Mid-term results of complex primary total knee arthroplasty using a rotating-hinge implant

BackgroundThe indications and outcomes of semi- or fully-constrained knee implants in primary total knee arthroplasty (TKA) are still controversially discussed. The present study aims to evaluate the mid-term results and complications of a modular/non-modular rotating-hinge implant in complex primary TKA.MethodsEighty-two patients (86 knees) following primary TKA were retrospectively evaluated with a mean follow-up of 63 months. The functional outcome was assessed using the American Knee Society Score (AKSS) and the Oxford Knee Score (OKS). A Visual Analog Scale (VAS) was used to determine pain levels. Implant survival and reoperation rates were estimated using competing risk analysis. Cox regression analysis was performed to evaluate the influence of modularity on implant survival.ResultsThe survival rate with the endpoint implant revision was 90% (95 %CI:83–98%) and the survival rate with the endpoint all reoperations was 84% (95 %CI:75–94%) at 7 years. The AKSS improved significantly from 24 (SD 14.9, range:0–69) preoperatively to 83 (SD 14.3, range:57–100) postoperatively (p < 0.001); functional AKSS improved significantly from 27 (SD 24.3, range:0–100) to 46 (SD: 32.9, range 0–100) (p = 0.003), and OKS from 19 (SD: 8.3, range:5–43) to 29 (SD: 10.7, range:6–48), respectively (p < 0.0001). VAS decreased significantly from 8 (SD: 2.6, range:0–10) preoperatively to 3 (SD: 2.9, range:0–9) postoperatively (p < 0.0001). There was no significant influence of modularity on revision rates comparing modular to non-modular implants (p = 0.072).ConclusionsThe present rotating-hinge implant provides substantial improvement in function and reduction of pain with good implant survival in the mid-term. Modularity was not associated with higher rates of revision.     

Insufficient lateral joint laxity after bicruciate-retaining total knee arthroplasty potentially influences kinematics during flexion: A biomechanical cadaveric study

BackgroundSoft tissue balancing in bicruciate-retaining (BCR) total knee arthroplasty (TKA) is a challenge that must be overcome to achieve excellent clinical outcomes. However, the optimal degree of joint laxity has yet to be clarified. This cadaveric study sought to examine joint laxity after BCR TKA using a navigation system.MethodsKnee joint laxity was quantified using an image-free navigation system in 8 intact fresh frozen cadavers under three conditions: the native knee, BCR TKA knee, and BCR TKA knee after anterior cruciate ligament resection. Rotational kinematics in the BCR TKA knee during flexion were compared according to whether joint laxity was increased or decreased.ResultsKnee joint laxity after BCR TKA under varus-valgus movement, anterior translation, and internal-external rotation loadings was similar to that of the native knee. However, lateral joint laxity was decreased during flexion in some cases. BCR TKA-treated knees with decreased lateral joint laxity at 90° of flexion demonstrated more limited tibial internal rotation in deep flexion than the native knee (p < 0.05). The loss of internal rotation in deep flexion was partly recovered by using a lateral insert with a posterior slope of +3°.ConclusionsRestoring optimal joint laxity was not always straightforward in BCR TKA if the 4 ligaments were preserved. Lateral joint laxity was potentially decreased in BCR TKA and may result in kinematic conflict during flexion. Surgeons should be aware of the need to achieve sufficient lateral joint laxity in this type of BCR TKA.     

CR-lipped bearing is an adequate functional solution to patients with perioperative excessive laxity in cruciate retaining total knee arthroplasty

BackgroundThe cruciate retaining lipped (CR-lipped) bearing is designed to provide more anterior-posterior (AP) stability and could be employed to resolve excessive intraoperative laxity during the cruciate retaining TKA (CR-TKA). The aim of the study was to determine whether the CR-lipped bearing in CR-TKAs with a perioperative excessive laxity allows equivalent functional results as compared to the standard CR articulation.MethodsA cohort of 111 TKAs with CR-lipped bearings was matched to a cohort of conventional CR bearings regarding age and sex. The CR-lipped bearing was used in patients with excessive knee AP laxity and the regular CR bearing was used in patients without excessive AP laxity during TKA. Various PROMs (WOMAC, KSS, SF-36) were assessed preoperatively and at 5-years postoperative in combination with revision rate and Range of Motion (ROM).ResultsPROMs did not differ significantly between both groups 5-years postoperatively. Mean ROM (flexion) 5-years postoperatively was not significantly different. The implant survivorship was 100% for both cohorts with revision for any reason as end point.ConclusionBased on these results, the CR-lipped bearing is a safe and effective solution for mild interoperatively assessed PCL laxity during CR-TKA without loss of function or decreased survivorship at 5 years. Peroperative conversion to a PS-TKA in order to obtain satisfactory functional scores might therefore not be necessary when mild PCL laxity is observed during surgery. Further research should focus on verifying this approach and longer follow-up is needed to generate data on long term survivorship.Level of evidenceLevel IV therapeutic, retrospective, cohort study.     

