COMPARISON OF TRANSCRANIAL AND TRANSSPHENOIDAL APPROACHES IN INTRA AND SUPRASELLAR PITUITARY ADENOMAS - SYSTEMATIC REVIEW.

Context: Pituitary adenomas are benign tumors, usually found in men in their 3rd and 5th decades of life, representing 10-15% of all intracranial tumors. The clinical manifestations include important endocrinological disturbances and visual impairment. Objective: This study aimed to determine the most suitable neurosurgical approach regarding the dimensions, extensions and invasiveness of tumor extensions. Design: This was a systematic review of the literature from 2002-2022, focused on clinical outcome, especially endocrinological state according to the surgical approach. Subjects and Methods: We performed an advanced search on Web of Science and PubMed databases on October 10th, 2022. The literature showed 300 studies in the last 20 years, and after we applied the inclusion and exclusion criteria's, 19 studies were fully read and analyzed. Results: Postoperative complications were reviewed in each surgical approach group, including visual impairment, new endocrinological disturbances, diabetes insipidus and cerebrospinal fluid leakage. Analyze of the endocrinological findings did not determined differences in transcranial groups from transsphenoidal groups. Overall complications were identified in the transcranial cohorts, while cerebrospinal fluid leakage still represent the main problem in transsphenoidal groups. The majority of studies found included extended endoscopic transsphenoidal approach, which shows results of great potential. Conclusions: For the surgical treatment of pituitary adenoma, transsphenoidal procedure with or without extended approaches is preferred, but they're cases when a craniotomy is mandatory for a feasible gross tumor resection. Combined "above and below" simultaneous procedure or a two-staged intervention is recommended for giant pituitary adenoma, to maximize tumor resection and lower the risk of cerebrospinal fluid leakage.

Centenary of Insulin Discovery (1921-2021): Nicolae Paulescu's Original Contributions.

Nicolae Paulescu (1869-1930) was born in Bucharest in an aristocratic family. His education from childhood to maturity (Paris University of Medicine) was marked by illustrious professors, even pioneers of their field. After completing his medical and scientific education in Paris under his mentor, Etienne Lancereaux, considered the founder of modern physiology, he returned to Romania where he founded the first Department of Physiology at "Carol Davila" University of Medicine and Pharmacy. His scientific career is marked by the publishing of 88 original research articles in renown international medical journals of the time and two Treatise on Physiology (comprising in total 8 volumes and 5976 pages). His activity as an endocrinologist reaches the peak with the discovery of insulin with the article Recherche sur le rôle du pancréas dans l'assimilation nutritive published in the Archives Internationales de Physiologie (Liege, Belgium) on August 31st, 1921. While he was not internationally or even nationally acclaimed for the discovery of insulin, his contribution to the reformation of the national education and medical system and the recommendation of his students to pioneers of their fields of interest still have reverberations even today.

Relationship between preterm birth and post-partum periodontal maternal status: a hospital-based Romanian study.

PURPOSE: This cross-sectional case-control study of post-partum women aimed to estimate whether maternal periodontitis was a predictive contributor to preterm birth and to identify other risk factors associated with preterm birth in our target population. METHODS: The case group included women who delivered preterm (74 cases) and the control group included women who had a normal term delivery (120 controls). Medical records, a 16-item questionnaire, and a full-mouth periodontal examination were used to collect information about socio-demographic characteristics, general health problems, birth-related information, behavioral factors and periodontal status. Logistic regression analysis was used to estimate the strength of the relationship between predictors and the categorical outcome variable, preterm birth. RESULTS: The bivariate analysis revealed the significant associations between preterm birth and socio-demographic factors (educational level, p = 0.003), antepartum smoking habit (p = 0.001) and birth weight lower than 2500 g (p < 0.001). The multivariate analysis highlighted that the presence of post-partum maternal periodontitis and its severity remained independent risk factors of preterm birth in the presence of antepartum smoking habit and route of delivery [adjusted OR 2.26, 95% CI (1.06; 4.82), respectively, OR 3.46, 95% CI (1.08; 11.15)]. CONCLUSION: Post-partum maternal periodontal disease and its severity might, in part, be considered as contributor to preterm deliveries before 37 weeks of gestation.

Craniopharyngiomas in children - experience of consecutive 152 operated cases.

