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Spontaneous regression of malignant neoplasms is extremely rare, but renal cell carcinomas (RCC) are most often associated with this phenomenon. We report a case of a patient with personal history of RCC, who underwent nephrectomy and no other oncological treatment. One year after nephrectomy, a lung metastasis was detected and kept under follow-up for 3 years. Its size increased over time until a needle biopsy was performed, and its metastatic nature confirmed. Wedge resection of the lung nodule was performed, and no neoplastic cells were found, suggesting its spontaneous regression after biopsy. Different theories have been proposed to explain this phenomenon and, in most cases, the mechanism seems to involve the activation of the immune system. This case supports the importance of reducing tumor burden and the impact of the disturbance of the tumor microenvironment caused by instrumentation, in improving immune system activation and its essential role in neoplasm regression.
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Carcinoma de Células Renales , Neoplasias Renales , Neoplasias Pulmonares , Nefrectomía , Humanos , Neoplasias Renales/patología , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/secundario , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Masculino , Regresión Neoplásica Espontánea , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
Diabetes mellitus is a prevalent chronic autoimmune disease with a high impact on global health, affecting millions of adults and resulting in significant morbidity and mortality. Achieving optimal blood glucose levels is crucial for diabetes management to prevent acute and long-term complications. Carbohydrate counting (CC) is widely used by patients with type 1 diabetes to adjust prandial insulin bolus doses based on estimated carbohydrate content, contributing to better glycemic control and improved quality of life. However, accurately estimating the carbohydrate content of meals remains challenging for patients, leading to errors in bolus insulin dosing. This review explores the current limitations and challenges in CC accuracy and emphasizes the importance of personalized educational programs to enhance patients' abilities in carbohydrate estimation. Existing tools for assessing patient learning outcomes in CC are discussed, highlighting the need for individualized approaches tailored to each patient's needs. A comprehensive review of the relevant literature was conducted to identify educational programs and assessment tools dedicated to training diabetes patients on carbohydrate counting. The research aims to provide insights into the benefits and limitations of existing tools and identifies future research directions to advance personalized CC training approaches. By adopting a personalized approach to CC education and assessment, healthcare professionals can empower patients to achieve better glycemic control and improve diabetes management. Moreover, this review identifies potential avenues for future research, paving the way for advancements in personalized CC training and assessment approaches and further enhancing diabetes management strategies.
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Glucemia , Diabetes Mellitus Tipo 1 , Carbohidratos de la Dieta , Humanos , Carbohidratos de la Dieta/administración & dosificación , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Educación del Paciente como Asunto , Control Glucémico/métodos , Insulina , Hipoglucemiantes/administración & dosificación , Calidad de Vida , ComidasRESUMEN
Effective antibody responses are essential to generate protective humoral immunity. Different inflammatory signals polarize T cells towards appropriate effector phenotypes during an infection or immunization. Th1 and Th2 cells have been associated with the polarization of humoral responses. However, T follicular helper cells (Tfh) have a unique ability to access the B cell follicle and support the germinal center (GC) responses by providing B cell help. We investigated the specialization of Tfh cells induced under type-1 and type-2 conditions. We first studied homogenous Tfh cell populations generated by adoptively transferred TCR-transgenic T cells in mice immunized with type-1 and type-2 adjuvants. Using a machine learning approach, we established a gene expression signature that discriminates Tfh cells polarized towards type-1 and type-2 response, defined as Tfh1 and Tfh2 cells. The distinct signatures of Tfh1 and Tfh2 cells were validated against datasets of Tfh cells induced following lymphocytic choriomeningitis virus (LCMV) or helminth infection. We generated single-cell and spatial transcriptomics datasets to dissect the heterogeneity of Tfh cells and their localization under the two immunizing conditions. Besides a distinct specialization of GC Tfh cells under the two immunizations and in different regions of the lymph nodes, we found a population of Gzmk+ Tfh cells specific for type-1 conditions. In human individuals, we could equally identify CMV-specific Tfh cells that expressed Gzmk. Our results show that Tfh cells acquire a specialized function under distinct types of immune responses and with particular properties within the B cell follicle and the GC.
