Craniofacial radiographic patterns of multiple myeloma in patients treated with bisphosphonates

Orientadores: Alan Roger dos Santos Silva, Mario Fernando de GoesTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de PiracicabaResumo: Esta tese de doutoramento avaliou a frequência e os padrões de manifestação radiográfica do mieloma múltiplo (MM) nos ossos craniofaciais por meio de investigações clinicopatológicas de natureza retrospectiva. Os resultados da consecução desta tese estão apresentados em 2 artigos. No primeiro capítulo (artigo 1), comparou-se uma série de 88 pacientes diagnosticados com MM que receberam bisfosfonatos administrados por via endovenosa (BFs e.v.) (grupo estudo) com a uma série de 100 pacientes diagnosticados com MM que não utilizaram BFs e.v. (grupo controle). Radiografias panorâmicas digitais foram estudadas em ambos os grupos para avaliação da presença (ou ausência) dos seguintes critérios: imagens osteolíticas solitárias, imagens osteolíticas múltiplas, osteoporose difusa, esclerose difusa, anormalidades de lâmina dura, alvéolo pós-extração não cicatrizado e sequestro ósseo. A análise dos dados revelou que múltiplas lesões osteolíticas (p=0.001), osteoporose difusa (p=0.001) e esclerose difusa (p=0.0036) foram mais frequentemente observadas em mandíbula do que em maxila em ambos os grupos estudados. A presença de lesão osteolítica solitária foi observada com menor frequência no grupo que recebeu BFs e.v. (p=0.0078, OR=0.1994, CI95%=0.057-0.696). As anormalidades de lâmina dura (p=0.0006, OR=2.447, CI95%=1.47-4.08) e alvéolo ósseo persistente (p=0.0021, OR=20.23, CI95%=1.158-353.3) também estavam associados ao tratamento com BFs e.v. Concluiu-se que o tratamento com BFs e.v. altera os padrões radiográficos de manifestação do MM em mandíbula e maxila. O segundo capítulo (artigo 2) comparou a frequência da detecção radiográfica de imagens osteolíticas do MM nos ossos craniofaciais de uma série de 155 pacientes por meio de três técnicas digitais (radiografia panorâmica, radiografia frontal e radiografia lateral de crânio). Radiografias panorâmicas detectaram imagens osteolíticas em 137 (88,3%) casos, radiografia frontal de crânio em 141 (91%) casos e radiografia lateral de crânio em 144 (93%) casos. Apenas 18 (11,61%) casos se manifestaram exclusivamente no crânio e 6 (3,87%) exclusivamente em mandíbula e maxila; entretanto, 129 (83,23%) pacientes apresentaram imagens osteolíticas sincrônicas em crânio, mandíbula e maxila. Concluiu-se que apesar da radiografia lateral de crânio ter apresentado maior frequência de detecção de imagens osteolíticas do MM, as três técnicas radiográficas utilizadas neste estudo demonstraram altas frequências de detecção de imagens osteolíticas relacionadas ao MM nos ossos craniofaciaisAbstract: This thesis evaluated the frequency and radiographic patterns of multiple myeloma (MM) in craniofacial bones through clinical, pathological and radiographic investigations in a retrospective approach. The results are presented in two papers. The first chapter (manuscript 1) compared a series of 88 patients diagnosed with MM who received intravenous bisphosphonates (i.v. BPs) (study group) with a series of 100 MM patients naive to i.v. BPs (group control).Digital panoramic radiographs were analized in both groups to evaluate the presence (or absence) of the following criteria: solitary osteolytic lesions, multiple osteolytic lesions, diffuse osteoporosis, diffuse sclerosis, abnormalities of the lamina dura, non-healing alveolar sockets and bone sequestration. Data analysis revealed multiple osteolytic lesions (p=0.001), diffuse osteoporosis (p=0.001) and diffuse sclerosis (p=0.0036) were more often observed in the mandible than in the maxilla in both studied groups. The presence of solitary osteolytic lesions showed to be reduced in the BPs group (p=0.0078, OR=0.1994, CI95%=0.057-0.696). Abnormalities of the lamina dura (p=0.0006, OR=2.447, CI95%=1.47-4.08) and non-healing alveolar sockets (p=0.0021, OR=20.23, CI95%=1.158-353.3) were also associated with BPs treatment. I.v. BPs therapy changes the typical radiographic patterns of MM in the jawbones. The second chapter (manuscript 2) compared the frequency of radiographic detection of osteolytic MM lesions in craniofacial bones of a series of 155 patients, using three digital techniques (panoramic radiograph, frontal radiograph and lateral radiograph of the skull). Panoramic radiographs detected osteolytic images in 137 (88.3%) cases, frontal radiograph of skull in 141 (91%) cases and lateral radiograph of skull in 144 (93%) cases. Eighteen (11.61%) cases showed images affecting exclusively the skull and 6 (3.87%) cases only affected mandible and maxilla; however, 129 (83.23%) patients presented MM osteolytic images synchronously affecting skull and jawbones. It was concluded that although the lateral radiograph of skull presented increased rates of osteolytic MM lesions detection, all studied radiographic techniques were effective in detecting osteolytic images related to MM in craniofacial bonesDoutoradoEstomatologiaDoutora em EstomatopatologiaCAPE

