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1.
Adv Exp Med Biol ; 1287: 169-181, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33034032

RESUMEN

The Notch signaling pathway controls normal embryonic development and tissue homeostasis of many cell types. It regulates cell proliferation, fate, differentiation, and cell death by short-range signaling between nearby cells that come in contact. The Notch pathway has also been critically involved in the pathobiology of a variety of malignancies, regulating cancer initiation and development, as well as early stages of cancer progression, by adjusting conserved cellular programs. Fibroblasts, an essential for tumor growth component of stroma, have also been affected by Notch regulation. Sequencing Notch gene mutations have been identified in a number of human tumors, revealing information on the progression of specific cancer types, such as ovarian cancer and melanoma, immune-associated tumors such as myeloid neoplasms, but especially in lymphocytic leukemia. Activation of the Notch can be either oncogenic or it may contain growth-suppressive functions, acting as a tumor suppressor in other hematopoietic cells, hepatocytes, skin, and pancreatic epithelium.


Asunto(s)
Progresión de la Enfermedad , Neoplasias/patología , Receptores Notch , Transducción de Señal , Genes Supresores de Tumor , Humanos , Neoplasias/genética , Oncogenes , Receptores Notch/metabolismo
2.
J Med Imaging Radiat Oncol ; 64(5): 668-670, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33001577

RESUMEN

This case report describes our early radiological experiences of middle-aged patients with COVID-19 at Westmead Hospital, Sydney. We found limited relationship between initial CT imaging appearances and progression to severe disease. The most effective use of imaging in COVID-19 is yet to be determined.


Asunto(s)
Infecciones por Coronavirus/diagnóstico por imagen , Enfermedades Pulmonares/diagnóstico por imagen , Enfermedades Pulmonares/virología , Neumonía Viral/diagnóstico por imagen , Radiografía Torácica , Tomografía Computarizada por Rayos X , Adulto , Australia/epidemiología , Betacoronavirus , Infecciones por Coronavirus/epidemiología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/epidemiología
3.
J Investig Med High Impact Case Rep ; 8: 2324709620963635, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33019829

RESUMEN

As COVID-19 (coronavirus disease 2019) spreads across the world multiple therapeutic interventions have been tried to reduce morbidity and mortality. We describe a case of collapsing focal sclerosing glomerulosclerosis (FSGS) and acute oxalate nephropathy in a patient treated with high-dose intravenous vitamin C for severe COVID-19 infection. Collapsing FSGS has been described in patients with COVID-19 infection associated with APOL-1; however, this case had collapsing FSGS developing in low-risk heterozygous APOL-1 variant, and we postulate that the intensity of the COVID-19 cytokine storm overwhelmed the protective state of APOL-1 heterozygosity. This case illustrates the importance of assessing the risk and benefit of planned therapeutic interventions on a case-by-case basis especially when there are still so many unknowns in the management of COVID-19 infection. Strong consideration should be given for performing a renal biopsy in patients who develop multifactorial acute kidney injury.


Asunto(s)
Ácido Ascórbico/efectos adversos , Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Glomeruloesclerosis Focal y Segmentaria/inducido químicamente , Hiperoxaluria/inducido químicamente , Glomérulos Renales/patología , Oxalatos/metabolismo , Neumonía Viral/tratamiento farmacológico , Enfermedad Aguda , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Ácido Ascórbico/administración & dosificación , Biopsia , Infecciones por Coronavirus/epidemiología , Progresión de la Enfermedad , Glomeruloesclerosis Focal y Segmentaria/diagnóstico , Humanos , Hiperoxaluria/diagnóstico , Hiperoxaluria/metabolismo , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/epidemiología , Vitaminas/administración & dosificación , Vitaminas/efectos adversos
4.
Radiographics ; 40(6): 1574-1599, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-33001783

RESUMEN

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in coronavirus disease 2019 (COVID-19), which was declared an official pandemic by the World Health Organization on March 11, 2020. The infection has been reported in most countries around the world. As of August 2020, there have been over 21 million cases of COVID-19 reported worldwide, with over 800 000 COVID-19-associated deaths. It has become apparent that although COVID-19 predominantly affects the respiratory system, many other organ systems can also be involved. Imaging plays an essential role in the diagnosis of all manifestations of the disease, as well as its related complications, and proper utilization and interpretation of imaging examinations is crucial. With the growing global COVID-19 outbreak, a comprehensive understanding of the diagnostic imaging hallmarks, imaging features, multisystemic involvement, and evolution of imaging findings is essential for effective patient management and treatment. To date, only a few articles have been published that comprehensively describe the multisystemic imaging manifestations of COVID-19. The authors provide an inclusive system-by-system image-based review of this life-threatening and rapidly spreading infection. In part 1 of this article, the authors discuss general aspects of the disease, with an emphasis on virology, the pathophysiology of the virus, and clinical presentation of the disease. The key imaging features of the varied pathologic manifestations of this infection that involve the pulmonary and peripheral and central vascular systems are also described. Part 2 will focus on key imaging features of COVID-19 that involve the cardiac, neurologic, abdominal, dermatologic and ocular, and musculoskeletal systems, as well as pediatric and pregnancy-related manifestations of the virus. Vascular complications pertinent to each system will be also be discussed in part 2. Online supplemental material is available for this article. ©RSNA, 2020.


