Botulinum toxin type a antinociceptive activity in trigeminal regions involves central transcytosis.

OBJECTIVE: Botulinum toxin type A (BoNT-A) provides lasting pain relief in patients with craniofacial pain conditions but the mechanisms of its antinociceptive activity remain unclear. Preclinical research revealed toxin axonal transport to the central afferent terminals, but it is unknown if its central effects involve transsynaptic traffic to the higher-order synapses. To answer this, we examined the contribution of central BoNT-A transcytosis to its action in experimental orofacial pain. MATERIAL AND METHODS: Male Wistar rats, 3-4 months old, were injected with BoNT-A (7 U/kg) unilaterally into the vibrissal pad. To investigate the possible contribution of toxin's transcytosis, BoNT-A-neutralizing antiserum (5 IU) was applied intracisternally. Antinocicepive BoNT-A action was assessed by duration of nocifensive behaviors and c-Fos activation in the trigeminal nucleus caudalis (TNC) following bilateral or unilateral formalin (2.5%) application into the vibrissal pad. Additionally, cleaved synaptosomal-associated protein of 25 kDa (cl-SNAP-25) immunoreactivity was analyzed in the bilateral TNC. RESULTS: Unilaterally injected BoNT-A reduced the nocifensive behaviors and bilateral c-Fos activation induced by formalin, which was accompanied by the toxin's enzymatic activity on both sides of the TNC. BoNT-A antinociceptive or enzymatic activities were prevented by the specific neutralizing antitoxin. BoNT-A contralateral action occurred independently from ipsilateral side nociception or contralateral trigeminal nerve-mediated axonal traffic. CONCLUSION: Herein, we demonstrate that antinociceptive action of pericranially administered BoNT-A involves transsynaptic transport to second order synapses and contralateral trigeminal nociceptive nuclei. These results reveal more complex central toxin activity, necessary to explain its clinical effectiveness in the trigeminal region-related pain states.

Psoas abscess during treatment with intravenous tocilizumab in a patient with rheumatoid arthritis: a case-based review.

Interleukin-6 receptor antagonist tocilizumab is a biologic drug used for treating patients with active rheumatoid arthritis (RA) who failed to respond to synthetic or other biologic disease-modifying antirheumatic drugs or where they were contraindicated. Interleukin-6 receptor blockade results in a decrease of disease activity but has some potential adverse effects, the most common being infections. We present a case of a 75-year-old female patient with long-lasting RA, several comorbidities and multiple prior therapies, who developed back pain and general malaise during tocilizumab intravenous treatment. The laboratory findings were typical of toxemia, and the imaging findings revealed large psoas muscle abscess. Surgical and antibiotic treatment was performed with a good outcome. To our knowledge, this has been the first case of a psoas abscess in a patient with RA treated with tocilizumab described in the literature so far. We also present a review of the literature regarding infection, and particularly abscess formation in patients treated with biological disease-modifying antirheumatic drugs, tocilizumab included.

Association between disease activity measured by RAPID3 and health-related quality of life in patients with rheumatoid arthritis.

Routine assessment of patient index data 3 (RAPID3) is a simple, valid and reliable tool designed to measure disease activity in patients with rheumatoid arthritis (RA). RA causes significant disability and diminishes health-related quality of life (HR-QoL). The aim of this study was to investigate how RAPID3 is related to HR-QoL in patients with RA. In this cross-sectional study performed at the tertiary outpatient clinic 68 consecutive patients (58 females, and 10 males) with established RA were enrolled. RAPID3 and EuroQoL-5D-3L (EQ-5D-3L) were used to measure disease activity and quality of life, respectively. Alongside, demographic and clinical data were obtained, as well as HAQ-DI as a measure of physical function, and Steinbrocker's score for radiographic damage. To test the relationships among RAPID3 and study variables we used the Pearson product-moment correlation coefficient, with the significance was set at P < 0.05. Linear and forward stepwise regression was used to show how variables of interest contributed to RAPID3. The mean value of RAPID3 (standard deviation, SD) was 14.12 (± 5.21), while the median (IQR) value of EQ-5D-3L was 0.51 (0.62-0.23). There was a high significant correlation (r = - 0.73) between RAPID3 scores and EQ-5D-3L. Among the other variables of interest, the strongest correlation was found between RAPID3 and intensity of pain (r = 0.88), while the EQ-5D-3L and pain were moderately correlated (r = - 0.68). In evaluating the influence of variables of interest on RAPID3, a forward stepwise regression model was constructed to evaluate whether VAS pain, EQ-5D-3L and EQ-VAS predicted RAPID3. The given variables significantly explained approximately 81% of the variation in RAPID3. Based on the results of this study RAPID3, a simple and practical tool to assess disease activity, reflects well HR-QoL in patients with established RA.

Clinical and MRI Outcomes After Surgical Treatment of Osteochondral Lesions of the Talus in Skeletally Immature Children.

