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The association between adverse childhood experiences and negative health outcomes is a public health concern, particularly affecting disadvantaged groups and contributing to health disparities. Pediatric nurse practitioners are well-positioned to address this issue, emphasizing the importance of incorporating social justice concepts into nursing education to develop a pediatric workforce with the necessary skills to curb health disparities. However, evidence-based approaches to incorporating these concepts into pediatric nursing education are limited. To address this gap, we describe an innovative educational intervention that harnesses the power of narratives to empower future pediatric nurse practitioners as champions of social justice and health equity.
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Experiencias Adversas de la Infancia , Enfermeras Practicantes , Humanos , Niño , Profesionales de Enfermería Pediátrica , Curriculum , Docentes , Justicia SocialRESUMEN
Abstract Newcastle disease (ND) is an infectious, highly contagious and lethal disease of avian species. It is considered that ducks are natural reservoir or carrier for Newcastle disease virus (NDV) and are resistant against different strains of NDV. Current study was designed to evaluate the pathogenesis of Newcastle disease in domestic ducks through histopathology, immunohistochemistry (IHC) and serum biochemical changes. For this purpose, eighty ducks were reared for 42 days and divided in two groups A and B. Ducks in group A were challenged with (NDV) at rate of 0.1 ml of ELD50 (virus titer 107.32/100µl) on second week of age, whereas Group B was control negative. Splenomegaly, atrophy of thymus and necrotic lesion in kidney were observed on 9th day of post infection. Hepatic degeneration and mononuclear cell infiltration were noticed in proventriculus and intestine in challenged ducks. Viral antigen detected in lungs, intestine, proventriculus and lymphoid organs of infected ducks through IHC. Albumin and total protein values were significantly low in infected groups A as compared to control group B. ALT, AST, and ALP values were significantly high in infected group A. On 5th and 7th day of post infection oropharyngeal swabs were negative for NDV and cloacal swabs were positive for NDV through Reverse transcriptase polymerase chain reaction. It is concluded that ducks are susceptible to NDV and virulent strain of NDV caused disease in ducks.
Resumo A doença de Newcastle (DN) é uma doença infecciosa, altamente contagiosa e letal de espécies aviárias. Considera-se que os patos são reservatórios ou portadores naturais do vírus da doença de Newcastle (VDN) e são resistentes a diferentes cepas de VDN. O presente estudo foi desenvolvido para avaliar a patogênese da DN em patos domésticos por meio de histopatologia, imuno-histoquímica (IHQ) e alterações bioquímicas séricas. Para este propósito, 80 patos foram criados por 42 dias e divididos em dois grupos A e B. Os patos do grupo A foram submetidos ao VDN a uma taxa de 0,1 ml de ELD50 (título viral de 107,32 / 100 µl) na segunda semana de idade, enquanto o Grupo B foi controle negativo. Esplenomegalia, atrofia do timo e lesão necrótica no rim foram observadas no 9º dia pós-infecção. Degeneração hepática e infiltração de células mononucleares foram observadas no proventrículo e intestino em patos infectados. Antígeno viral foi detectado em pulmões, intestino, proventrículo e órgãos linfoides de patos infectados por IHQ. Os valores de albumina e proteína total foram significativamente baixos no grupo A infectado em comparação com o grupo B. Os valores de ALT, AST e ALP foram significativamente altos no grupo A. No 5º e no 7º dia após a infecção, os esfregaços orofaríngeos foram negativos para VDN, enquanto os esfregaços cloacais foram positivos para VDN por meio da reação em cadeia da polimerase via transcriptase reversa. Conclui-se que os patos são suscetíveis ao VDN e à cepa virulenta de VDN que causou doenças em patos.
