Efficacy of a high-observation protocol in major head and neck cancer surgery: A prospective study

ABSTRACT

Background

The purpose of this study was to optimize an existing clinical care pathway (CCP) for head and neck cancer with a high-observation protocol (HOP) and to determine the effect on length of intensive care unit (ICU) admission and length of stay in hospital (LOS).

Methods

The HOP mandated initiation of spontaneous breathing trials before the conclusion of the surgery, weaning of sedation, and limiting mechanical ventilation. All patients with head and neck cancer undergoing primary surgery on the HOP were compared to a historical cohort regarding length of ICU admission, ICU readmissions, and LOS.

Results

Ninety-six and 52 patients were observed in "historical" and "HOP" cohorts. The length of ICU admission (1.9 vs 1.2 days; p = .021), LOS (20.3 vs 14.1 days; p = .020), and ICU readmissions (10.4% vs 1.9%; p = .013) were significantly decreased in the "HOP" cohort.

Conclusion

Rapid weaning of sedation and limiting mechanical ventilation may contribute to a shorter length of ICU admission and LOS, as well as decreased ICU readmissions. © 2017 Wiley Periodicals, Inc. Head Neck, 2017

http://ift.tt/2sNiOt5

High Gpx1 expression predicts poor survival in laryngeal squamous cell carcinoma

Several studies have demonstrated that abnormal glutathione peroxidases 1 (Gpx1) expression can influence the biological behavior of malignant cells. However, the roles of Gpx1 in laryngeal squamous cell carcinoma (LSCC) remain unknown. The purpose of this study is to analyze the Gpx1 expression and prognostic significance in LSCC patients.

http://ift.tt/2tndU31

Metabolic control and periodontal treatment decreases elevated oxidative stress in the early phases of type 1 diabetes onset

Publication date: October 2017
Source:Archives of Oral Biology, Volume 82
Author(s): Cüneyt A. Aral, Özlem Nalbantoğlu, Bilge G. Nur, Mustafa Altunsoy, Kübra Aral
ObjectiveRecently, increasing concern has been focused on the contribution of oxidative stress in the pathology of periodontal disease and diabetes mellitus. Firstly, the present study aimed to analyze gingival crevicular fluid (GCF), salivary, and serum oxidative status in children with type 1 diabetes mellitus (T1DM) at diagnosis and systemically healthy children with and without gingivitis. Additionally, the diabetic patients were reevaluated after diabetes and periodontal treatment.DesignThe study groups were composed of 32 T1DM patients at diagnosis, and age- and gender-matched thirty-six systemically healthy children with (G) and without (H) gingivitis. The diabetic patients who took insulin therapy (1.5 units/kg/day totally) and periodontal treatment (oral hygiene education with professional scaling) were reevaluated after 3 months. The levels of total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were recorded.ResultsGCF, salivary, and serum OSI were elevated in group T1DM compared to the other groups at baseline (p<0.05), and decreased in group T1DM at reevaluation compared to baseline (p<0.05). GCF OSI was positively correlated with periodontal clinical parameters (p<0.05). Glycated hemoglobin was positively correlated with GCF TOS (r=0.302, p=0.007), GCF OSI (r=0.346, p=0.002), salivary TOS (r=0.326, p=0.046), and serum TOS (r=0.239, p=0.044).ConclusionThe instability in the oxidative status that accompanies diabetes may be considered a significant pathogenic factor of diabetes-related periodontal inflammation.



http://ift.tt/2sJY3Og

Mucoepidermoid carcinoma-associated expression of MUC5AC, MUC5B and mucin-type carbohydrate antigen sialyl-Tn in the parotid gland

Publication date: October 2017
Source:Archives of Oral Biology, Volume 82
Author(s): Johannes H. Matse, Wiresh K. Bharos, Enno C.I. Veerman, Elisabeth Bloemena, Jan G.M. Bolscher
ObjectivesThe aberrant expression of mucins and mucin-type carbohydrates has been described in many types of cancer, including mucoepidermoid carcinoma (MEC), a malignant salivary gland tumor. In this study, we examined the aberrant expression patterns of mucins (MUC1, MUC4, MUC5AC and MUC5B), simple mucin-type carbohydrate antigens (Tn, sialyl-Tn and T) and mature carbohydrate antigens (Lewis^a and sulfo-Lewis^a antigens) in MEC originating from the parotid gland, which normally does not secrete mucins.DesignWe conducted an immunohistochemical study to investigate the presence of mucins and carbohydrates in 24 MEC samples originating from the parotid gland and in surrounding normal tissue of the same gland in comparison 6 samples of normal salivary glands. The expression levels were compared with respect to the histological grading. Furthermore, 24 MEC samples from non-parotid salivary glands were included.ResultsWe observed loss of topology of membrane-bound MUC1 and MUC4, and de novo expression of MUC5AC, MUC5B and sialyl-Tn in MEC that originated in the parotid gland. Furthermore, mucins MUC1, MUC4 and carbohydrate antigens Tn, sialyl-Tn, T, Lewis^a and sulfo-Lewis^a were overexpressed in MEC samples compared to surrounding normal salivary gland tissues. MUC1 was expressed in both low- and high grade MECs, whereas MUC4 was not expressed in high grade MECs of the parotid gland.ConclusionDuring the development of MEC in the parotid gland, the genes for gel-forming secretory mucins are switched on. Besides these MEC tissues overexpress short oligosaccharides, suggesting that the glycosylation machinery is altered.



http://ift.tt/2tHIbJx

Stimulatory effect of Aggregatibacter actinomycetemcomitans DNA on proinflammatory cytokine expression by human gingival fibroblasts

Publication date: October 2017
Source:Archives of Oral Biology, Volume 82
Author(s): Uriel Soto-Barreras, Gabriela Cortés-Sandoval, Ruben Dominguez-Perez, Alejandra Loyola-Leyva, Panfilo-Raymundo Martinez-Rodriguez, Juan Pablo Loyola-Rodriguez
ObjectiveWhile different virulence factors have been reported of Aggregatibacter actinomycetemcomitans (Aa), there is little information about the stimulatory effect of its DNA. The main purpose of this study was to assess the inflammatory response of human gingival fibroblasts (HGFs) stimulated with A. actinomycetemcomitans DNA.DesignCytokine levels of IL-6, IL-1α and TNF-α were measured on the supernatant of HGFs activated with 10, 25, 50 and 100μg/ml DNA of Aa during 24h. Primary cultures of HGFs were infected with Aa and its DNA at different times and concentrations to compare its cytotoxic effect. Cell damage and adhesion of Aa to HGFs were evaluated under light microscopy and Scanning electron microscopy respectively.ResultsThere was a statistical difference (p<0.05) in cytokine expression in HGFs activated by bacterial DNA with a dose dependent on IL-6 expression and a significantly elevated expression of IL-1α and TNF-α compared to Human DNA negative control. Substantial morphological alterations were observed after infection of A. actinomycetemcomitans in HGFs but not with bDNA exposure. Aggregatibacter actinomycetemcomitans showed a high rate of adhesion and cell damage to HGFs after 30min.ConclusionsGenomic DNA of A. actinomycetemcomitans could be a factor in the pathogenesis of periodontitis that might play a major role in the inflammatory response.

Graphical abstract

http://ift.tt/2sKiLOb

Quantitative study of the proportion of the pore volume of human fluorotic enamel filled by resin infiltrant

Publication date: October 2017
Source:Archives of Oral Biology, Volume 82
Author(s): Frederico Barbosa de Sousa, Isabel Maria Porto Lelis, Regina Célia Bressan Queiroz Figueiredo, Andressa Cavalcanti Pires, Raquel Fernanda Gerlach
AimCapillarity theory predicts that the pore volume infiltrated by a liquid in a body with tubular capillaries is directly proportional to the capillary radius. The expected volume available for infiltration is the loosely bound water volume, which can be related to the capillary radii. We tested the hypothesis that the proportion of the pore volume infiltrated by resin infiltrant (Vratioresin) is correlated and agrees with the proportion of the pore volume with loosely bound water (Vratioa2).DesignSeven human fluorotic third molars (4 unerupted and 3 erupted; TF scores 4 to 7; fluoride content of inner coronal dentin ranged from 143 to 934μg Fluoride/g) were prepared and resin infiltration was performed during 10min in fluorotic enamel ground sections. Penetration depths were measured (polarizing microscopy and CLSM) and mineral volume and non-mineral volumes were measured at histological points (n=92) along transversal lines traced from the enamel surface to the enamel-dentin junction.ResultsNo well-mineralized surface layer was found. Infiltration depths ranged from 250μm to 900μm. Vratioresin ranged from 1.8 to 17.7% (mean of 10.13%±4.1%), was lower than Vratioa2 (p<0 Hedge's g=1.51, 95% CI: 1.18/1.83), and correlated positively with Vratioa2 (R=0.684; 95% CI: 0.557/0.780) and negatively with the air volume remained after infiltration (R=−0.79; 95% CI: −0.698/−0.780). Vratioa2 exceeded Vratioresin in 5% (1/4 of Vratioa2) on average.ConclusionVratioa2 and Vratioresin correlated well, but lacked good agreement. Organic matter, firmly bound water and air remained in enamel pores after resin infiltration.



http://ift.tt/2sKdDJw

Potential chemotherapeutic effects of diosgenin, zoledronic acid and epigallocatechin-3-gallate on PE/CA-PJ15 oral squamous cancer cell line

Publication date: October 2017
Source:Archives of Oral Biology, Volume 82
Author(s): Eduardo Pons-Fuster López, Qin-tong Wang, Wei Wei, Pia López Jornet
ObjectiveTo study the potential chemotherapeutic effects of Diosgenin, zoledronic acid and Epigallocatechin-3-gallate on oral squamous cell cancer (OSCC).Materials and methodsCell viability, migration, apoptosis and cell cycle evaluation assays were performed in order to assess the effects of different doses of Diosgenin, zoledronic acid and Epigallocatechin-3-gallate on the PE/CA-PJ15 cell line.ResultsDoses of 100μM of diosgenin or zoledronic acid reduced cell viability significantly after 72h (p<0.001), as well as increasing apoptosis (p<0.05 and p<0.01 respectively). All three agents reduced cell migration and altered the cell cycle, each at a different phase of the cycle.Conclusionwhile DG and ZA reduced cell viability, increased apoptosis, inhibited cell migration and modified the cell cycle in different ways, EGCG only modified the cell cycle and reduced cell migration. These agents present a potential chemotherapeutic effect on PE/CA-PJ15 OSSC cell line, which have to be further studied.



