Prediabetes and diabetes prevalence in the Workers’ Oral Health Study

Abstract

Objective

To examine the association between periodontitis, diabetes, and prediabetes, assessed by fasting plasma glucose (FPG).

Materials and methods

Workers' Oral Health Study is a cross-sectional survey conducted on a representative sample of the Spanish employed population including 5154 participants (59.5% men, aged 16–65). Examination of periodontal status assessed Community Periodontal Index (CPI) and clinical attachment levels (CAL). Biochemical determinations included fasting plasma glucose (FPG), triglycerides, and total cholesterol. Logistic regression analysis with adjustment for potential confounders was used to evaluate the association between periodontitis and abnormal glucose regulation.

Results

Ninety-five participants (2.2%) of the study population had diabetes, while 373 (8.8%) presented prediabetes. Prediabetes was not associated with CPI or CAL in fully adjusted multivariate logistic regressions models. Diabetes was significantly associated with subjects having a CPI 4 after adjustment for potential confounders (odds ratio OR = 1.9, 95% confidence interval (CI) 1.1–3.1). This association was stronger in subjects < 45 years (OR = 4.0, 95% CI 1.2–12.7).

Conclusion

Periodontitis was associated with diabetes mellitus, but not with prediabetes, in a representative sample of the Spanish employed population. The association was stronger for younger subjects, which emphasizes the need for early detection of diabetes in younger patients affected by periodontitis, particularly because periodontal therapy may help to improve glycemic control.

Clinical relevance

Periodontitis is associated with diabetes mellitus, having at the same time a negative effect on glycemic control. It is important to develop proper early diagnosis strategies for both conditions, particularly in young male adults.

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Prevalence of low lean mass in patients with adult growth hormone deficiency with or without low‐dose growth hormone therapy

Abstract

Objective

The importance of muscle mass has been emphasized in various studies, and growth hormone (GH) deficiency is tightly associated with lean mass loss. Therefore, we aimed to investigate the prevalence of low lean mass in patients with adult growth hormone deficiency (AGHD) who received or did not receive GH therapy.

Methods

In this retrospective study, we included patients diagnosed with AGHD by using the insulin tolerance test (ITT) in our hospital. Patients without completed follow‐up data were excluded, and data for 56 patients were analysed. Twenty‐six patients who had received GH therapy for more than 6 months, based on the medical record, were included in the GH group and received recombinant human growth hormone (rhGH) at a dose of 0.5 IU/day. Thirty patients who had not previously received GH treatment were included in the non‐GH group. Many anthropometric and blood biochemical indicators were measured. Body composition was measured on a dual‐energy X‐ray‐absorptiometry (DXA) scanner. Low lean mass was defined as a skeletal muscle index (SMI) less than 7.0 kg/m² in males or 5.7 kg/m² in females. Statistical analyses were performed using GraphPad Prism 5.0.

Results

Compared to the non‐GH group, the patients who received GH therapy had significantly lower total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐c), and fasting plasma glucose (FPG). The percentage of patients with low lean mass in GH and non‐GH groups was 30.77% and 60%, respectively. The percentage of total lean was lower in the GH group than in the non‐GH group, but the difference in total lean mass was not statistically significant. Conversely, patients with GH treatment had significantly lower fat mass and percentage than non‐GH‐treated patients (p<0.05). The GH group had significantly higher serum levels of both IGF‐1 and IGFBP3. Moreover, both IGF‐1 and IGFBP3 were significantly correlated with SMI (r²=0.275, p=0.003, and r²=0.138, p=0.005, respectively).

Conclusions

Our data showed that AGHD patients who received low‐dose GH treatment had a lower prevalence of low lean mass than those who did not receive GH treatment. Patients with GH treatment had significantly lower cardiovascular risk factors, especially the lipid profile.

This article is protected by copyright. All rights reserved.

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Medical Therapy in Patients with Endogenous Hypoglycaemia: is Euglycaemia Achievable?

Abstract

Context

While the only curative treatment for patients with endogenous hypoglycaemia related to inappropriate insulin or to insulin growth factor 2 (IGF2) secretion is surgery, medical treatment to normalise plasma glucose levels can be useful.

Objective

The aim of this prospective single centre study was to assess whether patients with endogenous hypoglycaemia, considered euglycaemic with medical treatments, experienced asymptomatic hypo‐ or hyperglycaemic excursions.

Patients and Methods

All patients with endogenous hypoglycaemia related to inappropriate insulin or to IGF2 secretion between 2012 and 2016 and considered normoglycaemic with medical treatment (absence of clinical hypoglycaemia and self‐monitoring blood glucose in the normal range) were enrolled and underwent a six‐day continuous glucose monitoring (CGM) recording.

Results

Twenty‐seven patients (inappropriate insulin secretion n=25 and IGF2 secretion n=2), treated with diazoxide (n=16), somatostatin analogues (n=7), glucocorticoids (n=3) or a combination of these treatments (n=1) were enrolled. Twenty‐five CGMs were analysed. CGM confirmed normoglycaemia in 11/25 patients (44%). Hypoglycaemias below 0.60 g/L were present in 7 patients (28%) and were associated with hyperglycaemic excursions above 1.40 g/L in 5 patients. Seven patients (28%) had only hyperglycaemic excursions. Based on these results, treatment was modified in 14 patients (56%).

Conclusion

Despite the disappearance of hypoglycaemia‐related clinical symptoms and normalisation of blood glucose self‐monitoring data, 56% of the patients with endogenous hypoglycaemia treated with medical therapy experienced asymptomatic hypo‐ and/or hyperglycaemia. Continuous glucose monitoring could be a useful approach to reveal and prevent hypo‐ or hyperglycaemic excursions.

This article is protected by copyright. All rights reserved.

