Loss of C2orf69 defines a fatal autoinflammatory syndrome in humans and zebrafish that evokes a glycogen-storage-associated mitochondriopathy.

Human C2orf69 is an evolutionarily conserved gene whose function is unknown. Here, we report eight unrelated families from which 20 children presented with a fatal syndrome consisting of severe autoinflammation and progredient leukoencephalopathy with recurrent seizures; 12 of these subjects, whose DNA was available, segregated homozygous loss-of-function C2orf69 variants. C2ORF69 bears homology to esterase enzymes, and orthologs can be found in most eukaryotic genomes, including that of unicellular phytoplankton. We found that endogenous C2ORF69 (1) is loosely bound to mitochondria, (2) affects mitochondrial membrane potential and oxidative respiration in cultured neurons, and (3) controls the levels of the glycogen branching enzyme 1 (GBE1) consistent with a glycogen-storage-associated mitochondriopathy. We show that CRISPR-Cas9-mediated inactivation of zebrafish C2orf69 results in lethality by 8 months of age due to spontaneous epileptic seizures, which is preceded by persistent brain inflammation. Collectively, our results delineate an autoinflammatory Mendelian disorder of C2orf69 deficiency that disrupts the development/homeostasis of the immune and central nervous systems.

Undersizing of the tibial component in Oxford unicompartmental knee arthroplasty (UKA) increases the risk of periprosthetic fractures.

INTRODUCTION: Tibial periprosthetic fractures (TPF) after unicompartmental knee arthroplasty (UKA) are a rare condition that affects about 1% of cases. Known risk factors include age, sex, body mass index (BMI), and bone density, as well as surgical technique and prosthesis design. The purpose of the study was to determine if undersizing of the tibial component in relation to the femoral component increases the risk of tibial periprosthetic fractures. MATERIAL AND METHODS: Over a 6-year-period 1542 patients with cemented (n = 363) and uncemented (n = 1179) medial UKA were retrospectively evaluated. Tibial periprosthetic fractures were identified and classified, and epidemiologic data were documented at follow-up. Undersizing was defined as a smaller tibial component compared to the femoral implant. The association of potential risk factors for TPF with the incidence of TPF was investigated with binominal logistic regression. RESULTS: Fourteen patients (0.9%) suffered from TPF at a median of 1 month after surgery. The mean follow-up period was 5.9 ± 1.7 years. Fractures were more common in cases with undersized tibial components [odds ratio (OR) 3.2, p < 0.05]. Furthermore, older age (OR 1.1, p < 0.05) and female sex (OR 6.5, p < 0.05) were identified as significant risk factors, while BMI (p = 0.8) and cemented implantation (p = 0.2) had no effect on fracture rate. Revision surgery included open reduction and internal fixation or conversion to total knee arthroplasty. CONCLUSIONS: Undersizing of implant sizes in UKA increases the risk for TPF especially in patients with small tibial implants. Therefore, mismatched implants should be avoided for UKA particularly when risk factors like obesity, older age, or female gender are present. Tibial periprosthetic fractures were successfully treated by open reduction and internal fixation or conversion to total knee arthroplasty.

Restoration of hip geometry after total hip arthroplasty: retrospective comparison of two short stems and one straight stem.

BACKGROUND: The preservation or restoration of hip geometry following total hip arthroplasty (THA) is of importance, considering that alterations in the centrum-collum-diaphysis (CCD)-angle, femoral offset (FO), acetabular offset (AO) and total offset (TO) change hip biomechanics. Therefore, the most suitable implant should be used. The aim of this study was to compare the ability of two short-stem-systems and one straight-stem-system to reconstruct hip geometry. METHODS: Two-hundred-fifty-one patients (mean age: 62.0 ± 10.0 years; 51.8% males) undergoing THA with three different stem types were retrospectively included, after excluding 11 patients with missing radiological follow-up. Pre- and postoperative radiographic images (group I, ANA.NOVA Alpha Schaft Proxy®, ImplanTec, 12 options: n = 99; group II, Optimys® Mathys, 24 options: n = 62; group III: Corail®-System, DePuy-Synthes, 76 options: n = 90) were analyzed. Differences in pre- and postoperative hip geometry (i.e. CCD, FO, AO, TO) were compared between groups with one-way-analysis-of-variance (ANOVA), and post-hoc t-tests. RESULTS: The CCD-angle increased by a mean of 8.4° ± 7.2° from pre-to postoperative, with no significant difference between groups (p = 0.097). Significantly larger increases in FO were observed for groups II (4.1 mm ± 7.8 mm) and III (4.9 ± 7.2 mm), in comparison to group I (1.6 ± 6.9 mm; p = 0.006). AO decreased by a mean of 2.2 ± 4.5 mm, with the largest decrease observed in group III (-3.3 ± 5.3 mm), and the smallest for group I (-1.4 ± 3.6 mm; p = 0.011). There was no significant difference in change of TO between groups (p = 0.177). CONCLUSIONS: Reconstruction of hip geometry using a single-version novel short-stem-system is achievable with comparable results to stem-systems offering multiple options.