A high physical activity level after total knee arthroplasty does not increase the risk of revision surgery during the first twelve years: A systematic review with meta-analysis and GRADE

BackgroundHigh physical activity (HPA) levels after total knee arthroplasty (TKA) might be related to increased wear and subsequent aseptic loosening, negatively affecting TKA survival. This systematic review studied the association between activity levels and risk of revision surgery at medium (3–10 years) and long term (>10 years) follow up in patients with TKA.MethodsDatabases (PubMed, Embase) were searched up to 12 October 2021. Studies comparing low physical activity (LPA) and HPA levels in TKA patients and related risk of revision surgery were eligible for inclusion. After data extraction and evaluation of methodological quality, a meta-analysis was performed. Quality of evidence was assessed using the GRADE framework. PROSPERO registration: CRD42020194284.ResultsFive cohort studies and one case–control study met the inclusion criteria, involving 4811 TKA procedures in 4263 patients (mean follow up 4–12 years). Five studies were of moderate methodological quality and one of low quality. Meta-analysis demonstrated no association between HPA level and an increased risk of all-cause revision surgery (risk ratio (RR) 0.62, 95 % confidence interval (CI) 0.24–1.63, level of certainty: very low) or revision surgery due to aseptic loosening (RR 1.33, 95 % CI 0.34–5.24, level of certainty: moderate). Only one study reported on survivorship, with an improved survivorship for the HPA group (odds ratio of 2.4, 95 % CI 1.2–4.7, level of certainty: low).ConclusionDuring the first 12 postoperative years after TKA, there seems to be no increased risk for revision surgery for patients with a HPA level compared with patients with an LPA level.     

Effect of ultrasound-guided selective sensory nerve blockade of the knee on pain management compared with periarticular injection for patients undergoing total knee arthroplasty: A prospective randomized controlled trial

BackgroundUltrasound-guided selective sensory nerve blockade (SSNB) of the knee, including an adductor canal block (ACB), anterior femoral cutaneous nerve block, and infiltration between the popliteal artery and posterior capsule of the knee may provide effective motor-sparing knee analgesia for total knee arthroplasty (TKA). We hypothesized that the SSNB would manage pain better on ambulation 24 hours postoperatively compared to periarticular infiltration (PAI), when combined with postoperative continuous ACB.MethodsSeventy-two patients undergoing elective TKA under spinal anesthesia were randomly assigned to either SSNB (SSNB group) or intraoperative PAI (PAI group). All patients received postoperative multimodal analgesia, including continuous ACB. The primary outcome was pain on ambulation 24 hours postoperatively. Secondary outcomes included rest and dynamic numerical rating scale pain score, intravenous morphine requirement, functional performance measures, adverse events, satisfaction, and length of stay.ResultsThere was no difference in pain score during movement between the groups (mean difference −0.48 [−1.38 to 0.42], p = 0.3) and other immediate overall pain scores 24 hours postoperatively. Patients in the SSNB group had significantly lower intravenous morphine requirement than the PAI group for 48 hours postoperatively (0 [0, 0] vs. 0 [0, 2]; p = 0.008). There was no intergroup difference in the performance-based measures, satisfaction, and length of stay.ConclusionsThe SSNB did not provide superior postoperative analgesia, or improvement in immediate functional performance. However, it may result in lower opioid consumption postoperatively when compared with the intraoperative PAI.     

Fast-track revision knee arthroplasty.

