Miracle-dz/UniFAR-FTUs huggingface dataset:
Use of surveillance for hepatocellular carcinoma among patients with cirrhosis in the United States

Surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is recommended but may not be performed. The extent and determinants of HCC surveillance are unknown. We conducted a population‐based United States cohort study of patients over 65 years of age to examine use and determinants of prediagnosis surveillance in patients with HCC who were previously diagnosed with cirrhosis. Patients diagnosed with HCC during 1994‐2002 were identified from the linked Surveillance, Epidemiology, and End‐Results registry–Medicare databases. We identified alpha‐fetoprotein (AFP) and ultrasound tests performed for HCC surveillance, and examined factors associated with surveillance. We identified 1,873 HCC patients with a prior diagnosis of cirrhosis. In the 3 years before HCC, 17% received regular surveillance and 38% received inconsistent surveillance. In a subset of 541 patients in whom cirrhosis was recorded for 3 or more years prior to HCC, only 29% received routine surveillance and 33% received inconsistent surveillance. Among all patients who received regular surveillance, approximately 52% received both AFP and ultrasound, 46% received AFP only, and 2% received ultrasound only. Patients receiving regular surveillance were more likely to have lived in urban areas and had higher incomes than those who did not receive surveillance. Before diagnosis, approximately 48% of patients were seen by a gastroenterologist/hepatologist or by a physician with an academic affiliation; they were approximately 4.5‐fold and 2.8‐fold, respectively, more likely to receive regular surveillance than those seen by a primary care physician only. Geographic variation in surveillance was observed and explained by patient and physician factors. Conclusion: Less than 20% of patients with cirrhosis who developed HCC received regular surveillance. Gastroenterologists/hepatologists or physicians with an academic affiliation are more likely to perform surveillance. HEPATOLOGY 2010
Examining Factors Associated with (In)Stability in Social Information Processing Among Urban School Children: A Latent Transition Analytic Approach

There is compelling evidence for the role of social information processing (SIP) in aggressive behavior. However, less is known about factors that influence stability versus instability in patterns of SIP over time. Latent transition analysis was used to identify SIP patterns over one year and examine how community violence exposure, aggressive behavior, and behavior regulation relate to (in)stability in SIP. Participants were 429 urban children (ages 7–13, M = 9.58; 86% African American). Latent transition analysis indicated four SIP profiles: stable low, decreasing, increasing, and stable high. Children with consistently high aggressive SIP reported the greatest community violence exposure and aggressive behavior. Compared to children who remained high on aggressive SIP, children whose aggressive SIP declined reported greater behavior regulation, suggesting that individual differences in executive function may account for stability in aggressive SIP during mid- to late childhood.
A meta‐analysis of randomized trials for the treatment of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) encompasses a histological spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). NAFLD carries a higher risk of cardio‐metabolic and liver‐related complications, the latter being confined to NASH and demanding specific treatment. We assessed the efficacy of proposed treatments for NAFLD/NASH by reviewing reports of randomized controlled trials (RCTs) on online databases and national and international meeting abstracts through January 2010. Primary outcome measure was histological improvement; secondary outcome was biochemical improvement; improvement in radiological steatosis was also evaluated. Two reviewers extracted articles using predefined quality indicators, independently and in duplicate. Main outcomes of randomized controlled trials (RCTs) were pooled using random‐effects or fixed‐effects models. Publication bias was assessed by funnel plots. Forty‐nine RCTs (30 in NASH) were included: 23 RCTs (22 in NASH, 1 in NAFLD) had post‐treatment histology. Most RCTs were small and did not exceed 1‐year duration. Weight loss, thiazolidinediones (especially pioglitazone), and antioxidants were most extensively evaluated. Weight loss was safe and dose‐dependently improved histological disease activity in NASH, but more than 50% of patients failed to achieve target weight loss. Thiazolidinediones improved steatosis and inflammation but yielded significant weight gain. RCTs with antioxidants yielded conflicting results and were heterogeneous with respect to type and dose of drug, duration, implementation of lifestyle intervention. Among the other agents, pentoxifylline, telmisartan and L‐carnitine improved liver histology in at least 1 RCT in NASH; polyunsaturated fatty acid (PUFA) ameliorated biochemical and radiological markers of NAFLD. Other approaches yielded negative results. Conclusion: Well‐designed RCTs of adequate size and duration, with histological endpoints, are needed to assess long‐term safety and efficacy of proposed treatments on patient‐oriented clinical outcomes. HEPATOLOGY 2010
The Need for New Therapies for Acute Ischaemic Stroke

