Challenges and opportunities for access to Advanced Therapy Medicinal Products in Brazil.

BACKGROUND AIMS: The marketing authorization of Advanced Therapy Medicinal Products (ATMPs) in Brazil is recent. The features of these therapies impose specialized regulatory action and are consequently challenging for developers. The goal of this study was to identify the industry's experience in clinical development, marketing authorization and access to ATMPs through the Unified Health System (SUS, acronym in Portuguese), from a regulatory perspective. METHODS: A survey containing structured questions was conducted among research participants who work at companies that commercialize ATMPs. A descriptive analysis was performed. RESULTS: We invited 15 foreign pharmaceutical companies, of which 10 agreed to participate. Overall, participants assessed that Brazil has a well-established regulatory system, especially the sanitary registration by the National Health Surveillance Agency (Anvisa), which ensures the quality, safety, and efficacy of the products. The Agency's good interaction with the regulated sector, the harmonization of sanitary and ethical assessment systems with other countries, and the analysis time in the biosafety assessment of Genetically Modified Organisms (GMOs) stand out as positive in industry's evaluation. On the other hand, it is important to advance the pricing regulation for these products since Brazilian regulations do not establish specific criteria for ATMP. One of the biggest challenges is the difficulty for the SUS in reimbursing these very high-cost therapies, especially using current Health Technology Assessment (HTA) methods. CONCLUSIONS: Considering the increasing number of approvals of cell and gene therapies in Brazil in the coming years, a close dialogue between the industry and the public sector is recommended to advance regulatory improvements (pricing and HTA). Additionally, the construction of policies to promote the national Health Economic-Industrial Complex, based on a mission-oriented vision that encourages innovative models of financing, especially those that consider risk-sharing and co-financing technologies, will help provide the population with universal, equitable and sustainable access to ATMP in the SUS.

Mesenchymal Stromal Cell-Based Products: Challenges and Clinical Therapeutic Options.

Mesenchymal stromal cell (MSC)-based advanced therapy medicinal products (ATMPs) are being tried in a vast range of clinical applications. These cells can be isolated from different donor tissues by using several methods, or they can even be derived from induced pluripotent stem cells or embryonic stem cells. However, ATMP heterogeneity may impact product identity and potency, and, consequently, clinical trial outcomes. In this review, we discuss these topics and the need to establish minimal criteria regarding the manufacturing of MSCs so that these innovative therapeutics may be better positioned to contribute to the advancement of regenerative medicine.

Metrics of care and cardiovascular outcomes in patients with ST-elevation myocardial infarction treated with pharmacoinvasive strategy: a decade-long network in a populous city in Brazil.

BACKGROUND: Pharmacoinvasive strategy is an effective myocardial reperfusion therapy when primary percutaneous coronary intervention (p-PCI) cannot be performed in a timely manner. METHODS: Authors sought to evaluate metrics of care and cardiovascular outcomes in a decade-long registry of a pharmacoinvasive strategy network for the treatment of ST-elevation myocardial infarction (STEMI). Data from a local network including patients undergoing fibrinolysis in county hospitals and systematically transferred to the tertiary center were accessed from March 2010 to September 2020. Numerical variables were described as median and interquartile range. Area under the curve (AUC-ROC) was used to analyze the predictive value of TIMI and GRACE scores for in-hospital mortality. RESULTS: A total of 2,710 consecutive STEMI patients aged 59 [51-66] years, 815 women (30.1%) and 837 individuals with diabetes (30.9%) were analyzed. The time from symptom onset to first-medical-contact was 120 [60-210] minutes and the door-to-needle time was 70 [43-115] minutes. Rescue-PCI was required in 929 patients (34.3%), in whom the fibrinolytic-catheterization time was 7.2 [4.9-11.8] hours, compared to 15.7 [6.8-22,7] hours in those who had successful lytic reperfusion. All cause in-hospital mortality occurred in 151 (5.6%) patients, reinfarction in 47 (1.7%) and ischemic stroke in 33 (1.2%). Major bleeding occurred in 73 (2.7%) patients, including 19 (0.7%) cases of intracranial bleeding. C-statistic confirmed that both scores had high predictive values for in-hospital mortality, demonstrated by TIMI AUC-ROC of 0.80 [0,77-0.84] and GRACE AUC-ROC of 0.86 [0.83-0.89]. CONCLUSION: In a real world registry of a decade-long network for the treatment of ST-elevation myocardial infarction based on the pharmacoinvasive strategy, low rates of in-hospital mortality and cardiovascular outcomes were observed, despite prolonged time metrics for both fibrinolytic therapy and rescue-PCI. Register Clinicaltrials.gov NCT02090712 date of first registration 18/03/2014.

