Do patients' and referral centers' characteristics influence multiple sclerosis phenotypes? Results from the Italian multiple sclerosis and related disorders register.

BACKGROUND: Multiple sclerosis (MS) is characterized by phenotypical heterogeneity, partly resulting from demographic and environmental risk factors. Socio-economic factors and the characteristics of local MS facilities might also play a part. METHODS: This study included patients with a confirmed MS diagnosis enrolled in the Italian MS and Related Disorders Register in 2000-2021. Patients at first visit were classified as having a clinically isolated syndrome (CIS), relapsing-remitting (RR), primary progressive (PP), progressive-relapsing (PR), or secondary progressive MS (SP). Demographic and clinical characteristics were analyzed, with centers' characteristics, geographic macro-areas, and Deprivation Index. We computed the odds ratios (OR) for CIS, PP/PR, and SP phenotypes, compared to the RR, using multivariate, multinomial, mixed effects logistic regression models. RESULTS: In all 35,243 patients from 106 centers were included. The OR of presenting more advanced MS phenotypes than the RR phenotype at first visit significantly diminished in relation to calendar period. Females were at a significantly lower risk of a PP/PR or SP phenotype. Older age was associated with CIS, PP/PR, and SP. The risk of a longer interval between disease onset and first visit was lower for the CIS phenotype, but higher for PP/PR and SP. The probability of SP at first visit was greater in the South of Italy. DISCUSSION: Differences in the phenotype of MS patients first seen in Italian centers can be only partly explained by differences in the centers' characteristics. The demographic and socio-economic characteristics of MS patients seem to be the main determinants of the phenotypes at first referral.

May chronic cough in chronic obstructive pulmonary disease be a contraindication of Percutaneous Endoscopic Gastrostomy placement: a case report.

BACKGROUND: Percutaneous Endoscopic Gastrostomy (PEG) can involve some complications, despite the good safety of its track record. The Buried Bumper Syndrome (BBS) is a rare, late and dangerous complication that consists in the erosion of the internal bumper through the gastric wall. Case presentation We report the development of BBS in a man with chronic obstructive pulmonary disease (COPD) who had a persistent chronic cough which was prevalently but not solely in the morning and required placement of a PEG tube for continuous infusion of Levodopa/carbidopa intestinal gel for advanced Parkinson's disease. CONCLUSION: We believe that COPD with chronic cough while not representing an absolute contraindication to PEG placement, may potentially cause BBS and therefore an appropriate regimen of tube care by expert personnel is mandatory in this setting.

The prevalence of sleep impairments and predictors of sleep quality among patients with asthma.

BACKGROUND: Sleep is a significant dimension of daily life. However, only a few studies have examined the sleep quality of asthmatics in a real-world clinical settings. OBJECTIVE: This study is aimed to estimate the prevalence of sleep impairments among asthmatic patients and examine the relationship between sleep quality, asthma control, rhinitis symptoms, and sociodemographic characteristics. METHODS: The present study adopted the observational cross-sectional research design that has been designed by the Italian Respiratory Society and used valid assessments to measure the study variables. RESULTS: Data from 1150 asthmatic patients (mean age 51.01 years ± 16.03) were subjected to analysis. 58.3% of the patients had impaired sleep quality (Pittsburgh Sleep Quality Index [PSQI] total scores > 5), and their mean PSQI score was 5.68 (SD = 3.4). A significant correlation emerged between sleep quality and asthma control (p = 0.0001) and a significant albeit weak correlation emerged between PSQI total scores and Total 5 Symptoms Score (r = 0.24, p = 0.0001). Sleep quality was significantly associated health-related quality of life [HRQoL]. (r = 0.50, p < 0.001). After exclusion of patients at risk for Obstructive Sleep Apnea Syndrome (OSAS) and Gastro Esophageal Reflux Disease (GERD), the most important determinants of PSQI score were HRQoL, In the entire sample asthma control is the strongest predictor of both sleep quality and HRQoL. CONCLUSIONS: The results of this real-world study highlight the prevalence, impact and predictors of sleep disturbances in asthmatic patients and suggest the need for physicians to detect poor sleep quality.

Clinical characterization of gingival type of burning mouth syndrome: a cross-sectional study.

