Differential Associations for Salivary Sodium, Potassium, Calcium, and Phosphate Levels with Carotid Intima Media Thickness, Heart Rate, and Arterial Stiffness

Salivary biomarkers may offer a noninvasive and easy sampling alternative in cardiovascular risk evaluation. The aim of the present study was to establish associations of salivary potassium, sodium, calcium, and phosphate levels with the cardiovascular phenotype determined by carotid ultrasound and carotid-femoral pulse wave velocity and to identify possible covariates for these associations. samples of nonstimulated whole buccal saliva were obtained from subjects with (; 59%) or without (; 41%) hypertension. The potassium concentrations were 10-fold higher in saliva compared with plasma, whereas sodium concentrations exhibited the reverse relation between saliva and blood. There were no significant correlations between the levels of sodium, potassium, or calcium in saliva and plasma. All salivary electrolytes, except sodium, were significantly associated with age. In age-adjusted analyses, salivary potassium was significantly associated with carotid artery intima media thickness (cIMT) and carotid-femoral pulse wave velocity, and these associations were at the limit of significance in multivariate analyses including prevalent cardiovascular disease and risk factors. Body mass index was a significant confounder for salivary potassium. Salivary phosphate was significantly associated with cIMT in the multivariate analysis. Salivary potassium, calcium, and phosphate levels were significantly associated with heart rate in the univariate age-adjusted as well as in two different multivariate models, whereas no significant associations between sodium and heart rate were observed. In conclusion, the differential association of salivary electrolytes with cardiovascular phenotypes indicates that these electrolytes should be further studied for their predictive value as noninvasive biomarkers for cardiovascular risk evaluation.

https://ift.tt/2QyFYjh

In vitro protein tyrosine phosphatase 1B inhibition and antioxidant property of different onion peel cultivars: A comparative study

The present study provides an insight into the bioactivity of waste onion peel toward diabetes and diabetic complications. Furthermore, the varying degree of TPC and TFC in different solvent extracts of two cultivars was compared and correlated with their potency. Overall result of the present study demonstrated onion peel as good food source to prevent diabetes and diabetic complications.

Abstract

The aim of the present study was a comparative investigation of water and 70% ethanol extracts derived from yellow and red onion (Allium cepa L.) peels against diabetes and diabetic complications. The total phenolic contents (TPCs) and total flavonoid contents (TFCs) of each cultivar, measured to assess phytochemical characteristics, showed a direct correlation with the in vitro antioxidant effects. Among the two captives, the yellow onion peel extract showed higher antioxidant activity than red one. However, all extracts exhibited significant protein tyrosine phosphatase 1B (PTP1B) inhibitory activity (IC₅₀; 0.30–0.86 μg/ml), showing water extracts more potent (IC₅₀; approximately 0.3 μg/mL), than the 70% ethanol extracts (IC₅₀; approximately 0.8 μg/ml). Similarly, in insulin‐resistant HepG2 cells, all extracts enhanced the glucose uptake and reduced the expression of PTP1B in a concentration‐dependent manner, water extract displaying better activity. Our results overall suggest that in vitro antioxidant and antidiabetic potentials vary among red and yellow cultivars and extracting solvents, which could therefore be a promising strategy to prevent diabetes and associated complications.

https://ift.tt/2A05SlP

Metformin Affects Heme Function as a Possible Mechanism of Action

Metformin elicits pleiotropic effects that are beneficial for treating diabetes, and as well as particular cancers and aging. In spite of its importance, a convincing and unifying mechanism to explain how metformin operates is lacking. Here we describe investigations into the mechanism of metformin action through heme and hemoprotein(s). Metformin suppresses heme production by 50% in yeast, and this suppression requires mitochondria function, which is necessary for heme synthesis. At high concentrations comparable to those in the clinic, metformin also suppresses heme production in human erythrocytes, erythropoietic cells and hepatocytes by 30-50%; the heme-targeting drug artemisinin operates at a greater potency. Significantly, metformin prevents oxidation of heme in three protein scaffolds, cytochrome c, myoglobin and hemoglobin, with Kd values < 3 mM suggesting a dual oxidation and reduction role in the regulation of heme redox transition. Since heme- and porphyrin-like groups operate in diverse enzymes that control important metabolic processes, we suggest that metformin acts, at least in part, through stabilizing appropriate redox states in heme and other porphyrin-containing groups to control cellular metabolism.

https://ift.tt/2UM1fV3

Mapping Oat Crown Rust Resistance Gene Pc45 Confirms Association with PcKM

Molecular mapping of crown rust resistance genes is important to effectively utilize these genes and improve breeding efficiency through marker-assisted selection. Pc45 is a major race-specific crown rust resistance gene initially identified in the wild hexaploid oat Avena sterilis in the early 1970s. This gene was transferred to cultivated oat (Avena sativa) and has been used as a differential for identification of crown rust races since 1974. Previous research identified an association between virulence to Pc45 and PcKM, a crown rust resistance gene in the varieties 'Kame' and 'Morton'. This study was undertaken to reveal the relationship between Pc45 and PcKM. Pc45 was studied in the crosses 'AC Morgan'/Pc45 and 'Kasztan'/Pc45, where Pc45 is the differential line carrying Pc45. F₂ progenies and F_2:3 families of both populations were inoculated with the crown rust isolate CR258 (race NTGG) and single gene segregation ratios were observed. SNP markers for PcKM were tested on these populations and linkage maps were generated. In addition, 17 newly developed SNP markers identified from genotyping-by-sequencing (GBS) data were mapped in these two populations, plus another three populations segregating for Pc45 or PcKM. Pc45 and PcKM mapped to the same location of Mrg08 (chromosome 12D) of the oat chromosome-anchored consensus map. These results strongly suggest that Pc45 and PcKM are the same resistance gene, but allelism (i.e. functionally different alleles of the same gene) or tight linkage (i.e. two tightly linked genes) cannot be ruled out based on the present data.

https://ift.tt/2PFHxqi

Serum Procalcitonin and Presepsin Levels in Patients with Generalized Pustular Psoriasis

Patients with generalized pustular psoriasis (GPP) often present with symptoms that must be differentiated from sepsis. Procalcitonin (PCT) and presepsin (P-SEP) are widely used as biomarkers for sepsis; therefore, we examined the serum PCT and P-SEP levels in patients with psoriatic diseases. The enrolled patients included 27 with psoriasis vulgaris (PV) (22 males, 5 females; mean age 47.7 years), 12 with psoriatic arthritis (PsA) (8 males, 4 females; mean age 51.3 years), and 15 with GPP (10 males, 5 females; mean age 63.7 years). The mean serum PCT levels in patients with PV, PsA, and GPP were 0.01 ng/mL (25th–75th percentile; 0.00–0.03), 0.013 ng/mL (0.00–0.03), and 0.12 ng/mL (0.05–0.18), respectively; the levels of PCT were higher for patients with GPP than with PV or PsA but were lower than the PCT cutoff value (0.5 ng/mL) for the diagnosis of infection. The mean serum P-SEP levels in patients with PV, PsA, and GPP were 144.9 pg/mL (25th–75th percentile; 78–181), 168.1 pg/mL (124–203), and 479.9 pg/mL (216–581), respectively. Unexpectedly, the levels of P-SEP in the patients with GPP were as high as the P-SEP cutoff value (317 to 647 pg/mL) used for the diagnosis of infection. We also found that neutrophils produced P-SEP, suggesting that the high serum P-SEP levels in patients with GPP might arise at least in part due to the P-SEP derived from neutrophils activated in GPP. Both serum PCT and P-SEP might therefore be useful as novel serum biomarkers for GPP because their levels were decreased by GPP treatments. However, the measurement of PCT might be more useful than the measurement of P-SEP for discriminating between GPP and sepsis.

https://ift.tt/2QypSq2

Perineural Invasion and Perineural Tumor Spread in Head and Neck Cancer: A Critical Review

Perineural invasion (PNI), the neoplastic invasion of nerves, is a common pathological finding in head and neck cancer that is associated with poor clinical outcomes. PNI is a histological finding of tumor cell infiltration and is distinct from perineural tumor spread (PNTS), which is macroscopic tumor involvement along a nerve extending from the primary tumor that is by definition more advanced, being radiologically or clinically apparent. Despite widespread acknowledgement of the prognostic significance of PNI/PNTS, the mechanisms underlying its pathogenesis remain largely unknown, and specific therapies targeting nerve invasion are lacking.

