Narcisa Martinez-Quiles | Raphaela Goldbach-Mansky
https://ift.tt/2zZSTQ3
Σάββατο 17 Νοεμβρίου 2018
Updates on autoinflammatory diseases
Symptomatic Primary Hyperparathyroidism as a Risk Factor for Differentiated Thyroid Cancer
Background. The primary hyperparathyroidism (PHPT) is a common disease for the endocrinologist. The concomitant thyroid disease and differentiated thyroid cancer (DTC) appear to be more frequent in patients with PHPT than in the general population. The aim of this study was to characterize patients with symptomatic PHPT with and without DTC and analyze frequency and risk factors. Methods. We consecutively studied patients with symptomatic PHPT diagnosed and treated at our center between 2013 and 2015. Patients with subclinical and syndromic forms of PHPT were excluded. Clinical and biochemical characteristics of patients with and without DTC were compared and risk factors were determined. All patients were studied with thyroid ultrasound and thyroid gammagraphy with TC-MIBI. Two expert surgeons performed all the surgical procedures. Results. In 59 patients included, we found 12 cases of PTC (20.3%). The final histopathological report of the PTC was 7 cases of follicular variant, 2 cases of oncocytic variant, 2 cases of classic variant, and 1 case of columnar cells variant of PTC. Patients with thyroid cancer were older than patients without thyroid cancer (62 ± 9.5 versus 52 ± 15.8, p = 0.03). Higher preoperative levels of iPTH were associated with PTC (p=0.03) [OR 5.16 (95% CI: 1.08-24.7)]. Conclusion. PTC is frequent in patients with symptomatic PHPT. Thyroid nodules in patients with symptomatic PHPT must be studied before parathyroidectomy. In symptomatic PHPT, higher level concentration of parathormone (PTH) was associated with higher risk of DTC.
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Association of antinuclear antibody status with clinical features and malignancy risk in adult-onset dermatomyositis
Antinuclear antibody testing is positive in most adults with dermatomyositis. There is a strong association between negative antinuclear antibody status and increased risk of underlying malignancy in adults with dermatomyositis. More frequent follow-up and malignancy screening may be warranted in adults with dermatomyositis and negative antinuclear antibody testing.
https://ift.tt/2TmJzig
Vulvar Paget disease: a national retrospective cohort study
Vulvar Paget disease is a rare skin disorder with unknown malignant potential. Recurrence rates are about 40%. The risk of developing invasive disease after a non-invasive diagnosis is 8%. Five-year disease specific survival of invasive disease is significantly worse than in non-invasive or micro-invasive disease: 50% versus 98%.
https://ift.tt/2A4ecQw
Melanomas of the head and neck have high local recurrence risk features and require tissue rearranging reconstruction more commonly than BCC and SCC: A comparison of indications for microscopic margin control prior to reconstruction in 13,664 tumors
Consensus guidelines specify indications for microscopic margin control of keratinocyte carcinoma but not melanoma. Head and neck melanomas have high local recurrence risk features and require tissue rearranging reconstruction more frequently than keratinocyte carcinoma. Consensus guidelines with clear indications for microscopic margin control may improve outcomes for high-risk melanomas.
https://ift.tt/2A32sxR
Comparative effectiveness of treatment of actinic keratosis with topical fluorouracil and imiquimod in the prevention of keratinocyte carcinoma: a cohort study
5-fluorouracil and imiquimod are frequently prescribed actinic keratosis treatments, but no studies have compared their effectiveness at preventing keratinocyte carcinoma in a real-world setting. Whereas 5-fluorouracil was more effective in reducing keratinocyte carcinoma risk overall, we found no differences in the short- or long-term risk of site-specific keratinocyte carcinoma.
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Menopause is associated with decreased postprandial ghrelin, while a history of anorexia nervosa is associated with increased total ghrelin
Abstract
Introduction
Middle age has been linked with various dysfunctional eating patterns in women. The hormone ghrelin is related to food intake, with plasma levels rising before eating and decreasing immediately afterwards. Animal research has shown that estradiol is an antagonist of ghrelin. Given that both menopause and anorexia nervosa (AN) are states characterised by reduced estradiol, the goal of the present study was to investigate for the first time whether menopausal status and a history of AN are linked with altered ghrelin levels in middle‐aged women. Based on previous research, we hypothesised that a) post‐menopausal women would demonstrate comparably increased ghrelin after food intake and b) women with a history of AN would exhibit increased total ghrelin levels.
Methods
Healthy, middle‐aged women (N=57) were recruited. N=31 were post‐menopausal and n=27 had a history of AN. Plasma was repeatedly collected before and after a meal standardised in terms of caloric content. Areas under the curves were calculated to indicate total (AUCg) and postprandial ghrelin (AUCi).
Results
Menopausal status was linked with postprandial ghrelin (AUCi ‐1.6±2.2 vs. ‐2.9±2.6; p=.058), while a history of AN was linked with total ghrelin (AUCg 36.2±5.6 vs. 39.0±3.7; p=.050). There were no interaction effects (both p>.466). A closer examination of the effects revealed that post‐menopausal women showed marginally greater decreases in ghrelin immediately after food intake (p=.064) and marginally greater re‐increases after 60 min (p=.084) when compared to pre‐menopausal women. Women with a history of AN had significantly higher total ghrelin when compared to women without a history of AN (p=.042).
Discussion
Post‐menopause was linked with higher sensitivity of ghrelin to food intake (trend), while a history of AN was related to greater total ghrelin. Future research should investigate to what extent the observed alterations in ghrelin may affect dysfunctional eating behaviour during middle age.
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Disentangling the heterogeneity of allergic respiratory diseases by latent class analysis reveals novel phenotypes
Abstract
Background
Refined phenotyping of allergic diseases may unravel novel phenotypes. Conjunctivitis as an independent disorder has never been approached.
Aim
To identify distinct classes of allergic respiratory diseases using latent class analysis (LCA) and distinguish each class using classification and regression tree (CART) analysis.
Methods
728 adults from the Portuguese general population study ICAR had a structured medical interview combined with blood collection, skin prick tests, spirometry with bronchodilation, and exhaled nitric oxide. LCA was applied to 19 variables. The CART algorithm selected the most likely variables distinguishing LCA‐classes.
Results
A six‐class model was obtained. Class 1 (25%): non‐allergic participants without bronchial or ocular symptoms. Classes 2 (22%) and 3 (11%): nasal and ocular (low levels) symptoms without nasal impairment, monosensitized (Class 2) or polysensitized (Class 3). Class 4 (13%): polysensitized participants with high levels of nasal and ocular symptoms, and nasal impairment. Classes 5 (16%) and 6 (14%): high level of nasal, bronchial and ocular symptoms with nasal impairment (non‐allergic or polysensitized, respectively). Participants in classes 5 and 6 had more bronchial exacerbations and unscheduled medical visits (p<0.001). Ocular symptoms were significantly higher in classes with nasal impairment, compared to those without impairment (p<0.001) or no nasal symptom (p<0.001). CART highlighted ocular symptoms as the most relevant variable in distinguishing LCA‐classes.
Conclusions
Novel severe phenotypes of participants with co‐occurrence of ocular, nasal and bronchial symptoms, and exacerbation‐prone were identified. The tree algorithm showed the importance of the ocular symptoms in the expression of allergic diseases phenotypes.
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Possible hints and pitfalls in diagnosing Peutz-Jeghers syndrome
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
https://ift.tt/2PxoN17
Dysregulated glucose homeostasis in congenital central hypoventilation syndrome
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
https://ift.tt/2QWlIV6
Targeted next generation sequencing in patients with maturity-onset diabetes of the young (MODY)
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
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Gamma‐delta T cell large granular lymphocyte leukemia with multiple cutaneous nodules that showed spontaneous regression
Abstract
T cell large granular lymphocyte leukemia (T‐LGLL) is a rare chronic lymphoproliferative disorder of mature post‐thymic large granular lymphocytes (LGL); either cytotoxic T‐lymphocytes or natural killer cells.1 Major phenotype of LGL cells is TCRαβ+CD3+CD4‐CD5+CD8+CD27‐CD28‐CD45‐CD57+.2 Less than 10% of cases express TCRγδ instead of TCRαβ.2 Most cases of T‐LGLL have an indolent course1 and its cutaneous manifestations have been poorly documented.
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Individual Risk Assessment Tool for School Age Asthma Prediction in UK Birth Cohort
Abstract
Background
Current published asthma predictive tools have moderate positive likelihood ratios (LR+) but high negative likelihood ratios (‐LR) based on their recommended cut‐offs, which limit their clinical usefulness.
Objective
To develop a simple clinically applicable asthma prediction tool within a population‐based birth cohort.
Method
Children from the Manchester Asthma and Allergy Study (MAAS) attended follow‐up at ages 3, 8 and 11 years. Data on pre‐school wheeze was extracted from primary‐care records. Parents completed validated respiratory questionnaires. Children were skin prick tested (SPT). Asthma at 8/11 years (school ‐age) was defined as parentally‐reported (1) physician‐diagnosed asthma and wheeze in the previous 12 months or (2) ≥3 wheeze attacks in the previous 12 months. An asthma prediction tool (MAAS APT) was developed using logistic regression of characteristics at age 3 years to predict school‐age asthma.