Femoral Head and Liner Exchange in Patients with Atraumatic Dislocation. Results of a Retrospective Study with 6 Years Follow-Up.

Background and Objectives: Femoral head and liner exchange is an established treatment for polyethylene wear but has had a more limited role in the treatment of other conditions including dislocation, because of concerns about an increased postoperative dislocation rate. Some authors have considered dislocation associated with polyethylene wear to be a contraindication for this procedure. Materials and Methods: Our retrospective review evaluated the outcome of head and liner exchange in a small consecutively operated heterogeneous cohort of 20 patients who presented with dislocation unrelated to trauma, component malposition or component loosening. Of this group, 12 had prior primary total hip arthroplasty, and 8 had prior revision total hip arthroplasty, and included 4 patients with prior revision for dislocation. Mean follow-up was 6 ± 3.5 years (range 1-145 months). Results: Kaplan-Meier analysis revealed a revision-free implant survival from any cause of 80% (confidence interval 95%:64.3-99.6%) at 5 years after head and liner exchange (index surgery). At final follow-up, 83.3% of patients (n = 10) with prior primary total hip arthroplasty and 62.5% of patients (n = 5) with prior revision total hip arthroplasty, had not required subsequent revision for any cause. None (0%) of the primary total hip arthroplasty group and 3 (38%) of the revision arthroplasty group had required revision for further dislocation. Of the eight revision arthroplasty patients, four had a prior revision for dislocation and three of these four patients required further revision for dislocation after index surgery. The fourth patient had no dislocation after index surgery. One additional patient who had prior revision surgery for femoral component fracture suffered dislocation after index surgery, but was successfully treated with closed reduction. Conclusions: In our study population, femoral head and liner exchange was an effective treatment option for patients with prior primary total hip arthroplasty and also for a highly select group of revision total arthroplasty patients with no prior history of dislocation. Femoral head and liner exchange does not appear to be a viable treatment option for patients who have had revision total arthroplasty after prior dislocations.

Mid-term to long-term results of primary arthroscopic Bankart repair for traumatic anterior shoulder instability: a retrospective study.

BACKGROUND: The arthroscopic method offers a less invasive technique of Bankart repair for traumatic anterior shoulder instability. The aim of the study is to determine the mid-/long-term functional outcome, failure rates and predictors of failure after primary arthroscopic Bankart repair for traumatic anterior shoulder instability. METHODS: A total of 100 patients were primarily operated using arthroscopic Bankart repair after traumatic anterior shoulder instability. Medical records were retrospectively reviewed, and patients were assessed using postal questionnaire after a mean follow-up of 8.3 years [3-14]. Clinical assessment was performed using Constant score, Rowe score, and American Shoulder and Elbow Surgeons score. RESULTS: The overall recurrence rate was 22%. The Kaplan-Meier failure-free survival estimates. were 80% at 5 years and 70% at 10 years. Nearly half (54.5%) of recurrences occurred at 2 years postoperative. Compared with normal shoulder, there were statistical differences in all 3 scores. Failure rate was significantly affected by age at the time of surgery with 86% of recurrence cases observed in patients aged 30 years or younger. Nevertheless, Younger age at the time of surgery (P = 0.007) as well age at the time of initial instability (P = 0.03) was found to correlate negatively with early recurrence within 2 years of surgery. Among those with recurrent instability, recurrence rate was found to be higher if there had been more than 5 instability episodes preoperatively (P = 0.01). Return to the preinjury sport and occupational level was possible in 41 and 78%, respectively. CONCLUSION: Failure-free survival rates dropped dramatically over time. Alternative reconstruction techniques should be considered in those aged ≤30 years due to the high recurrence rate.

Does the degree of osteoarthritis influence the clinical outcome after anatomic total shoulder arthroplasty?

