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Resumen: Introducción: La fascitis plantar supone la principal causa de dolor en el talón en pacientes de mediana edad. En los casos crónicos, la dorsiflexión limitada del tobillo producida por contractura aislada del gastrocnemio se considera el principal factor de riesgo de padecerla. Por lo que en los últimos años se ha incrementado el número de pacientes intervenidos mediante fasciotomía proximal de gemelo medial (FPGM) para tratar la fascitis plantar crónica. Material y métodos: Revisión sistemática siguiendo las guías PRISM. Hemos realizado una búsqueda bibliográfica en las bases de datos PubMed, Science Direct, Cochrane Library y Web of Science. Se encontraron 184 artículos. La extracción de datos fue realizada utilizando el software Covidence, y se realizó un análisis de calidad y riesgo de sesgo de los artículos incluidos, basada en Cochrane risk of bias Tool 2.0. Resultados: Fueron incluidos tres artículos en la revisión, dos ensayos clínicos aleatorizados y un estudio de cohortes con un total de 138 pacientes. En los estudios analizados los pacientes tras la FPGM presentaban mejorías significativas en la valoración del dolor y en la escala de la American Orthopaedic Foot & Ankle Society (AOFAS), con niveles altos de satisfacción de los pacientes. Se encontraron aumentos en el ángulo de dorsiflexión del tobillo tras 12 meses de seguimiento, sin pérdidas de fuerza del gastrocnemio. La tasa de complicaciones fue baja y menores con la FPGM que con la fasciotomía plantar (FP). Conclusión: La fasciotomía proximal de gastrocnemio medial aporta beneficio clínico en los pacientes con fascitis plantar crónica, con baja probabilidad de complicaciones y con una satisfacción alta de los pacientes. Abstract: Introduction: Plantar fasciitis is the main cause of heel pain in middle-aged patients. In chronic cases, limited ankle dorsiflexion caused by isolated gastrocnemius contracture is considered the main risk factor for suffering it. Therefore, in recent years the number of patients operated on by proximal fasciotomy of the medial gastrocnemius (FPGM) has increased to treat chronic plantar fasciitis. Material and methods: Systematic review following the PRISMA guidelines. We have carried out a bibliographic search in Pubmed, Science Direct, Cochrane Library and Web of Science databases. One hundred and eighty-four articles were found. Data extraction was performed using the Covidence software, and a quality and risk of bias analysis of the included articles was performed based on the Cochrane risk of bias Tool 2.0. Results: Three articles were included in the review: two randomized clinical trials and one cohort study with a total of 138 patients. In the analyzed studies, patients after proximal fasciotomy of the medial gastrocnemius showed significant improvements in pain and in the AOFAS score with high levels of patient satisfaction. Increases in ankle dorsiflexion angle were found after 12 months of follow-up, with no loss of gastrocnemius strength. The complication rate was low and fewer occurred in the proximal fasciotomy compared to plantar fasciotomy. Conclusion: Proximal fasciotomy of the medial gastrocnemius provides clinical benefit in patients with chronic plantar fasciitis, with a low probability of complications and high patient satisfaction.

Purpose: To evaluate the efficacy and safety of the combination of olaparib plus trastuzumab in patients with HER2-positive advanced breast cancer (ABC) and germinal BRCA mutations (gBRCAm). Methods: OPHELIA (NCT03931551) was a single-arm, open-label, phase 2 clinical trial. Patients aged ≥18 years diagnosed with HER2-positive ABC with germinal deleterious mutations in BRCA1 or BRCA2 who had received at least one prior systemic regimen for advanced disease were enrolled. Patients received olaparib plus trastuzumab until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was investigator-assessed clinical benefit rate for at least 24 weeks as per RECIST v.1.1. Key secondary endpoints included overall response rate (ORR) and safety profile. Results: A total of 68 pre-treated HER2-positive ABC patients were screened. Due to slow accrual the trial was stopped after enrolling 5 patients instead of the planned sample size of 20. Four patients achieved clinical benefit (80.0 %, 95 % CI; 28.4–99.5, p