BackgroundLimited data exist on fast-track protocols in relation to revision knee arthroplasty. Hence, the aim of this study was to report length of stay (LOS), risk of LOS > 5 days and readmission ≤ 90 days after revision knee arthroplasty in centers with a well-established fast-track protocol in both primary and revision surgery.MethodsAn observational cohort study from the Centre for Fast-track Hip and Knee Replacement and the Danish Knee Arthroplasty Register. We included elective aseptic major component revision knee arthroplasties consecutively from 6 dedicated fast-track centers from 2010 to 2018.Results1439 revision knee arthroplasties were analyzed, including 900 total revisions, 171 large partial revisions (revision of either femoral or tibia component) and 368 revisions of unicompartmental knee arthroplasty (UKA) to total knee arthroplasty (TKA). Mean age was 65 years (SD 10.9) and 66% were females. Mean LOS was 3.7 days (SD 3.9) in the study period, but decreased to 2.4 days (SD 1.3) in 2018. Risk factors for LOS > 5 days was ≥ 1 previous revision, use of walking aid, BMI > 35, ages < 50, 70–79 and ≥ 80 years, whereas revision of UKA to TKA and large partial revision were negatively associated. The 90-day readmission and mortality risk was 9.1% and 0.5%. Cardiac disease and use of walking aid were associated with increased risk of readmission ≤ 90 days.ConclusionElective aseptic major component revision knee arthroplasty using similar fast-track protocols as in primary TKA is safe with short and decreasing LOS.     

Comparison of the clinical and patient-reported outcomes between medial stabilized and posterior stabilized total knee arthroplasty: A systematic review and meta-analysis

BackgroundTotal knee arthroplasty (TKA) is effective in relieving pain and improving function in patients with end-stage knee osteoarthritis. Both medial stabilized total knee arthroplasty (MS-TKA) and posterior stabilized total knee arthroplasty (PS-TKA) can achieve satisfactory clinical results, but comparisons between MS-TKA and PS-TKA have yielded contradictory conclusions. This systematic review and meta-analysis were performed to investigate the differences in clinical and patient-reported outcomes (PROMs) between MS-TKA and PS-TKA.MethodsIn December 2020, systematic searches of the following databases were undertaken: Pubmed, Embase, Cochrane Library, Clinical Trials.gov. Studies with PROMs comparing MS-TKA to PS-TKA were included. Meta-analysis was conducted for range of motion (ROM), Knee Society Score (KSS), Knee Society Functional Score (KFS), Forgotten Joint Score (FJS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Oxford Knee Score (OKS).ResultsThere were 17 studies included in this review, 13 studies used for quantitative analysis, and 4 studies used for qualitative synthesis. Meta-analysis concluded that the WOMAC mean difference (MD) for MS-TKA was 1.55 higher than for PS-TKA (MD = −1.55; 95 %CI = −2.45 to −0.64, P = 0.0008); however, this difference was less than the minimum clinically important difference (MCID) value of 15. Assessment using the OKS determined that the MD for PS-TKA was 0.58 higher than for MS-TKA (MD = 0.58; 95 %CI = 0.25 to 0.91, P = 0.0006); again, this MD was less than the MCID value of 5. There were no significant differences between MS-TKA and PS-TKA when assessed by ROM (P = 0.23), KSS (P = 0.13), KFS (P = 0.61), or FJS (P = 0.22).ConclusionDerived from numerous sources, utilizing a multitude of validated functional and patient-reported outcome assessment tools, there was no clinically evident advantage of MS-TKA compared to PS-TKA.RegistrationThe registration number on PROSPERO is CRD42021228555.     

Intraoperative changes in medial joint gap after posterior femoral condylar resection,posterior osteophyte removal,and femoral component placement during primary total knee arthroplasty

Background“Mid-flexion stability” is important for superior patient satisfaction following total knee arthroplasty (TKA). Thus, it is important to control medial joint gap intraoperatively as a countermeasure. However, reports on the precise intraoperative changes in medial joint gap during TKA are scarce. This study evaluated the intraoperative changes in medial joint gap during TKA.MethodsWe studied 167 knees with varus osteoarthritis that underwent 80 cruciate-retaining (CR) and 87 posterior-stabilized (PS) TKAs between January 2018 and December 2020. We measured the intraoperative changes in medial joint gap with a tensor device at 137.5 N.ResultsThe medial joint gap after posterior femoral condylar resection was significantly increased not only at 90° of flexion but also at 0° of extension in CR and PS TKAs (p < 0.01). The medial joint gap after posterior osteophyte removal was significantly increased not only at 0° of extension but also at 90° of flexion in CR and PS TKAs (p < 0.01). The medial joint gap at 0° of extension was reduced by 0.60 mm after femoral component placement in PS TKA.ConclusionSurgeons need to pay close attention to these intraoperative changes in medial joint gap by measuring the medial joint gap before and after each procedure or assuming the changes in those values before bone cutting to achieve superior patient satisfaction following TKA.     

