Mohs micrographic surgery in immunosuppressed vs immunocompetent patients: Results of a prospective nationwide cohort study (REGESMOHS, Spanish registry of Mohs surgery).

BACKGROUND: Immunosuppressed (IS) patients, particularly solid organ transplant recipients and those on immunosuppressive therapy, face a higher incidence and recurrence of nonmelanoma skin cancers (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Mohs micrographic surgery (MMS) is the preferred treatment for high-risk NMSC due to its high cure rate and margin examination capabilities. However, IS patients may experience more complications, such as surgical site infections, and a greater risk of recurrence, making their outcomes a subject of interest. OBJECTIVES: This study aimed to compare IS and immunocompetent (IC) patients undergoing MMS for NMSC in terms of baseline characteristics, intra- and post-surgical complications, and postoperative recurrence rates. METHODS: The study utilized data from the REGESMOHS registry, a 7-year prospective cohort study in Spain. It included 5226 patients, categorizing them into IC (5069) and IS (157) groups. IS patients included solid organ transplant recipients, those on immunosuppressive treatments, individuals with haematological tumours and HIV-positive patients. Patient data, tumour characteristics, surgical details and outcomes were collected and analysed. RESULTS: IS patients demonstrated a higher proportion of SCC, multiple synchronous tumours and tumours invading deeper structures. Complex closures, unfinished MMS and more surgical sections were observed in the IS group. Although intra-operative morbidity was higher among IS patients, this difference became non-significant when adjusted for other variables such as year of surgery, antiplatelet/anticoagulant treatment or type of closure. Importantly, IS patients had a substantially higher recurrence rate (IRR 2.79) compared to IC patients. CONCLUSIONS: This study suggests that IS patients may be at a higher risk of development of AE such as bleeding or tumour necrosis and are at a higher risk of tumour recurrence. Close follow-up and consideration of the specific characteristics of NMSC in IS patients are crucial. Further research with extended follow-up is needed to better understand the long-term outcomes for this patient group.

Rural residence and health-related quality of life in a sample of Spain perimenopausal women.

BACKGROUND: The prevalence and severity of perimenopausal symptoms are typically associated with multiple factors, including demographic characteristics. The sociodemographic characteristics of women living in rural areas differ from those residing in urban areas, and it has been suggested that these differences could potentially influence the prevalence of symptoms experienced during perimenopause. OBJECTIVES: To evaluate if perimenopausal women living in Spanish rural areas have a higher prevalence of perimenopausal symptoms and assess their influence on health-related quality of life. METHODS: A cross-sectional study was conducted in a sample of 270 perimenopausal women residing in rural and urban areas. The participants completed the Cervantes Scale Short Version and Beck Depression Inventory 2. RESULTS: Perimenopausal women in rural areas reported a higher incidence of perimenopausal symptoms and a lower perception of health-related quality of life compared to those in urban areas, as evidenced by higher scores on the total Cervantes Scale Short Version scale (33.2 (±16.2) vs. 26.4 (±18.1), p = .001). No differences in the Beck Depression Inventory 2 score were detected. CONCLUSIONS: Perimenopausal women residing in rural areas of Spain reported a higher prevalence of perimenopausal symptoms and experienced a poorer Health-Related Quality of Life compared to those living in urban areas of Spain.

Prospective, multicenter, uncontrolled study on the effectiveness and safety of a hyaluronic acid water-based vaginal lubricant in alleviating vaginal dryness and dyspareunia.