http://ift.tt/2tHNR66

Metabolic control and periodontal treatment decreases elevated oxidative stress in the early phases of type 1 diabetes onset

Publication date: October 2017
Source:Archives of Oral Biology, Volume 82
Author(s): Cüneyt A. Aral, Özlem Nalbantoğlu, Bilge G. Nur, Mustafa Altunsoy, Kübra Aral
ObjectiveRecently, increasing concern has been focused on the contribution of oxidative stress in the pathology of periodontal disease and diabetes mellitus. Firstly, the present study aimed to analyze gingival crevicular fluid (GCF), salivary, and serum oxidative status in children with type 1 diabetes mellitus (T1DM) at diagnosis and systemically healthy children with and without gingivitis. Additionally, the diabetic patients were reevaluated after diabetes and periodontal treatment.DesignThe study groups were composed of 32 T1DM patients at diagnosis, and age- and gender-matched thirty-six systemically healthy children with (G) and without (H) gingivitis. The diabetic patients who took insulin therapy (1.5 units/kg/day totally) and periodontal treatment (oral hygiene education with professional scaling) were reevaluated after 3 months. The levels of total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were recorded.ResultsGCF, salivary, and serum OSI were elevated in group T1DM compared to the other groups at baseline (p<0.05), and decreased in group T1DM at reevaluation compared to baseline (p<0.05). GCF OSI was positively correlated with periodontal clinical parameters (p<0.05). Glycated hemoglobin was positively correlated with GCF TOS (r=0.302, p=0.007), GCF OSI (r=0.346, p=0.002), salivary TOS (r=0.326, p=0.046), and serum TOS (r=0.239, p=0.044).ConclusionThe instability in the oxidative status that accompanies diabetes may be considered a significant pathogenic factor of diabetes-related periodontal inflammation.



http://ift.tt/2sJY3Og

Mucoepidermoid carcinoma-associated expression of MUC5AC, MUC5B and mucin-type carbohydrate antigen sialyl-Tn in the parotid gland

Publication date: October 2017
Source:Archives of Oral Biology, Volume 82
Author(s): Johannes H. Matse, Wiresh K. Bharos, Enno C.I. Veerman, Elisabeth Bloemena, Jan G.M. Bolscher
ObjectivesThe aberrant expression of mucins and mucin-type carbohydrates has been described in many types of cancer, including mucoepidermoid carcinoma (MEC), a malignant salivary gland tumor. In this study, we examined the aberrant expression patterns of mucins (MUC1, MUC4, MUC5AC and MUC5B), simple mucin-type carbohydrate antigens (Tn, sialyl-Tn and T) and mature carbohydrate antigens (Lewis^a and sulfo-Lewis^a antigens) in MEC originating from the parotid gland, which normally does not secrete mucins.DesignWe conducted an immunohistochemical study to investigate the presence of mucins and carbohydrates in 24 MEC samples originating from the parotid gland and in surrounding normal tissue of the same gland in comparison 6 samples of normal salivary glands. The expression levels were compared with respect to the histological grading. Furthermore, 24 MEC samples from non-parotid salivary glands were included.ResultsWe observed loss of topology of membrane-bound MUC1 and MUC4, and de novo expression of MUC5AC, MUC5B and sialyl-Tn in MEC that originated in the parotid gland. Furthermore, mucins MUC1, MUC4 and carbohydrate antigens Tn, sialyl-Tn, T, Lewis^a and sulfo-Lewis^a were overexpressed in MEC samples compared to surrounding normal salivary gland tissues. MUC1 was expressed in both low- and high grade MECs, whereas MUC4 was not expressed in high grade MECs of the parotid gland.ConclusionDuring the development of MEC in the parotid gland, the genes for gel-forming secretory mucins are switched on. Besides these MEC tissues overexpress short oligosaccharides, suggesting that the glycosylation machinery is altered.



http://ift.tt/2tHIbJx

Stimulatory effect of Aggregatibacter actinomycetemcomitans DNA on proinflammatory cytokine expression by human gingival fibroblasts

Publication date: October 2017
Source:Archives of Oral Biology, Volume 82
Author(s): Uriel Soto-Barreras, Gabriela Cortés-Sandoval, Ruben Dominguez-Perez, Alejandra Loyola-Leyva, Panfilo-Raymundo Martinez-Rodriguez, Juan Pablo Loyola-Rodriguez
ObjectiveWhile different virulence factors have been reported of Aggregatibacter actinomycetemcomitans (Aa), there is little information about the stimulatory effect of its DNA. The main purpose of this study was to assess the inflammatory response of human gingival fibroblasts (HGFs) stimulated with A. actinomycetemcomitans DNA.DesignCytokine levels of IL-6, IL-1α and TNF-α were measured on the supernatant of HGFs activated with 10, 25, 50 and 100μg/ml DNA of Aa during 24h. Primary cultures of HGFs were infected with Aa and its DNA at different times and concentrations to compare its cytotoxic effect. Cell damage and adhesion of Aa to HGFs were evaluated under light microscopy and Scanning electron microscopy respectively.ResultsThere was a statistical difference (p<0.05) in cytokine expression in HGFs activated by bacterial DNA with a dose dependent on IL-6 expression and a significantly elevated expression of IL-1α and TNF-α compared to Human DNA negative control. Substantial morphological alterations were observed after infection of A. actinomycetemcomitans in HGFs but not with bDNA exposure. Aggregatibacter actinomycetemcomitans showed a high rate of adhesion and cell damage to HGFs after 30min.ConclusionsGenomic DNA of A. actinomycetemcomitans could be a factor in the pathogenesis of periodontitis that might play a major role in the inflammatory response.

Graphical abstract

http://ift.tt/2sKiLOb

Quantitative study of the proportion of the pore volume of human fluorotic enamel filled by resin infiltrant

Publication date: October 2017
Source:Archives of Oral Biology, Volume 82
Author(s): Frederico Barbosa de Sousa, Isabel Maria Porto Lelis, Regina Célia Bressan Queiroz Figueiredo, Andressa Cavalcanti Pires, Raquel Fernanda Gerlach
AimCapillarity theory predicts that the pore volume infiltrated by a liquid in a body with tubular capillaries is directly proportional to the capillary radius. The expected volume available for infiltration is the loosely bound water volume, which can be related to the capillary radii. We tested the hypothesis that the proportion of the pore volume infiltrated by resin infiltrant (Vratioresin) is correlated and agrees with the proportion of the pore volume with loosely bound water (Vratioa2).DesignSeven human fluorotic third molars (4 unerupted and 3 erupted; TF scores 4 to 7; fluoride content of inner coronal dentin ranged from 143 to 934μg Fluoride/g) were prepared and resin infiltration was performed during 10min in fluorotic enamel ground sections. Penetration depths were measured (polarizing microscopy and CLSM) and mineral volume and non-mineral volumes were measured at histological points (n=92) along transversal lines traced from the enamel surface to the enamel-dentin junction.ResultsNo well-mineralized surface layer was found. Infiltration depths ranged from 250μm to 900μm. Vratioresin ranged from 1.8 to 17.7% (mean of 10.13%±4.1%), was lower than Vratioa2 (p<0 Hedge's g=1.51, 95% CI: 1.18/1.83), and correlated positively with Vratioa2 (R=0.684; 95% CI: 0.557/0.780) and negatively with the air volume remained after infiltration (R=−0.79; 95% CI: −0.698/−0.780). Vratioa2 exceeded Vratioresin in 5% (1/4 of Vratioa2) on average.ConclusionVratioa2 and Vratioresin correlated well, but lacked good agreement. Organic matter, firmly bound water and air remained in enamel pores after resin infiltration.



http://ift.tt/2sKdDJw

Potential chemotherapeutic effects of diosgenin, zoledronic acid and epigallocatechin-3-gallate on PE/CA-PJ15 oral squamous cancer cell line

Publication date: October 2017
Source:Archives of Oral Biology, Volume 82
Author(s): Eduardo Pons-Fuster López, Qin-tong Wang, Wei Wei, Pia López Jornet
ObjectiveTo study the potential chemotherapeutic effects of Diosgenin, zoledronic acid and Epigallocatechin-3-gallate on oral squamous cell cancer (OSCC).Materials and methodsCell viability, migration, apoptosis and cell cycle evaluation assays were performed in order to assess the effects of different doses of Diosgenin, zoledronic acid and Epigallocatechin-3-gallate on the PE/CA-PJ15 cell line.ResultsDoses of 100μM of diosgenin or zoledronic acid reduced cell viability significantly after 72h (p<0.001), as well as increasing apoptosis (p<0.05 and p<0.01 respectively). All three agents reduced cell migration and altered the cell cycle, each at a different phase of the cycle.Conclusionwhile DG and ZA reduced cell viability, increased apoptosis, inhibited cell migration and modified the cell cycle in different ways, EGCG only modified the cell cycle and reduced cell migration. These agents present a potential chemotherapeutic effect on PE/CA-PJ15 OSSC cell line, which have to be further studied.



http://ift.tt/2tHNR66

The absence of CD56 expression can differentiate papillary thyroid carcinoma from other thyroid lesions

http://orlhealth.blogspot.com/2017/06/the-absence-of-cd56-expression-can.html

The neural cell adhesion molecule CD56 is an antigen important for the differentiation of the follicular epithelium. Recent studies have reported low or absent expression of CD56 in papillary thyroid carcinoma (PTC) and its presence in normal thyroid tissue, benign thyroid lesions, and most follicular non-PTC tumors. Aim: We wish to estimate the value of CD56 in the differentiation of PTC (including follicular variant-PTC [FV-PTC]) from other nontumoral lesions and follicular thyroid neoplasias. Settings and Design: This was a retrospective, case–control study. Subjects and Methods: We analyzed the expression of CD56 in normal thyroid follicular tissue, 15 nonneoplastic thyroid lesions (nodular hyperplasia, Graves' disease, and chronic lymphocytic thyroiditis/Hashimoto), and 38 thyroid follicular cell neoplasms (25 cases of PTC). The immunohistochemical reactions were performed on sections stained with anti-CD56 antibody. Statistical Analysis Used: We used the Chi-square test, values of P< 0.05 being considered statistically significant. Risk analysis was applied on these studied groups, by calculating the odds ratio (OR) value. Results: Our results indicated that CD56 immunoexpression had differentiated PTC from benign nonneoplastic lesions (P = 0.002), as well as from follicular neoplasias (P = 0.046). There were no significant differences regarding CD56 expression between FV-PTC and classical PTC (P = 0.436). The immunoexpression of CD56 has differentiated PTC from other thyroid non-PTC lesions (P < 0.001), with 26.4 OR value. Conclusions: CD56 has been proved to be a useful marker in the diagnosis of PTC, including FV-PTC. Its absence can help differentiate FV-PTC from other thyroid nodules with follicular patterns.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Estimated Blood Loss: In the Equation of the Beholder

No abstract available

http://ift.tt/2suOH6O

Determination of Perioperative Blood Loss: Accuracy or Approximation?

