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La inyección de toxina botulínica en el detrusor es un tratamiento validado, de segunda línea, de la incontinencia urinaria por hiperactividad vesical en los pacientes no neurológicos y en los pacientes neurológicos cuando existe una hiperactividad del detrusor asociada. Se trata de una neurotoxina producida por la bacteria anaerobia Clostridium botulinum,de la que sólo se comercializan dos serotipos en Francia para su uso urológico: onabotulinumtoxina A (Botox) y abobotulinumtoxina A (Dysport). Sólo la onabotulinumtoxina ha obtenido una autorización de comercialización en Francia para las inyecciones en el detrusor. La toxina botulínica tiene una acción curaromimética por bloqueo de la transmisión nerviosa en la unión neuromuscular estriada. Esta acción es reversible y requiere reinyecciones reiteradas cada 6-9 meses aproximadamente. La inyección se realiza por vía endoscópica bajo anestesia local o general, comenzando con la dosis con 50 U en pacientes no neurológicos y de 200 U en los pacientes con patologías neurológicas. En los pacientes no neurológicos, la toxina botulínica permite mejorar los síntomas de hiperactividad vesical y la calidad de vida de los pacientes. En los pacientes neurológicos, además de mejorar la calidad de vida, las inyecciones de toxina botulínica permiten también limitar las presiones del detrusor y proteger el aparato urinario superior a largo plazo. Se requiere un seguimiento riguroso de los pacientes para detectar la aparición de efectos secundarios o un posible escape de la toxina.

Systemic sclerosis (SSc) is an autoimmune disease characterized by progressive organ damage, which can be measured using the Scleroderma Clinical Trials Consortium Damage Index (SCTC‐DI). We aimed to identify whether distinct trajectories of damage accrual exist and to determine which variables are associated with different trajectory groups. Incident cases of SSc (<2 years) were identified in the Australian Scleroderma Interest Group and Canadian Scleroderma Research Group prospective registries. Group‐based trajectory modeling was used to identify SCTC‐DI trajectories over the cohort's first 5 annual visits. Baseline variables associated with trajectory membership in a univariate analysis were examined in multivariable models. A total of 410 patients were included. Three trajectory groups were identified: low (54.6%), medium (36.2%), and high (10.3%) damage. Patients with faster damage accrual had higher baseline SCTC‐DI scores. Older age (odds ratio [OR] 1.57 [95% confidence interval (95% CI) 1.18–2.10]), male sex (OR 2.55 [95% CI 1.10–5.88]), diffuse disease (OR 6.7 [95% CI 2.57–17.48]), tendon friction rubs (OR 5.4 [95% CI 1.86–15.66]), and elevated C‐reactive protein level (OR 1.98 [95% CI 1.49–2.63]) increased the odds of being in the high‐damage group versus the reference (low damage), whereas White ethnicity (OR 0.31 [95% CI 0.12–0.75]) and anticentromere antibodies (OR 0.24 [95% CI 0.07–0.77]) decreased the odds. We identified 3 trajectories of damage accrual in a combined incident SSc cohort. Several characteristics increased the odds of belonging to worse trajectories. These findings may be helpful in recognizing patients in whom early aggressive treatment is necessary.

Although kneading is a typical process step in pharmaceutical manufacturing, little fundamental research has been conducted on the characterization and quantification of the consistency of a wet powder mass. In [...]

Little is known about long-term efficacy and tolerance of intra-detrusor injections of abobotulinumtoxinA for management of idiopathic overactive bladder (OAB). We report long-term efficacy and compliance of abobotulinumtoxinA in patients treated for OAB.

Objectives: Scleroderma renal crisis is a rare but serious complication affecting 2%–15% of patients with systemic sclerosis. Despite treatment with angiotensin-converting enzyme inhibitors, outcomes for scleroderma renal crisis patients are still poor. The cellular signaling mechanisms in scleroderma renal crisis are not yet known. Mammalian target of rapamycin, comprised of the subunits mTORC1 and mTORC2, has been shown to be activated in vascular lesions of renal transplant patients with anti-phospholipid antibody syndrome. Given the similarities between the pathophysiology of scleroderma renal crisis and anti-phospholipid antibody syndrome, we hypothesized that the mammalian target of rapamycin pathway would also be activated in the renal vasculature of patients with scleroderma renal crisis.Methods: We retrospectively analyzed renal biopsies of five patients with scleroderma renal crisis in the Canadian Scleroderma Research Group cohort. Immunostaining was performed using anti-P-S6RP antibodies to evaluate the phosphorylation of mTORC1, and anti-Rictor and anti-S473 to determine activation of mTORC2.Results: Four of the five patients showed mTORC1 activation in arteriolar endothelial cells, and three of the five patients showed mTORC1 activation in the arterial endothelial cells. Two of four samples showed Rictor expression in the arteriolar and arterial endothelial cells, showing mTORC2 activation. There was no expression of mTORC1 or mTORC2 in samples from two healthy controls.Conclusion: We demonstrate that both mTORC1 and mTORC2 are activated in renal biopsies with typical histologic features of scleroderma renal crisis. Dual mammalian target of rapamycin inhibitors are currently available and in development. These findings could inform further research into novel treatment targets for scleroderma renal crisis.

