Recommendations for the use of next-generation sequencing (NGS) for patients with advanced cancer in 2024: a report from the ESMO Precision Medicine Working Group.

BACKGROUND: Advancements in the field of precision medicine have prompted the European Society for Medical Oncology (ESMO) Precision Medicine Working Group to update the recommendations for the use of tumour next-generation sequencing (NGS) for patients with advanced cancers in routine practice. METHODS: The group discussed the clinical impact of tumour NGS in guiding treatment decision using the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) considering cost-effectiveness and accessibility. RESULTS: As for 2020 recommendations, ESMO recommends running tumour NGS in advanced non-squamous non-small-cell lung cancer, prostate cancer, colorectal cancer, cholangiocarcinoma, and ovarian cancer. Moreover, it is recommended to carry out tumour NGS in clinical research centres and under specific circumstances discussed with patients. In this updated report, the consensus within the group has led to an expansion of the recommendations to encompass patients with advanced breast cancer and rare tumours such as gastrointestinal stromal tumours, sarcoma, thyroid cancer, and cancer of unknown primary. Finally, ESMO recommends carrying out tumour NGS to detect tumour-agnostic alterations in patients with metastatic cancers where access to matched therapies is available. CONCLUSION: Tumour NGS is increasingly expanding its scope and application within oncology with the aim of enhancing the efficacy of precision medicine for patients with cancer.

Efficacy of an aloe vera, chamomile, and thyme cosmetic cream for the prophylaxis and treatment of mild dermatitis induced by radiation therapy in breast cancer patients (the Alantel study).

Objectives: Radiation-induced dermatitis (RD) is one of the most common toxicities in radiation therapy (RT) patients. Corticosteroids, immunosuppressants, and natural products (NPs) have been used as treatment. The objective was to evaluate the efficacy of a NPs-based cream (Alantel®) to reduce the incidence of RD in women with breast cancer undergoing RT treatment. Design: We conducted a controlled, randomized, double-blind clinical trial. Setting: Radiation Oncology Unit of the Reina Sofía Hospital and 5 Primary Care centers of the Cordoba and Guadalquivir Health District (Spain). Interventions: Patients assigned to the experimental group (GTA) were treated with Alantel, while those in the control group (GTE) were treated with a moisturizer and emollient cream. Main outcome measures: The primary outcome variable was the incidence of RD. RD-free time, duration of RD, quality of life, and product safety were also assessed. Results: Seventy patients were included in the study, 35 in the GTA and 35 in the GTE. The incidence of RD was lower in the GTA (71.4%) than in the GTE (91.4%) after 4 weeks of follow-up (RR = 0.78; NNT = 5; p < 0.031). The Skindex-29 questionnaire showed differences in the statement: "My skin condition makes it hard to work or do hobbies" (17.1% in the GTE vs. 2.9% in GTA; p = 0.024). Conclusions: The higher efficacy of Alantel® compared to the control cream in reducing the incidence of RD in women with breast cancer has been demonstrated.

Circulating tumor DNA analysis of the phase III VOYAGER trial: KIT mutational landscape and outcomes in patients with advanced gastrointestinal stromal tumor treated with avapritinib or regorafenib.

