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Jeppe Vejlgaard Rasmussen,1,2 Anders El-Galaly,3– 5 Theis Muncholm Thillemann,6 Steen Lund Jensen3– 5 1Department of Orthopaedic Surgery, Herlev-Gentofte Hospital, Copenhagen, Denmark; 2Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 3Department of Orthopaedic Surgery, Aalborg University Hospital, Aalborg, Denmark; 4Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; 5Interdisciplinary Orthopedics, Aalborg University Hospital, Aalborg, Denmark; 6Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus, DenmarkCorrespondence: Jeppe Vejlgaard RasmussenDepartment of Orthopaedic Surgery, Herlev and Gentofte Hospital, Gentofte Hospitalsvej 1, Hellerup, 2900, DenmarkTel +45 3867 3321Email jeppe.vejlgaard.rasmussen@regionh.dkPurpose: The Danish Shoulder Arthroplasty Registry (DSR) is a nationwide database providing data for research and health care monitoring. The aim of this study was to validate the DSR by (1) assessing registration completeness, (2) comparing key variables with information from medical records, (3) assessing the number and proportion of missing data for key variables.Materials and Methods: The completeness of registration in the DSR from 2006– 2015 was assessed for primary arthroplasties by comparing the number of arthroplasties reported to the DSR with the number of arthroplasties recorded by the Danish National Patient Register which is an administrative database used by the Danish healthcare authorities to monitor all hospitalizations including shoulder arthroplasty surgery. Positive predictive values (PPV) were used to estimate the accuracy of the reporting in a randomly selected population. Information retrieved from medical records were used as gold standard. The number of missing values for each variable was evaluated to depict if these registrations were missing at random.Results: The completeness of reporting was 94.4. The PPV for the three major indications: osteoarthritis, fracture and rotator cuff arthropathy was 92%, 97%, and 94%, respectively. PPV was high for resurfacing arthroplasty (93%) and reverse shoulder arthroplasty (93%), but low for total shoulder arthroplasty (79%) and hemiarthroplasty (83%). The proportion of missing data in DSR was less than 1% for age, gender, previous surgery, indication and arthroplasty type and these can be regarded as missing at random.Conclusion: The study showed that data from the DSR are sufficiently valid to be used for research and quality monitoring. Lower PPV’s for total shoulder arthroplasty and hemiarthroplasty are possibly related to inadequate definitions and mutually nonexclusive items in the reporting form. Regular validation is necessary since the data reported to the registry continuously evolve because of changes in clinical practice.Keywords: shoulder, arthroplasty, registry, completeness, accuracy, positive predictive value

Background and Purpose: There is controversy regarding the results of stemmed and stemless total shoulder arthroplasty (TSA) used for osteoarthritis. Therefore, we aimed to compare revision rates of stemmed and stemless TSA and to examine the impact of metal-backed glenoid components., Methods: We included all patients reported to the Danish Shoulder Arthroplasty Register from January 1, 2012 to December 31, 2022 with an anatomical TSA used for osteoarthritis. Primary outcome was revision (removal or exchange of components) for any reason., Results: 3,338 arthroplasties were included. The hazard ratio for revision of stemless TSA adjusted for age and sex was 1.83 (95% confidence interval [CI] 1.21-2.78) with stemmed TSA as reference. When excluding all arthroplasties with a metal-backed glenoid component, the adjusted hazard ratio for revision of stemless TSA was 1.37 (CI 0.85-2.20). For the Eclipse stemless TSA system, the adjusted hazard ratio for revision of a metal-backed glenoid component was 8.75 (CI 2.40-31.9) with stemless Eclipse with an all-polyethylene glenoid component as reference., Conclusion: We showed that the risk of revision of stemless TSAs was increased and that it was related to their combination with metal-backed glenoid components.

Background: There is substantial evidence that operative treatment reduces the risk of nonunion but offers no long-term functional gains compared with nonoperative treatment. Despite some studies citing quicker recovery with surgery, the promise of accelerated functional recovery remains under-investigated. The aim of this meta-analysis of randomized controlled trials was to investigate the possible early functional gains (≤6 months) after operative treatment of displaced midshaft clavicular fractures compared with nonsurgical treatment., Methods: A systematic search was performed to identify randomized controlled trials comparing plate osteosynthesis with nonoperative treatment. We evaluated shoulder function outcomes measured by Constant Score or Disability of the Arm, Shoulder, and Hand (DASH) questionnaire. Other outcomes of interest were sick leave and return to previous activity (work, leisure)., Results: Ten studies including 1333 patients were included. The mean difference in DASH score after 6 weeks was 9.4 points (95% confidence interval [CI] 13.7-5.1) in favor of operative treatment. At 3 months, the difference was 3.6 points (95% CI 6.9-0.4), and at 6 months, the difference was 3.2 points (95% CI 5.2-1.1), both in favor of operative treatment. Results for Constant Score were similar to that of DASH score., Conclusion: This meta-analysis shows that there is an early functional gain at six weeks following plate fixation of midshaft clavicular fractures compared with nonoperative treatment. At three and six months, the functional gain is lesser and not clinically relevant., (© 2024 The Authors.)

Background: Little is known about the feasibility of progressive shoulder exercises (PSE) for patients with glenohumeral osteoarthritis (OA) or rotator cuff tear arthropathy (CTA). The aim of this study was to investigate whether 12 weeks of PSE is feasible in patients with glenohumeral OA or CTA eligible for shoulder arthroplasty. Moreover, to report changes in shoulder function and range of motion (ROM) following the exercise program., Methods: Twenty patients were included. Eighteen patients (11 women, 15 with OA), mean age 70 years (range 57-80), performed 12 weeks of PSE with one weekly physiotherapist-supervised and two weekly home-based sessions. Feasibility was measured by dropout rate, adverse events, pain, and adherence to PSE. At baseline and end of intervention, patients completed the Western Ontario Osteoarthritis of the Shoulder (WOOS) score and Disabilities of the Arm, Shoulder and Hand (DASH). Data to assess feasibility were analyzed using descriptive statistics., Results: Two patients dropped out and no adverse events were observed. Sixteen of the eighteen patients (89%) had a high adherence (≥ 70%) to the physiotherapist-supervised sessions. Acceptable pain levels were reported; in 76% of all exercise sessions with no numeric rating scale (NRS) score over five for any exercise. WOOS improved with a mean of 23 points (95% CI 13;33), and DASH improved with a mean of 13 points (95% CI 6;19)., Conclusion: Adherence to PSE was high and dropout rates were low. PSE is feasible, safe and may relieve shoulder pain, improve function and ROM in patients with glenohumeral OA or CTA. The patient-experienced gains after PSE seem clinically relevant and should be compared to arthroplasty surgery in a RCT setting., Trial Registration: According to Danish law, this study did not need an approval by the Central Denmark Region Committee on Health Research Ethics. Approval from The Danish Data Protection Agency (journal number 1-16-02-15-20) was obtained., (© 2022. The Author(s).)

Background: The main long-term benefit of operative treatment of displaced midshaft clavicular fractures is the reduction in nonunion risk, and as this risk is generally low, the ideal approach would be to operate only patients at high risk of nonunion. However, most current surgical decision models use baseline variables to estimate the nonunion risk, and the value of these models remains unclear. Pain in the early weeks after fracture could be potentially be an indirect measurement of fracture healing, and so it is a potential proxy variable that could lead to simpler prediction models., Questions/purposes: (1) Is pain a possible proxy variable for the development of symptomatic nonunion after nonoperative treatment of midshaft clavicular fractures? (2) How reliable is the model we created that uses pain as a proxy variable for symptomatic nonunion of nonoperatively treated clavicle fractures?, Methods: In this secondary retrospective analysis of an earlier randomized trial, we studied prospectively collected data from 64 nonoperatively treated patients aged 18 years to 60 years. In the original randomized trial, we compared operative and nonoperative treatment of displaced midshaft clavicular fractures. In all, 150 patients were included in the study, of whom 71 received nonoperative treatment. Patients were predominantly males (75%, 48 of 64) with a mean age of 38 ± SD 12 years; most fractures were comminuted and shortened more than 1 cm. All 71 patients who were nonoperatively treated were potentially eligible for this secondary analysis; of those, 11% (8 of 71) were lost to follow-up, leaving 63 patients from the nonoperative treatment arm and one patient from the operative treatment arm (who declined surgical treatment after randomization but was followed in this group according to the intention-to-treat principle) for analysis here. Nonunion was defined as lack of callus formation, persistent fracture lines and/or sclerotic edges of the bones at the fracture site on plain radiographs at 6 months follow-up. Nonunions were regarded as symptomatic if pain, tenderness, and local crepitation were present at the fracture site. Seventeen percent (11 of 64) of patients had symptomatic nonunions. After investigating differences in early pain scores between the union and nonunion groups, we defined the VASratio as the VAS pain score at 4 weeks divided by the VAS pain score at 2 weeks. Week 2 VAS pain score was chosen as baseline after visual inspection of a linear mixed model that showed increased divergence in pain scores between union and nonunion group at 2 weeks after fracture. Week 4 was chosen as the cutoff because we wanted a reasonable time frame for the detection of pain reduction and did not want to delay surgical treatment more than necessary. Odds ratios for various risk factors were calculated using logistic regression analyses. We used a receiver operating characteristic curve analysis to identify cutoff values for the VASratio., Results: An increase in absolute pain score at 4 weeks after fracture (odds ratio 1.8 per 1 point increase [95% confidence interval 1.1 to 3.4]) was associated with an increased risk of nonunion 6 months after fracture. Likewise, we found that an increasing VASratio (OR 1.02 per 0.01 point increase [95% CI 1.002 to 1.06]) was also associated with nonunion. Receiver operating curve analysis found that the best cutoff value of VASratio was about 0.6. Patients with a VASratio above 0.6 had a relative risk of developing nonunion of 18 (95% CI 2 to 130) compared with patients with a VASratio below 0.6. Sparse-data bias could be present, as is evident from this wide confidence interval, though even at the low end of the confidence interval, the relative risk was 2, which may still improve surgical decision-making., Conclusion: A pain score that exhibits no or minimal change from 2 to 4 weeks after nonoperative treatment of a displaced midshaft fracture of the clavicle is associated with a high risk that symptomatic nonunion will develop. Patients with no or minimal change in pain in the early weeks may be candidates for surgery to reduce the risk of symptomatic nonunion. As this was a retrospective study, with a risk of sparse-data bias, the predictive value of the VASratio needs to be further investigated in large prospective studies before clinical use., Level of Evidence: Level III, diagnostic study., Competing Interests: All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2020 by the Association of Bone and Joint Surgeons.)

