RESUMO
BACKGROUND: It is estimated that one-third of patients presenting with unilateral joint pain have contralateral osteoarthritis (OA) at first presentation. Most studies have primarily examined White patient cohorts. The purpose of this study was to determine the prevalence of contralateral joint OA for patients presenting for unilateral total knee (TKA), unicompartmental knee (UKA) or total hip arthroplasty (THA) among Asian, Native Hawaiian/Pacific Islander and White patients. METHODS: Bilateral radiographic reports at initial presentation of 2,312 subjects who underwent unilateral arthroplasties (332 UKAs, 933 TKAs and 1,047 THAs) were reviewed. The presence of contralateral OA was recorded and compared by racial group and type of arthroplasty performed. Parametric statistical analyses were performed to determine differences between groups. Multivariable analyses were completed for each arthroplasty group to determine the influence on the presence of contralateral OA, presented as odds ratios and 95% confidence intervals. RESULTS: Contralateral joint OA was present in 86.7%, 90.4% and 70.4% of UKA, TKA and THA patients, respectively. Concurrent hip OA was present in 41.6% and 59.5% of UKA and TKA patients. No racial differences in the prevalence of contralateral knee OA were found for knee arthroplasty patients. White patients (74.6%) had a greater prevalence of contralateral hip OA compared to Asians (66.5%, p = 0.037) amongst THA recipients. Increased age and body mass index were significantly associated with the presence of contralateral knee OA. Increased age, being male and being White were significant contributors for the presence of contralateral hip OA. CONCLUSION: The prevalence of contralateral joint OA and concurrent hip OA is high in all three racial groups. Due to the extensive prevalence of contralateral and concurrent knee and hip OA, bilateral radiographic evaluation should be considered for all patients presenting with unilateral hip or knee pain due to OA.
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Artroplastia de Quadril , Artroplastia do Joelho , Osteoartrite do Quadril , Osteoartrite do Joelho , Feminino , Humanos , Masculino , Articulação do Joelho/cirurgia , Havaiano Nativo ou Outro Ilhéu do Pacífico , Osteoartrite do Quadril/diagnóstico por imagem , Osteoartrite do Quadril/epidemiologia , Osteoartrite do Quadril/cirurgia , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/epidemiologia , Osteoartrite do Joelho/cirurgia , Prevalência , Brancos , AsiáticoRESUMO
PURPOSE: Deep inspiration breath-hold (DIBH) is crucial in reducing the lung and cardiac dose for treatment of left-sided breast cancer. We compared the stability and reproducibility of two DIBH techniques: Active Breathing Coordinator (ABC) and VisionRT (VRT). MATERIALS AND METHODS: We examined intra- and inter-fraction positional variation of the left lung. Eight left-sided breast cancer patients were monitored with electronic portal imaging during breath-hold (BH) at every fraction. For each patient, half of the fractions were treated using ABC and the other half with VRT, with an equal amount starting with either ABC or VRT. The lung in each portal image was delineated, and the variation of its area was evaluated. Intrafraction stability was evaluated as the mean coefficient of variation (CV) of the lung area for the supraclavicular (SCV) and left lateral (LLat) field over the course of treatment. Reproducibility was the CV for the first image of each fraction. Daily session time and total imaging monitor units (MU) used in patient positioning were recorded. RESULTS: The mean intrafraction stability across all patients for the LLat field was 1.3 ± 0.7% and 1.5 ± 0.9% for VRT and ABC, respectively. Similarly, this was 1.5 ± 0.7% and 1.6 ± 0.8% for VRT and ABC, respectively, for the SCV field. The mean interfraction reproducibility for the LLat field was 11.0 ± 3.4% and 14.9 ± 6.0% for VRT and ABC, respectively. Similarly, this was 13.0 ± 2.5% and 14.8 ± 9% for VRT and ABC, respectively, for the SCV. No difference was observed in the number of verification images required for either technique. CONCLUSIONS: The stability and reproducibility were found to be comparable between ABC and VRT. ABC can have larger interfractional variation with less feedback to the treating therapist compared to VRT as shown in the increase in geometric misses at the matchline.