Introduction: Plantar fasciitis is the main cause of heel pain in middle-aged patients. In chronic cases, limited ankle dorsiflexion caused by isolated gastrocnemius contracture is considered the main risk factor for suffering it. Therefore, in recent years the number of patients operated on by proximal fasciotomy of the medial gastrocnemius (FPGM) has increased to treat chronic plantar fasciitis. Material and methods: Systematic review following the PRISMA guidelines. We have carried out a bibliographic search in Pubmed, Science Direct, Cochrane Library and Web of Science databases. One hundred and eighty-four articles were found. Data extraction was performed using the Covidence software, and a quality and risk of bias analysis of the included articles was performed based on the Cochrane risk of bias Tool 2.0. Results: Three articles were included in the review: two randomised clinical trials and one cohort study with a total of 138 patients. In the analysed studies, patients after proximal fasciotomy of the medial gastrocnemius showed significant improvements in pain and in the AOFAS score with high levels of patient satisfaction. Increases in ankle dorsiflexion angle were found after 12 months of follow-up, with no loss of gastrocnemius strength. The complication rate was low and fewer occurred in the proximal fasciotomy compared to plantar fasciotomy. Conclusion: Proximal fasciotomy of the medial gastrocnemius provides clinical benefit in patients with chronic plantar fasciitis, with a low probability of complications and high patient satisfaction. Resumen: Introducción: La fascitis plantar supone la principal causa de dolor en el talón en los pacientes de mediana edad. En los casos crónicos, la dorsiflexión limitada del tobillo producida por contractura aislada del gastrocnemio se considera el principal factor de riesgo de padecerla. Por lo que en los últimos años se ha incrementado el número de pacientes intervenidos mediante fasciotomía proximal de gemelo medial (FPGM) para tratar la fascitis plantar crónica. Material y métodos: Revisión sistemática siguiendo las guías PRISM. Hemos realizado una búsqueda bibliográfica en las bases de datos PubMed, Science Direct, Cochrane Library y Web of Science. Se encontraron 184 artículos. La extracción de datos fue realizada utilizando el software Covidence, y se realizó un análisis de calidad y riesgo de sesgo de los artículos incluidos, basada en Cochrane risk of bias Tool 2.0. Resultados: Fueron incluidos 3 artículos en la revisión, 2 ensayos clínicos aleatorizados y un estudio de cohortes con un total de 138 pacientes. En los estudios analizados los pacientes tras la FPGM presentaban mejorías significativas en la valoración del dolor y en la escala de la American Orthopaedic Foot & Ankle Society (AOFAS), con niveles altos de satisfacción de los pacientes. Se encontraron aumentos en el ángulo de dorsiflexión del tobillo tras 12 meses de seguimiento, sin pérdidas de fuerza del gastrocnemio. La tasa de complicaciones fue baja y menores con la FPGM que con la fasciotomía plantar (FP). Conclusión: La fasciotomía proximal de gastrocnemio medial aporta beneficio clínico en los pacientes con fascitis plantar crónica, con baja probabilidad de complicaciones y con una satisfacción alta de los pacientes.