Background and purpose - Most newer randomized studies examining plate fixation and nonoperative treatment of midshaft clavicular fractures utilize both Disabilities of the Arm, Shoulder and Hand (DASH) and Constant-Murley score (CS) in the evaluation of patient outcomes. Compared with DASH, the use of CS requires on-site trained personnel and patient visits to obtain the score. The use of both DASH and CS should provide extra value compared with the use of a single functional outcome score; if this value is not provided, the combined use is not necessary. We evaluated the agreement between DASH and CS in patients with displaced midshaft clavicular fractures.Patients and methods - We used prospectively collected data from 146 patients enrolled in a randomized study comparing operative and nonoperative treatment of midshaft clavicular fractures. We determined correlation between DASH and CS at all follow-up points and calculated mean bias in the Bland-Altman plot.Results - We found moderate to high correlation (from 0.82 at 6 weeks' follow-up to 0.58 at 1-year follow-up) between DASH and CS score, and a small bias (2.21 [95% CI 0.22-4.20]) in the Bland-Altman plot.Interpretation - In patients with displaced midshaft clavicular fractures DASH and CS measures the same degree of disability. Unless specifically studying strength and range of motion, we recommend the sole use of DASH as it would eliminate potential observer-induced bias along with removing the economic and logistic burden of obtaining CS without compromising the value of the collected data.

Background: Revision TKA is a serious adverse event with substantial consequences for the patient. As the demand for TKA rises, reducing the risk of revision TKA is becoming increasingly important. Predictive tools based on machine-learning algorithms could reform clinical practice. Few attempts have been made to combine machine-learning algorithms with data from nationwide arthroplasty registries and, to the authors' knowledge, none have tried to predict the likelihood of early revision TKA., Question/purposes: We used the Danish Knee Arthroplasty Registry to build models to predict the likelihood of revision TKA within 2 years of primary TKA and asked: (1) Which preoperative factors were the most important features behind these models' predictions of revision? (2) Can a clinically meaningful model be built on the preoperative factors included in the Danish Knee Arthroplasty Registry?, Methods: The Danish Knee Arthroplasty Registry collects patients' characteristics and surgical information from all arthroplasties conducted in Denmark and thus provides a large nationwide cohort of patients undergoing TKA. As training dataset, we retrieved all preoperative variables of 25,104 primary TKAs from 2012 to 2015. The same variables were retrieved from 6170 TKAs conducted in 2016, which were used as a hold-out year for temporal external validation. If a patient received bilateral TKA, only the first knee to receive surgery was included. All patients were followed for 2 years, with removal, exchange, or addition of an implant defined as TKA revision. We created four different predictive models to find the best performing model, including a regression-based model using logistic regression with least shrinkage and selection operator (LASSO), two classification tree models (random forest and gradient boosting model) and a supervised neural network. For comparison, we created a noninformative model predicting that all observations were unrevised. The four machine learning models were trained using 10-fold cross-validation on the training dataset after adjusting for the low percentage of revisions by over-sampling revised observations and undersampling unrevised observations. In the validation dataset, the models' performance was evaluated and compared by density plot, calibration plot, accuracy, Brier score, receiver operator characteristic (ROC) curve and area under the curve (AUC). The density plot depicts the distribution of probabilities and the calibration plot graphically depicts whether the predicted probability resembled the observed probability. The accuracy indicates how often the models' predictions were correct and the Brier score is the mean distance from the predicted probability to the observed outcome. The ROC curve is a graphical output of the models' sensitivity and specificity from which the AUC is calculated. The AUC can be interpreted as the likelihood that a model correctly classified an observation and thus, a priori, an AUC of 0.7 was chosen as threshold for a clinically meaningful model., Results: Based the model training, age, postfracture osteoarthritis and weight were deemed as important preoperative factors within the machine learning models. During validation, the models' performance was not different from the noninformative models, and with AUCs ranging from 0.57 to 0.60, no models reached the predetermined AUC threshold for a clinical useful discriminative capacity., Conclusion: Although several well-known presurgical risk factors for revision were coupled with four different machine learning methods, we could not develop a clinically useful model capable of predicting early TKA revisions in the Danish Knee Arthroplasty Registry based on preoperative data., Clinical Relevance: The inability to predict early TKA revision highlights that predicting revision based on preoperative information alone is difficult. Future models might benefit from including medical comorbidities and an anonymous surgeon identifier variable or may attempt to build a postoperative predictive model including intra- and postoperative factors as these may have a stronger association with early TKA revisions.

Background and purpose - Proximal humerus fractures (PHF) may result in sequelae indicating arthroplasty. We report cumulative survival rates and reasons for revision after arthroplasty for proximal humerus fracture sequelae (PHFS).Patients and methods - Data were derived from the Nordic Arthroplasty Register Association. The Kaplan-Meier method was used to illustrate survival rates. A scaled Schoenfeld residual plot was used to report the risk of revision for men relative to women in patients who were treated with reverse shoulder arthroplasty (RSA). Revision was defined as removal or exchange of any component or the addition of a glenoid component.Results - 30,190 primary arthroplasties were reported from 2004 to 2016, of which 3,245 were for PHFS. The estimated 1-, 5-, and 10-year cumulative survival rates (95% CI) were 96% (95-97), 90% (89-92), and 86% (83-88) for stemmed hemiarthroplasty and 94% (92-95), 89% (87-91), and 86% (82-90) for RSA with a median time to revision of 18 months (IQR 9-44) and 3 months (IQR 0-17). The risk of revision for men relative to women in patients who were treated with RSA was 3.2 (1.9-5.1) 0-1 year after surgery and 1.9 (0.9-4.1) 1-8 years after surgery. The estimated 1-, 5-, and 10-year cumulative survival rates (95% CI) were 94% (92-96), 88% (85-90), and 80% (75-86) for men and 95% (94-96), 86% (84-89), and 81% (77-84) for young patients.Interpretation - Shoulder arthroplasty for PHFS was associated with lower survival rates, compared with previously published results of shoulder arthroplasty for acute PHF. The low arthroplasty survival rates for men and young patients especially are worrying.

Background and purpose - Both medial unicompartmental knee arthroplasties (UKA) and high tibial osteotomies (HTO) are reliable treatments for isolated medial knee osteoarthritis. However, both may with time need conversion to a total knee arthroplasty (TKA). We conducted the largest nationwide registry comparison of the survival of TKA following UKA with TKA following HTO.Patients and methods - From the Danish Knee Arthroplasty Registry, aseptic conversions to TKA from UKA and TKA converted from HTO within the period of 1997-2018 were retrieved. The Kaplan-Meier method and the Cox proportional hazards regression were used to estimate the survival and hazard ratio (HR) for revision, considering confounding by indication utilizing propensity-score based inverse probability of treatment weighting (PS-IPTW).Results - PS-IPTW yielded a well-balanced pseudo-cohort (standard mean difference (SMD) < 0.1 for all covariates, except implant supplementation) of 963.8 TKAs following UKA and 1139.1 TKAs following HTO. The survival of TKA following UKA was significantly less than that of TKA following HTO with a 5-year estimated survival of 0.88 (95% confidence interval (CI) 0.85-0.90) and 0.94 (CI 0.93-0.96), respectively. The differences in survival corresponded to an implant-supplementation adjusted HR of 2.7 (CI 2.4-3.1) for TKA following UKA compared with TKA following HTO.Interpretation - Previous UKA more than doubled the revision risk of a subsequent TKA compared with previous HTO. This potential risk should be considered in the shared treatment decision of patients who are candidates for both UKA and HTO.