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Neoplasias da Mama , Neoplasias Unilaterais da Mama , Humanos , Feminino , Estudos Prospectivos , Planejamento da Radioterapia Assistida por Computador , Neoplasias Unilaterais da Mama/diagnóstico por imagem , Neoplasias Unilaterais da Mama/radioterapia , Reprodutibilidade dos Testes , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/radioterapia , Suspensão da Respiração , CoraçãoRESUMO
PURPOSE: Describe an early-adopting institution's experience with online adaptive radiation for stereotactic partial breast irradiation. METHODS AND MATERIALS: Retrospective review of 22 women treated between May 2021 and March 2022 with adaptive stereotactic partial breast irradiation. A total of 106 of 110 fractions were evaluated for dosimetric changes in target coverage and organ-at-risk (OAR) dose. Patient set up with stereotactic wooden frame and adapted per fraction. Treatment and planning times were collected prospectively by radiation therapists. RESULTS: Scheduled PTV30 Gy was <95% in 72.1% and <90% in 38.5% of fractions, and both PTV and CTV coverage were improved significantly after adaption, and 83.7% of fractions were delivered as adapted per physician choice. There was no difference in OAR coverage. Average adaptive treatment planning took 15 min and average time-on-couch was 34.4 min. CONCLUSIONS: Adaptive stereotactic breast irradiation resulted in improved target coverage with equivalent dosing to OARs in an efficient and tolerated treatment time. Improved target coverage allowed for decreased PTV margins compared to prior trial protocols that may improve acute and late toxicities.
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Órgãos em Risco , Radiocirurgia , Humanos , Feminino , Dosagem Radioterapêutica , Órgãos em Risco/efeitos da radiação , Estudos de Viabilidade , Planejamento da Radioterapia Assistida por Computador/métodos , Radiocirurgia/métodosRESUMO
The yeast Sup35 protein misfolds into the infectious [PSI+] prion, which is then propagated by the severing activity of the molecular chaperone, Hsp104. Unlike other yeast prions, this prion is unique in that it is efficiently cured by the overexpression as well as the inactivation of Hsp104. However, it is controversial whether curing by overexpression is due to the dissolution of the prion seeds by the trimming activity of Hsp104 or the asymmetric segregation of the prion seeds between mother and daughter cells which requires cell division. To answer this question, we conducted experiments and found no difference in the extent of curing between mother and daughter cells when half of the cells were cured by Hsp104 overexpression in one generation. Furthermore, curing was not affected by the lack of Sir2 expression, which was reported to be required for asymmetric segregation of the [PSI+] seeds. More importantly, when either hydroxyurea or ethanol were used to inhibit cell division, the extent of curing by Hsp104 overexpression was not significantly reduced. Therefore, the curing of [PSI+] by Hsp104 overexpression is not due to asymmetric segregation of the prion seeds, but rather their dissolution by Hsp104.
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Príons , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Príons/metabolismo , SolubilidadeRESUMO
The Coronavirus disease 2019 (COVID-19) pandemic has led to a significant increase in worldwide morbidity and mortality. Patients with COVID-19 are at risk for developing a variety of cardiovascular conditions including acute coronary syndromes, stress-induced cardiomyopathy, and myocarditis. Patients with COVID-19 who develop ST-elevation myocardial infarction (STEMI) are at a higher risk of morbidity and mortality when compared with their age- and sex-matched STEMI patients without COVID-19. We review current knowledge on the pathophysiology of STEMI in patients with COVID-19, clinical presentation, outcomes, and the effect of the COVID-19 pandemic on overall STEMI care.