Asunto(s)
Betacoronavirus/fisiología , Infecciones por Coronavirus/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Pandemias , Neumonía Viral/diagnóstico por imagen , Tromboembolia/diagnóstico por imagen , Trombosis/diagnóstico por imagen , Angiografía/métodos , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Síndrome de Liberación de Citoquinas/etiología , Síndrome de Liberación de Citoquinas/fisiopatología , Progresión de la Enfermedad , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Inflamación , Peptidil-Dipeptidasa A/fisiología , Neumonía Viral/complicaciones , Neumonía Viral/epidemiología , Neumonía Viral/virología , Arteria Pulmonar/diagnóstico por imagen , Receptores Virales/fisiología , Síndrome de Dificultad Respiratoria del Adulto/diagnóstico por imagen , Síndrome de Dificultad Respiratoria del Adulto/etiología , Evaluación de Síntomas , Tromboembolia/sangre , Tromboembolia/etiología , Trombosis/sangre , Trombosis/etiología , Microangiopatías Trombóticas/diagnóstico por imagen , Microangiopatías Trombóticas/etiología , Tomografía Computarizada por Rayos X/métodos , Ultrasonografía/métodos
5.
Int J Med Sci ; 17(16): 2468-2476, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33029089

RESUMEN

Rationale: Coronavirus disease 2019 (COVID-19) was first announced in Wuhan, and has rapidly evolved into a pandemic. However, the risk factors associated with the severity and mortality of COVID-19 are yet to be described in detail. Methods: We retrospectively reviewed the information of 1525 cases from the Leishenshan Hospital in Wuhan. Univariate and multivariate Cox regression analyses were generated to explore the relationship between procalcitonin (PCT) level and the progression and prognosis of COVID-19. Univariate and multivariate logistic regression analyses were performed to explore the relationship between disease severity in hospitalized patients and their PCT levels. Survival curves and the cumulative hazard function for COVID-19 progression were conducted in the two groups. To further detect the relationship between the computed tomography score and survival days, curve-fitting analyses were performed. Results: Patients in the elevated PCT group had a higher incidence of severe and critical severity conditions (P < 0.001), death, and higher computed tomography (CT) scores. There was an association between elevated PCT levels and mortality in the univariate ((hazard ratio [1], 3.377; 95% confidence interval [2], 1.012-10.344; P = 0.033) and multivariate Cox regression analysis (HR, 4.933; 95% CI, 1.170-20.788; P = 0.030). Similarly, patients with elevated PCT were more likely to have critically severe disease conditions in the univariate (odds ratio [2], 7.247; 95% CI, 3.559-14.757; P < 0.001) and multivariate logistic regression analysis (OR, 10.679; 95% CI, 4.562-25.000; P < 0.001). Kaplan-Meier curves showed poorer prognosis for patients with elevated PCT (P = 0.024). The CT score 1 for patients with elevated PCT peaked at day 40 following the onset of symptoms then decreased gradually, while their total CT score was relatively stable. Conclusion: PCT level was shown as an independent risk factor of in-hospital mortality among COVID-19 patients. Compared with inpatients with normal PCT levels, inpatients with elevated PCT levels had a higher risk for overall mortality and critically severe disease. These findings may provide guidance for improving the prognosis of patients with critically severe COVID-19.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/etiología , Infecciones por Coronavirus/mortalidad , Neumonía Viral/etiología , Neumonía Viral/mortalidad , Polipéptido alfa Relacionado con Calcitonina/sangre , Anciano , Antibacterianos/uso terapéutico , Antivirales/uso terapéutico , Betacoronavirus/efectos de los fármacos , China/epidemiología , Comorbilidad , Infecciones por Coronavirus/diagnóstico por imagen , Infecciones por Coronavirus/tratamiento farmacológico , Progresión de la Enfermedad , Femenino , Hospitalización , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/diagnóstico por imagen , Pronóstico , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
6.
BMC Infect Dis ; 20(1): 724, 2020 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-33008310