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Echocardiography and monitoring patients receiving dopamine agonist therapy for hyperprolactinaemia: A joint position statement of the British Society of Echocardiography, the British Heart Valve Society and the Society for Endocrinology

Summary

This is a joint position statement of the British Society of Echocardiography, the British Heart Valve Society and the Society for Endocrinology on the role of echocardiography in monitoring patients receiving dopamine agonist (DA) therapy for hyperprolactinaemia. Evidence that DA pharmacotherapy causes abnormal valve morphology and dysfunction at doses used in the management of hyperprolactinaemia is extremely limited. Evidence of clinically significant valve pathology is absent, except for isolated case reports around which questions remain. Attributing change in degree of valvar regurgitation, especially in mild and moderate tricuspid regurgitation, to adverse effects of DA in hyperprolactinaemia should be avoided if there are no associated pathological changes in leaflet thickness, restriction or retraction. Note must be taken that even where morphological change in leaflet structure and function may be suspected, grading is semi‐quantitative on echocardiography and may vary between different machines, ultrasound settings and operators. Decisions regarding discontinuation of medication should only be made after review of serial imaging by an echocardiographer experienced in analysing drug‐induced valvulopathy or carcinoid heart disease. A standard transthoracic echocardiogram should be performed before a patient starts DA therapy for hyperprolactinaemia. Repeat transthoracic echocardiography should then be performed at 5 years after starting cabergoline in patients taking a total weekly dose less than or equal to 2 mg. If there has been no change on the 5‐year scan, repeat echocardiography could continue at 5‐yearly intervals. If a patient is taking more than a total weekly dose of 2 mg, then annual echocardiography is recommended.

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A juvenile male case of dermatofibrosarcoma protuberans on the breast

https://ift.tt/2XwX2Gq

Accidental re‐exposure causing repeated severe acute generalized exanthematous pustulosis

https://ift.tt/2SD0hII

Reply to: “Could Isotretinoin flare Hidradentis suppurativa? A Case Series”

Abstract

We read with interest the manuscript recently published by Gallagher¹et al. concerning eight patients with severe acne who were treated with isotretinoin and developed hidradenitis suppurativa (HS). Conversely to the authors, we experienced flares in patients with HS treated with retinoids. We report three cases of patients with moderate‐severe HS localized in their axillae and groins.

This article is protected by copyright. All rights reserved.

https://ift.tt/2XE6hEK

[18F]‐Fluorodeoxy‐D‐glucose uptake in prurigo nodules induced by the membranous expression of glucose transporter

Abstract

Positron emission tomography‐computed tomography (PET/CT) is a valuable imaging modality for assessing malignant tumours; however, the aberrant uptake of [¹⁸F]‐fluorodeoxy‐D‐glucose (FDG) is sometimes observed in benign skin lesions such as corns, seborrhoeic keratosis, viral warts, condyloma acuminatum, rhinophymas, and acne vulgaris^1,2. We encountered a case of prurigo nodularis associated with abnormal uptake of FDG and evaluated the expression of the glucose transporter in the lesions. A 55‐year‐old male with a pulmonary metastasis of malignant melanoma received nivolumab. After three years' nivolumab administration, a PET/CT was performed to evaluate the effect of the immunotherapy.

This article is protected by copyright. All rights reserved.

https://ift.tt/2SzdBxm

Extending the phenotypic spectrum associated with mosaicism for GJB2 mutations

Abstract

Cutaneous mosaicism is a common phenomenon resulting from postzygotic mutations. Mosaic skin lesions are manifold, and they may be accompanied by abnormalities of other organs. Here we investigated a young man with complex clinical features as part of a mosaic phenotype.

This article is protected by copyright. All rights reserved.

https://ift.tt/2XuDUc4

miR‐145‐5p regulates fibrotic features of recessive dystrophic epidermolysis bullosa skin fibroblasts

Summary

Background

Recessive dystrophic epidermolysis bullosa (RDEB) is a skin fragility disorder caused by mutations in the COL7A1 gene encoding type VII collagen, a cutaneous basement membrane component essential for epidermal‐dermal adhesion. Hallmarks of the disease are unremitting blistering and chronic wounds with severe inflammation and fibrosis. microRNAs are post‐transcriptional regulators of gene expression also implicated in fibrotic processes. However, the role of microRNAs in RDEB fibrosis is almost unexplored.

Objectives

Our study aimed at identifying microRNAs deregulated in primary RDEB skin fibroblasts (RDEBFs) and at characterizing their function in RDEB fibrosis.

Methods

qRT‐PCR was used to screen RDEBFs for the expression levels of a group of microRNAs deregulated in hypertrophic scars and keloids, pathological conditions with abnormal wound healing and fibrosis. Contractility, proliferation and migration rate were evaluated by different in vitro assays in RDEBFs transfected with a miR‐145‐5p inhibitor. qRT‐PCR and western blot analysis provided the expression levels of fibrotic markers and miR‐145‐5p targets.

Results

The miR‐143/145 cluster was up‐regulated in RDEBFs with respect to fibroblasts from healthy subjects. RDEBFs transfected with a miR‐145‐5p inhibitor showed attenuated fibrotic traits, i.e. contraction, proliferation and migration, accompanied by reduced expression of the contractile proteins α‐smooth muscle actin and transgelin. These effects were associated with the up‐regulation of kruppel like factor 4 transcriptional repressor and the down‐regulation of Jagged 1, a known inducer of fibrosis.

Conclusions

Our results highlight the pro‐fibrotic role of miR‐145‐5p and its regulatory networks in RDEB, shedding light on novel disease pathomechanisms and targets for future therapeutic approaches.

This article is protected by copyright. All rights reserved.