Stroke creates the fourth highest burden of disease worldwide, and is the leading cause of adult long-term disability in developed countries. These factors mean that stroke has a high associated cost for healthcare systems, and a potentially devastating effect on family and carers. One of the main reasons why patients have such a poor prognosis is a lack of treatment options. Recombinant tissue plasminogen activator (rt-PA) is the only treatment currently licensed to treat selected patients with acute ischaemic stroke. However, only 1–8.5% of hospitalised patients receive treatment with rt-PA due to the short time window for administration (within 3 h of symptom onset), risk of intracerebral haemorrhage, need for a computed tomography scan, and exclusions due to other specific criteria. For acute ischaemic stroke, well-tolerated treatments that offer an extended therapeutic window are urgently needed to decrease disability, aid neurological recovery and improve patient prognosis. Neuroprotective agents potentially offer benefit to stroke patients without the associated haemorrhagic risk of thrombolytic therapy. Such agents target the ischaemic penumbra and aim to reduce the risk of brain injury and long-term disability by disrupting the cellular, biochemical, and metabolic consequences of infarction following exposure to ischaemia. Future directions should involve developing a neuroprotective compound that is safe, well tolerated and effective in a broad range of patients.
Freeze-dried B.C.G

It will be observed that when aneurysms causing subarachnoid haemorrhage are reviewed according to their anatomical site there is a consistently lower mortality rate in the groups dealt with conservatively. It should be pointed out that selection of cases has played little, if any, part; the control series was largely drawn from material acquired during a period of time when little good was thought likely to accrue from surgical methods of treatment. It is during the last few years that surgery has been attempted in almost every case. No attention has been paid to the presence of other disease processes present at the time of the patient's admission to hospital. Such factors are, of course, important and must be taken into consideration when larger numbers of case records dealing with specially sited aneurysms become available for study. In assessing the state of survivors of treatment, whether medical or surgical, " slight " indicates the presence of abnormal neurological signs which do not, however, hamper the patient in leading his normal life. The term " severe" is self-explanatory. Conclusions
Carriage of a tumor necrosis factor polymorphism amplifies the cytotoxic T‐lymphocyte antigen 4 attributed risk of primary biliary cirrhosis: Evidence for a gene–gene interaction

Common genetic variants significantly influence complex diseases such as primary biliary cirrhosis (PBC). We recently reported an association between PBC and a single nucleotide polymorphism (rs231725) of the immunoreceptor gene cytotoxic T‐lymphocyte antigen 4 (CTLA4). We hypothesized that PBC risk attributed to this polymorphism might be increased by propensity to an overly robust inflammatory response. Thus, we examined its potential interaction with the commonly studied −308AG promoter polymorphism (rs1800629) of the tumor necrosis factor (TNF) gene for which the variant TNF2A allele causes increased TNF production. The polymorphisms were genotyped in 866 PBC patients and 761 controls from independent US and Canadian registries; the effects of individual single nucleotide polymorphisms (SNPs) and their interaction on PBC risk was assessed by logistic regression. The reported association of PBC with the CTLA4 “A/A” genotype was replicated in the Canadian cohort and significant for PBC risk in the combined data (odds ratio [OR], 1.68; P = 0.0005). TNF2A allele frequency was elevated in PBC patients, but only reached borderline significance using the combined data (OR, 1.21; P = 0.042). Analysis showed that TNF2A carriage was significantly increased in CTLA4 “A/A” PBC patients compared with CTLA4 “A/A” controls (39.7% versus 16.5%, P = 0.0004); no apparent increase of TNF2A carriage was noted in CTLA4 “A/G” or “G/G” individuals. Finally, interaction under a logistic model was highly significant, as TNF2A carriage in combination with the CTLA4 “A/A” genotype was present in 6.5% of PBC patients, compared with 1.7% of controls (OR, 3.98; P < 0.0001). Conclusion: TNF2A amplifies the CTLA4 rs231725 “A/A” genotype risk for PBC. Although the mechanisms remain unclear, the premise that deficiency in T‐cell regulation resulting in an increased risk of PBC is amplified by overexpression of an important proinflammatory cytokine provides a basis for future functional studies. HEPATOLOGY 2010
Perivascular Spaces and the Two Steps to Neuroinflammation

