A potential therapeutic strategy based on acute oxidative stress induction for wild-type NRF2/KEAP1 lung squamous cell carcinoma.

Extensive efforts have been conducted in the search for new targetable drivers of lung squamous cell carcinoma (LUSC); to date, however, candidates remain mostly unsuccessful. One of the oncogenic pathways frequently found to be active in LUSC is NFE2L2 (NRF2 transcription factor), the levels of which are regulated by KEAP1. Mutations in NFE2L2 or KEAP1 trigger NRF2 activation, an essential protector against reactive oxygen species (ROS). We hypothesized that the frequency of NRF2 activation in LUSC (∼35 %) may reflect a sensitivity of LUSC to ROS. Results from this study reveal that whereas tumors containing active forms of NRF2 were protected, ROS induction in wild-type NFE2L2/KEAP1 LUSC cells triggered ferroptosis. The mechanism of ROS action in normal-NRF2 LUSC cells involved transient NRF2 activation, miR-126-3p/miR-126-5p upregulation, and reduction of p85ß and SETD5 levels. SETD5 levels reduction triggered pentose pathway gene levels increase to toxic values. Simultaneous depletion of p85ßPI3K and SETD5 triggered LUSC cell death, while p85ßPI3K and SETD5 overexpression rescued survival of ROS-treated normal-NRF2 LUSC cells. This shows that the cascade involving NRF2 > miR-126-3p, miR-126-5p > p85ßPI3K and SETD5 is responsible for ROS-induced cell death in normal-NRF2 LUSC. Transient ROS-induced cell death is shown in 3D spheroids, patient-derived organoids, and in xenografts of wild-type NFE2L2/KEAP1 LUSC cells, supporting the potential of acute local ROS induction as a therapeutic strategy for LUSC patients with normal-NRF2.

Evaluation of pneumatosis intestinalis as a complication of lung transplantation.

INTRODUCTION: Pneumatosis intestinalis is a radiological finding characterized by the presence of gas in the bowel wall that is associated with multiple entities. Our aim is to know its incidence in lung transplant patients, its physiopathology and its clinical relevance. METHODS: A search of patients with pneumatosis intestinalis was performed in the database of the Lung Transplant Unit of our hospital. The presence of pneumatosis after transplantation was confirmed in all of them and relevant demographic, clinical and imaging variables were collected to evaluate its association and clinical expression, as well as the therapeutic approach after the findings. RESULTS: The incidence of pneumatosis intestinalis after lung transplantation in our center was 3.1% (17/546), developing between 9 and 1270 days after transplantation (mean, 198 days; median 68 days). Most of the patients were asymptomatic or with mild symptoms, without any major analytical alterations, and with a cystic and expansive radiological appearance. Pneumoperitoneum was associated in 70% of the patients (12/17). Conservative treatment was chosen in all cases. The mean time to resolution was 389 days. CONCLUSION: Pneumatosis intestinalis in lung transplant patients is a rare complication of uncertain origin, which can appear for a very long period of time after transplantation. It has little clinical relevance and can be managed without other diagnostic or therapeutic interventions.

Strategy for the management of acute postoperative pain in day surgery centres in Spain. DUCMA 2.0. project.

INTRODUCTION: Adequate treatment of acute postoperative pain is one of the quality requirements in ambulatory surgery and its suboptimal management is associated with delayed discharge, unplanned admissions and late admissions after home discharge. The aim of the present study was to learn about the organizational strategy for the management of postoperative pain in ambulatory surgery units (ASU) in Spain. METHODS: A cross-sectional, multicenter study was carried out based on an electronic survey on aspects related to the management of acute postoperative pain in different ASUs in our country. RESULTS: We recruited 133 ASUs of which 85 responded to the questions on the management of postoperative pain. Of the ASUs that responded, 80% had specific protocols for pain management and 37.6% provided preoperative information on the analgesic plan. The assessment of postoperative pain is carried out in 88.2% of the ASUs in the facility and only 56.5% at home. All ASUs use multimodal analgesia protocols; however, 68.2% report the use of opioids for the treatment of moderate to severe pain. Home invasive analgesia strategies are minimally used by the surveyed ASUs. CONCLUSIONS: The DUCMA study highlights that the practice of pain treatment in day surgery remains a challenge in our country and is not always in agreement with national guidelines. The results suggest the need to establish strategies to improve clinical practice and homogenize pain management in ambulatory surgery.