https://ift.tt/2SzboSA

Hematologic Complications of Immune Checkpoint Inhibitors

AbstractImmune checkpoint inhibitors have improved outcomes for patients with numerous hematological and solid cancers. Hematologic toxicities have been described, but the spectrum, timing, and clinical presentation of these complications are not well understood. We used the World Health Organization's pharmacovigilance database of individual‐case‐safety‐reports (ICSRs) of adverse drug reactions, VigiBase, to identify cases of hematologic toxicities complicating immune checkpoint inhibitor therapy. We identified 168 ICSRs of immune thrombocytopenic purpura (ITP), hemolytic anemia (HA), hemophagocytic lymphohistiocytosis, aplastic anemia, and pure red cell aplasia in 164 ICSRs. ITP (n = 68) and HA (n = 57) were the most common of these toxicities and occurred concomitantly in four patients. These events occurred early on treatment (median 40 days) and were associated with fatal outcome in 12% of cases. Ipilimumab‐based therapy (monotherapy or combination with anti‐programmed death‐1 [PD‐1]) was associated with earlier onset (median 23 vs. 47.5 days, p = .006) than anti‐PD‐1/programmed death ligand‐1 monotherapy. Reporting of hematologic toxicities has increased over the past 2 years (98 cases between January 2017 and March 2018 vs. 70 cases before 2017), possibly because of increased use of checkpoint inhibitors and improved recognition of toxicities. Future studies should evaluate incidence of hematologic toxicities, elucidate risk factors, and determine the most effective treatment algorithms.Key Points. Immune‐mediated hematologic toxicities are a potential side effect of immune checkpoint inhibitors (ICIs).Providers should monitor complete blood counts during treatment with ICIs.Corticosteroids are the mainstay of treatment for immune‐mediated hematologic toxicities.Further research is needed to define patient‐specific risk factors and optimal management strategies for hematologic toxicities.

https://ift.tt/2tFVw6W

Hospital Volume Versus Good Clinical Practice

https://ift.tt/2H6hec9

The Other Opioid Crisis: Just Another Drug Shortage?

https://ift.tt/2tKuATM

The experience of an Endocrinology Division on the use of tyrosine multikinase inhibitor therapy in patients with radioiodine-resistant differentiated thyroid cancer

Abstract

Purpose

To describe the experience of our Division of Endocrinology with multikinase inhibitor (MKI) treatment in radioiodine-resistant differentiated thyroid cancer (DTC) patients.

Methods

Adults patients with a diagnosis of DTC treated with an MKI drug from March 2011 to October 2018 were registered into a retrospective database. Primary objectives were: the assessment of progression-free survival (PFS) and radiographic response evaluated according to RECIST v. 1.1. Adverse events (AEs) were evaluated by using Common Terminology Criteria for Adverse Events v. 5.0.

Results

Twenty-two patients were treated with MKIs (21 with sorafenib, one with lenvatinib as first-line treatment). Seven patients required a second-line therapy with lenvatinib and one patient required a third-line treatment with pazopanib. Median duration of treatment was 11.2 (4.8–79.6) months. Best responses with sorafenib were partial response (PR) in two patients (11%), stable disease (SD) >6 months in 13 patients (72%), and progressive disease (PD) in three patients (17%). Best responses with second-line lenvatinib were PR in one patient (33%) and SD in two patients (66%). Median PFS was 31.5 months. AEs were present in 19 (90%) patients under sorafenib. The most common AEs were hand–foot syndrome (HFS) (67%), diarrhea (52%), and hypertension (52%). Definitive withdrawal was necessary in only one patient (4.7%).

Conclusions

Our study reflects the real-world clinical experience of an Endocrinology Division on the management of radioiodine-resistant DTC patients with sorafenib and lenvatinib, showing a beneficial therapeutic effect with acceptable tolerability.

https://ift.tt/2tFvfpv

Bone Mineral Density and Estimated Hip Strength in Men with Anorexia Nervosa, Atypical Anorexia Nervosa and Avoidant/Restrictive Food Intake Disorder

Summary

Objective

Few bone mineral density (BMD) data are available in men with anorexia nervosa (AN), and none in those with atypical AN (ATYP) (AN psychological symptoms without low weight) or avoidant/restrictive food intake disorder (ARFID) (restrictive eating without AN psychological symptoms). We investigated the prevalence and determinants of low BMD and estimated hip strength in men with these disorders.

Design

Cross‐sectional: two centers.

Patients

103 men, 18‐63y: AN (n=26), ARFID (n=11), ATYP (n=18), healthy controls (HC) (n=48).

Measurements

Body composition, BMD, and estimated hip strength (section modulus and buckling ratio) by DXA (Hologic). Serum 25OH vitamin D was quantified, as was daily calcium intake in a subset of subjects.

Results

Mean BMI was lowest in AN and ARFID, higher in ATYP, and highest in HC (AN 14.7±1.8, ARFID 15.3±1.5, ATYP 20.6±2.0, HC 23.7±3.3 kg/m²) (p<0.0005). Mean BMD Z‐scores at spine and hip were lower in AN and ARFID, but not ATYP, than HC (PA spine AN ‐2.05±1.58, ARFID ‐1.33±1.21, ATYP ‐0.59±1.77, HC ‐0.12±1.17) (p<0.05). 65% AN, 18% ARFID, 33% ATYP, and 6% HC had BMD Z‐scores <‐2 at ≥1 site (AN and ATYP vs HC, p<0.01). Mean section modulus Z‐scores were lower in AN than HC (p<0.01). Lower BMI, muscle mass, and vitamin D levels (R=0.33‐0.64), as well as longer disease duration (R=‐0.51‐ ‐0.58), were associated with lower BMD (p<0.05).

Conclusions

Men with AN, ARFID, and ATYP are at risk for low BMD. Men with these eating disorders who are low weight, or who have low muscle mass, long illness duration, and/or vitamin D deficiency, may be at particularly high risk.

This article is protected by copyright. All rights reserved.

https://ift.tt/2H6bNtL

CHEK2 Alleles Predispose to Renal Cancer in Poland

Carlo et al reported that CHEK2 mutations were the most common inherited mutations found in 254 unselected patients with advanced renal cancer in the United States. In 2004, we reported that the CHEK2 missense mutation I157T was associated with a 2-fold increased risk of renal cancer in Poland. To extend our earlier findings, we have begun a new study of CHEK2 mutations. Thus far, we have genotyped 835 patients with invasive renal cancer (including 264 included in the prior study) and 8302 cancer-free, population-based, adult control participants for 4 CHEK2 founder alleles: 1 missense mutation (I157T) and 3 truncating mutations (1100delC, IVS2 + 1G>A, del5395). The I157T allele was present in 78 participants with renal cancer and 410 control participants (odds ratio [OR], 2.0; 95% CI, 1.6-2.6; P < .001) (unpublished data, 2018). A truncating mutation was present in 20 participants and 80 control participants (OR, 2.5; 95% CI, 1.5-4.1; P = .0003) (unpublished data, 2018). Unlike the situation for breast cancer, but similar to the situation for colon cancer, the risk of cancer associated with the missense allele was similar to that of the truncating alleles. In Poland, the number of I157T mutations in patients with renal cancer outnumbered the 1100delC mutations by 193 to 4 (unpublished data, 2018), whereas in the United States, the 1100delC alleles outnumbered the I157T alleles by 7 to 2. The lifetime risk of renal cancer in Poland is 1% (Polish Cancer Registry) and even if the risk is doubled, we do not believe that the risk is sufficiently high to warrant ultrasound screening of CHEK2 carriers.

