Ultrasound Doppler enthesitis shows sensitivity to change after biological therapy in spondyloarthritis and psoriatic arthritis patients.

OBJECTIVE: To explore the sensitivity to change in power Doppler (PD) enthesitis in active spondyloarthritis (SpA) and psoriatic arthritis (PsA) patients. METHOD: This was a longitudinal study in patients with SpA and PsA with active disease [patients starting or switching to biological disease-modifying anti-rheumatic drugs (bDMARDs)]. The MAdrid Sonographic Enthesitis Index (MASEI) was performed at baseline and at 3 and 6 month visits. The MASEI and Outcome Measures in Rheumatology (OMERACT) PD enthesitis definitions were checked. Reliability analysis among three readers was performed with ultrasound (US)-recorded videos. RESULTS: US examinations of 25 patients were included; 16 (64%) had SpA and nine (36%) PsA. The median (interquartile range, IQR) age was 49 (41-61) years, and 13 patients (52%) were female. The median (IQR) 28-joint Disease Activity Score of 3.6 (2.3-4.2), Bath Ankylosing Spondylitis Disease Activity Index of 6.7 (6.1-7.4), and C-reactive protein value of 8.2 (1.6-20) reflected moderate to high disease activity at baseline. Both MASEI and OMERACT PD enthesitis improved significantly at 3 and 6 month follow-up (p < 0.05) and showed sensitivity to change (standard error of measurement = 0.47 and 0.61, respectively). Improvement in clinical activity outcomes was significantly associated with decreases in MASEI and OMERACT PD enthesitis counts (p < 0.05). The MASEI and OMERACT PD definitions had excellent reliability (kappa = 0.918 and 0.865, respectively). CONCLUSION: PD enthesitis significantly improved at 3 and 6 month follow-up in patients undergoing bDMARD therapy. Both MASEI and OMERACT PD US enthesitis reflect response to treatment.

Use of Diode Laser for Lip Repositioning, Evolution of the Conventional Technique. A Case Report.

INTRODUCTION: LipStaT® lip repositioning surgery using a diode laser for the management of gummy smiles offers promising and consistent long-term results. OBJECTIVE: To describe the technique through a clinical case, including its indications, preoperative evaluation, surgical approach, and recommendations after the intervention. CASE REPORT: A 29-year-old woman with excessive gingival display (EGD) of 4 mm when smiling; the LipStaT® technique was performed with a 940 nm diode laser to remove a strip of mucosa by ablating the epithelial tissue, and thus, achieve aesthetic, harmonic and functional results. The inflammation and postoperative pain were treated with the diode laser assisted lymphatic drainage technique. After follow-up, a satisfactory tissue response was observed, and no pain or inflammation was reported. CONCLUSION: The use of a 940 nm diode laser proved to be an effective treatment option for patients with a gummy smile, allowing control of intraoperative bleeding and improvement of the healing process obtaining predictable long-term results.

Bivalent engagement of endothelial surface antigens is critical to prolonged surface targeting and protein delivery in vivo.

Targeted drug delivery to the endothelium has the potential to generate localized therapeutic effects at the blood-tissue interface. For some therapeutic cargoes, it is essential to maintain contact with the bloodstream to exert protective effects. The pharmacokinetics (PK) of endothelial surface-targeted affinity ligands and biotherapeutic cargo remain a largely unexplored area, despite obvious translational implications for this strategy. To bridge this gap, we site-specifically radiolabeled mono- (scFv) and bivalent (mAb) affinity ligands specific for the endothelial cell adhesion molecules, PECAM-1 (CD31) and ICAM-1 (CD54). Radiotracing revealed similar lung biodistribution at 30 minutes post-injection (79.3% ± 4.2% vs 80.4% ± 10.6% ID/g for αICAM and 58.9% ± 3.6% ID/g vs. 47.7% ± 5.8% ID/g for αPECAM mAb vs. scFv), but marked differences in organ residence time, with antibodies demonstrating an order of magnitude greater area under the lung concentration vs. time curve (AUCinf 1698 ± 352 vs. 53.3 ± 7.9 ID/g*hrs for αICAM and 1023 ± 507 vs. 114 ± 37 ID/g*hrs for αPECAM mAb vs scFv). A physiologically based pharmacokinetic model, fit to and validated using these data, indicated contributions from both superior binding characteristics and prolonged circulation time supporting multiple binding-detachment cycles. We tested the ability of each affinity ligand to deliver a prototypical surface cargo, thrombomodulin (TM), using one-to-one protein conjugates. Bivalent mAb-TM was superior to monovalent scFv-TM in both pulmonary targeting and lung residence time (AUCinf 141 ± 3.2 vs 12.4 ± 4.2 ID/g*hrs for ICAM and 188 ± 90 vs 34.7 ± 19.9 ID/g*hrs for PECAM), despite having similar blood PK, indicating that binding strength is more important parameter than the kinetics of binding. To maximize bivalent target engagement, we synthesized an oriented, end-to-end anti-ICAM mAb-TM conjugate and found that this therapeutic had the best lung residence time (AUCinf 253 ± 18 ID/g*hrs) of all TM modalities. These observations have implications not only for the delivery of TM, but also potentially all therapeutics targeted to the endothelial surface.

