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PURPOSE: To provide a treatment-focused review and develop basic treatment guidelines for patients diagnosed with pineal anlage tumor (PAT). METHODS: Prospectively collected data of three patients with pineal anlage tumor from Germany was combined with clinical details and treatment information from 17 published cases. RESULTS: Overall, 20 cases of PAT were identified (3 not previously reported German cases, 17 cases from published reports). Age at diagnosis ranged from 0.3 to 35.0 (median: 3.2 ± 7.8) years. All but three cases were diagnosed before the age of three years. For three cases, metastatic disease at initial staging was described. All patients underwent tumor surgery (gross-total resection: 9, subtotal resection/biopsy: 9, extent of resection unknown: 2). 15/20 patients were alive at last follow-up. Median follow-up for 10/15 surviving patients with available follow-up and treatment data was 2.4 years (0.3-6.5). Relapse was reported for 3 patients within 0.8 years after diagnosis. Five patients died, 3 after relapse and 2 from early postoperative complications. Two-year-progression-free- and -overall survival were 65.2 ± 12.7% and 49.2 ± 18.2%, respectively. All 4 patients who received intensive chemotherapy including high-dose chemotherapy combined with radiotherapy (2 focal, 2 craniospinal [CSI]) had no recurrence. Focal radiotherapy- and CSI-free survival rates in 13 evaluable patients were 46.2% (6/13) and 61.5% (8/13), respectively. CONCLUSION: PAT is an aggressive disease mostly affecting young children. Therefore, adjuvant therapy using intensive chemotherapy and considering radiotherapy appears to comprise an appropriate treatment strategy. Reporting further cases is crucial to evaluate distinct treatment strategies.
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Neoplasias Encefálicas , Glándula Pineal , Pinealoma , Neoplasias Supratentoriales , Adolescente , Adulto , Niño , Preescolar , Humanos , Lactante , Adulto Joven , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/cirugía , Recurrencia Local de Neoplasia/patología , Glándula Pineal/cirugía , Glándula Pineal/patología , Pinealoma/diagnóstico , Pinealoma/cirugía , Recurrencia , Neoplasias Supratentoriales/patología , Resultado del TratamientoAsunto(s)
Edema Corneal , Queratocono , Fotoquimioterapia , Humanos , Queratocono/diagnóstico , Queratocono/tratamiento farmacológico , Edema Corneal/diagnóstico , Edema Corneal/tratamiento farmacológico , Edema Corneal/etiología , Córnea , Fármacos Fotosensibilizantes/uso terapéutico , Reactivos de Enlaces Cruzados/uso terapéutico , Riboflavina/uso terapéutico , Rayos Ultravioleta , Topografía de la Córnea , Sustancia PropiaRESUMEN
Adaptation of immune cells to tissue-specific microenvironments is a crucial process in homeostasis and inflammation. Here, we show that murine effector type 2 innate lymphoid cells (ILC2s) from various organs are equally effective in repopulating ILC2 niches in other anatomical locations where they adapt tissue-specific phenotypes of target organs. Single-cell transcriptomics of ILC2 populations revealed upregulation of retinoic acid (RA) signaling in ILC2s during adaptation to the small intestinal microenvironment, and RA signaling mediated reprogramming of kidney effector ILC2s toward the small intestinal phenotype in vitro and in vivo. Inhibition of intestinal ILC2 adaptation by blocking RA signaling impaired worm expulsion during Strongyloides ratti infection, indicating functional importance of ILC2 tissue imprinting. In conclusion, this study highlights that effector ILC2s retain the ability to adapt to changing tissue-specific microenvironments, enabling them to exert tissue-specific functions, such as promoting control of intestinal helminth infections.