Background: There is an important gap in knowledge about the effectiveness of nonoperative treatment (exercise) for patients with traumatic primary and recurrent anterior shoulder dislocations (ASDs)., Purpose/hypothesis: The purpose of this study was to assess the efficacy and safety of physical therapist-supervised, shoulder instability neuromuscular exercise (SINEX) versus self-managed, home-based, standard care shoulder exercise (HOMEX) in patients with traumatic ASDs. The hypothesis was that SINEX would have a larger effect and fewer adverse events compared with HOMEX., Study Design: Randomized controlled trial; Level of evidence, 2., Methods: A total of 56 participants with radiographically verified, trauma-initiated primary or recurrent ASDs and self-reported decreased shoulder function were randomized to 12 weeks of either SINEX or HOMEX. The SINEX program consisted of 7 exercises, individually progressing from basic (2 × 20 repetitions each day) to elite (2 × 10 repetitions, 3 times weekly). The HOMEX program included 5 shoulder exercises performed 3 times weekly (2 × 10 repetitions). The primary outcome was the Western Ontario Shoulder Instability Index (WOSI) score, ranging from 0 (best possible) to 2100. The between-group minimal clinically important difference at 12 weeks was 250 points. Secondary outcomes included WOSI subdomain scores, patient-reported ratings of kinesiophobia and pain, objective shoulder function, patient satisfaction, and number of adverse events., Results: The between-group mean difference in the WOSI total score at 12 weeks significantly favored SINEX over HOMEX (-228.1 [95% CI, -430.5 to -25.6]). SINEX was furthermore superior to HOMEX in most of the secondary outcomes (3/4 subdomains of the WOSI and pain level during the past 7 days as well as clinical signs of anterior shoulder instability). Also, although not statistically significant, less than half the proportion of the SINEX patients compared with the HOMEX patients (3/27 [11%] vs 6/24 [25%], respectively; P = .204) underwent or were referred for shoulder stabilizing surgery. Satisfaction with both exercise programs was high, and no serious adverse events were reported., Conclusion: Neuromuscular shoulder exercise (SINEX) was superior to standard care exercise (HOMEX) in patients with traumatic ASDs. Further long-term follow-ups on treatment effects are needed., Registration: NCT02371928 (ClinicalTrials.gov identifier)., Competing Interests: The authors declared that there are no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2020.)

Background: Reverse shoulder arthroplasty (RSA) has gained popularity in the treatment of proximal humeral fractures (PHFs), especially in elderly patients. The purpose of this study was to investigate the use of RSA implants for acute PHFs and risk of revision, as well as risk factors for revision., Methods: RSA implants for acute PHFs were identified from the Nordic Arthroplasty Register Association registry data from 2004 to 2016. Kaplan-Meier survival analysis was used to calculate implant survival. Cox multiple regression analysis was used to calculate the adjusted revision rate for sex, age, country of operation, and year of surgery., Results: The study included 1523 RSA implants for PHFs (84% women; average age, 77 years; average follow-up time, 2.5 years). The 5-year cumulative implant survival rate was 97% (confidence limits, 95.5% and 98%). Revision was performed for 33 implants (2%). The most common reason for revision was instability, occurring in 11 cases (0.7%), followed by fracture, occurring in 6 (0.4%), and infection, occurring in 5 (0.3%). Four different arthroplasty brands were used in this cohort, with the Delta Xtend in two-thirds of cases (n = 1025). Age younger than 60 years and male sex were associated with slightly higher rates of revision; however, these differences did not reach statistical significance (hazard ratio of 2.02 with P  = .075 and hazard ratio of 3.23 with P  = .057, respectively)., Conclusion: The use of RSA for acute PHFs is increasing in the Nordic countries. The short-term risk of revision is low. The main reason for revision of RSA for this indication is instability., (© 2019 The Author(s).)

Background and purpose - Osteoarthritis has become the most common indication for shoulder arthroplasty in Denmark, and the treatment strategies have changed towards the use of anatomical total shoulder arthroplasty and reverse shoulder arthroplasty. We investigated whether changes in the use of arthroplasty types have changed the overall patient-reported outcome from 2006 to 2015. Patients and methods - We included 2,867 shoulder arthroplasties performed for osteoarthritis between 2006 and 2015 and reported to the Danish Shoulder Arthroplasty Registry. The Western Ontario Osteoarthritis of the Shoulder (WOOS) index at 1 year was used as patient-reported outcome. The raw score was converted to a percentage of a maximum score. General linear models were used to analyze differences in WOOS. Results - The proportion of anatomical total shoulder arthroplasty and reverse shoulder arthroplasty increased from 3% and 7% in 2006 to 53% and 27% in 2015. The mean WOOS score was 70 (SD 26) after resurfacing hemiarthroplasties (n = 1,258), 68 (SD 26) after stemmed hemiarthroplasty (n = 500), 82 (SD 23) after anatomical total shoulder arthroplasties (n = 815), and 74 (SD 23) after reverse shoulder arthroplasties (n = 213). During the study period, the overall WOOS score increased with 18 (95% CI 12-22) in the univariate model and 10 (CI 5-15) in the multivariable model, and the WOOS scores for anatomical total shoulder arthroplasty increased by 14 (CI 5-23). Interpretation - We found an increased WOOS score from 2006 to 2015, which was primarily related to a higher proportion of anatomical total shoulder arthroplasty and reverse shoulder arthroplasty towards the end of the study period, and to improved outcome of anatomical total shoulder arthroplasty.

Background: Patients with non-operated traumatic primary anterior shoulder dislocation (PASD) are assumed to have less shoulder impairment than patients with recurrent anterior shoulder dislocations (RASD). This may impact treatment decision strategy. The aim was to study whether patients with non-operated traumatic PASD have less shoulder impairment than those with RASD., Methods: In a cross-sectional study baseline data from patients with PASD and RASD in a randomised controlled trial of non-operative shoulder exercise treatment were used. Shoulder function was self-reported (Western Ontario Shoulder Instability (WOSI), Tampa Scale of Kinesiophobia (TSK), General Health (EQ-5D-VAS), Numeric Pain Rating Scale (NPRS)), and measured (Constant-Murley shoulder Score (CMS total), CMS - Range of Motion (CMS-ROM, CMS - strength, proprioception, clinical tests)., Results: In total, 56 patients (34 (28 men) with PASD and 22 (21 men) with RASD) (mean age 26 years) participated. WOSI total was 1064 and 1048, and TSK above 37 (indicating high re-injury fear) was present in 33 (97%) and 21 (96%) of the groups with PASD and RASD, with no group difference. CMS total (66.4 and 70.4), CMS-ROM (28.7 and 31.5), CMS-strength (injured shoulder: 7.6 kg and 9.1 kg), proprioception and clinical tests were the same. Furthermore, 26 (76%) with PASD and 13 (59%) with RASD reported not to have received non-operative shoulder treatment., Conclusions: Non-operated patients with PASD and self-reported shoulder trouble three-six weeks after initial injury do not have less shoulder impairment (self-reportedly or objectively measured) than non-operated patients RASD and self-reported shoulder trouble three-six weeks after their latest shoulder dislocation event.

Background: In a clinical setting, a visual evaluation of post-implant radiographs is often used to assess the restoration of glenohumeral joint anatomy after resurfacing hemiarthroplasty and is a part of the decision-making process, in combination with other parameters, when evaluating patients with inferior clinical results. However, the reliability of this method of visual evaluation has not been reported. The aim of this study was to investigate the inter- and intra-observer agreement among experienced shoulder surgeons assessing overstuffing, implant positioning, and size following resurfacing hemiarthroplasty using plain standardized radiographs., Methods: Six experienced shoulder surgeons independently classified implant inclination, size of the implant and if the joint seemed overstuffed, in 219 cases of post-implant radiographs. All cases were classified twice 3 weeks apart. Only radiographs with an anterior-posterior projection with a freely visible joint space were used. Non-weighted Cohen's kappa values were calculated for each coder pair and the mean used as an estimate of the overall inter-observer agreement., Results: The overall inter-observer agreement for implant size (kappa, 0.48 and 0.41) and inclination angle was moderate in both rounds (kappa, 0.46 and 0.44), but only a fair agreement was found concerning the evaluation for stuffing of the joint (kappa, 0.24 and 0.28). Intra-observer agreement for implant size and stuffing ranged from fair to substantial while the agreement for inclination was moderate to substantial., Conclusions: Our results indicate that a visual evaluation of plain radiographs may be inadequate to evaluate overstuffing, implant positioning, and size following resurfacing hemiarthroplasty using plain standardized radiographs. Future studies may contribute to elucidate whether reliability increases if consensus on clear definitions and standardized methods of evaluation is made.

