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This case report delves into the intricate medical history of an 85-year-old male who experienced a myriad of health challenges throughout his years. With a medical history full of conditions, such as stroke, sinus bradycardia, chronic obstructive pulmonary disease, severe pulmonary hypertension, and chronic gastritis, the patient´s health profile is further complicated by prostatic hypertrophy, persistent dorsalgia and lumbalgia, the presence of a thyroid nodule, and a recent onset of hypothyroidism. Among the diverse medical conditions of this patient, our narrative is primarily centered on his latest diagnosis: non-Hodgkin´s lymphoma. Non-Hodgkin´s lymphoma is not just a mere addition to his already complex medical history; it is a malignant neoplasm that shapes worldwide patterns of cancer mortality. The first indicators that led to this discovery were the patient´s complaints of persistent pain in the left lateral neck region associated with dysphagia. This was not an isolated symptom; the patient also reported a month-long history of asthenia, myalgias, weakness around the pelvic girdle, fatigue, and hyporexia, depicting a concerning clinical picture. Advanced diagnostic tools, namely ultrasound and computed tomography, shed light on submaxillary and cervical adenopathies. To corroborate such findings and get a definitive diagnosis of malignancy, a fine-needle aspiration was advised. Through this case, we aim not only to describe a clinical scenario but to highlight the challenges involved in the diagnosing and treatment of non-Hodgkin ´s lymphoma, especially in elderly patients. The overlap of multiple comorbidities adds further complexity to the scene, demanding meticulous care and expertise. This report serves as an educational tool for oncology experts, as well as testimony to the complexities of patient care in the oncology diagnostic and treatment setting.
Este reporte de caso se centra en el intricado historial médico de un varon de 85 años que experimenta una miriada de problemas de salud a lo largo de sus años. Con un historial médico lleno de afecciones, como accidente cerebrovascular, bradicardia sinusal, enfermedad pulmonar obstructiva crónica, hipertensión pulmonar grave y gastritis crónica, el perfil de salud del paciente se complica aún más por la presencia de hipertrofia prostática, dorsalgia y lumbalgia persistentes, la presencia de un nódulo tiroideo y el reciente diagnóstico de hipotiroidismo. Entre las diversas afecciones de este paciente, nuestra narración se centra principalmente en su último diagnóstico: linfoma no Hodgkin. El linfoma no hodgkiniano no es un mero añadido a su ya complejo historial médico; es una neoplasia maligna que configura las tendencias de mortalidad por cáncer a nivel mundial. Los primeros indicadores que llevaron a este descubrimiento fueron las quejas del paciente por dolor persistente en la región lateral izquierda del cuello, asociado a disfagia. No se trataba de un síntoma aislado, ya que el paciente también refería desde hacía un mes astenia, mialgias, debilidad alrededor de la cintura pélvica, fatiga e hiporexia, lo que describía un cuadro clínico preocupante. Las herramientas diagnósticas avanzadas, a saber, la ecografía y la tomografía computarizada, arrojaron luz sobre las adenopatías submaxilares y cervicales. revelaron sobre las adenopatías submaxilares y cervicales.
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Linfoma no Hodgkin , Humanos , Masculino , Anciano de 80 o más Años , Linfoma no Hodgkin/diagnóstico , Linfoma no Hodgkin/terapia , Tomografía Computarizada por Rayos XRESUMEN
Proton-pump inhibitors (PPIs) are the most administered first-line treatment for eosinophilic esophagitis (EoE). However, only around half of EoE patients respond histologically to a double dosage of PPI. In addition, 70% of responders maintain EoE in remission after tapering the PPI dose. In order to avoid endoscopy with biopsies-the only accurate method of assessing PPI response-efforts have been made to identify PPI responder patients. The clinical or endoscopic features and biomarkers evaluated so far, however, have not proven to be sufficient in predicting PPI response. Although new approaches based on omics technologies have uncovered promising biomarkers, the specialized and complex procedures required are difficult to implement in clinical settings. Alternatively, PPI pharmacogenetics based on identifying variations in CYP2C19 and STAT6 genes have shown promising results in EoE, and could easily be performed in most laboratories. Other genetic variations have also been associated with PPI response and may explain those cases not related to CYP2C19 or STAT6. Here, we provide an overview of PPI treatment in EoE and evidence of how genetic variations in CYP2C19 and other genes could affect PPI effectiveness, and also discuss studies evaluating the role of pharmacogenetics in predicting PPI response in patients with EoE.