BACKGROUND: Various different interventions can be used to reduce surgical blood loss; however, there is no "gold standard" for accurately measuring the volume of perioperative blood loss, and this makes it difficult to assess the efficacy of these interventions. METHODS: We used data from a previous multicenter double-blind randomized clinical trial in patients undergoing total hip arthroplasty in which we compared 2 regimens for administering tranexamic acid versus placebo. We assessed direct measures (external blood loss) and indirect estimates (using the formulas of Bourke, Gross, Mercuriali, and Camarasa and a new formula we have developed) using analysis of variance to compare estimated volumes of blood loss among the study groups. In addition, intraclass correlation coefficients (ICCs) and Bland–Altman diagrams were used to compare the estimated volumes of blood loss obtained with each formula. RESULTS: The mean estimated external blood loss was 909 ± 324 mL, and the mean estimates of blood loss calculated using the formulas of Gross, Bourke and Smith, and Camarasa were 1308 ± 555, 1091 ± 454, and 1641 ± 945 mL, respectively, whereas we obtained a value of 1511 ± 919 mL with the new formula at day 2. In all cases, the results favored the use of tranexamic acid (P

http://ift.tt/2suLEf4

Irregular Outcomes: Predictors of New Atrial Fibrillation After Noncardiac Surgery

No abstract available

http://ift.tt/2susshn

Predictors, Prognosis, and Management of New Clinically Important Atrial Fibrillation After Noncardiac Surgery: A Prospective Cohort Study

BACKGROUND: Despite the frequency of new clinically important atrial fibrillation (AF) after noncardiac surgery and its increased association with the risk of stroke at 30 days, there are limited data informing their prediction, association with outcomes, and management. METHODS: We used the data from the PeriOperative ISchemic Evaluation trial to determine, in patients undergoing noncardiac surgery, the association of new clinically important AF with 30-day outcomes, and to assess management of these patients. We also aimed to derive a clinical prediction rule for new clinically important AF in this population. We defined new clinically important AF as new AF that resulted in symptoms or required treatment. We recorded an electrocardiogram 6 to 12 hours postoperatively and on the 1st, 2nd, and 30th days after surgery. RESULTS: A total of 211 (2.5% [8351 patients]; 95% confidence interval, 2.2%–2.9%) patients developed new clinically important AF within 30 days of randomization (8140 did not develop new AF). AF was independently associated with an increased length of hospital stay by 6.0 days (95% confidence interval, 3.5–8.5 days) and vascular complications (eg, stroke or congestive heart failure). The usage of an oral anticoagulant at the time of hospital discharge among patients with new AF and a CHADS2 score of 0, 1, 2, 3, and ≥4 was 6.9%, 10.2%, 23.0%, 9.4%, and 33.3%, respectively. Two independent predictors of patients developing new clinically important AF were identified (ie, age and surgery). The prediction rule included the following factors and assigned weights: age ≥85 years (4 points), age 75 to 84 years (3 points), age 65 to 74 years (2 points), intrathoracic surgery (3 points), major vascular surgery (2 points), and intra-abdominal surgery (1 point). The incidence of new AF based on scores of 0 to 1, 2, 3 to 4, and 5 to 6 was 0.5%, 1.0%, 3.1%, and 5.3%, respectively. CONCLUSIONS: Age and surgery are independent predictors of new clinically important AF in the perioperative setting. A minority of patients developing new clinically important AF with high CHADS2 scores are discharged on an oral anticoagulant. There is a need to develop effective and safe interventions to prevent this outcome and to optimize the management of this event when it occurs.

http://ift.tt/2suL2Ww

Unsuccessful treatment of progressive macular hypomelanosis with oral isotretinoin

http://ift.tt/2tmK1zS

Inoperable infiltrative basal cell carcinoma successfully treated with vismodegib

Abstract

Basal cell carcinoma (BCC) is the most common skin cancer but usually has a good prognosis. However, there is a subset of BCC cases with a less favorable prognosis. For patients with locally advanced, recurrent or metastatic BCCs who are not suitable for surgery or radiotherapy, small-molecule drug inhibitors of hedgehog pathway are a new therapeutic opportunity. Here, we present a case of infiltrative BCC with multiple recurrences. Wide excision with reconstructive plastic surgery was performed initially with adjuvant radiotherapy. Due to multiple recurrences afterward, radiotherapy, topical imiquimod and oral itraconazole were used but were not effective. Finally, the patient was treated with vismodegib which led to a complete response. Moreover, the patient's symptoms due to the locally diffused cancer resolved.

http://ift.tt/2sN88ef

International Journal of Otolaryngology and Head & Neck Surgery Vol.6,No.3 (May 2017)

A New Modality of Treatment for Adult Laryngeal Haemangioma by Coblation: A Case Report
Coblation, Laryngeal Haemangioma, Propranolol
Paper Information Full Paper: PDF (Size:328KB)
DOI: 10.4236/ijohns.2017.63005

Altered Serum Lipids in the Cases of Head and Neck Cancer Associated with the Habit of Tobacco Consumption
Lipids, Cholesterol, Triglycerides, Head and Neck Cancer
Paper Information Full Paper: PDF (Size:488KB)
DOI: 10.4236/ijohns.2017.63006

http://ift.tt/2m3QcEl

FDA Approves Delafloxacin (Baxdela) for Skin Infections

The new antibiotic works against both gram-positive and gram-negative bacteria, including MRSA.
FDA Approvals

http://ift.tt/2sJgZN9

Transnasal endoscopic removal of bilateral postoperative maxillary cysts after aesthetic orthognathic ssurgery: Differences from that of Caldwell-Luc operations

Publication date: Available online 19 June 2017
Source:Auris Nasus Larynx
Author(s): Hyung Chae Yang, Sung Hoon Kang, Sung Ho Yoon, Hyong-Ho Cho
Postoperative maxillary cysts (PMCs) after orthognathic surgery are a rare disease condition. In this study, we reported first case of bilateral PMCs after cosmetic orthognathic surgery which was treated via the intranasal endoscopic approach. In addition, we compared the characteristics of PMCs after aesthetic orthognathic surgery with those of PMCs after Caldwell-Luc operation. We expect that this case will be helpful to surgeons who encounter similar cases.



http://ift.tt/2sQAnZb

Otolaryngology consultation tracheostomies and complex patient population

Publication date: Available online 17 June 2017
Source:American Journal of Otolaryngology
Author(s): Kristan P. Alfonso, Michael R. Kaufman, Emily V. Dressler, Meng Liu, Rony K. Aouad
PurposeTo assess for the differences in patients undergoing tracheostomy by the otolaryngology consult service versus other specialties.Materials and methodsA series of 1035 tracheostomies performed at our institution from January 2013 through November 2015 was retrospectively reviewed. Patient-related factors that contribute to procedural difficulty were reviewed.Results805 consecutive tracheostomies were included. Otolaryngology performed 176/805 (21.8%) tracheostomies as a consulting service. Morbidly obese patients were three times as likely to be referred to otolaryngology as other services (adjusted OR: 3.23; 95% CI: 2.21–4.72). Mean BMI was 36.38kg/m² for Consults vs. 28.69kg/m² for Others and morbidly obese patients had a mean BMI of 49.84kg/m² vs. 42.68kg/m² for Consults and Others respectively (p<0.001). Patients with upper airway compromise (8.5% of Consults vs. 1.6% for Others) had 5.5 times higher odds to be performed by otolaryngology (adjusted OR: 5.46; 95% CI: 2.24–13.28). Otolaryngology performed 81.8% of awake tracheostomies (n=9/11). There were significantly higher proportions of patients with diabetes, renal, pulmonary and cardiovascular disease in the Consults groups vs. Others (p<0.05).ConclusionsMore complex tracheostomies are being referred to and performed by otolaryngology at our institution. Difficult and challenging tracheostomies seem to be the "standard" for otolaryngologists.



http://ift.tt/2tlEb1D

Triple Therapy Potent Approach in Aggressive Skin Cancer

Novel approach that recruits multiple pathways involved in a rare and aggressive skin cancer produces unprecedented responses to treatment.
Medscape Medical News

http://ift.tt/2sijDss

Gamma-delta (γδ) T-cell lymphoma – another case unclassifiable by World Health Organization classification: a case report

We present a case of gamma-delta T-cell lymphoma that does not fit the current World Health Organization classifications.

http://ift.tt/2rOxOSO

SOCS1 Is a Key Molecule That Prevents Regulatory T Cell Plasticity under Inflammatory Conditions [IMMUNE REGULATION]