Personalized volumetric assessment of lower body muscles in patients with knee injuries: A descriptive case series

BackgroundPatients with knee joint pathology present with variable muscular responses across the muscles of the lower limb and pelvis. Conventional approaches to characterizing muscle function are limited to gross strength assessments that may overlook subtle changes both in the thigh, hip and shank musculature.PurposeTo describe individualized patterns of lower extremity muscle volumes in patients with knee pathologies.MethodsThis was a retrospective case series performed in a University medical center. Nine patients diagnosed with meniscus tear recommended to undergo meniscectomy volunteered. Participants underwent 3.0 Tesla magnetic resonance imaging (MRI) of the lower extremities. Thirty-five MRI-derived muscle volumes were compared between limbs and expressed as percentage asymmetry. For additional context, z-scores were also calculated for mass- and height-normalized muscles and pre-determined muscle groupings relative to a normative database.ResultsThere were no consistent patterns observed when considering between-limb asymmetries among all patients. The ankle musculature (dorsiflexors, plantar flexors, and invertors) was the only muscle group to be consistently smaller than normal for all patients, with the psoas major and flexor hallucis longus being the only individual muscles. The severity or chronicity of injury and presence of surgical intervention did not appear to have a clear effect on muscle volumes.ConclusionPatients with a history of meniscal pathology demonstrate inconsistent patterns of lower extremity muscle volumes about the hip, knee, and ankle between limbs and in comparison to uninjured individuals. These data support the need for individualized assessment and intervention in this population.     

Evaluation of different coatings of the tibial tray in uncemented total knee arthroplasty. A randomized controlled trial with 5 years follow-up with RSA and DEXA

BackgroundRegenerex® is a porous titanium construct with a 3D interconnecting pore structure and biomechanical characteristics close to that of normal trabecular bone. This study aimed to compare the Regenerex (VR) to the non-interconnecting pore structure Porous Plasma Spray (VP) on tibial implants for total knee arthroplasty (TKA) at 5 years.MethodsWe enrolled and randomized 61 patients (mean age = 63(49–71) years, Female/Male = 35/26) who were planned for an uncemented Vanguard TKA (Biomet, Warsaw, Indiana, USA) to receive either a VR or a VP coated tibial component (31/29). We performed radiostereometric analysis (RSA) and Dual Energy X-ray Absorptiometry (DEXA) postoperatively, and at three, six, 12, 24 and 60 months with measurements of migration. In total 55 patients attended the 5-year follow-up.ResultsOne patient died and four were reoperated during the 60-months period; none due to aseptic loosening. All reoperations were in the VR-group. The mean (range) 60-months MTPM was 1.4 mm (0.5–3.7) for the VP-group and 1.8 mm (0.4–4.9) for the VR-group (p = 0.8). The 24 to 60-months mean (range) MTPM was −0.3 mm (−5 to 1.24) in the VP-group and 0.2 mm (−0.4 to 3.5) in the VR-group (p = 0.8).ConclusionWe did not find any statistically significant differences between the VP- and VR-group and both groups show recognizable migration. We will continue to follow the groups for years to come.     