The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression.

Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such markers in the context of clinical trials evaluating upfront treatment in high-risk SMM (HR SMM) has not been explored yet, precluding the identification of baseline genomic alterations leading to drug resistance. For this reason, we carried out next-generation sequencing and fluorescent in-situ hybridization studies on 57 HR and ultra-high risk (UHR) SMM patients treated in the phase II GEM-CESAR clinical trial (NCT02415413). DIS3, FAM46C, and FGFR3 mutations, as well as t(4;14) and 1q alterations, were enriched in HR SMM. TRAF3 mutations were specifically associated with UHR SMM but identified cases with improved outcomes. Importantly, novel potential predictors of treatment resistance were identified: NRAS mutations and the co-occurrence of t(4;14) plus FGFR3 mutations were associated with an increased risk of biological progression. In conclusion, we have carried out for the first time a molecular characterization of HR SMM patients treated with an intensive regimen, identifying genomic predictors of poor outcomes in this setting.

[Management of chronic non-oncologic pain by multicomponent programs using non-pharmacologic therapies: A systematic review of the literature]. / Manejo del dolor crónico no oncológico con programas multicomponentes de terapias no farmacológicas: revisión sistemática de la literatura.

Chronic pain is a public health problem suffered by 20% of the world's population. Pharmacological approaches are insufficient, so a multi-therapeutic approach that also includes non-pharmacological therapies (psychological therapies, meditation, physical exercise, healthy habits, etc.) is proposed. The aim of this review was to review the existing scientific evidence on the effect of multicomponent programs with non-pharmacological therapies in people with chronic non-oncologic pain. To this end, a search for scientific articles was carried out in three databases (PubMed, Web of Science and PsycINFO) and 17 articles were selected, following the PRISMA recommendations. The patients who participated in these programs were mostly women, aged 18 to 80years, working or on sick leave due to pain, with secondary education or less and married. The most frequent pain was musculoskeletal, mainly low back pain. All the articles studied the effectiveness of two or more therapies, highlighting psychological therapies, physical exercise and education. Positive results were obtained in the reduction of different variables such as pain, pain catastrophizing, anxiety and depression, in addition to improving functionality and quality of life. It has also been shown that patients' prior expectations regarding the intervention influence its effectiveness. Although throughout the review there was great heterogeneity in the interventions, in the evaluation methods and in the results themselves, it can be concluded that multicomponent programs show positive results in the management of chronic pain, and should therefore be incorporated as a routine therapeutic treatment.

The A1/A2 ß-casein genotype of cows, but not their horn status, influences peptide generation during simulated digestion of milk.

The effect of the horn status of cows on their milk composition and quality is a controversial research topic. In this study, 128 milk samples from 64 horned and 64 disbudded Brown Swiss and Original Braunvieh cows were collected from alpine farms where both horned and disbudded cows were grazing on mountain pastures. The samples were analyzed for their detailed composition and protein digestion in a simulated in vitro digestion (INFOGEST). To exclude probable influences on digestion, the ß-CN genotype with its variants A1 and A2 was also included in the study. The effects of horn status and ß-CN genotype were investigated in linear mixed models, which included additional influencing random factors such as Original Braunvieh blood proportion, stage of lactation, and farm. Horn status did not have any effect on milk composition or digestion. In contrast, milk from A1A1 cows showed a different protein digestion than milk of A1A2 and A2A2 cows in the gastric phase, including smaller amounts of ß-casomorphin(BCM)21-associated peptides and larger amounts of BCM11-associated peptides. Abundances of BCM7 did not differ between ß-CN genotypes. At the end of the intestinal phase, the digested milk of A1A1 and A2A2 ß-CN genotypes did not differ.