https://ift.tt/2IIQgKj

Digital Breast Tomosynthesis vs Digital Mammography Screening Outcomes

This cohort study compares cancer detection rate by patient age and breast density as well as cancer detection and prognosis outcomes when using digital breast tomosynthesis vs digital mammography alone for breast cancer screening.

https://ift.tt/2The2kA

Honesty in Medicine—An Approach to Patients With Cancer Who Initially Reject Conventional Treatment

This essay describes one physician's approach to patients with cancer who question their initial decision to forgo conventional definitive treatment.

https://ift.tt/2IIXPQX

Breast Cancer Screening Using Digital Breast Tomosynthesis

Digital breast tomosynthesis (DBT), a form of mammography approved by the US Food and Drug Administration in 2011, involves the acquisition of projection images that are reconstructed into thin sections of the breast. Despite emerging evidence that use of DBT improves cancer detection and reduces false-positive examination results when compared with 2-dimensional digital mammography (DM), questions remain regarding its performance across different patient subgroups, the size and stage of the cancers detected, and long-term patient outcomes. In this issue of JAMA Oncology, Conant and colleagues report outcomes of breast cancer screening using DBT vs DM among 96 269 women aged 40 to 74 years across 3 research centers in the Population-Based Research Optimizing Screening Through Personalized Regimens (PROSPR) consortium. Based on data from 50 971 screening examinations using DBT and 129 369 screening examinations using DM, the authors conclude that DBT screening was associated with higher cancer detection rates and lower recall rates across all ages and density groups. In addition, the authors report that DBT-detected cancers were more likely to be smaller and node negative than were DM-detected cancers, particularly among women aged 40 to 49 years.

https://ift.tt/2Tn31OC

Peripheral Neuropathy

This patient page describes the risks, symptoms, complications, and recommended treatment options for chemotherapy-induced peripheral neuropathy.

https://ift.tt/2IFDagN

CHEK2 Alleles Predispose to Renal Cancer in Poland—In Reply

In Reply The 2.0 to 2.5 odds ratio for renal cancer for different CHEK2 variants reported by Zlowocka-Perlowska and colleagues in their letter closely approximates our pooled analysis that showed an odds ratio of 3.0 (95% CI, 1.3-5.8). Of note, Zlowocka-Perlowska et al have found a single CHEK2 founder mutation (I157T) in a striking 9.3% of renal cancer cases in Poland thus far, but they describe the risk for this mutation as being similar to other truncating CHEK2 mutations. With tumor-normal genotyping now being conducted across multiple cancer types to guide preventive care and target therapies, population-specific variant–level analysis such as the analysis performed by Zlowocka-Perlowska et al will facilitate more precise cancer risk estimates.

https://ift.tt/2ThqKzR

Assessment of Blood Tumor Mutational Burden as a Potential Biomarker for Immunotherapy in Non–Small Cell Lung Cancer

This study explores whether blood tumor mutational burden estimated by a next-generation sequencing gene panel is associated with clinical outcomes of patients with non–small cell lung cancer treated with anti–programmed cell death 1 and anti–programmed cell death ligand 1 agents.

https://ift.tt/2IId3G2

Maintenance Therapies for Hodgkin and Non-Hodgkin Lymphomas After Autologous Transplantation

This consensus project reports the findings of the American Society for Blood and Marrow Transplantation, Center for International Blood and Marrow Transplant Research, and European Society for Blood and Marrow Transplantation expert panel, which convened to formulate consensus recommendations regarding the use of maintenance and/or consolidation therapies after autologous hematopoietic cell transplantation in patients with lymphoma.

https://ift.tt/2TsEGap

Use, Safety, and Efficacy of Single-Patient Use of the FDA Expanded Access Program

This study assesses the outcomes of single-patient use of the US Food and Drug Administration Expanded Access program.

https://ift.tt/2IIkcpU

Sonocatalytic degradation of butylparaben in aqueous phase over Pd/C nanoparticles

Abstract

In the present work, the sonocatalytic degradation of butylparaben was investigated using Pd immobilized on carbon black as the sonocatalyst. The presence of 25 mg/L 10Pd/C significantly increased the removal rate of butylparaben and the observed kinetic constant increased from 0.0126 to 0.071 min⁻¹, while the synergy index between sonolysis and adsorption was 70.7%. The BP degradation followed pseudo-first-order kinetics with the apparent kinetic constant decreased from 0.071 to 0.030 min⁻¹ when the initial concentration of butylparaben increased from 0.5 to 2 mg/L. The process was being favored slightly under alkaline conditions. The presence of organic matter (20 mg/L humic acid) reduced the apparent kinetic constant more than two times. The addition of chlorides up to 250 mg/L did not significantly reduce the rate of reaction, while the presence of 250 mg/L bicarbonates reduced the observed kinetic constant from 0.071 to 0.0472 min⁻¹. The prepared catalyst retains the efficiency after five subsequent experiments since the apparent kinetic constant was only slightly decreased from 0.071 to 0.059 min⁻¹.

https://ift.tt/2ED3Uua

The experience of an Endocrinology Division on the use of tyrosine multikinase inhibitor therapy in patients with radioiodine-resistant differentiated thyroid cancer

Abstract

Purpose

To describe the experience of our Division of Endocrinology with multikinase inhibitor (MKI) treatment in radioiodine-resistant differentiated thyroid cancer (DTC) patients.

Methods

Adults patients with a diagnosis of DTC treated with an MKI drug from March 2011 to October 2018 were registered into a retrospective database. Primary objectives were: the assessment of progression-free survival (PFS) and radiographic response evaluated according to RECIST v. 1.1. Adverse events (AEs) were evaluated by using Common Terminology Criteria for Adverse Events v. 5.0.

