[[Translated article]Melanoma Registry of the Spanish Academy of Dermatology and Venereology (REGESMEL): Description and Data in its First Year of Operation. / Registro de Melanoma de la Academia Española de Dermatología y Venereología (REGESMEL): descripción y datos en el primer año de funcionamiento.

INTRODUCTION: The incidence of melanoma is growing in Spain. The prognostic stages of patients with melanoma are determined by various biological factors, such as tumor thickness, ulceration, or the presence of regional or distant metastases. The Spanish Academy of Dermatology and Venereology (AEDV) has encouraged the creation of a Spanish Melanoma Registry (REGESMEL) to evaluate other individual and health system-related factors that may impact the prognosis of patients with melanoma. The aim of this article is to introduce REGESMEL and provide basic descriptive data on to its first year in service. METHODS: REGESMEL is a prospective, multicentre cohort of consecutive patients with invasive cutaneous melanoma that includes demographics, staging, individual, and health care-related baseline data, while storing the patients' health records and surgical treatment received. RESULTS: A total of 450 cases of invasive cutaneous melanoma from 19 participant centres were included, with a predominance of thin melanomas ≤ 1 mm thick (54.7%), mainly located on the posterior trunk (35.2%). Selective sentinel lymph node biopsy was performed in 40.7% of the cases. Most cases of melanoma were suspected by the patient (30.4%), or his/her dermatologist (29.6%). Patients received care mainly in public health centers (85.2%), with tele-dermatology resources being used in 21.6% of the cases. CONCLUSIONS: The distribution of the pathological and demographic variables of melanoma cases is consistent with data from former studies. REGESMEL has already recruited patients from 15 Spanish provinces and given its potential representativeness, it renders the Registry as an important tool to address a wide range of research questions.

Diet changes due to urbanization in South Africa are linked to microbiome and metabolome signatures of Westernization and colorectal cancer.

Transition from traditional high-fiber to Western diets in urbanizing communities of Sub-Saharan Africa is associated with increased risk of non-communicable diseases (NCD), exemplified by colorectal cancer (CRC) risk. To investigate how urbanization gives rise to microbial patterns that may be amenable by dietary intervention, we analyzed diet intake, fecal 16 S bacteriome, virome, and metabolome in a cross-sectional study in healthy rural and urban Xhosa people (South Africa). Urban Xhosa individuals had higher intakes of energy (urban: 3,578 ± 455; rural: 2,185 ± 179 kcal/d), fat and animal protein. This was associated with lower fecal bacteriome diversity and a shift from genera favoring degradation of complex carbohydrates (e.g., Prevotella) to taxa previously shown to be associated with bile acid metabolism and CRC. Urban Xhosa individuals had higher fecal levels of deoxycholic acid, shown to be associated with higher CRC risk, but similar short-chain fatty acid concentrations compared with rural individuals. Fecal virome composition was associated with distinct gut bacterial communities across urbanization, characterized by different dominant host bacteria (urban: Bacteriodota; rural: unassigned taxa) and variable correlation with fecal metabolites and dietary nutrients. Food and skin microbiota samples showed compositional differences along the urbanization gradient. Rural-urban dietary transition in South Africa is linked to major changes in the gut microbiome and metabolome. Further studies are needed to prove cause and identify whether restoration of specific components of the traditional diet will arrest the accelerating rise in NCDs in Sub-Saharan Africa.

Melanoma Registry of the Spanish Academy of Dermatology and Venereology (REGESMEL): Description and Data in its First Year of Operation. / Registro de Melanoma de la Academia Española de Dermatología y Venereología (REGESMEL): descripción y datos en el primer año de funcionamiento.