https://ift.tt/2SNNHqr

Needs and Challenges for Radiation Oncology in the Era of Precision Medicine

Precision radiation oncology necessitates the systematic curation of clinically relevant heterogeneity at the patient, disease state and treatment level, in turn, relating these measures to the longitudinal health outcomes of the irradiated cancer patient to gain personalized prediction and therapeutic insights. Leveraging the database and imaging platforms intrinsic to characterizing the heterogeneity of radiation therapy to develop an effective informatics infrastructure amongst a network of institutions is a critical goal to realize precision radiation oncology.

https://ift.tt/2CgTQ95

Activities for the Development of Targeted Radionuclide Therapy in Japan

Abstract

Targeted radionuclide therapy (TRT) is unique because of its efficacy and its theranostic feature in the era of precision medicine. So far, introduction of new TRT has not been going well in Japan due to several reasons including strict regulations, shortage of facilities for TRT, and insufficient reimbursement for TRT in clinic. Japanese community had several strategies to develop TRT in these 10 years, including the establishment of the National Conference for Nuclear Medicine Theranostics in which physicians, scientists, patients, people supporting patients, and industrial people gather. To promote TRT with supports from the government, the preparatory committee for the establishment of Japan Foundation of Medical Isotope Development (JAFMID) was launched. I would like to call TRT "Precision Nuclear Medicine." When we can add genomic information here, we can put it to new stage of cancer therapy. It is time for us.

https://ift.tt/2QwjLSW

Nuclear Theranostics in Turkey

Abstract

Nuclear theranostics functions as a bridge which connects targeted diagnosis to targeted therapy, just like Turkey functions as a geographical bridge which connects Asia to Europe. This unique geographical site of the country plays an important role with regard to introduction of novel scientific and technologic improvements, which originate from one continent to another, in the era of accelerated information. The first nuclear medicine practice in Turkey started in the beginning of 1950s with the first radioiodine treatment, which actually was a debut for nuclear theranostics in Turkey, years before many other countries in the world. For the time being, along with radioiodine treatment, many other theranostic applications such as I-131 MIBG treatment, Lu-177/Y-90 DOTA peptide treatment, Lu-177 PSMA treatment, Y-90 microsphere treatment, and bone palliative treatment are being performed in many centers countrywide. As science and technology improves, novel theranostic applications are eagerly awaited to be introduced in near future. This paper summarizes the story of nuclear theranostics in Turkey and aims to give an overview on the current status of theranostic applications in Turkey.

https://ift.tt/2Bn11uG

Development and Validation of a Scoring System That Includes Corrected QT Interval For Risk Analysis of Patients With Cirrhosis and Gastrointestinal Bleeding

The electrocardiographic QT interval is frequently prolonged in patients with cirrhosis. Acute gastrointestinal bleeding further prolongs corrected QT (QTc) in patients with cirrhosis, which has been associated with increased risk of death within 6 weeks. We aimed to confirm these findings and develop a mortality risk index that incorporates QTc.

https://ift.tt/2QzyQmP

Emergence of oncogenic‐enhancing hepatitis B virus X gene mutants in patients receiving suboptimal entecavir treatment

Abstract

Entecavir is a widely used nucleoside analogue for antiviral therapy against chronic hepatitis B virus (HBV) infection. Despite its remarkable efficacy in suppressing HBV replication, a substantial proportion of cirrhotic patients still developed hepatocellular carcinoma (HCC) after entecavir treatment (1). Presumably, it is largely attributed to the existing precancerous hepatocytes, which sturdily progresses into cancer despite effective viral suppression. HBV X (HBx) protein is a well‐known oncogenic protein. Here, we explored an alternative possibility that oncogenic‐enhancing mutations developed in HBx in HCC patients having received entecavir treatment.

This article is protected by copyright. All rights reserved.

https://ift.tt/2rCK372

SIRT4 Depletion Promotes HCC Tumorigenesis through Regulating AMPKα/mTOR Axis

Abstract

Sirtuin 4 (SIRT4) has been reported to play a vital role in the maintenance of glutamine catabolism and ATP homeostasis, but its character in hepatocellular carcinomas (HCCs) remains obscure. In this study, we observed low expression of SIRT4 in both HCC cell lines and HCCs from patients. Decreased disease‐free survival time is associated with low tumor levels of SIRT4 in patients. Deficiency of SIRT4 facilitated liver tumor development and lung metastasis in xenografts and KO mice by promoting the colony formation and migration of hepatoma cells and enhancing the sphere formation of HCCs. Mechanistically, SIRT4 deletion augmented mammalian target of rapamycin (mTOR) signaling by inactivating AMPKα through regulation of glutamine catabolism and subsequent AMP/LKB1 axis. Blockage of mTOR by rapamycin or inhibition of glutaminolysis abolished the discrepancy in tumorigenic capacity between SIRT4‐depleted hepatoma cells and control cells. Suppression of LKB1 or promotion of AMP by metformin also abrogated the hyper‐proliferative phenotype caused by SIRT4 loss, which further confirmed that LKB1/AMPKα/mTOR axis is required in SIRT4‐deficiency‐promoted HCC tumorigenesis. Conclusion SIRT4 could exert its tumor suppressive function in HCC by inhibiting glutamine metabolism and thereby increasing the ADP/AMP levels to phosphorylate AMPKα via LKB1, which blocks mTOR signaling pathway.

This article is protected by copyright. All rights reserved.

https://ift.tt/2Ljpg1z

Prum’s Aesthetic Theory of Evolution: Beauty Happens and it can Change a Great Many Things

https://ift.tt/2CfTgIL

Effects of Selenium-Enriched Yeast Improved Aflatoxin B1-Induced Changes in Growth Performance, Antioxidation Capacity, IL-2 and IFN-γ Contents, and Gene Expression in Mice

Abstract

Sixty Kunming mice were randomly assigned into three groups. Mice in a control group were fed a basal diet, while mice in AFB1 group and AFB1-Se group were fed the basal diet supplemented with 250 μg/kg AFB1 or the basal diet supplemented with 250 μg/kg AFB1 and 0.2 mg/kg selenium as selenium-enriched yeast, respectively. On day 30 of the experiment, growth performance, glutathione peroxidase (GSH-Px) activities, total antioxidant capacity (T-AOC) levels, and malondialdehyde (MDA) contents in liver, interleukin-2 (IL-2), and interferon-γ (IFN-γ) contents in serum, and cytochrome P3a11 (Cyp3a11), IL-2, IFN-γ, and GSH-Px1 mRNA levels in liver were determined. The results showed that final weights, weight gains, T-AOC levels, GSH-Px1, and IFN-γ mRNA levels in AFB1-Se group and control group were higher or significantly higher than those in AFB1 group (P < 0.05 or P < 0.01), respectively. Body length gains in AFB1 group were lower than those in the control group (P < 0.05), while there was no significant difference between the AFB1-Se and control groups (P > 0.05). IL-2 contents and liver IL-2 mRNA levels in AFB1-Se group were significantly higher than those in the AFB1 group and control group (P < 0.01), and IL-2 contents in the control group were also significantly higher than those in the AFB1 group (P < 0.01). IFN-γ contents in AFB1-Se group and AFB1 group were significantly higher than those in control group (P < 0.01), while IFN-γ contents in AFB1-Se group were significantly lower than those in AFB1 group (P < 0.01). Cyp3a11 mRNA levels in AFB1-Se group and AFB1 group were significantly higher than those in the control group (P < 0.01). The results indicated that selenium-enriched yeast could partly reduce the toxicity induced by AFB1 in mice, including improving growth performance, antioxidation capacity, IL-2 and IFN-γ contents, and enhancing IL-2, IFN-γ, and GSH-Px1 mRNA levels.

https://ift.tt/2zZ3go6

Salivary Nickel and Chromium Levels in Orthodontic Patients with and Without Periodontitis: a Preliminary Historical Cohort Study

Abstract

Many periodontal patients may need orthodontic treatment. Alterations in oral environment particularly the reduction of pH in periodontal patients could affect metal ion release from orthodontic appliances. However, there is no study on metal ion release in periodontal patients. The aim of this preliminary study was to comparatively evaluate, for the first time, salivary levels of nickel and chromium in periodontal patients (versus healthy controls) under orthodontic treatment for 2 months. In this in vivo study, 40 subjects were evaluated. Patient selection and standardization of orthodontic treatment protocols were prospectively designed and performed. Two groups of n = 20 each (control: healthy orthodontic patients, cohort: orthodontic patients with periodontitis) underwent similar protocols of fixed orthodontic treatment for 2 months. After 2 months, salivary nickel and chromium concentrations of the case and cohort groups were measured using inductively coupled plasma mass spectrometry (ICP-MS). The values were compared between the two groups using t test. There were 10 men and 10 women in each group. The mean age of patients was 34.6 ± 3.6 years old. The salivary level of nickel was 338.2 ± 235.5 ng/ml and 182.8 ± 116.5 ng/ml in the cohort and control groups, respectively (P = 0.0118). The salivary level of chromium was 7.4 ± 3.15 ng/ml in the cohort and 6.35 ± 2.39 ng/ml in the control group (P = 0.2214). Salivary level of nickel might be considerably higher in periodontal patients undergoing 2 months of orthodontic treatment compared to orthodontic patients with healthy gingivae.

