Radiofrequency treatment of cervicogenic headache

Objectives: In the clinical management of facial pain, a possible cervical origin must be considered. A clinical exploration is therefore essential. The disorder originates in the intimate connections between the cranial portion of the spinal cord and the trigeminal system. Although solid evidence supporting the use of radiofrequency (RF) treatment is lacking, it remains one of the management options to be taken into account. The present study evalu - ates the efficacy of RF in application to cervicogenic headache. Study design: We present three cases of severe facial pain arising from different cervical structures. Results: In two cases the pain originated in cervical roots C2 and C3, while in the third patient the trigger point was located at the level of the atlantoaxial joint. Pulsed RF was applied for 4 minutes at the dorsal ganglion of C2 and C3 in the first two cases, and for 8 minutes at intraarticular level in the third patient. The pain gradually sub - sided during the first month in all cases. The first two patients reported 70% improvement after one month, 60% improvement after 6 months, and 30-50% after one year, versus baseline. The third patient reported complete pain resolution lasting approximately 5 months, after which the pain reappeared with the same intensity as before. Conclusions: Radiofrequency is a satisfactory treatment option, affording adequate analgesia, though the effects are sometimes temporary

Trans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma: implications for immunotherapy

Immunotherapy; Liver neoplasmsInmunoterapia; Neoplasias hepáticasImmunoteràpia; Neoplàsies hepàtiquesBackground Modulation of adaptive immunity may underscore the efficacy of trans-arterial chemoembolization (TACE). We evaluated the influence of TACE on T-cell function by phenotypic lymphocyte characterization in samples of patients undergoing surgery with (T+) or without (T-) prior-TACE treatment. Methods We profiled intratumoral (IT), peritumoral (PT) and non-tumoral (NT) background tissue to evaluate regulatory CD4+/FOXP3+ (T-reg) and immune-exhausted CD8+/PD-1+ T-cells across T+ (n=58) and T− (n=61). We performed targeted transcriptomics and T-cell receptor sequencing in a restricted subset of samples (n=24) evaluated in relationship with the expression of actionable drivers of anti-cancer immunity including PD-L1, indoleamine 2,3 dehydrogenase (IDO-1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), Lag-3, Tim-3 and CD163. Results We analyzed 119 patients resected (n=25, 21%) or transplanted (n=94, 79%) for Child-Pugh A (n=65, 55%) and Barcelona Clinic Liver Cancer stage A (n=92, 77%) hepatocellular carcinoma. T+ samples displayed lower IT CD4+/FOXP3+ (p=0.006), CD8+ (p=0.002) and CD8+/PD-1+ and NT CD8+/PD-1+ (p<0.001) compared with T−. Lower IT (p=0.005) and NT CD4+/FOXP3+ (p=0.03) predicted for improved recurrence-free survival. In a subset of samples (n=24), transcriptomic analysis revealed upregulation of a pro-inflammatory response in T+. T+ samples were enriched for IRF2 expression (p=0.01), an interferon-regulated transcription factor implicated in cancer immune-evasion. T-cell clonality and expression of PD-L1, IDO-1, CTLA-4, Lag-3, Tim-3 and CD163 was similar in T+ versus T−. Conclusions TACE is associated with lower IT density of immune-exhausted effector cytotoxic and T-regs, with significant upregulation of pro-inflammatory pathways. This highlights the pleiotropic effects of TACE in modulating the tumor microenvironment and strengthens the rationale for developing immunotherapy alongside TACE.DJP is supported by grant funding from the Wellcome Trust Strategic Fund (PS3416) and by the Cancer Research UK Postdoctoral bursary (C57701/A26137). AF is supported by grant from Instituto de Salud Carlos III (PI18/00542)

Assessing the impact of COVID-19 on liver cancer management (CERO-19)

