Open AccessFeature PaperArticle
Integrating Autism Care through a School-Based Intervention Model: A Pilot Study
J. Clin. Med. 2017, 6(10), 97; doi:10.3390/jcm6100097 -
Abstract
The purpose of this pilot study is to determine the feasibility of monitoring the progress of children with an autism spectrum disorder (ASD) both in school and at home to promote a school-based integrated care model between parents, teachers, and medical providers. This
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The purpose of this pilot study is to determine the feasibility of monitoring the progress of children with an autism spectrum disorder (ASD) both in school and at home to promote a school-based integrated care model between parents, teachers, and medical providers. This is a prospective cohort study. To monitor progress, outcome measures were administered via an online platform developed for caregivers and teachers of children (n = 30) attending a school specializing in neurodevelopmental disorders and using an integrated medical and education program. Longitudinal analysis showed improvements in a novel scale, the Teacher Autism Progress Scale (TAPS), which was designed to measure key autism-related gains in a school environment (2.1-point improvement, p = 0.004, ES = 0.324). The TAPS showed a strong and statistically significant correlation, with improvement in aberrant behavior (r = −0.50; p = 0.008) and social responsiveness (r = −0.70; p < 0.001). The results also showed non-statistically significant improvements in aberrant behavior, social responsiveness, and quality of life over time at both school and home. To assess feasibility of ongoing progress measurement, we assessed missing data, which showed caregivers were more likely to miss surveys during summer. Results demonstrate the value and feasibility of online, longitudinal data collection in school to assist with individualized education planning and collaborative care for children with ASD. Lessons learned in this pilot will support school outcomes researchers in developing more efficacious, collaborative treatment plans between clinicians, caregivers, and teachers. Full article
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Open AccessCase Report
X-pert MTB/RIF® Diagnosis of Twin Infants with Tuberculosis in Da Nang, Viet Nam
J. Clin. Med. 2017, 6(10), 96; doi:10.3390/jcm6100096 -
Abstract
4-month-old twins were diagnosed with X-pert MTB/RIF® confirmed tuberculosis (TB)[...] Full article
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Open AccessFeature PaperArticle
Myocardial Expression of Macrophage Migration Inhibitory Factor in Patients with Heart Failure
J. Clin. Med. 2017, 6(10), 95; doi:10.3390/jcm6100095 -
Abstract
Macrophage migration inhibitory factor (MIF) is a pleiotropic inflammatory protein and contributes to several different inflammatory and ischemic/hypoxic diseases. MIF was shown to be cardioprotective in experimental myocardial ischemia/reperfusion injury and its expression is regulated by the transcription factor hypoxia-inducible factor (HIF)-1α. We
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Macrophage migration inhibitory factor (MIF) is a pleiotropic inflammatory protein and contributes to several different inflammatory and ischemic/hypoxic diseases. MIF was shown to be cardioprotective in experimental myocardial ischemia/reperfusion injury and its expression is regulated by the transcription factor hypoxia-inducible factor (HIF)-1α. We here report on MIF expression in the failing human heart and assess myocardial MIF in different types of cardiomyopathy. Myocardial tissue samples from n = 30 patients were analyzed by quantitative Real-Time PCR. MIF and HIF-1α mRNA expression was analyzed in myocardial samples from patients with ischemic (ICM) and non-ischemic cardiomyopathy (NICM) and from patients after heart transplantation (HTX). MIF expression was elevated in myocardial samples from patients with ICM compared to NICM. Transplanted hearts showed lower MIF levels compared to hearts from patients with ICM. Expression of HIF-1α was analyzed and was shown to be significantly increased in ICM patients compared to patients with NICM. MIF and HIF-1α mRNA is expressed in the human heart. MIF and HIF-1α expression depends on the underlying type of cardiomyopathy. Patients with ICM show increased myocardial MIF and HIF-1α expression. Full article
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Open AccessFeature PaperArticle
Cancer and the LGBTQ Population: Quantitative and Qualitative Results from an Oncology Providers’ Survey on Knowledge, Attitudes, and Practice Behaviors
J. Clin. Med. 2017, 6(10), 93; doi:10.3390/jcm6100093 -
Abstract