BACKGROUND: The aim of this study is to investigate the prevalence of localized intraoral neuropathic pain in a cluster of patients who reported the involvement of gingival site as only clinical manifestation of dysesthesia, analysing type and distribution of symptoms. MATERIAL AND METHODS: Burning mouth syndrome (BMS) patients were enrolled in the study. Patients were screened through laboratory test and a conventional oral examination with periodontal chart. A questionnaire to collect data on symptoms, oral site involved, quality of sleep, anxiety was submitted to all the patients. RESULTS: A total of 236 patients were recruited. Seventy-six patients (32.2%) presented generalized type, whereas 160 (67.8%) had localized type. In the localized BMS group, the gingiva was involved in 70 patients and in 33 of these it was the only site involved. In the gingival subgroup, 35 patients reported burning, 29 pain and 24 xerostomia. CONCLUSIONS: To best our knowledge, this study is the first that analyses gingival involvement as the only site in BMS and it could encourage further investigations to understand the etiopathogenesis of gingival BMS.

Efficacy and safety of the first-in-class imidazoline-2 receptor ligand CR4056 in pain from knee osteoarthritis and disease phenotypes: a randomized, double-blind, placebo-controlled phase 2 trial.

OBJECTIVE: CR4056 is a selective imidazoline-2 (I2) receptor ligand with potent analgesic activity in animal pain models. This proof-of-concept study tested CR4056 efficacy and safety in patients with knee osteoarthritis (OA) and different phenotypes. DESIGN: This is a multicenter, randomized, double-blind, placebo-controlled trial. Knee OA patients with moderate to severe pain received CR4056 (women 100 mg bid; men 200 mg bid) or placebo (both genders) for 14 days. The primary outcome was the change in WOMAC pain score (0-100 scale) compared to placebo, analyzed in the intention-to-treat population and pre-defined OA phenotypes. RESULTS: 213 patients were treated with CR4056 (92 women; 52 men) or placebo (69 overall). After 14 days, median WOMAC pain improvements were 10 points on placebo and 14, 20 and 16 in women, men, and pooled CR4056 groups (P = 0.184, 0.030 and 0.070 vs placebo, respectively). Pre-specified subgroup analysis in the metabolic OA phenotype (BMI ≥ 27.5 kg/m2, N = 156) showed statistically significant differences in all CR4056-treated groups vs placebo of 12-18 points. Conversely, there were too few patients with a neuropathic or inflammatory phenotype for a meaningful analysis. CR4056 was well tolerated; the most common adverse event was mild headache. CONCLUSIONS: Although the primary endpoint was met in males only, this exploratory phase 2 trial shows that CR4056 might be an effective analgesic against knee OA pain, especially in overweight patients representing the metabolic OA phenotype. These findings, along with the broad-spectrum analgesic activity of CR4056 in animal models, warrant further clinical investigation in OA and other pain conditions. CLINICAL TRIAL REGISTRATION NUMBER: EudraCT 2015-001136-37.

Subclinical motor impairment assessed with an engineered glove correlates with magnetic resonance imaging tissue damage in radiologically isolated syndrome.

BACKGROUND: An engineered glove measuring finger motor performance previously showed ability to discriminate early-stage multiple sclerosis (MS) patients from healthy controls (HCs). Radiologically isolated syndrome (RIS) classifies asymptomatic subjects with brain magnetic resonance imaging (MRI) abnormalities suggestive of multiple sclerosis. METHODS: Seventeen asymptomatic subjects with RIS and 17 HCs were assessed. They performed finger-to-thumb opposition sequences at their maximal velocity, metronome-paced bimanual movements and conventional and diffusion tensor MRI. RESULTS: Subjects with RIS showed lower (P = 0.005) maximal velocity and higher (P = 0.006) bimanual coordination impairment than HCs. In RIS, bimanual coordination correlated with T2-lesion volume, fractional anisotropy and radial diffusivity in the white matter. CONCLUSIONS: These findings point out the relevance of fine hand measures as a robust marker of subclinical disability.

Allergy in adolescent population (14-18 years) living in Campania region (Southern Italy). A multicenter study.

