commence a national work to align the definitions but suggests that this matter is raised to an international level as part of the current work to agree upon definitions for assessment of donor AR.

Estimation of SARS-CoV-2 Infection Fatality Rate by Real-time Antibody Screening of Blood Donors.

BACKGROUND: The pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has tremendous consequences for our societies. Knowledge of the seroprevalence of SARS-CoV-2 is needed to accurately monitor the spread of the epidemic and to calculate the infection fatality rate (IFR). These measures may help the authorities make informed decisions and adjust the current societal interventions. The objective was to perform nationwide real-time seroprevalence surveying among blood donors as a tool to estimate previous SARS-CoV-2 infections and the population-based IFR. METHODS: Danish blood donors aged 17-69 years giving blood 6 April to 3 May were tested for SARS-CoV-2 immunoglobulin M and G antibodies using a commercial lateral flow test. Antibody status was compared between geographical areas, and an estimate of the IFR was calculated. Seroprevalence was adjusted for assay sensitivity and specificity taking the uncertainties of the test validation into account when reporting the 95% confidence intervals (CIs). RESULTS: The first 20 640 blood donors were tested, and a combined adjusted seroprevalence of 1.9% (95% CI, .8-2.3) was calculated. The seroprevalence differed across areas. Using available data on fatalities and population numbers, a combined IFR in patients <70 years is estimated at 89 per 100 000 (95% CI, 72-211) infections. CONCLUSIONS: The IFR was estimated to be slightly lower than previously reported from other countries not using seroprevalence data. The IFR is likely severalfold lower than the current estimate. We have initiated real-time nationwide anti-SARS-CoV-2 seroprevalence surveying of blood donations as a tool in monitoring the epidemic.

Validation of a standardized donor health questionnaire across substances of human origin.

BACKGROUND AND OBJECTIVES: A donor health questionnaire (DHQ) aims to ensure the safety of donors and recipients of transfusions or transplantations with blood components, plasma-derived medicinal products, tissues, haematopoietic stem cells and medically assisted reproduction (in short substances of human origin; SoHO). Currently, many different DHQs exist across countries and SoHO. TRANSPOSE (TRANSfusion and transplantation PrOtection and SElection of donors) developed and validated a standardized DHQ to use across countries and SoHO. We tested whether participants understand the questions and provide honest answers. METHODS: For the validation of the standardized DHQ, two demographically representative online surveys were conducted in Germany (N = 3329) and Austria (N = 3432). We surveyed whether participants understood each DHQ question and would answer the questions truthfully. We used experimental settings to test whether there is a difference between mode of administration (print vs. online), the order of the questions (subject vs. chronological order), and the positioning of the general state of health question (beginning vs. end) in the DHQ. Using regression models, we tested the DHQ's impact on participant mood after completion and on socially desirable response behaviour. RESULTS: Participants understood the DHQ questions well and would answer them honestly. Nevertheless, the data show different levels of understanding and honesty when responding. Administration mode was the only characteristic that had a significant influence on mood, with the online version resulting in a more favourable mood in comparison to the printed version. CONCLUSION: The DHQ was well understood and had a low dishonest tendency. Our findings can serve as an impulse for further research on DHQ criteria across other SoHO and countries.

How donor selection criteria can be evaluated with limited scientific evidence: lessons learned from the TRANSPOSE project.

BACKGROUND AND OBJECTIVE: Donor selection criteria (DSC) are a vital link in the chain of supply of Substances of Human Origin (SoHO) but are also subject to controversy and differences of opinion. Traditionally, DSC have been based on application of the precautionary principle. MATERIALS AND METHODS: From 2017 to 2020, TRANSPOSE (TRANSfusion and transplantation PrOtection and SElection of donors), a European research project, aimed to identify discrepancies between current DSC by proposing a standardized risk assessment method for all SoHO (solid organs excluded) and all levels of evidence. RESULTS: The current DSC were assessed using a modified risk assessment method based on the Alliance of Blood Operators' Risk-based decision-making framework for blood safety. It was found that with limited or diverging scientific evidence, it was difficult to reach consensus and an international standardized method for decision-making was lacking. Furthermore, participants found it hard to disregard their local guidelines when providing expert opinion, which resulted in substantial influence on the consensus-based decision-making process. CONCLUSIONS: While the field of donation-safety research is expanding rapidly, there is an urgent need to formalize the decision-making process regarding DSC. This includes the need for standardized methods to increase transparency in the international decision-making process and to ensure that this is performed consistently. Our framework provides an easy-to-implement approach for standardizing risk assessments, especially in the context of limited scientific evidence.