Results

Twenty-two patients were treated with MKIs (21 with sorafenib, one with lenvatinib as first-line treatment). Seven patients required a second-line therapy with lenvatinib and one patient required a third-line treatment with pazopanib. Median duration of treatment was 11.2 (4.8–79.6) months. Best responses with sorafenib were partial response (PR) in two patients (11%), stable disease (SD) >6 months in 13 patients (72%), and progressive disease (PD) in three patients (17%). Best responses with second-line lenvatinib were PR in one patient (33%) and SD in two patients (66%). Median PFS was 31.5 months. AEs were present in 19 (90%) patients under sorafenib. The most common AEs were hand–foot syndrome (HFS) (67%), diarrhea (52%), and hypertension (52%). Definitive withdrawal was necessary in only one patient (4.7%).

Conclusions

Our study reflects the real-world clinical experience of an Endocrinology Division on the management of radioiodine-resistant DTC patients with sorafenib and lenvatinib, showing a beneficial therapeutic effect with acceptable tolerability.

https://ift.tt/2tFvfpv

Removal of metronidazole and amoxicillin mixtures by UV/TiO 2 photocatalysis: an insight into degradation pathways and performance improvement

Abstract

The degradation efficiencies and pathways of metronidazole (MNZ) and amoxicillin (AMX) in binary mixtures by UV/TiO₂ photocatalysis were studied. The presence of AMX significantly decreased the degradation of MNZ, whereas the existence of MNZ slightly reduced the degradation of AMX. This is basically due to the difference in attack ability of oxidizing agents present during TiO₂ photocatalysis. All oxidizing agents (hydroxyl radicals, superoxide radicals, and holes) could attack AMX molecules, but hydroxyl radicals showed insignificant attack ability in MNZ degradation. In TiO₂ photocatalysis of binary mixture, six transformation products were recognized by a high-resolution LC-QTof/MS. Because of competitive effect, only one product was sourced from MNZ degradation and four others were formed due to AMX degradation. The remaining one was a new product of the side reaction. This work indicated that the molecular structure of AMX determined its preferred degradation in a mixture. It not only affected the removal of antibiotics but also figured out the appearance of transformation products. In contrast to single systems, the extent of degradation reduced for each antibiotic in the presence of the second antibiotic was related to the availability of degradation pathways of each antibiotic. Moreover, suitable pH programming was applied to enhance the mineralization of the mixtures.

https://ift.tt/2XwQjfF

A Prospective Study of Apatinib Plus Concurrent Neoadjuvant Chemoradiotherapy in Patients With Esophageal Squamous Cell Carcinoma

Condition:   Esophageal Squamous Cell Carcinoma
Intervention:   Combination Product: Apatinib,Paclitaxel,Cisplatin,RT
Sponsor:   Hebei Medical University Fourth Hospital
Not yet recruiting

https://ift.tt/2EiImBP

Increased risk of tuberculosis in oral cancer patients in an endemic area: a nationwide population-based study

Abstract

Objectives

We investigated the incidence of tuberculosis (TB) in patients with newly diagnosed oral cancer and analyzed the risk factors for TB development and mortality in oral cancer patients.

Materials and methods

We used Taiwan's National Health Insurance Database to determine the incidence of TB and to analyze the risk factors for TB in patients newly diagnosed with oral cancer. From 2000 to 2011, we identified 40,327 oral cancer patients and the same number of subjects from the general population matched for sex, age, and comorbidities at a 1:1 ratio.

Results

Compared with the matched cohort, oral cancer patients exhibited a higher risk for TB (adjusted hazard ratio (aHR) 2.36, 95% confidence interval (CI) 2.06–2.71). Age ≥ 50 (aHR 1.90, 95% CI 1.57–2.29), being male (aHR 1.98, 95% CI 1.36–2.89), having diabetes mellitus (aHR 1.31, 95% CI 1.05–1.64), alcohol use disorder (aHR 1.42, 95% CI 1.06–1.89), human immunodeficiency virus (HIV) (aHR 8.24, 95% CI 2.05–33.14), chemotherapy (aHR 1.41, 95% CI 1.15–1.72), and radiotherapy for oral cancer (aHR 1.92, 95% CI 1.57–2.36) were identified as independent risk factors for TB in oral cancer patients. Hyperlipidemia was an independent protective factor for TB in oral cancer patients.

Conclusion

Old age, male sex, diabetes mellitus, alcohol use disorder, and HIV were independent risk factors for TB in patients with oral cancer.

Clinical relevance

High-risk oral cancer patients should be regularly screened for TB, especially those in endemic areas.

https://ift.tt/2EnbHuX

A novel BiVO 4 -GO-TiO 2 -PANI composite for upgraded photocatalytic performance under visible light and its non-toxicity

Abstract

A novel non-toxic hybrid BiVO₄-GO-TiO₂-polyaniline (PANI) (BVGT-PANI) composite with superior photocatalysis was successfully prepared via a one-pot hydrothermal reaction. The structural and morphological characterizations of the synthesized compounds were analyzed by a series of techniques. We found excellent photocatalytic efficiencies for methylene blue (MB) and phenol degradation under visible light irradiation after adhering the PANI to the photocatalyst. The degradation rates of MB and phenol reach up to approximately 85% and 80%, respectively, after 3 h of irradiation. For photodegradation MB, BVGTA exhibit the highest k_app rate constant of about 1.06 × 10⁻² min⁻¹, which is about 1.63-fold faster than BVG and 2.94-fold faster than BVGT. For photodegradation of phenol, BVGTA exhibits the highest k_app rate constant, of about 8.86 × 10⁻³min⁻¹, which is about 1.2-fold faster than BVG and 1.96-fold faster than BVGT. Furthermore, vitro toxicity test against Bacillus subtilis and Staphylococcus aureus demonstrated that the nanophotocatalyst is non-toxic.

https://ift.tt/2EEeCRq

Typical characteristics of children with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency: a single-centre experience and review of the literature