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The combination of bedaquiline, pretomanid, and linezolid (BPaL) has become a preferred regimen for treating multidrug- and extensively drug-resistant tuberculosis (TB). However, treatment-limiting toxicities of linezolid and reports of emerging bedaquiline and pretomanid resistance necessitate efforts to develop new short-course oral regimens. We recently found that the addition of GSK2556286 increases the bactericidal and sterilizing activity of BPa-containing regimens in a well-established BALB/c mouse model of tuberculosis. Here, we used this model to evaluate the potential of new regimens combining bedaquiline or the more potent diarylquinoline TBAJ-587 with GSK2556286 and the DprE1 inhibitor TBA-7371, all of which are currently in early-phase clinical trials. We found the combination of bedaquiline, GSK2556286, and TBA-7371 to be more active than the first-line regimen and nearly as effective as BPaL in terms of bactericidal and sterilizing activity. In addition, we found that GSK2556286 and TBA-7371 were as effective as pretomanid and the novel oxazolidinone TBI-223 when either drug pair was combined with TBAJ-587 and that the addition of GSK2556286 increased the bactericidal activity of the TBAJ-587, pretomanid, and TBI-223 combination. We conclude that GSK2556286 and TBA-7371 have the potential to replace pretomanid, an oxazolidinone, or both components, in combination with bedaquiline or TBAJ-587.
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Mycobacterium tuberculosis , Nitroimidazoles , Oxazolidinonas , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis , Animales , Ratones , Diarilquinolinas/farmacología , Diarilquinolinas/uso terapéutico , Antituberculosos/uso terapéutico , Antituberculosos/farmacología , Linezolid/farmacología , Linezolid/uso terapéutico , Tuberculosis/tratamiento farmacológico , Nitroimidazoles/farmacología , Oxazolidinonas/farmacología , Oxazolidinonas/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológicoRESUMEN
BACKGROUND: HLA-DQA1*05 carriage has been associated with an increased risk of immunogenicity in patients with immune-mediated inflammatory diseases treated with tumour necrosis factor-alpha [TNF-a] antagonists. Results have shown an inconsistent association with a loss of response [LOR] in patients with inflammatory bowel disease [IBD], which could be modified when using proactive optimisation and association with immunomodulatory drugs. AIMS: To define the association of HLA-DQA1*05 on anti-drug antibody development and loss of response [LOR] to anti-TNF-a in IBD. METHODS: We searched MEDLINE, EMBASE, and SCOPUS, for the period up to August 2023, to identify studies reporting the risk of immunogenicity and/or LOR in IBD patients with HLA-DQA1*05 genotype. RESULTS: A total of 24 studies comprising 12 papers, 11 abstracts and one research letter, with a total of 5727 IBD patients, were included. In a meta-analysis of 10 studies [2984 patients; 41.9% with HLA-DQA1*05 genotype], HLA-DQA1*05 carriers had higher risk of immunogenicity compared with non-carriers (risk ratio, 1.54; 95% confidence interval [CI], 1.23â -â 1.94; I2â =â 62%) [low certainty evidence]. Lack of therapeutic drug monitoring [TDM] increased immunogenicity in the presence of risk human leukocyte antigen [HLA] [risk ratio 1.97; 95% CI, 1.35â -â 2.88; I2â =â 66%], whereas proactive TDM revoked this association [very low certainty of evidence]. A meta-analysis of six studies [765 patients] found that risk for secondary LOR was higher among HLA-DQA1*05 carriers [hazard ratio 2.21; 95% CI, 1.69â -â 2.88; I2â =â 0%] [very low certainty evidence], although definition and time to assessment varied widely among studies. CONCLUSION: HLA-DQA1*05 carriage may be associated with an increased risk of immunogenicity and secondary LOR in IBD patients treated with TNF-a antagonists.