El microquimerismo y la lactancia: un legado inmunológico perdurable de la madre al hijo / Microchimerism and lactation: a long-lasting immunologic legacy from mother to child

Resumen La interacción entre la madre y el feto durante el embarazo se ha estudiado exhaustivamente. Una de estas interacciones es el microquimerismo, el cual se caracteriza por un intercambio madre-feto de células y material genético. Adicional a la gestación, la madre hereda más células por medio de la lactancia, donde se transfieren biocomponentes (células, anticuerpos y bacterias comensales) que juegan un papel importante en la adaptación del recién nacido al medio. Las consecuencias de este microquimerismo posparto genera beneficios directos en los primeros meses de vida, previniendo enfermedades e infecciones, induciendo tolerancia a moléculas inocuas, así como favoreciendo el entrenamiento inmunitario del recién nacido, con respuestas dirigidas y beneficios en la vida adulta. Es destacable que el microquimerismo materno podría interpretarse como un legado inmunológico en el neonato, el cual es perdurable para algunos de sus componentes y definitorio en el correcto desarrollo de la progenie.

Abstract The interaction between mother and fetus during pregnancy has been extensively studied. One of these interactions is the microchimerism, which is characterized by a mother-fetus exchange of cells and genetic material. In addition to gestation, the mother inherits more cells through lactation, in which biocomponents (cells, antibodies, and commensal bacteria) that play an important role in the adaptation of the newborn to the environment are transferred. The consequences of this post-partum microchimerism generate direct benefits in the first months of life, preventing diseases and infections, inducing tolerance to innocuous molecules, as well as favoring the immunological training of the newborn, with specialized responses and benefits in adult life. It is noteworthy that maternal microchimerism could be interpreted as an immunological legacy in the neonate, which is lasting for some of its components, and defining in the correct development of the progeny.

[Impact of a multicomponent program with nonpharmacological therapies for patients with chronic pain]. / Impacto de un programa multicomponente con terapias no farmacológicas para pacientes con dolor crónico.

INTRODUCTION: 25.9% of Spanish people suffer from chronic pain. An integrated, interdisciplinary approach is recommended, with pharmacological and non-pharmacological therapies, involving patients in their self-care. OBJECTIVE: To evaluate the effectiveness and impact on resources of a program with non-pharmacological therapies in the control of non-oncological chronic pain in the short and medium term. MATERIAL AND METHODS: Quasi-experimental before-after study, follow-up 3-6 months, measuring: pain, well-being, quality of life, self-esteem, resilience, anxiety/depression (validated scales); patient-reported outcomes of workshop impact on pain management, habits and mood; ED and office visits; drug consumption and employment status. RESULTS: One hundred and forty-two patients completed the program; 131 (92.3%) were women, age: 56.0. Decreased: pain (scale 0-10) (start: 6.0; end of workshop: 4.0; 3 months: 5.0); anxiety (12.9; 10.4; 8.8) and depression (12.3; 7.23; 6.47) (scales 0-21). They increased: well-being (scale 0-10) (4.0; 6.0; 4.0); quality of life (scale 0-1) (0.418; 0.580; 0.536); health status (scale 0-100) (47.5; 60.0; 60.0); self-esteem (scale 9-36) (24.1; 27.5; 26.7); resilience (scale 6-30) (14.8; 17.4; 18.6). Patient-reported outcomes were performed by 136 patients at the end of the workshop and 79 at 3 months: pain decreased (end of program: 104, 76.5%; 3 months: 66, 83.5%); medication decreased (96, 76.2%; 60, 78.9%); habits improved (112, 88.2%; 69, 90.8%). Forty patients (37.4%) reduced visits to the emergency room, 40 (37.4%) reduced scheduled visits. Overall satisfaction: 9.8 out of 10. CONCLUSIONS: Patients learn to mitigate their pain, participate in their self-care and improve their quality of life, self-esteem and emotional state. The effects remained for 3-6 months.

Early Estrogen Replacement Therapy Attenuates Cardiac Dysfunction Caused by Aging and Ovariectomy in Female Wistar Rats.