Results
Of 336 children with physician‐confirmed wheeze by age 3 years, 117(35%) had school‐age asthma. Logistic regression selected 5 significant risk factors which formed the basis of the MAAS APT: wheeze after exercise; wheeze causing breathlessness; cough on exertion; current eczema and SPT sensitisation(maximum score 5). A total of 281(84%) children had complete data at age 3 years and were used to test the MAAS APT. Children scoring ≥3 were at high risk of having asthma at school‐age(PPV>75%; +LR 6.3,‐LR 0.6), whereas children who had a score of 0 had very low risk(PPV 9.3%; LR 0.2).
Conclusion
MAAS APT is a simple asthma prediction tool which could easily be applied in clinical and research settings.
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Prognostic factors and survival in adenoid cystic carcinoma of the sinonasal cavity
Abstract
Background
Optimal treatment and prognostic factors affecting long‐term survival in patients with sinonasal adenoid cystic carcinoma (ACC) have yet to be clearly defined.
Methods
We conducted a retrospective review of patients treated with curative intent from 1980‐2015 at MD Anderson Cancer Center.
Results
One hundred sixty patients met inclusion criteria, including 8 who were treated with radiotherapy alone. Median follow‐up time was 55 months. The 5‐year overall survival (OS) and disease‐free survival (DFS) rates were 67.0% and 49.0%, respectively. The 10‐year OS and DFS rates were 44.8% and 25.4%, respectively. Factors that portended for poor survival on multivariate analysis were recurrent disease, any solid type histology, epicenter in the sinus cavity, the presence of facial symptoms, or the original disease not treated with surgery. There was no association between surgical margin status or nodal status and survival.
Conclusion
In this large cohort of patients with sinonasal ACC with extended follow‐up, long‐term survival is better than reported in prior literature. Future research should target patients with adverse risk factors.
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Cryosurgery combined with topical interventions for actinic keratosis: A systematic review and meta‐analysis
Summary
Background
Actinic keratoses (AK) are early in situ carcinomas of the skin due to cumulative sun exposure. Cryosurgery is an easy and practicable lesion‐directed approach for isolated lesions.
Objectives
To investigate if an upfront combination of cryosurgery with a topical intervention is superior to cryosurgery alone for AK.
Methods
We performed a systematic literature research in Medline, Embase, and CENTRAL and hand‐searched pertinent trial registers for eligible randomized controlled trials until 17 July 2018. Results from individual studies were pooled using a random‐effects model. The risk of bias was estimated with the Cochrane Risk of Bias Tool and the quality of evidence of the outcomes with the GRADE approach.
Results
Out of 1,758 records initially identified, 9 studies with a sample size of 1,644 patients were included. Cryosurgery in combination with a topical approach showed significantly higher participant complete clearance rates compared to monotherapy (RR 1·74, 95% CI 1·25‐2·43, I²=73%, 8 studies. The participant partial clearance rate was not statistically different (RR 1·64, 95% CI 0·88‐3·03, I²=77%, 3 studies). The number of patients who completed the study protocol and did not withdraw due to adverse events was equal in both groups (RR 0·98, 95% CI 0·95‐1·01, I²=75%, 7 studies). The studies were estimated at high risk for selective reporting bias.
Conclusions
Our results suggest superiority of a combination regimen regarding AK clearance with equal tolerability. This study highlights the importance of a field‐directed approach in patients with multiple AK or field‐cancerization.
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Efficacy of nivolumab monotherapy against acral lentiginous melanoma and mucosal melanoma in Asian patients
Abstract
Early clinical trials showed that treatment with anti‐programmed death‐1 (anti‐PD‐1) agents, such as nivolumab and pembrolizumab, led to marked improvements in the prognosis of advanced melanoma patients. However, most of the large‐scale studies of such treatment mainly analyzed the efficacy of anti‐PD‐1 agents in Caucasian populations. Since the clinical subtypes of melanoma differ widely among populations, and the response to anti‐PD‐1 agents is known to vary among the clinical subtypes of the disease, the efficacy of anti‐PD‐1 agents in Asian populations remains unclear.
This article is protected by copyright. All rights reserved.
https://ift.tt/2Q6aQqe
Cryosurgery combined with topical interventions for actinic keratosis: A systematic review and meta‐analysis
Summary
Background
Actinic keratoses (AK) are early in situ carcinomas of the skin due to cumulative sun exposure. Cryosurgery is an easy and practicable lesion‐directed approach for isolated lesions.
Objectives
To investigate if an upfront combination of cryosurgery with a topical intervention is superior to cryosurgery alone for AK.
Methods
We performed a systematic literature research in Medline, Embase, and CENTRAL and hand‐searched pertinent trial registers for eligible randomized controlled trials until 17 July 2018. Results from individual studies were pooled using a random‐effects model. The risk of bias was estimated with the Cochrane Risk of Bias Tool and the quality of evidence of the outcomes with the GRADE approach.
Results
Out of 1,758 records initially identified, 9 studies with a sample size of 1,644 patients were included. Cryosurgery in combination with a topical approach showed significantly higher participant complete clearance rates compared to monotherapy (RR 1·74, 95% CI 1·25‐2·43, I²=73%, 8 studies. The participant partial clearance rate was not statistically different (RR 1·64, 95% CI 0·88‐3·03, I²=77%, 3 studies). The number of patients who completed the study protocol and did not withdraw due to adverse events was equal in both groups (RR 0·98, 95% CI 0·95‐1·01, I²=75%, 7 studies). The studies were estimated at high risk for selective reporting bias.
Conclusions
Our results suggest superiority of a combination regimen regarding AK clearance with equal tolerability. This study highlights the importance of a field‐directed approach in patients with multiple AK or field‐cancerization.
This article is protected by copyright. All rights reserved.
https://ift.tt/2DqMvos
Efficacy of nivolumab monotherapy against acral lentiginous melanoma and mucosal melanoma in Asian patients
Abstract
Early clinical trials showed that treatment with anti‐programmed death‐1 (anti‐PD‐1) agents, such as nivolumab and pembrolizumab, led to marked improvements in the prognosis of advanced melanoma patients. However, most of the large‐scale studies of such treatment mainly analyzed the efficacy of anti‐PD‐1 agents in Caucasian populations. Since the clinical subtypes of melanoma differ widely among populations, and the response to anti‐PD‐1 agents is known to vary among the clinical subtypes of the disease, the efficacy of anti‐PD‐1 agents in Asian populations remains unclear.
This article is protected by copyright. All rights reserved.
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Sex‐related differences in response to zinc pyrithione shampoo versus non‐anti‐dandruff shampoo
Abstract
Objective
Sex‐related differences in skin properties may be expected to impact on dandruff formation and treatment. A meta‐analysis approach was undertaken to investigate potential differences between males and females in response to zinc pyrithione (ZnPT) treatment versus non‐anti‐dandruff (AD) shampoo. A separate pooled statistical analysis of ceramide and total protein loss endpoints was also undertaken to assess potential sex‐related differences in stratum corneum properties that might influence response to ZnPT versus non‐AD shampoo in subjects with dandruff.
Methods
The meta‐analysis approach included data from 17 half‐head, double‐blind, randomized studies (N=2088) undertaken in Asia to assess the effectiveness of 1% ZnPT shampoo and/or non‐AD shampoo in reducing dandruff severity, as assessed by Total Weighted Head Score Adherent Flake (TWHS‐AF) methodology. Treatment duration was 4 weeks, with TWHS‐AF measured at weekly intervals. Data from an additional three studies (N=143) conducted in Asia were included in the pooled analysis of ceramide levels and protein loss from scalp skin of subjects with dandruff.
Results
Response to 1% ZnPT versus non‐AD shampoo was greater in males than in females at all time points; after 4 weeks, the between‐treatment difference in TWHS‐AF was −17.5 (95% confidence interval [CI] −19.5, −15.5) in males and −11.1 (−13.2, −8.9) in females. Sex‐related differences were observed between males and females in response to both 1% ZnPT and non‐AD shampoos. Males had a stronger response than females to treatment with 1% ZnPT shampoo, while dandruff decreased to a greater extent in females than in males when using non‐AD shampoo. Statistically significant sex‐related differences in ceramide levels and total protein loss were observed (both P<0.01). Ceramide levels were 0.76 times lower (95% CI 0.60, 0.97) in males than in females, while total protein loss was 1.4 times greater (95% CI 1.1, 1.9) in males than in females.
Conclusion
Males show a greater response than females to 1% ZnPT shampoo, while females show a greater response than males to non‐AD shampoo. These findings may in part be explained by the sex‐related differences observed in stratum corneum properties, which may make males more prone to dandruff than females.