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


https://ift.tt/2IIHBr0

Serum omentin-1 levels in obese children

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


https://ift.tt/2TmxqMW

A pilot study on newborn screening for congenital adrenal hyperplasia in Beijing

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


https://ift.tt/2IHaKmz

The role of endogenous nitric oxide in melatonin-improved tolerance to lead toxicity in maize plants

Abstract

Melatonin (MT) and nitric oxide (NO) are known as scavengers of free radicals and an antioxidant against biotic and abiotic stresses in plant defense systems. However, whether NO interplays role in MT-induced antioxidant defense remains to be determined in the plants exposed to lead (Pb) toxicity. So, two experiments were designed to evaluate the role of NO in MT-mediated tolerance of maize plants to Pb stress. In the initial experiment, prior to starting different treatments, a solution of 0.05- or 0.10-mM MT was sprayed every other day for a period of 10 days to the leaves of maize plants exposed to Pb stress (0.1-mM PbCl₂). Pb toxicity significantly caused reduction in plant biomass (both fresh and dry), PSII maximum efficiency (F_v/F_m), total chlorophyll, leaf potassium (K), calcium (Ca), and leaf water potential, but it resulted in increased levels of proline, hydrogen peroxide (H₂O₂), malondialdehyde (MDA), electron leakage (EL), leaf Pb, and endogenous NO. An addition experiment was set up to further understand whether NO played role in mitigation of Pb toxicity in maize plants by MT using scavengers of NO and cPTIO combined with the MT treatments. MT-induced tolerance to Pb toxicity was totally eliminated by cPTIO by reversing endogenous NO. The present results clearly indicated that MT mediated the endogenous NO to improve tolerance of maize plants to Pb toxicity. This evidence was also supported by the increases of H₂O₂ and MDA and reduces some antioxidant enzyme activities tested as well as the plant growth inhibition and increased leaf Pb content by application of MT combined with cPTIO.

https://ift.tt/2TnoYgt

CD8 + T-bet+ cells as a predominant biomarker for inclusion body myositis

Publication date: Available online 28 February 2019

Source: Autoimmunity Reviews

Author(s): Gaëlle Dzangué-Tchoupou, Kuberaka Mariampillai, Loïs Bolko, Damien Amelin, Wladimir Mauhin, Aurélien Corneau, Catherine Blanc, Yves Allenbach, Olivier Benveniste

Abstract

Background

Myositis is a heterogeneous group of muscular auto-immune diseases with clinical and pathological criteria that allow the classification of patients into different sub-groups. Inclusion body myositis is the most frequent myositis above fifty years of age. Diagnosing inclusion body myositis requires expertise and is challenging. Little is known concerning the pathogenic mechanisms of this disease in which conventional suppressive-immune therapies are inefficacious.

Objectives

Our aim was to deepen our understanding of the immune mechanisms involved in inclusion body myositis and identify specific biomarkers.

Methods

Using a panel of thirty-six markers and mass cytometry, we performed deep immune profiling of peripheral blood cells from inclusion body myositis patients and healthy donors, divided into two cohorts: test and validation cohorts. Potential biomarkers were compared to myositis controls (anti-Jo1-, anti-3-hydroxyl-3-methylglutaryl CoA reductase-, and anti-signal recognition particle-positive patients).

Results

Unsupervised analyses revealed substantial changes only within CD8+ cells. We observed an increase in the frequency of CD8+ cells that expressed high levels of T-bet, and containing mainly both effector and terminally differentiated memory cells. The senescent marker CD57 was overexpressed in CD8 + _T-bet+ cells of inclusion body myositis patients. As expected, senescent CD8 + _T-bet+CD57+ cells of both patients and healthy donors were CD28_nullCD27_nullCD127_null. Surprisingly, non-senescent CD8 + _T-bet+CD57- cells in inclusion body myositis patients expressed lower levels of CD28, CD27, and CD127, and expressed higher levels of CD38 and HLA-DR compared to healthy donors. Using classification and regression trees alongside receiver operating characteristics curves, we identified and validated a frequency of CD8 + _T-bet+ cells >51.5% as a diagnostic biomarker specific to inclusion body myositis, compared to myositis control patients, with a sensitivity of 94.4%, a specificity of 88.5%, and an area under the curve of 0.97.

Conclusion

Using a panel of thirty-six markers by mass cytometry, we identify an activated cell population (CD8 + _T-bet+CD57- CD28_lowCD27_lowCD127_low CD38+ HLA-DR+) which could play a role in the physiopathology of inclusion body myositis, and identify CD8 + _T-bet+ cells as a predominant biomarker of this disease.

https://ift.tt/2IGSb1R

Endogenous double-stranded Alu RNA elements stimulate IFN-responses in relapsing remitting multiple sclerosis

Publication date: Available online 28 February 2019

Source: Journal of Autoimmunity

Author(s): Maxwell J. Heinrich, Caroline A. Purcell, Andrea J. Pruijssers, Yang Zhao, Charles F. Spurlock, Subramaniam Sriram, Kristen M. Ogden, Terence S. Dermody, Matthew B. Scholz, Philip S. Crooke, John Karijolich, Thomas M. Aune

Abstract

Various sensors that detect double-stranded RNA, presumably of viral origin, exist in eukaryotic cells and induce IFN-responses. Ongoing IFN-responses have also been documented in a variety of human autoimmune diseases including relapsing-remitting multiple sclerosis (RRMS) but their origins remain obscure. We find increased IFN-responses in leukocytes in relapsing-remitting multiple sclerosis at distinct stages of disease. Moreover, endogenous RNAs isolated from blood cells of these same patients recapitulate this IFN-response if transfected into naïve cells. These endogenous RNAs are double-stranded RNAs, contain Alu and Line elements and are transcribed from leukocyte transcriptional enhancers. Thus, transcribed endogenous retrotransposon elements can co-opt pattern recognition sensors to induce IFN-responses in RRMS.

https://ift.tt/2Nxl679

Mummification manoeuvre for paediatric dermatology procedures

Publication date: Available online 28 February 2019

Source: Journal of the American Academy of Dermatology

Author(s): Priya Prabhakaran Nair

https://ift.tt/2NvUXFO

Dapsone advantages over trimethoprim-sulfamethoxazole for Pneumocystis pneumonia prophylaxis in immunobullous patients

