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.

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.

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.

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.

Fetal Megacystis: Associated Structural Abnormalities and Obstetric Outcomes.

Purpose: We evaluated the obstetrical outcomes, ultrasonographic characteristics, and final diagnosis in pregnancies with fetal megacystis (FM). Methods: We evaluated the obstetrical outcomes and associated structural abnormalities of fetuses with FM detected between FM between 2000 and 2021. Results: 17 FM were diagnosed, 16 had follow up. 16 were early megacystis. 14/16 (87.5%) of pregnancies were terminated, 1/16 (6.25%) resulted in intrauterine death, and 1/16 (6.25%) survived. FM was associated with 13 other abnormal sonographic findings in 12/16 (75%) pregnancies. The most common associated ultrasound abnormality was umbilical cord cyst in 3/16 (18.75%). Recognized etiologies included posterior urethral valves (2), trisomy 18 (2), trisomy 13 (1), Prune Belly syndrome (1), and Megacystis-Microcolon-Hypoperistalsis syndrome (1). Conclusion: Most FM are detected in the 2nd trimester, most are electively terminated, are associated with other ultrasonic abnormalities in 75%, most commonly umbilical cord cyst, and have an identifiable cause in 44%.

Eficacia y seguridad de una alternativa a la terapia hormonal de la menopausia: extracto purificado de polen / Efficacy and safety of an alternative to menopausal hormone therapy: purified cytoplasm of pollen

Los síntomas vasomotores (SVM) se encuentran entre los síntomas más comunes de la transición a la menopausia. Más del 70% de las mujeres de mediana edad informan SVM en algún momento durante la transición a la menopausia, y para un tercio de las mujeres los SVM son muy frecuentes o graves. Muchas mujeres recurren a terapias naturales para tratar los SVM. Esta revisión se centra en una de esas opciones naturales: el extracto purificado de polen (Serelys®). Se realizó una búsqueda e identificación de artículos publicados hasta octubre de 2022 recopilados de sistemas de búsqueda electrónicos, como Google Scholar, MEDLINE, PubMed y Scopus. Las palabras de búsqueda fueron “Vasomotor symptoms”, “menopause” AND “pollen”. 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 los SVM.

Vasomotor symptoms (VMS) are among the most common symptoms of the menopausal transition. More than 70% of middle-aged women report VMS at some point during the menopausal transition, and for a third of women, VMS is very common or severe. Many women turn to natural therapies to treat VMS. This review focuses on one such natural option, purified pollen extract (Serelys®). The information available until October 2022 was collected via the library and electronic search systems such as Google Scholar, MEDLINE, PubMed, and Scopus. The search words were: “Vasomotor symptoms”, “menopause” AND “pollen”. Preclinical studies point to a mechanism of action in its involvement in the serotonergic system, as well as its binding to dopamine receptors. Clinical studies demonstrate the safety and positive effect on VMS.

Frühzeitiges Absetzen des paramedianen Stirn-Interpolationslappens unter Verwendung von kutanem Ultraschall.

HINTERGRUND UND ZIELE: Der paramediane Stirnlappen ist ein Interpolationslappen, bei dem Gewebe von der Stirn in die Nasenregion transplantiert wird. Die Blutversorgung erfolgt über die Arteria supratrochlearis. Üblicherweise wird der vaskuläre Stiel zwischen dem 14. und dem 21. postoperativen Tag abgesetzt; diese Zeit könnte allerdings zu lang bemessen sein. Wir wollen zeigen, dass der paramediane Stirnlappen bereits vor der in der Literatur angegebenen Zeit abgesetzt werden kann, und demonstrieren den Nutzen des kutanen Ultraschalls für die Bestimmung des optimalen Zeitpunkts. PATIENTEN UND METHODEN: Unsere Studie mit Patienten, deren Nasendefekt durch eine paramediane Stirnlappenplastik rekonstruiert wurde, war als prospektive Beobachtungsstudie angelegt. Einschlusskriterium waren Hautdefekte von mehr als 2 cm Größe an der Nasenspitze, dem Nasenrücken oder den Nasenflügeln nach onkologischer Operation. Zwölf Patienten wurden in die Studie aufgenommen. Eine retrospektive Kohorte wurde zur Analyse der Kostenminderung herangezogen. ERGEBNISSE: Die durchschnittliche Dauer bis zur etablierten Vaskularisierung betrug 6,6 Tage, gemessen mittels Ultraschall. Die durchschnittliche Zeit bis zum Absetzen des Transplantatstiels betrug 6,9 Tage. Es wurden keine schwerwiegenden Komplikationen beobachtet. SCHLUSSFOLGERUNGEN: Der paramediane Stirnlappen kann bereits vor der traditionell üblichen Zeit abgesetzt werden. Ultraschall ist eine zuverlässige und kostengünstige Methode, um die individuell am besten geeignete Zeit zum Absetzen des Transplantatstiels zu bestimmen.

Early division of the paramedian forehead interpolated flap using cutaneous ultrasound.

BACKGROUND AND OBJECTIVES: The paramedian forehead flap is an interpolated flap, consisting of the transfer of tissue from the forehead region to the nasal area, irrigated by the supratrochlear artery. Traditionally, the vascular pedicle is divided at between 14 and 21 days. However, this time could be overestimated. Our objective is to demonstrate that the paramedian forehead flap can be divided before that set out in the literature and to demonstrate the usefulness of cutaneous ultrasound to determine the optimal time for division. PATIENTS AND METHODS: A prospective observational study, including patients who required nasal defect reconstruction with a paramedian forehead flap, was designed. The inclusion criteria were: nasal tip, dorsum or alar skin defects following oncological surgery, larger than 2 cm. Twelve patients were included. A retrospective cohort was used to perform a cost reduction analysis. RESULTS: The average time to flow, measured by ultrasound, was 6.6 days. The average number of days to division of the pedicle was 6.9 days. No serious complications were reported. CONCLUSIONS: The paramedian forehead flap can be divided before the traditional reported time. Ultrasound is a reliable and cost-effective technique to determine and individualize pedicle division time.

Etiopathogenesis of ovarian cancer. An inflamm-aging entity?

Ovarian cancer is one of the most common gynecologic cancers and has the highest mortality rate. The risk/protective factors of ovarian cancer suggest that its etiology is multifactorial. Several factors are involved in age-related increases in carcinogenesis, including the accumulation of senescent cells, inflammaging (a chronic inflammatory state that persists in the elderly), and immunosenescence (aging of the immune system) changes associated with poor immune surveillance. At sites of inflammation, exposure to high levels of inflammatory mediators, such as reactive oxygen species, cytokines, prostaglandins, and growth factors, contributes to increased cell division and genetic and epigenetic changes. These exposure-induced changes promote excessive cell proliferation, increased survival, malignant transformation, and cancer development. Furthermore, the proinflammatory tumor microenvironment contributes to ovarian cancer metastasis and chemoresistance. This narrative review of the literature was carried out to delineate the possible role of inflammaging in the etiopathogenesis of ovarian cancer development. We discuss the current carcinogenic hypotheses, sites of origin, and etiological factors of ovarian cancer. Treatment of inflammation may represent an attractive strategy for both the prevention and therapy of ovarian cancer.

Alopecia Neoplastica Inducing Underlying Lytic Skull Metastasis.

Alopecia neoplastica is a rare type of cutaneous metastasis. The most frequent presentation consists of red-violaceous nodular scarring alopecia located at the parietal area. The most frequent primary tumor locations are the breast and gastrointestinal tract. We report a case of alopecia neoplastica that induced an underlying lytic bone metastasis. After a rigorous literature search, we could not find another case showing this mechanism.