RESUMEN

BACKGROUND: Spinal neuroschistosomiasis (SN) is one of the most severe clinical presentations of schistosomiasis infection and an ectopic form of the disease caused by any species of Schistosoma. In Brazil, all cases of this clinical manifestation are related to Schistosoma mansoni, the only species present in the country. Although many cases have been reported in various endemic areas in Brazil, this is the first time in the literature that SN is described in two brothers. CASE PRESENTATION: Two cases of SN were accidentally diagnosed during an epidemiological survey in an urban area endemic for schistosomiasis transmission. Both patients complained of low back pain and muscle weakness in the lower limbs. Sphincter dysfunction and various degrees of paresthesia were also reported. The patients' disease was classified as hepato-intestinal stage schistosomiasis mansoni at the onset of the chronic form. A positive parasitological stool test for S. mansoni, clinical evidence of myeloradicular damage and exclusion of other causes of damage were the basic criteria for diagnosis. After treatment with praziquantel and corticosteroid, the patients presented an improvement in symptoms, although some complaints persisted. CONCLUSIONS: It is important to consider SN when patients come from areas endemic for transmission of schistosomiasis mansoni. Clinical physicians and neurologists should consider this diagnostic hypothesis, because recovery from neurological injuries is directly related to early treatment. As, described here in two brothers, a genetic predisposition may be related to neurological involvement. Primary care physicians should thus try to evaluate family members and close relatives in order to arrive at prompt schistosomiasis diagnosis in asymptomatic individuals and propose treatment in an attempt to avoid progression to SN.


Asunto(s)
Neuroesquistosomiasis/diagnóstico por imagen , Schistosoma mansoni , Esquistosomiasis mansoni/diagnóstico por imagen , Enfermedades de la Columna Vertebral/diagnóstico por imagen , Adulto , Animales , Brasil/epidemiología , Progresión de la Enfermedad , Familia , Humanos , Masculino , Debilidad Muscular , Neuroesquistosomiasis/fisiopatología , Hermanos , Enfermedades de la Columna Vertebral/fisiopatología
7.
J Cardiothorac Surg ; 15(1): 290, 2020 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-33008483

RESUMEN

BACKGROUND: Pulmonary arteriovenous malformations are uncommon conditions of abnormal communications between pulmonary arteries and veins, which are most commonly congenital in nature. Although such condition is not extremely rare, it is a challenge to the differential diagnosis of pulmonary problems such as hypoxemia and pulmonary lesions. CASE PRESENTATION: We report a meaningful case of a 23-year-old male presented with elevated hemoglobin (23.0 g/dl) on admission. Physical examination revealed cyanosis, digital clubbing and low oxygen saturation on room air. The patient was initially diagnosed as polycythemia vera while the subsequent result of bone marrow aspiration was negative. During further assessment, pulmonary arteriovenous malformations were detected by CT pulmonary angiography. Lobectomy was successfully performed with significant increase in oxygen saturation from 86 to 98%. The hemoglobin decreased to almost normal level of 14.9 g/dl 3 months after surgery and the patient had been followed up for nearly 5 years. CONCLUSIONS: Pulmonary arteriovenous malformations should be suspected in patients with central cyanosis, digital clubbing, polycythemia, pulmonary lesion and without cardiac malformations. Embolization or surgery is strongly recommended to reduce the risks caused by pulmonary arteriovenous malformations.


Asunto(s)
Fístula Arteriovenosa/diagnóstico por imagen , Fístula Arteriovenosa/cirugía , Arteria Pulmonar/anomalías , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/cirugía , Venas Pulmonares/anomalías , Tuberculosis/complicaciones , Fístula Arteriovenosa/complicaciones , Angiografía por Tomografía Computarizada , Progresión de la Enfermedad , Humanos , Masculino , Neumonectomía , Venas Pulmonares/diagnóstico por imagen , Venas Pulmonares/cirugía , Adulto Joven
8.
Colomb Med (Cali) ; 51(2): e4327, 2020 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-33012892

RESUMEN

Throughout the COVID-19 pandemic, the main risk factors associated with the progression to severe disease or death have been typically advanced age, diabetes mellitus, obesity, high blood pressure, heart disease, and chronic pneumopathy. Because of their immunosuppression status, persons with HIV were also expected to have a higher susceptibility to infection or a poor clinical evolution. So far, this has not been confirmed to happen, giving way to hypotheses about the role of immunosuppression or the use of antiretrovirals, which could explain this paradox. In this article we present the existing data on the epidemiology and characteristics of HIV-COVID-19 co-infection, discuss the available evidence on the possible factors involved in the evolution of individuals affected by both viruses, analyze other determinants that may negatively affect persons with HIV during the pandemic, and present recommendations for the prevention and care of COVID-19 infection in the context of HIV.