Immune cells enter the central nervous system (CNS) from the circulation under normal conditions for immunosurveillance and in inflammatory neurologic diseases. This review describes the distinct anatomic features of the CNS vasculature that permit it to maintain parenchymal homeostasis and which necessitate specific mechanisms for neuroinflammation to occur. We review the historical evolution of the concept of the blood-brain barrier and discuss distinctions between diffusion/transport of solutes and migration of cells from the blood to CNS parenchyma. The former is regulated at the level of capillaries, whereas the latter takes place in postcapillary venules. We summarize evidence that entry of immune cells into the CNS parenchyma in inflammatory conditions involves 2 differently regulated steps: transmigration of the vascular wall into the perivascular space and progression across the glia limitans into the parenchyma.
Early-Onset Familial Lewy Body Dementia With Extensive Tauopathy: A Clinical, Genetic, and Neuropathological Study

We describe a Spanish family in which 3 of 4 siblings had dementia with Lewy bodies, 2 of them starting at age 26 years and the other at 29 years. The father has recently been diagnosed with Lewy body disease, with onset at 77 years. Neuropathological examination of the brain of the index patient disclosed unusual features characterized by diffuse Lewy body disease and generalized neurofibrillary tangle pathology but with no amyloid deposits in any region. Moreover, Lewy body pathology colocalized with neurofibrillary tangles in most affected neurons. Mutation screening that included all coding exons of presenilin 1 (PSEN1), presenilin 2 (PSEN2), &agr;-synuclein (SNCA), &bgr;-synuclein (SNCB), microtubule-associated protein tau (MAPT), leucine-rich repeat kinase 2 (LRRK2), glucocerebrosidase (GBA), and exons 16 and 17 of the amyloid precursor protein (APP) genes did not identify any mutation. Genome-wide single nucleotide polymorphism was performed in 4 family members and ruled out any pathogenic duplication or deletion in the entire genome. In summary, we report a unique family with pathologically confirmed early-onset dementia with Lewy bodies with widespread tau and &agr;-synuclein deposition. The absence of mutations in genes known to cause Lewy body disease suggests that a novel locus or loci are implicated in this neurodegenerative disease.
Future Directions in Childhood Adversity and Youth Psychopathology

Despite long-standing interest in the influence of adverse early experiences on mental health, systematic scientific inquiry into childhood adversity and developmental outcomes has emerged only recently. Existing research has amply demonstrated that exposure to childhood adversity is associated with elevated risk for multiple forms of youth psychopathology. In contrast, knowledge of developmental mechanisms linking childhood adversity to the onset of psychopathology—and whether those mechanisms are general or specific to particular kinds of adversity—remains cursory. Greater understanding of these pathways and identification of protective factors that buffer children from developmental disruptions following exposure to adversity is essential to guide the development of interventions to prevent the onset of psychopathology following adverse childhood experiences. This article provides recommendations for future research in this area. In particular, use of a consistent definition of childhood adversity, integration of studies of typical development with those focused on childhood adversity, and identification of distinct dimensions of environmental experience that differentially influence development are required to uncover mechanisms that explain how childhood adversity is associated with numerous psychopathology outcomes (i.e., multifinality) and identify moderators that shape divergent trajectories following adverse childhood experiences. A transdiagnostic model that highlights disruptions in emotional processing and poor executive functioning as key mechanisms linking childhood adversity with multiple forms of psychopathology is presented as a starting point in this endeavour. Distinguishing between general and specific mechanisms linking childhood adversity with psychopathology is needed to generate empirically informed interventions to prevent the long-term consequences of adverse early environments on children’s development.
Coffee reduces liver damage in a rat model of steatohepatitis: The underlying mechanisms and the role of polyphenols and melanoidins