Putting the spotlight on donation-related risks and donor safety - are we succeeding in protecting donors?

BACKGROUND AND OBJECTIVE: The European consortium project TRANSPOSE (TRANSfusion and transplantation: PrOtection and SElection of donors) aimed to assess and evaluate the risks to donors of Substances of Human Origin (SoHO), and to identify gaps between current donor vigilance systems and perceived risks. MATERIALS AND METHODS: National and local data from participating organizations on serious and non-serious adverse reactions in donors were collected from 2014 to 2017. Following this, a survey was performed among participants to identify risks not included in the data sets. Finally, participants rated the risks according to severity, level of evidence and prevalence. RESULTS: Significant discrepancies between anticipated donor risks and the collected data were found. Furthermore, many participants reported that national data on adverse reactions in donors of stem cells, gametes, embryos and tissues were not routinely collected and/or available. CONCLUSIONS: These findings indicate that there is a need to further develop and standardize donor vigilance in Europe and to include long-term risks to donors, which are currently underreported, ensuring donor health and securing the future supply of SoHO.

Autograft type affects muscle strength and hop performance after ACL reconstruction. A randomised controlled trial comparing patellar tendon and hamstring tendon autografts with standard or accelerated rehabilitation.

PURPOSE: To evaluate and compare changes in quadriceps and hamstring strength and single-leg-hop (SLH) test performance over the first 24 postoperative months in patients who underwent anterior cruciate ligament reconstruction (ACLR) with bone-patellar tendon-bone (BPTB) or hamstring tendon (HT) autografts and followed either a standard or an accelerated rehabilitation protocol. METHODS: A total of 160 patients undergoing ACLR were randomised in four groups depending on the graft that was used and the rehabilitation protocol (40 BPTB/standard rehab, 40 BPTB/accelerated rehab, 40 HT/standard rehab, 40 HT/accelerated rehab). Isokinetic concentric quadriceps and hamstring strength at 90°/s and the SLH test performance were assessed preoperatively and 4,6,8,12 and 24 months postoperatively. The results were reported as the limb symmetry index (LSI) at the same time point. Linear mixed models were used to compare the groups at the different time points. RESULTS: An average quadriceps strength LSI of 78.4% was found preoperatively. After ACLR, the LSI first decreased at 4 months and then increased from 6 to 24 months, reaching an overall value of 92.7% at the latest follow-up. The BPTB group showed a significantly decreased LSI at 4, 6, 8 and 12 months compared with the HT group. No significant differences between the graft groups were found at 24 months. An average hamstring strength LSI of 84.6% was found preoperatively. After ACLR, the LSI increased from 4 to 24 months in the BTPB group. In the HT group, the LSI first decreased at 4 months and then increased from 6 to 24 months. An LSI of 97.1% and 89.1% was found at the latest follow-up for the BPTB and the HT group, respectively. The HT group showed a significantly decreased LSI at all follow-ups compared with the BPTB group. An average SLH test LSI of 81% was found preoperatively. After ACLR, the LSI increased from 4 to 24 months, reaching 97.6% overall at the latest follow-up. The BPTB group showed a significantly decreased LSI only at 4 months postoperatively compared with the HT group. No significant differences in any of the three tests were found between the standard and accelerated rehabilitation groups for either of the graft groups at any time point. CONCLUSION: Muscle strength and SLH test performance recovered progressively after ACLR overall, but they did not all fully recover, as the injured leg performed on average less than 100% compared with the uninjured leg even 24 months postoperatively. After ACLR, inferior quadriceps strength and a poorer SLH test performance were found at 4, 6, 8 and 12 months and at 4 months, respectively, for the BTPB group compared with the HT group. Persistent, inferior hamstring strength was found at all postoperative follow-ups in the HT group. Rehabilitation, standard or accelerated, had no significant impact on the recovery of muscle strength and SLH test performance after ACLR in any of the graft groups. LEVEL OF EVIDENCE: Level I.

