Can the Dose of Belimumab be Reduced in Patients with Systemic Lupus Erythematosus?

OBJECTIVES: The aims of this study were to investigate the prevalence of dose reduction in patients with SLE treated with belimumab (BEL) in Spain, analyze treatment modalities, and determine impact on control of disease activity. METHODS: Retrospective longitudinal and multicentre study of SLE patients treated with BEL. Data on disease activity, treatments and outcomes were recorded before and after reduction (6-12 months), and they were compared. RESULTS: A total of 324 patients were included. The dose was reduced in 29 patients (8.9%). The dosing interval was increased in 9 patients receiving subcutaneous BEL and in 6 patients receiving intravenous BEL. The dose per administration was reduced in 16 patients.Pre-reduction status was remission (2021 DORIS) in 15/26 patients (57.7%) and LLDAS in 23/26 patients (88.5%). After reduction, 2/24 patients (8.3%) and 3/22 patients (13.6%) lost remission at 6 months and 12 months, respectively (not statistically significant [NS]). As for LLDAS, 2/23 patients (8.7%) and 2/21 patients (9.5%) lost their status at 6 and 12 months, respectively (NS). Significantly fewer patients were taking glucocorticoids (GCs) at their 12-month visit, although the median dose of GCs was higher at the 12-month visit (5 [0.62-8.75] vs 2.5 [0-5] at baseline). CONCLUSION: Doses of BEL can be reduced with no relevant changes in disease activity-at least in the short term-in a significant percentage of patients, and most maintain the reduced dose. However, increased clinical or serologic activity may be observed in some patients. Consequently, tighter post-reduction follow-up is advisable.

Role of PI3K, ERK1/2, and JAK2 Kinases in the Cardioprotective Effect of Deltorphin II during Cardiac Reperfusion.

The signaling mechanism of the cardioprotective effect of deltorphin II was studied in models of coronary occlusion (45 min) and reperfusion (120 min) in male Wistar rats. We used the selective δ2-opioid receptor agonist deltorphin II (0.12 mg/kg), which was administered intravenously 5 min before reperfusion, the PI3K inhibitor wortmannin (0.025 mg/kg), the ERK1/2 blocker PD-098059 (0.5 mg/kg), the inhibitor JAK2 AG490 (3 mg/kg). All kinase blockers were administered 10 min before reperfusion. The infarct-limiting effect of deltorphin II is associated with the activation of PI3K and ERK1/2 and does not depend on JAK2.

The Role of NO Synthase, MPT pore, and Protein Kinase A in the Cardioprotective Effect of the Opioid Receptor Agonist Deltorphin II.

In male Wistar rats, coronary occlusion (45 min) and reperfusion (120 min) were modeled. Selective δ2-opioid receptor agonist (deltorphin II, 0.12 mg/kg) was administered intravenously 5 min before reperfusion; NO synthase inhibitor (L-NAME, 10 mg/kg), MPT pore blocker (atractyloside, 5 mg/kg), and protein kinase A inhibitor (H-89, 10 µg/kg) were administered intravenously 10 min before reperfusion. Deltorphin II administered before reperfusion led to a 2-fold decrease in the infarct size. The infarct-limiting effect of deltorphin II was associated with blockade of MPT pore. Protein kinase A and NO synthase were not involved in the cardioprotective effect of deltorphin II.

Correction to: Fraction of high-grade cervical intraepithelial lesions attributable to genotypes targeted by a nonavalent HPV vaccine in Galicia, Spain.

After publication of the article [1], it was brought to our attention that the author E. López-Díez is missing their second affiliation. The author would also like to indicate an affiliation to "Universidade de Vigo, Pontevedra, Spain".

Can we afford to offer pre-exposure prophylaxis to MSM in Catalonia? Cost-effectiveness analysis and budget impact assessment.

