Immunological classification of renal cell carcinoma patients based on phenotypic analysis of immune check-point molecules

Abstract

Objectives

To clarify comprehensive immunological signature patterns of tumour tissue-infiltrating lymphocytes in patients with renal cell carcinoma and show its clinical significance.

Materials and methods

We investigated the surface marker expressions of tumour tissue-infiltrating lymphocytes quantitatively and classified them based on their functional populations. We extracted 109 sets of tumour tissue-infiltrating lymphocytes from 80 patients who underwent surgical resection of renal cell carcinoma, of which 44 tumour tissue-infiltrating lymphocytes were multiply extracted from 15 patients. Each tumour tissue-infiltrating lymphocyte was characterised on the basis of functional T-cell populations using ten surface marker expressions measured by flow cytometry.

Results

All sets of the tumour tissue-infiltrating lymphocytes were classified into three groups, which correlated significantly with Fuhrman grade (OR 0.253, 95% CI 0.094–0.678, P = 0.006). Importantly, both overall metastasis-free survival (HR 0.449, 95% CI 0.243–0.832, P = 0.011) and recurrence-free survival (HR 0.475, 95% CI 0.238–0.948, P = 0.035) of the patients with the higher marker expressions were significantly inferior to those of the patients with the lower marker expressions by multivariate analysis. Six specific genes for this classification identified by microarray analysis verified our results using the TCGA KIRC data set. In addition, we discovered the presence of intra-tumoural diversity in the classification of 3 (20%) of the 15 patients.

Conclusions

This study showed that the presence of classable diversity in the immunological signature of tumour tissue-infiltrating lymphocytes correlated with prognosis and tumour aggressiveness that was observed even within individual tumours in some patients with renal cell carcinoma.

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Intraoperative naloxone reduces remifentanil-induced postoperative hyperalgesia but not pain: a randomized controlled trial

Abstract

Background

Intraoperative use of a high-dose remifentanil may induce postoperative hyperalgesia. Low-dose naloxone can selectively reverse some adverse effects of opioids without compromising analgesia. We thus hypothesized that the intraoperative use of a high-dose remifentanil combined with a low-dose naloxone infusion reduces postoperative hyperalgesia compared with the use of remifentanil alone.

Methods

Patients undergoing elective thyroid surgery were randomly assigned into one of three groups, depending on the intraoperative effect-site concentration of remifentanil, with or without a continuous infusion of naloxone: 4 ng ml⁻¹ remifentanil with 0.05 μg kg⁻¹ h⁻¹ naloxone in the high-remifentanil with naloxone group, and 4 or 1 ng ml⁻¹ remifentanil with a placebo in the high- or low-remifentanil groups, respectively. We measured the pain thresholds (primary outcome) to mechanical stimuli using von Frey filaments and incidence of hyperalgesia on the peri-incisional area 24 h after surgery. We also measured pain intensity, analgesic consumptions and adverse events up to 48 h after surgery.

Results

The pain threshold presented as von Frey numbers [median (interquartile range)] was significantly lower in the high-remifentanil group (n=31) than in the high-remifentanil with naloxone (n=30) and the low-remifentanil (n=30) groups [3.63 (3.22–3.84) vs 3.84 (3.76–4.00) vs 3.80 (3.69–4.08), P=0.011]. The incidence of hyperalgesia was also higher in the high-remifentanil group than in the other groups [21/31 vs 10/30 vs 9/30, P=0.005]. Postoperative pain intensity, analgesic consumptions and adverse events were similar between groups.

Conclusions

The intraoperative use of low-dose naloxone combined with high-dose remifentanil reduced postoperative hyperalgesia but not pain.

Clinical trial registration

NCT02856087.

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Role of in-situ simulation for training in healthcare: opportunities and challenges.