Knee function 30 years after ACL reconstruction: a case series of 60 patients.

Background and purpose - Until now, there have been no studies beyond 30 years after anterior cruciate ligament (ACL) reconstruction. We report knee function a mean 31 years after ACL reconstruction.Patients and methods - This cohort comprised a case series of 60 patients with a mean follow-up of 31 years (28-33) after ACL reconstruction. Patients were evaluated with the International Knee Documentation Committee (IKDC) objective assessment, Knee injury Osteoarthritis Outcome Score (KOOS), Tegner Activity Scale, radiography, and MRI.Results - 30 patients showed an intact ACL graft and 30 a ruptured or missing ACL graft. 40 patients had osteoarthritis in the tibiofemoral compartment and 24 patients in the patellofemoral compartment. Patients with intact ACL grafts scored higher than those with ruptured or missing ACL grafts when it comes to KOOS Sport/Rec. The Hodges Lehmann estimated median difference between groups was 15 (95% CI 0-35). The KOOS scores were lower in the group with ruptured or missing ACL grafts when compared with a healthy-knee reference group of males in terms of Pain, mean difference -8 (CI -15 to -1), Symptoms, mean difference -18 (CI -27 to -9), and Sport/Rec, mean difference -21 (CI -34 to -8). In the group with intact ACL grafts, the KOOS score was lower than a healthy-knee reference group of males in terms of Symptoms, mean difference -12 (CI -21 to -3). Scores for all subgroups of KOOS were higher in patients without osteoarthritis. The IKDC overall clinical assessment outcome was worse in patients with a ruptured or missing ACL graft. The Hodges Lehmann estimated median difference between groups was 1 (CI 0-1).Interpretation - Patients with an intact ACL graft reported higher sports activity and recreation, as measured with KOOS, than patients with a ruptured or missing ACL graft. Patients with severe osteoarthritis reported lower sports activity and recreation, as measured with KOOS.

Age, gender, quadriceps strength and hop test performance are the most important factors affecting the achievement of a patient-acceptable symptom state after ACL reconstruction.

PURPOSE: To assess the percentage of patients achieving an acceptable symptom state 2 years after primary anterior cruciate ligament reconstruction (ACLR) and to identify factors affecting its achievement, in a large cohort. METHODS: Patients who underwent primary ACLR at Capio Artro Clinic, Stockholm, Sweden, from 2005 to 2015, were identified in our clinic registry. Patients who had completed the Knee injury and Osteoarthritis Outcome Score (KOOS) at the 2-year follow-up were included. The primary outcome was the achievement of a patient-acceptable symptom state (PASS) for each KOOS subscale. A multivariate logistic regression analysis was used to determine whether patient age, gender, time from injury to surgery, pre-injury Tegner activity level, graft type, cartilage injury, the presence of medial meniscus (MM) or lateral meniscus (LM) resection or repair and the recovery of 6-month symmetrical (limb symmetry index [LSI] of ≥ 90%) isokinetic quadriceps or hamstring strength and single-leg-hop test performance were factors associated with the achievement of a PASS for each KOOS subscale. RESULTS: A total of 2335 primary ACLRs were included. More than 60% of the patients reported a PASS on four of the five KOOS subscales. Age ≥ 30 years and an LSI of ≥ 90% for 6-month isokinetic quadriceps strength increased the odds of achieving a PASS across all KOOS subscales. Female gender reduced the odds of achieving a PASS on the Pain (OR 0.76; 95% CI 0.62-0.94; P = 0.01), activities of daily living (ADL) (OR 0.79; 95% CI 0.64-0.97; P = 0.02) and sport and recreation (OR 0.72; 95% CI 0.58-0.89; P = 0.003) subscales. The presence of an MM repair reduced the odds of achieving a PASS on the Pain (OR 0.59; 95% CI 0.36-0.96; P = 0.03) subscale. Hamstring tendon (HT) autograft rather than bone-patellar tendon-bone (BPTB) autograft showed increased odds (OR 2.02; 95% CI 1.31-3.10; P = 0.001), whereas a cartilage injury showed reduced odds (OR 0.73; 95% CI 0.55-0.97; P = 0.03) of achieving a PASS on the sport and recreation subscale. An LSI of ≥ 90% for 6-month single-leg-hop test performance increased the odds of achieving a PASS on the ADL (OR 1.37; 95% CI 1.09-1.71; P = 0.005), Sport and Recreation (OR 1.40; 95% CI 1.11-1.77; P = 0.004), and quality of life (OR 1.28; 95% CI 1.00-1.63; P = 0.04) subscales. CONCLUSION: More than 60% of the patients reported an acceptable symptom state on four of the five KOOS subscales 2 years after primary ACLR. Age ≥ 30 years and female gender were the non-modifiable factors that consistently increased and reduced, respectively, the odds of achieving a PASS. A symmetrical 6-month isokinetic quadriceps strength and single-leg-hop test performance were the modifiable factors that consistently increased the opportunity of achieving a PASS 2 years after primary ACLR. LEVEL OF EVIDENCE: III.