BACKGROUND: The literature on the osteochondral lesion of the talus (OLT) in skeletally immature children is scarce and little is known about the clinical outcomes and the radiologic appearance of these lesions after surgical treatment. The aim of this study was to assess mid-term clinical and magnetic resonance imaging (MRI) outcomes after arthroscopic microfracture (AM) of OLT in skeletally immature children. METHODS: Thirteen patients with OLT treated by AM before skeletal maturity were included in the study. The Berndt and Harty outcome question, the Single Assessment Numeric Evaluation question, and the Martin questionnaire were used to obtain patients' subjective satisfaction with their operated ankle. Functional outcomes preoperatively and postoperatively were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) score. MRI scans were performed postoperatively using a magnetic resonance observation of cartilage repair tissue (MOCART) scoring system for 11 ankles. RESULTS: The median age was 15 years (range, 13 to 16 y) and the median follow-up period was 5.6 years (range, 3.8 to 13.6 y). According to the Berndt and Harty outcome question, good clinical results were reported in 10 (76.9%) and fair in 3 (23.1%) patients. The postoperative AOFAS score was significantly improved when compared with the preoperative AOFAS score, with a mean increase of 35 points (P<0.001). The overall MOCART score was 65 (range, 10 to 75). MRI variables of the MOCART scoring system showed no association with clinical outcomes. CONCLUSIONS: AM seems to be an effective surgical method for the treatment of OLT in skeletally immature children. LEVEL OF EVIDENCE: Level IV-therapeutic studies, case series.

Evaluation of the Head Multislice Computed Tomography Scan in Emergency Department.

The aim of the study was to examine the prevalence of head injuries, acute stroke and brain tumors obtained from computed tomography (CT) scans in the emergency department (ED) during a one-year period. We also assessed the potential effect of seasons on the occurrence of stroke, head trauma and tumors found on CT scans, expressed in monthly intervals. This retrospective review included all patients that underwent emergency head CT from the hospital database. A total of 3888 head CT examinations were performed in adult patients presenting to ED and 1424 CT scans had at least one pathologic finding meeting diagnostic criteria for the study. Of the total number of CT scans analyzed, acute stroke was identified in 552 (14.19%), head trauma in 660 (16.97%), and brain tumor in 212 (5.45%) patients. Head trauma was more commonly found in males (n=465, 70.45%) than in females (n=195, 29.54%). Acute stroke was slightly more common in males than in females. Brain tumors were more frequently found in female patients. There were monthly variations in the number of head injuries and acute stroke diagnosed during the study period. Men and elderly patients were found to account for the greatest number of traumatic head injuries and therefore are at the highest risk of possible brain injury.

VERTEBRAL OSTEOMYELITIS IN ADULT PATIENTS--CHARACTERISTICS AND OUTCOME.

The aim of the study was to assess disease characteristics and outcome in patients with vertebral osteomyelitis (VO). A two medical centre retrospective cohort study was performed by chart review after discharge of 110 patients with confirmed VO treated during a 5-year period. Patients were divided in two groups: patients with uncomplicated VO and patients with complicated VO. All patients underwent clinical and biological examinations and magnetic resonance imaging (MRI) according to the same protocol. Patients with complicated VO were significantly older (p = 0.038). They were longer treated with antibiotics parenterally (p = 0.047) and more often surgically (p < 0.001). In these patients, high Charlson comorbidity index (CCI) score was more often observed (p = 0.024), as well as liver cirrhosis (p = 0.013) and degenerative spine disease (p = 0.007) as comorbidities. Patients with advanced MRI changes of VO had a modified CCI score of 2 or more (p = 0.006). They more often experienced neurological deficit (p = 0.021). Staphylococcus aureus was the most frequently isolated bacterium from blood and tissue samples. Advanced MRI changes and complicated VO were more often observed in patients with high CCI score due to impaired immune system caused by chronic comorbid disease(s) or modulation of immunity with medications. High CCI scores were more frequently associated with positive blood cultures due to bacteremia because of impaired immunity. Patients with complicated VO were longer treated with antibiotics parenterally and more often surgically treated for phlegmon and abscess formation. Liver cirrhosis and degenerative spine disease, which were more often found in patients with complicated VO, obviously impacted the course of the disease.

Sever's disease complicated with osteomyelitis.

Sever's disease is juvenile osteochondrosis of calcaneus, manifested with posterior heel pain and mild swelling, usually in young athletes, caused by repetitive microtrauma. The standard diagnostic procedures include radiographs and ultrasound examination. It is a self-limiting condition, usually treated conservatively. We present a case of Sever's disease complicated with calcaneal osteomyelitis. A 9-year-old boy with a several month history of left heel pain was admitted to our institution for further clinical evaluation and therapy. Bilateral Sever's disease was clinically diagnosed, confirmed by radiographs and ultrasound examination. Magnetic resonance imaging (MRI) showed osteolytic zone in the posterior left calcaneus with peripheral enhancement after contrast administration and surrounding bone and subcutaneous edema, suggestive of osteomyelitis. After six weeks of parenteral antibiotic treatment, the patient's condition improved. Follow up MRI performed 3 months later showed significant regression of osteolytic lesion and replacement with granulation tissue surrounded with new bone formation. To our knowledge and literature search, this is a previously unreported complication of Sever's disease. MRI should be done in all atypical cases of Sever's disease to rule out any other possible disorders including osteomyelitis.