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Assaigs clínics; Càncer de fetgeCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Ensayos clínicos; Cáncer de hígadoCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Clinical trials; Liver cancerBackground & aims: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic. Methods: An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave. Results: Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia, and Africa (73.7%, 17.1%, 5.3%, 2.6%, and 1.3% per continent, respectively). Eighty-seven percent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening programme, 50% cancelled curative and/or palliative treatments for LC, and 41.7% modified the liver transplantation programme. Forty-five out of 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service before the COVID-19 pandemic (n = 19/37). Conclusions: The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with liver cancer. Modifications in screening, diagnostic, and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision-making. Lay summary: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems globally. Herein, we assessed the impact of the first wave pandemic on patients with liver cancer and found that routine care for these patients has been majorly disrupted, which could have a significant impact on outcomes.There was no funding for this study

Diagnosis and treatment of hepatocellular carcinoma. Update of the consensus document of the AEEH, AEC, SEOM, SERAM, SERVEI, and SETH

tHepatocellular carcinoma (HCC) is the most common primary liver neoplasm and one of the most com-mon causes of death in patients with cirrhosis of the liver. In parallel, with recognition of the clinicalrelevance of this cancer, major new developments have recently appeared in its diagnosis, prognosticassessment and in particular, in its treatment. Therefore, the Spanish Association for the Study of theLiver (AEEH) has driven the need to update the clinical practice guidelines, once again inviting all thesocieties involved in the diagnosis and treatment of this disease to participate in the drafting and appro-val of the document: Spanish Society for Liver Transplantation (SETH), Spanish Society of DiagnosticRadiology (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Associa-tion of Surgeons (AEC) and Spanish Society of Medical Oncology (SEOM). The clinical practice guidelinespublished in 2016 and accepted as National Health System Clinical Practice Guidelines were taken as thereference documents, incorporating the most important recent advances. The scientific evidence and thestrength of the recommendation is based on the GRADE system.nEl carcinoma hepatocelular (CHC) es la neoplasia primaria de hígado más frecuente y una de las causasde muerte más común en los pacientes afectos de cirrosis hepática. Simultáneamente al reconocimientode la relevancia clínica de esta neoplasia, en los últimos a˜nos han aparecido novedades importantes enel diagnóstico, evaluación pronóstica y, especialmente, en el tratamiento del CHC. Por tal motivo, desdela Asociación Espa˜nola para el Estudio del Hígado (AEEH) se ha impulsado la necesidad de actualizarlas guías de práctica clínica, invitando de nuevo a todas las sociedades involucradas en el diagnósticoy tratamiento de esta enfermedad a participar en la redacción y aprobación del documento: SociedadEspa˜nola de Trasplante Hepático (SETH), Sociedad Espa˜nola de Radiología Médica (SERAM), SociedadEspa˜nola de Radiología Vascular e Intervencionista (SERVEI), Asociación Espa˜nola de Cirujanos (AEC) ySociedad Espa˜nola de Oncología Médica (SEOM). Se han tomado como documentos de referencia las guíasde práctica clínica publicadas en 2016, aceptadas como Guía de Práctica Clínica del Sistema Nacional deSalud, incorporando los avances más importantes que se han obtenido en los últimos a˜nos. La evidenciacientífica y la fuerza de la recomendación se basa en el sistema GRADE

Biocompatibility, bioactivity and immunomodulatory properties of three calcium silicate-based sealers: an in vitro study on hPDLSCs