Pre-exposure prophylaxis (PrEP) effectiveness has been well established. This study aims to assess the cost-effectiveness of providing PrEP, estimate the number of eligible MSM, and its budget impact in Catalonia. Cost-effectiveness analysis compared costs of on daily basis and "on demand" PrEP to prevent one infection with lifetime costs of one HIV infection. We estimated the total cost of providing PrEP by estimating number of eligible MSM, and included in the budget impact assessment antiretroviral and laboratory costs. Costs were lower for the on-demand PrEP group by €64015.1 and the incremental benefit was nearly 15 life-years and 17 quality-adjusted life-years gained. The incremental cost-effectiveness ratio (ICER) was cost-effective at €6281.62 when undiscounted PrEP was given daily. On-demand PrEP can be considered cost-saving in 20 years if the price is reduced by 90%. The number of eligible MSM in Catalonia ranges from 5,989 to 10,972. At current antiretroviral costs, the annual cost would range between €25.3-46.7 million/year (on demand PrEP), and €42.9-78.7 million/year (daily basis PrEP). PrEP is most cost-effective if targeted towards groups with high incidence rates of over 3%/year. Beneficial ICER depends on reducing the current price of Truvada® and ensuring that effectiveness is maintained at high levels.

Fraction of high-grade cervical intraepithelial lesions attributable to genotypes targeted by a nonavalent HPV vaccine in Galicia, Spain.

BACKGROUND: Human papillomavirus (HPV) bivalent and quadrivalent vaccines have been widely implemented in worldwide organized immunization programs. A nonavalent HPV vaccine is now available in several countries. The objective was to describe the fraction of squamous non-invasive high-grade cervical intraepithelial lesions attributable to genotypes targeted by bi-quadrivalent vaccines and by nonavalent vaccine according to age and diagnosis in women living in the city of Vigo (Galicia, Spain). METHODS: Cervical scrapings (2009-2014) of women with histological diagnosis of cervical intraepithelial neoplasia grade 2 (CIN2, n = 145) and grade 3-carcinoma in situ (CIN3-CIS, n = 244) were tested with Linear Array HPV Genotyping test (Roche diagnostics, Mannheim, Germany). Hierarchical estimation of the fraction attributable to HPV 16/18 or HPV 31/33/45/52/58 detected alone or in combination was calculated. Absolute additional fraction attributable to genotypes targeted by nonavalent vaccine compared to genotypes targeted by bi-quadrivalent vaccines was calculated as the increment of attributable cases with respect to all studied cases. Age group 1, 2 and 3 included women 18 to 34, 35-44 and ≥45 years old, respectively. EPIDAT 3.1 was used. RESULTS: Fraction attributable to genotypes targeted by bi-quadrivalent vaccines was 59% CIN2 vs. 69% CIN3-CIS (p < 0.001). It was 63/51/50% of CIN2 and 78/66/45% of CIN3-CIS in age group 1, 2, 3, respectively. Fraction attributable to genotypes targeted by nonavalent vaccine was 86% CIN2 and 86% CIN3-CIS. It was 87/91/75% of CIN2 and 90/86/76% of CIN3-CIS in age group 1, 2, 3, respectively. Fraction attributable to genotypes targeted by these vaccines tended to decrease as age increased (p-trend <0.05). Globally, absolute additional attributable fraction was 16%, 26% and 29% in age group 1, 2 and 3, respectively (p < 0.005). CONCLUSIONS: Absolute additional fraction of CIN2 and CIN3-CIS attributable to genotypes targeted by nonavalent vaccine was observed in women of any age, especially in those over 35 years old.

Description of Patients Undergoing Mohs Surgery in Spain: Initial Report on Data From the Spanish Registry of Mohs Surgery (REGESMOHS).

INTRODUCTION: The Spanish registry of Mohs micrographic surgery started collecting data in July 2013. The aim of the registry is to report on the use of this technique in Spain and the outcomes achieved. In the present article, we describe the characteristics of patients and the tumors treated. MATERIAL AND METHODS: This is a prospective cohort study of patients treated with Mohs micrographic surgery. The participating centers are hospitals where at least one intervention of this type is performed each week. All patients considered for Mohs micrographic surgery in participating centers are included in the registry except those who have been declared legally incompetent. RESULTS: Between July 2013 and October 2014, data from 655 patients were included in the registry. The most common tumor involved was basal cell carcinoma, and the most common histological subtype was infiltrative basal cell carcinoma. Most of the tumors treated were located on the face or scalp, and the most common site was the nose. Almost 40% of the tumors treated were recurrent or persistent, and preoperative tumor size was similar to that reported in other European studies and in Australia. In total, 45.5% of patients had received previous surgical treatment. CONCLUSION: The findings are similar to those reported in other studies, and the data collected are useful for assessing whether the results of studies carried out elsewhere are applicable in Spain.