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Inmunidad Innata , Tretinoina , Ratones , Animales , Tretinoina/farmacología , Linfocitos , Intestinos , Inflamación , CitocinasRESUMEN
BACKGROUND: The outcome of children with refractory or relapsed soft tissue sarcoma (STS) is extremely poor. Whereas larger clinical trials evaluated specific treatment modalities, real-life data on individual multimodal therapeutic strategies, given alone or in combination, are scarce. PATIENTS AND METHODS: We retrospectively analyzed the clinical course of 18 pediatric patients with progression of or relapsed STS treated between 2008 and 2018 in our institution. RESULTS: A total of 18 patients (median age 12.4 years) suffered from progression or relapse of alveolar (n=7), embryonal (n=5), undifferentiated (n=2) rhabdomyosarcoma or desmoplastic small round cell tumor (n=4). 14 patents had an initial stage IV disease. All but one patient died. Median survival was 12.5 months. Shortest survival was seen in patients with systemic progression of the disease, longest in patients with local relapse. Patients with an Oberlin score<2 at the time of relapse had a significant longer time of survival than those with a score≥2. No significant advantage of a specific therapeutic modality was observed. DISCUSSION: We critically analyzed the clinical course in the real-life setting, in which various treatment options were applied to an individual patient according to the best of available data. We observed that some patients died within a short period of time despite multiple treatment modalities, which underlines the need for better prognostic parameters. CONCLUSION: In addition to well characterized clinical factors such as local or systemic relapse, the Oberlin score could be helpful in counselling patients and their families for choosing the best strategy of care.
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Protocolos de Quimioterapia Combinada Antineoplásica , Sarcoma , Humanos , Niño , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/terapia , Sarcoma/terapia , Sarcoma/patología , Pronóstico , Enfermedad Crónica , Progresión de la EnfermedadRESUMEN
PURPOSE: Intracranial germ cell tumors (iGCT) comprise germinoma and non-germinoma. Their diagnosis predominantly relies on biopsy as only one-fifth of patients present with elevated biomarkers (AFP/ß-HCG) in serum or cerebrospinal fluid (CSF). MicroRNAs (miR/miRNA) have emerged as non-invasive biomarkers in extracranial GCT and may potentially facilitate non-invasive diagnosis in iGCT. METHODS: We analyzed eight miRNAs in serum and CSF from the miR-371~373- and miR-302/367-clusters and four miRNAs differentially expressed in iGCT tissue (miR-142-5p/miR-146a-5p/miR-335-5p/miR-654-3p) from eight iGCT patients (age 10-33 years) and 12 control subjects by pre-amplified RT-qPCR. MiR-30b-5p (serum) and miR-204-5p (CSF) acted as reference genes. ΔCt-values were expressed as [Formula: see text] after standardization against controls. RESULTS: Between iGCT and control patients' serum ΔCt-values of miR-371a-3p (p = 0.0159), miR-372-3p (p= 0.0095, miR-367 (p = 0.0190), miR-302a (p = 0.0381) and miR-302d-3p (p = 0.0159) differed significantly. Discriminatory pattern in CSF was similar to serum as miR-371a (p = 0.0286), miR-372-3p (p = 0.0028), miR-367-3p (p = 0.0167) and miR-302d-3p (p = 0.0061) distinguished between patients and controls. Abundant [Formula: see text] levels of each of these miRNAs were found across all serum and CSF samples including biomarker-negative patients. CONCLUSION: With the largest data set so far, we underline the suitability of miR-371a, miR-372, miR-367 and miR-302d in serum and CSF for diagnosis of iGCT, particularly in biomarker-negative germinoma. Diagnosis of iGCT by miRNA analysis is a feasible and valid approach, particularly as serum can be readily obtained by a less invasive procedure. MiRNA analysis may discriminate iGCT from other tumors with similar radiological findings and may allow to monitor response to therapy as well as early relapse during follow-up.
