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1.
Sci Transl Med ; 16(750): eadi4125, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38838135

RESUMO

Chronic inflammation is a constitutive component of many age-related diseases, including age-related macular degeneration (AMD). Here, we identified interleukin-1 receptor-associated kinase M (IRAK-M) as a key immunoregulator in retinal pigment epithelium (RPE) that declines during the aging process. Rare genetic variants of IRAK3, which encodes IRAK-M, were associated with an increased likelihood of developing AMD. In human samples and mouse models, IRAK-M abundance in the RPE declined with advancing age or exposure to oxidative stress and was further reduced in AMD. Irak3-knockout mice exhibited an increased incidence of outer retinal degeneration at earlier ages, which was further exacerbated by oxidative stressors. The absence of IRAK-M led to a disruption in RPE cell homeostasis, characterized by compromised mitochondrial function, cellular senescence, and aberrant cytokine production. IRAK-M overexpression protected RPE cells against oxidative or immune stressors. Subretinal delivery of adeno-associated virus (AAV)-expressing human IRAK3 rescued light-induced outer retinal degeneration in wild-type mice and attenuated age-related spontaneous retinal degeneration in Irak3-knockout mice. Our data show that replenishment of IRAK-M in the RPE may redress dysregulated pro-inflammatory processes in AMD, suggesting a potential treatment for retinal degeneration.


Assuntos
Quinases Associadas a Receptores de Interleucina-1 , Camundongos Knockout , Estresse Oxidativo , Degeneração Retiniana , Epitélio Pigmentado da Retina , Animais , Humanos , Masculino , Camundongos , Senescência Celular , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Quinases Associadas a Receptores de Interleucina-1/genética , Degeneração Macular/metabolismo , Degeneração Macular/patologia , Degeneração Macular/genética , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Degeneração Retiniana/metabolismo , Degeneração Retiniana/patologia , Degeneração Retiniana/genética , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia
2.
World Neurosurg ; 189: 7-9, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38815924

RESUMO

Periodontoid pannus formation is a pathologic condition caused by a multitude of different etiologies, however, it is most commonly due to rheumatoid arthritis. In these cases, the pannus is typically located in the retro-odontoid space ventral to the spinal cord, leading to progressive neural compression. We describe in this report, a patient who presented with progressive high cervical myelopathy, who on imaging revealed both a retro-odontoid pannus and a posterior C1-C2 mass causing severe circumferential compression of the spinal cord. The patient was successfully treated with a C1-C2 laminectomy and occipitocervical fusion. Periodontoid pannus is a common entity; however, the presence of a C1-C2 posterior pannus is a unique finding. To our knowledge, circumferential pannus at C1-C2 causing neural compression is a clinical entity that has not been previously reported.

3.
PLoS One ; 19(5): e0304054, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38776338

RESUMO

This study explores the Hydrothermal Carbonization (HTC) treatment of lignocellulosic biomass blends, delving into the influence of several key parameters: temperature, additive nature and dosage, residence time, and biomass composition. Rapeseeds, Pinus radiata sawdust, oat husks, and pressed olive served as the studied biomasses. One hundred twenty-eight experiments were conducted to assess the effects on mass yield (MY), energy yield (EY), higher heating value (HHV), and final ash content (ASH) by a Factorial Experimental Design. The derived model equations demonstrated a robust fit to the experimental data, averaging an R2 exceeding 0.94, affirming their predictive accuracy. The observed energy yield ranged between 65% and 80%, notably with sawdust and olive blends securing EY levels surpassing 70%, while rapeseed blends exhibited the highest HHV at 25 MJ/kg. Temperature emerged as the most influential factor, resulting in an 11% decrease in MY and a substantial 2.20 MJ/kg increase in HHV. Contrastingly, blend composition and additive presence significantly impacted ASH and EY, with all blends exhibiting increased ASH in the presence of additives. Higher initial hemicellulose and aqueous extractive content in raw biomass correlated proportionally with heightened HHV.