Higher frequency of osteoarthritis in patients with ACL graft rupture than in those with intact ACL grafts 30 years after reconstruction.

PURPOSE: The aim was to assess the results of anterior cruciate ligament (ACL) reconstruction regarding graft failure, knee laxity, and osteoarthritis (OA) from a longterm perspective. It was hypothesized that intact ACL graft reduces the risk for increased OA development. METHODS: The cohort comprised 60 patients with a median follow-up 31 (range 28-33) years after ACL reconstruction. They were evaluated with magnetic resonance imaging, radiography, KT-1000 arthrometer and the pivot shift test. RESULTS: Out of the 60 patients, 30 (50%) showed an intact ACL graft and 30 (50%) a ruptured or absent ACL graft. Patients with ruptured ACL grafts had more medial tibiofemoral compartment OA than those with an intact ACL graft (p = 0.0003). OA was asymmetric in patients with ruptured ACL grafts with more OA in the medial than in the lateral tibiofemoral compartment (p = 0.013) and the patellofemoral compartment (p = 0.002). The distribution of OA between compartments was similar in patients with an intact ACL graft. KT-1000 values of anterior knee laxity were higher in patients with ruptured compared to those with intact ACL grafts (p = 0.012). Side-to-side comparisons of anterior knee laxity showed higher KT-1000 values in patients with ruptured ACL graft (p = 0.0003) and similar results in those with intact graft (p = 0.09). The pivot shift grade was higher in the group with a ruptured ACL graft (p < 0.0001). CONCLUSIONS: Median 31 (range 28-33) years after ACL reconstruction, 50% of the patients showed an intact ACL graft and no side-to-side difference regarding anterior knee laxity. Patients with ruptured ACL grafts had more OA of the medial tibiofemoral compartment than those with intact ACL grafts. LEVEL OF EVIDENCE: Retrospective cohort study, Level III.

Only one patient out of five achieves symmetrical knee function 6 months after primary anterior cruciate ligament reconstruction.