Summary: Adolescents (Ad) constitute a difficult to manage population among individuals suffering from asthma. The aim of our study was to assess the prevalence, clinical characteristics and age of onset of allergic sensitization and clinical symptoms in a sample of atopic Ad living in the Campania region (Southern Italy). Sixteen Allergy units or Centers belonging to the Italian Association of Hospital and Territorial Allergologists (AAIITO, Campania region) participated in this cross-sectional study. A case report form (CRF) was specifically designed for this study and commercial allergen extracts used for screening SPTs were provided by ALK-Abelló Group (Milan, Italy). A total of 443 patients were examined (females, f 220, 49.6 %; males, m 223, 50.3%). Dust mites represent the most common sensitizing agents in allergic Ad living in Campania region (Dermatoph. pteronyssinus 67.4% and Dermatoph. farinae 66.5%), followed by Parietaria (58.9%), grasses (45.8%), Artemisia vulgaris (16.7%), Olea Europaea (32.2%), dog dander (17.1%), cat dander (20.0%), Alternaria alternata (8.1%), Cupressus sempervirens (4.9%), Betula pendula (4.7%), other allergens (19.4%). An interesting comparison has been made between clinical data of our Ad with data of elderly patients (E). The role of allergic sensitization is significantly higher in Ad compared to E. Dermatophagoides pteronyssinus is the first sensitizing allergen in Ad and the last in E. Parietaria constitutes the first sensitizing pollen both in Ad and E, the percentage of sensitization is higher in Ad. Another important difference is the higher prevalence of As, as only symptom, in E compared to Ad (19.7% versus 7.6%). In conclusion, our findings confirm the high prevalence and clinical significance of airway allergic sensitization in the adolescents living in Campania region.

ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is a complex disease of the central nervous system. As new drugs are becoming available, knowledge on diagnosis and treatment must continuously evolve. There is therefore a need for a reference tool compiling current data on benefit and safety, to aid professionals in treatment decisions and use of resources across Europe. The European Committee of Treatment and Research in Multiple Sclerosis (ECTRIMS) and the European Academy of Neurology (EAN) have joined forces to meet this need. The objective was to develop an evidence-based clinical practice guideline for the pharmacological treatment of people with MS to guide healthcare professionals in the decision-making process. METHODS: This guideline has been developed using the GRADE methodology and following the recently updated EAN recommendations for guideline development. Clinical questions were formulated in PICO format (patient, intervention, comparator, outcome) and outcomes were prioritized according to their relevance to clinical practice. An exhaustive literature search up to December 2016 was performed for each question and the evidence is presented narratively and, when possible, combined in a meta-analysis using a random-effects model. The quality of evidence for each outcome was rated into four categories - very high, high, low and very low - according to the risk of bias. GRADE evidence profiles were created using GRADEprofiler (GRADEpro) software (Version 3.6). The recommendations with assigned strength (strong, weak) were formulated based on the quality of evidence and the risk-benefit balance. Consensus between the panellists was reached by use of the modified nominal group technique. RESULTS: A total of 10 questions have been agreed, encompassing treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and treatment strategies in MS and pregnancy. The guideline takes into account all disease-modifying drugs approved by the European Medicine Agency at the time of publication. A total of 20 recommendations were agreed by the guideline working group members after three rounds of consensus.

News on Climate Change, Air Pollution, and Allergic Triggers of Asthma.

The rising frequency of obstructive respiratory diseases during recent years, in particular allergic asthma, can be partially explained by changes in the environment, with the increasing presence in the atmosphere of chemical triggers (particulate matter and gaseous components such as nitrogen dioxide and ozone) and biologic triggers (aeroallergens). In allergic individuals, aeroallergens stimulate airway sensitization and thus induce symptoms of bronchial asthma. Over the last 50 years, the earth's temperature has risen markedly, likely because of growing concentrations of anthropogenic greenhouse gas. Major atmospheric and climatic changes, including global warming induced by human activity, have a considerable impact on the biosphere and on the human environment. Urbanization and high levels of vehicle emissions induce symptoms of bronchial obstruction (in particular bronchial asthma), more so in people living in urban areas compared than in those who live in rural areas. Measures need to be taken to mitigate the future impact of climate change and global warming. However, while global emissions continue to rise, we must learn to adapt to climate variability.