INTRODUCTION: The incidence of melanoma is rising in Spain. The prognostic stages of patients with melanoma are determined by various biological factors, such as tumor thickness, ulceration, or the presence of regional or distant metastases. The Spanish Academy of Dermatology and Venereology (AEDV) has encouraged the creation of a Spanish Melanoma Registry (REGESMEL) to evaluate other individual and health system-related factors that may impact the prognosis of patients with melanoma. The aim of this article is to introduce REGESMEL and provide basic descriptive data for its first year of operation. METHODS: REGESMEL is a prospective, multicentre cohort of consecutive patients with invasive cutaneous melanoma that collects demographic and staging data as well as individual and healthcare-related baseline data. It also records the medical and surgical treatment received by patients. RESULTS: A total of 450 cases of invasive cutaneous melanoma from 19 participant centres were included, with a predominance of thin melanomas≤1mm thick (54.7%), mainly located on the posterior trunk (35.2%). Selective sentinel lymph node biopsy was performed in 40.7% of cases. Most cases of melanoma were suspected by the patient (30.4%), or his/her dermatologist (29.6%). Patients received care mainly in public health centers (85.2%), with tele-dermatology resources being used in 21.6% of the cases. CONCLUSIONS: The distribution of the pathological and demographic variables of melanoma cases is consistent with data from former studies. REGESMEL has already recruited patients from 15 Spanish provinces and given its potential representativeness, it renders the Registry as an important tool to address a wide range of research questions.

De-escalating axillary management after neoadjuvant chemotherapy in breast cancer: The ratio of positive sentinel lymph nodes matters.

BACKGROUND: De-escalation of axillary surgery in breast cancer (BC) patients diminishes sequelae without compromising cancer outcomes. Surgical management of the axilla is challenging after neoadjuvant treatment. We aimed to identify the factors associated with residual axillary disease amenable to lymphadenectomy in patients with positive sentinel lymph node biopsy (SLNB). METHODS: We conducted a retrospective observational study in Hospital 12 de Octubre (Spain). We included BC patients with positive SLNB who underwent axillary dissection after neoadjuvant chemotherapy. Univariate and multivariate logistic regression models were performed to identify independent predictors of residual axillary disease. We estimated the ratio of positive nodes in SLNB and assessed the diagnostic validity of this ratio in relation to residual axillary disease. RESULTS: We included 103 patients in the study. Residual axillary disease was identified in 54 patients (52.4%). Clinically node positive status at diagnosis (OR = 18.3, 95%CI: 4.0-83.6) and a ratio of positive nodes in SLNB ≥0.5 (OR = 6.5, 95%CI 41.7-23.7) were associated with residual axillary disease. The sensitivity and negative predictive value of a ratio of positive nodes in SLNB ≥0.5 were 87% (95%CI 75.1%-94.6%) and 75% (95%CI 55.1%-89.3%), respectively. CONCLUSIONS: In our study, for patients with positive SLNB after neoadjuvant chemotherapy, stage N+ at diagnosis and a ratio of positive nodes in SLNB ≥0.5 were independent risk factors of positive residual axillary disease. This ratio is a feasible measure with a good diagnostic validity for residual axillary disease and could be used as a guiding factor in the surgical management of these patients.

Irreversible electroporation: Beyond the limits of tumor ablation.

Irreversible Electroporation (IRE) is a non-thermal tumor ablation technique. High-voltage electrical pulses are applied between pairs of electrodes inserted around and/or inside a tumor. The generated electric current induces the creation of nanopores in the cell membrane, triggering apoptosis. As a result, IRE can be safely used in areas near delicate vascular structures where other thermal ablation methods are contraindicated. Currently, IRE has demonstrated to be a successful ablation technique for pancreatic, renal, and liver tumors and is widely used as a focal therapeutic option for prostate cancer. The need for specific anesthetic management and accurate parallel placement of multiple electrodes entails a high level of complexity and great expertise from the interventional team is required. Nevertheless, IRE is a very promising technique with a remarkable systemic immunological capability and may impact on distant metastases (abscopal effect).