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Genotipo , Cadenas alfa de HLA-DQ , Enfermedades Inflamatorias del Intestino , Factor de Necrosis Tumoral alfa , Humanos , Cadenas alfa de HLA-DQ/genética , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/inmunología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Insuficiencia del TratamientoRESUMEN
Eosinophilic esophagitis (EoE) is a chronic, progressive, type 2 inflammatory disease with increasing global prevalence. An eosinophil-predominant inflammation that permeates the epithelium and deeper esophageal layers characterizes the disease. Several cytokines, mainly derived from inflammatory T-helper 2 (Th2) cells and epithelial cells, are involved in perpetuating inflammatory responses by increasing surface permeability and promoting tissue remodeling characterized by epithelial-mesenchymal transition (EMT) and collagen deposition. This leads to esophageal strictures and narrow caliber esophagi, which are proportional a patient's age and untreated disease length. Pathophysiological mechanisms leading to EoE have been described in recent years, and transforming growth factor beta (TGF)-beta have been involved in fibrotic phenomena in EoE. However, evidence on the dependence of these phenomena on TGF-beta is scarce and contradictory. This review provides state-of-the art knowledge on intimate mechanisms of esophageal fibrosis in EoE and its clinical consequences.
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Esofagitis Eosinofílica , Humanos , Citocinas , Células Epiteliales , Transición Epitelial-Mesenquimal , EpitelioRESUMEN
BACKGROUND: Antithyroid drug-induced agranulocytosis (AIA) (neutrophils <500/µL) is a rare but serious complication in the treatment of hyperthyroidism. METHODOLOGY: Adult patients with AIA who were followed up at 12 hospitals in Spain were retrospectively studied. A total of 29 patients were studied. The etiology of hyperthyroidism was distributed as follows: Graves' disease (n = 21), amiodarone-induced thyrotoxicosis (n = 7), and hyperfunctioning multinodular goiter (n = 1). Twenty-one patients were treated with methimazole, as well as six patients with carbimazole and two patients with propylthiouracil. RESULTS: The median (IQR) time to development of agranulocytosis was 6.0 (4.0-11.5) weeks. The most common presenting sign was fever accompanied by odynophagia. All of the patients required admission, reverse isolation, and broad-spectrum antibiotics; moreover, G-CSF was administered to 26 patients (89.7%). Twenty-one patients received definitive treatment, thirteen patients received surgery, nine patients received radioiodine, and one of the patients required both treatments. Spontaneous normalization of thyroid hormone values occurred in six patients (four patients with amiodarone-induced thyrotoxicosis and two patients with Graves' disease), and two patients died of septic shock secondary to AIA. CONCLUSIONS: AIA is a potentially lethal complication that usually appears around 6 weeks after the initiation of antithyroid therapy. Multiple drugs are required to control hyperthyroidism before definitive treatment; additionally, in a significant percentage of patients (mainly in those treated with amiodarone), hyperthyroidism resolved spontaneously.