BACKGROUND: The current treatment paradigm of imatinib-resistant metastatic gastrointestinal stromal tumor (GIST) does not incorporate KIT/PDGFRA genotypes in therapeutic drug sequencing, except for PDGFRA exon 18-mutant GIST that is indicated for avapritinib treatment. Here, circulating tumor DNA (ctDNA) sequencing was used to analyze plasma samples prospectively collected in the phase III VOYAGER trial to understand how the KIT/PDGFRA mutational landscape contributes to tyrosine kinase inhibitor (TKI) resistance and to determine its clinical validity and utility. PATIENTS AND METHODS: VOYAGER (N = 476) compared avapritinib with regorafenib in patients with KIT/PDGFRA-mutant GIST previously treated with imatinib and one or two additional TKIs (NCT03465722). KIT/PDGFRA ctDNA mutation profiling of plasma samples at baseline and end of treatment was assessed with 74-gene Guardant360® CDx. Molecular subgroups were determined and correlated with outcomes. RESULTS: A total of 386/476 patients with KIT/PDGFRA-mutant tumors underwent baseline (pre-trial treatment) ctDNA analysis; 196 received avapritinib and 190 received regorafenib. KIT and PDGFRA mutations were detected in 75.1% and 5.4%, respectively. KIT resistance mutations were found in the activation loop (A-loop; 80.4%) and ATP-binding pocket (ATP-BP; 40.8%); 23.4% had both. An average of 2.6 KIT mutations were detected per patient; 17.2% showed 4-14 different KIT resistance mutations. Of all pathogenic KIT variants, 28.0% were novel, including alterations in exons/codons previously unreported. PDGFRA mutations showed similar patterns. ctDNA-detected KIT ATP-BP mutations negatively prognosticated avapritinib activity, with a median progression-free survival (mPFS) of 1.9 versus 5.6 months for regorafenib. mPFS for regorafenib did not vary regardless of the presence or absence of ATP-BP/A-loop mutants and was greater than mPFS with avapritinib in this population. Secondary KIT ATP-BP pocket mutation variants, particularly V654A, were enriched upon disease progression with avapritinib. CONCLUSIONS: ctDNA sequencing efficiently detects KIT/PDGFRA mutations and prognosticates outcomes in patients with TKI-resistant GIST treated with avapritinib. ctDNA analysis can be used to monitor disease progression and provide more personalized treatment.

Influence of HER2 expression on prognosis in metastatic triple-negative breast cancer-results from an international, multicenter analysis coordinated by the AGMT Study Group.

BACKGROUND: Triple-negative breast cancer (TNBC) is associated with poor prognosis, and new treatment options are urgently needed. About 34%-39% of primary TNBCs show a low expression of human epidermal growth factor receptor 2 (HER2-low), which is a target for new anti-HER2 drugs. However, little is known about the frequency and the prognostic value of HER2-low in metastatic TNBC. PATIENTS AND METHODS: We retrospectively included patients with TNBC from five European countries for this international, multicenter analysis. Triple-negativity had to be shown in a metastatic site or in the primary breast tumor diagnosed simultaneously or within 3 years before metastatic disease. HER2-low was defined as immunohistochemically (IHC) 1+ or 2+ without ERBB2 gene amplification. Survival probabilities were calculated by the Kaplan-Meier method, and multivariable hazard ratios (HRs) were estimated by Cox regression models. RESULTS: In total, 691 patients, diagnosed between January 2006 and February 2021, were assessable. The incidence of HER2-low was 32.0% [95% confidence interval (CI) 28.5% to 35.5%], with similar proportions in metastases (n = 265; 29.8%) and primary tumors (n = 425; 33.4%; P = 0.324). The median overall survival (OS) in HER2-low and HER2-0 TNBC was 18.6 and 16.1 months, respectively (HR 1.00; 95% CI 0.83-1.19; P = 0.969). Similarly, in multivariable analysis, HER2-low had no significant impact on OS (HR 0.95; 95% CI 0.79-1.13; P = 0.545). No difference in prognosis was observed between HER2 IHC 0/1+ and IHC 2+ tumors (HR 0.89; 95% CI 0.69-1.17; P = 0.414). CONCLUSIONS: In this large international dataset of metastatic TNBC, the frequency of HER2-low was 32.0%. Neither in univariable nor in multivariable analysis HER2-low showed any influence on OS.

Bilateral pericapsular nerves group (PENG) block for analgesia in pediatric hip surgery.

Effective management and control of peri- and postoperative pain in hip surgery is essential in order to minimize the use of opioids and their adverse effects. Effective regional analgesia for hip pain is made particularly challenging by the complex innervation of the hip joint. Standard regional techniques can be associated with complications, including incomplete anesthesia, hypotension, or lower limb weakness. We present the case of a 5-year-old girl with a history of infantile cerebral palsy who underwent bilateral varus derotation osteotomy and adductor tenotomy due to paralytic dislocation. She received bilateral PENG block and femoral cutaneous nerve block-a simple technique that covers all the nerves involved in the sensory innervation of the joint capsule without the need for multiple injections.

Increased frequency of CD14+HLA-DR-/low cells in type 2 diabetes patients with poor glycemic control.