Acute pneumococcal myelitis in an adult patient.

Pneumococcal meningitis represents the most severe community-acquired bacterial meningitis. The disease is frequently associated with various complications. We present a case of pneumococcal meningitis in an immunocompetent adult patient treated with hypothermia. The disease course was complicated with severe myelitis and consequent paraplegia which is an extremely rare complication of pneumococcal disease.

[Diagnosis and conservative treatment of low back pain: review and guidelines of the Croatian Vertebrologic Society]. / Dijagnostika i konzervativno lijecenje krizobolje: pregled i smjernice Hrvatskog Vertebroloskog Drustva.

Low back pain (LBP) is a very common condition with high costs of patient care. Medical doctors of various specialties from Croatia have brought an up-to-date review and guidelines for diagnosis and conservative treatment of low back pain, which should result in the application of evidence-based care and eventually better outcomes. As LBP is a multifactorial disease, it is often not possible to identify which factors may be responsible for the onset of LBP and to what extent they aggravate the patient's symptoms. In the diagnostic algorithm, patient's history and clinical examination have the key role. Furthermore, most important is to classify patients into those with nonspecific back pain, LBP associated with radiculopathy (radicular syndrome) and LBP potentially associated with suspected or confirmed severe pathology. Not solely a physical problem, LBP should be considered through psychosocial factors too. In that case, early identification of patients who will develop chronic back pain will be helpful because it determines the choice of treatment. In order to make proper assessment of a patient with LBP (i.e. pain, function), we should use validated questionnaires. Useful approach to a patient with LBP is to apply the principles of content management. Generally, acute and chronic LBP cases are treated differently. Besides providing education, in patients with acute back pain, advice seems to be crucial (especially to remain active), along with the use of drugs (primarily in terms of pain control), while in some patients spinal manipulation (performed by educated professional) or/and short-term use of lumbosacral orthotic devices can also be considered. The main goal of treating patients with chronic LBP is renewal of function, even in case of persistent pain. For chronic LBP, along with education and medical treatment, therapeutic exercise, physical therapy and massage are recommended, while in patients with a high level of disability intensive multidisciplinary biopsychosocial approach has proved to be effective.

[Novelties in pathophysiology, radiology diagnostics and conservative treatment of painful spine conditions and deformities]. / Novosti u patofiziologiji, radioloskoj dijagnostici i konzervativnom lijecenju bolnih stanja i deformacija kraljeznice.

Spinal pain, especially chronic low-back pain is one of the most prominent health and healthcare problems. Better understanding of pain pathophysiology and more precise visualization using modern imaging techniques help us to focus our intervention and obtain better outcome. In most patients with spine conditions symptoms and function resolve with conservative treatment. In this article we report on novelties in pathophysiology of spinal pain, magnetic resonance imaging and conservative treatment options (medications, therapeutic exercise, physical therapy and orthoses) of painful spine conditions and scoliosis. Apart from being informative, together with the corresponding article about novelties in invasive/surgical treatment, this special focus article on recent developments in this area can be used as an aid in decision making when approaching these patients.

Correlation between magnetic resonance imaging and histopathology in differentiation of pancreatic diseases.

In the last four decades, the incidence of pancreatic cancer has tripled in Western countries. More than 90% of all pancreatic cancers are detected in the advanced stage of the disease when surgical treatment is no longer possible and survival after initial diagnosis is usually very short. The aim of this study was to correlate magnetic resonance imaging (MRI) established diagnosis of chronic pancreatitis, benign lesion and malignant neoplasm with final histopathology. The study included 29 patients in whom the nature of pancreatic pathology could not be determined clinically and by other imaging modalities including abdominal ultrasonography, endoscopic retrograde cholangiopancreatography and multislice computed tomography. MRI examination was performed and radiological report was compared with histopathology assessment of the pancreatic lesion detected. The data obtained indicated systematic conformity between radiological and histopathology findings, confirmed high diagnostic accuracy of MRI for selected pancreatic pathology, and demonstrated the role of MRI as a problem solving diagnostic imaging modality in undetermined pancreatic changes.

[Diagnostic imaging in assessment of rheumatic diseases]. / Radioloske metode u oslikavanju reumatskih bolesnika.

Rheumatic diseases represent one of the most common health problems for which patients visit the doctor. This fact imposes the need for verification of clinical symptoms and clear presentation ofpathomorphyology changes primarily because of the best methods of treatment selection. A wide range of diagnostic imaging modalities are available today: conventional radiography, conventional myelography, computed tomography (CT), CT myelography, magnetic resonance imaging (MRI), MR or CT artrography, spinal cord angiography, ultrasound and scintigraphy, and combined radiological methods and scintigraphy (PET-CT). Each of the above methods has its own importance, advantages and limitations. Sometimes a method excludes the other, and often support each another in setting the final diagnosis. For the proper choice of radiological imaging methods that will give us insight into the problem, a good knowledge of their capabilities, and a clear clinical inquiry are necessary. But most of all, good cooperation of clinicians and radiologists who should be diagnostic team responsible for that sets the indication for radiological examination is essential.