Background: Despite growing social acceptance, the LGBTQ population continues to face barriers to healthcare including fear of stigmatization by healthcare providers, and providers’ lack of knowledge about LGBTQ-specific health issues. This analysis focuses on the assessment of quantitative and qualitative responses from a
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Background: Despite growing social acceptance, the LGBTQ population continues to face barriers to healthcare including fear of stigmatization by healthcare providers, and providers’ lack of knowledge about LGBTQ-specific health issues. This analysis focuses on the assessment of quantitative and qualitative responses from a subset of providers who identified as specialists that treat one or more of the seven cancers that may be disproportionate in LGBTQ patients. Methods: A 32-item web-based survey was emailed to 388 oncology providers at a single institution. The survey assessed: demographics, knowledge, attitudes, and practice behaviors. Results: Oncology providers specializing in seven cancer types had poor knowledge of LGBTQ-specific health needs, with fewer than half of the surveyed providers (49.5%) correctly answering knowledge questions. Most providers had overall positive attitudes toward LGBTQ patients, with 91.7% agreeing they would be comfortable treating this population, and would support education and/or training on LGBTQ-related cancer health issues. Conclusion: Results suggest that despite generally positive attitudes toward the LGBTQ population, oncology providers who treat cancer types most prevalent among the population, lack knowledge of their unique health issues. Knowledge and practice behaviors may improve with enhanced education and training on this population’s specific needs. Full article
Open AccessArticle
Diagnostic Accuracy of FebriDx: A Rapid Test to Detect Immune Responses to Viral and Bacterial Upper Respiratory Infections
J. Clin. Med. 2017, 6(10), 94; doi:10.3390/jcm6100094 -
Abstract
C-reactive protein (CRP) and myxovirus resistance protein A (MxA) are associated with bacterial and viral infections, respectively. We conducted a prospective, multicenter, cross-sectional study of adults and children with febrile upper respiratory tract infections (URIs) to evaluate the diagnostic accuracy of a rapid
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C-reactive protein (CRP) and myxovirus resistance protein A (MxA) are associated with bacterial and viral infections, respectively. We conducted a prospective, multicenter, cross-sectional study of adults and children with febrile upper respiratory tract infections (URIs) to evaluate the diagnostic accuracy of a rapid CRP/MxA immunoassay to identify clinically significant bacterial infection with host response and acute pathogenic viral infection. The reference standard for classifying URI etiology was an algorithm that included throat bacterial culture, upper respiratory PCR for viral and atypical pathogens, procalcitonin, white blood cell count, and bandemia. The algorithm also allowed for physician override. Among 205 patients, 25 (12.2%) were classified as bacterial, 53 (25.9%) as viral, and 127 (62.0%) negative by the reference standard. For bacterial detection, agreement between FebriDx and the reference standard was 91.7%, with FebriDx having a sensitivity of 80% (95% CI: 59–93%), specificity of 93% (89–97%), positive predictive value (PPV) of 63% (45–79%), and a negative predictive value (NPV) of 97% (94–99%). For viral detection, agreement was 84%, with a sensitivity of 87% (75–95%), specificity of 83% (76–89%), PPV of 64% (63–75%), and NPV of 95% (90–98%).FebriDx may help to identify clinically significant immune responses associated with bacterial and viral URIs that are more likely to require clinical management or therapeutic intervention, and has potential to assist with antibiotic stewardship. Full article
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Open AccessFeature PaperArticle
History and Outcome of Febrile Neutropenia Outside the Oncology Setting: A Retrospective Study of 76 Cases Related to Non-Chemotherapy Drugs
J. Clin. Med. 2017, 6(10), 92; doi:10.3390/jcm6100092 -
Abstract
Background: Despite major advances in its prevention and treatment, febrile neutropenia remains a most concerning complication of cancer chemotherapy. Outside the oncology setting, however, only few data are currently available on febrile neutropenia related to non-chemotherapy drugs. We report here data on 76