Epidemiological data associate coffee consumption with a lower prevalence of chronic liver disease and a reduced risk of elevated liver enzyme levels (γ glutamyl transpeptidase and alanine aminotransferase), advanced liver disease and its complications, and hepatocellular carcinoma. Knowledge of the mechanisms underlying these effects and the coffee components responsible for these properties is still lacking. In this study, 1.5 mL/day of decaffeinated coffee or its polyphenols or melanoidins (corresponding to approximately 2 cups of filtered coffee or 6 cups of espresso coffee for a 70‐kg person) were added for 8 weeks to the drinking water of rats who were being fed a high‐fat, high‐calorie solid diet (HFD) for the previous 4 weeks. At week 12, HFD + water rats showed a clinical picture typical of advanced nonalcoholic steatohepatitis compared with control rats (normal diet + water). In comparison, HFD + coffee rats showed: (1) reduced hepatic fat and collagen, as well as reduced serum alanine aminotransferase and triglycerides; (2) a two‐fold reduced/oxidized glutathione ratio in both serum and liver; (3) reduced serum malondialdehyde (lipid peroxidation) and increased ferric reducing antioxidant power (reducing activity); (4) reduced expression of tumor necrosis factor α (TNF‐α), tissue transglutaminase, and transforming growth factor β and increased expression of adiponectin receptor and peroxisome proliferator‐activated receptor α in liver tissue; and (5) reduced hepatic concentrations of proinflammatory TNF‐α and interferon‐γ and increased anti‐inflammatory interleukin‐4 and interleukin‐10. Conclusion: Our data demonstrate that coffee consumption protects the liver from damage caused by a high‐fat diet. This effect was mediated by a reduction in hepatic fat accumulation (through increased fatty acid β‐oxidation); systemic and liver oxidative stress (through the glutathione system); liver inflammation (through modulation of genes); and expression and concentrations of proteins and cytokines related to inflammation. (HEPATOLOGY 2010;52:1652‐1661)
Implementation of family interventions in routine clinical practice following staff training programs: A major cause for concern

Abstract The efficacy of family interventions in schizophrenia is now well established. Major reviews of the literature all conclude that family psycho-educational interventions result in reduced relapse rates, hospitalisation rates and costs of care, in improved compliance with medication, and that they are applicable across cultures. However, there is no evidence that family approaches to schizophrenia are being offered on a global scale in mental health services. A number of studies have shown that clinicians can be trained effectively in family intervention skills, but there are major obstacles to the implementation of these interventions in routine clinical practice. The present study describes the results of a survey of 86 therapists who received training in Behavioural Family Therapy (BFT); 70% of therapists reported that they had used the approach in their work, but the mean number of families seen per therapist was only 1.7. Forty per cent of the families were seen by 8% of the therapists trained.
Drug‐induced acute liver failure: Results of a U.S. multicenter, prospective study

Acute liver failure (ALF) due to drug‐induced liver injury (DILI), though uncommon, is a concern for both clinicians and patients. The Acute Liver Failure Study Group has prospectively collected cases of all forms of acute liver failure since 1998. We describe here cases of idiosyncratic DILI ALF enrolled during a 10.5‐year period. Data were collected prospectively, using detailed case report forms, from 1198 subjects enrolled at 23 sites in the United States, all of which had transplant services. A total of 133 (11.1%) ALF subjects were deemed by expert opinion to have DILI; 81.1% were considered highly likely, 15.0% probable, and 3.8% possible. Subjects were mostly women (70.7%) and there was overrepresentation of minorities for unclear reasons. Over 60 individual agents were implicated, the most common were antimicrobials (46%). Transplant‐free (3‐week) survival was poor (27.1%), but with highly successful transplantation in 42.1%, overall survival was 66.2%. Transplant‐free survival in DILI ALF is determined by the degree of liver dysfunction, specifically baseline levels of bilirubin, prothrombin time/international normalized ratio, and Model for End‐Stage Liver Disease scores. Conclusion: DILI is an uncommon cause of ALF that evolves slowly, affects a disproportionate number of women and minorities, and shows infrequent spontaneous recovery, but transplantation affords excellent survival. (HEPATOLOGY 2010)
The Relationship Between Lipid Peroxidation and LDL Desialylation in Experimental Atherosclerosis