CONTEXT: Craniopharyngiomas (CPH) are benign tumors, rarely encountered in children, representing 5-6% of all intracranial tumors. OBJECTIVE: This study aimed to analyze the surgical management and quality of life in a series of CPH pediatric cases. DESIGN: This was a multicenter study performed over a 25-year period (1994 - 2019) in Bucharest. SUBJECTS AND METHODS: 152 children (0-17 years old) were treated for CPH. Preoperative manifestations were intracranial hypertension, endocrine dysfunction, visual impairment, ataxia, intellectual performance decrease. RESULTS: Considering all surgical approaches used, we advocate for pterional approach to best fit in CPH. We achieved gross-total removal (GTR) in 83 cases (54.4%), near-total resection (NTR) in 13 cases (9%), partial resection (PTR) in 51 cases (33.3%). 5 cases were biopsies (3.2%). Gamma Knife Surgery was performed in 10 cases (6.5%), all recurrences. At 6 months GOS revealed: Good Recovery 70 cases (46.2%), Moderate Disability 62 cases (40.7%), Severe Disability 13 (8.5%), Vegetative State 2 cases (1.3%), Deceased 5 cases (3.2%). Complications were: diabetes insipidus (89.3%); hypopituitarism (66.4%); hypothalamic damage (17.7%); visual deterioration (18.4%). CONCLUSIONS: Surgery remains the main option, but GTR complications prove the necessity for a multidisciplinary approach. Outcome predicting factors are: age, tumor size, hydrocephalus degree, hypothalamic dysfunction.

Surgical Difficulties in a Case of Left Ophthalmic Artery Ruptured Aneurysm Associated with Right ICA hypoplasia - Case Report.

The authors present a rare case of a ruptured left ophthalmic artery aneurysm associated with right ICA hypoplasia in a 49 year old female. The particularity of the case lies in the fact that the patient had a hypoplastic right ICA which was associated with an intracranial aneurysm. In this case we present,surgery was mandatory as it represented the patient'€™s only chance for a favorable outcome, given the lack of an adequate team specialized in endovascular coiling. Unlike many neurosurgical centers in Western Europe and the US where endovascular approaches have overtaken microsurgery, in Romania open microsurgery is frequently performed as it allows neurosurgeons to perfectly control the environment in which they operate and minimizes possible complications of coiling or stenting which become more and more frequent in other countries.

Multidisciplinary management of adult low grade gliomas.

BACKGROUND: Adult hemispheric low grade gliomas (LGG) cover a pathologic spectrum which has specific clinical, histological and molecular characteristics. The optimal management of these tumors is still a controversial topic in international literature. METHODS: We evaluated scientific papers from the literature (Medline and Cochrane Library to date) and we compared the results found there with our experience, trying to create a pattern of treatment of our own. RESULTS AND CONCLUSIONS: The advances in microsurgical and neuromonitoring techniques, as well as in neuroimaging, allow for a more aggressive resection of LGG with a significant improvement in overall survival and quality of life. The potential risks of the "wait and see" policy and the neurotoxicity of radiotherapy are challenged by the benefits of careful surgical resection and up-front chemotherapy. The present day treatment strategy, based on recent evidence, should include a maximal surgical resection when possible, with the full preservation of the patients ability, and delayed radiotherapy. The role of temozolomide in the management of LGG and the identification of the therapeutic modality with the best quality of life profile will be determined by ongoing trials. The further characterization of prognostic relevance of molecular markers and data from advanced imaging techniques needs an intensification of research and validation efforts. ABBREVIATIONS: LGG: low grade gliomas, WHO: World Health Organization, OS: overall survival, PFS: progression-free survival, MRI: Magnetic resonance imaging, MRS: Magnetic resonance spectroscopy, MPFS: malignant progression-free survival, rCBV: Relative Cerebral Blood Volume, QOL: quality of life, FLAIR: Fluid attenuated inversion recovery, MGMT: O6-methylguanine DNA methyltransferase enzyme, DSC MR imaging: Dynamic Susceptibility Contrast Perfusion MR imaging, 1H-MRS: Proton Magnetic Resonance Spectroscopy, IDH1: isocitrate dehydrogenase 1 gene, SPECT: Single-photon emission computed tomography, PET: Positron emission tomography, DTI-FT: Diffuse Tensor Imaging-fiber tracking technique, DES: direct electrical stimulation, EEG: Electroencephalography, EcoG: Electrocorticography, MEP: motor evoked potentials, EMG: Electromyography, AED: anti-epileptic drugs, TMZ: Temozolomide, EORTC: European Organization for Research and Treatment of Cancer, NCCTG: North Central Cancer Treatment Group, RTOG: Radiation Therapy Oncology Group, ECOG: Eastern Cooperative Oncology Group, EOR: extent of resection, Gy: Gray (unit), GyE: gray equivalent, RT: radiation therapy, IMRT: image-guided intensity modulated radiotherapy, FSRT: fractionated stereotactic radiotherapy, SRS: proton therapy or stereotactic radiosurgery, LET: high-linear energy transfer beams, RBE: relative biological effectiveness, CTCAE: Common Terminology Criteria for Adverse Events, PCV: procarbazine, lomustine, and vincristine chemotherapy.