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Germinoma , MicroARNs , Humanos , Niño , Adolescente , Adulto Joven , Adulto , Recurrencia Local de Neoplasia , MicroARNs/genética , Biomarcadores , Germinoma/genética , Biomarcadores de Tumor/genéticaRESUMEN
Purpose: Pathologic conditions in the cornea, such as transplant rejection or trauma, can lead to corneal neovascularization, creating a high-risk environment that may compromise subsequent transplantation. This study aimed to evaluate the impact of different types of corneal injury on hemangiogenesis (HA), lymphangiogenesis (LA) and immune cell pattern in the cornea. Methods: We used five different corneal injury models, namely, incision injury, alkali burn, suture placement, and low-risk keratoplasty, as well as high-risk keratoplasty and naïve corneas as control. One week after incision and 2 weeks after all other different injuries, corneal HA and LA were quantified by morphometric analysis. In addition, immune cell patterns of the whole cornea and the recipient rim were analyzed by immunohistochemistry. Immune cells in the draining lymph nodes (dLNs) were quantified by flow cytometry. Results: Different types of corneal injury caused significantly different HA and LA responses (both P < 0.0001). The infiltration of corneal macrophages, dendritic cells, neutrophils, major histocompatibility complex (MHC) II+ cells, CD4+ T cells, and CD8+ T cells varied significantly in different high-risk settings (all P < 0.0001). Both the expression of MHC II on macrophages (P = 0.0005) and the frequency of MHC II+ dendritic cells (P = 0.0014) in the draining lymph nodes were significantly different across the various high-risk scenarios. Conclusions: Murine high-risk settings caused by different underlying pathologies vary significantly in their (lymph)angiogenic and inflammatory cell patterns. Therefore, anti(lymph)angiogenic or immunomodulatory strategies to prevent and/or treat immune responses after subsequent corneal transplantation may need to be customized according to their immune-vascular "signatures."
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Lesiones de la Cornea , Neovascularización de la Córnea , Trasplante de Córnea , Ratones , Humanos , Animales , Córnea/metabolismo , Neovascularización de la Córnea/metabolismo , Rechazo de Injerto , Linfangiogénesis , Lesiones de la Cornea/metabolismo , Ratones Endogámicos BALB C , Modelos Animales de EnfermedadRESUMEN
Nasopharyngeal carcinoma (NPC) in children and young adults has been treated within two consecutive prospective trials in Germany, the NPC-91 and the NPC-2003 study of the German Society of Pediatric Oncology and Hematology (GPOH). In these studies, multimodal treatment with induction chemotherapy, followed by radio (chemo)therapy and interferon-beta maintenance, yielded promising survival rates even after adapting total radiation doses to tumor response. The outcome of 45 patients in the NPC-2003 study was reassessed after a median follow-up of 85 months. In addition, we analyzed 21 further patients after closure of the NPC-2003 study, recruited between 2011 and 2017, and treated as per the NPC-2003 study protocol. The EFS and OS of 66 patients with locoregionally advanced NPC were 93.6% and 96.7%, respectively, after a median follow-up of 73 months. Seven patients with CR after induction therapy received a reduced radiation dose of 54 Gy; none relapsed. In young patients with advanced locoregional NPC, excellent long-term survival rates can be achieved by multimodal treatment, including interferon-beta. Radiation doses may be reduced in patients with complete remission after induction chemotherapy and may limit radiogenic late effects.
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Enzima Convertidora de Angiotensina 2 , COVID-19 , SARS-CoV-2 , Conjuntiva , Humanos , Receptores ViralesAsunto(s)
Enzima Convertidora de Angiotensina 2/metabolismo , COVID-19/transmisión , Neoplasias de la Conjuntiva/metabolismo , SARS-CoV-2/fisiología , Serina Endopeptidasas/metabolismo , Carcinoma/metabolismo , Carcinoma/patología , Carcinoma/virología , Conjuntiva/metabolismo , Conjuntiva/virología , Neoplasias de la Conjuntiva/patología , Neoplasias de la Conjuntiva/virología , Humanos , Melanoma/metabolismo , Melanoma/patología , Melanoma/virología , Nevo/metabolismo , Nevo/patología , Nevo/virologíaRESUMEN
Although it is well established that microbial infections predispose to autoimmune diseases, the underlying mechanisms remain poorly understood. After infection, tissue-resident memory T (TRM) cells persist in peripheral organs and provide immune protection against reinfection. However, whether TRM cells participate in responses unrelated to the primary infection, such as autoimmune inflammation, is unknown. By using high-dimensional single-cell analysis, we identified CD4+ TRM cells with a TH17 signature (termed TRM17 cells) in kidneys of patients with ANCA-associated glomerulonephritis. Experimental models demonstrated that renal TRM17 cells were induced by pathogens infecting the kidney, such as Staphylococcus aureus, Candida albicans, and uropathogenic Escherichia coli, and persisted after the clearance of infections. Upon induction of experimental glomerulonephritis, these kidney TRM17 cells rapidly responded to local proinflammatory cytokines by producing IL-17A and thereby exacerbate renal pathology. Thus, our data show that pathogen-induced TRM17 cells have a previously unrecognized function in aggravating autoimmune disease.