AIMS: Type 2 diabetes (T2DM) is associated with alterations of the immune response and T2DM patients have an increased risk for infections and certain sorts of cancers. Although CD14+HLA-DR-/low cells have emerged as important mediators of immunosuppression in several pathologies, including cancer and non-malignant diseases, the presence of these cells in T2DM is not fully characterized. METHODS: In this study, we evaluated the frequency of CD14+HLA-DR-/low cells in non-obese T2DM patients and their association with glycemic control. Peripheral blood mononuclear cells were isolated from healthy controls (HC, n = 24) and non-obese T2DM patients (n = 25), the population was evaluated by flow cytometry, and an analysis of correlation between cell frequencies and clinical variables was performed. RESULTS: CD14+HLA-DR-/low monocytes were expanded in patients with T2DM compared to HC regardless of weight. Among the subjects with T2DM, the frequency of CD14+HLA-DR-/low was higher in patients with poor glycemic control (HbA1c > 9%) compared to those with better glycemic control (HbA1c < 9%) and, positively correlated with the years since the diagnosis of T2DM, the age of the patients and the glycemic index. CONCLUSIONS: An increased frequency of CD14+HLA-DR-/low cells in the blood of T2DM patients was recorded. The influence of hyperglycemia seems to be independent of obesity, but related to glycemic control and age.

Analysis of outcomes of emergency general and gastrointestinal surgery during the COVID-19 pandemic.

BACKGROUND: Few surgical studies have provided adjusted comparative postoperative outcome data among contemporary patients with and without COVID-19 infection and patients treated before the pandemic. The aim of this study was to determine the impact of performing emergency surgery in patients with concomitant COVID-19 infection. METHODS: Patients who underwent emergency general and gastrointestinal surgery from March to June 2020, and from March to June 2019 in 25 Spanish hospitals were included in a retrospective study (COVID-CIR). The main outcome was 30-day mortality. Secondary outcomes included postoperative complications and failure to rescue (mortality among patients who developed complications). Propensity score-matched comparisons were performed between patients who were positive and those who were negative for COVID-19; and between COVID-19-negative cohorts before and during the pandemic. RESULTS: Some 5307 patients were included in the study (183 COVID-19-positive and 2132 COVID-19-negative during pandemic; 2992 treated before pandemic). During the pandemic, patients with COVID-19 infection had greater 30-day mortality than those without (12.6 versus 4.6 per cent), but this difference was not statistically significant after propensity score matching (odds ratio (OR) 1.58, 95 per cent c.i. 0.88 to 2.74). Those positive for COVID-19 had more complications (41.5 versus 23.9 per cent; OR 1.61, 1.11 to 2.33) and a higher likelihood of failure to rescue (30.3 versus 19.3 per cent; OR 1.10, 0.57 to 2.12). Patients who were negative for COVID-19 during the pandemic had similar rates of 30-day mortality (4.6 versus 3.2 per cent; OR 1.35, 0.98 to 1.86) and complications (23.9 versus 25.2 per cent; OR 0.89, 0.77 to 1.02), but a greater likelihood of failure to rescue (19.3 versus 12.9 per cent; OR 1.56, 95 per cent 1.10 to 2.19) than prepandemic controls. CONCLUSION: Patients with COVID-19 infection undergoing emergency general and gastrointestinal surgery had worse postoperative outcomes than contemporary patients without COVID-19. COVID-19-negative patients operated on during the COVID-19 pandemic had a likelihood of greater failure-to-rescue than prepandemic controls.

Bilateral pericapsular nerves group (PENG) block for analgesia in pediatric hip surgery. / Bloqueo bilateral del grupo de nervios pericapsulares (PENG) como analgesia en cirugía de cadera infantil.

Effective management and control of peri- and postoperative pain in hip surgery is essential in order to minimize the use of opioids and their adverse effects. Effective regional analgesia for hip pain is made particularly challenging by the complex innervation of the hip joint. Standard regional techniques can be associated with complications, including incomplete anesthesia, hypotension, or lower limb weakness. We present the case of a 5-year-old girl with a history of infantile cerebral palsy who underwent bilateral varus derotation osteotomy and adductor tenotomy due to paralytic dislocation. She received bilateral PENG block and femoral cutaneous nerve block - a simple technique that covers all the nerves involved in the sensory innervation of the joint capsule without the need for multiple injections.