PURPOSE: To assess the percentage of patients achieving symmetrical knee function 6 months after primary anterior cruciate ligament (ACL) reconstruction (ACLR) and to identify factors affecting its achievement, in a large cohort. METHODS: Data were extracted from our clinic database. Patients who underwent primary ACLR from 2000 to 2015 and were assessed with the isokinetic quadriceps and hamstring muscles strength tests and single-leg-hop test at the 6-month follow-up were included in the study. Demographic data, information on the graft used, cartilage injuries and concomitant meniscal surgery were reviewed. Patients who reached a limb symmetry index (LSI) of ≥ 90% in all three tests were considered to have achieved symmetrical knee function. A multivariate logistic regression analysis was used to determine whether patient age, gender, time from injury to surgery, pre-injury Tegner activity level, graft type, cartilage injury and the presence of medial meniscus (MM) or lateral meniscus (LM) resection or repair were factors associated with the achievement of symmetrical knee function 6 months after primary ACLR. RESULTS: A total of 4093 patients (54.3% males) with a mean age of 28.3 ± 10.7 years were included. Data from all three tests were available for 3541 patients. The proportion of patients that achieved a LSI of ≥ 90% was 35.7%, 47.3% and 67.9% for isokinetic quadriceps muscle strength, hamstring muscles strength and the single-leg-hop test, respectively. A total of 693 patients (19.6%) achieved symmetrical knee function, reaching a LSI of ≥ 90% in all three tests. Older age (≥ 30 years) (OR, 0.50; 95% CI 0.41-0.61; P < 0.001), MM resection (OR, 0.75; 95% CI 0.57-0.98; P = 0.03) and MM repair (OR, 0.63; 95% CI 0.40-0.98; P = 0.04) reduced the odds, whereas the use of hamstring tendon (HT) autograft (OR, 2.28; 95% CI 1.51-3.45; P < 0.001) over bone-patellar tendon-bone (BPTB) autograft increased the odds of achieving symmetrical knee function. CONCLUSION: Only 19.6% of the patients achieved symmetrical knee function 6 months after primary ACLR. Age ≥ 30 years, MM resection and MM repair reduced the chance, whereas the use of HT autograft over BPTB autograft increased the chance of achieving symmetrical knee function 6 months after primary ACLR. This study shows that most of the patients are yet to regain symmetrical knee function 6 months after primary ACLR and, moreover, it identifies several factors affecting its achievement in a large cohort. The results of this study should be used to counsel patients about their expected functional recovery and to optimize rehabilitation and maximize knee function after ACLR. LEVEL OF EVIDENCE: III.

Contralateral knee hyperextension is associated with increased anterior tibial translation and fewer meniscal injuries in the anterior cruciate ligament-injured knee.

PURPOSE: To investigate the influence of hyperextension of the contralateral healthy knee on anterior tibial translation (ATT) and the presence of associated injuries in the anterior cruciate ligament (ACL)-injured knee. METHODS: A local patient data register containing the surgical and clinical data of patients undergoing ACL reconstruction was analyzed. Patients were divided into groups according to the degree of hyperextension of the contralateral knee: normal (Group A ≤ 0°), mild (Group B 1°-5°), moderate (Group C 6°-10°), and severe (Group D > 10°). The ATT was measured in both knees preoperatively and 6 months postoperatively using the KT-1000 arthrometer. The presence of associated meniscal and cartilage injuries was noted. Using multivariate analysis, Groups B, C, and D were compared with Group A, using this group as a reference. RESULTS: A total of 10,957 patients were available in the register and 8502 (Group A n = 4335, Group B n = 3331, Group C n = 771, Group D n = 65) were included in the final analysis. Groups B (10.3 mm; 95% CI 0.06-0.042, p < 0.0001) and C (10.6 mm; 95% CI 0.23-0.89, p = 0.006) showed significantly greater preoperative ATT in the injured knee compared with the control group (10.1 mm). Moreover, at the 6-month follow-up, greater ATT was observed for Groups B (8.5 mm; 95% CI 0.13-0.45, p < 0.0001), C (8.5 mm; 95% CI 0.02-0.60, p = 0.035), and D (9.1 mm; 95% CI - 0.08-1.77, p = 0.082) compared with Group A (8.2 mm). Meniscal injuries were less frequent in patients with contralateral hyperextension [Group B 903 (27.1%) p < 0.0001, Group C 208 (27.0%) p = 0.0003, and Group D 12 (18.5%), 0.012] compared with the control group [Group A 1479 (34.1%)]. CONCLUSION: Contralateral knee hyperextension is associated with greater pre- and postoperative ATT in the ACL-injured knee. In patients with contralateral knee hyperextension, concomitant injuries to the menisci are less frequent. Surgeons should consider grafts with superior properties regarding postoperative anteroposterior laxity to patients with contralateral knee hyperextension. LEVEL OF EVIDENCE: Retrospective cohort study, Level IV.

Postoperative septic arthritis after anterior cruciate ligament reconstruction: does it affect the outcome? A retrospective controlled study.