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Follicular pancreatitis (FP) is an extremely odd entity characterized by the presence of a pseudotumor that histologically presents lymphoid aggregates and germinal centers. The authors present the case of a 67-year-old woman with epigastric pain and jaundice. Endoscopic ultrasonography (EUS) was performed, revealing a 14x15 mm hypoechoic area with irregular edges in the head of the pancreas. The in situ cytological study showed polymorphic lymphoid cellularity, without atypia suggesting neoplasia. The cell block and the immunohistochemical study showed a polyclonal population with a pattern suggestive of FP. The patient presented spontaneous clinical improvement. The EUS follow up three months later shown pancreatic parenchyma with homogeneous echogenicity and no space occupying lesions were indentified. Since the diagnosis of FP has been reached after surgery in most cases, the treatment is not well established. However, no recurrences have been reported after surgery and spontaneous resolution has been observed in incomplete resections, which suggests the indication for conservative management. Diagnostic EUS has a fundamental role in the differential diagnosis between FP and pancreatic neoplasms, two entities with very different prognosis, and makes it possible to avoid, in the case of FP, unnecessary surgeries with the associated morbidity and mortality.
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OBJECTIVE: There is hardly any information on the consumption of healthcare resources by older people with differentiated thyroid cancer (DTC). We analyzed these consumptions in older patients with DTC and compared patients 75 years and older with subjects aged 60-74 years. METHODS: A multicenter, retrospective analysis was designed. We recorded three groups of health resources consumption (visits, diagnostic procedures, and therapeutic procedures) and identified a subgroup of patients with high consumption of resources. We compared patients aged between 60-74 years (group 1) with patients aged 75 and over (group 2). RESULTS: We included 1654 patients (women, 74.4%), of whom 1388 (83.9%) belonged to group 1 and 266 (16.1%) to group 2. In group 2, we found a higher proportion of patients requiring emergency department visits (7.9 vs. 4.3%, P = 0.019) and imaging studies (24.1 vs. 17.3%; P = 0.012) compared to group 1. However, we did not find any significant difference between both groups in the consumption of other visits, diagnostic procedures, or therapeutic procedures. Overall, 340 patients (20.6%) were identified as high consumers of health resources, 270 (19.5%) in group 1 and 70 (26.3%) in group 2 (P = 0.013). Multivariate logistic regression analysis showed that the risk of recurrence and mortality, radioiodine treatment, tumor size, and vascular invasion were significantly related to the high global consumption of resources. However, the age was not significantly related to it. CONCLUSION: In patients with DTC over 60 years of age, advanced age is not an independent determining factor in the consumption of health resources.
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Adenocarcinoma , Neoplasias de la Tiroides , Humanos , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Radioisótopos de Yodo/uso terapéutico , Neoplasias de la Tiroides/patología , Adenocarcinoma/tratamiento farmacológico , Tiroidectomía/métodosRESUMEN
Eosinophilic esophagitis (EoE) is a chronic, Th2-inflammatory disease of the esophagus that can severely affect food intake. Currently, diagnosis and assessing response to treatment of EoE is highly invasive and requires endoscopy with esophageal biopsies. Finding non-invasive and accurate biomarkers is important for improving patient well-being. Unfortunately, EoE is usually accompanied by other atopies, which make it difficult to identify specific biomarkers. Providing an update of circulating EoE biomarkers and concomitant atopies is therefore timely. This review summarizes the current knowledge in EoE blood biomarkers and two of its most common comorbidities, bronchial asthma (BA) and atopic dermatitis (AD), focusing on dysregulated proteins, metabolites, and RNAs. It also revises the current knowledge on extracellular vesicles (EVs) as non-invasive biomarkers for BA and AD, and concludes with the potential use of EVs as biomarkers in EoE.