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Abstract Newcastle disease (ND) is an infectious, highly contagious and lethal disease of avian species. It is considered that ducks are natural reservoir or carrier for Newcastle disease virus (NDV) and are resistant against different strains of NDV. Current study was designed to evaluate the pathogenesis of Newcastle disease in domestic ducks through histopathology, immunohistochemistry (IHC) and serum biochemical changes. For this purpose, eighty ducks were reared for 42 days and divided in two groups A and B. Ducks in group A were challenged with (NDV) at rate of 0.1 ml of ELD50 (virus titer 107.32/100µl) on second week of age, whereas Group B was control negative. Splenomegaly, atrophy of thymus and necrotic lesion in kidney were observed on 9th day of post infection. Hepatic degeneration and mononuclear cell infiltration were noticed in proventriculus and intestine in challenged ducks. Viral antigen detected in lungs, intestine, proventriculus and lymphoid organs of infected ducks through IHC. Albumin and total protein values were significantly low in infected groups A as compared to control group B. ALT, AST, and ALP values were significantly high in infected group A. On 5th and 7th day of post infection oropharyngeal swabs were negative for NDV and cloacal swabs were positive for NDV through Reverse transcriptase polymerase chain reaction. It is concluded that ducks are susceptible to NDV and virulent strain of NDV caused disease in ducks.
Resumo A doença de Newcastle (DN) é uma doença infecciosa, altamente contagiosa e letal de espécies aviárias. Considera-se que os patos são reservatórios ou portadores naturais do vírus da doença de Newcastle (VDN) e são resistentes a diferentes cepas de VDN. O presente estudo foi desenvolvido para avaliar a patogênese da DN em patos domésticos por meio de histopatologia, imuno-histoquímica (IHQ) e alterações bioquímicas séricas. Para este propósito, 80 patos foram criados por 42 dias e divididos em dois grupos A e B. Os patos do grupo A foram submetidos ao VDN a uma taxa de 0,1 ml de ELD50 (título viral de 107,32 / 100 µl) na segunda semana de idade, enquanto o Grupo B foi controle negativo. Esplenomegalia, atrofia do timo e lesão necrótica no rim foram observadas no 9º dia pós-infecção. Degeneração hepática e infiltração de células mononucleares foram observadas no proventrículo e intestino em patos infectados. Antígeno viral foi detectado em pulmões, intestino, proventrículo e órgãos linfoides de patos infectados por IHQ. Os valores de albumina e proteína total foram significativamente baixos no grupo A infectado em comparação com o grupo B. Os valores de ALT, AST e ALP foram significativamente altos no grupo A. No 5º e no 7º dia após a infecção, os esfregaços orofaríngeos foram negativos para VDN, enquanto os esfregaços cloacais foram positivos para VDN por meio da reação em cadeia da polimerase via transcriptase reversa. Conclui-se que os patos são suscetíveis ao VDN e à cepa virulenta de VDN que causou doenças em patos.
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Animales , Virus de la Enfermedad de Newcastle , Patos , Enfermedad de Newcastle/diagnósticoRESUMEN
Osteogenesis imperfecta is a rare genetic disorder of type 1 collagen which primarily affects children and leads to recurrent bone fractures. In addition, spinal abnormalities can also occur. We report a case of a 13-year-old male with osteogenesis imperfecta type III, associated with severe femur deformity and thoracic kyphoscoliosis, who developed neurological injury after lower extremity surgery. The patient was in a supine position when general anesthesia was administered. The operation lasted for approximately 250 minutes, and anesthesia for 310 minutes, with an estimated blood loss of 600 cc. Apart from a low mean arterial pressure value (45 mm Hg) intraoperatively, the procedure was uneventful. Early postoperatively, he developed spinal paralysis at the level of T4-T7, and an MRI of the spine demonstrated high signal intensity within the spinal cord from level T3 to T7. Subsequently, he was admitted to the pediatric intensive care unit for further assessment and management. Follow-up revealed recovery of paralysis after 12 months.
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We theoretically and numerically investigate the performance of tilted Bragg gratings in planar waveguides, fabricated by direct UV writing in photosensitive silica, to couple light out of a chip. An analytic expression is derived for the coupling efficiency and validated numerically by finite element simulations. Using the analytic result, we can design gratings to generate output beams in free space of any specific shape and calculate their overall power coupling efficiency. Our simulations indicate that for currently achievable grating index contrasts devices of millimeter length are most suitable for this technology.