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8 “S” in oral cancer
Publication date: January 2019
Source: Oral Oncology, Volume 88
Author(s): Sameep S. Shetty, U.S. Vishal Rao
https://ift.tt/2Q6jghe
Comparative effectiveness of primary radiotherapy versus surgery in elderly patients with locally advanced oropharyngeal squamous cell carcinoma
Publication date: January 2019
Source: Oral Oncology, Volume 88
Author(s): David J. Sher, Jingsheng Yan, Andrew Day, Baran D. Sumer, Nhat-Long Pham, Saad Khan, Hong Zhu
Abstract
Objectives
To determine the comparative effectiveness of primary radiotherapy (RT) and primary surgery (PS) for locally advanced oropharyngeal squamous cell carcinoma (OPSCC).
Materials and methods
Eligible individuals were patients in the SEER-Medicare registry diagnosed with locally advanced OPSCC between 2000 and 2011. Patients were categorized as receiving either primary RT ± chemotherapy, or PS ± adjuvant RT or chemoradiotherapy (CRT). Overall survival (OS) was analyzed using Cox multivariable analysis (MVA). Risks of gastrostomy dependence (GD), esophageal stricture (ES), and osteoradionecrosis (ORN) were analyzed using logistic regression.
Results
A total of 2754 patients (69% RT, 31% PS) were included in this cohort, with a median age of 72 years. Patients treated with RT, CRT and PS experienced 3-year OS outcomes of 36.1%, 52.8%, and 54.9%, respectively (p < 0.001). Increasing age, unmarried status, increasing comorbidity, lower income, base of tongue (BOT) site, higher stage, no prior PET, and RT alone (but not CRT) were associated with inferior OS. Independent predictors of GD at 6 months included black race, BOT site, advanced stage, and CRT. The risks of ORN and stricture were not associated with treatment modality. Concurrent chemotherapy improved OS with definitive RT but had no impact in adjuvant RT. Only cisplatin- and taxane-containing regimens improved OS, but all concurrent agents, including cetuximab, significantly worsened GD.
Conclusion
Local therapy decisions for locally advanced OPSCC must be individualized, with CRT increasing acute and chronic GD. The differential survival impact of concurrent chemotherapy in the definitive and adjuvant setting may be a consideration in decision-making.
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High-risk pathological features at the time of salvage surgery predict poor survival after definitive therapy in patients with head and neck squamous cell carcinoma
Publication date: January 2019
Source: Oral Oncology, Volume 88
Author(s): Sulsal Haque, Vidhya Karivedu, Muhammed K. Riaz, David Choi, Logan Roof, Sarah Z. Hassan, Zheng Zhu, Roman Jandarov, Vinita Takiar, Alice Tang, Trisha Wise-Draper
Abstract
Objectives
Salvage surgical resection is the preferred treatment for head and neck squamous cell carcinoma (HNSCC) patients who develop locally recurrent disease after failing primary therapy. However, salvage surgical resection is not always feasible, and survival outcomes for those that do undergo salvage remain poor. It is well known that patients with adverse pathological features (extracapsular extension (ECE) of lymph nodes (LN), positive margins, perineural invasion (PNI), lymphovascular invasion (LVI), and multiple LN metastases) at the time of primary surgical resection are likely to have relatively poor outcomes. However, the impact of adverse pathological features on outcomes in the salvage setting remains controversial.
Materials and Methods
We retrospectively analyzed 73 patients at a single institution from 2008 to 2017 who developed recurrence and subsequently underwent salvage surgery (SS) after definitive curative-intent therapy including radiation. Demographic and disease control outcomes were reviewed. Kaplan-Meier curves were used to estimate relapse free survival (RFS) and overall survival (OS).
Results
Median age at diagnosis was 61 years (range 40–86), 49/73 (67%) were male, and 55/73 (75%) had smoked. Patients with any adverse pathological features at SS had worse RFS (HR 3.15 p = 0.0008) and worse OS (3.97 p = 0.0008). Patients who relapsed <6 months after initial therapy had worse OS (HR 2.96 p = 0.004).
Conclusions
Patients with adverse pathological features at time of salvage surgery as well as those who have an early recurrence after definitive treatment and salvage surgery have worse outcomes. Prospective studies are necessary to clarify which patients should receive more intense treatment at salvage.
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Accuracy of computer-assisted surgery in mandibular reconstruction: A postoperative evaluation guideline
Publication date: January 2019
Source: Oral Oncology, Volume 88
Author(s): Gustaaf J.C. van Baar, Niels P.T.J. Liberton, Tymour Forouzanfar, Henri A.H. Winters, Frank K.J. Leusink
Abstract
Comparing accuracy results for mandibular reconstructions using computer-assisted surgery (CAS) is limited due to heterogeneity in image acquisition, extent of mandibular resection, and evaluation methodologies between studies. We propose a practical, feasible and reproducible guideline for standardizing evaluation methods to allow valid comparisons of postoperative results and facilitate meta-analyses in the future. It offers a guide to imaging, data comparison, volume assessment of 3-dimensional models, classification of defects, and it also contains a quantitative accuracy evaluation method.
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A myxoma in the temporomandibular joint: Case report and review of the literature
Publication date: January 2019
Source: Oral Oncology, Volume 88
Author(s): A. Cinza, F. Monje, J.J. Fernandez de Mera
https://ift.tt/2Q7lAVi
Postoperative myxedema coma in patients undergoing major surgery: Case series
Publication date: Available online 16 November 2018
Source: Auris Nasus Larynx
Author(s): Daniel Yafit, Narin Nard Carmel-Neiderman, Nadav Levy, Avrham Abergel, Alexander Niv, Ravit Yanko-Arzi, Arik Zaretski, Anat Wengier, Dan M. Fliss, Gilad Horowitz
Abstract
Objective
Myxedema coma is a serious complication of hypothyroidism that can be precipitated by major surgery. It is extremely rare, with only a few reports in the literature. This study aims to present a relatively large case series of post-surgical myxedema coma and to analyze medical and surgical risk factors.
Methods
Analysis of the patients' surgical records and medical charts.
Results
Four patients developed postoperative myxedema coma and were evaluated for risk factors. Three had known hypothyroidism. Two had undergone large head and neck composite resections necessitating a free flap repair for malignant disease. One had undergone coronary artery bypass graft for ischemic heart disease, and another had undergone endoscopic cholecystectomy for complicated cholecystitis. All four patients required prolonged hospitalization, including treatment in the intensive care unit. One patient had undergone full cardiopulmonary resuscitation directly related to the myxedema coma state.
Conclusion
We present a series of four patients who developed myxedema coma following major surgery. We recommend that patients with known hypothyroidism who are scheduled for major surgery should be tested for thyroid function status and assessed for postoperative risk of hypothyroidism. Those who develop complications following major surgery, should be immediately tested for thyroid function to rule out myxedema coma.
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MiR-196b affects the progression and prognosis of human LSCC through targeting PCDH-17
Publication date: Available online 16 November 2018
Source: Auris Nasus Larynx
Author(s): Min Luo, Gang Sun, Jing-wu Sun
Abstract
Objective
To explore the effect of miR-196bon the biological features of human laryngeal squamous cell carcinoma (LSCC) through targeting PCDH-17.
Methods
miR-196b and PCDH-17 expressions were determined in tissues, and the targeting relation of miR-196b and PCDH-17 was verified through dual-luciferase reporter system. In vitro, Hep-2 cells were divided into the Control, miR-196b inhibitors, miR-NC, PCDH-17, and miR-196b mimics + PCDH-17 groups. The miR-196b and PCDH-17 expressions were determined by qRT-PCR or/and Western blot, and the biological features by MTT, Annexin V-FITC/PI, wound-healing and Transwell assays.
Results
MiR-196b was found to be up-regulated, while PCDH-17 was down-regulated in a negative correlation in LSCC patients, which was related to histological grade and TNM stage. And low expression of miR-196b and high expression of PCDH-17 contributed to an increase in the 5-year-survival rate of LSCC patients. Besides, miR-196b directly targeted PCDH-17, while miR-196b inhibitors could up-regulate the PCDH-17 in Hep-2 cells. Moreover, miR-196b inhibitors and PCDH-17 curbed Hep-2 cell proliferation but facilitated the apoptosis, with decreases in cell invasion and migration. In addition, no statistical significance was found in cell proliferation, apoptosis, invasion and migration between Control group and miR-196b mimics + PCDH-17 group.
Conclusion
LSCC patients exhibited the up-regulated miR-196b and down-regulated PCDH-17, which are correlated with the major clinical features and prognosis. Inhibiting miR-196b may suppress proliferation, migration and invasion abilities, and promote apoptosis of Hep-2 cells via targeting PCDH-17.
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Cerebellar large B-cell lymphoma: a case report
Primary central nervous system lymphoma is a rare, malignant non-Hodgkin lymphoma that can arise in the brain, spinal cord, eye, leptomeninges, or cranial nerves. Primary central nervous system lymphoma is rar...