Background: The capsule formulation of CDK4/6 inhibitor palbociclib has reduced solubility at gastric pH > 4.5 and may have decreased activity when used with proton-pump inhibitors (PPI). Herein, we report the effect of PPI on palbociclib capsule activity and safety in the PARSIFAL study. Methods: First-line endocrine-sensitive, hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) patients received palbociclib capsules plus fulvestrant or letrozole. The primary endpoint was progression-free survival (PFS). This post-hoc analysis compared PPI use. Patients were PPI-naïve (N-PPI) if not on PPI during the study, and either early (E-PPI) or long-term PPI (LT-PPI) if on PPI at study entry or for at least ≥⅔ of treatment, respectively. PPI groups were not mutually exclusive. Results: Among 486 patients, 66.9 % were N-PPI, 13.2 % E-PPI, 18.7 % LT-PPI, and 11.5 % of the PPI users were defined as neither. Median PFS (mPFS) was 29.6 months in the study population, 28.7 months in N-PPI, 23.0 months in E-PPI (Hazard Ratio [HR] 1.5; 95%Confidence Interval [CI] 1.1–2.2; p = 0.024), and 23.0 months in LT-PPI (HR 1.4; 95%CI 1.0–1.9; p = 0.035). By landmark analysis, PPI use was associated with poorer mPFS at 3 and 12 months. Grade ≥3 hematological adverse events occurred in 71.7 % of N-PPI, 57.8 % of E-PPI (p = 0.021), and 54.9 % of LT-PPI (p = 0.003). Dose reductions and dosing delays due to hematological toxicity occurred in 70.8 % of N-PPI, 56.3 % of E-PPI (p = 0.018), and 52.7 % of LT-PPI (p = 0.002). Conclusions: PPI use may reduce palbociclib capsule toxicity, dose modifications, and clinical activity in HR+/HER2- ABC.

Introduction: Advancements in monoclonal antibodies, tyrosine kinase inhibitors, and antibody drug conjugates (ADCs) have notably enhanced outcomes for metastatic HER2-positive breast cancer patients. Despite the expanding treatment options and clinical complexities, determining the optimal sequence of HER2-targeted therapies remains partly uncertain, influenced by various factors. Methods: To refine HER2-positive metastatic breast cancer management, particularly regarding tucatinib's position, a Steering Committee of leading oncologists in breast cancer care devised a panel of statements via a Delphi approach, focusing on five key topics: general clinical management, therapeutic approaches for patients with HER2-positive breast cancer and brain metastases, treatment sequence, and tucatinib's safety and efficacy. Results: A total of 29 statements were deliberated, with strong consensus achieved for most. However, no consensus emerged regarding the management of brain progression alongside stable extracranial disease: 48 % advocated for switching to tucatinib, while 53 % favored a stereotactic brain radiotherapy (SBRT) approach if feasible. Conclusion: The unanimous consensus attained in this Delphi panel, particularly regarding tucatinib's efficacy and safety, underscores oncologists' recognition of its clinical significance based on existing trial data. These findings align closely with current literature, shedding light on areas necessitating further investigation, not thoroughly explored in prior studies. Moreover, the results underscore the scarcity of data on managing brain progression alongside stable extracranial disease, emphasizing the imperative for dedicated research to address these gaps and yield definitive insights.

Aims: Rotator cuff (RC) injuries are characterized by tendon rupture, muscle atrophy, retraction, and fatty infiltration, which increase injury severity and jeopardize adequate tendon repair. Epigenetic drugs, such as histone deacetylase inhibitors (HDACis), possess the capacity to redefine the molecular signature of cells, and they may have the potential to inhibit the transformation of the fibro-adipogenic progenitors (FAPs) within the skeletal muscle into adipocyte-like cells, concurrently enhancing the myogenic potential of the satellite cells. Methods: HDACis were added to FAPs and satellite cell cultures isolated from mice. The HDACi vorinostat was additionally administered into a RC injury animal model. Histological analysis was carried out on the isolated supra- and infraspinatus muscles to assess vorinostat anti-muscle degeneration potential. Results: Vorinostat, a HDACi compound, blocked the adipogenic transformation of muscle-associated FAPs in culture, promoting myogenic progression of the satellite cells. Furthermore, it protected muscle from degeneration after acute RC in mice in the earlier muscle degenerative stage after tenotomy. Conclusion: The HDACi vorinostat may be a candidate to prevent early muscular degeneration after RC injury. Cite this article: Bone Joint Res 2024;13(4):169–183.