BACKGROUND: The degree of preoperative osteoarthritis has been shown to influence the postoperative outcome and the patients' satisfaction rate in hip and knee joint replacement surgery. However, no corresponding information is available for total shoulder arthroplasty (TSA). We therefore set out to evaluate the influence of preoperatively measured end-stage osteoarthritis on the postoperative clinical outcome of TSA. METHODS: A retrospective analysis of 103 anatomic total shoulder replacements (96 patients) was performed. Patients were evaluated radiologically with X-rays in two planes and clinically using the Constant and Murley score (CS) and the self-reported satisfaction with the result. The degree of osteoarthritis was radiographically analyzed with the aid of the classifications according to Kellgren/Lawrence, Gerber, Guyette, and Allain and according to whether complete narrowing of the glenohumeral joint was present or not [bone-on-bone contact (BOB) or no bone-on-bone contact (No BOB)]. RESULTS: The clinical results of TSA did not differ significantly among the various stages of osteoarthritis in any of the classifications (p > 0.05). The CS was significantly higher postoperatively for both the BOB and the No BOB group (p < 0.0001). Patients with BOB had a significantly lower CS preoperatively than patients with No BOB (p = 0.0172). In addition, the preoperative pain level was significantly higher in patients with BOB (p = 0.014). Postoperatively, no significant difference in CS (p = 0.6738) was found between the BOB group and the No BOB group. The mean improvement in CS was not statistically significant (p = 0.2218). CONCLUSION: In contrast to hip and knee joint replacement procedures, a milder grade of osteoarthritis does not adversely influence the functional result or subjective satisfaction rate after TSA. The degree of osteoarthritis on conventional X-rays has no bearing on the postoperative clinical outcome. Therefore, the decision on when to carry out anatomic total shoulder arthroplasty should depend on the patient's pain level and loss of quality of life.

Fifty-six percent of proximal femoral cortical hypertrophies 6 to 10 years after Total hip arthroplasty with a short Cementless curved hip stem - a cause for concern?

BACKGROUND: Thigh pain and cortical hypertrophies (CH) have been reported in the short term for specific short hip stem designs. The purpose of the study was to investigate 1) the differences in clinical outcome, thigh pain and stem survival for patients with and without CHs and 2) to identify patient and surgery-related factors being associated with the development of CHs. METHODS: A consecutive series of 233 patients with 246 hips was included in the present retrospective diagnostic cohort study, who had received a total hip arthroplasty (THA) between December 2007 and 2009 with a cementless, curved, short hip stem (Fitmore, Zimmer, Warsaw, IN, USA). Clinical and radiographic follow-up, including the radiographic parameters for hip geometry reconstruction, were prospectively assessed 1, 3, and 6 to 10 years after surgery. RESULTS: Cortical hypertrophies were observed in 56% of the hips after a mean of 7.7 years, compared to 53% after 3.3 years being mostly located in Gruen zone 3 and 5. There was no significant difference for the Harris Hip Score and UCLA score for patients with and without CHs. Only one patient with a mild CH in Gruen zone 5 and extensive heterotopic ossifications around the neck of the stem reported thigh pain. The Kaplan Meier survival rate after 8.6 years was 99.6% (95%-CI; 97.1-99.9%) for stem revision due to aseptic loosening and no association with CHs could be detected. Postoperative increase in hip offset was the only risk factor being associated with the development of CHs in the regression model (ΔHO; OR 1.1 (1.0-1.2); p = 0.001). CONCLUSIONS: The percentage of cortical hypertrophies remained almost constant in the mid-term compared to the short-term with the present cementless short hip stem design. The high percentage of cortical hypertrophies seems not be a cause for concern with this specific implant in the mid-term. LEVEL OF EVIDENCE: Diagnostic Level IV.

Diagnostic performance of 3D-multi-Echo-data-image-combination (MEDIC) for evaluating SLAP lesions of the shoulder.