Aging Triggers Mitochondrial Dysfunction in Mice.

Direct analysis of isolated mitochondria from old mice enables a better understanding of heart senescence dysfunction. Despite a well-defined senescent phenotype in cardiomyocytes, the mitochondrial state in aged cardiomyocytes is still unclear. Here, we report data about mitochondrial function in old mice. Isolated cardiomyocytes' mitochondria were obtained by differential centrifugation from old and young mice hearts to perform functional analyses of mitochondrial O2 consumption, transmembrane potential, ROS formation, ATP production, and swelling. Our results show that mitochondria from old mouse hearts have reduced oxygen consumption during the phosphorylative states of complexes I and II. Additionally, these mitochondria produced more ROS and less ATP than those of young hearts. Mitochondria from old hearts also showed a depolarized membrane potential than mitochondria from young hearts and, as expected, a greater electron leak. Our results indicate that mitochondria from senescent cardiomyocytes are less efficient in O2 consumption, generating more ROS and producing less ATP. Furthermore, the phosphorylative state of complexes I and II presents a functional defect, contributing to greater leakage of protons and ROS production that can be harmful to the cell.

Landscape of Brazilian research and development public funding in advanced therapies: lessons learned and a roadmap for middle-income economies.

BACKGROUND AIMS: Advanced therapy medicinal products (ATMPs) have reached the forefront of biotechnological innovation, partly due to public funders' efforts in the early stages of research and development (R&D). Data on investment in R&D of ATMPs are recognized as scarce, particularly in developing countries. Because of the numerous peculiarities of the Brazilian health system and the science and technology (S&T) system, the country is a good example for the evaluation of public investments in R&D of ATMPs. The aim of this study is to analyze the evolution of investments made by the Ministry of Health (MoH) of Brazil and partners in the ATMP field between 2004 and 2020. METHODS: A descriptive analysis was performed based on secondary data. The analysis was based on S&T and innovation research and support for research infrastructure in the field. The database was stratified by year of funding, ATMP type, type of study or research infrastructure project, amount invested in the project, targeted disease for which clinical trials in ATMPs were developed and financing sector (health, education, S&T and economic). RESULTS: The investments coordinated by MoH (61.5%) in partnership with the S&T, education and economic sectors (38.5%) consisted of Int$137.35 million in 282 ATMP projects. Funding included S&T and innovation research (67% of the total amount) and projects to implement or maintain infrastructure in selected research centers (32.98%). With regard to global convergence, cell therapy was the type of ATMP that most benefited from public investment, totaling 82.23% of the total funding in the analyzed period. Cardiology (29%) and neurology (21%) were the main focus of clinical trials. Following the global trend of public sector R&D funding, the number of basic and pre-clinical research projects represented 78.06% of the total number of projects. CONCLUSIONS: Despite the need to implement improvements in ATMP R&D financing policy in Brazil, the country has made important steps in the field and can serve as a benchmark for other countries with socioeconomic similarities. Among the main lessons are the prioritization of research aligned with the health needs of the population, cross-sector articulation by the health policymaker to coordinate R&D efforts of the sector and formulation of a specific sector policy (Programa Genomas Brasil, the Brazilian National Program of Genomic and Precision Medicine) to promote knowledge translation.

Optimizing the Decellularized Porcine Liver Scaffold Protocol.