Exploring the potential of Physics-Informed Neural Networks to extract vascularization data from DCE-MRI in the presence of diffusion.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is widely used to assess tissue vascularization, particularly in oncological applications. However, the most widely used pharmacokinetic (PK) models do not account for contrast agent (CA) diffusion between neighboring voxels, which can limit the accuracy of the results, especially in cases of heterogeneous tumors. To address this issue, previous works have proposed algorithms that incorporate diffusion phenomena into the formulation. However, these algorithms often face convergence problems due to the ill-posed nature of the problem. In this work, we present a new approach to fitting DCE-MRI data that incorporates CA diffusion by using Physics-Informed Neural Networks (PINNs). PINNs can be trained to fit measured data obtained from DCE-MRI while ensuring the mass conservation equation from the PK model. We compare the performance of PINNs to previous algorithms on different 1D cases inspired by previous works from literature. Results show that PINNs retrieve vascularization parameters more accurately from diffusion-corrected tracer-kinetic models. Furthermore, we demonstrate the robustness of PINNs compared to other traditional algorithms when faced with noisy or incomplete data. Overall, our results suggest that PINNs can be a valuable tool for improving the accuracy of DCE-MRI data analysis, particularly in cases where CA diffusion plays a significant role.

Allelic variants of the estrogen receptor genes and frailty phenotype in postmenopausal women.

OBJECTIVE: The prevalence of frailty has been related to menopause. Our main objective was to investigate whether single nucleotide polymorphisms (SNPs) of the estrogen receptor (ER) ERα and ERß genes were related to the frailty phenotype in a population of community-dwelling postmenopausal women. METHODS: A cross-sectional study was performed in which we selected five SNPs, three in the ERα gene and two in the ERß. Linear regression was used to estimate the percentage of phenotypic variance after adjusting for confounding variables. RESULTS: A total of 470 women (mean ± standard deviation age 63.83 ± 8.16 years) were included, of whom 137 women were frail. The SNP rs3798577 of the ERα gene was the only variant associated with frailty, but this significance faded in the multivariant analysis. Body mass index (p = 0.012), number of comorbidities (0 vs. ≥2, p = 0.002) and two reproductive variables, number of miscarriages (none vs. ≥2, p = 0.036) and of childbirths (one vs. ≥3, p = 0.008), were independently related to frailty. CONCLUSION: The five SNPs of the ERα and ERß genes tested were not correlated with frailty. Other SNPs of the ER warrant analysis to clarify whether variance in the gene response affects frailty status.

Treatment of thyroglossal cyst using Koempel's technique: initial experience. / Tratamiento del quiste tirogloso mediante técnica de Koempel. Experiencia inicial.

INTRODUCTION: In spite of being inaccurate in terms of suprahyoid dissection, Sistrunk's procedure is the gold-standard technique in the treatment of thyroglossal cyst. Since it was first described in 2014, the modifications introduced by Koempel have allowed for a more reproducible suprahyoid approach. We present our initial experience with this technique. METHODS: A retrospective study of patients with thyroglossal cyst undergoing Koempel's technique in our institution from 2021 to 2022 was carried out. Demographic, clinical, and histological data was collected. RESULTS: In the study period, 5 patients -3 girls and 2 boys- underwent surgery. Median age and weight were 5 years (2-6) and 16 kg (14-25), respectively. All patients had suffered from previous infections, with 60% having cutaneous fistulization. In 2 patients, surgery was indicated following Sistrunk's procedure as a result of recurrence. Median operating time was 77 minutes (57-110), with the genioglossal muscle plane being identified in the 5 patients. No immediate complications were recorded, and diagnosis of thyroglossal cyst was histologically confirmed in all cases. One of the formerly recurrent patients had recurrence following surgery, but it was subclinical and incidentally diagnosed at control ultrasonography. The remaining patients had no recurrences after a median 8-month (1-12) follow-up period. CONCLUSIONS: Koempel's technique allows for a safe and reproducible approach of the suprahyoid segment. It is an attractive option in complicated cases as a result of previous infection or recurrence.

