Endoprosthetic reconstruction of massive bone defects has become the reconstruction method of choice after limb-sparing resection of primary malignant tumors of the long bones. Given the improved ...survival rates of patients with extremity bone sarcomas, an increasing number of patients survive but have prosthetic complications over time. Several studies have reported on the outcome of first endoprosthetic complications. However, no comprehensive data, to our knowledge, are available on the likelihood of an additional complication and the associated risk factors, despite the impact of this issue on the affected patients.
(1) What are the types and timing of complications and the implant survivorship free from revision after the first complication? (2) Does survivorship free from repeat revision for a second complication differ by anatomic sites? (3) Is the type of first complication associated with the risk or the type of a second complication? (4) Are patient-, tumor-, and treatment-related factors associated with a higher likelihood of repeat revision?
Between 1993 and 2015, 817 patients underwent megaprosthetic reconstruction after resection of a tumor in the long bones with a single design of a megaprosthetic system. No other prosthetic system was used during the study period. Of those, 75% (616 of 817) had a bone sarcoma. Seventeen patients (3%) had a follow-up of less than 6 months, 4.5% (27 of 599) died with the implant intact before 6 months and 43% (260 of 599 patients) underwent revision. Forty-three percent of patients (260 of 599) experienced a first prosthetic complication during the follow-up period. Ten percent of patients (26 of 260) underwent amputation after the first complication and were excluded from further analysis. Second complications were classified using the classification of Henderson et al. to categorize surgical results. Briefly, this system categorizes complications as wound dehiscence (Type 1); aseptic loosening (Type 2); implant fractures or breakage and periprosthetic fracture (Type 3); infection (Type 4); and tumor progression (Type 5). Implant survival curves were calculated with the Kaplan-Meier method and compared using the log-rank test. Hazard ratios (HR) were estimated with their respective 95% CIs in multivariate Cox regression models.
A second complication occurred in 49% of patients (115 of 234) after a median of 17 months (interquartile range IQR 5 to 48) after the surgery for the first complication. The time to complication did not differ between the first (median 16 months; IQR 5 to 57) and second complication (median 17 months; IQR 5 to 48; p = 0.976). The implant survivorship free from revision surgery for a second complication was 69% (95% CI 63 to 76) at 2 years and 46% (95% CI 38 to 53) at 5 years. The most common mode of second complication was infection 39% (45 of 115), followed by structural complications with 35% (40 of 115). Total bone and total knee reconstructions had a reduced survivorship free from revision surgery for a second complication at 5 years (HR 2.072 95% CI 1.066 to 3.856; p = 0.031) compared with single joint replacements. With the numbers we had, we could not show a difference between the survivorship free of revision for a second complication based on the type of the first complication (HR 0.74 95% CI 0.215 to 2.546; p = 0.535). We did not detect an association between total reconstruction length, patient BMI, and patient age and survivorship free from revision for a second complication. Patients had a higher risk of second complications after postoperative radiotherapy (HR 1.849 95% CI 1.092 to 3.132; p = 0.022) but not after preoperative radiotherapy (HR 1.174 95% CI 0.505 to 2.728; p = 0.709). Patients with diabetes at the time of initial surgery had a reduced survivorship free from revision for a second complication (HR 4.868 95% CI 1.497 to 15.823; p = 0.009).
Patients who undergo revision to treat a first megaprosthetic complication must be counseled regarding the high risk of future complications. With second complications occurring relatively soon after the first revision, regular orthopaedic follow-up visits are advised. Preoperative rather than postoperative radiotherapy should be performed when possible. Future studies should evaluate the effectiveness of different approaches in treating complications considering implant survivorship free of revision for a second complication.
Level III, therapeutic study.
Introduction
Postnatal cytomegalovirus (CMV) infection of immunocompetent hosts is usually inapparent but typically results in lifelong latency. Congenital CMV infections as well as CMV infections in ...patients with immunodeficiencies have been linked to major cerebellar pathology. Patients with severe mental illness have been repeatedly found to have smaller cerebellum, and they may be particularly susceptible to CMV infections. Finally, both animal and human studies have shown a differential male and female immune response to CMV.