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BACKGROUND: Pulmonary embolism (PE) is a common acute life-threatening cardiovascular disorder. It is the third most common cause of hospital-related death and early detection and management of PE are crucial. The study aimed to evaluate the association between vital signs and laboratory investigations with PE. METHODS: This is a retrospective, hospital records-based, observational study, conducted among patients who were admitted to the emergency department of King Saud Medical City in Riyadh, Saudi Arabia with a suspected diagnosis of PE during the period of March 2021 to March 2022. Data were collected by searching patients' files and recording demographic data, and information about the clinical presentation, workup, and outcome. Data were entered and analyzed using SPSS version 26 (IBM, Armonk, NY), utilizing Chi-square statistics to test differences between groups, and logistic regression analyses to identify predictors of PE. RESULTS: The study included 92 patients, with a preponderance of females (70.7%), and those aged 40-60 years (51.1%). Diabetes mellitus (44.6%), and hypertension (30.4%) were the most common comorbidities among others, while shortness of breath (SOB) (83.7%), and chest pain (44.6%) were among the most commonly reported symptoms. A majority of patients had tachycardia (64.1%), while about half had low oxygen saturation (51.5%), and nearly one-third had tachypnea (29.3%), which was more predominant among those not diagnosed with PE. Logistic regression analysis revealed that SOB, respiratory rate, and oxygen saturation were the only significant predictors of PE. CONCLUSION: Although being an integral part of the initial assessment in the hospital, measuring the vital signs is not always reflective of the likelihood of PE, and they should not be the only metric relied upon to make decisions about treatment approaches in patients with PE. Physicians should ensure the employment of evidence-based clinical prediction rules and guidelines when diagnosing and managing PE.
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BACKGROUND: Coronavirus disease-2019 (COVID-19) is a global pandemic health problem that causes a wide spectrum of clinical manifestations and considerable mortality rates. Unfortunately, recovered patients who survive COVID-19 may continue to report a wide variety of clinical manifestations of multisystem affection such as pulmonary embolism, deep vein thrombosis, acute myocardial infarction, depression, anxiety, myalgia, dyspnea, and fatigue. OBJECTIVE: We aimed to summarize the current literature regarding the prevalence of post-COVID- 19 manifestations. METHODS: We conducted a systematic review of post-COVID-19 manifestations by searching MEDLINE via PubMed, Scopus, Web of Science (WOS), EBSCO, Wily, and World health organization (WHO) databases. Screening, study selection, data extraction, data synthesis, and quality assessment were made by two independent reviewers. RESULTS: Of 1,371 references, 817 references remained after removing duplicates. Reviews, case reports, commentaries, and any article containing non-original information were excluded. According to the eligibility criteria for this systematic review, 12 studies were included for qualitative synthesis. The overall prevalence of post-COVID-19 manifestations ranged from 35% to 90.5%. Fatigue, dyspnea, neuropsychological disorders, and pain were the most frequent post-COVID-19 symptoms. CONCLUSION: This systematic review showed that 35% to 90.5% of recovered patients who survive COVID-19 continue to have a wide variety of clinical manifestations, including fatigue, dyspnea, neuropsychological disorders, and pain as the most frequent post-COVID-19 symptoms.
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COVID-19 , Humanos , SARS-CoV-2 , Fatiga , Disnea , Dolor , Síndrome Post Agudo de COVID-19RESUMEN
Newcastle disease (ND) is an infectious, highly contagious and lethal disease of avian species. It is considered that ducks are natural reservoir or carrier for Newcastle disease virus (NDV) and are resistant against different strains of NDV. Current study was designed to evaluate the pathogenesis of Newcastle disease in domestic ducks through histopathology, immunohistochemistry (IHC) and serum biochemical changes. For this purpose, eighty ducks were reared for 42 days and divided in two groups A and B. Ducks in group A were challenged with (NDV) at rate of 0.1 ml of ELD50 (virus titer 107.32/100µl) on second week of age, whereas Group B was control negative. Splenomegaly, atrophy of thymus and necrotic lesion in kidney were observed on 9th day of post infection. Hepatic degeneration and mononuclear cell infiltration were noticed in proventriculus and intestine in challenged ducks. Viral antigen detected in lungs, intestine, proventriculus and lymphoid organs of infected ducks through IHC. Albumin and total protein values were significantly low in infected groups A as compared to control group B. ALT, AST, and ALP values were significantly high in infected group A. On 5th and 7th day of post infection oropharyngeal swabs were negative for NDV and cloacal swabs were positive for NDV through Reverse transcriptase polymerase chain reaction. It is concluded that ducks are susceptible to NDV and virulent strain of NDV caused disease in ducks.