Vitamin E protection of obesity-enhanced vascular calcification in uremic rats.

This study aimed to determine the extent of extraskeletal calcification in uremic Zucker rats, by comparing obese and lean phenotypes, and to evaluate the influence of vitamin E (VitE) on the development of calcifications in both uremic rats and human vascular smooth muscle cells (HVSMCs) cultured in vitro. Zucker rats of lean and obese phenotypes with normal renal function [control (C); C-lean and C-obese groups] and with uremia [5/6 nephrectomy (Nx); Nx-lean and Nx-obese groups] and uremic rats treated with VitE (Nx-lean + VitE and Nx-obese + VitE groups) were studied. Uremic groups were subjected to Nx, fed a 0.9% phosphorus diet, and treated with calcitriol (80 ng/kg ip). The aortic calcium concentration was significantly higher (P < 0.05) in Nx-obese rats (10.0 ± 2.1 mg/g tissue) than in Nx-lean rats (3.6 ± 1.3 mg/g tissue). A decrease in plasma glutathione peroxidase activity was observed in Nx-obese rats compared with Nx-lean rats (217.2 ± 18.2 vs. 382.3 ± 15.5 nmol·min(-1)·ml(-1), P < 0.05). Treatment with VitE restored glutathione peroxidase activity and reduced the aortic calcium concentration to 4.6 ± 1.3 mg/g tissue. The differences in mineral deposition between Nx-lean, Nx-obese, Nx-lean + VitE, and Nx-obese + VitE rats were also evidenced in other soft tissues. In HVSMCs incubated with high phosphate, VitE also prevented oxidative stress and reduced calcium content, bone alkaline phosphatase, and gene expression of core-binding factor-α1. In conclusion, uremic obese rats develop more severe calcifications than uremic lean rats and VitE reduces oxidative stress and vascular calcifications in both rats and cultures of HVSMCs.

Azelaic acid in the treatment of acne in adult females: case reports.

Acne, one of the most common skin problems in dermatological practice, is a condition that affects not only adolescents but also adults. While approximately 80% of cases occurring in adulthood are persistent from teenage years, around 20% are described as 'late-onset' disease, appearing for the first time in adulthood. The disease can be triggered by hormonal changes (including a change from one contraceptive to another), or it can be induced by certain nonhormonal medications, emotional stress, and various underlying diseases such as polycystic ovary syndrome. In many cases acne becomes a chronic skin condition with undulating activity, including improvement and relapse phases, and is often experienced as a major psychological burden. It is, therefore, even more important to provide an effective as well as a safe and tolerable treatment. The spectrum of topical acne treatments has expanded substantially in recent years and various topical medications are available, ranging from azelaic acid, antibiotics, retinoids and benzoyl peroxide to several fixed combinations of these active compounds. The following case collection illustrates how 15% azelaic acid gel, as a well-established monotherapy, can be successfully employed to treat mild-to-moderate forms of adult female acne.

Impact of device resistances in the performance of graphene-based terahertz photodetectors.

In recent years, graphene field-effect-transistors (GFETs) have demonstrated an outstanding potential for terahertz (THz) photodetection due to their fast response and high-sensitivity. Such features are essential to enable emerging THz applications, including 6G wireless communications, quantum information, bioimaging and security. However, the overall performance of these photodetectors may be utterly compromised by the impact of internal resistances presented in the device, so-called access or parasitic resistances. In this work, we provide a detailed study of the influence of internal device resistances in the photoresponse of high-mobility dual-gate GFET detectors. Such dual-gate architectures allow us to fine tune (decrease) the internal resistance of the device by an order of magnitude and consequently demonstrate an improved responsivity and noise-equivalent-power values of the photodetector, respectively. Our results can be well understood by a series resistance model, as shown by the excellent agreement found between the experimental data and theoretical calculations. These findings are therefore relevant to understand and improve the overall performance of existing high-mobility graphene photodetectors.

[Prevalence, knowledge and control of arterial hypertension in vulnerable neighborhoods of Argentina: A Cross-sectional Study]. / Estudio de prevalencia, conocimiento y control de la hipertensión arterial en barrios vulnerables de Argentina.