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The diagnosis of a child's complex chronic illness may impact family relationships and cohesion. The Impact on Family Scale (IFS) is an instrument used to assess the parental perception of the effects of children's chronic illness on family life. With a sample of 110 mothers and fathers between the ages of 29 and 50 who have a child with a complex chronic illness, we examine evidence of the validity of the IFS for use in Portugal within this specific family configuration, (1) comparing its factor structure with the original one; (2) assessing its reliability; and (3) evaluating its relationship with life satisfaction and family cohesion/acceptance. As expected, CFA analysis showed that IFS is a one-factor reliable instrument with 12 items (Cronbach's alpha = 0.910), which are negatively correlated with satisfaction with life (r = -0.229, p = 0.016) and positively correlated with family acceptance and cohesion (r = 0.363; p < 0.001). The results support the validity of the IFS in families with children and adolescents with a complex chronic illness. The implications of the use of this instrument for research and professional practice is analyzed.
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Padres , Humanos , Femenino , Masculino , Enfermedad Crónica/psicología , Adulto , Padres/psicología , Niño , Persona de Mediana Edad , Adolescente , Encuestas y Cuestionarios , Portugal , Reproducibilidad de los Resultados , Relaciones Familiares/psicología , Percepción , Satisfacción PersonalAsunto(s)
Cirugía Torácica , Humanos , Cirugía Torácica/educación , España , Portugal , Europa (Continente) , Internado y Residencia/métodosRESUMEN
INTRODUCTION: Thymectomy remains a mainstay of treatment in Thymomatous (T) and Nonthymomatous (nT) Myasthenia Gravis (MG), with improved clinical outcomes and reduced need for medical treatment, however, there is little research regarding long-term follow-up. We aim to assess the impact of surgery on the long-term outcome of patients with MG at our center. METHODS: Retrospective analyses of MG patients submitted to thymectomy between 2007 and 2017 at the thoracic surgery department of CHUC. Clinical assessment was performed according to the MG Foundation of America (MGFA) Clinical Classification (cMGFA). The follow-up was categorized according to the MGFA Post-intervention Status (MGFA-PIS) and cMGFA. Statistical analysis was performed with SPSS, to a significance level of 5%. RESULTS: Thirty-seven patients underwent extended thymectomy and 67.6% were female. Median age at diagnosis was 46.68±19.2 years. Most patients (83.8%) had anti-acetylcholine receptor antibodies and 81.1% had generalized forms of MG. Many patients (67.6%) had surgery less than 12 months after the clinical diagnosis. TMG was present in 19 (51.4%) patients. Compared to nTMG, these patients were older (54.06±17.9 vs 40.17±19.4 years) and most were men (52.9% vs 16.7%). We obtained a good outcome in most patients in the first (81.1%), second (86.1%), and fifth (84.8%) year of follow-up. There was a shift towards better prognosis categories in the good outcome group: 9.1% CSR, 3.0% PR, and 66,7% MM in the fifth year. Preoperative medical treatment did not influence the long-term follow-up outcome. A shorter time to surgery (< 12 months) correlated with better outcomes at year 5 (p=0.016). CONCLUSION: Thymectomy led to a sustained clinical improvement in our cohort, allowing for a reduced need for medication. A shorter time to surgery seems to have a positive influence on long-term prognosis. We expect that an extended follow-up would improve our results.
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Miastenia Gravis , Timectomía , Masculino , Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Timectomía/métodos , Resultado del Tratamiento , Estudios Retrospectivos , Miastenia Gravis/cirugía , PronósticoRESUMEN
Desmoid tumors are soft tissue neoplasms arising from fascial and muscle-aponeurotic structure. These tumors are locally aggressive and have a high recurrence rate, even after complete resection. We present the case of a female with a giant intrathoracic desmoid tumor. She underwent complete surgical resection with no disease recurrence. Desmoid tumors' natural history is not well defined and is often enigmatic, making these tumors difficult to manage. Currently, for intrathoracic desmoid tumors, medical treatment is the recommended approach, nevertheless, surgery can be considered in selected patients.