There are few existing methods for shortening the decellularization period for a human-sized whole-liver scaffold. Here, we describe a protocol that enables effective decellularization of the liver obtained from pigs weigh 120 ± 4.2 kg within 72 h. Porcine livers (approx. 1.5 kg) were decellularized for 3 days using a combination of chemical and enzymatic decellularization agents. After trypsin, sodium deoxycholate, and Triton X-100 perfusion, the porcine livers were completely translucent. Our protocol was efficient to promote cell removal, the preservation of extracellular matrix (ECM) components, and vascular tree integrity. In conclusion, our protocol is efficient to promote human-sized whole-liver scaffold decellularization and thus useful to generate bioengineered livers to overcome the shortage of organs.

High-frequency (22-MHz) ultrasound for assessing the depth of basal cell carcinoma invasion.

BACKGROUND: High-frequency ultrasound (HFUS) has been studied in the diagnosis and therapeutic management of basal cell carcinoma (BCC). The accuracy of this method for location of deep margins remains unknown. This study evaluates HFUS for localization of deep surgical margins in BCC. MATERIALS AND METHODS: Ultrasound images of 83 lesions from 67 patients with clinical and dermoscopic diagnosis of BCC were compared with histopathological findings. Pearson's correlation coefficient was used to assess the relationship between thickness as measured by HFUS and histopathology. RESULTS: A strong correlation between HFUS and histopathological measurements was identified (r = 0.9744, P < .001). HFUS had sensitivity of 96%, specificity of 84%, and accuracy of 91% for measurement of deep tumor margins. Factors affecting tumor measurement on HFUS include marked basophilic degeneration of collagen, presence of peritumoral hypertrophic glands or hair follicles, fibrosis, and dense inflammatory changes related to the tumor itself or to prior procedures. CONCLUSION: High-frequency ultrasound was effective in localizing deep tumor margins in BCC. Therefore, we believe that this diagnostic imaging method is important when selecting a therapeutic approach, considering Mohs micrographic surgery, and evaluating the surgical site.

Anatomical evaluation of the relationship between the maxillary posterior teeth and maxillary sinus.

Knowledge of the anatomical relationships between the maxillary sinus (MS) and posterior teeth is important to prevent complications when endodontic or oral surgical procedures are performed. The aim of this study was to evaluate the relationships between the root apices of maxillary posterior teeth and the MS floor. Three oral radiologists evaluated 851 posterior teeth (1969 roots) imaged with cone beam computed tomography. The roots were analyzed individually in parasagittal sections, on which the most superior point of the apex was observed. A qualitative evaluation was performed, and each root was assigned a proximity score: 1, root invaginating the MS; 2, root in close contact with the MS floor; 3, root with no relationship with the MS; and 4, root with a measurable proximity to the MS. For roots classified as score 4, the distance to the MS floor was measured (quantitative analysis). Student t tests, 1-way analysis of variance, and simple linear regression analysis were performed (P < 0.05). The qualitative analysis revealed that the mesiobuccal root of the second molar had a pronounced proximity to the MS. The quantitative analysis revealed no differences in distance to the MS between right and left posterior teeth or between the different roots of the same tooth. In relation to the MS, the second molar was positioned closest, followed by the first molar, second premolar, and first premolar. Except for the comparison between mean distances of the second premolar and first molar (P = 0.11), the differences between groups of teeth were statistically significant (P < 0.05). Simple linear regression analysis showed that the more posterior the tooth was in relation to the midline, the shorter the mean distance from the root apex to the MS floor (P < 0.05). The mesiobuccal roots of second molars were closest to the MS. Second molars exhibited the shortest distances between their root apices and the MS and the greatest number of roots that were invaginating or in close contact with the MS. Therefore, second molars require special attention when endodontic or oral surgical approaches involve those regions.

Metabolomic profiling suggests systemic signatures of premature aging induced by Hutchinson-Gilford progeria syndrome.