We previously showed that regulatory T cells (Tregs) from T cell–specific Socs1-deficient mice (Socs1^fl/flLck-Cre⁺ mice) easily convert into Th1- or Th17-like cells (ex-Tregs), which lose Foxp3 expression and suppressive functions in vivo. Because Tregs in Socs1^fl/flLck-Cre⁺ mice are constantly exposed to a large amount of inflammatory cytokines produced by non-Tregs in vivo, in this study we analyzed Treg-specific Socs1-deficient mice (Socs1^fl/flFoxp3^YFP-Cre mice). These mice developed dermatitis, splenomegaly, and lymphadenopathy that were much milder than those in Socs1^fl/flLck-Cre⁺ mice. A fate mapping study revealed that Socs1 deficiency accelerated the conversion of Tregs to Foxp3^–IFN-⁺ ex-Tregs in the tumor microenvironment and suppressed tumor growth. When transferred into Rag2^–/– mice, Tregs from Socs1^fl/flLck-Cre⁺ mice easily lost Foxp3 expression, whereas those from Socs1^fl/flFoxp3^YFP-Cre mice maintained Foxp3 expression. Although Tregs from Socs1^fl/flLck-Cre⁺ mice produced IFN- after a 3-d culture in response to anti-CD3/CD28 Ab stimulation in vitro, Tregs from Socs1^fl/flFoxp3^YFP-Cre mice did not. This finding suggested that the inflammatory conditions in Socs1^fl/flLck-Cre⁺ mice modified the born nature of Socs1-deficient Tregs. To investigate this mechanism, Tregs from Socs1^fl/flFoxp3^YFP-Cre mice were cultured with APCs from Socs1^fl/flLck-Cre⁺ mice. These APCs facilitated STAT4 phosphorylation, IFN- production, and loss of Foxp3 expression in Tregs from Socs1^fl/flFoxp3^YFP-Cre mice in an IL-12–dependent manner. The results indicate that Socs1-deficient Tregs tend to convert into ex-Tregs under the inflammatory conditions in which APCs are highly activated, and that SOCS1 could be a useful target for enhancement of anti-tumor immunity.

http://ift.tt/2sPQs0S

Physiologic Thymic Involution Underlies Age-Dependent Accumulation of Senescence-Associated CD4+ T Cells [IMMUNE REGULATION]

Immune aging may underlie various aging-related disorders, including diminished resistance to infection, chronic inflammatory disorders, and autoimmunity. PD-1⁺ and CD153⁺ CD44^high CD4⁺ T cells with features of cellular senescence, termed senescence-associated T (SA-T) cells, increasingly accumulate with age and may play a role in the immune aging phenotype. In this article, we demonstrate that, compared with young mice, the aged mouse environment is highly permissive for spontaneous proliferation of transferred naive CD4⁺ T cells, and it drives their transition to PD-1⁺ and CD153⁺ CD44^high CD4⁺ T cells after extensive cell divisions. CD4⁺ T cells with essentially the same features as SA-T cells in aged mice are also generated from naive CD4⁺ T cells after extensive cell divisions under severe T-lymphopenic conditions by gamma irradiation or in developmental T cell defect, often in association with spontaneous germinal centers, as seen in aged mice. The increase in SA-T cells is significantly enhanced after thymectomy at the young adult stage, along with accelerated T cell homeostatic proliferation, whereas embryonic thymus implantation in the late adult stage markedly restricts the homeostatic proliferation of naive CD4⁺ T cells in the host and delays the increase in SA-T cells. Our results suggest that reduced T cell output due to physiologic thymic involution underlies the age-dependent accumulation of SA-T cells as a result of increasing homeostatic proliferation of naive CD4⁺ T cells. SA-T cells may provide a suitable biomarker of immune aging, as well as a potential target for controlling aging-related disorders.

http://ift.tt/2rwPtiu

TLR-Induced Murine Dendritic Cell (DC) Activation Requires DC-Intrinsic Complement [INNATE IMMUNITY AND INFLAMMATION]

Induction of proinflammatory T cell immunity is augmented by innate dendritic cell (DC) maturation commonly initiated by TLR signaling. We demonstrate that ligation of TLR3, TLR4, and TLR9 induces murine DC production of complement components and local production of the anaphylatoxin C5a. In vitro, ex vivo, and in vivo analyses show that TLR-induced DC maturation, as assessed by surface phenotype, expression profiling by gene array, and functional ability to stimulate T cell responses, requires autocrine C3a receptor and C5a receptor (C3ar1/C5ar1) signaling. Studies using bone marrow chimeric animals and Foxp3-GFP/ERT2-Cre/dTomato fate-mapping mice show that TLR-initiated DC autocrine C3ar1/C5ar1 signaling causes expansion of effector T cells and instability of regulatory T cells and contributes to T cell–dependent transplant rejection. Together, our data position immune cell–derived complement production and autocrine/paracrine C3ar1/C5ar1 signaling as crucial intermediary processes that link TLR stimulation to DC maturation and the subsequent development of effector T cell responses.

http://ift.tt/2sPHfFY

Enhanced Effector Functions Due to Antibody Defucosylation Depend on the Effector Cell Fc{gamma} Receptor Profile [IMMUNOTHERAPY AND VACCINES]

Abs of the IgG isotype are glycosylated in their Fc domain at a conserved asparagine at position 297. Removal of the core fucose of this glycan greatly increases the affinity for FcRIII, resulting in enhanced FcRIII-mediated effector functions. Normal plasma IgG contains ~94% fucosylated Abs, but alloantibodies against, for example, Rhesus D (RhD) and platelet Ags frequently have reduced fucosylation that enhances their pathogenicity. The increased FcRIII-mediated effector functions have been put to use in various afucosylated therapeutic Abs in anticancer treatment. To test the functional consequences of Ab fucosylation, we produced V-gene–matched recombinant anti-RhD IgG Abs of the four different subclasses (IgG1–4) with and without core fucose (i.e., 20% fucose remaining). Binding to all human FcR types and their functional isoforms was assessed with surface plasmon resonance. All hypofucosylated anti-RhD IgGs of all IgG subclasses indeed showed enhanced binding affinity for isolated FcRIII isoforms, without affecting binding affinity to other FcRs. In contrast, when testing hypofucosylated anti-RhD Abs with FcRIIIa-expressing NK cells, a 12- and 7-fold increased erythrocyte lysis was observed with the IgG1 and IgG3, respectively, but no increase with IgG2 and IgG4 anti-RhD Abs. Notably, none of the hypofucosylated IgGs enhanced effector function of macrophages, which, in contrast to NK cells, express a complex set of FcRs, including FcRIIIa. Our data suggest that the beneficial effects of afucosylated biologicals for clinical use can be particularly anticipated when there is a substantial involvement of FcRIIIa-expressing cells, such as NK cells.

http://ift.tt/2sQ1u6n

Access Guide to Antigen Receptor Genes [PILLARS OF IMMUNOLOGY]

http://ift.tt/2rx21X3

In This Issue [IN THIS ISSUE]

http://ift.tt/2sQ1tiP

Pillars Article: A Role for Histone Acetylation in the Developmental Regulation of V(D)J Recombination. Science. 2000. 287: 495-498 [PILLARS OF IMMUNOLOGY]

http://ift.tt/2sPT4Mg

T Follicular Helper Cell-Derived IL-4 Is Required for IgE Production during Intestinal Helminth Infection [INFECTIOUS DISEASE AND HOST RESPONSE]

IgE production plays a crucial role in protective as well as pathogenic type 2 immune responses. Although the cytokine IL-4 is required for the development of IgE-producing plasma cells, the source of IL-4 and cellular requirements for optimal IgE responses remain unclear. Recent evidence suggests that T follicular helper (Tfh) cells are the primary producer of IL-4 in the reactive lymph node during type 2 immune responses. As Tfh cells are also required for the development of plasmablasts derived from germinal center and extrafollicular sources, we hypothesized that this cell subset is essential for the IgE plasmablast response. In this study, we show that during intestinal helminth infection, IL-4 derived from Tfh cells is required for IgE class switching and plasmablast formation. Notably, early IgE class switching did not require germinal center formation. Additionally, Tfh cell–derived IL-4 was required to maintain the Th2 response in the mesenteric lymph nodes of infected mice. Collectively, our results indicate that IL-4–producing Tfh cells are central orchestrators of the type 2 immune response in the reactive lymph nodes during parasitic helminth infection.

http://ift.tt/2sPW6jR

Inducing Mucosal IgA: A Challenge for Vaccine Adjuvants and Delivery Systems [BRIEF REVIEWS]

Mucosal IgA or secretory IgA (SIgA) are structurally equipped to resist chemical degradation in the harsh environment of mucosal surfaces and enzymes of host or microbial origin. Production of SIgA is finely regulated, and distinct T-independent and T-dependent mechanisms orchestrate Ig α class switching and SIgA responses against commensal and pathogenic microbes. Most infectious pathogens enter the host via mucosal surfaces. To provide a first line of protection at these entry ports, vaccines are being developed to induce pathogen-specific SIgA in addition to systemic immunity achieved by injected vaccines. Mucosal or epicutaneous delivery of vaccines helps target the inductive sites for SIgA responses. The efficacy of such vaccines relies on the identification and/or engineering of vaccine adjuvants capable of supporting the development of SIgA alongside systemic immunity and delivery systems that improve vaccine delivery to the targeted anatomic sites and immune cells.

http://ift.tt/2rxdCVY

Single-Cell RNA Sequencing Reveals Expanded Clones of Islet Antigen-Reactive CD4+ T Cells in Peripheral Blood of Subjects with Type 1 Diabetes [SYSTEMS IMMUNOLOGY]

The significance of islet Ag-reactive T cells found in peripheral blood of type 1 diabetes (T1D) subjects is unclear, partly because similar cells are also found in healthy control (HC) subjects. We hypothesized that key disease-associated cells would show evidence of prior Ag exposure, inferred from expanded TCR clonotypes, and essential phenotypic properties in their transcriptomes. To test this, we developed single-cell RNA sequencing procedures for identifying TCR clonotypes and transcript phenotypes in individual T cells. We applied these procedures to analysis of islet Ag-reactive CD4⁺ memory T cells from the blood of T1D and HC individuals after activation with pooled immunodominant islet peptides. We found extensive TCR clonotype sharing in Ag-activated cells, especially from individual T1D subjects, consistent with in vivo T cell expansion during disease progression. The expanded clonotype from one T1D subject was detected at repeat visits spanning >15 mo, demonstrating clonotype stability. Notably, we found no clonotype sharing between subjects, indicating a predominance of "private" TCR specificities. Expanded clones from two T1D subjects recognized distinct IGRP peptides, implicating this molecule as a trigger for CD4⁺ T cell expansion. Although overall transcript profiles of cells from HC and T1D subjects were similar, profiles from the most expanded clones were distinctive. Our findings demonstrate that islet Ag-reactive CD4⁺ memory T cells with unique Ag specificities and phenotypes are expanded during disease progression and can be detected by single-cell analysis of peripheral blood.