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Fibromatosis Agresiva , Neoplasias de los Tejidos Blandos , Humanos , Femenino , Fibromatosis Agresiva/diagnóstico , Recurrencia Local de Neoplasia , Diagnóstico Diferencial , Músculos/patologíaRESUMEN
Age-related immunosenescence is characterized by progressive dysfunction of adaptive immune response and increased autoimmunity. Nevertheless, the impact of aging on CD4+ regulatory T cells that are master regulators of the immune system remains largely unclear. Here, we report cellular and molecular hallmarks of regulatory T cells derived from murine lymphoid and adipose tissues at 3, 18, and 24 mo of age, respectively, by analyzing their heterogeneity that displays dynamic changes in transcriptomic effector signatures at a single-cell resolution. Although the proportion of regulatory T cells among total Cd4+ T cells, as well as their expression levels of Foxp3, did not show any global change with time, we have identified 6 transcriptomically distinct clusters of regulatory T cells with cross-tissue conserved hallmarks of aging, including increased numbers of proinflammatory regulatory T cells, reduced precursor cells, increased immature and mature T follicular regulatory cells potentially supported by a metabolic switch from oxidative phosphorylation to glycolysis, a gradual loss of CD150hi regulatory T cells that support hematopoiesis, and increased adipose tissue-specific regulatory T cells that are associated with metabolic disease. To dissect the impact of immunosenescence on humoral immunity, we propose some potential mechanisms underlying T follicular regulatory cell-mediated dysfunction by interactome analysis on T follicular regulatory cells, T follicular helper cells, and B cells during aging. Lastly, spatiotemporal analysis further revealed trajectories of regulatory T-cell aging that demonstrate the most significant changes in marrow and adipose tissues that might contribute to the development of age-related immunosenescence and type 2 diabetes. Taken together, our findings could provide a better understanding of age-associated regulatory T-cell heterogeneity in lymphoid and adipose tissues, as well as regulatory T-cell hallmarks during progressive adaptation to aging that could be therapeutically targeted for rejuvenating the aging immune system in the future.
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Diabetes Mellitus Tipo 2 , Linfocitos T Reguladores , Ratones , Animales , Linfocitos T Colaboradores-Inductores , Diabetes Mellitus Tipo 2/metabolismo , Envejecimiento/genética , Perfilación de la Expresión GénicaRESUMEN
The management of patients with oligometastatic non-small cell lung cancer has undergone significant improvement in recent years. The combination of increase in sensitivity of diagnostic tests, development in systemic therapies, surgical techniques and radiotherapy allowing radical ablative treatment of metastases have significantly influenced the treatment of advanced lung cancer, mainly in the patients in which these treatment modalities converge.We report a rare case of a young patient with an oligometastatic lung adenocarcinoma with a single synchronous brain metastasis, who underwent aggressive locoregional and systemic therapies and is still in annual follow-up with excellent quality of life and progression-free survival of 164 months.
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Adenocarcinoma del Pulmón , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/terapia , Calidad de Vida , Terapia CombinadaRESUMEN
Resumo Enquadramento: A triagem de prioridades caracteriza-se por um complexo processo de tomada de decisão que visa avaliar a gravidade clínica. Objetivo: Analisar relações entre as características socioprofissionais dos enfermeiros de um serviço de urgência e a perceção das competências de tomada de decisão na triagem. Metodologia: Estudo descritivo-correlacional e transversal. A amostra foi de 47 enfermeiros e para a recolha de dados recorreu-se ao Triage Decision Making Inventory, versão portuguesa. Resultados: Na perceção das competências de tomada de decisão, as características cognitivas/confiança na habilidade obtiveram a média mais elevada (4,94 ± 0,420) e a Intuição a média mais baixa (4,44 ± 0,697). Observaram-se correlações significativas entre as características cognitivas/confiança na habilidade, intuição, pensamento crítico do triador e o tempo de experiência no serviço de urgência, bem como, entre a idade do triador, a experiência profissional e as características cognitivas/confiança na habilidade. Conclusão: A tomada de decisão na triagem é influenciada positivamente pela experiência no serviço de urgência, sendo as características cognitivas/confiança na habilidade as competências mais valorizadas pelos enfermeiros.