[Clinical pharmacy activities coordination in an adult psychiatry unit: Clinical and medicoeconomic impact of pharmaceutical interventions]. / Coordination des activités de pharmacie clinique dans une unité de psychiatrie adulte : impact clinique et médicoéconomique des interventions pharmaceutiques.

OBJECTIVE: Coordination and evaluation of clinical pharmacy activities are necessary to optimize their achievement. Their coordination throughout patient care program was studied in an adult psychiatry unit. The purpose was to evaluate clinical and medicoeconomic impact of pharmaceutical interventions (PIs). METHOD: During five weeks, a full time pharmaceutical presence in the unit allowed medication reconciliation, medication review and multiprofessional meetings. A multiprofessional assessment of PIs impact has been achieved with the CLEO® tool and a determination of direct drug costs was realized. RESULTS: All activities combined, 190 PIs were issued, half during multiprofessional meetings, with an acceptance rate of 67.9% (100% for PIs realized during direct interactions with clinicians). All clinical pharmacy activities demonstrated relevance according to CLEO® scale's dimensions. Around 400€ were saved on direct drug costs and an avoidance of potential prolongation of hospitalization was identified in 6 PIs. CONCLUSION: PIs number, acceptance rate and evaluation results show individual impact of activities, their complementarily and the added value of their coordination. Collaboration between professionals contributed to an efficient and secure medication management. These results are reasons to optimize clinical pharmacy practice in the healthcare facility.

Ultrasonography of enthesis in psoriatic arthritis: a descriptive and reliability analysis of elemental lesions and power Doppler subtypes.

Objective: To evaluate the reliability and prevalence of enthesis ultrasound (US) elemental lesions in patients with psoriatic arthritis (PsA), using the Madrid Sonographic Enthesis Index (MASEI) and Outcome Measures in Rheumatology (OMERACT) definitions.Methods: The study included 27 PsA patients with metacarpophalangeal joint swelling. An US rheumatologist performed the MASEI examination. Prevalence and reliability of the included elemental lesions [structure, thickness, erosion, enthesophytes, power Doppler (PD), and bursae] were evaluated. In addition, three other PD definitions were checked: PD OMERACT (≤ 2 mm to the bone profile), PD enthesis-tendon (> 2 mm from the bone profile), and PD bursa. Short (3-5 s) videos of US examinations were recorded for reliability assessment.Results: MASEI and all PD definitions showed good to excellent reliability. The best reliability values were found in erosions, bursae, and PD. When present, the PD signal always appeared in more than one location of the evaluated areas. Enthesis Doppler was present in 81.5% of patients. Abnormal tendon structure and enthesophytes were the most prevalent lesions.Conclusion: MASEI demonstrates to be a reliable tool in PsA. All enthesis US Doppler definitions demonstrate to be reliable for its use in PsA with minimal differences, being PD MASEI the most sensitive in active patients.

Progestin-associated shift of meningioma mutational landscape.