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Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Infecciones Bacterianas/inmunología , Linfocitos T CD4-Positivos/inmunología , Candidiasis/inmunología , Glomerulonefritis/inmunología , Riñón/inmunología , Subgrupos de Linfocitos T/inmunología , Animales , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/microbiología , Candida albicans , Glomerulonefritis/microbiología , Humanos , Memoria Inmunológica , Masculino , Ratones Endogámicos DBA , Ratones TransgénicosRESUMEN
A wide spectrum of immunological functions has been attributed to Interleukin 9 (IL-9), including effects on the survival and proliferation of immune and parenchymal cells. In recent years, emerging evidence suggests that IL-9 expression can promote tissue repair in inflammatory conditions. However, data about the involvement of IL-9 in kidney tissue protection is very limited. Here, we investigated the role of IL-9 in Adriamycin-induced nephropathy (AN), a mouse model for proteinuric chronic kidney disease. Compared to wild type mice, IL-9 knockout (Il9-/-) mice with AN displayed accelerated development of proteinuria, aggravated glomerulosclerosis and deterioration of kidney function. At an early stage of disease, the Il9-/- mice already displayed a higher extent of glomerular podocyte injury and loss of podocyte number compared to wild type mice. In the kidney, T cells and innate lymphoid cells produced IL-9. However, selective deficiency of IL-9 in the innate immune system in Il9-/-Rag2-/- mice that lack T and B cells did not alter the outcome of AN, indicating that IL-9 derived from the adaptive immune system was the major driver of tissue protection in this model. Mechanistically, we could show that podocytes expressed the IL-9 receptor in vivo and that IL-9 signaling protects podocytes from Adriamycin-induced apoptosis in vitro. Finally, in vivo treatment with IL-9 effectively protected wild type mice from glomerulosclerosis and kidney failure in the AN model. The detection of increased serum IL-9 levels in patients with primary focal and segmental glomerulosclerosis further suggests that IL-9 production is induced by glomerular injury in humans. Thus, IL-9 confers protection against experimental glomerulosclerosis, identifying the IL-9 pathway as a potential therapeutic target in proteinuric chronic kidney disease.
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Glomeruloesclerosis Focal y Segmentaria , Podocitos , Animales , Doxorrubicina/toxicidad , Glomeruloesclerosis Focal y Segmentaria/inducido químicamente , Glomeruloesclerosis Focal y Segmentaria/genética , Glomeruloesclerosis Focal y Segmentaria/prevención & control , Humanos , Inmunidad Innata , Interleucina-9 , Linfocitos , Ratones , Proteinuria/inducido químicamente , Proteinuria/prevención & controlRESUMEN
Since their identification as a separate family of leukocytes, Innate lymphoid cells (ILCs) have been shown to play crucial roles in immune-mediated diseases and repair mechanisms that restore tissue integrity after injury. ILCs mainly populate non-lymphoid tissues where they form intricate circuits with parenchymal cells to regulate tissue immunity and organ homeostasis. However, the specific phenotype and function of ILC populations that reside in specific anatomical locations, such as the kidney, still remains poorly understood. In this review, we discuss tissue-specific properties of kidney-residing ILCs and summarize recent advances in the understanding of ILC biology in kidney diseases that might pave the way for development of novel treatment strategies in humans.
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Inmunidad Innata/inmunología , Linfocitos/inmunología , Nefritis/inmunología , Insuficiencia Renal Crónica/inmunología , Animales , Glomerulonefritis/inmunología , HumanosRESUMEN
Tumors of the central nervous system represent the largest group of solid tumors found in pediatric patients. Pilocytic astrocytoma is the most common pediatric glioma, mostly located in the posterior fossa. The majority of brainstem tumors, however, are classified as highly aggressive diffuse intrinsic pontine gliomas (DIPGs) and their prognosis is dismal.The authors report on the case of a neonate in whom MRI and neuropathological assessment were used to diagnose DIPG. Before initiation of the planned chemotherapy, the tumor regressed spontaneously, and the newborn exhibited a normal neurological development. Meanwhile, Illumina Human Methylation450 BeadChip analysis reclassified the tumor as pilocytic astrocytoma of the posterior fossa.In conclusion, the authors advocate not initiating immediate intensive therapy in newborns with brain tumors, even with classical appearance of a DIPG; rather, they would like to encourage a biopsy to define the best individual therapeutic approach and avoid ineffective chemotherapy.