Diagnosis and management of tropomyosin receptor kinase (TRK) fusion sarcomas: expert recommendations from the World Sarcoma Network.

Sarcomas are a heterogeneous group of malignancies with mesenchymal lineage differentiation. The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions as tissue-agnostic oncogenic drivers has led to new personalized therapies for a subset of patients with sarcoma in the form of tropomyosin receptor kinase (TRK) inhibitors. NTRK gene rearrangements and fusion transcripts can be detected with different molecular pathology techniques, while TRK protein expression can be demonstrated with immunohistochemistry. The rarity and diagnostic complexity of NTRK gene fusions raise a number of questions and challenges for clinicians. To address these challenges, the World Sarcoma Network convened two meetings of expert adult oncologists and pathologists and subsequently developed this article to provide practical guidance on the management of patients with sarcoma harboring NTRK gene fusions. We propose a diagnostic strategy that considers disease stage and histologic and molecular subtypes to facilitate routine testing for TRK expression and subsequent testing for NTRK gene fusions.

Type 2 diabetes mellitus metabolic control correlates with the phenotype of human monocytes and monocyte-derived macrophages.

AIMS: Monocytes and macrophages express cell-surface markers indicative of their inflammatory and activation status. In this study, we investigated whether these markers are affected or correlated in non-obese T2D subjects, or glycemic/metabolic control variables. METHODS: Clinical data was recorded, and peripheral blood drawn from T2D patients (n = 28) and control subjects (n = 27). Isolated monocytes were evaluated by flow cytometry for the expression of CD14, CD16, and the phenotypic markers for the different states of activation spectrum, such as pro-inflammatory (M1) (HLA-DR, CD86), anti-inflammatory/pro-resolving (M2) (CD163, CD206, MERTK, PD-L1) and metabolically-activated (MMe) (CD36, ABCA-1). From a subset of individuals, monocytes-derived macrophages (MDM) were obtained and evaluated for phenotypic markers. A correlation analysis was performed between the clinical variables and the marker expression. RESULTS: The frequency of CD14++CD16- monocytes was lower in T2D patients and it correlates negatively with poor control in glycemic and metabolic variables. T2D monocytes expressed lower levels of HLA-DR, CD86, PD-L1, and CD163, which correlated negatively with poor metabolic control. In MDM from T2D patients, HLA-DR, CD86 and CD163 expression was lower and it inversely correlated with deficient glycemic or metabolic control parameters. CONCLUSION: The glycemic/metabolic control associated with T2D influences monocyte and MDM phenotypes toward an immune-suppressive phenotype.

Surgical treatment for male infertility. / Tratamiento quirúrgico de la infertilidad masculina.

Given the nature of the multiple causes of male infertility, some of them are «reversible¼ and can be managed with a surgical procedure to recover, in some cases, the fertilizing capacity of the male reproductive tract. With appropriate use of diagnostic tools and clinical judgement, the physician can identify the ideal candidates for these procedures. Together with the expertise and experience of the surgeon, these treatments can manage to resolve the barrier, and men may become fertile again. In this chapter, we will review some of the most commonly used surgical procedures for the treatment of male infertility and make a brief description of their technical details.

mTORC1 Prevents Epithelial Damage During Inflammation and Inhibits Colitis-Associated Colorectal Cancer Development.

Epithelial cells lining the intestinal mucosa constitute a selective-semipermeable barrier acting as first line of defense in the organism. The number of those cells remains constant during physiological conditions, but disruption of epithelial cell homeostasis has been observed in several pathologies. During colitis, epithelial cell proliferation decreases and cell death augments. The mechanism responsible for these changes remains unknown. Here, we show that the pro-inflammatory cytokine IFNγ contributes to the inhibition of epithelial cell proliferation in intestinal epithelial cells (IECs) by inducing the activation of mTORC1. Activation of mTORC1 in response to IFNγ was detected in IECs present along the crypt axis and in colonic macrophages. mTORC1 inhibition enhances cell proliferation, increases DNA damage in IEC. In macrophages, mTORC1 inhibition strongly reduces the expression of pro-inflammatory markers. As a consequence, mTORC1 inhibition exacerbated disease activity, increased mucosal damage, enhanced ulceration, augmented cell infiltration, decreased survival and stimulated tumor formation in a model of colorectal cancer CRC associated to colitis. Thus, our findings suggest that mTORC1 signaling downstream of IFNγ prevents epithelial DNA damage and cancer development during colitis.

