Murine studies suggest that aortic-root dilation in Marfan's syndrome is due to excessive signaling by transforming growth factor β (TGF-β) and can be mitigated by TGF-β antagonists, such as ...angiotensin II–receptor blockers (ARBs). This study reviewed data on 18 pediatric patients with Marfan's syndrome who had begun ARB therapy and had been followed for at least 12 months. The rate of increase in aortic-root diameter was significantly slowed after the initiation of ARB therapy.
This study reviewed data on pediatric patients with Marfan's syndrome who had begun ARB therapy. The rate of increase in aortic-root diameter was significantly slowed after the initiation of ARB therapy.
Marfan's syndrome, an autosomal dominant connective-tissue disorder affecting approximately 1 in 5000 people, is caused by mutations in the gene encoding fibrillin-1 (
FBN1
).
1
,
2
FBN1
mutations lead to defects in multiple organ systems, of which the most life-threatening is progressive enlargement and dissection of the aortic root.
3
,
4
Current medical management of Marfan's syndrome is focused on serial cardiac-imaging studies and the use of pharmacologic agents to reduce hemodynamic stress on the aortic wall. Pharmacologic treatment often involves the use of beta-adrenergic–receptor antagonists (beta-blockers), although other agents, such as angiotensin-converting–enzyme (ACE) inhibitors and calcium-channel blockers, have been used . . .
Loeys-Dietz syndrome is a connective tissue disorder predisposing individuals to aortic and arterial aneurysms. Presenting with a wide spectrum of multisystem involvement, medical management for some ...individuals is complex. This review of literature and expert opinion aims to provide medical guidelines for care of individuals with Loeys-Dietz syndrome.
Retrospective matched case cohort.
Compare postoperative opioid utilization and prescribing behaviors between patients with Marfan syndrome (MFS) and adolescent idiopathic scoliosis (AIS) after ...posterior spinal fusion (PSF).
Opioids are an essential component of pain management after PSF. However, due to the potential for opioid use disorder and dependence, current analgesic strategies aim to minimize their use, especially in younger patients. Limited information exists on opioid utilization after PSF for syndromic scoliosis.
Twenty adolescents undergoing PSF with MFS were matched with patients with AIS (ratio, 1:2) by age, sex, degree of spinal deformity, and the number of vertebral levels fused. Inpatient and outpatient pharmaceutical data were reviewed for the quantity and duration of opioid and adjunct medications. Prescriptions were converted to morphine milligram equivalents (MMEs) using CDC's standard conversion factor.
Compared with patients with AIS, patients with MFS had significantly greater total inpatient MME use (4.9 vs . 2.1 mg/kg, P ≤ 0.001) and longer duration of intravenous patient-controlled anesthesia (3.4 vs . 2.5 d, P = 0.001). Within the first 2 postop days, MFS patients had more patient-controlled anesthesia boluses (91 vs . 52 boluses, P = 0.01) despite similar pain scores and greater use of adjunct medications. After accounting for prior opioid use, MFS was the only significant predictor of requesting an opioid prescription after discharge (odds ratio: 4.1, 95% CI: 1.1-14.9, P = 0.03). Patients with MFS were also more likely to be discharged with a more potent prescription (1.0 vs . 0.72 MME per day/kg, P ≤ 0.001) and to receive a longer-duration prescription (13 vs . 8 d, P = 0.005) with a greater MME/kg (11.6 vs . 5.6 mg/kg, P ≤ 0.001) as outpatients.
Despite a similar intervention, patients with MFS and AIS seem to differ in their postoperative opioid usage after PSF, presenting an opportunity for further research to assist clinicians in better anticipating the analgesic needs of individual patients, particularly in light of the ongoing opioid epidemic.