INTRODUCTION: Hutchinson-Gilford Progeria Syndrome (HGPS) is an extremely rare genetic disorder. HGPS children present a high incidence of cardiovascular complications along with altered metabolic processes and an accelerated aging process. No metabolic biomarker is known and the mechanisms underlying premature aging are not fully understood. OBJECTIVES: The present work aims to evaluate the metabolic alterations in HGPS using high resolution mass spectrometry. METHODS: The present study analyzed plasma from six HGPS patients of both sexes (7.7 ± 1.4 years old; mean ± SD) and eight controls (8.6 ± 2.3 years old) by LC-MS/MS in high-resolution non-targeted metabolomics (Q-Exactive Plus). Targeted metabolomics was used to validate some of the metabolites identified by the non-targeted method in a triple quadrupole (TSQ-Quantiva). RESULTS: We found several endogenous metabolites with statistical differences between control and HGPS children. Multivariate statistical analysis showed a clear separation between groups. Potential novel metabolic biomarkers were identified using the multivariate area under ROC curve (AUROC) based analysis, showing an AUC value higher than 0.80 using only two metabolites, and tending to 1.00 when increasing the number of metabolites in the AUROC model. Taken together, changed metabolic pathways involve sphingolipids, amino acids, and oxidation of fatty acids, among others. CONCLUSION: Our data show significant alterations in cellular energy use and availability, in signal transduction, and lipid metabolites, adding new insights on metabolic alterations associated with premature aging and suggesting novel putative biomarkers.

Back pain and sagittal spine alignment in obese patients eligible for bariatric surgery.

OBJECTIVE: The objective of this research was to evaluate the prevalence of cervical and lumbar pain in obese patients eligible for bariatric surgery and to investigate possible changes in sagittal spine alignment in these patients. METHODS: The following parameters were compared in 30 obese patients and a control group of 25 non-obese volunteers: body mass index, prevalence of cervical and lumbar pain assessed by visual analog scale (VAS), Neck Disability Index [NDI] and Oswestry Disability Index [ODI], as well as radiographic parameters of the spine and pelvis measured with Surgimap software. RESULTS: The cervical and lumbar VAS and the NDI and ODI were significantly worse in obese patients. Compared with the control group, the cervical sagittal vertical axis (cSVA) of the obese group had higher variance (p value = 0.0025) and the cervical lordosis was diminished (p value = 0.0023). Thoracic kyphosis, lumbar lordosis, and the pelvic parameters were not significantly different between the groups. CONCLUSIONS: Obese patients demonstrated lower functional performance compared with their non-obese counterparts, while cervical lordosis was diminished and the cSVA was increased in obese patients. These slides can be retrieved under Electronic Supplementary Material.

Initial experience with the use of fractional flow reserve in the hemodynamic evaluation of transplant renal artery stenosis.

OBJECTIVE: To describe and standardize an original protocol for fractional flow reserve (FFR) pre and postangioplasty in an initial series of patients with clinically manifested transplant renal artery stenosis (TRAS). BACKGROUND: There is no data in the literature about the use of FFR in TRAS. METHODS: Patients with TRAS detected in a noninvasive study were referred to diagnostic angiography and stenosis considered visually severe (≥ 60%) were included. After selective cannulation, a PressureWire 0.014" (Certus™-St. Jude Medical) was advanced to the distal portion of the vessel. Resting Pd/Pa ratio (ratio of mean distal to lesion and mean proximal pressures) and translesional systolic pressure gradient were obtained and FFR and hyperemic translesional systolic and mean pressure gradients (HSG and HMG) were registered after papaverine induced maximum hyperemia-pre and poststent implantation. Creatinine levels and office blood pressure measurements were registered at the baseline, 6 and 12 months after intervention. RESULTS: Ten consecutive patients had successful stent implantation and were included. After treatment, significant increase in FFR (0.76 ± 0.09 vs. 0.96 ± 0.04, P < 0.001) and reduction in systolic hyperemic gradients (-41.40 ± 19.18, P < 0.001) and mean (-24.00 ± 11.65, P < 0.001) were observed. A strong negative correlation was observed between FFR and percent stenosis diameter-%SD (r = -0.89, P < 0.001) and HSG (r = -0.9, P < 0.001) as well as a strong positive correlation between FFR and baseline Pd/Pa ratio (r = 0.9, P < 0.001). CONCLUSION: FFR was a well-tolerated, valid and reproducible tool during percutaneous intervention for TRAS. Good correlation was observed between FFR and others hemodynamic parameters of lesion severity.