Allergic sensitization to common pets (cats/dogs) according to different possible modalities of exposure: an Italian Multicenter Study.

BACKGROUND: The query "are there animals at home?" is usually administered for collecting information on anamnesis. This modality to consider exposure to pet allergens constitutes a potential bias in epidemiological studies and in clinical practice. The aim of our study was to evaluate/quantify different modalities of exposure to cat/dog in inducing allergic sensitization. METHODS: Thirty Italian Allergy units participated in this study. Each centre was required to collect the data of at least 20 consecutive outpatients sensitized to cat/dog allergens. A standardized form reported all demographic data and a particular attention was paid in relieving possible modalities of exposure to cat/dog. RESULTS: A total 723 patients sensitized to cat/dog were recorded, 359 (49.65%) reported direct pet contact, 213 patients (29.46%) were pet owners, and 146 subjects (20.19%) were exposed to pets in other settings. Other patients were sensitized by previous pet ownership (150-20.75%) or indirect contact (103-14.25%), in 111 subjects (15.35%) any contact was reported. CONCLUSIONS: Only 213 patients (29.46%) would be classified as "exposed to animals" and 510 (70.54%) as "not exposed" according to usual query. Our classification has shown that many "not-exposed" subjects (399-55.19%) were "really exposed". The magnitude of exposure to pet allergens at home is not related exclusively to pet ownership. These considerations should be taken into account during the planning of epidemiological studies and in clinical practice for the management of pet allergic individuals.

Microguided Endodontics: a method to achieve minimally invasive access cavity preparation and root canal location in mandibular incisors using a novel computer-guided technique.

AIM: To present a novel miniaturized and minimally invasive treatment approach for root canal localization in mandibular incisors with pulp canal calcification and apical periodontitis. SUMMARY: A 51-year-old male patient presented with pain from his mandibular incisors. The patient had a history of severe dental trauma over 30 years ago. Both mandibular central incisors (teeth 31, 41) were tender to percussion and had a yellowish discoloration. They did not respond to thermal and electrical sensitivity tests. Two periapical radiographs from different projections revealed severe pulp canal calcifications and signs of periapical periodontitis. To facilitate the 'Microguided Endodontics' technique, a CBCT and an intra-oral surface scan were aligned using special software. This allowed the virtual planning of optimal access cavities up to the apical third of the root. In this technique, a 3D-printed template guides a customized drill to the orifice of the root canal. After negotiation of the root canals, conventional root canal treatment was performed. This case report demonstrates that minimally invasive and apically extended access cavities are feasible in mandibular incisors with this technique. KEY LEARNING POINTS: The 'Microguided Endodontics' technique is a safe and minimally invasive method for root canal location and prevention of technical failures in anterior teeth with pulp canal calcification.

Analysis of the reliability of the Italian version of the Oral Behaviours Checklist and the relationship between oral behaviours and trait anxiety in healthy individuals.

BACKGROUND: The Oral Behaviours Checklist (OBC) is a valid 21-item instrument quantifying the self-reported frequency of oral behaviours. An Italian version (OBC-It) has been released recently. Anxiety and oral behaviours are known to be associated in individuals with oro-facial pain due to temporomandibular disorders (TMD). However, information about this relationship in pain-free individuals is still limited. OBJECTIVES: The aim of this study was to test the reliability of the OBC-It and its reduced version (OBC-It 6), focusing on tooth clenching-related wake-time oral behaviours, and the effect of patient instructions on reliability. A second aim was to test the association between trait anxiety and oral behaviours in pain-free individuals. METHODS: Two hundred and eighty-two TMD-free students, divided into 2 groups (Group A, n = 139, mean age ± SD = 22.6 ± 5.4 years; Group B, n = 143, 23.7 ± 4.2 years), filled in the State-Trait Anxiety Inventory and the OBC-It. Group B received instructions about the OBC-It, while Group A did not. After 2 weeks, both groups filled in the OBC-It again. However, Group B was further divided into 2 subgroups, B1 and B2 . The first received the same instructions again, while B2 did not. RESULTS: The test-retest reliability of the OBC-It (A: ICC = .87; B1 : ICC = .94; B2 : ICC = .95) and OBC-It 6 (A: ICC = .85; B1 : ICC = .89; B2 : ICC = .93) was excellent in all groups. Trait anxiety was weakly associated with OBC-It only in women (R2  = .043, P = .021). CONCLUSIONS: The OBC-It is a reliable tool but further subjects' instructions might be needed. Trait anxiety has a limited effect on oral behaviours in TMD-free subjects.