Purpose of review: Simulation has now been acknowledged as an important part of training in healthcare, and most academic hospitals have a dedicated simulation center. In-situ simulation occurs in patient care units with scenarios involving healthcare professionals in their actual working environment. The purpose of this review is to describe the process of putting together the components of in-situ simulation for training programs and to review outcomes studied, and challenges with this approach. Recent findings: In-situ simulation has been used to 'test-drive' new centers, train personnel in new procedures in existing centers, for recertification training and to uncover latent threats in clinical care areas. It has also emerged as an attractive alternative to traditional simulations for institutions that do not have their own simulation center. Summary: In-situ simulation can be used to improve reliability and safety especially in areas of high risk, and in high-stress environments. It is also a reasonable and attractive alternative for programs that want to conduct interdisciplinary simulations for their trainees and faculty, and for those who do not have access to a fully functional simulation center. Further research needs to be done in assessing effectiveness of training using this method and the effect of such training on clinical outcomes. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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NonOperating Room Anesthesia: distancing from invasive surgery, embracing the era of interventional medicine.

No abstract available

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Recent advances of simulation in obstetric anesthesia.

Purpose of review: Simulation training in obstetric anesthesia has become widespread in recent years. Simulations are used to train staff and trainees, assess and improve team performance, and evaluate the work environment. This review summarizes current research in these categories. Recent findings: Simulation to improve individual technical skills has focused on induction of general anesthesia for emergent cesarean delivery, an infrequently encountered scenario by anesthesia trainees. Low- and high-fidelity simulation devices for the learning and practicing neuraxial and non-neuraxial procedures have been described, and both are equally effective. The use of checklists in obstetric emergencies has become common as and post-scenario debriefing techniques have improved. Although participant task performance improves, whether participants retain learned skills or whether simulation improves patient outcomes has not yet been established. Tools to assess teamwork during simulation have been developed, but none have been rigorously validated. In-situ vs. offsite simulations do not differ in effectiveness. Summary: Simulation allows for practice of tasks and teamwork in a controlled manner. There is little data whether simulation improves patient outcomes and metrics to predict the long-term retention of skills by simulation participants have not been developed. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Evaluation of fibroblast growth factor activity exerted by placental extract used as a cosmetic ingredient

Summary

Background

The biological activities claimed for placental extract (PE) in its medical and cosmetic applications are largely assumed to be the combined effects of its various signaling molecules and nutritional constituents. But there are considerable uncertainties about this assumption.

Aims

To determine the specific biological activity of PE at a molecular level.

Methods

Fibroblast growth factor (FGF) activity was assessed based on the ability to induce proliferation of FGF receptor (FGFR)-overexpressing BaF3 cells.

Results

Porcine PE (PPE), an ingredient in numerous cosmetics, activated proliferation of BaF3 cells overexpressing FGFR subtypes 1c, 2c, 2b, 3c, or 4, that is, all the major FGFR subtypes. The effect was suppressed largely or partially when the cells were treated with a FGFR inhibitor PD173074, and the FGFR-negative BaF3 parent cells exhibited minimal growth promotion as compared to the FGFR-expressing BaF3 cells. The high (>10 kDa) and low (<3 kDa) molecular weight fractions of PPE were effective activators of FGFR signaling. PPE was found to contain sulfated glycosaminoglycans, including heparin/heparan sulfate and chondroitin sulfate, which serve as both structural stabilizers of FGFs and indispensable cofactors for FGF-FGFR signaling.

Conclusions

These results indicate that PPE is capable of evoking FGF signaling in cells via FGFRs. Given that recombinant FGFs have proven useful for medical/cosmetic purposes, our results suggest that the medical/cosmetic utility of PPE is provided at least partly through the activation of FGF signaling in epidermal, dermal, and subdermal tissues.

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Novel immunologic mechanisms in eosinophilic esophagitis

Julie M Caldwell | Misu Paul | Marc E Rothenberg

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Urinary biomarker CXCL10, identifying site specific allograft inflammation in renal transplantation.

No abstract available

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Altered Th17 pathway in tolerant kidney transplant patients: a 'chicken-or-the-egg' dilemma?.