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Asma , Dermatitis Atópica , Esofagitis Eosinofílica , Vesículas Extracelulares , Humanos , Esofagitis Eosinofílica/patología , Biomarcadores/metabolismo , Vesículas Extracelulares/metabolismoRESUMEN
Defective few-layered graphene mesostructures (DFLGMs) are produced from graphite flakes by high-energy milling processes. We obtain an accurate control of the generated mesostructures, as well as of the amount and classification of the structural defects formed, providing a functional material for microwave absorption purposes. Working under far-field conditions, competitive values of minimum reflection loss coefficient (RLmin) = -21.76 dB and EAB = 4.77 dB are achieved when DFLGMs are immersed in paints at a low volume fraction (1.95%). One step forward is developed by combining them with the excellent absorption behavior that offers amorphous Fe73.5Si13.5B9Cu1Nb microwires (MWs), varying their filling contents, which are below 3%. We obtain a RLmin improvement of 47% (-53.08 dB) and an EAB enhancement of 137% (4 dB) compared to those obtained by MW-based paints. Furthermore, a fmin tunability is demonstrated, maintaining similar RLmin and EAB values, irrespective of an ideal matching thickness. In this scenario, the Maxwell-Garnet standard model is valid, and dielectric losses mainly come from multiple reflections, interfacial and dielectric polarizations, which greatly boost the microwave attenuation of MWs. The present concept can remarkably enhance not only the MW attenuation but can also apply to other microwave absorption architectures of technological interest by adding low quantities of DFLGMs.
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A jejunal varix with high transfusion requirement is treated by double-balloon enteroscopy with cyanoacrylate/ lipiodol with radiological control. The patient had not gastrointestinal hemorrhage or transfusion requeriment after 8 months follow up. Our recent previous article in Rev Esp Enferm Dig on advanced therapeutics by enteroscopy is referenced, providing this new therapeutic possibility.
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Enteroscopía de Doble Balón , Várices , Humanos , Cianoacrilatos , Yeyuno/diagnóstico por imagen , Endoscopía Gastrointestinal , Várices/diagnóstico por imagen , Várices/terapia , Hemorragia Gastrointestinal/diagnóstico por imagen , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapiaRESUMEN
AIMS AND OBJECTIVES: The objectives of this study were to assess the benefits of a caregiver training programme on the cognitive and functional status of older adults, and to compare the effects of this programme according to type of caregiver (professional vs. family caregiver). BACKGROUND: Due to demographic changes that have resulted in an aging population, the role of caregiver of an older adult has become very important in recent years. DESIGN AND METHODS: The sample was composed of 160 older adults: (a) 100 received care from caregivers who had taken the three-month training programme (treatment group), of which 60 were professional caregivers and 40 were family caregivers, and (b) 60 received care from caregivers who had not taken the programme (control group). In order to evaluate programme effects on cognitive and functional status, we used both direct measures answered by the older adults (MMSE, CAPE and EuroQol) and caregiver reports (Barthel and RMPBC). We used a quasi-experimental, pre-post design. We followed SQUIRE 2.0 guidelines for reporting. RESULTS: The results showed that older adults who were cared for by caregivers that had participated in the training programme showed gains in quality of life and cognitive ability and maintenance of functional ability. Within the treatment group, although everyone significantly improved their scores, the older adults cared for by family caregivers improved in more of the cognitive sub-items than did their peers in the professional caregiver group. CONCLUSIONS: The data obtained show that a caregiver training programme based on cognitive stimulation produces cognitive, functional and health-related quality-of-life benefits in older adults. Furthermore, the caregivers reported increased satisfaction with their work. RELEVANCE TO CLINICAL PRACTICE: The improvements obtained in the older adults and in caregivers show the relevance of this type of intervention when working in the clinical field of caregiving.