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Background: Despite major advances in its prevention and treatment, febrile neutropenia remains a most concerning complication of cancer chemotherapy. Outside the oncology setting, however, only few data are currently available on febrile neutropenia related to non-chemotherapy drugs. We report here data on 76 patients with febrile neutropenia related to non-chemotherapy drugs, followed up in a referral center within a university hospital. Patients and methods: Data from 76 patients with idiosyncratic drug-induced febrile neutropenia were retrospectively reviewed. All cases were extracted from a cohort study on agranulocytosis conducted at the Strasbourg University Hospital (Strasbourg, France). Results: Mean patient age was 52.2 years old (range: 18–93) and gender ratio (F/M) 1.6, with several comorbidities present in 86.8% of patients. The most common causative drugs were: antibiotics (37.4%), antithyroid drugs (17.2%), neuroleptic and anti-epileptic agents (13.1%), non-steroidal anti-inflammatory agents and analgesics (8%), and platelet aggregation inhibitors (8%). Main clinical presentations upon hospitalization included isolated fever (30%), sore throat, acute tonsillitis and sinusitis (18.4%), documented pneumonia (18.4%), septicemia (14.5%), and septic shock (6.6%). Mean neutrophil count at nadir was 0.13 × 10(9)/L (range: 0–0.48). While in hospital, 22 patients (28.9%) worsened clinically and required intensive care unit placement. All patients were promptly treated with broad-spectrum antibiotics, and 45 (59.2%) with hematopoietic growth factors. Mean duration of hematological recovery (neutrophil count ≥1.5 × 10(9)/L) was 7.5 days (range: 2–21), which was reduced to 0.7 days (range: 2–16) (p = 0.089) with hematopoietic growth factors. Outcome was favorable in 89.5% of patients, whereas eight died. Conclusions: Like in oncology and myelosuppressive chemotherapy settings, idiosyncratic febrile neutropenia is typically serious, about 40% of patients exhibiting severe pneumonia, septicemia, and septic shock, with a mortality rate of 10%. Like in febrile, chemotherapy-related neutropenia, modern and timely management (immediate broad spectrum antibiotherapy, hematopoietic growth factors) may reduce infection-related mortality. All practitioners should be aware of this potential side-effect that may even occur in the event of “daily medication” exposure. Full article
Open AccessReview
Comparison of Minimal Residual Disease Detection by Multiparameter Flow Cytometry, ASO-qPCR, Droplet Digital PCR, and Deep Sequencing in Patients with Multiple Myeloma Who Underwent Autologous Stem Cell Transplantation
J. Clin. Med. 2017, 6(10), 91; doi:10.3390/jcm6100091 -
Abstract
Multiple myeloma (MM) is a hematological malignancy with a poor prognosis, characterized by clonal proliferation of plasma cells in the bone marrow (BM). Relapse due to undetected minimal residual disease (MRD) is the leading cause of death among patients with MM. This review
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Multiple myeloma (MM) is a hematological malignancy with a poor prognosis, characterized by clonal proliferation of plasma cells in the bone marrow (BM). Relapse due to undetected minimal residual disease (MRD) is the leading cause of death among patients with MM. This review summarizes the methods and prognostic value of MRD assessment in BM and autografts from MM patients who underwent autologous stem cell transplantation (ASCT) by multiparameter flow cytometry (MFC), allele-specific oligonucleotide real-time quantitative PCR (ASO-qPCR), droplet digital PCR (ddPCR), and next-generation sequencing (NGS)-based detection methods. MRD assessment using NGS-based approaches has clear prognostic value and better sensitivity compared to traditional methods. Full article
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Open AccessFeature PaperReview
Process and Pitfalls of Sperm Cryopreservation
J. Clin. Med. 2017, 6(9), 89; doi:10.3390/jcm6090089 -
Abstract
Sperm cryopreservation has been utilized routinely for over 40 years to preserve fertility in men undergoing cancer therapy and allow conception for infertile couples. This article provides a concise and up-to-date review of the literature and covers the latest advances in sperm cryopreservation
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Sperm cryopreservation has been utilized routinely for over 40 years to preserve fertility in men undergoing cancer therapy and allow conception for infertile couples. This article provides a concise and up-to-date review of the literature and covers the latest advances in sperm cryopreservation and its array of clinical indications. Over recent years, the scope of clinical indications used for sperm cryopreservation has expanded widely. Consequently, more patient groups are eligible for sperm freezing, requiring specialist resources and higher running costs. Although sperm cryopreservation prior to cancer therapy is readily available in many countries, referral rates by oncology specialists and levels of patient engagement with cryopreservation services are both reported as low. Furthermore, sperm banking continues to raise ethical issues such whether sperm donation should be anonymous and whether sperm can be utilized posthumously by the surviving partner without consent from the patient. This review focuses on the technological advances and ethical controversies in sperm cryopreservation, and how better understanding of these issues could lead to improved access to fertility preserving treatment for patients. Full article