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In recent years, the cytokine interleukin (IL)-22 attracted considerable attention due to its important immunoregulatory function in barrier tissues, such as the gut, lung, and skin. Although a regenerative role of IL-22 in renal tubular damage has been demonstrated, the role of IL-22 in the immunopathogenesis of glomerular injury is still unknown. Here, we demonstrate that the IL-22 receptor is expressed in the glomerular compartment of the kidney and that IL-22 expression increases in the renal cortex after induction of glomerular injury in a mouse model for crescentic glomerulonephritis (cGN, nephrotoxic nephritis). We identified γδ T cells and TH17 cells as major sources for IL-22 in the nephritic kidney. However, neither genetic or antibody-mediated deletion of IL-22 nor genetic deficiency in its endogenous inhibitor IL-22Rα2 (IL-22 binding protein) resulted in substantial phenotypic differences in mice with cGN with respect to crescent formation, tubulointerstitial damage, and kidney function impairment. Similarly, we did not observe significant differences between wild-type or IL-22-deficient mice in a mouse model of secondary focal and segmental glomerulosclerosis (adriamycin-induced nephropathy). As shown previously, we detected concomitant upregulation of IL-17A and IFN-γ production by T cells during the course of cGN, providing alternative cytokine pathways that mediate glomerular injury in this model. In conclusion, we show here that endogenous IL-22 expression is redundant in different forms of glomerular injury, indicating that the IL-22-directed therapies that are being tested in various human diseases might not affect the kidney in patients with glomerular disease.
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Glomerulonefritis/metabolismo , Interleucinas/metabolismo , Animales , Femenino , Glomerulonefritis/inmunología , Glomerulonefritis/patología , Inmunidad Celular/inmunología , Inmunidad Humoral/inmunología , Interferón gamma/biosíntesis , Interleucinas/genética , Riñón/patología , Corteza Renal/metabolismo , Glomérulos Renales/metabolismo , Túbulos Renales/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores de Interleucina/metabolismo , Linfocitos T/metabolismo , Interleucina-22RESUMEN
Innate lymphoid cells (ILCs) are important regulators of the immune response and play a crucial role in the restoration of tissue homeostasis after injury. GATA-3+ IL-13- and IL-5-producing group 2 innate lymphoid cells (ILC2s) have been shown to promote tissue repair in barrier organs, but despite extensive research on ILCs in the recent years, their potential role in autoimmune diseases is still incompletely understood. In the present study, we investigate the role of ILC2s in the MRL/MpJ-Faslpr (MRL-lpr) mouse model for severe organ manifestation of systemic lupus erythematosus (SLE). We show that in these MRL-lpr mice, progression of lupus nephritis is accompanied with a reduction of ILC2 abundance in the inflamed renal tissue. Proliferation/survival and cytokine production of kidney-residing ILC2s was suppressed by IFN-γ and, to a lesser extent, by IL-27 which were produced by activated T cells and myeloid cells in the nephritic kidney, respectively. Most importantly, restoration of ILC2 numbers by IL-33-mediated expansion ameliorated lupus nephritis and prevented mortality in MRL-lpr mice. In summary, we show here that development of SLE-like kidney inflammation leads to a downregulation of the renal ILC2 response and identify an ILC2-expanding therapy as a promising treatment approach for autoimmune diseases.