Background: Meningiomas are the most common primary tumor of the central nervous system. The relationship between meningioma and progestins is frequently mentioned but has not been elucidated. Patients and methods: We identified 40 female patients operated for a meningioma after long-term progestin therapy and performed targeted next generation sequencing to decipher the mutational landscape of hormone-related meningiomas. A published cohort of 530 meningiomas in women was used as a reference population. Results: Compared with the control population of meningiomas in women, progestin-associated meningiomas were more frequently multiple meningiomas [19/40 (48%) versus 25/530 (5%), P < 10-12] and located at the skull base [46/72 (64%) versus 241/481 (50%), P = 0.03]. We found a higher frequency of PIK3CA mutations [14/40 (35%) versus 18/530 (3%), P < 10-8] and TRAF7 mutations [16/40 (40%) versus 140/530 (26%), P < 0.001] and a lower frequency of NF2-related tumors compared with the control population of meningiomas [3/40 (7.5%) versus 169/530 (32%), P < 0.001]. Conclusion: This shift in mutational landscape indicates the vulnerability of certain meningeal cells and mutations to hormone-induced tumorigenesis. While the relationship between PIK3CA mutation frequency and hormone-related cancers such as breast and endometrial cancer is well-known, this hormonally induced mutational shift is a unique feature in molecular oncology.

Colonic Bacteroides are positively associated with trabecular bone structure and programmed by maternal vitamin D in male but not female offspring in an obesogenic environment.

BACKGROUND/OBJECTIVES: The gut microbiota is determined early in life, possibly including pregnancy. Pioneering data suggest vitamin D, a nutrient important for bone health, affects this microbiota. We found that high maternal vitamin D lowered circulating lipopolysaccharide (LPS), improved intestinal barrier and bone health in male but not female offspring in an obesogenic environment. This study determined if high maternal dietary vitamin D programs Bacteroides and Prevotella and whether this associates with bone mineral content, density and structure of male and female adult offspring fed an obesogenic diet. METHODS: C57BL/6J females received an AIN93G diet with high or low vitamin D from before mating until weaning. Post-weaning, male and female offspring remained on their respective vitamin D level or were switched and fed a high fat and sucrose diet until killing (age 7 months). Bacteroides and Prevotella were quantified in dams' feces and offspring colonic contents. LPS concentrations, bone mineral density and content, strength and structure data were integrated from our previous studies in the same mice. Spearman correlations were completed between Bacteroides and LPS, and bone outcomes. RESULTS: There was a maternal vitamin D effect on colonic Bacteroides but not Prevotella (dam diet: <0.001 and 0.735) in adult male offspring, independent of dams fecal Bacteroides before birth (P=0.998). In males, but not females, Bacteroides correlated with LPS (r=-0.488, P=0.018), trabecular femur peak load (r=0.362, P=0.033), vertebral trabecular separation (r=-0.605, P=0.006), trabecular number (r=0.614, P=0.005) and bone volume fraction (r=0.549, P=0.015). CONCLUSIONS: Dietary vitamin D programs Bacteroides in male adult offspring only, which correlated negatively with systemic inflammation and positively with bone strength and structure. This may have implications on maternal diet and nutritional guidelines targeting sexes in a different manner.

Genome-wide association analysis of body conformation traits in Mexican Holstein cattle using a mix of sampled and imputed SNP genotypes.

In arid and semi-arid zones, animal health and production are closely correlated with body conformation traits. These selected traits, in turn, allow livestock to adapt unfavorable soil and environmental conditions. The primary objective of this study was to perform a genome-wide association analysis for a set of sampled and imputed SNPs with 16 conformation traits in a population of Holstein cows from a desert area of Northwestern Mexico. Imputation from 6K to 50K SNPs was performed as a low-cost optimization strategy. Results show eight SNPs associated with two conformation traits. The Udder Depth trait resulted in seven associated SNPs from chromosome 10, that related to Marbling Score, Milk Yield, Fat Yield, Protein Yield, and Protein Percentage Quantitative Trait Loci (QTLs). The Body Depth trait resulted in one associated SNP from chromosome 2, although no QTL relation was found. The discovery of genes associated with conformation traits may be indicative of the adaptive selection pressures the Holstein breed has undergone in response to the extreme weather conditions found in the northwestern areas of Mexico. Results of this study indicate that traits such as stature and body depth may be used as indicators of cows' potential genetic merits for milk, fat, and protein production.