Assuntos
Biocombustíveis , Biomassa , Biocombustíveis/análise , Lignina/química , Temperatura , Pinus/química , Olea/química , Brassica rapa/química , Temperatura Alta
4.
Clin Transl Oncol ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578537

RESUMO

BACKGROUND: Retrospective data suggest an association between bevacizumab efficacy and the incidence of arterial hypertension (AHT). Additionally, epigenetic mechanisms have been related to AHT. METHODS: This prospective observational study conducted by GEICAM Spanish Breast Cancer Research Group included metastatic breast (MBC) or colorectal (mCRC) cancer patients treated with bevacizumab-containing chemotherapy as first-line treatment. Blood pressure (BP) levels were measured (conventional and 24-h Holter monitoring) at baseline and up to cycle 3. Primary endpoint assessed BP levels increase as predictive factor for progression-free survival (PFS). Germline DNA methylation profile was explored in pre-treatment blood samples; principal component analysis was used to define an epigenetic predictive score for increased BP levels. RESULTS: From Oct-2012 to Jul-2016, 143 (78 MBC and 65 mCRC) patients were included. The incidence of AHT according to guidelines was neither predictive of PFS nor of best overall tumor response (BOR). No statistically significant association was observed with systolic BP nor diastolic BP increment for PFS or BOR. Grade 3 and 4 adverse events were observed in 37 and 5% of patients, respectively. We identified 27 sites which baseline methylation status was significantly associated to BP levels increase secondary to bevacizumab-containing chemotherapy. CONCLUSIONS: Neither the frequency of AHT nor the increase of BP levels were predictive of efficacy in MBC and mCRC patients treated with bevacizumab-containing chemotherapy. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT01733628.

6.
Orphanet J Rare Dis ; 19(1): 26, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38279137

RESUMO

BACKGROUND: Hereditary leiomyomatosis and renal cell cancer syndrome is a rare autosomal dominant hereditary syndrome. Previously, we published the largest cohort of FH mutation carriers in Spain and observed a highly recurrent missense heterozygous variant, FH(NM_000143.4):c.1118A > G p.(Asn373Ser), in 104 individuals from 31 apparently unrelated families. Here, we aimed to establish its founder effect and characterize the associated clinical phenotype. RESULTS: Haplotype analysis confirmed that families shared a common haplotype (32/38 markers) spanning 0.61-0.82 Mb, indicating this recurrent variant was inherited from a founder ancestor. Cutaneous and uterine leiomyomatosis were diagnosed in 64.6% (64/99) and 98% (50/51) of patients, respectively, and renal cell cancer was present in 10.4% (10/96). The pathogenic FH_c.1118A > G variant is a Spanish founder mutation that originated 12-26 generations ago. We estimate that the variant may have appeared between 1370 and 1720. Individuals carrying this founder mutation had similar frequency of renal cell cancer and a higher frequency of renal cysts and leiomyomas than those in other cohorts of this syndrome. CONCLUSIONS: In the Spanish province of Alicante there is a high prevalence of HLRCC because of the founder mutation FH c.1118A > G; p.(Asn373Ser). The characterization of founder mutations provides accurate and specific information regarding their penetrance and expressivity. In individuals with suspected HLRCC from the province of Alicante, genetic testing by direct analysis of the founder FH c.1118A > G; p.(Asn373Ser) mutation may be a faster and more efficient diagnostic tool compared with complete gene sequencing.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Leiomiomatose , Síndromes Neoplásicas Hereditárias , Neoplasias Cutâneas , Neoplasias Uterinas , Feminino , Humanos , Leiomiomatose/genética , Leiomiomatose/patologia , Neoplasias Renais/genética , Neoplasias Cutâneas/patologia , Mutação/genética , Síndrome
7.
World Neurosurg ; 182: 116-123, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38042293