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COVID-19 , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , COVID-19/complicações , COVID-19/epidemiologia , Pandemias , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Infarto do Miocárdio com Supradesnível do Segmento ST/terapiaRESUMO
Over 3 million paediatric patients globally and ~50 000 in the United States are estimated to be infected with HCV. Eradicating HCV in children helps prevent liver fibrosis, cirrhosis and hepatocellular carcinoma; reduces extra-hepatic manifestations of HCV; improves quality of life; and increases survival. The 2019 American Association for the Study of Liver Diseases-Infectious Diseases Society of America (AASLD-IDSA) guidelines now recommend direct-acting antiviral (DAA) treatment with an approved regimen for all children and adolescents with HCV infection aged ≥3 years. We conducted a descriptive review of the new DAA treatments for HCV infection in the paediatric population. Ledipasvir/sofosbuvir (LDV/SOF) and sofosbuvir with ribavirin (SOF/RBV) are now approved for those ≥3 years old under specific clinical scenarios; sofosbuvir/velpatasvir (SOF/VEL) is the only pangenotypic agent approved for those ≥6 years or ≥17 kg, and glecaprevir/pibrentasvir (GLE/PIB) is approved for adolescents ≥12 years old or ≥45 kg. These DAA regimens are well-tolerated and have comparable sustained virologic response rates at 12 weeks post-treatment compared to those reported in adults (close to 100%). The introduction of DAAs has significantly changed the landscape of HCV treatment in adults and children with HCV infection and has increased confidence that the 2030 World Health Organization elimination goal may be attainable. Further studies are warranted to determine the optimal treatment for children with HCV infection, including timing, regimen and duration. Additionally, with the recent paediatric approvals, long-term safety data are needed.
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Antivirais , Hepatite C , Pediatria , Adolescente , Adulto , Ácidos Aminoisobutíricos/uso terapêutico , Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Criança , Pré-Escolar , Ciclopropanos/uso terapêutico , Erradicação de Doenças , Quimioterapia Combinada , Fluorenos/uso terapêutico , Genótipo , Hepacivirus , Hepatite C/tratamento farmacológico , Hepatite C/prevenção & controle , Humanos , Lactamas Macrocíclicas/uso terapêutico , Leucina/análogos & derivados , Leucina/uso terapêutico , Prolina/análogos & derivados , Prolina/uso terapêutico , Pirrolidinas/uso terapêutico , Qualidade de Vida , Quinoxalinas/uso terapêutico , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Sulfonamidas/uso terapêutico , Resposta Viral Sustentada , Resultado do Tratamento , Organização Mundial da SaúdeRESUMO
BACKGROUND & AIMS: Complex benign rectal polyps can be managed with transanal surgery or with endoscopic resection (ER). Though the complication rate after ER is lower than transanal surgery, recurrence is higher. Patients lost to follow up after ER might therefore be at increased risk for rectal cancer. We evaluated the costs, benefits, and cost effectiveness of ER compared to 2 surgical techniques for removing complex rectal polyps, using a 50-year time horizon-this allowed us to capture rates of cancer development among patients lost from follow-up surveillance. METHODS: We created a Markov model to simulate the lifetime outcomes and costs of ER, transanal endoscopic microsurgery (TEM), and transanal minimally invasive surgery (TAMIS) for the management of a complex benign rectal polyp. We assessed the effect of surveillance by allowing a portion of the patients to be lost to follow up. We calculated the cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio or each intervention over a 50-year time horizon. RESULTS: We found that TEM was slightly more effective than TAMIS and ER (TEM, 19.54 QALYs; TAMIS, 19.53 QALYs; and ER, 19.53 QALYs), but ER had a lower lifetime discounted cost (ER cost $7161, TEM cost $10,459, and TAMIS cost $11,253). TEM was not cost effective compared to ER, with an incremental cost-effectiveness ratio of $485,333/QALY. TAMIS was dominated by TEM. TEM became cost effective when the mortality from ER exceeded 0.63%, or if the loss to follow up rate exceeded 25.5%. CONCLUSIONS: Using a Markov model, we found that ER, TEM, and TAMIS have similar effectiveness, but ER is less expensive, in management of benign rectal polyps. As the rate of loss to follow up increases, transanal surgery becomes more effective relative to ER.