A modern minimally invasive transcallosal approach to the third ventricle. A personal experience of 30 patients.

INTRODUCTION: Expansive processes around the third ventricle have always been a major neurosurgical challenge. Despite all the technological and scientific progress recorded over the last few years, third ventricle tumors are still a very difficult pathology to approach due to their formidable complexity.Treating such a tumor demands a good knowledge of local anatomy, pathophysiology, pathology and a good capacity to integrate all the data gathered from the patient prior to and during surgery. Last but not least, the correct means to approach such a tumor involves using modern neuronavigation technology which might be too expensive to access in certain clinics (1,2). OBJECTIVE: This article presents the personal experience of the authors, gathered while using a novel surgical approach,configured to maximize the success rate of interventions for tumors within the third ventricle, without using neuronavigation technology. MATERIALS AND METHODS: The authors have developed a study of neuroanatomy using 30 adult human brains, without any pathological lesions, harvested during routine autopsies and analysed using a a standard protocol (Protocol of the Ludwig-Maximilians University Clinic of Neurosurgery, Laboratory of Microanatomy - Munich, Germany). The authors assessed a series of anatomic elements which were later used as landmarks to build the neurosurgical operative field. After completing the anatomic study the authors moved on to record morphometric data for 30 volunteers. The authors used sagittal T1 weighted images. The volunteers were males and females, all adults, with the mean age of 45.3 years. (The age interval: 21-83 years, sex distribution: 17 males and 13 females). The images were digitally enhanced and the specific targets were outlined using Corel Draw, thus allowing for a systematic identification of contours and landmarks. Each contour was recorded and saved as a sequence of dots. The next stage of the study, after having studied all the data recorded, consisted of establishing the appropriate transcallosal surgical corridor (transforaminal or inter forniceal) for each of the 30 patients (not to be mistaken with the 30 volunteers)who were admitted for third ventricle tumors and who were included in this study. After having performed surgery for there section of the above mentioned third ventricle tumors, the authors observed pre- and postoperative clinical data which were corroborated with the neuropsychological examination which was also performed prior to and after surgery. CONCLUSIONS: The results obtained through observation and anatomical measurements have proven to be highly valuable in determining a standard access corridor through the corpuscallosum. The data gathered and the patient's MRI exam images helped obtain an optimal surgical corridor of the third ventricle. In what regards the surgical act in 23 cases (77%) the authors managed to achieve a complete resection of the tumor.In 6 cases (20%) the authors managed a subtotal resection of the tumors. In a single case the authors performed only a biopsy. A number of 24 patients (80%) achieved an excellent outcome (Glasgow Outcome Scale - GOS V). Minor deficits were recorded in 5 patients (17%) (disabled but independent)(GOS IV) No cases were recorded with serious impairment(GOS III) or vegetative state (GOS II). One patient with anaplastic glioma died 4 months after surgery after an initial favorable evolution. The tumor had spread to the hypothalamus. A single postoperative complication was linked to the surgical approach in a 73-year-old female patient who suffered a venous infarction due to a venous thrombosis in atributary vein of the superior sagittal sinus in the access area.The patient, after a slow recovery managed to improve her condition reaching GOS IV. There were no other complications connected to the surgical act.

Treatment overview of axial spondyloarthritis in 2023.

The treatment of patients with axial spondyloarthritis (axSpA) is characterized by non-pharmacological and pharmacological treatment options. It may depend on the type and extent of musculoskeletal and extramusculoskeletal manifestations. Recent data on non-pharmacological treatment options, such as physical activity, physiotherapy, and modification of lifestyle factors, are summarized in this review. Moreover, we have provided an overview on non-steroidal anti-inflammatory drugs and the ever-expanding number of biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs, respectively). In addition to data on efficacy and safety, the review also encompasses data on switching/cycling, tapering, and treatment selection for specific patient subgroups to optimize treatment outcomes.