https://ift.tt/2S5m1NB

LARGE expression in different types of muscular dystrophies other than dystroglycanopathy

Alpha-dystroglycan (αDG) is an extracellular peripheral glycoprotein that acts as a receptor for both extracellular matrix proteins containing laminin globular domains and certain arenaviruses. An important en...

https://ift.tt/2CflCmw

Morphologic characteristics of severe basilar artery atherosclerotic stenosis on 3D high-resolution MRI

Two-dimensional high-resolution MRI (2D HRMRI) faces many technical challenges for fully assessing morphologic characteristics of inherent tortuous basilar arteries. Our aim was to investigate remodeling mecha...

https://ift.tt/2SRtjou

Production and Measurement of Organic Particulate Matter in a Flow Tube Reactor

This paper describes the operation procedure for the flow tube reactor and related data collection. It shows the protocols for setting the experiments, recording data and generating the number-diameter distribution as well as the particle mass information, which gives useful information about chemical and physical properties of the organic aerosols.

https://ift.tt/2GrSiNQ

Chronic GI bleeding in a middle-aged woman

Clinical presentation

A middle-aged woman without any underlying systemic disease was referred to our hospital due to a 1-month history of recurrent black diarrhoea and anaemia. At presentation, her vital signs were stable and the physical examination was unremarkable except for pale conjunctiva. Laboratory tests showed iron-deficiency anaemia with a haemoglobin concentration of 7.3 g/dL (reference range, 11.1–15.1 g/dL). As she had no severe symptoms of anaemia, we administered oral iron preparations without blood transfusion and her anaemia was gradually corrected. Oesophagogastroduodenoscopy, colonoscopy and contrast-enhanced abdominal CT revealed no cause of bleeding, so obscure GI bleeding was suspected. Capsule enteroscopy revealed black fluid in the proximal small intestine, and subsequent peroral double-balloon enteroscopy detected a 1 cm diameter hemispheric elevated lesion at the upper jejunum (figure 1A, B). The lesion was non-pulsatile and hard in consistency, appearing as a submucosal tumour (SMT). An ulcer was located at the top of the...

https://ift.tt/2GkuZFD

Role of TLR4 in the gut-brain axis in Parkinsons disease: a translational study from men to mice

Objective

Recent evidence suggesting an important role of gut-derived inflammation in brain disorders has opened up new directions to explore the possible role of the gut-brain axis in neurodegenerative diseases. Given the prominence of dysbiosis and colonic dysfunction in patients with Parkinson's disease (PD), we propose that toll-like receptor 4 (TLR4)-mediated intestinal dysfunction could contribute to intestinal and central inflammation in PD-related neurodegeneration.

Design

To test this hypothesis we performed studies in both human tissue and a murine model of PD. Inflammation, immune activation and microbiota composition were measured in colonic samples from subjects with PD and healthy controls subjects and rotenone or vehicle-treated mice. To further assess the role of the TLR4 signalling in PD-induced neuroinflammation, we used TLR4-knockout (KO) mice in conjunction with oral rotenone administration to model PD.

Results

Patients with PD have intestinal barrier disruption, enhanced markers of microbial translocation and higher pro-inflammatory gene profiles in the colonic biopsy samples compared with controls. In this regard, we found increased expression of the bacterial endotoxin-specific ligand TLR4, CD3+ T cells, cytokine expression in colonic biopsies, dysbiosis characterised by a decrease abundance of SCFA-producing colonic bacteria in subjects with PD. Rotenone treatment in TLR4-KO mice revealed less intestinal inflammation, intestinal and motor dysfunction, neuroinflammation and neurodegeneration, relative to rotenone-treated wild-type animals despite the presence of dysbiotic microbiota in TLR4-KO mice.

Conclusion

Taken together, these studies suggest that TLR4-mediated inflammation plays an important role in intestinal and/or brain inflammation, which may be one of the key factors leading to neurodegeneration in PD.

https://ift.tt/2GhS1N7

Rates and characteristics of postcolonoscopy colorectal cancer in the Swedish IBD population: what are the differences from a non-IBD population?

Objective

The rate of postcolonoscopy colorectal cancer (PCCRC) is considered a key quality indicator of colonoscopy; little is known about PCCRC in IBD.

Design

A population-based cohort study of colonoscopies in Sweden from 2001 to 2010 was conducted. Individuals with a colorectal cancer (CRC) detected within 36 months after a colonoscopy were identified and stratified on UC, Crohn's disease (CD) or non-IBD. The CRCs were classified as detected CRCs (dCRC) (0–6 months) or as PCCRCs (6–36 months). PCCRC rates were calculated by the number of false negative/(the number of true positive+the number of false negative) colonoscopies. Poisson regression analysis was employed to examine the association between PCCRC and IBD (CD and UC) diagnosis, age, gender, location, time period and comorbidities.

Results

We identified 348 232 colonoscopies in 270 918 individuals. Of these, 27 123 were performed on 14 597 individuals with CD, and 51 572 were performed on 26 513 individuals with UC. There were 13 317 CRCs in the non-IBD group, 133 in the CD group and 281 in the UC group. The PCCRC rate in the CD group was 28.3% and 41.0% in the UC group. The RR for a PCCRC was 3.82 (95% CI 2.94 to 4.96) in CD and 5.89 (95% CI 5.10 to 6.80) in UC, compared with non-IBD. The highest risk was observed among rectal cancer location in CD and in younger individuals with UC.

Conclusion

The high rates of PCCRC in young patients with UC and for rectal cancer location in CD might affect future performance of IBD surveillance.

https://ift.tt/2R0kX0a

Idiopathic Pulmonary Fibrosis for Cardiologists: Differential Diagnosis, Cardiovascular Comorbidities, and Patient Management

Abstract

The presence of rare comorbidities in patients with cardiovascular disease (CVD) presents a diagnostic challenge to cardiologists. In evaluating these patients, cardiologists are faced with a unique opportunity to shorten diagnosis times and direct patients towards correct treatment pathways. Idiopathic pulmonary fibrosis (IPF), a type of interstitial lung disease (ILD), is an example of a rare disease where patients frequently demonstrate comorbid CVD. Both CVD and IPF most commonly affect a similar patient demographic: men over the age of 60 years with a history of smoking. Moreover, IPF and heart failure (HF) share a number of symptoms. As a result, patients with IPF can be misdiagnosed with HF and vice versa. This article aims to increase awareness of IPF among cardiologists, providing an overview for cardiologists on the differential diagnosis of IPF from HF, and describing the signs and symptoms that would warrant referral to a pulmonologist with expertise in ILD. Once patients with IPF have received a diagnosis, cardiologists can have an important role in managing patients who are candidates for a lung transplant or those who develop pulmonary hypertension (PH). Group 3 PH is one of the most common cardiovascular complications diagnosed in patients with IPF, its prevalence varying between reports but most often cited as between 30% and 50%. This review summarizes the current knowledge on Group 3 PH in IPF, discusses data from clinical trials assessing treatments for Group 1 PH in patients with IPF, and highlights that treatment guidelines recommend against these therapies in IPF. Finally, this article provides the cardiologist with an overview on the use of the two approved treatments for IPF, the antifibrotics pirfenidone and nintedanib, in patients with IPF and CVD comorbidities. Conversely, the impact of treatments for CVD comorbidities on patients with IPF is also discussed.

Funding: F. Hoffmann-La Roche, Ltd.

Plain Language Summary: Plain language summary available for this article.

https://ift.tt/2zY4YX2

Efficacy and Safety of CFTR Corrector and Potentiator Combination Therapy in Patients with Cystic Fibrosis for the F508del-CFTR Homozygous Mutation: A Systematic Review and Meta-analysis

Abstract

Introduction

Cystic fibrosis (CF) is a progressive, genetic disease that causes persistent lung infections and limits the ability to breathe over time. The combination of a cystic fibrosis transmembrane conductance regulator (CFTR) corrector and potentiator has provided a benefit by decreasing sweat chloride concentration in CF for the F508del-CFTR homozygous mutation, but it remains controversial in lung function, nutritional status, clinical score and safety.