Patient outcomes and amotosalen/UVA-treated platelet utilization in massively transfused patients.

BACKGROUND: Amotosalen/UVA-treated platelet concentrates (PCs) have demonstrated efficacy for treating and preventing bleeding in clinical trials and in routine use; however, most studies were performed in haematology/oncology patients. We investigated efficacy during massive transfusion (MT) in general hospitalized patients. METHODS: Universal amotosalen/UVA treatment (INTERCEPT Blood System) of platelets was introduced at a large Austrian medical centre. We performed a retrospective cohort analysis comparing component use, in-hospital mortality and length of stay after MT that included platelet transfusion, for two periods (21 months each) before and after implementation. RESULTS: A total of 306 patients had MT. Patients were mostly male (74%) and ≥18 years old (99%), including 93 liver transplant, 97 cardiac or vascular surgery and 51 trauma patients. There were no differences in demographics between the periods. Component use on the day and within 7 days of the MT event was unchanged post-IBS implementation, except trauma patients received fewer RBCs on the day. The mean ratio of RBC:platelets:plasma on the day of the MT was close to 1:1:1 in both periods, except for liver transplants with MT who received more plasma components. Overall, in-hospital mortality (preimplementation = 27·6% vs. postimplementation = 24·0%; P = 0·51) and median time to discharge (preimplementation = 27 vs. postimplementation = 23 days; P = 0·37) did not change, except for cardiac and vascular surgery patients who were discharged earlier. CONCLUSION: The introduction of amotosalen/UVA-treated, pathogen-reduced PC did not adversely affect clinical outcomes in massively transfused patients in terms of blood product usage, in-hospital mortality and length of stay for a range of clinical indications for platelet transfusion support.

Impact of platelet pathogen inactivation on blood component utilization and patient safety in a large Austrian Regional Medical Centre.

BACKGROUND: In clinical studies, pathogen inactivation (PI) of platelet concentrates (PC) with amotosalen and UVA light did not impact patient risk for haemorrhage but may affect transfusion frequency and component utilization. We evaluated the influence of platelet PI on PC, red cell concentrate (RCC) and plasma use and safety in routine practice in a large regional hospital. STUDY DESIGN AND METHODS: Comparative effectiveness of conventional vs. PI-treated PC was analysed during two 21-month periods, before and after PI implementation. RESULTS: Similar numbers of patients were transfused in the pre-PI (control, 1797) and post-PI (test, 1694) periods with comparable numbers of PC (8611 and 7705, respectively). The mean numbers of PC per patient transfused (4·8 vs. 4·5, P = 0·43) were not different but days of PC support (5·9 vs. 5·0, P < 0·01) decreased. Most patients received RCC (86·8% control vs. 84·8% test, P = 0·90) with similar mean numbers transfused (10·8 vs. 10·2 RCC, P = 0·22), and fewer patients (55·4% control vs. 44·7% test, P < 0·01) received less plasma units (mean 9·9 vs. 7·8, respectively, P < 0·01) in the test period. The frequencies of transfusion-related adverse events (AE) were comparable (1·3% vs. 1·4%, P = 0·95). Analysis of haematology-oncology (522 control, 452 test), cardiac surgery (739 control, 711 test), paediatric (157 control, 130 test) and neonate (23 control, 20 test) patients revealed no increase in PC, plasma and RCC utilization, or AE. CONCLUSION: Component utilization and patient safety were not impacted by adoption of PI for PC. RCC use per patient was comparable, suggestive of no increase in significant bleeding.

Effect of organizational features on patient satisfaction with care in Italian multiple sclerosis centres.