Background and purpose - It is unclear whether previous osteosynthesis is a risk factor for inferior outcome following shoulder arthroplasty for a proximal humeral fracture. We used data from the Danish Shoulder Arthroplasty Registry (DSR) to examine this question. Patients and methods - All 285 patients treated with a shoulder arthroplasty after failed osteosynthesis of a proximal humeral fracture reported to DSR from 2006 to 2013 were included. Each case was matched with 2 controls (570) treated with a primary shoulder arthroplasty for an acute proximal humeral fracture. Patient reported outcome was assessed using the Western Ontario Osteoarthritis of the Shoulder index (WOOS) and the relative risk of revision was reported. Results - The mean WOOS was 46 (SD 25) for a shoulder arthroplasty after failed osteosynthesis and 52 (27) after a primary shoulder arthroplasty. The relative risk of revision for a shoulder arthroplasty after failed osteosynthesis was 2 with a primary arthroplasty for fracture as reference. In a separate analysis of patients treated by locking plate the mean WOOS was 46 (24), with a relative risk of revision at 1.5 with a primary arthroplasty as reference. Interpretation - Compared with primary arthroplasty for proximal humeral fracture, we found an inferior patient-reported outcome and a substantial risk of revision for patients treated with a shoulder arthroplasty after failed osteosynthesis for a proximal humeral fracture. The risk and burdens of additional surgery should be accounted for when deciding on the primary surgical procedure.

Objective: To report the10-year survival rates of different shoulder arthroplasty types used for glenohumeral osteoarthritis., Design: Data from 2004 to 2013 was prospectively collected by the national shoulder arthroplasty registers in Denmark, Norway and Sweden and merged into a harmonized dataset under the umbrella of the Nordic Arthroplasty Register Association. The common dataset included data that all three registers could deliver and where consensus regarding definitions could be made. Revision was defined as removal or exchange of any component or the addition of a glenoid component., Results: The cumulative survival rates at 10 years after resurfacing hemiarthroplasty (RHA) (n = 1,923), stemmed hemiarthroplasty (SHA) (n = 1,587) and anatomical total shoulder arthroplasty (TSA) (n = 2,340) were 0.85, 0.93 and 0.96 respectively (P < 0.001, Log rank test). RHA (HR: 2.5; CI 1.9-3.4, P < 0.001) and SHA (HR: 1.4; CI 1.0-2.0, P < 0.04) had an increased risk of revision compared to TSA. Gender, age and period of surgery were included in the Cox regression model. For patients below 55 years, the 10-year cumulative survival rates were 0.75 (RHA, n = 354), 0.81 (SHA, n = 146), and 0.87 (TSA, n = 201)., Conclusions: Anatomical TSA had the highest implant-survival rate. Young patients had, independently of the arthroplasty type, lower implant-survival rates. The treatment of young patients with end-stage osteoarthritis remains a challenge., (Copyright © 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: Progressive high-load exercise (PHLE) has led to positive clinical results in patients with patellar and Achilles tendinopathy. However, its effects on rotator cuff tendinopathy still need to be investigated., Purpose: To assess the clinical effects of PHLE versus low-load exercise (LLE) among patients with rotator cuff tendinopathy., Study Design: Randomized controlled trial; Level of evidence, 1., Methods: Patients with rotator cuff tendinopathy were recruited and randomized to 12 weeks of PHLE or LLE, stratified for concomitant administration of corticosteroid injection. The primary outcome measure was change from baseline to 12 weeks in the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, assessed in the intention-to-treat population., Results: A total of 100 patients were randomized to PHLE (n = 49) or LLE (n = 51). Mean changes in the DASH questionnaire were 7.11 points (95% CI, 3.07-11.16) and 8.39 points (95% CI, 4.35-12.44) in the PHLE and LLE groups, respectively; this corresponded to a statistically nonsignificant adjusted mean group difference of -1.37 points (95% CI, -6.72 to 3.99; P = .61). Similar nonsignificant results were seen for pain, range of motion, and strength. However, a significant interaction effect was found between the 2 groups and concomitant corticosteroid use ( P = .028), with the largest positive change in DASH in favor of PHLE for the group receiving concomitant corticosteroid., Conclusion: The study results showed no superior benefit from PHLE over traditional LLE among patients with rotator cuff tendinopathy. Further investigation of the possible interaction between exercise type and corticosteroid injection is needed to establish optimal and potentially synergistic combinations of these 2 factors., Registration: NCT01984203 (ClinicalTrials.gov identifier): Rotator Cuff Tendinopathy Exercise Trial (RoCTEx)., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: R.C. is a paid consultant for AbbVie, Amgen, Axellus A/S, Bristol-Meyers Squibb, Cambridge Weight Plan, Celgene, Eli Lilly, Hospira, MSD, Norpharma, Novartis, Orkla Health, Pfizer, Roche, Sobi, and Takeda; has received grants from Axellus A/S, AbbVie, Cambridge Weight Plan, Janssen, MSD, Mundipharma, Novartis, and Roche; has received payment for lectures from Abbott, Amgen, Axellus, Bayer HealthCare Pharmaceuticals, Biogen Idec, Bristol-Meyers Squibb, Cambridge Weight Plan, Ipsen, Janssen, Laboratoires Expanscience, MSD, Mundipharma, Norpharma, Novartis, Pfizer, Roche, Rottapharm-Madaus, Sobi, and Wyeth; has received grants for manuscript preparation from Axellus, Bristol-Meyers Squibb, Cambridge Weight Plan, and Aleris-Hamlet (via Norpharma); has received payment for development of educational presentations from Bristol-Meyers Squibb, MSD, and Pfizer; and received reimbursement for travel/accommodations/meeting expenses from Abbott, AbbVie, Axellus, Bristol-Myers Squibb, Cambridge Weight Plan, Celgene, Laboratoires Expanscience, Norpharma, Novartis, Pfizer, Roche, Rottapharm-Madaus, and Wyeth. This work was supported by the Region of Southern Denmark’s Research Fund, the Danish Rheumatism Association, the Ryholts Foundation, and the Danish Physiotherapy Association Foundation for Advancement of Research, Education, and Information. K.G.I. was funded by 1-year fellowships from Hospital Lillebaelt–Vejle Hospital, University of Southern Denmark, and Region of Southern Denmark. The Musculoskeletal Statistics Unit at the Parker Institute (R.C.) is supported by grants from the Oak Foundation.

Background and purpose - For more than half a century, stemmed hemiarthroplasty (SHA) has been used in the treatment of comminuted and displaced fractures of the proximal humerus. Reverse shoulder arthroplasty (RSA) has been increasingly popular in cases where it is difficult to obtain satisfactory fixation of the tuberosities. We report revision rates and reasons for revision after shoulder arthroplasty for acute fractures of the proximal humerus. Patients and methods - This study was based on a common dataset from the Nordic Arthroplasty Register Association (NARA), which includes data reported to the national shoulder arthroplasty registries in Denmark, Sweden, and Norway. We included 6,756 shoulder arthroplasties performed for acute fractures between 2004 and 2013. Results - There were 6,112 SHAs (90%) and 565 RSAs (8.4%). The cumulative arthroplasty survival rate after 5 years was 0.96 for both SHA and RSA. The relative risk of revision of RSA was 1.4 (95% CI: 0.9-2.2) with SHA as reference. For both types of arthroplasty, the most common reason for revision was infection (SHA 0.8%, RSA 2.1%). The relative risk of revision due to infection was 3.1 (95% CI: 1.6-5.9) for RSA with SHA as reference. The relative risk of revision for patients who were less than 75 years of age was 2.8 (95% CI: 2.0-3.8) compared to older patients. Interpretation - Revision after shoulder arthroplasty for acute fractures was rare. Survival rates were similar between SHA and RSA, but RSA had a statistically significant and clinically relevant higher risk of revision because of infection.