Open AccessFeature PaperArticle
Measurement of Respiratory Chain Enzyme Activity in Human Renal Biopsy Specimens
J. Clin. Med. 2017, 6(9), 90; doi:10.3390/jcm6090090 -
Abstract
Background: Mitochondrial disorders can present as kidney disease in children and be difficult to diagnose. Measurement of mitochondrial function in kidney tissue may help diagnosis. This study was to assess the feasibility of obtaining renal samples and analysing them for respiratory chain
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Background: Mitochondrial disorders can present as kidney disease in children and be difficult to diagnose. Measurement of mitochondrial function in kidney tissue may help diagnosis. This study was to assess the feasibility of obtaining renal samples and analysing them for respiratory chain enzyme activity. Methods: The subjects were children undergoing a routine diagnostic renal biopsy, in whom a clinical condition of renal inflammation, scarring and primary metabolic disorder was unlikely. A fresh sample of kidney was snap frozen and later assayed for the activities of respiratory chain enzyme complexes I, II/III, and IV using spectrophotometric enzyme assay, and expressed as a ratio of citrate synthase activity. Results: The range of respiratory chain enzyme activity for complex I was 0.161 to 0.866 (mean 0.404, SD 0.2), for complex II/III was 0.021 to 0.318 (mean 0.177, SD 0.095) and for complex IV was 0.001 to 0.025 (mean 0.015, SD 0.006). There were correlations between the different activities but not between them and the age of the children or a measure of the amount of chronic damage in the kidneys. Conclusion: It is feasible to measure respiratory chain enzyme activity in routine renal biopsy specimens. Full article
Open AccessArticle
Gut Microbiota-Dependent Trimethylamine-N-oxide and Serum Biomarkers in Patients with T2DM and Advanced CKD
J. Clin. Med. 2017, 6(9), 86; doi:10.3390/jcm6090086 -
Abstract
Trimethylamine-N-oxide (TMAO) is a product of dietary, gut microbiome, and tissues metabolism. Elevated blood TMAO levels are associated with heart attack, stroke and chronic kidney disease (CKD). The purpose of our study was to investigate the gut microbiota associated with trimethylamine
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Trimethylamine-N-oxide (TMAO) is a product of dietary, gut microbiome, and tissues metabolism. Elevated blood TMAO levels are associated with heart attack, stroke and chronic kidney disease (CKD). The purpose of our study was to investigate the gut microbiota associated with trimethylamine (TMA) production, the precursor of TMAO, and the serum levels of TMAO and inflammatory biomarkers associated with type 2 diabetes mellitus (T2DM) and CKD. Twenty adults with T2DM and advanced CKD and 20 healthy adults participated in the study. Analyses included anthropometric and metabolic parameters, characterization of TMA producing gut microbiota, and concentrations of TMAO, lipopolysaccharides (LPS) endotoxin, zonulin (Zo) gut permeability marker, and serum inflammatory and endothelial dysfunction biomarkers. Diversity of the gut microbiota was identified by amplification of V3–V4 regions of the 16S ribosomal RNA genes and DNA sequencing. TMAO was quantified by Mass Spectrometry and serum biomarkers by ELISA. The significance of measurements justified by statistical analysis. The gut microbiome in T2DM-CKD patients exhibited a higher incidence of TMA-producing bacteria than control, p < 0.05. The serum levels of TMAO in T2DM-CKD patients were significantly higher than controls, p < 0.05. TMAO showed a positive correlation with Zo and LPS, inflammatory and endothelial dysfunction biomarkers. A positive correlation was observed between Zo and LPS in T2DM-CKD subjects. An increased abundance of TMA-producing bacteria in the gut microbiota of T2DM-CKD patients together with excessive TMAO and increased gut permeability might impact their risk for cardiovascular disease through elevation of chronic inflammation and endothelial dysfunction. Full article
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Open AccessFeature PaperCase Report
Can Diet Help Non-Obese Individuals with Non-Alcoholic Fatty Liver Disease (NAFLD)?