Évaluer la faisabilité, l’efficacité et la tolérance de l’utilisation des lasers Greenlight™ et Holmium comme techniques d’incontinentation pour traiter une dyssynergie vésicosphinctérienne neurogène (DVS).

Obesity is implicated in rheumatoid arthritis (RA) development, severity, outcomes, and treatment response. We estimated the independent effects of overweight and obesity on ability to achieve sustained remission (sREM) in the 3 years following RA diagnosis. Data were from the Canadian Early Arthritis Cohort, a multicenter observational trial of early RA patients treated by rheumatologists using guideline‐based care. sREM was defined as Disease Activity Score in 28 joints (DAS28) <2.6 for 2 consecutive visits. Patients were stratified by body mass index (BMI) as healthy (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2), and obese (≥30 kg/m2). Cox regression was used to estimate the effect of the BMI category on the probability of achieving sREM over the first 3 years, controlling for age, sex, race, education, RA duration, smoking status, comorbidities, baseline DAS28, Health Assessment Questionnaire disability index, C‐reactive protein level, and initial treatment. Of 982 patients, 315 (32%) had a healthy BMI, 343 (35%) were overweight, and 324 (33%) were obese; 355 (36%) achieved sREM within 3 years. Initial treatment did not differ by BMI category. Compared to healthy BMI, overweight patients (hazard ratio [HR] 0.75 [95% confidence interval (95% CI) 0.58–0.98]) and obese patients (HR 0.53 [95% CI 0.39–0.71]) were significantly less likely to achieve sREM. Rates of overweight and obesity were high (69%) in this early RA cohort. Overweight patients were 25% less likely, and obese patients were 47% less likely, to achieve sREM in the first 3 years, despite similar initial disease‐modifying antirheumatic drug treatment and subsequent biologic use. This is the largest study demonstrating the negative impact of excess weight on RA disease activity and supports a call to action to better identify and address this risk in RA patients.

Le but de notre étude a été d’évaluer la survie sans récidive biologique et d’en déterminer des facteurs prédictifs, des patients ayant un cancer de la prostate sans métastase ganglionnaire clinicoradiologique (cN0) lors du bilan préopératoire, ayant eu une prostatectomie totale avec curage ganglionnaire mettant en évidence une atteinte métastatique ganglionnaire (pN+).

To report long-term outcomes after I-Stop TOMS™ implantation for PPI.

Le cancer du testicule est un cancer rare touchant principalement l’adulte jeune. Il est découvert dans 70 % des cas au stade localisé. Sa prise en charge nécessite une évaluation et un traitement rapide afin d’éviter une extension métastatique précoce. L’objectif principal de notre étude est de décrire les pratiques de prise en charge chez les patients atteints d’une tumeur localisée du testicule.

Les syndromes douloureux pelviens sont des pathologies chroniques altérant la qualité de vie des patients. Peu d’études ont évalué l’intérêt de la neuromodulation des racines sacrées dans cette indication. L’objectif de l’étude était d’évaluer l’impact de la neuromodulation des racines sacrées chez les patients présentant un syndrome douloureux pelvien.

Les diverticules urétraux sont une entité rare, mais non exceptionnelle. L’abord vaginal est la voie de référence pour aborder les diverticules postérieurs. Cependant, les diverticules antérieurs ou en fer à cheval sont difficiles d’accès par voie vaginale avec un risque d’exérèse incomplète. L’objectif de cette vidéo était de présenter une technique de cure de diverticule urétral antérieur par voie cœlioscopique robot-assistée.

Depuis la loi du 4 juillet 2001, la vasectomie est reconnue comme méthode de contraception masculine. Nous rapportons l’expérience de la pratique de vasectomie au sein d’un centre hospitalo-universitaire.