Approximately 80% of Japanese osteoarthritic patients fall out of the safety range in restricted kinematically-aligned total knee arthroplasty in an analysis of preoperative long-leg radiograms

BackgroundRestricted kinematically-aligned total knee arthroplasty (KA-TKA) is a reasonable modification to avoid the alignment outlier that may cause implant failure. However, despite a noted high incidence of constitutional varus in Japanese individuals, there has been no investigation into how many knees require the restriction in restricted KA-TKA (RKA-TKA) among Japanese patients. Therefore, we conducted a study using preoperative long-leg radiograms.MethodsWe studied long-leg radiographs of 228 knees in 114 consecutive patients. The numbers of knees within the safety range and their corrective osteotomy angle in the restriction algorithms advocated by Almaawi et al. (2017) and MacDessi et al. (2020) were evaluated.ResultsAccording to the algorithms used by Almaawi et al. and MacDessi et al., out of 228 knees, 46 (20%) and 39 (17%) fell within the safety range, respectively. The mean correction angles of the hip-knee-ankle angle, lateral distal femoral angle and medial proximal tibial angle were 2.8 ± 3.4°, 0.4 ± 1.4° and 2.4 ± 2.8° in the algorithm used by Almaawi et al., while they were −4.9 ± 4.7°, 1.1 ± 2.5° and −6.0 ± 3.4° in the algorithm used by MacDessi et al. Most of the knees needed to be restricted in order to perform RKA-TKA, regardless of the algorithm used.ConclusionsBased on a preoperative analysis of long-leg radiograms in a Japanese population, most knees fall out of the safety range in RKA-TKA. Surgeons must consider whether to allow component outlier or to perform corrective osteotomy that likely requires soft tissue release.     

Quality validation of platelets obtained from the Haemonetics and Trima Accel automated blood-collection systems

BackgroundPlatelet transfusion is required to treat haemo-oncology or trauma patients. Platelet apheresis (PA) performed with apheresis equipment has increased rapidly in recent years. Leucocyte-reduced platelet apheresis (LRPA) can reduce the risk of platelet refractoriness and febrile nonhemolytic transfusion reactions (FNHTRs) for transfusion. Accordingly, this study aimed to investigate and compare the platelet metabolic and functional responses between PA performed with Haemonetics and LRPA performed with Trima Accel cell separator.MethodsThe qualities of platelets collected through PA and LRPA were evaluated in terms of visual appearance, morphology, platelet-aggregation changes, metabolic activities, and bacterium-screening test during 5-day storage. Statistical analyses included two-sample t-test and generalised estimating equation(GEE) method.ResultsDuring 5-day storage in LRPA, residual leucocytes were all <1.0×10⁶, and the parameters of platelet function were as follows: platelet aggregated to agonists such as adenosine 5′-diphosphate (ADP) and collagen, and the extent of shape change and pO₂ showed no statistically significant difference between PA and LRPA. The hypotonic shock reaction (HSR) on days 0, 1, and 3 were significantly higher in LRPA than in PA (71.78±6.92 vs. 64.10±7.42; P=0.002; 71.53±8.98 vs. 62.96±9.84; P=0.007; 68.05±7.28 vs. 57.76±6.80; P<0.0001, respectively). Values of mean platelet volume (MPV) were statistically larger in PA than in LRPA on days 0, 1, and 3. On day 5, the swirling score was higher in LRPA than in PA. The mean lactate levels had no statistically significant difference between PA and LRPA. Moreover, no growth was observed through bacterium-screening test conducted on 40 samples.ConclusionComparison of LRPA and PA products collected from the Trima Accel and Haemonetics automated blood-collection systems, respectively, revealed that both products possessed good platelet qualities even though additional processes are needed to reduce leucocytes. Furthermore, investigating the outcomes of other apheresis instruments with focus on the safety of donors, products, and recipients is necessary.     

Ghrelin level as a biomarker for knee osteoarthritis severity and appearance in HIV + patients