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Cuidadores , Calidad de Vida , Humanos , Anciano , Cuidadores/psicología , Envejecimiento , Actividades Cotidianas , CogniciónRESUMEN
Metastatic pheochromocytoma and paraganglioma (PPGL) have poor prognosis and limited therapeutic options. The recent advent of immunotherapies showing remarkable clinical efficacies against various cancer types offers the possibility of novel opportunities also for metastatic PPGL. Most PPGLs are pathogenically linked to inactivating mutations in genes encoding different succinate dehydrogenase (SDH) subunits. This causes activation of the hypoxia-inducible factor 2 (HIF2)-mediated transcriptional program in the absence of decreased intratumoral oxygen levels, a phenomenon known as pseudohypoxia. Genuine hypoxia in a tumor creates an immunosuppressive tumor microenvironment. However, the impact of pseudohypoxia in the immune landscape of tumors remains largely unexplored. In this study, tumoral expression of programmed death-ligand 1 (PD-L1) and HIF2α and tumor infiltration of CD8 T lymphocytes (CTLs) were examined in PPGL specimens from 102 patients. We assessed associations between PD-L1, CTL infiltration, HIF2α expression, and the mutational status of SDH genes. Our results show that high PD-L1 expression levels in tumor cells and CTL tumor infiltration were more frequent in metastatic than nonmetastatic PPGL. However, this phenotype was negatively associated with SDH mutations and high HIF2α protein expression. These data were validated by analysis of mRNA levels of genes expressing PD-L1, CD8, and HIF2α in PPGL included in The Cancer Genome Atlas database. Further, PD-L1 and CD8 expression was lower in norepinephrine than epinephrine-secreting PPGL. This in silico analysis also revealed the low PD-L1 or CD8 expression levels in tumors with inactivating mutations in VHL or activating mutations in the HIF2α-coding gene, EPAS1, which, together with SDH-mutated tumors, comprise the pseudohypoxic molecular subtype of PPGL. These findings suggest that pseudohypoxic tumor cells induce extrinsic signaling toward the immune cells promoting the development of an immunosuppressive environment. It also provides compelling support to explore the differential response of metastatic PPGL to immune checkpoint inhibitors. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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Neoplasias de las Glándulas Suprarrenales , Paraganglioma , Feocromocitoma , Humanos , Feocromocitoma/genética , Feocromocitoma/patología , Antígeno B7-H1/genética , Paraganglioma/genética , Paraganglioma/patología , Neoplasias de las Glándulas Suprarrenales/genética , Neoplasias de las Glándulas Suprarrenales/patología , Fenotipo , Microambiente TumoralRESUMEN
This paper explores the key factors influencing mental health professionals' behavioral intention to adopt virtual humans as a means of affect recognition training. Therapies targeting social cognition deficits are in high demand given that these deficits are related to a loss of functioning and quality of life in several neuropsychiatric conditions such as schizophrenia, autism spectrum disorders, affective disorders, and acquired brain injury. Therefore, developing new therapies would greatly improve the quality of life of this large cohort of patients. A questionnaire based on the second revision of the Unified Theory of Acceptance and Use of Technology (UTAUT2) questionnaire was used for this study. One hundred and twenty-four mental health professionals responded to the questionnaire after viewing a video presentation of the system. The results confirmed that mental health professionals showed a positive intention to use virtual reality tools to train affect recognition, as they allow manipulation of social interaction with patients. Further studies should be conducted with therapists from other countries to reach more conclusions.
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Fe-Co alloys are the most important soft magnetic materials, which are successfully used for a wide range of applications. In this work, the magnetic properties of lanthanide-substituted (Fe0.65Co0.35)0.95(RE2O3)0.05 (RE = La, Nd, and Sm) nanoparticles, prepared by mechanical alloying, are reported. Our comprehensive studies (X-ray diffraction, Mössbauer spectroscopy, scanning electron microscopy with X-ray energy dispersive spectrometry, SQUID magnetometry and differential scanning calorimetry) have revealed different properties, depending on the dopant type. The RE2O3 addition led to a decrease in the crystallite size and to an increase in the internal microstrain. Moreover, because of the high grain fragmentation tendency of RE2O3, the cold welding between Fe-Co ductile particles was minimized, indicating a significant decrease in the average particle size. The parent Fe0.65Co0.35 alloy is known for its soft ferromagnetism. For the La-substituted sample, the magnetic energy product was significantly lower (0.450 MG·Oe) than for the parent alloy (0.608 MG·Oe), and much higher for the Sm-substituted compound (0.710 MG·Oe). The processing route presented here, seems to be cost-effective for the large-scale production of soft magnetic materials.