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Interferón gamma/metabolismo , Interleucina-33/metabolismo , Interleucinas/metabolismo , Lupus Eritematoso Sistémico/patología , Nefritis Lúpica/patología , Linfocitos T/inmunología , Animales , Células Cultivadas , Regulación hacia Abajo , Factor de Transcripción GATA3/metabolismo , Interleucina-13/metabolismo , Interleucina-5/metabolismo , Riñón/metabolismo , Lupus Eritematoso Sistémico/inmunología , Nefritis Lúpica/inmunología , Masculino , Ratones , Ratones Endogámicos MRL lprRESUMEN
XCL1 is the ligand for XCR1, a chemokine receptor uniquely expressed on cross-presenting dendritic cells (DC) in mouse and man. We are interested in establishing therapeutic vaccines based on XCL1-mediated targeting of peptides or proteins into these DC. Therefore, we have functionally analyzed various XCL1 domains in highly relevant settings in vitro and in vivo. Murine XCL1 fused to ovalbumin (XCL1-OVA) was compared to an N-terminal deletion variant lacking the first seven N-terminal amino acids and to several C-terminal (deletion) variants. Binding studies with primary XCR1+ DC revealed that the N-terminal region stabilizes the binding of XCL1 to its receptor, as is known for other chemokines. Deviating from the established paradigm for chemokines, the N-terminus does not contain critical elements for inducing chemotaxis. On the contrary, this region appears to limit the chemotactic action of XCL1 at higher concentrations. A participation of the XCL1 C-terminus in receptor binding or chemotaxis could be excluded in a series of experiments. Binding studies with apoptotic and necrotic XCR1-negative cells suggested a second function for XCL1: marking of stressed cells for uptake into cross-presenting DC. In vivo studies using CD8+ T cell proliferation and cytotoxicity as readouts confirmed the critical role of the N-terminus for antigen targeting, and excluded any involvement of the C-terminus in the uptake, processing, and presentation of the fused OVA antigen. Together, these studies provide basic data on the function of the various XCL1 domains as well as relevant information on XCL1 as an antigen carrier in therapeutic vaccines.
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Quimiocinas C , Células Dendríticas/inmunología , Portadores de Fármacos , Ovalbúmina , Receptores de Quimiocina/inmunología , Proteínas Recombinantes de Fusión , Animales , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/inmunología , Proliferación Celular/efectos de los fármacos , Quimiocinas C/química , Quimiocinas C/genética , Quimiocinas C/farmacología , Quimiotaxis/efectos de los fármacos , Quimiotaxis/inmunología , Células Dendríticas/citología , Portadores de Fármacos/química , Portadores de Fármacos/farmacología , Ratones , Ratones Transgénicos , Ovalbúmina/química , Ovalbúmina/genética , Ovalbúmina/farmacología , Dominios Proteicos , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/farmacología , Relación Estructura-Actividad , Vacunas/química , Vacunas/genética , Vacunas/farmacologíaRESUMEN
OBJECTIVE: Evaluate the impact of endoscopic partial inferior turbinectomy (EPIT) associated with primary rhinoseptoplasty on quality-of-life outcomes (QOL), complications, and surgical duration. STUDY DESIGN: Randomized clinical trial. METHODS: Individuals with nasal obstruction aged ≥ 16 years who were candidates for functional and aesthetics primary rhinoseptoplasty were evaluated from March 2014 through May 2015. Eligible participants were randomly allocated to rhinoseptoplasty with or without EPIT (excision of one-third of the inferior turbinates). RESULTS: Fifty patients were studied. Most were Caucasian and had moderate/severe allergic rhinitis symptoms. Mean age was 36 ( ± 14.5) years. Rhinoseptoplasty was associated with improvement in all QOL scores irrespective of turbinate intervention (P < 0.001). Analysis of covariance was conducted to control for potential confounders. There was no difference between the groups in absolute score changes for Nasal Obstruction Symptom Evaluation-Portuguese (NOSE-p) (-50.5 vs. -47.6; P = 0.723), Rhinoplasty Outcome Evaluation (ROE) (47 vs. 44.8; P = 0.742), and all World Health Organization Quality of Life Scale-Abbreviated (WHOQOL-bref) score domains (P > 0.05). There were no differences between the groups regarding presence of the complications. Surgical duration was higher in the EPIT group (212 minutes ± 7.8 vs. 159.1 ± 5.6; P ? 0.001). CONCLUSIONS: Turbinate reduction through EPIT during primary rhinoseptoplasty did not improve short-term general and specific QOL outcomes. The use of EPIT increases surgical time considerably without improving QOL scores. There was no difference in postoperative incidence of complications, suggesting that EPIT is a safe technique. LEVEL OF EVIDENCE: 1b. Laryngoscope, 128:57-63, 2018.