Objectives
We evaluated whole cerebellar grey matter volumes (CGMV) in CMV immunoglobulin G (IgG) seropositive (CMV+) and seronegative (CMV-) patients with severe mental illness and healthy controls (HC). We hypothesized that CMV seropositivity, reflecting previous infection and current latency, is associated with smaller CGMV in patients but not in HC, and that such a putative association may be sex-dependent.
Methods
We included 529 adult patients with severe mental illness (CMV+ 57%, women 48%), i.e., 324 patients with schizophrenia spectrum disorders and 205 patients with bipolar spectrum disorders, and 494 HC (CMV+ 56%, women 45%). MRI scans were obtained with a 1.5T Siemens scanner (n=596) and two 3.0T General Electric scanners (n=427), and processed with FreeSurfer v6.0. Circulating CMV IgG concentrations were measured with immunoassays. In age-, scanner- and estimated total intracranial volume-adjusted analyses of covariance (ANCOVAs), we investigated main and interaction effects of CMV status and sex on CGMV in patients and HC.
Results
CMV+ patients had smaller CGMV than CMV- patients (p=0.042). There was no CGMV difference between CMV+ and CMV- HC (p=0.858). The adjusted CGMV means in CMV+ patients and CMV- patients were 115078 mm
3
and 116725 mm
3
, respectively (p=0.042); the adjusted CGMV means in CMV+ and CMV- HC were 117980 mm
3
and 117840 mm
3
, respectively (p=0.858) (Image). Among patients, a trend towards CMV-by-sex interaction (p=0.073) was found. Post-hoc analyses showed a significant CMV-CGMV association in the female patient group (p=0.005), with no association among male patients (p=0.840).
Image:
Conclusions
CMV IgG seropositivity is associated with smaller cerebellum in severe mental illness, an effect driven by the female patients, but not among HC. This may indicate a CMV-related deleterious impact on cerebellum restricted to patients.
Disclosure of Interest
None Declared
Endoprosthetic reconstruction of massive bone defects has become the reconstruction method of choice after limb-sparing resection of primary malignant tumors of the long bones. Given the improved ...survival rates of patients with extremity bone sarcomas, an increasing number of patients survive but have prosthetic complications over time. Several studies have reported on the outcome of first endoprosthetic complications. However, no comprehensive data, to our knowledge, are available on the likelihood of an additional complication and the associated risk factors, despite the impact of this issue on the affected patients.
(1) What are the types and timing of complications and the implant survivorship free from revision after the first complication? (2) Does survivorship free from repeat revision for a second complication differ by anatomic sites? (3) Is the type of first complication associated with the risk or the type of a second complication? (4) Are patient-, tumor-, and treatment-related factors associated with a higher likelihood of repeat revision?
Between 1993 and 2015, 817 patients underwent megaprosthetic reconstruction after resection of a tumor in the long bones with a single design of a megaprosthetic system. No other prosthetic system was used during the study period. Of those, 75% (616 of 817) had a bone sarcoma. Seventeen patients (3%) had a follow-up of less than 6 months, 4.5% (27 of 599) died with the implant intact before 6 months and 43% (260 of 599 patients) underwent revision. Forty-three percent of patients (260 of 599) experienced a first prosthetic complication during the follow-up period. Ten percent of patients (26 of 260) underwent amputation after the first complication and were excluded from further analysis. Second complications were classified using the classification of Henderson et al. to categorize surgical results. Briefly, this system categorizes complications as wound dehiscence (Type 1); aseptic loosening (Type 2); implant fractures or breakage and periprosthetic fracture (Type 3); infection (Type 4); and tumor progression (Type 5). Implant survival curves were calculated with the Kaplan-Meier method and compared using the log-rank test. Hazard ratios (HR) were estimated with their respective 95% CIs in multivariate Cox regression models.