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Pólipos Adenomatosos/cirurgia , Ressecção Endoscópica de Mucosa/economia , Proctoscopia/economia , Neoplasias Retais/cirurgia , Microcirurgia Endoscópica Transanal/economia , Pólipos Adenomatosos/economia , Pólipos Adenomatosos/patologia , Análise Custo-Benefício , Custos e Análise de Custo , Ressecção Endoscópica de Mucosa/métodos , Humanos , Cadeias de Markov , Pessoa de Meia-Idade , Proctoscopia/métodos , Anos de Vida Ajustados por Qualidade de Vida , Neoplasias Retais/economia , Neoplasias Retais/patologia , Microcirurgia Endoscópica Transanal/métodos , Carga TumoralRESUMO
We examined three waves of National HIV Behavioral Surveillance surveys of persons who inject drugs (PWID) in San Francisco to assess meeting UNAIDS 90-90-90 targets. Diagnosis of PWID living with HIV increased from 64.4% in 2009 to 80.5% in 2015. Antiretroviral treatment among those diagnosed did not improve (63.8% in 2009, 62.9% in 2015). Programs in San Francisco have not achieved the first two UNAIDS targets for PWID by 2015. In a context of a rising opioid epidemic, there is urgent need for increased case finding of PWID living with HIV who are undiagnosed with rapid linkage to treatment.
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Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/epidemiologia , Abuso de Substâncias por Via Intravenosa/epidemiologia , Adulto , Sistema de Vigilância de Fator de Risco Comportamental , Feminino , Infecções por HIV/diagnóstico , Inquéritos Epidemiológicos , Humanos , Masculino , Avaliação de Programas e Projetos de Saúde , São Francisco/epidemiologia , Adulto JovemRESUMO
OBJECTIVE. The purpose of this study was to evaluate the utility of CT texture analysis (CTTA) in differentiating low-attenuation renal cell carcinoma (RCC) from renal cysts on unenhanced CT. MATERIALS AND METHODS. Ninety-four patients with low-attenuation RCC on unenhanced CT were compared with a cohort of 192 patients with benign renal cysts. CT characteristics (size and minimum, maximum, and mean attenuation) and CTTA features were recorded using an ROI approximately two-thirds the size of the mass. Masses were subjectively assessed by two expert genitourinary readers and two novice readers using a 5-point Likert scale (1 = definite cyst, 5 = definite renal cell carcinoma). Results of first-order CTTA and subjective evaluation were compared using ROC analysis. RESULTS. The group of 94 patients with low-attenuation RCC included 62 men and 32 women (mean age, 58.0 years). On unenhanced CT, the RCC were larger than 10 mm and of a median size of 50 mm with less than or equal to 20 HU (mean attenuation, 16 ± 4 HU). Of the RCC cohort, 83 were clear cell subtype. The cohort of 192 patients included 134 men and 58 women (mean age, 64.7 years) with benign renal cysts greater than 10 mm and a median size of 27 mm and less than or equal to 20 HU (mean attenuation, 9 ± 6 HU). The mean follow-up time was 6.2 years. Mean entropy in the low-attenuation RCC group (4.1 ± 0.7) was significantly higher than in the cyst group (2.8 ± 1.3, p < 0.0001). Entropy showed an ROC AUC of 0.89, with sensitivity of 84% and specificity of 80% at threshold 3.9. The AUC was better than subjective evaluation by novice readers (AUC, 0.77) and comparable to subjective evaluation by two expert readers (AUC, 0.90). A model combining the three best texture features (unfiltered mean gray-level attenuation, coarse entropy, and kurtosis) showed an improved AUC of 0.92. CONCLUSION. High entropy revealed with CTTA may be used to differentiate low-attenuation RCC from cysts at unenhanced CT; this technique performs as well as expert readers.