Discurs dictat en el context d’un Acte de Reconeixement de la UAB a la trajectòria acadèmica en defensa dels drets de les dones i col·lectius dissidents, atorgat dels de l’Observatori per a la Igualtat, en Commemoració Dia internacional de la dona treballadora (8M). Es construeix una narrativa fruit d’una dedicació de trenta-vuit anys a la UAB que s’organitza entorn els inicis, referents acadèmics, memòria familiar intergeneracional i vincle amb recerca i docència. Es focalitza en un treball d’articulació entre els Estudis de Gènere i la Salut Mental, posant de relleu la crítica teòrico-epistemològica a la intersecció, viscuda en pell pròpia, entre el Gènere, el Poder i la Ciència, en relació amb la Ciència Psicològica i implicacions de la construcció científico-cultural de la Identitat sexual binària en relació a la Ciència de la Salut Mental. Narrativa construïda des del compromís amb el pensament feminista interseccional i per a una psicologia emancipadora i incloent.

Summary: Background: Hyperglycaemia is an early and frequent adverse event during alpelisib treatment. METALLICA aimed to evaluate prophylactic metformin to prevent or reduce hyperglycaemia occurrence in patients with HR+/HER2−/PIK3CA-mutated advanced breast cancer (ABC). Methods: Between August 13th, 2020 and March 23rd, 2022, this 2-cohort, phase 2, multicentre, single-arm trial (NCT04300790) enrolled patients with HR+/HER2−/PIK3CA-mutated ABC: cohort A, normal glycaemia (fasting plasma glucose

Resumen: Introducción: El tratamiento de las fracturas vertebrales metastásicas sin compresión neural se realiza con técnicas percutáneas de cementación. El aumento de presión intratumoral por estas técnicas puede enviar células tumorales al torrente sanguíneo. Para evitar esa diseminación y mejorar el tratamiento del dolor se han introducido las técnicas de ablación que permitirían crear una cavidad en el tumor previo a la cementación o directamente necrosar la metástasis cuando el tamaño es pequeño. Material: Presentamos la experiencia con la ablación de dos hospitales y dos técnicas de ablación distintas. El primer grupo usó la ablación por radiofrecuencia (ARF) en 14 pacientes (26 vértebras) de los cuales en cuatro se asoció una artrodesis vertebral. El segundo grupo usó la ablación por microondas (AMO); 93 pacientes (129 lesiones) sin asociar instrumentación vertebral. Resultados: En el grupo de ARF la mejoría del dolor en la escala visual analógica (EVA) fue de 7,7 a 2,6 a las seis semanas. No hubo complicaciones derivadas de la ablación. En la mayoría de los casos se asoció la cementación. En el grupo de AMO la mejoría del dolor en EVA pasó de 6,8 a 1,7 a las seis semanas. En todos los casos se asoció la cementación. No hubo complicaciones derivadas de la ablación. Conclusiones: La asociación de las técnicas de ablación a la cementación vertebral es una técnica segura, que permite mejorar notablemente el dolor del paciente y puede ayudar al control de la enfermedad. Abstract: Introduction: Treatment of metastatic vertebral fractures without neural compression is performed with percutaneous cementation techniques. The increase in intratumoral pressure by these techniques can send tumor cells into the bloodstream. To prevent this dissemination and improve pain treatment, ablation techniques have been introduced that would allow the creation of a cavity in the tumor prior to cementation or directly necrosing the metastasis when its size is small. Material: We present the experience with ablation of two hospitals and two different ablation techniques. The first group used radiofrequency ablation (A) in 14 patients (26 vertebrae), 4 of whom underwent vertebral arthrodesis. The second group used microwave ablation (B) in 93 patients (129 lesions) without associated vertebral instrumentation. Results: In group A pain improvement in VAS was 7.7–2.6 at 6 weeks. There were no complications derived from the ablation. In most cases cementation was associated. In the group B pain improvement in VAS went from 6.8–1.7 at 6 weeks. Cementation was associated in all cases. There were no complications derived from the ablation. Conclusion: The association of ablation techniques with vertebral cementation is a safe technique that significantly improves the patient's pain and can help control the disease.