BACKGROUND: Superior labral anterior to posterior (SLAP) lesions remain a clinical and diagnostic challenge in routine (non-arthrographic) MR examinations of the shoulder. This study prospectively evaluated the ability of 3D-Multi-Echo-Data-Image-Combination (MEDIC) compared to that of routine high resolution 2D-proton-density weighted fat-saturated (PD fs) sequence using 3 T-MRI to detect SLAP lesions using arthroscopy as gold standard. METHODS: Seventeen consecutive patients (mean age, 51.6 ± 14.8 years, 11 males) with shoulder pain underwent 3 T MRI including 3D-MEDIC and 2D-PD fs followed by arthroscopy. The presence or absence of SLAP lesions was evaluated using both sequences by two independent raters with 4 and 14 years of experience in musculoskeletal MRI, respectively. During arthroscopy, SLAP lesions were classified according to Snyder's criteria by two certified orthopedic shoulder surgeons. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 3D-MEDIC and 2D-PD fs for detection of SLAP lesions were calculated with reference to arthroscopy as a gold standard. Interreader agreement and sequence correlation were analyzed using Cohen's kappa coefficient. Figure 1 demonstrates the excellent visibility of a proven SLAP lesion using the 3D-MEDIC and Fig. 2 demonstrates a false-positive case. RESULTS: Arthroscopy revealed SLAP lesions in 11/17 patients. Using 3D-MEDIC, SLAP lesions were diagnosed in 14/17 patients by reader 1 and in 13/17 patients by reader 2. Using 2D-PD fs, SLAP lesions were diagnosed in 11/17 patients by reader 1 and 12/17 patients for reader 2. Sensitivity, specificity, PPV, and NPV of 3D-MEDIC were 100.0, 50.0, 78.6, and 100.0% for reader 1; and 100.0, 66.7, 84.6, and 100% for reader 2, respectively. Sensitivity, specificity, PPV, and NPV of 2D-PD fs were 90.9, 83.3, 90.9, and 83.3% for reader 1 and 100.0, 83.3, 91.7, and 100.0% for reader 2. The combination of 2D-PD fs and 3D-MEDIC increased specificity from 50.0 to 83.3% for reader 1 and from 66.7 to 100.0% for reader 2. Interreader agreement was almost perfect with a Cohen's kappa of 0.82 for 3D-MEDIC and 0.87 for PD fs. CONCLUSIONS: With its high sensitivity and NPV, 3D-MEDIC is a valuable tool for the evaluation of SLAP lesions. As the combination with routine 2D-PD fs further increases specificity, we recommend incorporation of 3D-MEDIC as an additional sequence in conventional shoulder protocols in patients with non-specific shoulder pain.

Size of ischial fibro-ostosis is associated with heterotopic ossification after total hip arthroplasty.

PURPOSE: The hypothesis of the present study was that degenerative fibro-ostosis (FO) of the ischial hamstring tendon insertion is a risk factor for heterotopic ossification (HO) following THA. METHODS: We followed 103 consecutive patients (43 males, 60 females, mean age 61 years) who underwent unilateral cementless THA for primary hip osteoarthritis and investigated the incidence of HO within the first 12 months after surgery. On pre-operative radiographs, a standardized evaluation for FO of the ischial hamstring tendon insertion concerning horizontal, vertical, and square dimensions was performed. HO was classified according to Brooker on radiographs at 12 months post-operatively. RESULTS: At follow-up, 56 patients (54%) had no radiographic evidence of HO, 23 (22%) were classified as Brooker I, 17 (17%) as II, 6 (6%) as III, and 1 (1%) as IV, respectively. Patients with post-operative HO had significantly greater vertical (3.0 mm vs. 2.3 mm, p = 0.001) and horizontal (47.9 mm vs. 39.1 mm, p = 0.025) dimensions of FO than patients without HO. Patients with FO and a vertical dimension of ≥ 2.5 mm were more likely to develop HO (55.6%) than patients with a vertical FO dimension of less than 2.5 mm (34.7%, OR = 2.35 p = 0.047). A weak correlation between the vertical and horizontal size of FO and the severity of HO was observed. CONCLUSION: Radiographic evidence of asymptomatic FO is a potential risk factor for the development of HO following THA and may be used as a simple diagnostic tool to pre-operatively identify patients at risk for post-operative HO. This association has not been previously described and further research to confirm the present findings and to justify additional prophylactic treatment in these patients is warranted.

Three dimensional gait analysis in patients with symptomatic component mal-rotation after total knee arthroplasty.