A second complication occurred in 49% of patients (115 of 234) after a median of 17 months (interquartile range IQR 5 to 48) after the surgery for the first complication. The time to complication did not differ between the first (median 16 months; IQR 5 to 57) and second complication (median 17 months; IQR 5 to 48; p = 0.976). The implant survivorship free from revision surgery for a second complication was 69% (95% CI 63 to 76) at 2 years and 46% (95% CI 38 to 53) at 5 years. The most common mode of second complication was infection 39% (45 of 115), followed by structural complications with 35% (40 of 115). Total bone and total knee reconstructions had a reduced survivorship free from revision surgery for a second complication at 5 years (HR 2.072 95% CI 1.066 to 3.856; p = 0.031) compared with single joint replacements. With the numbers we had, we could not show a difference between the survivorship free of revision for a second complication based on the type of the first complication (HR 0.74 95% CI 0.215 to 2.546; p = 0.535). We did not detect an association between total reconstruction length, patient BMI, and patient age and survivorship free from revision for a second complication. Patients had a higher risk of second complications after postoperative radiotherapy (HR 1.849 95% CI 1.092 to 3.132; p = 0.022) but not after preoperative radiotherapy (HR 1.174 95% CI 0.505 to 2.728; p = 0.709). Patients with diabetes at the time of initial surgery had a reduced survivorship free from revision for a second complication (HR 4.868 95% CI 1.497 to 15.823; p = 0.009).
Patients who undergo revision to treat a first megaprosthetic complication must be counseled regarding the high risk of future complications. With second complications occurring relatively soon after the first revision, regular orthopaedic follow-up visits are advised. Preoperative rather than postoperative radiotherapy should be performed when possible. Future studies should evaluate the effectiveness of different approaches in treating complications considering implant survivorship free of revision for a second complication.
Level III, therapeutic study.
IntroductionEarly-onset schizophrenia (EOS) is a relatively uncommon disorder with psychotic symptoms emerging before 18 years of age. Although still under debate, EOS may be a more severe disorder ...relative to adult-onset schizophrenia (AOS), with worse prognosis. Cognitive deficits are a core feature of schizophrenia, accounting for a large part of the detrimental effect of the disorder and may reflect underlying neurodevelopmental disturbances. Some but not all previous studies show that the magnitude of cognitive deficits, including intelligence quotient (IQ), in patients with schizophrenia is dependent on the age of onset.ObjectivesWe aimed to assess IQ in adult patients with EOS and AOS, and healthy controls. We hypothesized that patients with EOS would show lower IQ than those with AOS, and both patient groups lower IQ than HC.MethodsWe included 136 adult patients with EOS (mean age: 24.7 (7.7) years, mean duration of illness: 9.3 (8.5) years, 50% women), 382 patients with AOS (mean age: 32.4 (9.5) years, mean duration of illness: 5.7 (6.6) years, 40.1% women) and 896 adult healthy controls (mean age: 33.2 (9.2) years, 47.1% women). We assessed current IQ with the Wechsler Abbreviated Scale of Intelligence (WASI) which yielded verbal (VIQ), performance (PIQ) and full-scale IQ (FIQ) scores. In a post-hoc analysis, we estimated premorbid IQ using the National Adult Reading Test (NART). We applied analyses of covariance (ANCOVAs) to investigate the putative differences in IQ scores and IQ change between patients with EOS, patients with AOS and healthy controls.ResultsIn sex-, and age-adjusted models, FIQ and PIQ, but not VIQ, were significantly lower in EOS than in AOS (p=0.03, p<0.001 and p=0.428, respectively) (Image). Patients with EOS had fewer years of education than patients with AOS (p<0.001); the PIQ but not the FIQ difference between EOS and AOS remained significant after adjustment for education years (p=0.016 and p=0.333, respectively). Both patient groups had significantly lower IQ scores than healthy controls (Image). Further, patients with EOS and patients with AOS did not significantly differ in estimated premorbid IQ (109 and 110 units, respectively, p=0.092), whereas patients with EOS had a significantly larger estimated IQ decline after the disease onset compared to patients with AOS (12 and 9 units decline, respectively, p=0.015).Image:ConclusionsOur findings show that adult patients with EOS have significantly lower PIQ and FIQ scores, and significantly larger IQ decline after the disease onset, but not lower premorbid IQ, compared to patients with AOS. The adolescent onset of psychotic symptoms is linked, as expected, to fewer total years of education, which appears to explain the lower FIQ but only partially the lower PIQ in EOS, which may thereby be linked to the disorder per se.Disclosure of InterestT. Calkova: None Declared, L. Mørch-Johnsen: None Declared, R. Elle Smelror: None Declared, K. Nordbø Jørgensen: None Declared, S. Cervenka: None Declared, K. Collste: None Declared, A. Vaskinn: None Declared, A. Margrethe Myhre: None Declared, O. A. Andreassen Consultant of: HealthLytix, Speakers bureau of: Lundbeck and Sunovion, T. Ueland: None Declared, I. Agartz: None Declared, D. Andreou: None Declared
This paper presents the first phase in the development and validation of a simple and reliable environmental (e)DNA method using conventional PCR to detect four species of non‐native freshwater fish: ...pumpkinseed Lepomis gibbosus, sunbleak Leucaspius delineatus, fathead minnow Pimephales promelas and topmouth gudgeon Pseudorasbora parva. The efficacy of the approach was demonstrated in indoor tank (44 l) trials in which all four species were detected within 24 h. Validation was through two field trials, in which L. gibbosus was detected 6–12 h after its introduction into outdoor experimental ponds and P. parva was successfully detected in disused fish rearing ponds where the species was known to exist. Thus, the filtration of small (30 ml) volumes of pond water was sufficient to capture fish eDNA and the approach emphasised the importance of taking multiple water samples of sufficient spatial coverage for detecting species of random or patchy distribution.