The aim of this article was to check the physical stability of the amorphous form of probucol at both standard storage and manufacturing conditions. Our studies clearly show that disordered form of the examined, cholesterol lowering, agent stored at ambient pressure does not reveal any tendency toward recrystallization. The physical stability of neat probucol stored at ambient pressure has been investigated (i) at room temperature by means of X-ray diffraction technique (XRD) as well as (ii) at T= 333 K by means of broadband dielectric spectroscopy (BDS). Due to the fact that compression is an important stage of drugs manufacturing we additionally performed physical stability tests of amorphous probucol at elevated pressure. The recrystallization tendency of the examined pharmaceutical has been tracked online from the initial and further up to a few hours after compression by means of the high pressure BDS technique. These experiments indicate that even very small pressure applied during the sample compression immediately induce its recrystallization. Since, the sensitivity on pressure eliminates probucol from the group of physically stable amorphous APIs, its stabilization is required. Taking into account that there are many scientific reports describing the positive effect of coadministration of probucol with the drug atorvastatin, we used the latter as probucol’s crystallization inhibitor.

Les traumatismes graves du bassin restent grevés d’un taux de mortalité élevé. Le mécanisme explicatif est principalement le choc hémorragique.

La courbe d’apprentissage du HoLEP est réputée difficile. Nous avons évalué l’intérêt d’un tutorat séquentiel en 3 étapes dans le processus de formation à la procédure au sein d’un centre universitaire.

Body concealment is a component of social avoidance among people with visible differences from disfiguring conditions, including systemic sclerosis (SSc). The study objective was to develop a measure of body concealment related to avoidance behaviors in SSc. Initial items for the Body Concealment Scale for Scleroderma (BCSS) were selected using item analysis in a development sample of 93 American SSc patients. The factor structure of the BCSS was evaluated in 742 Canadian patients with single‐factor, 2‐factor, and bifactor confirmatory factor analysis models. Convergent and divergent validity were assessed by comparing the BCSS total score with the Brief‐Satisfaction with Appearance Scale (Brief‐SWAP) and measures of depressive symptoms and pain. A 2‐factor model (Comparative Fit Index [CFI] 0.99, Tucker‐Lewis Index [TLI] 0.98, Root Mean Square Error of Approximation [RMSEA] 0.08) fit substantially better than a 1‐factor model (CFI 0.95, TLI 0.94, RMSEA 0.15) for the 9‐item BCSS, but the Concealment with Clothing and Concealment of Hands factors were highly correlated (α = 0.79). The bifactor model (CFI 0.99, TLI 0.99, RMSEA 0.08) also fit well. In the bifactor model, the omega coefficient was high for the general factor (ω = 0.80), but low for the Concealment with Clothing (ω = 0.01) and Concealment of Hands (ω = 0.33) factors. The BCSS total score correlated more strongly with the Brief‐SWAP Social Discomfort (r = 0.59) and Dissatisfaction with Appearance (r = 0.53) subscales than with measures of depressive symptoms and pain. The BCSS sum score is a valid indicator of body concealment in SSc that extends the concepts of body concealment and avoidance beyond the realms of body shape and weight to concerns of individuals with visible differences from SSc.

Married persons have, on average, better mental health than nonmarried persons. Among married persons, marital satisfaction is associated with better mental health. Studies on mental health in married and nonmarried persons that consider marital satisfaction have categorized patients as satisfied versus unsatisfied, which reduces statistical power and does not generate clinically useful information on mental health across the satisfaction spectrum. Our objective was to demonstrate a novel regression approach to evaluate mental health in women with systemic sclerosis (SSc), comparing married and unmarried women, accounting for continuously measured marital satisfaction. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES‐D) and marital satisfaction with the Dyadic Adjustment Scale‐7. A single multiple linear regression model was used to predict CES‐D scores from marital status and, among married women, continuously measured marital satisfaction, controlling for demographic and clinical characteristics. Of 725 women, 494 (68%) were married or living as married. On average, married women had mean CES‐D scores that were 2.0 points (0.19 SDs) lower than unmarried women (P= 0.013). Among married women, a 1.0 SD increase in marital satisfaction was associated with a 2.2 point (0.21 SDs) decrease in CES‐D scores (P< 0.001). Married women whose marital satisfaction scores were below the 19th percentile had greater predicted depressive symptoms than unmarried women. Married women's predicted CES‐D scores ranged from 6.7 points lower to 6.9 points higher than those of unmarried women, depending on marital satisfaction. Comparisons of mental health in married and unmarried patients with rheumatic diseases should include continuously measured marital satisfaction.

Évaluer les données de la littérature concernant les effets de la neuromodulation sacrée (SNS) urinaire sur les troubles digestifs autre que l’incontinence fécale.