Methods

The authors performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of combination therapy on lung function, nutritional status, clinical score and safety in CF for the F508del-CFTR homozygous mutation. Web of Science, Cochrane Central Register of Controlled Trials, Medline, and Embase were searched. The registered PROSPERO number was CRD42018085875.

Results

Five RCTs, including a total of 1637 participants with the F508del-CFTR homozygous mutation who accepted CFTR corrector and potentiator combination therapy along with basic treatment were enrolled in this analysis. Primary analysis revealed that combination therapy improved the percent of predicted FEV₁ (ppFEV₁) (MD 2.38, 1.62–3.15, P < 0.00001), Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score (MD 2.59, 0.96–4.22, P = 0.002) and body-mass index (BMI) (MD 0.21, 0.03–0.39, P = 0.02). In the secondary analysis, combination therapy had no impact on the number of participants reporting adverse events (OR 0.88, 0.58–1.33, P = 0.53), but increased the proportion of discontinued treatments due to adverse events (OR 2.71, 1.3–5.63, P = 0.008).

Conclusions

CFTR corrector and potentiator combination therapy effectively improves lung function, nutritional status and clinical score in CF patients with the F508del-CFTR homozygous mutation, and has an acceptable safety profile.

https://ift.tt/2RXqt0W

Evaluation of Physicochemical and Biological Stability of 36-Months-Aged SB5 (Adalimumab Biosimilar) for 4 Weeks at Room Temperature

Abstract

Introduction

Tumor necrosis factor (TNF-alpha) inhibitors, such as adalimumab, have shown success in treating autoimmune inflammatory diseases but are associated with substantial financial burdens to the healthcare system. Biosimilars, which are highly similar to biologic agents, offer the potential to reduce the financial burden of treatment. In the case of TNF-alpha inhibitors, they may also offer improved stability and enable prolonged use. SB5, an adalimumab biosimilar, has shown equivalent efficacy and comparable safety to its reference product in clinical trials. Currently, SB5 is approved for storage for 36 months at 2–8 °C and may be stored at room temperature (25 °C) for a maximum period of 14 days. The objective of this study was to evaluate the stability of SB5, aged to its shelf-life of 36 months, at room temperature (25 ± 2 °C) and 60 ± 5% relative humidity (RH) for a period of 4 weeks, which is longer by 14 days than that of SB5 currently approved in the European Union.

Methods

This study evaluated the stability of SB5, aged to its shelf-life of 36 months, at room temperature (25 ± 2 °C) for a period of 4 weeks. Three independent batches of 36 months-aged SB5 were stored at 25 ± 2 °C and 60 ± 5% RH for 4 weeks. Samples were tested at 0, 2, and 4 weeks.

Results

Color, clarity, visible particles, pH, protein concentration, and particulate matter were consistent among the batches, and all the test results met the acceptance criteria at each time point. Percent charge variance was maintained over time. Percent of high molecular weight species detected, total purity, relative binding activity by TNF-alpha, and relative potency by TNF-alpha neutralization did not change over time within each batch, and all values were within the acceptance criteria limits.

Conclusion

SB5 aged for 36 months is physicochemically and biologically stable for 4 weeks at 25 ± 2 °C and 60 ± 5% RH, which is 2 weeks longer than the alternative storage condition as approved by the European Medicines Agency, which is at 25 °C for a period of up to 14 days.

Funding

Samsung Bioepis Co., Ltd.

https://ift.tt/2Cgi2Zr

Overexpression of the cancer stem cell marker CD133 confers a poor prognosis in invasive breast cancer

Abstract

Purpose

CD133/ prominin 1 is a cancer stem cell marker associated with cancer progression and patient outcome in a variety of solid tumours, but its role in invasive breast cancer (BC) remains obscure. The current study aims to assess the prognostic value of CD133 expression in early invasive BC.

Methods

CD133 mRNA was assessed in the METABRIC cohort and at the proteomic level using immunohistochemistry utilising a large well-characterised BC cohort. Association with clinicopathological characteristics, expression of other stem cell markers and patient outcome were evaluated.

Results

High expression of CD133 either in mRNA or protein levels was associated with characteristics of poor prognosis including high tumour grade, larger tumour size, high Nottingham Prognostic Index, HER2 positivity and hormonal receptor negativity (all; p < 0.001). High CD133 expression was positively associated with proliferation biomarkers including p16, Cyclin E and Ki67 (p < 0.01). Tumours expressing CD133 showed higher expression of other stem cell markers including CD24, CD44, SOX10, ALDHA3 and ITGA6. High expression of CD133 protein was associated with shorter BC-specific survival (p = 0.026). Multivariate analysis revealed that CD133 protein expression was an independent risk factor for shorter BC-specific survival (p = 0.038).

Conclusion

This study provides evidence for the prognostic value of CD133 in invasive BC. A strong positive association of BC stem cell markers is observed at the protein level. Further studies to assess the value of stem cell markers individually or in combination in BC is warranted.

https://ift.tt/2GiI7uM

Pregnant in prison: An integrative literature review

Publication date: Available online 14 December 2018

Source: Women and Birth

Author(s): Adele Baldwin, Agnieszka Sobolewska, Tanya Capper

Abstract

Background

Pregnant women in prisons are recognised as a marginalised group. However, there is a limited understanding of the women's unique maternity needs and how correctional institutions and maternity service providers respond to these needs.

Aim

The aims of the review are threefold.

1.

Identify pregnant women's needs during the antenatal, birthing and postnatal periods in prison.

2.

Examine how the pregnant incarcerated women's needs are met by the correctional institutions.

3.

Explore what maternity services are available and how these services are provided.

Method

An integrative literature review was undertaken. A comprehensive search strategy using seven electronic databases resulted in the retrieval of 363 articles. Of them, 32 peer-reviewed studies met the final selection criteria and were included in this review which utilised the Critical Appraisal Skills Program tools and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart. Thematic analysis identified universal themes.

Findings

Three dominant themes emerged related to the experience of pregnant women in prison: (1) risks and vulnerability factors; (2) prison enablers and supports; and (3) prison barriers. Extant research on risks and vulnerability factors is disproportionate to research examining how prisons can enable or obstruct responding to the women's perinatal needs. Limited research on the midwifery support available to the women in prison is available. Significantly, only two out of 32 reviewed papers include research directly conducted with the pregnant women in prison.

Conclusion

Pregnant women in prisons have complex needs. More research is required to understand how prisons can enhance the pregnancy experience by engaging pregnant women in prisons as research participants.

https://ift.tt/2LkFkzU

Complementary medicine products: Information sources, perceived benefits and maternal health literacy

Publication date: Available online 14 December 2018

Source: Women and Birth

Author(s): Larisa A.J. Barnes, Lesley Barclay, Kirsten McCaffery, Parisa Aslani

Abstract

Background

Maternal health literacy plays an important role in women's decisions regarding health care during pregnancy and lactation. This systematic review aimed to investigate the use of complementary medicine products by pregnant and breastfeeding women; information sources accessed, and the role health literacy plays in women's use of complementary medicine products.

Methods

Seven databases were searched for peer-reviewed quantitative or mixed- methods studies (1995–2017). Thematic analysis identified key themes regarding women's use of complementary medicine products for perceived benefits to the mother, pregnancy, baby and/or breastfeeding process.

Results

4574 papers were identified; 56 met the inclusion criteria. Most (n = 53) focused on the use of complementary medicine products during pregnancy; six focused on use in lactation. Herbal medicines were the main complementary medicine product type discussed (n = 46) for both pregnancy and breastfeeding. Women perceived complementary medicine products to be beneficial in supporting their own pre and postnatal health, their pregnancies, growing foetuses, labour and birth, and/or breastfeeding. Health care professionals, followed by other interpersonal relationships and the media were the most commonly reported information sources accessed.

An interactive model of health literacy revealed that information sources within a woman's health literacy environment, combined with other information sources, influenced her decision making regarding complementary medicine product use.

Conclusions

Pregnant and breastfeeding women use complementary medicine products for various self-perceived benefits related to their own, unborn or breastfeeding babies' health. Examining these with reference to an interactive health literacy model helps identify the decision-making process mothers undergo when choosing to use complementary medicine products.

https://ift.tt/2CgoL5p

Receipt of information about diet by pregnant women: A cross-sectional study

Publication date: Available online 14 December 2018

Source: Women and Birth

Author(s): Jamie Bryant, Amy E. Waller, Emilie C. Cameron, Rob W. Sanson-Fisher, Alexis J. Hure

Abstract

Problem

Given the influence of diet on infant and maternal health outcomes, adequate knowledge about nutrition during pregnancy is critical.