Abstract Background: Priority triage is a complex decision-making process used to assess clinical severity. Objective: This study aims to explore the association between the socio-professional characteristics of emergency department nurses and their perceptions of decision-making skills during triage. Methodology: A cross-sectional descriptive-correlational study was conducted with a sample of 47 nurses. The Portuguese version of the Triage Decision-Making Inventory (TDMI) was used for data collection. Results: Regarding nurses' perceptions of their decision-making skills, the highest mean score (4.94 ± 0.420) was found in cognitive characteristics/Skill confidence and the lowest mean score in Intuition (4.44 ± 0.697). Significant correlations were found between cognitive characteristics/skill confidence, intuition, and critical thinking and the length of experience in emergency departments, as well as between cognitive characteristics/Skill confidence and the triage nurses' age and professional experience. Conclusion: Experience in the emergency department has a positive impact on triage decision-making skills. Nurses place the highest value on cognitive characteristics/skill confidence.
Resumen Marco contextual: El triaje de prioridades se caracteriza por un complejo proceso de toma de decisiones dirigido a evaluar la gravedad clínica. Objetivo: Analizar la relación entre las características socioprofesionales del personal de enfermería de un servicio de urgencias y su percepción de las competencias para la toma de decisiones en el triaje. Metodología: Estudio descriptivo-correlacional de corte transversal. La muestra estuvo constituida por 47 enfermeros y los datos se recogieron mediante el Triage Decision-Making Inventory, versión portuguesa. Resultados: En la percepción de las competencias para la toma de decisiones, las características cognitivas/confianza en la habilidad tuvieron la media más alta (4,94 ± 0,420) y la Intuición tuvo la media más baja (4,44 ± 0,697). Se observaron correlaciones significativas entre las características cognitivas/confianza en la habilidad, la Intuición y el pensamiento crítico del enfermero de triaje, y la antigüedad en el servicio de urgencias, así como entre la edad del enfermero de triaje, la experiencia profesional y las características cognitivas/confianza en la habilidad. Conclusión: La toma de decisiones en el triaje está positivamente influenciada por la experiencia en urgencias, y las características cognitivas/confianza en la habilidad son las competencias más valoradas por los enfermeros.
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Interleukin-2 (IL-2) engineered versions, with biased immunological functions, have emerged from yeast display and rational design. Here we reshaped the human IL-2 interface with the IL-2 receptor beta chain through the screening of phage-displayed libraries. Multiple beta super-binders were obtained, having increased receptor binding ability and improved developability profiles. Selected variants exhibit an accumulation of negatively charged residues at the interface, which provides a better electrostatic complementarity to the beta chain, and faster association kinetics. These findings point to mechanistic differences with the already reported superkines, characterized by a conformational switch due to the rearrangement of the hydrophobic core. The molecular bases of the favourable developability profile were tracked to a single residue: L92. Recombinant Fc-fusion proteins including our variants are superior to those based on H9 superkine in terms of expression levels in mammalian cells, aggregation resistance, stability, in vivo enhancement of immune effector responses, and anti-tumour effect.