Publication date: Available online 27 February 2019

Source: Journal of the American Academy of Dermatology

Author(s): Spyros M. Siscos, Brett C. Neill, Isadore S. Tarantino, Daniel J. Aires, Anand Rajpara

https://ift.tt/2GO1nQh

A Do-It-Yourself incubator for autologous melanocyte-keratinocyte transplantation surgery – a resource-poor alternative

Publication date: Available online 27 February 2019

Source: Journal of the American Academy of Dermatology

Author(s): Sandip Agrawal, Aseem Sharma, Rachita Dhurat

https://ift.tt/2NvULGA

Effectiveness and safety of dupilumab for the treatment of atopic dermatitis in a real-life French multicenter adult cohort

Publication date: Available online 27 February 2019

Source: Journal of the American Academy of Dermatology

Author(s): Sarah Faiz, Jonathan Giovannelli, Céline Podevin, Marie Jachiet, Jean-David Bouaziz, Ziad Reguiai, Audrey Nosbaum, Audrey Lasek, Marie-Christine Ferrier le Bouedec, Aurélie Du Thanh, Nadia Raison-Peyron, Florence Tetart, Anne-Benedicte Duval-Modeste, Laurent Misery, François Aubin, Anne Dompmartin, Cécile Morice, Catherine Droitcourt, Angèle Soria, Jean-Philippe Arnault

Abstract

Background

Dupilumab is the first biologic available to treat atopic dermatitis (AD). Its effectiveness and safety were demonstrated in clinical trials.

Objective

We sought to assess the effectiveness and safety of dupilumab in adults with AD in a real-life French multicenter retrospective cohort.

Methods

Patients were included between March 2017 and April 2018. Efficacy outcomes were collected both at baseline and three months (M3), when available, including SCORAD (Scoring Atopic Dermatitis) and EASI (Eczema Area and Severity Index) scores. Adverse events (AE) were recorded at the follow-up.

Results

We included 241 patients. The median follow-up time was 3.8±3.7 months. SCORAD75 and EASI75 were achieved in 27/163 (16.6%) and 40/82 (48.8%) patients, respectively. The median SCORAD and EASI at M3 were significantly lower compared with baseline (25±21 vs 56±27.4, p<10^-9 and 4.1±6.8 vs 17.9±15.4, p<10^-9, respectively). Conjunctivitis was reported in 84/241 (38.2%) patients. The proportion of eosinophilia (>500/mm³) during follow-up (57%) was higher than at baseline (33.7%) (n=172, p<10^-6). Dupilumab was stopped in 42 cases, 27 of which were due to an AE.

Limitations

No control group, missing data.

Conclusion

This real-life study demonstrated results similar to clinical trials, with regard to dupilumab effectiveness, but revealed a higher frequency of conjunctivitis and eosinophilia.

https://ift.tt/2GR01UH

Intonation guides sentence processing in the left inferior frontal gyrus

Publication date: Available online 27 February 2019

Source: Cortex

Author(s): Constantijn L. van der Burght, Tomás Goucha, Angela D. Friederici, Jens Kreitewolf, Gesa Hartwigsen

Abstract

Speech prosody, the variation in sentence melody and rhythm, plays a crucial role in sentence comprehension. Specifically, changes in intonational pitch along a sentence can affect our understanding of who did what to whom. To date, it remains unclear how the brain processes this particular use of intonation and which brain regions are involved. In particular, one central matter of debate concerns the lateralisation of intonation processing. To study the role of intonation in sentence comprehension, we designed a functional MRI experiment in which participants listened to spoken sentences. Critically, the interpretation of these sentences depended on either intonational or grammatical cues. Our results showed stronger functional activity in the left inferior frontal gyrus (IFG) when the intonational cue was crucial for sentence comprehension compared to when it was not. When instead a grammatical cue was crucial for sentence comprehension, we found involvement of an overlapping region in the left IFG, as well as in a posterior temporal region. A further analysis revealed that the lateralisation of intonation processing depends on its role in syntactic processing: activity in the IFG was lateralised to the left hemisphere when intonation was the only source of information to comprehend the sentence. In contrast, activity in the IFG was right-lateralised when intonation did not contribute to sentence comprehension. Together, these results emphasise the key role of the left IFG in sentence comprehension, showing the importance of this region when intonation establishes sentence structure. Furthermore, our results provide evidence for the theory that the lateralisation of prosodic processing is modulated by its linguistic role.

https://ift.tt/2IG0GKp

Characteristics and prevalence of plaque psoriasis in patients with palmoplantar pustulosis

Abstract

Background

Palmoplantar pustulosis (PPP) is a chronic pustular skin condition on palms and soles. The disease is often seen in combination with plaque psoriasis, and whether PPP is a variant of psoriasis has been debated. The disease prevalence of PPP and co‐occurring psoriasis is not yet established and the patient group remains understudied.

Objectives

To estimate the prevalence of PPP and co‐occurring psoriasis in three population‐based cohorts and provide information on patient demographics and characteristics.

Methods

Administrative healthcare registries and insurance databases from the US, Denmark and Germany were used as data sources. Patients with PPP were defined by a single ICD‐10 code for PPP during a one‐year period. Information regarding co‐occurring plaque psoriasis and other comorbidities were extracted. Furthermore, use of anti‐psoriatic medication was identified.

Results

A total of 1435, 751 and 1832 patients with PPP were identified in the US, Danish and German populations, with an estimated one‐year prevalence of 0.009%, 0.005%, and 0.08%, respectively. Plaque psoriasis was prevalent in 14.2% to 61.3% of patients with PPP. Patients with co‐occurring psoriasis had an overall higher prevalence of psoriatic arthritis. Similarly, medication use was more prevalent in PPP patients with co‐occurring psoriasis, especially pronounced was the use of biologic therapies.

Conclusions

This large observational study on patients with PPP provides detailed information regarding patient demographics, comorbidities, and medication use. The one‐year prevalence of PPP varied in the three studied populations, possibly due to differences in diagnostics and recording practices. Psoriasis was frequently co‐occurring in patients with PPP.