Introduction: Knowledge of how abstracts may be se-lected for medical conferences in an efficient and reliable manner is sparse. To improve abstract selection, the Danish Orthopaedic Society implemented the International Society of the Knee (ISK) quality-of-reporting system and visual analogue scale (VAS) scoring for abstract evaluation at its 2014 Annual Congress. We sought to find out if a simple VAS score was more reliable than a multiple-question system for assessment of over-all abstract quality., Methods: A total of 214 abstracts were submitted for review. All abstracts were reviewed by 3 reviewers using a VAS score and the ISK score. Of the 214, 71 abstracts were reviewed again 6 months later to estimate intra-rater agreement., Results: The VAS and the ISK score were poorly correlated (r = 0.64), and the ISK score demonstrated a better intra- and interrater agreement (p < 0.001). The VAS scores of all abstracts were more widely distributed than the ISK scores, which clustered around values in the 50-70 range. Chronbach's alpha for the ISK score was 0.66 (95% confidence interval: 0.62-0.68)., Conclusions: The VAS score has a poorer intra- and interrater agreement than the ISK score, and the two scores do not correlate well. VAS scores were more widely distributed, which is beneficial when selecting a scientific programme, but the score is unreliable. We continue to use the ISK score, although its reliability may still be improved., Funding: none., Trial Registration: not relevant., (Articles published in the Danish Medical Journal are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

Background: Anterior shoulder dislocation is a common injury and may have considerable impact on shoulder-related quality of life (QoL). If not warranted for initial stabilising surgery, patients are mostly left with little to no post-traumatic rehabilitation. This may be due to lack of evidence-based exercise programmes. In similar, high-impact injuries (e.g. anterior cruciate ligament tears in the knee) neuromuscular exercise has shown large success in improving physical function and QoL. Thus, the objective of this trial is to compare a nonoperative neuromuscular exercise shoulder programme with standard care in patients with traumatic anterior shoulder dislocations (TASD)., Methods/design: Randomised, assessor-blinded, controlled, multicentre trial. Eighty patients with a TASD will be recruited from three orthopaedic departments in Denmark. Patients with primary or recurrent anterior shoulder dislocations due to at least one traumatic event will be randomised to 12 weeks of either a standardised, individualised or physiotherapist-supervised neuromuscular shoulder exercise programme or standard care (self-managed shoulder exercise programme). Patients will be stratified according to injury status (primary or recurrent). Primary outcome will be change from baseline to 12 weeks in the patient-reported QoL outcome questionnaire, the Western Ontario Shoulder Instability Index (WOSI)., Discussion: This trial will be the first study to compare the efficacy and safety of two different nonoperative exercise treatment strategies for patients with TASD. Moreover, this is also the first study to investigate nonoperative treatment effects in patients with recurrent shoulder dislocations. Lastly, this study will add knowledge to the shared decision-making process of treatment strategies for clinical practice., Trial Registration: ClinicalTrials.gov, identifier: NCT02371928 . Registered on 9 February 2015 at the National Institutes of Health Clinical Trials Protocol Registration System.

Background: Rotator cuff rupture is associated with dysfunction, pain and muscular weakness related to the upper extremity. Some evidence exists to support the beneficial effect of exercises but there is lack of evidence of which exercises imply the best effect and how physiotherapy should be administered. Therefore, the purpose of this study was to examine the effect of a neuromuscular exercise program for patients with irreparable rotator cuff rupture., Methods: Based on sample-size calculations thirty patients with chronic irreparable rotator cuff tears (of at least m. supraspinatus and m. infraspinatus) was consecutively included. Twenty-four patients completed the five months training to restore function with focus on centering the humeral head in the glenoid cavity trough strengthening m. deltoideus anterior and m. teres minor. The primary outcome measure was Oxford Shoulder Score which was completed at baseline, 3 and 5 months follow-up. One-way, repeated-measure ANOVA was used if data was normally distributed. Secondary outcome measures included EQ-5D, range of motion, strength and muscle activity. Paired t-test and Wilcoxon Signed Ranks Test was used to the appropriate outcomes., Results: Improvements was seen for both primary and secondary outcomes from baseline to follow-up. Oxford Shoulder Score improved from 25.6 (SD 8.1) at baseline to 33.8 (SD 8.7) at 3 months (p = 0.004) and 37.2 (SD 8.2) at five months (p < 0.001). Range of motion in abduction significantly increased by 34.4° (95 % CI: 11.6-57.2). Strength measured in flexion 45, flexion 90 and abduction also significantly increased at 5 months by 10.2 (95 % CI: 0.8-19.6), 7.0 (95 % CI: 0.0-14.0) and 12.3 (95 % CI: 3.4-21.3) respectively. The remaining outcomes for range of motion and strengths only showed small and non-significant changes. Furthermore patients reported higher levels of quality of life and reduced level of pain after five months., Conclusion: Following a five months exercise protocol patients with irreparable rotator cuff tears showed increased function in their symptomatic shoulder, reduced pain and increased quality of life. This study therefore supports the use of exercise therapy in patients with irreparable rotator cuff rupture., Trial Registration: This study is approved by The National Committee on Health Research Ethics (N-20120040) and registered retrospectively at ClinicalTrials.gov in April 2016 ( NCT02740946 ).

Global momentum around women's, children's, and adolescents' health, coupled with the ambitious and equalizing agenda of the Sustainable Development Goals (SDGs), has exposed a tension between the need for comprehensive, multi-actor, rights-based approaches that seek to "close the gaps" and a growing economic and political imperative to demonstrate efficiency, effectiveness, and returns on specific investments. To address this challenge, this paper proposes a framework to measure "results" in a way that offers a more nuanced understanding of the impact of human rights-based approaches and their complexity, as well as their contextual, multi-sectoral, and evolving nature. We argue that the impact of human rights-based approaches is best measured across a spectrum of change-at the individual, programmatic, structural, and societal levels. Such an analysis would allow for more accurate assessments of the cumulative effect of these changes. The paper also underscores the long-overdue need to better define the parameters of a human rights-based approach to health. This is an important part of the research agenda on human rights and health in the context of the SDGs and the Global Strategy for Women's, Children's and Adolescents' Health, and amid calls for better measurement and greater accountability for resources, results, and rights at all levels. While this paper focuses on women's, children's, and adolescents' health, the proposed framework can apply as readily to other areas of health and provides a new frame of reference for assessing the impact of human rights-based approaches., (Copyright © 2015 Thomas, Kuruvilla, Hinton, Jensen, Magar, Bustreo. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Transthoracic echocardiography (TTE) is a widely used cardiac imaging technique that all cardiologists should be able to perform competently. Traditionally, TTE competence has been assessed by unstructured observation or in test situations separated from daily clinical practice. An instrument for assessment of clinical TTE technical proficiency including a global rating score and a checklist score has previously shown reliability and validity in a standardised setting. As clinical test situations typically have several sources of error giving rise to variance in scores, a more thorough examination of the generalizability of the assessment instrument is needed., Methods: Nine physicians performed a TTE scan on the same three patients. Then, two raters rated all 27 TTE scans using the TTE technical assessment instrument in a fully crossed, all random generalizability study. Estimated variance components were calculated for both the global rating and checklist scores. Finally, dependability (phi) coefficients were also calculated for both outcomes in a decision study., Results: For global rating scores, 66.6% of score variance can be ascribed to true differences in performance. For checklist scores this was 88.8%. The difference was primarily due to physician-rater interaction. Four random cases rated by one random rater resulted in a phi value of 0.81 for global ratings and two random cases rated by one random rater showed a phi value of 0.92 for checklist scores., Conclusions: Using the TTE checklist as opposed to the TTE global rating score had the effect of minimising the largest source of error variance in test scores. Two cases rated by one rater using the TTE checklist are sufficiently reliable for high stakes examinations. As global rating is less time consuming it could be considered performing four global rating assessments in addition to the checklist assessments to account for both reliability and content validity of the assessment.

Background: Shoulder pain is the third most common musculoskeletal disorder, often affecting people's daily living and work capacity. The most common shoulder disorder is the subacromial impingement syndrome (SIS) which, among other pathophysiological changes, is often characterised by rotator cuff tendinopathy. Exercise is often considered the primary treatment option for rotator cuff tendinopathy, but there is no consensus on which exercise strategy is the most effective. As eccentric and high-load strength training have been shown to have a positive effect on patella and Achilles tendinopathy, the aim of this trial is to compare the efficacy of progressive high-load exercises with traditional low-load exercises in patients with rotator cuff tendinopathy., Methods/design: The current study is a randomised, participant- and assessor-blinded, controlled multicentre trial. A total of 260 patients with rotator cuff tendinopathy will be recruited from three outpatient shoulder departments in Denmark, and randomised to either 12 weeks of progressive high-load strength training or to general low-load exercises. Patients will receive six individually guided exercise sessions with a physiotherapist and perform home-based exercises three times a week. The primary outcome measure will be change from baseline to 12 weeks in the patient-reported outcome Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire., Discussion: Previous studies of exercise treatment for SIS have not differentiated between subgroups of SIS and have often had methodological flaws, making it difficult to specifically design target treatment for patients diagnosed with SIS. Therefore, it was considered important to focus on a subgroup such as tendinopathy, with a specific tailored intervention strategy based on evidence from other regions of the body, and to clearly describe the intervention in a methodologically strong study., Trial Registration: The trial was registered with Clinicaltrials.gov ( NCT01984203 ) on 31 October 2013.