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Upregulation of tumor PD-L1 by neoadjuvant chemoradiotherapy (neoCRT) confers improved survival in patients with lymph node metastasis of locally advanced rectal cancers
Abstract
The expression of programmed cell death 1 ligand 1 (PD-L1) and interferon-γ (IFN-γ) is of great interest for the development of chemoradiotherapy and immune checkpoint inhibitor treatments. Patients with nodal metastasis (pN+) tend to have a poor prognosis, even after neoadjuvant chemoradiotherapy (neoCRT) and surgical treatment. In this study, we examined the roles of tumor PD-L1 and IFN-γ before and after neoCRT in locally advanced rectal cancer (LARC) patients. Our results demonstrate that patients with high PD-L1 expression in post-neoCRT tissues exhibit improved 5-year disease-free survival (DFS) and overall survival (OS) compared with those with low PD-L1 expression (p < 0.001). Furthermore, in the pN+ population, patients with high PD-L1 expression in post-neoCRT tissues exhibit improved 5-year DFS and OS. PD-L1 and IFN-γ upregulation increased in tumor tissues after neoCRT, and patients with high PD-L1 and high IFN-γ exhibit improved 5-year DFS and OS (p = 0.04 and p = 0.001, respectively). To the best of our knowledge, this study is the first to demonstrate that PD-L1 upregulation in a pN+ cohort correlates with improved prognosis, which is similar to that in patients without nodal metastasis. Moreover, this study verified that PD-L1 and IFN-γ were upregulated by neoCRT treatment in LARC patients and demonstrated that neoCRT may be useful not only for immune checkpoint inhibitor treatment but also for reinvigorating preexisting anti-cancer immunity.
https://ift.tt/2BcWWdD
Evidence for respiratory viruses interactions in asymptomatic preschool-aged children
Publication date: Available online 16 November 2018
Source: Allergologia et Immunopathologia
Author(s): K. Douros, D. Kotzia, C. Kottaridi, A. Giotas, B. Boutopoulou, E. Bozas, V. Matziou, K. Priftis, V. Papaevangelou
Abstract
Aim
To prospectively evaluate interferences between viruses of the upper respiratory tract in asymptomatic preschool children.
Methods
Nasal-pharyngeal swabs from 233 preschool aged children were prospectively collected over four consecutive time periods, during one school year. The samples were tested using a RT-PCR DNA/RNA microarray system for nine respiratory viruses.
Results
Respiratory syncytial virus (RSV) was a predictor of the presence of influenza virus (INFL) (OR: 9.12, CI: 1.52–54.75, p = 0.016), and similarly, INFL predicted the presence of RSV (OR: 4.01, CI: 1.14–14.16, p = 0.030). Also, rhinovirus (RV) was a predictor of adenovirus (ADV) presence (OR: 3.66, CI: 1.10–12.14, p = 0.034), and similarly, ADV predicted the presence of RV (OR: 4.05, CI: 1.02–16.05, p = 0.046). No other significant associations between viruses were observed.
Conclusion
Our results indicate that respiratory viruses found in carrier stage in asymptomatic children may interact with other viruses and even facilitate their settling in the upper respiratory tract. The pathophysiological role of these interactions is not yet clear.
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Correlation of OX40 ligand on B cells with serum total IgE and IL-4 levels by CD4+ T cells in allergic rhinitis
Publication date: Available online 16 November 2018
Source: Allergologia et Immunopathologia
Author(s): S. Fouladi, M. Masjedi, M. G. Hakemi, R. Ghasemi, N. Eskandari
Abstract
Introduction and objectives
Allergic rhinitis (AR) is a classic Th2-mediated disease, with important contributions to the pathology of interleukins 4, 5, and 13. The co-stimulatory molecule of OX40 and its ligand interaction participate in the immune response by regulation of Th1/Th2 cells balance. Considering the paucity of information on the relation between OX40 ligand (OX40L) and AR, this study aimed to examine its expression on B lymphocytes.
Patients and methods
This case–control study consisted of 20 AR patients and 20 healthy subjects. The serum level of total immunoglobulin E (IgE) was measured using the electro-chemiluminescence (ECL) technology. The percentage of B-lymphocytes expressing OX40L was assessed by flow cytometry. The amounts of IL-4 in CD4+ T cells culture supernatant was also measured by the enzyme-linked immunosorbent assay (ELISA).
Results
OX40L expression on B lymphocytes of patients was significantly higher than the control group (44.32 ± 19.21% vs. 2.79 ± 2.48% respectively, p < 0.001). In AR patients, OX40L expression correlated positively with the levels of serum total IgE and IL-4 produced by CD4+ T lymphocytes (p < 0.01 – p < 0.05) respectively.
Conclusions
Collectively, the findings of this work suggest that there is a relationship between the OX40L expression level on B lymphocytes and allergic markers such as IgE and IL-4 in patients with allergic rhinitis.
https://ift.tt/2PCqNFv
The cortical face network of the prosopagnosic patient PS with fast periodic stimulation in fMRI
Publication date: Available online 17 November 2018
Source: Cortex
Author(s): Xiaoqing Gao, Quoc C. Vuong, Bruno Rossion
Abstract
Following brain damage, the patient PS suffers from selective impairment in recognizing individuals by their faces, i.e. prosopagnosia. Her case has been documented in more than 30 publications to date, informing about the nature of individual face recognition and its neural basis. Here we report new functional neuroimaging data obtained on PS with a recently developed fast periodic stimulation functional imaging (FPS-fMRI) paradigm combining high sensitivity, specificity and reliability in identifying the cortical face-selective network (Gao et al., 2018). We define the extent of the large and reliable face-selective activation in the lateral section of the right middle fusiform gyrus, i.e. right FFA, which forms a single cluster of activation lying at the anterior border of the patient's main lesion in the inferior occipital gyrus. The contribution of posterior face-selective responses in the right or left inferior occipital gyrus is ruled out, strongly supporting the view that face-selective activity emerges in the right middle fusiform gyrus of the patient's brain from non-face-selective inputs from early visual areas. Despite this, low-level visual cues, i.e. amplitude spectrum of images, do not contribute to neural face-selective responses anywhere in the patient's cortical face network. This sensitive face-localizer approach also reveals an intact face-selective network anterior to the fusiform gyrus, including clusters in the ventral anterior temporal lobe (occipito-temporal sulcus and temporal pole) and the inferior frontal gyrus, with a right hemispheric dominance. Overall, with the exception of the left inferior occipital gyrus, the cortical face network of the prosopagnosic patient PS appears remarkably similar to typical individuals in non-brain damaged regions. However, unlike in neurotypical adults tested in the present study, including age-matched controls, a novel paradigm based on FPS-FMRI confirms that the patient's face network is insensitive to differences between rapidly presented pictures of unfamiliar individual faces, in line with her prosopagnosia.
https://ift.tt/2qQJQNl
Covert Attention Beyond the Range of Eye-movements: Evidence for a Dissociation between Exogenous and Endogenous orienting
Publication date: Available online 17 November 2018
Source: Cortex
Author(s): Soazig Casteau, Daniel T. Smith
Abstract
The relationship between covert shift of attention and the oculomotor system has been the subject of numerous studies. A widely held view, known as Premotor Theory, is that covert attention depends upon activation of the oculomotor system. However, recent work has argued that Premotor Theory is only true for covert, exogenous orienting of attention and that covert endogenous orienting is largely independent of the oculomotor system. To address this issue we examined how endogenous and exogenous covert orienting of attention was affected when stimuli were presented at a location outside the range of saccadic eye movements. Results from Experiment 1 showed that exogenous covert orienting was abolished when stimuli were presented beyond the range of saccadic eye movements, but preserved when stimuli were presented within this range. In contrast, in Experiment 2 endogenous covert orienting was preserved when stimuli appeared beyond the saccadic range. Finally, Experiment 3 confirmed the observations of Exp.1 and 2. Our results demonstrate that exogenous, covert orienting is limited to the range of overt saccadic eye movements, whereas covert endogenous orienting is not. These results are consistent with a weak, exogenous-only version of Premotor Theory.
https://ift.tt/2FttYKI
Mapping Whole Brain Connectivity Changes: The Potential Impact of Different Surgical Resection Approaches for Temporal Lobe Epilepsy
Publication date: Available online 17 November 2018
Source: Cortex
Author(s): Natalie Busby, Ajay D. Halai, Geoffrey J.M. Parker, David J. Coope, Matthew A. Lambon Ralph
Abstract
In neurosurgery there are several situations that require transgression of the temporal cortex. For example, a subset of patients with temporal lobe epilepsy require surgical resection (most typically, en-bloc anterior temporal lobectomy). This procedure is the gold standard to alleviate seizures but is associated with chronic cognitive deficits. In recent years there have been multiple attempts to find the optimum balance between minimising the size of resection in order to preserve cognitive function, while still ensuring seizure freedom. Some attempts involve reducing the distance that the resection stretches back from the temporal pole, whilst others try to preserve one or more of the temporal gyri. More recent advanced surgical techniques (selective amygdalo-hippocamptectomies) try to remove the least amount of tissue by going under (sub-temporal), over (trans-Sylvian) or through the temporal lobe (middle-temporal), which have been related to better cognitive outcomes. Previous comparisons of these surgical techniques focus on comparing seizure freedom or behaviour post-surgery, however there have been no systematic studies showing the effect of surgery on white matter connectivity. The main aim of this study, therefore, was to perform systematic 'pseudo-neurosurgery' based on existing resection methods on healthy neuroimaging data and measuring the effect on long-range connectivity. We use anatomical connectivity maps (ACM) to determine long-range disconnection, which is complementary to existing measures of local integrity such as fractional anisotropy or mean diffusivity. ACMs were generated for each diffusion scan in order to compare whole-brain connectivity with an 'ideal resection', nine anterior temporal lobectomy and three selective approaches. For en-bloc resections, as distance from the temporal pole increased, reduction in connectivity was evident within the arcuate fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and the uncinate fasciculus. Increasing the height of resections dorsally reduced connectivity within the uncinate fasciculus. Sub-temporal amygdalohippocampectomy resections were associated with connectivity patterns most similar to the 'ideal' baseline resection, compared to trans-Sylvian and middle-temporal approaches. In conclusion, we showed the utility of ACM in assessing long-range disconnections/disruptions during temporal lobe resections, where we identified the sub-temporal resection as the least disruptive to long-range connectivity which may explain its better cognitive outcome. These results have a direct impact on understanding the amount and/or type of cognitive deficit post-surgery, which may not be obtainable using local measures of white matter integrity.