No abstract available

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Long-term effects of pancreas transplantation on diabetic retinopathy and incidence and predictive risk factors for early worsening.

Background: Limited data are available regarding the long-term effects of pancreas transplantation on the progression of diabetic retinopathy (DR) and the incidence of and associated risk factors for early worsening of DR. Methods: Patients who underwent successful pancreas transplantation between January 2007 and October 2015 and were followed for >= 1 year were consecutively enrolled. Variables regarding demographic, systemic, metabolic, and surgical factors were reviewed for each patient. DR progression was defined as i) development or aggravation of macular edema requiring intravitreal injections and/or ii) progression of DR severity requiring panretinal photocoagulation (PRP) and/or pars planar vitrectomy (PPV). Early worsening was defined as progression within 1 year of posttransplant. Results: Three hundred and 3 eyes of 153 patients were included in the analysis. At the pretransplant ocular evaluation, 221 eyes (72.9 %) showed advanced DR with history of PRP and/or PPV. During a mean follow-up period of 4.2 years, 62 eyes (20.5%) experienced DR progression, and early worsening was noted in 57 eyes (18.8%). DR with recent PRP within pretransplant 1 year and pancreas transplant alone were significant risk factors for early worsening. Conclusions: In 4 out 5 patients who received pancreas transplant, the degree of DR remained stable over time after transplantation. Meanwhile, early worsening of DR could occur in patients at risk, particularly within the first posttransplant year. We suggest that physicians should have a high index of suspicion and carefully monitor for early worsening of DR, and timely manage possible ocular deterioration. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Marked decrease in urgent listing for liver transplantation over time: evolution of characteristics and outcomes of Status-1 liver transplantation.

Background: Approximately 5% of liver transplants annually are performed urgently with "status-1" designation. This study aims to determine if the demand, characteristics and outcome for status-1 liver transplantation has changed over time. Methods: We utilized the Scientific Registry of Transplant Patients (2003-2015) to characterize 2352 adult patients who underwent 2408 status-1 liver transplants and compared them between Era1 (2003-6/2009) and Era2 (7/2009 -2015). Results: Overall, there were fewer liver transplants performed with the Status-1 designation in Era2 than Era1 (1099 vs 1309). Although the number of urgent liver transplants was relatively constant with successive years, the proportion transplanted with Status-1 designation decreased markedly over time. Era2 patients were older (43.2 vs 41.7 years, p=0.01) and less likely be ABO-incompatible (1.1% vs 2.4%, p=0.01) or re-transplant (77 vs 124, p=0.03). In terms of disease etiology, the largest group was "ALF, nonspecified" (43.4%). There was no difference in proportion with drug-induced liver injury (DILI), but the subset of herbal/dietary supplements increased in Era2 (1.3% vs 0.46 %, p=0.04). Survival was increased in Era2 in the overall cohort and for patients with autoimmune disease (p

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Role of human CD200 overexpression in pig-to-human xenogeneic immune response compared with human CD47 overexpression.

Background: Macrophages play important roles in xenograft rejection. Here, we investigated whether overexpression of human CD200 or CD47 in porcine endothelial cells (PEC) can suppress macrophages activation in xenogeneic immune responses. Methods: PECs and human macrophages were incubated together, harvested and analyzed for in vitro macrophage phagocytic and cytotoxicity activity, and cytokine release. Next, PEC were injected into renal subcapsular space of humanized mice. On day 10 posttransplantation, we analyzed xenograft survival and perigraft inflammatory cell infiltrations in PEC-to-humanized mouse transplantation. Results: PECs highly expressing human CD200, CD47, or both CD47/CD200 were established by lentiviral vector transduction. Both CD200 and CD47 suppressed in vitro macrophage phagocytic and cytotoxic activity against PECs; decreased TNF-[alpha], IL-1[beta], and IL-6 secretion; and increased IL-10 secretion. However, simultaneous overexpression of CD200 and CD47 did not show additive effects. Next, PECs were transplanted into NSG mice, and human monocytes and lymphocytes were adoptively transferred 1 day after xenotransplantation. PEC xenograft cell death and apoptosis were decreased in the CD200-PEC and CD47/CD200-PEC groups. Perigraft infiltration of human T cells was suppressed by CD47; CD200 suppressed infiltration of human macrophages to a greater extent than CD47; and the CD47/CD200-PEC group exhibited the lowest level of leukocyte infiltration. In summary, overexpression of CD200 in PECs suppressed xenogeneic activation of human macrophages and improved survival of PEC xenografts in humanized mice; however, co-expression of CD200 and CD47 did not show additive effects. Conclusions: Therefore, overexpression of human CD200 in donor pigs could constitute a promising strategy for overcoming xenograft rejection. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Coexistence of Bilirubin >=10 mg/dL and Prothrombin Time-International Normalized Ratio >=1.6 on Day 7: A Strong Predictor of Early Graft Loss after Living Donor Liver Transplantation.