Treatment with CD34+ hematopoietic stem/progenitor cells has been shown to improve functional recovery in nonhuman models of ischemic stroke via promotion of angiogenesis and neurogenesis. We aimed to determine the safety and feasibility of treatment with CD34+ cells delivered intra-arterially in patients with acute ischemic stroke. This was the first study in human subjects. We performed a prospective, nonrandomized, open-label, phase I study of autologous, immunoselected CD34+ stem/progenitor cell therapy in patients presenting within 7 days of onset with severe anterior circulation ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score≥8). CD34+ cells were collected from the bone marrow of the subjects before being delivered by catheter angiography into the ipsilesional middle cerebral artery. Eighty-two patients with severe anterior circulation ischemic stroke were screened, of whom five proceeded to treatment. The common reasons for exclusion were age>80 years (n=19); medical instability (n=17), and significant carotid stenosis (n=13). The procedure was well tolerated in all patients, and no significant treatment-related adverse effects occurred. All patients showed improvements in clinical functional scores (Modified Rankin Score and NIHSS score) and reductions in lesion volume during a 6-month follow-up period. Autologous CD34+ selected stem/progenitor cell therapy delivered intra-arterially into the infarct territory can be achieved safely in patients with acute ischemic stroke. Future studies that address eligibility criteria, dosage, delivery site, and timing and that use surrogate imaging markers of outcome are desirable before larger scale clinical trials., (©AlphaMed Press.)

Brachypodium distachyon is a non-domesticated cereal. Nonetheless, Brachypodium was recently introduced as a model plant for temperate cereals. This study compares grain starch metabolism in Brachypodium and barley (Hordeum vulgare). In Brachypodium, we identified and annotated 28 genes involved in starch metabolism and identified important motifs including transit peptides and putative carbohydrate-binding modules (CBMs) of the families CBM20, CBM45, CBM48, and CBM53. Starch content was markedly lower in Brachypodium grains (12%) compared to barley grains (47%). Brachypodium starch granules were doughnut shaped and bimodally distributed into distinct small B-type (2.5-10 µm) and very small C-type (0.5-2.5 µm) granules. Large A-type granules, typical of cereals, were absent. Starch-bound phosphate, important for starch degradation, was 2-fold lower in Brachypodium compared with barley indicating different requirements for starch mobilization. The amylopectin branch profiles were similar and the amylose content was only slightly higher compared with barley cv. Golden Promise. The crystallinity of Brachypodium starch granules was low (10%) compared to barley (20%) as determined by wide-angle X-ray scattering (WAXS) and molecular disorder was confirmed by differential scanning calorimetry (DSC). The expression profiles in grain for most genes were distinctly different for Brachypodium compared to barley, typically showing earlier decline during the course of development, which can explain the low starch content and differences in starch molecular structure and granule characteristics. High transitory starch levels were observed in leaves of Brachypodium (2.8% after 14h of light) compared to barley (1.9% after 14h of light). The data suggest important pre-domesticated features of cereals., (© The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

The indications for surgical intervention in complex fractures of the proximal humerus are disputed. In elderly patients with poor bone stock it may be impossible to obtain satisfactory fixation of the tuberosities to a hemiarthroplasty (HA). In such cases primary insertion of a reverse shoulder arthroplasty (RSA) has been suggested. We aimed to review clinical studies reporting benefits and harms of RSA in acute fractures. A systematic review. We included 18 studies containing 430 RSA in acute fractures. We found no randomized clinical trials. Four studies compared outcome after RSA with a historical control group of HA. The median constant score was 58 (range 44-68) which is comparable to previous reviews of HA in 4-part fractures. Complications included dislocation, infection, hematoma, instability, neurological injury, reflex sympathetic dystrophy, intraoperative fractures, periprosthetic fractures, and baseplate failure. Scapular notching was reported in 11 studies with a median value of 25% (range 0-94). Heterogeneity of study designs and lack of primary data precluded statistical pooling of data. No high quality evidence was identified. Based on the available evidence the use of RSA in acute fractures is questionable. The complication rate was high and the clinical implications of long term scapular notching are worrying. Randomized studies with long term follow up using the latest techniques of tubercular reinsertion in RSA toward HA should be encouraged.

Background: Starch is stored in higher plants as granules composed of semi-crystalline amylopectin and amorphous amylose. Starch granules provide energy for the plant during dark periods and for germination of seeds and tubers. Dietary starch is also a highly glycemic carbohydrate being degraded to glucose and rapidly absorbed in the small intestine. But a portion of dietary starch, termed "resistant starch" (RS) escapes digestion and reaches the large intestine, where it is fermented by colonic bacteria producing short chain fatty acids (SCFA) which are linked to several health benefits. The RS is preferentially derived from amylose, which can be increased by suppressing amylopectin synthesis by silencing of starch branching enzymes (SBEs). However all the previous works attempting the production of high RS crops resulted in only partly increased amylose-content and/or significant yield loss., Results: In this study we invented a new method for silencing of multiple genes. Using a chimeric RNAi hairpin we simultaneously suppressed all genes coding for starch branching enzymes (SBE I, SBE IIa, SBE IIb) in barley (Hordeum vulgare L.), resulting in production of amylose-only starch granules in the endosperm. This trait was segregating 3:1. Amylose-only starch granules were irregularly shaped and showed peculiar thermal properties and crystallinity. Transgenic lines retained high-yield possibly due to a pleiotropic upregualtion of other starch biosynthetic genes compensating the SBEs loss. For gelatinized starch, a very high content of RS (65 %) was observed, which is 2.2-fold higher than control (29%). The amylose-only grains germinated with same frequency as control grains. However, initial growth was delayed in young plants., Conclusions: This is the first time that pure amylose has been generated with high yield in a living organism. This was achieved by a new method of simultaneous suppression of the entire complement of genes encoding starch branching enzymes. We demonstrate that amylopectin is not essential for starch granule crystallinity and integrity. However the slower initial growth of shoots from amylose-only grains may be due to an important physiological role played by amylopectin ordered crystallinity for rapid starch remobilization explaining the broad conservation in the plant kingdom of the amylopectin structure.

Background: Orthopaedic surgeons disagree considerably when classifying fractures of the proximal humerus. However, the clinical implications of low observer agreement remain unclear. The purpose of the study was to compare the agreement on Neer classification with the agreement on treatment recommendations., Methods: We conducted a multi-centre observer-study. Five experienced shoulder surgeons independently assessed a consecutive series of 193 radiographs at two occasions three months apart. All pairs of radiographs were classified according to Neer. Subsequently, the observers were asked to recommend one of three treatment modalities for each case: non-operative treatment, locking plate osteosynthesis, or hemiarthroplasty., Results: At both classification rounds mean kappa-values for inter-observer agreement on treatment recommendations (0.48 and 0.52) were significantly higher than the agreement on Neer classification (0.33 and 0.36) (p < 0.001 at both rounds). The highest mean kappa-values were found for inter-observer agreement on non-surgical treatment (0.59 and 0.55). In 36% (345 out of 965) of observations an observer changed Neer category between first and second classification round. However, in only 34% of these cases (116 out of 345) the observers changed their treatment recommendations., Conclusions: We found a significantly higher agreement on treatment recommendations compared to agreement on fracture classification. The low observer agreement on the Neer classification reported in several observer studies may have less clinical importance than previously assumed. However, inter-observer agreement did not exceed moderate levels.

Background: Fractures of the proximal humerus are common injuries and account for 4-5 percent of all fractures, second only to hip and wrist fractures. The incidence is positively correlated with age and osteoporosis, and is likely to increase. Displaced four-part fractures are among the most severe injuries, accounting for 2-10 percent of proximal humeral fractures. The optimal intervention is disputed. Two previous randomised trials were very small and involved a noticeable risk of bias, and systematic reviews consequently conclude that there is inadequate basis for evidence-based treatment decisions. We aim to compare the effect of osteosynthesis with angle-stable plate with non-surgical management, and the effect of primary hemiarthroplasty with both osteosynthesis and non-surgical management., Methods/design: We will conduct a randomised, multi-centre, clinical trial including patients from ten national shoulder units within a two-year period. We plan to include 162 patients. A central randomisation unit will allocate patients. All patients will receive a standardised three-month rehabilitation program of supervised physiotherapy regardless of treatment allocation. Patients will be followed at least one year. The primary outcomes will be the overall score on the Constant Disability Scale, and its pain subscale, measured at 12 months. A blinded physiotherapist will carry out the assessments. Other secondary outcomes are Oxford Shoulder Score, and general health status (Short Form-36).

Evidence is growing in support of the role of stem cells as an attractive alternative in treatment of liver diseases. Recently, we have demonstrated the feasibility and safety of infusing CD34(+) adult stem cells; this was performed on five patients with chronic liver disease. Here, we present the results of long-term follow-up of these patients. Between 1 x 10(6) and 2 x 10(8) CD34(+) cells were isolated and injected into the portal vein or hepatic artery. The patients were monitored for side effects, toxicity and changes in clinical, haematological and biochemical parameters; they were followed up for 12-18 months. All patients tolerated the treatment protocol well without any complications or side effects related to the procedure, also there were no side effects noted on long-term follow-up. Four patients showed an initial improvement in serum bilirubin level, which was maintained for up to 6 months. There was marginal increase in serum bilirubin in three of the patients at 12 months, while the fourth patient's serum bilirubin increased only at 18 months post-infusion. Computed tomography scan and serum alpha-foetoprotein monitoring showed absence of focal lesions. The study indicated that the stem cell product used was safe in the short and over long term, by absence of tumour formation. The investigation also illustrated that the beneficial effect seemed to last for around 12 months. This trial shows that stem cell therapy may have potential as a possible future therapeutic protocol in liver regeneration.

