Miracle-dz/UniFAR-FTUs huggingface dataset:
Evolution of hepatic steatosis in patients with advanced hepatitis C: Results from the hepatitis C antiviral long‐term treatment against cirrhosis (HALT‐C) trial

Hepatic steatosis is a common histologic feature in patients with chronic hepatitis C (CHC) but there are no large longitudinal studies describing the progression of steatosis in CHC. We examined changes in steatosis on serial biopsies among CHC patients participating in the Hepatitis C Antiviral Long‐term Treatment against Cirrhosis (HALT‐C) Trial. All 1050 patients in the trial had advanced fibrosis at baseline biopsy and were documented not to have had a sustained virological response to peginterferon and ribavirin. Most (94%) patients had genotype 1 infection. At least one protocol follow‐up biopsy was read on 892 patients, and 699 had the last biopsy performed 3.5 years after randomization. At enrollment, 39% had cirrhosis and 61% had bridging fibrosis; 18%, 41%, 31%, and 10% had steatosis scores of 0, 1, 2, and 3 or 4, respectively. The mean steatosis score decreased in the follow‐up biopsies in both the interferon‐treated patients and controls with no effect of treatment assignment (P = 0.66). A decrease in steatosis score by ≥1 point was observed in 30% of patients and was associated with both progression to cirrhosis and continued presence of cirrhosis (P = 0.02). Compared to patients without a decrease in steatosis, those with a decrease in steatosis had worse metabolic parameters at enrollment, and were more likely to have a decrease in alcohol intake, improvement in metabolic parameters, and worsening liver disease (cirrhosis, esophageal varices, and deterioration in liver function). Conclusion: Serial biopsies demonstrated that in patients with CHC, steatosis recedes during progression from advanced fibrosis to cirrhosis. Decreased alcohol intake and improved metabolic parameters are associated with a decline in steatosis and may modulate hepatitis C progression. (HEPATOLOGY 2009.)
Satisfaction With Initial Screen and Compliance With Biennial Breast Screening at Centers With and Without Nurses

Background: A woman's experience during her initial breast screen can influence her participation in subsequent screening. Objective: The purpose of this study was to determine the association between a woman's satisfaction with her initial screening experience and compliance to biennial screening at centers with and without nurses. Methods: A stratified random sample of compliers and noncompliers to biennial screening was selected from a cohort of 16 858 eligible women aged 50 to 65 years attending centers with and without nurses for their initial screen at the Ontario Breast Screening Program in 2002. Of these eligible women, 3387 were sent questionnaires, 2640 (77.9%) were contacted, and 1901 (72.0%) were interviewed. The association between satisfaction with initial screen and compliance was estimated separately for centers with and without nurses using logistic regression. Results: Women attending centers with nurses were significantly less likely to comply with their next screen after their clinical breast examination if they were not completely satisfied with the service they received (odds ratio, 0.21; 95% confidence interval, 0.08-0.57) or agreed that the clinical breast examination caused discomfort to their breasts (odds ratio, 0.65; 95% confidence interval, 0.45-0.94). In addition, women attending centers with or without nurses were significantly less likely to comply if they did not understand why they needed to return for screening. Conclusions: Nurses at screening centers have an opportunity to significantly impact a woman's compliance to biennial breast screening by providing a positive initial screening experience. Implications for Practice: Emphasis should be placed on improving a woman's overall satisfaction with her initial screening experience.
PCSK9 impedes hepatitis C virus infection in vitro and modulates liver CD81 expression