Deep learning-based lower back pain classification and detection from T2-weighted magnetic resonance images

Abstract. Lower back pain (LBP) is a common physiological condition that affects 50–80% of the adult population at some point in their lives. For example, the economic load of LBP in Sweden was estimated to be approx. at C740 million in 2011. In LBP diagnostics, magnetic resonance imaging (MRI) is often used. MRI is used to visualize the structures in the lumbar region of the spine such as disks, bones, and spaces between the vertebral bones where nerves pass through. The lumbar spine refers to the lowest five vertebrae and intervertebral discs of the spine. MRI provides a detailed picture of the lumbar spine to get visual confirmation of any abnormalities potentially related to LBP to support the diagnosis process. The goal of this thesis was to investigate visual patterns related to LBP in T2-weighted MR images measured with a fast spin-echo sequence on a GE Healthcare Signa HDxt 1.5 T MRI system. A convolutional neural network was used to classify MRIs into symptomatic and asymptomatic cases and to develop a fully automated pain prediction process. A total of 526 MRI examinations with supporting pain questionnaires from the Northern Finland Birth Cohort 1966 (NFBC1966) were used. Three different datasets were created for the experiments: i) a dataset with mid-sagittal slices from the center of the spine from each examination, ii) a dataset with mid-sagittal slices and its immediate neighboring slices, and similarly, iii) a dataset with five middle-most sagittal slices. In each dataset, individual slices were considered as independent samples, i.e., inputs for the classification method. The developed classification method yielded the best results when the input dataset comprised of three middle-most slices (Balanced Accuracy score (BACC) of 0.709 ± 0.011, Average Precision (AP) of 0.467 ± 0.025, and Area Under Receiver Operating Characteristic curve (ROC-AUC) of 0.740 ± 0.008). The baseline model trained using only the mid-sagittal slice for classification yielded the lowest classification scores (BACC of 0.546 ± 0.032, AP of 0.403 ± 0.007, and ROC-AUC of 0.667 ± 0.008) followed by the model trained with the dataset with five middle-most slices (BACC of 0.675 ± 0.008, AP of 0.369 ± 0.009, and ROCAUC of 0.619 ± 0.011). To conclude, this work suggests that the developed deep learning-based classification pipeline could be used for LBP diagnostics of lumbar spine MRI. LBP diagnostics is heavily based on degenerative MRI findings and deep learning has the potential to supplement these visual assessments objectively. The developed method could be helpful, for example, in identifying negative cases in order to enhance the workflow of routine diagnostic imaging tasks.Alaselkäkivun luokittelu ja havainnointi T2-painotetuista magneettikuvista syväoppimista hyödyntäen. Tiivistelmä. Alaselkäkipu on yleinen fysiologinen tila, joka vaikuttaa 50:stä 80:een %:iin aikuisväestöstä jossain vaiheessa heidän elämäänsä. Ruotsissa alaselkäkipuun liittyvän taloudellisen kuormituksen on arvioitu olleen noin 740 miljoonaa euroa vuonna 2011. Alaselkäkivun syyn etsimiseen käytetään tyypillisesti magneettikuvausta (MRI). MRI:tä käytetään lannerangan alueen rakenteiden, kuten levyjen, luiden ja selkärangan luiden välisten tilojen, joissa hermot kulkevat, visualisoimiseen. Lannerangalla tarkoitetaan selkärangan viittä alinta nikamaa ja levyä. MRI tarjoaa diagnoosin tukemiseksi yksityiskohtaisen kuvan lannerangasta mahdollistaen alaselkäkipuun mahdollisesti liittyvien poikkeamien visuaalisen tarkastelun. Tämän opinnäytetyön tavoitteena oli tutkia alaselkäkipuun liityviä muutoksia T2-painotetuissa magneettikuvissa, jotka kuvattiin GE Healthcare Signa HDxt 1,5 T magneettikuvauslaitteistolla nopeaa spin-kaikusekvenssiä käyttäen. Kuvien luokitteluun käytettiin konvoluutioneuroverkkoja oireellisiin ja oireettomiin tapauksiin täysautomatisen kivun ennustusmenetelmän kehittämiseksi. Aineistona käytettiin yhteensä 526 tutkimusta Pohjois-Suomen syntymäkohortista 1966 (NFBC1966). Testejä varten luotiin kolme erilaista aineistoa: i) keskisagittaaliset viipalekuvat, ii) keskisagittaaliset viipalekuvat ja niiden naapuriviipaleet, sekä vastaavasti iii) viisi keskimmäisintä viipalekuvaa, joita hyödynnettiin itsenäisinä näytteinä, eli luokitusmenetelmän syötteinä. Kehitetty luokitusmenetelmä tuotti parhaat tulokset kun syötejoukkona olivat keskisagittaaliset viipalekuvat ja niiden naapuriviipaleet (Balanced Accuracy score (BACC) 0,709 ± 0,011, Average Precision (AP) 0,467 ± 0,025, ja Area Under Receiver Operating Characteristic curve (ROC-AUC) 0,740 ± 0,008). Keskisagittaalisten viipalekuvien avulla koulutettu vertailumalli tuotti alhaisimmat luokittelutulokset (BACC 0.546 ± 0.032, AP 0.403 ± 0.007, and ROC-AUC 0.667 ± 0.008), ja seuraavaksi paras malli oli viidellä keskimmäisellä viipalekuvalla koulutettu malli (BACC 0.675 ± 0.008, AP 0.369 ± 0.009, and ROC-AUC 0.619 ± 0.011). Tämä työ antaa viitteitä siitä, että syväoppimiseen perustuvaa menetelmää voitaisiin käyttää lannerangan MRI-aineistosta suoritettavaan alaselkäkivun diagnosointiin. Alaselkäkivun diagnostiikka perustuu vahvasti MRIrappeumalöydöksiin, ja syväoppimisella on edellytyksiä täydentää objektiivisella tavalla näitä visuaalisia arvioita. Kehitetystä menetelmästä voisi olla apua esimerkiksi negatiivisten tapausten tunnistamisessa rutiininomaisten diagnostisten kuvantamistehtävien työnkulun tehostamiseksi