Neuromuscular electrical stimulation improves exercise tolerance in patients with advanced heart failure on continuous intravenous inotropic support use-randomized controlled trial.

OBJECTIVE: To evaluate the impact of a short-term neuromuscular electrical stimulation program on exercise tolerance in hospitalized patients with advanced heart failure who have suffered an acute decompensation and are under continuous intravenous inotropic support. DESIGN: A randomized controlled study. SUBJECTS: Initially, 195 patients hospitalized for decompensated heart failure were recruited, but 70 were randomized. INTERVENTION: Patients were randomized into two groups: control group subject to the usual care ( n = 35); neuromuscular electrical stimulation group ( n = 35) received daily training sessions to both lower extremities for around two weeks. MAIN MEASURES: The baseline 6-minute walk test to determine functional capacity was performed 24 hours after hospital admission, and intravenous inotropic support dose was daily checked in all patients. The outcomes were measured in two weeks or at the discharge if the patients were sent back home earlier than two weeks. RESULTS: After losses of follow-up, a total of 49 patients were included and considered for final analysis (control group, n = 25 and neuromuscular electrical stimulation group, n = 24). The neuromuscular electrical stimulation group presented with a higher 6-minute walk test distance compared to the control group after the study protocol (293 ± 34.78 m vs. 265.8 ± 48.53 m, P < 0.001, respectively). Neuromuscular electrical stimulation group also demonstrated a significantly higher dose reduction of dobutamine compared to control group after the study protocol (2.72 ± 1.72 µg/kg/min vs. 3.86 ± 1.61 µg/kg/min, P = 0.001, respectively). CONCLUSION: A short-term inpatient neuromuscular electrical stimulation rehabilitation protocol improved exercise tolerance and reduced intravenous inotropic support necessity in patients with advanced heart failure suffering a decompensation episode.

Ultrasonography of Hands and Wrists in the Diagnosis of Complications of Chikungunya Fever.

The purpose of this series was to describe the ultrasonographic and radiographic manifestations of changes to the hands and wrists in 50 patients with chronic musculoskeletal symptoms secondary to Chikungunya fever during the 2016 outbreak that occurred in Rio de Janeiro, Brazil. Most of the plain radiographs were normal (62%). The most common ultrasonographic findings were small joint synovitis (84%), wrist synovitis (74%), finger tenosynovitis (70%), and cellulitis (50%). In most cases, power Doppler did not show an increase in synovial vascular flow. The plain radiographs showed no specific findings, whereas the ultrasound images revealed synovial compromise and neural thickening.

Cell therapies for Chagas disease.

In this review of cell therapies in Chagas disease, we cover aspects related to the disease, its treatment and world demographics, before proceeding to describe the preclinical and clinical trials performed using cell therapies in the search for an alternative therapy for the most severe and lethal form of this disease, chronic chagasic cardiomyopathy.

Bone marrow cell migration to the heart in a chimeric mouse model of acute chagasic disease.

