BACKGROUND:This study attempted to identify where motion occurs after total ankle replacement, the difference in range-of-motion contributions between fixed-bearing and mobile-bearing total ankle ...replacements, and the contribution of abnormal peritalar motion. We hypothesized that sagittal plane radiographic assessment would demonstrate that actual ankle motion through the prosthesis is less than the total arc of ankle motion that may be observed clinically secondary to contributions from adjacent joints.
METHODS:Patients underwent routine standardized weight-bearing maximum dorsiflexion and plantar flexion sagittal radiographs. Sagittal plane ankle and foot measurements were performed on each dorsiflexion and plantar flexion radiograph to determine the total arc of ankle motion, actual ankle motion through the prosthesis, motion through the subtalar and talonavicular joints, and midfoot motion. Motion radiographs were routinely made at 1 year postoperatively and at the time of the most recent follow-up. A minimum follow-up of 2 years was required of all patients.
RESULTS:There were 197 patients who met the inclusion criteria (75 INBONE, 52 Salto Talaris, and 70 STAR prostheses). The mean time to the latest radiographs (and standard deviation) was 42.9 ± 18.8 months. The mean actual ankle motion through the prosthesis was 25.9° ± 12.2°, which was significantly less (p < 0.001) than the mean total motion arc of 37.6° ± 12.0°. The motion of the ankle accounted for 68% of total range of motion, and motion of the peritalar joints accounted for 32%. There was no significant difference (p > 0.05) among the 3 prostheses or when comparing fixed and mobile-bearing designs for both ranges of motion.
CONCLUSIONS:This study demonstrates that actual ankle motion after total ankle replacement is approximately 12° less than the total arc of motion that might be observed clinically because of increased midfoot and subtalar motion.
LEVEL OF EVIDENCE:Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
IMPORTANCE: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a frequent cause of adult-onset leukodystrophy known to be caused by autosomal dominant mutations in the ...CSF1R (colony-stimulating factor 1) gene. The discovery that CSF1R mutations cause ALSP led to more accurate prognosis and genetic counseling for these patients in addition to increased interest in microglia as a target in neurodegeneration. However, it has been known since the discovery of the CSF1R gene that there are patients with typical clinical and radiologic evidence of ALSP who do not carry pathogenic CSF1R mutations. These patients include those in whom the pathognomonic features of axonal spheroids and pigmented microglia have been found. Achieving a genetic diagnosis in these patients is important to our understanding of this disorder. OBJECTIVE: To genetically characterize a group of patients with typical features of ALSP who do not carry CSF1R mutations. DESIGN, SETTINGS, AND PARTICIPANTS: In this case series study, 5 patients from 4 families were identified with clinical, radiologic, or pathologic features of ALSP in whom CSF1R mutations had been excluded previously by sequencing. Data were collected between May 2014 and September 2015 and analyzed between September 2015 and February 2016. MAIN OUTCOMES AND MEASURES: Focused exome sequencing was used to identify candidate variants. Family studies, long-range polymerase chain reaction with cloning, and complementary DNA sequencing were used to confirm pathogenicity. RESULTS: Of these 5 patients, 4 were men (80%); mean age at onset of ALSP was 29 years (range, 15-44 years). Biallelic mutations in the alanyl-transfer (t)RNA synthetase 2 (AARS2) gene were found in all 5 patients. Frameshifting and splice site mutations were common, found in 4 of 5 patients, and sequencing of complementary DNA from affected patients confirmed that the variants were loss of function. All patients presented in adulthood with prominent cognitive, neuropsychiatric, and upper motor neuron signs. Magnetic resonance imaging in all patients demonstrated a symmetric leukoencephalopathy with punctate regions of restricted diffusion, typical of ALSP. In 1 patient, brain biopsy demonstrated axonal spheroids and pigmented microglia, which are the pathognomonic signs of ALSP. CONCLUSIONS AND RELEVANCE: This work indicates that mutations in the tRNA synthetase AARS2 gene cause a recessive form of ALSP. The CSF1R and AARS2 proteins have different cellular functions but overlap in a final common pathway of neurodegeneration. This work points to novel targets for research and will lead to improved diagnostic rates in patients with adult-onset leukoencephalopathy.
BACKGROUND:The popularity of total ankle replacement as a treatment for end-stage arthritis continues to grow. The purpose of this study was to assess changes in ankle kinetics and kinematics from a ...preoperative time point through two years postoperatively in patients who had received either a fixed-bearing or a mobile-bearing implant.