Favorable Waitlist and Posttransplant Outcomes in Children and Adolescent Patients Supported With Durable Continuous-Flow Ventricular Assist Devices.

Pediatric centers are implanting durable adult continuous-flow ventricular assist devices (CFVADs) in children who are smaller than the industry-recommended size. Waitlist and posttransplant outcomes data in pediatric patients supported with CFVADs as a bridge to transplant are limited. We analyzed the United Network of Organ Sharing and Organ Procurement and Transplantation Network registry to identify patients aged ≤18 years with a CFVAD at the time of listing or transplantation. Patients were stratified by body surface area (BSA; >1.5 vs. ≤1.5 m(2) ) at time of listing. We identified 138 patients with a durable CFVAD during the listing period (100 with BSA >1.5 m(2) , 38 with BSA ≤1.5 m(2) ). Patients with BSA ≤1.5 m(2) were more likely to have a noncardiomyopathy diagnosis (18% vs. 4%, p = 0.007) and to be implanted with a centrifugal-flow rather than an axial-flow device (74% vs. 30%, p = 0.001). There was no difference in failure-free waitlist survival between BSA groups (p = 0.99) among patients with a CFVAD at listing. Posttransplantation survival was 100% and 88% at 1 and 5 years, respectively, for the entire cohort and did not differ by BSA group (p = 0.99). Consequently, waitlist and posttransplant outcomes are favorable for pediatric CFVAD recipients. Small patients (≤1.5 m(2) ) had pre- and posttransplant outcomes similar to those of larger patients that met the industry-recommended size for implantation.

Maternal vitamin D beneficially programs metabolic, gut and bone health of mouse male offspring in an obesogenic environment.

BACKGROUND/OBJECTIVES: Vitamin D is an anti-inflammatory nutrient and a determinant of bone health. Some prospective studies suggest that maternal vitamin D status is positively associated with offspring bone mass. We found that serum concentrations of lipopolysaccharide (LPS), an inflammatory molecule related to adiposity, insulin resistance and bone resorption, is lower in healthy mouse offspring exposed to high dietary vitamin D during pregnancy and lactation. LPS reaches the circulation via the gut. This study investigated whether maternal vitamin D programs metabolic, gut and bone health of male offspring in an obesogenic environment. METHODS: C57BL/6J dams received an AIN-93G diet with high (H) or low (L) vitamin D during pregnancy and lactation. At weaning, offspring remained on their dam's vitamin D level (LL or HH) or were switched (LH or HL) and fed a high fat (44.2%) and sucrose (19.8%) diet. Glucose response, adiposity, systemic inflammation (LPS, cytokines), intestinal permeability and mass, strength and microarchitecture of trabecular and cortical bone were assessed in 7-month-old male offsprings. RESULTS: Higher maternal dietary vitamin D resulted in lower intestinal permeability (fecal albumin, P=0.010) and benefited trabecular but not cortical bone structure at the distal femur (higher trabecular number, P=0.022; less trabecular separation, P=0.015) and lumbar vertebra 2 (bone volume/total volume%, P=0.049). Higher maternal and offspring vitamin D resulted in lower fasting glucose (HH versus LL, P=0.039) and serum LPS concentrations (dam diet, P=0.011; pup diet, P=0.002). Higher offspring vitamin D resulted in lower epididymal fat pad relative weight (P=0.006). The serum concentrations of IL-6 and TNF-α did not differ among groups. CONCLUSIONS: Maternal dietary vitamin D beneficially programs intestinal permeability and systemic LPS concentration, which is accompanied by stronger trabecular bone in an obesogenic environment. Thus, the gut may mediate vitamin D effects. Moreover, optimizing vitamin D in early life may be critical for later health.

Slipped capital femoral epiphysis in adults: case report and review of literature.

Slipped capital femoral epiphysis (SCFE) mainly affects overweight prepubertal children. It is usually idiopathic, but endocrinological diseases are proposed as the main cause. SCFE occurs before the closing of the femoral physis, which generally occurs at 18 years in males and 16 years in females, therefore it is considered a children's disease. However, there have been several reports of adults with SCFE and some familial cases. We present a case of bilateral SCFE in a 47 years old female with possible relationship with inhaled corticosteroids, and for the first time we collect and analyze all published cases in adults.