Asunto(s)
Infecciones por Coronavirus/epidemiología , Infecciones por VIH/epidemiología , Neumonía Viral/epidemiología , Coinfección , Infecciones por Coronavirus/prevención & control , Progresión de la Enfermedad , Infecciones por VIH/virología , Humanos , Pandemias/prevención & control , Neumonía Viral/prevención & control , Factores de Riesgo
9.
Signal Transduct Target Ther ; 5(1): 219, 2020 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-33024082

RESUMEN

Convalescent plasma (CP) transfusion has been indicated as a promising therapy in the treatment for other emerging viral infections. However, the quality control of CP and individual variation in patients in different studies make it rather difficult to evaluate the efficacy and risk of CP therapy for coronavirus disease 2019 (COVID-19). We aimed to explore the potential efficacy of CP therapy, and to assess the possible factors associated with its efficacy. We enrolled eight critical or severe COVID-19 patients from four centers. Each patient was transfused with 200-400 mL of CP from seven recovered donors. The primary indicators for clinical efficacy assessment were the changes of clinical symptoms, laboratory parameters, and radiological image after CP transfusion. CP donors had a wide range of antibody levels measured by serology tests which were to some degree correlated with the neutralizing antibody (NAb) level. No adverse events were observed during and after CP transfusion. Following CP transfusion, six out of eight patients showed improved oxygen support status; chest CT indicated varying degrees of absorption of pulmonary lesions in six patients within 8 days; the viral load was decreased to a negative level in five patients who had the previous viremia; other laboratory parameters also tended to improve, including increased lymphocyte counts, decreased C-reactive protein, procalcitonin, and indicators for liver function. The clinical efficacy might be associated with CP transfusion time, transfused dose, and the NAb levels of CP. This study indicated that CP might be a potential therapy for severe patients with COVID-19.


Asunto(s)
Anticuerpos Neutralizantes/administración & dosificación , Anticuerpos Antivirales/administración & dosificación , Betacoronavirus/patogenicidad , Infecciones por Coronavirus/terapia , Neumonía Viral/terapia , Adulto , Anciano , Antivirales/uso terapéutico , Betacoronavirus/inmunología , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/diagnóstico por imagen , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/patología , Progresión de la Enfermedad , Femenino , Humanos , Inmunización Pasiva/métodos , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/diagnóstico por imagen , Neumonía Viral/inmunología , Neumonía Viral/patología , Polipéptido alfa Relacionado con Calcitonina/sangre , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X , Carga Viral
10.
Medicine (Baltimore) ; 99(41): e22247, 2020 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-33031264

RESUMEN

BACKGROUND: Small nucleolar RNA host gene 12 (SNHG12) has been demonstrated to be a long noncoding RNA (lncRNA) that facilitates the progression of several solid malignant tumors. However, whether the expression level of SNHG12 in solid malignant tumors is associated with patients prognosis have not been investigated. METHODS: We systematically searched PubMed, EMBASE and Cochrane Library from Jan 1, 1950 to Mar 24, 2020 for randomized controlled trials published in English on SNHG12 expression in solid malignant tumors. We used the Newcastle-Ottawa Scale to assess the quality of articles. The HRs and 95%CI that extracted from Kaplan-Meier curves were used to perform the forest plot using a fixed-effects model. The meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Thirteen articles containing 821 patients were included in this systematic review and meta-analysis. The result showed that high lncRNA SNHG12 expression is significantly associated with poor overall survival (OS) (HR = 1.94, 95% CI: 1.56-2.41, P < .001) and the studies are lack of statistically significant heterogeneity (P= .878, I = 0.0%). Beggs plot and Eggers test were applied to testify no publication bias existence in these studies. Subgroup analyses were performed and the result showed that TNM stage, lymph node metastasis and tumor type can influence the patients outcome, while there was no significantly correlation between SNHG12 expression and gender. CONCLUSIONS: The systematical review and meta-analysis synthetically analyzed 13 articles including 821 patients with ten types of solid malignant tumors, concluding that higher lncRNA SNHG12 expression is significantly associated with worse clinical prognosis.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante/genética , ARN Nucleolar Pequeño/genética , Progresión de la Enfermedad , Humanos , Pronóstico
11.
Medicine (Baltimore) ; 99(41): e22476, 2020 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-33031278