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Therapeutic monoclonal antibodies (mAbs), including immune checkpoint inhibitors (ICIs), are an important breakthrough for the treatment of cancer and have dramatically changed clinical outcomes in a wide variety of tumours. However, clinical response varies among patients receiving mAb-based treatment, so it is necessary to search for predictive biomarkers of response to identify the patients who will derive the greatest therapeutic benefit. The interaction of mAbs with Fc gamma receptors (FcγR) expressed by innate immune cells is essential for antibody-dependent cellular cytotoxicity (ADCC) and this binding is often critical for their in vivo efficacy. FcγRIIa (H131R) and FcγRIIIa (V158F) polymorphisms have been reported to correlate with response to therapeutic mAbs. These polymorphisms play a major role in the affinity of mAb receptors and, therefore, can exert a profound impact on antitumor response in these therapies. Furthermore, recent reports have revealed potential mechanisms of ICIs to modulate myeloid subset composition within the tumour microenvironment through FcγR-binding, optimizing their anti-tumour activity. The purpose of this review is to highlight the clinical contribution of FcγR polymorphisms to predict response to mAbs in cancer patients.
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The NOTCH signaling pathway is an evolutionarily conserved family of transmembrane receptors, ligands, and transcription factors. The NOTCH signaling is activated in many biological processes including nephrogenesis, tubulogenesis, and glomerulogenesis, as well as during pathological situations. Activation of Notch signaling is characterized by successive proteolytic cleavages triggered by the interaction between membrane-bound Notch receptors and ligands expressed on neighboring cells. In chronic kidney diseases, activation of the canonical NOTCH signaling pathway has been described. The following protocols will allow the direct assessment of Jagged-1/NOTCH signaling activation in biopsies of patients with chronic kidney diseases and in murine experimental models of renal damage.
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Receptores Notch , Insuficiencia Renal Crónica , Animales , Biopsia , Proteínas de Unión al Calcio/metabolismo , Proteínas Portadoras/metabolismo , Humanos , Proteína Jagged-1/genética , Riñón/metabolismo , Ligandos , Ratones , Receptores Notch/metabolismo , Transducción de Señal/fisiologíaRESUMEN
PURPOSE: We investigated whether age at diagnosis of differentiated thyroid carcinoma (DTC) may be a risk factor for structural disease and mortality after primary treatment in aging patients. METHODS: A multicenter, retrospective analysis including patients older than 60 years at DCT diagnosis was designed. All subjects were treated by surgery with or without radioiodine adjuvant therapy and had a minimum follow-up of one year. We compared elderly patients (group 1, 60-74 years) with very old patients (group 2, ≥75 years). RESULTS: The study involved 1668 patients (74.3% women, median age 67 years, 87.6% papillary thyroid cancer, 73.3% treated with radioiodine), including 1397 in group 1 and 271 in group 2. Patients in group 2 had larger tumor size (1.8 [0.8-3.0] vs 1.5 [0.7-2.8] cm; P = 0.005), higher proportions of tumors with vascular invasion (23.8 vs 16.4%; P = 0.006), and lower proportion of lymphocytic thyroiditis (18.6 vs 24.9%; P = 0.013) than subjects in group 1. Kaplan-Meier survival analysis showed that patients in group 2 had significantly lower structural disease-free survival (DFS) and overall survival (OS) than patients in group 1 (P = 0.035 and <0.001, respectively). In multivariate Cox regression analysis, age was a risk factor significantly associated with OS. However, age was significantly associated with DFS in unadjusted analysis and in analysis adjusted by gender and risk classification variables, but not when pathological and therapy-related variables were introduced in the model. On the other hand, patients who received radioiodine had worse DFS (P < 0.001) compared to those who did not. CONCLUSION: Although age is a conditioning factor for OS, very old patients do not have a greater risk of developing structural disease throughout the follow-up than elderly patients with DTC.