Background: Early allograft dysfunction (EAD) defined by serum total bilirubin (TB) >=10 mg/dL or prothrombin time-international normalized ratio (PT-INR) >=1.6 on postoperative day 7 (POD7) or aminotransferase >2000 IU/L within the first week, is associated with early graft loss after deceased-donor liver transplantation. We aimed to determine the prognostic impact of the EAD definition in living-donor liver transplantation (LDLT). Methods: We analyzed the validity of the EAD definition and its impact on early graft survival in 260 adult recipients who underwent primary LDLT. Results: Eighty-four (32.3%) patients met the EAD criteria; 59 (22.7%) and 46 (17.7%) patients had TB >=10 mg/dL and PT-INR >=1.6 on POD7, respectively, and 22 (8.5%) patients satisfied both criteria. Graft survival differed significantly when stratified according to TB >=10 mg/dL and PT-INR >=1.6 (p=1.6 resulted in higher graft mortality (RR=3.87, p<.0001 at rr="2.97," p as did tb>=10 mg/dL (RR=1.89, p=0.027 at 90-day; RR=1.91, p=0.006 at 180-day). Coexistence of TB >=10 mg/dL and PT-INR >=1.6 was strongly associated with early graft loss (59.1%, RR=6.97 at 90-day; 68.2%, RR=5.75 at 180-day). In Cox regression analysis, PT-INR >=1.6 and TB >=10 mg/dL on POD7 were significant risk factors for early graft loss (hazard ratio =4.10 [95% CI: 2.35-7.18], p=10 mg/dL and/or PT-INR >=1.6 on POD7 predicted early graft loss after LDLT, and their coexistence worsened patient outcomes. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Monocyte and macrophage immunometabolism in atherosclerosis

Abstract

Atherosclerosis is characterized by chronic low grade inflammation of arteries that results in the development of lipid dense plaques. Chronic inflammation induced by Western-type diet is associated with the risk of developing atherosclerosis, and new insights shed light on the importance of metabolic and functional reprogramming in monocytes and macrophages for progression of atherosclerosis. This review aims to provide an overview of our current understanding into how the metabolic reprogramming of glucose, cholesterol, fatty acid, and amino acid metabolism in macrophages contributes to inflammation during atherosclerosis. Recent insights suggest that transcriptional and epigenetic adaptation within innate immune cells (termed trained immunity) play an important role in the pathogenesis of atherosclerosis. We propose that metabolic changes induced by pro-atherogenic lipoproteins partly mediate these changes in trained macrophages. Finally, we discuss the possibility of manipulating cellular metabolism of immune cells for targeted therapeutic intervention against atherosclerosis.

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Preventing new sensitization and asthma onset by allergen immunotherapy: the current evidence.