RESUMEN

RATIONALE: Sciatica is usually caused by lumbar spine disease; the incidence of sciatica from extra-spinal causes is noted to be only about 0.09%. PATIENT CONCERNS: We report a case of a 92-year-old man who came to the neurologist outpatient department due to left buttock pain and numbness that radiated to the left lower leg in the recent 6 months and progressed rapidly over 10 days. DIAGNOSIS: We arranged magnetic resonance imaging for lumbar nerve lesion. Magnetic resonance imaging showed a common iliac artery mycotic aneurysm, at about 6.3 cm in diameter, which compressed the psoas muscle, nerve plexus, and vein. INTERVENTIONS: We used a left-side iliac bifurcation stent graft of 12 mm in diameter for aneurysm repair. An internal iliac artery with a stent graft of 10 mm x 5 cm. An abdomen aortic aneurysm stent was inserted, 1 cm beneath the right renal artery from the right side femoral artery. OUTCOMES: After endovascular repair and 4 weeks of antibiotic treatment, he could walk again, and no sciatica was noted. We repeated computed tomography 5 months after the operation and noted that the size of the iliac artery aneurysm decreased without stent graft migration or extravasation. Our patient recovered from sciatic and left leg weakness; above all, he could walk again. LESSONS: We suggest practitioners check for common iliac artery aneurysms in the diagnosis of symptoms mimicking spinal cord origin sciatica, especially in elder patients.


Asunto(s)
Aneurisma Ilíaco/complicaciones , Aneurisma Ilíaco/diagnóstico por imagen , Síndromes de Compresión Nerviosa/etiología , Ciática/etiología , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Ceftriaxona/uso terapéutico , Progresión de la Enfermedad , Humanos , Aneurisma Ilíaco/microbiología , Aneurisma Ilíaco/cirugía , Imagen por Resonancia Magnética , Masculino , Stents
12.
Wiad Lek ; 73(8): 1717-1722, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33055340

RESUMEN

OBJECTIVE: The aim: This study aims to determine specific predictive factors of bronchiectasis exacerbations. PATIENTS AND METHODS: Materials and methods: 47 patients with bronchiectasis were prospectively recruited into the study in Dnipro, Ukraine. Following the number of exacerbations during the previous year, they were divided into two groups: frequent exacerbators - ≥ 3 cases per year (n = 24) and non-frequent exacerbators - < 3 cases per year (n = 23). Demographic and anthropometric data, medical history, smoking status, shortness of breath by Modified Medical Research Council Dyspnea Scale, sputum culture, respiratory function by computed spirometry, disease severity by Bronchiectasis Severity index and FACED scales were evaluated in both groups. RESULTS: Results: The factors found to be independently associated with frequent exacerbations were: overweight, airway obstruction, longer duration of the disease, more severe dyspnea, greater number of involved pulmonary lobes and presence of one or more comorbid conditions. Non-influencing factors were: underweight, age, sex, smoking status and, unexpectedly, presence of Pseudomonas aeruginosa or other pathogens in sputum culture. CONCLUSION: Conclusions: Particular attention is required for patients with bronchiectasis who have overweight, airway obstruction, longer duration of the disease, more severe dyspnea, the greater number of involved pulmonary lobes and presence of one or more comorbid conditions in order to correct modifiable risk factors of future exacerbations.


Asunto(s)
Bronquiectasia , Adulto , Bronquiectasia/epidemiología , Progresión de la Enfermedad , Humanos , Índice de Severidad de la Enfermedad , Espirometría , Ucrania
13.
Wiad Lek ; 73(8): 1765-1770, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33055349

RESUMEN

OBJECTIVE: The aim of the publication was to review available data on epidemiology, pathophysiological and clinical aspects of HFmrEF as a specific HF pattern. PATIENTS AND METHODS: Materials and methods: We carried out the analysis of the publications that appeared during last decade, related to the different aspects of HFmrEF. The literature search was conducted by use of Google Web Search and PubMed search engines by the following key words: heart failure, left ventricular ejection fraction, mid-range, as well as their combinations. CONCLUSION: Conclusions: Patients with specific HF pattern «HFmrEF¼ demonstrate multidirectional dynamic of systolic heart function with the possibility of transition to the category of reduced or preserved LVEF. Such patients need to be evaluated individually. Their management is based on neurohumoral modulators in order to prevent further LV dysfunction progression and repeated decompensation of HF.