Objectives: To assess the biocompatibility, bioactivity, and immunomodulatory properties of three new calcium silicate cement-based sealers: Ceraseal (CS), Totalfill BC Sealer (TFbc) and WellRoot ST (WR-ST) on human periodontal ligament stem cells (hPDLSCs). Materials and Methods: HPDLSCs were isolated from extracted third molars from healthy patients. Eluates (1:1, 1:2, and 1:4 ratio) and sample discs of CS, TFbc and WR-ST after setting were prepared. A series of assays were performed: cell characterization, cell metabolic activity (MTT assay) cell attachment and morphology (SEM assay), cell migration (wound-healing assay), cytoskeleton organization (phaloidin-based assay); IL-6 and IL-8 release (ELISA); differentiation marker expression (RT-qPCR assay), and cell mineralization (Alizarin Red S staining). HPDLSCs cultured in unconditioned (negative control) or osteogenic (positive control) culture media were used as a comparison. Statistical significance was established at p<0.05. Results: All the tested sealers exhibited similar results in the cytocompatibility assays (cell metabolic activity, migration, attachment, morphology, and cytoskeleton organization) compared with a negative control group. CS and TFbc exhibited an upregulation of at least one osteo/cementogenic marker compared to the negative and positive control groups. CS and TFbc also showed a significantly higher calcified nodule formation than the negative and positive control groups. Both the marker expression and calcified nodule formation were significantly higher in CS-treated cells than TFbc treated cells. WR-ST exhibited similar results to the control group. CS and TFbc-treated cells exhibited a significant downregulation of IL-6 after 72h of culture compared to the negative control group (p<0.05). Conclusion: All the tested sealers exhibited an adequate cytocompatibility. CS significantly enhances cell differentiation by upregulating the expression of key genes associated with bone and cementum formation. Additionally, CS was observed to facilitate the mineralization of the extracellular matrix effectively. In contrast, the effects of TFbc and WR-ST on these processes were less pronounced compared to CS. Furthermore, both CS and TFbc exhibited an anti-inflammatory potential, contributing to their potential therapeutic benefits in regenerative endodontics. Clinical relevance: This is the first study to compare the biological properties and immunomodulatory potential of Ceraseal, Totalfill BC Sealer, and WellRoot ST. The results act as supporting evidence for their use in root canal treatment

Plant Breeding and Management Strategies to Minimize the Impact of Water Scarcity and Biotic Stress in Cereal Crops under Mediterranean Conditions

Wheat and rice are two main staple food crops that may suffer from yield losses due to drought episodes that are increasingly impacted by climate change, in addition to new epidemic outbreaks. Sustainable intensification of production will rely on several strategies, such as efficient use of water and variety improvement. This review updates the latest findings regarding complementary approaches in agronomy, genetics, and phenomics to cope with climate change challenges. The agronomic approach focuses on a case study examining alternative rice water management practices, with their impact on greenhouse gas emissions and biodiversity for ecosystem services. The genetic approach reviews in depth the latest technologies to achieve fungal disease resistance, as well as the use of landraces to increase the genetic diversity of new varieties. The phenomics approach explores recent advances in high-throughput remote sensing technologies useful in detecting both biotic and abiotic stress effects on breeding programs. The complementary nature of all these technologies indicates that only interdisciplinary work will ensure significant steps towards a more sustainable agriculture under future climate change scenarios.info:eu-repo/semantics/publishedVersio

EASL-ILCA Clinical Practice Guidelines on Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) emerges inside the liver from bile ductules to the second-order bile ducts, represents the second most frequent primary liver cancer besides hepatocellular carcinoma and, unfortunately, is globally increasing in term of incidence. The silent presentation, late diagnosis, the highly aggressive nature and resistance to treatments lead to alarming mortality. Early diagnosis, molecular characterization, accurate staging and personalized multidisciplinary treatments represent challenges for researchers and physicians. Unfortunately, these challenges are beset by the high heterogeneity of iCCA at the clinical, genomic, epigenetic and molecular levels that very often preclude successful management. Nonetheless, in the last few years, progress has been achieved in molecular characterization, surgical management and targeted therapies. The recent advance together with the awareness that iCCA represents a distinct entity amongst the CCA family, led the ILCA and EASL governing boards to commission and charge international experts to draft dedicated guidelines to aid physicians towards an evidence-based approach for the diagnostic, prognostic, and therapeutic management of iCCA

The effect of a live music therapy intervention on critically ill paediatric patients in the intensive care unit: A quasi-experimental pretest-posttest study