Background: Surgical resection is the only therapeutic option with curative effect on malignant liver tumours, but in over 70% of cases, this is not a feasible option. A prospective study was performed to assess the short- and long-term effects of intraoperative radiofrequency ablation on unresectable liver metastases., Patients: Between 1997 and 2001, 57 patients (mean age 61.9 years; range 31-83 years) with 297 unresectable liver metastases (colorectal adenocarcinoma, n=38; carcinoid tumour, n=4; malignant melanoma, n=3; other metastases, n=12) underwent intraoperative radiofrequency ablation., Results: No mortality was observed in patients managed solely with radiofrequency ablation. Eight postoperative complications occurred in eight patients (14%). Three occurred when radiofrequency ablation was combined with resection. Of the 33 patients completely ablated, 30 patients are still alive and 21 are disease-free after a median follow-up of 18.1 months (range 2-43). Ten patients underwent more than one intraoperative radiofrequency ablation episode. Overall survival was 72.5% at 1 year and 52.5% at 3 years. Complete ablation and the number of lesions were significant independent prognostic factors for survival, with p<0.001 and p<0.0001, respectively., Conclusion: Radiofrequency ablation is a safe and effective option for patients with inoperable liver metastases without extra hepatic disease. Prospective controlled trials comparing the results of different treatments are required to assess which patients will benefit best from this emerging new treatment.

Objective: To assess a new bloodless technique using radiofrequency energy for segmental liver resection of hepatic tumors., Summary Background Data: Liver resection remains a formidable surgical procedure; safe performance requires a high level of training and skill. Intraoperative blood loss during liver resection remains a major concern because it is associated with a higher rate of postoperative complications and shorter long-term survival., Methods: From January 2000 to June 2001, 15 patients with various hepatic tumors were operated on using radiofrequency energy to remove the tumor in its entirety. Radiofrequency energy was applied along the margins of the tumor to create "zones of necrosis" before resection with a scalpel., Results: No blood transfusions were required. The mean blood loss during resection was 30 +/- 10 mL. No mortality or morbidity was observed. The median postoperative stay was 8 days (range 5-9). No liver recurrence was detected in patients undergoing resection with this technique during follow-up periods ranging from 2 to 20 months., Conclusions: Segmental and wedge liver resection assisted by radiofrequency is safe. This novel technique offers a new method for transfusion-free resection.

Background and Aims: E1B-deleted virus dl1520 (ONYX-015) has been previously used in clinical trials mainly for treatment of head and neck tumors, and has been shown to have beneficial effects independent of p53 status. The main aim of this investigation was to carry out a preclinical study for assessment of the use of dl1520 in in vitro and in vivo hepatocellular carcinoma (HCC) models with various p53 status (deleted, mutant, and wild type), and study the ultrastructural changes in the carcinoma cells during and following treatment with dl1520., Methods: dl1520 (ONYX-015) virus was used for treatment of three HCC cell lines in culture, then for treatment of developed xenografts in SCID mice. The effects of dl1520 on HCC cell growth and accompanied morphological changes were assessed by various techniques including transmission electron microscopy. dl1520 infection was confirmed using polymerase chain reaction and immunolabeling at transmission electron microscopy level., Results: dl1520 was effective in killing cells and inhibiting HCC cell growth both in vitro and in vivo. The cell killing was at higher levels in cells possessing abnormal p53. Survival rates in SCID mice treated with dl1520 were statistically significantly higher in HCC tumors with deleted and mutant p53, than in tumors with wild-type p53., Conclusions: The findings in this study suggest that dl1520 could be safely and effectively used for treatment of HCC dependent on the p53 status of the cells in vivo. Characteristic morphological changes that took place in the dl1520-treated HCC cells/tumors were distinct at transmission electron microscopy level and are the first of their kind to be reported.

In a recent study we have demonstrated that interleukin 8 (IL-8) and tumour necrosis factor alpha (TNF-alpha) serum levels correlate positively with the severity of acute pancreatitis (AP), induced by bile acid injected into the pancreatic duct of rabbits. In this article we describe the effect of an IL-10 analogue IT9302 and a monoclonal anti-IL-8 (mon. IL-8) antibody on the content of several pro-inflammatory cytokines in the serum of rabbits, after induction of AP. We found that the serum content of inflammatory cytokines IL-8, IL-1beta, TNF-alpha and monocyte chemoattractant protein 1 (MCP-1) are increased during AP. Injection of IT9302 or mon. IL-8 antibody, diminish the concentration of these cytokines in the serum, with the exception that mon. IL-8 antibody actually increased the circulating level of MCP-1. In addition, intravenous administration of IT9302 increased the serum levels of IRAP, an IL-1beta receptor antagonistic cytokine. Furthermore, intravenous injection of mon. IL-8 antibody increased serum levels of IL-4. It can be concluded that both the human IL-10 analogue IT9302 and mon. IL-8 antibody are able to alter the pro-inflammatory cytokine levels in rabbits suffering from experimentally induced AP., (Copyright 2002 Elsevier Science Ltd.)

Clinical studies were performed with a recombinant mutant adenovirus with an E1B 55-kDa deletion, dl1520, to assess its toxicity and efficacy in patients with irresectable primary and secondary liver tumors. A phase I study showed that dl1520 was well tolerated when administered directly intratumorally, intraarterially, or intravenously up to a dose of 3 x 10(11) PFU. Ultrastructural examination of tissue showed the presence of adenovirus in cell cytoplasm around the nucleus and revealed two dissimilar end points of cell death after virus infection: a preapoptotic sequence and necrosis. A phase II study showed that the combination of dl1520 and 5-fluorouracil (5-FU), when infused into the hepatic artery, was well tolerated. Further improvement in the recombinant vector design will be needed in order to achieve better clinical response.

Background: Interleukin 8 (IL-8) has recently been proposed to have an important role in mediating the development of the systemic sequelae associated with severe acute pancreatitis., Aims: To define the role of IL-8 in acute pancreatitis by neutralising its effects with a monoclonal anti-IL-8 antibody (WS-4), in a rabbit model of severe acute pancreatitis., Methods: Acute pancreatitis was induced by retrograde injection of 5% chenodeoxycholic acid into the pancreatic duct and duct ligation. Twenty rabbits were divided equally into two groups: acute pancreatitis controls received physiological saline and the treated group received WS-4, 30 minutes before induction of acute pancreatitis., Results: Pretreatment of animals with WS-4 resulted in significant down regulation of serum IL-8 and tumour necrosis factor alpha (TNF-alpha) from three to six hours after induction of acute pancreatitis (p = 0.011 and 0.047 for IL-8 and 0.033 and 0.022 for TNF-alpha, respectively). In addition, a significant reduction in the CD11b and CD18 positive cells and the amount of interstitial neutrophil infiltration in the lungs from WS-4 treated animals was seen. In contrast, WS-4 did not alter the amount of pancreatic necrosis and the serum concentrations of amylase, lipase, calcium, and glucose., Conclusion: WS-4 cannot change the amount of pancreatic necrosis induced by injection of 5% bile acid, but does reduce the acute lung injury, presumably through inhibition of circulating IL-8 and TNF-alpha, and CD11b/CD18 in lung tissue. Therefore, a role of IL-8 in the progression of acute pancreatitis and the development of its systemic complications is suggested.

Interleukin 10 (IL-10) is a recently described natural endogenous immunosuppressive cytokine that has been identified in human, murine, and other organisms. Human IL-10 (hIL-10) has high homology with murine IL-10 (mIL-10) as well as with an Epstein-Barr virus genome product BCRFI. This viral IL-10 (vIL-10) shares a number of activities with hIL-10. IL-10 significantly affects chemokine biology, because human IL-10 inhibits chemokine production and is a specific chemotactic factor for CD8+ T cells. It suppresses the ability of CD4+ T cells, but not CD8+ T cells, to migrate in response to IL-8. A nonapeptide (IT9302) with complete homology to a sequence of hIL-10 located in the C-terminal portion (residues 152-160) of the cytokine was found to possess activities that mimic some of those of hIL-10. These are: (i) inhibition of IL-1beta-induced IL-8 production by peripheral blood mononuclear cell, (ii) inhibition of spontaneous IL-8 production by cultured human monocytes, (iii) induction of IL-1 receptor antagonistic protein production by human monocytes, (iv) induction of chemotactic migration of CD8+ human T lymphocytes in vitro, (v) desensitization of human CD8+ T cells resulting in an unresponsiveness toward rhIL-10-induced chemotaxis, (vi) suppression of the chemotactic response of CD4+ T human lymphocytes toward IL-8, (vii) induction of IL-4 production by cultured normal human CD4+ T cells, (viii) down-regulation of tumor necrosis factor-alpha production by CD8+ T cells, and (ix) inhibition of class II major histocompatibility complex antigen expression on IFN-gamma-stimulated human monocytes. Another nonapeptide (IT9403) close to the NH2-terminal part of hIL-10 did not reveal cytokine synthesis inhibitory properties, but proved to be a regulator of mast cell proliferation. In conclusion, we have identified two functional domains of IL-10 exerting different IL-10 like activities, an observation that suggests that relatively small segments of these signal proteins are responsible for particular biological functions.