Aims

To examine among women receiving antenatal care the proportion who: (1) believe information about diet should be provided as part of routine antenatal care; (2) recall receiving advice about diet as part of care including: (a) when information was provided, (b) the healthcare provider who gave information, and (c) the format in which it was provided; and (3) attitudes towards information received.

Methods

A cross-sectional survey was conducted with women attending a public antenatal clinic in New South Wales, Australia. Women were eligible to participate if they were: pregnant or had given birth in the previous 10 weeks; ≥18 years; and had at least one prior antenatal appointment for their current pregnancy.

Findings

A total of 223 women (64% consent rate) participated. While the majority (86%) believed healthcare providers should be giving dietary information to pregnant women, only 63% recalled receiving information during their current pregnancy. Most often it was given by a midwife (76%). Information was initially provided in the first (52%) or second (38%) trimester, in both written and verbal form (60%). Approximately one third of participants felt overwhelmed or confused by which foods should be avoided during pregnancy.

Conclusions

A third of women did not recall receiving advice about diet as part of routine antenatal care. There is a need to develop a pathway to provide women with reliable, comprehensive advice about diet early in pregnancy.

https://ift.tt/2LpUmVr

A systematic review of prevalence and risk factors of postpartum depression in Chinese immigrant women

Publication date: Available online 14 December 2018

Source: Women and Birth

Author(s): Jiarui Chen, Wendy M. Cross, Virginia Plummer, Louisa Lam, Siyuan Tang

Abstract

Background

As the number of immigrants grows, the health of Chinese immigrant women, especially their perinatal health, has gradually attracted public attention. Our review has two main purposes. First, estimate the prevalence of postpartum depressive symptoms in Chinese immigrant women, and then determine risk factors for postpartum depressive symptoms among these women.

Methods

The following databases: MEDLINE, Embase, Scopus, Web of Science, PsycINFO and PubMed were used in literature search from their commencements until November 21st 2017. The Joanna Briggs Institute (JBI) Critical Appraisal instruments were used to evaluate the quality of the article. Four studies met the inclusion criteria, contributed to our review and meta-analysis.

Result

The prevalence of postpartum depression is high in Chinese immigrant women. Risk factors for postpartum depression in Chinese immigrant women were defined as lack of social support, unstable economic status, and acculturation.

Conclusion

There have been few studies on postpartum depression among Chinese immigrant women. Existing studies have shown a high prevalence of postpartum depression in Chinese immigrant women. Moreover, there is an urgent need for studies on postpartum depression among Chinese immigrant women informing better understanding, programs of care and improving the perinatal health status of Chinese immigrant women.

https://ift.tt/2CgBhlz

An early feasibility study of the Nativis Voyager® device in patients with recurrent glioblastoma: first cohort in US

CNS Oncology, Ahead of Print.


https://ift.tt/2SNUL6j

TP53 inactivation and expression of methylation-associated proteins in gastric adenocarcinoma with enteroblastic differentiation

Abstract

Gastric adenocarcinoma with enteroblastic differentiation (GAED) is a rare variant of aggressive adenocarcinoma. We demonstrated previously that GAED is genetically characterized by frequent TP53 mutation. In this study, we aimed to further clarify the mechanism of inactivation of TP53 in GAED in the light of promoter methylation of TP53, and expression of methylation-associated proteins such as Ten-eleven translocation (TET) 1 and 5-hydroxymethylcytosine (5-hmc) in addition to ATM mutations. We analyzed 51 cases of GAED. The ATM mutation was detected in only one case. Promoter methylation of TP53 was detected in 18% and frequency of loss of heterozygosity (LOH) at TP53 locus was 37.2%. Reduced TET1 expression was found in 29 cases (56.9%) and was significantly associated with advanced stage (p = 0.01), lymph node metastasis (p = 0.04), and macroscopic type (p = 0.01). Reduced 5-hmc expression was found in 28 cases (54.9%) and was significantly associated with advanced stage (p = 0.01), gender (p = 0.01), tumor location (p = 0.03), tumor size (p = 0.01), and lymph node metastasis (p = 0.01). Among 9 cases with TP53 promoter methylation, reduced expression of TET1 was observed in 6 cases, and reduced expression of 5-hmc was observed in 5 cases. Reduced expression of both TET1 and 5-hmc was significantly associated with adverse clinical outcomes. In summary, promoter methylation of TP53 is partly involved in loss of p53 expression. Aberrant methylation by reduced TET1 and 5-hmc may be involved in the development of aggressive GAED.

https://ift.tt/2LkHzTP

Phase III trials examining the efficacy of cetirizine ophthalmic solution 0.24% compared to vehicle for the treatment of allergic conjunctivitis in the conjunctival allergen challenge model

https://ift.tt/2Gg8GAJ

Jockey injuries during the Siena “Palio”. A 72-year analysis of the oldest horse race in Italy

Publication date: Available online 15 December 2018

Source: Injury

Author(s): Mattia Fortina, Pietro Maniscalco, Christian Carulli, Luigi Meccariello, Giovanni Battista Colasanti, Serafino Carta

Abstract

Introduction

Horse racing is a hazardous sport. We analyzed the incidence and characteristics of jockey injuries in a typical horse race.

Methods

We analyzed all injuries sustained by 224 jockeys in the last 72 years.

Results

It was found that in 96.1% of the races there was at least one fall and in 28.6% of the races 50% or more of the jockeys fell. In 43.4% of the falls, the jockey was taken to the emergency room. Comparing thePalio with traditional races in other countries, a higher injury incidence rate was observed for every 100 falls (109.884 vs 27-59) and a lower concussion rate/100 falls (0.97 vs 1.8-7.4).

Conclusion

The Palio is one of the most threatening races that continues today. Jockeys are at greater risk for a fall than any other race in the world.

https://ift.tt/2En1osr

Comparison of plate and intramedullary nail fixation of extra-articular tibial fractures: a retrospective study exploring hidden blood loss

Publication date: Available online 14 December 2018

Source: Injury

Author(s): Ji-Qi Wang, Ze-Xin Chen, Wei-Jun Guo, You-Ming Zhao, Peng-Luo

Abstract

Purpose

To explore the hidden blood loss (HBL) in treatment of extra-articular tibial fractures with plate and intramedullary nail fixation.

Methods

We conducted a retrospective study including 209 consecutive patients treated by plate (Group LCP) or intramedullary nail fixation (Group IMN) for extra-articular tibial fractures between January 2015 to December 2017. Demographics, intraoperative data, perioperative laboratory values, transfusion rate, and early complications were collected and analyzed.

Results

Of 209 patients, 96 patients fixed with IMN and 113 fixed with LCP. The average HBL was 272.71 ± 57.88 ml in Group LCP and 507.66 ± 109.81 ml in Group IMN, and there was statistical difference in the HBL between two groups (p < 0.001). The Hb and Hct loss, surgical duration, and postoperative number of anemic patients in Group IMN were significantly higher than in Group LCP (p < 0.001), and IMN fixation has a significantly higher rate of transfusion (p = 0.027), whereas patients in group IMN has significantly less VBL (p < 0.001), shorter postoperative hospital stay (p < 0.001), and less superficial infection (p = 0.014).