BACKGROUND AND PURPOSE: Receiving clear, complete and up-to-date information and having a satisfying relationship with the health professional (HP) are of primary importance for MS patients. Healthcare organization plays a key role in promoting an effective relationship and communication between patients and HPs. The present study aims to explore which care organization and service characteristics provided by Italian MS centres best predict patients' satisfaction with healthcare. METHODS: Eighty-one centres and 707 patients (502 women, mean age 40.5 years, SD 10.2; mean education 12.2 years, SD 3.6; time since diagnosis 5.9 years, SD 1.5) were included in the analysis. The care organization and service provided by each centre were evaluated in comparison with the National Institute for Health and Care Excellence (NICE) guidelines on management of MS. Patients' satisfaction with care was measured using the patient self-assessed questionnaire 'Comunicazione medico-paziente nella Sclerosi Multipla, revised' section 2 (COSM-R section 2). RESULTS: The clinical characteristics of patients significantly affected their satisfaction. A multivariate regression model showed that higher patients' satisfaction (COSM-R score) was inversely associated with hospital size (number of patients under care) (ß = -0.21, 95% confidence interval -0.35; -0.07) and directly associated with psychological interventions (ß = 2.44, 95% confidence interval 0.29; 4.59). CONCLUSIONS: Multiple sclerosis patients from larger hospitals are less satisfied with the information received and the relationship with HPs. Building an individualized relationship between patients and HPs and tailoring the communication of information improve patients' satisfaction. Such a goal is probably less likely to be accomplished in larger centres with many incoming patients. Moreover, when the centres also provide structured psychological interventions, the patients are more satisfied.

Evaluation of the intraepithelial papillary capillary loops in benign and malignant oral lesions by in vivo Virtual Chromoendoscopic Magnification: a preliminary study.

This preliminary study aims to establish the Virtual Chromoendoscopic Magnification (VCM) feasibility to visualize and distinguish the Intraepithelial Papillary Capillary Loops (IPCL) patterns of benign oral pathologies from malignant ones. Thirty-one consecutive subjects affected by oral lesions/pathologies underwent white light examination and VCM imaging by the Narrow Band Imaging System (Olympus Medical Systems Corp., Tokyo, Japan). A class system of four IPCL types corresponding to progressive vessel disarray was adopted. IPCL type IV were considered criterion of “malignancy”. A histopathological exam completed the diagnosis: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. IPCL patterns of benign oral entities ranged from types I to III. IPCL type IV was associated with malignancy in 4 out of 6 cases. Sensitivity, specificity, PPV, and NPV were 100%, 93%, 67% and 100%, respectively. This study preliminarily describes IPCL patterns of different oral mucosal diseases and confirms the association between IPCL IV and oral cancer.

Preserving the PCL during the tibial cut in total knee arthroplasty.

PURPOSE: Previous studies have shown that the PCL insertion may be damaged during the tibial cut performed in total knee arthroplasty. We investigated the maximum thickness of a tibial cut that preserves the PCL insertion and to what extent the posterior slope of the tibial cut and that of the patient's tibial plateaus affect the outcome. METHODS: MR images of 83 knees were analysed. The maximum thickness of a tibial cut that preserves the PCL using a posterior slope of 0°, 3°, 5° and parallel to the patient's slope of the tibial plateau, was evaluated. Correlations between the results and the degrees of the posterior slope of the patient's tibial plateaus were also investigated. RESULTS: The maximum thickness of a tibial cut that preserves the entire PCL insertion was, on average, 5.5, 4.7, 4.2 and 3.1 mm when a posterior slope of 0°, 3°, 5° and parallel to the patients' tibial plateaus was used, respectively. When the 25th percentile was considered, the maximum thickness of a tibial cut that preserved the PCL was 4 and 3 mm with a tibial cut of 0° and 5° of posterior slope, respectively. The maximum thickness of a tibial cut that preserved the PCL was significantly greater in patients with a sagittal slope of the tibial plateaus more than 8° than in those with a sagittal slope less than 8°. CONCLUSION: In cruciate retaining implants, the PCL insertion may be spared in the majority of patients by performing a tibial cut of 4 mm, or even less when a posterior slope of 3°-5° is used. The clinical relevance of our study is that the execution of a conservative tibial cut, followed by a second tibial resection to achieve the thickness required for the tibial component to be implanted, may be an alternative technique to spare the PCL in CR TKA. LEVEL OF EVIDENCE: II.