BACKGROUND: Vaginal dryness (VD) represents a significant concern affecting women across diverse life stages, encompassing both pre- and postmenopausal women at any age. Dyspareunia, defined by genital pain that can be experienced before, during, or after intercourse, is often associated with vaginal dryness. AIM: This study aimed to evaluate the effectiveness and safety of a water-based vaginal lubricant with hyaluronic acid to reduce sexual discomfort associated with vaginal dryness. METHODS: A prospective, multicenter, uncontrolled clinical investigation was conducted over a three-month period in women aged 18 years or older experiencing pain or difficulty during sexual intercourse for whom the use of a vaginal lubricant was recommended. RESULTS: Significant improvements were observed in the FSFI scores, indicating enhanced sexual function (p < .001). Vaginal dryness symptoms, including irritation, dryness, itching, and dyspareunia, significantly decreased after product use (p < .001). CLINICAL IMPLICATIONS: This study contributes to the limited scientific knowledge on the application of lubricants in the context of symptoms associated with VD. STRENGTHS & LIMITATIONS: In addition to the short study period, inherent limitations of the study design, and lack of placebo control, it is pertinent to acknowledge that some of the pros used in this study were not based on validated questionnaires. However, as far as we know, this study is the only one that analyzes well-being and sexual pleasure as results using a lubricant formulated with hyaluronic acid. CONCLUSION: This tested vaginal lubricant with hyaluronic acid has demonstrated efficacy in improving vaginal dryness and female sexual function, particularly in reducing pain and improving lubrication during sexual intercourse, and showed a favorable safety profile, with minimal and transient adverse events.

Analysis of the Association between Copy Number Variation and Ventricular Fibrillation in ST-Elevation Acute Myocardial Infarction.

Sudden cardiac death due to ventricular fibrillation (VF) during ST-elevation acute myocardial infarction (STEAMI) significantly contributes to cardiovascular-related deaths. Although VF has been linked to genetic factors, variations in copy number variation (CNV), a significant source of genetic variation, have remained largely unexplored in this context. To address this knowledge gap, this study performed whole exome sequencing analysis on a cohort of 39 patients with STEAMI who experienced VF, aiming to elucidate the role of CNVs in this pathology. The analysis revealed CNVs in the form of duplications in the PARP2 and TTC5 genes as well as CNVs in the form of deletions in the MUC15 and PPP6R1 genes, which could potentially serve as risk indicators for VF during STEAMI. The analysis also underscores notable CNVs with an average gene copy number equal to or greater than four in DEFB134, FCGR2C, GREM1, PARM1, SCG5, and UNC79 genes. These findings provide further insight into the role of CNVs in VF in the context of STEAMI.

Neuromyelitis optica associated with the use of Atezolizumab in a patient with advanced lung adenocarcinoma.

Immune checkpoint inhibitors (ICIs) are a pharmacological group increasingly used in Oncology and Hematology. These treatments can lead to autoimmune complications, with neurological conditions, especially central nervous system (CNS) involvement, being rare. We describe a case of seropositive neuromyelitis optica in a patient with locally advanced lung adenocarcinoma treated with Atezolizumab.

Preliminary Investigation on Efficacy and Safety of Substance P-Coated Stent for Promoting Re-Endothelialization: A Porcine Coronary Artery Restenosis Model.

BACKGROUND: Current polymer-based drug-eluting stents (DESs) have fundamental issues about inflammation and delayed re-endothelializaton of the vessel wall. Substance-P (SP), which plays an important role in inflammation and endothelial cells, has not yet been applied to coronary stents. Therefore, this study compares poly lactic-co-glycolic acid (PLGA)-based everolimus-eluting stents (PLGA-EESs) versus 2-methacryloyloxyethyl phosphorylcholine (MPC)-based SP-eluting stents (MPC-SPs) in in-vitro and in-vivo models. METHODS: The morphology of the stent surface and peptide/drug release kinetics from stents were evaluated. The in-vitro proliferative effect of SP released from MPC-SP is evaluated using human umbilical vein endothelial cell. Finally, the safety and efficacy of the stent are evaluated after inserting it into a pig's coronary artery. RESULTS: Similar to PLGA-EES, MPC-SP had a uniform surface morphology with very thin coating layer thickness (2.074 µm). MPC-SP showed sustained drug release of SP for over 2 weeks. Endothelial cell proliferation was significantly increased in groups treated with SP (n = 3) compared with the control (n = 3) and those with everolimus (n = 3) (SP: 118.9 ± 7.61% vs. everolimus: 64.3 ± 12.37% vs. the control: 100 ± 6.64%, p < 0.05). In the animal study, the percent stenosis was higher in MPC-SP group (n = 7) compared to PLGA-EES group (n = 7) (MPC-SP: 28.6 ± 10.7% vs. PLGA-EES: 16.7 ± 6.3%, p < 0.05). MPC-SP group showed, however, lower inflammation (MPC-SP: 0.3 ± 0.26 vs. PLGA-EES: 1.2 ± 0.48, p < 0.05) and fibrin deposition (MPC-SP: 1.0 ± 0.73 vs. PLGA-EES: 1.5 ± 0.59, p < 0.05) around the stent strut. MPC-SP showed more increased expression of cluster of differentiation 31, suggesting enhanced re-endothelialization. CONCLUSION: Compared to PLGA-EES, MPC-SP demonstrated more decreased inflammation of the vascular wall and enhanced re-endothelialization and stent coverage. Hence, MPC-SP has the potential therapeutic benefits for the treatment of coronary artery disease by solving limitations of currently available DESs.