INTRODUCCION: La intervención de Sistrunk es el gold-standard en el tratamiento del quiste tirogloso pese a su imprecisión en cuanto a la disección suprahioidea. Tras su descripción en 2014, las modificaciones introducidas por Koempel, han permitido un abordaje suprahioideo más reproducible. Presentamos nuestra experiencia inicial con esta técnica. METODOS: Estudio retrospectivo de los pacientes con quiste tirogloso intervenidos mediante técnica de Koempel en nuestro centro en el periodo 2021-2022, recogiéndose datos demográficos, clínicos e histológicos. RESULTADOS: Durante el periodo de estudio se intervinieron 5 pacientes (3 mujeres/2 varones), con una mediana de edad y peso de 5 años (2-6) y 16 kg (14-25) respectivamente. Todos los casos habían sufrido infecciones previas presentando fistulización cutánea el 60%. En 2 de los pacientes se indicó la cirugía por recidiva tras intervención de Sistrunk. La mediana del tiempo quirúrgico fue de 77minutos (57-110) identificándose el plano del músculo geniogloso en los 5 pacientes. No hubo complicaciones inmediatas y el diagnóstico de quiste tirogloso se confirmó histológicamente en todos los casos. Uno de los pacientes del grupo con recidiva previa, presentó recidiva tras la intervención, siendo esta subclínica y diagnosticada incidentalmente tras ecografía de control. El resto de los pacientes no presentó ninguna recurrencia tras un seguimiento mediana de 8 meses (1-12). CONCLUSIONES: La técnica de Koempel permite un abordaje seguro y reproducible del segmento suprahioideo siendo una opción atractiva en casos complicados por infección o recidiva previa.

[Translated article] Requirements for Accessing New Dermatology Drugs in Spain: Results of the EQUIDAD Study.

BACKGROUND: Although the Spanish Ministry of Health prepares national therapeutic positioning reports (TPRs) and drug reimbursement policies, each of the country's 17 autonomous communities (ACs) is responsible for health care services and prescription requirements in its territory. The aim of the EQUIDAD study was to describe and explore potential differences in prescription requirements for new dermatology drugs across the autonomous communities. MATERIAL AND METHODS: Cross-sectional study conducted in April and May, 2023. Two dermatologists with management responsibilities from each autonomous community reported on territorial and more local prescription requirements for drugs covered by national TPRs issued between 2016 and 2022. RESULTS: Thirty-three researchers from 17 autonomous communities participated. The data submitted revealed between-community inequities in access to new drugs. Overall, 64.7% of the regions imposed additional prescription requirements to those mentioned in the TPRs for psoriasis. This percentage was lower for atopic dermatitis (35.3%) and melanoma (11.8%). The most common requirement for accessing a new drug was a previous prescription for another drug. Differences and additional requirements were also detected at the local level (i.e., differences between hospitals within the same autonomous community). CONCLUSIONS: Spain's autonomous communities have multiple regional and local prescription requirements that are not aligned with national TPR recommendations. These differences result in inequitable access to new drugs for both patients and practitioners across Spain.

Last twenty-years activity of cardiovascular tissue banking in Barcelona.

The Barcelona Tissue Bank was established from the merge of two previous multi-tissue banks. Potential donors are screened by Donor Center staff and multi-tissue retrieval is performed by specialized own teams. Tissue processing and preservation is performed in clean room facilities by specialised personnel. After quality control of both donor and all tissues results, the heart valves and vascular segments are stored until medical request. The aim of this report is to present the cardiovascular tissue activity and retrospectively evaluate the outcomes of the changes performed in last 20 years. Cardiovascular tissue from 4088 donors was received, specifically 3115 hearts and 2095 vascular segments were processed and evaluated. A total of 48% of the aortic valves, 68% of the pulmonary valves and 75% of the vascular segments were suitable for transplant. The main reason for discarding tissue was macroscopic morphology followed by microbiological results, for both valves and arteries. Altogether, 4360 tissues were distributed for transplantation: 2032 (47%) vascular segments, 1545 (35%) pulmonary valves and 781 (18%) aortic valves. The most common indication for aortic valve surgery was the treatment of endocarditis, while for pulmonary valves, it was congenital malformation reconstruction. Vascular segments were mainly used for reconstruction after ischemia. During this period, a number of changes were made with the goal of enhancing tissue quality, safety and efficacy. These improvements were achieved through the use of a new antibiotic cocktail, increasing of donor age criteria and changing the microbiological control strategy.