Three-dimensional patellar tendon fibre kinematics in navigated TKA with and without patellar resurfacing.

PURPOSE: Physiological elongation and orientation of patellar tendon fibres are among the scopes of total knee arthroplasty, but little is known in the three dimensions. The study aims to assess in vitro these variations at the intact and replaced knee, with and without patellar resurfacing. It was hypothesised that fibre patterns differ before and after prosthesis implantation, and between specific prosthesis designs. It was also expected that patellar resurfacing would affect relevant results. METHODS: Measurements from 16 intact cadaver knees free from anatomical defects are here reported using a surgical navigation system. Data were collected at the intact joint and after implantation with cruciate-retaining or posterior-stabilised prosthesis designs, with and without patellar resurfacing. Relevant anatomical landmarks and patellar tendon attachments were digitised. Anatomical reference frames in the femur, tibia and patella were defined to measure component implantation parameters. Representative tendon fibres were defined as the straight line segments joining the two extremities. Changes in length and orientation of these fibres were calculated and reported versus flexion at the intact knee and after prosthesis implantation, both with and without patellar resurfacing. RESULTS: A good intra- and inter-specimen repeatability was found at the intact and replaced knees. In both prosthesis designs, the patterns of fibre lengthening were similar to those in the intact knee, though significant differences were observed before and after patellar resurfacing. Corresponding fibre orientations in the frontal and sagittal planes showed significantly smaller ranges than those in the corresponding intact joints. More natural patterns were observed in the knees implanted with the posterior-stabilised design. Significant correlations were identified between patellar component implantation parameters and both patellar tendon fibre elongation and orientation. CONCLUSIONS: Differences, however small, in patellar tendon fibre elongation and orientation were observed after total knee arthroplasty. The posterior-stabilised design provided better results, whereas patellar resurfacing affected significantly normal patellar function. In the clinical practice, the present findings can contribute to the understanding of current prosthesis designs and patellar resurfacing, recommending also enhanced care during this surgery.

LACC1 polymorphisms in inflammatory bowel disease and juvenile idiopathic arthritis.

The function of the Laccase domain-containing 1 (LACC1) gene is unknown, but genetic variation at this locus has been reported to consistently affect the risk of Crohn's disease (CD) and leprosy. Recently, a LACC1 missense mutation was found in patients suffering from monogenic forms of CD, but also systemic juvenile idiopathic arthritis. We tested the hypothesis that LACC1 single nucleotide polymorphisms (SNPs), in addition to CD, are associated with juvenile idiopathic arthritis (JIA, non-systemic), and another major form of inflammatory bowel disease, ulcerative colitis (UC). We selected 11 LACC1 tagging SNPs, and tested their effect on disease risk in 3855 Swedish individuals from three case-control cohorts of CD, UC and JIA. We detected false discovery rate corrected significant associations with individual markers in all three cohorts, thereby expanding previous results for CD also to UC and JIA. LACC1's link to several inflammatory diseases suggests a key role in the human immune system and justifies further characterization of its function(s).

Thunderstorm-related asthma: what happens and why.

The fifth report issued by the Intergovernmental Panel on Climate Change forecasts that greenhouse gases will increase the global temperature as well as the frequency of extreme weather phenomena. An increasing body of evidence shows the occurrence of severe asthma epidemics during thunderstorms in the pollen season, in various geographical zones. The main hypotheses explaining association between thunderstorms and asthma claim that thunderstorms can concentrate pollen grains at ground level which may then release allergenic particles of respirable size in the atmosphere after their rupture by osmotic shock. During the first 20-30 min of a thunderstorm, patients suffering from pollen allergies may inhale a high concentration of the allergenic material that is dispersed into the atmosphere, which in turn can induce asthmatic reactions, often severe. Subjects without asthma symptoms, but affected by seasonal rhinitis can also experience an asthma attack. All subjects affected by pollen allergy should be alerted to the danger of being outdoors during a thunderstorm in the pollen season, as such events may be an important cause of severe exacerbations. In light of these observations, it is useful to predict thunderstorms and thus minimize thunderstorm-related events.