Synovial sarcoma (SS) is a rare soft-tissue tumor characterized by a monomorphic blue spindle cell histology and variable epithelial differentiation. Morphologically, SSs may be confused with other sarcomas. Systemic treatment is more effective for patients with high-risk SSs, patients with advanced disease, and younger patients. However, further studies are required to find new prognostic biomarkers. Herein, we describe the morphological, molecular, and clinical findings, using a wide immunohistochemical panel, of a series of SS cases. We studied 52 cases confirmed as SSs by morphological diagnosis and/or molecular studies. Clinical data (gender, age, tumor size, tumor location, resection margins, adjuvant treatment, recurrences, metastasis, and survival) were also retrieved for each patient. All the available H&E slides were examined by four pathologists. Three tissue microarrays (TMAs) were constructed for each of the tumors, and a wide immunohistochemical panel was performed. For time-to-event variables, survival analysis was performed using Kaplan–Meier curves and log-rank testing, or Cox regression. Statistical significance was considered at p < 0.05. The mean age of our patients was 40.33, and the median was 40.5 years. We found a predominance of males versus females (1.7:1). The most frequent morphological subtype was monophasic. TRPS1, SS18-SSX, and SSX-C-terminus were positive in 96% of cases. GLI1 expression was strong in six and focal (cytoplasmic) in twenty patients. Moreover, BCOR was expressed in more than half of SSs. Positive expression of both proteins, BCOR and GLI1, was correlated with a worse prognosis. Multivariate analysis was also performed, but only BCOR expression appeared to be significant. The combination of GLI1 and BCOR antibodies can be used to group SSs into three risk groups (low, intermediate, and high risk). We hypothesize that these findings could identify which patients would benefit from receiving adjuvant treatment and which would not. Moreover, these markers could represent therapeutic targets in advanced stages. However, further, larger series of SSs and molecular studies are necessary to corroborate our present findings.

Background: The COVID-19 pandemic is the biggest global health problem in the last hundred years. The efficacy of the vaccine to protect against severe disease is estimated to be 70–95% according to the studies carried out, although there are aspects of the immune response to the vaccine that remain unclear. Methods: Humoral and cellular immunity after the administration of three doses of the Pfizer–BioNTech and Oxford AstraZeneca vaccines against SARS-CoV-2 over one year and the appearance of post-vaccination COVID-19 were studied. SARS-CoV-2 IgG and IgA antibodies, αβ and γδ T-cell subsets, and their differentiation stages and apoptosis were analyzed. Results: Anti-SARS-CoV-2 IgG and IgA antibodies showed a progressive increase throughout the duration of the study. This increase was the greatest after the third dose. The highest levels were observed in subjects who had anti-SARS-CoV-2 antibodies prior to vaccination. There was an increase in CD4+ αβ, CD8+ γδ and TEM CD8+ γδ T cells, and a decrease in apoptosis in CD4+ CD8+ and CD56+ αβ and γδ T cells. Post-vaccination SARS-CoV-2 infection was greater than 60%. The symptoms of COVID-19 were very mild and were related to a γδ T cell deficit, specifically CD8+ TEMRA and CD56+ γδ TEM, as well as lower pre-vaccine apoptosis levels. Conclusions: The results unveil the important role of γδ T cells in SARS-CoV-2-vaccine-mediated protection from the disease.