Background: Music therapy as a nonpharmacological means of managing patient pain, anxiety, and discomfort is a recognised technique, although it is not widely used in the paediatric intensive care unit (PICU). Aim: The aim of this study was to assess the clinical effect of a live music therapy intervention on vital signs and levels of discomfort and pain for paediatric patients in the PICU. Methods: This was a quasi-experimental pretesteposttest study. The music therapy intervention was carried out by two music therapists who were specifically trained, each possessing a master's degree in the field of hospital music therapy. Ten minutes before the start of the music therapy session, the investigators recorded the vital signs of the patients and assessed their levels of discomfort and pain. The procedure was repeated at the start of the intervention; at 2, 5, and 10 min during the intervention; and at 10 min following the conclusion of the intervention. Results: Two hundred fifty-nine patients were included; 55.2% were male, with a median age of 1 year (0 e21). A total of 96 (37.1%) patients suffered a chronic illness. The main reason for PICU admission was respiratory illness, at 50.2% (n ¼ 130). Significantly lower values were observed for heart rate (p ¼ 0.002), breathing rate (p < 0.001), and degree of discomfort (p < 0.001) during the music therapy session. Conclusions: Live music therapy results in reduced heart rates, breathing rates, and paediatric patient discomfort levels. Although music therapy is not widely used in the PICU, our results suggest that using interventions such as that used in this study could help reduce patient discomfor

Challenges in Liver Transplantation for Hepatocellular Carcinoma: A Review of Current Controversies.

Liver transplantation (LT) remains one of the most effective treatments for hepatocellular carcinoma (HCC) and significantly enhances patient survival. However, the application of LT for HCC faces challenges owing to advancements in cancer-specific treatment modalities and the increased burden of patients comorbidities. This narrative review explores current controversies and advancements in LT for HCC. Key areas of focus include the management of comorbidities and patient education by advanced practice nurses, impacts of frailty on waitlists and post-LT outcomes, selection criteria for LT in the era of new downstaging tools, role of radiology in patient selection, and implications of potential immunotherapy use both before and after LT. Additionally, the importance of immunosuppression management with strategies aimed at minimizing rejection while considering the risk of HCC recurrence and the role of surveillance for HCC recurrence is highlighted. This review also underscores the importance of a multidisciplinary approach for optimizing outcomes in patients with HCC undergoing LT

Activated Lymphocytes and Increased Risk of Dermatologic Adverse Events during Sorafenib Therapy for Hepatocellular Carcinoma

Altres ajuts: Asociación Española Contra el Cáncer PI044031Hepatocellular carcinoma is the second cause of cancer-related death worldwide. Of those advanced-stage patients who are treated with sorafenib, those who develop early dermatologic adverse events have a better prognosis. These events are possibly immune-related. Therefore, we analyzed the phenotype of 52 sorafenib-treated patients' circulating lymphocytes throughout treatment. We found that different co-stimulatory and immune exhaustion markers, such as Programmed cell death protein 1 (PD-1) and DNAX accessory molecule 1 (DNAM-1) amongst others, correlate with the probability of developing these adverse events, both before and during the treatment. We also compared the phenotype of those lymphocytes expressing DNAM-1 with those that do not, and while NK DNAM-1-expressing cells have a co-stimulatory phenotype, T DNAM-1-expressing cells are immune-suppressors. Overall, we set a rationale for the combination of sorafenib and immune-targeted therapies; and for the use of immune markers (such as DNAM-1) for patients' prognosis evaluation. Advanced hepatocellular carcinoma patients treated with sorafenib who develop early dermatologic adverse events (eDAEs) have a better prognosis. This may be linked to immune mechanisms, and thus, it is relevant to assess the association between peripheral immunity and the probability of developing eDAEs. Peripheral blood mononuclear cells of 52 HCC patients treated with sorafenib were analyzed at baseline and throughout the first eight weeks of therapy. T, B, Natural Killer cells, and their immune checkpoints expression data were characterized by flow cytometry. Cytokine release and immune-suppression assays were carried out ex vivo. Cox baseline and time-dependent regression models were applied to evaluate the probability of increased risk of eDAEs. DNAM-1, PD-1, CD69, and LAG-3 in T cells, plus CD16 and LAG-3 in NK cells, are significantly associated with the probability of developing eDAEs. While NK DNAM-1 + cells express activation markers, T DNAM-1 + cells induce immune suppression and show immune exhaustion. This is the first study to report an association between immune checkpoints expression in circulating immune cells and the increased incidence of eDAEs. Our results support the hypothesis for an off-target role of sorafenib in immune modulation. We also describe a novel association between DNAM-1 and immune exhaustion in T cells