Integración de Un Sistema Robótico de Terapia Ocupacional para Extremidades Superiores con Estimulación Visual/Táctil de Los Pacientes / Integration of an Occupational-Therapy Robotic System for Upper Limbs with Visual/tactile Stimulation of Patients

Resumen: Los ejercicios tradicionales de rehabilitación de extremidades superiores tienen como objetivo principal recuperar la fuerza o rango de movimiento del área lesionada de los pacientes. Una opción alternativa que se ha presentado en los últimos años es el uso de interfaces hápticas, las cuales han mostrado ser herramientas potenciales en el apoyo de las terapias de rehabilitación. En este artículo se presenta un sistema de rehabilitación háptico de movimientos finos en extremidades superiores, cuya característica principal es que los usuarios del sistema pueden interactuar de forma visual y táctil con objetos virtuales mezclados con escenarios reales logrando con ello un ambiente de realidad aumentada. El sistema fue probado en dos etapas, ambas con sujetos que presentaban un grado de discapacidad en extremidades superiores. Los datos recopilados fueron trayectorias seguidas, errores de seguimiento y la actividad muscular obtenida por medio de electromiografía; esta información recolectada permitió analizar de forma cuantitativa el grado de avance de los pacientes. Además, se consideraron las valoraciones hechas por fisioterapeutas, concluyendo que el sistema propuesto puede ser utilizado como una herramienta viable que complementa a las terapias de rehabilitación convencionales.

Abstract: Traditional upper limb rehabilitation exercises are primarily aimed at regaining the strength or range of motion of the patients' injured area. An alternative option that has been presented in the last years is the use of haptic interfaces, which have shown their potential as tools that support rehabilitation therapies. This article presents a haptic system of rehabilitation for fine upper limb movements, whose main characteristic is that users of the system can interact in a visual and tactile fashion with virtual objects mixed with real scenarios, thereby achieving an augmented reality environment. The system was tested in two stages, both with subjects who had a degree of disability in upper limbs. The data collected were followed trajectories, follow-up errors and the muscular activity obtained by means of electromyography; the collected information enabled the analysis, in a quantitative way, of the degree of progress of the patients. In addition, the assessments made by physiotherapists were considered, concluding that the proposed system can be used as a viable complementary tool for conventional rehabilitation therapies.

[3D printed medical devices and anatomical models: What kind of distribution and which uses in French hospitals?] / Dispositifs médicaux et modèles anatomiques produits par impression 3D : quelle diffusion et quelles utilisations dans les établissements de santé français ?

3D printing plays an increasingly important role in the medical sector and particularly in surgery. Nowadays, numerous manufacturers benefit from this technology to produce their medical devices and some hospitals have also purchased 3D printers. In this context, the aim of the present study was to study the distribution and the use of 3D printing in French hospitals in order to its main features in surgery. By conducting a national survey, we targeted hospitals equipped with 3D printers and those using external providers to benefit from this technology. Forty-seven hospitals were identified as using 3D printing including eight equipped with in-house 3D printers. This work gives us a first picture of 3D printing for hospital use in France and it raises questions about hospital pharmacists' involvement in 3D printed medical device production.

Functional gastrointestinal disorders in children from low socio-economic status and Helicobacter pylori infection.

BACKGROUND: Most studies on functional gastrointestinal disorders (FGIDs) in children are based on data from the northern hemisphere. Scientific reports are arising in South American population, but little is still known about children from low socio-economic status (SES), where Helicobacter pylori infection is endemic. Our objective was to evaluate the prevalence of FGIDs in school children from low SES and its relationship with H. pylori infection. METHODS: Children from 3 public schools of low SES from Santiago de Chile were included. Students completed the Rome III Questionnaire and a survey about other symptoms. Also, the 13 C urea breath test determined the presence of H. pylori infection. RESULTS: Five hundred six children were included, where 48% were male, with a median age of 15.7 years (range 7.1-19.6). Forty-two percent had some FGID, aerophagia and functional constipation being the most frequent. Females (adjusted OR 1.5, 95% CI [1.1, 2.2]), those children with parents within the lowest level of education (adjusted OR 1.6, 95% CI: 1.1-2.4), and family history of gastric cancer (adjusted OR 1.9, 95% CI: 1.2-3.1) were related to FGIDs. The prevalence of H. pylori infection was 55.9% (95% CI [50.7, 60.9]). In multivariable analysis, the presence of abdominal pain (OR 1.55, 95% CI [1.02, 2.36]), but not FGIDs, was related to H. pylori infection. CONCLUSIONS: FGIDs are common in low SES students. A low educational level of the household head, family history of gastric cancer. and being female are related to the development of FGIDs. In this study, no relationship between the presence of H. pylori and FGIDs was found.