Conclusions

There was a significant amount of hidden blood loss after reamed intramedullary nail fixation for extra-articular tibial fractures, which was much higher than expected. In view of the morbidity of acute anaemia and transfusion, we suggest that for patients who suffer from extra-articular tibial fractures with multiple injuries, or those with low haemoglobin preoperatively, plates might be more suitable than nail fixation.

https://ift.tt/2EyihBn

Correction to: Subclinical nodular goiter associated with Hurthle cell, papillary, and adenomatoid hyperplasic nodules in the dromedary camel in the Sultanate of Oman

The original published version of this article contained a mistake in the name of Remya R. Nair. It was incorrectly presented as Remya R. Nir.

https://ift.tt/2zVUiIg

Cancers, Vol. 10, Pages 518: RNA-Sequencing Analysis of Adrenocortical Carcinoma, Pheochromocytoma and Paraganglioma from a Pan-Cancer Perspective

Cancers, Vol. 10, Pages 518: RNA-Sequencing Analysis of Adrenocortical Carcinoma, Pheochromocytoma and Paraganglioma from a Pan-Cancer Perspective

Cancers doi: 10.3390/cancers10120518

Authors: Joakim Crona Samuel Backman Staffan Welin David Taïeb Per Hellman Peter Stålberg Britt Skogseid Karel Pacak

Adrenocortical carcinoma (ACC) and pheochromocytoma and paraganglioma (PPGL) are defined by clinicopathological criteria and can be further sub-divided based on different molecular features. Whether differences between these molecular subgroups are significant enough to re-challenge their current clinicopathological classification is currently unknown. It is also not fully understood to which other cancers ACC and PPGL show similarity to. To address these questions, we included recent RNA-Seq data from the Cancer Genome Atlas (TCGA) and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) datasets. Two bioinformatics pipelines were used for unsupervised clustering and principal components analysis. Results were validated using consensus clustering model and interpreted according to previous pan-cancer experiments. Two datasets consisting of 3319 tumors from 35 disease categories were studied. Consistent with the current classification, ACCs clustered as a homogenous group in a pan-cancer context. It also clustered close to neural crest derived tumors, including gliomas, neuroblastomas, pancreatic neuroendocrine tumors, and PPGLs. Contrary, some PPGLs mixed with pancreatic neuroendocrine tumors or neuroblastomas. Thus, our unbiased gene-expression analysis of PPGL did not overlap with their current clinicopathological classification. These results emphasize some importances of the shared embryological origin of these tumors, all either related or close to neural crest tumors, and opens for investigation of a complementary categorization based on gene-expression features.

https://ift.tt/2Lk2Jlk

Sudden unexpected infantile death due to undiagnosed ventricular septal defect-associated heart failure with single coronary artery

Abstract

Ventricular septal defect (VSD) generally has a good prognosis unless complicated by heart failure (HF). We report a case of sudden infant death because of clinically undiagnosed VSD in a seemingly healthy 16-day-old boy. Although a cardiac murmur was auscultated at birth, detailed clinical examination was not performed. Medicolegal autopsy revealed a perimembranous large VSD with a single coronary artery. The infant was diagnosed to have had HF based on the increased weight of the heart and extremely high serum brain natriuretic peptide levels. Histological examination revealed the degeneration of cardiomyocytes. The large VSD was thought to be the major cause of HF, although single coronary artery–associated cardiomyopathy might have also partially contributed to it. The decline in the physiological neonatal pulmonary resistance, which occurs over the first 1 or 2 weeks following birth, led to the acute progression of HF, resulting in circulatory collapse and sudden death. Detailed clinical examination should be performed for neonates with cardiac murmur to prevent avoidable death.

https://ift.tt/2EzNeVI

Vitamin D Supplements Don’t Reduce Cancer Incidence

Vitamin D Supplements Don't Reduce Cancer Incidence, Trial Shows
12/13/2018
	In the largest-ever randomized trial testing vitamin D for cancer prevention, the supplement did not lower the risk of developing cancer. The Vitamin D and Omega-3 Trial (VITAL) includes a nationally representative sample of nearly 26,000 participants.

Indian Journal of Nephrology (Indian J Nephrol)