RESUMO

BACKGROUND: Autologous cranioplasty has been used for decades and is the gold standard treatment in patients who underwent decompressive craniectomy (DC). One of the most common methods to store the cranial bone flap is cryopreservation at very low temperatures (-70 to -80°). The only way to achieve these low temperatures is by using special freezers which are not always available in all medical facilities, especially in low-resource centers. This paper describes our experience with the storage of cranial bone flaps in freezers of conventional refrigerators. METHODS: This retrospective study included patients treated with autologous cranioplasty, operated between 2015 and 2020. The cranial bone flap was stored at -18°C in the freezer of conventional refrigerators. Complications and outcomes were analyzed and compared with reports of patients in whom ultra-low temperature freezers were used for bone flap preservation. RESULTS: Twenty-five patients were included. The average follow-up period was 33 months. Trauma was the most common cause of DC, followed by stroke. The mean age was 36.7. Aseptic bone flap resorption was observed in 4 cases (16%). No cases of infection were observed. CONCLUSIONS: The use of freezers from conventional refrigerators may be an acceptable alternative for the preservation of the cranial bone flap in facilities where special freezers are not available. The rate of aseptic bone necrosis and infections observed in this paper was similar to the incidence of these complications reported in studies where ultra-low temperatures were used.


Assuntos
Reabsorção Óssea , Craniectomia Descompressiva , Procedimentos de Cirurgia Plástica , Humanos , Adulto , Estudos Retrospectivos , Região de Recursos Limitados , Craniectomia Descompressiva/métodos , Retalhos Cirúrgicos/cirurgia , Crânio/cirurgia , Reabsorção Óssea/etiologia , Complicações Pós-Operatórias/etiologia
8.
Acta Neurochir (Wien) ; 165(12): 3963-3967, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37950756

RESUMO

BACKGROUND: Lateral lumbar interbody fusion supplemented with insertion of pedicle screws is a surgical procedure that has gained popularity in the last years, becoming an important tool in the armamentarium of spine surgeons. In recent years, there is a trend to complete both procedures in a single position, thus avoiding flipping the patient prone to insert the pedicle screws. METHODS: We describe a step-by-step workflow of the robotic-assisted technique for multilevel lateral lumbar interbody fusion supplemented with posterior instrumentation. The surgical procedure is performed in a single lateral position. For access to L4-5 or L5-S1, an oblique abdominal incision is performed in the same position, and the desired disc space is approached through an oblique or anterior corridor in the retroperitoneal space. CONCLUSION: Robotic-assisted single-position lateral for multilevel circumferential lumbar interbody fusion is a safe and effective procedure in patients where lumbar stabilization is required. This technique provides patients with a faster recovery and low risk of complications.


Assuntos
Parafusos Pediculares , Procedimentos Cirúrgicos Robóticos , Fusão Vertebral , Humanos , Coluna Vertebral , Fusão Vertebral/métodos , Vértebras Lombares/cirurgia
9.
bioRxiv ; 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37808640

RESUMO

Unchecked, chronic inflammation is a constitutive component of age-related diseases, including age-related macular degeneration (AMD). Here we identified interleukin-1 receptor-associated kinase (IRAK)-M as a key immunoregulator in retinal pigment epithelium (RPE) that declines with age. Rare genetic variants of IRAK-M increased the likelihood of AMD. IRAK-M expression in RPE declined with age or oxidative stress and was further reduced in AMD. IRAK-M-deficient mice exhibited increased incidence of outer retinal degeneration at earlier ages, which was further exacerbated by oxidative stressors. The absence of IRAK-M disrupted RPE cell homeostasis, including compromised mitochondrial function, cellular senescence, and aberrant cytokine production. IRAK-M overexpression protected RPE cells against oxidative or immune stressors. Subretinal delivery of AAV-expressing IRAK-M rescued light-induced outer retinal degeneration in wild-type mice and attenuated age-related spontaneous retinal degeneration in IRAK-M-deficient mice. Our data support that replenishment of IRAK-M expression may redress dysregulated pro-inflammatory processes in AMD, thereby treating degeneration.