Human PCSK9 is known to enhance the degradation of membrane‐bound receptors such as the hepatocyte low‐density lipoprotein receptor (LDLR), ApoER2, and very low‐density lipoprotein receptor. Because the LDLR is suspected to be involved in hepatitis C virus (HCV) entry, we also tested whether PCSK9 can affect the levels of CD81, a major HCV receptor. Interestingly, stable expression of PCSK9 or a more active membrane‐bound form of the protein (PCSK9‐ACE2) resulted in a marked reduction in CD81 and LDLR expression. Therefore, we analyzed the antiviral effect of PCSK9 in vitro using the HCV genotype 2a (JFH1) virus. The results clearly demonstrated that cells expressing PCSK9 or PCSK9‐ACE2, but not the ACE2 control protein, were resistant to HCV infection. Furthermore, addition of purified soluble PCSK9 to cell culture supernatant impeded HCV infection in a dose‐dependent manner. As expected, HuH7 cells expressing PCSK9‐ACE2 were also resistant to infection by HCV pseudoparticles. In addition, we showed that CD81 cell surface expression is modulated by PCSK9 in an LDLR‐independent manner. Finally, in the liver of single Pcsk9 and double (Pcsk9 + Ldlr) knockout mice, both LDLR and/or CD81 protein expression levels were significantly reduced, but not those of transferrin and scavenger receptor class B type 1. Conclusion: Our results demonstrate an antiviral effect of the circulating liver PCSK9 on HCV in cells and show that PCSK9 down‐regulates the level of mouse liver CD81 expression in vivo. Therefore, we propose that the plasma level and/or activity of PCSK9 may modulate HCV infectivity in humans. (HEPATOLOGY 2009.)
Independent effects of physical activity in patients with nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease, characterized by elevated liver enzymes, central obesity, and insulin resistance, is becoming increasingly prevalent. The effects of changes in physical activity on the metabolic profile of this group have not been reported. We assessed at 3 months the impact of a behavior change‐based lifestyle intervention on physical activity and the effects of this change on the metabolic profile of people with fatty liver disease. In all, 141 participants with nonalcoholic fatty liver disease were prospectively enrolled into either a low‐ or moderate‐intensity lifestyle intervention or to a control group. Physical activity was assessed using a validated reporting tool and physical fitness was measured using the YMCA protocol on a cycle ergometer. Individualized counseling to increase physical activity was provided. Overall, 96% of participants attended the 3‐month follow‐up assessment. Participants in the moderate‐ and low‐intensity intervention groups were 9 times more likely to increase physical activity by an hour or more per week compared to controls. Patients increasing or maintaining their reported physical activity to ≥150 minutes/week, and those who increased their objective levels of fitness, had the greatest improvements in liver enzymes and other metabolic indices compared to those who were least active. This effect was independent of weight loss and was corroborated by an objective measure of fitness. There was no dose‐response effect on liver enzymes with incremental increases in physical activity above 60 minutes/week. Conclusion: Lifestyle counseling interventions are effective in improving physical activity behavior. Maintaining or increasing physical activity provides health benefits for patients with fatty liver, independent of changes in weight. (HEPATOLOGY 2009.)
Cricoid pressure: an alternative view

Although the use of cricoid pressure (CP) seems to make intuitive sense, its scientific basis is weak at best and lacking at worst. It is based on studies of saline regurgitation in cadavers and a study of a small number of patients. More than 40 years after Sellick’s description of CP, still no randomized controlled trial has been conducted to assess, let alone prove, the effectiveness of CP in preventing pulmonary aspiration of gastric content. Relying solely on CP as a preventive measure has numerous pitfalls. We possibly endanger more patients by interfering with optimal airway management than we save lives through prevention of aspiration of gastric content. It is potentially dangerous to consider CP to be effective in most cases and to become complacent about the many factors that contribute to regurgitation and aspiration. By today’s standards, CP can hardly be considered an evidence-based practice.
Change and Predictors of Social Support in Caregivers of Newly Diagnosed Oral Cavity Cancer Patients During the First 3 Months After Discharge

Background: Caregivers of oral cavity cancer patients report stress during caregiving time. Objective: This study aimed to examine changes in social support and predictors in caregivers of oral cavity cancer patients over the 3 months after patients’ first discharge. Methods: This was a prospective longitudinal study. Caregivers of oral cavity cancer patients with planned discharge were recruited from inpatient wards and the outpatient department at a major medical center in Taiwan. Caregivers’ needs and satisfaction with available social support were assessed at 4 time points: before discharge and at 1 week, 1 month, and 3 months after the first discharge. The generalized estimating equation was used to determine predictive factors of social support. Results: Caregivers had mild-to- moderate levels of needs and were satisfied with available social support during the first 3 months after discharge. The peak for both overall and individual needs of social support was before discharge. Caregivers overall and individual satisfaction with social support peaked at 3 months after discharge. Spouse caregivers had greater overall needs for social support. Caregivers with longer caregiving time were associated with dissatisfaction during the first 3 months after discharge. Conclusions: Caregivers of oral cavity cancer patients had unmet needs of social support, especially wife caregivers. Implications for Practice: A comprehensive assessment of caregiver needs and satisfaction with available social support is necessary to improve caregiving for oral cavity cancer patients and address the concerns of caregivers in a timely manner.
Nurse-Patient Communication in Follow-up Consultations After Head and Neck Cancer Treatment