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of women's mortality, linked to aging and reduced estrogen during menopause. Estrogen replacement therapy (ERT) is suggested for CVDs prevention. Yet, its timing initiation remains contentious. Thus, we aimed to evaluate the effect of early and late estrogen therapy on cardiac function and lipid metabolism in ovariectomized old female Wistar rats. METHODS: Fifty randomized female Wistar rats were included in 5 groups (n = 10, 18 months old): (1) Sham, (2) 10 weeks post ovariectomy (Ovx-10 w), (3) 10 weeks post Ovx + early estrogen replacement therapy (Ovx 10 w-early ERT), (4) 20 weeks post Ovx (Ovx-20 w) and (5) Ovx 20 w-late ERT. Three days (early ERT) or 10 weeks (late ERT) after surgery 17-ß estradiol was given (5 µg/kg/day), and 10 weeks after the start of ERT, we assessed cardiac function by echocardiography, electrocardiography, and cardiac catheterization. Estradiol, cholesterol, triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels were determined. Cardiac histology was performed with Masson's staining. RESULTS: Ovariectomy (Ovx) increases left ventricle internal systolic diameter (0.4 vs 0.3 cm, *p = 0.020) and decreases shortening fraction (40 vs 54 %, *p = 0.030) regardless of therapy. ERT prevents the increase in left ventricle mass after 10 weeks post-Ovx and the ejection fractionreduction after 20 weeks. Lower P wave amplitudes (18.8 vs 24.2 ms, *p = 0.013) were found in the Ovx-20 w group. A longer duration of the QRS complex after 20 weeks post-Ovx with and without ERT was found (32.5 and 32.1 vs 28.3 ms, *p = 0.003; *p = 0.007). Diastolic blood pressure was higher 20 weeks post-Ovx (86 vs 76 mmHg, *p = 0.047), regardless of ERT. The left ventricle (LV) -dP/dt was decreased in Ovx groups without ERT (-750 vs -1320 mmHg, *p = 0.034). An increase in LV collagen deposition was found in the Ovx 10 w group vs Sham (9.58 vs 4.54 %, *p = 0.028). Early ERT avoids the increase in body weight, cholesterol and LDL caused by Ovx. CONCLUSIONS: Ovariectomy causes time-dependent alterations in lipid metabolism, morphology, electrical activity, and heart contractile function. Early but not late ERT prevents some of these effects.

Chitosan for the treatment of inflammation of the oral mucosa: A systematic review.

BACKGROUND: Chitosan is a cheap, accessible, nontoxic, biocompatible, and biodegradable compound. Also, this polysaccharide possesses antibacterial and anti-inflammatory properties. Consequently, a wide range of chitosan applications in the dentistry field has been explored. This work aimed to conduct a systematic review to address the clinical efficacy of chitosan for the treatment of oral mucositis. MATERIAL AND METHODS: The design of the included studies were observational studies, randomized clinical trials (RCT), and non-randomized clinical trials (non-RCT), whereas, a series of cases, in vivo, and in vitro studies were excluded. The search was performed in PubMed, Web of Science, Scopus, Dentistry and Oral Sciences Source, and ClinicalTrials. Gray literature was searched at Google Scholar. Relevant data from all included studies were recorded. The risk of bias (using RoB 2) and the quality (using Grading of Recommendations Assessment, Development, and Evaluation, GRADE) assessments were carried out. RESULTS: From the 8413 records screened, 5 clinical trials fully met the eligibility criteria, which comprised a total of 192 participants suffering oral lesions and pain related to oral mucositis. 100% of the included studies exhibited a high risk of bias. The quality of the studies was between low and very low. CONCLUSIONS: The results of the included studies suggest that chitosan can diminish pain and improve the healing of ulcers in oral mucositis. However, there is no conclusive evidence of chitosan as a superior treatment for oral mucositis compared with other current therapies.

Diadenosine pentaphosphate regulates dendrite growth and number in cultured hippocampal neurons.