The spectrum of foot deformities in Loeys-Dietz syndrome Badin, Daniel; Dietz, 3rd, Harry C; Sponseller, Paul D
Journal of pediatric orthopaedics. B,
2023-Jan-01, 2023-01-00, 20230101, Letnik:
32, Številka:
1
Journal Article
Recenzirano
Loeys-Dietz syndrome (LDS) is characterized by a wide spectrum of musculoskeletal manifestations, including foot deformities. The spectrum of foot deformities in LDS has not been previously ...characterized. Our objective was to describe the incidence and characteristics of foot deformities in LDS. We retrospectively reviewed the demographic, clinical and imaging data for patients diagnosed with LDS who were seen at our Orthopedic surgery department from 2008 to 2021. We performed descriptive analyses and compared distributions of deformities by LDS genetic mutations. Of the 120 patients studied, most presented for evaluation of foot deformities ( N = 56, 47%) and scoliosis ( N = 45; 38%). Ninety-seven patients (81%) had at least one foot deformity, and 87% of these patients had bilateral foot deformities. The most common deformities were pes planovalgus (53%) and talipes equinovarus (34%). Of patients with foot deformities, 58% presented for evaluation of the feet. Of patients with pes planovalgus, only 17% presented for evaluation of the feet. Among patients with pes planovalgus, 2% underwent surgery and 16% used orthotics compared with 76% and 42%, respectively, for patients with talipes equinovarus. We found no association between deformities and genetic mutations. Bilateral foot deformities are highly prevalent in patients with LDS and are the most common reason for presentation to orthopedic surgeons. Although pes planovalgus is the most common deformity, it rarely prompted surgical treatment. Orthopedic surgeons treating LDS patients should be aware of the unique characteristics of foot deformities in LDS.
Valve-sparing aortic root replacement in children: Outcomes from 100 consecutive cases Fraser, Charles D.; Liu, Rui Han; Zhou, Xun ...
Journal of thoracic and cardiovascular surgery/The Journal of thoracic and cardiovascular surgery/The journal of thoracic and cardiovascular surgery,
March 2019, 2019-03-00, 20190301, Letnik:
157, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Valve-sparing root replacement is an attractive alternative to composite mechanical or biologic prostheses for aortic root aneurysms in children. Data on outcomes in pediatric patients are limited. ...We present our institutional experience with 100 consecutive pediatric valve-sparing aortic root procedures.
All children who underwent valve-sparing root replacement at our institution from May 1997 to August 2017 were identified, and echocardiographic and clinical data were reviewed. The primary end point was mortality, and secondary end points included complications, further interventions, and subsequent valvular dysfunction.
Median age at operation was 13.6 years (interquartile range, 9.42-15.9); 51 patients (51%) had Marfan syndrome, and 39 patients (39%) had Loeys–Dietz syndrome. Mean preoperative maximum sinus diameter was 4.4 ± 0.71 cm (z score 7.3 5.7-9.3). Most patients (n = 80, 80%) underwent reimplantation procedures with a Valsalva graft. Four patients (4%) underwent David I reimplantation with a straight-tube graft, 13 patients (13%) underwent a Yacoub remodeling procedure, and 3 patients (3%) underwent a Florida sleeve procedure. Perioperative valve-sparing root replacement mortality was 2% (n = 2). Six patients required late reintervention for development of pseudoaneurysms. Eight patients underwent additional aortic surgery. Average time to reoperation was 7.23 ± 4.56 years. Of the 84 patients undergoing a reimplantation procedure, 5 (5.9%) underwent late valve replacement versus 5 (33.3%) of the 15 patients who received a remodeling procedure (P = .001).
Valve-sparing root replacement is a safe and effective option for children with aortic root aneurysms in children. The reimplantation procedure is preferred. Late aortic insufficiency and pseudoaneurysm formation remain late concerns.
Loeys-Dietz syndrome (LDS) is a rare autosomal-dominant connective tissue disorder caused by genetic mutations in the transforming growth factor-β (TGFβ) signaling pathway. In addition to vascular ...malformations, patients with LDS commonly present with bone and tendon abnormalities, including joint laxity. While TGFβ signaling dysregulation has been implicated in many of these clinical manifestations, the degree to which it influences the tendinopathy and tendon healing issues in LDS has not been determined.
Wound healing after patellar tendon transection was compared between wild-type (WT) and Tgfbr2-mutant (LDS) mice (7 mice per group). In all mice, the right patellar tendon was transected at midsubstance, while the left was untouched to serve as a control. Mice were euthanized 6 weeks after surgery. Tendon specimens were harvested for histopathologic grading according to a previously validated scoring metric, and gene expression levels of Mmp2, Tgfb2, and other TGFβ-signaling genes were assayed. Between-group comparisons were made using 1-way analysis of variance with post hoc Tukey honestly significant difference testing.
Expression levels of assayed genes were similar between LDS and WT tendons at baseline; however, at 6 weeks after patellar tendon transection, LDS tendons showed sustained elevations in Mmp2 and Tgfb2 compared with baseline values; these elevations were not seen in normal tendons undergoing the same treatments. Histologically, untreated LDS tendons had significantly greater cellularity and cell rounding compared with untreated WT tendons, and both WT and LDS tendons had significantly worse histologic scores after surgery.