J. Clin. Med. 2017, 6(9), 88; doi:10.3390/jcm6090088 -
Abstract
Subjects diagnosed with non-alcoholic fatty liver disease (NAFLD) or hepatic steatosis are usually obese or overweight. NAFLD has also been reported in many non-obese healthy subjects as an incidental finding during imaging. Subjects with early-stage NAFLD who are otherwise healthy are often left
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Subjects diagnosed with non-alcoholic fatty liver disease (NAFLD) or hepatic steatosis are usually obese or overweight. NAFLD has also been reported in many non-obese healthy subjects as an incidental finding during imaging. Subjects with early-stage NAFLD who are otherwise healthy are often left unmanaged in current clinical practice; it is not clear if an early intervention in those individuals would be of any benefit in preventing NAFLD progression to more serious conditions. Since many of these subjects are non-alcoholic and have a normal body mass index (BMI), an intensive lifestyle change program is not usually recommended. This report presents an otherwise healthy non-alcoholic subject with incidental NAFLD having a normal BMI and a waist circumference below 90 cm who successfully reversed his condition by undertaking a lifestyle intervention. The case report is expected to encourage large cohort studies to substantiate the benefits of dietary interventions in alleviating hepatic steatosis among non-obese individuals. Full article
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Open AccessFeature PaperReview
Technical Advances in the Measurement of Residual Disease in Acute Myeloid Leukemia
J. Clin. Med. 2017, 6(9), 87; doi:10.3390/jcm6090087 -
Abstract
Outcomes for those diagnosed with acute myeloid leukemia (AML) remain poor. It has been widely established that persistent residual leukemic burden, often referred to as measurable or minimal residual disease (MRD), after induction therapy or at the time of hematopoietic stem cell transplant
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Outcomes for those diagnosed with acute myeloid leukemia (AML) remain poor. It has been widely established that persistent residual leukemic burden, often referred to as measurable or minimal residual disease (MRD), after induction therapy or at the time of hematopoietic stem cell transplant (HSCT) is highly predictive for adverse clinical outcomes and can be used to identify patients likely to experience clinically evident relapse. As a result of inherent genetic and molecular heterogeneity in AML, there is no uniform method or protocol for MRD measurement to encompass all cases. Several techniques focusing on identifying recurrent molecular and cytogenetic aberrations or leukemia-associated immunophenotypes have been described, each with their own strengths and weaknesses. Modern technologies enabling the digital quantification and tracking of individual DNA or RNA molecules, next-generation sequencing (NGS) platforms, and high-resolution imaging capabilities are among several new avenues under development to supplement or replace the current standard of flow cytometry. In this review, we outline emerging modalities positioned to enhance MRD detection and discuss factors surrounding their integration into clinical practice. Full article
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Open AccessCase Report
Efficacy of Octocog Alfa (Advate) in a Child with Type 3 von Willebrand Disease and Alloantibodies
J. Clin. Med. 2017, 6(9), 85; doi:10.3390/jcm6090085 -
Abstract
Von Willebrand disease (VWD) is the most frequent inherited bleeding disorder and is caused by either a quantitative and/or qualitative defect of the multimeric glycoprotein vonWillebrand factor (VWF).[...] Full article
Open AccessFeature PaperArticle
Feasibility of Serial 6-min Walk Tests in Patients with Acute Heart Failure
J. Clin. Med. 2017, 6(9), 84; doi:10.3390/jcm6090084 -
Abstract
Background: Functional status assessment is common in many cardiovascular diseases but it has undergone limited study in the setting of acute heart failure (AHF). Accordingly, we performed a pilot study of the feasibility of the six-minute walk test (6MWT) at the emergency department