Assessment of fetal cardiomyopathy in early-stage twin-twin transfusion syndrome: comparison between commonly reported cardiovascular assessment scores.

OBJECTIVES: To assess the relationship between commonly reported fetal cardiomyopathy scoring systems in early-stage twin-twin transfusion syndrome (TTTS). METHODS: We reviewed retrospectively 100 cases of Quintero Stages I and II TTTS referred to our center for evaluation from 2008 to 2010. The cases were divided into groups of 25, representing each of four grades of TTTS cardiomyopathy as assessed by Cincinnati stage: no cardiomyopathy, Stage IIIa, Stage IIIb and Stage IIIc. Spearman correlation (rs ) was calculated between the Children's Hospital of Philadelphia (CHOP) score, cardiovascular profile score (CVPS), Cincinnati stage and myocardial performance index (MPI). RESULTS: There was a weak correlation between the Cincinnati stage and the CHOP score (rs = 0.36) and CVPS (rs = -0.39), while correlation was strong between the CHOP score and CVPS (rs = -0.72). MPI elevation was concordant with Cincinnati stage more frequently (82% of cases) than were ventricular hypertrophy (43%) or atrioventricular valve regurgitation (28%). 51% of fetuses with minimally elevated CHOP score (0-1) and 48% of fetuses with minimally depressed CVPS (9-10) had significant elevation (Z-score ≥ +3) in right ventricular or left ventricular MPI. CONCLUSIONS: MPI has a strong influence on grading the severity of fetal cardiomyopathy using the Cincinnati stage among fetuses with mild TTTS. Furthermore, significant elevation of the MPI is common among fetuses with mild disease as assessed by the CHOP score and CVPS. These differences should be understood when assessing and grading cardiomyopathy in TTTS, particularly in early (Quintero Stages I and II) disease.

Aqueous dispersions of organogel nanoparticles - potential systems for cosmetic and dermo-cosmetic applications.

OBJECTIVE: The preparation and physicochemical characterization of organogel nanoparticles dispersed in water have been developed. These systems could be employed as nanocarrier for cosmetic applications or as hydrophobic reservoirs for drug delivery. METHODS: Gelled particles of organic liquid and 12-hydroxystearic acid (organogelator) were obtained by hot emulsification (T>Tgel), with a surfactant (acetylated glycol stearate) and polymers (sodium hyaluronate and polyvinyl alcohol) as stabilizing agents, and cooling at room temperature (T

[Consensus document on ultrasound training in Intensive Care Medicine. Care process, use of the technique and acquisition of professional skills]. / Documento de consenso para la formación en ecografía en Medicina Intensiva. Proceso asistencial, uso de la técnica y adquisición de competencias profesionales.

Ultrasound has become an essential tool in assisting critically ill patients. His knowledge, use and instruction requires a statement by scientific societies involved in its development and implementation. Our aim are to determine the use of the technique in intensive care medicine, clinical situations where its application is recommended, levels of knowledge, associated responsibility and learning process also implement the ultrasound technique as a common tool in all intensive care units, similar to the rest of european countries. The SEMICYUC's Working Group Cardiac Intensive Care and CPR establishes after literature review and scientific evidence, a consensus document which sets out the requirements for accreditation in ultrasound applied to the critically ill patient and how to acquire the necessary skills. Training and learning requires a structured process within the specialty. The SEMICYUC must agree to disclose this document, build relationships with other scientific societies and give legal cover through accreditation of the training units, training courses and different levels of training.

The Dural Dark-Side Approach for falcine and tentorial meningioma: A surgical series of five patients.