Purpose of review: Specific allergen immunotherapy is considered a key candidate for a successful preventive intervention in atopic diseases. The strong association of atopic manifestations such as rhinitis and asthma with atopic sensitizations (specific serum IgE) provide a rationale for early intervention in childhood and adolescence. Recent findings: Currently, the documentation of the disease-modifying intervention effects is limited to the secondary prevention of asthma symptoms in children with allergic rhinoconjunctivitis. These effects appear to be rather allergen specific than nonspecific. Summary: Documentation on disease modification including a reduction of asthma symptoms in children, particularly with grass pollen tablets has become quite robust. It is not clear up to now, if the new onset of allergic sensitizations can be modified. So far data on primary prevention are not conclusive. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Approaches to the removal of T-lymphocytes to minimize graft-versus-host disease in patients with primary immunodeficiencies who do not have a matched sibling donor.

Purpose of review: Since the advent of T-lymphocyte depletion in hematopoietic stem cell transplantation (HSCT) for primary immunodeficiency, survival following this procedure has remained poor compared to results when using matched sibling or matched unrelated donors, over the last 40 years. However, three new techniques are radically altering the approach to HSCT for those with no matched donor, particularly those with primary immunodeficiencies which are not severe combined immunodeficiency. Recent findings: Three main techniques of T-lymphocyte depletion are altering donor choice for patients with primary immunodeficiencies and have improved transplant survival for primary immunodeficiencies to over 90%, equivalent to that for matched sibling and matched unrelated donor transplants. CD3+ T cell receptor (TCR)[alpha][beta]+ CD19+ depletion, CD45RA depletion and use of posttransplant cyclophosphamide give similar overall survival of 90%, although viral reactivation remains a concern. Further modification of CD3+ TCR[alpha][beta]+ CD19+ depletion by adding back inducible caspase-9 suicide gene-modified CD3+ TCR[alpha][beta]+ T-lymphocytes may further improve outcomes for patients with systemic viral infection. Summary: Over the last 5 years, the outcomes of HSCT using new T-lymphocyte depletion methods have improved to the extent that they are equivalent to outcomes of matched sibling donors and may be preferred in the absence of a fully matched sibling donor, over an unrelated donor to reduce the risk of graft versus host disease. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Critical appraisal of the unmet needs in the treatment of chronic spontaneous urticaria with omalizumab: an Italian perspective.

Purpose of review: The humanized anti-IgE antibody omalizumab has been available for patients with chronic spontaneous urticaria (CSU) in Italy since 2015. This review summarizes the unresolved issues and unmet therapeutic needs associated with omalizumab and discusses practical recommendations for its use in the management of CSU. Recent findings: Although modern second-generation H1-antihistamines are the standard of care for patients with CSU, adjunctive treatments (including omalizumab) may be required for effective control of symptoms in many patients. Evidence from clinical trials and experience from daily clinical practice suggest that the use of omalizumab in patients with CSU who have inadequate response to H1-antihistamines remains challenging. Summary: Based on current international guidelines, omalizumab labelling information and our experience in clinical practice, we provide treatment recommendations regarding the use of omalizumab in patients with CSU. These include: optimal treatment duration, the use of concomitant antihistamine therapy, the definition and management of disease relapse after treatment, and the management of patients with late or no response to treatment. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Attentional Modulation of Envelope-Following Responses at Lower (93–109 Hz) but Not Higher (217–233 Hz) Modulation Rates

Abstract

Directing attention to sounds of different frequencies allows listeners to perceive a sound of interest, like a talker, in a mixture. Whether cortically generated frequency-specific attention affects responses as low as the auditory brainstem is currently unclear. Participants attended to either a high- or low-frequency tone stream, which was presented simultaneously and tagged with different amplitude modulation (AM) rates. In a replication design, we showed that envelope-following responses (EFRs) were modulated by attention only when the stimulus AM rate was slow enough for the auditory cortex to track—and not for stimuli with faster AM rates, which are thought to reflect 'purer' brainstem sources. Thus, we found no evidence of frequency-specific attentional modulation that can be confidently attributed to brainstem generators. The results demonstrate that different neural populations contribute to EFRs at higher and lower rates, compatible with cortical contributions at lower rates. The results further demonstrate that stimulus AM rate can alter conclusions of EFR studies.