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Background: Functional status assessment is common in many cardiovascular diseases but it has undergone limited study in the setting of acute heart failure (AHF). Accordingly, we performed a pilot study of the feasibility of the six-minute walk test (6MWT) at the emergency department (ED) presentation and through the hospitalization in patients with AHF. Methods and Results: From November 2014 to February 2015, we conducted a multicenter, observational study of ED patients, aged 18–85 years, whose primary ED admission diagnosis was AHF. Other criteria for enrollment included a left ventricular ejection fraction ≤40%, systolic blood pressure between 90 and 170 mmHg, and verbal confirmation that the patient was able to walk >30 m at the baseline, prior to ED presentation. Study teams were uniformly trained to administer a 6MWT. Patients underwent a baseline 6MWT within 24 h of ED presentation (Day 1) and follow-up 6MWTs at 24 (Day 2), 48 (Day 3), and 120 h (Day 5). A total of 46 patients (65.2% male, 73.9% African American) had a day one mean walk distance of 137.3 ± 78 m, day 2 of 170.9 ± 100 m, and day 3 of 180.8 ± 98 m. The 6MWT demonstrated good reproducibility, as the distance walked on the first 6MWT on Day 3 was similar to the distance on the repeated 6MWT the same day. Conclusions: Our pilot study demonstrates the feasibility of the 6MWT as a functional status endpoint in AHF patients. A larger study in a more demographically diverse cohort of patients is necessary to confirm its utility and association with 30-day heart failure (HF) events. Full article
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Open AccessFeature PaperCase Report
Unexplained Dyspnea in a Young Adult with Epstein–Barr Virus Infectious Mononucleosis: Pulmonary Involvement or Co-Infection with Mycoplasmapneumoniae Pneumonia?
J. Clin. Med. 2017, 6(9), 83; doi:10.3390/jcm6090083 -
Abstract
Clinically, in young immunocompetent adults, Epstein-Barr virus (EBV) usually manifests as infectious mononucleosis (IM). Typical clinical findings of EBV IM include fever, profound fatigue, pharyngitis, bilateral posterior cervical adenopathy, and splenomegaly. Respiratory involvement with EBV IM may occur, but is distinctly rare. We
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Clinically, in young immunocompetent adults, Epstein-Barr virus (EBV) usually manifests as infectious mononucleosis (IM). Typical clinical findings of EBV IM include fever, profound fatigue, pharyngitis, bilateral posterior cervical adenopathy, and splenomegaly. Respiratory involvement with EBV IM may occur, but is distinctly rare. We present a case of a 20 year old female who with classic EBV IM, but was inexplicably dyspneic and hypoxemic. Further diagnostic testing confirmed co-infection with Mycoplasma pneumoniae. As a non-zoonotic atypical community-acquired pneumonia (CAP), M. pneumoniae may rarely be accompanied by severe hypoxemia and even acute respiratory distress syndrome. She represented a diagnostic dilemma regarding the cause of her hypoxemia, i.e., due to EBV IM with pulmonary involvement or severe M. pneumoniae CAP. The patient slowly recovered with respiratory quinolone therapy. Full article
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Open AccessFeature PaperReview
IL-23 and Th17 Disease in Inflammatory Arthritis
J. Clin. Med. 2017, 6(9), 81; doi:10.3390/jcm6090081 -
Abstract
IL-23, which is composed of p19 and p40 subunits, is a proinflammatory cytokine that contributes to the formation and maintenance of Th17 cells in inflammatory autoimmune diseases. IL-23 is a human osteoclastogenic cytokine and anti-IL-23 antibody attenuates paw volume and joint destruction in