BackgroundKnee Osteoarthritis (KOA) is a multifactorial disease with several mechanisms to promote articular cartilage damage. New molecules, such as ghrelin, have been recently reported to participate in the pathogenesis and progression of KOA. In HIV + patients, arthralgias are the most frequent musculoskeletal manifestations, mainly affecting joints such as the knee. Also, it has been reported that HIV + patients have a reduction of ghrelin even with treatment compared to HIV- patients. However, there is no report in the literature evaluating ghrelin and KOA in the HIV + population. We aimed to evaluate whether serum ghrelin levels can function as a biomarker for OA in HIV + patients.MethodsWe recruited 40 patients, 20 HIV+, and 20 HIV- controls, and grouped as follows: HIV+/KOA+; HIV+/KOA-; HIV-/KOA+; HIV-/KOA-. Clinical features were obtained during clinical visits. Peripheral blood samples were acquired to measure serum ghrelin levels.ResultsThe HIV+/KOA + group significantly reduced serum ghrelin levels when compared with the other groups. Comparing the ghrelin levels with the patients’ nadir of CD4⁺ T-cells count, we identified a statistically significant negative correlation in the KOA- group (r = −0.80, P < 0.007). An ROC curve analysis, for the accuracy of ghrelin levels to identified HIV+/KOA + from HIV+/KOA- patients, found an area under the curve of 0.83 (95 % CI 0.65–0.10; P = 0.017), with a cut-off < 4026 pg/mL serum ghrelin levels, with a sensitivity of 0.62 (95 % CI 0.32–0.86), and a specificity of 0.10 (95 % CI 0.59–0.10).ConclusionThis study shows the potential use of ghrelin levels as a biomarker for KOA in the high-risk HIV population that should be further analyzed.     

Immune and gene expression profiling during tacrolimus to everolimus conversion early after liver transplantation

Early elimination of tacrolimus in favor of everolimus can improve renal function in liver transplant recipients. However, as this approach increases the risk of acute rejection, it may benefit from predictive biomarkers guiding weaning. We enrolled 20 recipients on stable tacrolimus + everolimus to undergo tacrolimus withdrawal early post-liver transplant. Blood samples were collected at month 3 (withdrawal initiation), 4 (withdrawal completion), 4.5 and 6 (both everolimus alone). 15 patients did not reject and 5 had mild rejection responding to tacrolimus resumption. Before tacrolimus withdrawal, eventual rejecters had higher percentages of CD56⁺ NK cells and CD19⁺CD27⁺CD24⁺ memory B cells, and lower levels of T cells expressing the exhaustion marker PD-1. Over time, memory B cells, Ki-67⁺CD3⁺ (proliferating) cells and CD4⁺CD127^-CD25^HIGH FOXP3⁺ Tregs increased in rejecters. Tregs also increased in non-rejecters over time. The number of differentially expressed genes progressively increased in rejecters, particularly in mTOR, Eukaryotic Initiation Factor 2, and Neuroinflammation signaling pathways. There was no difference in anti-HLA antibodies between the groups. In summary, blood mononuclear cell and gene expression may predict successful vs. failed early tacrolimus withdrawal in liver transplant recipients. While needing validation, these preliminary findings highlight the potential for cellular and molecular biomarkers to guide decision-making during tacrolimus weaning.     

Subchondroplasty in the treatment of bone Marrow lesion in early Knee Osteoarthritis: A systematic review of clinical and radiological outcomes

BackgroundKnee osteoarthritis (KOA) is increasingly prevalent in North American society. The significant societal burden it represents makes it essential to promote and target new treatments in earlier phases of the disease. Among others, subchondroplasty is a newly documented technique using calcium phosphate injection targeting the osteochondral lesions preceding KOA, also known as Bone Marrow Lesions (BMLs). This article aimed to review the existing literature on clinical and radiological outcomes of subchondroplasty in the treatment of BMLs in KOA.MethodA systematic review was performed using PubMed, Embase, Medline and Cochrane Database of Systematic Reviews. Studies on calcium phosphate injections into BMLs for KOA and its clinical and radiological outcomes were screened and reviewed by independent evaluators.ResultsAfter screening, ten articles were included, totaling 540 patients. Follow-up ranged from 6 months to 7 years. Overall, the procedure showed significant functional and quality of life improvement, as well as pain relief, as shown by Patients-Reported Outcomes Measures (PROMs). There were very few complications reported, the most important being leakage of calcium phosphate outside the targeted site. Conversion rate to total knee arthroplasty (TKA) ranged from 14 % to 30 % at 2 years post-procedure. Long term radiological outcomes have been poorly documented.ConclusionsSubchondroplasty is a promising avenue for the treatment of KOA. However, quality evidence is still required before any real conclusions and practical management guidelines can be drawn. Prospective, randomized studies with a control group and a rigorous assessment of long-term clinical and radiological outcomes are recommended.     