http://ift.tt/2sQ05wO

Macrophage-Mediated Inflammation in Normal and Diabetic Wound Healing [BRIEF REVIEWS]

The healing of cutaneous wounds is dependent on the progression through distinct, yet overlapping phases of wound healing, including hemostasis, inflammation, proliferation, and resolution/remodeling. The failure of these phases to occur in a timely, progressive fashion promotes pathologic wound healing. The macrophage (M) has been demonstrated to play a critical role in the inflammatory phase of tissue repair, where its dynamic plasticity allows this cell to mediate both tissue-destructive and -reparative functions. The ability to understand and control both the initiation and the resolution of inflammation is critical for treating pathologic wound healing. There are now a host of studies demonstrating that metabolic and epigenetic regulation of gene transcription can influence M plasticity in wounds. In this review, we highlight the molecular and epigenetic factors that influence M polarization in both physiologic and pathologic wound healing, with particular attention to diabetic wounds.

http://ift.tt/2sQhnJZ

The Influence of MHC Class II on B Cell Defects Induced by Invariant Chain/CD74 N-Terminal Fragments [IMMUNE SYSTEM DEVELOPMENT]

The invariant chain (CD74) mediates assembly and targeting of MHC class II (MHCII) complexes. In endosomes, CD74 undergoes sequential degradation by different proteases, including cathepsin S (CatS) and the intramembrane protease signal peptide peptidase-like 2a (SPPL2a). In their absence, CD74 N-terminal fragments (NTFs) accumulate. In SPPL2a^–/– B cells, such an NTF impairs endosomal trafficking and BCR signal transduction. In mice, this leads to a loss of splenic B cells beyond the transitional stage 1. To gain insight into CD74 determinants and the role of MHCII, we compared B cells from CatS^–/–, SPPL2a^–/–, and SPPL2a-MHCII double-deficient mice. We assessed differentiation of B cells in bone marrow and spleen and analyzed their endosomal morphology, BCR expression, and signal transduction. We demonstrate that MHCII is dispensable for the B cell phenotype of SPPL2a^–/– mice, further supporting a CD74-intrinsic effect. Despite significant vacuolization of endosomal compartments similar to SPPL2a^–/– B cells, CatS^–/– traditional stage 1 B cells show unimpaired degradation of endocytic cargo, have intact BCR signaling, and do not exhibit any relevant defects in maturation. This could indicate that CD74 NTF–induced structural changes of endosomes are not directly involved in these processes. We further found that the block of CD74 degradation in CatS^–/– B cells is incomplete, so that NTF levels are significantly lower than in SPPL2a^–/– B cells. This suggests a dose dependency and threshold for the CD74 NTF–associated impairment of B cell signaling and maturation. In addition, different functional properties of the longer, MHCII-bound CD74 NTF could contribute to the milder phenotype of CatS^–/– B cells.

http://ift.tt/2sPT5ji

Cutting Edge: Origins, Recruitment, and Regulation of CD11c+ Cells in Inflamed Islets of Autoimmune Diabetes Mice [CUTTING EDGE]

In NOD mice, CD11c⁺ cells increase greatly with islet inflammation and contribute to autoimmune destruction of pancreatic β cells. In this study, we investigated their origin and mechanism of recruitment. CD11c⁺ cells in inflamed islets resembled classical dendritic cells based on their transcriptional profile. However, the majority of these cells were not from the Zbtb46-dependent dendritic-cell lineage. Instead, monocyte precursors could give rise to CD11c⁺ cells in inflamed islets. Chemokines Ccl5 and Ccl8 were persistently elevated in inflamed islets and the influx of CD11c⁺ cells was partially dependent on their receptor Ccr5. Treatment with islet Ag-specific regulatory T cells led to a marked decrease of Ccl5 and Ccl8, and a reduction of monocyte recruitment. These results implicate a monocytic origin of CD11c⁺ cells in inflamed islets and suggest that therapeutic regulatory T cells directly or indirectly regulate their influx by altering the chemotactic milieu in the islets.

http://ift.tt/2rx3BIh

The Role of Shed PrPc in the Neuropathogenesis of HIV Infection [INFECTIOUS DISEASE AND HOST RESPONSE]

HIV-1 enters the CNS soon after peripheral infection and causes chronic neuroinflammation and neuronal damage that leads to cognitive impairment in 40–70% of HIV-infected people. The nonpathogenic cellular isoform of the human prion protein (PrP^c) is an adhesion molecule constitutively expressed in the CNS. Previously, our laboratory showed that shed PrP^c (sPrP^c) is increased in the cerebrospinal fluid of HIV-infected people with cognitive deficits as compared with infected people with no impairment. In this article, we demonstrate that CCL2 and TNF-α, inflammatory mediators that are elevated in the CNS of HIV-infected people, increase shedding of PrP^c from human astrocytes by increasing the active form of the metalloprotease ADAM10. We show that the consequence of this shedding can be the production of inflammatory mediators, because treatment of astrocytes with rPrP^c increased secretion of CCL2, CXCL-12, and IL-8. Supernatants from rPrP^c-treated astrocytes containing factors produced in response to this treatment, but not rPrP^c by itself, cause increased chemotaxis of both uninfected and HIV-infected human monocytes, suggesting a role for sPrP^c in monocyte recruitment into the brain. Furthermore, we examined whether PrP^c participates in glutamate uptake and found that rPrP^c decreased uptake of this metabolite in astrocytes, which could lead to neurotoxicity and neuronal loss. Collectively, our data characterize mediators involved in PrP^c shedding and the effect of this sPrP^c on monocyte chemotaxis and glutamate uptake from astrocytes. We propose that shedding of PrP^c could be a potential target for therapeutics to limit the cognitive impairment characteristic of neuroAIDS.

http://ift.tt/2sQ1tPR

Cutting Edge: Dual TCR{alpha} Expression Poses an Autoimmune Hazard by Limiting Regulatory T Cell Generation [CUTTING EDGE]

Despite accounting for 10–30% of the T cell population in mice and humans, the role of dual TCR-expressing T cells in immunity remains poorly understood. It has been hypothesized that dual TCR T cells pose an autoimmune hazard by allowing self-reactive TCRs to escape thymic selection. We revisited this hypothesis using the NOD murine model of type 1 diabetes. We bred NOD mice hemizygous at both TCRα and β (TCRα^+/– β^+/–) loci, rendering them incapable of producing dual TCR T cells. We found that the lack of dual TCRα expression skewed the insulin-specific thymocyte population toward greater regulatory T (T_reg) cell commitment, resulting in a more tolerogenic T_reg to conventional T cell ratio and protection from diabetes. These data support a novel hypothesis by which dual TCR expression can promote autoimmunity by limiting agonist selection of self-reactive thymocytes into the T_reg cell lineage.

http://ift.tt/2sPM16l

SLC46 Family Transporters Facilitate Cytosolic Innate Immune Recognition of Monomeric Peptidoglycans [INNATE IMMUNITY AND INFLAMMATION]

Tracheal cytotoxin (TCT), a monomer of DAP-type peptidoglycan from Bordetella pertussis, causes cytopathology in the respiratory epithelia of mammals and robustly triggers the Drosophila Imd pathway. PGRP-LE, a cytosolic innate immune sensor in Drosophila, directly recognizes TCT and triggers the Imd pathway, yet the mechanisms by which TCT accesses the cytosol are poorly understood. In this study, we report that CG8046, a Drosophila SLC46 family transporter, is a novel transporter facilitating cytosolic recognition of TCT, and plays a crucial role in protecting flies against systemic Escherichia coli infection. In addition, mammalian SLC46A2s promote TCT-triggered NOD1 activation in human epithelial cell lines, indicating that SLC46As is a conserved group of peptidoglycan transporter contributing to cytosolic immune recognition.

http://ift.tt/2sPT4fe

Aeroallergens Induce Reactive Oxygen Species Production and DNA Damage and Dampen Antioxidant Responses in Bronchial Epithelial Cells [ALLERGY AND OTHER HYPERSENSITIVITIES]

Exposure to environmental allergens is a major risk factor for asthma development. Allergens possess proteolytic activity that is capable of disrupting the airway epithelium. Although there is increasing evidence pointing to asthma as an epithelial disease, the underlying mechanism that drives asthma has not been fully elucidated. In this study, we investigated the direct DNA damage potential of aeroallergens on human bronchial epithelial cells and elucidated the mechanisms mediating the damage. Human bronchial epithelial cells, BEAS-2B, directly exposed to house dust mites (HDM) resulted in enhanced DNA damage, as measured by the CometChip and the staining of DNA double-strand break marker, H2AX. HDM stimulated cellular reactive oxygen species production, increased mitochondrial oxidative stress, and promoted nitrosative stress. Notably, expression of nuclear factor erythroid 2–related factor 2–dependent antioxidant genes was reduced immediately after HDM exposure, suggesting that HDM altered antioxidant responses. HDM exposure also reduced cell proliferation and induced cell death. Importantly, HDM-induced DNA damage can be prevented by the antioxidants glutathione and catalase, suggesting that HDM-induced reactive oxygen and nitrogen species can be neutralized by antioxidants. Mechanistic studies revealed that HDM-induced cellular injury is NADPH oxidase (NOX)-dependent, and apocynin, a NOX inhibitor, protected cells from double-strand breaks induced by HDM. Our results show that direct exposure of bronchial epithelial cells to HDM leads to the production of reactive oxygen and nitrogen species that damage DNA and induce cytotoxicity. Antioxidants and NOX inhibitors can prevent HDM-induced DNA damage, revealing a novel role for antioxidants and NOX inhibitors in mitigating allergic airway disease.

http://ift.tt/2rwV9ZJ

IL-6 Signaling Regulates Small Intestinal Crypt Homeostasis [MUCOSAL IMMUNOLOGY]