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Carcinoma de Células Renais/diagnóstico por imagem , Doenças Renais Císticas/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Interpretação de Imagem Radiográfica Assistida por Computador , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
Following a stroke, mirror movements are unintended movements that appear in the non-paretic hand when the paretic hand voluntarily moves. Mirror movements have previously been linked to overactivation of sensorimotor areas in the non-lesioned hemisphere. In this study, we hypothesized that mirror movements might instead have a subcortical origin, and are the by-product of subcortical motor pathways upregulating their contributions to the paretic hand. To test this idea, we first characterized the time course of mirroring in 53 first-time stroke patients, and compared it to the time course of activities in sensorimotor areas of the lesioned and non-lesioned hemispheres (measured using functional MRI). Mirroring in the non-paretic hand was exaggerated early after stroke (Week 2), but progressively diminished over the year with a time course that parallelled individuation deficits in the paretic hand. We found no evidence of cortical overactivation that could explain the time course changes in behaviour, contrary to the cortical model of mirroring. Consistent with a subcortical origin of mirroring, we predicted that subcortical contributions should broadly recruit fingers in the non-paretic hand, reflecting the limited capacity of subcortical pathways in providing individuated finger control. We therefore characterized finger recruitment patterns in the non-paretic hand during mirroring. During mirroring, non-paretic fingers were broadly recruited, with mirrored forces in homologous fingers being only slightly larger (1.76 times) than those in non-homologous fingers. Throughout recovery, the pattern of finger recruitment during mirroring for patients looked like a scaled version of the corresponding control mirroring pattern, suggesting that the system that is responsible for mirroring in controls is upregulated after stroke. Together, our results suggest that post-stroke mirror movements in the non-paretic hand, like enslaved movements in the paretic hand, are caused by the upregulation of a bilaterally organized subcortical system.
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Lateralidade Funcional/fisiologia , Córtex Motor/fisiopatologia , Transtornos dos Movimentos/etiologia , Acidente Vascular Cerebral/complicações , Adulto , Idoso , Feminino , Dedos/fisiopatologia , Humanos , Processamento de Imagem Assistida por Computador , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/diagnóstico por imagem , Transtornos dos Movimentos/diagnóstico por imagem , Oxigênio/sangue , Desempenho Psicomotor/fisiologiaRESUMO
AIMS: The reaction to diagnosis and quality of life (QOL) in autosomal dominant tubulointerstitial kidney disease (ADTKD) due to UMOD and MUC mutations from the time of diagnosis until treatment for end-stage kidney disease (ESKD) has not been characterized. It is unclear how asymptomatic patients react to a positive genetic test result. MATERIALS AND METHODS: A cross-sectional survey concerning QOL and genetic testing was delivered to 622 individuals who had undergone genetic testing from families with known ADTKD. RESULTS: 286 of 622 individuals completed the survey, including 61 (21%) genetically unaffected, 36 (12%) with stage 1, 2 chronic kidney disease (CKD), 51 (18%) stage 3, 41 (14%) stage 4 pre-dialysis, 50 (17%) receiving dialysis, and 47 (16%) s/p kidney transplantation. Of 55 respondents who thought they had normal kidney function at the time of testing and were found to have ADTKD, 51 (93%) were happy testing was performed, 3 (5%) neutral, and 1 (2%) neutral/unhappy. 42 of 183 (23%) affected individuals stated that ADTKD "has a substantial effect and I think about it daily," 47 (26%) think about ADTKD weekly, 48 (26%) monthly, and 48 (26%) less than monthly. The mean PROMIS anxiety score was similar between unaffected and affected individuals and the general population. Depression was present in 41% of affected vs. 23% of unaffected individuals (p = 0.01). CONCLUSION: Genetic testing of presymptomatic patients for ADTKD is reasonable when requested. This study provides reassurance regarding the impact on QOL of the increased use of genetic testing to diagnose kidney disease. ADTKD has a significant impact on QOL, with depression, not anxiety, being more prevalent in affected individuals.