Objective: To investigate the occurrence of compartment syndrome and the results of fasciotomy in vascular surgical patients., Design: Retrospective study of case records from 1980-1994., Materials: Fifty-seven limbs in 53 patients had fasciotomies following surgical revascularisation. Fifty-three (93%) limbs were acutely ischaemic, while four (7%) had undergone elective vascular surgery. Forty-four (77%) limbs had signs of compartment syndrome, while 13 (23%) fasciotomies were prophylactic., Methods: The fasciotomies were done as subcutaneous procedures (n = 40), as double-incision fasciotomies (n = 11), or by an unknown method (n = 6). The skin incisions were closed primarily in 26 (46%) cases, delayed primarily in 11 (19%) cases, and by skin grafting in eight cases (14%)., Results: Five (13%) subcutaneous fasciotomies required revision. Surgical debridement was required in four (7%) limbs. At discharge, 36 (68%) patients had kept their limbs, 11 (21%) patients were amputated, and six (11%) had died. No complications relating to the fasciotomies were observed., Conclusions: Compartment syndrome is usually related to acute ischaemia and rarely following elective vascular surgery. Subcutaneous fasciotomy does not always ensure sufficient decompression of all four lower leg compartments. Complications related to fasciotomy are rare.

Interleukin-8 (IL-8), a neutrophil-activating cytokine, also activates certain T cell functions such as chemotaxis. We additionally find (n = 6) that recombinant (rIL-8; 1-100 ng/ml), when added to 24 h culture of human CD4+ T cells, suppressed the spontaneous production of IL-4 (50-85%). Steady state production of Il-4 was typically around 30 pg/ml, determined by use of a solid- phase immunoabsorbant assay. De novo synthesis of IL-4 from CD4+ T cells cultured for 3 days was also evaluated by use of detection of [35S]methionine incorporation, as visualized by autoradiography of 2-D gels, and showed that IL-8 suppressed IL-4 production. This suppression of IL-4 production was confirmed in the cytosol fraction by use of Western blotting. The effect of IL-8 (100 ng/ml) was comparable to that of 10 ng/ml recombinant interferon-gamma, both strongly suppressing IL-4 production. The regulatory effect of IL-8 on IL-4 production was also indicated by the fact that addition of a neutralizing monoclonal anti-IL-8 antibody (WS.4) enhanced the spontaneous IL-4 production when added to the culture of CD4+ T cells, thereby probably inactivating the effect of IL-8 originating from the cultured T cells. Also, we observed that IL-4 mRNA expression was down-regulated when the CD4+ T cells were cultured for 12 h in the presence of 100 ng/ml IL-8. The suppression of IL-4 mRNA expression could be prevented by adding anti-IL-8 (20 microgram/ml) or IL-10 (100 ng/ml) l h before adding rIL-8. Thus, IL-8 may be an important regulator of CD4+ T cell-derived IL-4, thereby possibly regulating the balance between humoral and cellular T cell-dependent responses.

Objective: Surgery results in a catabolic state of postoperative stress, where the efficiency of the liver to convert amino acids to urea is increased. This study measured the metabolic consequences of the less traumatic laparoscopic surgery in elective cholecystectomy compared with traditional open surgery technique., Summary Background Data: The authors previously have shown that open cholecystectomy doubles the urea synthesis measured by the means of the functional hepatic nitrogen clearance. Glucagon and cortisol increased by 50% (p < 0.05) and 75% (p < 0.05), respectively, after open cholecystectomy., Methods: Patients undergoing uncomplicated elective laparoscopic cholecystectomies were included. Preoperatively and on the first postoperative day, blood and urine samples were drawn every hour under basal conditions and during amino acid infusion. The urea synthesis rate was calculated from the urea excreted in urine and accumulated in total body water. Functional hepatic nitrogen clearance was quantified as the slope of the linear relation between blood amino-N concentration and the urea synthesis rate. The results were compared with an historic matched group of patients who underwent open cholecystectomies and were studied by the same protocol., Results: The laparoscopic cholecystectomy increased the functional hepatic nitrogen clearance by only 25% (from 8.7 +/- 0.9 to 11.1 +/- 1.5 mL/sec [mean +/- SEM; p < 0.05]), compared with a doubling after open cholecystectomy (from 9.4 +/- 0.9 to 17.6 +/- 3.3 mL/sec [p < 0.05]). The difference between the groups was significant (p < 0.05). Neither glucagon nor cortisol increased significantly after laparoscopic cholecystectomy., Conclusions: The laparoscopic technique results in a much smaller postoperative hepatic catabolic stress response and probably reduced tissue loss of amino-N. This may be important for the more rapid convalescence and reduced postoperative fatigue.

Measurements of rates of dissolution of typical insulation wool fibers (glasswool and basalt based stonewool) and an experimental fiber were made using a flow-through equipment. The liquids used were a modified Gamble's solution, adjusted to pH 4.8 and 7.7 +/- 0.2, respectively. The dissolution of SiO2 and CaO was determined over periods of up to three months. The rate of dissolution of stonewool fibers was lower than that of glasswool fibers at pH 7.7, whereas the opposite was true at pH 4.8. The stonewool fibers dissolve congruently, but glasswool fibers tend to dissolve with leaching. The rates of dissolution of fibers of different compositions, including insulation wool (glasswool, basalt-based stonewool, slagwool) and experimental fibers were screened using a stationary set-up. Both the chemical composition and pH influenced the rates of dissolution. At pH 7.7 alumina was a determining component and at pH 4.8 the content of SiO2 and CaO was determinant. One experimental fiber with a high content of alumina was an exception having a fairly high rate of dissolution both at pH 4.8 and 7.7.

This study was designed to determine the occurrence and topographical distribution of galanin-like immunoreactivity (GAL-LI) in the porcine gallbladder and sphincter of Oddi and to investigate the pharmacologic effect of GAL on gallbladder and sphincter of Oddi motility. By radioimmunoassay the concentration of GAL-LI in the gallbladder was 2.75 +/- 0.23, 9.73 +/- 1.33 in the common bile duct and 5.10 +/- 0.37 in the sphincter of Oddi (pmol/g +/- SE). By immunohistochemistry GAL-LI was found exclusively in ganglionic cells and in nerve fibers among the smooth muscle bundles. Gallbladder and sphincter of Oddi pressures were recorded before and during 5-minute local intraarterial infusion of 4, 8, 19, 39, 78 and 194 ng GAL - Kg-1 - min-1 in 12 anaesthetized pigs. GAL in doses greater than or equal to 39 ng.kg-1.min-1 significantly reduced sphincter of Oddi phasic wave frequency (4.8 +/- 0.4 vs. 2.1 +/- 0.5; p = 0.004) and sphincter of Oddi motility index (70.2 +/- 6.02 vs. 27.7 +/- 8.3; p = 0.002) but did not affect gallbladder pressure. We conclude that the distribution of GAL-LI in the sphincter of Oddi and the effect that a pharmacologic dose of GAL has on sphincter of Oddi motor activity, suggests that GAL may be involved in the physiologic control of bile flow in the pig.

The responses of gastric inhibitory polypeptide (GIP) and insulin to intraduodenal and IV triglyceride infusions were measured in 11 late fetal and 10 neonatal pigs. Basal plasma glucose, insulin, and GIP concentrations were lower in fetal than in neonatal pigs. In the fetal pigs, plasma glucose increased slightly during intraduodenal and IV triglyceride infusions, whereas plasma insulin remained unchanged during the tests. No significant changes were observed in plasma GIP concentration following intraduodenal triglyceride infusion in the fetal pigs, but plasma GIP fell during the IV infusion of triglyceride in these pigs (p less than 0.01). In the neonatal pigs, plasma glucose and insulin remained unaffected by intraduodenal and triglyceride infusions. Plasma GIP did not change during the IV triglyceride infusion, but exhibited a paradoxical decline after the intraduodenal triglyceride infusion (p less than 0.05). It is concluded that the GIP-cell response to an oral triglyceride load is suppressed in late fetal and neonatal pigs. The abolished GIP response to oral triglycerides could play a causal role in the inactivity of the enteroinsular axis which is seen in both human and animal neonates.