PURPOSE: Purpose of the present cohort study was the determination of lower body function and rotation in patients with symptomatic component mal-rotation after total knee arthroplasty using instrumented 3D gait analysis. METHODS: A consecutive series of 12 patients (61.3 years ± 11.4 years) were included suffering under remaining pain or limited range of motion at least six months after total knee arthroplasty. A CT-scan according to the protocol of Berger et al. and instrumented 3D gait analysis were carried out including clinical examination, videotaping, and kinematic analysis using a Plug-in Gait model. Outcome variables were temporospatial parameters as well as kinematics in sagittal and transversal plane. Data for reference group were collected retrospectively and matched by age and gender. RESULTS: Temporospatial parameters of the study group showed decreased velocity, cadence, and step length as well as increased step time. Single limb support was reduced for the affected limb. In sagittal plane, maximum knee flexion during swing phase was reduced for the replaced knee joint. In transverse plane, there was hardly any difference between affected and non-affected limb. Compared to the reference group, both limbs show significant increased internal ankle rotation and external hip rotation. There were significant strong linear correlations between ankle rotation and hip rotation as well as ankle rotation and radiological tibial mal-rotation. CONCLUSIONS: Patients with symptomatic component mal-rotation after total knee arthroplasty showed typically functional deficits. The affected and non-affected limb showed significant increased internal ankle rotation and external hip rotation, while only the affected, replaced knee showed reduced internal knee rotation. Identification of rotational abnormalities of hip and ankle joints seems to be mandatory in TKA to identify the patient group with external hip rotation, internal ankle rotation, and an elevated risk for symptomatic rotational TKA component mal-alignment.

Additive Influence of Hip Offset and Leg Length Reconstruction on Postoperative Improvement in Clinical Outcome After Total Hip Arthroplasty.

BACKGROUND: There is a lack of prospective studies investigating the additive effect of both acetabular and femoral reconstruction parameters on the functional outcome following total hip arthroplasty (THA). METHODS: The aim of this prospective cohort study was to determine the combined influence of hip geometry reconstruction and component positioning on the clinical outcome following primary THA for unilateral osteoarthritis. We prospectively assessed the clinical outcome and radiographic parameters for hip geometry reconstruction, component position, and orientation using validated measurements for the operated hip compared to the contralateral native hip in a consecutive series of 113 patients with primary unilateral cementless THA. The correlation of reconstruction parameters was investigated using a multivariate polynomial regression model for the dependent variable ΔHHS (difference between the Harris hip scores preoperatively and 2.0-4.8 years postoperatively). Target zones for hip reconstruction and component positioning were investigated for an association with superior clinical outcome. RESULTS: The regression model demonstrated a significant correlation for the ΔHHS and both hip offset (HO) reconstruction and leg length difference. Patients with accurate to slightly increased HO reconstruction combined with balanced leg length demonstrated a significantly higher ΔHHS than patients outside this zone (HO: 5 ± 5 and LLD: 0 ±5 mm, P = .029). This finding could be confirmed for 2 enlarged zones (zone 1: HO, 7.5 ± 7.5 and LLD, 2.5 ± 7.5 mm, P = .028; zone 2: HO, 7.5 ± 7.5 and LLD, 7.5 ± 7.5 mm, P = .007). CONCLUSION: HO and leg length reconstruction demonstrated an additive effect on clinical outcome and surgeons should aim for high accuracy in the reconstruction of both factors.

Functional midterm follow-up comparison of stemless total shoulder prostheses versus conventional stemmed anatomic shoulder prostheses using a 3D-motion-analysis.

BACKGROUND: The aim of this study is to compare the functional midterm outcome of stemless shoulder prostheses with standard anatomical stemmed shoulder prostheses and to show that the STEMLESS results are comparable to the STEMMED with respect to active maximum range of shoulder motion (ROM) and Constant score (CS). METHODS: Seventeen patients underwent total shoulder arthroplasty (TSA) in 25 shoulder joints. Stemless TSA was performed in 12 shoulder joints (group STEMLESS), third-generation stemmed TSA in 13 shoulder joints (group STEMMED). Functional results were documented using the CS. 3D-motion-analysis using the Heidelberg upper extremity model (HUX) was conducted to measure active maximum (ROM). RESULTS: The group STEMLESS achieved a CS of 67.9 (SD 12.0) points and the group STEMMED of 70.2 (SD 5.8 points) without significant difference between the groups (p = 0.925). The maximum ROM of the group STEMLESS, ascertained by 3-D-motion-analysis, was in forward flexion 125.5° (SD 17.2°), in extension 49.4° (SD 13.8°), in abduction 126.2° (SD 28.5°) and in external rotation 40.3° (SD 13.9°). The maximum ROM of the group STEMMED, also ascertained by 3-D-motion analysis, was in forward flexion 135.0° (SD 16.8°), in extension 47.2° (SD 11.5°), in abduction 136.3° (SD 24.2°) and in external rotation 40.1° (SD 12.2°). The maximum ROM of the STEMLESS group was lower in forward flexion and abduction, higher in extension and almost identical in external rotation. But there was no significant difference (forward flexion p = 0.174, extension p = 0.470, abduction p = 0.345, external rotation p = 0.978). CONCLUSION: Both types of shoulder prostheses achieve a similar and good active ROM and similar results in CS. TRIAL REGISTRATION: DRKS00013166 , retrospectively registered, 11.10.2017.