https://ift.tt/2qSNFle
Brain activity in struggling readers before intervention relates to future reading gains
Publication date: Available online 16 November 2018
Source: Cortex
Author(s): Tehila Nugiel, Mary Abbe Roe, W.Patrick Taylor, Paul T. Cirino, Sharon R. Vaughn, Jack M. Fletcher, Jenifer Juranek, Jessica A. Church
Abstract
Neural markers for reading-related changes in in response to intervention may represent biomarkers that could inform intervention plans as a potential index of the malleability of the reading network in struggling readers. Particularly interesting is the role of activation outside the reading network, especially in executive control networks important for reading comprehension. However, it is unclear whether any intervention-related executive control changes in the brain are specific to reading tasks or reflect more domain general changes. Brain changes associated with reading gains over time were compared for a sentence comprehension task as well as for a non-lexical executive control task (a behavioral inhibition task) in upper-elementary struggling readers, and in grade-matched non-struggling readers. Functional MRI scans were conducted before and after 16 weeks of reading intervention. Participants were grouped as improvers and non-improvers based on the consistency and size of post-intervention gains across multiple post-test measures. Engagement of the right fusiform during the reading task, both before and after intervention, was related to gains from remediation. Additionally, pre-intervention activation in regions that are part of the default-mode network (precuneus) and the fronto-parietal network (right posterior middle temporal gyrus) separated improvers and non-improvers from non-struggling readers. None of these differences were observed during the non-lexical inhibitory control task, indicating that the brain changes seen related to intervention outcome in struggling readers were specific to the reading process.
https://ift.tt/2FsjnQm
A simple technique to increase field of view (FOV) of a USB dematoscope
Publication date: Available online 16 November 2018
Source: Journal of the American Academy of Dermatology
Author(s): Deepak Jakhar, Ishmeet Kaur
https://ift.tt/2FpoCQN
Skin Diseases of the Breast and Nipple Part 2: Inflammatory and Infectious Diseases
Publication date: Available online 16 November 2018
Source: Journal of the American Academy of Dermatology
Author(s): Reid A. Waldman, Justin Finch, Jane M. Grant-Kels, Diane Whitaker-Worth
Abstract
Certain dermatologic conditions are unique to the breast and nipple, whereas others may incidentally involve these structures. All require a nuanced approach to diagnosis and treatment due to the functional, sexual and aesthetic importance of this area. The lactating patient requires special management since certain treatment options are contraindicated. All dermatologic conditions involving the breast and nipple require careful evaluation since breast malignancy can be mistaken for a benign condition or may trigger the development of certain dermatologic conditions. This article reviews common and uncommon inflammatory and infectious conditions of the breast and nipple and provides insight into diagnosis and treatment of this heterogeneous group of diseases. For the purposes of this article, these conditions are divided into 4 distinct categories: 1) Dermatitis; 2) Radiation-induced Changes; 3) Mastitis; and 4) miscellaneous dermatologic conditions of the breast and nipple.
https://ift.tt/2qQzxZy
Skin Diseases of the Breast and Nipple Part I: Benign and Malignant Tumors
Publication date: Available online 16 November 2018
Source: Journal of the American Academy of Dermatology
Author(s): Reid A. Waldman, Justin Finch, Jane M. Grant-Kels, Christina Stevenson, Diane Whitaker-Worth
Abstract
Evaluation and management of dermatologic diseases of the breast and nipple requires an understanding of the unique anatomy of the breast and nipple as well as an awareness of the significant emotional, cultural, and sexual considerations that may come into play when treating this anatomic area. Part I of this 2 Part CME Series reviews breast anatomy, congenital breast anomalies, and benign and malignant breast tumors. Specifically, an emphasis is placed on inflammatory breast cancer and breast cancer with non-inflammatory skin involvement as well as on cutaneous metastases to the breast and from breast cancer. Familiarity of the dermatologist with the cutaneous manifestations of breast cancer will facilitate the diagnosis of breast malignancy and assist with staging, prognostication, and evaluation for recurrence. This article also discusses genodermatoses that predispose to breast pathology and provides imaging recommendations for evaluating a palpable breast mass.
https://ift.tt/2FpoCAh
A Simulation-Based Workshop to Improve Dermatologists’ Communication Skills: A Pilot for Continuing Medical Education
Abstract
Introduction
Communication skills influence the quality of health care and patient experience; both may affect provider reimbursement. There are few opportunities available for practicing physicians to receive direct feedback on communication in patient encounters. The purpose of this simulation-based patient encounter workshop was for dermatologists to practice and obtain feedback on their communication skills.
Methods
In March 2016, dermatologists participated in a workshop with four simulated patient encounters. Cases were developed based on a prior needs assessment. Standardized patient educators evaluated participants' communication using the Master Interview Rating Scale and provided verbal feedback. Physicians rated the usefulness of the simulation and the feedback received through a survey upon workshop completion.
Results
Of the 170 physicians who registered, 103 participated in the simulation. The workshop was highly rated in meeting its three learning objectives (score of 4.5–4.6 out of a maximum score of 5). The lowest-rated communication skills were as follows: allowing the patient to share their narrative thread (3.1), summarizing the patient's history from the provider (3.8), and assessing patient understanding (3.8).
Conclusions
Participants reported that this communication workshop effectively satisfied its learning objectives. Opportunities to practice and improve communication skills as part of continuing medical education will benefit the clinical experience of patients and physicians alike, and the workshop may be formatted to serve physicians of other specialties. The lowest-scoring communication areas identified in this study present an opportunity to develop a tailored curriculum for physician–patient communication in the future.
https://ift.tt/2TkY71J
Treg/Th17 imbalance is associated with poor autoimmune hepatitis prognosis
Publication date: Available online 16 November 2018
Source: Clinical Immunology
Author(s): Yuli Liu, Weiming Yan, Wei Yuan, Peng Wang, Da Huang, Xiaoping Luo, Qin Ning
https://ift.tt/2Q2vHL1
Excision of preauricular sinus with abscess drainage in children
Publication date: Available online 16 November 2018
Source: American Journal of Otolaryngology
Author(s): Lizhi Wang, Lai Wei, Weili Lu, Ziye Liu, Meiyi Wang, Zhiqiang Wang
Abstract
Purpose
To introduce a feasible approach for excising a preauricular sinus with abscess in children.
Materials and methods
Patients under 14 years old with a preauricular sinus abscess and volunteering for surgery were involved in this study.
Results
Neither recurrence nor local deformity was found in these patients with a follow-up of 3 to 72 months.
Conclusions
Excising the preauricular sinus with abscess in children is a feasible approach to treatment.
https://ift.tt/2OOQihn
Role of P2X3 receptors in scratching behavior in mouse models
Publication date: Available online 17 November 2018
Source: Journal of Allergy and Clinical Immunology
Author(s): Miho Shiratori-Hayashi, Ayumi Hasegawa, Honami Toyonaga, Tsugunobu Andoh, Takeshi Nakahara, Makiko Kido-Nakahara, Masutaka Furue, Yasushi Kuraishi, Kazuhide Inoue, Xinzhong Dong, Makoto Tsuda
https://ift.tt/2TmQqbe
Tipping the balance: a biased nanobody antagonist of CCR3 with potential for the treatment of eosinophilic inflammation
Publication date: Available online 17 November 2018
Source: Journal of Allergy and Clinical Immunology
Author(s): James E. Pease, Timothy J. Williams
https://ift.tt/2A23ZEn
Patterns of Congenitally Missing Teeth of Non-syndromic and Syndromic Patients Treated at a Single-Center over the Past Thirty Years
Publication date: Available online 16 November 2018
Source: Archives of Oral Biology
Author(s): Simone Heuberer, Christian Ulm, Werner Zechner, Brenda Laky, Georg Watzak
Abstract
Objectives
Literature regarding congenitally-missing-teeth (CMT) is lacking especially on CMT-patterns. Thus, the aim of this study was to present an in-depth analysis of 843 patients with CMT treated at a single-center over the past thirty years.