PURPOSE: To determine whether the outcome after septic arthritis after anterior cruciate ligament reconstruction (ACLR) is inferior compared with uncomplicated ACLR when treated promptly by use of a standard protocol. METHODS: At Capio Artro Clinic, 4,384 primary ACLRs were performed during 2001-2009. All patients with postoperative septic arthritis were retrospectively reviewed, and 43 met the inclusion criteria. Twenty-seven patients agreed to re-examination (infection group) and were compared with 27 matched patients with uncomplicated ACLR (control group). The mean follow-up period was 60 months and 66 months in the infection group and control group, respectively. Re-examination included objective (radiographs, physical examination, functional testing, range of motion, strength, stability, International Knee Documentation Committee questionnaire) and subjective (Knee Injury and Osteoarthritis Outcome Score, Tegner score, Lysholm score, European Quality of Life-5 Dimensions, subjective satisfaction questions, Single Assessment Numeric Evaluation of knee function, visual analog scale pain rating) evaluation. RESULTS: There were no significant differences in objective knee function between the groups at follow-up. For subjective knee function, no significant differences between the groups were detected with the Single Assessment Numeric Evaluation score, pain during activity, or Lysholm score. The infection group scored lower on 4 of 5 Knee Injury and Osteoarthritis Outcome Score subscales: pain (P = .014), function in daily living (P = .008), sports/recreation (P = .015), and quality of life (P = .007). The infection group scored lower versus control patients on the Tegner score (P = .001) and European Quality of Life-5 Dimensions scores (P = .004). Both groups improved over time, but the control group scored better only on the Tegner score (P = .004). CONCLUSIONS: Septic arthritis after ACLR did not result in inferior objective knee function compared with uncomplicated ACLR. Subjectively, infection patients were as satisfied as non-infection patients, but rehabilitation took longer and fewer patients returned to sports. The findings of this study suggest that anterior cruciate ligament grafts may be retained with prompt, thorough arthroscopic lavage and debridement; correct antibiotics according to cultures; and repeated arthroscopy if necessary. LEVEL OF EVIDENCE: Level III, retrospective case-control therapeutic study.

Long-term follow-up of nonoperatively and operatively treated acute primary patellar dislocation in skeletally immature patients.

PURPOSE: The present study reports a long-term follow-up of acute primary patellar dislocation in patients with open physes. The purpose of the study was to evaluate knee function and recurrence rates after surgical and nonsurgical treatment of patellar dislocation. METHODS: A total of 51 patients, including 29 girls and 22 boys, who were 9-14 years of age at the time of injury, were retrospectively evaluated. The minimum follow-up time was 5 years. Thigh muscle torque, range of motion, the squat test, the knee injury and osteoarthritis outcome score (KOOS), the Kujala score, and the recurrence rate were registered. Radiological predisposing factors at the time of injury were determined. RESULTS: Quality of life and sports/recreation were the most affected subscales, according to KOOS, and a reduced Kujala score was also observed in all treatment groups. The surgically treated patients had a significantly lower recurrence rate. Those patients also exhibited reduced muscle performance, with a hamstring to quadriceps ratio (H/Q) of 1.03. The recurrence rate was not correlated with knee function. CONCLUSIONS: Patellar dislocation in children influences subjective knee function in the long term. Surgery appears to reduce the recurrence rate, but subjective knee function was not restored.

Genome-wide association study reveals a locus in ADARB2 for complete freedom from headache in Danish Blood Donors.

Headache disorders are the most common disorders of the nervous system. The lifetime prevalence of headache disorders show that some individuals never experience headache. The etiology of complete freedom from headache is not known. To assess genetic variants associated with complete freedom from headache, we performed a genome-wide association study of individuals who have never experienced a headache. We included 63,992 individuals (2,998 individuals with complete freedom from headache and 60,994 controls) from the Danish Blood Donor Study Genomic Cohort. Participants were included in two rounds, from 2015 to 2018 and in 2020. We discovered a genome-wide significant association, with the lead variant rs7904615[G] in ADARB2 (EAF = 27%, OR = 1.20 [1.13-1.27], p = 3.92 × 10-9). The genomic locus was replicated in a non-overlapping cohort of 13,032 individuals (539 individuals with complete freedom from headache and 12,493 controls) from the Danish Blood Donor Study Genomic Cohort (p < 0.05, two-sided). Participants for the replication were included from 2015 to 2020. In conclusion, we show that complete freedom from headache has a genetic component, and we suggest that ADARB2 is involved in complete freedom from headache. The genomic locus was specific for complete freedom from headache and was not associated with any primary headache disorders.