METHODS:Ninety patients who received a primary total ankle replacement (forty-nine mobile-bearing and forty-one fixed-bearing) were examined. Three-dimensional joint mechanics and ground reaction forces were measured during level walking preoperatively and one and two years postoperatively. Patient-reported and functional outcomes were also collected. Data were analyzed with use of a 3 × 2 repeated-measures analysis of variance (ANOVA) to determine significant differences between implant types and across time (α = 0.05).
RESULTS:No significant difference was observed in the ankle motion or step time between implant types or across time. However, there was a greater increase in the peak plantar flexion moment and the Short Form-36 (SF-36) total score across time in the fixed-bearing group than in the mobile-bearing group. Conversely, visual analog scale (VAS) pain scores exhibited greater improvement in the mobile-bearing group than in the fixed-bearing group. Independent of implant type, a significant improvement was observed in walking speed, results of the functional tests, spatiotemporal variables, patient-reported outcomes, and vertical ground reaction forces. Independent of time, the fixed-bearing group demonstrated a significant increase in both the weight-acceptance and the propulsion ground reaction forces compared with the mobile-bearing group. The mobile-bearing group completed the Sit-to-Stand test significantly faster.
CONCLUSIONS:All of the observed changes suggest improved or maintenance of function following total ankle replacement. In general, the group with a fixed-bearing implant demonstrated improvements in ankle moment and ground reaction forces, while the mobile-bearing-implant group demonstrated improvements in patient-reported pain outcome. There were few significant changes between the two implant types.
LEVEL OF EVIDENCE:Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
Adjuvant systemic therapies are now routinely used following resection of stage III melanoma, however accurate prognostic information is needed to better stratify patients. We use differential ...expression analyses of primary tumours from 204 RNA-sequenced melanomas within a large adjuvant trial, identifying a 121 metastasis-associated gene signature. This signature strongly associated with progression-free (HR = 1.63, p = 5.24 × 10
) and overall survival (HR = 1.61, p = 1.67 × 10
), was validated in 175 regional lymph nodes metastasis as well as two externally ascertained datasets. The machine learning classification models trained using the signature genes performed significantly better in predicting metastases than models trained with clinical covariates (p
= 7.03 × 10
), or published prognostic signatures (p
< 0.05). The signature score negatively correlated with measures of immune cell infiltration (ρ = -0.75, p < 2.2 × 10
), with a higher score representing reduced lymphocyte infiltration and a higher 5-year risk of death in stage II melanoma. Our expression signature identifies melanoma patients at higher risk of metastases and warrants further evaluation in adjuvant clinical trials.
Background. Ankle arthritis is a major cause of disability. Orthopaedic literature suggests improvement in health-related quality of life (HRQOL) after total ankle arthroplasty (TAA). This has not ...been compared with improvements observed in successful orthopaedic and nonorthopaedic procedures, including anterior cervical discectomy/fusion (ACDF), total knee arthroplasty (TKA), coronary artery bypass grafting (CABG), and orthotopic liver transplant (OLT). We hypothesize that the effects after TAA are comparable to several successful surgical procedures. Methods. 500 consecutive TAA patients were included and grouped with 2 other large series. Short Form-36 (SF36) were collected at standardized intervals. A systematic literature review identified studies comparing preoperative and postoperative SF36 physical (PCS) and mental component summary (MCS) scores. Using meta-analyses, we pooled the data for each procedure to compare with the TAA group. Results. Patients in all cohorts had preoperative SF36 MCS and PCS scores that were significantly lower than that in the general population. Improvements in HRQOL after TAA were not statistically different from improvements reported in PCS and MCS after ACDF, TKA, and OLT. However, improvement in PCS after TAA was better than that observed after CABG. Conclusions. Disability with ankle arthritis is severe. Disability associated with cervical disc disease, knee arthrosis, coronary artery disease, and liver failure is also severe, with surgical intervention providing major improvements in HRQOL postoperatively. The improvement in HRQOL after TAA did not differ statistically from ACDF, TKA, CABG, and OLT. Our investigation suggests that the HRQOL benefits of TAA meet benchmarks set by some of modern medicine’s best.