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Endoscopía/métodos , Obstrucción Nasal/cirugía , Tabique Nasal/cirugía , Calidad de Vida , Rinoplastia/métodos , Cornetes Nasales/cirugía , Adulto , Estética , Femenino , Humanos , Masculino , Tempo Operativo , Complicaciones Posoperatorias , Resultado del TratamientoRESUMEN
It has become evident that nonlymphoid tissues are populated by distinct subsets of innate and adaptive lymphocytes that are characterized by minimal exchange with recirculating counterparts. Especially at barrier sites, such as the skin, gut, and lung, these tissue-resident lymphocyte populations are ideally positioned to quickly respond to pathogens and other environmental stimuli. The kidney harbors several classes of innate and innate-like lymphocytes that have been described to contribute to this tissue-resident population in other organs, including innate lymphoid cells, natural killer cells, natural killer T cells, mucosal-associated invariant T cells, and γδ T cells. Additionally, a substantial proportion of the adaptive lymphocytes that are found in the kidney displays a surface phenotype suggestive of tissue residency, such as CD69+CD4+ T cells. In this review, we summarize recent advances in the understanding of tissue-resident lymphocyte populations, review the available evidence for the existence of these populations in the kidney, and discuss the potential physiologic and pathophysiologic roles thereof in kidney.
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Inmunidad Innata , Enfermedades Renales/inmunología , Riñón/citología , Riñón/inmunología , Linfocitos/inmunología , Inmunidad Adaptativa , Animales , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Humanos , Memoria Inmunológica , Células Asesinas Naturales/inmunología , Células T Asesinas Naturales/inmunología , Subgrupos de Linfocitos T/inmunologíaRESUMEN
Inflammatory myofibroblastic tumor (IMT) and its subtype epithelioid inflammatory myofibroblastic sarcoma (EIMS) are rare soft-tissue tumors. As about 50% of IMT and 100% of EIMS contain activating rearrangements of the anaplastic lymphoma kinase (ALK) gene, targeted kinase inhibition of ALK by compounds such as crizotinib is a potential treatment option. We performed a literature review and analyzed a total of 30 patients with IMT/EIMS treated with crizotinib. A total of 12 patients achieved complete or partial remission. As preliminary data are promising, a prospective study evaluating crizotinib treatment in patients with unresectable/multifocal ALK+ IMT/EIMS is warranted.
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Quinasa de Linfoma Anaplásico/antagonistas & inhibidores , Crizotinib/uso terapéutico , Proteínas de Neoplasias/antagonistas & inhibidores , Neoplasias de Tejido Muscular/tratamiento farmacológico , Neoplasias de Tejido Muscular/enzimología , Femenino , Humanos , Inflamación/tratamiento farmacológico , Inflamación/enzimología , MasculinoRESUMEN
Innate lymphoid cells (ILCs) have an important role in the immune system's response to different forms of infectious and noninfectious pathologies. In particular, IL-5- and IL-13-producing type 2 ILCs (ILC2s) have been implicated in repair mechanisms that restore tissue integrity after injury. However, the presence of renal ILCs in humans has not been reported. In this study, we show that ILC populations are present in the healthy human kidney. A detailed characterization of kidney-residing ILC populations revealed that IL-33 receptor-positive ILC2s are a major ILC subtype in the kidney of humans and mice. Short-term IL-33 treatment in mice led to sustained expansion of IL-33 receptor-positive kidney ILC2s and ameliorated adriamycin-induced glomerulosclerosis. Furthermore, the expansion of ILC2s modulated the inflammatory response in the diseased kidney in favor of an anti-inflammatory milieu with a reduction of pathogenic myeloid cell infiltration and a marked accumulation of eosinophils that was required for tissue protection. In summary, kidney-residing ILC2s can be effectively expanded in the mouse kidney by IL-33 treatment and are central regulators of renal repair mechanisms. The presence of ILC2s in the human kidney tissue identifies these cells as attractive therapeutic targets for CKD in humans.