RESUMO
Selective serotonin re-uptake inhibitors (SSRI) widely used in the treatment of depression, anxiety, obsessive compulsive disorder, fibromyalgia, and migraine are among the most heavily prescribed drug class in the United States (US). Along with an overall rise in SSRI use, these medications are increasingly used by pregnant individuals and recent preclinical and clinical studies have indicated that SSRIs may increase the prevalence of congenital abnormalities and birth defects of the craniofacial region. Our group has developed pre-clinical models of study, including those that mimic the clinical use of SSRI in mice. Here we designed a study to interrogate a commonly prescribed SSRI drug, Citalopram, for its effects on craniofacial and dental development when introduced in utero. Pre-natal exposure to a clinically relevant dose of citalopram resulted in changes in craniofacial form identified by an increase in endocast volume in SSRI exposed postnatal day 15 mouse pups. More specifically, cranial length and synchondrosis length increased in SSRI exposed pups as compared to control pups of the same age. Additionally, growth center (synchondrosis) height and width and palate length and width decreased in SSRI exposed pups as compared to control un-exposed pups. Effects of SSRI on the molars was minimal. Craniofacial growth and development continue to be an area of interest in the investigation of in utero pharmaceutical drug exposure. Altogether these data indicate that prenatal SSRI exposure affects craniofacial form in multiple tissues and specifically at growth sites and centers of the skull.
Assuntos
Citalopram , Anormalidades Craniofaciais , Inibidores Seletivos de Recaptação de Serotonina , Crânio , Animais , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Camundongos , Feminino , Gravidez , Citalopram/farmacologia , Crânio/efeitos dos fármacos , Anormalidades Craniofaciais/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Modelos Animais de Doenças , MasculinoRESUMO
PURPOSE: A large prospective cohort was used (1) to evaluate the overall ability of magnetic resonance imaging (MRI) to detect Outerbridge grade III and IV cartilage defects found during surgery and (2) to identify the specific MRI findings most associated with these cartilage defects so that the practicing hip arthroscopist can better predict cartilage injury before surgery. METHODS: All patients undergoing hip arthroscopy between February 2015 and May 2017 at 1 institution were enrolled in a prospective cohort. Intra-articular findings were documented at the time of surgery. MRI reports were retrospectively reviewed for radiologist-reported articular cartilage, osseous, or synovial abnormalities. Sensitivity and specificity of MRI findings were calculated; multivariate logistic regression analysis determined which findings were associated with high-grade chondral damage at the time of arthroscopy and used to create an online risk calculator, https://orthop.washington.edu/hiprisk/. RESULTS: Of 598 patients who underwent hip arthroscopy, 550 had MRI reports available for review (92%). Grade III and IV cartilage injuries were reported on arthroscopy in 70 patients (13%) of average age 33 ± 13 years. On univariate analyses, individual MRI findings were not sensitive in detection of articular cartilage injury (mean 22%; range, 1.4%-46%), but positive findings were highly specific (mean 90%,; range, 76%-99%). Multivariate analysis revealed that older age (odds ratio [OR] 1.09 [1.06-1.11], P < .001) and osseous findings such as subchondral cyst or edema (OR 4.77 [2.51-9.05], P < .001) were most predictive of grade III and IV defects (P < .001). CONCLUSION: MRI was a specific but not sensitive tool in diagnosing articular cartilage injury. Surgeons should be aware that osseous findings such as cysts or edema are highly predictive of full-thickness cartilage loss in FAI. LEVEL OF EVIDENCE: Level III, development of diagnostic criteria (consecutive patients with consistently applied reference standard, no blinding).