10.
PLoS One ; 18(9): e0291838, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37729330

RESUMO

Global population growth and rising consumption levels have significantly increased resource use and energy demand, leading to higher greenhouse gas concentrations and increased waste output. As a result, alternative waste treatment methods for sustainable municipal solid waste (MSW) management are crucial. This research evaluates the efficiency of integrating hydrothermal carbonization (HTC) and gasification for an optimized MSW biomass blend. HTC was conducted for one hour at 220°C in a 5 L reactor, followed by gasification in a hybrid porous medium gasifier. The study investigated the effects of different filtration speeds on combustion temperature and hydrogen concentrations. The results showed that a filtration speed of 35 cm/s resulted in a maximum combustion temperature of 1035.7°C. The temperature remained consistent across filter speeds, while higher velocities yielded higher hydrogen concentrations. Additionally, increasing the filtration velocity raised temperatures in the hybrid bed while increasing the volumetric fraction of biomass decreased maximum temperatures. This research contributes to the understanding of merging HTC and gasification for MSW biomass blend treatment, aiming to reduce environmental impacts and costs while promoting renewable resources for long-term energy production.


Assuntos
Febre , Resíduos Sólidos , Humanos , Porosidade , Biomassa , Hidrogênio
11.
Cancers (Basel) ; 15(5)2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36900229

RESUMO

OBJECTIVE: To analyze, in a cohort of acromegalic patients, the results of the efficiency and safety of radiosurgery (CyberKnife), as well as the prognostic factors associated with disease remission. MATERIAL AND METHODS: Observational, retrospective, longitudinal, and analytical study that included acromegalic patients with persistent biochemical activity after initial medical-surgical treatment, who received treatment with CyberKnife radiosurgery. GH and IGF-1 levels at baseline after one year and at the end of follow-up were evaluated. RESULTS: 57 patients were included, with a median follow-up of four years (IQR, 2-7.2 years). The biochemical remission rate was 45.6%, 33.33% achieved biochemical control, and 12.28% attained biochemical cure at the end of follow-up. A progressive and statistically significant decrease was observed in the comparison of the concentrations of IGF-1, IFG-1 x ULN, and baseline GH at one year and at the end of follow-up. Both cavernous sinus invasion and elevated baseline IGF-1 x ULN concentrations were associated with an increased risk of biochemical non-remission. CONCLUSION: Radiosurgery (CyberKnife) is a safe and effective technique in the adjuvant treatment of GH-producing tumors. Elevated levels of IGF x ULN before radiosurgery and invasion of the cavernous sinus by the tumor could be predictors of biochemical non-remission of acromegaly.

12.
Genes (Basel) ; 14(2)2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36833429

RESUMO

Hereditary breast and ovarian cancer syndrome (HBOC) is a clinical entity characterized by an increased risk of developing breast and ovarian cancer. The genetic diagnosis is based on the identification of heterozygous germinal variants in HBOC susceptibility genes. However, it has recently been described that constitutional mosaic variants can contribute to the aetiology of HBOC. In constitutional mosaicism, individuals have at least two genotypically distinct populations of cells that arise from an early post-zygote event. The mutational event occurs early enough in development to affect several tissues. It is detected in germinal genetic studies as low variant allele frequency (VAF) variants (<30%) that are generally overlooked during the prioritization process. Constitutional mosaic variants can affect both somatic and germinal cells, and thus can be passed to the offspring and have important consequences for genetic counselling. In this work, we report the c.9648+1G>A mosaic variant in the BRCA2 gene and propose a diagnostic algorithm to deal with potential mosaic findings identified by Next Generation Sequencing (NGS).


Assuntos
Síndrome Hereditária de Câncer de Mama e Ovário , Neoplasias Ovarianas , Humanos , Feminino , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Genes BRCA2 , Mosaicismo , Mutação , Neoplasias Ovarianas/genética , Proteína BRCA2/genética
13.
Int J Spine Surg ; 16(3): 521-529, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35772984