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Patos , Enfermedad de Newcastle , Virus de la Enfermedad de Newcastle , Animales , Enfermedad de Newcastle/diagnósticoRESUMEN
The aim of the present study was to compare the sensitivity between Alvarado and RIPASA score for the diagnosis of acute appendicitis patients. A comparative study was conducted in the Dhaka National Medical College Hospital, Bangladesh from July 2015 to December 2015. The study was approved by the institutional ethical committee. Most of the appendicitis patients belonged to the between 21-30 years which was 64(32%). Male appendicitis patients (52%) are more than the female patients (48%). Majority of the patients (69%) complains pain occurs in the Right iliac fossa. Sensitivity of Alvarado scores was 81.60%, specificity 74.58%, accuracy 79.35%, positive and negative predictive values were 87.18% and 65.67% respectively. RIPASA score's sensitivity was 85.6%, specificity 69.49%, accuracy 80.40%, positive and negative predictive values were 85.60% and 85.60% respectively. This study reported that RIPASA score is significantly shown higher diagnostic accuracy then that Alvarado score.
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Apendicitis , Enfermedad Aguda , Apendicectomía , Apendicitis/diagnóstico , Bangladesh/epidemiología , Femenino , Humanos , Masculino , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
The WSE is a highly polar, gummy and mucilaginous bioactive content of the Nigella sativa (L.) seeds. This study reports the anxiolytic and anti-inflammatory effects of WSE investigated using Elevated Plus Maze (EPM) and Hole-Board Test (HBT) in adult mice and human RBCs haemolysis inhibition and protein denaturation respectively. The oral WSE treatment (100 & 200 mg/kg b.w/day) for 72 hours has exhibited slightly better anxiolytic effect (p < 0.05) through the time span (92.33 & 93.33 s) spent in the opened arms of EPM vs. diazepam (1 mg/kg b.w i.p/day; 69.33 s). In HBT, only WSE (200 mg/kg b.w/day) has shown a promising number of mean head pokes (13.27 times/min) vs. diazepam (12.87 times/min). The WSE (62.5-500 µg/mL) exposure has exhibited 40.14-72.18% protection against lysis of RBCs vs. aspirin (57.04-71.48%) whilst 62.67-67.66% inhibition of protein denaturation vs. diclofenac sodium (43.11-80.64%). The current findings suggested WSE has promising anxiolytic and anti-inflammatory activities.
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Ansiolíticos , Antiinflamatorios , Nigella sativa , Animales , Ansiolíticos/aislamiento & purificación , Ansiolíticos/farmacología , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Ansiedad/tratamiento farmacológico , Eritrocitos/efectos de los fármacos , Humanos , Aprendizaje por Laberinto , Ratones , Nigella sativa/química , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Semillas/químicaRESUMEN
In this paper we present the first example of waveguides fabricated by UV writing in non-hydrogen loaded Ge-doped planar silica with 213 nm light. Single mode waveguides were fabricated and the numerical apertures and mode field diameters were measured for a range of writing fluences. A peak index change of 5.3 x 10-3 was inferred for the waveguide written with 70 kJ cm-2. The refractive index change is sufficient to match the index structure of standard optical fiber. Uniformity of the written structures was measured and a propagation loss of 0.39 ± 0.03 dB cm-1 was determined through cutback measurements.
