Plasmalogens are a unique class of membrane glycerophospholipids containing a fatty alcohol with a vinyl-ether bond at the sn-1 position, and enriched in polyunsaturated fatty acids at the sn-2 ...position of the glycerol backbone. These two features provide novel properties to these compounds. Although plasmalogens represent up to 20% of the total phospholipid mass in humans their physiological roles have been challenging to identify, and are likely to be particular to different tissues, metabolic processes and developmental stages. Their biosynthesis starts in peroxisomes, and defects at these steps cause the malformation syndrome, Rhizomelic Chondrodysplasia Punctata (RCDP). The RCDP phenotype predicts developmental roles for plasmalogens in bone, brain, lens, lung, kidney and heart. Recent studies have revealed secondary plasmalogen deficiencies associated with more common disorders and allow us to tease out additional pathways dependent on plasmalogen functions. In this review, we present current knowledge of plasmalogen biology in health and disease. This article is part of a Special Issue entitled: Metabolic Functions and Biogenesis of peroxisomes in Health and Disease.
► Plasmalogen synthesis and regulation. ► Unique roles ascribed to these molecules: anti-oxidants, membrane structure, signal transduction. ► Primary plasmalogen deficiency disease states: RCDP. ► Secondary plasmalogen deficiency disease states: respiratory disorders, Alzheimer disease. ► Plasmalogen replacement therapy.
Purpose
The currently used system to classify the lower limb alignment (neutral, varus, valgus) does not consider the orientation of the joint line or its relationship to the overall lower limb ...alignment. Similarly, current total knee arthroplasty (TKA) alignment concepts do not sufficiently consider the variability of the native coronal alignment. Therefore, the purpose of this study was (1) to introduce a new classification system for the lower limb alignment, based on phenotypes, and (2) to compare the alignment targets of different TKA alignment concepts with the native alignment of non-osteoarthritic patients.
Methods
Two recent articles phenotyped the lower limb, the femur and tibia of 308 non-osteoarthritic knees of 160 patients male to female ratio = 102:58, mean age ± standard deviation 30 ± 7 years (16–44 years). The present study introduces functional knee phenotypes, which are a combination of all previously introduced phenotypes. The functional knee phenotypes therefore enable an evaluation of all parameters in relation to each other and thus a comprehensive analysis of the coronal alignment. The existing functional knee phenotypes in the female and male population were investigated. In addition, how many non-osteoarthritic knees had an alignment within the range of current TKA alignment targets (mechanical, anatomical and restricted kinematic alignment) was investigated. Therefore, it was defined which functional knee phenotypes represented a target of the TKA alignment concepts and which percentage of the population had such a phenotype.
Results
Out of 125 possible functional knee phenotypes, 43 were found (35 male, 26 and 18 mutual). The most common functional knee phenotype in males was NEU
HKA
0° + NEU
FMA
0° + NEU
TMA
0° (19%), followed by VAR
HKA
3° + NEU
FMA
0° + VAR
TMA
0° (8.2%). The most common functional knee phenotype in females was NEU
HKA
0° + NEU
FMA
0° + NEU
TMA
0° (17.7%), closely followed by NEU
HKA
0° + NEU
FMA
0° + VAL
TMA
0° (16.6%). The functional knee phenotype representing a mechanical alignment target was found in 5.6% of the males and 3.6% of the females. The phenotype representing an anatomical alignment target was found in 18% of the males and 17% in females. Five of the nine phenotypes representing a restricted kinematic alignment target were found in this population (male 5, female 4, mutual 4). They represented 31.3% of all males and 45.1% of all females.
Conclusion
A more individualized approach to TKA alignment is needed. The functional knee phenotypes enable a simple, but detailed assessment of a patient’s individual anatomy and thereby could be a helpful tool to individualize the approach to TKA.
Level of clinical evidence
III, retrospective cohort study.
Adrenoleukodystrophy (ALD) is a rare X‐linked disease caused by a mutation of the peroxisomal ABCD1 gene. This review summarizes our current understanding of the pathogenic cell‐ and tissue‐specific ...roles of lipid species in the context of experimental therapeutic strategies and provides an overview of critical historical developments, therapeutic trials and the advent of newborn screening in the USA. In ALD, very long‐chain fatty acid (VLCFA) chain length‐dependent dysregulation of endoplasmic reticulum stress and mitochondrial radical generating systems inducing cell death pathways has been shown, providing the rationale for therapeutic moiety‐specific VLCFA reduction and antioxidant strategies. The continuing increase in newborn screening programs and promising results from ongoing and recent therapeutic investigations provide hope for ALD.