INTRODUCTION: Falcine or tentorial meningioma can be complex to resect. When large meningiomas are located in eloquent areas, a direct ipsilateral surgical approach may cause brain injury and postoperative neurological deficits. In this series, 5 patients were surgically treated using a contralateral transfalcine or transtentorial approach to minimize brain retraction. This strategy was called the Dural Dark-Side Approach (DDSA). The aim was to analyze the quality of tumor resection and postoperative outcome. MATERIAL AND METHODS: In our department, from June 2018 to January 2020, 5 patients underwent microsurgical DDSA for resection of 4 falcine and 1 tentorial meningioma. All tumors were selected on the following two criteria: large>40mm diameter tumor, with surrounding functional cortex. Clinical and radiologic data were retrospectively analyzed. RESULTS AND DISCUSSION: Mean follow-up was 20 months. No patients required use of a rigid retractor during surgery. Gross total resection was performed in 3 patients and near-total resection in 2. All patients had favorable neurologic outcome. Postoperative MRI showed no ipsilateral or contralateral brain lesions. CONCLUSION: This series suggested that meticulous DDSA allows excellent resection in selected large falcine or tentorial meningioma. The approach offered a safe and effective surgical corridor without injuring the surrounding healthy parenchyma.

Inhibition of the immunoproteasome modulates innate immunity to ameliorate muscle pathology of dysferlin-deficient BlAJ mice.

Muscle repair in dysferlinopathies is defective. Although macrophage (Mø)-rich infiltrates are prominent in damaged skeletal muscles of patients with dysferlinopathy, the contribution of the immune system to the disease pathology remains to be fully explored. Numbers of both pro-inflammatory M1 Mø and effector T cells are increased in muscle of dysferlin-deficient BlAJ mice. In addition, symptomatic BlAJ mice have increased muscle production of immunoproteasome. In vitro analyses using bone marrow-derived Mø of BlAJ mice show that immunoproteasome inhibition results in C3aR1 and C5aR1 downregulation and upregulation of M2-associated signaling. Administration of immunoproteasome inhibitor ONX-0914 to BlAJ mice rescues muscle function by reducing muscle infiltrates and fibro-adipogenesis. These findings reveal an important role of immunoproteasome in the progression of muscular dystrophy in BlAJ mouse and suggest that inhibition of immunoproteasome may produce therapeutic benefit in dysferlinopathy.

Impulse control disorders and dopaminergic treatments in Parkinson's disease.

A group of disorders sharing a failure to resist an impulse to perform a typically pleasurable activity that is finally harmful to the person or to others are known under the common denomination of impulse control disorders (ICDs). These behaviors, possibly previously neglected by lack of awareness, are increasingly reported among PD patients. Compelling evidence has stressed the relation between dopaminergic replacement and development of ICDs in PD, especially but not exclusively, with dopamine agonist therapy. Besides dopaminergic replacement, younger age, smoking habit, presence of familiar gambling problems and alcohol abuse can increase the risk. ICDs in PD may greatly affect patients and caregivers quality of life, stressing the importance of their screening. Management strategies include a careful use of dopaminergic therapy using the lowest effective doses.

Estimation of the body center of mass velocity during gait of people with transfemoral amputation from force plate data integration.

BACKGROUND: Body Center Of Mass velocity assessment is a prerequisite for several applications in prosthetic control and rehabilitation monitoring. Force plate data integration is a promising alternative to full-body quantitative analysis of segmental kinematics to estimate the velocity. Still, it remains to be implemented and validated for people with transfemoral amputation. METHODS: Two methods were used (force plate based and pelvic markers based) for Body Center Of Mass velocity estimation in a clinical context. The two methods were comparatively assessed on overground walking data of eight people with transfemoral amputation in a laboratory equipped with a motion capture system and force plates compared to reference estimation derived from a full body segmental gait analysis. The 'Methods' agreement with the reference was quantified from the Bland and Altman procedure. FINDINGS: The estimation of Body Center Of Mass velocity from force plate data integration was considered acceptable in terms of limits of agreement. In addition, the hypotheses used to determine integration constants were evaluated and shown to be reasonable as far as the walking direction is well controlled. INTERPRETATION: Results demonstrate the possibility to use the force plate method to assess the Body Center Of Mass velocity of people with transfemoral amputation for straight walking on level ground. An estimation from the velocity of pelvic markers can also be a relevant alternative as soon as the walking velocity remains low. Further investigation will deal with the impact of the errors on the computation of derived parameters such as individual limb power.