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Epidemiological evidence suggests that cadmium (Cd) is one of the causative factors of prostate cancer, but the effect of Cd on benign prostatic hyperplasia (BPH) remains unclear. This study aimed to determine whether Cd exposure could malignantly transform BPH1 cells and, if so, to dissect the mechanism of action. We deciphered the molecular signaling responsible for BPH1 transformation via RNA-sequencing and determined that Cd induced the expression of zinc finger of the cerebellum 2 (ZIC2) in BPH1 cells. We noted Cd exposure increased ZIC2 expression in the Cd-transformed BPH1 cells that in turn promoted anchorage-independent spheroids and increased expression of stem cell drivers, indicating their role in stem cell renewal. Subsequent silencing of ZIC2 expression in transformed cells inhibited spheroid formation, stem cell marker expression, and tumor growth in nude mice. At the molecular level, ZIC2 interacts with the glioma-associated oncogene family (GLI) zinc finger 1 (GLI1), which activates prosurvival factors (nuclear factor NFκB, B-cell lymphoma-2 (Bcl2), as well as an X-linked inhibitor of apoptosis protein (XIAP)) signaling in Cd-exposed BPH1 cells. Conversely, overexpression of ZIC2 in BPH1 cells caused spheroid formation confirming the oncogenic function of ZIC2. ZIC2 activation and GLI1 signaling induction by Cd exposure in primary BPH cells confirmed the clinical significance of this oncogenic function. Finally, human BPH specimens had increased ZIC2 versus adjacent healthy tissues. Thus, we report direct evidence that Cd exposure induces malignant transformation of BPH via activation of ZIC2 and GLI1 signaling.
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Haemophagocytosis encompasses phagocytosis of erythrocytes, leukocytes, platelets and their precursors by macrophages in bone marrow and other tissues. Haemophagocytic lymphohistiocytosis (HLH) usually presents with high fever, pancytopenia, splenomegaly, lymphadenopathy, haemophagocytosis in bone marrow, liver, lymphnodes or CSF. We report coagulase negative Staphylococcus induced HLH in a 16 year old boy presenting with high grade fever, lymphadenopathy, hepatosplenomegaly, pancytopenia with neutropenic sepsis in the department of Medicine, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh on 28th November 2016. He responded to high dose dexamethasone and management of neutropenic sepsis. This might give a guidance in the management of haemophagocytic syndrome at the earliest time to prevent morbidity and mortality.
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Fiebre/etiología , Linfohistiocitosis Hemofagocítica/diagnóstico , Sepsis/complicaciones , Staphylococcus/aislamiento & purificación , Adolescente , Bangladesh , Médula Ósea , Dexametasona , Glucocorticoides/uso terapéutico , Humanos , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Linfohistiocitosis Hemofagocítica/microbiología , Masculino , Neutropenia , Pancitopenia , Esplenomegalia/etiología , Resultado del TratamientoRESUMEN
BACKGROUND: We sought to determine the effect of the travel distance on mortality and quality outcomes after radical cystectomy in a large multi-institutional cohort. PATIENTS AND METHODS: A total of 3957 patients who had undergone radical cystectomy for urothelial carcinoma at 6 North American tertiary care institutions were included. The association of travel distance with quality-of-care endpoints, 90-day mortality, and long-term survival were evaluated. RESULTS: The median patient age was 69 years (interquartile range, 61-76 years), and most patients were men (80%). Most patients had clinical stage T2 (45.2%) and T1 (24.7%) tumors. The median distance to the treatment facility was 102.9 miles (interquartile range, 24-271 miles). Patients residing in the first quartile of travel distance to treatment facility (< 24 miles) had lower usage of neoadjuvant chemotherapy compared with patients in the fourth distance quartile (adjusted odds ratio, 1.58; 95% confidence interval, 1.22-2.05; P = .001). Patients in the first distance quartile were also less likely to experience a delay in time to cystectomy (> 3 months) compared with patients with a greater travel distance (adjusted odds ratio, 0.673; 95% confidence interval, 0.532-0.851). Distance to the treatment facility was not associated with 90-day mortality or cancer-specific or all-cause mortality on multivariate analysis. CONCLUSION: Despite the potential health care disparities for bladder cancer patients residing distant to a regional surgical oncology facility, the study results suggest that the travel distance is not a barrier to appropriate oncologic care at regional tertiary care centers.