ORIGINAL ARTICLES
	Epidemiology and outcomes of acute kidney injury in critically ill: Experience from a tertiary care center	p. 413
	PS Priyamvada, R Jayasurya, Vijay Shankar, S Parameswaran DOI:10.4103/ijn.IJN_191_17   There is only limited information on the epidemiology and outcomes of acute kidney injury (AKI) in critically ill patients from low- and middle-income countries. This study aims to identify the etiology, short-term outcomes, and determinants of mortality in patients with AKI admitted to multiple medical and surgical Intensive Care Units (ICU's) in a tertiary care center. The study also aims to compare the clinical characteristics and outcomes of community-acquired AKI (CAAKI) and hospital-acquired AKI (HAAKI). A prospective, observational study was done from June 2013 to October 2015. All patients over 18 years with AKI admitted in various medical and surgical ICU's seeking nephrology referral were included. AKI was defined according to KDIGO criteria. The follow-up period was 30 days. A total of 236 patients were recruited from five medical and nine surgical ICU's. Majority (73.3%) were males. About 53.38% patients had CAAKI, whereas 46.61% had HAAKI. The predominant etiologies for AKI were sepsis (22.4%), trauma due to road traffic accidents (21.18%), acute abdomen (perforation, acute pancreatitis, bowel gangrene, intestinal obstruction and cholangitis) (18.64%), and cardiac diseases (10.59%). Sepsis and acute abdomen were the most common causes of CAAKI, whereas trauma and cardiac causes were the predominant causes of HAAKI (P < 0.05). Patients with HAAKI were younger, admitted in surgical units, had lower SOFA scores, lower serum creatinine, lesser need for dialysis, longer hospital stay, and earlier stages of AKI compared to patients with CAAKI (P < 0.05). The 30-day mortality was 52.54%. The mortality was not different between CAAKI and HAAKI (56.3% vs. 48.18%; relative risk = 0.86: 95% confidence interval 0.67–1.1). The mortality was similar across different stages of AKI.
	[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta
	Skin microcirculatory changes in relation to arteriovenous fistula maturation	p. 421
	Siew Cheng Chai, Wan Azman Wan Sulaiman, Arman Zaharil Mat Saad, Aida Hanum Rasool, Amran Ahmed Shokri DOI:10.4103/ijn.IJN_402_17   Maturation of arteriovenous fistula (AVF) involves complex vascular remodeling. In this study, we evaluated the changes of skin microvascular perfusion over the extremity with AVF maturation using the laser Doppler fluximetry (LDF). A total of 45 patients with chronic kidney disease, Stages IV–V, were included; they had undergone AVF creation from July 2014 to June 2016 at our institute. The measurement of skin microvascular perfusion was accomplished proximal and distal to the fistula anastomosis site: pre- and post-operative day 1, week 2, week 6, and week 12. Thirty-two patients with mean age of 55.6 had achieved AVF maturation. There were 40.6% radial-based and 59.4% brachial-based AVF. There was a 32.8% reduction of mean skin perfusion distal to the fistula by day 1 compared to the baseline perfusion; however, perfusion increased 47% by week 2 compared to day 1 and no dramatic change was subsequently noted. There was an increase of mean skin perfusion, proximal to fistula anastomosis, over 12 weeks with 35.8% at day 1 from the baseline. However, the changes of the mean skin perfusion were not statistically significant. There was no significant relation of skin perfusion changes with the type of fistula, diabetes mellitus, hypertension, and hyperlipidemia. LDF successfully detected the subclinical change of skin microvascular perfusion in relation to AVF creation. Reduction of skin perfusion distal to the fistula suggests that in patients with existing perfusion inadequacy of extremities, they may experience ischemic symptoms as early as day 1 postoperation, and require close monitoring for distal limb ischemic-related complications.
	[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta
	Urinary neutrophil gelatinase-associated lipocalin and urinary soluble CXCL16 as biomarkers of activity in pediatric lupus nephritis	p. 427
	MA El-Gamasy, W El-Naghy DOI:10.4103/ijn.IJN_265_17   One of the challenges of treating patients with lupus nephritis (LN) is to assess disease activity. The aim of this study was to measure the urinary neutrophil gelatinase-associated lipocalin (uNGAL) and urinary soluble chemokine (C-X-C motif) ligand 16 (CXCL16) levels in children and adolescents with systemic lupus erythematosus (SLE) and investigate whether they are elevated in active LN. This study was conducted on 80 patients diagnosed as SLE by the Systemic Lupus International Collaborating Clinics criteria and 60 apparently healthy individuals as controls. Global and renal disease activities were evaluated by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and renal SLEDAI, respectively. uNGAL and urinary CXCL16 were measured for all participants by ELISA. Renal biopsy was done for all cases at initial diagnosis and was graded using ISN/RPS classification. uNGAL and CXCL16 were higher in patients than in the controls (8.9 ± 3.56 ng/dl and 1067 ± 367 ug/L vs. 2.26 ± 1.95 ng/dl and 471 ± 106 ug/L, respectively). uNGAL had higher sensitivity and specificity than urinary CXCL16 as predictor of LN (95% and 90% vs. 85% and 80%, respectively). There was significant positive correlations between uNGAL levels, 24-h urinary proteins (r = 0.732, P = 0.001), and SLEDAI (r = 0.359, P = 0.001). There was also significant positive correlations between urinary CXCL16 levels, 24-h urinary proteins (r = 0.47, P = 0.001), and SLEDAI (r = 0.17, P = 0.001). uNGAL and CXCL16 were reliable indicators of the activity of LN.
	[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta
	Optimization of treatment modality in elderly end-stage renal disease population: Peritoneal dialysis versus transplant	p. 433
	A Kaul, MR Behera, R Kishore, B Karthikeyan, DS Bhadauria, P Mishra, N Prasad, A Gupta, RK Sharma DOI:10.4103/ijn.IJN_305_17   Despite kidney transplantation (KT) being considered as the best treatment modality for end-stage renal disease (ESRD), patient and graft survival in the elderly population is poorer than younger individuals. Many authors argue that prolonged life expectancy outweighs the risk of remaining on dialysis, but few studies had compared the treatment modalities, especially with peritoneal dialysis (PD). A retrospective study was conducted at a tertiary care institute to compare outcome of elderly ESRD patients, who received KT with those continued on PD; and to evaluate the predictors of patient survival. Patient survival at 1 year was (76.2% vs. 91.1%); 5 years (53.7% vs. 21.8%); and 10 years (35.6% vs. 0.00%) among KT and PD population, respectively. Infection was the most common cause of death among KT group (35 [41.2%] vs. 34 [28.2%]) while cardiovascular mortality in PD group (55 [46.2%] vs. 7 [8.2%]). Technique survival at 1, 5, and 10 years in PD group was 92.8%, 58.5%, and 0%, respectively. Similarly, graft survival at 1, 5, and 10 years in KT group was 98.7%, 90.2%, and 90.2%, respectively. Multivariate analysis showed body mass index (BMI) (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.82–0.93, p < 0.001), and albumin (HR 0.55, 95% CI 0.37–0.80, p = 0.002) were significant predictors of survival. In the 1st year, patient survival was better in PD than KT, but after adjustment for BMI and albumin, both short-term and long-term survival in elderly KT group was better than that of PD. Hence, elderly ESRD patients should not be barred from KT just because of age.
	[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta
	Role of blood oxygen level-dependent MRI in differentiation of acute renal allograft dysfunction	p. 441
	Hira Lal, Ezaz Mohamed, Neelam Soni, Priyank Yadav, Manoj Jain, Dharmendra Bhadauria, Anupma Kaul, Narayan Prasad, Amit Gupta, RK Sharma DOI:10.4103/ijn.IJN_43_18   Early graft dysfunction after renal transplantation manifests as acute rejection (AR) or acute tubular necrosis (ATN). Blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging is a noninvasive method of assessing tissue oxygenation, which may be useful for predicting acute allograft dysfunction. This was a prospective study involving 40 patients scheduled for renal transplantation from August 2012 to August 2014. In addition, 15 healthy donors were also enrolled in this study. All recipients underwent BOLD MR imaging (MRI) and R2* mapping 10–20 days after transplant, and additionally within 48 h of biopsy if there was any evidence of graft dysfunction. The healthy donors underwent BOLD MRI 1–2 days before surgery. The biopsies were grouped into AR, ATN, and no evidence of AR or ATN. The mean medullary R2*, cortical R2*, corticomedullary gradient, and medullary: cortical R2* ratio were compared between groups using one-way analysis of variance. Spearman's correlation and multinomial linear regression were applied to determine the influence factors of R2* value. Overall, nine patients had graft dysfunction. Six were reported as AR, two as ATN, and one as no evidence of ATN or rejection. The mean medullary and cortical R2* were significantly higher in ATN group compared with AR and normal group, whereas the mean medullary and cortical R2* of AR group were significantly lower than normal group. The corticomedullary gradient of AR group was significantly lower compared with ATN and normal group. Medullary R2*:cortical R2* ratio was significantly lower in AR group compared with normal group. No significant difference was noted between the 15 donors and patients with normal graft function. R2* values on BOLD MRI are significantly decreased in AR allografts and increased in an early stage of ATN allografts, suggesting that BOLD MRI can become a valuable tool for discriminating between AR and ATN.
	[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta
	Prevalence and clinical correlates of white coat effect in patients with chronic kidney disease and the role of automated blood pressure device in its assessment	p. 448
	Srinivas Shenoy, Shankar Prasad Nagaraju, Nileshwar R Rau, Ravindra A Prabhu, Uday Venkat Mateti, Dharshan Rangaswamy, Indu R Rao, Karan Saraf DOI:10.4103/ijn.IJN_418_17   Context: Hypertension in chronic kidney disease (CKD) is an important modifiable cardiovascular risk factor. Patients with CKD can have clinically significant white coat effect (WCE), making routine clinic blood pressure (BP) measurements an unreliable indicator of actual BP control. Automated BP monitoring is useful in identifying WCE. The utility of automated BP monitoring has seldom been part of clinical practice in developing countries. Aim: The goal of this study was to estimate the prevalence and determinants of WCE in adult patients with CKD in an outpatient setting using an automated BP device. Materials and Method: In this prospective observational study, patients with CKD attending the nephrology clinic over a period of 6 months (January 2016 to July 2016), who were suspected to have WCE by the treating physician, were assigned to measurement of BP by both the standardized manual BP recording by a single nephrologist and with automated machine as per a defined protocol. Clinical, demographic characters that would influence outcomes were also studied. Results: Among 118 patients with CKD with suspected WCE, 57.6% showed WCE. The mean systolic and diastolic BPs were significantly lower with automated machine when compared with manual BP recordings in patients with WCE (p = 0.04). WCE was seen in all stages of CKD. Occurrence of WCE in CKD was not dependent on factors such as old age, sex, diabetes mellitus, or smoking status in our study. Conclusion:WCE is a highly prevalent and underdiagnosed entity in patients with CKD. Automated machine is a useful and time-saving tool in detection of WCE in patients with CKD attending the outpatient clinic and guide management.
	[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta
	Acute pyelonephritis: A single-center experience	p. 454
