Miracle-dz/UniFAR-FTUs huggingface dataset:
Interactions between primary sclerosing cholangitis and inflammatory bowel disease: implications in the adult liver transplant setting

ABSTRACT Introduction: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease which is associated with inflammatory bowel disease (IBD) in most cases. As there is currently no medical therapy which alters the natural history of PSC, liver transplantation may be required. Areas covered: We searched for articles in PubMed and critically reviewed current literature on the interrelationship between PSC and IBD with a specific focus on considerations for patients in the liver transplant setting. Expert commentary: PSC is an uncommon disease which limits available studies to be either retrospective or contain relatively small numbers of patients. Based on observations from these studies, the behavior and complications of PSC and IBD impact on each other both before and after a liver transplant. Both these autoimmune conditions and their associated cancer risk also influence patient selection for transplantation and may be impacted by immunosuppression use post-transplant. Hence, a complex interplay exists between PSC, IBD and liver transplantation which requires clarification with ongoing research.
Safety aspects of midazolam.

1 The LD50 in the rat and the mouse is about 1600 mg/kg (oral administration) and 75 mg/kg (rat) and 50 mg/kg (mouse) on intravenous administration. 2 Subchronic oral studies over 13 weeks in doses of 5, 15 and 45 mg/kg/day in the dog and 50, 100 and 200 mg/kg/day in the rat have demonstrated minimal toxicity for midazolam, as for other benzodiazepines. High doses produced increased liver weight in the rat and the expected increases in alkaline phosphatase in the dog (species-specific reaction). Detailed blood and urine analyses as well as histological examination of organs produced no indication of changes relevant for man. 3 Subchronic parenteral studies (i.v. and i.m. for five weeks) using up to 6 mg/kg/day in dogs and rats showed the compound to be not only systemically, but also locally, extremely well tolerated. 4 Reproduction toxicology studies have shown that midazolam is neither embryotoxic nor teratogenic and that it has no effect on the fertility and post-natal development of animals. 5 In the AMES test and the fluctuation test, midazolam had no mutagenic effect.
Compliance With Infectious Diseases Society of America Guidelines for Ophthalmologic Evaluation of Patients With Candidemia

Background: Although ophthalmologic examination is recommended for patients with candidemia, the rate of compliance with this recommendation is unknown. Method: We reviewed records for 100 consecutive adult patients who had candidemia. Results: Candida albicans was the pathogen in 55. Among the 80 patients who had an eye examination, 3 had endophthalmitis, and 2 had chorioretinitis. One of the 20 patients who had no examination later presented with endophthalmitis. Among 74 patients for whom an infectious diseases consultation was obtained, 66 (89%) had an ophthalmology consultation compared with 14 (54%) of 26 patients for whom an infectious diseases consultation was not obtained (P < 0.001). Conclusion: Infectious diseases consultation improves adherence to suggested guidelines for the evaluation of candidemia.
Exercise intolerance in pulmonary hypertension: mechanism, evaluation and clinical implications

ABSTRACT Introduction: Exercise intolerance in pulmonary hypertension (PH) is a major factor affecting activities of daily living and quality of life. Evaluation strategies (i.e., non-invasive and invasive tests) are integral to providing a comprehensive assessment of clinical and functional status. Despite a growing body of literature on the clinical consequences of PH, there are limited studies discussing the contribution of various physiological systems to exercise intolerance in this patient population. Areas covered: This review, through a search of various databases, describes the physiological basis for exercise intolerance across the various PH etiologies, highlights the various exercise evaluation methods and discusses the rationale for exercise training amongst those diagnosed with PH. Expert commentary: With the growing importance of evaluating exercise capacity in PH (class 1, Level C recommendation), understanding why exercise performance is altered in PH is crucial. Thus, the further study is required for better quality evidence in this area.
Inflammatory bowel disease: A paradigm for the link between coagulation and inflammation