During the establishment of neuronal circuits, axons and dendrites grow and branch to establish specific synaptic connections. This complex process is highly regulated by positive and negative extracellular cues guiding the axons and dendrites. Our group was pioneer in describing that one of these signals are the extracellular purines. We found that extracellular ATP, through its selective ionotropic P2X7 receptor (P2X7R), negatively regulates axonal growth and branching. Here, we evaluate if other purinergic compounds, such as the diadenosine pentaphosphate (Ap5A), may module the dynamics of dendritic or axonal growth and branching in cultured hippocampal neurons. Our results show that Ap5A negatively modulates the dendrite's growth and number by inducing transient intracellular calcium increases in the dendrites' growth cone. Interestingly, phenol red, commonly used as a pH indicator in culture media, also blocks the P2X1 receptors, avoided the negative modulation of Ap5A on dendrites. Subsequent pharmacological studies using a battery of selective P2X1R antagonists confirmed the involvement of this subunit. In agreement with pharmacological studies, P2X1R overexpression caused a similar reduction in dendritic length and number as that induced by Ap5A. This effect was reverted when neurons were co-transfected with the vector expressing the interference RNA for P2X1R. Despite small hairpin RNAs reverting the reduction in the number of dendrites caused by Ap5A, it did not avoid the dendritic length decrease induced by the polyphosphate, suggesting, therefore, the involvement of a heteromeric P2X receptor. Our results are indicating that Ap5A exerts a negative influence on dendritic growth.

Consecuencias inmunológicas de la infección materna por VIH en el recién nacido no infectado / Immunologic consequences of maternal HIV infection in the uninfected newborn

Resumen Con la implementación de estrategias de cuidado perinatal, la tasa de transmisión vertical del virus de inmunodeficiencia humana (VIH) ha disminuido considerablemente en el mundo. A pesar de no mostrar cargas virales, los infantes expuestos al VIH no infectados (ENI) cursan en sus primeros meses de vida con mayores tasas de morbimortalidad. Esto se relaciona con enfermedades infecciosas por microorganismos oportunistas y menor respuesta a las vacunas en comparación con infantes sin exposición al virus, lo que sugiere alteraciones en su sistema inmunitario. En esta revisión abordamos diferentes evidencias de alteraciones en las respuestas inmunitarias innatas y adaptativas de infantes ENI que pudieran explicar esta disfuncionalidad inmunitaria. Adicionalmente, este conocimiento ayuda a entender cómo se desarrolla el sistema inmunitario desde los primeros momentos de gestación que servirán para encontrar alternativas de manejo y terapias para el bienestar de los infantes con esta condición.

Abstract With the implementation of perinatal care strategies, the rate of vertical transmission of human immunodeficiency virus (HIV) has decreased considerably worldwide. Despite the absence of viral loads, infants exposed to HIV not infected during gestation have higher morbidity and mortality rates. This is found to be related to infectious diseases by opportunistic microorganisms and lower response to vaccines in their first months of life compared to non-HIV exposed infants, suggesting alterations in their immune system. In this review we address different evidence of alterations in the innate and adaptive immune responses of HIV exposed infants that could explain their immune dysfunctionality. Additionally, this knowledge helps to understand how the immune system develops from the early stages of gestation and will serve to find management alternatives and therapies for the welfare of the infants with this condition.

Recommendations by the Spanish Society of Rheumatology on risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis.

OBJECTIVE: To present recommendations based on the available evidence and the consensus of experts, for risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis. METHODS: Clinical research questions relevant to the purpose of the document were identified. These questions were reformulated in PICO format (patient, intervention, comparison, outcome or outcome) by a panel of experts, selected based on their experience in the area. A systematic review of the evidence was carried out, grading according to the GRADE criteria (Grading of Recommendations Assessment, Development, and Evaluation). Specific recommendations were then formulated. RESULTS: 6 PICO questions were proposed by the panel of experts based on their clinical relevance and the existence of recent information regarding the risk of occurrence of serious infections, the risk of reactivation of the hepatitis B virus, the risk of reactivation of the virus varicella-zoster, the risk of appearance of skin (melanoma and non-melanoma) or haematological cancer, the risk of appearance of thromboembolic disease and the risk of progression of the human papilloma virus. A total of 28 recommendations were formulated, structured by question, based on the evidence found and the consensus of the experts. CONCLUSIONS: The SER recommendations on risk management of treatment with biologic therapies and JAK inhibitors in rheumatoid arthritis are presented.