Childhood allergy susceptibility: The role of the immune system development in the in-utero period

Expression of allergic diseases in very early childhood indicates that early life events play a significant role in childhood allergy development. The developmental origins of allergy hypothesis suggest events initiated in the in-utero period derived from the interaction between maternal, placental, and fetal factors may contribute to childhood allergy susceptibility. Environmental impacts on placental function and fetal programming are imperative in defining illness risk during pregnancy. Fetal programming, a process by which an injury delivered during a critical period of development, causes immediate adaptive responses with long-term consequences on an organism’s structure or function. During pregnancy, the maternal immune response is skewed towards Th2-related humoral responses, hence increasing the susceptibility of childhood allergy development. Maternal atopic phenotype markedly increases the probability of her offspring developing an allergic predisposition. Combination of in utero events – which include maternal asthma or infection, and exposures to maternal allergy which changes the placental function – can alter placental cytokine expression and could predispose offspring to an allergic phenotype. All these events may affect embryology and fetal immune system development. Interestingly, the mechanism and role of the in-utero events on the developmental origins of allergy are not clearly understood; this will be addressed in this review.(199 words)     

Transcatheter arterial embolization of abnormal neovessels in a swine model of knee arthritis

BackgroundIn recent years, transcatheter arterial embolization (TAE) using imipenem/cilastatin (IPM/CS) has attracted attention as a treatment for relieving osteoarthritis (OA) pain. However, IPM/CS is not approved by Japanese medical insurance for use as an embolic material. Therefore, it is necessary to develop new embolic materials for TAE to relieve OA pain. The purpose of this study was to develop a swine model of knee arthritis and embolize abnormal neovessels (ANs) using two different embolic materials. We compared the embolic effects and tissue damage in knees.MethodsKnee arthritis was induced by intra-articular injection of papain into 12 knees in six female swine. The swine were divided into two groups of three swine each (six knees per group) for embolization of ANs in the knees with either IPM/CS or soluble gelatin sponge particles (SGSs). Three days after embolization, we compared the embolic effects using angiography and the tissue damage histopathologically.ResultsANs were observed in all 12 knees at 42 days after papain injection. The ANs disappeared and the patent arteries were recanalized 3 days after TAE in all 12 knees. Histopathological evaluation revealed synovitis changes, such as synovial thickening and inflammatory cell infiltration, in all 12 knees. There was no evidence of skin or muscle necrosis in either group. The appearance of ANs, recanalization of the parent arteries, and histopathological outcomes were not significantly different between the two groups.ConclusionSGSs were as safe as IPM/CS for TAE of ANs in this swine model of knee arthritis.     

Prevalence of lymphedema among Anderson-Fabry disease patients: A report from the Fabry registry

BackgroundAnderson-Fabry disease (AFD) is a rare X-linked lysosomal storage disease due to a genetic variation in the α-galactosidase A (GLA) gene. As a result, the activity of the α-galactosidase A (AGAL-A) enzyme is reduced or absent, which causes sphingolipid deposition within different body parts. AFD typically manifests with cardiovascular, renal, cerebrovascular, and dermatologic involvement. Lymphedema is caused by sphingolipid deposition within lymphatics. Lymphedema can cause intolerable pain and limit daily activities. Very limited data exist on lymphedema in AFD patients.MethodsUsing data from the Fabry Registry (NCT00196742) with 7671 patients included (44% males and 56% females), we analyzed the prevalence of lymphedema among AFD patients who were ever assessed for lymphedema and studied the age of first reported lymphedema. Additionally, we assessed whether patients received AFD-specific treatment at some point during their clinical course. The data was stratified by gender and phenotype.ResultsOur study showed that lymphedema occurred in 16.5% of the Fabry Registry patients who were ever assessed for lymphedema (n = 5487). Male patients when compared to female patient have higher prevalence (21.7% vs 12.7%) and experienced lymphedema at a younger age (median age at first reported lymphedema of 43.7 vs 51.7 years). When compared to other phenotypes, classic phenotype has the highest prevalence of lymphedema with the earliest reported lymphedema. Among those who reported lymphedema, 84.5% received AFD-specific treatment during their clinical course.ConclusionsLymphedema is a common manifestation of AFD in both genders, with a tendency to present later in female patients. Recognition of lymphedema can offer an important opportunity for intervention and potential impact on associated morbidity. Additional future studies are needed to characterize the clinical implications of lymphedema in AFD patients and identify additional treatment options for this growing population.