&NA; Inflammatory bowel diseases (IBDs) are associated with platelet activation and an increased risk for thromboembolism. While the mechanisms that underlie the altered platelet function and hypercoagulable state in IBD remain poorly understood, emerging evidence indicates that inflammation and coagulation are interdependent processes that can initiate a vicious cycle wherein each process propagates and intensifies the other. This review addresses the mechanisms that may account for the mutual activation of coagulation and inflammation during inflammation and summarizes evidence that implicates a role for platelets and the coagulation system in the pathogenesis of human and experimental IBD. The proposed link between inflammation and coagulation raises the possibility of targeting the inflammation–coagulation interface to reduce the morbidity and mortality associated with IBD. (Inflamm Bowel Dis 2009)
Oral and intravenous iron treatment in inflammatory bowel disease: Hematological response and quality of life improvement

Background: The aim was to evaluate the efficacy and tolerance of oral and intravenous iron treatment in anemic inflammatory bowel disease (IBD) patients, considering both hematological and quality‐of‐life outcomes. Methods: We performed a prospective multicenter study in IBD patients with iron deficiency anemia. Patients having hemoglobin >10 g/dL were prescribed oral ferrous sulfate. If hemoglobin <10 g/dL, intravenous (sucrose) iron was administered. Oral iron‐intolerant patients were changed to intravenous treatment. Clinical (Truelove/Harvey–Bradshaw), hematological (response defined as hemoglobin normalization), and quality‐of‐life (shortened CCVEII‐9 questionnaire) evaluations were performed at baseline and at 3 and 6 months. Results: 100 IBD patients (59 Crohn's disease, 41 ulcerative colitis) were included. Mean basal hemoglobin levels were 10.8 ± 1.3 g/dL (range, 6.6–12.9). Seventy‐eight patients received oral treatment and 22 intravenous iron. Hemoglobin normalization was achieved in 86% of patients: 89% with oral, and 77% with intravenous iron. An IBD activity increase was not demonstrated in any patient. Four patients (5.1%) showed oral iron intolerance leading to discontinuation of treatment. No adverse events were reported for intravenous iron. Hemoglobin correlated with CCVEII‐9 (P < 0.001). The CCVEII‐9 score increased in patients who normalized hemoglobin levels in 3 months (from 58 ± 9 to 73 ± 10) or 6 months (54 ± 9, 68 ± 12, and 74 ± 10) (P < 0.001). Conclusions: Oral iron treatment is effective and well tolerated in most IBD patients, and does not exacerbate the symptoms of the underlying IBD. Intravenous iron, on the other hand, is an effective and safe alternative treatment for iron deficiency anemia in more severely anemic or intolerant patients. Anemia correction with iron treatment is associated with a relevant improvement in the patients' quality of life. (Inflamm Bowel Dis 2009)
The diagnosis and management of respiratory viral infections in cystic fibrosis

ABSTRACT Introduction: Respiratory viruses, such as those that cause influenza and the common cold, are a regular feature of life for the entire human population. Among people with CF, these viruses are associated with prolonged respiratory illness and show a clear association with pulmonary exacerbations which in turn are associated with lung function decline and risk of death. Human rhinovirus is the most commonly encountered respiratory viral pathogen in CF although adenovirus, bocavirus, coronavirus, influenza, parainfluenza, metapneumovirus and respiratory syncytial virus are all also responsible for infections in this population. Areas covered: This article reviews the epidemiology, clinical impact and therapeutic options for respiratory virus infection in both children and adults with CF. Expert commentary: The management of CF to date has largely focused on airway clearance strategies, nutritional support and aggressive antibacterial therapy. We highlight the significant role that respiratory viruses play in CF lung disease and argue that these pathogens represent an under-exploited target in the battle to control patients’ symptoms and disease progression.
Pulmonary fibrosis, part II: state-of-the-art patient management