Gut homeostasis is a tightly regulated process requiring finely tuned complex interactions between different cell types, growth factors, or cytokines and their receptors. Previous work has implicated a role for IL-6 and mucosal immune cells in intestinal regeneration following injury and in promoting inflammation and cancer. We hypothesized that IL-6 signaling could also modulate crypt homeostasis. Using mouse in vitro crypt organoid and in vivo models, this study first demonstrated that exogenous IL-6 promoted crypt organoid proliferation and increased stem cell numbers through pSTAT3 activation in Paneth cells. Immunolabeling studies showed that the IL-6 receptor was restricted to the basal membrane of Paneth cells both in vitro and in vivo and that the crypt epithelium also expressed IL-6. Either a blocking Ab to the IL-6 receptor or a neutralizing Ab to IL-6 significantly reduced in vitro basal crypt organoid proliferation and budding, and in vivo significantly reduced the number of nuclei and the number of Lgr5EGFP-positive stem cells per crypt compared with IgG-treated mice, with the number of Paneth cells per crypt also significantly reduced. Functional studies demonstrated that IL-6–induced in vitro crypt organoid proliferation and crypt budding was abrogated by the Wnt inhibitor IWP2. This work demonstrates that autocrine IL-6 signaling in the gut epithelium regulates crypt homeostasis through the Paneth cells and the Wnt signaling pathway.

http://ift.tt/2sPHdOm

Airway Epithelial Cells Are Crucial Targets of Glucocorticoids in a Mouse Model of Allergic Asthma [ALLERGY AND OTHER HYPERSENSITIVITIES]

Although glucocorticoids (GCs) are a mainstay in the clinical management of asthma, the target cells that mediate their therapeutic effects are unknown. Contrary to our expectation, we found that GC receptor (GR) expression in immune cells was dispensable for successful therapy of allergic airway inflammation (AAI) with dexamethasone. Instead, GC treatment was compromised in mice expressing a defective GR in the nonhematopoietic compartment or selectively lacking the GR in airway epithelial cells. Further, we found that an intact GR dimerization interface was a prerequisite for the suppression of AAI and airway hyperresponsiveness by GCs. Our observation that the ability of dexamethasone to modulate gene expression in airway epithelial cells coincided with its potency to resolve AAI supports a crucial role for transcriptional regulation by the GR in this cell type. Taken together, we identified an unknown mode of GC action in the treatment of allergic asthma that might help to develop more specific therapies in the future.

http://ift.tt/2sPHYak

Comprehensive Approach for Identifying the T Cell Subset Origin of CD3 and CD28 Antibody-Activated Chimeric Antigen Receptor-Modified T Cells [NOVEL IMMUNOLOGICAL METHODS]

The outcome of therapy with chimeric Ag receptor (CAR)-modified T cells is strongly influenced by the subset origin of the infused T cells. However, because polyclonally activated T cells acquire a largely CD45RO⁺CCR7^– effector memory phenotype after expansion, regardless of subset origin, it is impossible to know which subsets contribute to the final T cell product. To determine the contribution of naive T cell, memory stem T cell, central memory T cell, effector memory T cell, and terminally differentiated effector T cell populations to the CD3 and CD28–activated CAR-modified T cells that we use for therapy, we followed the fate and function of individually sorted CAR-modified T cell subsets after activation with CD3 and CD28 Abs (CD3/28), transduction and culture alone, or after reconstitution into the relevant subset-depleted population. We show that all subsets are sensitive to CAR transduction, and each developed a distinct T cell functional profile during culture. Naive-derived T cells showed the greatest rate of proliferation but had more limited effector functions and reduced killing compared with memory-derived populations. When cultured in the presence of memory T cells, naive-derived T cells show increased differentiation, reduced effector cytokine production, and a reduced reproliferative response to CAR stimulation. CD3/28-activated T cells expanded in IL-7 and IL-15 produced greater expansion of memory stem T cells and central memory T cell–derived T cells compared with IL-2. Our strategy provides a powerful tool to elucidate the characteristics of CAR-modified T cells, regardless of the protocol used for expansion, reveals the functional properties of each expanded T cell subset, and paves the way for a more detailed evaluation of the effects of manufacturing changes on the subset contribution to in vitro–expanded T cells.

http://ift.tt/2sPRyK1

Occludin Expression in Epidermal {gamma}{delta} T Cells in Response to Epidermal Stress Causes Them To Migrate into Draining Lymph Nodes [ALLERGY AND OTHER HYPERSENSITIVITIES]

Epidermal T cells that reside in the front line of the skin play a pivotal role in stress immune surveillance. However, it is not clear whether these cells are involved in further induction of immune responses after they are activated in dysregulated epidermis. In this study, we found that activated T cells expressed occludin and migrated into draining lymph nodes in an occludin-dependent manner. Epidermal T cells in occludin-deficient mice exhibited impairments in morphology changes and motility, although they expressed activation markers at levels comparable to those in wild-type cells. Occludin deficiency weakened the induction of allergen-induced contact hypersensitivity, primarily as the result of the impaired migration of epidermal T cells. Thus, occludin expression by epidermal T cells upon activation in response to epidermal stress allows them to move, which could be important for augmentation of immune responses via collaboration with other cells.

http://ift.tt/2rwGqxT

Monoclonal Invariant NKT (iNKT) Cell Mice Reveal a Role for Both Tissue of Origin and the TCR in Development of iNKT Functional Subsets [IMMUNE REGULATION]

Invariant NKT (iNKT) cell functional subsets are defined by key transcription factors and output of cytokines, such as IL-4, IFN-, IL-17, and IL-10. To examine how TCR specificity determines iNKT function, we used somatic cell nuclear transfer to generate three lines of mice cloned from iNKT nuclei. Each line uses the invariant Vα14Jα18 TCRα paired with unique Vβ7 or Vβ8.2 subunits. We examined tissue homing, expression of PLZF, T-bet, and RORt, and cytokine profiles and found that, although monoclonal iNKT cells differentiated into all functional subsets, the NKT17 lineage was reduced or expanded depending on the TCR expressed. We examined iNKT thymic development in limited-dilution bone marrow chimeras and show that higher TCR avidity correlates with higher PLZF and reduced T-bet expression. iNKT functional subsets showed distinct tissue distribution patterns. Although each individual monoclonal TCR showed an inherent subset distribution preference that was evident across all tissues examined, the iNKT cytokine profile differed more by tissue of origin than by TCR specificity.

http://ift.tt/2rx8Ibs

Olfaction and Its Correlates in Allergic Rhinitis: A Case Control Study

Abstract

Olfactory dysfunction is frequent in rhinological disease. It has been attributed to nasal obstruction leading to impairment of transport of odorants to the olfactory epithelium or to inflammation in the olfactory cleft. We assessed olfaction in allergic rhinitis and correlated the olfactory score with other variables; in order to elucidate the pathogenesis of olfactory impairment in allergic rhinitis. Forty patients of allergic rhinitis (skin prick test positive) and forty healthy controls were included. The groups were evaluated for olfactory score, nasal airflow, peripheral eosinophilia, and levels of IgE and IL-5 in nasal secretions. The combined olfactory score in the patients was lower than that in controls. The score was better in patients with a better nasal airflow, but no significant association was found between the two. The peripheral eosinophilia and IgE and IL-5 level in nasal secretions was significantly higher in patients but demonstrated no significant correlation with the olfactory score. Allergic rhinitis patients had a decreased olfactory score; which weakly correlated to the nasal airflow. Local IgE and IL-5 were elevated in allergic rhinitis but did not show a significant correlation with olfactory scores. Our study concludes that both factors exist in allergic rhinitis but which factor is significantly responsible for hyposmia is not clear.

http://ift.tt/2sHUbgJ

Cytokine Profiling in a Familial Case of Autoimmune Lymphoproliferative Syndrome with Co-mutations of FAS and MEFV

Pediatric Allergy, Immunology, and Pulmonology Jun 2017, Vol. 30, No. 2: 120-125.


http://ift.tt/2sI1ViH

Relationship Between Vitamin D Status and Viral Pneumonia in Children

Pediatric Allergy, Immunology, and Pulmonology Jun 2017, Vol. 30, No. 2: 86-91.


http://ift.tt/2tG1ToH

Prediction of Refractory Mycoplasma Pneumoniae Pneumonia in Pediatric Patients

Pediatric Allergy, Immunology, and Pulmonology Jun 2017, Vol. 30, No. 2: 92-96.


http://ift.tt/2sIBKs5

Cytokine Profiling in a Familial Case of Autoimmune Lymphoproliferative Syndrome with Co-mutations of FAS and MEFV

Pediatric Allergy, Immunology, and Pulmonology Jun 2017, Vol. 30, No. 2: 120-125.


http://ift.tt/2rJIsPz

Relationship Between Vitamin D Status and Viral Pneumonia in Children

Pediatric Allergy, Immunology, and Pulmonology Jun 2017, Vol. 30, No. 2: 86-91.


http://ift.tt/2st9jfJ

Prediction of Refractory Mycoplasma Pneumoniae Pneumonia in Pediatric Patients

Pediatric Allergy, Immunology, and Pulmonology Jun 2017, Vol. 30, No. 2: 92-96.


http://ift.tt/2rJlTKJ

Olfaction and Its Correlates in Allergic Rhinitis: A Case Control Study

Abstract

Olfactory dysfunction is frequent in rhinological disease. It has been attributed to nasal obstruction leading to impairment of transport of odorants to the olfactory epithelium or to inflammation in the olfactory cleft. We assessed olfaction in allergic rhinitis and correlated the olfactory score with other variables; in order to elucidate the pathogenesis of olfactory impairment in allergic rhinitis. Forty patients of allergic rhinitis (skin prick test positive) and forty healthy controls were included. The groups were evaluated for olfactory score, nasal airflow, peripheral eosinophilia, and levels of IgE and IL-5 in nasal secretions. The combined olfactory score in the patients was lower than that in controls. The score was better in patients with a better nasal airflow, but no significant association was found between the two. The peripheral eosinophilia and IgE and IL-5 level in nasal secretions was significantly higher in patients but demonstrated no significant correlation with the olfactory score. Allergic rhinitis patients had a decreased olfactory score; which weakly correlated to the nasal airflow. Local IgE and IL-5 were elevated in allergic rhinitis but did not show a significant correlation with olfactory scores. Our study concludes that both factors exist in allergic rhinitis but which factor is significantly responsible for hyposmia is not clear.

http://ift.tt/2sHUbgJ

Successful conservative treatment of severe frostbite lesions in a Greenlandic Inuit