	L Umesha, SM Shivaprasad, EN Rajiv, MM Satish Kumar, V Leelavathy, CG Sreedhara, MR Niranjan DOI:10.4103/ijn.IJN_219_16   Acute pyelonephritis (APN), although a common clinical entity, still not much is known about the clinical profile in the Indian scenario. We prospectively collected clinical, biochemical, and radiological data of patients hospitalized with a diagnosis of APN from March 2014 to June 2016. A total of 296 cases were included in the study. Mean age was 53.85 ± 9.78 years. Male to females ratio was 1.93:1. Among the risk factors recognized for complicated pyelonephritis (PN), diabetes mellitus (DM) (54.4%) was the most common factor followed by renal calculi (14.4%), benign prostatic hyperplasia (6.7%), immunocompromised state (3.3%), stricture urethra and meatal stenosis (3.3%), and neurogenic bladder (2%). Urinary culture was negative in 153 (51.7%) and positive in 143 patient (48.3%). Most common organism isolated was Escherichia coli (29.7%), followed by Klebsiella pneumoniae (5.4%), pseudomonas (5.4%), Enterococcus (4.4%), and Proteus in 10 (3.4%). Serum creatinine of more than 1.5 mg/dl at admission was seen in 96.3% patients; 40% of them had underlying chronic kidney disease with DM being the most common. Multiorgan dysfunction either at admission or during the course in hospital stay was seen in 31.8% patients. Twelve (2%) had emphysematous PN. Six patients had Class II, 4 had Class III, 1 with Class I, and another with Class IV. A total of 18 deaths were noted (6.1%). Hemoglobin <10 g/dl, serum creatinine at admission >1.5 mg/dl, HbA1c% >10%, and immunosuppression had statistically significant association with the development of multiorgan dysfunction on univariate analysis, but on multivariate analysis, only hemoglobin, HbA1c%, and immunosuppression reached statistical significance. Even with attributable risk of mortality, only hemoglobin, HbA1c%, and immunosuppression reached statistical significance on multivariate analysis. HbA1c% adds to the predictive parameters to recognize at-risk patients to intensify the treatment and avoid complications.
	[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta
CASE REPORTS
	Hepatitis C virus-associated membranoproliferative glomerulonephritis treated with directly acting antiviral therapy	p. 462
	S Nayak, A Kataria, MK Sharma, A Rastogi, E Gupta, A Singh, SC Tiwari DOI:10.4103/ijn.IJN_235_17   Hepatitis C virus (HCV) infection has been shown to affect kidneys with various histopathological pattern on the kidney biopsy. These commonly include a membranoproliferative glomerulonephritis (MPGN) pattern with mixed cryoglobulinemia (CG), thrombotic microangiopathy, membranous nephropathy, and vasculitis affecting medium and small vessels of the kidneys causing polyarteritis nodosa. It has been rarely associated with MPGN without detectable CG. We present one such patient who presented to us with HCV-associated MPGN without detectable CG, who recovered completely with directly acting antiviral therapy without any immunosuppression.
	[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta
	Systemic lupus erythematosus with linear IgA bullous dermatosis and renal vascular lesions: An extremely rare association	p. 465
	R Malipatel, V Gnanapriya, A Manocha, YK Inchara DOI:10.4103/ijn.IJN_200_17   We report a rare case of systemic lupus erythematosus presenting initially with cutaneous manifestations of linear IgA bullous dermatosis. Later the patient developed renal abnormalities due to thrombotic microangiopathy and lupus nephritis with inflammatory necrotizing vasculitis. Paucity of immune deposits was observed on Immunofluorescence. This association of SLE with these cutaneous and renal lesions is rarely reported in the literature.
	[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta
	Xanthogranulomatous pyelonephritis: Intrahepatic and intrathoracic extension	p. 468
	U Anandh, N Birajdar, R Kumar, S Babu DOI:10.4103/ijn.IJN_213_17   A 32-year-old female presented to us with worsening cough and expectoration, low-grade fever, and malaise for 3 months. She gave a history of pregnancy loss secondary to urinary tract infection (UTI) a year back. At that time, she was told to have an obstructive right renal calculus. She also had a history of recurrent UTI in the past 1 year. She had no other comorbidities. Her clinical evaluation revealed an enlarged right kidney and reduced air entry in the right hemithorax. Radiological investigations revealed a large right kidney invading into the inferior surface of the right lobe of the liver and the right pleural space. A clinical diagnosis of xanthogranulomatous pyelonephritis was made, and she was advised nephrectomy. Intraoperatively, the right kidney was found to invade both the right lobe of the liver and the right pleural cavity through a right diaphragmatic defect. Histopathology of the kidney revealed the presence of foamy histiocytes suggestive of xanthogranulomatous pyelonephritis. Invasive xanthogranulomatous pyelonephritis is known, however, invasion into the extra-abdominal structures has not been reported in the literature. Our case is a rare manifestation of a rare clinical entity – xanthogranulomatous pyelonephritis.
	[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta
	Crystalline nephropathy in renal transplant: A series of 4 cases	p. 472
	K Mnif, S Yaich, M Mars, K Kammoun, F Fendri, K Charfeddine, F Jarraya, T Boudawara, J Hachicha DOI:10.4103/ijn.IJN_76_17   Crystals are particles of endogenous inorganic or organic composition that can trigger kidney injury when deposited or formed inside the kidney. The most common forms of crystalline nephropathies (CNs) are nephrocalcinosis and oxalate nephropathy. The causes of early allograft dysfunction are changing constantly, and recently calcium oxalate (CaOx) crystal deposition has been added to this list. CaOx deposition in renal allograft is important and probably under-recognized cause of delayed graft function that requires adequate awareness with early intervention to improve the allograft outcome. Here, we describe four cases of irreversible renal graft injury due to CNs.
	[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta
	Allopurinol-induced drug reactions with eosinophilia and systemic symptoms syndrome with interstitial nephritis	p. 477
	T Aatif, J Fatihi, H El Annaz, O Qamouss DOI:10.4103/ijn.IJN_166_17   Allopurinol-induced drug reactions with eosinophilia and systemic symptoms (DRESS) is a severe illness related to hypersensitivity syndrome characterized by fever, skin rash, lymph node enlargement, hematological abnormalities, especially eosinophilia and atypical lymphocytosis, and single or multiple organ involvement. The syndrome is difficult to diagnose in view of its clinical heterogeneity and long latency period within 8 weeks after start treatment. We report a case of DRESS syndrome in a 64-year-old man, induced by allopurinol treatment for asymptomatic hyperuricemia, started 8 weeks earlier but stopped only 3 days after because of the onset of rash. The diagnosis was retained due to combining of interstitial nephritis with the clinical findings of fever, skin rash, cervical lymphadenopathy, eosinophilia, and reactivation of human herpesviruses specifically HHV-6. The glucocorticoids were started to relieve hypersensitivity. Five days later, the patient became afebrile, and the rash improved significantly. However, interstitial nephritis with renal function impairment progressed to severe azotemia, and even anuria requiring hemodialysis. Allopurinol-induced DRESS syndrome is associated with significant mortality, and care must, therefore, be exercised when given this drug.
	[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta
	Autosomal dominant polycystic kidney disease: Presence of hypomorphic alleles in PKD1 Gene	p. 482
	S Pandita, D Khullar, R Saxena, IC Verma DOI:10.4103/ijn.IJN_236_17   Autosomal dominant polycystic kidney disease is characterized by multiple cysts in both kidneys manifesting in adult life. In general, the disorder is caused by a pathogenic variant in one allele of PKD1 or PKD2 genes, while the other allele is normal. Pathogenic variants in both the alleles are rare and have variable phenotypes, from lethal or perinatal presentation to a mild form in later adulthood, depending on the type of variant. Here, we describe a proband with two variants (p.Thr1773Ile and p.Ala1871Thr in trans) in PKD1 gene, who presented with disease at age 24 years. Both the parents and one brother had a variant in one allele, the other being wild type only and had normal ultrasound findings. Segregation studies suggest that both the variants may act as "hypomorphic" or "incompletely penetrant" alleles and acting together resulted in haploinsufficiency of protein PC1 in renal cells, leading to cystogenesis in the proband. The consequences of the presence of two hypomorphic variants have been poorly documented in literature. We reviewed the few published cases having two hypomorphic variants and the data conform to the conclusions that we reached by study of the family described. It is emphasized that to resolve the significance of suspected hypomorphic variants, segregation studies in the parents and siblings are essential.
	[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta
	An unusual association of renal cell carcinoma and renal malakoplakia with focal segmental glomerulosclerosis in an elderly patient	p. 485
	M Vijayan, P Koshy, R Parthasarathy, M Mathew, G Abraham DOI:10.4103/ijn.IJN_289_17   The association of malignancy and glomerulonephritis may be missed, especially in elderly patients. Here, we report a case of eosinophilic variant of renal cell carcinoma and renal parenchymal malakoplakia discovered on renal biopsy in a patient with steroid-dependent nephrotic syndrome. The presence of malakoplakia in our biopsy was probably due to systemic steroid therapy for glomerulonephritis, presence of concomitant asymptomatic urinary tract infection, and/or history of diabetes mellitus. The patient had remission of proteinuria following laparoscopic removal of the tumor, indicating probable remission of glomerulonephritis.
	[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta
	Kidney transplantation from a hepatitis C virus-positive donor to a hepatitis C virus-negative recipient	p. 488
	M Kamalkiran, V Ravikiran, C Shashidhar, K. V. R Prasad, V Yeldandi DOI:10.4103/ijn.IJN_267_17   Kidney transplantation from a hepatitis C virus (HCV)-positive donor to an HCV-negative recipient till recently has been a contraindication. In view of the excellent sustained virological response (SVR) rates with directly acting antiviral agents, HCV-positive donors are being considered for the HCV-negative recipients in a few centers. We report the successful transplantation of an HCV-negative recipient transplanted with an HCV-positive donor kidney. Donor was treated with sofosbuvir and ribavirin for 12 weeks. At 10th and 16th weeks of starting treatment, her HCV-RNA PCR was negative. Three weeks later, transplantation was performed with basiliximab induction and triple immunosuppression with tacrolimus, mycophenolate, and prednisolone. The recipient was administered sofosbuvir and ribavirin for 12 weeks. He attained good graft function with a stable creatinine. His serial alanine transaminases were normal on 3rd, 6th, and 12th months, respectively. Six months posttransplant his anti-HCV antibody, and HCV-RNA PCR were negative.
	[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta
LETTERS TO EDITOR
	Cystinuria in a 13-Month-Old girl with absence of mutations in the SLC3A1 and SLC7A9 genes	p. 490
	MD Al-Mendalawi DOI:10.4103/ijn.IJN_46_18
	[HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta
	Improving crossmatch techniques and graft outcomes	p. 491
	L Vincent DOI:10.4103/ijn.IJN_362_17
	[HTML Full text]  [PDF]  [Sword Plugin for Repository]Beta
	Estimated glomerular filtration rate using creatinine-based chronic kidney disease epidemiology collaboration equation	p. 492
	AA Rani, V Viswanathan DOI:10.4103/ijn.IJN_439_17
	[HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [Sword Plugin for Repository]Beta