ABSTRACT Introduction: While many pharmacologic therapies for the treatment of idiopathic pulmonary fibrosis (IPF) have been evaluated via randomized, placebo-controlled clinical trials (RCTs) conducted over the past two decades, most therapies have been shown to be ineffective or even potentially harmful. However, a number of recently completed RCTs have shown significant efficacy for pirfenidone and nintedanib for the treatment of IPF. Areas covered: This manuscript reviews recent advances in the management of IPF and other forms of fibrosing interstitial lung disease (ILD) with an emphasis on IPF. The material upon which this discussion is based was obtained from various published texts and manuscripts identified via literature searching (e.g. PubMed). Expert commentary: Anti-fibrotic drugs are now available for clinical use and perceived as standard-of-care therapies that have the potential to blunt disease progression for many patients with IPF. However, these agents do not necessarily stop disease progression or have a significant impact on mortality, and more effective pharmacologic therapies are needed for patients with IPF. Additionally, whether anti-fibrotic agents can be effective therapies for other forms of pulmonary fibrosis, which often have radiologic and histopathologic manifestations that mimic IPF, is being evaluated in a number of RCTs.
Mild chronic obstructive pulmonary disease: why spirometry is not sufficient!

ABSTRACT Introduction: Chronic obstructive pulmonary disease (COPD) – an inflammatory disease of the airways, alveoli and lung microvasculature – is a leading cause of death worldwide. Smokers with milder airway obstruction constitute the majority of patients with this disease. Many studies have shown increased morbidity, activity-related dyspnea, exercise intolerance and mortality in such patients, compared with age-matched healthy populations. Clinical evaluation of symptomatic smokers with ostensibly mild airway obstruction poses a challenge in clinical practice as spirometry can obscure extensive heterogeneous pathophysiological impairment. Areas covered: A detailed review of the evidence for complex biological, physiological and radiological abnormalities in smokers who barely fit arbitrary spirometric criteria for COPD diagnosis. A brief discussion of the debate about current diagnostic spirometric criteria for COPD that can lead to diagnostic confusion and, in-some-instances, to inappropriate management. Finally, we provide a review of the clinical implications of these structural and functional abnormalities and try to build a solid rationale for earlier detection and effective, timely management. Expert commentary: The prevalence of mild COPD among smokers is high, yet under-diagnosis remains a major problem and there is lack of evidence-based management recommendations for this sub-population. Further tests beyond spirometry are useful in uncovering patho-physiological derangements that are clinically relevant.
The paradigm shift to end tuberculosis. Are we ready to assume the changes?

ABSTRACT Introduction: Tuberculosis (TB) is the number one infectious disease killer and exemplifies the most neglected of them. Drug-susceptible TB presents with high mortality especially in atypical forms, disproportionally affecting immunosuppressed and vulnerable populations. The drug-resistant TB (DR-TB) epidemic, a world crisis, is sustained and increased through person-to-person transmission in households and the community. TB diagnostics and treatment in recent years are highly evolving fields. New rapid molecular tests are changing the perspectives in diagnosis and resistance screening. Also, new drugs and shorter regimens for DR-TB are appearing. For the first time in recent history, a large number of randomized control trials are incoming. Areas covered: This article reviews most TB advances including new diagnostic tests, drugs, and regimens and outlines upcoming drug trials while disclosing the potential gaps the in development of patient-centered systems and current organizational challenges leading to a delay in the uptake of these innovations. Expert commentary: Innovations are occurring, but not many are implemented on a wide scale in developing countries. TB health systems and staff are not getting updated in parallel. More efforts and funds are needed not only to implement current novelties but also to research for future solutions to eliminate TB.
Healthcare burden of inflammatory bowel disease in the United States: more than pain and diarrhea.