RESUMO

BACKGROUND: Patients with epilepsy have a higher risk of skeletal injuries, and some of these fractures occur in the spine during a seizure. Seizure-induced spinal fractures (SISF) are unusual injuries that typically occur in the thoracolumbar spine. Because these skeletal injuries are not well described in the literature, this article aims to analyze the characteristics of this uncommon clinical entity. METHODS: A PubMed and Scopus search adhering to preferred reporting items for systematic reviews and meta-analyses guidelines was performed to include studies reporting patients with SISF. The data gathered from this review were analyzed to characterize this condition. RESULTS: The search yielded 34 articles with a total of 38 patients with SISF. All studies were case reports (level 5 evidence). Most fractures occurred in the thoracic and lumbar spine, and the most common injuries were type A1 and A4 fractures according to the AO spine classification system. Different characteristics of SISF are described including demographics, clinical findings, imaging, and treatment. CONCLUSIONS: SISF should be ruled out in patients who have a recent history of seizures and who report persistent dorsolumbar pain or neurological deficit. SISF usually occurs in the thoracolumbar spine and less frequently in the cervical spine. This review shows that different patterns of neurological deficits, some of them severe, may occur in approximately a quarter of patients with SISF. CLINICAL RELEVANCE: This study provides awareness of an uncommon spine condition. Physicians should suspect SISF in patients with persistent dorsolumbar pain after a seizure.

14.
Infectio ; 26(2): 193-196, Jan.-June 2022. graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1356268

RESUMO

Resumen Scedosporium sp. es un género de hongos filamentosos que de forma infrecuente se relaciona a infecciones localizadas o diseminadas en pacientes inmunocom prometidos, o inmunocompetentes con trauma penetrante contaminado. Reportamos el caso de un paciente masculino de 31 años con antecedente de trauma penetrante por arma de fuego requiriendo enucleación de su ojo izquierdo, quien 12 años posterior al trauma inicial presenta necrosis de la cavidad anoftálmica con extrusión del implante y lisis del párpado inferior, finalmente identificando Scedosporium sp. como germen causal, y un mucocele en el seno frontal como reservorio. El paciente recibió tratamiento médico con voriconazol sistémico, desbridamiento quirúrgico amplio, y resección endoscópica del quiste de retención mucoso, con una evolución satisfactoria. Las infecciones micóticas de la cavidad anoftálmica son infrecuentes, requiriendo una alta sospecha diagnóstica y trata miento agresivo para evitar consecuencias potencialmente devastadoras.


Abstract Scedosporium sp. is a genus of filamentous fungi that is infrequently related to localized or disseminated infections in either immunocompromised patients, or immunocompetent patients with penetrating contaminated trauma. We report the case of a 31-year-old patient with a history of penetrating gunshot wound that required enucleation of his left eye, who 12 years after initial trauma presents necrosis of the anophthalmic socket with implant extrusion and lysis of inferior eyelid, finally identifying the causal agent to be Scedosporium sp. The patient received medical treatment with systemic voriconazole, and wide surgical debridement, with a satisfactory evolution. Fungal infections of anophthalmic sockets are infrequent, requiring a high diagnostic suspicion and aggressive treatment to avoid potentially devastating consequences.

15.
Biomimetics (Basel) ; 7(2)2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35466255

RESUMO

We have studied the external surface (elytra) of the Sonoran Desert beetle (Eleodes eschscholtzii). Our aim was to assess whether this species has similar traits to some beetles from the Namibian Desert that are known to have hierarchical micropatterns that allow for water harvesting. We have conducted scanning electron microscopy (SEM) and apparent contact angle experiments on specimens collected at two sampling sites with different ambient humidity. The results show that the beetle's external surface microstructure is composed of a compact array of polygons with randomly scattered protuberances. The density of the polygons in the microstructure is different for individuals collected in different sites: the polygon array is denser in the more humid site and less dense in the drier site. The measured contact angles also depend on the sampling site. For individuals collected in the drier site, the average apparent contact angle is 70°, whereas for the more humid site, the average apparent contact angle is 92°. FT-IR experiments are consistent with the presence of hydrophobic wax compounds in the studied surfaces. Our investigation opens new questions that are currently being addressed by experiments that are underway. For instance, it would be interesting to know whether the observed nanopatterns could be used in biomimetic devices for water harvesting purposes.