In this article, we highlight the benefits coming from the application of amorphous protic ionic systems as active pharmaceutical ingredients (APIs). Using the case of the sumatriptan (STR) drug, we show that the conversion of nonionic API to partially ionized amorphous protic succinate salt (STR SUCC) brings a substantial improvement in apparent solubility. Since in general the disordered systems reveal a tendency to self-arrangement during storage, the dominant part of this article is dedicated to the physical stability issue of sumatriptan and its ionic counterpart. To recognize the crystallization tendency of the studied systems, the calorimetric measurements were performed. Additionally, the role of ion dynamics in spontaneous nucleation of amorphous sumatriptan succinate is discussed. The differential scanning calorimetry analysis of ionic and nonionic sumatriptan reveals many similarities in thermal properties of these APIs as well as distinct differences in their resistance against crystallization in the supercooled liquid state. To determine the long-term physical stability of STR SUCC at room temperature conditions, the time scale of structural relaxation below their glass transition temperatures is estimated. We show that in contrast to nonionic materials, ταpredictions of STR SUCC are much more complex and require aging experiments.

La névralgie du nerf pudendal est une pathologie de diagnostic et traitement difficile. Elle est souvent liée à une compression du nerf lors de son passage entre les ligaments sacro-épineux et sacro-tubéral. La libération du nerf est le plus souvent réalisée par voie trans-glutéale. Notre objectif était de démontrer l’impact de la libération du nerf pudendal par voie robot-assistée sur la symptomatologie douloureuse.

La cystostomie continente de type Mitrofanoff a été initialement décrite par voie ouverte sur une population pédiatrique. Depuis 2017, nous proposons cette chirurgie par voie cœlioscopique robot-assistée, en l’absence de contre-indication, dans un souci d’épargne pariétale et de récupération plus rapide du transit. Nous rapportons ici la technique chez une patiente de 17 ans pour laquelle un Mitrofanoff sans entéroplastie d’agrandissement a été réalisé.

Melting curves of Ca‐perovskite (pure CaSiO3) were determined by ab initio density functional theory, using two solid‐liquid coexistence methods and two free energy approaches, in the form of thermodynamic integration and two‐phase thermodynamics. The melting curves based on the solid‐liquid coexistence methods and thermodynamic integration rise steeply from 2000 K at 14 GPa to 7000 K at 136 GPa. The melting temperature at 136 GPa is 1400 K higher than previous ab initio predictions. The high thermal stability of Ca‐perovskite is linked to its high‐symmetry isometric structure and consistent with experiments, demonstrating that Ca‐perovskite is the most refractory phase in basaltic compositions in the lower mantle pressure range. The steep dT/dp slope of the melting curve also shows that the Ca‐perovskite liquidus field expands relative to those of bridgmanite and silica with increasing pressure, in agreement with experimental evidence from simple and complex systems. Melting of mantle minerals provides key information for understanding our planet's thermal evolution from the early stage of magma ocean crystallization to the present partial melting that is likely to occur near the core‐mantle boundary. We determined the melting curve of Ca‐perovskite (CaSiO3), the third most abundant mineral in the Earth's lower mantle, in a wide pressure range up to the core‐mantle boundary pressure. Several atomistic simulation methods were used and show that Ca‐perovskite melts about 2000 K higher than bridgmanite at the pressure conditions of lowermost mantle. This agrees with the experimental findings that Ca‐perovskite is the last mineral to disappear when basaltic rocks undergo partial melting in the lower mantle. The Ca‐perovskite (CaSiO3) melting curve determined to 136 GPa by four ab initio atomistic simulation methodsA high melting temperature of about 7000 K at the core‐mantle boundary suggests a wide liquidus field in the system CaO‐MgO‐SiO2Ca‐perovskite is the first liquidus phase in basaltic compositions in the lowermost mantle The Ca‐perovskite (CaSiO3) melting curve determined to 136 GPa by four ab initio atomistic simulation methods A high melting temperature of about 7000 K at the core‐mantle boundary suggests a wide liquidus field in the system CaO‐MgO‐SiO2 Ca‐perovskite is the first liquidus phase in basaltic compositions in the lowermost mantle