BACKGROUND: Chagas disease is a public health problem caused by infection with the protozoan Trypanosoma cruzi. There is currently no effective therapy for Chagas disease. Although there is some evidence for the beneficial effect of bone marrow-derived cells in chagasic disease, the mechanisms underlying their effects in the heart are unknown. Reports have suggested that bone marrow cells are recruited to the chagasic heart; however, studies using chimeric mouse models of chagasic cardiomyopathy are rare. OBJECTIVES: The aim of this study was to investigate the migration of bone marrow cells to the heart after T. cruzi infection in a model of chagasic disease in chimeric mice. METHODS: To obtain chimerical mice, wild-type (WT) C57BL6 mice were exposed to full body irradiation (7 Gy), causing bone marrow ablation. Then, bone marrow cells from green fluorescent protein (GFP)-transgenic mice were infused into the mice. Graft effectiveness was confirmed by flow cytometry. Experimental mice were divided into four groups: (i) infected chimeric (iChim) mice; (ii) infected WT (iWT) mice, both of which received 3 × 104 trypomastigotes of the Brazil strain; (iii) non-infected chimeric (Chim) mice; and (iv) non-infected WT mice. FINDINGS: At one-month post-infection, iChim and iWT mice showed first degree atrioventricular block with decreased heart rate and treadmill exercise parameters compared to those in the non-infected groups. MAIN CONCLUSIONS: iChim mice showed an increase in parasitaemia, myocarditis, and the presence of amastigote nests in the heart tissue compared to iWT mice. Flow cytometry analysis did not detect haematopoietic progenitor cells in the hearts of infected mice. Furthermore, GFP+ cardiomyocytes were not detected in the tissues of chimeric mice.

Exercise-Induced Abnormal Increase of Systolic Pulmonary Artery Pressure in Adult Patients With Sickle Cell Anemia: An Exercise Stress Echocardiography Study.

BACKGROUND: Pulmonary hypertension (PH) at rest is a risk factor for death in patients with sickle cell anemia (SCA). Exercise echocardiography (EE) can detect latent PH. We sought to investigate the occurrence of exercise-induced abnormal response of systolic pulmonary artery pressure (SPAP) in adult patients with SCA and normal SPAP at rest, and to identify the independent predictors of this abnormal response. METHODS AND RESULTS: Forty-four adult patients with SCA and normal SPAP at rest (tricuspid regurgitant jet flow velocity [TRV] <2.5 m/sec) were studied and divided into 2 groups: exhibiting normal SPAP after treadmill EE (TRV ≤ 2.7 m/sec) (G1), and exhibiting abnormal exercise-induced increase of SPAP (TRV > 2.7 m/sec) (G2). TRV cutoff points at rest and during EE were based on data from healthy-matched control subjects. Abnormal response of SPAP with exercise occurred in 57% of the sample (G2), with mean TRV level of 3.39 ± 0.41 m/sec (range 2.8-4.5 m/sec), significantly higher than those of G1 (2.29 ± 0.25 m/sec, range 2.0-2.7 m/sec; P < 0.001). Multivariate analysis identified TRV value in resting conditions ≥2.25 m/sec (P < 0.05), left atrial volume index ≥41 mL/m2 (P < 0.05), and a E/e'-waves ratio ≥6.3 (P < 0.05) as independent predictors of exercise-induced increase of SPAP. CONCLUSION: We concluded that adult patients with SCA and normal SPAP at rest may exhibit abnormal exercise-induced increase in SPAP, which was independently related to resting TRV levels, and indices of diastolic impairment and left ventricular filling pressure.

Magnetic Resonance Image Evaluation of Temporomandibular Joint Osteophytes: Influence of Clinical Factors and Artrogenics Changes.

This research aims to examine the presence of osteophyte in patients with arthrogenic temporomandibular disorders through magnetic resonance imaging (MRI); to investigate the influence of sex and clinical symptoms in its prevalence; and the position of the osteophytes in the condyle. The study was based on 100 MRI and on reports of patients, which corresponded to the evaluation of 200 joints. Patients of both sexes were aged from 18 to 82 years (average = 49.48) and were subjected to the aforementioned examination from January 2006 to March 2009. The assessment considered the type of disc displacement, the presence of effusion, bone marrow edema, condyle changes, joint noise and pain. The MRI machine used was the GE Signa HDX (General Electric, Milwaukee, WI), with T1 and T2-weighted, 1.5 T magnetic field, sagittal oblique (mouth closed, mouth open) and coronal (mouth closed) imaging, with spherical surface coil and an asymmetric matrix. All images were interpreted by an experienced radiologist. A total of 28% (n = 56) of the temporomandibular joints showed osteophytes on the anterior surface of the mandible. No relationship was found between sex and osteophytes. The authors found a statistically significant difference between osteophytes and disc displacement without reduction (P < 0.001). The presence of osteophytes suggested a possible cause and effect relationship between osteoarthritis and disc displacement without reduction; the osteophyte was always located in the anterior surface of condyle, regardless of the sex variable; no significant difference was found between osteophytes and the main complaints of the patient.