Levels of Evidence: Level III: Systematic review
Automotive fuel cell technology has made considerable progress, and hydrogen fuel cell vehicles are regarded as a possible long-term solution to reduce carbon dioxide emissions, reduce fossil fuel ...dependency and increase energy efficiency. Even though great strides have been made, durability is still an issue. One key challenge is controlling MEA contamination. Metal ion contamination within the membrane and the effects on fuel cell performance were investigated. Given the possible benefits of using stainless steel or aluminum for balance-of-plant components or bipolar plates, cations of Al, Fe, Ni and Cr were studied. Membranes were immersed in metal sulfide solutions of varying concentration and then assembled into fuel cell MEAs tested in situ. The ranking of the four transition metals tested in terms of the greatest reduction in fuel cell performance was: Al
3+
≫
Fe
2+
>
Ni
2+, Cr
3+. For iron-contaminated membranes, no change in cell performance was detected until the membrane conductivity loss was greater than approximately 15%.
Background:
Metal component failure in total ankle arthroplasty (TAA) is difficult to treat. Traditionally, conversion to an arthrodesis has been advocated. Revision TAA surgery has become more ...common with availability of revision implants and refinement of bone-conserving primary implants. The goal of this study was to analyze the clinical results and patient-reported outcomes for patients undergoing revision total ankle arthroplasty.
Methods:
We retrospectively reviewed prospectively collected data on 52 patients with a mean age of 63.5 ± 9.6 years who had developed loosening or collapse of major metal components following primary TAA. These patients were compared to a case-matched control group of 52 primary TAAs performed at the host institution with a minimum of 2 years’ follow-up. Cases of isolated polyethylene exchange, infection, or extra-articular realignment procedures were excluded. The American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot score, Short Form 36 (SF-36), Short Musculoskeletal Function Assessment (SMFA), and pain scores were prospectively collected. Clinical data was collected through review of the electronic medical record to identify reasons for clinical failure, where clinical failure was defined as second revision or conversion to arthrodesis or amputation.
Results:
The identified causes of failure of primary TAA were aseptic loosening of both components (42%), talar component subsidence/loosening (36%), coronal talar subluxation (12%), tibial loosening (8%), and talar malrotation (2%). Thirty-one patients (59.5%) underwent revision of all components, 20 (38.5%) just the talar and polyethylene components, and one (2%) the tibial and polyethylene components. The average time to revision was 5.5 years ± 5.4 with a follow-up of 3.1 years ± 1.5 after revision. Eleven (21.2%) revision arthroplasties required further surgery: 6 required conversion to arthrodesis and 5 required second revision TAA. Pain scores, SF-36 scores, SMFA scores, and AOFAS Hindfoot scores all improved after revision surgery but never reached the same degree of improvement seen after primary TAA.
Conclusions:
Clinical and patient-reported outcomes of revision ankle arthroplasty after metal component failure significantly improved after surgery, although the recovery time was longer. In this series, 21.2% of revision TAAs required a second revision TAA or arthrodesis surgery. Various prostheses performed similarly when used for revision surgery. Revision TAA can offer significant improvements postoperatively.
Level of Evidence:
Level III, therapeutic.
Background:
The Comprehensive Care for Joint Replacement (CJR) model provides bundled payments for in-hospital and 90-day postdischarge care of patients undergoing total ankle arthroplasty (TAA). ...Defining patient factors associated with increased costs during TAA could help identify modifiable preoperative patient factors that could be addressed prior to the patient entering the bundle, as well as determine targets for cost reduction in postoperative care.
Methods:
This study is part of an institutional review board–approved single-center observational study of patients undergoing TAA from January 1, 2012, to December 15, 2016. Patients were included if they met CJR criteria for inclusion into the bundled payment model. All Medicare payments beginning at the index procedure through 90 days postoperatively were identified. Patient, operative, and postoperative characteristics were associated with costs in adjusted, multivariable analyses. One hundred thirty-seven patients met inclusion criteria for the study.
Results:
Cerebrovascular disease (intracranial hemorrhages, strokes, or transient ischemic attacks) was initially associated with increased costs (mean, $5595.25; 95% CI, $1710.22-$9480.28) in adjusted analyses (P = .005), though this variable did not meet a significance threshold adjusted for multiple comparisons. Increased length of stay, discharge to a skilled nursing facility (SNF), admissions, emergency department (ED) visits, and wound complications were significant postoperative drivers of payment.
Conclusion:
Common comorbidities did not reliably predict increased costs. Increased length of stay, discharge to an SNF, readmission, ED visits, and wound complications were postoperative factors that considerably increased costs. Lastly, reducing the rates of SNF placement, readmission, ED visitation, and wound complications are targets for reducing costs for patients undergoing TAA.
Level of Evidence:
Level II, prognostic prospective cohort study.