The aim of this article is to examine the crystallization tendencies of three chemically related amorphous anti-inflammatory agents, etoricoxib, celecoxib, and rofecoxib. Since the molecular mobility is considered as one of the factors affecting the crystallization behavior of a given material, broadband dielectric spectroscopy was used to gain insight into the molecular dynamics of the selected active pharmaceutical ingredients. Interestingly, our experiments did not reveal any significant differences in their relaxation behavior either in the supercooled liquid or in the glassy state. Hence, as a possible explanation for the enhanced physical stability of etoricoxib, its ability to undergo a tautomerization reaction was recognized. The occurrence of intramolecular proton transfer in the disordered etoricoxib was proven experimentally by time-dependent dielectric and infrared (IR) measurements. Additionally, IR spectroscopy combined with density functional theory calculations pointed out that in the etoricoxib drug, being in fact a binary mixture of tautomers, the individual isomers may interact with each other through a hydrogen bonding network. A possible explanation of this issue was achieved by performing dielectric experiments at elevated pressure. Since compression results in etoricoxib recrystallization, the possible influence of pressure on the observed stabilization effect is also carefully discussed.

Objective.Fatigue is a crucial determinant of quality of life across rheumatic diseases, but the lack of agreed-upon standards for identifying clinically significant fatigue hinders research and clinical management. Case definition criteria for cancer-related fatigue were proposed for inclusion in the International Classification of Diseases. The objective was to evaluate whether the cancer-related fatigue case definition performed equivalently in women with breast cancer and systemic sclerosis (SSc) and could be used to identify patients with chronic illness-related fatigue.Methods.The cancer-related fatigue interview (case definition criteria met if ≥ 5 of 9 fatigue-related symptoms present with functional impairment) was completed by 291 women with SSc and 278 women successfully treated for breast cancer. Differential item functioning was assessed with the multiple indicator multiple cause model.Results.Items 3 (concentration) and 10 (short-term memory) were endorsed significantly less often by women with SSc compared with cancer, controlling for responses on other items. Omitting these 2 items from the case definition and requiring 4 out of the 7 remaining symptoms resulted in a similar overall prevalence of cancer-related fatigue in the cancer sample compared with the original criteria (37.4% vs 37.8%, respectively), with 97.5% of patients diagnosed identically with both definitions. Prevalence of chronic illness-related fatigue was 36.1% in SSc using 4 of 7 symptoms.Conclusion.The cancer-related fatigue criteria can be used equivalently to identify patients with chronic illness-related fatigue when 2 cognitive fatigue symptoms are omitted. Harmonized definitions and measurement of clinically significant fatigue will advance research and clinical management of fatigue in rheumatic diseases and other conditions.

Objective.To develop and validate, as a measure of overall health status, a Frailty Index (FI) for patients (n = 1372) in the Canadian Scleroderma Research Group (CSRG) Registry.Methods.Forty-four items were selected from the CSRG database as health deficits and recoded using FI criteria. To test construct validity, we compared measurement properties of the CSRG-FI to other FI, and related it to measures of damage, age, and time since diagnosis. To test criterion validity, we compared the baseline FI to that at last recorded visit and to mortality.Results.The mean CSRG-FI was 0.33 with a sub-maximal limit of 0.67. In patients with diffuse disease, the mean was 0.38(SD 0.14); in patients with limited disease, the mean was 0.31(SD 0.13). The CSRG-FI was weakly (but significantly) correlated with the Rodnan Skin Score (r = 0.28 in people with diffuse disease; 0.18 with limited) and moderately with the Physician Assessment of Damage (r = 0.51 for both limited and diffuse). The risk of death increased with higher FI scores and with higher physician ratings of damage. The area under the receiver operating characteristic curve for the baseline FI in relation to death was 0.75, higher than for other measures (range: 0.57–0.67).Conclusion.The FI quantifies overall health status in people with scleroderma and predicts mortality. Whether the FI might help with decisions about who might best be served by more aggressive treatment, such as bone marrow transplantation, needs to be evaluated.