Computed Tomography Shows High Fracture Prevalence Among Physically Active Forager-Horticulturalists With High Fertility

Modern humans have more fragile skeletons than other hominins, which may result from physical inactivity. Here, we test whether reproductive effort also compromises bone strength, by measuring using computed tomography thoracic vertebral bone mineral density (BMD) and fracture prevalence among physically active Tsimane forager-horticulturalists. Earlier onset of reproduction and shorter interbirth intervals are associated with reduced BMD for women. Tsimane BMD is lower versus Americans, but only for women, contrary to simple predictions relying on inactivity to explain skeletal fragility. Minimal BMD differences exist between Tsimane and American men, suggesting that systemic factors other than fertility (e.g. diet) do not easily explain Tsimane women’s lower BMD. Tsimane fracture prevalence is also higher versus Americans. Lower BMD increases Tsimane fracture risk, but only for women, suggesting a role of weak bone in women’s fracture etiology. Our results highlight the role of sex-specific mechanisms underlying skeletal fragility that operate long before menopause

Causes and consequences of temporomandibular joint diseases

Temporomandibular joint disorders (TMJD), a subgroup of Temporomandibular disorders (TMD), has a multifactorial etiology with still largely unknown pathophysiology. Although many risk factors have been proposed, few population-based studies have been conducted. There are known associations between TMJD and mental and behavioral disorders (MBD) and musculoskeletal diseases (MSD). MBD and MSD cause high work disability and are the leading causes for sick leave (SL) and disability pension (DP) both globally and in Sweden. However, no studies have investigated work disability among patients with TMJD (pwTMJD) or the effect of MBD and MSD comorbidity on work disability among pwTMJD. This thesis includes all Swedish citizens aged ≥18 registered between 1998 and 2016 in the National Patient Registry with a TMJD diagnosis or TMJD surgical procedure code. These pwTMJD (n=33 316) were matched to a comparison cohort (n=333 160) from the Total Population Registry. pwTMJD were categorized depending on whether they had received surgical treatment or not, and on the number of surgical procedures. Study I shows that pwTMJD have 2–3 times more mean annual days of SL and DP than the general population and that patients who had undergone several surgical treatments were most dependent on these benefits. The increased work disability among pwTMJD was noticeable as early as five years before first time diagnosis or treatment. Study II and Study III investigate the probability of developing TMJD among individuals with and without MBD/MSD. Study II shows that many MBD increase the probability of TMJD and that individuals with MBD had a higher risk of needing repeated surgical procedures compared to individuals with no MBD. Study III shows that virtually all MSD increase the probability of TMJD, especially TMJD that require repeated surgical procedures. Study IV further examines the impact of MBD and MSD comorbidity on mean annual days of SL and DP among pwTMJD compared to the general population, by using strata of comorbidity. The results show that both MBD and MSD comorbidity by themselves have a large impact on the use of social insurance benefits but that combined MBD/MSD comorbidity had the largest impact on SL and DP. Regardless of comorbidity, pwTMJD displayed the highest mean annual days of SL and DP in almost all strata of comorbidity. In conclusion, the results in this thesis show that MBD and MSD are strong predictors for the development of TMJD. The results also show that pwTMJD have more work disability than the general population, and that this increased dependence on social insurance benefits is strongly influenced by comorbidities. These findings emphasize how pwTMJD are suffering from their condition and that a multimodal approach is warranted, preferably steered by national guidelines designed by specialists in orofacial pain and function, oral and maxillofacial surgeons, and colleagues from the medical field