Surgical treatment of retrorectal tumors: a plea for a laparoscopic approach.

INTRODUCTION: Retrorectal tumors (RRTs) are rare and often surgically excised due to the risk of malignant degeneration and compressive or obstructive symptoms. The approach for excision has traditionally been based on tumor location and performed using either a transabdominal or perineal approach depending on the position of the tumor. The advent of minimally invasive surgery, however, has challenged this paradigm. Here, we determined the applicability and potential advantages of a laparoscopic transabdominal approach in a series of 23 patients with RRTs. MATERIAL AND METHODS: We included 23 patients presenting with RRTs treated at the Surgical Gastrointestinal Unit at Hospital de Sant Pau that were registered prospectively since 1998. The preoperative evaluation consisted of colonoscopy, CT scan and/or MRI, mechanical bowel lavage, and antibiotic therapy. Signed consent was obtained from all patients for a laparoscopic transabdominal approach unless the tumor was easily accessible via a perineal approach. In case of recurrence, a transanal endoscopic microsurgery (TEM) approach was considered. Surgical details, immediate morbidity, and short- and long-term outcomes were recorded. RESULTS: Of the 23 RRT cases evaluated, 16 patients underwent a laparoscopic transabdominal approach and 6 underwent a perineal approach. No patients required conversion to open surgery. In the laparoscopic transabdominal group, the mean operating time was 158 min, the average postoperative hospital stay was 5 days, and postoperative morbidity was 18%. Three patients had recurrent RRTs, two of the three underwent surgical reintervention. The third patient was radiologically stable and close follow-up was decided. CONCLUSION: Our results show that laparoscopic transabdominal excision of RRT is a safe and effective technique, offering the potential advantages of less invasive access and reduced morbidity. This approach challenges the traditional paradigm of excision of these infrequent tumors based solely on tumor location and offers a viable alternative for the treatment of these infrequent tumors.

Functional Characterization of Four Olive Squalene Synthases with Respect to the Squalene Content of the Virgin Olive Oil.

The release of new olive cultivars with an increased squalene content in their virgin olive oil is considered an important target in olive breeding programs. In this work, the variability of the squalene content in a core collection of 36 olive cultivars was first studied, revealing two olive cultivars, 'Dokkar' and 'Klon-14', with extremely low and high squalene contents in their oils, respectively. Next, four cDNA sequences encoding squalene synthases (SQS) were cloned from olive. Sequence analysis and functional expression in bacteria confirmed that they encode squalene synthases. Transcriptional analysis in distinct olive tissues and cultivars indicated that expression levels of these four SQS genes are spatially and temporally regulated in a cultivar-dependent manner and pointed to OeSQS2 as the gene mainly involved in squalene biosynthesis in olive mesocarp and, therefore, in the olive oil. In addition, the biosynthesis of squalene appears to be transcriptionally regulated in water-stressed olive mesocarp.

[15th Post-ECTRIMS Meeting: a review of the latest developments presented at the 2022 ECTRIMS Congress (Part II)]. / XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (II).

INTRODUCTION: On 4 and 5 November 2022, Madrid hosted the 15th edition of the Post-ECTRIMS Meeting, where neurologists specialised in multiple sclerosis outlined the latest developments presented at the 2022 ECTRIMS Congress, held in Amsterdam from 26 to 28 October. AIM: To synthesise the content presented at the 15th edition of the Post-ECTRIMS Meeting, in an article broken down into two parts. DEVELOPMENT: This second part describes the new developments in terms of therapeutic strategies for escalation and de-escalation of disease-modifying therapies (DMT), when and in whom to initiate or switch to highly effective DMT, the definition of therapeutic failure, the possibility of treating radiologically isolated syndrome and the future of personalised treatment and precision medicine. It also considers the efficacy and safety of autologous haematopoietic stem cell transplantation, different approaches in clinical trial design and outcome measures to assess DMT in progressive stages, challenges in the diagnosis and treatment of cognitive impairment, and treatment in special situations (pregnancy, comorbidity and the elderly). In addition, results from some of the latest studies with oral cladribine and evobrutinib presented at ECTRIMS 2022 are shown.