Exploring protein-protein interactions and oligomerization state of pulmonary surfactant protein C (SP-C) through FRET and fluorescence self-quenching.

Pulmonary surfactant (PS) is a lipid-protein complex that forms films reducing surface tension at the alveolar air-liquid interface. Surfactant protein C (SP-C) plays a key role in rearranging the lipids at the PS surface layers during breathing. The N-terminal segment of SP-C, a lipopeptide of 35 amino acids, contains two palmitoylated cysteines, which affect the stability and structure of the molecule. The C-terminal region comprises a transmembrane α-helix that contains a ALLMG motif, supposedly analogous to a well-studied dimerization motif in glycophorin A. Previous studies have demonstrated the potential interaction between SP-C molecules using approaches such as Bimolecular Complementation assays or computational simulations. In this work, the oligomerization state of SP-C in membrane systems has been studied using fluorescence spectroscopy techniques. We have performed self-quenching and FRET assays to analyze dimerization of native palmitoylated SP-C and a non-palmitoylated recombinant version of SP-C (rSP-C) using fluorescently labeled versions of either protein reconstituted in different lipid systems mimicking pulmonary surfactant environments. Our results reveal that doubly palmitoylated native SP-C remains primarily monomeric. In contrast, non-palmitoylated recombinant SP-C exhibits dimerization, potentiated at high concentrations, especially in membranes with lipid phase separation. Therefore, palmitoylation could play a crucial role in stabilizing the monomeric α-helical conformation of SP-C. Depalmitoylation, high protein densities as a consequence of membrane compartmentalization, and other factors may all lead to the formation of protein dimers and higher-order oligomers, which could have functional implications under certain pathological conditions and contribute to membrane transformations associated with surfactant metabolism and alveolar homeostasis.

La relación entre la transición a la menopausia y los trastornos del estado de ánimo / The relationship between menopause transition and mood disorders

Este estudio tuvo como objetivo examinar la relación entre la transición a la menopausia y los trastornos del estado de ánimo, específicamente la ansiedad y la depresión. Se llevó a cabo una revisión narrativa de la literatura relevante sobre la transición a la menopausia y los trastornos del estado de ánimo. Se revisaron estudios que se enfocaron en el impacto de los cambios hormonales durante la menopausia en el bienestar psicológico y se evaluaron diversas opciones de tratamiento para los trastornos del estado de ánimo. La disminución de los niveles hormonales de estrógenos y progesterona durante la menopausia puede llevar a diversos cambios psicológicos, como ansiedad y depresión. La terapia hormonal con estrógenos solo o en combinación con progesterona puede mejorar los síntomas depresivos en mujeres en la menopausia, pero este tratamiento no está exento de riesgos. Otros tratamientos no hormonales, como la terapia cognitivo-conductual, el ejercicio y una buena higiene del sueño, también pueden ser efectivos para manejar los trastornos del estado de ánimo. Se concluyó que existe una compleja interacción entre factores hormonales, biológicos y psicosociales para desarrollar intervenciones efectivas que mejoren el bienestar psicológico de las mujeres en la menopausia.