Frostbite may cause lesions. The severity ranges from superficial wounds to severe cases with loss of limbs and tissue. Hence, proper treatment is of utmost importance. We present a case of an 18-year-old man from Arctic Greenland who was admitted with severe frostbite lesions involving both hands. The patient had fallen asleep outside during extreme temperatures. He was treated conservatively with proper wound care, antibiotics and intensive physical therapy. The patient made a full recovery without sequelae. The current report emphasises that non-operative treatment should be attempted for frostbite lesions, as conservative treatment often results in good outcomes.

http://ift.tt/2sPHOzw

Mistaken identity: haemoglobinuria secondary to paravalvular leak masking as haematuria

Haemolytic anaemia caused by a paravalvular leak presenting as progressively worsening red urine. Haemoglobinuria was easily mistaken for gross haematuria, resulting in extensive invasive urological investigation that proved to be futile. Further investigation following an emergency admission led to the realisation that intravascular haemolysis secondary to a paravalvular leakâ"presenting 43 years following metallic valve insertionâ"was the cause of discoloured urine and newly presenting symptomatic anaemia. This case highlights that there remains other causes of what often appears to be haematuria, and further exploration of alternative causes should be considered when no urological cause is found.

http://ift.tt/2rwd8zA

A Rare Case Of Sigmoid Colon Perforation With Subsequent Psoas Abscess Collection With Extensive Involvement Of The Sartorius Muscle

A middle-aged man was admitted with worsening hip pain, fevers and reduced mobility. These symptoms were preceded by a mechanical fall but despite regular analgesia, symptoms did not resolve. His prior medical history included ischaemic heart disease, hypertension and hypercholesterolaemia. A trauma and orthopaedic review revealed a painful left hip with reduced range of motion. In addition, some mild tenderness in the left iliac fossa was noted. Blood tests revealed markedly raised inflammatory markers. Plain radiographs and ultrasound were normal. MRI scan found a massive left iliopsoas collection secondary to perforated diverticular disease of the sigmoid colon. The patient was managed with intravenous antibiotics and the collection was drained percutaneously. Approximately 500 mL of pus was aspirated. The patient made an excellent recovery with interval imaging showing a reduction in the collection size.

http://ift.tt/2sPF7hD

Thyrotoxic periodic paralysis as an initial presentation of Graves disease in a Saudi patient

Thyrotoxic periodic paralysis (TPP) is a well-known complication of hyperthyroidism, characterised by recurrent flaccid paralysis with hypokalaemia. To date, only five cases of this rare disorder have been reported in Saudi Arabia. Here, we report an additional case involving a 25-year-old Saudi man who presented with lower limb paralysis and severe hypokalaemia. Clinically, he showed symptoms and signs suggestive of Graves' disease, which was confirmed by laboratory investigations. Carbimazole, a beta-blocker and potassium replacement were administered, resulting in dramatic improvement of the TTP. This case emphasises the importance of considering TPP in patients with acute muscle weakness and the importance of promptly initiating treatment and preventing relapse of TPP.

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Beyond cervical lipomas: myoclonus, gait disorder and multisystem involvement leading to mitochondrial disease

Madelung's disease (benign symmetric lipomatosis) is a rare syndrome in which there are multiple lipomas around the neck, upper limbs and trunk in the context of chronic alcoholism. We report on a female patient with lipomas and slightly progressive myoclonus, neuropathy, myopathy, ataxia and respiratory systemic involvement (labelled in the past as Madelung's disease). Multisystem involvement and family history of lipomas led to the development of mitochondrial genetic tests, which can assess two concurrent mitochondrial mutations: the m.8344A>G mutation in MT-TK gene, related MERRF (myoclonic epilepsy with ragged-red fibre) phenotype and m.14484T>C mutation in the MT-ND6 gene responsible for Leber hereditary optic neuropathy phenotype.

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Imaging findings in Steideles complex

Description

Steidele's complex is an eponym to interrupted aortic arch (IAA), which is characterised by complete anatomic discontinuity between the aortic arch and the descending aorta (DA). It is a very rare congenital anomaly that occurs in 19 per million live births.1 Based on the site of interruption, it is classified into three types: type A (30%–40%) when it occurs beyond the left subclavian artery, type B (51%–70%) when it occurs between the left carotid artery and the left subclavian artery and type C (1%–5%) when it occurs between the brachiocephalic artery and the left common carotid artery.2 DA originates from the pulmonary artery through a patent ductus arteriosus (PDA). IAA is invariably associated with a ventricular septal defect (VSD) in majority of cases. IAA is associated with a high mortality rate of 75% at 1 month and 90% at 1 year, in the absence of operative intervention.3 We describe a...

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Retrorectal tumour simulating vaginal birth: an exceptional case of emergency surgery indication

Cystic retrorectal tumours are a very rare entity that pose a problem in differential diagnosis between congenital cyst and other lesions. We present a 49-year-old female patient presenting a perineal bulge which was discovered simulating a vaginal birth associated with prolapsed haemorrhoids grade IV. The interest of this case resides in the surgical indication of a big presacral cyst demonstrated via CT causing acute intense pain due to pelvic organ compression, as no emergent surgery management has been reported up to date.

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Lipoma of right pyriform sinus

We present a case of large mass arising from the right pyriform sinus extending inferiorly to the postcricoid area and superiorly to the right aryepiglottic fold causing a foreign body sensation and obstructive symptoms, its histological examination following the endoscopic surgical excision showed a lipoma. We are also describing the endoscopic, radiological and intraoperative findings with a brief literature review.

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Acute pneumatosis cystoides intestinalis with atrophic desmosis of the colon in a child

Acute pneumatosis cystoides intestinalis (PCI) has been described after bone marrow transplantation (BMT). Several case series have demonstrated successful conservative treatment of PCI in children. We present a child with Fanconi anaemia, who developed severe graft versus host disease of the gastrointestinal tract, skin and liver after BMT and an acute, severe form of PCI. Our case report illustrates the complexity of diagnostic and therapeutic procedures in PCI in immunocompromised children.

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'Carbuncle in diabetes: a problem even today!

Description

A 65-year-old man presented with fever and painful swelling at the back for last 2 weeks. His prior history was significant for long-standing type 2 diabetes of 20 years duration and systemic hypertension. Clinical examination showed red, swollen, painful carbuncle with gangrenous patch at the centre and multiple pus points (figure 1). Investigations revealed elevated white blood cell count with neutrophil predominance and high random blood sugar, 340 mg/dL (normal, <140 mg/dL). He was started on insulin and good glycaemic control was achieved. Aggressive debridement of the local affected area was done. Tissue culture was positive for Staphylococcus aureus and he was treated with amoxicillin and clavulanic acid to which he responded well. On follow-up, his debrided wound was granulating well. Carbuncle, also called as infective gangrene of skin and subcutaneous tissue, is most commonly caused by S. aureus that usually starts as a furuncle/boil around the root of a hair...

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New approach to improve the keratinised peri-implant soft tissues in patients with intraoral osteocutaneous reconstruction using a free flap

Publication date: Available online 17 June 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): N. Patel, D. Patel, J. Kwok




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Why don’t we mention “impact on intimacy” when we ask patients to give consent for treatment of oral cancer?

Publication date: Available online 17 June 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): R. Ratansi, J. Hoole, D.A. Mitchell, A. Kanatas




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Re: Ipsilateral full-thickness skin grafts to repair the donor site defect of a radial forearm free flap: a reflection on technique

Publication date: Available online 17 June 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): A.V. Parbhoo




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Psychiatric disorders with systemic retinoids: a systematic review of case reports

Abstract

The question of the association between isotretinoin and the development of psychiatric disorders has been debated for the past 20 years. Some authors have argued that similar psychiatric symptoms or disorders could also be induced by other systemic retinoids¹. However, few reports have included a formal assessment of the causal link between systemic retinoids and psychiatric disorders.

This article is protected by copyright. All rights reserved.

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Error and Root Cause Analysis

1I032A063I00

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Endocrine problems in the critically ill 1: diabetes and glycaemic control

1A012C013J02

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Can atrophic erosive oral lichen planus promote cardiovascular diseases? A population-based study

Abstract

Objectives

Lichen planus has been recently associated with an increased risk of cardiovascular diseases (CVDs). The oral manifestations can be divided into white hyperkeratotic lesions (WL) and atrophic erosive lesions (RL). The aim of this report was to compare the presence of CVDs between patients affected by WL or RL, to test the hypothesis that RL are associated with an increased incidence of CVDs.

Subjects And Methods

Patients were analysed through a complete collection of all the risk factors for CVDs. The primary endpoint was the occurrence of a cardiovascular event -acute coronary syndrome (ACS), any revascularization or stroke/TIA. A multivariable logistic regression model, adjusted for age at diagnosis, body mass index, smoking, alcohol consumption, diabetes, hypertension, CVDs familiarity and periodontitis was performed.

Results

A prospective cohort of 307 patients has been evaluated; 185 (60.3%) had WL and 122 RL (39.7%). Twenty-four patients had a CVD. ACS occurred more frequently in RL (adjusted odd ratio 5.83; 95%CI: 1.16-29.39), mainly due to the higher risk of it after the histological diagnosis of OLP (odd ratio 4.23; 95%CI: 0.66-27.23).

Conclusion

Patients with RL could possibly have a higher risk of developing ACS. Further analysis on larger cohort are however warranted.

This article is protected by copyright. All rights reserved.

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Predicting massive transfusion in placenta previa

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Distinctive pathological and clinical features of lung carcinoids with high proliferation index

Abstract

Typical (TCs) and atypical carcinoids (ACs) are defined based on morphological criteria, and no grading system is currently accepted to further stratify these entities. The 2015 WHO classification restricts the Ki-67 role to biopsy or cytology samples, rather than for prognostic prediction. We aimed to investigate whether values and patterns of Ki-67 alone would allow for a clinically meaningful stratification of lung carcinoids, regardless of histological typing. Ki-67 proliferation index and pattern (homogeneous versus heterogeneous expression) were assessed in a cohort of 171 TCs and 68 ACs. Cases were subdivided into three Ki-67 ranges (<4/4–9/≥10%). Correlations with clinicopathological data, univariate and multivariate survival analyses were performed. The majority of cases (61.5%) belonged to the <4% Ki-67 range; 25.1 and 13.4% had a proliferation index of 4–9% and ≥10%, respectively. The <4% Ki-67 subgroup was significantly enriched for TCs (83%, p < 0.0001); ACs were more frequent in the subgroup showing Ki-67 ≥ 10% (75%, p < 0.0001). A heterogeneous Ki-67 pattern was preferentially seen in carcinoids with a Ki-67 ≥10% (38%, p < 0.02). Mean Ki-67 values ≥4 and ≥10% identified categories of poor prognosis both in terms of disease-free and overall survival (p = 0.003 and <0.0001). At multivariate analysis, the two thresholds did not retain statistical significance; however, a Ki-67 ≥ 10% identified a subgroup of dismal prognosis even within ACs (p = 0.03) at univariate analysis. Here, we describe a subgroup of lung carcinoids showing brisk proliferation activity within the necrosis and/or mitotic count-based categories. These patients were associated with specific clinicopathological characteristics, to some extent regardless of histological subtyping.