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Colonization of the middle turbinate

Publication date: Available online 2 October 2017
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): C. Djian, A.-L. Gaultier, S. Chartier, O. Laccourreye




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Psoriasis Patients Face Increased Risk of Heart Attacks and Death

People with psoriasis, a chronic inflammatory disease, may be more likely than others to experience heart attacks and strokes at least in part because inflammation damages their vascular system, a recent study suggests.
Reuters Health Information

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Liquid biopsy: An emerging prognostic and predictive tool in Head and Neck Squamous Cell Carcinoma (HNSCC). Focus on Circulating Tumor Cells (CTCs)

Publication date: November 2017
Source:Oral Oncology, Volume 74
Author(s): P. Economopoulou, I. Kotsantis, E. Kyrodimos, E.S. Lianidou, A. Psyrri
Molecular diversity and continuing evolution of metastatic tumors are not easily captured by tissue biopsies. Development of non-invasive diagnostic tools, such asanalysis of circulating tumor DNA (ctDNA), Circulating Tumor Cells (CTCs) and exosomes provides the opportunity to assess a blood sample in order to monitor tumor change and extract molecular information from cancers at a given time. "Liquid biopsy", which refers to molecular analysis of tumor's genetic features based on circulating genetic material in the peripheral blood, is already used to monitor disease response and track mechanisms of drug resistance in solid tumors. Head and Neck Squamous Cell Carcinoma (HNSCC) is a malignancy associated with advanced disease at presentation and dismal outcomes; furthermore, there is lack of biomarkers to monitor disease burden. Incorporation of liquid biopsy in the management of HNSCC might help identify patients with occult metastatic disease earlier and in a non-invasive manner. Herein, we aim to review current knowledge regarding CTCs and ctDNA in HNSCC and address open questions in this fast-evolving field of research.



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40-year incidence trends for oropharyngeal squamous cell carcinoma in the United States

Publication date: November 2017
Source:Oral Oncology, Volume 74
Author(s): Nosayaba Osazuwa-Peters, Matthew C. Simpson, Sean T. Massa, Eric Adjei Boakye, Jastin L. Antisdel, Mark A. Varvares
ObjectivesTo determine differences in oropharyngeal squamous cell carcinoma (OPSCC) incidence between 1975 and 2014 stratified by race, sex, and age.Materials and methodsWe obtained age-adjusted OPSCC incidence rates for race and sex groups from 1975 to 2014 using the Surveillance, Epidemiology, and End Results 9 database. We defined OPSCC as cancers of the base of tongue, lingual/palatine tonsil, oropharynx, soft palate, uvula, and Waldeyer's ring. We used Joinpoint analyses to determine incidence trends for race/sex/age groupings.ResultsThere were 38,624 oropharyngeal primary tumors in the analyses. Males accounted for 74% of sample population, and whites accounted for 84% of tumors. Overall, there was a 57.3% increase in incidence of oropharyngeal between 1975 and 2014. For blacks and whites, average incidence was lower for females than males. Rates for black males aged ≥50years was highest for most of the follow-up time but decreased sharply around 1988 and were surpassed by the significant increase in incidence in white males aged 50–59 (1995–2014 APC=4.07, p<0.001) and ≥60years (2002–2014 APC=4.25, p<0.001). For males aged ≥60, whites had higher rates than blacks starting in 2010. OPSCC incidence in White males (10.99 per 100,000 person-years) surpassed rates in Blacks (10.14 per 100,000 person-years) beginning in 2008.ConclusionOPSCC has significantly increased in the United States in the last 40 years. This overall increase in OPSCC can primarily be attributed to white males. OPSCC prevention and early detection efforts could target these demographic factors to decrease rising OPSCC incidence.