Expression of ganglioside 9-O acetyl GD3 in undifferentiated embryonic stem cells.

Embryonic stem cells (ES cells) express a transient and heterogeneous pattern of molecules, which suggests a notable mechanism to control self-renewal avoid the differentiation into germ layers. We show that 9-O-acetyl GD3 (9OacGD3), a highly expressed b-series ganglioside in neural stem (NS) cells, is expressed in undifferentiated mouse ES cells in a heterogeneous fashion. After sorting, undifferentiated 9OacGD3(+) ES cell population had higher levels of nestin and Sox2 mRNA than the 9OacGD3(-) cells. Even with elevated expression of these neural transcription factors, 9OacGD3(+) cells did not give rise to more neural progenitors than 9OacGD3(-) cells. Expression of 9OacGD3 was recovered from 9OacGD3(-) cell population, demonstrating that expression of this ganglioside in mouse embryonic stem cells is transient, and does not reflect cell fate. Our findings show that the ganglioside 9OacGD3 is expressed heterogeneously and transiently in ES cells, and this expression corresponds to higher levels of Sox2 and Nestin transcripts.

Intraobserver and interobserver agreement of Goutallier classification applied to magnetic resonance images.

BACKGROUND: Fatty infiltration of the muscle bellies is an important prognostic factor in rotator cuff tears. It was described initially in computed tomography examinations, and there is an ongoing debate about whether magnetic resonance (MR) is a reliable method for staging fatty infiltration. This study sought to determine intraobserver and interobserver agreement for Goutallier's classification of fatty infiltration of the rotator cuff as evaluated through MR imaging. MATERIALS AND METHODS: Twenty MR examinations of the shoulder showing full-thickness tear of the supraspinatus tendon, with or without associated lesions, were evaluated by 3 radiologists with experience in musculoskeletal system imaging and 3 fellowship-trained shoulder surgeons. The evaluators classified the fatty infiltration of the supraspinatus muscle according to the guidelines proposed by Goutallier et al. After 8 weeks, they re-evaluated the examinations, without access to their previous reports. Weighted κ index values were determined for intraobserver and interobserver agreement analyses, and intraobserver agreement κ values are reported with 95% confidence intervals (CIs). RESULTS: The mean intraobserver agreement was 0.832 among the orthopedists (CI > 95%) and 0.741 among the radiologists (CI > 95%). Interobserver agreement was 0.8214 (evaluation 1) and 0.7231 (evaluation 2) among the orthopedists (P < .0001) and 0.6627 (evaluation 1) and 0.6067 (evaluation 2) among the radiologists (P < .0001). Intraobserver agreement was not associated with length of experience or frequency of routine evaluations. CONCLUSIONS: When it is applied to MR images of rotator cuff musculature, Goutallier's fatty infiltration staging rubric yielded highly significant intraobserver and interobserver agreement.

A Study of the Association Between Sleep Bruxism, Low Quality of Sleep, and Degenerative Changes of the Temporomandibular Joint.

The aim of this study was to evaluate the presence of degenerative bone changes of the temporomandibular joint (TMJ) in individuals suffering from sleep bruxism (SB), associating these characteristics with the quality of sleep. For this, we followed the International Classification of Sleep Disorders for the diagnosis of SB, in addition to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) for the classification of TMD and cone beam computed tomography. It was found that 97.7% of the individuals with bruxism had at least 1 RDC/TMD group III diagnosis, 75.6% of the subjects considered their sleep quality as poor, and the largest group (23%) had centric bruxism. There was no significant association between the pattern of sleep quality (P = 0.36), the type of SB (P = 0.277), and the presence of degenerative changes of the TMJ. Regardless of the quality of sleep and the type of bruxism presented, the prevalence of degenerative bone disorders was high (67%) among women with a mean age of 46 years and a clinical diagnosis of SB.