Design
Age, date-of-birth-year, gender, medical- and family-history, CMT-types, -numbers, -severity, -region, -symmetry, -patterns using the tooth agenesis code (TAC), and -growth types of all clinically and radiographically diagnosed CMT-patients were collected. Age and occurrence of syndromes were used to divide CMT-patients into non-syndromic patients older than nine years (group1) and syndromic CMT-patients (group2). Groups were compared especially regarding gender and CMT-severity.
Results
The average CMT-number per patient was 5.5 (group1, n = 816, 59.9% female) and 15.1 (group2, n = 27, 29.6% female). There were significant less male (40.1% vs. 70.4%, respectively; P = 0.002) as well as significantly less male-oligodontia (44.8% vs. 73.9%, respectively; P = 0.009) in group1 than in group2. Group1 resulted in decreased prevalence of similar CMT-patterns with severity; the most prevalent CMT was the 2nd premolar; there were no significant differences between the right and left side, whereas more CMT affected the maxilla; the majority of patients presented with bilateral-CMT (82.8%); females were more affected by CMT but more males had severer forms; certain single CMT differed by gender, and CMT was related to first-grade-relatives.
Conclusion
The majority of CMT-patients presented with hypodontia. Furthermore, same CMT-patterns seem more like to be present in patients with milder forms of tooth agenesis. Gender-specific association regarding CMT-number, severity groups, and single CMT were detected.
https://ift.tt/2KcXNxK
Cluster analysis of autoimmune rheumatic diseases based on autoantibodies. New insights for polyautoimmunity
Publication date: Available online 17 November 2018
Source: Journal of Autoimmunity
Author(s): Nicolás Molano-González, Manuel Rojas, Diana M. Monsalve, Yovana Pacheco, Yeny Acosta-Ampudia, Yhojan Rodríguez, Monica Rodríguez-Jimenez, Carolina Ramírez-Santana, Juan-Manuel Anaya
Abstract
Autoimmune diseases (ADs) are a chronic and clinically heterogeneous group of diseases characterized by share common immunopathogenic mechanisms and risk factors (i.e., the autoimmune tautology), which explain the fact that one AD may coexist with others (i.e., polyautoimmunity - PolyA). In the present exploratory study, a mixed-cluster analysis of the most common autoimmune rheumatic diseases (ARDs) was done. A total of 187 consecutive women with established systemic lupus erythematosus (n = 70), rheumatoid arthritis (n = 51), systemic sclerosis (n = 35) and Sjögren's syndrome (n = 31) were included. A comprehensive clinical, autoantibody and cytokine assessment was simultaneously done. Total PolyA was registered in 142 (75.9%) patients. Six clusters were obtained, built mainly on autoantibodies: PolyA-I to -VI. The PolyA-III cluster showed the highest frequency of overt PolyA (p = 0.01), and the PolyA-I, -III, and -IV clusters exhibited the highest positivity for IL-12/23p40 (p = 0.015). These results provide new insights into the pathophysiology of PolyA and warrant prospective validation to enable development of a more accurate taxonomy of ARDs.
https://ift.tt/2DrxKBL
A multi-epitope DNA vaccine enables a broad engagement of diabetogenic T cells for tolerance in Type 1 diabetes
Publication date: Available online 17 November 2018
Source: Journal of Autoimmunity
Author(s): Jorge Postigo-Fernandez, Rémi J. Creusot
Abstract
Type 1 diabetes (T1D) is caused by diabetogenic T cells that evaded tolerance mechanisms and react against multiple β-cell antigens. Antigen-specific therapy to reinstate tolerance (typically using a single β-cell antigen) has so far proved unsuccessful in T1D patients. Plasmid DNA (pDNA)-mediated expression of proinsulin has demonstrated transient protection in clinical trials, but long-lasting tolerance is yet to be achieved. We aimed to address whether pDNA delivery of multiple epitopes/mimotopes from several β-cell antigens efficiently presented to CD4+ and CD8+ T cells could also induce tolerance. This approach significantly delayed T1D development, while co-delivery of pDNA vectors expressing four full antigens protected more mice. Delivery of multiple epitopes resulted in a broad engagement of specific T cells, eliciting a response distinct from endogenous epitopes draining from islets. T-cell phenotypes also varied with antigen specificity. Unexpectedly, the repertoire of T cells reactive to the same epitope was highly polyclonal. Despite induction of some CD25+ Foxp3+ regulatory T cells, protection from disease did not persist after treatment discontinuation. These data demonstrate that epitope-based tolerogenic DNA vaccines constitute effective precision medicine tools to target a broad range of specific CD4+ and CD8+ diabetogenic T-cell populations for prevention or treatment of T1D.
https://ift.tt/2Dt83kr
Assessment of TILs, IDO-1, and PD-L1 in resected non-small cell lung cancer: an immunohistochemical study with clinicopathological and prognostic implications
Abstract
Several cancers, especially non-small cell lung cancer (NSCLC), are able to escape the immunosurveillance of tumor-infiltrating lymphocytes (TILs); among the molecules involved, the indoleamine 2,3-dioxygenase 1 (IDO-1) and the programmed cell death ligand-1 (PD-L1) play a crucial role. These aspects are of great interest in the current immunotherapeutic era, therefore the current study analyses the TILs, IDO-1, and PD-L1 interactions and their correlations with clinicopathological parameters and prognosis in NSCLC. One hundred ninety-three NSCLC surgical specimens, formalin-fixed, and paraffin-embedded were assessed for TILs density, TILs localization, IDO-1 (clone 4.16H1), and PD-L1 (clone E1L3N) immunohistochemical expressions. This data was correlated with clinicopathological parameters, disease free, and overall survivals. IDO-1 and PD-L1 high expressions were related to the solid pattern of adenocarcinomas (respectively p = 0.036 and p = 0.026); high PD-L1 expression was correlated with squamous histotype (p = 0.048). IDO-1 overexpression correlated with former smokers (p = 0.041), higher adenocarcinoma stages (p = 0.039), and with both higher TILs density and PD-L1 expression (respectively p = 0.025 and p = 0.0003). A better prognosis was associated with TILs intratumoral or mixed localizations (p = 0.029). TILs localization affects NSCLC prognosis; the higher expression of IDO-1 and PD-L1 in poorly differentiated and more aggressive lung adenocarcinomas, as well as the correlation between high PD-L1 expression and squamous cell histotype, confirm the more efficient immunoescaping of these NSCLC subgroups.
https://ift.tt/2KbN5HQ
Prostaglandin E2 decrease in induced sputum of hypersensitive asthmatics during oral challenge with aspirin
Abstract
Background
A special regulatory role for prostaglandin E2 (PGE2) has been postulated in Nonsteroidal anti‐inflammatory drugs (NSAIDs)‐exacerbated respiratory disease (NERD).
Objective
To investigate the effect of systemic aspirin (acetylsalicylic acid) administration on airways PGE2 biosynthesis in induced sputum supernatant (ISS) among subjects with NERD or aspirin‐tolerant asthma with chronic rhinosinusitis with nasal polyposis (ATA‐CRSwNP), as well as healthy controls (HC).
Methods
Induced sputum (IS) was collected from patients with NERD (n=26), ATA‐CRSwNP (n=17), and HC (n=21) at baseline and after aspirin challenge. Sputum differential cell count and IS supernatant (ISS) levels of prostanoids: PGE2, 8‐iso‐PGE2, tetranor‐PGE‐M, 8‐iso PGF2α and leukotriene C4, D4 and E4 were determined using mass spectrometry. Urinary excretion of LTE4 was measured by ELISA.
Results
NERD subjects had elevated sputum eosinophilic count as compared to ATA‐CRSwNP and HC (median NERD 9.1%, ATA‐CRSwNP 2.1% and HC 0.4%; P<0.01). Baseline ISS levels of PGE2 were higher in asthmatics as compared to HC at baseline (NERD vs. HC P=0.04, ATA‐CRSwNP vs. HC P<0.05). Post‐challenge ISS levels of PGE2 compared to baseline significantly decreased in NERD and HC (P<0.01 and P=0.01), but not in ATA‐CRSwNP. In NERD a similar decrease of PGE2 as in HC resulted from 2.8 times lower dose of aspirin.
Conclusions
Aspirin‐precipitated bronchoconstriction is associated with a decrease in airway PGE2 biosynthesis. These results support the mechanism of PGE2 biosynthesis inhibition as a trigger for bronchoconstriction in NERD.
This article is protected by copyright. All rights reserved.