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Cochlear Implantation in Patients with Keratitis-Ichthyosis-Deafness Syndrome: A Report of Two Cases

Background. Keratitis-ichthyosis-deafness (KID) syndrome is a syndrome which presents with hearing loss and visual and keratinization disorders. In such patients, hearing aids cannot be effectively used in the rehabilitation of hearing loss because of the frequent blockage of the external ear canal with epithelial debris and due to dry and tense skin of the external ear canal. Moreover, severe or profound hearing loss also limits the benefits gained from the conventional hearing aids. On the other hand, cochlear implantation is a method that has been used in limited cases in the literature. Case Report. This study presents the results of cochlear implantation applied in our clinic to two children who had been diagnosed with KID. Audiological assessments before and after the cochlear implant operation were performed using pure-tone audiometry, immittance audiometry, and auditory brainstem response (ABR), and the postoperative follow-up was conducted using pure-tone audiometry. Conclusion. Skin problems, visual disturbances, and other additional problems complicate the short-term and long-term rehabilitation after implantation in individuals with KID syndrome. Close monitoring should be exercised due to possible skin complications that may develop during the postoperative period. The families and rehabilitation teams should be warned about the possible visual disturbances and skin complications.

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Asthma predisposition and respiratory syncytial virus infection modulate transient receptor potential vanilloid 1 function in children's airways

Publication date: Available online 2 October 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Terri J. Harford, Fariba Rezaee, Rachel G. Scheraga, Mitchell A. Olman, Giovanni Piedimonte




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Transfer of maternal immunity and programming of the newborn immune system

Abstract

As placental mammals, the pregnant women and the fetus have intense and prolonged interactions during gestation. There is increasing evidence that multiple molecular as well as cellular components originating in pregnant women are transferred to the fetus. The transfer of maternal antibodies has long been recognized as a central component of newborn immunity against pathogens. More recent studies indicate that inflammatory mediators, micronutrients, microbial products and maternal cells are transferred in utero and influence the fetal immune system. Together, these multiple signals are likely to form a complex network of interactions that program the neonatal immune system and tune its homeostatic regulation. Maternal disorders, in particular infectious diseases, modify these signals and may thereby alter immunity in early life. Understanding maternal programming of the newborn immune system could provide a basis for interventions promoting child health.

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Issue Information

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Observational Study of Definitive (Chemo)Radiotherapy on Patients With Esophageal Cancer

Conditions:   Esophagus Cancer;   Chemoradiation;   Chemotherapy Effect;   Radiotherapy Side Effect
Intervention:  
Sponsors:   Chinese Academy of Medical Sciences;   Hebei Medical University Fourth Hospital;   Fujian Cancer Hospital;   Anyang Tumor Hospital;   The First Affiliated Hospital with Nanjing Medical University;   Affiliated Hospital of Hebei University;   Tianjin Medical University Cancer Institute and Hospital;   Beijing Hospital;   Tengzhou Central People's Hospital;   PLA Army General Hospital
Recruiting

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Onkologie

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Auf der Welle des „Allergie-Tsunami“ surfen

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Ranitidine-induced black tongue: A case report

Abstract

Black tongue is a rare, benign, self-limiting disorder caused by certain conditions and some medications. We report the first case of a child diagnosed with black tongue associated with ranitidine use. We report our case to emphasize the rare side effect of this frequently used drug. Health care professionals should be aware of the likelihood of ranitidine-induced black tongue in clinical practice.

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“Dots and lines”: A melanonychia striata in regression: Report of a case

Abstract

A 2-year-old Caucasian boy with melanonychia striata with multiple striking pits on the nail plate of one fingernail is described. Nail disorders often pose diagnostic and therapeutic challenges for clinicians, especially melanonychia striata, because of the fear of a subungual melanoma. Only a few childhood cases of melanonychia striata have been described, and the multiple pits are even less common. Dots distributed along melanotic lines is a finding referred to as "dots and lines" and can be a sign of regression of melanonychia in childeren.

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A prospective study evaluating the utility of a 2-mm biopsy margin for complete removal of histologically atypical (dysplastic) nevi

Complete removal of individual dysplastic nevi (DN) is often accomplished by a second surgical procedure after the initial biopsy. The choice to perform the second procedure is strongly influenced by histopathologic margin status of the initial biopsy specimen.

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