The GUIDE-IT (GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) trial demonstrated that a strategy to “guide” application of guideline-directed medical therapy ...(GDMT) by reducing amino-terminal pro–B-type natriuretic peptide (NT-proBNP) was not superior to GDMT alone.
The purpose of this study was to examine the prognostic meaning of NT-proBNP changes following heart failure (HF) therapy intensification relative to the goal NT-proBNP value of 1,000 pg/ml explored in the GUIDE-IT trial.
A total of 638 study participants were included who were alive and had available NT-proBNP results 90 days after randomization. Rates of subsequent cardiovascular (CV) death/HF hospitalization or all-cause mortality during follow-up and Kansas City Cardiomyopathy Questionnaire (KCCQ) overall scores were analyzed.
A total of 198 (31.0%) subjects had an NT-proBNP ≤1,000 pg/ml at 90 days with no difference in achievement of NT-proBNP goal between the biomarker-guided and usual care arms. NT-proBNP ≤1,000 pg/ml by 90 days was associated with longer freedom from CV/HF hospitalization or all-cause mortality (p < 0.001 for both) and lower adjusted hazard of subsequent HF hospitalization/CV death (hazard ratio: 0.26; 95% confidence interval: 0.15 to 0.46; p < 0.001) and all-cause mortality (hazard ratio: 0.34; 95% confidence interval: 0.15 to 0.77; p = 0.009). Regardless of elevated baseline concentration, an NT-proBNP ≤1,000 pg/ml at 90 days was associated with better outcomes and significantly better KCCQ overall scores (p = 0.02).
Patients with heart failure with reduced ejection fraction whose NT-proBNP levels decreased to ≤1,000 pg/ml during GDMT had better outcomes. These findings may help to understand the results of the GUIDE-IT trial. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment GUIDE-IT; NCT01685840)
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AbstractObjectivesTo characterize the clinical severity of covid-19 associated with the alpha, delta, and omicron SARS-CoV-2 variants among adults admitted to hospital and to compare the ...effectiveness of mRNA vaccines to prevent hospital admissions related to each variant.DesignCase-control study.Setting21 hospitals across the United States.Participants11 690 adults (≥18 years) admitted to hospital: 5728 with covid-19 (cases) and 5962 without covid-19 (controls). Patients were classified into SARS-CoV-2 variant groups based on viral whole genome sequencing, and, if sequencing did not reveal a lineage, by the predominant circulating variant at the time of hospital admission: alpha (11 March to 3 July 2021), delta (4 July to 25 December 2021), and omicron (26 December 2021 to 14 January 2022).Main outcome measuresVaccine effectiveness calculated using a test negative design for mRNA vaccines to prevent covid-19 related hospital admissions by each variant (alpha, delta, omicron). Among patients admitted to hospital with covid-19, disease severity on the World Health Organization’s clinical progression scale was compared among variants using proportional odds regression.ResultsEffectiveness of the mRNA vaccines to prevent covid-19 associated hospital admissions was 85% (95% confidence interval 82% to 88%) for two vaccine doses against the alpha variant, 85% (83% to 87%) for two doses against the delta variant, 94% (92% to 95%) for three doses against the delta variant, 65% (51% to 75%) for two doses against the omicron variant; and 86% (77% to 91%) for three doses against the omicron variant. In-hospital mortality was 7.6% (81/1060) for alpha, 12.2% (461/3788) for delta, and 7.1% (40/565) for omicron. Among unvaccinated patients with covid-19 admitted to hospital, severity on the WHO clinical progression scale was higher for the delta versus alpha variant (adjusted proportional odds ratio 1.28, 95% confidence interval 1.11 to 1.46), and lower for the omicron versus delta variant (0.61, 0.49 to 0.77). Compared with unvaccinated patients, severity was lower for vaccinated patients for each variant, including alpha (adjusted proportional odds ratio 0.33, 0.23 to 0.49), delta (0.44, 0.37 to 0.51), and omicron (0.61, 0.44 to 0.85).ConclusionsmRNA vaccines were found to be highly effective in preventing covid-19 associated hospital admissions related to the alpha, delta, and omicron variants, but three vaccine doses were required to achieve protection against omicron similar to the protection that two doses provided against the delta and alpha variants. Among adults admitted to hospital with covid-19, the omicron variant was associated with less severe disease than the delta variant but still resulted in substantial morbidity and mortality. Vaccinated patients admitted to hospital with covid-19 had significantly lower disease severity than unvaccinated patients for all the variants.
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