We present the first mechanistic insight into the effect of LDS on tendons and tendon healing. The morphologic differences between LDS and WT tendons at baseline may help explain the increased risk of tendon/ligament dysfunction in patients with LDS, and the differential healing response to injury in LDS may account for the delayed healing and weaker repair tissue.
Level V.
A genomic screen and statistical linkage analysis of 202 families with at least two individuals with idiopathic scoliosis was performed.
To identify candidate regions or the autosomal loci that may ...be involved in the expression of familial idiopathic scoliosis.
A large sample of families with individuals having idiopathic scoliosis (202 families; 1,198 individuals) was ascertained; diagnoses were based on physical examination and radiographic criteria.
Model-independent linkage analysis of qualitative and quantitative traits (degree of lateral curvature) related to scoliosis was used to screen genotyping data from 391 markers in the 202 families. Subsets of families were determined before genotyping based on the most likely mode of inheritance for each family (autosomal dominant vs. X-linked dominant). Fine mapping results corroborated linkage in the primary candidate regions.
Candidate regions on chromosomes 6, 9, 16, and 17 were considered to have the strongest evidence for linkage across all subsets considered.
Linkage analyses have identified several candidate regions, a significant step in defining the genetic etiology of this disorder.
BACKGROUND:Loeys-Dietz syndrome is a connective tissue disorder characterized by vascular, craniofacial, and musculoskeletal malformation. Our goal was to report the manifestations, surgical ...treatment, and complications in the cervical spine in patients with Loeys-Dietz syndrome.
METHODS:We reviewed the clinical and cervical spine imaging data of eighty patients with Loeys-Dietz syndrome who were seen at our institution from January 2005 through January 2014. Their mean age at presentation was 17.3 years (range, three months to seventy-five years). We tested associations with use of the Fisher exact test (type of TGF-βR transforming growth factor-beta receptor mutation and cervical abnormalities) and the Student t test (age at presentation and type of TGF-βR mutation) (significance, p = 0.05).
RESULTS:Vertebral anomalies and cervical instability were common; we found no significant association of TGF-βR-type with cervical abnormalities or age at presentation. Twenty-eight patients had atlas defects (anterior and/or posterior arch defects or hypoplasia), fifty-three had axis malformations (elongation, apex-anterior dens angulation, or spondylolysis), and twelve had focal kyphosis. Ten patients had hypoplastic subaxial vertebrae, leading to focal kyphosis (eight) and subaxial instability (nine). Eight patients had atlantoaxial instability. Of the thirteen patients with cervical instability, nine were treated surgicallyfusion (eight patients) and halo application (one) (mean age, four years; range, three months to twelve years). Postoperative complications (seven patients) were pseudarthrosis, failure of fixation, junctional kyphosis or instability, and development of occipital-cervical instability.
CONCLUSIONS:Cervical midline defects (most often C1-C3) are common in Loeys-Dietz syndrome. Patients have a high prevalence of cervical instability, particularly a pattern of instability at C2-C3 associated with C3 vertebral body hypoplasia and C2-C3 focal kyphosis. Patients requiring surgery typically present in early childhood.
LEVEL OF EVIDENCE:Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Mitral valve degeneration is a key component of the pathophysiology of Marfan syndrome. The biomechanical consequences of aging and genetic mutation in mitral valves are poorly understood because of ...limited tools to study this in mouse models. Our aim was to determine the global biomechanical and local cell-matrix deformation relationships in the aging and Marfan related Fbn1 mutated murine mitral valve. To conduct this investigation, a novel stretching apparatus and gripping method was implemented to directly quantify both global tissue biomechanics and local cellular deformation and matrix fiber realignment in murine mitral valves. Excised mitral valve leaflets from wild-type and Fbn1 mutant mice from 2 weeks to 10 months in age were tested in circumferential orientation under continuous laser optical imaging. Mouse mitral valves stiffen with age, correlating with increases in collagen fraction and matrix fiber alignment. Fbn1 mutation resulted in significantly more compliant valves (modulus 1.34 ± 0.12 vs. 2.51 ± 0.31 MPa, respectively, P<.01) at 4 months, corresponding with an increase in proportion of GAGs and decrease in elastin fraction. Local cellular deformation and fiber alignment change linearly with global tissue stretch, and these slopes become more extreme with aging. In comparison, Fbn1 mutated valves have decoupled cellular deformation and fiber alignment with tissue stretch. Taken together, quantitative understanding of multi-scale murine planar tissue biomechanics is essential for establishing consequences of aging and genetic mutations. Decoupling of local cell-matrix deformation kinematics with global tissue stretch may be an important mechanism of normal and pathological biomechanical remodeling in valves.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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