Three-dimensional motion analysis for validation of shoulder internal rotation.

BACKGROUND: 10% of the points for the Constant-Murley score (CMS) are allocated for the capacity for internal rotation (IR), measured as unassisted active movement of the dorsum of the hand or the thumb to reach different anatomical landmarks. However, there is little information about the validity of this method and no three-dimensional measurement of the degree of IR that is necessary to reach these landmarks. METHODS: Sixteen volunteers with healthy shoulders were recruited. The degree of IR was defined using the following landmarks as described in the CMS: (1) lateral aspect of thigh, (2) buttock, (3) sacroiliac joint, (4) level of waist, (5) vertebra T12, (6) interscapular. The validity of IR measurement was assessed by simultaneous 3D motion analysis. RESULTS: Using the thumb as pointer, there were significant increases in IR from 39.3° at position 1 to 80.4° at position 2, followed by 105.1°, 108.6°, 110.1°, and 125.3° at position 3-6. Taking the dorsum of the hand as pointer, there were significant increases in IR between all positions, starting from 71.2° (position 1) and followed by 99.3°, 104.1°, 110.3°, 115.2°, and 119.7° at positions 2 to 6. Comparing the two measurement methods, a significant difference was found for the amount of IR between positions 1 and 2. CONCLUSION: Measurement of IR as described in the CMS is a suitable method. However, there was an increase of only 10° in IR between positions 3 and 5, which may be hard to measure with a standard goniometer in clinical practice.

Exploring Trends of C and N Isotope Fractionation to Trace Transformation Reactions of Diclofenac in Natural and Engineered Systems.

Although diclofenac ranks among the most frequently detected pharmaceuticals in the urban water cycle, its environmental transformation reactions remain imperfectly understood. Biodegradation-induced changes in 15N/14N ratios (εN = -7.1‰ ± 0.4‰) have indicated that compound-specific isotope analysis (CSIA) may detect diclofenac degradation. This singular observation warrants exploration for further transformation reactions. The present study surveys carbon and nitrogen isotope fractionation in other environmental and engineered transformation reactions of diclofenac. While carbon isotope fractionation was generally small, observed nitrogen isotope fractionation in degradation by MnO2 (εN = -7.3‰ ± 0.3‰), photolysis (εN = +1.9‰ ± 0.1‰), and ozonation (εN = +1.5‰ ± 0.2‰) revealed distinct trends for different oxidative transformation reactions. The small, secondary isotope effect associated with ozonation suggests an attack of O3 in a molecular position distant from the N atom. Model reactants for outer-sphere single electron transfer generated large inverse nitrogen isotope fractionation (εN = +5.7‰ ± 0.3‰), ruling out this mechanism for biodegradation and transformation by MnO2. In a river model, isotope fractionation-derived degradation estimates agreed well with concentration mass balances, providing a proof-of-principle validation for assessing micropollutant degradation in river sediment. Our study highlights the prospect of combining CSIA with transformation product analysis for a better assessment of transformation reactions within the environmental life of diclofenac.

Compound-Specific Stable Isotope Fractionation of Pesticides and Pharmaceuticals in a Mesoscale Aquifer Model.

Compound-specific isotope analysis (CSIA) receives increasing interest for its ability to detect natural degradation of pesticides and pharmaceuticals. Despite recent laboratory studies, CSIA investigations of such micropollutants in the environment are still rare. To explore the certainty of information obtainable by CSIA in a near-environmental setting, a pulse of the pesticide bentazone, the pesticide metabolite 2,6-dichlorobenzamide (BAM), and the pharmaceuticals diclofenac and ibuprofen was released into a mesoscale aquifer with quasi-two-dimensional flow. Concentration breakthrough curves (BTC) of BAM and ibuprofen demonstrated neither degradation nor sorption. Bentazone was transformed but did not sorb significantly, whereas diclofenac showed both degradation and sorption. Carbon and nitrogen CSIA could be accomplished in similar concentrations as for "traditional" priority pollutants (low µg/L range), however, at the cost of uncertainties (0.4-0.5‰ (carbon), 1‰ (nitrogen)). Nonetheless, invariant carbon and nitrogen isotope values confirmed that BAM was neither degraded nor sorbed, while significant enrichment of (13)C and in particular (15)N corroborated transformation of diclofenac and bentazone. Retardation of diclofenac was reflected in additional (15)N sorption isotope effects, whereas isotope fractionation of transverse dispersion could not be identified. These results provide a benchmark on the performance of CSIA to monitor the reactivity of micropollutants in aquifers and may guide future efforts to accomplish CSIA at even lower concentrations (ng/L range).