Background: Adequate provider-patient communication is viewed as an important aspect of good quality (cancer) care, supports patients’ stress control, and can positively influence health outcomes. Objective: The objective of this study was to describe nurse-patient communication in 2 consecutive follow-up consultations after head and neck cancer, with or without a partner present. Methods: This was a descriptive observational study of 17 video-recorded, coded, and analyzed consultations of 10 head and neck cancer patients and 6 partners. Results: Nurses adequately responded to about 25% of patients’ and partners’ emotional cues. In almost 75%, nurses responded to cues using distancing behaviors. The majority of informational questions of both patients and partners were adequately answered. Comparison of consecutive visits showed small differences for patients’ and partners’ cue-emission and for nurses’ responsive behaviors between visits 1 and 2. Conclusion: Nurses adequately responded to informational questions from patients and partners. However, they seemed to be less observant of and able to address emotional cues. Communication on nurse-patient-partner interaction deserves further research in a much larger sample and over a longer time period. Implication for Practice: Nurses’ awareness of the importance of adequate cue responding is vital, as is the choice to “unlearn” the predominant distancing behaviors. The needs and the role of the patients’ partner in consultations and managing consultations require further attention in training and professional practice.
The Effect of Depression on Functional Abilities Among Great Lakes American Indians

Depression is becoming recognized as a prime factor affecting older adults' functional abilities and disability. However, there is a scarcity of data on depression in older adult American Indians and none on the impact of depression on functional skills in this group. Using a sample of 314 American Indians from urban and rural areas, depression was found to be a significant predictor of Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) abilities even after demographic variables and comorbid medical illness were accounted for. Because American Indians have higher Comorbid Medical Illnesses (CMI) than do members of the dominant culture, the results of the current study heighten the need for assessment and treatment of depression in older American Indians.
Pharmacotherapeutic blood pressure management in a chronic kidney disease patient.

C kidney disease (CKD) is associated with increased mortality, cardiovascular events, and hospitalizations. In the United States, the prevalence of CKD has increased to 8.1%, with hypertension being the second leading cause of end stage renal disease (ESRD) next to diabetes. Hypertension is also a complication of CKD associated with cardiovascular morbidity and mortality. A diagnosis of hypertension is present in 60% to 80% of patients with CKD. Notably, only 20% of cases of hypertension in these patients are controlled with the use of antihypertensives. Goals of therapy for hypertension in patients with CKD focus on preventing the onset and slowing the progression of kidney disease as well as reducing the risk of cardiovascular disease (CVD). Guidelines from the Kidney Disease Outcomes Quality Initiative (KDOQI), the American Diabetes Association (ADA), and the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) all recommend a goal blood pressure of less than 130/80 mm Hg in patients with renal disease. Thus, appropriate therapeutic drug selection for the treatment of hypertension in patients with CKD is essential for the prevention of morbidity and mortality associated with CVD and ESRD. The risk of CVD doubles with each increment of 20/10 mm Hg, starting at blood pressures of 115/75 mm Hg. Controlling hypertension in patients with CKD frequently requires the use of multidrug regimens. This column reviews the clinical use of evidence-based antihypertensive treatment strategies in patients with CKD.
Cholangiocarcinoma in cirrhosis: Absence of contrast washout in delayed phases by magnetic resonance imaging avoids misdiagnosis of hepatocellular carcinoma

This study assesses the magnetic resonance (MR) features of intrahepatic cholangiocarcinoma (ICC) in patients with cirrhosis with specific analysis of the contrast enhancement pattern. Cholangiocarcinoma may show increased contrast uptake in the arterial phase, and, if washout in the delayed venous phase were to be detected, the noninvasive diagnostic criteria proposed in the American Association for the Study of Liver Diseases guidelines would be refuted. We reviewed the MR findings of 25 patients with cirrhosis with 31 histologically confirmed ICC nodules. Signal intensity on basal T1‐weighted and T2‐weighted images and characteristics of enhancement after contrast administration on arterial, portal, and delayed phase were registered. Enhancement pattern was defined according to the behavior of the lesions in each phase, and dynamic pattern was described according to the progression of enhancement throughout the different phases. The most frequent pattern displayed by ICC was a progressive contrast uptake (80.6%). Stable contrast enhancement was registered in 19.4%. None of the ICCs showed a washout pattern, a profile that is specific for hepatocellular carcinoma (HCC). The ICC dynamic behavior differed significantly according to tumor size: progressive enhancement pattern was the most frequent (20 of 25 cases) in lesions larger than 20 mm, whereas the stable pattern was mainly identified in nodules smaller than 20 mm. The most characteristic MR contrast pattern in ICC in cirrhosis is a progressive contrast uptake throughout the different phases, whereas contrast washout at delayed phases is not observed. Because stable enhancement pattern without washout also can be registered in small HCC nodules, the evaluation of delayed phase is mandatory for a proper nodule characterization. If washout is not registered, a biopsy should be mandatory for diagnosis. (HEPATOLOGY 2009.)
Monitoring Diabetic Nephropathy by Circulating Gangliosides