16.
Sci Total Environ ; 828: 154474, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35276176

RESUMO

Climate change is the world's greatest challenge today, the reason why it is urgent to optimize industrial processes and find new renewable energy sources. Hydrothermal carbonization (HTC) is one of the Waste-to-Energy technologies with greater projections due to its operative advantages. However, for its large-scale implementation, there are challenges related to the variability of the composition of the waste biomass and the seasonal and geographical availability. This research applied the Life Cycle Analysis methodology to evaluate the environmental impacts caused by three biomasses blends as raw material in the HTC process at laboratory scale. The blends analyzed considered different organic fractions of municipal solid waste (food and pruning) and sewage sludge. The results showed that blend 1 had a lower environmental impact for the case of production in the experimental laboratory level, compared with blends 2 and 3. This is mainly due to its greater calorific value and mass yield, which allows obtaining more hydrochar compared with the other blends, increasing the energy efficiency of the process. Also, between 87.94% and 98.00% of the energy reduction is required to obtain neutral impacts regarding the energy requirements in the experimental laboratory level scenario and the Chilean energy matrix. The processing of blends in HTC has excellent potential in a context where municipal solid wastes have been disposed in sanitary landfills or dumps, as in most emerging countries. Since this study incorporated data from the literature, future studies should perform an elemental analysis to provide experimental and differentiated data.


Assuntos
Carbono , Esgotos , Biomassa , Resíduos Sólidos , Temperatura
17.
Neurosurg Rev ; 45(3): 2013-2026, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35184233

RESUMO

Primary intraventricular hemorrhage (PIVH) is a special subtype of intraventricular hemorrhage (IVH) without a hemorrhagic parenchymal component. Different conditions may cause this uncommon hemorrhage including trauma, vascular anomalies, coagulation disorders, and others. Frequently, PIVH is associated with structural vascular anomalies such as aneurysms, arteriovenous malformations, and dural fistulas. Traditionally, hypertension has been considered a predisposing factor for PIVH. A wide variety of studies have been published describing patients with PIVH; however, studies describing exclusively patients with hypertensive PIVH are lacking in the literature. For this reason, the features of PIVH secondary to hypertension are not well described. The purpose of this study is to analyze and describe the characteristics of hypertensive PIVH. A PubMed and Scopus search adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed to include studies reporting patients with hypertensive PIVH. The search yielded 19 articles reporting retrospective case series. The diagnosis of hypertensive PIVH should be established in patients meeting the following criteria: (a) elevation of blood pressure is observed at admission, (b) a cerebral angiography is negative for vascular anomalies, and (c) other causes of intracranial hemorrhage are ruled out. The prognosis is poorer in patients who present with low Glasgow Coma Score (GCS), old age, hydrocephalus, or more extensive intraventricular bleeding. The results of this study show that hypertension is the most common cause of PIVH, followed by hemorrhage caused by vascular anomalies. Hypertension may be a direct cause of PIVH, but also it may be a predisposing factor for bleeding in cases of an associated vascular anomaly.


Assuntos
Hemorragia Cerebral , Hipertensão , Pressão Sanguínea/fisiologia , Hemorragia Cerebral/diagnóstico , Ventrículos Cerebrais , Humanos , Hipertensão/complicações , Estudos Retrospectivos , Resultado do Tratamento
18.
Eur J Surg Oncol ; 48(5): 1123-1132, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34872775