This study aimed to examine the relationship between menopause transition and mood disorders, specifically anxiety and depression. The authors conducted a narrative review of relevant literature on menopause transition and mood disorders. They reviewed studies that focused on the impact of hormonal changes during menopause on psychological well-being and evaluated various treatment options for mood disorders. The decline in estrogen and progesterone hormone levels during menopause can lead to various psychological changes, such as anxiety and depression. Hormonal therapy with estrogen alone or in combination with progesterone can improve depressive symptoms in menopausal women, but this treatment is not without risks. Other non-hormonal treatments, such as cognitive-behavioral therapy, exercise, and good sleep hygiene, can also be effective in managing mood disorders. The study highlights the need for recognition of the complex interplay between hormonal, biological, and psychosocial factors in developing effective interventions to improve the psychological well-being of menopausal women. Further research is needed to fully understand the potential relationship between menopause transition and mood disorders.

Carcinoma micropapilar infiltrante de la mama. Pronóstico a largo plazo / Invasive micropapillary carcinoma of the breast. Long term outcome

Introducción: el carcinoma micropapilar infiltrante (CMI) es una variante histológica inusual y potencialmente agresiva caracterizada por primera vez en 1993 por Siriangkul et al. y que no formó parte de la clasificación de la Organización Mundial de la Salud (OMS) hasta 2003, como tumor mamario epitelial. Representa menos del 2% del total de carcinomas invasivos de la mama y se presupone que presenta un pronóstico desfavorable en comparación con otros carcinomas convencionales debido a su elevado tropismo vascular y linfático. Material y métodos: hasta la fecha no existe ningún estudio con un número elevado de pacientes procedentes de un único centro (> 100 casos) con un periodo de seguimiento largo (> 20 años) que compare la supervivencia del CMI con otros carcinomas convencionales no micropapilares. Se ha llevado a cabo un estudio retrospectivo, observacional con un total de 401 pacientes: 174 con CMI y 227 con otros carcinomas convencionales. Resultados: el CMI presenta mayor grado histológico, mayor afectación ganglionar y mayor riesgo de metástasis a distancia en comparación con otros carcinomas convencionales de características similares. Sin embargo, en el análisis multivariante considerando factores pronósticos como edad, tamaño tumoral, afectación ganglionar y grado histológico, no se observan diferencias estadísticamente significativas para la supervivencia global y libre de enfermedad entre los CMI diagnosticados en el mismo periodo de tiempo que los casos pareados del grupo control y otros carcinomas convencionales. Conclusión: la supervivencia global y libre de enfermedad es similar entre el CMI y otros carcinomas convencionales a igual edad, tamaño tumoral, grado histológico y afectación ganglionar. (AU)

Introduction: Invasive Micropapillary Carcinoma of the breast (IMPC) is an unusual and aggressive histological variant characterized for the first time in 1993 by Siriangkul et al. and classified by the World Health Organization in 2003 as an epithelial breast tumor. It represents less than 2% of all invasive carcinomas of the breast and is presumed to have an unfavorable prognosis compared to other conventional carcinomas due to its high vascular and lymphatic tropism. Material and methods: Until now, there is no study with a large number of patients from a single center with a long follow-up period that compares the survival of IMPC with other conventional non-micropapillary carcinomas. A retrospective, observational study has been carried out with a total of 401 patients: 174 with IMPC and 227 with other conventional carcinomas. Results: IMPC has a higher histological grade, greater lymph node involvement and a higher risk of distant metastasis compared to other conventional carcinomas. However, in the multivariate analysis considering date of diagnosis, age, tumor size, lymph node involvement and histological grade as variables, no statistically significant differences were observed for overall and disease- free survival between IMPC and other conventional carcinomas. Conclusion: Overall and disease-free survival is similar between IMPC and other conventional carcinomas considering same age, tumor size, histological grade, and lymph node involvement. (AU)

Bullous Pemphigoid Developed after the COVID-19 Vaccine.