On the feasibility of using motor imagery EEG-based brain-computer interface in chronic tetraplegics for assistive robotic arm control: a clinical test and long-term post-trial follow-up.

STUDY DESIGN: Survey and long-term clinical post-trial follow-up (interviews/correspondence) on nine chronic, post spinal cord injury (SCI) tetraplegics. OBJECTIVE: To assess feasibility of the use of Electroencephalography-based Brain-Computer Interface (EEG-BCI) for reaching/grasping assistance in tetraplegics, through a robotic arm. SETTINGS: Physical and (neuromuscular) Rehabilitation Medicine, Cardiology, Neurosurgery Clinic Divisions of TEHBA and UMPCD, in collaboration with 'Brain2Robot' (composed of the European Commission-funded Marie Curie Excellence Team by the same name, hosted by Fraunhofer Institute-FIRST), in the second part of 2008. METHODS: Enrolled patients underwent EEG-BCI preliminary training and robot control sessions. Statistics entailed multiple linear regressions and cluster analysis. A follow-up-custom questionnaire based-including patients' perception of their EEG-BCI control capacity was continued up to 14 months after initial experiments. RESULTS: EEG-BCI performance/calibration-phase classification accuracy averaged 81.0%; feedback training sessions averaged 70.5% accuracy for 7 subjects who completed at least one feedback training session; 7 (77.7%) of 9 subjects reported having felt control of the cursor; and 3 (33.3%) subjects felt that they were also controlling the robot through their movement imagination. No significant side effects occurred. BCI performance was positively correlated with beta (13-30 Hz) EEG spectral power density (coefficient 0.432, standardized coefficient 0.745, P-value=0.025); another possible influence was sensory AIS score (range: 0 min to 224 max, coefficient -0.177, standardized coefficient -0.512, P=0.089). CONCLUSION: Limited but real potential for self-assistance in chronic tetraplegics by EEG-BCI-actuated mechatronic devices was found, which was mainly related to spectral density in the beta range positively (increasing therewith) and to AIS sensory score negatively.

CD4+ T-cell-epitope escape mutant virus selected in vivo.

Mutations in viral genomes that affect T-cell-receptor recognition by CD8+ cytotoxic T lymphocytes have been shown to allow viral evasion from immune surveillance during persistent viral infections. Although CD4+ T-helper cells are crucially involved in the maintenance of effective cytotoxic T-lymphocyte and neutralizing-antibody responses, their role in viral clearance and therefore in imposing similar selective pressures on the virus is unclear. We show here that transgenic virus-specific CD4+ Tcells, transferred into mice persistently infected with lymphocytic choriomeningitis virus, select for T-helper epitope mutant viruses that are not recognized. Together with the observed antigenic variation of the same T-helper epitope during polyclonal CD4+ T-cell responses in infected pore-forming protein-deficient C57BL/6 mice, this finding indicates that viral escape from CD4+ T lymphocytes is a possible mechanism of virus persistence.

The influence of technical factors on sonoelastographic assessment of solid breast nodules.