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IL-23, which is composed of p19 and p40 subunits, is a proinflammatory cytokine that contributes to the formation and maintenance of Th17 cells in inflammatory autoimmune diseases. IL-23 is a human osteoclastogenic cytokine and anti-IL-23 antibody attenuates paw volume and joint destruction in CIA rats. IL-23 levels in serum and synovial fluid are high in rheumatoid arthritis (RA) patients, and IL-23 may be a useful biomarker for the diagnosis of RA. In addition, IL-23 affects the pathogenesis of inflammation and bone destruction through interaction with other cytokines such as IL-17 and TNF-α. Furthermore, polymorphisms of IL23R are a risk factor for ankylosing spondylitis (AS) and psoriatic arthritis (PsA), which indicates that IL-23 is also involved in the pathogenesis of spondyloarthritis (SpA). Finally, IL-17 and IL-23 inhibitors reduce the clinical manifestations of SpA. Thus, the IL-23/Th17 pathway is a therapeutic target for the treatment of inflammatory arthritis. Full article
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Open AccessFeature PaperReview
Acute Kidney Injury in Heart Failure Revisited—The Ameliorating Impact of “Decongestive Diuresis” on Renal Dysfunction in Type 1 Acute Cardiorenal Syndrome: Accelerated Rising Pro B Naturetic Peptide Is a Predictor of Good Renal Prognosis
J. Clin. Med. 2017, 6(9), 82; doi:10.3390/jcm6090082 -
Abstract
There is mounting evidence that forward heart failure as manifested by low cardiac output alone does not define the degree of renal dysfunction in cardiorenal syndrome. As a result, the term “congestive renal failure” was coined in 2012 by Ross to depict the
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There is mounting evidence that forward heart failure as manifested by low cardiac output alone does not define the degree of renal dysfunction in cardiorenal syndrome. As a result, the term “congestive renal failure” was coined in 2012 by Ross to depict the role of renal venous hypertension in type 1 acute cardiorenal syndrome. If so, aggressive decongestive therapies, either through mechanical ultrafiltration with dialysis machines or pharmacologic ultrafiltration with potent diuretics, would lead to improved cardio and renal outcomes. Nevertheless, as recently as 2012, a review of this literature had concluded that a renal venous hypertension-directed approach using diuretics to manage cardio-renal syndrome was yet to be fully investigated. We, in this review, with three consecutive case series, describe our experience with pharmacologic decongestive diuresis in this paradigm of care and argue for studies of such therapeutic interventions in the management of cardiorenal syndrome. Finally, based on our observations in the Renal Unit, Mayo Clinic Health System, in Northwestern Wisconsin, we have hypothesized that patients with cardiorenal syndrome presenting with accelerated rising Pro B Naturetic Peptide levels appear to represent a group that would have good cardio- and renal-outcomes with such decongestive pharmacologic therapies. Full article
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Open AccessFeature PaperArticle
Use of FGF-21 as a Biomarker of Mitochondrial Disease in Clinical Practice
J. Clin. Med. 2017, 6(8), 80; doi:10.3390/jcm6080080 -
Abstract
Recent work has suggested that fibroblast growth factor-21 (FGF-21) is a useful biomarker of mitochondrial disease (MD). We routinely measured FGF-21 levels on patients who were investigated at our centre for MD and evaluated its diagnostic performance based on detailed genetic and other
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Recent work has suggested that fibroblast growth factor-21 (FGF-21) is a useful biomarker of mitochondrial disease (MD). We routinely measured FGF-21 levels on patients who were investigated at our centre for MD and evaluated its diagnostic performance based on detailed genetic and other laboratory findings. Patients’ FGF-21 results were assessed by the use of age-adjusted z-scores based on normalised FGF-21 values from a healthy population. One hundred and fifty five patients were investigated. One hundred and four of these patients had molecular evidence for MD, 27 were deemed to