Asunto(s)
Insuficiencia Cardíaca , Función Ventricular Izquierda , Progresión de la Enfermedad , Humanos , Volumen Sistólico , Sístole
14.
Vestn Oftalmol ; 136(5): 58-66, 2020.
Artículo en Ruso | MEDLINE | ID: mdl-33056965

RESUMEN

PURPOSE: To evaluate the influence of prolonged neuroprotective therapy on disease progression in patients with primary open-angle glaucoma (POAG) with compensated intraocular pressure (IOP). MATERIAL AND METHODS: The study included 147 patients with stages I-II POAG (249 eyes) who were randomized into the main (69 patients, 119 eyes) and control groups (78 patients, 130 eyes). Patients of the main group underwent retinalamin treatment course every 6 months. Patients were examined before enrolling and then every 3 months during the 24-months follow-up including optical coherence tomography (OCT; RNFL - retinal nerve fiber layer, NRR - neuroretinal rim, GCL - ganglion cell layer) and static perimetry (MD - mean deviation, PSD - pattern standard deviation). RESULTS: Visual acuity and refraction did not change in either group (p>0.05). IOP increased in the control group (p=0.033). There was no difference between the groups by the 24th month (p=0.87). No MD changes were noted in the main (p=0.45) and control groups (p=0.27). PSD changed in the main (4.84±3.21 and 6.01±2.584 dB in the beginning and the end, respectively, p=0.0004) and the control groups (3.46±2.23 and 5.86±2.26 dB, respectively; p<0.0001). The groups differed in MD and PSD initially (p=0.15; p=0.02) and became equal by the end (p=0.59; p=0.53). RNFL did not change significantly in the main group (p=0.078) and decreased from 83.5±22.47 to 76.7±20.7 µm in the control group (p=0.001); no differences between the groups were noted in the beginning (p=0.276) or in the end of the study (p=0.524). NRR increased in the main group from 222±88.94 to 231±99.3 (p=0.012), and decreased in the control group from 248±87.09 to 234±96.2 (p=0.0006); no differences were found between groups in the beginning or in the end of the study (p=0.109; p=0.909). GCL thickness did not change either in the main, or in the control group (p=0.211; p=0.16), with no difference between the group noted in the beginning or the end of the study (p=0.44; p=0.51). CONCLUSION: Regular treatment with retinalamin arrests the development of glaucomatous optic neuropathy. Longer-term research is required to study its influence on the visual function and the quality of life.


Asunto(s)
Glaucoma , Calidad de Vida , Progresión de la Enfermedad , Humanos , Fibras Nerviosas , Células Ganglionares de la Retina
15.
Lancet Oncol ; 21(10): 1331-1340, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-33002437

RESUMEN

BACKGROUND: Adjuvant radiotherapy has been shown to halve the risk of biochemical progression for patients with high-risk disease after radical prostatectomy. Early salvage radiotherapy could result in similar biochemical control with lower treatment toxicity. We aimed to compare biochemical progression between patients given adjuvant radiotherapy and those given salvage radiotherapy. METHODS: We did a phase 3, randomised, controlled, non-inferiority trial across 32 oncology centres in Australia and New Zealand. Eligible patients were aged at least 18 years and had undergone a radical prostatectomy for adenocarcinoma of the prostate with pathological staging showing high-risk features defined as positive surgical margins, extraprostatic extension, or seminal vesicle invasion; had an Eastern Cooperative Oncology Group performance status of 0-1, and had a postoperative prostate-specific antigen (PSA) concentration of 0·10 ng/mL or less. Patients were randomly assigned (1:1) using a minimisation technique via an internet-based, independently generated allocation to either adjuvant radiotherapy within 6 months of radical prostatectomy or early salvage radiotherapy triggered by a PSA of 0·20 ng/mL or more. Allocation sequence was concealed from investigators and patients, but treatment assignment for individual randomisations was not masked. Patients were stratified by radiotherapy centre, preoperative PSA, Gleason score, surgical margin status, and seminal vesicle invasion status. Radiotherapy in both groups was 64 Gy in 32 fractions to the prostate bed without androgen deprivation therapy with real-time review of plan quality on all cases before treatment. The primary endpoint was freedom from biochemical progression. Salvage radiotherapy would be deemed non-inferior to adjuvant radiotherapy if freedom from biochemical progression at 5 years was within 10% of that for adjuvant radiotherapy with a hazard ratio (HR) for salvage radiotherapy versus adjuvant radiotherapy of 1·48. The primary analysis was done on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, NCT00860652. FINDINGS: Between March 27, 2009, and Dec 31, 2015, 333 patients were randomly assigned (166 to adjuvant radiotherapy; 167 to salvage radiotherapy). Median follow-up was 6·1 years (IQR 4·3-7·5). An independent data monitoring committee recommended premature closure of enrolment because of unexpectedly low event rates. 84 (50%) patients in the salvage radiotherapy group had radiotherapy triggered by a PSA of 0·20 ng/mL or more. 5-year freedom from biochemical progression was 86% (95% CI 81-92) in the adjuvant radiotherapy group versus 87% (82-93) in the salvage radiotherapy group (stratified HR 1·12, 95% CI 0·65-1·90; pnon-inferiority=0·15). The grade 2 or worse genitourinary toxicity rate was lower in the salvage radiotherapy group (90 [54%] of 167) than in the adjuvant radiotherapy group (116 [70%] of 166). The grade 2 or worse gastrointestinal toxicity rate was similar between the salvage radiotherapy group (16 [10%]) and the adjuvant radiotherapy group (24 [14%]). INTERPRETATION: Salvage radiotherapy did not meet trial specified criteria for non-inferiority. However, these data support the use of salvage radiotherapy as it results in similar biochemical control to adjuvant radiotherapy, spares around half of men from pelvic radiation, and is associated with significantly lower genitourinary toxicity. FUNDING: New Zealand Health Research Council, Australian National Health Medical Research Council, Cancer Council Victoria, Cancer Council NSW, Auckland Hospital Charitable Trust, Trans-Tasman Radiation Oncology Group Seed Funding, Cancer Research Trust New Zealand, Royal Australian and New Zealand College of Radiologists, Cancer Institute NSW, Prostate Cancer Foundation Australia, and Cancer Australia.