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Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/cirugía , Anciano , Cistectomía , Supervivencia sin Enfermedad , Femenino , Disparidades en Atención de Salud , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Oportunidad Relativa , Calidad de la Atención de Salud , Centros de Atención Terciaria , Resultado del TratamientoAsunto(s)
Páncreas/diagnóstico por imagen , Pancreatitis/diagnóstico por imagen , Radiografía Abdominal/métodos , Tomografía Computarizada por Rayos X/métodos , Enfermedad Aguda , Análisis Costo-Beneficio , Humanos , Páncreas/patología , Radiografía Abdominal/economía , Reproducibilidad de los Resultados , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/economíaRESUMEN
OBJECTIVE: To improve risk stratification for recurrence prognostication in patients with localised clear cell renal cell carcinoma (ccRCC). PATIENTS AND METHODS: In all, 367 patients with non-metastatic ccRCC were included. The cohort was divided into a training and validation set. Using tissue microarrays, immunostaining was performed for 24 biomarkers representative of key pathways in ccRCC. Using Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression, we identified several markers that were used to construct a risk classifier for risk of disease recurrence. RESULTS: The median (interquartile range) follow-up was 63.5 (24.0-85.3) months. Five out of 24 markers were selected by LASSO Cox regression for the risk classifier: N-cadherin, E-cadherin, Ki67, cyclin D1 and phosphorylated eukaryotic initiation factor 4E binding protein-1 (p-4EBP1). Patients were classified as either low, intermediate or high risk of disease recurrence by tertiles of risk score. The 5-year recurrence-free survival (RFS) was 93.8%, 87.7% and 70% for patients with low-, intermediate- and high-risk scores, respectively (P < 0.001). Patients with a high marker score had worse RFS on multivariate analysis adjusted for age, gender, race and the Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score (hazard ratio 3.66, 95% confidence interval 1.58-8.49, P = 0.003 for high vs low marker score in the overall cohort). The five-marker classifier increased the concordance index of the clinical model in both the training and validation sets. CONCLUSION: We developed a five-marker-based prognostic tool that can effectively classify patients with ccRCC according to risk of disease recurrence after surgery. This tool, if prospectively validated, could provide individualised risk estimation for patients with ccRCC.
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Biomarcadores de Tumor/análisis , Carcinoma de Células Renales/química , Carcinoma de Células Renales/cirugía , Neoplasias Renales/química , Neoplasias Renales/cirugía , Recurrencia Local de Neoplasia/epidemiología , Nefrectomía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/secundario , Femenino , Humanos , Neoplasias Renales/diagnóstico , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Adulto JovenRESUMEN
PURPOSE: To evaluate whether anti-inflammatory agents affect outcomes in patients receiving intravesical BCG therapy for high-grade (HG) non-muscle-invasive bladder cancer (NMIBC). METHODS: We reviewed the records of 203 patients in a prospective database of HG NMIBC from 2006 to 2012 at a single institution. Patients who had muscle-invasive disease (n = 32), low-grade pathology (n = 4), underwent early cystectomy within 3 months (n = 25), had <3 months of follow-up (n = 11), or did not receive an induction course of intravesical BCG (n = 32) were excluded. Clinicopathologic data were tabulated including demographics, comorbidities, pathologic stage and grades, intravesical therapy, and concomitant use of aspirin, NSAIDs, COX inhibitors, and statins. Multivariate Cox regression analysis explored predictive factors for recurrence, progression (stage progression or progression to cystectomy), cancer-specific survival (CSS), and overall survival (OS). RESULTS: Ninety-nine patients with HG NMIBC who received at least one induction course of intravesical BCG were identified, with median follow-up of 31.4 months. There were 20 (20.2 %) deaths, including 6 (6.1 %) patients with bladder cancer-related mortality. 13 % patients experienced tumor progression and 27 % underwent cystectomy following failure of intravesical therapy. Anti-inflammatory use included statins (65 %), aspirin (63 %), or non-aspirin NSAIDs/COX inhibitors (26 %). Anti-inflammatory use was not significantly predictive of recurrence, progression, or mortality outcomes on Cox regression. CIS stage was associated with higher progression, while age, BMI, and Charlson score were independent predictors of overall mortality. CONCLUSION: Despite speculation of inhibitory effects on BCG immunomodulation there was no evidence that anti-inflammatory agents impacted oncologic outcomes in patients receiving BCG for HG NMIBC.