have disorders other than MD (non-MD), and 24 had possible MD. Patients with defects in mitochondrial DNA (mtDNA) maintenance (n = 32) and mtDNA rearrangements (n = 17) had the highest median FGF-21 among the MD group. Other MD patients harbouring mtDNA point mutations (n = 40) or mutations in other autosomal genes (n = 7) and those with partially characterised MD had lower FGF-21 levels. The area under the receiver operating characteristic curve for distinguishing MD from non-MD patients was 0.69. No correlation between FGF-21 and creatinine, creatine kinase, or cardio-skeletal myopathy score was found. FGF-21 was significantly associated with plasma lactate and ocular myopathy. Although FGF-21 was found to have a low sensitivity for detecting MD, at a z-score of 2.8, its specificity was above 90%. We suggest that a high serum concentration of FGF-21 would be clinically useful in MD, especially in adult patients with chronic progressive external ophthalmoplegia, and may enable bypassing muscle biopsy and directly opting for genetic analysis. Availability of its assay has thus modified our diagnostic pathway. Full article
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Open AccessArticle
The Fragility Index in a Cohort of Pediatric Randomized Controlled Trials
J. Clin. Med. 2017, 6(8), 79; doi:10.3390/jcm6080079 -
Abstract
Data suggest inadequacy of common statistical techniques for reporting outcomes in clinical trials. The Fragility Index can measure how many events the statistical significance hinges on, and may facilitate better interpretation of trial results. This study aimed to assess the Fragility Index in
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Data suggest inadequacy of common statistical techniques for reporting outcomes in clinical trials. The Fragility Index can measure how many events the statistical significance hinges on, and may facilitate better interpretation of trial results. This study aimed to assess the Fragility Index in pediatric randomized controlled trials (RCTs) with statistically significant findings published in high-quality medical journals. A Fragility Index was calculated on included trials with dichotomous positive outcomes. Analysis of the relationship between trial characteristics and the Fragility Index was performed. Of the 429 abstracts screened, 17 met the inclusion criteria and underwent analysis. The median Fragility Index was 7 with an interquartile range of 2–11. In 41% of the studies, the number of patients lost to follow-up or withdrawn prior to analysis was equal to or greater than the Fragility Index. There was no correlation between the RCT sample size and the Fragility Index (r = 0.249, p = 0.335) nor the event group size and the Fragility Index (r = 0.250, p = 0.334). There was a strong negative correlation between the original p-value and the Fragility Index (r = −0.700, p = 0.002). The Fragility Index is a calculated metric that may assist in applying clinical relevance to statistically significant outcomes in pediatric randomized controlled trials with dichotomous outcomes. Full article
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Open AccessBrief Report
Impact of Larger Sputum Volume on Xpert® MTB/RIF Assay Detection of Mycobacterium tuberculosis in Smear-Negative Individuals with Suspected Tuberculosis
J. Clin. Med. 2017, 6(8), 78; doi:10.3390/jcm6080078 -
Abstract
As a strategy to improve the sensitivity of nucleic acid-based testing in acid-fast bacilli (AFB) negative samples, larger volumes of sputum (5–10 mL) were tested with Xpert® MTB/RIF from 176 individuals with smear-negative sputum undergoing tuberculosis evaluation. Despite larger volumes, this strategy
[...] Read more.
As a strategy to improve the sensitivity of nucleic acid-based testing in acid-fast bacilli (AFB) negative samples, larger volumes of sputum (5–10 mL) were tested with Xpert® MTB/RIF from 176 individuals with smear-negative sputum undergoing tuberculosis evaluation. Despite larger volumes, this strategy had a suboptimal sensitivity of 50% (4/8). Full article