Time to Wound Healing and Major Adverse Limb Events in Patients with Critical Limb Ischemia Treated with Endovascular Revascularization.

BACKGROUND: There are few studies that quantify the impact of time to wound healing on outcomes after endovascular revascularization of critical limb ischemia (CLI). METHODS: In this retrospective study, 179 patients with CLI and tissue loss were assessed for adverse events after endovascular therapy. Associations between time to wound healing and outcomes were determined via Cox proportional hazards analysis. The long-term probability of events was assessed with Kaplan-Meier analysis. The primary end point was major adverse limb events (MALE-major amputation, surgical endarterectomy, or bypass). Secondary end points were major amputation, need for repeat endovascular therapy, and mortality. RESULTS: After multivariable adjustment for time-dependent wound healing, age, renal function, diabetes, and Rutherford class, independent predictors of MALE included the presence of an unhealed wound (hazard ratio [HR], 5.2; 95% confidence interval (CI), 2.3-11.8; P < 0.0001) and creatinine ≥ 2.0 (HR, 2.4; 95% CI, 1.4-4.3; P = 0.003). On Kaplan-Meier analysis, the probability of MALE was greater in patients with unhealed wounds compared with healed wounds (log-rank P < 0.0001). Patients whose wounds healed within 4 months had a lower probability of MALE than patients who did not heal by 4 months (log-rank, P = 0.04). Unhealed wounds were also independently associated with major amputation (HR, 9.0; 95% CI, 2.6-31.1; P = 0.0004), and patients whose wounds healed by 3 months had less major amputation (log-rank, P = 0.04). Unhealed wounds were independently associated with increased risk of mortality (HR, 42.7; 95% CI, 5.7-319.0; P = 0.002) but not repeat revascularization. CONCLUSIONS: Unhealed wounds are an independent risk factor for MALE, major amputation, and mortality after endovascular treatment of CLI. Wound healing within 3 months is associated with less risk of major amputation, and within 4 months less risk of MALE. A focus should be on achieving wound healing as fast as possible in this population.

Definition of anatomical zero positions for assessing shoulder pose with 3D motion capture during bilateral abduction of the arms.

BACKGROUND: Surgical interventions at the shoulder may alter function of the shoulder complex. Clinically, the outcome can be assessed by universal goniometry. Marker-based motion capture may not resemble these results due to differing angle definitions. METHODS: The clinical inspection of bilateral arm abduction for assessing shoulder dysfunction is performed with a marker based 3D optical measurement method. An anatomical zero position of shoulder pose is proposed to determine absolute angles according to the Neutral-0-Method as used in orthopedic context. Static shoulder positions are documented simultaneously by 3D marker tracking and universal goniometry in 8 young and healthy volunteers. Repetitive bilateral arm abduction movements of at least 150° range of motion are monitored. Similarly a subject with gleno-humeral osteoarthritis is monitored for demonstrating the feasibility of the method and to illustrate possible shoulder dysfunction effects. RESULTS: With mean differences of less than 2°, the proposed anatomical zero position results in good agreement between shoulder elevation/depression angles determined by 3D marker tracking and by universal goniometry in static positions. Lesser agreement is found for shoulder pro-/retraction with systematic deviations of up to 6°. In the bilateral arm abduction movements the volunteers perform a common and specific pattern in clavicula-thoracic and gleno-humeral motion with maximum shoulder angles of 32° elevation, 5° depression and 45° protraction, respectively, whereas retraction is hardly reached. Further, they all show relevant out of (frontal) plane motion with anteversion angles of 30° in overhead position (maximum abduction). With increasing arm anteversion the shoulder is increasingly retroverted, with a maximum of 20° retroversion. The subject with gleno-humeral osteoarthritis shows overall less shoulder abduction range of motion but with increased out-of-plane movement during abduction. CONCLUSIONS: The proposed anatomical zero definition for shoulder pose fills the missing link for determining absolute joint angles for shoulder elevation/depression and pro-/retraction. For elevation-/depression the accuracy suits clinical expectations very well with mean differences less than 2° and limits of agreement of 8.6° whereas for pro-/retraction the accuracy in individual cases may be inferior with limits of agreement of up to 24.6°. This has critically to be kept in mind when applying this concept to shoulder intervention studies.