T he overall cost of healthcare in the United States has been growing, in part because of the increasing number of patients with chronic illness. Kappelman et al estimated the direct health care costs of children and adults with Crohn’s disease (CD) or ulcerative colitis (UC) in the US. They examined medical, surgical, and pharmaceutical insurance claims using the PharMetrics Patient-Centric Database for the time period between January 2003 and December 2004. In terms of demographics, this database provides a representative sample of the American population with commercial insurance. Each case was compared with 3 controls without inflammatory bowel disease (IBD). Cases and controls were matched for demographic factors including age, gender, health plan, and geographic location. The study population consisted of 9056 CD patients and their 24,829 matched controls, and 10,364 UC patients and their 28,160 matched controls. The mean age of IBD patients analyzed was 42 years for CD and 45 years for UC. Approximately 8% of CD patients and 5% of UC patients were under the age of 20 years. There was a slightly higher percentage of women than men with IBD. The authors found that the mean total costs were $10,952 per year for patients with CD and $2,898 for their matched controls. The mean treatment cost for CD was $8265 per patient-year. Pharmaceutical services constituted the highest percentage (35.3%) of these direct costs, with infliximab being the most expensive medication. Outpatient and hospitalization services closely followed with accounting for 33.3% and 31.4% of direct costs, respectively. Interestingly, surgical hospitalizations accounted for 40% of hospitalization expenses. For patients with UC, the mean total costs were $7948 per year and $2715 for their matched controls. The mean treatment cost for UC was $5,066 per patient-year. Hospitalizations were responsible for the highest percentage (37.6%) of these direct costs, followed by outpatient (34.9%) and pharmaceutical services (27.5%). Surgical hospitalizations accounted for 42% of hospitalization expenses. Oral and rectal aminosalicylates constituted the highest percentage of medication expenses for UC patients. The annual disease-attributable direct costs of IBD were estimated to be $3.6 billion for CD and $2.7 billion for UC. Patients in the top 1% of costs were responsible for a skewed proportion of overall costs. Children under age 20 years incurred higher annual expenses compared to adults. Children with CD had an estimated mean healthcare cost of $9555 compared to $8094 for adults with CD. For UC, the cost of caring for a child was almost double than that of caring for an adult ($10,063 versus $4610). Gender and geographical location did not play a large factor in healthcare costs.
Need for standardization in population‐based quality of life studies: A review of the current literature

&NA; In this systematic review we focus on the current use of and knowledge on health related quality of life in unselected, population‐based IBD cohorts. We made a systematic literature search and included for comprehensive review papers that described a population‐based cohort and that used validated HRQoL instruments. We show that even studies defined by the authors as population‐based do not always meet the criteria set for being population‐based. The heterogeneity of the study populations we have reviewed emphasizes that “population‐based” must be defined very meticulously and that study populations need to be scrutinized with regard to all characteristics of the cohort before one can compare their results. Different definitions of study populations as population‐based affect outcomes. We also show that use of the same HRQoL questionnaires does not guarantee comparable results as there are several different versions of the questionnaires, the different translations are not always comparable and at last there are several methods of computing and presenting the data. Detailed accumulation of knowledge and thorough meta analyses is therefore difficult hence we find it necessary to raise a discussion on the need of standardization in this field of research and we make some simple recommendations on factors we find important. (Inflamm Bowel Dis 2010)
Animal Welfare Policy , and the principles of the NIH Guide for the Care and Use of Laboratory Animals

0006-291X/$ see front matter 2013 Elsevier Inc. All rights reserved. http://dx.doi. org/10.1016/j.bbrc. 2013.08. 056 Abbreviations: miR, micro RNA; UCP2, uncoupling protein 2; siRNA, silencing RNA; IL-1b, interleukin 1 beta; THP1, human monocyte cell line. ⇑ Corresponding author. Fax: +1 813 974 8575. E-mail address: nkollipu@health.usf. edu (N. Kolliputi). 1 These authors contributed equally to this work. Sayantani Bandyopadhyay , Troy Lane , Rajanbabu Venugopal, Prasanna Tamarapu Parthasarathy, Young Cho, Lakshmi Galam, Richard Lockey, Narasaiah Kolliputi ⇑
Glucose variability and survival in critically ill children: Allostasis or harm?*