Objective.Antinuclear antibodies (ANA) occur in up to 95% of patients with systemic sclerosis (SSc). In most, SSc-associated antibodies are detected (i.e., centromere, topoisomerase I, RNA polymerase III, PM/Scl, Ro52/TRIM21, and U1RNP). Ribonuclease P protein subunit p25, (Rpp25) is an autoantigenic component of the Th/To complex. The contribution of anti-Th/To and anti-Rpp25 antibodies to ANA positivity in patients with SSc remains unknown.Methods.Sera from 873 patients with SSc were tested for ANA, and SSc-associated antibodies were measured. Samples without antibodies to extractable nuclear antigens (ENA; n = 53, ANA+/ENA−), were analyzed by immunoprecipitation (IP) and metabolically labeled proteins and for anti-Rpp25 antibodies (n = 50) by a chemiluminescent immunoassay (CLIA) and Rpp25 ELISA.Results.Anti-Th/To antibodies occurred in 19/53 (36%), as determined by IP, and were the most common autoantibody in ANA+/ENA− SSc. Of those samples, 50/53 were available for additional testing by CLIA and ELISA. Anti-Rpp25 antibodies were detected in 12 (24% CLIA) or 10 (20% ELISA) of 50 patients. Receiver-operating characteristic curve analysis showed similar discrimination between Th/To IP-positive (n = 19) and -negative samples (n = 31) by CLIA and ELISA (area under the curve 0.90 vs 0.87; p = 0.6691). The positive percent agreement between IP and CLIA or ELISA was 12/19 (63.2%, 95% CI 38.4–83.7%) or 10/19 (52.6%, 95% CI 73.3–94.2%), respectively. Negative percent agreement was 100% for both assays.Conclusion.Autoantibodies to the Th/To autoantigen are important in patients with SSc who have been considered negative for SSc-specific or SSc-associated antibodies by widely available commercial assays. Rpp25 can be considered a major target of anti-Th/To antibodies. Assays detecting anti-Th/To and anti-Rpp25 antibodies may be important in SSc.

Objective.To describe the clinical and serological features of systemic sclerosis sine scleroderma (ssSSc) in a multicentered SSc cohort.Methods.Data from 1417 subjects in the Canadian Scleroderma Research Group registry were extracted to identify subjects with ssSSc, defined as SSc diagnosed by an expert rheumatologist, but without any sclerodactyly or skin involvement prior to baseline study visit or during followup. Clinical and serological features of ssSSc subjects were compared to limited (lcSSc) and diffuse cutaneous SSc (dcSSc) subjects.Results.At the first registry visit, only 57 subjects (4.0%) were identified as having ssSSc. Of these, 30 (2.1%) were reclassified as lcSSc within 1.9 years. Thus, only 27 ssSSc subjects (1.9%) remained, with mean followup of 2.4 years. Clinical profiles of ssSSc were generally similar or milder compared to lcSSc, and milder than dcSSc, including rates of interstitial lung disease (25.9% ssSSc, 25.4% lcSSc, 40.3% dcSSc). Patients with ssSSc had serological profiles similar to those with lcSSc, including high rates of anticentromere antibodies (50.0% ssSSc, 47.5% lcSSc, 12.1% dcSSc), and low rates of antitopoisomerase I (16.7% ssSSc, 7.0% lcSSc, 21.8% dcSSc) and anti-RNA polymerase III (0 ssSSc, 11.1% lcSSc, 34.9% dcSSc).Conclusion.The condition ssSSc is rare and resembles lcSSc. These observations suggest that ssSSc is most likely a forme fruste of lcSSc, and that the absence of skin involvement may in part be related to misclassification arising from early or subtle skin involvement. There is little evidence to consider ssSSc as a distinct clinical or serological subset of SSc.

Objective.Interstitial lung disease (ILD) is a common complication of systemic sclerosis (SSc) and causes death. Once lung fibrosis occurs, disease course may become stable or decline. Little is known about risks for progression. We studied SSc–gastroesophageal (GE) involvement in relation to worsening forced vital capacity (FVC) on pulmonary function tests (PFT) to investigate whether it was related to progression. Our objective was to determine whether GE reflux and dysphagia are associated with progressive moderate/severe ILD as measured by PFT over 3 years.Methods.The Canadian Scleroderma Research Group is a multicenter SSc database that collects data annually. Using indicators of GE involvement and annual PFT, comparisons were made between no/mild ILD, stable moderate/severe ILD, and progressive moderate/severe ILD groups based on changes of FVC. Multivariate analyses determined associations between GE factors and ILD development and progression.Results.There were 1043 patients with SSc (mean age 55.7 yrs, mean disease duration 10.8 yrs); one-quarter had pulmonary fibrosis on chest radiograph that was related to FVC percentage predicted (Spearman’s rho −0.39; p < 0.01). Physician indicators such as esophageal dysmotility (p = 0.009) and postesophageal dilatation (p = 0.041), and patient indicators such as difficulty swallowing (p = 0.016) and waking up choking (p = 0.026) were associated with low FVC. In comparing progressive and stable moderate/severe FVC (< 70% predicted), early satiety (p = 0.018) and a combination term of postdilatation and choking (p = 0.042) increased risk of progression of ILD. Topoisomerase I was not associated with progression over followup.Conclusion.Symptoms of esophageal dysmotility were associated with worsening FVC in SSc, especially if both need for esophageal dilatation and choking were present.