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Nefropatias/genética , Nefropatias/psicologia , Mucina-1/genética , Mutação , Qualidade de Vida , Uromodulina/genética , Adulto , Idoso , Estudos Transversais , Feminino , Testes Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the few cancers whose incidence continues to increase. The goal of the current study was to investigate the presentation and survival trends of patients with HCC presenting to a university hospital between 1998 and 2015. METHODS: Study data were ascertained by individual chart review with survival data also supplemented by National Death Index query up to December 31, 2015. Patients were divided into three 6-year groups by diagnosis date (1998-2003, 2004-2009, and 2010-2015). RESULTS: A total of 2106 consecutive patients with HCC were included. The majority of patients had either hepatitis C (56.7%) or hepatitis B (22.1%), but cases of nonalcoholic steatohepatitis HCC increased by 68% over the most recent time period. Screening/surveillance identified 61% of HCC cases, but only 31% of these patients underwent curative treatment, which did not increase significantly over time. The overall median survival was 29.8 months (2.48 years) and without improvement over time. On multivariable analysis, Asian or Hispanic ethnicity, meeting Milan criteria, and receiving any of the standard HCC treatments were found to be significantly associated with improved survival, but diagnosis time period and liver disease etiology were not. CONCLUSIONS: Over the last 18 years, the percentage of cases of nonalcoholic steatohepatitis HCC has increased but not overall survival. It is interesting to note that only 31% of patients with HCC identified via screening/surveillance received any curative treatment. Further research is needed to better understand the barriers to curative care for patients with HCC and the causes of the lack of improvement in survival in the more recent patient cohort. Cancer 2018;124:2588-98. © 2018 American Cancer Society.
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Carcinoma Hepatocelular/mortalidade , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Neoplasias Hepáticas/mortalidade , Mortalidade/tendências , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/estatística & dados numéricos , Quimioembolização Terapêutica/tendências , Feminino , Hepatectomia/estatística & dados numéricos , Hepatectomia/tendências , Hepatite B/patologia , Hepatite B/virologia , Hepatite C/patologia , Hepatite C/virologia , Humanos , Incidência , Estimativa de Kaplan-Meier , Fígado/patologia , Fígado/virologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Transplante de Fígado/estatística & dados numéricos , Transplante de Fígado/tendências , Masculino , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/patologia , Cuidados Paliativos/estatística & dados numéricos , Cuidados Paliativos/tendências , Estudos Retrospectivos , Fatores de Tempo , Estados Unidos/epidemiologiaRESUMO
Impaired hand function after stroke is a major cause of long-term disability. We developed a novel paradigm that quantifies two critical aspects of hand function, strength, and independent control of fingers (individuation), and also removes any obligatory dependence between them. Hand recovery was tracked in 54 patients with hemiparesis over the first year after stroke. Most recovery of strength and individuation occurred within the first 3 mo. A novel time-invariant recovery function was identified: recovery of strength and individuation were tightly correlated up to a strength level of ~60% of estimated premorbid strength; beyond this threshold, strength improvement was not accompanied by further improvement in individuation. Any additional improvement in individuation was attributable instead to a second process that superimposed on the recovery function. We conclude that two separate systems are responsible for poststroke hand recovery: one contributes almost all of strength and some individuation; the other contributes additional individuation.NEW & NOTEWORTHY We tracked recovery of the hand over a 1-yr period after stroke in a large cohort of patients, using a novel paradigm that enabled independent measurement of finger strength and control. Most recovery of strength and control occurs in the first 3 mo after stroke. We found that two separable systems are responsible for motor recovery of hand: one contributes strength and some dexterity, whereas a second contributes additional dexterity.
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Dedos/fisiopatologia , Recuperação de Função Fisiológica , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/diagnóstico por imagem , Adulto JovemRESUMO
BACKGROUND: We used metabolic risk factors to estimate the prevalence and clinical significance of nonalcoholic fatty liver disease in Asian Americans with hepatocellular carcinoma (HCC). METHODS: This is a retrospective cohort study of 824 consecutive Asian HCC patients at Stanford University Medical Center from 1998 to 2015. Patients were subdivided as: Chinese, other East Asian (Japanese and Korean), South East Asian (Vietnamese, Thai, and Laotian), Maritime South East Asian (MSEA: Malaysian, Indonesian, Filipino, and Singaporean), and South West Asian (Indian, Pakistani, and Middle Eastern). Metabolic risk factors studied were body mass index, hypertension, type II diabetes, and hyperlipidemia. RESULTS: Most patients were male (76%) with mean age 63 years. Metabolic risk factors were highly prevalent on presentation and increased over time (P<0.001), as did the prevalence of cryptogenic HCC (P<0.004). Compared with other Asian subgroups, MSEAs had the highest body mass index (26.3) and higher rates of type II diabetes (44% vs. 23% to 35%, P=0.004), hypertension (59% vs. 38% to 55%, P=0.04), and cryptogenic HCC (15% vs. 4% to 10%, P=0.01). They were more likely to be symptomatic on presentation (44% vs. 32% to 58%, P=0.07), less likely to present within Milan criteria (34% vs. 35% to 63%, P<0.0001), and trended toward decreased 10-year survival rates compared with other ethnic subgroups (9% vs. 25% to 32%, P=0.07). CONCLUSIONS: Metabolic risk factors were increasingly prevalent among Asian Americans with HCC. MSEAs, who had the highest incidence of these risk factors, had more advanced tumor stage and trended toward worse survival.