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Evolución Molecular Dirigida , Subunidad beta del Receptor de Interleucina-2 , Interleucina-2 , Biblioteca de Péptidos , Humanos , Subunidad beta del Receptor de Interleucina-2/química , Interleucina-2/química , Interleucina-2/genética , Interleucina-2/metabolismo , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Evolución Molecular Dirigida/métodos , Dominios Proteicos , Animales , Ratones , Línea Celular TumoralRESUMEN
OBJECTIVES: The main goal of this study was to characterise the frequency and phenotype of B, T follicular helper (Tfh) and T follicular regulatory (Tfr) cells in peripheral blood and the cytokine environment present in circulation in children with extended oligoarticular juvenile idiopathic arthritis (extended oligo JIA) and polyarticular JIA (poly JIA) when compared with healthy controls, children with persistent oligoarticular JIA (persistent oligo JIA) and adult JIA patients. METHODS: Blood samples were collected from 105 JIA patients (children and adults) and 50 age-matched healthy individuals. The frequency and phenotype of B, Tfh and Tfr cells were evaluated by flow cytometry. Serum levels of APRIL, BAFF, IL-1ß, IL-2, IL-4, IL-6, IL-10, IL-17A, IL-21, IL-22, IFN-γ, PD-1, PD-L1, sCD40L, CXCL13 and TNF were measured by multiplex bead-based immunoassay and/or ELISA in all groups included. RESULTS: The frequency of B, Tfh and Tfr cells was similar between JIA patients and controls. Children with extended oligo JIA and poly JIA, but not persistent oligo JIA, had significantly lower frequencies of plasmablasts, regulatory T cells and higher levels of Th17-like Tfh cells in circulation when compared with controls. Furthermore, APRIL, BAFF, IL-6 and IL-17A serum levels were significantly higher in paediatric extended oligo JIA and poly JIA patients when compared with controls. These immunological alterations were not found in adult JIA patients in comparison to controls. CONCLUSIONS: Our results suggest a potential role and/or activation profile of B and Th17-like Tfh cells in the pathogenesis of extended oligo JIA and poly JIA, but not persistent oligo JIA.
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Artritis Juvenil , Interleucina-17 , Humanos , Niño , Interleucina-6 , Subgrupos de Linfocitos T , CitocinasRESUMEN
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis (MS) are two complex and multifactorial diseases whose patients experience persistent fatigue, cognitive impairment, among other shared symptoms. The onset of these diseases has also been linked to acute herpesvirus infections or their reactivations. In this work, we re-analyzed a previously-described dataset related to IgG antibody responses to 6 herpesviruses (CMV - cytomegalovirus; EBV - Epstein-Barr virus; HHV6 - human herpesvirus-6; HSV1 and HSV2 - herpes simplex virus-1 and -2, respectively; VZV - varicella-zoster virus) from the United Kingdom ME/CFS biobank. The primary goal was to report the underlying symptomology and its association with herpesvirus IgG antibodies using data from 4 disease-trigger-based subgroups of ME/CFS patients (n = 222) and patients with MS (n = 46). The secondary objective was to assess whether serological data could distinguish ME/CFS and its subgroup from MS using a SuperLearner (SL) algorithm. There was evidence for a significant negative association between temporary eye insight disturbance and CMV antibody concentrations and for a significant positive association between bladder problems and EBV antibody concentrations in the MS group. In the ME/CFS or its subgroups, the most significant antibody-symptom association was obtained for increasing HSV1 antibody concentration and brain fog, a finding in line with a negative impact of HSV1 exposure on cognitive outcomes in both healthy and disease conditions. There was also evidence for a higher number of significant antibody-symptom associations in the MS group than in the ME/CFS group. When we combined all the serological data in an SL algorithm, we could distinguish three ME/CFS subgroups (unknown disease trigger, non-infection trigger, and an infection disease trigger confirmed in the lab at the time of the event) from the MS group. However, we could not find the same for the remaining ME/CFS group (related to an unconfirmed infection disease). In conclusion, IgG antibody data explains more the symptomology of MS patients than the one of ME/CFS patients. Given the fluctuating nature of symptoms in ME/CFS patients, the clinical implication of these findings remains to be determined with a longitudinal study. This study is likely to ascertain the robustness of the associations during natural disease course.