Linfoma no Hodgkin estadio IV con metástasis mamaria y vaginal / Non Hodgkin lymphoma stage IV with breast and vaginal metastasis

Resumen ANTECEDENTES: La afectación mamaria por un linfoma es poco frecuente; casi siempre se trata de linfomas tipo B que se caracterizan por falta de especificidad clínica y radiológica, lo que dificulta el diagnóstico diferencial con tumoraciones mamarias de otro origen. CASO CLÍNICO: Paciente de 72 años de edad, con antecedentes de hipercolesterolemia, hipertensión arterial, artrosis y depresión, con dos partos y menopausia a los 55 años. Madre con antecedente de cáncer de mama posmenopáusico. En la mamografía de la mama derecha se encontró una masa retroareolar de 8 cm, de contornos mal definidos y una adenopatía axilar con engrosamiento cortical. La biopsia reportó un linfoma no Hodgkin B de alto grado. Se administraron 8 ciclos de quimioterapia con el esquema R-CHOP. Luego de este esquema el PET-TC mostró una lesión mamaria derecha residual, metabólicamente inactiva, sin enfermedad nodal ni extramamaria supra ni infradiafragmática. CONCLUSIONES: Una neoplasia maligna mamaria no siempre se trata de un carcinoma ductal o lobulillar. Es necesario valorar la posibilidad de otras estirpes histológicas o, incluso, de una afectación metastásica. La entrevista y exploración adecuadas son fundamentales para una buena orientación diagnóstica.

Abstract BACKGROUND: The mammary affectation by a lymphoma is not frequent; it almost always involves type B lymphomas. It is characterized by a lack of clinical and radiological specificity, which makes differential diagnosis difficult with mammary tumors of another origin. CLINICAL CASE: A 72-year-old patient with a history of hypercholesterolemia, hypertension, osteoarthritis and depression, with two deliveries and menopause at 55 years of age. Mother with a history of postmenopausal breast cancer. The mammography of the right breast reported the existence of a retroareolar mass of 8 cm, of ill-defined contours and an axillary adenopathy with cortical thickening. The biopsy reported a high-grade non-Hodgkin B lymphoma. 8 cycles of chemotherapy were administered with the R-CHOP scheme. After this procedure, the PET-CT showed a residual, metabolically inactive right mammary lesion, with nodal or extramammary supra or infradiaphragmatic disease. CONCLUSIONS: A malignant mammary neoplasm is not always a ductal or lobular carcinoma. It is necessary to evaluate the possibility of other histological strains or, even, of a metastatic affectation. The adequate interview and exploration are fundamental for a good diagnostic orientation.

Susceptibility of dry-cured tuna to oxidative deterioration and biogenic amines generation: I. Effect of NaCl content, antioxidant type and ageing.

This study aimed to assess lipid oxidation and biogenic amine (BA) development in "muxama", a dry-cured tuna muscle product, as affected by salt content, antioxidant type and ageing time. Overall, BA contents decreased with NaCl level (2785.1mgkg-1, 1148.1mgkg-1 and 307.7mgkg-1) and increased with ageing time (366.2mgkg-1, 1711.8mgkg-1 and 2959.2mgkg-1 in the final product (T0), and after 1 (T1) and 3 (T3) months of ageing, respectively). Regardless of the test conditions, the most concentrated BA was always tyramine. For the ageing periods considered in the present study, malondialdehyde formation was affected by the NaCl level, with the saltiest samples exhibiting lower content. Rosemary and sage extracts represented promising technological options for preserving muxama from oxidation and to minimize the presence of a fishy flavour and odour, but this treatment may cause the colour to lose some of its redness and become less appealing.