Objectives: To assess whether individual blood glucose variability in critically ill children is associated with increased mortality and to define the temporal patterns of blood glucose variability during critical illness in children. Design: Retrospective cohort study. Setting: A 20-bed pediatric intensive care unit in a children's hospital. Patients: Patients aged 0–20 yrs and with at least 12 blood glucose measurements taken within the first 72 hrs of pediatric intensive care unit admission. Interventions: None. Measurements and Main Results: A total of 101 eligible patients had 3,144 measured blood glucose concentrations with 16% mortality. Nonsurvivors had higher median blood glucose concentrations (129 mg/dL vs. 118 mg/dL, p < .01), more hyperglycemia (blood glucose >200 mg/dL) (88% vs. 59%, p < .05), and more hypoglycemia (blood glucose <60 mg/dL) (56% vs. 15%, p < .01) than survivors. The mean blood glucose range (257 mg/dL vs. 185 mg/dL, p < .01) and the blood glucose variability (63 mg/dL vs. 45 mg/dL, p = .02) were greater in nonsurvivors compared with survivors. Blood glucose variability tertiles were proportionately associated with increasing mortality: 6% vs. 15% vs. 27% (p = .07). Compared with survivors, daily blood glucose variability was significantly higher in nonsurvivors during the first 48 hrs of admission and after 1 wk of admission. After controlling for confounders, individual blood glucose variability was associated with higher pediatric intensive care unit mortality for each mg/dL of blood glucose concentration (adjusted odds ratio, 1.03; 95% confidence interval, 1.01–1.05). Conclusions: Glucose variability is common in critically ill children and is associated with increased mortality. Whereas early alterations in blood glucose may represent allostasis, later fluctuations in blood glucose may represent an alteration of autoregulation with resulting higher mortality. Control of variability may need to be incorporated into glycemic control regimens. (Pediatr Crit Care Med 2010; 11:707–712)
Colonic epithelial upregulation of interleukin 22 (IL-22) in patients with ulcerative colitis.

To the Editor: Inflammatory bowel disease (IBD) is a chronic inflammatory disease thought to be mediated by dysfunctional innate and/or adaptive immunity. This aberrant immune response leads to the secretion of harmful cytokines that destroy the epithelium of the gastrointestinal tract and thus cause further inflammation. Interleukin (IL)-22, a member of the IL-10 subfamily, is a recently identified T-cell-derived cytokine. Expression of IL-22 is induced in several human inflammatory conditions, including IBD. A recent article published by Sugimoto et al found that IL-22 gene delivery led to rapid amelioration of local intestinal inflammation in a dextran sulfate sodium-induced model of acute colitis. Expression of the IL-22 receptor is restricted to innate immune cells; however, the role of IL22 in ulcerative colitis (UC) patients has not yet been defined. This is the first study to our best knowledge with a larger sample that explores IL-22 gene expression from rectal biopsies in patients with UC. We measured the IL22 gene expression from rectum biopsies of UC patients from September 2008 to September 2009. All individuals were divided in 3 groups: 1) active UC (n 1⁄4 26); 2) long-term UC remission (n 1⁄4 11); and 3) a healthy control group (n 1⁄4 18). Expression of mRNA IL-22 was measured with a real-time polymerase chain reaction (RT-PCR) method. The following primers were used: IL-22 forward: ccctcaatctgataggttccag and reverse: gcaggtcatcaccttcaatatg; GADPH forward: gcccaatac gaccaaatcc and reverse: agccacatcgctcagaca for normalization. These results showed that IL-22 mRNA expression was upregulated in rectal mucosa from patients with active UC compared to UC patients in remission and healthy controls (P < 0.04 and P < 0.0001, respectively). Interestingly, the expression of IL-22 was also significantly increased in remission UC as compared to normal controls (P < 0.01) as shown in Figure 1. We also found that IL-22 gene expression correlated with histological activity (r 1⁄4 0.63 P < 0.0007) by Spearman correlation test. These findings confirmed the potential role of the IL-22 gene in the pathogenesis of UC and suggests that IL-22 might be involved as a defense mechanism by enhanced mucus production. In conclusion, gene expression of IL-22 was found to be increased from rectal biopsies in patients with UC.