BONE AND JOINT SURGERY

Total hip arthroplasty with cemented Lubinus SP II prosthesis is well analyzed in the Sweden National Hip Arthroplasty Register. There are only few reports from the other countries concerning survival analysis of this implant in short and mid-term follow-up. Eesti Arst 2007; 86(8):533-60

Skills in Rheumatology

This Open Access book presents practical approaches to managing patients affected by various rheumatological diseases, allowing readers to gain a better understanding of the various clinical expressions and problems experienced by these patients. Discussing rheumatology from an organ systems perspective, it highlights the importance ofdetailed musculoskeletal examinations when treating patients affected by rheumatological diseases. The book first explores the latest diagnostic approaches and offers key tips for accurate musculoskeletal examinations before addressing the various treatment modalities, with a particular focus on the most common joints involved in rheumatoid arthritis: the wrists and the metacarpophalangeal joints (2nd and 3rd). Featuring easy-to-understand flow diagrams and explaining the common medical problems associated with rheumatic disease, such as shortness of breath and anemia, it is not only a valuable resource to rheumatologists, but will also appeal to medical students, junior residents, and primary healthcare physicians

The Effect of Patient Reminders on Osteoporosis Screenings

Osteoporosis is characterized by reduction of bone mass and compromised bone strength, resulting in an increased fracture risk. Since a reduction of bone mass has been shown to be predictive of future fracture risk, prevention strategies target screening those patients at risk for decreased bone mass by using bone mineral density (BMD) dual energy x-ray absorptiometry (DXA) scans. Current national guidelines recommend that all women 65 years and older undergo BMD testing using central DXA every two years. Despite these recommendations, women age 65 years and older still do not participate in this screening. Greater rates of osteoporosis screening could be achieved by identifying an efficient, effective way for healthcare providers and patients to schedule DXA scans. The purpose of this EBP project was to determine if a mailed patient reminder would increases BMD screening rates in women at risk for osteoporosis, as compared to the previous practice of provider recommendation during a scheduled visit. The Stetler Model was used to guide the EBP project, and Kotter and Cohen’s eight steps for successful change provided support for the behavioral change. The population of focus consisted of female Medicare recipient’s age 65 years and older who were active patients within a Midwestern community care clinic in the fall of 2013. Overall, the mailed reminder for osteoporosis screening demonstrated effectiveness in improving BMD screening rates. At the end of the 12-week project, the percentage of female Medicare recipients who were up to date in their BMD screening increased from 17.07% to 31.40%. Those participating in BMD screening during the 12-intervention intervention period ranged in age from 65 to 98. Of the 47 female patients who were not up to date and had a DXA scan as a result of the intervention, a significantly larger percentage were patients of the physician (87.23%) versus patients of the NP (12.77%) who focused on women\u27s wellness during routine office visits (χ² = 9.824, p = .002)