PURPOSE: The aim of the study was to assess the influence of technical factors and/or lesion characteristics on the final elastographic score in solid breast nodules. MATERIALS AND METHODS: Patients with solid breast masses examined between May 2007 and May 2008 in the Radiology Department of Cluj District University Hospital were included in the study. All lesions were examined with conventional ultrasound, Doppler ultrasound and sonoelastography, according to a preset protocol. The influence of the following factors on the elastographic score was evaluated: type of section (sagittal versus transverse); size of region of interest (small versus large); amplitude and frequency of movement; initial compression (light versus strong); angulation (perpendicular versus angulated transducer); characteristics of the lesion (size and location). The reference diagnosis was the histopathology diagnosis and, in twenty cases, short-term follow-up. RESULTS: Ninety-two patients with a mean age of 48.11 years and 101 breast nodules were included in the study. The overall sensitivity and specificity for elastography were 79 % [68-88 %] and 79 % [65 - 89 %], respectively, with a negative predictive value of 74 % [60-85 %] and a positive predictive value of 84 % [72-91 %]. The following factors did not influence the elastographic score: type of section (scores on transverse and longitudinal section, Z = -0.641, p = 0.552); the amplitude and frequency of movements during the elastographic examination (Cochran's Q concordance = 0.706, p = 0.872); strong initial compression in the case of benign nodules (Z = 0.000, p = 1.000); size of the lesions. Of the elastographically benign nodules, 9 were false negative and of the 46 elastographically malignant nodules, 12 were false positive. The following factors influenced the elastographic scores: size of the region of interest (the scores were significantly different when small or large region of interest was used, Z = -0.671, p < 0.0001); transducer angulation (Z = -5.42, p < 0.0001); strong initial compression in the case of malignant nodules (Z = -6.044, p < 0.0001) and the location of the mass in the vicinity of the chest wall. CONCLUSION: The most important factors that influence the final elastographic score, leading to false negative results, are the size of the region of interest, the initial compression and angulation of the transducer, while the frequency and amplitude of movement during the examination proved to be of no importance as long as the images were obtained within a range of assessment usefulness. Changing the scanning parameters never led to false positive results in the case of malignant breast masses.

[Web-based learning in musculoskeletal ultrasound]. / Webbasiertes Lernen in der Sonographie des Bewegungsapparates.

Education and training in musculoskeletal ultrasound (MSUS) comprises attendance at theoretical and practical courses and independent study. Web-based learning as a novel teaching method has previously been described. The present study summarizes normal and pathological findings in a web-based approach using widely accepted guidelines. In a prospective study over a period of 3 years normal and pathological images of the musculoskeletal system have been documented and catalogued. Overall 1240 ultrasound images and 183 ultrasound videos were collected. A total of 14.4% were normal and 85.6% were pathological MSUS findings; 61% concerned the upper extremity, while 39% were images and videos of the lower limbs. The most captured conditions included synovitis (33.3%), pathologies of the tendons e.g., tenosynovitis or tendinosis (19.6%) and normal findings (14.4%). The most represented diseases were rheumatoid arthritis (20%), calcium deposition disease (8.2%), gout (7.1%) and osteoarthritis (6.9%). The images and videos were edited and integrated in a web-based tool.

[Paralysis of the oculomotor nerve caused by aneurysm--general facts and a case report]. / Paralizia nervului oculomotorde cauza anevrismala--date generale. Prezentare de caz clinic.

One of the most frequent etiology of oculomotor nerve palsy are intracerebral aneurysms. Due to anatomical facts (its course and main relations with vascular structures of the brain) lesions of the oculomotor nerve often occur. In this paper there are presented essential issues concerning neuroanatomy of the III-rd cranial nerve pair main locations of the cerebral aneurysms in order to investigate the effect of nerve compression, clinical data regarding the palsy of the oculomotor nerve due to a cerebral aneurysm, the treatment and post surgery recovery followed by a clinical report.

Impairment of CD4(+) T cell responses during chronic virus infection prevents neutralizing antibody responses against virus escape mutants.

We have shown previously that neutralizing antibodies (nAbs) are important contributors to the long-term immune control of lymphocytic choriomeningitis virus infection, particularly if cytotoxic T cell responses are low or absent. Nevertheless, virus escape from the nAb response due to mutations within the surface glycoprotein gene may subsequently allow the virus to persist. Here we show that most of the antibody-escape viral mutants retain their immunogenicity. We present evidence that the failure of the infected host to mount effective humoral responses against emerging neutralization-escape mutants correlates with the rapid loss of CD4(+) T cell responsiveness during the establishment of viral persistence. Similar mechanisms may contribute to the persistence of some human pathogens such as hepatitis B and C viruses, and human immunodeficiency virus.

Which subgroup of patients with rheumatoid arthritis benefits from switching to rituximab versus alternative anti-tumour necrosis factor (TNF) agents after previous failure of an anti-TNF agent?