ABSTRACT High serum total cholesterol concentration has been strongly connected with atherosclerosis in numerous studies. Being the main carrier of cholesterol in blood, low-density lipoprotein (LDL) is also the principal lipoprotein causing atherosclerosis. Sialic acids are a family of amino sugars that are commonly found as terminal oligosaccharide residues on glycoproteins and are sialylated on their apolipoprotein and glycolipid constituents. In several studies, it was demonstrated that LDL has a 2.5- to 5-fold lower content of sialic acid in patients with coronary artery disease compared with healthy subjects. The role of oxidatively modified LDL in the pathogenesis has been well documented. These studies have focused on modifications in the lipid and protein parts of LDL. But recently, desialylated LDL and its relation with the oxidation mechanisms have received attention in the pathogenesis of atherosclerosis and coronary artery disease (CAD). From these points, we have performed atheroma plaques in an experimental atherosclerosis model with rabbits and examined the LDL and plasma sialic acid and thiobarbituric acid reactive substance (TBARS) levels in the same model. We also have determined serum sialidase enzyme activities relevant with these parameters. LDL sialic acid levels were significantly decreased in the progression of the atherosclerosis (by the 30th, 60th, and 90th days). LDL and plasma TBARS levels and plasma sialidase enzyme activities were significantly elevated by the same time periods. In conclusion, serum sialidase enzyme may play an important role in the desialylation mechanism, and reactive oxygen substance (ROS) may affect this reaction.
Repeated radiofrequency ablation for management of patients with cirrhosis with small hepatocellular carcinomas: A long‐term cohort study

In most patients with cirrhosis, successful percutaneous ablation or surgical resection of hepatocellular carcinoma (HCC) is followed by recurrence. Radiofrequency ablation (RFA) has proven effective for treating HCC nodules, but its repeatability in managing recurrences and the impact of this approach on survival has not been evaluated. To this end, we retrospectively analyzed a prospective series of 706 patients with cirrhosis (Child‐Pugh class ≤B7) who underwent RFA for 859 HCC ≤35 mm in diameter (1‐2 per patient). The results of RFA were classified as complete responses (CRs) or treatment failures. CRs were obtained in 849 nodules (98.8%) and 696 patients (98.5%). During follow‐up (median, 29 months), 465 (66.8%) of the 696 patients with CRs experienced a first recurrence at an incidence rate of 41 per 100 person‐years (local recurrence 6.2; nonlocal 35). Cumulative incidences of first recurrence at 3 and 5 years were 70.8% and 81.7%, respectively. RFA was repeated in 323 (69.4%) of the 465 patients with first recurrence, restoring disease‐free status in 318 (98.4%) cases. Subsequently, RFA was repeated in 147 (65.9%) of the 223 patients who developed a second recurrence after CR of the first, restoring disease‐free status in 145 (98.6%) cases. Overall, there were 877 episodes of recurrence (1‐8 per patient); 577 (65.8%) of these underwent RFA that achieved CRs in 557 (96.5%) cases. No procedure‐related deaths occurred in 1,921 RFA sessions. Estimated 3‐ and 5‐year overall and disease‐free (after repeated RFAs) survival rates were 67.0% and 40.1% and 68.0 and 38.0%, respectively. Conclusion: RFA is safe and effective for managing HCC in patients with cirrhosis, and its high repeatability makes it particularly valuable for controlling intrahepatic recurrences. (HEPATOLOGY 2011)
The Intersection of the Medicare End-Stage Renal Disease (ESRD) Benefit and Hospice: An Overview for Home Care and Hospice Clinicians

End-of-life care is underutilized in patients with kidney failure despite high mortality and multiple comorbid conditions. Recent revisions in the Medicare Benefit Policy Manual and the Conditions for Coverage for End-Stage Renal Disease provide a clearer understanding for referral to palliative and hospice care. There are recommendations to improve end-of-life care in this complicated population.