A 91-year-old man presented with pruriginous tense blisters and erosions on the upper and lower extremities (Figures 1A and 1B). Mucous membranes were unaffected and Nikolsky's sign was negative. These lesions appeared 48 hours after the administration of the second dose of the Pfizer-BioNTech COVID-19 vaccine. The patient had received the first dose of the same vaccine 23 days prior to the onset of lesions. He did not suffer from any other post-vaccination adverse effects.

Cell lipid droplet heterogeneity and altered biophysical properties induced by cell stress and metabolic imbalance.

Lipid droplets (LD) are important regulators of lipid metabolism and are implicated in several diseases. However, the mechanisms underlying the roles of LD in cell pathophysiology remain elusive. Hence, new approaches that enable better characterization of LD are essential. This study establishes that Laurdan, a widely used fluorescent probe, can be used to label, quantify, and characterize changes in cell LD properties. Using lipid mixtures containing artificial LD we show that Laurdan GP depends on LD composition. Accordingly, enrichment in cholesterol esters (CE) shifts Laurdan GP from ∼0.60 to ∼0.70. Moreover, live-cell confocal microscopy shows that cells present multiple LD populations with distinctive biophysical features. The hydrophobicity and fraction of each LD population are cell type dependent and change differently in response to nutrient imbalance, cell density, and upon inhibition of LD biogenesis. The results show that cellular stress caused by increased cell density and nutrient overload increased the number of LD and their hydrophobicity and contributed to the formation of LD with very high GP values, likely enriched in CE. In contrast, nutrient deprivation was accompanied by decreased LD hydrophobicity and alterations in cell plasma membrane properties. In addition, we show that cancer cells present highly hydrophobic LD, compatible with a CE enrichment of these organelles. The distinct biophysical properties of LD contribute to the diversity of these organelles, suggesting that the specific alterations in their properties might be one of the mechanisms triggering LD pathophysiological actions and/or be related to the different mechanisms underlying LD metabolism.

El alivio natural: Sauzgatillo (Vitex agnus-castus) para el síndrome premenstrual y la dismenorrea / The natural relief: Chasteberry (Vitex agnus-castus) for premenstrual syndrome and dysmenorrhea

El síndrome premenstrual es un trastorno común en mujeres en edad reproductiva y se caracteriza por al menos un síntoma físico, emocional o conductual, que aparece en la fase lútea del ciclo menstrual y se resuelve poco después del inicio de la menstruación. Los tratamientos convencionales para el dolor perimenstrual cíclico tienen inconvenientes que incluyen efectos secundarios, interferencia con la función reproductiva de las mujeres o escasa efectividad en el alivio de los síntomas. Muchas mujeres recurren a terapias naturales para tratar una gran variedad de síntomas menstruales. Esta revisión se centra en una de esas opciones naturales, el Sauzgatillo (Vitex agnus-castus). Se realizó una búsqueda e identificación de artículos publicados hasta mayo de 2022 recopilados por medio de sistemas de búsqueda electrónicos como Google Scholar, Medline, PubMed y Scopus. Las palabras de búsqueda fueron: “Premenstrual syndrome”, “dysmenorrhea” AND “Vitex agnus-castus”. Los estudios preclínicos señalan un mecanismo de acción en su implicación sobre el sistema serotoninérgico, así como su unión a los receptores de dopamina. Los estudios clínicos demuestran la seguridad y el efecto positivo sobre el síndrome premenstrual y la dismenorrea.

Premenstrual syndrome is a common disorder in women of reproductive age and is characterized by at least one physical, emotional, or behavioral symptom, which appears in the luteal phase of the menstrual cycle and resolves shortly after the onset of menstruation. Conventional treatments for cyclical perimenstrual pain have drawbacks that include side effects, interference with womens reproductive function, or limited effectiveness in relieving symptoms. Many women turn to natural therapies to treat a wide variety of menstrual symptoms. This review focuses on one of those natural options, Chasteberry (Vitex agnus-castus). The information available until May 2022 was collected via the library and electronic search systems such as Google Scholar, Medline, PubMed, and Scopus. The search words were: “Premenstrual syndrome”, “dysmenorrhea” AND “Vitex agnus-castus”. Preclinical studies point to a mechanism of action in its involvement in the serotoninergic system, as well as its binding to dopamine receptors. Clinical studies prove safety and positive effect on premenstrual syndrome and dysmenorrhea.