Purpose
There is a lack of knowledge about the joint line orientation of the femur and tibia in non-osteoarthritic knees. The primary purpose of the present study was to evaluate the orientation of ...the joint lines in native non-osteoarthritic knees using 3D-reconstructed CT scans. The secondary purpose was to identify knee phenotypes to combine the information of the femoral and tibial alignment.
Methods
A total of 308 non-osteoarthritic knees of 160 patients (male to female ratio = 102:58, mean age ± standard deviation 30 ± 7 years (16–44 years) were retrospectively included from our registry. All patients received CT of the knee according to the Imperial Knee Protocol. The orientation of the femoral and tibial joint line was measured in relation to their mechanical axis (femoral mechanical angle, FMA, and tibial mechanical angle, TMA) using a commercially planning software (KneePLAN 3D, Symbios, Yverdon les Bains, Switzerland). The values of FMA and TMA were compared between males and females. Descriptive statistics, such as means, ranges, and measures of variance (e.g. standard deviations), were presented. Based on these results, phenotypes were introduced for the femur and tibia. These phenotypes, based on FMA and TMA values, consist of a mean value and cover a range of ± 1.5° from this mean (3° increments). The distribution of femoral and tibial phenotypes, and their combinations (knee phenotypes) were calculated for the total group and for both genders.
Results
The overall mean FMA ± standard deviation (SD) was 93.4° ± 2.0° and values ranged from 87.9° varus to 100° valgus. The overall mean TMA ± SD was 87.2° ± 2.4° with a range of 81.3° varus to 94.6° valgus. FMA and TMA showed significant gender differences (
p
< 0.01). Females showed more valgus alignment than males. The most common femoral phenotype was neutral in both genders. The most common tibial phenotype was neutral in the male knees (62.8%) and valgus (41.6%) in the female knees. In males, the most frequent combination (knee phenotype) was a neutral phenotype in the femur and a neutral phenotype in the tibia (25.6%). In females, it was a neutral femoral phenotype and a valgus tibial phenotype (28.3%).
Conclusion
3D-reconstructed CT scans confirmed the great variability of the joint line orientation in non-osteoarthritic knees. The introduced femoral and tibial phenotypes enable the evaluation of the femoral and tibial alignment together (knee phenotypes). The variability of knee phenotypes found in this young non-osteoarthritic population clearly shows the need for a more individualized approach in TKA.
Level of evidence
III.
Purpose
Recently introduced total knee arthroplasty (TKA) alignment strategies aim to restore the pre-arthritic alignment of an individual patient. The native alignment of a patient can only be ...restored with detailed knowledge about the native and osteoarthritic alignment as well as differences between them. The first aim of this study was to assess the alignment of a large series of osteoarthritic (OA) knees and investigate whether femoral and tibial joint lines vary within patients with the same overall lower limb alignment. The secondary aim was to compare the alignment of OA patients to the previously published data of non-OA patients. This information could be useful for surgeons considering implementing one of the new alignment concepts.
Material
Coronal alignment parameters of 2692 knee OA patients were measured based on 3D reconstructed CT data using a validated planning software (Knee-PLAN
®
, Symbios, Yverdon les Bains, Switzerland). Based on these measurements, patients' coronal alignment was phenotyped according to the functional knee phenotype concept. These phenotypes represent an alignment variation of either the overall alignment, the femoral joint line orientation or the tibial joint line orientation. Each phenotype is defined by a specific mean and covers a range of ± 1.5° from this mean. Mean values and distribution among the phenotypes are presented and compared between two populations (OA patients of this study and non-OA patients of a previously published study) as well as between HKA subgroups (varus, valgus and neutral) using
t
tests and Chi-square tests (
p
< 0.05).
Results
Femoral and tibial joint lines varied within patients with the same overall lower limb alignment. A total of 162 functional knee phenotypes were found (119 males, 136 females and 94 mutual phenotypes). Mean values differed between the OA and non-OA population, but differences were small (< 2°) except for the overall alignment (e.g. HKA). The distribution of OA and non-OA patients among the phenotypes differed significantly, especially among the limb phenotypes.
Conclusion
Differences between OA and non-OA knees are small regarding coronal femoral and tibial joint line orientation. Femoral and tibial joint line orientation of osteoarthritic patients can, therefore, be used to estimate their native coronal alignment and plan an individualized knee alignment.
Level of clinical evidence
III.