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Modified technique of total hepatectomy in polycystic liver disease with caval flow preservation: the exposure left lateral sectionectomy
Background Liver transplantation (LT) for polycystic liver disease (PLD) is rare, extremely challenging and hemorrhagic, without standard approach. Moreover, LT for PLD presents the highest mortality rate (12 to 18%) among all causes of LT. In this setting, the combination of difficult mobilization of a heavy polycystic native liver with narrow access to inferior vena cava (IVC) and fragile venous wall may lead to venous tearing and cataclysmic bleeding during dissection. The aim of this study was to evaluate a modified technique of total hepatectomy in order to limit hazardous liver manipulation and improve exposure of IVC in patients with massive hepatomegaly related to PLD: the exposure left lateral sectionectomy (ELLS). Methods From 2011 to 2018, ELLS was performed during LT for PLD. Key technical points for safe and fast ELLS include avoidance of left triangular ligament section and placement of a tape behind the left lateral section allowing its ascension and prior dissection of the hepatic pedicle to limit bleeding. The transection plane is mainly composed of cysts, with limited parenchyma, this allows for rapid and bloodless transection using electric scalpel. Results Fifteen patients had ELLS with no postoperative death or intraoperative complication. Median ELLS duration was 16 min and no massive bleeding occurred during this step. During total hepatectomy, median blood loss was 500 ml and no patient required total caval clamping. All patients were alive at the end of the follow-up. Conclusions ELLS during LT for PLD facilitates total hepatectomy with vena cava and caval flow preservation. Corresponding author: Prof. Olivier Soubrane, MD, PhD, Département de Chirurgie Hépato-pancréato-biliaire, AP-HP Hôpital Beaujon, Clichy, 100 Boulevard du Général Leclerc, 92210 Clichy, France. Tel: 01 40 87 52 52. Fax: 01 40 87 50 67. Mail: olivier.soubrane@aphp.fr ORCID : 0000 0002 4668 9275 Autorship page: Participated in research design: FC, OS, FD Participated in the writing of the paper : BL, OS, FD, Participated in the performance of the research: OS, FC; TY Contributed new reagents or analytic tools: SD, EW, MC, CF Participated in data analysis: AS, FD, SD, EW, MC, CF Disclosure of conflict of interest: The authors of this manuscript have no conflicts of interest to disclose. Disclosure of funding: None Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2DLxFdl
https://ift.tt/2DLxFdl
ENDOTHELIAL GLYCOCALYX SHEDDING PREDICTS DONOR ORGAN ACCEPTABILITY AND IS ASSOCIATED WITH PRIMARY GRAFT DYSFUNCTION IN LUNG TRANSPLANT RECIPIENTS
Background The endothelial glycocalyx, a sieve-like structure located on the luminal surface of all blood vessels, has been found to be integral to regulation of capillary permeability and mechanotransduction. Given this, we investigated the role of endothelial glycocalyx breakdown products in organ donors and recipients in terms of acceptability for transplant and risk of primary graft dysfunction (PGD). Methods Endothelial glycocalyx breakdown products were measured in the peripheral blood of 135 intended and actual organ donors. Breakdown product levels were tested for association with donor demographic and clinical data, organ acceptability for transplant along with lung recipient outcomes (n=35). Liquid chromatography mass-spectrometry analysis was performed to confirm glycosaminoglycan levels and sulphation patterns on donor samples (n=15). In transplant recipients (n=50), levels were measured pre-transplant and daily for 4 days post-transplant. Levels were correlated with PGD severity and intubation time. Results Decreased hyaluronan levels in peripheral blood independently predicted organ acceptability in intended and actual donors (OR 0.96; (95%CI: 0.93-0.99) p=0.026). Furthermore, high donor syndecan-1 levels were associated with PGD in recipients (3142(1575-4829) vs 6229(4009-8093)pg/ml; p=0.045). In recipient blood, levels of syndecan-1 were correlated with severe (Grade 2-3) PGD at 72 hrs post-transplant (5982((3016-17191) vs 3060(2005-4824))pg/ml; p=0.01). Conclusions Endothelial glycocalyx breakdown occurs in lung transplant donors and recipients and predicts organ acceptability and development of PGD. Glycocalyx breakdown products may be useful biomarkers in transplantation, and interventions to protect the glycocalyx could improve transplant outcomes. Corresponding Author/ Reprint requests: Daniel Chambers, MBBS, MD, Queensland Lung Transplant Service, Level 1, Administration Building, The Prince Charles Hospital, Rode Rd, Chermside, Queensland, 4032, Australia. Telephone: +61-7-31394000. Fax +61-7-31395696. E-mail address: daniel.chambers@health.qld.gov.au Authors contributions: Timothy M Sladden contributed to research design, performance of the research, data analysis and writing of the paper. Stephanie Yerkovich and Daniel C Chambers contributed equally to research design, data analysis and writing of the paper. Michelle Grant, Michael Trotter and Peter Hopkins contributed to data collection and/ or analysis and critical revision of the manuscript. Xinyue Liu and Fuming Zhang contributed to performance of research, data analysis and writing of the paper. Robert J Linhardt contributed to analytic tools, data analysis and writing of the paper. Disclosures: The authors declare no conflicts of interest. Funding: This research was funded by a Program Grant from the Prince Charles Hospital Foundation and National Health and Medical Research Council Project Grant # 1103862. Neither funding source were involved in the research or manuscript preparation. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2RWxUFb
https://ift.tt/2RWxUFb
A Propensity Matched Survival Analysis: Do Simultaneous Liver-Lung Transplant Recipients Need a Liver?
Background There is debate whether simultaneous lung-liver transplant (LLT) long-term outcomes warrant allocation of 2 organs to a single recipient. We hypothesized that LLT recipients would have improved posttransplant survival compared to matched single-organ lung recipients with an equivalent degree of liver dysfunction. Methods The OPTN/UNOS STAR file was queried for adult candidates for LLT and isolated lung transplantation from 2006-2016. Waitlist mortality and transplant odds were calculated for all candidates. Donor and recipient demographic characteristics were compiled and compared. LLT recipients were matched 1:2 with a nearest neighbor method to single-organ lung recipients. Kaplan-Meier methods with log-rank test compared long-term survival between groups. Univariate regression was used to calculate the association of LLT and mortality within 6-months of transplant. A proportional hazards model was used to calculate risk-adjusted mortality after 6-months posttransplantation. Results Thirty-eight LLT patients were matched to 75 single-organ lung recipients. After matching, no differences in baseline demographics or liver function were observed between cohorts. Length of stay was significantly longer in LLT recipients compared to isolated lung recipients (45.89 days vs. 22.44 days, p
https://ift.tt/2DHV1jT
https://ift.tt/2DHV1jT
Cell-free microRNA miR-505-3p in graft preservation fluid is an independent predictor of delayed graft function after kidney transplantation
Background Delayed graft function (DGF), a common complication after transplantation of deceased donor kidneys, affects both short- and long-term outcomes. Currently available biomarkers during graft preservation lack sensitivity in predicting risk for DGF. The aim of this study is to identify cell-free microRNA biomarkers in graft preservation fluid predictive of DGF after kidney transplantation. Methods Vascular bed preservation fluid was collected from 48 kidney grafts from DCD or DBD (donation after circulatory death or brain death) donors. MiRNA profiles were determined by PCR array (n=8) and validated by RT-qPCR (n=40). Graft function post-transplantation was defined as immediate good function (IF) or DGF. Results A total of 223 miRNAs fulfilled the pre-set parameters (Ct
https://ift.tt/2RX5yL6
https://ift.tt/2RX5yL6
Deceased brain dead donor liver transplantation and utilization in the United States: nighttime and weekend effects
Background Understanding factors that contribute to liver discards and non-usage is urgently needed to improve organ utilization. Methods With SRTR data, we studied a national cohort of all U.S. adult, deceased brain dead donor, isolated livers available for transplantation from 2003-2016, including organ-specific and system-wide factors that may affect organ procurement and discard rates. Results Of 73,686 available livers, 65,316 (88.64%) were recovered for transplant, of which 6,454 (9.88%) were ultimately discarded. Livers that were not procured or, upon recovery, discarded were more frequently from older, heavier, HCV+, and more comorbid donors (p
https://ift.tt/2DJnRAj
https://ift.tt/2DJnRAj
Demographic and clinical characteristics of spinal calcinosis in systemic sclerosis: Possible association with peripheral angiopathy
Abstract
The objective was to evaluate the demographic and clinical characteristics of systemic sclerosis (SSc) patients with spinal calcinosis. Paraspinal and intraspinal calcinosis was assessed blindly by orthopedic surgeons specializing in spinal diseases using chest high‐resolution computed tomography (CT) that was performed for the screening and prospecting of interstitial lung disease in 159 Japanese SSc patients. Among these patients, we identified 27 (17%) with spinal calcinosis, and the most common site was cervical level at 77.8% (21/27). The frequency of spinal calcinosis in the late stage was higher than in the early stage (44.4% vs 29.6%). Multiple calcinosis was identified in 18.5% (5/27). The frequency of paraspinal calcinosis only was 59.3%, intraspinal calcinosis only 18.5%, and both intraspinal and paraspinal calcinosis 22.2%. Among SSc patients, 4.4% (7/159) had CT‐based evidence of spinal cord compression. Among cases with spinal cord compression, only one had neurological symptoms, and surgical removal improved the symptoms. The other six SSc patients with spinal calcinosis (3.8% of 159) had no symptoms. Male sex (29.6%) and severe peripheral vasculopathy such as digital ulcers (55.6%) and acro‐osteolysis (33.3%) were significantly more frequent in the SSc patients with spinal calcinosis than in the SSc patients without spinal calcinosis (10.6%, 32.6% and 14.4%, respectively). Our results suggest that severe peripheral vasculopathy may be associated with the development of spinal calcinosis. Because SSc patients are prone to spinal calcinosis, when SSc patients claim symptoms such as pain, numbness and movement disorder of the extremities, spinal calcinosis is a complication that should be taken into consideration.