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Background: Hepatocellular adenoma (HCA) is an uncommon solid, solitary, benign liver lesion that develops in an otherwise normal-appearing liver. Hemorrhage and malignant transformation are the most important complications. Risk factors for malignant transformation include advanced age, male gender, use of anabolic steroids, metabolic syndrome, larger lesions, and beta-catenin activation subtype. The identification of higher risk adenomas enables the selection of patients most suitable for aggressive treatment and those who benefit with surveillance, minimizing the risks for these predominantly young patients. Case Presentation. We present the case of a 29-year-old woman with a history of oral contraceptive intake for 13 years, which was sent to evaluation in our Hepato-Bilio-Pancreatic and Splenic Unit because of a large nodular lesion in segment 5 of the liver, compatible with HCA, and was proposed to surgical resection. Histological and immunohistochemical investigation revealed an area with atypical characteristics, suggesting malignant transformation. Conclusions: HCAs share similar imaging characteristics and histopathological features with hepatocellular carcinomas; therefore, immunohistochemical and genetic studies assumes great importance to discriminate adenomas with malignant transformation. Beta-catenin, glutamine synthetase, glypican-3, and heat-shock protein 70 are promising markers to identify higher risk adenomas.
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Immune checkpoint blockade reaches remarkable clinical responses. However, even in the most favorable cases, half of these patients do not benefit from these therapies in the long term. It is hypothesized that the activation of host immunity by co-delivering peptide antigens, adjuvants, and regulators of the transforming growth factor (TGF)-ß expression using a polyoxazoline (POx)-poly(lactic-co-glycolic) acid (PLGA) nanovaccine, while modulating the tumor-associated macrophages (TAM) function within the tumor microenvironment (TME) and blocking the anti-programmed cell death protein 1 (PD-1) can constitute an alternative approach for cancer immunotherapy. POx-Mannose (Man) nanovaccines generate antigen-specific T-cell responses that control tumor growth to a higher extent than poly(ethylene glycol) (PEG)-Man nanovaccines. This anti-tumor effect induced by the POx-Man nanovaccines is mediated by a CD8+ -T cell-dependent mechanism, in contrast to the PEG-Man nanovaccines. POx-Man nanovaccine combines with pexidartinib, a modulator of the TAM function, restricts the MC38 tumor growth, and synergizes with PD-1 blockade, controlling MC38 and CT26 tumor growth and survival. This data is further validated in the highly aggressive and poorly immunogenic B16F10 melanoma mouse model. Therefore, the synergistic anti-tumor effect induced by the combination of nanovaccines with the inhibition of both TAM- and PD-1-inducing immunosuppression, holds great potential for improving immunotherapy outcomes in solid cancer patients.
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Melanoma , Macrófagos Asociados a Tumores , Ratones , Animales , Línea Celular Tumoral , Inmunoterapia , Linfocitos T CD8-positivos , Microambiente TumoralRESUMEN
The coevolution of multiple specialized T follicular regulatory cell subsets has led to fine-tuning of human germinal center responses in providing optimal antibody production and preventing events leading to autoimmunity (see the related Research Article by Le Coz et al.).
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Centro Germinal , Linfocitos T Reguladores , Humanos , Autoinmunidad , Formación de AnticuerposRESUMEN
Misdiagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) can occur when different case definitions are used by clinicians (relative misdiagnosis) or when failing the genuine diagnosis of another disease (misdiagnosis in a strict sense). This problem translates to a recurrent difficulty in reproducing research findings. To tackle this problem, we simulated data from case-control studies under misdiagnosis in a strict sense. We then estimated the power to detect a genuine association between a potential causal factor and ME/CFS. A minimum power of 80% was obtained for studies with more than 500 individuals per study group. When the simulation study was extended to the situation where the potential causal factor could not be determined perfectly (e.g., seropositive/seronegative in serological association studies), the minimum power of 80% could only be achieved in studies with more than 1000 individuals per group. In conclusion, current ME/CFS studies have suboptimal power under the assumption of misdiagnosis. This power can be improved by increasing the overall sample size using multi-centric studies, reporting the excluded illnesses and their exclusion criteria, or focusing on a homogeneous cohort of ME/CFS patients with a specific pathological mechanism where the chance of misdiagnosis is reduced.