Patients with knee osteoarthritis often receive glucocorticoid (GC) or hyaluronic acid (HA) injections to alleviate symptoms. This study evaluated the impact of Triamcinolone Hexacetonide (a GC), HA, ...and a combination of both on bovine osteochondral grafts exposed to IL-1β and IL-17 in an ex vivo culture. Metabolic activity increased with GC treatment. GCs and GCs/HA counteracted cytokine effects, with gene expressions similar to untreated controls, while HA alone did not. However, HA improved the coefficient of friction after two weeks. The highest friction values were observed in GC-containing and cytokine-treated groups. Cytokine treatment reduced tissue proteoglycan content, which HA could mitigate, especially in the GC/HA combination. This combo also effectively controlled proteoglycan release, supported by reduced sGAG release. Cytokine treatment led to surface cell death, while GCs, HA, or their combination showed protective effects against inflammation. The GC/HA combination had the best overall results, suggesting its potential as a superior treatment option for osteoarthritis.
Peroxisome biogenesis disorders in the Zellweger spectrum (PBD-ZSD) are a heterogeneous group of genetic disorders caused by mutations in PEX genes responsible for normal peroxisome assembly and ...functions. As a result of impaired peroxisomal activities, individuals with PBD-ZSD can manifest a complex spectrum of clinical phenotypes that typically result in shortened life spans. The extreme variability in disease manifestation ranging from onset of profound neurologic symptoms in newborns to progressive degenerative disease in adults presents practical challenges in disease diagnosis and medical management. Recent advances in biochemical methods for newborn screening and genetic testing have provided unprecedented opportunities for identifying patients at the earliest possible time and defining the molecular bases for their diseases. Here, we provide an overview of current clinical approaches for the diagnosis of PBD-ZSD and provide broad guidelines for the treatment of disease in its wide variety of forms. Although we anticipate future progress in the development of more effective targeted interventions, the current guidelines are meant to provide a starting point for the management of these complex conditions in the context of personalized health care.
•There is a pressing need for formalized clinical guidelines for PBD-ZSD.•We provide an overview of current clinical approaches for the diagnosis of PBD-ZSD.•We provide treatment guidelines for the major affected organ systems in PBD-ZSD.•This is a starting point for effective clinical management of PBD-ZSD.
Purpose
For coronal alignment in total knee arthroplasty (TKA) most surgeons use the patient’s individual hip-knee shaft (HKS) angle (angle between the anatomical axis and the mechanical axis of the ...femur). The major problem of the sole use of HKS angle is that the individual patient’s distal femoral asymmetry is not considered. The purpose of this study was to determine the variability of the HKS angle, the mechanical femoral angle (FMA) and to evaluate whether or not one of the two angles is more important for TKA alignment strategy. It was the hypothesis that HKS and FMA are not directly related to each other and hence HKS should not be considered as guide for coronal alignment.
Methods
Prospectively collected CT data of 1480 consecutive patients who underwent 3D reconstructed CT scans before TKA was used for this retrospective registry study 882 women and 598 men, mean age ± standard deviation 71 ± 9 years (34–99 years). The CT protocol was modified according to the Imperial Knee Protocol, which is a lowdose CT protocol that includes high-resolution 0.75-mm slices of the knee and 3-mm slices of the hip and ankle joints. All measurements were done using Symbios
®
3D knee preoperative planning’s software (Symbios, Yverdon les Bains, Switzerland). The HKS, FMA and hip-knee-ankle (HKA) angles were measured. Angles measured were displayed as mean, standard deviation (SD) and range. In addition, the angles were shown as percentages after categorization. The HKS was categorized between 3° and 9° in 1° increments. The FMA was categorized between 83.5° and 98.5° in 3° increments. The HKA was categorized between 12.5° varus 5.5° valgus in 3° increments. Pearson correlations were used to investigate correlation of HKS and FMA (
p
< 0.05).
Results
The HKS angle was not constant at 7° but averaged 6°, and ranged from 2.5° to 9°. The FMA angle was on average 93° but varied more than 20°, ranging from 75° (varus) to 104° (valgus). The mean HKA ± SD was − 3.4° ± 5.7° (range − 23.0° to 15.0°). The mean HKSSD was 5.6° ± 0.9° (range 2.5°–8.8°). The mean FMASD was 92.6° ± 2.8° (range 75.2°–103.5°). The Pearson correlations of all measured angles are presented in Table 1. HKS significantly correlated negatively with HKA and FMA (
p
< 0.001). FMA and HKA were strongly correlated with each other (
p
< 0.0001). Considering the HKS angle as a constant angle can induce a deviation of up to 5° with respect to an orthogonal distal femoral cutting objective. The great variability of the FMA angle implies that the FMA seems more relevant than the HKS angle to define the strategy of realignment of the lower limb. However, then patient specific instrumentation has to be used to precisely transfer the planning to the surgical technique. Having the aim of a more personalized TKA alignment in mind the individual constitutional knee phenotype should be taken into account.
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