This article is protected by copyright. All rights reserved.

https://ift.tt/2Tm5dpF

Primary lymphangioma circumscriptum of the vulva presenting as warty plaques

Abstract

Lymphangioma circumscriptum is a benign hamartomatous malformation involving the lymphatic system of skin and subcutaneous tissue. It can involve any part of the body with maximum predilection for proximal parts of limbs. Vulvar involvement is quite infrequent. Based on the aetiopathogenesis, it can be either primary or secondary, with the secondary form being relatively more common in vulva. We report an exceedingly rare case of primary lymphangioma circumscriptum in a post‐menopausal female presenting with multiple warty, papulo‐nodular lesions on both labia majora. The patient was diagnosed histopathologically and managed surgically by wide local excision with primary closure.

https://ift.tt/2T4JjYD

Modeling the non-point source pollution risks by combing pollutant sources, precipitation, and landscape structure

Abstract

Traditional models of nutrient simulation usually focus on the pollutant sources and precipitation, lacking the quantification of landscape structure. We developed a new prediction model of pollution risks by combing pollutant sources, precipitation, and landscape structure, which was defined as the source-precipitation-landscape model (SPLM). The SPLM was applied to simulate the non-point source (NPS) total nitrogen (TN) exports in one of the largest river basins in China (the Haihe River Basin, HRB). TN concentrations of 35 sampling catchments in 2013 were used to test the accuracy of the SPLM. Simulated results showed that (1) the SPLM had a relative high accuracy in the simulation of NPS TN export and intensity, especially for TN intensity. (2) The mean TN export and intensity of all the 1578 catchments in the HRB were 441.97 t and 2.08 t/km², respectively. (3) The TN export intensities differed greatly among the sub-basins in the HRB, ranging from 0.64 to 6.81 t/km². On the whole, the TN export intensities of the plain sub-basins (e.g., the Tuhaimajia River, the Heilonggang River, and the Beisihe River) were much higher than those of mountainous sub-basins (e.g., the Yongding River, the Beisanhe River, and the Luanhe River). (4) The contributions to TN exports, from high to low, were land use (38.82%), livestock husbandry (33.57%), and rural population (27.61%). Among all the ten pollution sources, arable land (30.87%), rural population (27.61%), and large livestock (17.73%) had the top three contributions to TN exports. This study provides a feasible tool for policymakers and administrators to develop workable management measures for the mitigation of NPS pollution. This SPLM can be extended to other regions in a rapid urbanization context.

https://ift.tt/2Ej3GqJ

Synergistic effects of chromium and copper on photosynthetic inhibition, subcellular distribution, and related gene expression in Brassica napus cultivars

Abstract

Nowadays, modern plant physiology focuses on complex behavior of metal co-contaminants in agrosystems. Keeping this in view, the current study was conducted to investigate the response of two Brassica napus cultivars (Zheda 622 and ZS 758) under co-contamination of copper (Cu²⁺) and chromium (Cr⁶⁺) to observe their effects on plant growth, photosynthetic parameters, and subcellular distribution of these metals in leaves and roots. The results showed that exposure to Cu and Cr causes decline in plant growth, including biomass and plant height. Significant decrease in pigment concentration and the photosynthetic activity [photosynthetic rate (Pn), stomatal conductance (Gs), and transpiration rate (E), maximal quantum yield of photosystem II (Fv/Fm)] in leaves was also observed. Results of subcellular distribution of metals showed that Cu and Cr were predominantly distributed in cell wall and soluble fraction of roots and leaves. Moreover, Cu and Cr in cellular fractions showed a synergistic accumulation pattern under combined metal stress treatment. Both cultivars showed increased levels of reactive oxygen species (ROS), i.e., hydrogen peroxide (H₂O₂) and superoxide radical (O₂^•−), and significant modulation in the activities of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), ascorbate peroxidase (APX)] under Cu/Cr alone or their combined treatments. Similarly, expression levels of defense-related genes, such as BnCat, BnApx, BnPrx, and BnSod, were also generally up-regulated compared with control. Electron micrographs (TEM) of the mesophyll and root tip cells indicated prominent alterations both in cellular and organelle levels. Additionally, Cr was found to be more toxic than Cu but less than their combined effect, as revealed by enhanced production of oxidative stress and a reduction in biomass production and photosynthetic activity. The present results also suggest that cultivar ZS 758 is more resistant to Cu/Cr than Zheda 622, due to better adapted metabolism and maintenance of structural integrity under metal stress.

https://ift.tt/2T9n5VD

Impact of emissions controls on ambient carbonyls during the Asia-Pacific Economic Cooperation summit in Beijing, China

Abstract

Beijing and its surrounding areas implemented a series of stringent measures to ensure good air quality during the Asia-Pacific Economic Cooperation (APEC) summit. These measures included restrictions on traffic, constructions, and industrial activities. The diurnal variations of carbonyls, 24-h PM_2.5, and its chemical species were investigated before, during, after APEC, and the 2015 summer. The average concentrations of carbonyls, formaldehyde, acetaldehyde, and acetone were decreased by 65.2%, 78.6%, 41.5%, and 55.6% during APEC, respectively. The concentrations of propene equivalent, the ozone formation potential, and the contribution to OH· removal by carbonyls during APEC were approximately 27–33% of those during the preceding interval. The temporal variation of carbonyls during APEC was similar to that of other air pollutants, except for O₃; however, the diurnal variation of carbonyls was consistent with that of O₃, with the highest values at noon and the lowest ones at night during APEC. Large variations in C1/C2 (0.95–9.41) and C2/C3 (5.70–15.71) were observed during the sampling period. The correlations analysis, diagnostical ratios, and diurnal variations of carbonyls indicated that primary sources were not an important source and secondary formation was the dominant source of atmospheric carbonyls during the entire period. The control measures not only reduced primary carbonyl emissions but also dramatically reduced secondary carbonyl precursors, such as NO_x and volatile organic compounds (VOCs), resulting in the low level of carbonyls during APEC. In addition, the potential health effects of carbonyls were evaluated and the cancer risk from formaldehyde and acetaldehyde was significantly higher before APEC than during the other intervals.

https://ift.tt/2H9t0CD