INTRODUCTION: Hypertension (HTN) represents the primary individual risk factor, contributing significantly to the global burden of cardiovascular diseases (CVD). In our country, epidemiological research has highlighted substantial variations in the prevalence of these risk factors across different populations. However, there is a lack of epidemiological studies assessing exclusive cardiovascular risk factors within vulnerable neighborhoods characterized by extremely limited economic resources, sociocultural challenges, and inadequate healthcare access. METHODS: A multicenter cross-sectional observational study was conducted among individuals residing in economically deprived and marginalized communities, including informal settlements and underprivileged neighborhoods. Simple random sampling of households was employed. Blood pressure measurements, anthropometric assessments, and epidemiological, economic, and sociocultural questionnaires were administered. Results encompass prevalence rates, awareness levels, and blood pressure control across diverse regions. Logistic regression was utilized to identify independent variables influencing primary outcomes. RESULTS: A total of 989 participants were analyzed. The overall prevalence of hypertension was 48.2%. About 82% had a body mass index (BMI) >25. Approximately 45.3% had less than 6 years of formal education. Independent association was established between education levels below 6 years and higher hypertension prevalence. Among hypertensive individuals, 44% were unaware of their condition, with only 17.2% achieving control, correlated with having health insurance and a higher educational background. Merely 24% were receiving combined therapy. CONCLUSION: The prevalence of hypertension within vulnerable neighborhoods is alarmingly high, surpassing rates in other social strata. Knowledge, treatment, and control levels of hypertension are suboptimal, comparable to other populations. Inadequate use of combination therapy was observed. This study underscores the urgent need for targeted interventions addressing cardiovascular risk factors in poor areas to mitigate the burden of CVD.

Comparison of different treatments for oestrous induction in seasonally anovulatory mares.

The aim of this study was to evaluate the effects of different treatments for induction and synchronization of oestrus and ovulation in seasonally anovulatory mares. Fifteen mares formed the control group (C), while 26 mares were randomly assigned to three treatment groups. Group T1 (n = 11) were treated with oral altrenogest (0.044 mg/kg; Regumate(®) ) during 11 days. Group T2 (n = 7) was intravaginally treated with 1.38 g of progesterone (CIDR(®) ) for 11 days. In group T3 (n = 8), mares were also treated with CIDR(®) , but only for 8 days. All mares received PGF2α 1 day after finishing the treatment. Sonographic evaluation of follicles, pre-ovulatory follicle size and ovulation time was recorded. Progesterone and leptin levels were analysed. Results show that pre-ovulatory follicles were developed after the treatment in 88.5% of mares. However, the pre-ovulatory follicle growth was dispersal, and sometimes it was detected when treatment was not finished. While in mares treated with intravaginal device, the follicle was soon detected (1.5 ± 1.2 days and 2.3 ± 2.0 days in T2 and T3 groups, respectively), in T1 group, the pre-ovulatory follicle was detected slightly later (3.9 ± 1.6 days). The interval from the end of treatment to ovulation did not show significant differences between groups (T1 = 13.1 ± 2.5 days; T2 = 11.0 ± 3.6 days; T3 = 13.8 ± 4.3 days). The pregnancy rate was 47.4%, similar to the rate observed in group C (46.7%; p > 0.05). Initial leptin concentrations were significantly higher in mares, which restart their ovarian activity after treatments, suggesting a role in the reproduction mechanisms in mares. It could be concluded that the used treatments may be effective for oestrous induction in mares during the late phase of the seasonally anovulatory period. Furthermore, they cannot synchronize oestrus, and then, it is necessary to know the reproductive status of mares when these treatments are used for oestrous synchronization.

Bilateral extensor digitorum brevis manus. / Extensor digitorum brevis manus bilateral.

INTRODUCTION: The extensor digitorum brevis manus (EDBM) is an accessory muscle of the dorsum of the hand that may appear as a painful mass. It is treated surgically, usually by excision of the muscle. CASE REPORT: 14-year-old male with bilateral painful masses on the dorsal aspect of his hands. Ultrasound confirmed the diagnosis of EDBM. Due to the associated symptoms, decision was made to conduct surgical treatment with resection of both muscle masses. DISCUSSION: EDBM is an infrequent cause of wrist pain, especially in children and adolescents. Surgical treatment has proven to have a significant impact on the improvement of the symptoms suffered by these patients.