Asunto(s)
Adenocarcinoma/radioterapia , Prostatectomía , Neoplasias de la Próstata/radioterapia , Terapia Recuperativa , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Australia , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Fraccionamiento de la Dosis de Radiación , Humanos , Masculino , Enfermedades Urogenitales Masculinas/epidemiología , Enfermedades Urogenitales Masculinas/etiología , Persona de Mediana Edad , Nueva Zelanda , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Radioterapia Ayuvante/efectos adversos , Terapia Recuperativa/efectos adversos , Resultado del Tratamiento
16.
Lancet Oncol ; 21(10): 1341-1352, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-33002438

RESUMEN

BACKGROUND: Adjuvant radiotherapy reduces the risk of biochemical progression in prostate cancer patients after radical prostatectomy. We aimed to compare adjuvant versus early salvage radiotherapy after radical prostatectomy, combined with short-term hormonal therapy, in terms of oncological outcomes and tolerance. METHODS: GETUG-AFU 17 was a randomised, open-label, multicentre, phase 3 trial done at 46 French hospitals. Men aged at least 18 years who had an Eastern Cooperative Oncology Group performance status of 1 or less, localised adenocarcinoma of the prostate treated with radical prostatectomy, who had pathologically-staged pT3a, pT3b, or pT4a (with bladder neck invasion), pNx (without pelvic lymph nodes dissection), or pN0 (with negative lymph nodes dissection) disease, and who had positive surgical margins were eligible for inclusion in the study. Eligible patients were randomly assigned (1:1) to either immediate adjuvant radiotherapy or delayed salvage radiotherapy at the time of biochemical relapse. Random assignment, by minimisation, was done using web-based software and stratified by Gleason score, pT stage, and centre. All patients received 6 months of triptorelin (intramuscular injection every 3 months). The primary endpoint was event-free survival. Efficacy and safety analyses were done on the intention-to-treat population. The trial is registered with ClinicalTrials.gov, NCT00667069. FINDINGS: Between March 7, 2008, and June 23, 2016, 424 patients were enrolled. We planned to enrol 718 patients, with 359 in each study group. However, on May 20, 2016, the independent data monitoring committee recommended early termination of enrolment because of unexpectedly low event rates. At database lock on Dec 19, 2019, the overall median follow-up time from random assignment was 75 months (IQR 50-100), 74 months (47-100) in the adjuvant radiotherapy group and 78 months (52-101) in the salvage radiotherapy group. In the salvage radiotherapy group, 115 (54%) of 212 patients initiated study treatment after biochemical relapse. 205 (97%) of 212 patients started treatment in the adjuvant group. 5-year event-free survival was 92% (95% CI 86-95) in the adjuvant radiotherapy group and 90% (85-94) in the salvage radiotherapy group (HR 0·81, 95% CI 0·48-1·36; log-rank p=0·42). Acute grade 3 or worse toxic effects occurred in six (3%) of 212 patients in the adjuvant radiotherapy group and in four (2%) of 212 patients in the salvage radiotherapy group. Late grade 2 or worse genitourinary toxicities were reported in 125 (59%) of 212 patients in the adjuvant radiotherapy group and 46 (22%) of 212 patients in the salvage radiotherapy group. Late genitourinary adverse events of grade 2 or worse were reported in 58 (27%) of 212 patients in the adjuvant radiotherapy group versus 14 (7%) of 212 patients in the salvage radiotherapy group (p<0·0001). Late erectile dysfunction was grade 2 or worse in 60 (28%) of 212 in the adjuvant radiotherapy group and 17 (8%) of 212 in the salvage radiotherapy group (p<0·0001). INTERPRETATION: Although our analysis lacked statistical power, we found no benefit for event-free survival in patients assigned to adjuvant radiotherapy compared with patients assigned to salvage radiotherapy. Adjuvant radiotherapy increased the risk of genitourinary toxicity and erectile dysfunction. A policy of early salvage radiotherapy could spare men from overtreatment with radiotherapy and the associated adverse events. FUNDING: French Health Ministry and Ipsen.