TITLE: XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (II).Introducción. El 4 y el 5 de noviembre se celebró en Madrid la Reunión Post-ECTRIMS, en la que neurólogos expertos en esclerosis múltiple resumieron las principales novedades presentadas en el congreso de ECTRIMS 2022, celebrado entre el 26 y el 28 de octubre en Ámsterdam. Objetivo. Sintetizar las ponencias que tuvieron lugar en la Reunión Post-ECTRIMS, en un artículo desglosado en dos partes. Desarrollo. En esta segunda parte, se presentan las novedades sobre las estrategias terapéuticas de escalado y desescalado de los tratamientos modificadores de la enfermedad (TME), cuándo y a quién iniciar o cambiar a TME de alta eficacia, la definición de fracaso terapéutico, la posibilidad de tratar el síndrome radiológico asilado, el futuro del tratamiento personalizado y la medicina de precisión, la eficacia y seguridad del autotrasplante de células madre hematopoyéticas, diferentes aproximaciones en el diseño de ensayos clínicos y en las medidas de resultados para evaluar TME en fases progresivas, retos en el diagnóstico y tratamiento del deterioro cognitivo, y tratamiento en situaciones especiales (embarazo, comorbilidad y personas mayores). Además, se muestran los resultados de algunos de los últimos estudios realizados con cladribina oral y evobrutinib presentados en el ECTRIMS 2022.

Basal Cell Carcinoma in the Southern Health Area of Tenerife. Key Clinical and Pathological Factors and Margin Status After Excision. / Carcinoma basocelular en el Área Sur de Salud de Tenerife. Características clínico-patológicas fundamentales y estado de los bordes tras exéresis.

BACKGROUND AND OBJECTIVE: Surgical excision is the treatment of choice for basal cell carcinoma (BCC). Complete excision with clear margins is important for reducing the risk of recurrence. The aims of this study were to describe the characteristics of BCCs in our health care area, calculate the percentage of positive margins after surgical excision, and determine the risk factors for incomplete excision. MATERIAL AND METHODS: Retrospective observational study of BCCs that were surgically removed at Hospital Universitario Nuestra Señora de Candelaria, in Santa Cruz de Tenerife, Spain, between January 1, 2014 and December 31, 2014. Information was collected on demographic, clinical, and histologic variables, surgical approach, margin status, and the department responsible. RESULTS: In total, 966 BCCs were diagnosed in 776 patients. Nine percent of tumors with complete data were biopsied, 89% were surgically excised, and 2% were removed by shave excision. The median age of patients with excised tumors was 71 years and 52% were men. BCCs were most often located on the face (59.1%). Surgical margins were analyzed in 506 cases, 17% of which had positive margins. Incomplete excision was significantly more common in tumors located on the face (22% vs. 10% for other locations) and in high-risk subtypes according to the World Health Organization classification (25% vs. 15% for low-risk subtypes). CONCLUSIONS: The characteristics of BCCs in our health care area are similar to those described elsewhere. Facial location and histologic subtype are risk factors for incomplete excision. Careful surgical planning is therefore important in the initial management of BCCs with these characteristics.

A multidisciplinary consensus statement on the optimal pharmacological treatment for metastatic hormone-sensitive prostate cancer.

Androgen deprivation therapy (ADT) is the mainstay treatment for metastatic hormone-sensitive prostate cancer (mHSPC). The addition of docetaxel or new hormone therapies (abiraterone, apalutamide, or enzalutamide) improves overall survival and is currently the standard of care. However, the decision on the specific regimen to accompany ADT should be discussed with the patient, considering factors such as possible associated toxicities, duration of treatment, comorbidities, patient preferences, as there is no sufficient evidence to recommend one regimen over the other in most cases. This paper summarizes the evidence on the management of mHSPC and provides consensus recommendations on the optimal treatment in combination with ADT in mHSPC patients, with special attention to the patient's clinical profile.