INTRODUCCION: El extensor digitorum brevis manus (EDBM) es un músculo accesorio del dorso de la mano que puede presentarse como una masa dolorosa. Su tratamiento es quirúrgico, generalmente consiste en la extirpación del mismo. CASO CLINICO: Varón de 14 años que presenta tumoraciones dolorosas bilaterales en la cara dorsal de las manos. La ecografía confirma el diagnóstico de EDBM. Debido a la sintomatología asociada, se decide tratamiento quirúrgico, con resección de ambas masas musculares. COMENTARIOS: El EDBM constituye una causa poco frecuente de dolor a nivel de la muñeca, especialmente en población infanto-juvenil. El tratamiento quirúrgico ha demostrado un impacto significativo en la mejoría de la sintomatología que presentan estos pacientes.

Quality of life in patients with non-muscle invasive bladder tumor undergoing adjuvant intravesical treatment.

INTRODUCTION: The objective of the study was to establish a possible relationship between mitomycin-C (MMC) and bacillus Calmette-Guérin (BCG) treatments and quality of life impairment. MATERIAL AND METHODS: Quasi-experimental, prospective, and longitudinal study including patients undergoing adjuvant treatment in NMIBC. The Short form-12 (SF-12) and Urogenital Distress Inventory-6 (UDI-6) questionnaires were used to measure quality of life. Questionnaire scores were compared between cases with MMC and BCG before induction (M1), at 4 weeks (M2) and at 2 months (M3). RESULTS: Of the 90 patients enrolled, 54 were in the BCG group and 36 in the MMC group. It was found that BCG patients had worse perceived physical quality of life compared to MMC patients in M2 (OR:2.59, p=0.046). In addition, significant changes were found in the urinary quality of life of patients on MMC treatment between the different time points (UDI-6 score: 33.33 in M1, 27.78 in M2 and 16.67 in M3, p=0.001). CONCLUSIONS: There are no differences in urinary quality of life between patients treated with MMC and BCG. Patients with MMC show a significant recovery of urinary quality of life from the completion of the induction course, which becomes even more significant after 2 months. In addition, BCG-treated patients have worse physical quality of life after 4 weeks of treatment than those treated with MMC.

Women in urology: what is their current situation in Spain?

OBJECTIVE: To analyze the current state of women in urology in Spain. MATERIAL AND METHODS: Descriptive study based on the results of an online survey sent between February and April 2020 through the database of the Residents and Young Urologists group (RAEU) of the Spanish Association of Urology (AEU). Characteristics of the survey and its results were analyzed. RESULTS: In total, 257 responses were obtained from 210 women (81.71%) and 47 men (18.29%) belonging to 111 hospitals. Statistically significant differences were observed (p < 0.001) with a higher proportion of men in all categories except for the group of young female and male attendings (29-39 years, p = 0.789), and the group of female residents against male residents (p = 0.814). The number of men was higher in hospitals with subspecialty units except for the Pelvic Floor Unit, where no statistically significant difference was observed (p = 0.06). Regarding positions of responsibility, only 7 out of 111 hospitals had female Department Chiefs. CONCLUSIONS: Women's representation in urology is increasing, mainly due to the younger generations. However, the access of these women to relevant positions is anecdotal.

Immobilization of ß-glucosidase in fixed bed reactor and evaluation of the enzymatic activity.

Adsorption of ß-glucosidase from almonds, an enzyme with big molecular size (130 kDa, 6.7 nm molecular diameter), on mesoporous SBA-15 silica in fixed bed column was studied. Previously, zeta potential analysis confirmed that the electrostatic interactions between ß-glucosidase and SBA-15 were the driving force of the immobilization process. The maximum difference in the zeta potential was 25 mV at pH 3.5. Adsorption isotherm was classified as an L3 (Langmuir type 3) curve according to the Giles classification and fitted to a double Langmuir equation. The adsorbed amount in a fixed bed column was around 3.5 times higher than the amount reached in the adsorption in batch. In addition, the ß-glucosidase was strongly immobilized on SBA-15 with only 7 % of leaching in the washing step with buffer solution. Immobilized ß-glucosidase was catalytically active in a continuous process, reaching 100 % substrate conversion and maintaining this activity level for more than 10 h without deactivation of the enzyme. Adsorption-desorption isotherms at 77 K before and after the adsorption were carried out, concluding that the adsorption of ß-glucosidase was produced blocking the pore mouth, so that a part of the enzyme penetrates inside and another part stays outside the pore.