Asunto(s)
Adenocarcinoma/radioterapia , Antagonistas de Andrógenos/administración & dosificación , Prostatectomía , Neoplasias de la Próstata/radioterapia , Terapia Recuperativa , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Anciano , Progresión de la Enfermedad , Francia , Humanos , Masculino , Enfermedades Urogenitales Masculinas/epidemiología , Enfermedades Urogenitales Masculinas/etiología , Uso Excesivo de los Servicios de Salud/prevención & control , Persona de Mediana Edad , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Radioterapia Ayuvante/efectos adversos , Terapia Recuperativa/efectos adversos , Análisis de Supervivencia , Resultado del Tratamiento
17.
Lancet Oncol ; 21(10): e463-e476, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-33002442

RESUMEN

Immunotherapy represents a paradigm shift in oncology treatment. The goal of immunotherapy is to overcome immunosuppression induced by a tumour and its microenvironment, thereby allowing the immune system to target and kill cancer cells. The immunotherapy era began when the first immune checkpoint inhibitor, ipilimumab, was approved for use almost a decade ago. This therapeutic approach is associated with distinct types of response, including processes such as pseudoprogression (ie, increased tumour burden via radiology, which is not accompanied by clinical deterioration) and hyperprogression (ie, rapid progression of the disease as a result of immunotherapy). In this Review, we focus on therapeutic approaches for patients who progress on immunotherapy. We review the different types of clinical responses associated with immunotherapy and describe treatment options for this population.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/terapia , Inmunoterapia/efectos adversos , Neoplasias/terapia , Algoritmos , Antineoplásicos Inmunológicos/efectos adversos , Progresión de la Enfermedad , Resistencia a Antineoplásicos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/inmunología , Humanos , Criterios de Evaluación de Respuesta en Tumores Sólidos , Terapia Recuperativa
18.
Nat Commun ; 11(1): 4952, 2020 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-33009368

RESUMEN

We present the Danish Disease Trajectory Browser (DTB), a tool for exploring almost 25 years of data from the Danish National Patient Register. In the dataset comprising 7.2 million patients and 122 million admissions, users can identify diagnosis pairs with statistically significant directionality and combine them to linear disease trajectories. Users can search for one or more disease codes (ICD-10 classification) and explore disease progression patterns via an array of functionalities. For example, a set of linear trajectories can be merged into a disease trajectory network displaying the entire multimorbidity spectrum of a disease in a single connected graph. Using data from the Danish Register for Causes of Death mortality is also included. The tool is disease-agnostic across both rare and common diseases and is showcased by exploring multimorbidity in Down syndrome (ICD-10 code Q90) and hypertension (ICD-10 code I10). Finally, we show how search results can be customized and exported from the browser in a format of choice (i.e. JSON, PNG, JPEG and CSV).


Asunto(s)
Progresión de la Enfermedad , Programas Informáticos , Algoritmos , Dinamarca , Humanos , Factores de Tiempo
19.
Nat Commun ; 11(1): 4968, 2020 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-33009413

RESUMEN

The outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread to become a worldwide emergency. Early identification of patients at risk of progression may facilitate more individually aligned treatment plans and optimized utilization of medical resource. Here we conducted a multicenter retrospective study involving patients with moderate COVID-19 pneumonia to investigate the utility of chest computed tomography (CT) and clinical characteristics to risk-stratify the patients. Our results show that CT severity score is associated with inflammatory levels and that older age, higher neutrophil-to-lymphocyte ratio (NLR), and CT severity score on admission are independent risk factors for short-term progression. The nomogram based on these risk factors shows good calibration and discrimination in the derivation and validation cohorts. These findings have implications for predicting the progression risk of COVID-19 pneumonia patients at the time of admission. CT examination may help risk-stratification and guide the timing of admission.


Asunto(s)
Infecciones por Coronavirus/diagnóstico , Progresión de la Enfermedad , Neumonía Viral/diagnóstico , Neumonía , Tomografía Computarizada por Rayos X/métodos , Adulto , Betacoronavirus , China , Técnicas de Laboratorio Clínico , Coinfección , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/fisiopatología , Femenino , Hospitalización , Humanos , Pulmón/diagnóstico por imagen , Pulmón/patología , Linfocitos , Masculino , Persona de Mediana Edad , Neutrófilos , Pandemias , Neumonía Viral/patología , Neumonía Viral/fisiopatología , Análisis de Regresión , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo
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