Requirements for Accessing New Dermatology Drugs in Spain: Results of the EQUIDAD Study. / Condicionantes de acceso a nuevos medicamentos dermatológicos en España: resultados del proyecto EQUIDAD.

BACKGROUND: Although the Spanish Ministry of Health prepares national therapeutic positioning reports (TPRs) and drug reimbursement policies, each of the country's 17 autonomous communities (ACs) is responsible for health care services and prescription requirements in its territory. The aim of the EQUIDAD study was to describe and explore potential differences in prescription requirements for new dermatology drugs across the autonomous communities. MATERIAL AND METHODS: Cross-sectional study conducted in April and May, 2023. Two dermatologists with management responsibilities from each autonomous community reported on territorial and more local prescription requirements for drugs covered by national TPRs issued between 2016 and 2022. RESULTS: Thirty-three researchers from 17 autonomous communities participated. The data submitted revealed between-community inequities in access to new drugs. Overall, 64.7% of the regions imposed additional prescription requirements to those mentioned in the TPRs for psoriasis. This percentage was lower for atopic dermatitis (35.3%) and melanoma (11.8%). The most common requirement for accessing a new drug was a previous prescription for another drug. Differences and additional requirements were also detected at the local level (i.e., differences between hospitals within the same autonomous community). CONCLUSIONS: Spain's autonomous communities have multiple regional and local prescription requirements that are not aligned with national TPR recommendations. These differences result in inequitable access to new drugs for both patients and practitioners across Spain.

Current approach to skin and soft tissue infections. Thinking about continuity of care.

Skin and soft tissue infections are a common reason for patients seeking inpatient and outpatient medical care. Surgery is an essential part of managing in many episodes. Careful evaluation of antibiotic therapy could help clinicians in early identification to patients with treatment failure and to consider an alternative approach or a new surgical revision in "focus control". With the arrival of new drugs, there is a need to refine the appropriate drug's decision-making. Drugs with a long half-life (long-acting lipoglycopeptides such as dalbavancin or oritavancin), which allows weekly administration (or even greater), can reduce hospital admission and length of stay with fewer healthcare resources through outpatient management (home hospitalization or day hospitals). New anionic fluoroquinolones (e.g. delafloxacin), highly active in an acidic medium and with the possibility of switch from the intravenous to the oral route, will also make it possible to achieve these new healthcare goals and promote continuity of care. Therefore, management should rely on a collaborative multidisciplinary group with experience in this infectious syndrome.

Urgent laparoscopic cholecystectomy as a result of acute calculous cholecystitis in Pediatrics. / Colecistectomía laparoscópica urgente por colecistitis aguda litiásica en Pediatría.

INTRODUCTION: In spite of the increase in the prevalence of cholelithiasis in the last decades, no recommendations regarding the best treatment of acute calculous cholecystitis (AC) in Pediatrics have been developed. CLINICAL CASE: 4-year-old, 20kg male patient with no significant history referred to our institution as a result of abdominal sepsis. The blood count showed leukocytosis, with normal hemoglobin and bilirubin levels, and a normal liver function. The abdominal ultrasonography revealed cholelithiasis, gallbladder hydrops, and an inflammatory process compatible with appendicular plastron. In the diagnostic laparoscopy, the appendix was macroscopically normal, and acute cholecystitis was observed. Given the patient's situation, and in cooperation with the General Surgery Department, laparoscopic cholecystectomy was carried out. The patient recovered uneventfully on hospitalization day 5 under piperacillin-tazobactam treatment. DISCUSSION: There are no recommendations regarding AC treatment in children. In septic patients, cooperation between general and pediatric surgeons allows urgent cholecystectomy to be considered as a safe option.