Patellar tendinopathy is a frequent overuse injury in sports that can cause significant pain and disability. It requires evidence-based guidelines on effective prevention and management. However, optimal treatments remain uncertain. We aimed to analyze available meta-analyses to summarize treatment recommendations, compare therapeutic modalities, examine included trials, and offer methodological suggestions to improve future systematic reviews. Meta-analyses were systematically searched for in PubMed (PROSPERO: CRD42023457963). A total of 21 meta-analyses were included. The AMSTAR-2 scale assessed study quality, which was low, with only 23.8% of the meta-analyses being of moderate quality, and none were considered to be of high quality. Heterogeneous outcomes are reported. Multiple platelet-rich plasma (PRP) injections appear superior to eccentric exercises and provide lasting improvements compared to eccentric exercises when conservative treatments fail. Extracorporeal shockwave therapy (ESWT) also seems superior to non-operative options and similar to surgery for patellar tendinopathy in the long term. However, evidence for eccentric exercise efficacy remains unclear due to inconclusive findings. Preliminary findings also emerged for genetic risk factors and diagnostic methods but require further confirmation. This review reveals a lack of high-quality evidence on optimal patellar tendinopathy treatments. While PRP and ESWT show promise, limitations persist. Further rigorous meta-analyses and trials are needed to strengthen the evidence base and guide clinical practice. Methodological enhancements are proposed to improve future meta-analyses.

Abstract Overexpression of the EPS15 Homology Domain containing 1 (EHD1) protein has been linked to tumorigenesis but whether its core function as a regulator of intracellular traffic of cell surface receptors plays a role in oncogenesis remains unknown. We establish that EHD1 is overexpressed in Ewing sarcoma (EWS), with high EHD1 mRNA expression specifying shorter patient survival. ShRNA-knockdown and CRISPR-knockout with mouse Ehd1 rescue established a requirement of EHD1 for tumorigenesis and metastasis. RTK antibody arrays identified IGF-1R as a target of EHD1 regulation in EWS. Mechanistically, we demonstrate a requirement of EHD1 for endocytic recycling and Golgi to plasma membrane traffic of IGF-1R to maintain its surface expression and downstream signaling. Conversely, EHD1 overexpression-dependent exaggerated oncogenic traits require IGF-1R expression and kinase activity. Our findings define the RTK traffic regulation as a proximal mechanism of EHD1 overexpression-dependent oncogenesis that impinges on IGF-1R in EWS, supporting the potential of IGF-1R and EHD1 co-targeting.

Resumen: Introducción y objetivo: El fibroxantoma atípico (FXA) y el sarcoma pleomórfico dérmico (SPD) son neoplasias de origen mesenquimal poco frecuentes. Debido a la baja incidencia del SPD y a una nomenclatura históricamente confusa existe poca información acerca de la verdadera agresividad de este tumor. Realizamos el presente estudio con el objetivo de identificar qué características clínicas y/o histológicas del SPD son predictoras de riesgo de recidiva. Material y método: Se diseñó un estudio bicéntrico observacional retrospectivo de 31 casos de SPD diagnosticados y tratados en el Hospital Clínico Universitario de Valencia y el Instituto Valenciano de Oncología, entre los años 2005 y 2020. Se realizó un análisis descriptivo de las características clínicas e histológicas, un análisis inferencial univariado y un análisis multivariado mediante la regresión de Cox. Resultados: En el análisis univariado, la recidiva tumoral (p

Abstract Stratification of recurrence risk is a cornerstone of early breast cancer diagnosis that informs a patient’s optimal treatment pathway. Several tools exist that combine clinicopathological and molecular information, including multigene assays, which can estimate risk of recurrence and quantify the potential benefit of different adjuvant treatment modalities. While the tools endorsed by treatment guidelines are supported by level I and II evidence and provide similar prognostic accuracy at the population level, they can yield discordant risk prediction at the individual patient level. This review examines the evidence for these tools in clinical practice and offers a perspective of potential future risk stratification strategies. Experience from clinical trials with cyclin D kinase 4/6 (CDK4/6) inhibitors in the setting of hormone receptor–positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) early breast cancer is provided as an illustrative example of risk stratification.