Are there differences between stemless and conventional stemmed shoulder prostheses in the treatment of glenohumeral osteoarthritis?

BACKGROUND: Conventional stemmed anatomical shoulder prostheses are widely used in the treatment of glenohumeral osteoarthritis. The stemless shoulder prosthesis, in contrast, is a new concept, and fewer outcome studies are available. Therefore, the purpose of the study was to investigate the early functional outcome and postoperative proprioception of a stemless prosthesis in comparison with a standard stemmed anatomic shoulder prosthesis. METHODS: Twelve patients (mean age 68.3 years [SD ± 5.4]; 5 female, 7 male) with primary glenohumeral osteoarthritis of the shoulder were enrolled, who underwent total shoulder arthroplasty (TSA) with a stemless total shoulder prosthesis, Total Evolution Shoulder System (TESS; Biomed, France). The control group consisted of twelve (age and gender matched) patients (mean age 67.8 years; [SD ± 7.1]; 9 female, 3 male), getting a TSA with a standard anatomic stemmed prosthesis, Aequalis Shoulder (Tournier, Lyon, France). Patients were examined the day before and six months after surgery. The pre- and postoperative Constant Score (CS) was evaluated and proprioception was measured in a 3D video motion analysis study using an active angle-reproduction (AAR) test. RESULTS: Comparing the postoperative CS, there was no significant difference between the groups treated with the TESS prosthesis (48.0 ± 13.8 points) and the Aequalis prosthesis (49.3 ± 8.6 points; p = 0.792). There was no significant difference in postoperative proprioception between the TESS group (7.2° [SD ± 2.8]) and the Aequalis group(8.7° [SD ± 2.7]; p = 0.196), either. Comparison of in the results of CS and AAR test pre- and postoperatively showed no significant differences between the groups. DISCUSSION: In patients with glenohumeral osteoarthritis, treated with TSA, the functional and the proprioceptive outcome is comparable between a stemless and a standard stemmed anatomic shoulder prosthesis at early followup. CONCLUSION: Further follow-up is necessary regarding the long-term performance of this prosthesis. TRIAL REGISTRATION: Current Controlled Trials DRKS 00007528 . Registered 17 November 2014.

Cortical hypertrophy with a short, curved uncemented hip stem does not have any clinical impact during early follow-up.

BACKGROUND: Short stems have become more and more popular for cementless total hip arthroplasty in the past few years. While conventional, uncemented straight stems for primary total hip arthroplasty (THA) have shown high survival rates in the long term, it is not known whether uncemented short stems represent a reasonable alternative. As cortical hypertrophy has been reported for short stems, the aim of this study was to determine the radiographic prevalence of cortical hypertrophy and to assess the clinical outcome of a frequently used short, curved hip stem. METHODS: We retrospectively studied the clinical and radiographic results of our first 100 consecutive THAs (97 patients) using the Fitmore® hip stem. Mean age at the time of index arthroplasty was 59 years (range, 19 - 79 years). Clinical outcome and radiographic results were assessed with a minimum follow-up of 2 years, and Kaplan-Meier survivorship analysis was used to estimate survival for different endpoints. RESULTS: After a mean follow-up of 3.3 years (range, 2.0 - 4.4 years), two patients (two hips) had died, and three patients (four hips) were lost to follow-up. Kaplan-Meier analysis estimated a survival rate of 100 % at 3.8 years, with revision for any reason as the endpoint. No femoral component showed radiographic signs of loosening. No osteolysis was detected. Cortical hypertrophy was found in 50 hips (63 %), predominantly in Gruen zone 3 and 5. In the cortical hypertrophy group, two patients (two hips; 4 %) reported some thigh pain in combination with pain over the greater trochanter region during physical exercise (UCLA Score 6 and 7). There was no significant difference concerning the clinical outcome between the cortical hypertrophy and no cortical hypertrophy group. CONCLUSIONS: The survival rate and both clinical and the radiographic outcome confirm the encouraging results for short, curved uncemented stems. Postoperative radiographs frequently displayed cortical hypertrophy but it had no significant effect on the clinical outcome in the early follow-up. Further clinical and radiographic follow-up is necessary to detect possible adverse, long-term, clinical effects of cortical hypertrophy.