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Granulomatöse Erkrankungen der Haut

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The length of patient and primary care time interval in the pathways to treatment in symptomatic oral cancer. A quantitative systematic review

Abstract

Background: Only a 5% improvement in overall survival to oral cancer has been achieved in the last 20 years. Almost half of all oral carcinomas are diagnosed at advanced stages essentially due to delay in the diagnosis. Objective of the review: to examine the relative length of the patient and primary care intervals in symptomatic oral cancer. Type of review: Quantitative systematic review. Search strategy: ((oral cancer OR oral squamous cell carcinoma OR oropharyngeal cancer) AND (time interval OR diagnostic delay)). Evaluation method: we computed 5 measures (patient, primary care, diagnosis, total diagnosis, and total treatment intervals). Most studies did not provide any dispersion measure. We then used the sample size of each study to compute a weighted average of the mean intervals. When the median was provided, we assumed normality of the distribution of the means and used the median as a proxy of the mean. Results: A total of 1,089 articles were identified and 22 met the inclusion criteria, reporting on 2710 patients from Europe, USA, India, Australia, Japan, Argentina, and Iran. The weighted average of patient interval was 80.3 days. Primary care interval was five times shorter: 15.8 days. The diagnostic interval was appreciably shorter (47.9 days) when compared with the patient interval during symptomatic period. Conclusions: Patient interval represents the major component of waiting times since the detection of the first signs/symptoms to the definitive diagnosis of oral cancer. Thus, strategies focused on high-risk patients should be prioritised. Interventions aimed at optimising the health systems should be implemented by monitoring and facilitating diagnostic and treatment pathways of oral cancer patients.

This article is protected by copyright. All rights reserved.

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Panorama Dermatologische Praxis

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Table of contents

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Masthead

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Exhaled breath profiles in the monitoring of loss of control and clinical recovery in asthma

Abstract

Background

Asthma is a chronic inflammatory airway disease, associated with episodes of exacerbations. Therapy with inhaled corticosteroids (ICS) targets airway inflammation, which aims to maintain and restore asthma control. Clinical features are only modestly associated with airways inflammation. Therefore, we hypothesized that exhaled volatile metabolites identify longitudinal changes between clinically stable episodes and loss of asthma control.

Objectives

To determine whether exhaled volatile organic compounds (VOCs) as measured by gas-chromatography / mass-spectrometry (GC/MS) and electronic nose (eNose) technology discriminate between clinically stable and unstable episodes of asthma.

Methods

23 patients with (partly) controlled mild to moderate persistent asthma using ICS were included in this prospective steroid-withdrawal study. Exhaled metabolites were measured at baseline, during loss of control and after recovery. Standardized sampling of exhaled air was performed, after which samples were analyzed by GC/MS and eNose. Univariate Analysis of Covariance (ANCOVA), followed by multivariate Principal Component Analysis (PCA) were used to reduce data dimensionality. Next paired t-tests were utilized to analyze within-subject breath profile differences at the different timepoints. Finally, associations between exhaled metabolites and sputum inflammation markers were examined.

Results

Breath profiles by eNose showed 95% (21/22) correct classification for baseline vs. loss of control and 86% (19/22) for loss of control vs. recovery. Breath profiles using GC/MS showed accuracies of 68% (14/22) and 77% (17/22) for baseline vs. loss of control and loss of control vs. recovery, respectively. Significant associations between exhaled metabolites captured by GC/MS and sputum eosinophils were found (Pearson r≥0.46, p<0.01).

Conclusions & Clinical Relevance

Loss of asthma control can be discriminated from clinically stable episodes by longitudinal monitoring of exhaled metabolites measured by GC/MS and particularly eNose. Part of the uncovered biomarkers were associated with sputum eosinophils. These findings provide proof of principle for monitoring and identification of loss of asthma control by breathomics.

This article is protected by copyright. All rights reserved.

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Different patterns of expression of cell cycle control and local invasion-related proteins in oral squamous cell carcinoma affecting young patients

Abstract

Oral squamous cell carcinoma (OSCC) predominantly affects males in the fifth decade of life; nevertheless, an increased incidence in young patients has been reported worldwide and the clinical and behavioral characteristics of tumors in this group are controversial and the literature shows divergent results

Purpose

To investigate the clinicopathological features and prognostic significance of the immunoexpression of cell cycle and local invasion proteins in OSCC affecting young patients (≤ 40 years old)

Methods

A tissue microarray was performed with 132 OSCC samples (61 cases of young patients vs. 71 cases of elderly patients) and submitted to immunohistochemical reactions with Ki67, p53, p16, Bcl-2, Cyclin D1, C-ErbB2, p21, Myc, EGFR, MMP-9, SMA, Cathepsin K and FGF-2 antibodies

Results

Clinicopathological features and survival rates were similar in both groups. Although overexpression of EGFR (p = 0.042) and MMP-9 (p = 0.001) was more frequent in young patients, only C-ErbB-2 (p = 0.048) and SMA (p = 0.048) expression correlated with lower DFS in this group of patients

Conclusion

Clinicopathological features and survival rates are similar between younger and older patients with OSCC. The different patterns of C-ErbB2, EGFR, MMP-9 and SMA expression between the groups merits further investigation to understand their role in the early tumor onset in young patients.

This article is protected by copyright. All rights reserved.

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Does personalised melanoma genomic risk information trigger conversations about skin cancer prevention and skin examination with family, friends and health professionals?

Abstract

Background

Receiving information about melanoma genomic risk might trigger conversations about skin cancer prevention and skin examinations.

Objectives

To explore conversations prompted by receiving personalised genomic risk of melanoma with family, friends and health professionals.

Methods

We used a mixed-methods approach. Participants without a personal history and unselected for a family history of melanoma (n=103, aged 21-69, 53% women) completed questionnaires 3-months after receiving a personalised melanoma genomic risk assessment. Semi-structured interviews were undertaken with 30 participants in high, average and low-risk genomic risk categories, and data were analysed thematically.

Results

From questionnaires, 74% of participants communicated their genomic risk information with family, 49% with friends. Communication with a health professional differed by risk level: 41%, 16% and 12% for high, average and low-risk, respectively (P=0.01). Qualitative analysis showed that perceived 'shared risk' and perceived interest of family and friends were motivations for discussing risk or prevention behaviours. The information prompted conversations with family and health professionals about sun protection and skin checks, and general conversations about melanoma risk with friends. Reasons for not discussing with family included existing personal or family health concerns, or existing high levels of sun protection behaviours among family members.

Conclusions

Personalised melanoma genomic risk information can prompt risk-appropriate discussions about skin cancer prevention and skin examinations with family and health professionals. Sharing this information with others might increase its impact on melanoma prevention and skin examination behaviours, and this process could be used to encourage healthy behaviour change within families.

This article is protected by copyright. All rights reserved.

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Molar incisor hypomineralization: proportion and severity in primary public school children in Graz, Austria

Abstract

Objective

The aim of this study was to determine the proportion and severity of molar incisor hypomineralization (MIH) in primary school children in Graz (southeast of Austria).

Materials and methods

In 1111 children aged 6 to 12 years (mean age 9.0 ± 1.2), a wet examination of all teeth was performed by three trained examiners using a dental chair, optimal illumination, a dental mirror, and a dental explorer. All teeth with MIH lesions were registered so that different definitions of MIH were applicable. According to the European Academy of Pediatric Dentistry criteria that were considered valid at the time of the investigation, MIH was diagnosed when at least one first primary molar (FPM) was affected.

Results

MIH was present in 78 children (7.0%). In 64 children (5.8%), at least one molar and one incisor were affected (so-called M + IH). Additionally, in 9 children, only incisors were affected. In 7 affected children, teeth other than FPMs and incisors had MIH lesions. Almost an equal number of males (38) and females (40) were affected. The upper and lower molars were equally affected. The upper incisors were more frequently affected than the lower ones. Demarcated enamel opacities were the predominant types of defects.

Conclusion

The proportion of MIH was 7.0% in Graz, which is similar to other comparable trials.

Clinical relevance

This study has proven that MIH is an existing dental problem in Graz.

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Trends in sleep studies performed for Medicare beneficiaries

Objectives/Hypothesis

To quantify trends and characteristics of sleep studies performed for Medicare beneficiaries in the United States.

Study Design

Retrospective longitudinal study of the Centers for Medicare and Medicaid Services' Part B National Summary Data and Medicare Provider Utilization and Payment Data from 2000 to 2014.

Methods

Sleep study data were analyzed according to type of study performed, total expenditure amount, provider specialty, and geographic location.

Results

In 2014, 845,569 sleep studies were completed by 1.4% of Medicare beneficiaries for a total of $189 million. Since 2010, annual expenditures for sleep studies have declined, whereas the number of studies performed has increased by 9.1%. In 2014, polysomnography, split-night polysomnography, and unattended home sleep studies accounted for 40%, 48%, and 12%, respectively, of total sleep studies. This represents a dramatic growth in the number of unattended sleep studies performed since 2000, when they represented only 0.9%. Pulmonologists, independent diagnostic testing facilities, and neurologists are the top specialties that bill for sleep studies. Sleep medicine is a growing specialty and ranked fifth among providers, whereas otolaryngologists ranked eighth.

Conclusions

The healthcare burden of administering sleep studies is substantial, although the annual cost is declining. Unattended sleep studies contribute to decreasing costs and should be considered for patients who meet the correct indications.

Level of Evidence

4 Laryngoscope, 2017

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