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Adyuvantes Inmunológicos/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Vacuna BCG/uso terapéutico , Carcinoma de Células Transicionales/tratamiento farmacológico , Inhibidores de la Ciclooxigenasa/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Administración Intravesical , Anciano , Aspirina/uso terapéutico , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/patología , Causas de Muerte , Cistectomía/estadística & datos numéricos , Bases de Datos Factuales , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Mortalidad , Músculo Liso/patología , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Carga Tumoral , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Proteins involved in tumor cell migration can potentially serve as markers of invasive disease. Activated Leukocyte Cell Adhesion Molecule (ALCAM) promotes adhesion, while shedding of its extracellular domain is associated with migration. We hypothesized that shed ALCAM in biofluids could be predictive of progressive disease. ALCAM expression in tumor (n = 198) and shedding in biofluids (n = 120) were measured in two separate VUMC bladder cancer cystectomy cohorts by immunofluorescence and enzyme-linked immunosorbent assay, respectively. The primary outcome measure was accuracy of predicting 3-year overall survival (OS) with shed ALCAM compared to standard clinical indicators alone, assessed by multivariable Cox regression and concordance-indices. Validation was performed by internal bootstrap, a cohort from a second institution (n = 64), and treatment of missing data with multiple-imputation. While ALCAM mRNA expression was unchanged, histological detection of ALCAM decreased with increasing stage (P = 0.004). Importantly, urine ALCAM was elevated 17.0-fold (P < 0.0001) above non-cancer controls, correlated positively with tumor stage (P = 0.018), was an independent predictor of OS after adjusting for age, tumor stage, lymph-node status, and hematuria (HR, 1.46; 95% CI, 1.03-2.06; P = 0.002), and improved prediction of OS by 3.3% (concordance-index, 78.5% vs. 75.2%). Urine ALCAM remained an independent predictor of OS after accounting for treatment with Bacillus Calmette-Guerin, carcinoma in situ, lymph-node dissection, lymphovascular invasion, urine creatinine, and adjuvant chemotherapy (HR, 1.10; 95% CI, 1.02-1.19; P = 0.011). In conclusion, shed ALCAM may be a novel prognostic biomarker in bladder cancer, although prospective validation studies are warranted. These findings demonstrate that markers reporting on cell motility can act as prognostic indicators.
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Molécula de Adhesión Celular del Leucocito Activado/orina , Biomarcadores de Tumor , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/orina , Molécula de Adhesión Celular del Leucocito Activado/genética , Molécula de Adhesión Celular del Leucocito Activado/metabolismo , Anciano , Estudios de Cohortes , Biología Computacional/métodos , Cistectomía/métodos , Bases de Datos Genéticas , Femenino , Expresión Génica , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Reproducibilidad de los Resultados , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/cirugíaRESUMEN
OBJECTIVE: To compare changes in renal function after radical nephrectomy for renal cell carcinoma (RCC) and radical nephroureterectomy for upper tract urothelial carcinoma (UTUC), and assess their effects on non-cancer-specific mortality (CSM). METHODS: Clinicopathologic data from 1114 patients with RCC or UTUC treated surgically from 1997 to 2013 were compiled. Patients who underwent nephron-sparing surgeries, had bilateral disease, received chemotherapy, or had <1 month of follow-up were excluded. Renal function (estimated glomerular filtration rate [eGFR]) was calculated preoperatively, 3 months postoperatively, and at last follow-up. Events were defined as ≥25% decline in eGFR from baseline. Event-free survival and non-CSM were assessed using Kaplan-Meier analysis. Multivariable Cox regression was performed to identify predictors of events. RESULTS: Four hundred thirty-five patients were included (317 radical nephrectomy, 118 radical nephroureterectomy). Median follow-up was 38.2 months. UTUC patients were older (P < .001), had worse Charlson score (P < .001), and more frequently used tobacco (P = .006). Median baseline eGFR was lower in UTUC patients (58.4 vs 74.9, P < .001). RCC patients experienced a larger event rate following surgery at first (56.8% vs 31.4%, P < .001) and last (51.7% vs 35.6%, P = .003) follow-up than UTUC patients. On Kaplan-Meier analysis, UTUC patients exhibited worse non-CSM (P < .001). Postsurgical decline in renal function was a significant predictor of non-CSM in RCC patients at first (hazard ratio = 4.71, P = .041) and last (hazard ratio = 4.56, P = .018) follow-up, whereas this was not the case for UTUC patients. CONCLUSION: UTUC patients had worse baseline eGFR and overall health status than RCC patients. RCC patients experienced greater postsurgical declines in renal function. These results shed light on differences in patient characteristics between these forms of kidney cancer and guide expectations for postoperative renal function.