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Asiático , Carcinoma Hepatocelular/etnologia , Diabetes Mellitus Tipo 2/etnologia , Neoplasias Hepáticas/etnologia , Hepatopatia Gordurosa não Alcoólica/etnologia , California/epidemiologia , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Prevalência , Estudos Retrospectivos , Fatores de RiscoRESUMO
Cancer metastasis is a key event in tumor progression associated not only with mortality but also significant morbidity. Metastatic disease can promote end-organ dysfunction and even failure through mass effect compression of various vital organs including the spinal cord. In such cases, prompt medical attention is needed to restore neurological function, relieve pain, and prevent permanent damage. The three therapeutic approaches to managing metastatic spinal cord compression include corticosteroids, surgery, and radiation therapy. Although each may improve patients' symptoms, their combination has yielded the best outcome. In cancer patients with clinical suspicion of spinal cord compression, dexamethasone should be initiated followed by surgical decompression, when possible, and radiation. The latter becomes the preferred treatment in patients with inoperable disease.
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Anti-Inflamatórios/uso terapêutico , Descompressão Cirúrgica , Dexametasona/uso terapêutico , Radioterapia , Compressão da Medula Espinal/terapia , Neoplasias da Coluna Vertebral/secundário , Terapia Combinada , Humanos , Radioterapia/efeitos adversos , Radioterapia/métodos , Compressão da Medula Espinal/etiologia , Neoplasias da Coluna Vertebral/complicaçõesRESUMO
BACKGROUND & AIMS: Hepatitis B virus (HBV) is the most common cause of hepatocellular carcinoma (HCC) worldwide. Unlike other liver diseases, HBV can cause HCC in the absence of cirrhosis. We investigated whether features of HCC in patients with HBV infection without cirrhosis and survival times differ from those of patients who develop HCC after cirrhosis. METHODS: We performed a retrospective cohort study of 487 consecutive cases of HBV-related HCC who were seen from 2000 through 2014 at a tertiary care center. Laboratory values, imaging results, and treatment information were obtained from subjects' medical records. Symptoms of HCC included weight loss, abdominal pain, or new hepatic decompensation. The primary outcome was overall survival, which was categorized as short-term survival (up to 3 years after the diagnosis of HCC) or long-term survival (3-10 years after diagnosis). RESULTS: The mean tumor size at diagnosis was significantly larger in patients without cirrhosis (6.4 ± 4.3 cm) than in patients with cirrhosis (5.0 ± 3.8 cm) (P = .0009). A significantly larger proportion of patients without cirrhosis had symptoms at diagnosis (43.8% vs 35.4% in patients without cirrhosis, P = .09). A significantly higher proportion of patients without cirrhosis survived for the long-term (P = .003), but there was no significant difference between groups in short-term survival (P = .37). Notably, the same proportions of asymptomatic patients with and without cirrhosis survived for the short-term (64.3% vs 64.2%, P = .73), but a lower proportion of asymptomatic patients with cirrhosis survived for the long-term (P = .015). In multivariate Cox regression analysis, cirrhosis was an independent predictor of death in 3-10 years (hazard ratio, 3.76; P = .003) but not in less than 3 years (P = .48). Symptoms at diagnosis predicted death within 3 years (hazard ratio, 1.76; P =.006) but not in 3-10 years (P = .15). CONCLUSIONS: Patients with HBV infection and HCC without cirrhosis present with larger tumors, and a larger percentage have symptoms of cancer than patients with cirrhosis. This may indicate that HCC surveillance is less than optimal for patients with HBV infection without cirrhosis. Despite this suboptimal surveillance, patients without cirrhosis have higher long-term survival than those with cirrhosis, especially when asymptomatic at diagnosis.