Gangliosides are multifunctional molecules, abundantly expressed in renal cell membrane but also in sera of patients with renal disease. The aim of this study was to quantify the serum levels of sialic acid-ganglioside in patients diagnosed with diabetes for an eventual biomarker stratification of patients with renal complications. We included 35 diabetic patients without metabolic complications, 35 patients with diabetic nephropathy, 35 non-diabetic individuals. We found that sialic acid ganglioside serum level was significantly increased in patients with diabetic nephropathy compared to the level obtained in patients with uncomplicated diabetes and to non-diabetic controls. A statistically significant positive correlation was obtained between serum levels of sialic acid gangliosides, HbA1c, and serum creatinine in patients with diabetes without complications. Moreover positive correlation was found between sialic acid ganglioside and blood glucose, HbA1c, urea, creatinine, microalbuminuria in patients with diabetic nephropathy. We can conclude that serum sialic acid-gangliosides are statistically increased in diabetic nephropathy positively correlated with microalbuminuria.
Incidence, risk factors, and survival of hepatocellular carcinoma in primary biliary cirrhosis: Comparative analysis from two centers

The limited information and divergent results on the prevalence, incidence, and risk factors for hepatocellular carcinoma (HCC) in patients with primary biliary cirrhosis (PBC) may be due to the low prevalence of the disease and geographical and environmental differences. Therefore, we analyzed the incidence, prevalence, survival, and risk factors for HCC in patients with PBC from two European centers (389 from Barcelona, Spain, and 327 from Padova, Italy) followed up for 9.3 ± 6.5 years. Gender, age, smoking habit, alcohol consumption, presence of hepatitis B surface antigen (HBsAg) or hepatitis C virus antibodies (anti‐HCV), and advanced histological stage (III‐IV) were evaluated as risk factors for tumor development. Twenty‐four patients (13 from Barcelona and 11 from Padova) developed HCC. The prevalence of HCC was similar in Barcelona (3.34%) and Padova (3.36%). The incidence was 0.35 and 0.37 per 100 patient‐years, respectively. Male gender, age >52 years, smoking habit, alcohol >40 g/day, HBsAg, and anti‐HCV were not associated with HCC. Advanced histological stage was the only factor associated with the development of HCC (odds ratio [OR]: 5.80, 95% confidence interval [CI]: 2.34‐14.38, P < 0.001). When analyzing the two series separately, male gender was associated with higher likelihood of HCC in Padova (OR: 8.09, 95% CI: 1.93‐33.8, P < 0.01). The median survival after the diagnosis of HCC was 36 months. Conclusion: The prevalence and incidence of HCC is similar in Spain and Italy and the advanced histological stage is the only risk factor associated with the development of HCC in PBC. The slight disparities observed between the two series might be explained by patient features on diagnosis of liver disease. (HEPATOLOGY 2009.)
Divergent adaptation of hepatitis C virus genotypes 1 and 3 to human leukocyte antigen–restricted immune pressure

Many hepatitis C virus (HCV) infections worldwide are with the genotype 1 and 3 strains of the virus. Cellular immune responses are known to be important in the containment of HCV genotype 1 infection, and many genotype 1 T cell targets (epitopes) that are presented by host human leukocyte antigens (HLAs) have been identified. In contrast, there is almost no information known about the equivalent responses to genotype 3. Immune escape mechanisms used by HCV include the evolution of viral polymorphisms (adaptations) that abrogate this host–viral interaction. Evidence of HCV adaptation to HLA‐restricted immune pressure on HCV can be observed at the population level as viral polymorphisms associated with specific HLA types. To evaluate the escape patterns of HCV genotypes 1 and 3, we assessed the associations between viral polymorphisms and specific HLA types from 187 individuals with genotype 1a and 136 individuals with genotype 3a infection. We identified 51 HLA‐associated viral polymorphisms (32 for genotype 1a and 19 for genotype 3a). Of these putative viral adaptation sites, six fell within previously published epitopes. Only two HLA‐associated viral polymorphisms were common to both genotypes. In the remaining sites with HLA‐associated polymorphisms, there was either complete conservation or no significant HLA association with viral polymorphism in the alternative genotype. This study also highlights the diverse mechanisms by which viral evasion of immune responses may be achieved and the role of genotype variation in these processes. Conclusion: There is little overlap in HLA‐associated polymorphisms in the nonstructural proteins of HCV for the two genotypes, implying differences in the cellular immune pressures acting on these viruses and different escape profiles. These findings have implications for future therapeutic strategies to combat HCV infection, including vaccine design. (HEPATOLOGY 2009.)