Objective.In systemic lupus erythematosus, socioeconomic status (SES) affects outcomes. SES can modify outcomes by altering timing of access to care and adherence. It is unknown whether SES affects systemic sclerosis (SSc) outcomes. Disease can affect income and cause work disability, thus education (completed long before SSc onset) may be a proxy for SES.Methods.The Canadian Scleroderma Research Group collects annual data on patients with SSc. Baseline data were used from a prevalent cohort. Education was stratified by whether participants completed high school. Regression models assessed effects of education on organ complications and survival.Results.In our study, 1145 patients with SSc had 11.0 ± 9.5 years' disease duration; 86% were women, with a mean age of 55.4 ± 12.1 years. About one-quarter did not complete high school; this was more common in older patients (p < 0.0001), men (p = 0.017), those with lower income (p < 0.0001), the unemployed (p < 0.054), smokers (p < 0.001), where DLCO was < 70% predicted (p = 0.009), in those with arthritis (p = 0.047), higher Health Assessment Questionnaire-Disability Index (p = 0.017), elevated erythrocyte sedimentation rate (p = 0.019), median C-reactive protein (p = 0.002), proteinuria (p = 0.016), steroid use ever (p = 0.039), and those more likely to have died in followup (12.7% vs 8.0%; p = 0.024). However, adjusting for confounders, there was no effect of education on mortality; whereas mortality was related to age, diffuse cutaneous SSc (dcSSc) subset, elevated pulmonary arterial (PA) pressure on echocardiography, low forced vital capacity expressed as percentage of predicted, and proteinuria (similar in the dcSSc subset and in limited cutaneous SSc), mortality was increased in older patients, those with elevated PA pressure, and those with low DLCO.Conclusion.Completing less education than high school was not associated with a worse prognosis in SSc after adjustment for confounding characteristics.

Patients with metastatic Colorectal Cancer (mCRC), in which primary tumors are KRAS mutated, have no response to anti-EGFR therapy. However, less than half of mCRC patients with KRAS wild-type primary tumors respond to anti-EGFR therapy. Other downstream effectors of the EGFR pathway are being analyzed to fine-tune KRAS predictive value. However, as the primary tumor is the tissue of analysis that determines the use of anti-EGFR therapy in advanced disease, a high concordance in the status of these effectors between primary tumors and related metastases is required. We analyzed the concordances of downstream EGFR effectors in tumoral pairs of primaries and related metastases in a series of KRAS wild-type patients. One hundred seventeen tumoral pairs from patients with CRC were tested for KRAS mutational status. The level of concordance in the presence of KRAS mutations was 91 between the primary tumor and related metastases. The 70 pairs with KRAS wild-type primary tumors were further analyzed for BRAF and PIK3CA mutational status and for EGFR, PTEN and pAKT expression, and the number of concordant pairs was 70 (100), 66 (94), 43 (61), 46 (66) and 36 (54), respectively. Our findings suggest that the mutational status of KRAS, BRAF and PIK3CA in the primary tumor is an adequate surrogate marker of the status in the metastatic disease. On the other hand, the immunohistochemical analysis of EGFR, PTEN and pAKT showed a much higher degree of discordance between primaries and related metastases.

Morphology, electronic structure, and CO adsorption of gold supported on well-ordered CeO2(111) thin films and CeOxnanoparticles were studied by scanning tunneling microscopy (STM), photoelectron spectroscopy (XPS), and infrared reflection absorption spectroscopy (IRAS). Ceria nanoparticles grown on crystalline thin silica films possess Ce in both the 3+ and 4+ oxidation states, with the former dominating in smaller particles. Upon deposition on CeO2(111) films, most of the Au particles are formed at the step edges. The particles on terraces grow presumably through the decoration of point defects, which are more numerous on reduced surfaces. Combined XPS and IRAS data show that partially charged Auδ+species are formed by deposition at low temperatures (∼100 K) and low coverages on both ceria supports. Formation of Auδ+on CeO2(111) films is kinetically limited and is attributed to the interaction of the gold ad-atoms with defects. In variance to extended ceria surfaces, where only metallic Au nanoparticles are observed at 300 K, the “cationic” gold species are formed in abundance on nano-CeOxand exhibit enhanced thermal stability. It is shown that nanoceria stabilizes small Au clusters, which may even be incorporated into the ceria nanoparticles at elevated temperatures.