Development and validation of a model to predict complex Mohs micrographic surgery in clinical practice: REGESMOSH scale.

INTRODUCTION: There is still a need to develop a simple algorithm to identify patients likely to need complex Mohs micrographic surgery (MMS) and optimize MMS schedule. The main objectives of this study are to identify factors associated with a complex MMS and develop a predictor model of the number of stages needed in surgery and the need for a complex closure. MATERIALS AND METHODS: A nationwide prospective cohort study (REGESMOHS, the Spanish Mohs surgery registry) was conducted including all patients with a histological diagnosis of basal cell carcinoma (BCC). Factors related to three or more stages and a complex closure (that needing a flap and/or a graft) were explored and predictive models were constructed and validated to construct the REGESMOSH scale. RESULTS: A total of 5226 patients that underwent MMS were included in the REGESMOHS registry, with 4402 (84%) having a histological diagnosis of BCC. A total of 3689 (88.9%) surgeries only needed one or two stages and 460 (11.1%) required three or more stages. A model to predict the need for three or more stages included tumour dimension, immunosuppression, recurrence, location in risk areas, histological aggressiveness and previous surgery. Regarding the closure type, 1616 (38.8%) surgeries were closed using a non-complex closure technique and 2552 (61.2%) needed a complex closure. A model to predict the need for a complex closure included histological aggressiveness, evolution time, patient age, maximum tumour dimension and location. CONCLUSION: We present a model to predict MMS needing ≥3 stages and a complex closure based on epidemiological and clinical data validated in a large population (with real practice variability) including different centres that could be easily implemented in clinical practice. This model could be used to optimize surgery schedule and properly inform patients about the surgery duration.

Maternal and cord blood betatrophin (angiopoietin-like protein 8) in pregnant women with gestational diabetes and normoglycemic controls: A systematic review, meta-analysis, and meta-regression.

AIMS: This systematic review and meta-analysis examined maternal and cord blood betatrophin levels in pregnant women with gestational diabetes mellitus (GDM) and normoglycemic controls. MATERIAL AND METHODS: PubMed, Cochrane Library, Embase, LILACS, WangFang, and China National Knowledge Infrastructure were searched for literature from inception until May 2022. The primary outcomes were maternal and cord blood betatrophin levels. A random-effect meta-analysis was used to estimate the pooled results. The mean differences (MDs) or standardised MDs (SMD) and their 95% confidence intervals (CIs) were calculated. I2 tests were used to evaluate the heterogeneity. The quality of studies was evaluated using the Newcastle-Ottawa Scale. RESULTS: Betatrophin levels were reported in 22 studies with a total of 3034 pregnant women, and in seven studies including cord blood from 456 infants. Women with GDM display higher betatrophin levels than the normoglycemic controls (SMD = 0.85, 95% CI: 0.38-1.31) during the second half of the pregnancy. The sensitivity analysis indicated that no single study had significantly influenced the betatrophin overall outcomes. There was heterogeneity between the studies as evidenced by high I2 values. Meta-regression analysis indicated a significant regression coefficient for maternal betatrophin and glycosilated haemoglobin. There was no significant difference in cord blood betatrophin in infants from women with and without GDM (SMD = 0.34, 95% CI: -0.15-0.83). Women with GDM also had significantly higher insulin, glucose, glycosylated haemoglobin, HOMA-IR, LDL-cholesterol, HDL-cholesterol, triglycerides, and body mass index compared with the normoglycemic controls. CONCLUSIONS: Maternal betatrophin levels were higher in women with GDM than in the normoglycemic controls. There was no difference in cord blood betatrophin. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022311372.