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Brain Protection Beyond the OR: Consensus Statement on Perioperative Neurocognitive Disorders (PND)
No abstract availablehttps://ift.tt/2DIY2Ah
Mild Perioperative Hypothermia and Myocardial Injury: A Retrospective Cohort Analysis
BACKGROUND: We tested the primary hypothesis that final intraoperative esophageal temperature is associated with increased odds of a composite of in-hospital all-cause mortality and myocardial injury within 7 days after noncardiac surgery. Secondary exposures were time-weighted average intraoperative temperature and areahttps://ift.tt/2qOYkNE
Going With the Flow: Cerebrovascular Disease and Autoregulation
No abstract availablehttps://ift.tt/2S16f6c
Cerebral Small Vessel, But Not Large Vessel Disease, Is Associated With Impaired Cerebral Autoregulation During Cardiopulmonary Bypass: A Retrospective Cohort Study
BACKGROUND: Impaired cerebral blood flow (CBF) autoregulation during cardiopulmonary bypass (CPB) is associated with stroke and other adverse outcomes. Large and small arterial stenosis is prevalent in patients undergoing cardiac surgery. We hypothesize that large and/or small vessel cerebral arterial disease is associated with impaired cerebral autoregulation during CPB. METHODS: A retrospective cohort analysis of data from 346 patients undergoing cardiac surgery with CPB enrolled in an ongoing prospectively randomized clinical trial of autoregulation monitoring were evaluated. The study protocol included preoperative transcranial Doppler (TCD) evaluation of major cerebral artery flow velocity by a trained vascular technician and brain magnetic resonance imaging (MRI) between postoperative days 3 and 5. Brain MRI images were evaluated for chronic white matter hyperintensities (WMHI) by a vascular neurologist blinded to autoregulation data. "Large vessel" cerebral vascular disease was defined by the presence of characteristic TCD changes associated with stenosis of the major cerebral arteries. "Small vessel" cerebral vascular disease was defined based on accepted scoring methods of WMHI. All patients had continuous TCD-based autoregulation monitoring during surgery. RESULTS: Impaired autoregulation occurred in 32.4% (112/346) of patients. Preoperative TCD demonstrated moderate-severe large vessel stenosis in 67 (25.2%) of 266 patients with complete data. In adjusted analysis, female sex (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.25–0.86; P = .014) and higher average temperature during CPB (OR, 1.23; 95% CI, 1.02–1.475; P = .029), but not moderate-severe large cerebral arterial stenosis (P = .406), were associated with impaired autoregulation during CPB. Of the 119 patients with available brain MRI data, 42 (35.3%) demonstrated WMHI. The presence of small vessel cerebral vascular disease was associated with impaired CBF autoregulation (OR, 3.25; 95% CI, 1.21–8.71; P = .019) after adjustment for age, history of peripheral vascular disease, preoperative hemoglobin level, and preoperative treatment with calcium channel blocking drugs. CONCLUSIONS: These data confirm that impaired CBF autoregulation is prevalent during CPB predisposing affected patients to brain hypoperfusion or hyperperfusion with low or high blood pressure, respectively. Small vessel, but not large vessel, cerebral vascular disease, male sex, and higher average body temperature during CPB appear to be associated with impaired autoregulation.https://ift.tt/2DGnNBz
Brain Protection Beyond the OR: Consensus Statement on Perioperative Neurocognitive Disorders (PND)
No abstract availablehttps://ift.tt/2DIY2Ah
Going With the Flow: Cerebrovascular Disease and Autoregulation
No abstract availablehttps://ift.tt/2S16f6c
The Perioperative Management of Ascending Aortic Dissection
Acute aortic syndromes are a distinct group of pathologies involving the wall of the aorta that present acutely and can be potentially fatal unless treated in a timely fashion. The syndrome is dominated by aortic dissections, which comprise ≥95% of all such presentations. Those involving the ascending aorta are particularly lethal and require specific and early surgical treatment compared to dissections involving other parts of the aorta. The surgical repair of an ascending aortic dissection presents multiple challenges to the anesthesiologist. Thoughtful management throughout the perioperative period is critical for minimizing the significant morbidity and mortality associated with this condition. In this narrative review, we provide an overview of the perioperative management of patients presenting for the surgical repair of an ascending aortic dissection. Preoperative discussion focuses on assessment, hemodynamic management, and risk stratification. The intraoperative section includes an overview of anesthetic management, transesophageal echocardiographic assessment, and coagulopathy, as well as surgical considerations that may influence anesthetic management.https://ift.tt/2DKCHXr
Cerebral Small Vessel, But Not Large Vessel Disease, Is Associated With Impaired Cerebral Autoregulation During Cardiopulmonary Bypass: A Retrospective Cohort Study
BACKGROUND: Impaired cerebral blood flow (CBF) autoregulation during cardiopulmonary bypass (CPB) is associated with stroke and other adverse outcomes. Large and small arterial stenosis is prevalent in patients undergoing cardiac surgery. We hypothesize that large and/or small vessel cerebral arterial disease is associated with impaired cerebral autoregulation during CPB. METHODS: A retrospective cohort analysis of data from 346 patients undergoing cardiac surgery with CPB enrolled in an ongoing prospectively randomized clinical trial of autoregulation monitoring were evaluated. The study protocol included preoperative transcranial Doppler (TCD) evaluation of major cerebral artery flow velocity by a trained vascular technician and brain magnetic resonance imaging (MRI) between postoperative days 3 and 5. Brain MRI images were evaluated for chronic white matter hyperintensities (WMHI) by a vascular neurologist blinded to autoregulation data. "Large vessel" cerebral vascular disease was defined by the presence of characteristic TCD changes associated with stenosis of the major cerebral arteries. "Small vessel" cerebral vascular disease was defined based on accepted scoring methods of WMHI. All patients had continuous TCD-based autoregulation monitoring during surgery. RESULTS: Impaired autoregulation occurred in 32.4% (112/346) of patients. Preoperative TCD demonstrated moderate-severe large vessel stenosis in 67 (25.2%) of 266 patients with complete data. In adjusted analysis, female sex (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.25–0.86; P = .014) and higher average temperature during CPB (OR, 1.23; 95% CI, 1.02–1.475; P = .029), but not moderate-severe large cerebral arterial stenosis (P = .406), were associated with impaired autoregulation during CPB. Of the 119 patients with available brain MRI data, 42 (35.3%) demonstrated WMHI. The presence of small vessel cerebral vascular disease was associated with impaired CBF autoregulation (OR, 3.25; 95% CI, 1.21–8.71; P = .019) after adjustment for age, history of peripheral vascular disease, preoperative hemoglobin level, and preoperative treatment with calcium channel blocking drugs. CONCLUSIONS: These data confirm that impaired CBF autoregulation is prevalent during CPB predisposing affected patients to brain hypoperfusion or hyperperfusion with low or high blood pressure, respectively. Small vessel, but not large vessel, cerebral vascular disease, male sex, and higher average body temperature during CPB appear to be associated with impaired autoregulation.https://ift.tt/2DGnNBz
Tranexamic Acid Dosing for Cardiac Surgical Patients With Chronic Renal Dysfunction: A New Dosing Regimen
BACKGROUND: Tranexamic acid (TXA) is a common antifibrinolytic agent used to minimize bleeding in cardiac surgery. Up to 50% cardiac surgical patients have chronic renal dysfunction (CRD). Optimal dosing of TXA in CRD remains poorly investigated. This is important as TXA is renally eliminated with accumulation in CRD. High TXA doses are associated with postoperative seizures. This study measures plasma TXA concentrations in CRD cardiac surgical patients for pharmacokinetic modeling and dose adjustment recommendations. METHODS: This prospective cohort study enrolled 48 patients with stages 1–5 CRD, classified by Kidney Disease Outcome Quality Initiative. Patients were separated into 2 treatment groups. A "low-risk" group underwent simple aortocoronary bypass or single-valve repair/replacement and received a 50 mg/kg TXA bolus. A "high-risk" group underwent redo, aortic, multiple valve or combination surgery and received the Blood Conservation Using Anti-fibrinolytics Trial dosing regimen (loading dose 30 mg/kg, infusion 16 mg/kg/h with 2 mg/kg in pump prime). Primary outcome identified changes in TXA clearance and distribution volume, which provided the rationale for dose adjustment. Descriptive clinical outcomes assessed postoperative seizures, blood loss, ischemic-thrombotic complications, in-hospital mortality, and length of hospital stay. RESULTS: TXA concentrations were elevated and sustained above the therapeutic threshold for approximately 12 hours in high-risk stages 3–5 groups, in accordance to CRD severity. CONCLUSIONS: Using a pharmacokinetic model, we propose a simple new TXA dosing regimen that optimizes maximal antifibrinolysis and avoids excessive drug dosing.https://ift.tt/2OQHRSC
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