Assuntos
Carcinoma Hepatocelular/epidemiologia , Hepatite B Crônica/complicações , Cirrose Hepática/complicações , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/mortalidade , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de SobrevidaAssuntos
Hipertensão Portal/cirurgia , Seleção de Pacientes , Derivação Portossistêmica Transjugular Intra-Hepática/métodos , Bilirrubina/sangue , Determinação da Pressão Arterial , Contraindicações de Procedimentos , Doença Hepática Terminal , Encefalopatia Hepática/epidemiologia , Veias Hepáticas/cirurgia , Humanos , Hipertensão Portal/fisiopatologia , Falência Hepática/epidemiologia , Veia Porta/cirurgia , Complicações Pós-Operatórias/epidemiologia , Índice de Gravidade de Doença , StentsRESUMO
Ferroptosis is a non-apoptotic form of cell death that can be triggered by inhibiting the system xc- cystine/glutamate antiporter or the phospholipid hydroperoxidase glutathione peroxidase 4 (GPX4). We have investigated how cell cycle arrest caused by stabilization of p53 or inhibition of cyclin-dependent kinase 4/6 (CDK4/6) impacts ferroptosis sensitivity. Here, we show that cell cycle arrest can enhance sensitivity to ferroptosis induced by covalent GPX4 inhibitors (GPX4i) but not system xc- inhibitors. Greater sensitivity to GPX4i is associated with increased levels of oxidizable polyunsaturated fatty acid-containing phospholipids (PUFA-PLs). Higher PUFA-PL abundance upon cell cycle arrest involves reduced expression of membrane-bound O-acyltransferase domain-containing 1 (MBOAT1) and epithelial membrane protein 2 (EMP2). A candidate orally bioavailable GPX4 inhibitor increases lipid peroxidation and shrinks tumor volumes when combined with a CDK4/6 inhibitor. Thus, cell cycle arrest may make certain cancer cells more susceptible to ferroptosis in vivo.
Assuntos
Ferroptose , Neoplasias , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Morte Celular , Peroxidação de Lipídeos , Ácidos Graxos Insaturados/metabolismo , Pontos de Checagem do Ciclo Celular , Neoplasias/tratamento farmacológicoRESUMO
Styrene dyes are useful imaging probes and fluorescent sensors due to their strong fluorogenic responses to environmental changes or binding macromolecules. Previously, indole-containing styrene dyes have been reported to selectively bind RNA in the nucleolus and cytoplasm. However, the application of these indole-based dyes in cell imaging is limited by their moderate fluorescence enhancement and quantum yields, as well as relatively high background associated with these green-emitting dyes. In this work, we have investigated the positional and electronic effects of the electron donor by generating regioisomeric and isosteric analogues of the indole ring. Select probes exhibited large Stokes shifts, enhanced molar extinction coefficients, and bathochromic shifts in their absorption and fluorescence wavelengths. In particular, the indolizine analogues displayed high membrane permeability, strong fluorogenic responses upon binding RNA, compatibility with fluorescence lifetime imaging microscopy (FLIM), low cytotoxicity, and excellent photostability. These indolizine dyes not only give rise to rapid, sensitive, and intense staining of nucleoli in live cells but can also resolve subnucleolar structures enabling highly detailed studies of nucleolar morphology. Furthermore, our dyes can partition into RNA coacervates and resolve the formation of multiphase complex coacervate droplets. These indolizine-containing styrene probes offer the highest fluorescence enhancement among the RNA-selective dyes reported in the literature; thus, these new dyes are excellent alternatives to the commercially available RNA dye, SYTO RNASelect, for visualizing RNA in live cells and in vitro.