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J. Clin. Med., Volume 6, Issue 9 (September 2017)

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Cover Story In acute myeloid leukemia, it has been widely established that persistent residual leukemic burden, [...] Read more.
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Research

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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
Received: 17 August 2017 / Revised: 1 September 2017 / Accepted: 4 September 2017 / Published: 11 September 2017
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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 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
Received: 7 July 2017 / Revised: 4 August 2017 / Accepted: 12 September 2017 / Published: 19 September 2017
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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 PaperArticle Measurement of Respiratory Chain Enzyme Activity in Human Renal Biopsy Specimens
J. Clin. Med. 2017, 6(9), 90; doi:10.3390/jcm6090090
Received: 6 July 2017 / Revised: 31 August 2017 / Accepted: 13 September 2017 / Published: 19 September 2017
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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

Review

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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
Received: 29 April 2017 / Revised: 6 July 2017 / Accepted: 26 August 2017 / Published: 29 August 2017
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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
(This article belongs to the Special Issue Th17 Cell in Autoimmune and Inflammatory Diseases)
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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
Received: 7 July 2017 / Revised: 16 August 2017 / Accepted: 23 August 2017 / Published: 29 August 2017
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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 PaperReview Technical Advances in the Measurement of Residual Disease in Acute Myeloid Leukemia
J. Clin. Med. 2017, 6(9), 87; doi:10.3390/jcm6090087
Received: 22 August 2017 / Revised: 9 September 2017 / Accepted: 13 September 2017 / Published: 19 September 2017
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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
(This article belongs to the Special Issue Role of Minimal Residual Disease Assessment in Hematological Cancers)
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Open AccessFeature PaperReview Process and Pitfalls of Sperm Cryopreservation
J. Clin. Med. 2017, 6(9), 89; doi:10.3390/jcm6090089
Received: 1 August 2017 / Revised: 31 August 2017 / Accepted: 12 September 2017 / Published: 19 September 2017
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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
[...] Read more.
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

Other

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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 Mycoplasma pneumoniae Pneumonia?
J. Clin. Med. 2017, 6(9), 83; doi:10.3390/jcm6090083
Received: 3 August 2017 / Revised: 23 August 2017 / Accepted: 24 August 2017 / Published: 4 September 2017
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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 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
Received: 16 July 2017 / Revised: 4 September 2017 / Accepted: 12 September 2017 / Published: 18 September 2017
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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 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
Received: 14 August 2017 / Revised: 11 September 2017 / Accepted: 13 September 2017 / Published: 19 September 2017
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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
[...] Read more.
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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