INTRODUCCION: Pese al aumento en la prevalencia de colelitiasis durante las últimas décadas, no se han desarrollado recomendaciones sobre el mejor tratamiento de la colecistitis aguda litiásica (CA) en Pediatría. CASO CLINICO: Paciente varón de 4 años y 20 kg de peso sin antecedentes de interés, que acude derivado por sepsis de origen abdominal. Analíticamente destaca leucocitosis con hemoglobina, función hepática y bilirrubina normales. La ecografía abdominal muestra colelitiasis, hidrops vesicular y proceso inflamatorio compatible con plastrón apendicular. En laparoscopia diagnóstica se observa apéndice macroscópicamente normal y colecistitis aguda. Ante la situación del paciente se realiza, conjuntamente con Cirugía General, colecistectomía laparoscópica. El paciente se recupera sin incidencias tras 5 días de ingreso bajo cobertura con piperacilina-tazobactam. COMENTARIOS: No existen recomendaciones sobre el tratamiento de la CA en niños. En los pacientes sépticos, la colaboración entre cirujanos pediátricos y cirujanos generales permite contemplar la colecistectomía urgente como una opción segura.

Maintenance olaparib rechallenge in patients with platinum-sensitive relapsed ovarian cancer previously treated with a PARP inhibitor (OReO/ENGOT-ov38): a phase IIIb trial.

BACKGROUND: Poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy is the standard of care for some patients with advanced ovarian cancer. We evaluated the efficacy and safety of PARP inhibitor rechallenge. PATIENTS AND METHODS: This randomized, double-blind, multicenter trial (NCT03106987) enrolled patients with platinum-sensitive relapsed ovarian cancer who had received one prior PARP inhibitor therapy for ≥18 and ≥12 months in the BRCA-mutated and non-BRCA-mutated cohorts, respectively, following first-line chemotherapy or for ≥12 and ≥6 months, respectively, following a second or subsequent line of chemotherapy. Patients were in response following their last platinum-based chemotherapy regimen and were randomized 2 : 1 to maintenance olaparib tablets 300 mg twice daily or placebo. Investigator-assessed progression-free survival (PFS) was the primary endpoint. RESULTS: Seventy four patients in the BRCA-mutated cohort were randomized to olaparib and 38 to placebo, and 72 patients in the non-BRCA-mutated cohort were randomized to olaparib and 36 to placebo; >85% of patients in both cohorts had received ≥3 prior lines of chemotherapy. In the BRCA-mutated cohort, the median PFS was 4.3 months with olaparib versus 2.8 months with placebo [hazard ratio (HR) 0.57; 95% confidence interval (CI) 0.37-0.87; P = 0.022]; 1-year PFS rates were 19% versus 0% (Kaplan-Meier estimates). In the non-BRCA-mutated cohort, median PFS was 5.3 months for olaparib versus 2.8 months for placebo (HR 0.43; 95% CI 0.26-0.71; P = 0.0023); 1-year PFS rates were 14% versus 0% (Kaplan-Meier estimates). No new safety signals were identified with olaparib rechallenge. CONCLUSIONS: In ovarian cancer patients previously treated with one prior PARP inhibitor and at least two lines of platinum-based chemotherapy, maintenance olaparib rechallenge provided a statistically significant, albeit modest, PFS improvement over placebo in both the BRCA-mutated and non-BRCA-mutated cohorts, with a proportion of patients in the maintenance olaparib rechallenge arm of both cohorts remaining progression free at 1 year.