BACKGROUND: Patients with rheumatoid arthritis (RA) with an inadequate response to TNF antagonists (aTNFs) may switch to an alternative aTNF or start treatment from a different class of drugs, such as rituximab (RTX). It remains unclear in which clinical settings these therapeutic strategies offer most benefit. OBJECTIVE: To analyse the effectiveness of RTX versus alternative aTNFs on RA disease activity in different subgroups of patients. METHODS: A prospective cohort study of patients with RA who discontinued at least one aTNF and subsequently received either RTX or an alternative aTNF, nested within the Swiss RA registry (SCQM-RA) was carried out. The primary outcome, longitudinal improvement in 28-joint count Disease Activity Score (DAS28), was analysed using multivariate regression models for longitudinal data and adjusted for potential confounders. RESULTS: Of the 318 patients with RA included; 155 received RTX and 163 received an alternative aTNF. The relative benefit of RTX varied with the type of prior aTNF failure: when the motive for switching was ineffectiveness to previous aTNFs, the longitudinal improvement in DAS28 was significantly better with RTX than with an alternative aTNF (p = 0.03; at 6 months, -1.34 (95% CI -1.54 to -1.15) vs -0.93 (95% CI -1.28 to -0.59), respectively). When the motive for switching was other causes, the longitudinal improvement in DAS28 was similar for RTX and alternative aTNFs (p = 0.40). These results were not significantly modified by the number of previous aTNF failures, the type of aTNF switches, or the presence of co-treatment with a disease-modifying antirheumatic drug. CONCLUSION: This observational study suggests that in patients with RA who have stopped a previous aTNF treatment because of ineffectiveness changing to RTX is more effective than switching to an alternative aTNF.

Infiltrating growing pattern xenografts induced by glioblastoma and anaplastic astrocytoma derived tumor stem cells.

OBJECTIVE: The number of evidences regarding the role of tumor stem cells (TSC) in the initiation and progression of high-grade astrocytomas became more and more numerous in the last years. This issue has been intensively tested in glioblastoma, but little attention has been paid for anaplastic astrocytoma. The main objective of this paper was to study the morphological characteristics of the xenografts developed from glioblastoma and anaplastic astrocytoma derived cancer stem cells. METHODS: The authors of this study successfully isolated and partial characterized primary cultures of glioblastoma and anaplastic astrocytoma derived TSC. Tumors stem cells have been stereotactically inoculated in nude mice brains and the xenografts have been studied using morphological and imunohistochemistry techniques. RESULTS: The tumor xenografts which have been established in nude mice using TSC had different characteristics when compared with U87 xenografts previously developed by our group, and depend of the origin type of the tumors (glioblastoma versus anaplastic astrocytoma). The diffuse growing pattern and cells infiltration have been more pronounced in both anaplastic astrocytoma and glioblastoma derived TSC xenografts compared with U87 line xenografts. CONCLUSION: Our results support the hypothesis regarding the role of TSC in the infiltration process of glioblastoma and anaplastic astrocytoma. The extensive infiltration growing patterns of these types of xenografts make them useful models for studying the invasion mechanisms in gliomas.

Comparative effectiveness of antitumour necrosis factor agents, biologics with an alternative mode of action and tofacitinib in an observational cohort of patients with rheumatoid arthritis in Switzerland.

BACKGROUND: Multiple biologic and targeted synthetic disease-modifying rheumatic drugs (b/tsDMARDs) are approved for the management of rheumatoid arthritis (RA), including TNF inhibitors (TNFi), bDMARDs with other modes of action (bDMARD-OMA) and Janus kinase inhibitors (JAKi). Combination of b/tsDMARDs with conventional synthetic DMARDs (csDMARDs) is recommended, yet monotherapy is common in practice. OBJECTIVE: To compare drug maintenance and clinical effectiveness of three alternative treatment options for RA management. METHODS: This observational cohort study was nested within the Swiss RA Registry. TNFi, bDMARD-OMA (abatacept or anti-IL6 agents) or the JAKi tofacitinib (Tofa) initiated in adult RA patients were included. The primary outcome was overall drug retention. We further analysed secondary effectiveness outcomes and whether concomitant csDMARDs modified effectiveness, adjusting for potential confounding factors. RESULTS: 4023 treatment courses of 2600 patients were included, 1862 on TNFi, 1355 on bDMARD-OMA and 806 on Tofa. TNFi was more frequently used as a first b/tsDMARDs, at a younger age and with shorter disease duration. Overall drug maintenance was significantly lower with TNFi compared with Tofa [HR 1.29 (95% CI 1.14 to 1.47)], but similar between bDMARD-OMA and Tofa [HR 1.09 (95% CI 0.96 to 1.24)]. TNFi maintenance was decreased when prescribed without concomitant csDMARDs [HR: 1.27 (95% CI 1.08 to 1.49)], while no difference was observed for bDMARD-OMA or Tofa maintenance with respect to concomitant csDMARDs. CONCLUSION: Tofa drug maintenance was comparable with bDMARDs-OMA and somewhat higher than TNFi. Concomitant csDMARDs appear to be required for optimal effectiveness of TNFi, but not for bDMARD-OMA or Tofa.