Intravascular papillary endotelial hiperplasia, the unusual diagnosis of an orbital mass.

Intravascular papillary endotelial hyperplasia is a bening vascular lesion that rarely involves the periocular region, nevertheless, it should be considered in the differential diagnosis of a periorbital mass. It is histopatologically characterized by intravascular fibrous papillary fronds covered by endothelial cells. Histopathological differentiation from angiosarcoma can be challenging but is very important to avoid aggressive treatments. Complete surgical excision is frequently curative. Uncompleted excision can lead to recurrences. We describe the clinical and histological findings of intravascular papillary endotelial hyperplasia in the left lower lid of a 72-year-old woman who had a painless mass since 15 years ago, that caused hypertropia of her left eye. Histopathological examination revealed intralesional calcification, which is not an usual feature in this entity. The patient underwent complete surgical resection of the mass and there was no evidence of recurrence after 5 months of follow-up after surgery.

Identification and characterization of Cri1, a locus controlling mortality during Citrobacter rodentium infection in mice.

Infection of inbred mouse strains with Citrobacter rodentium represents an ideal model to reveal the genetic factors controlling host resistance to noninvasive enteric bacterial pathogens. We have chosen a positional cloning approach to identify putative gene(s) that control the known difference in survival between resistant C57BL/6J and susceptible C3H/HeJ and C3H/HeOuJ mice. Our work has identified one major locus within proximal chromosome 15 that is responsible for the marked susceptibility of both C3H strains, and we formally exclude Tlr4 from control of survival to this pathogen. We have named this new host resistance locus Cri1 (Citrobacter rodentium infection 1). The Cri1 genetic interval currently spans ∼16 Mb and it confers survival to the infection in a recessive manner. Transfer of the Cri1 locus from the surviving B6 mice into a congenic mouse with a C3Ou genetic background confirms its overall chromosomal localization and its highly significant effect on host survival. The C3Ou.B6-Cri1 mice thus produced have also enabled us to dissociate the control of mouse survival from the control of bacterial load early in the infection as well as from control of colonic hyperplasia.

[Paramedian forehead flap for the reconstruction of extensive nasal defects]. / Colgajo fronto-nasal paramedial en la reconstrucción de defectos nasales extensos.

BACKGROUND: The Department of Dermatology at Hospital Universitario de Guadalajara in Spain is a referral center for Mohs micrographic surgery. Consequently, we are regularly faced with the problem of repairing large surgical defects on the nose. The paramedian forehead flap is currently one of the techniques of choice for the repair of such defects. MATERIALS AND METHODS: We review our experience in the repair of nasal defects using the paramedian forehead flap over the period from 2004 to 2008. We describe the surgical technique, complications, and final results. RESULTS: Ten patients (mean age, 75.1 years) were treated using this flap. Two patients also required cartilage grafts and reconstruction of the internal nasal lining. The most common complications were bleeding (60%) and partial necrosis (10%). The final cosmetic and functional results were considered good or excellent in 90% of cases. CONCLUSIONS: The forehead flap continues to be one of the best options for the closure of surgical defects of the nasal pyramid larger than 2 cm. Adequate knowledge and careful application of the technique allows excellent results to be obtained with few complications.

Diagnostic approach to small-bowel wall thickening: Beyond Crohn's disease and cancer.

Although small-bowel wall thickening is a common manifestation of Crohn's disease and tumors, many other entities can give rise to similar imaging findings. The small bowel is difficult to access by endoscopy, so radiologic imaging tests play an essential role in the diagnosis of conditions involving the small bowel. The main objectives of this paper are to explain the definition of small-bowel wall thickening, analyze the patterns of involvement seen in multidetector computed tomography (MDCT) with intravenous contrast administration, and provide an image-based review of the different causes of small-bowel wall thickening. The differential diagnosis must include many entities because wall thickening can result from immune-mediated, infectious, or vascular causes, as well as from toxicity and other lesser-known entities. As the imaging appearance of many of these conditions overlap, clinical and laboratory findings are necessary to support the imaging diagnosis.