Purpose
This study first analyzes implant survival of this single design modular rotating hinge knee and identifies potential risk factors for failure and evaluates joint function using the ...postoperative WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score, active flexion and extension deficit.
Methods
131 prostheses implanted for failure of prior total knee arthroplasty (
n
= 120) or complex primary procedures (
n
= 11) using a single modular implant (MUTARS—modular universal tumor and revision system GenuX, Implantcast, Buxtehude, Germany) between 2006 and 2014 including 73 patients treated for periprosthetic joint infection with a two-stage revision protocol were retrospectively identified. Implant survival was assessed using the Kaplan–Meier method; potential risk factors were identified using the log-rank test, as well as non-parametric analysis. Postoperative function was assessed using the WOMAC and measurement of range of motion.
Results
After a median follow-up of 62 months, 37 implants required implant revision (28%). Five-year survival was 69.7% 95% CI (confidence interval) 60.9–78.5 with periprosthetic (re-) infection being the main cause for failure (15%), followed by aseptic loosening (9%). In cases of periprosthetic infection, infection-free survival was 83% at 5 years (95% CI 74–92) with twelve patients suffering reinfection (16%).While body mass index (
p
= 0.75), age (
p
= 0.16) or indication for rotating hinge knee arthroplasty (
p
= 0.25) had no influence on survival, Charlson comorbidity score (CCI) (
p
= 0.07) and number of previous revision surgeries (
p
= 0.05) correlated with implant failure. There was trend (
p
= 0.1) for improved survival in fully cemented implants. Mean postoperative WOMAC was 127(range 55–191), 11 patients (15%) had limited knee extension.
Conclusions
Rotating hinge total knee arthroplasty using a single modular implant shows acceptable survival rates and function compared to previous studies with (re-)infection being the most relevant mode of failure. Patients with a high CCI and multiple previous surgeries are at increased risk for failure.
Level of evidence
Retrospective cohort study, III.
Schizophrenia is thought to be a neurodevelopmental disorder with neuronal migration, differentiation and maturation disturbances. Tau is a microtubule-associated protein with a crucial role in these ...processes. Lower circulating tau levels have been reported in adults with schizophrenia, but this association has not been investigated in adolescent psychosis. We aimed to test the hypotheses that a) adolescents with early-onset psychosis (EOP; age of onset <18 years) display lower plasma tau concentrations compared to healthy controls, and b) among patients with psychosis, tau levels are linked to structural brain measures associated with the microtubule-associated tau (MAPT) gene and psychosis. We included 37 adolescent patients with EOP (mean age 16.4 years) and 59 adolescent healthy controls (mean age 16.2 years). We investigated putative patient-control differences in plasma total tau concentrations measured by a Single molecule array (Simoa) immunoassay. We explored the correlations between tau and selected structural brain measures based on T1-weighted MRI scans processed in FreeSurfer v6.0. We found significantly lower plasma tau concentrations in patients compared to healthy controls (p = 0.017, partial eta-squared = 0.061). Tau was not associated with antipsychotic use or the antipsychotic dosage. Among patients but not healthy controls, tau levels were positively correlated with the cortical orbitofrontal surface area (p = 0.013, R-squared = 0.24). The results are suggestive of a tau-related neurodevelopmental disturbance in adolescent psychosis.
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