Long-term immunogenicity after yellow fever vaccination in immunosuppressed and healthy individuals.

BACKGROUND: The live-attenuated yellow fever vaccine (YFV) is generally contraindicated in immunosuppressed patients. Our aim was to investigate if immunosuppressive therapy impairs the long-term protection against yellow fever virus in patients who had received YFV prior to the start of their immunosuppressive therapy. METHODS: Our study examined 35 healthy individuals and 40 immunosuppressed patients with autoimmune diseases or organ transplants. All individuals had received YFV prior to the onset of their immunosuppression. We analysed the long-term influence of the immunosuppressive therapy on the YFV protective immunity by measuring neutralising antibodies (NA) with the Plaque Reduction Neutralisation Test (PRNT). We assessed risk factors for a negative PRNT result (titre below 1: 10) and their influence on the magnitude of the NA. RESULTS: A median time interval of 21.1 years (interquartile range 14.4-31.3 years) after the YFV in all patients, a total of 35 immunosuppressed patients (88%) were seropositive (PRNT ≥ 1:10) compared to 31 patients (89%) in the control group. The geometric mean titres of NA did not differ between the groups. The duration of an underlying rheumatic disease was the only risk factor found for a lower magnitude of NA. An insufficient level of NA was found in nine subjects (12%) who had received a single dose of YFV (in one subject, the number of YFV doses was unknown). CONCLUSION: The use of an immunosuppressive drug started after the administration of the YFV did not affect long-term persistence of NA. A second dose of YFV may be necessary to secure long-term immunity.

A review of published reports on neuroprotection in spinal cord injury.

STUDY DESIGN: Literature review. OBJECTIVES: To review the main published current neuroprotection research trends and results in spinal cord injury (SCI). SETTING: This paper is the result of a collaboration between a group of European scientists. METHODS: Recent studies, especially in genetic, immune, histochemical and bio (nano)-technological fields, have provided new insight into the cellular and molecular mechanisms occurring within the central nervous system (NS), including SCIs. As a consequence, a new spectrum of therapies aiming to antagonize the 'secondary injury' pathways (that is, to provide neuroprotection) and also to repair such classically irreparable structures is emerging. We reviewed the most significant published works related to such novel, but not yet entirely validated, clinical practice therapies. RESULTS: There have been identified many molecules, primarily expressed by heterogenous glial and neural subpopulations of cells, which are directly or indirectly critical for tissue damaging/sparing/re-growth inhibiting, angiogenesis and neural plasticity, and also various substances/energy vectors with regenerative properties, such as MAG (myelin-associated glycoprotein), Omgp (oligodendrocyte myelin glycoprotein), KDI (synthetic: Lysine-Asparagine-Isoleucine 'gamma-1 of Laminin Kainat Domain'), Nogo (Neurite outgrowth inhibitor), NgR (Nogo protein Receptor), the Rho signaling pathway (superfamily of 'Rho-dopsin gene-including neurotransmitter-receptors'), EphA4 (Ephrine), GFAP (Glial Fibrillary Acidic Protein), different subtypes of serotonergic and glutamatergic receptors, antigens, antibodies, immune modulators, adhesion molecules, scavengers, neurotrophic factors, enzymes, hormones, collagen scar inhibitors, remyelinating agents and neurogenetic/plasticity inducers, all aiming to preserve/re-establish the morphology and functional connections across the lesion site. Accordingly, modern research and experimental SCI therapies focus on several intricate, rather overlapping, therapeutic objectives and means, such as neuroprotective, neurotrophic, neurorestorative, neuroreparative, neuroregenerative, neuro(re)constructive and neurogenetic interventions. CONCLUSION: The first three of these therapeutical directions are generically assimilated as neuroprotective, and are synthetically presented and commented in this paper in an attempt to conceptually systematize them; thus, the aim of this article is, by emphasizing the state-of-the art in the domain, to optimize theoretical support in selecting the most effective pharmacological and physical interventions for preventing, as much as possible, paralysis, and for maximizing recovery chances after SCI.