The low-temperature deposition of Au and Pd atoms on thin SiO2films grown on Mo(112) has been studied by scanning tunneling microscopy (STM), infrared reflection absorption spectroscopy, and CO adsorption. On the monolayer films, gold forms three-dimensional nanoparticles at temperatures as low as 10 K and does not affect the phonon spectra of the silica films. On the other hand, palladium exhibits structure-dependent behavior. Pd deposition leads to a red-shift of the phonon frequency of the monolayer and not of the multilayer films. The amount of CO that may adsorb on the Pd particles formed on the “O-poor” monolayer films is much smaller than that on the “O-rich” films (with an additional O-layer on the Mo surface) and multilayer films. These experimental findings have been rationalized on the basis of density functional theory calculations showing that the Pd atoms penetrate into the hexagonal rings of the silica network and bind at the SiO2/Mo interface, which in turn depends on the atomic structure of the film. This bonding is very strong on the O-poor films so that Pd is unable to bind CO, while on the O-rich films CO may even pull out the Pd atoms from the interface thus promoting aggregation and particle formation. The Pd migration into the film has been directly supported by low-temperature STM images.

Objective. To identify the determinants of medication non-adherence in women with fibromyalgia (FM).Methods. Participants included 10 rheumatologists and 127 women recruited from tertiary care hospitals and the community. Demographic, clinical and psychosocial characteristics and patient–physician discordance were assessed at the baseline visit. Non-adherence was assessed 2 weeks later. Multivariable generalized estimating equations were used to identify determinants of non-adherence to medication.Results. The average age of the women was 50.4 (s.d. 10.5) yr and the mean disability score was 60.3 (16.0) yr. Sixty (47.2%) women were non-adherent to medication; 20 (33.3%) of these were intentionally non-adherent, 24 (40.0%) were unintentionally non-adherent, and the remaining subjects were both. Overall non-adherence was predicted by higher patient–physician discordance. Unintentional non-adherence was predicted by community subjects, not being under a rheumatologist’s care, less disease activity, less use of instrumental coping, and higher patient–physician discordance. Intentional non-adherence was predicted by shorter duration under a rheumatologist’s care and higher patient–physician discordance.Conclusion. The therapeutic relationship, in addition to clinical and psychosocial characteristics, influenced non-adherence to medication.

The objective of this study was to assess whether the APOEPittsburgh variant (APOE*4P) is associated to Alzheimer's disease (AD) in a population from Madrid (Spain). APOE*4P variant is caused by an exonic mutation which results in the substitution of proline-28 for leucine-28, only present in APOE*4 alleles. A study in a US population associated this APOE variant with an increased risk for AD, about five times higher than the risk attributed to APOE*4 carriers overall. One hundred and seventeen cases of late-onset AD and 121 matched control subjects from Madrid (Spain) were included. We studied the APOE polymorphism and the APOE*4P occurrence, by PCR and restriction analysis, and plasma lipids levels using standard protocols. As expected, APOE*4 was significantly overrepresented in AD cases. The APOE*4P mutation was observed in heterozygous state in four subjects, two AD (1.71%) and two controls (1.65%). APOE*4P did not confer higher risk for AD, globally (odds ratio 0.14; 95% confidence interval (CI) 0.02–1.12) or respect to APOE*4 carriers (odds ratio 0.14; 95% CI 0.02–1.24). There were no differences in plasma lipids levels among genotype groups. The mutation frequency in controls was higher in our sample than in the US one (1.65 and 0.18%, respectively; Fisher test P = 0.049). Our results suggest that this variant is not so uncommon in our population and is not directly related to AD, contrary to what has been proposed for other populations. © 2003 Wiley-Liss, Inc.

FTIR with attenuated total reflectance spectroscopy was used to study in situ adsorption of enzymes at water–solid interfaces to better understand how conformational changes may monitor enzymatic activity. Because the adsorption process depends on hydrophobic and electrostatic interactions, conformational changes were studied as a function of the nature of the adsorbing substrates, which are hydrophobic or hydrophilic in character. The adsorption kinetics of two examples of serine enzymes, α-chymotrypsin (α-chym) and Humicola lanuginosa lipase (HLL), were studied. The secondary structure and solvation of the adsorbed enzymes were both compared to the dissolved enzymes. The positively charged α- chym was adsorbed on a negatively charged hydrophilic support with minor structural changes, but the negatively charged lipase had no affinity for a similar support. Both enzymes were strongly retained on the hydrophobic support. The secondary and tertiary structures of the α-chym adsorbed on the hydrophobic support were strongly altered, which correlates to the inhibition of enzymatic hydrolysis. The specific solvation obtained for the adsorbed HLL is consistent with the existence of the open conformer in relation to the enhanced enzymatic activity at the water–hydrophobic interface. © 2002 Wiley Periodicals, Inc. Biopolymers (Biospectroscopy) 67: 323–326, 2002