RESUMO

INTRODUCTION: Retrospective studies and meta-analyses suggest that upfront primary tumour resection (UPTR) confers a survival benefit in patients with asymptomatic unresectable metastatic colorectal cancer (mCRC) undergoing chemotherapy, however a consensus of its role in routine clinical practice in the current era of targeted therapies is lacking. This retrospective study aimed to analyse the survival benefit of UPTR in terms of tumour location and mutational status, in patients with synchronous mCRC receiving chemotherapy and targeted therapy. PATIENTS AND METHODS: Survival was analysed in a pooled cohort of synchronous mCRC patients treated with a first-line anti-VEGF or anti-EGFR inhibitor in seven trials of the Spanish TTD group, according to UPTR, tumour-sidedness and mutational profiling. RESULTS: Of 1334 eligible patients, 642 (48%) had undergone UPTR. UPTR was associated with significantly longer overall survival (OS; 25.0 vs 20.3 months; HR 1.30, 95%CI 1.15-1.48; p < 0.0001). UPTR was associated with significant OS benefit in both left-sided (HR 1.38, 95%CI 1.13-1.69; p = 0.002) and right-sided (HR 1.39, 95%CI 1.00-1.94; p = 0.049) tumours, RASwt (HR 1.29, 95%CI 1.05-1.60; p = 0.016) and BRAFwt (HR 1.49, 95%CI 1.21-1.84; p = 0.0002) tumours, and treatment with anti-EGFRs (HR 1.47, 95%CI 1.13-1.92; p = 0.004) and anti-VEGFs (HR 1.25, 95%CI 1.08-1.44; p = 0.003). Multivariate analysis identified number of metastatic sites, RAS status, primary tumour location and UPTR as independent prognostic factors for OS. CONCLUSION: Considering the selection bias inherent to this study, our results support UPTR before first-line anti-EGFR or anti-VEGF targeted therapy in right and left-sided asymptomatic unresectable synchronous mCRC patients. RAS/BRAF mutational status may also influence UPTR function.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/patologia , Humanos , Neoplasias Retais/tratamento farmacológico , Estudos Retrospectivos
19.
Andes Pediatr ; 93(4): 579-584, 2022 Aug.
Artigo em Espanhol | MEDLINE | ID: mdl-37906858

RESUMO

The Epstein Barr virus is an infectious disease with a high worldwide prevalence, which can present multiple systemic manifestations. The ophthalmological findings are the least frequent and nonspe cific and, therefore, its diagnosis is complicated and delayed; however, it should always be considered as a diagnostic possibility in the presence of atypical ocular and periocular inflammatory clinical pictures. OBJECTIVE: To describe the clinical case of a patient with the presence of a conjunctival mass as the first finding in Epstein Barr virus infection. CLINICAL CASE: A 4-year-old boy with a 4-day history of left upper eyelid edema and ptosis associated with a large, fast-growing, elevated, painful, and salmon-colored upper bulbar conjunctival mass with extension to the upper fornix associated with bilateral cervical and inguinal lymphadenopathy. Initially, a lymphoproliferative disorder was suspected, with blood count with lymphocytosis and atypical lymphocytes, elevated lactate dehydro genase, peripheral blood smear with an increase in white blood cells and some atypical lymphocytes, bone marrow aspirate with a predominance of granulocytes and predominantly CD8-positive T lym phocytes and an increase in Gamma-Delta T lymphocytes. The orbit CT scan showed thickening of the left upper eyelid with peripheral enhancement and the abdominal CT scan showed splenomegaly. Biopsy confirmed chronic Epstein Barr virus infection with positive IgM and indeterminate IgG anti bodies. Symptomatic management was indicated with satisfactory evolution and complete resolution of the conjunctival lesion and lymphadenopathy. CONCLUSION: Epstein Barr virus infection should be considered as a possible diagnosis in atypical ocular and periocular inflammatory manifestations in the pediatric population.


Assuntos
Infecções por Vírus Epstein-Barr , Linfadenopatia , Masculino , Humanos , Criança , Pré-Escolar , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Herpesvirus Humano 4 , Linfadenopatia/complicações
20.
Br J Neurosurg ; 36(1): 105-107, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29943648

RESUMO

This paper presents the case of a 68 years old male who was admitted to the hospital after being attacked by another person. The main clinical signs were confusion and severe periorbital edema, findings of gunshot injury were not evident initially. However, a CT scan showed findings compatible with an orbito-cranial perforating gunshot injury. To the best of the author's knowledge, cases like this have not been reported in the literature. This report shows us that an orbito-cranial gunshot injury should be ruled out in cases of severe periorbital edema, especially if the cause of the injury remains unidentified.


Assuntos
Ferimentos por Arma de Fogo , Idoso , Edema , Humanos , Masculino , Crânio , Tomografia Computadorizada por Raios X , Ferimentos por Arma de Fogo/complicações , Ferimentos por Arma de Fogo/diagnóstico por imagem , Ferimentos por Arma de Fogo/cirurgia
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